Académique Documents
Professionnel Documents
Culture Documents
PEDIATRIC SURGERY
Content Strategist: Michael Houston
Content Development Specialist: Alexandra Mortimer
Content Coordinators: Sam Crowe/Humayra Rahman Khan
Project Managers: Srividhya Vidhya Shankar/Sukanthi Sukumar
Designer: Miles Hitchen
Illustration Manager: Jennifer Rose
Illustrator: Antbits
Marketing Manager: Abigail Swartz
ASHCRAFTS
PEDIATRIC
SURGERY
SIXTH EDITION
J. Patrick Murphy, MD
Professor of Surgery
Chief, Section of Urology
Department of Surgery
Childrens Mercy Hospital
Kansas City, MO, USA
Daniel J. Ostlie, MD
Surgeon-in-Chief, American Family Childrens Hospital
WARF Professor of Pediatric Surgery
Chief, Pediatric Surgery
Department of Surgery
University of Wisconsin
Madison, WI, USA
Associate Editor
Shawn D. St. Peter, MD
Professor of Surgery
Director, Center for Prospective Trials
Department of Surgery
Childrens Mercy Hospital
Kansas City, MO, USA
No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Details on how to seek permission, further
information about the Publishers permissions policies and our arrangements with organizations such as
the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website:
www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
Publisher (other than as may be noted herein).
Video clip 34.1 Trans Anal Pullthrough Cincinnati Childrens Hospital Medical Center
Video clip 35.1 Rectourethral Fistula Repair Cincinnati Childrens Hospital Medical Center
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the
most current information provided (i) on procedures featured or (ii) by the manufacturer of each
product to be administered, to verify the recommended dose or formula, the method and duration of
administration, and contraindications. It is the responsibility of practitioners, relying on their own
experience and knowledge of their patients, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products
liability, negligence or otherwise, or from any use or operation of any methods, products,
instructions, or ideas contained in the material herein.
ISBN: 978-1-4557-4333-9
Printed in China
xi
xii Video Contents
(Cincinnati Childrens Hospital Medical Center) 47.2 Laparoscopic Resection of a Splenic Cyst
KuoJen Tsao George W. Holcomb III
35 Imperforate Anus and Cloacal Malformations
35.1 Rectourethral Fistula Repair
Marc A. Levitt Alberto Pea
51 Undescended Testes and Testicular Tumors
51.1 Two-Staged Laparoscopic Orchiopexy for a Left
(Cincinnati Childrens Hospital Medical Center) Non-Palpable Testis
George W. Holcomb III
36 Fecal Incontinence and Constipation
(From Atlas of Pediatric Laparoscopy and Thoracoscopy,
36.1 Appendicostomy for Antegrade Enemas for Holcomb etal, Copyright 2008, with permission from
Patients with Fecal Incontinence Elsevier.)
Marc A. Levitt Alberto Pea
This textbook represents the sixth edition of a textbook Barbara Juarez, and Jeanette Whitney without whose
which was first published in 1980 under the direction of efforts this book would not have been possible. They
Drs. Tom Holder and Keith Ashcraft. One of the under- have done a remarkable job in helping us in so many ways
lying tenets of this book has always been to make it as with the task of editing this book. We also thank Dr.
readable as possible. In the Preface of the second edition, Rand ODonnell, President/CEO of Childrens Mercy
Drs. Holder and Ashcraft wrote Our intent is to provide Hospital, who has given us the support and resources
a book that has a clear explanation of a subject done in a needed to produce this book.
readable style. For this edition and previous ones, authors The editors have dedicated this edition to our former
have been selected because of their expertise about their senior partner, Dr. Ron Sharp, who recently retired from
chapters subject matter and their writing ability. Also, practice at Childrens Mercy Hospital. Ron was instru-
because many pediatric general surgeons outside the mental in the founding of our burn and trauma programs,
United States have a significant part of their practice in and directed these two programs for almost thirty years.
urology, we have continued to emphasize this subject in During his career, he was board certified in general
the sixth edition. As minimally invasive surgery (MIS) surgery, pediatric surgery, and surgical critical care. He
continues to weave its way more and more into main- was known as the go to person for advice and help with
stream pediatric surgery and urology, the MIS approach a complicated surgical problem. In addition to trauma,
is emphasized in most of the chapters as well. burns and critical care, he had a long-standing interest
There are many new figures and tables in this edition. and expertise in the repair of pectus excavatum, and was
In addition, most of the figures and artwork are in color. the one who conceptualized making a small subxyphoid
There are only a few figures in which the color version incision so that the surgeon can use his/her finger to
is not available. We feel the color photographs and draw- direct the substernal bar across the mediastinum and help
ings add significantly to the readability of the book. In protect the heart when performing the Nuss operation.
addition, there are 30 videos that accompany this edition Although his talents will be missed, we have all benefitted
and most depict the minimally invasive approach to a from his association and expertise.
particular surgical condition. These videos are accessible
via our Expert Consult website (expertconsult.com). George W. Holcomb III, MD MBA
There is a code in the front of this book that allows access J. Patrick Murphy, MD
to the online version of the book and the videos. Daniel J. Ostlie, MD
The editors would like to acknowledge the tireless Shawn D. St. Peter, MD
efforts of our administrative assistants Linda Jankowski,
xiii
List of Contributors
David Juang, MD
Assistant Professor of Surgery; Director, Trauma, Burns
& Surgical Critical Care Director, Surgical Critical
Care Fellowship, Department of Surgery, Childrens
Mercy Hospital, University of MissouriKansas
City, Kansas City, MO, USA
Ch 13 Burns, Video 29.1 Laparoscopic Repair of Pyloric
Atresia
List of Contributors xix
Ellen Shapiro, MD
Professor of Urology; Director, Pediatric Urology,
Department of Urology, New York University School
of Medicine, New York, NY, USA
Ch 57 Posterior Urethral Valves
xxii List of Contributors
Of all pediatric patients, the neonate possesses the most Special problems with the preterm infant include the
distinctive and rapidly changing physiologic characteris- following:
tics. These changes are necessary because the newborn 1. Weak suck reflex
must adapt from placental support to the extrauterine 2. Inadequate gastrointestinal absorption
environment. There is also early organ adaptation, and 3. Hyaline membrane disease (HMD)
the physiologic demands of rapid growth and develop- 4. Intraventricular hemorrhage
ment. This chapter will emphasize the dynamic physio- 5. Hypothermia
logic alterations of the neonate. 6. Patent ductus arteriosus
Newborns are classified based on gestational age vs 7. Apnea
weight, and gestational age vs head circumference and 8. Hyperbilirubinemia
length. Preterm infants are those born before 37 weeks 9. Necrotizing enterocolitis (NEC)
of gestation. Term infants are those born between 37 and
42 weeks of gestation, while post-term infants have a
gestation that exceeds 42 weeks. Babies whose weight is SPECIFIC PHYSIOLOGIC PROBLEMS
below the 10th percentile for age are considered small-
for-gestational-age (SGA). Those at or above the 90th
OF THE NEWBORN
percentile are large-for-gestational-age (LGA). The Glucose Metabolism
babies whose weight falls between these extremes are
appropriate-for-gestational-age (AGA). Further subclas- The fetus maintains a blood glucose value 7080% of
sified, premature infants are characterized as moderately maternal value by facilitated diffusion across the placenta.
low birth weight if they weigh between 15012500g, There is a build-up of glycogen stores in the liver, skel-
very low birth weight between 10011500g and extremely eton, and cardiac muscles during the later stages of fetal
low birth weight if less than 1000g. development, but little gluconeogenesis. The newborn
SGA newborns are thought to suffer intrauterine must depend on glycolysis until exogenous glucose is
growth retardation (IUGR) as a result of placental, supplied. Following delivery, the baby depletes its hepatic
maternal, or fetal abnormalities. Conditions associated glycogen stores within two to three hours. The newborn
with IUGR are shown in Figure 1-1. SGA infants have a is severely limited in his or her ability to use fat and
body weight below what is appropriate for their age, yet protein as substrates to synthesize glucose. When total
their body length and head circumference are age appro- parenteral nutrition (TPN) is needed, the glucose infu-
priate. To classify an infant as SGA, the gestational age sion rate should be initiated at 46mg/kg/min and
must be estimated by the physical findings summarized advanced 12mg/kg/min to a goal of 12mg/kg/min.
in Table 1-1.
Although SGA infants may weigh the same as prema- Hypoglycemia
ture infants, they have different physiologic characteris-
tics. Due to intrauterine malnutrition, body fat levels are Clinical signs of hypoglycemia are nonspecific and subtle.
frequently below 1% of the total body weight. This lack Seizure and coma are the most common manifestations
of body fat increases the risk of hypothermia with SGA of severe hypoglycemia. Neonatal hypoglycemia is gen-
infants. Hypoglycemia is the most common metabolic erally defined as a glucose level lower than 50mg/dL.1
problem for neonates and develops earlier in SGA infants Infants who are at high risk for developing hypoglycemia
due to higher metabolic activity and reduced glycogen are those who are premature, SGA, and born to mothers
stores. The red blood cell (RBC) volume and the total with gestational diabetes, severe preeclampsia, and
blood volume are much higher in the SGA infant com- HELLP (hemolysis, elevated liver enzymes, low platelet
pared with the preterm AGA or the non-SGA full-term count). Newborns that require surgical procedures are at
infant. This rise in RBC volume frequently leads to poly- particular risk of developing hypoglycemia; therefore, a
cythemia, with an associated rise in blood viscosity. Due 10% glucose infusion is typically started on admission to
to an adequate length of gestation, the SGA infant has the hospital. Hypoglycemia is treated with an infusion of
pulmonary function approaching that of an AGA or a 12mL/kg (48mg/kg/min) of 10% glucose. If an emer-
full-term infant. gency operation is required, concentrations of up to 25%
Infants born before 37 weeks of gestation, regardless glucose may be used. Traditionally, central venous access
of birth weight, are considered premature. The physical has been a prerequisite for glucose infusions exceeding
exam of the premature infant reveals many abnormalities. 12.5%. During the first 36 to 48 hours after a major
3
4 SECTION I General
surgical procedure, it is common to see wide variations causal relationship has not been established. Congenital
in serum glucose levels. hyperinsulinism refers to an inherited disorder that is the
most common cause of recurrent hypoglycemia in the
infant. This group of disorders was previously referred to
Hyperglycemia
as nesidioblastosis, which is a misnomer. Nesidioblastosis
Hyperglycemia is a common problem with the use of is a term used to describe hyperinsulinemic hypoglycemia
parenteral nutrition in very immature infants who are less attributed to dysfunctional pancreatic beta cells with a
than 30 weeks gestation and less than 1.1kg birth weight. characteristically abnormal histological appearance.
These infants are usually fewer than 3 days of age and
are frequently septic.2 This hyperglycemia appears to be
associated with both insulin resistance and relative insulin
Calcium
deficiency, reflecting the prolonged catabolism seen in Calcium is actively transported across the placenta. Of
very low birth weight infants.3 Historically, neonatal the total amount of calcium transferred across the pla-
hyperglycemia has been linked to intraventricular hem- centa, 75% occurs after 28 weeks gestation.4 This obser-
orrhage, dehydration, and electrolyte losses; however, a vation partially accounts for the high incidence of
hypocalcemia in preterm infants. Neonates are predis-
posed to hypocalcemia due to limited calcium stores,
5000
renal immaturity, and relative hypoparathyroidism sec-
Large ondary to suppression by high fetal calcium levels. Some
post-term
Term infant infants are at further risk for neonatal calcium distur-
infant of bances due to the presence of genetic defects, pathologi-
diabetic
4000 90th% cal intrauterine conditions, or birth trauma.5 Hypocalcemia
Trans- is defined as an ionized calcium level of less than
Preterm
position 1.22mmol/L (4.9mg/dL).6 At greatest risk for hypocal-
Error in
calculation of infant of
of aorta cemia are preterm infants, newborn surgical patients,
3000 gestational age diabetic Altitude and infants of complicated pregnancies, such as those of
probably 10th% diabetic mothers or those receiving bicarbonate infu-
Grams
TABLE 1-1 Clinical Criteria for Classification of Low Birth Weight Infants
3738 Weeks
Criteria 36 Weeks (Premature) (Borderline Premature) 39 Weeks (Term)
Plantar creases Rare, shallow Heel remains smooth Creases throughout sole
Size of breast nodule Not palpable to <3mm 4mm Visible (7mm)
Head hair Cotton wool quality Silky; each strand can be
distinguished
Earlobe Shapeless, pliable with little Rigid with cartilage
cartilage
Testicular descent and Small scrotum with rugal patch; Gradual descent Enlarged scrotum creased with
scrotal changes testes not completely rugae; fully descended testes
descended
Adapted from Avery ME, Villee D, Baker S, etal. Neonatology. In: Avery ME, First LR, editors. Pediatric Medicine. Baltimore:
William & Wilkins; 1989. p. 148.
1 Physiology of the Newborn 5
Hemoglobin O2 affinity
O2 release
At birth, nearly 80% of circulating hemoglobin is fetal PCO2
(a2A2F). When infant erythropoiesis resumes at about 2 80 [H+]
to 3 months of age, most new hemoglobin is adult. When Temperature
2,3 -DPG
the oxygen level is 27mmHg, 50% of the bound oxygen
HgbF
is released from adult hemoglobin (P50 = 27mmHg).
% O2 Hb saturation
60 O2 affinity
Reduction of hemoglobins affinity for oxygen allows O2 release
more oxygen to be released into the tissues at a given PCO2
oxygen level as shown in Figure 1-2. [H+]
Fetal hemoglobin has a P50 value 68mmHg lower 40
Temperature
than that of adult hemoglobin. This lower P50 value 2,3 -DPG
allows more efficient oxygen delivery from the placenta
to the fetal tissues. The fetal hemoglobin equilibrium
curve is shifted to the left of the normal adult hemoglobin 20
equilibrium curve. Fetal hemoglobin binds less avidly to
2,3-diphosphoglycerate (2,3-DPG) compared to adult P50 values
hemoglobin causing a decrease in P50.8 This is somewhat
of a disadvantage to the newborn because lower periph-
eral oxygen levels are needed before oxygen is released 20 40 60 80
from fetal hemoglobin. By 4 to 6 months of age in a term PO2 (mmHg)
FIGURE 1-2 The oxygen dissociation curve of normal adult
blood is shown in red. The P50, the oxygen tension at 50%
TABLE 1-2 Estimation of Blood Volume oxygen saturation, is approximately 27mmHg. As the curve
shifts to the right, the affinity of hemoglobin for oxygen
Group Blood Volume (mL/kg) decreases and more oxygen is released. Increases in PCO2,
temperature, 2,3-DPG, and hydrogen ion concentration facili-
Premature infants 85100 tates the unloading of O2 from arterial blood to the tissue. With
Term newborns 85 a shift to the left, unloading of O2 from arterial blood into the
>1 month 75 tissues is more difficult. Causes of a shift to the left are mirror
3 months to adult 70 images of those that cause a shift to the right: decreases in
temperature, 2,3-DPG, and hydrogen ion concentration. (Modi-
Adapted from Rowe PC, editor. The Harriet Lane Handbook. fied from Glancette V, Zipursky A. Neonatal hematology. In: Avery
11th eds. Chicago: Year Book Medical; 1987. p. 25. GB, editor, Neonatology. Philadelphia: JB Lippincott; 1986. p. 663.)
6 SECTION I General
80
Thermoregulation 510%
Newborns have difficulty maintaining body temperature TBW
due to their relatively large surface area, poor thermal
regulation, and small mass to act as a heat sink. Heat loss 60
% Body weight
may occur owing to: (1) evaporation (wet newborn);
(2) conduction (skin contact with cool surface); (3) con-
vection (air currents blowing over newborn); and (4) ICF
40
radiation (non-contact loss of heat to cooler surface,
which is the most difficult factor to control). Thermone-
utrality is the range of ambient temperatures that the ECF
newborn can maintain a normal body temperature with
a minimal metabolic rate by vasomotor control. The criti-
cal temperature is the temperature that requires adaptive
20
metabolic responses to the cold in an effort to replace
lost heat. Infants produce heat by increasing metabolic
activity by shivering like an adult, nonshivering thermo- 2 4 6 8 6 12 3 6 9 12
genesis, and futile cycling of ions in skeletal muscle.21 Birth Months Years
Brown adipose tissue (BAT) may be involved in ther- Age
moregulatory feeding and sleep cycles in the infant with
FIGURE 1-3 FrissHansens classic chart relating total body
an increase in body temperature signaling an increase in weight (TBW) and extracellular (ECF) and intracellular (ICF) fluid
metabolic demand.22 The uncoupling of mitochondrial to percentage of body weight, from early gestation to adoles-
respiration that occurs in BAT where energy is not con- cence. (Adapted from Welch KJ, Randolph JG, Ravitch MM, etal,
served in ATP but rather is released as heat may be editors. Pediatric Surgery. 4th ed. Chicago: Year Book Medical;
rendered inactive by vasopressors, anesthetic agents, and 1986. p. 24.)
nutritional depletion.2325 Failure to maintain thermone-
utrality leads to serious metabolic and physiologic conse-
quences. Double-walled incubators offer the best birth in the term infant, GFR quickly increases to 60mL/
thermoneutral environment, whereas radiant warmers min/1.73m2 by 2 weeks of age. GFR reaches adult
cannot prevent convection heat loss and lead to higher levels by 18 months to 2 years of age. A preterm infant
insensible water loss. In the operating room, special care has a GFR that is only slightly slower than that of a
must be exercised to maintain the neonates body tem- full-term infant. In addition to this difference in GFR,
perature in the normal range. the concentrating capacity of the preterm and the
full-term infant is well below that of the adult. An
infant responding to water deprivation increases urine
FLUIDS AND ELECTROLYTES osmolarity to a maximum of 600mOsm/kg. This is in
contrast to the adult, whose urine concentration can
At 12 weeks of gestation, the fetus has a total body water reach 1200mOsm/kg. It appears that the difference in
content that is 94% of body weight. This amount concentrating capacity is due to the insensitivity of the
decreases to 80% by 32 weeks gestation and 78% by collecting tubules of the newborn to antidiuretic hormone.
term (Fig. 1-3). A further 35% reduction in total body Although the newborn cannot concentrate urine as
water content occurs in the first 3 to 5 days of life. Body efficiently as the adult, the newborn can excrete very
water continues to decline and reaches adult levels dilute urine at 3050mOsm/kg. Newborns are unable to
(approximately 60% of body weight) by 1 1 2 years of age. excrete excess sodium, an inability thought to be due to
Extracellular water also declines by 1 to 3 years of age. a tubular defect. Term babies are able to conserve sodium,
Premature delivery requires the newborn to complete but premature infants are considered salt wasters because
both fetal and term water unloading tasks. Surprisingly, they have an inappropriate urinary sodium excretion,
the premature infant can complete fetal water unloading even with restricted sodium intake.
by one week following birth. Postnatal reduction in
extracellular fluid volume has such a high physiologic
priority that it occurs even in the presence of relatively
Neonatal Fluid Requirements
large variations of fluid intake.26 To estimate fluid requirements in the newborn requires
an understanding of: (1) any preexisting fluid deficits
Glomerular Filtration Rate and or excesses; (2) metabolic demands; and (3) losses.
Early Renal Function Because these factors change quickly in the critically ill
newborn, frequent adjustments in fluid management
The glomerular filtration rate (GFR) of newborns is are necessary (Table 1-4). Hourly monitoring of intake
slower than that of adults.27 From 21mL/min/1.73m2 at and output allows early recognition of fluid balance that
8 SECTION I General
gestation. Fetuses born during this phase are unable to inner surface of the alveoli preventing the alveoli from
survive because respiration is not possible. In the canal- collapsing during expiration, thereby improving air
icular phase, respiration is made possible because thin- exchange. Three exogenous surfactants are available:
walled terminal sacs (primordial alveoli) have developed (1) surfactant derived from bovine or porcine lung;
at the ends of the respiratory bronchioles and the lung (2) synthetic surfactant without protein components;
tissue is well vascularized. No actual alveoli are seen until and (3) synthetic surfactant containing protein compo-
24 to 26 weeks gestation, during the terminal saccular nents. A human derived surfactant was tested but is not
phase. The airblood surface area for gas diffusion is currently in use.
limited should the fetus be delivered at this age. The The most efficacious administration method is cur-
terminal saccular phase is defined by the establishment rently under investigation. The standard approach is to
of the bloodair barrier that allows gas exchange for the instill aliquots into an endotracheal tube. The indications
survival of the fetus should it be born prematurely. for the use of surfactant include: (1) intubated infants
Between 24 and 28 weeks, the cuboidal and columnar with RDS; (2) intubated infants with meconium aspira-
cells flatten and differentiate into type I (lining cells) and/ tion syndrome (MAS) requiring more than 50% oxygen;
or type II (granular) pneumocytes. Between 26 and 32 (3) intubated infants with pneumonia and an oxygen
weeks of gestation, terminal air sacs begin to give way to index great than 15; and (4) intubated infants with pul-
air spaces. At the same time, the phospholipids that con- monary hemorrhage that have clinically deteriorated. Its
stitute pulmonary surfactant begin to line the terminal efficacy is uncertain in neonates with pulmonary hemor-
lung air spaces. Surfactant is produced by type II pneu- rhage and pneumonia. Worse outcomes are associated
mocytes and is extremely important in maintaining alveo- with surfactant use in CDH.30,31
lar stability. During the alveolar phase, further budding The acute pulmonary effects of surfactant therapy are
of these air spaces occurs and alveoli become numerous, improved lung function and alveolar expansion leading
a process that continues postnatally until the age of 3 to to improved oxygenation, which results in a reduction in
8 years.29 the need for mechanical ventilation and extracorporeal
The change in the ratio of the amniotic phospholipids oxygenation.3234
(lecithin: sphingomyelin) is used to assess fetal lung Two meta-analyses support the use of surfactant
maturity. A ratio greater than 2 is considered compatible therapy in infants with RDS to reduce air leak syndromes,
with mature lung function. Absence of adequate sur- pneumothorax, bronchopulmonary dysplasia (BPD), pul-
factant leads to HMD or respiratory distress syndrome monary interstitial emphysema, and mortality.35,36 The
(RDS). HMD is present in 10% of premature infants. INSURE (INtubate, SURfactant, Extubate) technique
Other conditions associated with pulmonary distress in consists of administration of surfactant followed by extu-
the newborn include delayed fetal lung absorption, meco- bation within one hour to nasal continuous positive
nium aspiration syndrome, intrapartum pneumonia, and airway pressure (nCPAP). Another randomized trial
developmental structural anomalies (e.g., congenital dia- demonstrated the reduced mortality and air leaks for
phragmatic hernia (CDH) and congenital lobar emphy- infants assigned to early surfactant treatment versus
sema). In all of these conditions, endotracheal intubation nCPAP alone.37 In large trials that reflect the current
and mechanical ventilation may be required for hypoxia, practice of treating infants at risk for the development of
CO2 retention, or apnea. Ventilator options and manage- RDS (administration of maternal steroids and the routine
ment depend on the clinical context and are further dis- stabilization on CPAP), the selective use of surfactant in
cussed in Chapter 7. infants with established RDS demonstrates a decreased
risk of chronic lung disease or death when compared to
infants who are more aggressively treated with prophy-
Surfactant lactic administration of surfactant.38
The development of exogenous surfactant in the 1990s Several adverse outcomes have been associated with
has significantly advanced the field of neonatology result- the use of surfactant (Table 1-5). Intraventricular hemor-
ing in reductions in the rates of neonatal mortality. Sur- rhage is one of the most worrisome potential side effects.
factant deficiency is the major cause of HMD. Surfactant However, meta-analyses of multiple trials have not shown
replacement therapy reduces the surface tension on the a statistically significant increase in this risk.35,36
reflects left atrial and filling pressure of the left ventricle. thermodilution measurements if blood is either extracted
Often, a wide discrepancy exists between left and right from or infused back into the cardiopulmonary circula-
atrial pressure if pulmonary disease, overwhelming sepsis, tion as seen with an intracardiac shunt, aortic stenosis,
or cardiac anomalies are present. Positive-pressure ven- lung embolism, and extracorporeal membrane oxygena-
tilation, pneumothorax, abdominal distention, or pericar- tion (ECMO).48
dial tamponade all elevate CVP.
Venous Oximetry
Pulmonary Artery
Mixed venous oxygen saturation (SvO2) is an indicator of
The pulmonary artery pressure catheter has altered the the adequacy of oxygen supply and demand in perfused
care of the child with severe cardiopulmonary derange- tissues. Oxygen consumption is defined as the amount of
ment by allowing direct measurement of cardiovascular oxygen consumed by the tissue as calculated by the Fick
variables at the bedside. With this catheter, it is possible equation:
to monitor CVP, pulmonary artery pressure, pulmonary
O2 consumption = Cardiac output Arterial
wedge pressure, and cardiac output. The catheter is
usually placed by percutaneous methods (as in the adult), venous oxygen content difference
except in the smallest pediatric patient in whom a cutdown Reflectance spectrophotometry is currently used for con-
is sometimes required. tinuous venous oximetry. Multiple wavelengths of light
When the tip of the catheter is in a distal pulmonary are transmitted at a known intensity by means of fiber
artery and the balloon is inflated, the resulting pressure optic bundles in a special pulmonary artery or right atrial
is generally an accurate reflection of left atrial pressure catheter. The light is reflected by RBCs flowing past the
because the pulmonary veins do not have valves. This tip of the catheter. The wavelengths of light are chosen
pulmonary wedge pressure represents left ventricular so that both oxyhemoglobin and deoxyhemoglobin are
filling pressure, which is used as a reflection of preload. measured to determine the fraction of hemoglobin satu-
The monitors display phasic pressures, but treatment rated with oxygen. The system requires either in vitro
decisions are made based on the electronically derived calibration by reflecting light from a standardized target
mean CVP. A low pulmonary wedge pressure suggests that represents a known oxygen saturation or in vivo
that blood volume must be expanded. A high or normal calibration by withdrawing blood from the pulmonary
pulmonary wedge pressure in the presence of continued artery catheter and measuring the saturation by labora-
signs of shock suggests left ventricular dysfunction. tory co-oximetry.
Cardiac output is usually measured in liters per minute. Mixed venous oxygen saturation values within the
Cardiac index represents the cardiac output divided by the normal range (6877%) indicate a normal balance
body surface area. The normalized cardiac index allows between oxygen supply and demand, provided that
the evaluation of cardiac performance without regard to vasoregulation is intact and distribution of peripheral
body size. The normal value for cardiac index is between blood flow is normal. Values greater than 77% are most
3.54.5L/min/m2. The determination of cardiac output commonly associated with syndromes of vasoderegula-
by the thermodilution technique is possible with a Swan tion, such as sepsis. Uncompensated changes in O2 satu-
Ganz pulmonary artery catheter. Accurate cardiac output ration, hemoglobin level, or cardiac output lead to a
determination depends on rapid injection, accurate meas- decrease in SvO2. A sustained decrease in SvO2 greater
urement of the injectant temperatures and volume, and than 10% should lead to measuring SaO2, hemoglobin
absence of shunting. Because ventilation affects the flow level, and cardiac output to determine the cause of the
into and out of the right ventricle, three injections should decline.49 The most common sources of error in measur-
be made at a consistent point in the ventilatory cycle, typi- ing SvO2 are calibration and catheter malposition. The
cally at end-expiration. most important concept in SvO2 monitoring is the advan-
Another study concluded that using right heart cath- tage of continuous monitoring, which allows early
eters in treating critically ill adult patients resulted in an warning of a developing problem.50
increased mortality.44 However, a consensus committee Although most clinical experience has been with pul-
report documents the continued safety and efficacy of monary artery catheters, right atrial catheters are more
right heart catheters in the care of critically ill children.45 easily inserted and may thus provide better information
A newer technique of deriving some of these data employs to detect hemodynamic deterioration earlier and permit
femoral arterial access and is gaining popularity in the more rapid treatment of physiologic derangements.51 A
pediatric intensive care unit: transcardiopulmonary ther- study has shown that, when oxygen consumption was
modilution monitoring device (pulse contour cardiac monitored and maintained at a consistent level, the right
output [PCCO]). atrial venous saturation was found to be an excellent
A proprietary PiCCO device has been developed, and monitor.52
employs a standard central venous catheter and a propri-
etary thermistor-tipped arterial catheter to assess hemo-
dynamic parameters via transpulmonary thermodilution. SHOCK
Manual calibration is required and must be performed
frequently (every hour) for reasonably accurate data.46 It Shock is a state in which the cardiac output is insufficient
is recommended to recalibrate the curve after interven- to deliver adequate oxygen to meet metabolic demands
tions are performed.47 This device may give incorrect of the tissues. Cardiovascular function is determined by
12 SECTION I General
preload, cardiac contractility, heart rate, and afterload. myocardial contractility. The and receptors are pro-
Shock may be classified broadly as hypovolemic, cardio- teins present in the sarcolemma of myocardial and vas-
genic, or distributive (systemic inflammatory response cular smooth muscle cells. The 1 receptors are
syndrome [SIRS]septic or neurogenic). predominantly in the heart and, when stimulated, result
in increased contractility of myocardium. The 2 recep-
tors are predominately in respiratory and vascular smooth
Hypovolemic Shock muscle. When stimulated, these receptors result in bron-
In infants and children, most shock situations are the chodilation and vasodilation. The 1-adrenergic recep-
result of reduced preload secondary to fluid loss, such as tors are located on vascular smooth muscle and result in
from diarrhea, vomiting, or blood loss from trauma. vascular constriction when stimulated. The 2 receptors
Preload is a function of blood volume. In most clinical are found mainly on prejunctional sympathetic nerve ter-
situations, right atrial pressure or CVP is the index of minals. The concept of dopaminergic receptors has also
cardiac preload. In situations in which left ventricular or been used to account for the cardiovascular effects of
right ventricular compliance is abnormal or in certain dopamine not mediated through or receptors. Activa-
forms of congenital heart disease, right atrial pressure tion of dopaminergic receptors results in decreased renal
may not correlate well with left atrial pressure. and mesenteric vascular resistance and, usually, increased
Hypovolemia results in decreased venous return to the blood flow. The most commonly used inotropic and
heart. Preload is reduced, cardiac output falls, and the vasoactive drugs are listed in Table 1-6.
overall result is a decrease in tissue perfusion. The first
step in treating all forms of shock is to correct existing Epinephrine
fluid deficits. Inotropic drugs should not be initiated until
adequate intravascular fluid volume has been established. Epinephrine is an endogenous catecholamine with - and
The speed and volume of the infusate are determined by -adrenergic effects. At low doses, the -adrenergic effect
the patients responses, particularly changes in blood predominates. These effects include an increase in heart
pressure, pulse rate, urine output, and CVP. Shock rate, cardiac contractility, cardiac output, and bronchiolar
resulting from acute hemorrhage is treated with the dilation. Blood pressure rises, in part, not only due to
administration of 20mL/kg of Ringers lactate solution increased cardiac output but also due to increased periph-
or normal saline as fluid boluses. If the patient does eral vascular resistance, which occurs with higher doses
not respond, a second bolus of crystalloid is given. as the -adrenergic effects become predominant. Renal
Type-specific or cross-matched blood is given to achieve blood flow may increase slightly, remain unchanged, or
an SvO2 of 70%. In newborns with a coagulopathy, we decrease depending on the balance between greater
provide fresh frozen plasma or specific factors as the cardiac output and changes in peripheral vascular resist-
resuscitation fluid. ance, which lead to regional redistribution of blood flow.
The rate and volume of resuscitation fluid given is Cardiac arrhythmias can be seen with epinephrine, espe-
adjusted based on feedback data obtained from monitor- cially with higher doses. Dosages for treating compro-
ing the effects of the initial resuscitation. After the initial mised cardiovascular function range from 0.051.0g/
volume is given, the adequacy of replacement is assessed kg/min. Excessive doses of epinephrine can cause wors-
by monitoring urine output, urine concentration, plasma ening cardiac ischemia and dysfunction from increased
acidosis, oxygenation, arterial pressure, CVP, and myocardial oxygen demand.
pulmonary wedge pressure, if indicated. When cardiac
failure is present, continued vigorous delivery of large
Isoproterenol
volumes of fluid may cause further increases in preload
to the failing myocardium and accelerates the downhill Isoproterenol is a -adrenergic agonist. It increases
course. In this setting, inotropic agents are given while cardiac contractility and heart rate, with little change in
monitoring cardiac and pulmonary function, as outlined systemic vascular resistance (SVR). The peripheral vas-
previously. cular -adrenergic effect and lack of a peripheral vascular
-adrenergic effect may allow reduction of left ventricu-
Cardiogenic Shock lar afterload. The intense chronotropic effect of isopro-
terenol produces tachycardia, which can limit its
Myocardial contractility is usually expressed as the ejec- usefulness. Isoproterenol is administered IV at a dosage
tion fraction that indicates the proportion of left ven- of 0.510.0g/kg/min.
tricular volume that is pumped. Myocardial contractility
is reduced with hypoxemia and acidosis. Inotropic drugs Dopamine
increase cardiac contractility. Inotropes are most effective
when hypoxemia and acidosis are corrected. In cases of Dopamine is an endogenous catecholamine with -
fluid-refractory shock and cardiogenic shock, inotropic adrenergic, -adrenergic, and dopaminergic effects. It is
drugs are necessary. Traditionally, administration of ino- both a direct and an indirect -adrenergic agonist.
tropes requires the adjunct of central venous access. Dopamine elicits positive inotropic and chronotropic
However, initial administration of pressors through responses by direct interaction with the receptor (direct
peripheral IVs may be prudent. effect) and by stimulating the release of norepinephrine
Adrenergic receptors are important in regulating from the sympathetic nerve endings, which interacts
calcium flux, which, in turn, is important in controlling with the receptor (indirect effect). At low dosages
1 Physiology of the Newborn 13
(<5g/kg/min), the dopaminergic effect of the drug pre- pressure in neonates, infants, and children. The precise
dominates, resulting in reduced renal and mesenteric dosages at which the desired hemodynamic effects are
vascular resistance and further blood flow to these organs. maximized are not known. The effects of low dosages of
The -adrenergic effects become more prominent at dopamine on blood pressure, heart rate, and renal func-
intermediate dosages (510g/kg/min), producing a tion were studied in 18 hypotensive, preterm infants.53
higher cardiac output. At relatively high dosages The blood pressure and diuretic effects were observed at
(1020g/kg/min), the -adrenergic effects become 2, 4, and 8g/kg/min. Elevations in heart rate were seen
prominent with peripheral vasoconstriction. only at 8g/kg/min. Further work is needed to better
Experience with the use of dopamine in pediatric characterize the pharmacokinetics and pharmacodynam-
patients suggests that it is effective in increasing blood ics of dopamine in children, especially in newborns.
14 SECTION I General
acidbase status (severe acidosis), and oxygenation (severe type-specific antibodies because of defects in the differ-
hypoxemia). These changes are significantly different entiation of B-lymphocytes into immunoglobulin-
from those seen in the adult animals that also experience secreting plasma cells and in T-lymphocyte-mediated
an improved survival of almost 600% (18.5 vs 3.1 hours) facilitation of antibody synthesis. In the term infant, total
compared with the immature animal. hemolytic complement activity, which measures the
The neonates host defense can usually respond suc- classic complement pathway, constitutes approximately
cessfully to ordinary microbial challenge. However, 50% of adult activity.78 The activity of the alternative
defense against major challenges appears limited, which complement pathway, secondary to lowered levels of
provides an explanation for the high mortality rate with factor B, is also decreased in the neonate.79 Fibronectin,
major neonatal sepsis. As in adults, the immune system a plasma protein that promotes reticuloendothelial clear-
consists of four major components: cell-mediated immu- ance of invading microorganisms, is deficient in neonatal
nity (T-cells), complement system, antibody-mediated cord plasma.80
immunity (B-cells), and macrophageneutrophil phago- The use of intravenous immunoglobulins (IVIGs) for
cytic system. The two most important deficits in newborn the prophylaxis and treatment of sepsis in the newborn,
host defenses that seem to increase the risk of bacterial especially the preterm, low birth weight infant, has been
sepsis are the quantitative and qualitative changes in the studied in numerous trials with varied outcomes. In one
phagocytic system and the defects in antibody-mediated study, a group of infants weighing 1500g was treated
immunity. with 500mg/kg of IVIG each week for four weeks and
The proliferative rate of the granulocytemacrophage compared with infants who were not treated with immu-
precursor has been reported to be at near-maximal capac- noglobulin.81 The death rate was 16% in the IVIG-
ity in the neonate. However, the neutrophil storage pool treated group compared with 32% in the untreated
is markedly reduced in the newborn compared with control group. Another recent analysis examined the role
the adult. After bacterial challenge, newborns fail to of IVIG to prevent and treat neonatal sepsis.82 A signifi-
increase stem cell proliferation and deplete their already cant (but only marginal) benefit was noted from prophy-
reduced neutrophil storage pool. Numerous in vitro lactic use of IVIG to prevent sepsis in low birth weight
abnormalities have been demonstrated in neonatal poly- premature infants. However, using IVIG to treat neona-
morphonuclear neutrophils, especially in times of stress tal sepsis produced a greater than 6% decrease in the
or infection.71 These abnormalities include decreased mortality rate. A review of nineteen randomized control
deformability, chemotaxis, phagocytosis, C3b receptor trials found a 3% decrease in the incidence of neonatal
expression, adherence, bacterial killing, and depressed sepsis in preterm infants without a significant difference
oxidative metabolism. Chemotaxis is impaired in neona- in all-cause and infection-related mortality when prophy-
tal neutrophils in response to various bacterial organisms lactic IVIG was administered.83 Based on the marginal
and antigenantibody complexes.72 Granulocytes are reduction of neonatal sepsis without a reduction in mor-
activated by their interaction with endothelial cells fol- tality, routine use of prophylactic IVIG cannot be
lowed by entry into secondary lymphoid issues via the recommended.
endothelial venules. Initial adhesion of granulocytes is Colony-stimulating factors (CSFs) are a family of
dependent on their expression of l-selectin, a cell adhe- glycoproteins that stimulate proliferation and differentia-
sion molecule expressed on the granulocyte cell surface. tion of hematopoietic cells of various lineages. GM-CSF
Evaluation of cord blood has demonstrated a significantly and granulocyte CSF (G-CSF) have similar physiologic
lower expression of l-selectin on granulocyte surfaces actions. Both stimulate the proliferation of bone marrow
when compared to older newborn (5 days old) and adult myeloid progenitor cells, induce the release of bone
samples, indicating a depressed level of interaction with marrow neutrophil storage pools, and enhance mature
vascular endothelial cells at the initial stage of adhesion.73 neutrophil effect or function.8284 Preliminary studies of
Although phagocytosis has additionally been demon- GM-CSF in neonatal animals demonstrate enhancement
strated to be abnormal in neonatal phagocytes, it appears of neutrophil oxidative metabolism as well as priming of
that this phenomenon is most likely secondary to neonatal neutrophils for enhanced chemotaxis and bacte-
decreased opsonic activity rather than an intrinsic defect rial killing. Both GM-CSF and G-CSF induce peripheral
of the neonatal polymorphonuclear neutrophils.74,75 Cur- neutrophilia within two to six hours of intraperitoneal
rently, there is inconclusive evidence to support or refute administration. This enhanced affinity for neutrophils
the routine use of granulocyte transfusions in the preven- returns to normal baseline level by 24 hours.85 Studies
tion or treatment of sepsis in the neonate.76 have confirm the efficacy and safety of G-CSF therapy
Preterm and term newborns have poor responses to for neonatal sepsis and neutropenia.86 Other investiga-
various antigenic stimuli, reduced gamma globulin levels tions have demonstrated no long-term adverse hemato-
at birth, and reduced maternal immunoglobulin supply logic, immunologic, or developmental effects from
from placental transport. Almost 33% of infants with a G-CSF therapy in the septic neonate. Prolonged prophy-
birth weight less than 1500g develop substantial hypog- lactic treatment in the very low birth weight neonate with
ammaglobulinemia.77 IgA and IgM levels are also low due recombinant GM-CSF has been shown to be well toler-
to the inability of these two immunoglobulins to cross ated and have a significant decrease in the rate of noso-
the placenta. Thus, neonates are usually more susceptible comial infections.87,88
to pyogenic bacterial infections because most of the anti- Unique to the newborn in septic shock is the persist-
bodies that opsonize pyogenic bacterial capsular antigens ence of fetal circulation and resultant pulmonary hyper-
are IgG and IgM. In addition, neonates do not produce tension.89 In fact, the rapid administration of fluid can
16 SECTION I General
further exacerbate this problem by causing left to right 7. Colozzi AE. Clamping of the umbilical cord. Its effect on the
shunting through a patent ductus arteriosus (PDA) and placental transfusion. N Engl J Med 1954;250:629.
8. Bauer C, Ludwig I, Ludwig M. Different effects of
subsequent congestive heart failure from ventricular 2,3-diphosphoglycerate and adenosine triphosphate on the oxygen
overload. Infants in septic shock with a new heart murmur affinity of adult and fetal human hemoglobin. Life Sci 1968;7:
should undergo a cardiac echocardiogram. If present, a 1339.
PDA may warrant treatment with indomethacin (pros- 9. Asch J, Wedgwood JF. Optimizing the approach to anemia in the
preterm infant: Is there a role for erythropoietin therapy? J Peri-
taglandin inhibitor) or surgical ligation to achieve closure, natol 1997;17:27682.
depending on the clinical picture. 10. Doyle JJ. The role of erythropoietin in the anemia of prematurity.
The critical care of a neonate/infant in septic shock Semin Perinatol 1997;21:207.
can be extremely challenging. Septic shock has a distinc- 11. King PJ, Sullivan TM, Leftwich ME, et al. Score for neonatal acute
tive clinical presentation and is characterized by an early physiology and phlebotomy blood loss predict erythrocyte transfu-
sions in premature infants. Arch Pediatr Adolesc Med 1997;151
compensated stage where one can see a decreased SVR, 2731.
an increase in cardiac output, tachycardia, warm extremi- 12. Maisels MJ. Whats in a name? Physiologic and pathologic jaun-
ties, and an adequate urine output. Later in the clinical dice: The conundrum of defining normal bilirubin levels in the
presentation, septic shock is characterized by an uncom- newborn. Pediatrics 2006;118:8057.
13. Osborn LM, Lenarsky C, Oakes RC, et al. Phototherapy in full-
pensated phase where one will see a decrease in intravas- term infants with hemolytic disease secondary to ABO incompat-
cular volume, myocardial depression, high vascular ibility. Pediatrics 1984;73:5206.
resistance, and a decreasing cardiac output.90 Manage- 14. Saugstad O. Optimal oxygenation at birth and in the neonatal
ment of these patients is based on the principles of source period. Neonatology 2007;91:31922.
control, antibiotics (broad-spectrum, institutionally based 15. Biglan AW, Cheng KP, Brown DR. Update on retinopathy of
prematurity. Intern Ophthalmol Clin 1989;29:24.
when possible and including antifungal agents as war- 16. National Institutes of Health. Cryotherapy for retinopathy of pre-
ranted), and supportive care. maturity cooperative group. Multicenter trial of cryotherapy for
Patients with severe septic shock often do not respond retinopathy of prematurity. Arch Ophthalmol 1988;106:4719.
to conventional forms of volume loading and cardiovas- 17. Ng E, Connolly B, McNamara J, et al. A comparison of laser
photocoagulation with cryotherapy for threshold retinopathy of
cular supportive medications. The administration of prematurity at 10 years: Part 1. Visual function and structural
arginine vasopressin has been shown to decrease mortal- outcome. Ophthalmol 2002;202:92835.
ity in adult patients with recalcitrant septic shock.91,92 18. Shalev B, Farr A, Repka M. Randomized comparison of diode laser
Vasopressin (see Table 1-6), also known as antidiuretic photocoagulation versus cryotherapy for threshold retinopathy of
hormone (ADH), is made in the posterior pituitary and prematurity: Seven-year outcome. Am J Ophthalmol 2002;132:
7680.
plays a primary role in water regulation by the kidneys. 19. Connolly B, McNamara J, Sharma S, et al. A comparison of laser
In septic shock, vasopressin has profound effects on phototherapy with trans-scleral cryotherapy for the treatment of
increasing blood pressure in intravascular depleted states. threshold retinopathy. Ophthalmol 1998;105:162831.
Sparked initially by a randomized, double-blinded, 20. American Academy of Pediatrics, Section on Ophthalmology, AAo
Ophth, AAo Ophth/Strabismus. Screening examination of prema-
placebo-controlled study in adults that demonstrated a ture infants for retinopathy of prematurity. Pediatrics 2006;117:
beneficial effect of vasopressin in recalcitrant septic 5726.
shock, its utilization in the pediatric population has 21. Lowell BB, Spiegelman BM. Towards a molecular understanding
become common.93,94 While a detailed discussion is of adaptive thermogenesis. Nature 2000;404:65260.
beyond the scope of this chapter, current trends suggest 22. Chardon K, Cardot V, Leke A, et al. Thermoregulatory control
of feeding and sleep in premature infants. Obesity 2006;14:
that ECMO may serve as rescue therapy in select patients 153542.
with profound sepsis and cardiopulmonary failure refrac- 23. Karlberg P, Moore RE, Oliver TK. The thermogenic response of
tory to other measures (reported ELSO database newborn the newborn infant to noradrenaline. Acta Paediatr Scand
survival 80%, older children 50%).94,95 1962;51:284.
24. Stein J, Cheu H, Lee M, et al. Effects of muscle relaxants, sedatives,
Given the difficult nature of caring for septic patients, narcotics and anesthetics on neonatal thermogenesis. In: Pannell
extensive investigation has been launched in attempt to M, editor. Surgical Forum, vol. 38. Chicago: American College of
identify patients at risk.9698 Early serum markers such as Surgeons; 1987. p. 76.
C-reactive protein, IL-6, and procalcitonin carry promise 25. Landsberg L, Young JB. Fasting, feeding and regulation of the
but warrant further validation. sympathetic nervous system. N Engl J Med 1978;198:1295.
26. Lorenz JM, Kleinman LI, Kotagal UR, et al. Water balance in very
low birth weight infants: Relationship to water and sodium intake
REFERENCES and effect on outcome. J Pediatr 1982;101:42332.
1. Sarafoglou K, Hoffmann G, Roth K. Pediatric Endocrinology and 27. Aperia A, Broberger O, Herin P, et al. Postnatal control of water
Inborn Errors of Metabolism. China: The McGraw-Hill Compa- and electrolyte homeostatis in pre-term and full-term infants. Acta
nies, Inc; 2009. Paediatr Scand 1983;305:615.
2. Dweck HS, Cassady G. Glucose intolerance in infants of very low 28. Fahimi D, Mohajeri S, Hajizadeh N, et al. Comparison between
birth weight, I: Incidence of hyperglycemia in infants of birth fraction excretions of urea and sodium in children with acute
weights 1,110 grams or less. Pediatr 1974;53:18995. kidney injury. Pediatr Nephrol 2009;24:240912.
3. Beardsall K, Dunger D. The physiology and clinical management 29. Thurlbeck WM. Lung growth and development. In: Thurlbeck
of glucose metabolism in the newborn. Endocr Dev 2007; WM, Churg AM, editor. Pathology of the Lung. 2nd ed. New
12:12437. York: Thieme Medical Publishers; 1995.
4. Ziegler EE, ODonnell AM, Nelson SE, et al. Body composition 30. Meurs KV, The Congenital Diaphragmatic Hernia Study Group.
of reference fetus. Growth 1976;40:329. Is surfactant therapy beneficial in the treatment of the term
5. Hsu SC, Levine MA. Perinatal calcium metabolism: Physiology newborn infant with congenital diaphragmatic hernia? J Pediatr
and pathophysiology. Semin Neonatol 2004;9:236. 2004;145:31216.
6. Thomas TC, Smith JM, White PC, Adhikari S. Transient neonatal 31. Lally KP, Lally PA, Langham MR, et al. Surfactant does not
hypocalcemia: Presentation and outcomes. Pediatrics 2012; improve survival rate in preterm infants with congenital diaphrag-
129:e14611467. matic hernia. J Pediatr Surg 2004;39:82933.
1 Physiology of the Newborn 17
32. Tooley WH, Clements JA, Muramatsu K, et al. Lung function in 58. Parrillo JE. Septic shock in humans. Advances in the understanding
prematurely delivered rabbits treated with a synthetic surfactant. of pathogenesis, cardiovascular dysfunction, and therapy. Ann
Am Rev Respir Dis 1987;136:6516. Intern Med 1990;113:22742.
33. Robertson B, Enhorning G. The alveolar lining of the premature 59. Danner R, Elin RJ, Hosline KM, et al. Endotoxin determinations
newborn rabbit after pharyngeal deposition of surfactant. Lab in 100 patients with septic shock. Clin Res 1988;36:453A.
Invest 1974;31:549. 60. McCloskey RV, Straube KC, Sanders C, et al. Treatment of septic
34. Shahed AI, Dargaville PA, Ohlsson A, et al. Surfactant for meco- shock with human monoclonal antibody HA-1A. A randomized,
nium aspiration syndrome in full term/near term infants. Cochrane double-blind, placebo-controlled trial. CHESS Trial Study Group.
Database Syst Reviews 2009:Art. No. CD002054. Ann Intern Med 1994;121:15.
35. Seger N, Soll R. Animal derived surfactant extract for treatment of 61. Rogy MA, Moldawer LL, Oldenburg HS, et al. Anti-endotoxin
respiratory distress syndrome. Cochrane Database Syst Reviews therapy in primate bacteremia with HA-1A and BPI. Ann Surg
2009;(3):Art. No. CD007636. 1994;220:7785.
36. Soll R. Synthetic surfactant for respiratory distress syndrome in 62. Ziegler EJ, Fisher CJ Jr, Sprung CL, et al. Treatment of gram-
preterm infants. Cochrane Database Syst Reviews 2009;(3):Art. negative bacteremia and septic shock with HA-1A human mono-
No. CD00149. clonal antibody against endotoxin. A randomized, double-blind,
37. Rojas MA, Lozano JM, Rojas MX, et al. Very early surfactant placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl
without mandatory ventilation in premature infants treated with J Med 1991;324:42936.
early continuous positive airway pressure: A randomized, control- 63. Tracey KJ, Lowry SF, Cerami A. Chachectin: A hormone that trig-
led trial. Pediatrics 2009;123:13742. gers acute shock and chronic cachexia. J Infect Dis 1988;157:
38. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus selective 41320.
use of surfactant in preventing morbidity and mortality in preterm 64. Nedwin GE, Svedersky LP, Bringman TS. Effect of interleukin-2,
infants. Cochrane Database Syst Reviews 2012;(3):Art. No. interferon-gamma and mitogens on the production of tumor
CD000510. necrosis factors alpha and beta. J Immunol 1985;135:24927.
39. Garg AK. Arterialized capillary blood [letter]. CMAJ 1972;107:16. 65. Jupin C, Anderson S, Damais C, et al. Toxic shock syndrome toxin
40. Glasgow JF, Flynn DM, Swyer PR. A comparison of descending 1 as an inducer of human tumor necrosis factors and gamma inter-
aortic and arterialized capillary blood in the sick newborn. CMAJ feron. J Exp Med 1988;167:75261.
1972;106:660. 66. Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachectin/TNF mono-
41. Siggaard-Andersen O. Acid-base and blood gas parameters clonal antibodies prevent septic shock during lethal bacteraemia.
arterial or capillary blood? Scand J Clin Lab Invest 1968;21:289. Nature 1987;330:6624.
42. Reynolds GJ, Yu VYH. Guidelines for the use of pulse oximetry in 67. Beutler B, Milsaark IW, Cerami AC. Passive immunization against
the non-invasive estimation of oxygen saturation in oxygen- cachectin/tumor necrosis factor protects mice from the lethal
dependent newborn infants. Aust Paediatr J 1988;24:34650. effects of endotoxin. Science 1981;229:86971.
43. McEvedy BAB, McLeod ME, Kirpalani H, et al. End-tidal carbon 68. Rosenstein M, Ettinghausen SE, Rosenberg SA. Extravasation of
dioxide measurements in critically ill neonates: A comparison of intravascular fluid mediated by the systemic administration of
sidestream capnometers. Can J Anaesth 1990;37:3226. recombinant interleukin-2. Immunology 1986;137:1735.
44. Connors A. The effectiveness of right heart catheterization in the 69. Ognibene FP, Rosenberg SA, Lotze M, et al. Interleukin-2 adminis-
initial care of critically ill patients. JAMA 1996;276:88997. tration causes reversible hemodynamic changes and left ventricular
45. Thompson AE. Pulmonary artery catheterization in children. New dysfunction similar to those seen in septic shock. Chest 1988;94:750.
Horiz 1997;5:24450. 70. Pryor RW, Hinshaw LB. Sepsis/septic shock in adults and children.
46. Hamzaoui O, Monnet X, Richard C. Effects of changes in vascular Pathol Immunopathol Res 1989;8:22230.
tone on the agreement between pulse contour and transpulmonary 71. Hill HR. Biochemical, structural and functional abnormalities of
thermodilution cardiac output measurements within an up to polymorphonuclear leukocytes in the neonate. Pediatr Res
6-hour calibration-free period. Crit Care Med 2008;36:43440. 1987;22:37582.
47. Bein B, Meybohm P, Cavus E. The reliability of pulse contour- 72. Miller M. Chemotactic function in the human neonate: Humoral
derived cardiac output during hemorrhage and after vasopressors and cellular aspects. Pediatr Res 1971;5:48792.
administration. Anesth Analg 2007;105:10713. 73. Moriguchi N, Yamamoto S, Isokawa S, et al. Granulocyte function
48. Gazit A, Cooper DS. Emerging technologies. Pediatr Crit Care and changes in ability with age in newborns; Report no,1: Flow
Med 2011;12:S55S61. cytometric analysis of granulocyte functions in whole blood.
49. Nelson LD. Application of venous saturation monitoring. In: Pediatr Int 2006;48:1721.
Civetta JM, Taylor RW, Kirby RR, editors. Critical Care. Philadel- 74. Miller ME. Phagocytosis in the newborn: Humoral and cellular
phia: JB Lippincott; 1988. p. 32734. factors. J Pediatr 1969;75:2559.
50. Norfleet EA, Watson CB. Continuous mixed venous oxygen satu- 75. Forman ML, Stiehm ER. Impaired opsonic activity but normal
ration measurement: A significant advance in hemodynamic moni- phagocytosis in low-birth-weight infants. N Engl J Med
toring? J Clin Monit Comput 1985;1:24558. 1969;281:92631.
51. Ko WJ, Chang CI, Chiu IS. Continuous monitoring of venous 76. Mohan P, Brocklehurst. Granulocyte transfusions for neonates with
oxygen saturation in critically-ill infants. J Formos Med Assoc confirmed or suspected sepsis. Cochrane Database Syst Reviews
1996;95:25862. 2003;(4):Art. No.: CD003956.
52. Hirschl RB, Palmer P, Heiss KF, et al. Evaluation of the right atrial 77. Cates KL, Rowe JC, Ballow M. The premature infant as a com-
venous oxygen saturation as a physiologic monitor in a neonatal promised host. Curr Probl Pediatr 1983;13:163.
model. J Pediatr Surg 1993;28:9015. 78. Anderson DC, Hughes J, Edwards MS, et al. Impaired chemotaxi-
53. DiSessa TG, Leitner M, Ti CC, et al. The cardiovascular effects genesis by type III group B streptococci in neonatal sera: Relation-
of dopamine in the severely asphyxiated neonate. J Pediatr ship to diminished concentration of specific anticapsular antibody
1981;99:7726. and abnormalities of serum complement. Pediatr Res 1983;
54. Perkin RM, Levin DL, Webb R, et al. Dobutamine: A hemody- 17:496502.
namic evaluation in children with shock. J Pediatr 1982; 79. Stossel TP, Alper CH, Rosen F. Opsonic activity in the newborn:
100:97783. Role of properidin. Pediatr 1973;52:1347.
55. Osborn D, Evans N, Klucklow M. Randomized trial of dobutamine 80. Gerdes JS, Yoder MC, Douglas SD, et al. Decreased plasma
versus dopamine in preterm infants with low systemic blood flow. fibronectin in neonatal sepsis. Pediatrics 1983;72:87781.
J Pediatr 2002;140:18391. 81. Chirico G, Rondini G, Plebani A, et al. Intravenous gamma globu-
56. Barton P, Garcia JK, Kitchen A, et al. Hemodynamic effects of I.V. lin therapy for prophylaxis of infection in high-risk neonates.
milrinone lactate in pediatric patients with septic shock. A prospec- J Pediatr 1987;110:43742.
tive double-blinded, randomized, placebo-controlled interven- 82. Clark SC, Kamen R. The human hematopoietic colony-stimulating
tional study. Chest 1996;109:130212. factors. Science 1987;236:122937.
57. Chang AC, Am A, Wernovsky G, et al. Milrinone: Systemic and 83. Ohlsson A, Lacy J. Intravenous immunoglobulin for preventing
pulmonary hemodynamic effects in neonates after cardiac surgery. infection in preterm and or low birth weight infants. Cochrane
Crit Care Med 1995;23:190714. Database Syst Reviews 2004(1):Art. No.: CD000361.
18 SECTION I General
84. Sieff CA. Hematopoietic growth factors. J Clin Invest 1987;79:1549. 91. Ruokonen E, Parviainen I, Usuaro A. Treatment of impaired per-
85. Barak Y, Leibovitz E, Mogilner B, et al. The in vivo effect of fusion in septic shock. Ann Med 2002;34:5907.
recombinant human granulocyte-colony stimulating factor in neu- 92. Dellinger RP. Cardiovascular management of septic shock. Crit
tropenic neonates with sepsis. Eur J Pediatr 1997;156:6436. Care Med 2003;31:94655.
86. Wolach B. Neonatal sepsis: Pathogenesis and supportive therapy 93. Malay MB, Ashton RC, Landry DW, et al. Low-dose vasopressin
[Review]. Semin Perinatol 1997;21:2838. in the treatment of vasodilatory septic shock. J Trauma 1999;
87. Cairo M, Seth T, Fanaroff A, et al. A double-blinded randomized 47:699703.
placebo controlled pilot study of RhGM-CSF in low birth weight 94. Brierley J, Carcillo JA, Choong K, et al. Clinical practice param-
neonates (LBWN): Preliminary results demonstrate a significant eters for hemodynamic support of pediatric and neonatal septic
reduction in nosocomial infections with Rhu-GM-CS. Pediatr Res shock: 2007 update from the American College of Critical Care
1996;39:294a. Medicine. Crit Care Med 37:66688, 2009.
88. Brancho F, Goldman S, Cairo M. Potential use of granulocyte 95. Yager P, Noviski N. Shock. Pediatr Rev 2010;21:31118.
colony-stimulating factor and granulocyte-macrophage colony- 96. Srinivasan L, Harris MC. New technologies for the rapid diagnosis
stimulating factor in neonates. Curr Opin Hematology of neonatal sepsis. Curr Opin Pediatr 2012;24:16571.
1998;5:31520. 97. Hofer N, Zacharias E, Muller W, et al. An update on the use of
89. Carcillo JA, Fields AI, Task Force Committee Members. Clinical C-reactive protein in early-onset neonatal sepsis: current insights
practice parameters for hemodynamic support of pediatric and neo- and new tasks. Neonatol 2012;102:2536.
natal patients septic shock. Crit Care Med 2002;30:136577. 98. Dilli D, Dilmer U. The role of interleukin-6 and C-reactive
90. Tobin JR, Wetzel RC. Shock and multi-organ system failure. In protein in non-thyroidal illness in premature infants followed in
Handbook of Pediatric Intensive Care, Rogers and Helfaer, eds. neonatal intensive care unit. J Clin Res Pediatr Endocrinol
1999. p. 32451. 2012;4:6671.
C H A P T E R 2
Despite advances in the field of nutritional support, the nutritional support is a priority in sick neonates and chil-
prevalence of malnutrition among hospitalized patients, dren. The goal of nutrition in this setting is to augment
especially those with a protracted clinical course, has the short-term benefits of the metabolic response to
remained largely unchanged over the last two decades.1,2 injury while minimizing long-term consequences. In
The provision of optimal nutritional therapy requires a general, the metabolic stress response is characterized by
careful assessment of energy needs and the provision of an increase in net muscle protein degradation and the
macronutrients and micronutrients via the most suitable enhanced movement of free amino acids through the
feeding route. The profound and stereotypic metabolic circulation (Fig. 2-1). These amino acids serve as the
response to injury places unique demands on the hospi- building blocks for the rapid synthesis of proteins that act
talized child. Standard equations available for estimating as mediators for the inflammatory response and struc-
energy needs have proven to be unreliable in this popula- tural components for tissue repair. The remaining amino
tion.3,4 In addition, children with critical illness have a acids not used in this way are channeled through the liver
marked net protein catabolism and often lack adequate where their carbon skeletons are utilized to create glucose
nutritional support.5 Ultimately, an individualized nutri- through gluconeogenesis. The provision of additional
tional regimen should be tailored for each child and dietary protein may slow the rate of net protein loss, but
reviewed regularly during the course of illness. An under- does not eliminate the overall negative protein balance
standing of the metabolic events that accompany illness associated with injury.7
and surgery in a child is the first step in implementing Carbohydrate and lipid turnover are also increased
appropriate nutritional support. several fold during the metabolic response. Although
these metabolic alterations would be expected to increase
overall energy requirements, data show that such an
THE METABOLIC RESPONSE TO STRESS increase is quantitatively variable, modest, and evanes-
cent. Overall, the energy needs of the critically ill or
The metabolic response to illness due to stressors such injured child are governed by the severity and persistence
as trauma, surgery, or inflammation has been well of the underlying illness or injury. Accurate assessment
described. Cuthbertson was the first investigator to of energy requirements in individual patients allows
realize the primary role that whole-body protein catabo- optimal caloric supplementation and avoids the deleteri-
lism plays in the systemic response to injury.6 Based on ous effects of both under- and overfeeding. Children
his work, the metabolic stress response has been concep- with critical illness demonstrate a unique hormonal
tually divided into two phases. The initial, brief ebb and cytokine profile characterized by an elevation in
phase is characterized by decreased enzymatic activity, serum levels of insulin, the catabolic hormones (gluca-
reduced oxygen consumption, low cardiac output, and a gons, cortisol, catecholamines), and specific cytokines
core temperature that may be subnormal. This is fol- known to interact with the inflammatory process.8
lowed by the hypermetabolic flow phase characterized Novel ways to manipulate these hormonal and cytokine
by increased cardiac output, oxygen consumption, and alterations with an aim to minimize the deleterious con-
glucose production. During this phase, fat and protein sequences induced by the stress response are a focus of
mobilization is manifested by increased urinary nitrogen research.
excretion and weight loss. This catabolic phase is medi-
ated by a surge in cytokines and the characteristic endo-
crine response to trauma or operation that results in an BODY COMPOSITION AND
increased availability of substrates essential for healing NUTRIENT RESERVES
and glucose production.
Neonates and children share similar qualitative meta- The body composition of the young child contrasts with
bolic responses to illness as adults, albeit with significant that of the adult in several ways that significantly affect
quantitative differences. The metabolic stress response nutritional requirements. Table 2-1 lists the macronutri-
is beneficial in the short term, but the consequences ent stores of the neonate, child, and adult as a percentage
of sustained catabolism are significant as the child of total body weight.9,10 Carbohydrate stores are limited
has limited tissue stores and substantial nutrient in all age groups and provide only a short-term supply of
requirements for growth. Thus the prompt institution of glucose. Despite this fact, neonates have a high demand
19
20 SECTION I General
KETONES
Fuel for brain TISSUE REPAIR
WOUND HEALING
Surgery
Glycolysis Urea
GLUCOSE
utilization
Hyperglycemia Fuel for
brain, RBC,
and kidneys
FIGURE 2-1 The metabolic changes associated with the pediatric stress response to critical illness and injury. In general, net protein
catabolism predominates and amino acids are transported from muscle stores to the liver, where they are converted to inflamma-
tory proteins and glucose through the process of gluconeogenesis.
TABLE 2-1 The Body Composition of Neonates, TABLE 2-2 Estimated Requirements for Energy
Children, and Adults as a and Protein in Healthy Humans of
Percentage of Total Body Weight Different Age Groups
Protein Fat Carbohydrate Protein Energy
Age (%) (%) (%) Age (g/kg/day) (kcal/kg/day)
Neonates 11 14 0.4 Neonates 2.2 120
Children (age 10 years) 15 17 0.4 Children (age 10 years) 1.0 70
Adults 18 19 0.4 Adults 0.8 35
for glucose and have shown elevated rates of glucose to produce glucose continues unabated.15 Neonates and
turnover when compared with those of the adult.11 children also share much higher baseline energy require-
This is thought to be related to the neonates increased ments. Studies have demonstrated that the resting energy
brain-to-body mass ratio because glucose is the primary expenditure for neonates is two to three times that of
energy source for the central nervous system. Neonatal adults when standardized for body weight.14,16 Clearly,
glycogen stores are even more limited in the early post- the childs need for rapid growth and development is a
partum period, especially in the preterm infant.12 Short large component of this increase in energy requirement.
periods of fasting can predispose the newborn to hypogly- Moreover, the relatively large body surface area of the
cemia. Thus when infants are burdened with illness or young child may increase heat loss and further contrib-
injury, they must rapidly turn to the breakdown of protein utes to elevations in energy expenditure.
stores to generate glucose through the process of The basic requirements for protein and energy in the
gluconeogenesis. healthy neonate, child, and adult, based on recent recom-
Lipid reserves are low in the neonate, gradually mendations by the National Academy of Sciences, are
increasing with age. Premature infants have the lowest listed in Table 2-2.17 As illustrated, the recommended
proportion of lipid stores as the majority of polyunsatu- protein provision for the neonate is almost three times
rated fatty acids accumulate in the third trimester.13 This that of the adult. In premature infants, a minimum
renders lipid less useful as a potential fuel source in the protein allotment of 2.8g/kg/day is required to maintain
young child.14 The most dramatic difference between in utero growth rates.18 The increased metabolic demand
adult and pediatric patients is in the relative quantity of and limited nutrient reserves of the infant mandates early
stored protein. The protein reserve of the adult is nearly nutritional support in times of injury and critical illness
twofold that of the neonate. Thus infants cannot afford to avoid negative nutritional consequences.
to lose significant amounts of protein during the course Accurate assessment of body composition is necessary
of a protracted illness or injury. An important feature of for planning nutritional intake, monitoring dynamic
the metabolic stress response, unlike in starvation, is that changes in the body compartments (such as the loss of
the provision of dietary glucose does not halt gluconeo- lean body mass), and assessing the adequacy of nutritional
genesis. Consequently, the catabolism of muscle protein supportive regimens during critical illness. Ongoing loss
2 Nutritional Support for the Pediatric Patient 21
of lean body mass is an indicator of inadequate dietary as high as 140kcal/kg/day. Although stress factors
supplementation and may have clinical implications in ranging from 1.0 to 2.7 have been applied to correct for
the hospitalized child. However, current methods of body these variations, calculated standardized energy expendi-
composition analysis (such as anthropometry, weight and ture equations have not been satisfactorily validated in
biochemical parameters) are either impractical for clini- critically ill children.2225
cal use or inaccurate in a subgroup of hospitalized chil- Indirect calorimetry measures VO2 (the volume of
dren with critical illness. One of the principal problems oxygen consumed) and VCO2 (the volume of CO2 pro-
in critically ill children is the presence of capillary leak, duced), and uses a correlation factor based on urinary
manifesting as edema and large fluid shifts. These make nitrogen excretion to calculate the overall rate of energy
anthropometric measurements invalid and other bedside production.26 The measurement of energy needs is indi-
techniques have not been validated. rect because it does not use direct temperature changes
to determine energy needs. Indirect calorimetry provides
a measurement of the overall respiratory quotient (RQ),
ENERGY EXPENDITURE DURING ILLNESS defined as the ratio of CO2 produced to O2 consumed
(VCO2/ VO2), for a given patient. Oxidation of carbohy-
For children with illness or undergoing operative inter- drate yields an RQ of 1.0, whereas fatty acid oxidation
vention, knowledge of energy requirements is important gives an RQ of 0.7. However, the role of the RQ as a
for the design of appropriate nutritional strategies. marker of substrate use and as an indicator of underfeed-
Dietary regimens that both under- and overestimate ing or overfeeding is limited. The bodys ability to metab-
energy needs are associated with injurious consequences. olize substrate may be impaired during illness, making
Owing to the high degree of individual variability in assumptions invalid about RQ values and substrate
energy expenditure, particularly in the most critically ill oxidation.
patients, the actual measurement of resting energy Although RQ is not a sensitive marker for adequacy
expenditure (REE) is recommended. of feeding in individual cases, RQ values greater than 1.0
The components of total energy expenditure (TEE) are generally associated with lipogenesis secondary to
for a child in order of magnitude are: resting REE, energy overfeeding.27,28 A recent study has suggested the utility
expended during physical activity (PA), and diet-induced of extremes of RQ in monitoring feeding adequacy,
thermogenesis (DIT). The sum of these components where an RQ higher than 0.85 reliably indicates the
determines the energy requirement for an individual. In absence of underfeeding and an RQ higher than 1.0 reli-
general, REE rates decline with age from infancy to ably indicates the presence of overfeeding.29 However,
young adulthood, at which time the rate becomes stable. numerous factors, related and unrelated to feeding, can
In children with critical illness, the remaining factors in alter the value of a measured RQ in critically ill patients,
the determination of total energy requirement are of e.g., hyperventilation, acidosis, effects of cardiotonic
reduced significance as PA is low and DIT (the heat agents and neuromuscular blocking, and an individual
generated by the consumption of food products) may not response to a given substrate load, injury, or disease.
be significant. Furthermore, in the setting of wide diurnal and day-to-
REE can be measured using direct or indirect methods. day variability of REE in critically ill individuals, the
The direct calorimetric method measures the heat extrapolation of short-term calorimetric REE measure-
released by a subject at rest and is based on the principle ments to 24-hour REE may introduce errors. The use of
that all energy is eventually converted to heat. In practice, steady-state measurements may decrease these errors.
the patient is placed in a thermally isolated chamber, and Steady state is defined by change in VO2 and VCO2 of
the heat dissipated is measured for a given period of <10% over a period of five consecutive minutes. The
time.19 This method is the true gold standard for meas- values for the mean REE from this steady-state period
ured energy expenditure. Direct calorimetry is not prac- may be used as an accurate representation of the 24-hour
tical for most hospitalized children and REE is often TEE in patients with low levels of physical activity.30 In
estimated using standard equations. Unfortunately, REE a patient who fails to achieve steady state and is metaboli-
estimates using standardized World Health Organization cally unstable, prolonged testing is required (minimum
(WHO) predictive equations are unreliable, particularly of 60 minutes), and 24-hour indirect calorimetry should
in underweight subjects.1921 be considered. With the advent of newer technology, the
REE estimation is difficult in critically ill or postop- application of indirect calorimetry at the bedside for con-
erative children. Their energy requirements show indi- tinuous monitoring shows promise.
vidual variation and are dependent upon severity of Indirect calorimetry is not accurate in the setting of
injury. For instance, an infant with respiratory distress air leaks around the endotracheal tube, ventilator circuit
on pressure support is likely to have high energy or through a chest tube, or in subjects on ECMO. High
requirement due to increased work of breathing. The inspired oxygen fraction (FiO2 >0.6) will also affect
same patient, when started on mechanical ventilation indirect calorimetry. Indirect calorimetry is difficult to
with muscle relaxants, is unlikely to have sustained high use in babies on ECMO because a large proportion of
energy requirements. Infants with congenital diaphrag- the patients oxygenation and ventilation is performed
matic hernia on extracorporeal membrane oxygenation through the membrane oxygenator. The use of indirect
(ECMO) support have been shown to have energy expen- calorimetry for assessment and monitoring of nutrition
ditures of approximately 90kcal/kg/day. Following extu- intake requires attention to its limitations and expertise
bation, the same patients may have energy requirements in the interpretation. Nonetheless, its application in
22 SECTION I General
children at high risk for underfeeding and overfeeding stress factors. On the other hand, unrecognized hyper-
may be helpful.31,32 metabolism in select individuals result in underfeeding
Nonradioactive stable isotope techniques have been with negative nutritional consequences.31 The variability
used to measure REE in the pediatric patient. Stable in energy requirements may result in cumulative energy
isotope technology has been available for many years and imbalances in the intensive care unit (ICU) over a period
was first applied for energy expenditure measurement in of time.32 A direct relationship has been reported between
humans in 1982.33,34 Both 13C-labeled bicarbonate and cumulative caloric imbalance and the mortality rate in
doubly labeled water (2H218O) have been used to measure critically ill surgical patients.48
TEE in pediatric surgical patients, and have been shown For practical purposes, the recommended dietary
to correlate well with indirect calorimetry.31,34,35 The caloric intake for healthy children may represent a rea-
13
C-labeled bicarbonate method allows the calculation of sonable starting point for the upper limit of caloric allot-
REE on the basis of infusion rate and the ratio of labeled ment in the hospitalized child.17 However, as discussed
to unlabeled CO2 in expired breath samples.35 Orally earlier, energy requirement estimates in select groups of
administered stable isotopes of water (2H2O and H218O) patients remain variable and possibly overestimated,
mix with the body water and the 18O is lost from the body mandating an accurate estimation using measured energy
as both water and CO2, while the 2H is lost from the body expenditure where available. Regular anthropometric
only as water. The difference in the rates of loss of the measurements plotted on a growth chart to assess the
isotopes 18O and 2H from the body reflects the rate of adequacy of caloric provision will allow relatively prompt
CO2 production, which can be used to calculate the detection of underfeeding or overfeeding in most cases.
TEE.3638 However, the doubly labeled water method has However, some critically ill children may be too sick for
its limitations in children with active capillary leak, regular weights or have changes in body water that make
decreased urine output, fluid overload, and diuretic use.36 anthropometric measurements unreliable.
In general, any increase in energy expenditure during
illness or after an operation is variable, and studies suggest
that the increase is far less than originally hypothesized. MACRONUTRIENT INTAKE
In children with severe burns, the initial REE during the
flow phase of injury is increased by 50% but then returns Protein Metabolism and Requirement
to normal during convalescence.39 In neonates with bron- During Illness
chopulmonary dysplasia, in which the illness increases
the patients work of breathing, a 25% elevation in energy Amino acids are the key building blocks required for
requirement is evident.40 Newborns undergoing major growth and tissue repair. The vast majority (98%) are
surgery have only a transient 20% increase in energy found in existing proteins, and the remainder reside in
expenditure that returns to baseline values within 12 the free amino acid pool. Proteins are continually
hours postoperatively, provided no major complications degraded into their constituent amino acids and resyn-
develop.41,42 Stable extubated neonates, five days after thesized through the process of protein turnover.
operation, have been shown to have REE comparable to The reutilization of amino acids released by protein
normal infants.43 Effective anesthetic and analgesic man- breakdown is extensive. Synthesis of proteins from
agement may play a significant role in muting the stress the recycling of amino acids is more than two times
response of the neonate. Studies have demonstrated no greater than from dietary protein intake. An advantage of
discernible increase in REE in neonates undergoing high protein turnover is that a continuous flow of amino
patent ductus arteriosus ligation who received intraop- acids is available for the synthesis of new proteins. This
erative fentanyl anesthesia and postoperative intravenous allows the body tremendous flexibility in meeting ever-
analgesic regimens.42 A retrospective stratification of sur- changing physiologic needs. However, the process of
gical infants into low- and high-stress cohorts based on protein turnover requires the input of energy to power
the severity of underlying illness found that high-stress both protein degradation and synthesis. At baseline,
infants undergo moderate short-term elevations in energy infants are known to have higher rates of protein
expenditure after operation, whereas low-stress infants turnover than adults. Healthy newborns have a
do not manifest any increase in energy expenditures protein-turnover rate of 612g/kg/day compared with
during the course of illness.44 Finally, by using stable 3.5g/kg/day in adults.49 Even greater rates of protein
isotopic methods, it has been found that the mean energy turnover have been measured in premature and low birth
expenditures of critically ill neonates on ECMO are weight infants.50 For example, it has been demonstrated
nearly identical to age- and diet-matched nonstressed that extremely low birth weight infants receiving no
controls.45 dietary protein can lose in excess of 1.2g/kg/day of
All these studies suggest that critically ill neonates endogenous protein.51 At the same time, infants must
have only a small and usually short-term increase in maintain a positive protein balance to attain normal
energy expenditure. Although children have increased growth and development, whereas the healthy adult can
energy requirements from increased metabolic turnover subsist with a neutral protein balance.
during illness, their caloric needs may be lower than In the metabolically stressed patient, such as the child
previously considered due to possible halted or slow with severe burn injury or cardiorespiratory failure
growth,46 and the use of sedation and muscle paralysis.47 requiring ECMO, protein turnover is doubled when
This could result in overfeeding when energy intake is compared with normal subjects.34,49 A study of critically
based on presumed or estimated energy expenditure with ill infants and children found an 80% increase in protein
2 Nutritional Support for the Pediatric Patient 23
turnover, which correlated with the duration of the criti- Increased muscle protein catabolism is a successful
cal illness.52 This process redistributes amino acids from short-term adaptation during critical illness, but it is
skeletal muscle to the liver, wound, and tissues taking part limited and ultimately harmful to the child with reduced
in the inflammatory response. The factors required for protein stores and elevated protein demands. Unless the
the inflammatory response (acutely needed enzymes, inciting stress is eliminated, the progressive breakdown
serum proteins, and glucose) are thereby synthesized of diaphragmatic, cardiac, and skeletal muscle can lead to
from degraded body protein stores. The well-established respiratory compromise, fatal arrhythmia, and loss of
increase in hepatically derived acute phase proteins lean body mass. Moreover, a prolonged negative protein
(including C-reactive protein, fibrinogen, transferrin, balance may have a significant impact on the childs
and -1-acid glycoprotein), along with the concomitant growth and development. Healthy, nonstressed neonates
decrease in transport proteins (albumin and retinol- require a positive protein balance of nearly 2g/kg/day.48,60
binding protein), is evidence of this protein redistribu- In contrast, critically ill, premature neonates requiring
tion. As substrate turnover is increased during the stress mechanical ventilation have a negative protein balance
response, rates of both whole-body protein degradation of 1g/kg/day.61,62 Critically ill neonates who require
and whole-body protein synthesis are accelerated. ECMO have exceedingly high rates of protein loss, with
However, protein breakdown predominates, thereby a net negative protein balance of 2.3g/kg/day.63 It has
leading to a hypercatabolic state with an ensuing net been well established that the extent of protein catabo-
negative protein and nitrogen balance.27 lism correlates with morbidity and mortality in surgical
Protein loss is evident in elevated levels of excreted patients.
urinary nitrogen during critical illness. For example, Fortunately, amino acid supplementation tends to
infants with sepsis demonstrate a severalfold increase in promote increased nitrogen retention and positive protein
the loss of urinary nitrogen that directly correlates with balance in critically ill patients.59,64 The mechanism
the degree of illness.53 Clinically, severe protein loss can appears to be an increase in protein synthesis while rates
be manifested by skeletal muscle wasting, weight loss, of protein degradation remain constant.60,61 Therefore
delayed wound healing, and immune dysfunction.54 In the provision of dietary protein sufficient to optimize
addition to the reprioritization of protein for tissue repair, protein synthesis, facilitate wound healing and the inflam-
healing and inflammation, the body appears to have an matory process, and preserve skeletal muscle mass is the
increased need for glucose production during times of single most important nutritional intervention in criti-
metabolic stress.55 The accelerated rate of gluconeogen- cally ill children. The quantity of protein needed to
esis during illness and injury is seen in both children and enhance protein accrual is greater in hospitalized sick
adults, and this process appears to be accentuated in children than in healthy children. Table 2-3 lists recom-
infants with low body weight.13,54 The increased produc- mended quantities of dietary protein for hospitalized
tion of glucose in times of illness is necessary as glucose children. Extreme cases of physiologic stress, including
represents a versatile energy source for tissues taking part the child with extensive burns or the neonate on ECMO,
in the inflammatory response. For example, it has been may necessitate additional protein supplementation to
shown that glucose utilization by leukocytes is signifi- meet metabolic demands.
cantly increased during the inflammatory response.56 The influence of macronutrient intake on protein
Unfortunately, the provision of additional dietary glucose balance has been explored in a limited number of
does not suppress the bodys need for increased glucose studies. A systematic review of all such studies in mechan-
production. Therefore, net protein breakdown continues ically ventilated children showed that a minimum of
to predominate.14,57,58 1.5g/kg/day protein and 57kcal/kg/day energy intake
Specific amino acids are transported from muscle to was needed to achieve a positive protein balance in this
the liver to facilitate hepatic glucose production. The group.62 However, it should be noted that toxicity from
initial step of amino acid catabolism involves removal of excessive protein administration can occur, particularly in
the toxic amino group (NH3). Through transamination, children with impaired renal and hepatic function. The
the amino group is transferred to -ketoglutarate, thereby provision of protein at levels greater than 3g/kg/day is
producing glutamate. The addition of another amino rarely indicated and is often associated with azotemia. In
group converts glutamate to glutamine, which is subse-
quently transported to the liver. Here, the amino groups
are removed from glutamine and detoxified to urea
through the urea cycle. The amino acid carbon skeleton TABLE 2-3 Recommended Protein
can then enter the gluconeogenesis pathway. Alterna- Requirements for Hospitalized
tively, in skeletal muscle, the amino group can be trans- Infants and Children
ferred to pyruvate, thereby forming alanine. When
alanine is transported to the liver and detoxified, pyruvate Estimated Protein
is reformed and can be converted to glucose through Age (years) Requirement (g/kg/day)
gluconeogenesis. The transport of alanine and pyruvate Extremely low birth weight up to 3.5
between peripheral muscle tissue and the liver is termed infants
the glucose-alanine cycle.59 Hence the transport amino Very low birth weight up to 3.0
02 2.03.0
acid systems involving glutamine and alanine provide 213 1.52.0
carbon backbones for gluconeogenesis, while facilitating 1318 1.01.5
the hepatic detoxification of ammonia by the urea cycle.
24 SECTION I General
premature neonates, the possible beneficial effects of short-term adaptive benefit of this response is outweighed
protein allotments of 33.5g/kg/day are being actively by the loss of protein in critical organs and the conse-
investigated in an effort to replicate intrauterine growth quent morbidity seen after the exhaustion of limited
rates. Studies using protein provisions of 6g/kg/day in protein reserves. This sustained protein breakdown
children have demonstrated significant morbidity, includ- cannot be stopped by increasing caloric intake alone (as
ing azotemia, pyrexia, strabismus, and lower IQ scores.64,65 is the case in starvation), but protein balance may be
restored by optimal (probably individual and disease spe-
cific) quantities of protein intake during this state. Future
Protein Quality
studies may also elucidate if specific amino acid mixtures
In addition to the sufficient quantity of dietary protein, may be of benefit to select subpopulations.
an increased focus has been placed on the protein quality
of nutritional provisions. The specific amino acid formu- Modulating Protein Metabolism
lation to best increase whole-body protein balance has
yet to be fully determined, although numerous clinical The dramatic increase in protein breakdown during criti-
and basic science research projects are actively focusing cal illness, coupled with the known association between
on this topic. It is known that infants have an increased protein loss and patient mortality and morbidity, has
requirement per kilogram for the essential amino acids stimulated a wide array of research efforts. The measure-
compared to the adult.66 In particular, neonates have ment of whole-body nitrogen balance through urine and
immature biosynthetic pathways that may temporarily stool was once the only way to investigate changes in
alter their ability to synthesize specific amino acids. One protein metabolism, but new and validated stable isotope
example is the amino acid histidine, which has been tracer techniques now allow precise measurement of
shown to be a conditionally essential amino acid in infants protein turnover, breakdown, and synthesis.74 However,
up to age 6 months. Data suggest that cysteine, taurine, the modulation of protein metabolism in critically ill
and proline also may be limited in the premature patients has been difficult. Dietary supplementation of
neonate.6770 Interest has also been expressed in the use amino acids increases protein synthesis, but appears to
of arginine as an immunonutrient to enhance the func- have no effect on rates of protein breakdown. Thus inves-
tion of the immune system in critically ill patients. tigators have recently focused on the use of alternative
Although preliminary studies show that arginine supple- anabolic agents to decrease protein catabolism. Studies
mentation may reduce the risk of infectious complica- have used various pharmacologic tools to achieve this
tions, its safety and efficacy in infants and children has goal, including growth hormone, insulin-derived growth
yet to be established.71 factor I (IGF-I), and testosterone, with varying degrees
The restricted availability of the amino acid cysteine of success.7577 One of the more promising agents,
may have clinical relevance in the critically ill child. however, may be the anabolic hormone insulin. Multiple
Cysteine is a required substrate for the production of studies have used insulin to reduce protein breakdown in
glutathione, the bodys major antioxidant. In critically ill healthy volunteers and adult burn patients.50,78 In chil-
children, cysteine turnover is increased significantly, dren with extensive burns, intravenous insulin has been
whereas rates of glutathione synthesis are decreased by shown to increase lean body mass and mitigate peripheral
60%. In this way, cysteine may become a conditionally muscle catabolism.79 A recent prospective, randomized
essential amino acid in the sick child. Recent experiments trial of more than 1500 adult postoperative patients in
have demonstrated that the enteral feeding of cysteine in the ICU demonstrated significant reductions in mortality
small quantities to rats dependent on total parenteral and morbidity with the use of intravenous insulin.80 Pre-
nutrition (TPN) significantly increases the hepatic con- liminary stable isotopic studies demonstrate that an intra-
centration of glutathione.72 The enteral supplementation venous insulin infusion may reduce protein breakdown
of cysteine in a pediatric nutritional regimen warrants by over 30% in critically ill neonates on ECMO.81 The
further basic science and clinical investigation. use of intensive insulin therapy for critically ill children
Glutamine is another amino acid that has been studied and adults continues to be another active and interesting
extensively in both children and adults in the ICU. area of clinical investigation. Some recent studies exam-
Glutamine is an important amino acid source for gluco- ining the role of insulin for tight glycemic control in
neogenesis, intestinal energy production, and ammonia critically ill patients have been less encouraging and are
detoxification. In healthy subjects, glutamine is a nones- discussed in the next section.
sential amino acid, although it has been hypothesized that
glutamine may become conditionally essential in criti- Carbohydrate Metabolism and
cally ill patients. Because it is difficult to keep glutamine
soluble in solution, standard TPN formulas do not
Requirement During Illness
include glutamine in the amino acid mixture. Although Glucose production and availability are a priority in the
preliminary data on glutamine supplementation in the pediatric metabolic stress response. Glucose is the
clinical setting are encouraging, numerous problems with primary energy source for the brain, erythrocyte, and
study methodology have been noted.73 Additional pro- renal medulla, and is used extensively in the inflammatory
spective, randomized trials are needed to define its utility response. Injured and septic adults demonstrate a three-
fully in both the adult and pediatric population. fold increase in glucose turnover, glucose oxidation, and
In summary, during illness and recovery from trauma gluconeogenesis.16 This increase is of particular concern
or surgery, there is increased protein catabolism. The in neonates who have an elevated glucose turnover at
2 Nutritional Support for the Pediatric Patient 25
baseline.10 Moreover, glycogen stores provide only a shown a high incidence of hypoglycemia in the treatment
limited endogenous supply of glucose in adults and an group and less impressive benefit.90 Although the inci-
even smaller reserve in the neonate. Thus the critically dence of hyperglycemia in children is high and may be
ill neonate has a greater glucose demand and reduced associated with increased mortality and length of stay,91
glucose stores. During illness, the administration of there are no data for similar benefits of tight glycemic
exogenous glucose does not halt the elevated rates of control in this patient population. Studies examining the
gluconeogenesis, and thus net protein catabolism contin- role of a tight glycemic control strategy in infants and
ues unabated.14 It is clear, however, that a combination of children are currently underway.
dietary glucose and amino acids can effectively improve
protein balance during critical illness, primarily through Lipid Metabolism and Requirements
augmentation of protein synthesis.
In the past, nutritional support regimens for critically
During Illness
ill patients used large amounts of glucose in an attempt Similar to protein and carbohydrate metabolism, the
to reduce endogenous glucose production. Unfortu- turnover of lipid is generally increased by critical illness,
nately, excess glucose increases CO2 production, engen- major surgery, and trauma in the pediatric patient.92
ders fatty liver, and does not result in a reduction in During the early ebb phase, triglyceride levels may ini-
endogenous glucose turnover.82 Thus a surplus of carbo- tially increase as the rate of lipid metabolism decreases.
hydrate may increase the ventilatory burden on the criti- However, this process reverses itself in the predominant
cally ill patient. In one study, adults in the ICU fed with flow phase, and during this time, critically ill adults have
high-glucose TPN demonstrate a 30% increase in oxygen demonstrated two- to fourfold increases in lipid turno-
consumption, a 57% increase in CO2 production, and a ver.93 Also, it has been shown that critically ill children
71% elevation in minute ventilation.83 In critically ill on mechanical ventilation have increased rates of fatty
infants, the conversion of excess glucose to fat has also acid oxidation.94 The increased lipid metabolism is
been correlated with increased CO2 production and thought to be proportional to the overall degree of illness.
higher respiratory rates.84 In addition, excessive carbohy- The process of lipid turnover involves the conversion of
drate may play a role in the genesis of TPN-associated free fatty acids and their glycerol backbone into triglyc-
cholestatic liver injury. Finally, some data in critically ill erides. Approximately 3040% of free fatty acids are oxi-
neonates have shown that excess caloric allotments of dized for energy. RQ values may decline during illness,
carbohydrate are paradoxically associated with an reflecting an increased utilization of fat as an energy
increased rate of net protein breakdown.85 source.95 This suggests that fatty acids are a prime source
When designing a nutritional regimen for the criti- of energy in metabolically stressed pediatric patients. In
cally ill child, excessive carbohydrate calories should be addition to the rich energy supply from lipid substrate,
avoided. A mixed fuel system, with both glucose and lipid the glycerol moiety released from triglycerides may be
substrates, should be used to meet the childs caloric converted to pyruvate and used to manufacture glucose.
requirements. When the postoperative neonate is fed a As seen with the other catabolic changes associated with
high-glucose diet, the corresponding RQ is approxi- illness and trauma, the provision of dietary glucose does
mately 1.0, and may be higher than 1.0 in selected not decrease fatty acid turnover in times of illness. The
patients, signifying increased lipogenesis.86 A mixed increased demand for lipid utilization in critical illness
dietary regimen of glucose and lipid (at 24g/kg/day) coupled with the limited lipid stores in the neonate puts
lowers the effective RQ in neonates to 0.83.87 This the metabolically stressed infant/child at high risk for the
approach provides the infant with full nutritional sup- development of essential fatty acid deficiency.96,97 Preterm
plementation while alleviating an increased ventilatory infants have been shown to develop biochemical evidence
burden and difficulties with hyperglycemia. of essential fatty acid deficiency two days after the initia-
Administration of high caloric (glucose load) diets in tion of a fat-free nutritional regimen.98
the early phase of critical illness may exacerbate hyperg- In the human, the polyunsaturated fatty acids linoleic
lycemia, increase carbon dioxide generation with an and linolenic acid are considered essential fatty acids
increased load on the respiratory system, promote hyper- because the body cannot manufacture them by desaturat-
lipidemia resulting from increased lipogenesis, and result ing other fatty acids. Linoleic acid is used by the body to
in a hyperosmolar state. Several reports have linked synthesize arachidonic acid, an important intermediary
hyperglycemia with increased mortality and established in prostaglandin synthesis. The prostaglandin family
the role of insulin-assisted tight glycemic control in includes the leukotrienes and thromboxanes, all of which
improving outcomes in critically ill adults.80,88,89 A remark- serve as mediators in wide-ranging processes such as vas-
able 43% reduction in mortality was reported in postcar- cular permeability, smooth muscle reactivity, and platelet
diac surgery patients in an adult ICU by implementing aggregation. If an individual lacks dietary linoleic acid,
strict glycemic control (arterial blood glucose levels the formation of arachidonic acid (a tetraene) cannot
below 110mg/dL) and using insulin infusion in the treat- occur, and eicosatrienoic acid (a triene) accumulates.
ment group compared with the control group (average Clinically, a fatty acid profile can be performed on human
blood glucose level of 150160mg/dL).80 The precise serum, and an elevated triene-to-tetraene ratio greater
mechanism(s) responsible for this beneficial effect of than 0.4 is characteristic of biochemical essential fatty
tight glycemic control with an insulin protocol remains acid deficiency, though this value is somewhat variable
unanswered. A recent meta-analysis of studies examining and dependent upon the specific laboratory assay utilized.
the role of tight glycemic control in adult ICUs has Signs of fatty acid deficiencies include dermatitis,
26 SECTION I General
PRECURSOR OF EICOSANOIDS
Arachidonic Eicosapentaenoic
acid acid
20:4n6 20:5n3
Cyclo- Cyclo-
Lipoxygenase Lipoxygenase
oxygenase oxygenase
Pro-inflammatory Anti-inflammatory
(within 2448 hourrs after ICU admission).108 The drug administration in the ICU and after discharge.
optimal route of nutrient delivery has not been systemati- Stoma site infection, obstruction, and tube dislodgement
cally studied in children. In the absence of a randomized- are common complications and must be identified and
controlled trial comparing the effects of EN vs PN, managed early. Malposition of the tube is frequently
many centers have adopted institutional guidelines. encountered with any of these devices either at placement
Current practice includes the initiation of gastric or post- or during the course of its use. Bedside screening methods
pyloric enteral feeding within 48hrs to 72hrs after to identify tip position range from auscultation during air
admission. PN is being used to supplement or replace insufflation to ultrasound-guided localization. However,
EN in those patients where EN alone is unable to meet feedings should be held when malposition of tip is sus-
the nutritional goal. pected. When in doubt, a contrast study may be needed
In children on EN, there are insufficient data to make to confirm tip position before recommencing feeds.
recommendations regarding the site of enteral feeding EN in critically ill children is often interrupted for a
(gastric vs postpyloric). Both enteral routes have been variety of reasons, some of which may be avoidable.114
successfully used for nutritional support of the critically Children with frequent interruptions have a higher reli-
ill child.109111 In a study examining the role of small ance on PN. Intolerance to enteral feeds may be a limit-
bowel feeding in 74 critically ill children randomized to ing factor and supplementation with PN in this group of
receive either gastric or postpyloric feeds, no significant patients allows for improved nutritional intake. Enteral
difference was observed in microaspiration, tube dis- feeds are held for a period of time before procedures such
placement and feeding intolerance between the two as elective endotracheal intubation, general anesthesia,
groups.112 The study was not powered to detect differ- procedural sedation, extubation, and other such interven-
ences in mortality and enteral feeds were interrupted in tions to lower the corresponding risk of aspiration. Most
a large number of subjects in this study. Also, caloric goals centers do not to use enteral feeds with patients who are
were met in only a small percentage of the population on multiple vasopressor drugs for hypotension or who
studied. A higher percentage of subjects in the small have evidence of bowel ischemia so as to limit the risk of
bowel group achieved their daily caloric goal when com- small bowel necrosis associated with rapid enteral
pared to the gastric fed group. Critically ill children feeding.115 In a subgroup of critically ill patients, TPN
receiving early (less than 24 hours after ICU admission) may be required for a period before initiation of enteral
postpyloric feeds have been shown to have better feeding feeds.
tolerance (decreased incidence of abdominal distension) Prospective cohort studies and retrospective chart
compared to those where post-pyloric feeding was initi- reviews have reported the inability to achieve the daily
ated late.113 caloric goal in many critically ill children.4,116 In a recent
It may be prudent to consider postpyloric feeds in study of mechanically ventilated children from 30 centers,
patients who do not tolerate gastric feeding or those who energy and protein intake were found to be grossly inad-
are at a high risk of aspiration. Transpyloric feeding may equate.117 By the end of the first week in the ICU just
be limited by the ability to obtain small bowel access and over 50% of the prescribed energy and protein were
the expertise and resources in individual ICUs are likely delivered. Patients with energy intake less than 66% of
to be variable. Operative placement of gastrostomy or the prescribed goal had higher mortality rates. The most
jejunostomy tubes allows long-term enteral feeding and common reasons for suboptimal enteral nutrient delivery
28 SECTION I General
in these studies were fluid restriction, procedures inter- intact intestinal function, PN is not indicated if enteral
rupting feeds, and feeding intolerance. In a study examin- feeds alone can maintain nutritional balance.
ing the endocrine and metabolic response of children The decision to initiate PN is based on the anticipated
with meningococcal sepsis, goal nutrition was achieved length of fasting, the underlying nutritional status of the
in only 25%.7 Similar observations have been made in a individual, and a careful examination of the risks associ-
group of 95 children in a pediatric ICU (PICU) where ated with PN use in relation to the consequences of poor
patients received a median of 58.8% (range 0277%) of nutritional intake. If the expected period during which
their estimated energy requirements.116 In this review, minimal or no EN will be provided to the child is longer
enteral feeding was interrupted on 264 occasions to allow than five days, the use of PN is prudent and probably
clinical procedures. In another review of nutritional beneficial. In children with underlying malnutrition, pre-
intake in 42 patients in a tertiary-level PICU over 458 maturity, or conditions associated with hypermetabolism,
days, actual energy intake was compared with estimated PN can be initiated earlier. The main limiting factor for
energy requirement.4 Only 50% of patients were reported provision of full nutritional support in the form of PN is
to have received full estimated energy requirements after the availability of central access. Administration of full
a median of seven days. Prolonged fluid resuscitation was PN requires a central venous catheter with its tip placed
a major factor hindering the achievement of estimated at the junction of superior vena cava and right atrium
energy requirements despite maximizing the energy (RA). If a lower extremity central line is utilized, the tip
content of the feedings. Protocols for use of transpyloric of the catheter should be placed at the junction of the
feeding tubes and changing from bolus to continuous inferior vena cava and RA. The large vessel diameter and
feeds during brief periods of intolerance are strategies maximal blood flow rate at these sites allows for the safe
that may help achieve estimated energy goals in this administration of the hypertonic PN. To avoid the com-
population. Consistently underachieved EN goals are plications associated with malpositioned tips of central
thought to be one of the reasons for the absence of a venous catheters, the practice at our institute is to docu-
beneficial effect in multiple studies and meta-analyses of ment the location of the central venous catheter tip prior
the efficacy of immunonutrition in preventing infec- to its use. Peripheral administration of PN in the absence
tion.118 Addressing preventable interruptions in enteral of an ideally located central venous catheter requires
feeding in critically ill children is essential to attaining dilution (maximum 900mosm/L) to avoid the risks of
goal feeds. At this time, there is not enough evidence to phlebitis and sclerosis. Osmolarity of the PN solution can
recommend the use of prokinetic medications, motility be calculated using available online calculators or simple
agents (for feeding intolerance or to facilitate enteral tube equations such as:
placement), prebiotics, probiotics, or synbiotics in criti-
cally ill children. Randomized studies comparing enteral {(dextrose grams / L 5) + ( protein grams / L 10)
feeds administered by bolus or continuously are also + ( lipid grams / L 1.5) + [( mEq / L of Na
lacking. + K + Ca + Mg ) 5]}.
In summary, EN must be initiated early in hospitalized
children with bowel activity. Postpyloric EN may be uti- Fluid and electrolytes status will guide the initial PN
lized in children with a high risk of aspiration or when prescription. The patients hydration, size, age, and
gastric feeding is either contraindicated or has failed. underlying disease will dictate the amount of the fluid to
Enterally administered feeds meet nutritional require- be administered. Fluid requirements in the pediatric age
ments in critically ill children with a functional gastroin- group are routinely estimated based on the Holliday
testinal system and have the advantages of low cost, Segar method (Table 2-4). PN should not routinely be
manageability, safety, and preservation of hepatic and used to replace ongoing losses. Fluid shifts, increased
other gastrointestinal function. Early introduction of insensible losses, drainage of bodily secretions, and renal
enteral feeds in critically ill patients helps to achieve posi- failure can complicate electrolyte management in these
tive protein and energy balance and restores nitrogen patients. PN should be prescribed daily after reviewing
balance during the acute state of illness. It maintains gut the electrolytes (Na+, K+, Cl, HCO3, Ca2+) and glucose
integrity and elicits release of growth factors and hor- to allow adjustments in the macro- and micronutrient
mones that maintain gut integrity and function.119 Despite composition. In sick patients with significant gastrointes-
its perceived benefits, current practice in ICUs shows tinal fluid loss (gastric, pancreatic, small intestinal, or
that a significant proportion of eligible patients do not bile), the measurement of electrolytes from the drained
receive EN.120 Fig. 2-4 offers an algorithm for initiating
and advancing EN in children admitted to the multidis-
ciplinary ICU at Childrens Hospital, Boston.
TABLE 2-4 Daily Fluid Requirement for Infants
Parenteral Nutrition and Children
PN provides intravenous administration of macronutri-
Maintenance Daily Fluid
ents and micronutrients to meet the nutritional require- Body Weight (kg) Requirement
ments when EN is not possible. Although widespread in
010 100mL/kg
its application, PN is associated with mechanical, infec- 1020 1000mL + 50mL/kg >10kg
tious, and metabolic complications and should only be >20 1500mL + 20mL/kg >20kg
used in carefully selected patients. In the setting of an
2 Nutritional Support for the Pediatric Patient 29
Unless contraindicated,* begin enteral nutrition support within 24 h of admission to the MSICU.
Box 1
A. Clears: If unable to protect airway
B. 1/2 strength formula:
Oral feeds Resume previously
Bolus Full if NPO >2 wk, malnourished,
Alert, unintubated, established feeding
feeds calories at risk for gut ischemia
strong cough and gag schedule as tolerated
(advance to FS formula after 24 h)
C. Full strength (FS) formula
D. Regular or specialty diet
A. To start:
Calculate 1/2 the volume of FS
feeds needed to meet caloric
requirements and divide by the
number of feedings per day.
Full
Same as Box 1 Usually 8 if <6 months and 6 if
calories
>6 months. If volume intolerant,
try small volume more frequent
bolus or continuous feeds.
Nasogastric/GT feeds B. To advance: Increase each
Bolus
Oral route inaccessible, feeding by 25% as tolerated
feeds
strong cough and gag
A. To start: 12 mL/kg/h
A. 1/2 strength formula:
(or 0.5 mL/kg/h if at risk
If NPO >2 wk, malnourished,
Full for gut ischemia)
at risk for gut ischemia
calories B. To advance:
(advance to FS formula after 24 h)
Nasojejunal/JT feeds <1 yr: 15 mL/h q3-4H
B. Full strength (FS) formula
High risk for aspiration >1 yr: 520 mL/h q4H
Continuous
(depressed gag reflex,
feeds
delayed gastric emptying,
GE reflux, bronchospasm) 520 mL/kg/d
Trophic
Full strength formula (Smaller volume in
feeds
larger patients)
*Contraindications include potential for endotracheal intubation/extubation within 4 hours; hemodynamically unstable requiring escalation
of therapy; postoperative ileus, upper gastrointestinal bleeding, at risk for NEC/intestinal ischemia, intestinal obstruction, post-allogenic
BMT who have GVHD or post-BMT patients prior to gut recontamination and in patients in whom care is being redirected.
FIGURE 2-4 Example of an algorithm for a feeding regimen and route for patients admitted to a multidisciplinary intensive care
unit. (Courtesy of Childrens Hospital, Boston.)
fluid is recommended. However, urgent changes in serum children and adults alike. Abnormalities of acid-base
electrolytes should not be managed by changes in PN physiology also can influence the nutritional regimen of
infusion rate or composition because these represent the hospitalized child. If a metabolic alkalosis from active
imprecise methods to treat a potentially serious diuresis or gastric suction occurs, chloride administration
electrolyte abnormality. In addition, careful attention to is used to correct the alkalosis. Severe, untreated alkale-
phosphate and magnesium levels is important. Hypo- mia may inhibit the patients respiratory drive, shift
phosphatemia may lead to hemolytic anemia, respiratory potassium intracellularly, decrease ionized calcium con-
muscle dysfunction, and cardiac failure. A significant centrations by increasing the affinity of albumin for
decrease in serum phosphate also may be seen with the calcium, and promote refractory cardiac arrhythmias.
re-feeding syndrome. In contrast, renal failure can result Metabolic acidosis is often seen in critically ill children
in the retention of phosphate and potassium, and nutri- and may be associated with hypotension, ischemia, or
tional allotments must be reduced accordingly. Magne- renal failure. In such patients, the use of acetate instead
sium deficiency can cause fatal cardiac arrhythmia in of chloride in the PN regimen may be helpful.121
30 SECTION I General
The three main macronutrients in PN are carbohy- studied. Reviews of both vitamin and trace mineral
drate, lipid, and protein. Protein is administered in the toxicity clearly demonstrate that excessive intake is a
form of crystalline amino acids starting at 0.5g/kg/day health risk.123,124
in preterm neonates and 1g/kg/day in others. The Careful biochemical monitoring is mandatory to
protein intake is advanced daily in increments of prevent acute and long-term complications from PN
1g/kg/day until the goal intake is achieved. Table 2-3 therapy. A PN profile is recommended at the initiation
lists recommended quantities of dietary protein needs for of therapy and then weekly. It includes serum levels of
hospitalized children. Dextrose provides the main source sodium, potassium, chloride, glucose, carbon dioxide,
of energy in PN and is initiated at a rate of 5mg/kg/min blood urine nitrogen, creatinine, albumin, magnesium,
using 510% concentration. The glucose infusion rate in phosphate, total and direct bilirubin, and transaminases.
mg/kg/min can be calculated with the help of the For children requiring PN longer than 30 days, selenium,
equation: iron, zinc, copper and carnitine levels may be checked. It
is essential to monitor daily vital statistics and routine
[(% dextrose ) (1 dL /100 mL ) (1000 mg / L g ) anthropometry to ensure adequate growth and develop-
( hourly rate in mL / h ) (1 h / 60 min ) ment. Critical care units benefit from the expertise of a
(1/ weight in kg)]. dedicated nutritionist who should be consulted on a
regular basis to guide the optimal nutritional intake of
Infusion rates higher than 12mg/kg/min are infrequently patients.
required and overfeeding with carbohydrate is associated
with lipogenesis (RQ >1.0), hepatic steatosis, hypergly
cemia, and osmotic diuresis. Three to 5% of the energy IMMUNE-ENHANCING DIETS
needs must be met using intravenous lipids, which are
usually initiated at a rate of 1g/kg/day, and advanced in Immunomodulation is thought to play a significant role
increments to reach a maximum of 3g/kg/day or 50% of in the response to an infectious insult and impacts
total energy intake. Intravenous lipids prevent essential outcome in children with sepsis. In 1996, Bone and
fatty acid deficiency and are a concentrated and isotonic colleagues outlined the role of the compensatory
source of energy. Triglyceride levels should be monitored anti-inflammatory response that follows the initial proin-
and intralipid infusion rate is lowered when hypertrigly flammatory response engendered by trauma or infec-
ceridemia is noted. As noted previously, available tion.125 Therapies aimed at modulating or stimulating the
evidence suggests that limiting lipids to 1g/kg/day may immune response have been a focus of many recent nutri-
be indicated in patients with intestinal failure-associated tional studies.
PN cholestasis or in those patients who are likely to Unfortunately investigations examining the role of
require a protracted course of PN.122 immune-enhancing diets in critically ill patients are
The vitamin and micronutrient (trace element) marred by heterogeneous clinical populations, methodo-
needs of healthy children and neonates are relatively logical flaws, and the use of nutritional formulations that
well defined in the literature.17 In the neonate and often contain multiple potentially active components.
child, required vitamins include the fat-soluble vitamins Thus, studies and meta-analyses offer conflicting conclu-
(A, D, E, and K) as well as the water-soluble vitamins: sions.69,114,121123 Furthermore, there are no published
ascorbic acid, thiamine, riboflavin, pyridoxine, niacin, studies specifically evaluating the role of immunonutri-
pantothenate, biotin, folate, and vitamin B12. Because tion in critically ill children. Potentially promising, but
vitamins are not consumed stoichiometrically in bio- unproven, additives include arginine, glutamine, cysteine,
chemical reactions but instead act as catalysts, the nucleic acids, and omega-3 fatty acids.
administration of large vitamin supplements in metaboli-
cally stressed states is not logical from a nutritional
standpoint. The trace elements required for normal CONCLUSION
growth and development include zinc, iron, copper, sele-
nium, manganese, iodide, molybdenum, and chromium. The nutritional status of children influences outcome in
Trace elements are usually used in the synthesis of the surgical patients. Malnutrition is associated with physi-
active sites of a ubiquitous and extraordinarily important ological instability and a longer ICU stay accompanied
class of enzymes called metalloenzymes. More than 200 by increased utilization of resources.126 The first step
zinc metalloenzymes alone exist, and both DNA and in implementing appropriate nutritional support is an
RNA polymerase are included in this group. As with understanding of the metabolic events that accompany
vitamins, these metalloenzymes act as catalytic agents. critical illness and surgery. Individualized, quantitative
Unless specific mineral losses occur, such as enhanced assessments of protein, carbohydrate, lipid, electrolyte,
zinc loss with severe diarrhea, large nutritional require- vitamin and micronutrient requirements are made,
ments would not be anticipated during critical illness. and the appropriate route of nutrient delivery is deter-
Selenium and carnitine may be added after 30 days of mined. This nutrition regimen needs to be reviewed and
exclusive PN administration. The addition of copper and amended regularly during the course of illness. The
manganese in the PN of children with cholestasis is con- goal of nutrition therapy in sick pediatric surgical
troversial and usually the dose is halved in view of their patients is to augment the short-term benefits of the
biliary excretion. The pharmacologic use of vitamins and metabolic stress response while minimizing any long-
trace minerals in pediatric illness has not been adequately term consequences.
2 Nutritional Support for the Pediatric Patient 31
25. Tilden SJ, Watkins S, Tong TK, et al. Measured energy expendi-
REFERENCES ture in pediatric intensive care patients. Am J Dis Child
1. Pollack MM, Wiley JS, Kanter R, et al. Malnutrition in critically 1989;143:4902.
ill infants and children. J Parenter Enteral Nutr 1982;6:204. 26. Ferrannini E. The theoretical bases of indirect calorimetry: A
2. Hults J, Joosten K, Zimmermann L, et al. Malnutriion in critically review. Metabolism 1988;37:287301.
il children: From admision to 6 months after discharge. Clin Nutr 27. Joosten KF, Verhoeven JJ, Hazelzet JA. Energy expenditure and
2004;23:22332. substrate utilization in mechanically ventilated children. Nutrition
3. Alexander E, Susla GM, Burstein AH, et al. Retrospective evalu- 1999;15:4448.
ation of commonly used equations to predict energy expenditure 28. Chwals WJ. Overfeeding the critically ill child: Fact or fantasy?
in mechanically ventilated, critically ill patients. Pharmacotherapy New Horiz 1994;2:14755.
2004;24:165967. 29. Hulst JM, van Goudoever JB, Zimmermann LJ, et al. Adequate
4. Chwals WJ, Bistrian BR. Predicted energy expenditure in criti- feeding and the usefulness of the respiratory quotient in critically
cally ill children: Problems associated with increased variability. ill children. Nutrition 2004;21:1928.
Crit Care Med 2000;28:26556. 30. McClave SA, Spain DA, Skolnick JL, et al. Achievement of steady
5. Rogers EJ, Gilbertson HR, Heine RG, et al. Barriers to state optimizes results when performing indirect calorimetry.
adequate nutrition in critically ill children. Nutrition 2003;19: J Parenter Enteral Nutr 2003;27:1620.
8658. 31. Mehta NM, Bechard LJ, Leavitt K, et al. Severe weight loss and
6. Cuthbertson D. Intensive-care-metabolic response to injury. Br J hypermetabolic paroxysmal dysautonomia following hypoxic
Surg 1970;57:71821. ischemic brain injury: The role of indirect calorimetry in the
7. Munro HN. Nutrition and muscle protein metabolism: Introduc- intensive care unit. J Parenter Enteral Nutr 2008;32:2814.
tion. Fed Proc 1978;37:22812. 32. Mehta NM, Bechard LJ, Leavitt K, et al. Cumulative
8. de Groof F, Joosten KF, Janssen JA, et al. Acute stress response energy imbalance in the pediatric intensive care unit: Role of
in children with meningococcal sepsis: Important differences targeted indirect calorimetry. J Parenter Enteral Nutr. 2009;
in the growth hormone/insulin-like growth factor I axis between 33:33644.
nonsurvivors and survivors. J Clin Endocrinol Metab 2002; 33. Schoenheimer R, Rittenberg D. Deuterium as an indicator in the
87:311824. study of intermediary metabolism. Science 1935;82:1567.
9. Fomon SJ, Haschke F, Ziegler EE, et al. Body composition of 34. Schoeller DA, van Santen E. Measurement of energy expenditure
reference children from birth to age 10 years. Am J Clin Nutr in humans by doubly labeled water method. J Appl Physiol
1982;35:116975. 1982;53:9559.
10. Forbes GB, Bruining GJ. Urinary creatinine excretion and lean 35. Shew SB, Beckett PR, Keshen TH, et al. Validation of a [13C]
body mass. Am J Clin Nutr 1976;29:135966. bicarbonate tracer technique to measure neonatal energy expendi-
11. Long CL, Spencer JL, Kinney JM, et al. Carbohydrate metabo- ture. Pediatr Res 2000;47:78791.
lism in man: Effect of elective operations and major injury. J Appl 36. Schoeller DA, Hnilicka JM. Reliability of the doubly labeled water
Physiol 1971;31:11016. method for the measurement of total daily energy expenditure in
12. Ogata ES. Carbohydrate metabolism in the fetus and neonate and free-living subjects. J Nutr 1996;126:348S54S.
altered neonatal glucoregulation. Pediatr Clin N Am 37. Schoeller DA, Kushner RF, Jones PJ. Validation of doubly labeled
1986;33:2545. water for measuring energy expenditure during parenteral nutri-
13. Herrera E, Amusquivar E. Lipid metabolism in the fetus and the tion. Am J Clin Nutr 1986;44:2918.
newborn. Diabetes Metab Res Rev 2000;16:20210. 38. Jones PJ, Winthrop AL, Schoeller DA, et al. Validation of doubly
14. Schulze KF, Stefanski M, Masterson J, et al. Energy expenditure, labeled water for assessing energy expenditure in infants. Pediatr
energy balance, and composition of weight gain in low birth Res 1987;21:2426.
weight infants fed diets of different protein and energy content. 39. Jahoor F, Desai M, Herndon DN, et al. Dynamics of the
J Pediatr 1987;110:7539. protein metabolic response to burn injury. Metabolism 1988;37:
15. Long CL, Kinney JM, Geiger JW. Nonsuppressability of gluco- 3307.
neogenesis by glucose in septic patients. Metabolism 1976; 40. Weinstein MR, Oh W. Oxygen consumption in infants with bron-
25:193201. chopulmonary dysplasia. J Pediatr 1981;99:95861.
16. Whyte RK, Haslam R, Vlainic C, et al. Energy balance and nitro- 41. Jones MO, Pierro A, Hammond P, et al. The metabolic response
gen balance in growing low birthweight infants fed human milk to operative stress in infants. J Pediatr Surg 1993;28:125862.
or formula. Pediatr Res 1983;17:8918. 42. Shew SB, Keshen TH, Glass NL, et al. Ligation of a patent ductus
17. National Academy of Sciences. Recommended Dietary Allow- arteriosus under fentanyl anesthesia improves protein metabolism
ances. 10th ed. Washington, DC: National Academy Press; 1989. in premature neonates. J Pediatr Surg 2000;35:127781.
18. Kashyap S, Schulze KF, Forsyth M, et al. Growth, nutrient reten- 43. Pierro A, Carnielli V, Filler RM, et al. Partition of energy metabo-
tion, and metabolic response in low birth weight infants fed lism in the surgical newborn. J Pediatr Surg 1991;26:5816.
varying intakes of protein and energy. J Pediatr 1988;113: 44. Chwals WJ, Letton RW, Jamie A, et al. Stratification of injury
71321. severity using energy expenditure response in surgical infants.
19. Seale JL, Rumpler WV. Comparison of energy expenditure meas- J Pediatr Surg 1995;30:11614.
urements by diet records, energy intake balance, doubly labeled 45. Jaksic T, Shew SB, Keshen TH, et al. Do critically ill surgical
water and room calorimetry. Eur J Clin Nutr 1997;51:85663. neonates have increased energy expenditure? J Pediatr Surg
20. Daly JM, Heymsfield SB, Head CA, et al. Human energy require- 2001;36:637.
ments: Overestimation by widely used prediction equation. Am J 46. Briassoulis G, Venkataraman S, Thompson AE. Energy expendi-
Clin Nutr 1985;42:11704. ture in critically ill children. Crit Care Med 2000;28:116672.
21. Schofield WN. Predicting basal metabolic rate, new standards and 47. Goran MI, Kaskoun M, Johnson R. Determinants of
review of previous work. Hum Nutr Clin Nutr 1985;39(Suppl resting energy expenditure in young children. J Pediatr 1994;
1):541. 125:3627.
22. Hunter DC, Jaksic T, Lewis D, et al. Resting energy expenditure 48. Bartlett RH, Dechert RE, Mault JR, et al. Measurement of metab-
in the critically ill: Estimations versus measurement. Br J Surg olism in multiple organ failure. Surgery 1982;92:7719.
1988;75:87578. 49. Beaufrere B. Protein turnover in low-birth-weight (LBW) infants.
23. Muller MJ, Bosy-Westphal A, Klaus S, et al. World Health Acta Paediatr Suppl 1994;405:8692.
Organization equations have shortcomings for predicting resting 50. Denne SC, Karn CA, Ahlrichs JA, et al. Proteolysis and phenyla-
energy expenditure in persons from a modern, affluent popula- lanine hydroxylation in response to parenteral nutrition in
tion: Generation of a new reference standard from a retrospective extremely premature and normal newborns. J Clin Invest
analysis of a German database of resting energy expenditure. Am 1996;97:74654.
J Clin Nutr 2004;80:137990. 51. Hay WW Jr, Lucas A, Heird WC, et al. Workshop summary:
24. Elwyn DH, Kinney JM, Askanazi J. Energy expenditure in surgi- Nutrition of the extremely low birth weight infant. Pediatrics
cal patients. Surg Clin North Am 1981;61:54556. 1999;104:13608.
32 SECTION I General
52. Cogo PE, Carnielli VP, Rosso F, et al. Protein turnover, lipolysis, 77. Yarwood GD, Ross RJ, Medbak S, et al. Administration of human
and endogenous hormonal secretion in critically ill children. Crit recombinant insulin-like growth factor-I in critically ill patients.
Care Med 2002;30:6570. Crit Care Med 1997;25:135261.
53. Mrozek JD, Georgieff MK, Blazar BR, et al. Effect of sepsis 78. Sakurai Y, Aarsland A, Herndon DN, et al. Stimulation of muscle
syndrome on neonatal protein and energy metabolism. J Perinatol protein synthesis by long-term insulin infusion in severely burned
2000;20:96100. patients. Ann Surg 1995;222:28394; 947.
54. Williamson DH, Farrell R, Kerr A, et al. Muscle-protein catabo- 79. Thomas SJ, Morimoto K, Herndon DN, et al. The effect of
lism after injury in man, as measured by urinary excretion of prolonged euglycemic hyperinsulinemia on lean body mass after
3-methylhistidine. Clin Sci Mol Med 1977;52:52733. severe burn. Surgery 2002;132:3417.
55. Pierro A. Metabolism and nutritional support in the surgical 80. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin
neonate. J Pediatr Surg 2002;37:81122. therapy in the critically ill patients. N Engl J Med
56. Meszaros K, Bojta J, Bautista AP, et al. Glucose utilization by 2001;345:135967.
Kupffer cells, endothelial cells, and granulocytes in endotoxemic 81. Agus MS, Javid PJ, Ryan DP, et al. Intravenous insulin decreases
rat liver. Am J Physiol 1991;260:G712. protein breakdown in infants on extracorporeal membrane oxy-
57. Denne SC, Karn CA, Wang J, et al. Effect of intravenous glucose genation. J Pediatr Surg 2004;39:83944.
and lipid on proteolysis and glucose production in normal new- 82. Tappy L, Schwarz JM, Schneiter P, et al. Effects of isoenergetic
borns. Am J Physiol 1995;269:E3617. glucose-based or lipid-based parenteral nutrition on glucose
58. Mitton SG, Garlick PJ. Changes in protein turnover after the metabolism, de novo lipogenesis, and respiratory gas exchanges in
introduction of parenteral nutrition in premature infants: Com- critically ill patients. Crit Care Med 1998;26:8607.
parison of breast milk and egg protein-based amino acid solutions. 83. Askanazi J, Rosenbaum SH, Hyman AI, et al. Respiratory changes
Pediatr Res 1992;32:44754. induced by the large glucose loads of total parenteral nutrition.
59. Felig P. The glucose-alanine cycle. Metabolism 1973;22: JAMA 1980;243:14447.
179207. 84. Jones MO, Pierro A, Hammond P, et al. Glucose utilization in the
60. Duffy B, Pencharz P. The effects of surgery on the nitrogen surgical newborn infant receiving total parenteral nutrition.
metabolism of parenterally fed human neonates. Pediatr Res J Pediatr Surg 1993;28:11215.
1986;20:325. 85. Shew SB, Keshen TH, Jahoor F, et al. The determinants of
61. Poindexter BB, Karn CA, Leitch CA, et al. Amino acids do not protein catabolism in neonates on extracorporeal membrane oxy-
suppress proteolysis in premature neonates. Am J Physiol genation. J Pediatr Surg 1999;34:108690.
2001;281:E4728. 86. Forsyth JS, Murdock N, Crighton A. Low birthweight infants and
62. Bechard LJ, Parrott JS, Mehta NM. Systematic review of the total parenteral nutrition immediately after birth. III. Randomised
influence of energy and protein intake on protein balance in criti- study of energy substrate utilisation, nitrogen balance, and carbon
cally ill children. J Pediatr 2012;161:3339. dioxide production. Arch Dis Child 1995;73:F1316.
63. Keshen TH, Miller RG, Jahoor F, et al. Stable isotopic quantita- 87. Jones MO, Pierro A, Garlick PJ, et al. Protein metabolism kinetics
tion of protein metabolism and energy expenditure in neonates in neonates: Effect of intravenous carbohydrate and fat. J Pediatr
on- and post-extracorporeal life support. J Pediatr Surg Surg 1995;30:45862.
1997;32:95862. 88. Krinsley JS. Association between hyperglycemia and increased
64. Goldman HI, Freudenthal R, Holland B, et al. Clinical effects of hospital mortality in a heterogeneous population of critically ill
two different levels of protein intake on low-birth-weight infants. patients. Mayo Clin Proc 2003;78:14718.
J Pediatr 1969;74:8819. 89. Laird AM, Miller PR, Kilgo PD, et al. Relationship of early
65. Goldman HI, Liebman OB, Freudenthal R, et al. Effects of early hyperglycemia to mortality in trauma patients. J Trauma
dietary protein intake on low-birth-weight infants: Evaluation at 2004;56:105862.
3 years of age. J Pediatr 1971;78:1269. 90. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight
66. Imura K, Okada A. Amino acid metabolism in pediatric glucose control in critically ill adults: A meta-analysis. JAMA
patients. Nutrition (Burbank, Los Angeles County, Calif 1998;14: 2008;300:93344.
1438. 91. Srinivasan V, Spinella PC, Drott HR, et al. Association of timing,
67. Miller RG, Jahoor F, Jaksic T. Decreased cysteine and proline duration, and intensity of hyperglycemia with intensive care unit
synthesis in parenterally fed, premature infants. J Pediatr Surg mortality in critically ill children. Pediatr Crit Care Med
1995;30:9537. 2004;5:32936.
68. Miller RG, Keshen TH, Jahoor F, et al. Compartmentation of 92. Jeevanandam M, Young DH, Schiller WR. Nutritional impact on
endogenously synthesized amino acids in neonates. J Surg Res the energy cost of fat fuel mobilization in polytrauma victims.
1996;63:199203. J Trauma 1990;30:14754.
69. Reeds PJ, Berthold HK, Boza JJ, et al. Integration of amino acid 93. Nordenstrom J, Carpentier YA, Askanazi J, et al. Metabolic utili-
and carbon intermediary metabolism: Studies with uniformly zation of intravenous fat emulsion during total parenteral nutri-
labeled tracers and mass isotopomer analysis. Eur J Pediatr tion. Ann Surg 1982;196:22131.
1997;156(Suppl 1):S508. 94. Coss-Bu JA, Klish WJ, Walding D, et al. Energy metabolism,
70. Zlotkin SH, Anderson GH. The development of cystathionase nitrogen balance, and substrate utilization in critically ill children.
activity during the first year of life. Pediatr Res 1982;16:658. Am J Clin Nutr 2001;74:6649.
71. Heyland DK, Novak F, Drover JW, et al. Should immunonutri- 95. Powis MR, Smith K, Rennie M, et al. Effect of major abdominal
tion become routine in critically ill patients? A systematic review operations on energy and protein metabolism in infants and chil-
of the evidence. JAMA 2001;286:94453. dren. J Pediatr Surg 1998;33:4953.
72. Dzakovic A, Kaviani A, Eshach-Adiv O, et al. Trophic enteral 96. Friedman Z, Danon A, Stahlman MT, et al. Rapid onset of
nutrition increases hepatic glutathione and protects against per- essential fatty acid deficiency in the newborn. Pediatrics 1976;58:
oxidative damage after exposure to endotoxin. J Pediatr Surg 6409.
2003;38:8447. 97. Paulsrud JR, Pensler L, Whitten CF, et al. Essential fatty acid
73. Duggan C, Gannon J, Walker WA. Protective nutrients and func- deficiency in infants induced by fat-free intravenous feeding. Am
tional foods for the gastrointestinal tract. Am J Clin Nutr J Clin Nutr 1972;25:897904.
2002;75:789808. 98. Giovannini M, Riva E, Agostoni C. Fatty acids in pediatric nutri-
74. Liu Z, Barrett EJ. Human protein metabolism: Its measurement tion. Pediatr Clin North Am 1995;42:86177.
and regulation. Am J Physiol 2002;283:E110512. 99. Van Aerde JE, Sauer PJ, Pencharz PB, et al. Metabolic conse-
75. Demling RH, Orgill DP. The anticatabolic and wound healing quences of increasing energy intake by adding lipid to parenteral
effects of the testosterone analog oxandrolone after severe burn nutrition in full-term infants. Am J Clin Nutr 1994;59:659
injury. J Crit Care 2000;15:1217. 62.
76. Takala J, Ruokonen E, Webster NR, et al. Increased mortality 100. Cleary TG, Pickering LK. Mechanisms of intralipid effect on
associated with growth hormone treatment in critically ill adults. polymorphonuclear leukocytes. J Clin Lab Immunol 1983;
N Engl J Med 1999;341:78592. 11:216.
2 Nutritional Support for the Pediatric Patient 33
101. Freeman J, Goldmann DA, Smith NE, et al. Association of intra- 114. Mehta NM, McAleer D, Hamilton S, et al. Challenges to optimal
venous lipid emulsion and coagulase-negative staphylococcal bac- enteral nutrition in a multidisciplinary pediatric intensive care
teremia in neonatal intensive care units. N Engl J Med unit. J Parenter Enteral Nutr 2010;34:3845.
1990;323:3018. 115. Munshi IA, Steingrub JS, Wolpert L. Small bowel necrosis associ-
102. Periera GR, Fox WW, Stanley CA, et al. Decreased oxygenation ated with early postoperative jejunal tube feeding in a trauma
and hyperlipemia during intravenous fat infusions in premature patient. J Trauma 2000;49:1635.
infants. Pediatrics 1980;66:2630. 116. Taylor RM, Preedy VR, Baker AJ, et al. Nutritional support in
103. Birkhahn RH, Long CL, Fitkin DL, et al. A comparison of the critically ill children. Clin Nutr 2003;22:3659.
effects of skeletal trauma and surgery on the ketosis of starvation 117. Mehta NM, Bechard LJ, Cahill N, et al. Nutritional practices and
in man. J Trauma 1981;21:51319. their relationship to clinical outcomes in critically ill childrenan
104. Lee S, Gura KM, Kim S, et al. Current clinical applications of international multicenter cohort study. Crit Care Med
omega-6 and omega-3 fatty acids. Nutr Clin Pract 2006;21: 2012;40:220411.
32341. 118. Atkinson S, Sieffert E, Bihari D. A prospective, randomized,
105. Lee S, Gura KM, Puder M. Omega-3 fatty acids and liver disease. double-blind, controlled clinical trial of enteral immunonutrition
Hepatology 2007;45:8415. in the critically ill. Guys Hospital Intensive Care Group. Crit
106. Gura KM, Duggan CP, Collier SB, et al. Reversal of parenteral Care Med 1998;26:116472.
nutrition-associated liver disease in two infants with short bowel 119. Briassoulis G, Tsorva A, Zavras N, et al. Influence of an aggressive
syndrome using parenteral fish oil: Implications for future man- early enteral nutrition protocol on nitrogen balance in critically
agement. Pediatrics 2006;118:e197201. ill children. J Nutr Biochem 2002;13:560.
107. Zaloga GP. Early enteral nutritional support improves outcome: 120. Heyland DK, Cook DJ, Guyatt GH. Enteral nutrition in the
Hypothesis or fact? Crit Care Med 1999;27:25961. critically ill patient: A critical review of the evidence. Intensive
108. Heyland DK, Dhaliwal R, Drover JW, et al. Canadian clinical Care Med 1993;19:43542.
practice guidelines for nutrition support in mechanically venti- 121. Peters O, Ryan S, Matthew L, et al. Randomised controlled trial
lated, critically ill adult patients. JPEN 2003;27:35573. of acetate in preterm neonates receiving parenteral nutrition. Arch
109. Briassoulis G, Zavras N, Hatzis T. Malnutrition, nutritional Dis Child 1997;77:F1215.
indices, and early enteral feeding in critically ill children. Nutri- 122. Garza JJ, Shew SB, Keshen TH, et al. Energy expenditure in ill
tion 2001;17:54857. premature neonates. J Pediatr Surg 2002;37:28993.
110. Briassoulis GC, Zavras NJ, Hatzis MT. Effectiveness and safety 123. Flodin NW. Micronutrient supplements: Toxicity and drug inter-
of a protocol for promotion of early intragastric feeding in criti- actions. Prog Food Nutr Sci 1990;14:277331.
cally ill children. Pediatr Crit Care Med 2001;12:11321. 124. Marks J. The safety of the vitamins: An overview. Int J Vitam Nutr
111. Chellis MJ, Sanders SV, Webster H, et al. Early enteral feeding Res Suppl 1989;30:1220.
in the pediatric intensive care unit. J Parenter Enteral Nutr 125. Bone RC, Grodzin CJ, Balk RA. Sepsis: A new hypothesis for
1996;20:713. pathogenesis of the disease process. Chest 1997;112:23543.
112. Meert KL, Daphtary KM, Metheny NA. Gastric vs. small bowel 126. Pollack MM, Ruttimann UE, Wiley JS. Nutritional depletions in
feeding in critically ill children receiving mechanical ventilation: critically ill children: Associations with physiologic instability and
A randomized controlled trial. Chest 2004;126:8728. increased quantity of care. J Parenter Enteral Nutr 1985;
113. Sanchez C, Lopez-Herce J, Carrillo A, et al. Early transpyloric 9:30913.
enteral nutrition in critically ill children. Nutrition 2007;
23:1622.
C H A P T E R 3
Anesthetizing children is an increasingly safe undertak- the risk of a motor vehicle collision on the way to the
ing. When discussing the risks and benefits of a childs hospital or surgery center is greater than the risk of death
operation with his or her family, surgeons should feel under anesthesia. However, risks of mortality and mor-
confident that their anesthesiology colleagues can provide bidity are increased in neonates and infants less than one
an anesthetic that facilitates the procedure while ensuring year of age, those who are ASA (American Society of
the childs safety. Providing optimal perioperative care for Anesthesiologists) status 3 or greater, and those who
children requires close collaboration between the surgeon require emergency surgery.5
and anesthesiologist on issues both large and small. This
chapter is designed to inform surgeons about the consid-
erations important to anesthesiologists. PREOPERATIVE ANESTHESIA
EVALUATION
RISKS OF ANESTHESIA All patients presenting for operations under anesthesia
benefit greatly from a thorough preanesthetic/preopera-
In an effort to reduce patient complications, anesthesi- tive assessment and targeted preparation to optimize any
ologists have carefully analyzed anesthetic morbidity coexisting medical conditions. The ASA physical status
and mortality over the past generation. Whereas anesthe- (PS) score is a means of communicating the condition of
sia was historically considered a dangerous enterprise, the patient. The PS is not intended to represent operative
serious anesthesia-related complications are now rela- risk and serves primarily as a common means of commu-
tively rare, especially in healthy patients. The reasons for nication among care providers (Table 3-1). Any child with
this improvement include advances in pharmacology, an ASA classification of 3 or greater should be seen by an
improved monitoring technology, increased rigor of sub- anesthesiologist prior to the day of surgery. This may be
specialty training, and the ability to target problems using modified in cases of hardship due to the distance from the
an analysis strategy. surgical venue or when the patient is well known to the
Quantifying the risk of pediatric anesthesia is difficult anesthesia service, and the childs health is unchanged.
due to the difficulty in determining whether complica- Finally, outstanding and unresolved medical issues may be
tions are attributable to the anesthetic, and if so, to what significant enough to warrant cancellation of the proce-
degree. The risk of cardiac arrest for children undergoing dure for optimization of anesthesia and/or further diag-
anesthesia was estimated in the 1990s to be 1:10,000.1,2 nostic workup.
However, these studies did not take patient co-morbidity
or the surgical condition into consideration. The risk of
a healthy child suffering cardiac arrest during myrin-
Criteria for Ambulatory Surgery
gotomy tube placement is significantly less than the like- Ambulatory surgery comprises 70% or more of the
lihood of a child with complex cardiac disease arresting caseload in most pediatric centers. Multiple factors
during a complex cardiac repair.3 should be considered when evaluating whether a child is
A recent review of cardiac arrests in anesthetized chil- suitable for outpatient surgery. Some states regulate the
dren compared 193 events from 19982004 to 150 events minimum age allowed in an ambulatory surgical center.
from 19941997.4 A reduction in medication-caused For example, the minimum age in Pennsylvania is six
arrests from 37% to 18% was identified, and was attrib- months. In most cases, the child should be free of severe
uted to the decline in halothane use (that causes myocar- systemic disease (ASA PS 1 or 2). Other factors that may
dial depression) and the advent of using sevoflurane (that determine the suitability of a child for outpatient surgery
is not associated with myocardial depression). There was are family and social dynamics. Some institutions utilize
also a reduction in unrecognized esophageal intubation a telephone screening evaluation process to determine
as a cause of arrest, due in large part to the advent of whether a patient can have their full anesthesia history
end-tidal carbon dioxide (ETCO2) monitoring, pulse oxi- and physical on the day of surgery rather than being
metry, and an increased awareness of the problem. evaluated in a preoperative evaluation clinic prior to
Recent large single center reports yield a current esti- surgery.6
mate of anesthesia-related mortality of 1:250,000 in Well-controlled systemic illnesses do not necessarily
healthy children. To put this into perspective for parents, preclude outpatient surgery, but any concerns must be
34
3 Anesthetic Considerations for Pediatric Surgical Conditions 35
Although serum electrolytes are not routinely screened, the scheduled surgery. These economic and social con-
electrolytes may be helpful in patients on diuretics. Pre- siderations deserve respectful attention. Symptoms that
operative glucose should be monitored in insulin- would tip the scales toward cancellation include the
dependent diabetic patients, and also in any patient who severity of illness, as measured by an intractable or pro-
has been receiving parenteral nutrition or intravenous ductive cough, bronchospasm, malaise, fever, or hypoxia
(IV) fluids with a dextrose concentration greater than 5% on pulse oximetry. In contrast, clear rhinorrhea with a
prior to surgery. simple cough is usually not sufficient grounds for cancel-
Routine screening for pregnancy in all females who lation, provided the family understands the very small
have passed menarche is strongly recommended. An age- chance of needing postoperative supplemental oxygen
based guideline (at our institution, any female 11 years of and bronchodilator therapy.
age or older) may be preferable. Although it is easiest to
perform a urine test for human chorionic gonadotropin The Former Preterm Infant
(hCG), if a patient cannot provide a urine sample, blood
can be drawn for serum hCG testing. Institutional policy Infants born prematurely (<37 weeks gestation) may
may allow the attending anesthesiologist to waive preg- exhibit sequelae such as bronchopulmonary dysplasia
nancy testing at their discretion. (BPD), gastroesophageal reflux, intraventricular hemor-
Certain medications, particularly anticonvulsants, rhage/hypoxicischemic encephalopathy (IVH/HIE), or
should be individually assessed regarding the need for laryngo/tracheomalacia or stenosis. Preterm infants are
preoperative blood levels. The nature of the planned also at increased risk for postoperative apnea after expo-
operation may also require additional studies. sure to anesthetic and analgesic agents.
chemoreceptors with blunted responses to hypoxia and dysfunction may, or may not, be present. However, the
hypercapnia, even without the additional burden of absence of signs and symptoms does not preclude the
anesthetic/opioid-induced respiratory depression. In possibility of life-threatening collapse of the airway or
addition, anesthetic agents decrease muscle tone in the cardiovascular obstruction upon induction of anesthesia.
upper airway, chest wall, and diaphragm, thereby further Patients presenting with anterior mediastinal masses
depressing the ventilatory response to hypoxia and hyper- (e.g., lymphoma) are at particularly high risk of airway
capnia. In the immediate neonatal period, immaturity of compromise and cardiovascular collapse with the induc-
the diaphragmatic musculature causes early fatigability, tion of general anesthesia due to compression of the
which may also contribute to apnea.12 Although postanes- trachea or great vessels when intrinsic muscle tone is lost
thetic apnea may be brief and resolve either spontane- and spontaneous respiration ceases.1517 When this occurs,
ously or with minor stimulation, in ex-premature infants there may not be airway compromise, but rather obstruc-
even brief apnea may result in significant hypoxia. tion of vascular inflow to the right atrium and/or outflow
Although most apneic episodes occur within the first two tract obstruction from the right or left ventricle.
hours after anesthesia, apnea can be seen up to 18 hours Preoperative evaluation should begin with a careful
postoperatively. history to elicit any respiratory symptoms. Common
This increased risk of apnea affects the postanesthetic symptoms of tracheal compression and tracheomalacia
care of infants born prematurely, mandating that those include cough, dyspnea, wheezing, chest pain, dysphagia,
at risk be admitted for cardiorespiratory monitoring. orthopnea, and recurrent pulmonary infections. Cardio-
Despite numerous studies on this issue, the postnatal age vascular symptoms may result from infiltration of the
at which this increased risk of apnea disappears is still pericardium and myocardium or compression of the
being debated. The results of a meta-analysis of pertinent pulmonary artery or superior vena cava. The diagnostic
studies indicated that a significant reduction occurred in evaluation includes chest radiographs and/or computed
the incidence of apnea at 52 to 54 weeks postconceptual tomography (CT) scans. Echocardiography may be useful
age.13 A hematocrit less than 30% was identified as an to assess the pericardial status, myocardial contractility,
independent risk factor, and it was recommended that and compression of the cardiac chambers and major
ex-premature infants with this degree of anemia be hos- vessels. Flow-volume loops and fluoroscopy can provide
pitalized postoperatively for observation regardless of the a dynamic assessment of airway compression that other
postconceptual age. However, conclusions drawn from tests cannot assess. Chest CT is helpful in planning the
this meta-analysis have been challenged. Moreover, the anesthetic technique and in evaluating the potential for
sample size of this study may not have been large enough airway compromise during anesthesia. Tumor-associated
to draw valid conclusions.14 superior vena cava syndrome develops rapidly and is
Until more patients are systematically studied, the poorly tolerated.
choice of when a former preterm infant can undergo an Premedication is inadvisable in most patients with an
outpatient operation is up to the discretion and personal anterior mediastinal mass as any loss of airway muscle
bias of the anesthesiologist and surgeon. Institutional tone may upset the balance between negative intratho-
policies most commonly mention ages of 44 weeks for racic pressure and gravity, resulting in airway collapse.
infants born at term (>37 weeks), and from 52 weeks to Once the decision is made to sedate or anesthetize the
60 weeks postconceptual age for infants born at <37weeks. child, maintenance of spontaneous respiration, regardless
Legal issues direct these practices in many institutions, of induction technique, is paramount. It is essential to
but regardless of the postconceptual age at the time of avoid the use of muscle relaxants because the subsequent
surgery, an infant should be hospitalized if any safety airway collapse can be fatal.
concerns arise during the operative or recovery period. Positioning the child is an important part of the anes-
Although the risk of apnea can be decreased with thetic plan for these patients. The sitting position favors
regional anesthesia and/or caffeine, our practice is to gravitational pull of the tumor toward the abdomen
admit all at-risk patients (those with a postconceptual age rather than allowing the tumor to fall posteriorly onto
of younger than 60 weeks), regardless of the anesthetic the airway and major vessels as occurs in the supine posi-
technique used, to monitored, high-surveillance inpatient tion. However, the sitting position makes intubation
units for 23 hours after anesthesia and operation. Simi- challenging. Thus, positioning the symptomatic child in
larly, infants born at term must be at least 1 month of age the lateral decubitus position is recommended. Turning
to be candidates for outpatient surgery because postanes- the child lateral or prone, or lifting the sternum, have
thetic apnea has been reported in full-term infants up to been shown to alleviate acute deterioration in ventilation
44 weeks postconceptual age.13 Figure 3-1 shows an algo- or cardiovascular collapse secondary to tumor compres-
rithm useful for decision making regarding eligibility for sion.18,19 In any patient with an increased potential for
day surgery in young infants. such obstruction, provision should be made for the avail-
ability of a rigid bronchoscope, the ability to move the
Anterior Mediastinal Mass operating room table to effect position changes, and the
ability to institute cardiopulmonary bypass or extracor-
It has long been recognized that the anesthetic manage- poreal membrane oxygenation (ECMO). Compression of
ment of the child with an anterior mediastinal mass is greater than 50% of the cross-sectional area of the trachea
very challenging and fraught with the risk of sudden on CT imaging has been suggested to identify a popula-
airway and cardiovascular collapse. Signs and symptoms tion at risk of airway collapse during induction of general
of positional airway compression and cardiovascular anesthesia.20
3 Anesthetic Considerations for Pediatric Surgical Conditions 39
Premature birth?
<37 weeks
Yes No
Yes No Yes No
FIGURE 3-1 This algorithm is useful for decision making regarding eligibility for outpatient surgery.
When possible, percutaneous biopsy of the mass using Preoperative Preparation and Evaluation
local anesthesia with or without judicious doses of seda-
tive medication is often ideal and poses the least risk to The spectrum of congenital and acquired cardiac lesions
the patient. In patients who have additional tissue sites is so varied that formulating one set of rules for evalua-
from which a biopsy can be obtained (e.g., cervical, axil- tion and perioperative care is nearly impossible. Children
lary, or inguinal lymph nodes), it may be safer to proceed with unrepaired or palliated heart disease, children
with the patient in a semi-sitting position using local requiring operation as a result of their cardiac disease,
anesthesia and carefully titrating sedation so that sponta- and children undergoing emergency surgery tend to be
neous ventilation is preserved. Recently, ketamine and more critically ill and require more intensive preopera-
dexmedetomidine have been shown to provide good tive preparation and assessment.
sedation with preservation of airway patency and sponta- Patients with CHD may be receiving antithrombotic
neous respiration in this setting.21 If progression to therapy for a variety of reasons, including the presence
general anesthesia is required and airway and/or vascular of systemic-to-pulmonary shunts, mechanical or biologi-
compression exists, standby ECMO capability is strongly cal prosthetic heart valves, a history of thrombosis involv-
recommended. ing a conduit or a shunt, recent transcatheter interventions
The inherent conflict between the need to obtain an or device placement, treatment of Kawasaki disease, and
accurate and timely tissue diagnosis and the very real the presence of risk factors for thromboembolic events
concern regarding the safe conduct of the anesthetic including Fontan physiology. No specific pediatric guide-
requires an open dialogue between the anesthesiologist, lines exist for the discontinuation of antithrombotic
surgeon, and oncologist to reach an agreement on strate- medications prior to an elective operation, and manage-
gies to achieve these goals. Many experts recommend ment strategies ideally should be coordinated between
the development and utilization of an algorithm for the childs cardiologist, surgeon, and anesthesiologist.
anesthetic management of the child with an anterior An emergency operation presents additional manage-
mediastinal mass (Fig. 3-2). The algorithm addresses ment issues and often adds risk in several areas. There
assessment of signs and symptoms, evaluation of cardio may be little time preoperatively to optimize the patients
pulmonary compromise, and treatment options.18,22,23 cardiac condition, along with difficulty in quickly obtain-
ing complete cardiology and surgical records. In these
cases, the anesthetic preoperative evaluation is distilled
Patients with Congenital Heart Disease into the most important factors, including the nature and
Each year in the U.S., nearly 32,000 children are born duration of the present illness, the childs underlying
with CHD. Extracardiac anomalies are seen in up to 30% cardiac disease, baseline status, and medications. Patients
of infants with CHD,24,25 and may necessitate operative with cyanosis, or those who depend on shunts for pulmo-
intervention in the neonatal period prior to repair nary blood flow (PBF), or those with single ventricle
or palliation of the cardiac lesion. Although physiologi- physiology who have undergone total cavopulmonary
cally well-compensated patients may undergo noncardiac anastomosis (Fontan procedure) require intravenous
surgery with minimal risk, certain patient groups hydration prior to induction of anesthesia if they are
have been identified as high risk: children less than 1 year hypovolemic. Based on the childs condition and the
of age, especially premature infants; patients with nature of the emergency, a decision can be made as to
severe cyanosis, poorly compensated congestive failure whether to proceed with the case with no further workup
or pulmonary hypertension; patients requiring emer- or a review of available old records, or whether new
gency surgery and patients with multiple coexisting consultations and studies should be obtained prior to
diseases.26 surgery.
40 SECTION I General
Chest radiograph
History and physical exam
Negative Positive
or 50% 50% None
FIGURE 3-2 This algorithm describes management of the patient with a large anterior mediastinal mass. GA, general anesthesia.
SVCS, superior vena cava syndrome. (Adapted from Cheung S, Lerman J. Mediastinal masses and anesthesia in children. In: Riazi J,
editor. The Difficult Pediatric Airway. Anesthesiol Clin North Am 1998;16:893910.)
Endocarditis Prophylaxis prophylaxis for any other form of CHD. For a more
comprehensive discussion, the reader is referred to the
The most recent American Heart Association (AHA) original publications.31,32
guidelines for perioperative antibiotic prophylaxis
emphasize evidence-based practice. Current opinion
reflects the view that endocarditis is more likely to Special Issues in Patients with CHD
result from frequent exposure to bacteremias occurring
Pulmonary Hypertension
as a consequence of activities of daily living than those
due to dental, gastrointestinal, or genitourinary tract Prolonged exposure of the pulmonary vascular bed to
procedures.2730 Except for the conditions listed in Box high flows secondary to left-to-right shunting, pulmo-
3-4, the AHA no longer recommends routine antibiotic nary venous obstruction, or high left atrial pressures can
3 Anesthetic Considerations for Pediatric Surgical Conditions 41
postoperative interrogation of permanent pacemakers.41 from the heart. However, systemic hypertension is fre-
All patients with an ICD should undergo preoperative quently seen in these children. At 18 months to 3 years
device interrogation with disabling of defibrillation capa- of age, a total cavopulmonary anastomosis, or Fontan
bility intraoperatively and resumption in the postopera- procedure, is performed. Surgeons usually choose to
tive period. Bipolar electrocautery should be utilized place a fenestration in the atrial baffle allowing right-to-
whenever possible in the patient with a pacemaker or left shunting to occur, and these patients often have
ICD. If monopolar electrocautery is used, the electrocau- hemoglobin-oxygen saturation of 8090%. The presence
tery return pad should be placed as far away from the of aorto-pulmonary collaterals or baffle leaks may also
pacing generator as possible, and the pacemaker result in decreased systemic oxygen saturation.
generator/leads axis should not be located between the It is clear that the patients volume status must be
operative site and the grounding pad. If the pacemaker assessed preoperatively. Patients with dehydration should
cannot be placed in an asynchronous mode and electro- have an IV placed and adequate hydration assured prior
cautery adversely affects it, cautery current should be to induction of anesthesia. Care should be taken to avoid
applied for not more than 1 second at a time, with 10 hypovolemia as PBF is dependent on preload. Normal
seconds between burses of current, to allow for mainte- sinus rhythm should be maintained if possible. Control-
nance of CO.42,43 led ventilation is appropriate for most procedures as long
as excessive airway pressures are avoided, and physiologic
levels of PEEP may be used to avoid atelectasis without
Single Ventricle Physiology
impairing PBF.
A brief review of the anatomy and physiology of patients Although many children with SV physiology may
with single ventricle (SV) abnormalities is essential to appear well, they are uniquely susceptible to physiologic
understanding the consequences of anesthesia in this perturbations, especially hypovolemia. Laparoscopic pro-
population. The anatomy of patients classified as having cedures, while presenting many advantages, should be
SV physiology may include any lesion or group of lesions carefully undertaken in these patients
in which a two-ventricle cardiac repair is not feasible.
Generally, either both AV valves enter a single ventricular
chamber, or there is atresia of an AV or semilunar valve.
The Difficult Pediatric Airway
Intracardiac mixing of systemic and pulmonary venous The patient with a difficult airway may require advanced
blood flow occurs, and the SV output is shared between airway management techniques in order to secure his/her
the pulmonary and systemic circulations. Patients with airway including the lighted stylet, the fiberoptic intubat-
relative hypoplasia of one ventricle, such as an unbal- ing stylet, the flexible fiberoptic bronchoscope, direct
anced AV canal defect or severe Ebstein anomaly, may laryngoscopy with intubating stylet, fiberoptic rigid
also undergo SV palliation operations. laryngoscopy, an anterior commissure scope, the laryn-
A series of three separate staged palliative cardiac sur- geal mask airway, cricothyrotomy, and tracheostomy.
geries are generally performed for most children with SV Anesthesiologists and facilities do not need availability of
physiology. After initial stage I palliation, patients are all of the listed techniques. When a difficult airway is
dependent on either a modified systemic-to-pulmonary anticipated, it is important to have all necessary airway
shunt or an RV to PA conduit to provide PBF. The ratio equipment present in the operating room (OR) before
of pulmonary to systemic blood flow is then dependent induction of anesthesia, as well as communication of the
on the balance between systemic vascular resistance difficult airway potential to all members of the OR team.
(SVR) and PVR, with patients vulnerable to perturba- Indirect intubation methods should be utilized rather
tions in PO2, PCO2, acidbase status, temperature, and than repeated attempts at direct laryngoscopy because
volume status. Oxygen saturations greater than 85% airway edema and bleeding increase with each attempt,
indicate pulmonary overcirculation and patients may decreasing the likelihood of success with subsequent indi-
exhibit symptoms of congestive heart failure (CHF). rect methods.44
Once the patient is anesthetized and mechanically venti- Patients that require additional approaches to obtain
lated, their oxygen saturation often increases, requiring an airway require additional OR time and, in certain
the adjustment of the FiO2 and PCO2 to target oxygen cases, continuation of intubation postoperatively may be
saturations between 7585%. An acute drop in oxygen necessary, mandating ICU admission. Most difficult
saturation along with the absence of a murmur indicates airways in the pediatric age group can be anticipated.
loss of shunt flow and is catastrophic. Immediate echocar- Unlike in adults, it is rare to encounter an unanticipated
diographic confirmation of shunt flow is crucial, with difficult airway in a normal-appearing child. Some con-
rapid institution of ECMO if necessary. genital syndromes associated with difficult airway man-
Patients usually undergo a second stage procedure, or agement are listed in Table 3-2.
bidirectional cavopulmonary anastomosis, at 3 to 6 The ASA has developed practice guidelines and an
months of age, with the anastomosis of the superior vena algorithm for management of the difficult airway. This
cava to the pulmonary circulation replacing the systemic- guideline and algorithm are continually updated and well
to-pulmonary shunt created during the first stage surgery. known to anesthesiologists.44 Although the guidelines
Oxygen saturations will continue to range from 7585% and algorithm are intended for use in adult patients, their
as patients are still mixing oxygenated and deoxygenated emphasis on the importance of having a clear primary
blood for ejection from the SV. Ventricular function is plan with multiple back-up contingency plans is equally
generally improved as the volume load has been removed applicable to infants and children.
3 Anesthetic Considerations for Pediatric Surgical Conditions 43
and patient position. In the supine or Trendelenburg duration of the insufflation. These factors should be con-
position, the venous return is less impaired when the sidered along with any pre-existing preoperative respira-
intra-abdominal pressure is kept below 15mmHg. The tory or cardiovascular compromise in planning the
position preferred for upper abdominal procedures is operation and anesthetic management. The magnitude of
reverse-Trendelenburg or supine. The head-up position the physiologic changes induced by either one-lung or
reduces venous return and CO.55 Several pediatric studies two-lung ventilation with insufflation is impacted by the
have utilized echocardiography (supine),56 impedance patients age, underlying co-morbid conditions, and anes-
cardiography (15 head-down),57 and continuous esopha- thetic agents utilized.
geal aortic blood flow echo-Doppler (supine)58 to assess Many thoracic procedures require lung deflation and
hemodynamic changes during laparoscopic surgery. minimal lung excursion on the operative side while ven-
These studies demonstrated significant reductions in tilating the contralateral lung. OLV is useful if the
stroke volume and cardiac index (CI), along with a sig- surgeon requires additional exposure. In the pediatric
nificant increase in SVR. Pneumoperitoneum was found patient, there are several options for attaining unilateral
to be associated with significant increases in left ventricu- lung isolation (Fig. 3-3).61
lar end-diastolic volume, left ventricular end-systolic Complications related to anesthetic management are
volume, and left ventricular end-systolic wall stress.56 All usually related to mechanical factors such as airway injury
three studies demonstrated a decrease in cardiac per- and malposition of the ETT. Additional problems related
formance and an increase in vascular resistance in healthy to physiologic alterations include hypoxemia and hyper-
patients undergoing laparoscopy for lower abdominal capnia. An unusual complication was reported during
procedures. The cardiovascular changes seen with attempted thoracoscopic resection of a congenital cystic
pneumoperitoneum (Box 3-5) occur immediately with adenomatoid malformation in a 3.5kg infant.62 During
creation of the pneumoperitoneum and resolve on CO2 insufflation, there was a sharp rise in ETCO2 accom-
desufflation. panied by severe hypoxemia and bradycardia. This was
due to occlusion of the ETT by blood. After immediate
conversion, it was discovered that there had been direct
Thoracoscopy insufflation into the cyst and that the cyst communicated
Thoracoscopy has advantages over open thoracotomy, directly with the tracheobronchial tree.
including reduced postoperative pain, decreased dura- Blood obstructing the ETT is a common occurrence
tion of hospitalization, improved cosmetic results, and during thoracic procedures, whether open or thoraco-
decreased incidence of chest wall deformity.59,60 An scopic, especially in infants in whom the ETT inner
optimal anesthetic plan considers potential respiratory diameter is so small and therefore at high risk for
derangements including ventilation-perfusion mismatch obstruction. Ventilatory parameters, such as increasing
which may result from positioning, CO2 insufflation into airway pressure during volume ventilation or decreasing
the pleural cavity, and single-lung ventilation. In addi- tidal volume during pressure ventilation, may precede
tion, much like insufflation during laparoscopy, hemody- desaturation and an increase in ETCO2 due to compro-
namic changes during chest insufflation can compromise mised ventilation associated with ETT obstruction.
preload, stroke volume, CI, and blood pressure.60 ETT suctioning, and if necessary, ETT lavage may be
In a study of 50 pediatric patients undergoing thora- required during the procedure to remove blood and/or
coscopy for a variety of operations, systolic and diastolic secretions.
blood pressures were significantly lower, and ETCO2 It is important to try to maintain a reasonable range
was significantly higher during thoracoscopy.60 After of elevated CO2 in neonates undergoing thoracoscopic
intrapleural CO2 insufflation, there was a statistically sig- procedures. Mukhtar and colleagues reported that per-
nificant increase in ETCO2 during one-lung ventilation missive hypercapnia with ETCO2 5070mmHg was
(OLV) compared with two-lung ventilation. On the other associated with improved cardiac output and arterial
hand, two-lung ventilation with CO2 insufflation was oxygen tension in neonates undergoing thoracoscopic
associated with a lower systolic and diastolic pressure ligation of patent ductus arteriosus.63 A case series in
than OLV. The increase in ETCO2 correlated with the which high-frequency oscillating ventilation (HFOV)
was used in neonates undergoing thoracoscopic proce-
dures has been reported.64 HFOV enables better CO2
elimination while optimizing the visualization for the
Physiologic Effects of Creation of a surgeons.
BOX 3-5
Pneumoperitoneum
Systemic vascular resistance POSTANESTHESIA CARE
Pulmonary vascular resistance
Stroke volume The recovery period for infants and children may be
Cardiac index more crucial than for adult patients with 34% of infants
PCO2
and children developing major complications in the
Functional residual capacity
pH recovery period, compared to only 0.5% of adults. Most
PO2 of these complications occur in the youngest children
Venous return (head up) (<2 years of age) and are most commonly respiratory
in nature.65
3 Anesthetic Considerations for Pediatric Surgical Conditions 45
A B
FIGURE 3-3 There are several methods available for single-lung ventilation in infants and children. (A) The most common method
is to use a conventional single-lumen endotracheal tube to intubate a main-stem bronchus. (B) Another technique is to position the
endotracheal tube in the trachea followed by insertion of a balloon-tipped bronchial blocker that is passed along the endotracheal
tube and occludes the ipsilateral main-stem bronchus. The position of the bronchial blocker is usually confirmed using fiberoptic
bronchoscopy.
many textbooks of pediatric anesthesiology and pain history of gastric ulcers. As NSAIDs such as ketorolac
management.81 Patients receiving PCA should be con- and ibuprofen affect platelet aggregation and adhesive-
tinuously monitored for cardiorespiratory depression by ness, their use is limited in many patients that are at risk
monitoring the echocardiogram, respiratory rate, and for postoperative bleeding, particularly children who
pulse oximetry.85 have undergone tonsillectomy.93,97 In addition, many
When PCA devices are not used, the intermittent orthopedic surgeons forbid the use of NSAIDS during
bolus administration of morphine to opioid-naive chil- and after operations in which new bone formation is
dren should be started at 0.050.1mg/kg every two to important (fractures, spine fusions) because NSAIDS
four hours. If the treatment of pain is initiated in the have been shown to impair osteoblastic activity.98 The
PACU or intensive care setting, similar doses may be extent to which this effect is clinically important is
administered every five to ten minutes until the child is unclear.99,100
comfortable.
Fentanyl is a synthetic opioid that usually has a rela- Regional and Local Anesthetic Techniques
tively short duration of action as a result of its rapid
distribution into fat and muscle due to its high lipid solu- As general anesthesia is nearly universal in children, pure
bility. With repeated dosing, the duration of action regional anesthesia is less common than in adults.
appears to increase.86 When compared with morphine, However, pediatric patients, including outpatients, are
fentanyl is about 100 times more potent. (Fentanyl excellent candidates for a host of regional blocks.101103
dosages are calculated in micrograms rather than milli- Some blocks require specialized equipment like a nerve
grams.) In controlled comparisons with equipotent stimulator or ultrasound, but others such as an ilioin-
dosages, morphine is generally found to provide guinal block can be performed by landmarks alone. Local
better, more long-lasting analgesia than fentanyl, but infiltration by the surgeon is encouraged when a neurax-
with more side effects such as pruritus, nausea, and ial or peripheral block is not performed.
vomiting.8789 Opioids with short half-lives like fentanyl Regional anesthetic techniques used concomitantly
may also demonstrate the development of much more with general anesthesia have had resurgence in both adult
rapid tolerance to its analgesic effects than morphine or and pediatric patients. These techniques include periph-
hydromorphone. eral nerve blocks, and caudal, epidural, or spinal blocks.
Hydromorphone is a well-tolerated alternative to These blocks include the rectus sheath block for umbili-
morphine and fentanyl, and is felt to cause less pruritus cal procedures, ilioinguinal block for inguinal procedures,
and sedation than morphine, with the few adult studies and the transversus abdominis plane block for lower
that exist suggesting equivalence rather than superior- abdominal procedures.104106
ity.90 It is five to seven times more potent than morphine, Clonidine has gained favor as an adjunct in regional
and its duration of action is similar to morphine, and anesthesia. A centrally acting alpha-2 agonist with anti-
longer than fentanyl. emetic and mild sedative effects, clonidine confers an
analgesic benefit as well. It has been shown to increase
the analgesic duration of caudal blocks to as long as 18
Nonsteroidal Anti-Inflammatory
hours.107 Clonidine has also been used effectively in epi-
Drugs (NSAIDs)
dural infusions. Moreover, rather than causing nausea or
As more and more pediatric operations are being per- pruritus, clonidine actually decreases the incidence of
formed on an outpatient basis, and with the goal of mini- postoperative nausea. In higher doses (2g/kg) given
mizing opioid dosing to reduce adverse effects, significant epidurally, clonidine may cause sedation, with some
interest has developed in the role of nonopioid analgesics authors recommending that children receiving this dose
for management of postoperative pain. Acetaminophen is be admitted for observation. Clonidine is not recom-
an effective analgesic for mild to moderate pain, and can mended for use in infants under 6 months of age.
be administered rectally in the perioperative period, In selected cases, peripheral nerve blocks appear to be
especially to infants. Rectal absorption is variable and a superior pain control modality. They offer the benefit
bioavailability is lower, mandating a higher initial dose of no systemic side effects (nausea, pruritus, sedation,
(3040mg/kg) than that administered orally (1015mg/ urinary retention) and often allow for faster recovery. It
kg).91,92 A rectal dose of 30mg/kg of acetaminophen has is increasingly common for these blocks to be performed
proved to have analgesic properties similar to 1mg/kg of under ultrasound guidance, which confers increased
ketorolac.93 In 2011, intravenous acetaminophen was accuracy of placement, which in turn allows the use of
approved for use in adults and children older than 2 years reduced local anesthetic volume, greater efficacy, and
of age in the U.S. improved efficiency. For orthopedic extremity surgery,
Ketorolac is an oral and parenteral NSAID shown to some children are being discharged home with peripheral
have excellent pain control characteristics unassociated nerve catheters which are removed at home by the parents
with PONV, or respiratory depression.9496 Dosage rec- two days postoperatively.108
ommendations are 0.5mg/kg intravenously (maximum
dose 30mg) every 6 to 8 hours for 48 hours. Due to its Prescribing Discharge Analgesics
effects on renal blood flow and tubular function, ketoro-
lac is contraindicated in patients with pre-existing impair- The surgeon or surgeons designee must take seriously
ment of renal function. Likewise, it should not be the responsibility of prescribing pain medications to be
administered to patients at risk for coagulopathy or a administered by the parents at home after discharge. This
48 SECTION I General
is important for all patients, but especially for ambulatory Criteria for Discharge Home from
surgery patients because of the rapid transition from BOX 3-6
the Postanesthesia Care Unit
PACU to home. It is imperative to clearly communicate
with the parent/guardian regarding the nature of the Return to preoperative level of consciousness
medications prescribed, assessment of pain, and realistic Normothermia (35.5C)
expectations for the course of pain in the days after No oxygen requirement (or return to baseline oxygen
surgery. It is important to emphasize the same issues that requirement)
are of concern when giving analgesics in the hospital: Return to preoperative level of motor function (excepting
right drug, right dose, right time. expected effects of nerve block)
Numerous studies looking at parental home analgesic Acceptable pain control
No ongoing vomiting, minimal nausea
administration after surgery have shown that parents Absence of surgical bleeding
commonly do not understand that some children may At least 30 minutes after last administration of opioid
become withdrawn and immobile in response to pain Discharge acceptable to surgeon
instead of crying.109 In addition, many parents fail to Oral intake (if required by surgeon)
administer prescribed pain medication even when they
recognize their child is having pain, in part because of
lack of specific instructions or because of fear of adverse
effects, including misperceptions about the potential for
addiction.110,111 Care must be taken to avoid advising
DISCHARGE CRITERIA
time-contingent (especially around the clock) dosing of
In general, children should be comfortable, awake, and
opioids because of the increased risk of nausea, vomiting,
stable, on room air or back to baseline oxygen supple-
constipation, but most importantly somnolence and res-
mentation, have age-appropriate vital signs, and be well
piratory depression.112
hydrated before discharge from outpatient surgery. These
With regard to choice of opioid, prescribers should be
variables have been quantified with the modified Aldrete
knowledgeable about recommended dosage and formula-
score (Table 3-4), which lists the important factors taken
tions available for various oral opioids. The most com-
into consideration for discharge. Most institutions require
monly prescribed opioid in children has been codeine
a modified Aldrete score of 9 or greater for discharge to
(more specifically acetaminophen with codeine). A recent
floor, but criteria for discharge home should be stricter,
publication has noted concerns about a number adverse
comprising the elements listed in Box 3-6.
effects of codeine administration.113 These include lack
of analgesic efficacy in approximately 510% of the pop-
ulation in whom low CYP2D6 activity leads to low or no
conversion of codeine to morphine in the body, which is
CONCLUSION
required for analgesia.114 More worrisome is the fact that
Many children who present for surgery are frightened
up to a third of individuals (depending on their ethnic
and uncomfortable. It is the pediatric surgeons and
origin) are ultrarapid metabolizers because of increased
anesthesiologists privilege to help calm and comfort
CYP2D6 activity. Codeine administration in these indi-
these children and their families in addition to providing
viduals results in high plasma levels of morphine which
the best possible anesthetic experience. Guiding the child
can cause respiratory depression, which is especially wor-
through an operation safely, with provision for analgesia
risome in children and especially in children with OSA.
and amnesia, are goals shared by both the anesthesiolo-
The risk of codeine administration to children who may
gist and surgeon alike. Open communication between
be unidentified ultrarapid metabolizers led the U.S. Food
surgical and anesthesia services from the time of schedul-
and Drug Administration to issue a safety alert in August,
ing through the peri- and postoperative periods facilitates
2012 regarding the risk of adverse events or death in
the achievement of these goals, and helps to ensure the
children given codeine after tonsillectomy and/or
best possible outcome for patients and their families.
adenoidectomy.115,116
Whether undergoing an operation on an inpatient or REFERENCES
an outpatient basis, infants and children should be
1. Chopra V, Bovill JG, Spierdijk J. Accidents, near accidents and
afforded the most effective pain relief possible along with complications during anesthesia: A retrospective analysis of a
a minimum of adverse effects. 10-year period in a teaching hospital. Anaesthesia 1990;45:36.
3 Anesthetic Considerations for Pediatric Surgical Conditions 49
2. Aubas S, Biboulet P, Daures JP, et al. Incidence and etiology of 27. Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk
cardiac arrest occurring during the peroperative period and in the factors for infective endocarditis. A population based, case-control
recovery room: Apropos of 102,468 anesthesia cases. Ann Fr study. Ann Intern Med 1998;129:7619.
Anesth Reanim 1991;10:43642. 28. Roberts GJ. Dentists are innocent! Everyday bacteremia is the real
3. Odegard KC, DiNardo JA, Kussman BD, et al. The frequency of culprit: A review and assessment of the evidence that dental surgi-
anesthesia-related cardiac arrests in patients with congenital heart cal procedures are the principal cause of endocarditis in children.
disease undergoing cardiac surgery. Anesth Analg 2007;105: Paediatr Cardiol 1999;20:31725.
33543. 29. Seymour RA, Lowry R, Whitworth JM, et al. Infective endocar-
4. Bhananker SM, Ramamoorthy C, Geiduschek JM, et al. ditis, dentistry and antibiotic prophylaxis; Time for a rethink? Br
Anesthesia-related cardiac arrest in children: Update from the Dent J 2000;189:61015.
Pediatric Perioperative Cardiac Arrest Registry. Anesth Analg 30. Durack D. Antibiotics for prevention of endocarditis during den-
2007;105:34450. tistry: Time to scale back? Ann Intern Med 1998;129:82931.
5. Flick RP, Sprung J, Harrison TE, et al. Perioperative cardiac 31. Horskotte D, Follath F, Gutschik E, et al. Guidelines on the
arrests in children between 1988 and 2005 at a tertiary referral prevention, diagnosis and treatment of infective endocarditis:
center. Anesthesiology 2007;106:22637. Executive summary. The task force on infective endocarditis of
6. Patel RI, Hannallah RS. Preoperative screening for pediatric the European Society of Cardiology. European Heart Journal
ambulatory surgery: Evaluation of a telephone questionnaire 2004;25:26776.
method. Anesth Analg 1992;75:25861. 32. Danchin N, Duval X, Leport C. Prophylaxis of infective endocar-
7. Zuckerberg AL. A hot mnemonic for the treatment of malignant ditis: French recommendations 2002. Heart 2005;91:71518.
hyperthermia. Anesth Analg 1993;77:1077. 33. Blaise G, Langleben D, Hubert B. Pulmonary arterial hyperten-
8. Cook-Sather SD, Harris KA, Chiavacci R, et al. A liberalizaed sion. Anesthesiology 2003;99:141532.
fasting guideline for formula-fed infants does not increase average 34. Fischer LG, Van Aken H, Burkle H. Management of pulmonary
gastric fluid volume before elective surgery. Anesth Analg hypertension: Physiological and pharmacological considerations
2003;96:9659. for anesthesiologists. Anesth Analg 2003;96:160316.
9. Tait AR, Reynolds PI, Gutstein HB. Factors that influence an 35. Friesen RH, Williams GD. Anesthetic management of children
anesthesiologists decision to cancel elective surgery for the child with pulmonary arterial hypertension. Pediatric Anesthesia
with an upper respiratory tract infection. J Clin Anesth 1995; 2008;18:20816.
7:4919. 36. Hakim TS, Michel RP, Chang HK. Effect of lung inflation on
10. Parnis SJ, Barker DS, Van Der Walt JH. Clinical predictors of pulmonary vascular resistance by arterial and venous occlusion.
anaesthetic complications in children with respiratory tract infec- J Appl Physiol 1982;53:111015.
tions. Paediatr Anaesth 2001;11:2940. 37. Luce JM. The cardiovascular effects of mechanical ventilation and
11. Tait AR, Malviya S, Voepel-Lewis T, et al. Risk factors for peri- positive end expiratory pressure. JAMA 1984;252:80711.
operative adverse respiratory events in children with upper respi- 38. Jardin F, Vieillard-Baron A. Right ventricular function and posi-
ratory tract infections. Anesthesiology 2001;95:299306. tive pressure ventilation in clinical practice: From hemodynamic
12. Rigatto H, Brady JP. Periodic breathing and apnea in preterm subsets to respiratory settings. Intensive Care Med 2003;29:
infants: Evidence for hypoventilation possibly due to central res- 142634.
piratory depression. Pediatrics 1972;50:20218. 39. Henriksson P, Varendh G, Lundstron MR. Haemostatic defects
13. Cot CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in in cyanotic congenital heart disease. Br Heart J 1979;41:237.
former preterm infants after inguinal herniorrhaphy: A combined 40. Silka MJ, Bar-Cohen Y. Pacemakers and implantable cardioverter-
analysis. Anesthesiology 1995;82:80922. defibrillators in pediatric patients. Heart Rhythm 2006;3:
14. Fisher D. When is the ex-premature infant no longer at risk for 13606.
apnea? Anesthesiology 1995;82:8078. 41. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS
15. Hammer GB. Anaesthetic management for the child with a medi- 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm
astinal mass. Paediatr Anaesth 2004;14:957. Abnormalities: A Report of the American College of Cardiology/
16. Yamashita M, Chin I, Horigome H. Sudden fatal cardiac arrest in American Heart Association Task Force on Practice Guidelines
a child with an unrecognized anterior mediastinal mass. Resuscita- (Writing Committee to Revise the ACC/AHA/NASPE 2002
tion 1990;19:1757. Guideline Update for Implantation of Cardiac Pacemakers and
17. Viswanathan S, Campbell CE, Crok RC. Asymptomatic undetec- Antiarrhythmia Devices): Developed in Collaboration with the
ted mediastinal mass: A death during ambulatory anesthesia. American Association for Thoracic Surgery and Society of Tho-
J Clin Anesth 1995;7:1515. racic Surgeons. Circulation 2008;117:e350408.
18. Lerman J.. Anterior mediastinal masses in children. Semin Anesth 42. Madigan JD, Choudhri AF, Chen J. et al. Surgical management
2007;26:13340. of the patient with an implanted cardiac device: Implications of
19. Cho Y, Suzuki S, Yokoi M, et al. Lateral position prevents respira- electromagnetic interference. Ann Surg 1999;230:63947.
tory occlusion during surgical procedure under general anesthesia 43. Practice Advisory for Perioperative Management of Patients with
in the patient of huge anterior mediastinal lymphoblastic lym- Cardiac Rhythm Management Devices. Pacemakers and Implant-
phoma. J Thorac Cardiovasc Surg 2004;52:4769. able Cardioverter-Defibrillators. Anesthesiology 2005;103:
20. Shamberger RC, Holzman RS, Griscom NT, et al. CT quantita- 18698.
tion of tracheal cross-sectional area as a guide to the surgical and 44. Litman RS. The difficult pediatric airway. In: Litman RS, editor.
anesthetic management of children with anterior mediastinal Pediatric AnesthesiaThe Requisites in Anesthesiology. Phila-
masses. J Pediatr Surg 1991;26:13842. delphia: Elsevier Mosby; 2004. p. 13546.
21. Mahmoud M, Tyler T, Sadhasivam S. Dexmedetomidine and 45. Standards for basic anesthetic monitoring (Approved by the ASA
ketamine for large anterior mediastinal mass biopsy. Paediatr House of Delegates on October 21, 1986 and last amended on
Anaesth 2008;18:101113. October 20, 2010.
22. Cheung S, Lerman J. Mediastinal masses and anesthesia in chil- 46. Pennant JH. Anesthesia for laparoscopy in the pediatric patient.
dren. Anesthesiol Clin North Am 1998;16:893910. Anesth Clin North Am 2001;19:6974.
23. Ricketts RR. Clinical management of anterior mediastinal tumors 47. Kudsi OY, Jones SA, Brenn BR. Carbon dioxide embolism in a
in children. Semin Pediatr Surg 2001;10:1618. 3-week-old neonate during laparoscopic pyloromyotomy: A case
24. Greenwood RD, Rosenthal A, Parisi L, et al. Extracardiac abnor- report. J Pediatr Surg 2009;44:8425.
malities in infants with congenital heart disease. Pediatrics 48. Taylor SP, Hoffman GM. Gas embolus and cardiac arrest during
1975;55:48592. laparoscopic pyloromyotomy in an infant. Can J Anaesth 2010;
25. Hoffman JI, Christianson R. Congenital heart disease in a cohort 57:7748.
of 19,502 births with long-term follow-up. Am J Cardiol 1978;42: 49. McHoney MC, Corizia L, Eaton S, et al. Carbon dioxide elimina-
6417. tion during laparoscopy in children is age dependent. J Pediatr
26. Hennein HA, Mendeloff EN, Cilley RE, et al. Predictors of post- Surg 2003;38:10510.
operative outcome after general surgical procedures in patients 50. Uzzo RG, Bilsky M, Mininberg DT, et al. Laparoscopic
with congenital heart disease. J Pediatr Surg 1994;29:86670. surgery in children with ventriculoperitoneal shunts: Effect of
50 SECTION I General
pneumoperitoneum on intracranial pressure preliminary expe- Anesthesiologists Task Force on Intraoperative Awareness.
rience. Pediatr Urol 1997;49:7537. Anesthesiology 2006;104:84764.
51. Fraser JD, Aguayo P, Sharp SW, et al. The safety of laparoscopy 77. Pollard RJ, Coyle JP, Gilbert RL, et al. Intraoperative awareness
in pediatric patients with ventriculoperitoneal shunts. J Laparoen- in a regional medical system: A review of 3 years data. Anesthe-
dosc Adv Surg Tech 2009;19:6758. siology 2007;106:26974.
52. Raskin J, Guillaume DJ, Ragel BT. Laparoscopic-induced pneu- 78. Davidson AJ, Huang GH, Czarnecki C, et al. Awareness during
mocephalus in a patient with a ventriculoperitoneal shunt. Pediatr anesthesia in children: A prospective cohort study. Anesth Analg
Neurosurg 2010;46:3901. 2005;100:65361.
53. Bozkurt P, Kaya G, Altintas F, et al. Systemic stress response 79. Mather L, Mackie J. The incidence of postoperative pain in chil-
during operations for acute abdominal pain performed via lapar- dren. Pain 1983;15:27182.
oscopy or laparotomy in children. Anaesthesia 2000;55:59. 80. Groenewald CB, Rabbitts JA, Schroeder DR, et al. Prevalence of
54. Bannister CF, Brosius KK, Wulkan M. The effect of insufflation moderate-severe pain in hospitalized children. Paediatr Anaesth
pressure on pulmonary mechanics in infants during laparoscopic 2012;22:6618.
surgical procedures. Paediatr Anaesth 2003;13:7859. 81. Malviya S, Polaner DM, Berde C. Acute Pain. In: Cote CJ,
55. Joris JL, Noirot DP, Legrand MJ, et al. Hemodynamic changes Lerman J, Todres ID, editors. A Practice of Anesthesia for Infants
during laparoscopic cholecystectomy. Anesth Analg 1993; and Children. 4th ed. Philadelphia: Saunders Elsevier; 2009.
76:106771. p. 93978.
56. Gentili A, Iannettone CM, Pigna A, et al. Cardiocirculatory 82. Merkel SI, Voepel-Lewis T, Shayevitz JR, et al. The FLACC: A
changes during videolaparoscopy in children: An echocardio- behavioral scale for scoring postoperative pain in young children.
graphic study. Paediatr Anaesth 2000;10:399406. Pediatr Nurs 1997;23:2937.
57. Kardos A, Vereczkey G, Pirot L, et al. Use of impedance cardi- 83. Pasternak GW, Zhang A, Tecott L. Developmental differences
ography to monitor haemodynamic changes during laparoscopy between high and low affinity opiate binding sites: Their relation-
in children. Paediatr Anaesth 2001;11:1759. ship to analgesia and respiratory depression. Life Sci 1980;
58. Gueugniaud P, Abisseror M, Moussa M, et al. The hemodynamic 27:118590.
effects of pneumoperitoneum during laparoscopic surgery in 84. Brown KA, Laferriere A, Lakheeram I, et al. Recurrent hypoxemia
healthy infants: Assessment by continuous esophageal aortic blood in children is associated with increased analgesic sensitivity to
flow echo-Doppler. Anesth Analg 1998;86:2903. opiates. Anesthesiology 2006;105:6659.
59. Haynes SR, Bonner S. Anaesthesia for thoracic surgery in chil- 85. Nelson KL, Yaster M, Kost-Byerly S, et al. A national survey of
dren. Paediatr Anaesth 2000;10:23751. American Pediatric Anesthesiologists: Patient-controlled analge-
60. Gentili A, Lima M, De Rose R, et al. Thoracoscopy in children: sia and other intravenous opioid therapies in pediatric acute pain
Anaesthesiological implications and case reports. Minerva management. Anesth Analg 2010;110:75460.
Anesthesiol 2007;73:16171. 86. Kay B, Rolly G. Duration of action of analgesia supplement of
61. Hammer GB. Single-lung ventilation in infants and children. anesthesia: A double-blind comparison between morphine, fenta-
Paediatr Anaesth 2004;14:98102. nyl, and sufentanil. Acta Anaesthesiol Belg 1977;28:2532.
62. Mukhtar AM, Dessouky NM. Unusual complication during pedi- 87. Claxton AR, McGuire G, Chung F, et al. Evaluation of morphine
atric thoracoscopy. Pediatr Anesth 2006;16:9868. versus fentanyl for postoperative analgesia after ambulatory surgi-
63. Mukhtar AM, Obayah GM, Elmasry A, et al. The therapeutic cal procedures. Anesth Analg 1997;84:50914.
potential of intraoperative hypercapnia during video-assisted tho- 88. Sanford Jr. TJ, Smith NT, Dec-Silver H, et al. A comparison of
racoscopy in pediatric patients. Anesth Analg 2008;106:848. morphine, fentanyl, and sufentanil anesthesia for cardiac surgery:
64. Mortellaro VE, Fike FB, Adibe OO, et al. The use of high- Induction, emergence, and extubation. Anesth Analg 1986;65:
frequency oscillating ventilation to facilitate stability during neo- 25966.
natal thoracoscopic operations. J Laparoendosc Adv Surg Tech 89. Lejus C, Roussiere G, Testa S, et al. Postoperative extradural
2011;21:8779. analgesia in children: Comparison of morphine with fentanyl. Br
65. Murat I, Constant I, Maudhuy H. Perioperative anaesthetic mor- J Anesth 1994;72:1569.
bidity in children: A database of 24,165 anaesthetics over a 90. Rapp SE, Egan KJ, Ross BK, et al. A multidimensional compari-
30-month period. Paediatr Anaesth 2004;14:15866. son of morphine and hydromorphone patient-controlled analge-
66. Patel RI, Hannallah RS. Anesthetic complications following pedi- sia. Anesth Analg 1996;82:10438.
atric ambulatory surgery: A 3-year study. Anesthesiology 1988; 91. Birmingham PK, Tobin MJ, Henthom TK, et al. Twenty-four
69:100912. hour pharmacokinetics of rectal acetaminophen in children.
67. Watcha MF, White PF. Postoperative nausea and vomiting: Its Anesthesiology 1997;87:24452.
etiology, treatment, and prevention. Anesthesiology 1992;77: 92. Montgomery CJ, McCormack JP, Reichert CC, et al. Plasma
16284. concentrations after high-dose (45mgkg-1) rectal acetami-
68. Weir PM, Munro HM, Reynolds PI, et al. Propofol infusion and nophen in children. Can J Anaesth 1995;42:9826.
the incidence of emesis in pediatric outpatient strabismus surgery. 93. Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation
Anesth Analg 1993;76:7604. of ketorolac tromethamine versus acetaminophen in pediatric ton-
69. Schreiner MS. Preoperative and postoperative fasting in children. sillectomy: Analgesia and bleeding. Anesth Analg 1995;80:
Pediatr Clin North Am 1994;41:11120. 2269.
70. Schreiner MS, Nicolson SC, Martin T, et al. Should children 94. Forrest JB, Heitlinger EL, Revell S. Ketorolac for postoperative
drink before discharge from day surgery? Anesthesiology pain management in children. Drug Saf 1997;16:30929.
1992;76:52833. 95. Gillis JC, Brogden RN. Ketorolac: A reappraisal of its pharmaco-
71. Koka BV, Jeon IS, Andre JM, et al. Postintubation croup in chil- dynamic and pharmacokinetic properties and therapeutic use in
dren. Anesth Analg 1977;56:5015. pain management. Drugs 1997;53:13988.
72. Schreiner MS, OHara I, Markakis DA, et al. Do children who 96. Yaster M. Non-steroidal anti-inflammatory drugs. In: Yaster M,
experience laryngospasm have an increased risk of upper respira- Krane EJ, Kaplan RF, Cote CJ, Lappe DG, editors: Pediatric pain
tory tract infection? Anesthesiology 1996;85:47580. management and sedation handbook. St Louis: Mosby Year Book;
73. von Ungern-Sternberg BS, Boda K, Chambers NA, et al. Risk 1997. p. 1927.
assessment for respiratory complications in paediatric anaesthesia: 97. Gunter JB, Varughese AM, Harrington JF, et al. Recovery and
A prospective cohort study. Lancet 2010;376:77383. complications after tonsillectomy in children: A comparison of
74. Khine HH, Corddry DH, Kettrick RG, et al. Comparison of ketorolac and morphine. Anesth Analg 1995;81:113641.
cuffed and uncuffed endotracheal tubes in young children during 98. Chang JK, Wang GJ, Tsai ST, et al. Nonsteroidal anti-
general anesthesia. Anesthesiology 1997;86:62731. inflammatory drug effects on osteoblastic cell cycle, cytotoxicity,
75. Orliaquet GA, Gall O, Savoldelli GL, et al. Case scenario: Peri- and cell death. Connect Tissue Res 2005;46:20010.
anesthetic management of laryngospasm in children. Anesthesiol- 99. Sucato DJ, Lovejoy JF, Agrawal S, et al. Postoperative ketorolac
ogy 2012;116:45871. does not predispose to pseudoarthrosis following posterior spinal
76. Practice advisory for intraoperative awareness and brain fusion and instrumentation for adolescent idiopathic scoliosis.
function monitoring: A report by the American Society of Spine 2008;33:111924.
3 Anesthetic Considerations for Pediatric Surgical Conditions 51
100. Li Q, Zhang Z, Cai Z. High-dose ketorolac affects adult spinal 109. Zisk RY, Grey M, Medoff-Cooper B, et al. The squeaky wheel
fusion: A meta-analysis of the effect of perioperative nonsteroidal gets the grease: Parental pain management of children treated for
anti-inflammatory drugs on spinal fusion. Spine 2011;36: bone fractures. Pediatr Emerg Care 2008;24:8996.
E4618. 110. Kankkunen P, Vehvilainen-Julkunen K, Pietila AM, et al. Is the
101. Marhofer P, Ivani G, Suresh S, et al. Everyday regional anesthesia sufficiency of discharge instructions related to childrens postop-
in children. Paediatr Anaesth 2012;22:9951001. erative pain at home after day surgery? Scand J Caring Sci
102. Lonnqvist PA. Blocks for pain management in children undergo- 2003;17:36572.
ing ambulatory surgery. Curr Opin Anaesthesiol 2011;24: 111. Fortier MA, MacLaren JE, Martin SR, et al. Pediatric pain after
62732. ambulatory surgery: Wheres the medication? Pediatrics 2009;
103. Willschke H, Marhofer P, Machata AM, et al. Current trends 124:e58895.
in paediatric regional anaesthesia. Anaesthesia 2010;65(Suppl 112. Sutters KA, Holdridge-Zeuner D, Waite S, et al. A descriptive
1):97104. feasibility study to evaluate scheduled oral analgesic dosing at
104. Willschke H, Kettner S. Pediatric regional anesthesia: Abdominal home for the management of postoperative pain in preschool
wall blocks. Paediatr Anaesth 2012;22:8892. children following tonsillectomy. Pain Med 2012;13:47283.
105. Gurnaney HG, Maxwell LG, Kraemer FW, et al. Prospective 113. Baugh RF, Archer SM, Mitchell RB, et al. Clinical practice guide-
randomized observer-blinded study comparing the analgesic effi- line: Tonsillectomy in children. Otolaryngol Head Neck Surg
cacy of ultrasound-guided rectus sheath block and local anaes- 2011;144:S130.
thetic infiltration for umbilical hernia repair. Br J Anaesth 2011; 114. Williams DG, Patel A, Howard RF. Pharmacogenetics of codeine
107:7905. metabolism in an urban population of children and its implications
106. Mai CL, Young MJ, Quraishi SA. Clinical implications of the for analgesic reliability. Br J Anaesth 2002;89:83945.
transversus abdominis plane block in pediatric anesthesia. Paediatr 115. Ciszkowski C, Madadi P, Phillips MS, et al. Codeine, ultrarapid-
Anaesth 2012;22:83140. metabolism genotype, and postoperative death. NEJM 2009;
107. Tripi PA, Palmer JS, Thomas S, et al. Clonidine increases duration 361:8278.
of bupivacaine caudal analgesia for ureteroneocystostomy: A 116. Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities
double-blind prospective trial. J Urol 2005;174:10813. after tonsillectomy in North American children. Pediatrics 2012;
108. Gurnaney H, Kraemer FW, Maxwell L, et al. Ambulatory con- 129:e13437.
tinuous peripheral nerve blocks in children and adolescents-
A longitudinal eight year single center study. Anesth Analg 2013;
in press.
C H A P T E R 4
Renal Impairment
Uri S. Alon Bradley A. Warady
been shown to correlate with GFR as well as or better urinary concentrating capacity of the term infant from 1
than serum creatinine.69 From about age 12 months and week to 2 months of age is about 800mOsm/L; from 2
up until age 50 years, normal serum cystatin C concentra- months to 3 years, about 1000mOsm/L; and beyond that
tions are similar in children and adults (0.701.38mg/L). age, about 1200mOsm/L.
Currently, the measurement of cystatin C has not been Noteworthy is the recent re-characterization of acute
incorporated into routine clinical practice. However, in renal failure as acute kidney injury (AKI) to better
the near future it may become a new tool in the assess- describe renal dysfunction.l5,16 Nonoliguric AKI occurs
ment of GFR. In contrast, a bedside equation is used to about as frequently as oliguric AKI. It is diagnosed when
estimate GFR: the patient with normal urine output has elevated serum
creatinine and urea nitrogen concentrations.
eGFR = 0.413 Height ( cm )/ serum creatinine ( mg / dL )
is probably the most commonly recognized type of RTA systemic blood pressure, tachycardia, and prolonged cap-
in both adults and children. The hyperkalemia inhibits illary refill time.
ammonia synthesis, resulting in decreased available Prerenal azotemia can be alleviated by improving
ammonia to serve as a urinary buffer. Therefore, a renal perfusion either by repleting the intravascular fluid
low urinary pH occurs despite decreased H+ secretion volume or by improving the cardiac output. The improved
(NH3 + H+ = NH4+). Type IV RTA is physiologically kidney function is recognized by increased urine output
equivalent to aldosterone deficiency, which is one cause and normalization of serum urea nitrogen and creatinine
of the disorder. In children, it may reflect true hypoaldos- concentrations. However, if renal hypoperfusion persists
teronism but it is much more common as a consequence for a significant period or if other nephrotoxic factors are
of renal parenchymal damage, especially that due to present, parenchymal kidney failure can result. Factors
obstructive uropathy. In children, the physiologic impair- that may predispose the patient to AKI include preexist-
ment of type IV RTA resolves in a few weeks to months ing congenital urinary anomalies or impaired kidney
after relief of an obstructive disorder.28 function, septicemia, hypoxemia, hemolysis, rhabdomy-
olysis, hyperuricemia, drug toxicity, and the use of
radiocontrast agents. Also, abdominal compartmental
ACUTE KIDNEY INJURY syndrome resulting from tense ascites may impair renal
perfusion. In this setting, kidney failure may be alleviated
Pathophysiology by abdominal decompression.35
fluid administration during anesthesia and surgery and BOX 4-1 Treatment of Hyperkalemia
for the management of persistent hypoperfusion, along
with decreased urinary output, can result in hypervo- CARDIAC PROTECTION
lemia, hypertension, heart failure, and pulmonary edema. Calcium gluconate, 10%, 0.51.0mL/kg body weight
In extreme cases, fluid administration must be decreased injected intravenously and slowly over 510min, with
to the minimum necessary to deliver essential medica- continuous monitoring of heart rate
tions. In less severe instances, and in euvolemic patients SHIFT OF POTASSIUM INTO THE INTRACELLULAR
with impaired kidney function, total fluid intake should COMPARTMENT
equal insensible water loss, urine volume, and any signifi-
Sodium bicarbonate, 12mEq/kg body weight intrave-
cant extrarenal fluid losses. Urine output must be moni- nously over ten to 20 minutes, provided that salt and
tored hourly and fluid management should be re-evaluated water overload is not a problem
every four to 12 hours, as clinically indicated. Valuable Glucose, 1g/kg body weight, and insulin, one unit per
information about the patients overall fluid status can be every 4g of glucose, intravenously over 2030 minutes
obtained by carefully monitoring blood pressure, pulse, Stimulants of 2-adrenergic receptors, such as salbuta-
and body weight. The preoperative values of these param- mol, intravenously or by inhalation
eters help serve as a baseline for postoperative evaluation.
ELIMINATION OF EXCESS POTASSIUM
Ideally, the patients hemodynamic status should be
assessed continuously by using central venous pressure Furosemide 1mg/kg, or higher in the face of decreased
monitoring. In patients with complicated cardiac prob- GFR
Cation exchange resin, sodium polystyrene sulfonate,
lems, a SwanGanz catheter that monitors pulmonary 1g/kg body weight, administered orally or rectally in
wedge pressure should be used. 2030% sorbitol or 10% glucose, 1g resin/4mL.
Fluid overload can lead to hyponatremia. In most Additional 70% sorbitol syrup may be given if consti-
cases, because total body sodium remains normal or pation occurs
high, the best way to normalize serum sodium concentra- Dialysis
tion is by restriction of fluid intake and enhancement
of urinary volume.39 In patients with acute symptomatic
hyponatremia, careful infusion of NaCl 3% solution the serum HCO3 concentration to 15mEq/L is usually
(512mEq Na/L or 0.5mEq/mL) may be given to correct satisfactory.40
hyponatremia. Rapid correction at a rate of 12mEq/h
over a two to three-hour period, with an increase of Dialysis
serum sodium level by 46mEq/L, is usually well toler-
ated and adequate. Infusion of 6mL/kg of 3% NaCl The inability to control the fluid and electrolyte or acid-
increases serum sodium concentration by about 5mEq/L. base disorders caused by renal failure necessitates the
Hyponatremia present for more than 24 to 48 hours initiation of dialysis. The indications for urgent dialysis
should not be corrected at a rate more rapid than arc persistent oligoanuria, hyperkalemia, metabolic aci-
0.5mEq/L/h. dosis, fluid overload, severe electrolyte and mineral dis-
In children with AKI, hyperkalemia often develops. turbances, and uremic syndrome.
The early sign of potassium cardiotoxicity is peaked T The most common indication for postoperative dialy-
waves on the electrocardiogram. Higher levels of serum sis in a child is hypervolemia caused by repeated attempts
potassium can cause ventricular fibrillation and cardiac at fluid resuscitation, administration of medications, and
asystole. The treatment of hyperkalemia is shown in total parenteral nutrition.41 Repeated intravenous cathe-
Box 4-1. Emergency treatment of hyperkalemia is ter flushes and endotracheal tube lavages can add a sig-
indicated when the serum potassium concentration nificant amount of water and solute to the total intake.
reaches 7.0mEq/L or when electrocardiographic changes Fluid overload in the postoperative patient can cause
are noted. pulmonary edema and hypertension and may have a sig-
In children with AKI, metabolic acidosis rapidly devel- nificant impact on patient recovery.42
ops. Owing to decreased kidney function, fewer hydro-
gen ions are excreted. Organic acids accumulate in the Dialysis Methods. The three modes of dialysis therapy
body, causing a reduction in the serum HCO3 concentra- include hemodialysis (HD), peritoneal dialysis (PD), and
tion. Although a child with uncompromised ventilatory continuous renal replacement therapy (CRRT). Although
capacity is able to hyperventilate and achieve partial com- PD has historically been used most often in children,
pensation, a child with compromised pulmonary function more recent data have revealed an increased use of CRRT
or a hypercatabolic state is at risk for profound acidosis. in those centers where the expertise and resources are
Metabolic acidosis is usually treated by administering available.38,41,43,44 Recognition of the needs of the patient,
NaHCO3. However, attention should be directed toward the resources of the treating facility, and the advantages
the excess sodium load associated with this mode of and disadvantages of each dialytic technique dictate
therapy. Because hypocalcemia develops in many patients which modality is best (Table 4-3).41
with AKI, treatment with alkali should be done cautiously The intrinsic factors that affect the efficacy of PD
to protect them from hypocalcemic tetany due to a shift include peritoneal blood flow, peritoneal vascular perme-
of ionized calcium from free to albumin-bound. It is not ability, and peritoneal surface area. Although removal of
necessary to correct the metabolic acidosis completely up to 50% of the peritoneal surface area does not seem
to prevent the untoward effects of acidemia. Increasing to interfere with dialysis efficacy, hypoperfusion of the
4 Renal Impairment 57
CRRT, continuous renal replacement therapy; HD, hemodialysis; PD, peritoneal dialysis.
a
Omphalocele, gastroschisis, frequent or extensive abdominal surgery. Varies, depending on the location of the hemodialysis catheter.
Adapted from Changler C, Barratt TM. Laboratory evaluation. In Holiday MA (ed): Pediatric Nephrology, 2nd ed. Baltimore,
Williams & Wilkins, 1987, pp. 28299.
peritoneal membrane vasculature renders PD ineffec- placement.51 A study in 2000 showed placement of a
tive.45 PD is feasible in the postoperative patient even in Tenckhoff catheter (Fig. 4-1) to be superior to the Cook
the presence of peritonitis or immediately after major catheter (Cook Medical, Bloomington, IN, USA) in
abdominal operations.43,4648 Increased intra-abdominal terms of complication-free survival.52 More recently,
pressure caused by the dialysis fluid can cause respiratory there is evidence for equal outcomes with the Cook Mul-
embarrassment and can contribute to leakage from the tipurpose Drainage catheter, a flexible catheter that is
incisions and the exit site of the PD catheter. If leakage placed at the bedside, in contrast to the Tenckhoff cath-
persists, the smallest effective dialysis fluid volume eter, which typically requires operative insertion.53
(1020mL/kg) can be tried. Common complications PD is performed with dialysis solutions that contain a
associated with PD are peritonitis, exit site infection, 1.5%, 2.5%, or 4.25% glucose concentration. Dialysate
dialysate leakage, catheter obstruction from omentum or with a 1.5% glucose concentration has an osmolality of
fibrin, and abdominal wall hernia. Sclerosing peritonitis 350mOsm/kg H2O, which is moderately hypertonic to
can also occur and is seen more commonly in females. It normal plasma (280295mOsm/kg H2O). Other factors
results in peritoneal scarring and can lead to bowel being equal, the higher the tonicity of the dialysate and
obstruction and perforation. Resection and stoma may be the greater the osmotic gradient between blood and dia-
needed due to concerns about healing with a primary lysate, the greater the ultrafiltrate (fluid removed from
repair. the body). Owing to the rapid movement of water and
The provision of antibiotics at the time of catheter glucose across the peritoneal membrane, the effect of PD
placement is recommended and may decrease the risk of on fluid removal is maximal when short dialysis cycles of
peritonitis.49,50 Also, the use of fibrin glue at the site of 20 to 30 minutes are used. When solutions containing
catheter entry into the peritoneum has been associated glucose concentrations higher than 1.5% are used, close
with a decreased incidence of dialysate leakage during the monitoring of the patients serum glucose concentration
immediate postoperative period and may be particularly is necessary. If hyperglycemia develops with a blood
beneficial when PD is initiated soon after catheter glucose concentration greater than 200mg/dL, it can be
58 SECTION I General
the oliguric form.66,71 The diagnosis of nonoliguric AKI Intrinsic Acute Kidney Injury
can be missed if patients at risk for developing renal
insufficiency are monitored solely by the evaluation of Intrinsic AKI occurs in 68% of admissions to the NICU
urine output without repeated assessments of the serum and implies the presence of renal cellular damage associ-
creatinine concentration. ated with impaired kidney function.65 Intrinsic AKI
The causes of AKI in newborns traditionally have been usually falls into one of the following categories: ischemic
divided into three categories: prerenal, intrinsic, and (acute tubular necrosis), nephrotoxic (aminoglycoside
postrenal (Box 4-2). This division, based on the site of antibiotics, indomethacin), congenital renal anomalies
the problem, has important implications because the (autosomal recessive polycystic kidney disease), and vas-
evaluation, treatment, and prognosis of the three groups cular lesions (renal artery or vein thrombosis), especially
can be quite different. with a solitary kidney.72
most useful is the FE Na. This factor is based on the Important systemic disturbances that may arise sec-
assumption that the renal tubules of the poorly perfused ondary to AKI include hyperkalemia, hyponatremia,
kidney reabsorb sodium avidly, whereas the kidney hypertension, hypocalcemia, hyperphosphatemia, and
with intrinsic renal disease and tubular damage is metabolic acidosis. All exogenous sources of potassium
unable to do so. Accordingly, in most cases of neonatal should be discontinued in patients with AKI. Despite this
oliguric renal failure secondary to intrinsic disease, the restriction, elevated serum potassium levels develop in
FE Na is >2.53.0%, a value that is different from that many neonates and must be treated aggressively due to
of the older child.62,70 The FE Na should be measured the potential for cardiac toxicity.34 Treatment should
before administering furosemide. In addition, the results be initiated by correction of metabolic acidosis with
should be interpreted with caution in the very premature NaHCO3. A dose of 12mEq/kg should be given intra-
infant who normally has an even higher (i.e., >5%) FE venously over a ten to 20-minute period, provided that
Na.64,80 salt and water balance is not problematic. The quantity
Ultrasonography commonly is the initial imaging of NaHCO3 to be prescribed also can be calculated in the
study.81 The urinary tract should be evaluated for the following manner:
presence of one or two kidneys and for their size, shape,
and location. A voiding cystourethrogram (VCUG) may (0.3 body weight [ kg ] base deficit [ mM ]).
also be necessary, specifically when the diagnosis of PUV
or vesicoureteral reflux is entertained. In most cases, a Associated hypocalcemia should be treated with the
VCUG is deemed preferable to radionuclide cystography intravenous administration of 10% calcium gluconate at
in this setting because of its superior ability to provide a dose of 0.51.0mL/kg injected slowly over a five- to
reliable anatomic information about the grading of vesi- 15-minute period with continuous monitoring of the
coureteral reflux or the appearance of the urethra.82 heart rate. If a progressive increase in the serum potas-
Antegrade pyelography or diuretic renography with sium concentration is noted, additional treatment meas-
either 99mTc-dimercaptosuccinic acid (DMSA) or 99mTc- ures may include the use of a sodiumpotassium exchange
dimercaptoacetyltriglycine (MAG3) may be needed to resin (sodium polystyrene sulfonate in 2030% sorbitol,
evaluate for ureteral obstruction. Finally, assessment of 1g/kg by enema), with recognition of its frequent
the differential kidney function may be performed with ineffectiveness and/or associated complications when
radioisotope scanning as well. used in low birth weight infants.84 The use of glucose
(0.51.0g/kg) followed by insulin (0.10.2 unit regular
insulin per gram glucose over a 1-hour period) may be
Management the preferred approach. Either intravenous salbutamol or
The treatment of neonatal AKI should proceed simulta- inhaled albuterol is an additional therapeutic option.8587
neously with the diagnostic workup. Bladder catheter Dialysis should be considered if these measures prove
placement is a good immediate therapy for PUV, whereas unsuccessful.48,87,88
high surgical drainage may be needed for other obstruc- Hyponatremia and systemic hypertension arc most
tive lesions in the neonate. The fluid challenge for the often related to over-hydration in the infant with oligu-
neonate should consist of 20mL/kg of an isotonic solu- ria. These problems should be treated initially with fluid
tion containing 25mEq/L of NaHCO3 infused over a restriction or water removal with dialysis, if necessary.
one- to two-hour period. In the absence of a prompt The addition of high-dose intravenous furosemide
diuresis of 2mL or more of urine per kilogram over one (5mg/kg) may be helpful. Serum sodium levels below
to two hours, intravenous furosemide at 13mg/kg may 125mEq/L can be associated with seizures, and levels
be helpful, As noted previously, the potential role of below 120mEq/L should be corrected rapidly to at least
low-dose (0.53.0g/kg/min) dopamine continues to be 125mEq/L by calculating the amount of sodium required
debated, but recent guidelines recommend against its use in the following manner:
to prevent or treat AKI.37,38 The failure to achieve
increased urinary output after volume expansion in the Na + ( mEq ) = ([ Na + ] Desired [ Na + ] Actual )
neonate with an adequate cardiac output and an unob- Weight ( kg ) 0.8
structed urinary tract indicates the presence of intrinsic
kidney disease and the need to manage oliguric or anuric When serum sodium levels are less than 120mEq/L and
kidney failure appropriately. are associated with symptoms (e.g., seizures), prompt
Maintenance of normal fluid balance is of primary treatment with hypertonic (3%) saline is indicated. The
concern in the management of the patient with AKI. provision of 1012mL/kg of 3% saline is generally
Daily fluid intake should equal insensible water loss, therapeutic.
urine output, and fluid losses from nonrenal sources. The treatment of persistent hypertension may
In term infants, insensible water losses amount to include parenterally administered hydralazine (0.15 to
3040mL/kg/day, whereas premature infants may 0.6mg/kg/dose), labetalol (0.20 to 1.0mg/kg/dose
require as much as 50100mL/kg/day.80,83 A frequent or 0.25 to 3.0mg/kg/hr infusion), or enalapril at (5.0
assessment of the neonates body weight is essential for to 10g/kg/dose). Orally administered amlodipine (0.05
fluid management. The electrolyte content of the fluids to 0.3mg/kg/dose) can be prescribed for the patient
administered should be guided by frequent laboratory who is without symptoms. Treatment of the patient with
studies. Insensible water losses are electrolyte free and marked or refractory hypertension can include intrave-
should be replaced by using 5% dextrose in water. nous sodium nitroprusside (0.5 to 10g/kg/min
4 Renal Impairment 61
infusion), nicardipine (1 to 4g/kg/min infusion), oxygenation, the mortality rate was 3.2 times higher than
or labetalol.89 Caution should be exercised when initiat- in those without AKI.102 Moreover, patients who required
ing therapy with captopril (initial oral dose, 0.01 to renal replacement therapy had 1.9 higher odds of death
0.05mg/kg/dose), owing to the profound hypotension than those who did not receive this therapy.
that can occur in neonates in association with higher
doses.90,91
In the infant in whom AKI does not fully resolve and OBSTRUCTIVE UROPATHY
becomes chronic renal failure (CKD), the development of
hyperphosphatemia (serum phosphorus level > 7mg/dL) Obstructive uropathy in the neonate is the most common
necessitates a low phosphorus infant formula and possibly renal abnormality diagnosed prenatally and is most often
calcium carbonate (50100mg/kg/day) as a phosphate the result of ureteropelvic junction obstruction, PUV, or
binder.89 The use of aluminum hydroxide as a binder is ureterovesical junction obstruction.73 Obstruction also
contraindicated, owing to its association with aluminum represents a significant cause of end-stage renal disease
toxicity in infants and children with renal insufficiency.90 in children, accounting for 13% of all cases.103 Accord-
No experience has been published about the use of newer, ingly, early recognition and treatment of these lesions are
noncalcium-containing phosphate-binding agents, such desirable because of the adverse effects that obstruction
as sevelamer, in the neonatal population.91,92 Hypocal- can have on kidney function.39,40,75,76,104 Regardless, after
cemia, as ref1ected by a low total serum calcium level, surgical intervention and relief of obstruction, alterations
often occurs in AKI in association with hypoalbuminemia. of GFR, renal blood flow, and renal tubular function can
Less commonly, the ionized calcium level is low and the still occur.76,104,105 Specifically, injury to the renal tubule
patient is symptomatic. In these cases, intravenous 10% can result in an impaired capacity to reabsorb sodium, to
calcium gluconate, 0.51.0mL/kg, over a five-minute concentrate urine, and to secrete potassium and hydro-
period with cardiac monitoring should be given until the gen, all of which can have profound clinical implications.
ionized calcium level is restored to the normal range. The resorption of other solutes, such as magnesium,
Metabolic acidosis may arise as a result of retention of calcium and phosphorus, may also be affected.76,105
hydrogen ions and may require NaHCO3 for correction. The ability of the renal tubule to reabsorb salt and
The dose of NaHCO3 to be given can be calculated as water after relief of the obstruction typically depends on
follows: whether the obstruction is unilateral or bilateral. In uni-
lateral obstruction, the proximal tubules of the juxtamed-
NaHCO3 ( mEq ) = ( Desired bicarbonate Observed ullary nephrons are unable to reabsorb salt and water
bicarbonate ) Weight ( kg ) 0.5 maximally, whereas the fractional reabsorption of salt and
water is increased in the superficial nephrons.105 However,
This dose may be given orally or added to parenteral the amount of sodium excreted by the previously
fluids and infused during several hours. obstructed kidney is not different from that of the con-
Adequate nutrition should be provided, with the goal tralateral kidney, because tubuloglomerular balance is
of 100120 calories and 12g of protein/kg/day, pro- maintained. In contrast, relief of bilateral obstruction or,
vided intravenously or orally. Additional protein may be on occasion, unilateral obstruction in neonates, results in
needed to account for dialysis related losses in those a postobstructive diuresis characterized by a marked ele-
patients receiving PD and CRRT.93,94 For neonates who vation in the absolute amount of sodium and water lost.106
can tolerate oral fluids, a formula containing low levels In part, these changes are a result of an osmotic diuresis
of phosphorus and aluminum, such as Similac PM 60/40 secondary to retained solutes, such as urea.106,107 Some
(Abbott Labs, Abbott Park, IL), is recommended. An contribution may also occur from atrial natriuretic factor,
aggressive approach to nutrition may well contribute to the plasma level of which is elevated during obstruction,
kidney recovery by providing necessary energy at the as well as from enhanced synthesis of prostaglandins.105
cellular level.34 Decreased renal medullary tonicity and decreased hydrau-
Although most neonates with AKI can be managed lic water permeability of the collecting duct in response
conservatively, occasional patients require PD or CRRT to ADH, the latter a result of reduced aquaporin chan-
for the treatment of the metabolic complications and nels, contribute to the impaired concentrating ability of
fluid overload.9597 The mortality rate in this group of the kidney.36,104
patients can be exceedingly high in the setting of AKI The clinical conditions associated with prolonged salt
post-cardiac surgery.47,98100 Apart from the need for wasting are severe volume contraction and circulatory
pressor support, the procedure was well tolerated in one impairment. Conditions associated with the concentrat-
report on the use of CRRT in 85 children weighing less ing abnormalities are secondary nephrogenic diabetes
than 10kg, with survival rates of 25% and 41% for those insipidus and hyponatremic dehydration. Accordingly,
weighing less than 3kg and from 310kg, respectively.97 management must ensure the provision of adequate
A recent retrospective study of PD treatment of AKI amounts of fluid and salt. Sodium intake should be moni-
post-cardiac surgery in 146 neonates and infants revealed tored by serum and urine electrolyte determinations.
that the mortality rate was decreased by more than Fluid intake should equal insensible losses, urine output,
40% in those patients who received early PD (day and nonrenal losses, and should be guided by frequent
of surgery or postoperative day 1) versus delayed PD assessments of body weight.
(postoperative day 2 or later).101 Finally, when AKI Ureteral obstruction also can result in the impairment
occurred in neonates receiving extracorporeal membrane of hydrogen and potassium secretion and the syndrome
62 SECTION I General
of hyperkalemia, hyperchloremic metabolic acidosis, or 18. Berglund F, Killander J, Pompeius R. Effect of trimethoprim-
type IV RTA.108110 This clinical situation appears to be sulfamethoxazole on the renal excretion of creatinine in man.
J Urol 1975;114:8028.
the result of the impaired turnover of the sodium- 19. Work D, Schwartz G. Estimating and measuring glomerular
potassium pump or a decreased responsiveness of the filtration rate in children. Curr Opin Nephrol Hypertens
distal renal tubule to the actions of aldosterone. In a 2008;17:3205.
portion of the patients with this presentation, the FE Na 20. Fadrowski J, Neu A, Schwartz GJ, et al. Pediatric GFR estimating
equations applied to adolescents in the general population. Clin J
is normal and the FE is inappropriately low, relative to Am Soc Nephrol 2011;6:142735.
the elevated serum level. Treatment is directed toward 21. Schwartz GJ, Schneider M, Maier P, et al. Improved equations
correcting the underlying obstructive abnormality as well estimating GFR in children with chronic kidney disease using an
as providing NaHCO3 to alleviate the metabolic acidosis immunonephelometric determination of cystatin C. Kidney Inf
and hyperkalemia. 2012;82(4):44553.
22. Hellerstein S, Holliday M, Grupe W, et al. Nutritional manage-
Finally, the outcome of obstructive uropathy in the ment of children with chronic renal failure. Summary of the task
neonate in terms of preservation of GFR is, in part, force on nutritional management of children with chronic renal
related to how promptly relief of obstruction occurs. In failure. Pediatr Nephrol, 1987;l:195211.
these patients, the serum creatinine obtained at age 12 23. Chantler C, Barratt T. Laboratory evaluation. In: Holliday M,
Barratt T, Vernier R, editors. Pediatric Nephrology. Baltimore:
months has been shown to be predictive of long-term Williams & Wilkins; 1987. p. 28299.
kidney function.39,40,76,104 Attempts to preserve renal func- 24. Srivastava T, Garg U, Alon U. Impact of standardization of cre-
tion with fetal surgery in the patient with obstructive atinine methodology on the assessment of glomerular filtration
uropathy have not proven to be successful.111 rate. Pediatr Res 2008;65:11316.
25. Steiner R. Interpreting the fractional excretion of sodium. Am J
Med 1984;77:699702.
REFERENCES 26. Halperin M, Goldstein M, Stinebaugh B, et al. Renal tubular
1. Brenner B, Dworkin L, Kchikawa L. Glomerular ultrafiltration. acidosis. In: Maxwell M, Kleeman C, Narins R, editors. Clinical
In: Brenner B, Rector F, editors. The Kidney, Vol.1. Philadelphia: Disorders of Fluid and Electrolyte Metabolism. New York:
WB Saunders; 1986. p. 12444. McGraw-Hill; 1987. p. 67589.
2. Hogg R, Stapleton F. Renal tubular function. In: Holliday M, 27. Rodriguez-Soriano J, Vallo A. Renal tubular acidosis. Pediatr
Barratt T, Vernier R, editors. Pediatric Nephrology. Baltimore: Nephrol 1990;4:26875.
Williams & Wilkins; 1987. p. 5977. 28. Alon U, Chan J. Inherited form of renal tubular acidosis. In:
3. Yared A, Ichikawa I. Renal blood flow and glomerular filtration Fernandes J, Saudubray J, Tada K, editors. Inherited Metabolic
rate. In: Holliday M, Barratt T, Vernier R, editors. Pediatric Diagnosis and Treatment. New York: Springer-Verlag; 1990.
Nephrology. Baltimore: Williams & Wilkins; 1987. p. 4558. p. 58595.
4. Perrone R, Madias N, Levey A. Serum creatinine as an index of 29. Wedekin M, Ehrich J, Offner G, et al. Aetiology and outcome of
renal function: New insights into old concepts. Clin Chem acute and chronic renal failure in infants. Nephrol Dial Transplant
1992;38:193353. 2008;23:157580.
5. Hellerstein S, Hunter J. Warady B. Creatinine excretion rates for 30. Goldstein S. Pediatric acute renal failure: Demographics and
evaluation of kidney function in children. Pediatr Nephrol treatment. In: Ronco C, Bellomo R, Brendolan A, editors. Sepsis,
1988;2:41924. Kidney and Multiple Organ Dysfunction. Basel: Karger; 2004.
6. Newman D, Thakkar H, Edwards R, et al. Serum cystatin C p. 28490.
measured by automated immunoassay: A more sensitive marker 31. Fadel F, Abdel Rahman A, Mohamed M, et al. Plasma neutrophil
of changes in GFR than serum creatinine. Kidney Int gelatinase-associated lipocalin as an early biomarker for prediction
1995;47:31218. of acute kidney injury after cardiopulmonary bypass in pediatric
7. Bokenkamp A, Domanetzki M, Zinck R, et al. Cystatin C serum cardiac surgery. Arch Med Sci 2012;8:2505.
concentrations underestimate glomerular filtration rate in renal 32. Devarajan P. Biomarkers for the early detection of acute kidney
transplant recipients. Clin Chem 1999;45:18668. injury. Curr Opin Pediatr 2011;23:194200.
8. Finney H, Newman D, Price C. Adult reference ranges for serum 33. Cohen M, Ritkind D. The pediatric abacus. Boca Raton: The
cystatin C, creatinine and predicted creatinine clearance. Ann Clin Parthenon Publishing Group; 2002.
Biochem 2000;31:4959. 34. Gaudio K, Siegel N, Pathogenesis and treatment of acute renal
9. Fisehbach M, Graff V, Terzie J, et al. Impact of age on reference failure. Pediatr Clin North Am 1987;34:77187.
values for serum concentration of cystatin C in children. Pediatric 35. Bailey J, Shapiro M. Abdominal compartment syndrome. Crit
Nephrol 2002;17:1046. Care Med 2000;4:239.
10. Schwartz GJ, Munoz A. Schneider M, et al. New equations to 36. Singh N, Kissoon N, Al-Mofada S, et al. Furosemide infusion
estimate GFR in children with CKD. J Am Soc Nephrol versus furosemide bolus in the postoperative pediatric cardiac
2009;20:62937. patient. Pediatr Res 1990;27:35A.
11. Moritz M, Ayus J. Prevention of hospital-acquired hyponatremia: 37. Kellum J, Decker JM. Use of dopamine in acute renal failure: A
A case for using isotonic saline. Pediatrics 2003;111:22730. meta-analysis. Crit Care Med 2001;29:152631
12. Moritz M, Ayus J. Hospital-acquired hyponatremiawhy are 38. Kidney Disease: Improving Global Outcomes (KDIGO) Acute
hypotonic parenteral fluids still being used? Nat Clin Pract Kidney Injury Work Group, KDIGO Clinical Practice Guideline
Nephrol 2007;3:37482. for Acute Kidney Injury. Kidney Int Suppl 2012;2:1138.
13. Holliday M, Segar W. The maintenance need for water in 39. Trachtman H. Sodium and water homeostasis. Pediatr Clin N Am
parenteral fluid therapy. Pediatrics 1957;19:82332. 1995;2:134363.
14. Polacek B, Vocel J, Neugebauerova L, et al. The osmotic concen- 40. Feld L, Cachero S, Springate J. Fluid needs in acute renal failure.
trating ability in healthy infants and children. Arch Dis Child Pediatr Clin N Am 1990;37:33750.
1965;40:2915. 41. Walters S, Porter C, Brophy P. Dialysis and pediatric acute kidney
15. Zappitelli M, Parikh C, Akcan-Arikan A, et al. Ascertainment and injury: Choice of renal support modality. Pediatr Nephrol
epidemiology of acute kidney injury varies with definition inter- 2008;24:3748.
pretation. Clin J Am Soc Nephrol 2008;3:94854. 42. Sutherland S, Zappitelli M, Alexander S, et al. Fluid overload and
16. Hui-Stickle S, Brewer E, Goldstein S. Pediatric ARF epidemiol- mortality in children receiving continuous renal replacement
ogy at a tertiary care center from 1999 to 2001. Am J Kidney Dis therapy: The prospective pediatric continuous renal replacement
2005;45:96101. therapy registry. Am J Kidney Dis 2010;55:31625.
17. Burry H, Dieppe P. Apparent reduction of endogenous creatinine 43. Sebestyen JF, Warady BA. Advances in pediatric renal replace-
clearance by salicylate treatment. Br Med 1976;2:1617. ment therapy. Adv Chronic Kidney Dis 2011;18:37683.
4 Renal Impairment 63
44. Warady B, Bunchman T. Dialysis therapy for children with 67. Akcan-Arikan A, Zappitelli M, Loftis L, et al. Modified RIFLE
acute renal failure: Survey results. Pediatr Nephrol 2000;15: criteria in critically ill children with acute kidney injury. Kidney
1113. Int 2007;71:102835.
45. Alon U, Bar-Maor JA, Bar-Joseph G. Effective peritoneal dialysis 68. Finney H, Newman D, Thakkar H, et al. Reference ranges for
in an infant with extensive resection of the small intestine. Am J plasma cystatin C and creatinine measurements in premature
Nephrol 1988;8:657. infants, neonates, and older children. Arch Dis Child.
46. Bonifati C, Pansini F, Torres D, et al. Antimicrobial agents and 2000;82:715.
catheter-related interventions to prevent peritonitis in peritoneal 69. Harmoinen A, Ylinen E, Ala-Houhala M, et al. Reference inter-
dialysis using evidence in the context of clinical practice. Int J Artif vals for cystatin C in pre- and full-term infants and children.
Organs 2006;29:419. Pediatr Nephrol 2000;15:1058.
47. Pedersen K, Hjortdal V, Christensen C, et al. Clinical outcome in 70. Andreoli S. Acute renal failure in the newborn. Semin Perinatol
children with acute renal failure treated with peritoneal dialysis 2004;28:11223.
after surgery for congenital heart disease. Kidney Int 2008;108: 71. Karlowicz M, Adelman R. Nonoliguric and oliguric acute renal
S816. failure in asphyxiated term neonates. Pediatr Nephrol 1995;9:
48. Zaritsky J, Warady B. Peritoneal Dialysis in the Newborn. 71822.
In: Kiessling S, Chisthti A, Alam S, editors. Kidney and Urinary 72. Blowey D, Ben D, Koren G. Interactions of drugs with the devel-
Tract Diseases in the Newborn. Springer Medical Publishing; oping kidney. Pediatr Clin N Am 1995;42:141531.
2012. 73. Elder J, Duckett J. Management of the fetus and neonate with
49. Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines hydronephrosis detected by prenatal ultrasonography. Pediatr
for the prevention and treatment of catheter-related infections Ann 1988;17:1928.
and peritonitis in pediatric patients receiving peritoneal dialysis: 74. Saphier C, Gaddipati S, Applewhite L, et al. Prenatal diagnosis
2012 update. Perit Dial Int 2012;32:S2986. and management of abnormalities in the urologic system. Clin
50. Bonifati C, Pansini F, Torres D, et al. Antimicrobial agents and Perinatol 2000;27:92145.
catheter-related interventions to prevent peritonitis in peritoneal 75. Chevalier R. Obstructive uropathy: State of the art. Pediatr Med
dialysis: Using evidence in the context of clinical practice. Int J Chir 2002;24:957.
Artif Organs 2006;29:419. 76. Kemper M, Muller-Wiefel D. Renal function in congenital anom-
51. Sojo E, Grosman M, Monteverde M, et al. Fibrin glue is useful alies of the kidney and urinary tract. Curr Opin Urol
in preventing early dialysate leakage in children on chronic peri- 2001;11:5715.
toneal dialysis. Perit Dial Int 2004;24:18690. 77. Gallini F, Maggio L, Romagnoli C, et al. Progression of renal
52. Chadha V, Warady B, Blowey D, et al. Tenckhoff catheters prove function in preterm neonates with gestational age < 32 weeks.
superior to Cook catheters in pediatric acute peritoneal dialysis. Pediatr Nephrol 2000;15:11924.
Am J Kidney Dis 2000;35:111116. 78. Feldman W, Guignard J. Plasma creatinine in the first month of
53. Auron A, Warady B, Simon S, et al. Use of the multipurpose life. Arch Dis Child 1982;57:1236.
drainage catheter for the provision of acute peritoneal dialysis in 79. Bellomo R, Chapman M, Finfer S, et al. Low-dose dopamine in
infants and children. Am J Kidney Dis 2007;49:6505. patients with early renal dysfunction: A placebo-controlled ran-
54. Bunchman T, Donckerwolcke R. Continuous arterial-venous dia- domised trial. Australian and New Zealand Intensive Care Society
hemofiltration and continuous veno-venous diahemofiltration in (ANZICS) Clinical Trials Group. Lancet 2000;356:213943.
infants and children. Pediatr Nephrol 1994;8:96102. 80. Anand S. Acute renal failure. In: Taeusch H, Ballard R, Avery M,
55. Hackbarth R, Bunchman T, Chua A, et al. The effect of vascular editors. Diseases of the Newborn. Philadelphia: W B Saunders;
access location and size on circuit survival in pediatric continuous 1991. p. 8945.
renal replacement therapy: A report from the PPCRRT registry. 81. Mercado-Deane M, Beeson J, John S. Ultrasound of renal insuf-
Int J Artif Organs 2007;30:111621. ficiency in neonates. Radiographics 2002;22:142938.
56. Strazdins V, Watson A, Harvey B, European Pediatric Peritoneal 82. Kraus S. Genitourinary imaging in children. Pediatr Clin N Am
Dialysis Working Group. Renal replacement therapy for acute 2001;48:1381424.
renal failure in children: European guidelines. Pediatr Nephrol 83. Roy R. Hydration of the low birth-weight infant. Clin Perinatol
2004;19:199207. 1975;2:393417.
57. Brophy P, Mottes T, Kudelka T, et al. AN-69 membrane reactions 84. Ohlsson A, Hosking M. Complications following oral administra-
are pH-dependent and preventable. Am J Kidney Dis 2001; tion of exchange resins in extremely low-birth-weight infants. Eur
38:1738. J Pediatr 1987;146:5714.
58. Brophy P, Somers M, Baum M, et al. Multi-centre evaluation of 85. Singh B, Sadiq H, Noguchi A, et al. Efficacy of albuterol inhala-
anticoagulation in patients receiving continuous renal replace- tion in treatment of hyperkalemia in premature neonates. J Pediatr
ment therapy (CRRT). Nephrol Dial Transplant 2005;20: 2002;141:1620.
141621. 86. Mildenberger E, Versmold H. Pathogenesis and therapy of non-
59. Chadha V, Garg U, Warady B, et al. Citrate clearance in children oliguric hyperkalemia of the premature infant. Eur J Pediatr
receiving continuous venovenous renal replacement therapy. 2002;161:41522.
Pediatr Nephrol 2002;17:81924. 87. Vemgal P, Ohlsson A. Interventions for non-oliguric hyperkalae-
60. Symons J, Chua A, Somers M, et al. Demographic characteristics mia in preterm neonates. Cochrane Database Syst Rev
of pediatric continuous renal replacement therapy: A report of the 2007;24(1):CD005257.
Prospective Pediatric Continuous Renal Replacement Therapy 88. Goldstein S. Advances in pediatric renal replacement therapy for
Registry. Clin J Am Soc Nephrol 2007;2:7328. acute kidney injury. Semin Dial 2011;24:18791.
61. Goldstein S, Somers M, Baum M, et al. Pediatric patients with 89. Alon U, Davidai G, Bentur L, et al. Oral calcium carbonate as
multi-organ system dysfunction syndrome receiving continuous phosphate binder in infants and children with chronic renal
renal replacement therapy. Kidney Int 2005;67:6538. failure. Miner Electrolyte Metab 1986;12:3205.
62. Chan J, Williams D, Roth K. Kidney failure in infants and chil- 90. American Academy of Pediatrics. Aluminum toxicity in infants
dren. Pediatr Rev 2002;23:4760. and children. Pediatrics 1996;97:41216.
63. Jetton J, Askenazi D. Update on acute kidney injury in the 91. Slatopolsky E, Burke S, Dillon M, et al. RenaGel, a nonabsorbed
neonate. Curr Opin Pediatr 2012;24:1916. calcium- and aluminum-free phosphate binder, lowers serum phos-
64. Whyte D, Fine R. Acute renal failure in children. Pediatr Rev phorus and parathyroid hormone. Kidney Int 1999;55:299307.
2008;29:299306. 92. Salusky I. A new era in phosphate binder therapy: What are the
65. Stapleton F, Jones D, Green R. Acute renal failure in neonates: options? Kidney Int 2006;105:S1015.
Incidence, etiology and outcome. Pediatr Nephrol 1987; 93. Zappitelli M, Goldstein S, Symons J, et al. Protein and calorie
1:31420. prescription for children and young adults receiving continuous
66. Drukker A, Guignard J. Renal aspects of the term and renal replacement therapy: A report from the Prospective Pediat-
preterm infant: A selective update. Curr Opin Pediatr 2002;14: ric Continuous Renal Replacement Therapy Registry Group. Crit
17582. Care Med 2008;36:323945.
64 SECTION I General
94. National Kidney Foundation. KDOQI Clinical Practice Guide- predict mortality in neonatal and pediatric noncardiac patients on
line for Nutrition in Children with CKD. Am J Kidney Dis extracorporeal membrane oxygenation. Pediatr Crit Care Med
2009;53:S1124. 2011;12:16.
95. Flynn J. Choice of dialysis modality for management of pediatric 103. North American Pediatric Renal Trials and Collaborative Studies
acute renal failure. Pediatr Nephrol 2002;17:619. (NAPRTCS). 2011 Annual Dialysis Report 2011.
96. Golej J, Kitzmueller E, Hermon M, et al. Low-volume peritoneal 104. Chevalier R, Kim A, Thornhill B, et al. Recovery following relief
dialysis in 116 neonatal and pediatric critical care patients. Eur J of unilateral ureteral obstruction in the neonatal rat. Kidney Int
Pediatr 2002;161:3859. 1999;55:793807.
97. Symons J, Brophy P, Gregory M, et al. Continuous renal replace- 105. Klahr S, Harris K, Purkerson M. Effects of obstruction on renal
ment therapy in children up to 10kg. Am J Kidney Dis functions. Pediatr Nephrol 1992;147:4302.
2003;41:9849. 106. Boone T, Allen T. Unilateral postobstructive diuresis in the
98. Pedersen K, Povlsen J, Christensen S, et al. Risk factors for acute neonate. J Urol 1992;147:43432.
rena1 failure requiring dialysis after surgery for congenital heart 107. Harris R, Yarger W. The pathogenesis of post-obstructive diure-
disease in children. Acta Anaesthesiol Scand 2007;51:13449. sis: The role of circulating natriuretic and diuretic factors, includ-
99. Blinder JJ, Goldstein SL, Lee W, et al. Congenital heart surgery ing urea. J Clin Invest 1975;56:8807.
in infants: Effects of acute kidney injury on outcomes. J Thorac 108. Rodriguez-Soriano J, Vallo A, Oliveros R, et al. Transient pseudo-
Cardiovasc Surg 2012;143:36874. hypoaldosteronism secondary to obstructive uropathy in infancy.
100. Baskin E, Saygili A, Harmanci K, et al. Acute renal failure and J Pediatr 1983:103:37580.
mortality after open-heart surgery in infants. Ren Fail 109. Yarger W, Buerkert J. Effect of urinary tract obstruction on renal
2005;27:55760. tubular function. Semin Nephrol 1982;2:1730.
101. Bojan M, Gioanni S, Vouhe P, et al. Early initiation of peritoneal 110. Alon U, Kordoff M, Broecker B, et al. Renal tubular acidosis
dialysis in neonates and infants with acute kidney injury following type IV in neonatal unilateral kidney diseases. J Pediatr
cardiac surgery is associated with a significant decrease in mortal- 1984;104:85560.
ity. Kidney Int 2012. 111. Hodges S, Patel B, McLorie G, et al. Posterior urethral valves.
102. Askenazi D, Ambalavanan N, Hamilton K, et al. Acute kidney Scientific World Journal 2009;14:111926.
injury and renal replacement therapy independently
C H A P T E R 5
Coagulopathies and
Sickle Cell Disease
Mukta Sharma Brian M. Wicklund Gerald M. Woods
Intrinsic
XIIa pathway (PTT)
XII
HMWK
K PK
HMWK
XIIa
HMWK
XI XIa
Extrinsic pathway (PT)
Ca2+
TF
IX IXa VIIa VII
VIIIa TF
Ca2+
Ca2+
PL
X X
Xa
Common pathway (PT)
Va
Ca2+
PL
When a vessel is disrupted, platelet adhesion occurs (glycoproteins IIb and IIIa) or fibrinogen are missing,
through the binding of collagen and vWF (found in the platelets do not aggregate.13,14 This results in Glanzmann
subendothelium) to the platelet membrane (Fig. 5-2). For thrombasthenia causing patients to have a serious, life-
platelet adhesion to occur, platelets must express specific long bleeding disorder.6
glycoprotein Ib receptors on their surface to bind the After aggregation, platelets function to enhance
vWF complex. If this specific glycoprotein is missing, thrombin formation. The platelet membrane provides
platelets are unable to adhere to areas of injury.8 Platelets specific binding sites for factors Xa and V causing effec-
in BernardSoulier syndrome lack glycoprotein Ib and tive assembly of the prothrombinase complex making
are unable to adhere and form the initial hemostatic thrombin.7 Thrombin formation makes a stable hemo-
plug.9 If the vWF is defective or deficient, platelets do static plug of adherent platelets surrounded by a network
not adhere to sites of vascular injury. The result is von of fibrin strands.
Willebrand disease, of which several specific types and
subtypes have been defined.1012 Very high concentrations Generation of Thrombin
of prostacyclin also can inhibit platelet adhesion to
exposed subendothelium.5 Thrombin is the enzyme responsible for transforming
liquid blood into a fibrin gel. The initial activation of
factor VII by tissue factor results in the production of
Platelet Aggregation
thrombin by the extrinsic system. Tissue factor is released
Aggregation is a complex reaction that involves platelet only after injury to the endothelial cells.
granule release, cleavage of membrane phospholipids by The majority of thrombin production results from the
phospholipases A2 and C, alterations in intracellular activation of the intrinsic coagulation system, not the
cyclic adenosine monophosphate levels, mobilization of extrinsic system. Exposed subendothelium converts
intracellular calcium, and the expression of fibrinogen factor XII to factor XIIa and thereby activates the intrin-
receptors on the platelet surface. If fibrinogen receptors sic pathway, although deficits in factor XII do not cause
5 Coagulopathies and Sickle Cell Disease 67
I
GP
lb
V
GP
GP
lb
2
GPlb Platelet IIb 3 1
GPlb
GPlb
vWF
Collagen
A B
IIb
IIb 3 3 Fg
GPlb
FIGURE 5-2 Schematic representation of ADP vWF
platelet adhesion and aggregation under flow TXA2 Thrombin
conditions. (A) Rolling of platelets over collagen- IIb3 GPlb IIb3
bound vWF mediated by GPIb. (B) Firm attach-
IIb3
IIb3
ment mediated by 21 and glycoprotein VI
GPlb
GPlb
IIb3
GPVI
GPVI
21
21
(GP VI) binding to collagen, and by IIb3)
binding tocollagen-bound vWF. (C) Platelet acti- Fibronectin Fibronectin
vation, secretion, and spreading. (D) Aggregate
formation. C D
a bleeding disorder. Activation of factors XI and IX plasminogen is converted into plasmin by tissue plas-
follows, and activated factor IX in combination with minogen activators. These activators are released from
factor VIII, calcium, and platelet phospholipid activates the vessel walls at the site of blood clotting. They bind
factor X. Activated factor VII, complexed with tissue to the fibrin clot and convert plasminogen to plasmin.
factor, activates factor IX. Factor Xa with factor V then Plasmin enzymatically degrades fibrin, fibrinogen, and
cleaves prothrombin into the active molecule thrombin, other plasma proteins, and this process results in the dis-
which can convert fibrinogen into fibrin.4,15 solution of formed clot.15,17
Formation of Fibrin
CLINICAL EVALUATION
When thrombin acts on fibrinogen, fibrin monomers
result after the proteolytic release of fibrinopeptides A There is currently no completely reliable screening test
and B. The monomeric fibrin then polymerizes into a available to evaluate hemostasis in the preoperative
gel.4,15 With additional stabilization of the fibrin gel pro- patients. A careful history, including a full family history,
vided by factor XIII, fibrin surrounds and stabilizes the remains the best means of uncovering mild bleeding
platelet plug. This process makes the multimeric fibrin problems, including von Willebrand disease or qualita-
more resistant to plasmin digestion and completes the tive platelet abnormalities.18 These disorders may easily
formation and stabilization of the blood clot.16 escape standard laboratory screening procedures, such as
Several regulatory proteins serve to localize thrombin prothrombin time (PT), activated partial thromboplastin
formation to the surface of the blood vessel. Endothelial time (aPTT), platelet count, and bleeding time. aPTT
cells have receptors for protein C. Protein S is a co-factor screening yields many false-positive results caused by
for the activation of protein C. Thrombomodulin is an both analytical problems and detection of clinically insig-
endothelial surface protein that acts in combination with nificant disorders. In addition, a normal aPTT may lead
thrombin to activate the bound protein C. Activated to a false sense of safety because it does not exclude all
protein C then degrades factors Va and VIIIa, which serious bleeding disorders. Because no method can reli-
inhibit thrombin formation.17 ably predict all bleeding complications, postoperative
Heparin-like anticoagulant molecules, present on monitoring remains important for all patients.19 Like-
endothelial cells, act in combination with antithrombin wise, patients with mild disorders who have not previ-
III to inhibit factors XIIa, XIa, IXa, and Xa and thrombin. ously undergone an operation may have no history of
Inhibition of these factors prevents the spread of clot to bleeding problems and might be identified preoperatively
uninjured adjacent vessels and the blockage of large only if screening tests are performed.18 It is important to
vessels by excessive clot formation.15,17 Endothelial cells, consider the history as the most important component of
as mentioned previously, produce PGI2 (prostacyclin), a a diagnostic strategy and to investigate thoroughly any
potent vasodilator and inhibitor of platelet aggregation story of unusual bleeding, even if the screening tests are
and adhesion. normal.20 Conversely, studies examining the utility of a
screening preoperative PT and aPTT in patients under-
going tonsillectomy and adenoidectomy concluded that
Fibrinolysis
routine screening with a PT and aPTT for all patients
The regulatory process that dissolves fibrin and regardless of history cannot be recommended.19,21 In
preserves vessel patency is called fibrinolysis. Circulating obtaining a history from the patient and parents, positive
68 SECTION I General
answers to the questions posed in Box 5-1 indicate the not consider medicine and has therefore not mentioned.
need for further evaluation.18,2224 Aspirin, ibuprofen, cough medications containing
If there is a history of abnormal bleeding, the follow- guaifenesin, and antihistamines can lead to platelet
ing points must be established. The type of bleeding (i.e., dysfunction or uncover a previously undiagnosed bleed-
petechiae, purpura, ecchymosis, and single or generalized ing disorder such as von Willebrand disease.26,27 The
bleeding sites) can give an indication of the underlying presence of other medical problems including renal
defect. Petechiae and purpura are most frequently associ- failure with uremia, hepatic failure, malignancies, gas-
ated with platelet abnormalities, either of function or trointestinal malabsorption, vascular malformations,
numbers. Von Willebrand disease is most frequently cardiac anomalies with or without repair, and autoim-
associated with mucosal bleeding, including epistaxis, mune disorders is essential to elicit because these may
whereas hemophilia is most often associated with bleed- have associated coagulopathies.
ing into joints or soft tissue ecchymosis, or both. Bleed- The physical examination is used to help narrow the
ing when the umbilical cord separates is most often differential diagnosis and guide the laboratory investiga-
associated with a deficiency in factor XIII, as is unex- tion of hemostatic disorders. Petechiae and purpuric
plained bleeding of the central nervous system.16,25 A bleeding occur with platelet and vascular abnormalities.
single bleeding site, such as repetitive epistaxis from the Mucocutaneous bleeding suggests a platelet disorder and
same nostril, is frequently indicative of a localized, ana- includes petechiae, ecchymoses, epistaxis, and genitouri-
tomic problem and not a system-wide coagulation defect. nary and gastrointestinal bleeding. Bleeding into poten-
The course or pattern of the bleeding (i.e., spontane- tial spaces such as joints, fascial planes, and the
ous or after trauma) and its frequency and duration is retroperitoneum is instead suggestive of a coagulation
important, and the pattern of inheritance (i.e., X-linked factor deficiency. Bleeding from multiple sites in an ill
or autosomal; recessive or dominant) can help narrow patient can be seen with disseminated intravascular coag-
the differential diagnosis (e.g., hemophilia A and B are ulation (DIC) or thrombotic thrombocytopenic purpura.
X-linked recessive diseases, whereas von Willebrand Hemophilia patients often have palpable purpura and
disease is autosomal dominant). deep muscle bleeding that is painful but may be difficult
Any previous or current drug therapy must be fully to detect. Findings compatible with a collagen disorder
documented, and a search is made for over-the-counter include the body habitus of Marfan syndrome; blue
medications that the patient might be taking but does sclerae; skeletal deformities; hyperextensible joints and
skin; and nodular, spider-like, or pinpoint telangiectasia.
Organomegaly may suggest an underlying malignancy,
whereas jaundice and hepatomegaly may be indicative of
Questions to Ask about Potential hepatic dysfunction.
BOX 5-1
Bleeding Problems
1. Is there any history of easy bruising, bleeding prob- LABORATORY EVALUATION
lems, or an established bleeding disorder in the
patient or any family members? When the bleeding history and/or family history suggest
2. Has excessive bleeding occurred after any previous
the possibility of a bleeding disorder, or if it is impossible
surgical procedure or dental work? Have the parents
or any siblings had excessive bleeding after any surgi- to obtain a history due to family or social circumstances,
cal or dental procedures, specifically tonsillectomy or it is customary to proceed with a series of laboratory
adenoidectomy? investigations to look for a possible bleeding diagnosis.
3. Have frequent nosebleeds occurred, and has nasal Generally, screening tests are performed first and should
packing or cautery been needed? Has bleeding include a blood cell count, PT, and aPTT (Fig. 5-3).20
without trauma occurred into any joint or muscle? Additional tests can measure fibrinogen levels, assess the
4. Does excessive bleeding or bruising occur after thrombin time, screen for inhibitors of specific coagula-
aspirin ingestion? tion factors, measure specific factor levels, and test for
5. Does significant gingival bleeding occur after tooth platelet function and von Willebrand disease.20,28 Patients
brushing?
also can be evaluated for evidence of DIC by using mul-
6. Has there been any significant postpartum
hemorrhage? tiple assays to test for the presence of various fibrinopep-
7. Has the patient been taking any medication that tides and products from the breakdown of fibrin or
might affect platelets or the coagulation system? fibrinogen.
8. If the patient is male and was circumcised, were any
problems noted with prolonged oozing after the
circumcision?
Platelet Count
9. If the patient is a child, do the parents remember The platelet count measures the adequacy of platelet
any bleeding problems when the umbilical cord numbers to provide initial hemostasis. Thrombocytope-
separated? nia (a platelet count of <150,000/L) is one of the most
10. If the patient is menstruating, does she have profuse
common problems that occur in hospitalized patients. As
menstruation?
11. Has the patient ever received any transfusions of stated previously, typical manifestations include mucocu-
blood or blood products? If so, what was the reason taneous bleeding. The risk of bleeding is inversely pro-
for the transfusion? portional to the platelet count. When the platelet count
is <50,000/L, minor bleeding occurs easily and the risk
5 Coagulopathies and Sickle Cell Disease 69
FVIII, FIX, FXI, FXII FVII deficiency Normal thrombin time Vascular compromise
deficiency Early warfarin treatment Liver disease Factor XIII deficiency
von Willebrand disease Early liver disease FII, FV, FX deficiency a2 -Antiplasmin
Heparin contamination Mild hypofibrinogenemia Weak lupus anticoagulant deficiency
or mild dysfibrinogenemia Warfarin
Vitamin K deficiency Mild disseminated
intravascular coagulation
*Repeating an abnormal coagulation screening with a mixture of 1 part patient plasma and 1 part normal plasma (mixing studies)
will normalize the test if a factor deficiency is present, but the screening test will remain abnormal if an anticoagulant is present. These
anticoagulants rarely are a cause of thromboembolic disease and even more rarely cause bleeding.
FIGURE 5-3 Screening tests for abnormal coagulation.
prothrombin, and fibrinogen and in patients with DIC or phasethe second wave of aggregationoccurs and pro-
severe liver disease.34,36 duces irreversible platelet aggregation. The second wave
of aggregation is due to release of the platelet granules
and thromboxane A2 synthesis. The release reaction is
Fibrinogen blocked by aspirin and is absent in patients with an inher-
The standard method for fibrinogen determination ited storage pool defect, congenital deficiency in throm-
measures clottable fibrinogen by using a kinetic assay. boxane A2 synthesis, or cyclooxygenase deficiency.7 The
Normal levels of fibrinogen are 150350mg/dL. As PFA-100 has become the test of choice to replace the
fibrinogen is the substrate for the final reaction in the bleeding time and is used to screen for a variety of dis-
formation of a clot and all plasma-based screening tests orders, but full characterization of platelet function
depend on the formation of a clot as the end point of the requires traditional platelet aggregation studies in a spe-
reaction, fibrinogen levels below 80mg/dL prolong cialized laboratory.
the PT, aPTT, and thrombin time and therefore make
the results uninterpretable. Large amounts of fibrin deg-
radation products interfere with the formation of fibrin
Specific Factor Assays
and cause an artificially low level of measured fibrinogen. Specific factor assays are available for all known coagula-
An immunologic-based assay for fibrinogen is used to tion, fibrinolysis, and anticoagulation factors to quantify
measure both clottable and nonclottable fibrinogen. This their levels in plasma. These tests are not indicated unless
test is most often used in identifying patients with a dys- a screening test result is abnormal. The only exception
fibrinogenemia in whom the functional level of fibrino- involves the patient with a history that is suggestive of
gen is low and the immunologic level is normal.34,36 von Willebrand disease, factor XIII deficiency, or dysfi-
brinogenemia. In these cases, the aPTT may not be sen-
sitive enough to detect the disorder. Further testing may
Inhibitor Screening Tests be justified on clinical suspicion based on the patients
Repeating the PT or aPTT by using a 1:1 mix of patient history.33,34 For von Willebrand disease, the workup con-
plasma with normal plasma is a useful procedure for sists of measuring factor VIII levels, vWF antigen levels,
investigating a prolonged PT or aPTT. Normal plasma ristocetin co-factor activity, and ristocetin-induced plate-
has, by definition, 100% levels of all factors. When mixed let aggregation. Analysis of the distribution of vWF mul-
with an equal volume of patient plasma, if there is a timers can be useful to the hematologist in identifying
minimum of 50% of any given factor present, the PT or the specific type of von Willebrand disease.1012
aPTT should normalize. Correction of the clotting time
suggests the presence of a factor deficiency whereas
lack of normalization suggests the presence of an inhibi-
Tests for Disseminated Intravascular
tor that interferes with either thrombin or fibrin Coagulation
formation.33,34 The tests that are available in most hospital laboratories
Two types of acquired inhibitors prolong the aPTT. for identification of DIC are semiquantitative fibrin or
One blocks or inactivates one of the intrinsic factors, fibrinogen degradation product assays, which involve a
whereas the other is a lupus-like inhibitor that interferes slide agglutination procedure or a d-dimer assay. An
with phospholipid-based clotting reactions. The first increased amount of these degradation products suggests
type of inhibitor occurs in 1015% of hemophilia A that either plasmin has circulated to lyse fibrin and fibrin-
patients and can occur spontaneously, but it is extremely ogen or the patients hepatic function is insufficient to
rare in nonhemophiliac children.37 The lupus-like inhibi- clear the small amounts of regularly produced degrada-
tor is associated not with bleeding problems but rather tion products. The d-dimer test is a slide agglutination
with an increased risk of thrombotic problems in adults. procedure that tests for the presence of two d subunits
Lupus-like inhibitors are mentioned because they com- of fibrin that are cross-linked by factor XIII. This test
monly cause prolongations of the aPTT.38 Specific inves- provides specific evidence that plasmin has digested the
tigation of either of these situations should be referred to fibrin clot and not fibrinogen. It is positive in patients
a coagulation reference laboratory. with DIC, in patients with resolving large intravascular
clots, and in patients with hepatic insufficiency. Specific
Platelet Function Studies assays to demonstrate the presence of soluble fibrin
monomer complexes or fibrinopeptides produced by
Platelet function studies measure in vitro platelet aggre- the conversion of prothrombin to thrombin are also
gation. In this procedure, platelet-rich plasma is incu- useful in some situations and available in specialized
bated with an agonist and then changes are noted in the laboratories.34,39
amount of light transmitted through the platelet suspen-
sion. Agonists used to induce platelet aggregation include
collagen, epinephrine, ADP, thrombin, and ristocetin. Thromboelastograph
Three distinct phases are seen in the reaction. The first Thromboelastograph is used as a functional measure of
is an initial change in the shape of the platelets, leading whole blood coagulation in pediatric cardiac surgical and
to a temporary decrease in light transmission. Next is the liver transplant patients, and is a useful monitor in
first wave of aggregation, which is a reversible platelet- patients with major trauma and patients with coagulation
platelet interaction. With additional stimulation, the final deficits.40
5 Coagulopathies and Sickle Cell Disease 71
intervention, and an adequate supply of clotting factor than FVIII to raise the plasma level. Infusion of 1 unit/
concentrate must be available to cover the childs needs kg of FIX will raise the plasma level only by 1%. Con-
before admission. The patient also must be screened for tinuous infusion of highly purified FIX, as well as FVIII,
the presence of an inhibitor to either FVIII or FIX during has been shown to prevent excessive peaks and troughs
the two to four weeks before the operation. A low-titer of factor levels, is simpler to manage, and decreases the
inhibitor may be overcome with increased doses of factor, cost by decreasing the overall amount of factor used. It
but high-titer inhibitors may require the use of activated has not shown to cause any problems with excess throm-
prothrombin complex concentrate (FEIBA) or recom- bosis.61 Recombinant FIX has a marked variability in
binant activated factor VII (rFVII) to bypass the effect dose response to infusions, and individual recovery
of the antibody against either FVIII or FIX. These studies may be needed before it is used for surgical
patients have been desensitized with daily doses of human hemostasis. Often, a 20% increase in dose is needed to
factor concentrate over a period of months to years, achieve the same factor levels as obtained by use of
restoring their response to regular infusions of factor plasma-derived FIX.62
VIII or IX.46,56,57
At our institution, on the day of surgery the hemo-
philia patient receives a bolus dose of factor (usually NEONATAL HEMOSTASIS
50units/kg of FVIII in hemophilia A patients), and a
continuous infusion of 48units/kg/h of FVIII (for the The newborns coagulation system is not fully mature
hemophilia A patient) is started to maintain a factor level until 6 months after birth. The lower levels of procoagu-
greater than 80% for the next one to two days.58 The lant, fibrinolytic, and anticoagulant proteins in neonatal
factor level is checked immediately before the operation patients complicate both operations and the care of sick
and is the final screen for the presence of an inhibitor. and preterm infants. Platelet counts are within the usual
The infusion is maintained throughout the procedure adult normal ranges. These platelets have a lower func-
and is then reduced on the second or third postoperative tion than those of adults, but enough to produce a normal
day to allow the plasma levels to decrease to 50%. bleeding time.62 Circulating coagulation factors do not
Replacement is continued for a full ten to 14 days. Daily cross the placenta, and infants with inherited deficiencies
factor levels are necessary to ensure appropriate levels. of clotting factors, fibrinolytic proteins, or natural anti-
For neurosurgical or orthopedic procedures, much longer coagulants may initially be seen in the neonatal period.
periods of factor coverageeven four to six weeksare Levels of fibrinogen, factor V, factor VIII, and vWF are
utilized, especially if significant physical therapy is within the adult normal range at birth.63 All other proco-
planned.41,46 agulants are at reduced levels, depending
Many hemophilia patients perform their own factor on gestational age. Vitamin K-dependent factors may
infusions at home supported by home care pharmacies. become further depressed in infants who are breast fed
With the advent of home nursing services, patients are and not given vitamin K at birth.62
being discharged home with prolonged periods of factor Of more concern are the low levels of anticoagulant
coverage. Hemophilia center personnel must be closely and fibrinolytic proteins. Very low levels of protein C
involved in the planning of these discharges to ensure have been associated with purpura fulminans in new-
that sufficient clotting factor is available at home and that borns. In sick infants, levels of antithrombin III and plas-
close follow-up is maintained during periods of scheduled minogen may be inadequate to deal with increased levels
home therapy. Hemophilia patients should not receive of clot-promoting activity in the blood. Sick infants with
any compounds that contain aspirin or ibuprofen. Any indwelling catheters are at significant risk of thrombotic
minor procedures that would require factor correction complications.64
should be combined with the major procedure, if possi-
ble, to save on the use of factor concentrate.
Previously, the hemophilia B patient undergoing an DISSEMINATED INTRAVASCULAR
operation had specific problems because of the thrombo- COAGULATION
genic risk inherent in the use of older FIX concentrates.
Since the advent of newer, more purified plasma-derived DIC is the inappropriate activation of both thrombin and
and recombinant-produced FIX concentrates, operative fibrin. It may follow sepsis, hypotension, hypoxemia,
interventions in hemophilia B patients have been per- trauma, malignancy, burns, and extracorporeal circula-
formed without excess thrombotic problems.59,60 tion. Hemorrhage due to the depletion of clotting factors
as well as thrombosis due to the excess formation of clot
are seen, and the end-organ damage caused by ischemia
CLOTTING FACTOR DOSING and impairment of blood flow causes irreversible disease
and death.65
Factor VIII is dosed differently from FIX, based on their Acute DIC is associated with the consumption of
half-lives. FVIII has an eight- to 12-hour half-life, and factors II, V, VIII, X, and XIII, as well as fibrinogen,
the infusion of 1 unit/kg of body weight increases the antithrombin III, plasminogen, and platelets. Review of
plasma level by 2%. If a severe hemophilia A patient the peripheral smear usually shows a microangiopathic
weighs 50kg, an infusion of 25 units/kg, or 1250 units, hemolytic anemia. The PT and aPTT may both be pro-
of FVIII will raise his factor level to 50%. FIX has a half- longed, and the fibrinogen level ultimately decreases as
life of 24 hours and must be infused in larger amounts the DIC worsens. The presence of d-dimers may indicate
5 Coagulopathies and Sickle Cell Disease 73
the presence of DIC, but they may also be elevated due of all aspirin-containing products one week before opera-
to thrombus or hepatic dysfunction. Antithrombin III tion permits correction of the cyclooxygenase deficiency
levels may be low, and the use of antithrombin III con- as new platelets are produced.6,70
centrates in septic shock may play a role in the future
treatment of DIC. However, adult studies have not shown
any improvement in mortality for patients with septi- DISORDERS OF THROMBIN GENERATION
cemia treated with antithrombin III.66 At present, the AND FIBRIN FORMATION
major therapy for DIC is correction of the underlying
disorder with fresh frozen plasma and platelet transfu- Patients with rare deficiencies of other clotting factors,
sions as indicated to support hemostasis. Low-dose such as factors XI, X, VII, V, prothrombin, and fibrino-
heparin infusions have not been shown to appreciably gen, can have clinical bleeding depending on the level of
improve the outcome.65,67 deficiency. Most of these disorders are inherited in an
autosomal recessive manner and can therefore affect both
male and female patients. Replacement therapy with
MANAGEMENT OF QUANTITATIVE AND fresh frozen plasma or, in certain situations, with pro-
QUALITATIVE PLATELET DISORDERS thrombin complex concentrates corrects the deficiency
and should be conducted under the direction of a
Thrombocytopenias are caused by either inadequate pro- hematologist.46,71
duction of platelets by the bone marrow, or by increased Vitamin K deficiency, both in the neonatal period and
destruction or sequestration of the platelets in the circu- from malabsorption, can cause deficiencies of factors II,
lation. The history and physical examination may be sug- VII, IX, and X. Treatment with 12mg of intravenous
gestive of a diagnosis that can be confirmed by laboratory vitamin K may begin to correct the deficiencies within
testing. Medication use, a family history of blood disor- four to six hours. However, if a procedure is contem-
ders, a history of recent viral infection, short stature, plated, fresh frozen plasma (15mL/kg) should be given
absent thumbs or radii, or a congenital malformation may with the vitamin K, and repeated. Also, the PT should be
indicate a defect in platelet production. The destruction monitored for correction of the coagulopathy before the
may be immunologic, as in immune thrombocytopenic operation. Laboratory monitoring should be maintained
purpura (ITP); mechanical, as in septicemia; or drug during the postoperative period to ensure continuation
induced, as in patients with sensitivity to heparin or cime- of the appropriate factor levels.5
tidine. Establishing the cause of the thrombocytopenia Patients with factor XIII deficiency often present with
determines the therapy needed to restore the platelet delayed bleeding from the umbilical cord, rebleeding
count in preparing the patient for operation. The clinical from wounds, intracranial hemorrhage, and poor wound
response to therapeutic modalities, such as a platelet healing. These problems may be treated with relatively
transfusion, can be important tests and can help direct small amounts of fresh frozen plasma (510mL/kg).
further investigations. In patients with immune-based Because factor XIII has a half-life of six days, this treat-
platelet consumptions, such as ITP, usually no response ment is usually needed only once to stop bleeding or at
is found to platelet transfusion. Moreover, only a very the time of operation.16,46 Patients with dysfibrinogene-
short response may be seen in patients with other causes mia or afibrinogenemia may be given fresh frozen plasma
of increased consumption. Management of the patient is or cryoprecipitate.46 There are ongoing trials looking at
then aimed at reducing the consumption and should a fibrinogen concentrate preparation infusion for these
involve consultation with a hematologist about the use of conditions.
corticosteroids, the use of intravenous immunoglobulin
or anti-d immunoglobulin, the discontinuation of medi-
cations, and other treatment modalities.68 FIBRINOLYTIC AND
If the thrombocytopenia is caused by a lack of produc- THROMBOTIC DISORDERS
tion of platelets, due to either aplastic anemia,
malignancy, or chemotherapy, transfusion with platelet Failure to control excess fibrinolysis can result in a bleed-
concentrates to increase the platelet count above a ing problem, and deficiencies of the naturally occurring
minimum of 50,000/L will allow minor procedures to anticoagulants may result in excess clot formation. A
be performed safely. Most surgeons and anesthesiologists severe hemorrhagic disorder due to a deficiency of 2-
prefer for the platelet count to be greater than 100,000/L antiplasmin has responded to treatment with aminocap-
before major surgery. Continued monitoring of platelet roic acid or tranexamic acid, both antifibrinolytic agents.37
counts is vital because further transfusions may be needed Congenital antithrombin III, protein S, and protein C
to keep the platelet count above 50,000/L for three to deficiencies are associated with recurrent thrombosis
five days after operation.69 and are usually controlled with oral anticoagulants.37
Qualitative platelet defects can be caused by rare con- Factor V Leiden, prothrombin G20210A, and other
genital defects such as BernardSoulier syndrome, Glanz- activated protein C resistance gene mutations will cause
mann thrombasthenia, or platelet storage pool disease. or add additional risk for thrombosis in proportion to
Alternatively, they can be caused by drug ingestions such their homozygous or heterozygous states.7274 Discon-
as an aspirin-induced cyclooxygenase deficiency. In these tinuation of the anticoagulation is needed before an
situations, transfusion of normal donor platelets provides operation. The patients will require replacement therapy
adequate hemostasis for the operation. Discontinuation during the procedure and in the postoperative period
74 SECTION I General
until the anticoagulation can be restarted. Depending on (S/HPFH). Sickle cell anemia is the most common and,
the deficiency, antithrombin III concentrates or fresh in general, the most severe form of SCD. Sickle 0-
frozen plasma can be used for replacement therapy. thalassemia patients have clinical manifestations similar
to patients with Hb SS disease. Sickle-C disease is the
second most common form of SCD and generally has a
RECOMBINANT ACTIVATED FACTOR VII more benign clinical course than does Hb SS or sickle
0-thalassemia. Sickle +-thalassemia and S/HPFH
Recombinant activated factor VII (rFVIIa) was developed patients also usually have a more benign clinical course.
for the treatment of bleeding in patients with hemophilia Patients with Hb SS disease and sickle 0-thalassemia
A or B who had inhibitors, and was approved by the generally have lower hemoglobin levels and present a
ultrasound Food and Drug Administration for this indi- greater risk under general anesthesia than do patients
cation in 1999.7577 Good hemostasis with few side effects with Hb SC disease and sickle +-thalassemia. Patients
has been found in patients with intracranial hemorrhage, with S/HPFH may actually have hemoglobin levels that
postlaparotomy and postpartum hemorrhage, hemor- approach or are normal.
rhage into the gluteal muscles (as a complication after The red cell membrane is abnormal in patients with
cholecystectomy), and for surgical prophylaxis for major SCD, and the red cell life span is shortened by hemolysis.
and minor procedures.7880 Home treatment programs for Intermittent episodes of vascular occlusion cause
those hemophilia patients who have inhibitors now use tissue ischemia, which results in acute and chronic
rFVIIa as front-line therapy for bleeding.81 Children have organ dysfunction.95 Consequently, patients with SCD
a more rapid rate of clearance (elimination mean half-life, require special considerations to prevent perioperative
1.32 hours in children vs 2.74 hours in adults).82 They complications.
also seem to have fewer side effects with this treat- Because of the nature of the complications of SCD,
ment.77,83 Although various dosages and schedules have people with this disorder are more likely than the
been studied, initial recommended therapy in hemophilia general population to need an operation during their
A or B with inhibitors is 90mg/kg intravenously every lifetime.96 According to one study, the most common
two hours until the bleeding is controlled.84 procedures were cholecystectomy; ear, nose, and throat
The off-label use of rFVIIa has been reported in procedures; orthopedic procedures; splenectomy; or
therapy-resistant severe bleeding from other conditions herniorrhaphy.97 Cholecystectomy, splenectomy, and
such as congenital factor VII deficiency, chronic liver orthopedic procedures are often required to treat com-
disease, and inherited platelet disorders.8587 Successes plications of SCD.
in patients without a known bleeding disorder who Children with SCD can require surgical evaluation
have trauma or postoperative hemorrhage also are and treatment either because of complications of their
described.83,85,88,89 These reports should be interpreted SCD or unrelated processes. Moreover, symptoms asso-
with caution because rFVIIa is currently not the standard ciated with vaso-occlusive episodes, such as abdominal
of care in any of these off-label uses and exceptional pain and bone pain with fever, may be difficult to distin-
circumstances impelled its use. It is highly recommended guish from other pathologic processes, such as cholecys-
that rFVIIa be administered under the supervision of a titis and osteomyelitis.
physician experienced in its use who can anticipate The differential diagnosis for acute abdominal pain in
the risks and respond to the complications, particularly a patient with SCD includes an uncomplicated sickle cell
risks of thrombosis, which are reported in 13% of acute pain episode (crisis), cholelithiasis, appendicitis,
patients.75,90,91 rFVIIa shows great promise in the emer- pancreatitis, ulcer, constipation, pneumonia, pericarditis,
gency treatment of uncontrolled hemorrhage for many and splenic sequestration. Whereas 50% of painful crises
situations, and is becoming the standard of care for the include abdominal pain, they are usually associated with
treatment of intracranial hemorrage.92 pain in the chest, back, and joints. However, although
previous episodes of pain that are similar in character
suggest an acute painful episode, the incidence of gall-
SICKLE CELL DISEASE stones, peptic ulcer disease, and pyelonephritis is
increased in these patients. Complications such as splenic
Sickle cell disease (SCD) is the most common disorder or hepatic sequestration are unique problems in patients
identified by neonatal blood screening with approxi- with this disease. Abdominal pain as a solitary symptom,
mately 2000 affected infants born in the ultrasound each especially when accompanied by fever, leukocytosis, and
year. Overall, the incidence of SCD exceeds that of most localized abdominal tenderness, is suggestive of pathol-
other serious genetic disorders, including cystic fibrosis ogy other than that which occurs with a sickle cell acute
and hemophilia.93,94 SCD is caused by a genetic mutation painful episode. A study that reviewed the presentation
that results in an amino acid change in the -globin and and management of acute abdominal conditions in adults
the production of sickle hemoglobin (Hb S) instead of with SCD suggested that a surgical condition is more
normal hemoglobin. The sickle cell gene, in combination likely if the pain does not resemble previous painful epi-
with any other abnormal -globin gene, results in SCD. sodes and if no precipitating event is found.98 Acute
There are many types of SCD. The most common painful episodes were relieved within 48 hours with
include sickle cell anemia (Hb SS), the sickle -thalassemias hydration and oxygen in 97% of patients, whereas no
(Hb S0 and Hb S+), hemoglobin SC disease (Hb SC) patient with a surgical disease achieved pain relief over
and sickle cell/hereditary persistence of fetal hemoglobin the same period with these modalities. The leukocyte
5 Coagulopathies and Sickle Cell Disease 75
count and serum bilirubin were not helpful in establish- Alloimmunization is minimized by using antigen-matched
ing the correct diagnosis. blood (matched for K, C, E, S, Fy, and Jk antigens).103
Vaso-occlusive episodes can also produce bone pain Regardless of transfusion status, strong multidisciplinary
and fever, symptoms that are difficult to differentiate collaboration is vital throughout the perioperative period.
from those of osteomyelitis. The majority of bone pain
in SCD is due to vaso-occlusion, but osteomyelitis sec- Intraoperative Management
ondary to Salmonella species or Staphylococcus aureus is not
infrequent.99,100 The presence of an immature leukocyte Anesthetic considerations are based more on the type of
count or elevation of the sedimentation rate, C-reactive operation than on the presence of SCD because no single
protein, or leukocyte alkaline phosphatase is suggestive anesthetic technique has been shown to be the gold
of a bone infection and may be an indication for aspira- standard. However, regional anesthetic techniques may
tion of the bone lesion. Radiographic studies including allow for opioid sparing postoperatively.104 The goals of
plain films, bone scan, or magnetic resonance imaging are anesthetic management are to avoid factors that predis-
generally less helpful but may be useful in arriving at the pose the patient to sickling (e.g., hypoxemia, hypother-
proper diagnosis when positive and combined with the mia, dehydration, and acidosis). Careful monitoring for
appropriate clinical findings.100 hypoxia, hypothermia, acidosis, and dehydration is essen-
tial. Monitoring should include arterial blood gases,
digital oxygen saturation, end-tidal carbon dioxide, tem-
Preoperative Assessment and Management perature, electrocardiogram, blood pressure, and urine
An optimal outcome requires careful preoperative, intra- output.104,108
operative, and postoperative management by a team con-
sisting of a surgeon, anesthesiologist, and hematologist. Postoperative Management
Potential sickle cell-related complications include acute
chest syndrome, pain episodes, hyperhemolytic crisis, As with the preoperative and intraoperative periods, it is
aplastic crisis, alloimmunization with delayed transfusion important to prevent hypothermia, hypoxia, and hypo-
reactions, and infections. The outcome of children with tension throughout the postoperative period. Before
SCD requiring a procedure is improved by careful atten- extubation, the patient should be awake and well-
tion to the cardiorespiratory, hemodynamic, hydration, oxygenated. Once extubated, the patient should be care-
infectious, neurologic, and nutritional status of the fully monitored with a digital oxygen saturation monitor
child.96,101103 If possible, procedures should be performed and the pulmonary status critically assessed on a continu-
when the child is in his or her usual state of health with ing basis. Continuous pulse oximetry should be provided
regard to the SCD. Attention should be directed toward in the early postoperative period. Assessment of fluid
chronic manifestations of disease because predictors of a status should continue until the patient has resumed
poor postoperative outcome include increased age, recent adequate oral intake and is able to maintain hydration
exacerbations of the disease, and preexisting infection without intravenous supplementation. All patients should
and pregnancy.104 Particular attention should be directed receive incentive spirometry as well as adequate hydra-
toward any recent history of acute chest syndrome, pneu- tion and oxygenation.
monia, wheezing, and alloimmunization. Special efforts Appropriate levels of analgesia (preferably by a con-
must be made to avoid perioperative hypoxia, hypother- tinuous intravenous line and patient-controlled analgesia,
mia, acidosis, and dehydration because any of these events if appropriate) should be provided so the patient is com-
can result in serious morbidity. fortable for ambulation and for vigorous pulmonary
Many centers perform preoperative transfusions with toilet. The patient must be monitored closely for the
the aim of reducing the complications of surgery and occurrence of pulmonary edema or atelectasis that can
anesthesia.105 The largest study that examined the role of progress to acute chest syndrome.109
transfusion in the preoperative management of sickle cell
anemia was a randomized study that compared exchange Specific Surgical Conditions
transfusion (with a goal of achieving an Hb value of
>10g/dL and Hb S value of <30%) versus simple transfu- Adenotonsillectomy
sion (to achieve an Hb value of >10g/dL).97 This study Adenotonsillectomy is a fairly common procedure in
concluded that not only was simple transfusion as effec- children with SCD. Adenotonsillar hypertrophy, which
tive as exchange transfusion in preventing perioperative may be associated with early functional hyposplenism and
complications, but it also provided a significantly lower obstructive sleep apnea (OSA) secondary to enlarged
rate of transfusion-related complications. The question adenoids, occurs somewhat frequently.96, 110,111 As with
about which procedures are safe to perform in children other types of surgery, preoperative transfusions should
with SCD without preoperative transfusion remains con- be performed before operation.112 Clinicians should be
troversial because there is a lack of randomized control- aware that postoperative complications may be greater in
led trials to answer this question. However, transfusion patients who are younger or have OSA.96,113
only to increase the Hb level to 10g/dL for major pro-
cedures and blood replacement for both profound anemia Cholelithiasis and Cholecystectomy
of less than 5g/dL and intraoperative hemorrhage appear
appropriate.106 Several studies suggest that minor proce- Abdominal operations such as cholecystectomy and
dures can be safely undertaken without transfusion.96,105,107 splenectomy are the most frequent abdominal procedures
76 SECTION I General
26. Shen YM, Frenkel EP. Acquired platelet dysfunction. Hematol 53. Lusher JM, Warrier I. Hemophilia. Pediatr Rev 1991;12:
Oncol Clin North Am 2007;21:64761.vi 27581.
27. George JNM, Shattil SJM. The clinical importance of acquired 54. Kasper CK, Boylen AL, Ewing NP, et al. Hematologic
abnormalities of platelet function. N Engl J Med 1991; management of hemophilia A for surgery. JAMA 1985;253:
324:2739. 127983.
28. Acosta M, Edwards R, Jaffee IM, et al. A practical approach to 55. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis
pediatric patients referred with an abnormal coagulation profile. versus episodic treatment to prevent joint disease in boys with
Arch Pathol Lab Med 2005;129:101116. severe hemophilia. N Engl J Med 2007;357:535.
29. Merck Manual Online Series: Thrombocytopenia and Platelet 56. Scharf R, Kucharski W, Nowak T. Surgery in hemophilia A
Dysfunction. In: Porter R, editor. Hematology and Oncology. patients with factor VIII inhibitor: 10-year experience. World J
Whitehouse Station, NJ: Merck & Co; 2008. Surg 1996;20:117181.
30. Kam PC. Anaesthetic management of a patient with thrombocy- 57. Jimenez-Yuste V, Rodriguez-Merchan EC, Alvarez MT, et al.
topenia. Curr Opin Anaesthesiol 2008;21:36974. Controversies and challenges in elective orthopedic surgery in
31. Harrison P. The role of PFA-100 testing in the investigation and patients with hemophilia and inhibitors. Semin Hematol
management of haemostatic defects in children and adults. Br J 2008;45:S647.
Haematol 2005;130:310. 58. Montgomery RE. Hemophilia and von Willebrand disease. In:
32. Koscielny J, von Tempelhoff GF, Ziemer S, et al. A practical Nathan D, Orkin S, editors. Nathan and Oskis Hematology of
concept for preoperative management of patients with impaired Infancy and Childhood. 6th ed. Philadelphia: WB Saunders; 2003.
primary hemostasis. Clin Appl Thromb Hemost 2004;10: p. 1547.
15566. 59. Scharrer I. The need for highly purified products to treat hemo-
33. Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an philia B. Acta Haematol 1995;94(Suppl 1):27.
abnormal prothrombin time, activated partial thromboplastin 60. Shapiro AD, Di Paola J, Cohen A, et al. The safety and efficacy
time, and bleeding time in adults. Mayo Clin Proc of recombinant human blood coagulation factor IX in previously
2007;82:86473. untreated patients with severe or moderately severe hemophilia
34. Wicklund B. The bleeding child: Congenital and acquired disor- B. Blood 2005;105:51825.
ders. In: Hillyer C, Strauss R, Luban N, editors. Handbook of 61. Kobrinsky N. Management of hemophilia during surgery. In:
Pediatric Transfusion Medicine. Boston: Elsevier; 2004. Forbes C, Aledort L, Madhok R, editors. Hemophilia. Oxford:
35. Israels S. Factor XIII deficiency. emedicine, Omaha: WebMD; Chapman & Hall; 1997. p. 242.
2007. 62. Shapiro AD. Coagulation factor concentrates. In: Goodnight S,
36. Goodnight S, Hathaway W, editors. Disorders of Hemostasis and Hathaway W, editors. Disorders of Hemostasis and Thrombosis:
Thrombosis. New York: McGraw-Hill; 2001. A Clinical Guide. New York: McGraw-Hill; 2001. p. 505.
37. Lusher J. Approach to the bleeding patient. In: Nathan D, Orkin 63. Andrew M, Paes B, Milner R, et al. Development of the human
S, editors. Nathan and Oskis Hematology of Infancy and Child- coagulation system in the full-term infant. Blood 1987;70:
hood. 5th ed. Philadelphia, WB: Saunders; 1998. 16572.
38. Shapiro SS, Thiagarajan P. Lupus anticoagulants. Prog Hemost 64. Gibson B. Normal and disordered coagulation. In: Hann I,
Thromb 1982;6:26385. Gibson B, Letsky E, editors. Fetal and Neonatal Haematology.
39. Levi M, Ten Cate H. Disseminated intravascular coagulation. London: Bailliere Tindall; 1991. p. 123.
N Engl J Med 1999;341:58692. 65. Bick RL. Disseminated intravascular coagulation and related syn-
40. Pivalizza E, Pivalizza P, Gottschalk L, et al. Celite-Activated dromes: A clinical review. Semin Thromb Hemost 1988;14:
Thrombelastography in Children. J Clin Anesth 2001;1:203. 299338.
41. Soucie J, Evatt B, Jackson D. Occurrence of hemophilia in the 66. van Beek EJ, von der Mohlen MA, ten Cate JW, et al. Anti-
United States. The Hemophilia Surveillance System Project thrombin III concentrate in the treatment of DIC: A retrospective
Investigators. Am J Hematol 1998;59:28894. follow-up study. Neth J Med 1994;45:20610.
42. Pool JG, Gershgold EJ, Pappenhagen AR. High-potency antihae- 67. Albisetti M, Andrew M. Hemostatic abnormalities. In: de Alarcon
mophilic factor concentrate prepared from cryoglobulin precipi- P, Werner E, editors. Neonatal Hematology. Cambridge: Cam-
tate. Nature 1964;203:312. bridge University Press; 2005. p. 31048.
43. Kasper CK, Lusher JM. Recent evolution of clotting factor con- 68. George JN. Diagnosis, clinical course, and management of
centrates for hemophilia A and B. Transfusion Practices Commit- idiopathic thrombocytopenic purpura. Curr Opin Hematol
tee. Transfusion 1993;33:42234. 1996;3:33540.
44. Mannucci PM, Chediak J. Treatment of von Willebrand disease 69. Jackson D. Management of thrombocytopenia. In: Coleman R,
with a high-purity factor VIII/von Willebrand factor concentrate: Hirsh J, Marder V, editors. Hemostasis and Thrombosis: Basic
A prospective, multicenter study. Blood 2002;99:4506. Principles and Clinical Practice. 2nd ed. Philadelphia: JB
45. Levine PH. Delivery of health care in hemophilia. Ann N Y Acad Lippincott; 1987. p. 530.
Sci 1975;240:2017. 70. Salzman E. Hemostatic problems in surgical patients. In: Coleman
46. Hilgartner MW. Factor Replacement Therapy. In: Hilgartner R, Hirsh J, Marder V, editors. Hemostasis and Thrombosis: Basic
MW, Pochedly C, editors. Hemophilia in the Child and Adult. Principles and Clinical Practice. 2nd ed. Philadelphia, JB:
New York: Raven Press; 1989. p. 126. Lippincott; 1987.
47. Soucie JM, Nuss R, Evatt B, et al. Mortality among males with 71. Greenberg C. Hemostasis: Pathophysiology and management
hemophilia: Relations with source of medical care. The Hemo- of clinical disorders. In: Sabiston DJ, editor. Sabistons
philia Surveillance System Project Investigators. Blood 2000; Essentials of Surgery. Philadelphia: WB Saunders; 1987.
96:43742. p. 79.
48. Report on the Universal Data Collection Program. Atlanta: 72. Bick RL. Prothrombin G20210A mutation, antithrombin, heparin
Centers for Disease Control and Prevention; 2005. co-factor II, protein C, and protein S defects. Hematol Oncol Clin
49. Kernoff PB, Lee CA, Karayiannis P, et al. High risk of non-A North Am 2003;17:936.
non-B hepatitis after a first exposure to volunteer or commercial 73. Nicolaes GA, Dahlback B. Activated protein C resistance
clotting factor concentrates: Effects of prophylactic immune (FV[Leiden]) and thrombosis: Factor V mutations causing
serum globulin. Br J Haematol 1985;60:46979. hypercoagulable states. Hematol Oncol Clin North Am 2003;17:
50. Troisi CL, Hollinger FB, Hoots WK, et al. A multicenter study 3761, vi.
of viral hepatitis in a United States hemophilic population. Blood 74. Whiteman T, Hassouna HI. Hypercoagulable states. Hematol
1993;81:41218. Oncol Clin North Am 2000;14:35577.viii.
51. MASAC Recommendations Concerning the Treatment of 75. Hay CR, Negrier C, Ludlam CA. The treatment of bleeding in
Hemophilia and Other Bleeding Disorders. National Hemophilia acquired haemophilia with recombinant factor VIIa: A multicen-
Foundation; revised. tre study. Thromb Haemost 1997;78:14637.
52. Mei B, Pan C, et al. Rational design of a fully active, long-acting 76. Hedner U. Recombinant coagulation factor VIIa: From the
PEGylated factor VIII for hemophilia A treatment. Blood concept to clinical application in hemophilia treatment in 2000.
2010;116(2):2709. Semin Thromb Hemost 2000;26:3636.
78 SECTION I General
77. Hedner U, Bjoern S, Bernvil SS, et al. Clinical experience with 99. Epps CH Jr, Bryant DD 3rd, Coles MJ, et al. Osteomyelitis in
human plasma-derived factor VIIa in patients with hemophilia A patients who have sickle-cell disease: Diagnosis and management.
and high-titer inhibitors. Haemostasis 1989;19:33543. J Bone Joint Surg Am 1991;73:128194.
78. Arkin S, Cooper HA, Hutter JJ, et al. Activated recombinant 100. Chambers JB, Forsythe DA, Bertrand SL, et al. Retrospective
human coagulation factor VII therapy for intracranial hemorrhage review of osteoarticular infections in a pediatric sickle cell age
in patients with hemophilia A or B with inhibitors: Results of the group. J Pediatr Orthop 2000;20:6825.
NovoSeven emergency-use program. Haemostasis 1998;28: 101. Sutton J, et al. Surgical management of patients with sickle cell
938. syndromes. In: Mankad V, Moore R, editors. Sickle Cell Disease:
79. Liebman HA, Chediak J, Fink KI, et al. Activated recombinant Pathophysiology, Diagnosis, and Management. Westport, CT:
human coagulation factor VII (rFVIIa) therapy for abdominal Praeger; 1992. p. 36486.
bleeding in patients with inhibitory antibodies to factor VIII. Am 102. Ware RE, Filston HC. Surgical management of children with
J Hematol 2000;63:10913. hemoglobinopathies. Surg Clin North Am 1992;72:122336.
80. Shapiro AD, Gilchrist GS, Hoots WK, et al. Prospective, ran- 103. Management of Sickle Cell Disease. 4th ed. NIH Publication No.
domised trial of two doses of rFVIIa (NovoSeven) in haemophilia 022117, 2002.
patients with inhibitors undergoing surgery. Thromb Haemost 104. Haxby E, Flynn F, Bateman C. Anaesthesia for patients with sickle
1998;80:7738. cell disease or other haemoglobinopathies. Anaesth Intensive Care
81. Santagostino E, Gringeri A, Mannucci PM. Home treatment with Med 2007;8:21719.
recombinant activated factor VII in patients with factor VIII 105. Amrolia PJ, Almeida A, Halsey C, et al. Therapeutic challenges
inhibitors: The advantages of early intervention. Br J Haematol in childhood sickle cell disease: I. Current and future treatment
1999;104:226. options. Br J Haematol 2003;120:72536.
82. Erhardtsen E. Pharmacokinetics of recombinant activated factor 106. Koshy M, Weiner SJ, Miller ST, et al. Surgery and anesthesia in
VII (rFVIIa). Semin Thromb Hemost 2000;26:38591. sickle cell disease. Cooperative Study of Sickle Cell Diseases.
83. Lusher J, Ingerslev J, Roberts H, et al. Clinical experience with Blood 1995;86:367684.
recombinant factor VIIa. Blood Coagul Fibrinolysis 1998; 107. Hirst C, Williamson L. Preoperative blood transfusions for sickle
9:11928. cell disease. Cochrane Database Syst Rev 2001. CD003149.
84. NovoSeven [package insert]. Princeton, NJ, Novo Nordisk, Inc., 108. Mankad A. Anesthetic management of patients with sickle cell
2006. disease. In: Mankad V, Moore R, editors. Sickle Cell Disease:
85. Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion Pathophysiology, Diagnosis, and Management. Westport, CT:
medicine. Transfusion 2002;42:11424. Praeger; 1992. p. 35163.
86. Mariani G, Testa MG, Di Paolantonio T, et al. Use of recom- 109. Castro O, Brambilla DJ, Thorington B, et al. The acute chest
binant, activated factor VII in the treatment of congenital factor syndrome in sickle cell disease: Incidence and risk factors. The
VII deficiencies. Vox Sang 1999;77:1316. Cooperative Study of Sickle Cell Disease. Blood 1994;84:6439.
87. Poon MC, dOiron R. Recombinant activated factor VII (Novo- 110. Kemp JS. Obstructive sleep apnea and sickle cell disease. J Pediatr
Seven) treatment of platelet-related bleeding disorders. Interna- Hematol Oncol 1996;18:1045.
tional Registry on Recombinant Factor VIIa and Congenital 111. Wali YA, al Okbi H, al Abri R. A comparison of two transfusion
Platelet Disorders Group. Blood Coagul Fibrinolysis 2000; regimens in the perioperative management of children with sickle
11(Suppl 1):S5568. cell disease undergoing adenotonsillectomy. Pediatr Hematol
88. Martinowitz U, Kenet G, Segal E, et al. Recombinant activated Oncol 2003;20:713.
factor VII for adjunctive hemorrhage control in trauma. J Trauma 112. Duke RL, Scott JP, Panepinto JA, et al. Perioperative management
2001;51:4319. of sickle cell disease children undergoing adenotonsillectomy.
89. McMullin NR, Kauvar DS, Currier HM, et al. The clinical and Otolaryngol Head Neck Surg 2006;134:3703.
laboratory response to recombinant factor VIIA in trauma and 113. Halvorson DJ, McKie V, McKie K, et al. Sickle cell disease
surgical patients with acquired coagulopathy. Curr Surg and tonsillectomy. Preoperative management and postoperative
2006;63:24651. complications. Arch Otolaryngol Head Neck Surg 1997;123:
90. Mahmoud A, Al-Ruzzeh S, McKeague H, et al. Systemic venous 68992.
thrombosis after recombinant factor VIIa in the control of bleed- 114. Lachman BS, Lazerson J, Starshak RJ, et al. The prevalence of
ing after cardiac surgery. Tex Heart Inst J 2007;34:4858. cholelithiasis in sickle cell disease as diagnosed by ultrasound and
91. OConnell KA, Wood JJ, Wise RP, et al. Thromboembolic adverse cholecystography. Pediatrics 1979;64:6013.
events after use of recombinant human coagulation factor VIIa. 115. Sarnaik S, Slovis TL, Corbett DP, et al. Incidence of cholelithiasis
JAMA 2006;295:2938. in sickle cell anemia using the ultrasonic gray-scale technique.
92. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the J Pediatr 1980;96:10058.
Management of Spontaneous Intracerebral Hemorrhage in 116. Suell MN, Horton TM, Dishop MK, et al. Outcomes for children
Adults. 2007 Update: A Guideline from the American Heart with gallbladder abnormalities and sickle cell disease. J Pediatr
Association/American Stroke Association Stroke Council, High 2004;145:61721.
Blood Pressure Research Council, and the Quality of Care and 117. Haberkern CM, Neumayr LD, Orringer EP, et al. Cholecystec-
Outcomes in Research Interdisciplinary Working Group; the tomy in sickle cell anemia patients: Perioperative outcome of 364
American Academy of Neurology affirms the value of this cases from the National Preoperative Transfusion Study. Preop-
guideline as an educational tool for neurologists. Stroke erative Transfusion in Sickle Cell Disease Study Group. Blood
2007;38:200123. 1997;89:153342.
93. American Academy of Pediatrics: Health supervision for children 118. Pappis CH, Galanakis S, Moussatos G, et al. Experience of
with sickle cell disease. Pediatrics 2002;109:52635. splenectomy and cholecystectomy in children with chronic
94. (CORN) TCoRNfGS. National Newborn Screening Report haemolytic anaemia. J Pediatr Surg 1989;24:5436.
1992. New York, 1995. 119. Stephens CG, Scott RB. Cholelithiasis in sickle cell anemia: Sur-
95. Lane PA. Sickle cell disease. Pediatr Clin North Am gical or medical management. Arch Intern Med 1980;140:
1996;43:63964. 64851.
96. Buck J, Davies SC. Surgery in sickle cell disease. Hematol Oncol 120. Ware R, Filston HC, Schultz WH, et al. Elective cholecystectomy
Clin North Am 2005;19:897902.vii in children with sickle hemoglobinopathies: Successful outcome
97. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison using a preoperative transfusion regimen. Ann Surg 1988;
of conservative and aggressive transfusion regimens in the peri- 208:1722.
operative management of sickle cell disease. The Preoperative 121. Miltenburg DM, Schaffer R 3rd, Breslin T, et al. Changing
Transfusion in Sickle Cell Disease Study Group. N Engl J Med indications for pediatric cholecystectomy. Pediatrics 2000;105:
1995;333:20613. 12503.
98. Baumgartner F, Klein S. The presentation and management of the 122. Ware RE, Schultz WH, Filston HC, et al. Diagnosis and manage-
acute abdomen in the patient with sickle-cell anemia. Am Surg ment of common bile duct stones in patients with sickle hemo-
1989;55:6604. globinopathies. J Pediatr Surg 1992;27:5725.
5 Coagulopathies and Sickle Cell Disease 79
123. Dubois F, Icard P, Berthelot G, et al. Coelioscopic cholecystec- 129. Emond AM, Collis R, Darvill D, et al. Acute splenic sequestration
tomy: Preliminary report of 36 cases. Ann Surg 1990;211:602. in homozygous sickle cell disease: Natural history and manage-
124. Gadacz TR, Talamini MA, Lillemoe KD, et al. Laparoscopic ment. J Pediatr 1985;107:2016.
cholecystectomy. Surg Clin North Am 1990;70:124962. 130. Aquino VM, Norvell JM, Buchanan GR. Acute splenic complica-
125. Tagge EP, Othersen HB Jr, Jackson SM, et al. Impact of laparo- tions in children with sickle cell-hemoglobin C disease. J Pediatr
scopic cholecystectomy on the management of cholelithiasis in 1997;130:9615.
children with sickle cell disease. J Pediatr Surg 1994;29:20913. 131. Pegelow CH, Wilson B, Overturf GD, et al. Infection in splenec-
126. Ware RE, Kinney TR, Casey JR, et al. Laparoscopic cholecystec- tomized sickle cell disease patients. Clin Pediatr 1980;19:1025.
tomy in young patients with sickle hemoglobinopathies. J Pediatr 132. Nouri A, de Montalembert M, Revillon Y, et al. Partial splenec-
1992;120:5861. tomy in sickle cell syndromes. Arch Dis Child 1991;66:10702.
127. Curro G, Meo A, Ippolito D, et al. Asymptomatic cholelithiasis 133. Svarch E, Vilorio P, Nordet I, et al. Partial splenectomy in chil-
in children with sickle cell disease: Early or delayed cholecystec- dren with sickle cell disease and repeated episodes of splenic
tomy? Ann Surg 2007;245:1269. sequestration. Hemoglobin 1996;20:393400.
128. Gill FM, Sleeper LA, Weiner SJ, et al. Clinical events in the first 134. Hicks BA, Thompson WR, Rogers ZR, et al. Laparoscopic
decade in a cohort of infants with sickle cell disease. Cooperative splenectomy in childhood hematologic disorders. J Laparoendosc
Study of Sickle Cell Disease. Blood 1995;86:77683. Surg 1996;6(Suppl 1):S314.
C H A P T E R 6
Extracorporeal Membrane
Oxygenation
Alejandro V. Garcia Arul S. Thirumoorthi Charles J.H. Stolar
Extracorporeal membrane oxygenation (ECMO) is a life- mechanical ventilation, and the trial was stopped before
saving technology that employs partial heart/lung bypass completion.9 However, Bartlett and colleagues noted that
for extended periods. It provides gas exchange and per- all of the patients in the study had irreversible pulmonary
fusion for patients with acute, reversible cardiac or res- fibrosis before the initiation of ECMO. In 1976, they
piratory failure. This affords the patients cardiopulmonary reported the first series of infants with ECMO.10 Six
system a time to rest, during which the patient is spared (43%) of 14 babies with respiratory distress syndrome
the deleterious effects of high airway pressure, high FiO2, survived. Many of these infants were premature and
traumatic mechanical ventilation, and impaired per- weighed less than 2kg. In addition, 22 patients with
fusion. As of 2011, the Extracorporeal Life Support meconium aspiration syndrome had a 70% survival rate,
Organization (ELSO) has registered approximately although these neonates tended to be larger.
40,000 neonates and children treated with ECMO for a Since then, despite study design issues, three rand-
variety of cardiopulmonary disorders. The number of omized controlled trials and a number of retrospective
centers providing extracorporeal support and reporting published reports have confirmed the efficacy of ECMO
to ELSO continues to increase along with the total over conventional mechanical ventilation.1118 By 1996,
number of cases.1 113 centers had ECMO programs registered with ELSO.1
Over the next two decades, improvements in technology,
a better understanding of the pathophysiology of pulmo-
HISTORY nary failure, and a greater experience using ECMO have
contributed to improved outcomes for infants with res-
The initial effort to develop extracorporeal bypass came piratory failure. In 2003, the University of Michigan
from cardiac surgeons. Their goal was to correct intra reported an association between ECMO volume and an
cardiac lesions and, therefore, they needed to arrest the observed reduction in neonatal mortality seen in that
heart, divert and oxygenate the blood, and perfuse the state between 1980 and 1999.19
patient so that repair could be performed. The first car- ELSO, formed in 1989, is a collaboration of health
diopulmonary bypass circuits involved cross circulation care professionals and scientists with an interest in
between the patient and another subject (usually the ECMO. The organization provides the medical com-
patients mother or father) acting as both the pump and munity with guidelines, training manuals and courses,
the oxygenator.2 and a forum in which interested individuals can meet and
The first attempts at establishing cardiopulmonary discuss the future of extracorporeal life support. The
bypass and oxygenation by complete artificial circuitry group also provides a registry to investigators for the
were constructed with disk-and-bubble oxygenators, and collection of data from most centers with an ECMO
were limited because of hemolysis encountered by direct program throughout the world. This database provides
mixing of oxygen and blood. The discovery of heparin valuable information for analysis of this life-saving
and the development of semipermeable membranes (sili- biotechnology.20,21
cone rubber) capable of supporting gas exchange by dif-
fusion were major advancements toward the development
of ECMO.3 During the 1960s and early 1970s, this sili- CLINICAL APPLICATIONS
cone membrane was configured into a number of oxy-
genator models.47 Neonates are the patients who benefit most from ECMO.
In 1972, the first successful use of prolonged cardio Cardiopulmonary failure in this population secondary to
pulmonary bypass was reported.8 The patient had sus- meconium aspiration syndrome (MAS), congenital dia-
tained a ruptured aorta following a motorcycle accident. phragmatic hernia (CDH), persistent pulmonary hyper-
Venoarterial extracorporeal bypass support was main- tension of the newborn (PPHN), and congenital cardiac
tained for three days. A multicenter prospective rand- disease are the most common pathophysiologic processes
omized trial sponsored by the National Heart, Lung, and requiring ECMO. In children, the most common disor-
Blood Institute (a branch of the National Institutes of ders treated with ECMO are viral and bacterial pneumo-
Health) studied the efficacy of ECMO for adult respira- nia, acute respiratory distress syndrome (ARDS), acute
tory distress syndrome. In 1979, they concluded that the respiratory failure (non-ARDS), sepsis, and cardiac
use of ECMO had no advantage over conventional disease. Treatment of patients who cannot be weaned
80
6 Extracorporeal Membrane Oxygenation 81
from bypass after cardiac surgery and patients with Treatment for PPHN is directed at decreasing right-
end-stage ventricular failure needing a bridge to heart to-left shunting and increasing pulmonary blood flow.
transplantation are areas where ECMO use is increas- Previously, most newborns were treated with hyperven-
ing.1,22,23 Some less frequently used indications for ECMO tilation, induction of alkalosis, neuromuscular blockade,
include respiratory failure secondary to smoke inhala- and sedation. Unfortunately, these therapies have not
tion,24 severe asthma,25 rewarming of hypercoagulopathic/ reduced morbidity, mortality, or the need for ECMO.
hypothermic trauma patients,26 and maintenance of an ECMO allows for the interruption of the hypoxia-
organ donor pending liver allograft harvest and induced negative cycle of increased smooth muscle tone
transplantation.27 and vasoconstriction. ECMO provides richly oxygenated
blood and allows the pulmonary blood pressure to return
to normal subsystemic values without the iatrogenic
PATHOPHYSIOLOGY OF NEWBORN complications encumbered by overly aggressive conven-
PULMONARY HYPERTENSION tional therapy.
Data recommending permissive hypercapnia and
Pulmonary vascular resistance (PVR) is the hallmark and spontaneous respirations as principles of treatment for
driving force of the fetal circulation. Normal fetal circu- these children have been reported.29 Hyperventilation
lation is characterized by PVR that exceeds systemic and neuromuscular blockade are not part of the treat-
pressures, resulting in higher right-sided heart pressures ment strategy. This strategy has decreased morbidity,
and, therefore, preferential right-to-left blood flow. The mortality, and the need for ECMO in several centers.
fetal umbilical vein carries oxygenated blood from the
placenta to the inferior vena cava via the ductus venosus.
Because of the high PVR, the majority of the blood that PATIENT SELECTION CRITERIA
reaches the right atrium from the inferior vena cava is
directed to the left atrium through the foramen ovale. The selection of patients as potential ECMO candidates
The superior vena cava delivers deoxygenated blood to continues to remain controversial. The selection criteria
the right atrium that is preferentially directed to the right are based on data from multiple institutions, patient
ventricle and pulmonary artery. This blood then takes the safety, and mechanical limitations related to the equip-
path of least resistance and shunts from the main pulmo- ment. The risk of performing an invasive procedure that
nary artery directly to the descending aorta via the ductus requires heparinization of a critically ill infant or child
arteriosus, bypassing the pulmonary vascular bed and the must be weighed against the predicted mortality of the
left side of the heart. Therefore, as a consequence of patient with conventional therapy alone. A predictive
these anatomic right-to-left shunts, the lungs are almost mortality of greater than 80% after exhausting all con-
completely bypassed during fetal circulation. ventional therapies is the criterion most institutions
At birth, with the infants initial breath, the alveoli follow to select patients for ECMO. These criteria are
distend and begin to fill with air. This is paralleled by subjective and will vary between facilities based on local
relaxation of the muscular arterioles of the pulmonary clinical experience and available technologies. All ECMO
circulation and the expansion of the pulmonary vascular centers must develop their own criteria and continually
bed. This leads to a rapid drop in PVR to below systemic evaluate their patient selection based on ongoing out-
levels that causes the left atrial pressure to become higher comes data.
than the right atrial pressure. The result is closure of the Recommended pre-ECMO studies are listed in Box
foramen ovale, and all venous blood flows from the right 6-1. The definition of conventional therapy is not con-
atrium to the right ventricle and into the pulmonary sistent for each indication. Nevertheless, ECMO is indi-
artery. The ductus arteriosus also closes at this time. cated when (1) there is a reversible disease process;
Therefore, all fetal right-to-left circulation ceases, com- (2) the ventilator treatment is causing more harm than
pleting separation of the pulmonary and systemic circula- good; and (3) tissue oxygenation requirements are not
tions. Anatomic closure of these structures takes several being met. A discussion of generally accepted selection
days to weeks. Thus, maintaining systemic pressure criteria for using neonatal ECMO follows.
greater than the pulmonary circulation is vital to sustain-
ing normal circulation.
Failure of the transition from fetal circulation to
newborn circulation is described as PPHN or persistent
fetal circulation (PFC).28 Clinically, PPHN is character- BOX 6-1 Recommended Pre-ECMO Studies
ized by hypoxemia out of proportion to pulmonary
parenchymal or anatomic disease. In hypoxic fetuses and Head ultrasonography
infants, the proliferation of smooth muscle in the arteri- Cardiac echocardiography
oles may extend far beyond the terminal bronchioles, Chest radiography
resulting in thickened and more reactive vessels. In Complete blood cell count, with platelets
Type and cross-match of blood
response to hypoxia, these vessels undergo significant
Electrolytes, calcium
self-perpetuating vasoconstriction. Although sometimes Coagulation studies (prothrombin time, partial thrombo-
idiopathic, PPHN can occur secondary to a number of plastin time, fibrinogen, fibrin degradation products)
disease processes such as MAS, CDH, polycythemia, and Serial arterial blood gas analysis
sepsis.
82 SECTION I General
ventilation was emphasized. Low-pressure ventilator set- These patients are plagued with pulmonary hypertension
tings were used and a persistent PaCO2 of 5060mmHg and have pulmonary hypoplasia, both on the ipsilateral
and a PaO2 of 50-70mmHg were allowed. With careful and contralateral sides. Often, pulmonary insufficiency
attention to maintaining a preductal oxygen saturation ensues and a vicious cycle of hypoxia, hypercarbia, and
greater than 90% or PaO2 of 60mmHg or greater, 15 acidosis is very detrimental. This process must be inter-
infants who met ECMO criteria with PPHN and in rupted by medical management, which has vastly
severe respiratory failure were initially treated with this improved over the past two decades with the use of per-
approach and survived without ECMO. missive hypercapnia/spontaneous respiration, pharmaco-
logic therapy, and delayed elective repair.
Risk Assessment Various other strategies have been tried to manage
critically ill newborns with CDH.39 High-frequency
Because of the invasive nature of ECMO, and the poten- oscillation may have its major role in forestalling respira-
tially life-threatening complications, investigators have tory failure when used as a front end strategy rather than
worked to develop an objective set of criteria to predict as a rescue therapy.40 Surfactant plays no more than an
which infants will have an 80% mortality without ECMO. anecdotal role. Nitric oxide may be helpful as a vasodila-
The two most commonly used measurements for neona- tor in the treatment of pulmonary hypertension in these
tal respiratory failure are the alveolar-arterial oxygen gra- patients. Other pulmonary vasculature vasodilators such
dient ([A a]DO2) and the oxygenation index (OI), which as epoprostenol, sildenafil, and iloprost are starting to
are calculated as follows: demonstrate significant efficacy in babies with CDH.
The primary indicator for ECMO in the CDH patient
( A a )DO2 = ( Patm 47)( FiO2 ) [( PaCO2 )/ 0.8] PaO2 occurs when tissue oxygen requirements are not being
met, as evidenced by progressive metabolic acidosis,
where Patm is the atmospheric pressure and FiO2 is the mixed venous oxygen desaturation, and multiple organ
inspired concentration of oxygen. failure. The other major indicator is mounting iatrogenic
pulmonary injury.
OI = MAP FiO2 100/ PaO2
The goal is to maintain preductal oxygen saturations
where MAP is the mean airway pressure. between 9095%. Spontaneous breathing is preserved by
Although criteria for ECMO varies from institution rigorously avoiding muscle relaxants.41,42 Sedation is used
and by diagnosis, it is generally accepted that, in the only as needed. Meticulous attention to maintaining a
setting of optimal management, an (Aa)DO2 greater than clear airway and the well-being of the infant is obvious,
625mmHg for more than four hours, or an (Aa)DO2 but critical. Permissive hypercapnia with spontaneous
greater than 600mmHg for more than 12 hours, or an OI respiration is initiated with intermittent mandatory ven-
of greater than 40 establishes both a relatively sensitive tilation (IMV), 3040 breaths per minute, equal I/E time,
and specific predictor of mortality. Other criteria used inspiratory gas flow of 57L/min, peak inspiratory pres-
by many institutions include a preductal PaO2 less than sure (PIP) of 2022cmH2O, and positive end-expiratory
3550mmHg for two to 12 hours or a pH of less than 7.25 pressure (PEEP) of 5cmH2O. The FiO2 is selected to
for at least two hours along with intractable hypotension. maintain preductal SaO2 greater than 90%. If this method
These are sustained values measured over a period of time of ventilation is not effective, as demonstrated by severe
and are not accurate predictors of mortality.14,20,3537 paradoxical chest movement, severe retractions, tachyp-
Patients with CDH are in their own category, and criteria nea, inadequate or labile oxygenation (preductal O2 satu-
for this disease are discussed later in this chapter. rations <80%), or PaCO2 greater than 60mmHg, then a
Older infants and children do not have as well-defined new mode of ventilation is needed.
criteria for high mortality risk. The ventilation index is High-frequency ventilation would be the next option.
determined by the following: It is delivered by setting the ventilator to IMV mode with
a rate of 100, inspiratory time of 0.3 seconds, an inspira-
Respiratory rate PaCO2 Peak inspiratory tory gas flow of 1012L, a PIP of 20, and a PEEP of 0
pressure / 1000 (due to auto-PEEP). The PIP is adjusted as needed based
on chest excursion, trying to maintain the PIP at less than
The combination of a ventilation index greater than 40 25mmHg. High-frequency oscillation can be instituted
and an OI more than 40 correlates with a 77% mortality.38 if the high-frequency ventilation is unable to improve the
A mortality of 81% is associated with an (Aa)DO2 hypoxia and hypercarbia using the same parameters just
greater than 580mmHg and a peak inspiratory pressure mentioned, but improvement may be temporary.
of 40cmH2O.38 Indications for support in patients with Before ECMO is initiated for an infant with CDH,
cardiac pathology are based on clinical signs such as hypo- the baby should first demonstrate some evidence of ade-
tension despite the administration of inotropes or volume quate lung parenchyma. Some programs use radiographic
resuscitation, oliguria (urine output < 0.5mL/kg/h), and parameters to determine adequate lung volumes. The
decreased peripheral perfusion. lung-to-head ratio (LHR) is measured by prenatal
ultrasonography (US).43,44 It is defined as the product
Congenital Diaphragmatic Hernia of the orthogonal diameters of the non-affected lung
divided by the head circumference. Severe pulmonary
Of most interest to pediatric surgeons are neonates with hypoplasia is considered when the LHR is less than 1.0
abdominal viscera in the thoracic cavity due to a CDH. and intermediate hypoplasia lies between 1.01.4.45
84 SECTION I General
Recent data have shown that an LHR threshold of 0.85 VV and DLVV bypass provide pulmonary support but
predicted mortality with 95% sensitivity and 64% spe- do not provide cardiac support. VV bypass is established
cificity.45 The LHR is operator dependent and can only by drainage from the right atrium via the right internal
be obtained in a narrow gestational window and therefore jugular vein with reinfusion into a femoral vein. DLVV
leads to poor reproducibility across different centers. is accomplished by means of a double-lumen catheter
Many centers believe the best method to evaluate pul- inserted into the right atrium via the right internal jugular
monary hypoplasia and predict outcome is to evaluate the vein. A major limitation of VV or DLVV ECMO is that
patient clinically. This is assessed by having a recorded a fraction of the infused oxygenated blood re-enters the
best PaCO2 less than 50mmHg and a preductal oxygen pump and, at high flows, may limit oxygen delivery due
saturation greater than 90% for a sustained period of at to recirculation. A limitation specific to DLVV is catheter
least one hour at any time in the clinical course. With size, which confines use of this method of support to
these criteria, successful ECMO should yield an overall larger neonates, infants, and smaller children. VV and
survival rate of 75% or better. If patients with lethal DLVV bypass have become the preferred method of
anomalies, overwhelming pulmonary hypoplasia, or extracorporeal support for all appropriate patients who
neurologic complications are not included, survival do not require cardiac support.20
approaches 85%.41,42,46
Cannulation
Extracorporeal Cardiopulmonary Cannulation can be performed with proper monitoring
Resuscitation in the neonatal or PICU under adequate sedation and
Studies demonstrate that 14% of pediatric intensive care intravenous anesthesia. The infant is positioned supine
unit (PICU) admissions suffer a cardiac arrest. Survival with the patients head at the foot of the bed. The head
to discharge for a patient who has an arrest in the PICU and neck are hyperextended over a shoulder roll and
ranges from 1442%. The ELSO data demonstrate that turned to the left. Local anesthesia is administered in the
approximately 73% of extracorporeal cardiopulmonary incision site. A transverse cervical incision is made along
resuscitation (ECPR) has been used for patients with the anterior border of the sternomastoid muscle, one
primary cardiac disease. Overall survival to discharge in finger-breadth above the right clavicle. The platysma
this population reached 38%.47 The American Heart muscle is divided, and dissection is carried down with the
Association recommends ECPR for in-hospital cardiac sternomastoid muscle retracted to expose the carotid
arrest refractory to initial resuscitation, secondary to a sheath. The sheath is opened, and the internal jugular
process that is reversible or amenable to heart transplan- vein, common carotid artery, and vagus nerve are identi-
tation. Conventional cardiopulmonary resuscitation fied (Fig. 6-1A). The vein is exposed first and encircled
(CPR) must have failed, no more than several minutes with proximal and distal ligatures. Occasionally it is nec-
should have elapsed, and ECMO must be readily avail- essary to ligate the inferior thyroid vein. The common
able. Future research needs to analyze long-term neuro- carotid artery lies medial and posterior, contains no
logic status amongst survivors and which patients will branches, and is mobilized in a similar fashion. The vagus
benefit the most with as little morbidity as possible. nerve should be identified and protected.
The arterial cannula (usually 10 French for newborns)
is measured so that the tip will lie in the ascending aorta.
Second Course of ECMO This is approximately one-third the distance between the
Approximately 3% of patients that are treated with sternal notch and the xiphoid. The venous cannula
ECMO will require a second course. The survival rates (usually 1214 French for neonates) is measured so that
for patients in this cohort are comparable to the first its tip lies in the distal right atrium which is approxi-
course. Negative prognostic indicators for second course mately half the distance between the suprasternal notch
ECMO patients include patients with renal impairment, and the xiphoid process. If time permits, an activated
higher number of first-course complications, age older clotting time (ACT) should be checked before heparini-
than 3 years old, or a prolonged second course.48 zation. The patient is then systemically heparinized
with100U/kg of heparin, which is allowed to circulate
for two to three minutes, which should produce an
METHODS OF EXTRACORPOREAL SUPPORT ACT of more than 300 seconds. The arterial cannula is
usually inserted first with VA bypass. The carotid artery
The goal of ECMO support is to provide an alternate is ligated cephalad. Proximal control is obtained, and a
means for oxygen delivery. Three different extracorpor- transverse arteriotomy is made near the cephalad ligature
eal configurations are used clinically: venoarterial (VA), (Fig. 6-1B). To help prevent intimal dissection, fine
venovenous (VV), and double-lumen single cannula Prolene sutures can be placed around the arteriotomy
venovenous (DLVV) bypass. The inception of ECMO and used for retraction when introducing the arterial
and its early days were characterized by VA ECMO cannula. The saline-filled cannula is inserted to its pre-
because it offered the ability to replace both cardiac and measured position and secured with two silk ligatures
pulmonary function. Venous blood is drained from the (2-0 or 3-0). A small piece of vessel loop (bumper) may
right atrium through the right internal jugular vein, and be placed under the ligatures on the anterior aspect of
oxygenated blood is returned via the right common the carotid to protect the vessel from injury during
carotid artery to the aorta. decannulation (Fig. 6-1C).
6 Extracorporeal Membrane Oxygenation 85
Venous cannula
Carotid Vessel
sheath
Superior
Artery
thyroid vein
cannula
Common
carotid
Internal artery Cannula
jugular
vein
A B Silastic
bumper
C
FIGURE 6-1 The cannulation procedure. (A) The carotid sheath is exposed, the sternocleidomastoid muscle is retracted laterally,
and the common carotid artery and the internal jugular vein are dissected free. (B) The patient is anticoagulated after the vessels
are dissected and ligated cephalad. The arterial cannula is passed into the junction of the innominate artery and the aorta. The
venous catheter is passed into the right atrium. (C) A polymeric silicone (Silastic) bumper is used to facilitate ligation of the can-
nulas. The two ligatures on each vessel are then tied together.
Venous blood is drained into a small reservoir or bladder (Venous return monitor alarm standing, pump cutting out)
through the cannula that is in the right atrium via the
right internal jugular vein (Fig. 6-3). The bladder is a
Give intravascular volume or decrease flow rate
3050mL reservoir that acts as a safety valve. If the
venous drainage does not keep up with arterial outflow
from the pump, the bladder volume will be depleted, Check venous catheter position; alleviate kinks in venous line
sounding an alarm, and automatically shutting off the (chest radiography or echocardiography)
pump. Sensors can be placed into the circuit to measure
arterial oxygen saturation, mixed venous saturation,
hematocrit, and pump flow. Hypovolemia is one of the Increase height of bed, reposition infant
most common causes of decreased venous inflow into the
circuit, but kinking and occlusion of the venous line
Check venous bladder function
should be suspected first. An algorithm for managing
pump failure due to inadequate venous return is shown
in Figure 6-4. Sedate infant as needed
Two types of ECMO pumps, centrifugal and roller
head, are used to pump blood through the membrane
oxygenator. Centrifugal pumps are dependent on ade- Place additional venous drainage cannula if required
quate preload and afterload, and have continuous flow.
FIGURE 6-4 Suggested algorithm for the management of inad-
The revolutions per minute (RPM) are adjusted to main- equate venous return during extracorporeal membrane oxy-
tain the desired flow rate. A low preload or high afterload genation. (Adapted from DeBerry BB, Lynch J, Chung DH,
will lead to lower flow despite a fixed RPM. Alternatively, Zwischenberger JB. Emergencies during ECLS and their manage-
roller pumps operate by displacing a fixed volume of ment. In: Van Meurs K, Lally KP, Peek G, Zwischenberger JB,
editors. ECMO: Extracorporeal Cardiopulmonary Support in Critical
blood per revolution and are afterload independent. The Care. 3rd ed. Ann Arbor, MI: Extracorporeal Life Support Organiza-
roller pumps are designed with microprocessors that tion; 2005. p. 13356.)
allow for calculation of the blood flow based on the
roller-head speed and tubing diameter of the circuit. The
pumps are connected to continuous pressure monitoring the oxygenator is based on the patients size with smaller
throughout the circuit and are servoregulated if pressures infants utilizing a pediatric oxygenator and larger patients
within the circuit exceed preset parameters. Another using an adult sized oxygenator.
safety device, the bubble detector (not depicted in Figure
6-3), is interposed between the pump and the membrane
oxygenator that halts perfusion to the patient if air is PATIENT MANAGEMENT ON ECMO
detected in the circuit.
The oxygenator consists of a hollow-fiber membrane Once the cannulas are connected to the circuit, bypass
made of polymethylpentene. This provides an interface is initiated, and the flow is slowly increased to 100150mL/
for blood and gas exchange. These oxygenators have kg/min. Continuous in-line monitoring of the (pre-
built-in heat exchangers to maintain patient normother- pump) SvO2 and arterial (post-pump) PaO2 as well as
mia. Oxygen diffuses through the membrane into the pulse oximetry is vital. The goal of VA ECMO is to
circuit, and carbon dioxide and water vapor diffuse from maintain an SvO2 of 3740mmHg and saturation of
the blood into the sweep gas. The size (surface area) of 6570%. VV ECMO is more difficult to monitor because
of recirculation, which may produce a falsely elevated
SvO2. Inadequate oxygenation and perfusion are indi-
cated by metabolic acidosis, oliguria, hypotension, ele-
ECMO CIRCUIT
vated liver function studies, and seizures. Arterial blood
gases should be monitored closely with PaO2 and PaCO2
maintained as close to normal levels as possible. The
oxygen level of the blood returning to the patient should
Arterial
line
Membrane be fully saturated. To increase a patients oxygen delivery
Venous
oxygenator on ECMO, one can either increase the ECMO flow rate
line Heat (~ cardiac output) or the hemoglobin can be increased to
Bridge exchanger
maintain hemoglobin at 15g/dL (~ oxygen content).
CO2 elimination is extremely efficient, and it is important
to adjust the sweep (gas mixing) to maintain a PaCO2 in
the range of 4045mmHg. This is important, especially
during weaning, because a low PaCO2 inhibits the infants
Oxymetrics probe Temp probe Bladder Pump spontaneous respiratory drive. Serial monitoring allows
connector timely adjustments. The arterial blood gas is measured
FIGURE 6-3 Venoarterial extracorporeal membrane oxygena- hourly. As soon as these parameters are met, all vasoactive
tion circuit. drugs are weaned and ventilator levels are adjusted to
6 Extracorporeal Membrane Oxygenation 87
rest settings. Gastrointestinal prophylaxis (H2 antago- into the soft tissues. The patient becomes edematous and
nists or proton pump inhibitors) is initiated, and mild often requires volume replacement (crystalloid, colloid,
sedation and analgesia are provided, usually with fentanyl or blood products) to maintain adequate intravascular
and midazolam. Paralyzing agents are avoided. Cefazolin and bypass flows, appropriate hemodynamics, and urine
is used for antimicrobial prophylaxis. Routine blood cul- output greater than 1mL/kg/h. By the third day of
tures should be obtained.20,49 A daily chest radiograph is bypass, diuresis of the excess extracellular fluid begins
performed. Opacification or white out is often noted and can be facilitated with the use of diuretics and, if
during the early ECMO course. The reasons for this are necessary, an in-line hemofilter.20,49
multifactorial and include decreased ventilatory pressures Selective hypothermia for cerebral ischemia/hypoxia
(both PIP and PEEP), reperfusion of the injured lung, may improve neurologic outcome. It is not yet clear if
and exposure of the blood to a foreign surface, causing whole body or cap cooling provides significant improve-
an inflammatory response with the release of cytokines. ment in ECMO outcomes. It is possible to maintain
A list of typical diagnostic tests is shown in Table 6-1. temperature of 34C for 45 hours on ECMO without
Heparin is administered (3060mg/kg/h) throughout increasing morbidity.52 The largest study to date is under-
the ECMO course to preserve a thrombus-free circuit. way in the UK. The Neonatal ECMO Study of Tempera-
ACTs should be monitored hourly and maintained at ture (NEST) is a multicenter prospective randomized
180220 seconds. A complete blood cell count should control trial of mild hypothermia versus normothermia
be obtained every six hours and coagulation profiles in neonates on ECMO.53
obtained daily. To prevent thrombocytopenia, platelets
are transfused to maintain a platelet count greater than
100,000/mm3. The use of fibrinogen and other clotting
Operative Procedure on ECMO
factors is controversial. Fresh frozen plasma should be Operations, such as CDH repair, can be performed while
considered in infants with international normalized ratio the child remains on bypass, but one must account for
(INR) levels >1.5 in order to replete coagulation cascade the continued postoperative anticoagulation. Hemor-
factors and allow for adequate anticoagulation. In cases rhagic complications are a frequent morbidity associated
of heparin resistance, anti-thrombin 3 levels should be with an operation on ECMO, and these complications
checked and repleted as necessary. The hematocrit should increase mortality. To try to avoid these problems, the
remain above 40% by using red blood cell transfusions platelet count should be greater than 150,000/mm3, the
so that oxygen delivery is maximized.20 ACT can be reduced to 180200 seconds, and ECMO
The volume management in patients on ECMO is flow is increased to full support. Moreover, it is impera-
very important and difficult. It is imperative that all tive that meticulous hemostasis is obtained throughout
inputs and outputs be diligently recorded and electrolytes the operation. The fibrinolysis inhibitor aminocaproic
monitored every six hours. Fluid losses should be repleted acid (100mg/kg) is administered just prior to incision,
and electrolyte abnormalities corrected. Patients should and is infused continuously (30mg/kg/h) until there is
receive maintenance fluids as well as adequate nutrition no evidence of bleeding.20,49
by using parenteral hyperalimentation. The first 48 to 72
hours on ECMO typically involve fluid extravasation Weaning and Decannulation
As the patient improves, less blood flow is required to
pass through the ECMO circuit and the flow can be
TABLE 6-1 General Studies Obtained weaned at a rate of 1020mL/h as long as the patient
During ECMO maintains good oxygenation and perfusion. The most
important guide to VA ECMO weaning is the SvO2. For
General Frequency and
Laboratory Study Comments
VV ECMO, it is the SaO2. Regardless of the cannulation
format, successful weaning is marked by stable acidbase
Chest radiography Daily balance and good urine output. Flows should be decreased
Cranial ultrasonography Only for neonates, the first
three days and then as
to 3050mL/kg/min, and the ACT should be at a higher
needed level (200240 seconds) to prevent thrombosis. Newer
Activated clotting time Every hour, more often if oxygenators have higher limits of allowable flow, which
outside of parameters may limit full weaning. Adjustable shunts placed across
Preoxygenator blood gas Every four hours the oxygenator allow higher overall flow to the oxygena-
Postoxygenator blood gas Every four hours
Patient blood gas Every six hours tor with a lower flow being delivered to the patient. Also,
Glucose monitoring test Every four hours flow probes placed on the arterial cannula can be used to
Complete blood cell count Every six hours; include a accurately guide weaning. Moderate conventional venti-
with platelets differential daily lator settings are used, but higher settings can be used if
Chem-7 Every six hours, including
magnesium, calcium, and
the patient needs to be weaned from ECMO urgently. If
phosphorus daily the child tolerates the low flow, all medications and fluids
Fibrinogen Daily and after infusion of should be switched to vascular access on the patient. The
cryoprecipitate and fresh cannulas are flushed and clamped, with the circuit bypass-
frozen plasma; may also ing the patient via the bridge. If it is possible that the
include prothrombin time
and D-dimer child may need to be returned to bypass, then the can-
nulas should be flushed with heparin (2U/mL). The
88 SECTION I General
patient is then observed for two to four hours. If this is of air embolism. Thus, all visible air bubbles should be
tolerated, decannulation can be accomplished. removed by filling the cannulas with heparinized saline.
Decannulation is performed under sterile conditions Other entry points in the circuit include all of the con-
with the patient in the Trendelenburg position. With the nectors and stopcocks as well as the membrane oxygena-
use of a short acting muscle relaxant to prevent air aspira- tor. Therefore, the circuit must be continually inspected.
tion into the vein, ventilator settings should be increased. Air on the arterial side requires removing the patient
The venous catheter is typically removed first, and the from bypass immediately. Next, the air should be aspi-
jugular vein is ligated. Repair of the carotid artery is rated from a port until all air has been removed. Air on
controversial. Short-term results demonstrate acceptable the venous side is not as urgent a problem, and the air
patency rates and equivalent short-term neurodevelop- can often be walked into the bladder where it can be
mental outcomes when compared with children undergo- aspirated without coming off bypass.
ing carotid artery ligation.54,55 Another study of neonates In the event that an air embolism reaches the patient,
who underwent arterial repair found a 72% incidence of the patient should be immediately taken off ECMO and
an occluded or highly stenotic right common carotid conventional ventilator settings adjusted to best meet the
artery at two years of age.56 Similar to other studies, there patients needs. The patient should be placed in the Tren-
was no significant difference in neurologic development delenburg position to prevent air from entering the cer-
when compared to controls. The incision should be irri- ebral circulation. Next, an attempt should be made to
gated and closed over a small drain, which is removed aspirate any accessible air out of the arterial cannula. If
24 hours later.20,49 air enters the coronary circulation, inotropic support may
be necessary. Before reinstituting ECMO, identifying
and correcting the cause of the air embolus is essential.
COMPLICATIONS
Mechanical Complications Neurologic Complications
Neurologic complications develop in 25% of infants and
Membrane Failure
children on ECMO.1 ICH, infarct, and seizure carry sig-
Failure of the membrane oxygenator is seen with a nificant mortality when encountered in ECMO patients.
decrease in oxygenation or retention of CO2. The cause Frequent neurologic examinations should be performed
of such complications include a fibrin clot or water con- and the use of paralytic agents avoided. The examination
densation, both of which diminish the oxygenators ability should include evaluation of alertness and interaction,
to transfer oxygen and CO2. Oxygenator failure has been spontaneous movements, eye exams, the presence of sei-
reported in 21.6% of respiratory ECMO runs in the neo- zures, fullness of the fontanelles, tone, and reflexes. Elec-
natal and pediatric population.1 The oxygenator should troencephalography (EEG) may also be helpful in the
not be subject to high pressures, which should be continu- neurologic evaluation. Cranial ultrasound should be per-
ously monitored. Pressure limits are specific for different formed on all neonates before initiating ECMO to iden-
manufacturers and for the size of the membrane. Clots in tify those patients in whom significant ICH already exists.
the oxygenator can be seen but the extent of the clot A retrospective analysis revealed that birth weight and
cannot be determined. The progressive consumption of gestational age were the most significant correlating
coagulation factors, such as platelets and fibrinogen, also factors with ICH in neonates on ECMO.33 Once the
indicates that the membrane may be progressively build- patient is placed on ECMO, ultrasound is repeated
ing clot, and the need to change the oxygenator should be during the first three days when indicated by the clinical
considered. Another sign of impending membrane failure condition. If the examination reveals a new moderate
is rising CO2 levels in the post-oxygenator blood. (grade II) hemorrhage or an expanding ICH, ECMO is
usually discontinued.
In the event that an ICH is suspected, or detected on
Accidental Decannulation
cranial ultrasound, and deemed to be small in size, it is
Securing the cannulas properly and taping the tubing reasonable to maintain a low ACT (180200 seconds)
to the bed will help prevent accidental decannulation. with a platelet count greater than 125,000150,000/mm3.
Unexpected decannulation is an emergency, and immedi- Serial head ultrasound should be performed to monitor
ate pressure should be applied to the cannula site along the progression of the hemorrhage.20
with discontinuation of bypass. Conventional ventilator
settings should be increased simultaneously. The cervical Cannula Site or Bleeding at Other Sites
incision must be immediately re-explored to prevent
further hemorrhage and the cannulas replaced if contin- The ECMO registry reports an 8.4% incidence of can-
ued bypass is needed. nulation site bleeding and a 13% incidence of other sur-
gical site bleeding.1 Contact of blood with the foreign
surface of the circuit activates the coagulation cascade.
Patient Complications The number of platelets and their function are also
affected. With anticoagulation, the risk of bleeding while
Air Embolism
undergoing an operation on ECMO is considerable. To
The ECMO circuit has several potential sources for entry reduce this risk, meticulous hemostasis needs to be main-
of air. The initial cannulation procedure can be a source tained during the procedure and before closure. If
6 Extracorporeal Membrane Oxygenation 89
necessary, the surgeon should employ topical hemostatic occurs after placing a child on ECMO may cause
agents. Lowering the ACT parameters to 180200 decreased renal perfusion. Alternatively, it may result
seconds and maintaining a platelet count of at least from the nonpulsatile blood flow that occurs with VA
125,000/mm3 can assist with hemostasis. If bleeding from ECMO. Once the patient is adequately volume resusci-
the cervical incision is greater than 10mL/h for two tated, and fluid shifts have stabilized, the use of furosem-
hours despite conservative treatment strategies, explora- ide (12mg/kg) can improve urine output. If the
tion may be needed.20 creatinine continues to rise, then renal ultrasound is rec-
Bleeding into previous operative sites occurs fre- ommended. The use of continuous hemofiltration,
quently and must be handled aggressively. A decreasing which can be added in-line to the ECMO circuit, is
hematocrit, an increasing heart rate, a decline in the another mechanism to assist in managing the fluid shifts,
blood pressure, or inadequate venous return are signs of hyperkalemia, and azotemia. Hemofiltration removes
ongoing hemorrhage. Treatment includes replenishing plasma water and dissolved solutes while retaining pro-
blood products, including coagulation factors, if neces- teins and the cellular components of the intravascular
sary. ACT parameters should be decreased to 180 to 200 space.20
seconds and the platelet count maintained greater than
125,000/mm3. Agents that inhibit fibrinolysis, such as Hypertension
aminocaproic acid, also can help prevent bleeding. The
use of recombinant activated factor VII (NovoSeven, The incidence of hypertension on ECMO varies from
Novo Nordisk, Inc., Princeton, NJ) has been described 28% to as high as 92%.58 According to the ELSO regis-
in the management of bleeding unresponsive to conven- try, 13% of ECMO patients require pharmacologic inter-
tional methods.57 This is an off-label use, and thrombosis vention.1 One group reported that detectable ICH
is a significant concern. Often, one must evacuate the occurred in 44% of their hypertensive patients and clini-
hematoma and explore for the cause as is often the case cally significant ICH developed in 27%.59 The patient
in the postcardiac surgery patient with an open chest and should be assessed initially for reversible causes of hyper-
central cannulation. If bleeding is not quickly controlled, tension, such as pain, hypercarbia, and hypoxia. Embolic
decannulation and stopping the anticoagulation may renal infarction is another cause of hypertension. Medical
need to be strongly considered. management includes the use of hydralazine, nitroglyc-
erin, and captopril.
Coagulation Abnormalities
Infection
ECMO patients have a coagulopathy secondary to con-
sumption by the circuit. Removal of the source and a The incidence of nosocomial infections during ECMO
circuit change is a logical approach. Disseminated intra- has been reported as high as 30%.1 Associated risk factors
vascular coagulation (DIC) occurs in approximately 2% include the duration of the ECMO course, the length of
of ECMO cases.1 DIC is characterized by the consump- hospitalization, and procedures performed before the ini-
tion of plasma clotting factors and platelets, resulting in tiation of ECMO or during the run.60 The ELSO registry
deposition of fibrin thrombi in the microvasculature. data from July 2011 describes an 8% culture-proven
Once the factor levels and platelet count decrease below infection rate in ECMO neonates and pediatric patients.1
certain levels, bleeding will occur. Sepsis, acidosis, This is remarkably low, considering the large surface area
hypoxia, and hypotension are the most common causes of the circuit, the duration of bypass, and the frequency
which is why ECMO patients are at risk for developing of access to the circuit. Fungal infections carry a signifi-
DIC. The most common cause of a coagulopathy is con- cantly higher hospital mortality rate, and sepsis carries
sumption of clotting factors by the circuit and rarely is it a higher morbidity and mortality rate in neonates.61,62
due to sepsis or DIC. Access to the circuit should be minimized and meticulous
sterile techniques are important.
Patent Ductus Arteriosus
The dramatic decrease in pulmonary hypertension, RESULTS
usually seen in the first 48 hours of an ECMO run, causes
dramatic changes in the neonates circulation. A left-to- ECMO is a prime example of the evolution from an
right shunt through the patent ductus arteriosus (PDA) experimental technique to a commonly used therapeutic
develops and causes less-efficient oxygenation, pulmo- approach. The ELSO registry has accumulated data since
nary edema, and poor peripheral perfusion. Usually, the the early 1980s from all registered centers throughout
PDA closes spontaneously with fluid restriction and diu- the world. The number of registered centers continues
resis. The use of indomethacin should be avoided because to rise, as does the number of ECMO cases. In 1992,
of its adverse effects on platelet function. Rarely is PDA over 1500 ECMO cannulations for neonatal respiratory
ligation required or indicated while on ECMO. disease were performed. In 2010, only 747 cases were
reported. The decline in case volume is likely due to
improvements in ventilation management and the addi-
Renal Failure
tion of new agents including inhaled nitric oxide, smooth
Oliguria is common in ECMO patients and is often seen muscle relaxants, exogenous surfactant, and high-
during the first 24 to 48 hours. The capillary leak that frequency oscillation.1,20
90 SECTION I General
Overall, ECMO-treated neonates function within the 20. In: Van Meurs K, Lally KP, Peek G, et al, editors. ECMO: Extra-
normal range and the rate of handicap appears to be corporeal Cardiopulmonary Support in Critical Care. 3rd ed. Ann
Arbor, MI: Extracorporeal Life Support Organization; 2005.
stable across studies with an average of 11%, ranging 21. In: Van Meurs K, editor. ECMO Specialist Training Manual. 3nd
from 2% to 18%.70,76,7989 This morbidity reflects how ed. Ann Arbor, MI: Extracorporeal Life Support Organization;
desperately ill these children are and is not a direct effect 2010.
of ECMO. 22. Gajarski RJ, Mosca RS, Ohye RG, et al. Use of extracorporeal life
support as a bridge to pediatric cardiac transplantation. J Heart
Lung Transplant 2003;22:2834.
23. Bae J, Frischer J, Waich M, et al. Extracorporeal membrane oxy-
REFERENCES genation in pediatric cardiac transplantation. J Pediatr Surg
1. Extracorporeal Life Support Organization. International 2005;40:10517.
Registry Report of the Extracorporeal Life Support Organization. 24. Lessin JS, el-Eid SE, Klein MD, et al. Extracorporeal membrane
Ann Arbor; University of Michigan Medical Center; July oxygenation in pediatric respiratory failure secondary to smoke
2011. inhalation injury. J Pediatr Surg 1996;31:12857.
2. Lillehei CW, Cohen M, Warden HE, et al. The direct-vision int- 25. Tobias JD, Garrett JS. Therapeutic options for severe, refractory
racardiac correction of congenital anomalies by controlled cross status asthmaticus: Inhalational anesthetic agents, extracorporeal
circulation. Surgery 1955;38:1129. membrane oxygenation and helium/oxygen ventilation. Paediatr
3. Clowes GHA Jr, Hopkins AL, Neville WE. An artificial lung Anesth 1997;7:4757.
dependent upon diffusion of oxygen and carbon dioxide through 26. Travis JA, Pranikoff T, Chang MC, et al. Extracorporeal rewarming
plastic membranes. J Thorac Surg 1956;32:6307. in trauma patients. Presented at the 13th Annual ELSO Confer-
4. Kolobow T, Zapol W, Pierce JE, et al. Partial extracorporeal gas ence, Scottsdale, Arizona, 2002.
exchange in alert new born lambs with a membrane artificial lung 27. Johnson LB, Plotkin JS, Howell CD, et al. Successful emergency
perfused via an AV shunt for periods up to 96 hours. Trans Am Soc transplantation of a liver allograft from a donor maintained on
Artif Intern Organs 1968;14:32834. extracorporeal membrane oxygenation. Transplantation 1997;
5. Osborn JJ, Bramson ML, Main FB, et al. Clinical experience with 63:91011.
a disposable membrane oxygenator. Bull Soc Int Chir 1966; 28. Gersony WM, Duc GV, Sinclair JC. PFC syndrome (persistence
25:34653. of the fetal circulation). Circulation 1969;40(Suppl. 111):87.
6. Peirce EC 2d, Thebaut AL, Kent BB, et al. Techniques of extended 29. Gupta A, Shantanu R, Rakesh S, et al. Inhaled nitric oxide and
perfusion using a membrane lung. Ann Thorac Surg 1971; gentle ventilation in the treatment of pulmonary hypertension of
12:45170. the newborna single-center 5-year experience. J Perinatol
7. Lande AJ, Edwards L, Block JH, et al. Prolonged cardiopulmonary 2002;22:43541.
support with a practical membrane oxygenator. Trans Am Soc Artif 30. Northway WH, Rosan RC, Porter DY. Pulmonary disease follow-
Intern Organs 1970;16:3526. ing respiratory therapy of hyaline membrane disease. N Engl J Med
8. Hill D, OBrien TG, Murray JJ, et al. Extracorporeal oxygenation 1967;276:35768.
for acute post-traumatic respiratory failure (shock-lung syndrome): 31. Kornhauser MS, Cullen JA, Baumgart S, et al. Risk factors for
Use of the Bramson Membrane Lung. N Engl J Med 1972; bronchopulmonary dysplasia after extracorporeal membrane oxy-
286:62934. genation. Arch Pediatr Adolesc Med 1994;148:8205.
9. Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane 32. Kim ES, Stolar CJ. ECMO in the newborn. Am J Perinatol
oxygenation in severe respiratory failure. JAMA 1979; 2000;17:34556.
242:21936. 33. Cilley RE, Zwischenberger JB, Andrews AF, et al. Intracranial
10. Bartlett RH, Gazzaniga AB, Jefferies MR, et al. Extracorporeal hemorrhage during extracorporeal membrane oxygenation in
membrane oxygenation (ECMO) cardiopulmonary support in neonates. Pediatrics 1986;78:699704.
infants. Trans Am Soc Artif Intern Organs 1976;22:8093. 34. Wung JT, James LS, Kilchevsky E, et al. Management of infants
11. Bartlett RH, Roloff DW, Cornell RG, et al. Extracorporeal circula- with severe respiratory failure and persistence of the fetal circula-
tion in neonatal respiratory failure: A prospective randomized tion, without hyperventilation. Pediatrics 1985;76:48894.
study. Pediatrics 1985;76:47987. 35. Beck R, Anderson KD, Pearson GD, et al. Criteria for extracor-
12. ORourke PP, Crone RK, Vacanti JP, et al. Extracorporeal mem- poreal membrane oxygenation in a population of infants with per-
brane oxygenation and conventional medical therapy in neonates sistent pulmonary hypertension of the newborn. J Pediatr Surg
with persistent pulmonary hypertension of the newborn: A pro- 1986;21:297302.
spective randomized study. Pediatrics 1989;84:95763. 36. Marsh TD, Wilkerson SA, Cook LN. Extracorporeal membrane
13. Firmin R. United Kingdom Neonatal ECMO Study. Presented at oxygenation selection criteria: Partial pressure of arterial oxygen
the 7th International ELSO Conference, Dearborn, Michigan, versus alveolar-arterial oxygen gradient. Pediatrics 1988;82:
1995. 1626.
14. Krummel TM, Greenfield LJ, Kirkpatrick BU, et al. Extracorpor- 37. Ortiz RM, Cilley RE, Bartlett RH. Extracorporeal membrane oxy-
eal membrane oxygenation in neonatal pulmonary failure. Pediatr genation in pediatric respiratory failure. Pediatr Clin North Am
Ann 1982;11:9058. 1987;34:3946.
15. Toomasion JM, Snedecor SM, Cornell RG, et al. National experi- 38. Rivera RA, Butt W, Shann F. Predictors of mortality in children
ence with extracorporeal membrane oxygenation for newborn res- with respiratory failure possible indications for ECMO. Anaesth
piratory failure: Data from 715 cases. Trans Am Soc Artif Intern Intensive Care 1990;18:3859.
Organs 1988;34:1407. 39. Garcia AV, Stolar CJH. Congenital diaphragmatic hernia and pro-
16. Stolar CJH, Snedecor SM, Bartlett RH. Extracorporeal membrane tective ventilation strategies in pediatric surgery. Surg Clin N Am
oxygenation and neonatal respiratory failure: Experience from 2012;92:65968.
the extracorporeal life support organization. J Pediatr Surg 40. Azarow K, Messineo A, Pearl R, et al. Congenital diaphragmatic
1991;26:56371. herniaa tale of two cities: The Toronto experience. J Pediatr Surg
17. ORourke PP, Stolar CJ, Zwischenberger JB, et al. Extracorporeal 1997;32:395400.
membrane oxygenation: Support for overwhelming pulmonary 41. Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic
failure in the pediatric population: Collective experience from hernia: Survival treated with very delayed surgery, spontaneous
the extracorporeal life support organization. J Pediatr Surg respiration, and no chest tube. J Pediatr Surg 1995;30:4069.
1993;28:5238. 42. Boloker J, Bateman DA, Wung JT, et al. Congenital diaphragmatic
18. Galantowicz ME, Stolar CJ. Extracorporeal membrane oxygena- hernia in 120 infants treated consecutively with permissive
tion for perioperative support in pediatric heart transplantation. hypercapnia/spontaneous respiration/elective repair. J Pediatr Surg
J Thorac Cardiovasc Surg 1991;102:14851. 2002;37:35766.
19. Campbell BT, Braun TM, Schumacher RE, et al. Impact of ECMO 43. Metkus AP, Filly RA, Stringer MD, et al. Sonographic predictors
on neonatal mortality in Michigan (19801999). J Pediatr Surg of survival in fetal diaphragmatic hernia. J Pediatr Surg
2003;38:2905. 1996;31:14851.
92 SECTION I General
44. Aspelund G, Fisher JC, Simpson LL, et al. Prenatal lung-head hernia with the use of combined multichannel intraluminal imped-
ratio: Threshold to predict outcome for congenital diaphragmatic ance and pH monitoring. J Pediatr Surg 2011;46:18816.
hernia. J Matern Fetal Neona 2012;25:101116. 69. Rajasingham S, Reed V, Glass P, et al. Congenital diaphragmatic
45. Graham G, Devine PC. Antenatal diagnosis of congenital dia- hernia: Outcome post-ECMO at 5 years. CNMC ECMO Sympo-
phragmatic hernia. Semin Perinatol 2005;29:6976. sium 1994;35.
46. Stolar CJH, Dillon PW, Reyes C, et al. Selective use of extracor- 70. Glass P, Wagner A, Papero P, et al. Neurodevelopmental status at
poreal membrane oxygenation in the management of congenital age five years of neonates treated with extracorporeal membrane
diaphragmatic hernia. J Pediatr Surg 1988;23:20711. oxygenation. J Pediatr 1995;127:44757.
47. Fiser RT, Morris MC. Extracorporeal cardiopulmonary resuscita- 71. Gershan L, Gershan W, Day S. Airway anomalies after ECMO:
tion in refractory pediatric cardiac arrest. Pediatr Clin North Am Bronchoscopic findings. CNMC ECMO Symposium 1992;65.
2008;55:92941. 72. Wagner A, Glass P, Papero P, et al. Neuropsychological outcome
48. Fisher JC, Stolar CJH, Cowles RA. Extracorporeal membrane oxy- of neonatal ECMO survivors at age 5. CNMC ECMO Symposium
genation of cardiopulmonary failure in pediatric patients: Is a 1994;31.
second course justified? J Surg Res 2008;148:1008. 73. DAgostino J, Bernbaum J, Gerdes M, et al. Outcome for infants
49. Frischer JS, Stolar CJH. Extracorporeal membrane oxygenation. with congenital diaphragmatic hernia requiring extracorporeal
In: Puri P, Hollwarth M, editors. Operative Pediatric Surgery. membrane oxygenation: The first year. J Pediatr Surg 1995;
Heidelberg: Springer; 2006. 30:1015.
50. Fisher JC, Jefferson RA, Kuenzler KA, et al. Challenges to cannula- 74. Van Meurs K, Robbins S, Reed V, et al. Congenital diaphragmatic
tion for extracorporeal support in neonates with right-sided con- hernia: Long-term outcome in neonates treated with extracorpor-
genital diaphragmatic hernia. J Pediatr Surg 2007;42:21238. eal membrane oxygenation. J Pediatr 1993;122:8939.
51. Haley MJ, Fisher JC, Ruiz-Elizalde AR, et al. Percutaneous distal 75. Atkinson J, Poon M. ECMO and the management of congenital
perfusion of the lower extremity following femoral cannulation diaphragmatic hernia with large diaphragmatic defects requiring a
for venoarterial ECMO in a small child. J Pediatr Surg 2009;44: prosthetic patch. J Pediatr Surg 1992;27:7546.
43740. 76. Adolph V, Ekelund C, Smith C, et al. Developmental outcome of
52. Horan M, Ichiba S, Firmin RK, et al. A pilot investigation of mild neonates treated with ECMO. J Pediatr Surg 1990;25:436.
hypothermia in neonates receiving extracorporeal membrane oxy- 77. Andrews A, Nixon C, Cilley R, et al. One-to-three year outcome
genation (ECMO). J Pediatr 2004;144:3018. for 14 neonatal survivors of extracorporeal membrane oxygenation.
53. Field DJ, Firmin R, Azzopardi DV, et al. Neonatal ECMO Study Pediatrics 1986;78:6928.
of Temperature (NEST)- a randomized controlled trial. BMC 78. Flusser H, Dodge N, Engle W, et al. Neurodevelopmental outcome
Pediatr 2010;10:24. and respiratory morbidity for ECMO survivors at 1 year of age.
54. Levy MS, Share JC, Fauza DO, et al. Fate of the reconstructed J Perinatol 1993;13:26671.
carotid artery after extracorporeal membrane oxygenation. 79. Glass P, Miller M, Short BL. Morbidity for survivors of extracor-
J Pediatr Surg 1995;30:10469. poreal membrane oxygenation: Neurodevelopmental outcome at
55. Cheung PY, Vickar DB, Hallgren RA, et al. Carotid artery 12 years of age. Pediatrics 1989;83:728.
reconstruction in neonates receiving extracorporeal membrane 80. Griffin M, Minifee P, Landry S, et al. Neurodevelopmental
oxygenation: A 4-year follow-up study. J Pediatr Surg 1997;32: outcome in neonates after ECMO: Cranial magnetic resonance
5604. imaging and ultrasonography correlation. J Pediatr Surg
56. Buesing KA, Kilian AK, Schaible T, et al. Extracorporeal mem- 1992;27:335.
brane oxygenation in infants with congenital diaphragmatic hernia: 81. Hofkosh D, Thompson A, Nozza R, et al. Ten years of ECMO:
Follow-up MRI evaluating carotid artery reocclusion and neuro- Neurodevelopmental outcome. Pediatrics 1991;87:54955.
logic outcome. Am J Roentgenol 2007;188:163642. 82. Krummel T, Greenfield L, Kirkpatrick B, et al. The early evalua-
57. Preston TJ, Olshove VF, Ayad O, et al. NovoSeven use in a non- tion of survivors after ECMO for neonatal pulmonary failure.
cardiac pediatric ECMO patient with uncontrolled bleeding. J Pediatr Surg 1984;19:58590.
J Extra Corpor Technol 2008;40:1236. 83. Schumacher R, Palmer T, Roloff D, et al. Follow-up of infants
58. Boedy RF, Goldberg AK, Howell CG, et al. Incidence of hyperten- treated with ECMO for newborn respiratory failure. Pediatrics
sion in infants on extracorporeal membrane oxygenation. J Pediatr 1991;87:4517.
Surg 1990;25:25861. 84. Towne B, Lott I, Hicks D, et al. Long-term follow-up of infants
59. Sell LL, Cullen ML, Lerner GR, et al. Hypertension during extra- and children treated with ECMO: A preliminary report. J Pediatr
corporeal membrane oxygenation: Cause, effect, and management. Surg 1985;20:41014.
Surgery 1987;102:72430. 85. Wildin S, Landry S, Zwischenberger J. Prospective, controlled
60. Coffin SE, Bell LM, Manning M, et al. Nosocomial infections in study of developmental outcome in survivors of ECMO: The first
neonates receiving extracorporeal membrane oxygenation. Infect 24 months. Pediatrics 1994;93:4048.
Control Hosp Epidemiol 1997;18:936. 86. Stolar CJ, Crisafi MA, Driscoll YT. Neurocognitive outcome for
61. Douglass BH, Keenan AL, Purohit DM. Bacterial and fungal infec- neonates treated with extracorporeal membrane oxygenation: Are
tion in neonates undergoing venoarterial extracorporeal membrane infants with congenital diaphragmatic hernia different? J Pediatr
oxygenation: An analysis of the registry data of the Extracorporeal Surg 1995;30:36672.
Life Support Organization. Artif Organs 1996;20:2028. 87. Davis D, Wilkerson S, Stewart D. Neurodevelopmental follow-up
62. Meyer DM, Jessen ME, Eberhart RC. Neonatal extracorporeal of ECMO survivors at 7 years. CNMC ECMO Symposium
membrane oxygenation complicated by sepsis. Extracorporeal Life 1995;34.
Support Organization. Ann Thorac Surg 1995;59:97580. 88. Stanley C, Brodsky K, McKee L, et al. Developmental profile of
63. Grimm P. Feeding difficulties in infants treated with ECMO. ECMO survivors at early school age and relationship to neonatal
CNMC ECMO Symposium 1993;25. EEG status. CNMC ECMO Symposium 1995;33.
64. Nield T, Hallaway M, Fodera C, et al. Outcome in problem feeders 89. Hack M, Taylor H, Klein N, et al. School-age outcomes in children
post-ECMO. CNMC ECMO Symposium 1990;79. with birthweights under 750g. N Engl J Med 1994;331:7539.
65. Glass P. Patient neurodevelopmental outcomes after neonatal 90. Friedman S, Chen C, Chapman JS, et al. Neurodevelopmental
ECMO. In: Arensman R, Cornish J, editors. Extracorporeal outcomes of congenital diaphragmatic hernia survivors followed in
Life Support. Boston: Blackwell Scientific Publications; 1993. a multidisciplinary clinic at ages 1 and 3. J Pediatr Surg 2008;43:
p. 24151. 103543.
66. Tarby T, Waggoner J. Are the common neurologic problems fol- 91. Leavitt AM, Watchko JF, Bennett FC, et al. Neurodevelopmental
lowing ECMO related to jugular bulb thrombosis? CNMC ECMO outcome following persistent pulmonary hypertension of the
Symposium 1994;110. neonate. J Perinatol 1987;7:28891.
67. Van Meurs K, Robbins S, Reed V, et al. Congenital diaphragmatic 92. Marron MJ, Crisafi MA, Driscoll JM Jr, et al. Hearing and neu-
hernia: Long-term outcome of neonates treated with ECMO. rodevelopmental outcome in survivors of persistent pulmonary
CNMC ECMO Symposium 1991;25. hypertension of the newborn. Pediatrics 1992;90:3926.
68. Pace MRD, Caruso AM, Farina F, et al. Evaluation of esophageal 93. Desai S, Stanley C, Graziani L, et al. Brainstem auditory evoked
motility and reflux in children treated for congenital diaphragmatic potential screening (BAEP) unreliable for detecting sensorineural
6 Extracorporeal Membrane Oxygenation 93
hearing loss in ECMO survivors: A comparison of neonatal BAEP 97. Campbell L, Bunyapen C, Gangarosa M, et al. The significance of
and follow-up behavioral audiometry. CNMC ECMO Symposium seizures associated with ECMO. CNMC ECMO Symposium
1994;62. 1991;26.
94. Haney B, Thibeault D, Sward-Comunelli S, et al. Ocular findings 98. Kumar P, Bedard M, Delaney-Black V, et al. Post-ECMO electro-
in infants treated with ECMO. CNMC ECMO Symposium encephalogram (EEG) as a predictor of neurological outcome.
1994;63. CNMC ECMO Symposium 1994;65.
95. Hahn J, Vaucher Y, Bejar R, et al. Electroencephalographic and 99. Scher M, Kosaburo A, Beggerly M, et al. Electrographic seizures
neuroimaging findings in neonates undergoing extracorporeal in preterm and full-term neonates: Clinical correlates, associated
membrane oxygenation. Neuropediatrics 1993;24:1924. brain lesions, and risk for neurologic sequelae. Pediatrics
96. Graziani L, Streletz L, Baumgart S, et al. Predictive value of neo- 1993;91:12834.
natal electroencephalograms before and during extracorporeal
membrane oxygenation. J Pediatr 1994;125:96975.
C H A P T E R 7
Amazingly, ventilation via tracheal cannulation was per- PHYSIOLOGY OF GAS EXCHANGE
formed as early as 1543 when Vesalius demonstrated the
ability to maintain the beating heart in animals with open
DURING MECHANICAL VENTILATION
chests.1 This technique was first applied to humans in
The approach to mechanical ventilation is best under-
1780, but there was little progress in positive-pressure
stood if the two variables of oxygenation and carbon
ventilation until the development of the FellODwyer
dioxide elimination are considered separately.14
apparatus. This device provided translaryngeal ventila-
tion using bellows and was first used in 1887 (Fig. 7-1).2,3
The DrinkerShaw iron lung, which allowed piston-
pump cyclic ventilation of a metal cylinder and concomi-
Carbon Dioxide Elimination
tant negative-pressure ventilation, became available in The primary purpose of ventilation is to eliminate carbon
1928 and was followed by a simplified version built by dioxide, which is accomplished by delivering tidal volume
Emerson in 1931.4 Such machines were the mainstays in (Vt) breaths at a designated rate. The product (Vtrate)
the ventilation of victims of poliomyelitis in the 1930s determines the minute volume ventilation (VE ). Although
through the 1950s. CO2 elimination is proportional to VE , it is, in fact,
In the 1920s, the technique of tracheal intubation was directly related to the volume of gas ventilating the
refined by Magill and Rowbotham.5,6 In World War II, alveoli because part of the VE resides in the conducting
the Bennett valve, which allowed cyclic application of airways or in nonperfused alveoli. As such, the portion of
high pressure, was devised to allow pilots to tolerate the ventilation that does not participate in CO2 exchange
high-altitude bombing missions.7 Concomitantly, the use is termed the dead space (Vd).15 In a patient with healthy
of translaryngeal intubation and mechanical ventilation lungs, this dead space is fixed or anatomic, and consists
became common in the operating room as well as in the of about one-third of the tidal volume (i.e., Vd/Vt=0.33).
treatment of respiratory insufficiency. However, applica- In a setting of respiratory insufficiency, the proportion of
tion of mechanical ventilation to newborns, both in the dead space (Vd/Vt) may be augmented by the presence of
operating room and in the intensive care unit (ICU), nonperfused alveoli and a reduction in Vt. Furthermore,
lagged behind that for children and adults. dead space can unwittingly be increased through the
The use of positive-pressure mechanical ventilation in presence of extensions of the trachea such as the endotra-
the management of respiratory distress syndrome (RDS) cheal tube, a pneumotachometer to measure tidal volume,
was described in 1962.8 It was the unfortunate death of an end-tidal CO2 monitor, or an extension of the ventila-
Patrick Bouvier Kennedy at 32 weeks gestation in 1963 tor tubing beyond the Y.
that resulted in additional National Institutes of Health Tidal volume is a function of the applied ventilator
(NIH) funding for research in the management of new- pressure and the volume/pressure relationship (compli-
borns with respiratory failure.9 The discovery of sur- ance), which describes the ability of the lung and chest
factant deficiency as the etiology of RDS in 1959, the wall to distend. At the functional residual capacity (FRC),
ability to provide positive-pressure ventilation in new- the static point of end expiration, the tendency for the
borns with respiratory insufficiency in 1965, and demon- lung to collapse (elastic recoil) is in balance with the
stration of the effectiveness of continuous positive airway forces that promote chest wall expansion.15 As each breath
pressure in enhancing lung volume and ventilation in develops, the elastic recoil of both the lung and chest wall
patients with RDS in 1971 set the stage for the develop- work in concert to oppose lung inflation. Therefore, pul-
ment of continuous-flow ventilators specifically designed monary compliance is a function of both the lung elastic
for neonates.1012 The development of neonatal ICUs recoil (lung compliance) and that of the rib cage and
(NICUs), hyperalimentation, and neonatal invasive and diaphragm (chest wall compliance).
noninvasive monitoring enhanced the care of newborns The compliance can be determined in a dynamic or
with respiratory failure and increased survival in preterm static mode. Figure 7-2 demonstrates the dynamic
newborns from 50% in the early 1970s to more than 90% volume/pressure relationship for a normal patient. Note
today.13 that application of 25cmH2O of inflating pressure (P)
94
7 Mechanical Ventilation in Pediatric Surgical Disease 95
%SvO2
The overall therapeutic goal of optimizing oxygena-
tion parameters is to maintain oxygen delivery (DO2) to
the tissues. Three variables determine DO2: cardiac 40
output (Q), hemoglobin concentration (Hgb), and arte-
rial blood oxygen saturation (SaO2). The product of these
three variables determines DO2 by the relation:
20
Pressure, volume
cardiac output, the effect of barotrauma, and the risk for
ventilator-induced lung injury with application of peak
inspiratory pressures greater than 3040cmH2O.32,33 Trigger
(time, pressure,
Furthermore, oxygen consumption can be elevated sec- or flow)
ondary to sepsis, burns, agitation, seizures, hyperthermia,
hyperthyroidism, and increased catecholamine produc-
tion or infusion. A number of interventions may be
applied to reduce VO2, such as sedation and mechanical FIGURE 7-6 Variables that characterize the mode of mechanical
ventilation. Paralysis may enhance the effectiveness of ventilation.
mechanical ventilation while simultaneously reducing
VO2.34,35 In the appropriate setting, hypothermia may be a pressure generated by the patient of approximately
induced with an associated reduction of 7% in VO2 with 1cmH2O will trigger the initiation of a breath. The
each 1C decrease in core temperature.36 sensitivity of the triggering device can be adjusted so that
patient work is minimized. Other ventilators detect the
reduction in constant ventilator tubing gas flow that is
MECHANICAL VENTILATION associated with patient initiation of a breath. Detection
of this decrease in flow results in initiation of a positive-
As discussed earlier, failure of gas exchange (CO2 elimi- pressure breath.
nation or oxygenation) may be an indication for mechani- The magnitude of the breath is controlled or limited
cal ventilation. The ventilator can also be used to reduce by one of three variables: pressure, volume, or flow. When
the work of breathing and decrease VO2. Finally, mechan- a breath is volume, pressure, or flow controlled, it indi-
ical ventilation is used in patients who are unable to cates that inspiration concludes once the limiting variable
breathe independently for neurologic reasons (primary is reached. Pressure-controlled or pressure-limited modes
hypoventilation, traumatic brain injury, inability to are the most popular for all age groups, although volume-
protect airway). control ventilation may be of advantage in preterm new-
borns.39,40 In the pressure modes, the respiratory rate, the
The Mechanical Ventilator and Its inspiratory gas flow, the PEEP level, the inspiratory/
expiratory (I/E) ratio, and the Paw are determined. The
Components ventilator infuses gas until the desired peak inspiratory
The ventilator must overcome the pressure generated by pressure (PIP) is provided. Zero-flow conditions are real-
the elastic recoil of the lung at end inspiration plus the ized at end inspiration during pressure-limited ventila-
resistance to flow at the airway. To do so, most ventilators tion. Therefore, in this mode, PIP is frequently equivalent
in the ICU are pneumatically powered by gas pressurized to end-inspiratory pressure (EIP) or plateau pressure.
at 50 pounds per square inch (psi). Microprocessor In many ventilators, the gas flow rate is fixed, although
controls allow accurate management of proportional some ventilators allow manipulation of the flow rate and
solenoid-driven valves, which carefully control infusion therefore the rate of positive-pressure development.
of a blend of air or oxygen into the ventilator circuit while Those with rapid flow rates will provide rapid ascent of
simultaneously opening and closing an expiratory valve.37 pressure to the preset maximum, where it will remain for
Additional components of a ventilator include a bacterial the duration of the inspiratory phase. This square wave
filter, a pneumotachometer, a humidifier, a heater/ pressure pattern results in decelerating flow during inspi-
thermostat, an oxygen analyzer, and a pressure manom- ration (Fig. 7-7). Airway pressure is front loaded, which
eter. A chamber for nebulizing drugs is usually incorpo- increases Paw, alveolar volume, and oxygenation without
rated into the inspiratory circuit. The Vt is not usually increasing PIP.41 However, one of the biggest advantages
measured directly. Rather, flow is assessed as a function of pressure-controlled or pressure-limited ventilation is
of time, thereby allowing calculation of Vt. The modes the ability to avoid lung over-distention and barotrauma/
of ventilation are characterized by three variables that volutrauma (discussed later). The disadvantage of
affect patient and ventilator synchrony or interaction: the pressure-controlled or pressure-limited ventilation is that
parameter used to initiate or trigger a breath, the param- delivered volume varies with airway resistance and pul-
eter used to limit the size of the breath, and the param- monary compliance, and may be reduced when short
eter used to terminate inspiration or cycle the breath inspiratory times are applied (Fig. 7-8).42 For this reason,
(Fig. 7-6).38 both Vt and VE must be monitored carefully.
Gas flow in most ventilators is triggered either by time Volume-controlled or volume-limited ventilation
(controlled breath) or by patient effort (assisted breath). requires delineation of the Vt, respiratory rate, and inspir-
Controlled ventilation modes are time triggered: the atory gas flow. Gas will be inspired until the preset Vt is
inspiratory phase is concluded once a desired volume, attained. The volume will remain constant despite
pressure, or flow is attained, but the expiratory time will changes in pulmonary mechanics, although the resulting
be the difference between the inspiratory time and the EIP and PIP may be altered. Flow-controlled or flow-
preset respiratory cycle time. In the assist mode, the limited ventilation is similar in many respects to volume-
ventilator is pressure or flow triggered. With the former, controlled or volume-limited ventilation. A flow pattern
7 Mechanical Ventilation in Pediatric Surgical Disease 99
Paw
80 * 10
*
* 8
60 VE * *
Paco2 (mmHg)
Pressure
VE (L/min)
PA 40
Auto-PEEP Paco2 4
0 PEEP
20
2
Time
0 0
0 10 20 30 40 50 60
0.6 1
VT VD / V T
Flow
0 *
0.4 * 0.8
VT or VD (L)
*
VD / VT
*
VD *
*
0.2 * * 0.6
FIGURE 7-7 Pressure and flow waveforms during pressure- * *
limited, time-cycled ventilation. Decelerating flow is applied, * *
which front loads the pressure during inspiration. Auto-positive
end-expiratory pressure is present when the expiratory time is 0 0.4
inadequate for complete expiration. (Reprinted from Marini JJ. 0 10 20 30 40 50 60
New options for the ventilatory management of acute lung injury. f (breaths/min)
New Horiz 1993;1:489503.)
FIGURE 7-8 Effect of rate on tidal volume (Vd/Vt) and minute
ventilation (VE) during pressure-limited ventilation. Note that VE
remains unchanged above 20 breaths/min. Simultaneously,
is predetermined, which effectively results in a fixed Vd/Vt and PaCO2 increase, despite an increase in respiratory rate.
(Reprinted from Nahum A, Burke WC, Ravenscraft SA. Lung
volume as the limiting component of inspiration. mechanics and gas exchange during pressure-control ventilation in
The ventilator breath is concluded based on one of dogs: Augmentation of CO2 elimination by an intratracheal catheter.
four variables: volume, time, pressure, or flow. With Am Rev Respir Dis 1992;146:96573.)
volume-cycled ventilation, inspiration is terminated
when a prescribed volume is obtained. Likewise, with is markedly increased in the spontaneously breathing
time-, pressure-, or flow-cycled ventilation, expiration patient. This mode of ventilation is no longer used.
begins after a certain period has passed, the airway
pressure reaches a certain value, or when the flow has
Intermittent Mandatory Ventilation
decreased to a predetermined level, respectively.
A factor that limits inspiration suggests that the chosen Intermittent mandatory ventilation (IMV) is time trig-
value limits the level of the variable during inspiration, gered, volume or pressure limited, and either time,
but the inspiratory phase does not necessarily conclude volume, or pressure cycled. A rate is set, as is a volume
once this value is attained. For instance, during pressure- or pressure parameter. Additional inspired gas is provided
limited ventilation, gas flow continues until a given pres- by the ventilator to support spontaneous breathing when
sure limit is attained. However, the inspiratory phase may additional breaths are desired. The difference between
continue beyond that point. The limitation only controls CMV and IMV is that, in the IMV mode, inspired gases
the magnitude of the breath but does not always deter- are provided to the patient during spontaneous breaths.43
mine the length of the inspiratory phase. In contrast, IMV is useful in patients who do not have respiratory
during pressure-controlled ventilation, both gas flow and drive such as those who are neurologically impaired or
the inspiratory phase terminate once the preset pressure pharmacologically paralyzed. Work of breathing is still
is reached because pressure is used to limit the magnitude elevated with this mode in the awake and spontaneously
of the breath and the gas flow. breathing patient.
ACV, assist-control ventilation; CMV, controlled mechanical ventilation; IMV, intermittent mandatory ventilation; PAV, proportional assist
ventilation; PSV, pressure support ventilation; SIMV, synchronized intermittent mandatory ventilation; VAPSV, volume-assured pressure
support ventilation; VSV, volume support ventilation.
a
Patient-controlled rate.
ventilator that a patient breath has been initiated. Venti- ventilation. It is similar in concept to ACV, in that mechan-
lated breaths are timed with the patients spontaneous ical support is provided for each spontaneous breath
respiration, but the number of supported breaths each and the patient determines the ventilator rate. During
minute is predetermined and remains constant. Additional each breath, inspiratory flow is applied until a predeter-
constant inspired gas flow is provided for use during any mined pressure is attained.50 As the end of inspiration
other spontaneous breaths. Advances in neonatal ventila- approaches, flow decreases to a level below a specified
tors have provided the means for detecting small altera- value (26L/min) or a percentage of peak inspiratory flow
tions in bias flow. As such, flow-triggered SIMV can be (at 25%). At this point, inspiration terminates. Although it
applied to newborns, which appears to enhance ventila- may apply full support, PSV is frequently used to support
tory patterns and allows ventilation with reduced airway the patient partially by assigning a pressure limit for each
pressures and FiO2.44,45 SIMV may be associated with a breath that is less than that required for full support.51 For
reduction in the duration of ventilation and the incidence example, in the spontaneously breathing patient, PSV can
of air leak in newborns in general, as well as in those pre- be sequentially decreased from full support to a PSV
mature infants with bronchopulmonary dysplasia (BPD) 510cmH2O above PEEP, allowing weaning while pro-
and intraventricular hemorrhage.46,47 viding partial support with each breath.52,53 Thus, Vt
during PSV may be dependent on patient effort. PSV
provides two advantages during ventilation of spontane-
Assist-Control Ventilation
ously breathing patients: (1) it provides excellent support
In the spontaneously breathing patient, brain stem reflexes and decreases the work of breathing associated with ven-
dependent on cerebrospinal fluid levels of CO2 and pH tilation; and (2) it lowers PIP and Paw while higher Vt and
can be harnessed to determine the appropriate breathing cardiac output levels may be observed.50,54,55
rate.15 As in SIMV, with assist-control ventilation (ACV) Pressure-triggered SIMV and PSV can be applied to
the assisted breaths can be either pressure triggered or newborns. Inspiration is terminated when the peak airway
flow triggered. The triggering-mechanism sensitivity can flow decreases to a set percentage between 525%. This
be set in most ventilators. In contrast to SIMV, the ventila- flow cutoff for inspiration, known as the termination sen-
tor supports all patient-initiated breaths. This mode is sitivity, can be adjusted. The higher the termination sen-
similar to IMV but allows the patient inherently to control sitivity value, the shorter is the inspiratory time. The
the ventilation and minimizes patient work of breathing in termination sensitivity function also may be disabled, at
adults and neonates.48,49 Occasionally, patients may hyper- which point ventilation is time cycled instead of flow
ventilate, such as when they are agitated or have neuro- cycled. There is a reduction in work of breathing and
logic injury. Heavy sedation may be required if agitation is sedation requirements when SIMV with pressure support
present. A minimal ventilator rate below the patients assist is applied to newborns.
rate should be established in case of apnea.
Volume Support Ventilation
Pressure Support Ventilation
Volume support ventilation (VSV) is similar to PSV
Pressure support ventilation (PSV) is a pressure- or except that a volume, rather than a pressure, is assigned
flow-triggered, pressure-limited, and flow-cycled mode of to provide partial support. Automation with VSV is
7 Mechanical Ventilation in Pediatric Surgical Disease 101
EIP
results in development of a greater Vt. Inspiration is
patient triggered and terminates with discontinuation
of patient effort. Rate, Vt, and inspiratory time are entirely
patient controlled. The predominant variable controlled
by the ventilator is the proportional response between
Pmus and the applied ventilator pressure. This propor-
tional assist (Paw/Pmus) can be increased until nearly all
patient effort is provided by the ventilator.60 Patient work
of breathing, dyspnea, and PIP are reduced.61,62 Elastance
and resistance are set, as is applied PEEP. Vt is variable,
and the risk of atelectasis is present. PAV produces similar
gas exchange with lower airway pressures when com-
pared with conventional ventilation in infants.63 Com-
Gas flow
support by varying airway pressure between one of two Airway Pressure Release Ventilation
settings: the inspiratory positive airway pressure (IPAP)
and the expiratory positive airway pressure (EPAP).69,70 Airway pressure release ventilation (APRV) is a unique
With patient effort, a change in flow is detected, and the approach to ventilation in which CPAP at high levels is
IPAP pressure level is developed. With reduced flow at used to enhance mean alveolar volume while intermittent
end expiration, EPAP is re-established. Therefore, this reductions in pressure to a release level provide a
device provides both ventilatory support and airway period of expiration (Fig. 7-10). Re-establishment of
distention during the expiratory phase; however, BiPAP CPAP results in inspiration and return of lung volume
ventilators should be used only to support the patient back to the baseline level. The advantage of APRV is a
who is spontaneously breathing. In fact, in a randomized reduction in PIP of approximately 50% in adult patients
trial of noninvasive ventilation (NIV) in a subset of pedi- with ARDS when compared with other more conven-
atric patients with lung injury, NIV improved hypoxemia tional modes of mechanical ventilation.86,87 Spontaneous
and decreased the rate of endotracheal intubation.71 In ventilation also is allowed throughout the cycle, which
neonates, a multicenter randomized trial demonstrated may enhance cardiac function and renal blood flow.88,89
decreased days of mechanical ventilation, chronic lung Some data suggest that V / Q matching may be
disease, and mortality when early CPAP was used instead improved and dead space reduced.90,91 In performing
of intubation and surfactant in preterm infants.72 APRV, tidal volume is altered by adjusting the release
pressure. Conceptually, ventilator management during
APRV is the inverse of other modes of positive-pressure
Inverse Ratio Ventilation ventilation in that the PIP, or CPAP, determines oxygena-
In the setting of respiratory failure, it would be helpful to tion, while the expiratory pressure (release pressure) is
enhance alveolar distention to reduce hypoxemia and used to adjust Vt and CO2 elimination.
shunt. One means to accomplish this is to maintain the APRV is very similar to modes of ventilation, such as
inspiratory plateau pressure for a longer proportion of IRV, that use prolonged I/E ratios; however, APRV
the breath.73 The inspiratory time may be prolonged to the appears to be better tolerated when compared with IRV
point at which the I/E ratio may be as high as 4:1.74 In in patients with acute lung injury/ARDS, as demon-
most circumstances, however, the I/E ratio is maintained strated by a reduced need for paralysis and sedation,
at approximately 2:1. Inverse ratio ventilation (IRV) is increased cardiac performance, decreased pressor use,
usually performed during pressure-controlled ventilation and decreased PIP requirements.92 APRV improved the
(PC-IRV), although prolonged inspiratory times can be lung perfusion, as measured by pulmonary blood flow
applied during volume-controlled ventilation by adding a and oxygen delivery, in infants who underwent repair of
decelerating flow pattern or an end-inspiratory pause to tetralogy of Fallot or cavopulmonary shunt.93 However,
the volume-controlled ventilator breath.75 One advantage the overall clinical experience with APRV is limited in
of IRV is the ability to recruit alveoli that are associated the pediatric population.94,95
with high-resistance airways that inflate only with pro-
longed application of positive pressure.76 Unfortunately, Management of the
IRV is associated with a profound sense of dyspnea in Mechanical Ventilator
patients who are awake and spontaneously breathing.
Therefore, heavy sedation and pharmacologic paralysis is IMV and SIMV may suffice for patients with normal
required during this ventilator mode. lungs, such as when needed after an operation.96 If the
As Et is reduced, the risk for incomplete expiration, patient is spontaneously breathing and is to be ventilated
identified by the failure to achieve zero-flow conditions for more than a brief period, a flow- or pressure-triggered
at end expiration, is increased. This results in auto- assist mode, pressure support, or PAV will result in
PEEP or a total PEEP greater than that of the preset or maximal support and minimal work of breathing.48,49
applied PEEP. Care should be taken to recognize the Ventilator modes that allow adjustment of specific details
presence of auto-PEEP and to incorporate it into the of pressure, flow, and volume are required in the patient
ventilation strategy to avoid barotrauma.77 IRV also may
negatively affect cardiac output and, therefore, decrease
DO2.78 Some studies using IRV revealed an increase in 30
Airway pressure
with severe respiratory failure. With all these modes, the with a high-Vt group (15mL/kg).106 A relation may also
ventilator rate, Vt or PIP, PEEP, and either inspiratory exist between ventilator gas flow rate and the develop-
time alone or I/E ratio (if ventilation is pressure limited) ment of lung injury.107 Positive blood cultures were found
must be assigned. Other secondary controls such as the in five of six animals exposed to high EIP, but rarely in
flow rate, the flow pattern, the trigger sensitivity for those with low EIP.108
assisted breaths, the inspiratory hold, the termination Together, the above data suggest that the method of
sensitivity, and the safety pressure limit also are set on ventilation has an effect on lung function and gas exchange
individual ventilators. The normal VE is 100150mL/ as well as a systemic effect, which may include transloca-
kg/min. The FiO2 is usually initiated at 0.50 and decreased tion of bacteria from the lungs. As such, avoidance of
based on pulse oximetry. All efforts should be made to high PIPs and lung over-distention should be a primary
maintain the FiO2 less than 0.60 to avoid alveolar nitro- goal of mechanical ventilation. Although the animal data
gen depletion and the development of atelectasis.97,98 suggests that high PIPs and volumes may be deleterious,
Oxygen toxicity likely is a result of this phenomenon, two multicenter studies have attempted to randomize
although free oxygen radical formation may play a role patients with ARDS to high and low peak pressure or
when an FiO2 greater than 0.40 is applied for prolonged volume strategies. The first failed to demonstrate a dif-
periods.99 A short inspiratory phase with a low I/E ratio ference in mortality or duration of mechanical ventilation
favors the expiratory phase and CO2 elimination, whereas in patients randomized to either the low-volume
longer I/E ratios enhance oxygenation. In the normal (7.20.8mL/kg) or the high-volume (10.81.0mL)
lung, I/E ratios of 1:3 and inspiratory time of 0.5 to 1 strategy, although the applied PIP was not elevated
second are typical. to what would commonly be considered injurious
levels in either group (low, 23.65.8cmH2O; high,
34.011.0cmH2O).109 Another study found similar
Strategies in Respiratory Failure results, but had similar design limitations.110 A survival
increase from 38% to 71% at 28 days, a higher rate of
Preventing Ventilator-Induced Lung Injury
weaning from mechanical ventilation, and a lower rate of
A decrease in pulmonary compliance and FRC is seen in barotrauma has been demonstrated in patients in whom
the patient with acute lung injury (PaO2/FiO2 ratio, 200 a lung-protective ventilator strategy was used. This strat-
300) or ARDS (PaO2/FiO2 ratio, <200). This is secondary egy consisted of lung distention to a level that prevented
to alveolar collapse and a decrease in the volume of lung alveolar collapse during expiration (see later) and avoid-
available for ventilation and, in turn, to decreased pulmo- ance of high distending pressures.111 One study identified
nary compliance. As a result, higher ventilator pressures a significant reduction over time in bronchoalveolar
are necessary to maintain Vt and VE . However, any lavage concentrations of polymorphonuclear cells
attempt to ventilate the patient with respiratory insuffi- (P<0.001), interleukin (IL)-1 (P<0.05), tumor necro-
ciency due to parenchymal disease with higher pressures sis factor (TNF)- (P<0.001), interleukin (IL)-8
can result in compromise of cardiopulmonary function (P<0.001), and IL-6 (P<0.005) and in the plasma con-
and the development of ventilator-induced lung injury.100 centration of IL-6 (P<0.002) among 44 patients rand-
The concept of ventilator-induced lung injury was first omized to receive a lung-protective strategy rather than
identified in 1974 by demonstrating the detrimental a conventional approach.112 The mean number of
effects of ventilation at PIP of 45cmH2O in rats.101 Elec- ventilator-free days at 28 days in the lung-protective
tron microscopy has been used to document an increased strategy group was higher than in the control group
incidence of alveolar stress fractures in ex-vivo, perfused (1211 vs. 48 days, respectively; P<0.01). However,
rabbit lungs exposed to transalveolar pressures more than mortality rates at 28 days from admission were not
30cmH2O.102 Other studies have demonstrated increases different.
in albumin leak, elevation of the capillary leak coefficient, The NIHs Acute Respiratory Distress Network con-
enhanced wet-to-dry lung weight, deterioration in gas vincingly demonstrated that mortality was reduced with
exchange, and augmented diffuse alveolar damage on his- the use of a low-volume (6mL/kg, mortality of 31%)
tology with application of increased airway pressure when compared with a high-volume (12mL/kg, mortal-
(4550cmH2O) in otherwise normal rats and sheep over ity of 39%; P=0.005) ventilator approach (Fig. 7-11).113
a 1- to 24-hour period.31,103,104 Pulmonary exposure to Interestingly, no difference was found in gas exchange or
high pressures may potentially worsen nascent respira- pulmonary mechanics between groups to account for the
tory insufficiency and, ultimately, lead to the develop- difference in mortality. The majority of clinicians are
ment of pulmonary fibrosis. now convinced that avoidance of high PIP and support
Such injury may be prevented during application of of lung recruitment, through the application of appropri-
high PIPs by strapping the chest, thereby preventing ate levels of PEEP (see later), should be a primary goal
lung over-distention, suggesting that alveolar distention of any mechanical ventilatory program.
or volutrauma is the injurious element, rather than
application of high pressures or barotrauma.105 A low-Vt Permissive Hypercapnia
(6mL/kg) approach to mechanical ventilation in rabbits
with Pseudomonas aeruginosa-induced acute lung injury To avoid ventilator-induced lung injury, practitioners
appears to be associated with enhancement in oxygena- have applied the concept of permissive hypercapnia. With
tion, increase in pH, increase in arterial blood pressure, this approach, PaCO2 is allowed to increase to levels as
and decrease in extravascular lung water when compared high as 120mmHg as long as the blood pH is maintained
104 SECTION I General
1.0 1200
0.9
0.8 1000
Proportion of patients
0.7
0.6 800
Volume (mL)
0.5
Lower tidal volumes 600
0.4 Survival UIP
0.3 Discharge
Traditional tidal volumes 400
0.2 Survival
0.1 Discharge
200
0.0
0 20 40 60 80 100 120 140 160 180 0
Days after randomization 0 10 20 30 40 50 60
FIGURE 7-11 Probability of survival and of being discharged Plateau pressure (cmH2O)
home and breathing without assistance during the first 180 days
after randomization in patients with acute lung injury and the FIGURE 7-12 Static pressure/volume curve demonstrating the
acute respiratory distress syndrome. The status at 180 days or Pflex point in a patient with acute respiratory distress syndrome.
at the end of the study was known for all but nine patients. (From Positive end-expiratory pressure should be maintained approxi-
The Acute Respiratory Distress Network. Ventilation with lower tidal mately 2cmH2O above that point. The upper inflection point
volumes as compared with traditional tidal volumes for acute lung (UIP) indicates the point at which lung over distention is begin-
injury and the acute respiratory distress syndrome. N Engl J Med ning to occur. Ventilation to points above the UIP should be
2000;342:13018.) avoided in most circumstances. (Reprinted from Roupie E,
Dambrosio M, Servillo G. Titration of tidal volume and induced
hypercapnia in acute respiratory distress syndrome. Am J Respir
Crit Care Med 1995;152:1218.)
in the 7.17.2 range by administration of buffers.114 Mor-
tality was reduced to 26% when compared with that
expected (53%; P<0.004) based on Acute Physiology and has been demonstrated that the distribution of infiltrates
Chronic Health Evaluation II (APACHE II) scores when and atelectasis in the supine patient with ARDS is pre-
low-volume, pressure-limited ventilation with permissive dominantly in the dependent regions of the lung.124 This
hypercapnia was applied in the setting of ARDS in is likely the result of compression due to the increased
adults.115 For burned children, the mortality rate was only weight of the overlying edematous lung. It has been
3.7% despite a high degree of inhalation injury when a shown that when the superimposed gravitational pressure
ventilator strategy used a PIP of 40cmH2O and accepted from the weight of the overlying lung exceeded the PEEP
an elevated PaCO2 as long as the arterial pH was greater applied to a given region of the lung, end-expiratory lung
than 7.20.116 Other studies suggested that a strategy of collapse increased, resulting in de-recruitment.125 Thus,
high-frequency (40120 breaths/min) ventilation with a application of PEEP may result in recruitment of these
low Vt, low PIP, high PEEP (730cmH2O), and mild atelectatic lung regions, simultaneously enhancing pul-
hypercapnia (PaCO2 from 45 to 60mmHg) enhances the monary compliance and oxygenation. PEEP and prone
survival rate in children with severe ARDS.117 positioning (see later) are more effective if the need for
ventilation is of extrapulmonary etiology rather than pul-
monary etiology.126
Using Protective Effects of PEEP
As a result of these new data and concepts, the approach
Although application of high, over distending airway to mechanical ventilation in the patient with respiratory
pressures appears to be associated with the development failure has changed drastically over the past few years
of lung injury, a number of studies have demonstrated (Box 7-1). Time-cycled, pressure-controlled ventilation
that application of PEEP or high-frequency oscillatory has become favored because of the ability to limit EIP to
ventilation (HFOV) may prevent lung injury by the noninjurious levels at a maximum of 35cmH2O.121 In
following mechanisms: (1) recruitment of collapsed infants and newborns, this EIP limit is set lower at
alveoli, which reduces the risk for over-distention of 30cmH2O. The Vt should be maintained in the range of
healthy units; (2) resolution of alveolar collapse, which in 6mL/kg.113 A lung-protective approach also incorporates
and of itself is injurious; and (3) avoidance of the shear lung distention and prevention of alveolar closure.
forces associated with the opening and closing of Pressure/volume curves should be developed on each
alveoli.118,119 In the older child with injured lungs, a patient at least daily so that the Pflex can be identified and
pressure of 812cmH2O is required to open alveoli the PEEP maintained above Pflex. If a pressure/volume
and to begin Vt generation.111,120,121 Alveoli will subse- curve cannot be determined, then Pflex can be assumed to
quently close unless the end-expiratory pressure is be in the 712cmH2O range, and PEEP, at that level or
maintained at such pressures, and cyclic opening and up to 2cmH2O higher, can be applied.121,127,128 Recruit-
closing is thought to be particularly injurious because of ment maneuvers that use intermittent sustained inflations
application of large shear forces.120 One way to avoid this of approximately 40cmH2O for up to 40 seconds often
process is through the application of PEEP to a point can be beneficial by initially inflating collapsed lung
above the inflection pressure (Pflex), such that alveolar regions.129 The inflation obtained with the recruitment
distention is maintained throughout the ventilatory cycle maneuver is then sustained by maintaining PEEP greater
(Fig. 7-12).122,123 In addition, as mentioned previously, it than Pflex.
7 Mechanical Ventilation in Pediatric Surgical Disease 105
Therefore, the concept of permissive hypercapnia, which Management of the Patient for
was discussed previously, is integral to the successful BOX 7-2 Whom Extubation Attempts Have
application of lung-protective strategies. PaCO2 levels Failed
greater than 100mmHg have been allowed with this
approach, although most practitioners prefer to maintain Frequent spontaneous breathing trials
the PaCO2 at less than 6070mmHg.115 Bicarbonate or Pressure support ventilation
tris-hydroxymethyl-aminomethane (THAM) can be used Caloric intake 10% above expenditure
to induce a metabolic alkalosis to maintain the pH at Minimize carbohydrate calories
greater than 7.20. Few significant physiologic effects are Diuresis to dry weight
observed with elevated PaCO2 levels as long as the pH is Treat infection
maintained at reasonable levels.145 If adequate CO2 elimi- Tracheostomy
nation cannot be achieved while limiting EIP to nonin-
jurious levels, then initiation of extracorporeal life support
(ECLS) should be considered. rates; (2) inspiratory force greater than 20cmH2O; (3)
The one situation in which it may be acceptable to VE less than 100mL/kg/min; and (4) SaO2 greater than
increase EIP to levels greater than 35cmH2O (30cmH2O 95%. If the patients status is unclear, transcutaneous CO2
in the infant and newborn) is in the patient with reduced monitoring, along with arterial blood gas analysis
chest wall compliance and relatively normal pulmonary (PaCO2<40mmHg; PaO2>60mmHg), may help in
compliance. As pulmonary compliance is a combination determining whether extubation is appropriate. The
of lung compliance and chest wall compliance, a decrease weaning trial should be brief, and under no circumstances
in chest wall compliance, such as due to abdominal dis- should it last longer than one hour. In most cases, the
tention, obesity, or chest wall edema, can markedly patient who tolerates spontaneous breathing through an
reduce pulmonary compliance despite reasonable lung endotracheal tube for only a few minutes will demon-
compliance. This situation is analogous to studies dis- strate enhanced capabilities once the tube is removed.
cussed previously in which the lungs remain uninjured Frequent causes of failed extubation include persistent
despite application of high airway pressures because the pulmonary parenchymal disease, interstitial fibrosis, and
chest is strapped to prevent lung over distention.105 This reduced breathing endurance. PSV is ideal for use in the
is a frequent problem in secondary respiratory failure due difficult-to-wean patient because it allows gradual appli-
to trauma, sepsis, and other disease processes observed cation of spontaneous support to enhance respiratory
among surgical patients, including tightly placed dress- strength and conditioning (Box 7-2).146 Enteral and
ings. A cautious increase in EIP in such patients may be parenteral nutrition should be adjusted to maintain the
warranted. Finally, a simple intervention, such as raising total caloric intake to no more than 10% above the esti-
the head of the bed, may have marked effects on FRC mated caloric needs of the patient. Excess calories will be
and gas exchange in such patients. converted to fat, with a high respiratory quotient and
increased CO2 production. Nutritional support high in
glucose will have a similar effect.150 Manipulation of feed-
Weaning From Mechanical Ventilation ings along with treatment of sepsis may reduce VCO2 and
Once a patient is spontaneously breathing and able to enhance weaning. Pulmonary edema should be treated
protect the airway, consideration is given to weaning with diuretics. Some patients will benefit from a trache-
from ventilator support. Weaning in the majority of chil- ostomy to avoid ongoing upper airway contamination, to
dren should take 2 days or less.57 The Fi O2 should be decrease dead space and airway resistance, and to provide
decreased to less than 0.40 before extubation. Simultane- airway access for evacuation of secretions during the
ously, PEEP should be lowered to 5cmH2O. The pres- weaning process. In addition, the issue of extubating the
sure support mode of ventilation is an efficient means for patient is removed by tracheostomy. Spontaneous breath-
weaning because the preset inspiratory pressure can be ing trials, therefore, are easy to perform, and the transi-
gradually decreased while partial support is provided for tion from the mechanical ventilator is a much smoother
each breath.146 Adequate gas exchange with a pressure and efficient process.151 In older patients, the tracheos-
support of 710cmH2O above PEEP in adults and new- tomy can be performed percutaneously in the ICU.152
borns is predictive of successful extubation.147 Another Long-term complications are fairly minimal in older
study in adults demonstrated that simple transition from patients. However, in newborns and infants, the rate of
full ventilator support to a T-piece, in which oxygen development of stenoses and granulation tissue may be
flow-by is provided, is as effective at weaning as is gradual significant.153,154
reduction in rate during IMV or pressure during PSV.148
In all circumstances, brief trials of spontaneous breathing
before extubation should be performed with flow-by NONCONVENTIONAL MODES
oxygen and CPAP. Prophylactic dexamethasone adminis- AND ADJUNCTS TO MECHANICAL
tration does not appear to increase the odds of a success-
ful extubation in infants, except in high risk patients who
VENTILATION
receive multiple doses starting at least four hours before High-Frequency Ventilation
extubation.149,150 Parameters during a T-piece trial that
indicate readiness for extubation include the following: The concept of high-frequency jet ventilation (HFJV)
(1) maintenance of the pretrial respiratory and heart was developed in the early 1970s to provide gas exchange
7 Mechanical Ventilation in Pediatric Surgical Disease 107
as a primary modality in the treatment of premature iNO-treated newborns (ECLS, 38%; P=0.001).179 The
infants with acute pulmonary dysfunction.174 incidence of chronic lung disease was also decreased in
newborns managed with iNO (7% vs 20%). Similar
results were noted for infants with persistent pulmonary
Inhaled Nitric Oxide Administration hypertension of the newborn (PPHN) who were on
Nitric oxide is an endogenous mediator that serves to HFOV. In another study, the need for ECLS was
stimulate guanylate cyclase in the endothelial cell to decreased from 55% in the control HFOV group to 14%
produce cyclic guanosine monophosphate (cGMP), in the combined iNO and HFOV group (P=0.007).180
which results in relaxation of vascular smooth muscle In a clinical trial conducted by the Neonatal Inhaled
(Fig. 7-14).175 NO is rapidly scavenged by heme moieties. Nitric Oxide Study (NINOS) Group, neonates born at
Therefore, iNO serves as a selective vasodilator of the 34 weeks or older gestational age with hypoxic respira-
pulmonary circulation, but is inactivated before reaching tory failure were randomized to receive 20ppm iNO or
the systemic circulation. Diluted in nitrogen and then 100% oxygen as a control.181 If a complete response,
mixed with blended oxygen and air, iNO is administered defined as an increase in PaO2 of more than 20mmHg
in doses of 180 parts per million (ppm). within 30 minutes after gas initiation, was not observed,
Pediatric patients with respiratory failure demonstrate then iNO at 80ppm was administered. Sixty-four per
increases in PaO2 with iNO at 20ppm.176 Unfortunately, cent of the control group and 46% of the iNO group died
a prospective, randomized, controlled trial investigating within 120 days or were treated with ECLS (P=0.006).
the effects of iNO therapy in children with respiratory No difference in death was found between the two groups
failure revealed that although pulmonary vascular resist- (iNO, 14% vs control, 17%), but significantly fewer
ance and systemic oxygenation were acutely improved at neonates in the iNO group required ECLS (39% vs
one hour by administration of 10ppm iNO, a sustained 54%). Follow-up at age 18 to 24 months failed to dem-
improvement at 24 hours could not be identified.177 onstrate a difference in the incidence of cerebral palsy,
Other studies have shown more promising results with rate of sensorineural hearing loss, and mental develop-
iNO. In one study, only 40% of the iNO-treated mental index scores between the control and iNO
term infants with pulmonary hypertension required patients.182 Other studies have similarly failed to identify
ECLS when compared with 71% of controls.178 a difference in pulmonary, neurologic, cognitive, or
These results were corroborated in another study by behavioral outcomes between survivors managed with
demonstrating a reduction in the need for ECLS in iNO and those in the conventional group.183
control newborns (ECLS, 64%) when compared with An associated, but separate, trial demonstrated no dif-
ference in mortality and a significant increase in the need
for ECLS when neonates with congenital disphragmatic
hernia (CDH) were treated with 20 or 80ppm of iNO
iNO versus 100% oxygen as control.184 It should be noted,
however, that some investigators have suggested that the
efficacy of iNO in patients with CDH may be more sub-
stantial after surfactant administration or at the point at
which recurrent pulmonary hypertension occurs.185 iNO
administration also may be helpful in the moribund CDH
+ Soluble guanylate patient until ECLS can be initiated.
cyclase Some concern has been expressed for the development
of intracranial hemorrhage in premature newborns
treated with iNO. More than a 25% increase in the
arterial/alveolar oxygen ratio (PaO2/PAO2) was observed
cGMP in ten of 11 premature newborns, with a mean gestational
age of 29.8 weeks and severe RDS, in response to admin-
GTP istration of 120ppm iNO.186 However, in seven of these
11 newborns, intracranial hemorrhage developed during
their hospitalization. Also, a meta-analysis of the three
completed studies evaluating the efficacy of iNO in pre-
Relaxation mature newborns suggested no significant difference in
5' GMP
survival, incidence of chronic lung disease, or rate of
development of intracranial hemorrhage between iNO
and controls.187
Zaprinast
NO is associated with the production of potentially
FIGURE 7-14 Mechanism of action of inhaled nitrous oxide toxic metabolites. When combined with O2, iNO pro-
(iNO) in inducing vascular smooth muscle relaxation. Zaprinast duces peroxynitrates, which can be damaging to epithelial
is a phosphodiesterase inhibitor that may increase the potency
and duration of the effect of iNO. GTP, guanosine triphosphate; cells and also can inhibit surfactant function.188,189 Nitro-
cGMP, cyclic guanosine monophosphate. (Reprinted from Hirschl gen dioxide, which is toxic, can be produced, and hemo-
RB. Innovative therapies in the management of newborns with globin can be oxidized to methemoglobin. Additional
congenital diaphragmatic hernia. Semin Pediatr Surg 1996;5: concerns exist about the immunosuppressive effects and
25565.)
the potential for platelet dysfunction.
7 Mechanical Ventilation in Pediatric Surgical Disease 109
20
* patients, mechanical ventilation must have been used for
15 Controls more than 48 hours.204,206 Microbial confirmation is not
* necessary for the NNIS/CDC criteria defined in Boxes
10 * Surfactant 7-3, 7-4 or 7-5, and the use of quantitative cultures for
* * * diagnosis in children and neonates is variable. The tech-
* * * *
5 * * * * * *
nique of fiberoptic bronchoalveolar lavage (BAL) has
0 been described in children, but is not routinely used.
6 0 6 12 18 24 30 36 42 Blind BAL findings of a bacterial index (defined as the
log10 of the colony-forming units of microorganisms per
Time (hours)
milliliter of BAL fluid) greater than 5 are the most reli-
FIGURE 7-15 The effect of exogenous surfactant administration able method for diagnosing VAP in mechanically venti-
on oxygen index in term newborns with meconium-aspiration
syndrome. (Reprinted from Findlay RD, Taeusch HW, Walther FJ.
lated children.207
Surfactant replacement therapy for meconium aspiration syndrome. Investigations on the treatment of VAP focus on
Pediatrics 1996;97:4852.) empirical use of antibiotics and duration of therapy.
110 SECTION I General
NNIS/CDC Criteria for Diagnosis gram-negative bacilli, however, benefited from the longer
of Ventilator-Associated Pneumonia duration of therapy with a reduced relapse rate. Finally,
BOX 7-4 patients treated for 8 days also had a reduced incidence
in Children Between Ages 1 and 12
Years of multidrug-resistant pathogens on relapse when com-
pared with those treated for 15 days.
Three of the following: Guidelines for the prevention of VAP have been estab-
Fever (>38.4C) or hypothermia (<37C) with no other lished based on current evidence by the VAP Guidelines
recognized cause Committee and the Canadian Critical Care Trials
Leukopenia (<4,000 white blood cells/mm3) or leukocy- Group.205 Recommended therapeutic interventions
tosis (15,000 white blood cells/mm3) include the orotracheal route for intubation, a ventilator
New onset of purulent sputum, change in character of circuit specific for each patient, circuit changes if soiled
sputum, increased respiratory secretions, or increased or damaged but no scheduled changes, change of heat
suctioning requirements
Rales or bronchial breath sounds
and moisture exchangers every 5 to 7 days or as indicated,
Worsening gas exchange (O2 desaturations [pulse oxime- use of a closed endotracheal suctioning system changed
try <94%], increased oxygen requirements, or increased for each patient and as clinically indicated, subglottic
ventilation demand) secretion drainage in patients expected to be mechani-
cally ventilated for more than 72 hours, and the head of
From NNIS/CDCNational Nosocomial Infections Surveillance System/ bed elevated at 45 degrees when possible. Consideration
Centers for Disease Control.
should be given to the use of rotating beds and oral anti-
septic rinses.213 Finally, in adult patients, a team approach
and implementation of a VAP bundle encompassing all
NNIS/CDC Criteria for Diagnosis the evidence-based guidelines has been shown to improve
BOX 7-5 of Ventilator-Associated Pneumonia outcomes.214
in Children Older Than 12 Years
REFERENCES
One of the following: 1. Baker AB. Artificial respiration, the history of an idea. Med Hist
Fever (>38C) with no other recognized cause 1971;15:33651.
Leukopenia (<4000 white blood cells/mm3) or leukocy- 2. Matas R. Intralaryngeal insufflation for the relief of acute surgical
tosis (12,000 white blood cells/mm3) pneumothorax: Its history and methods with a description of
the latest devices for this purpose. J Am Med Assoc 1900;23:
Two of the following:
146873.
New onset of purulent sputum, change in character of 3. Daily WJ, Smith PC. Mechanical ventilation of the newborn
sputum, increased respiratory secretions, or increased infant. I Curr Prob Pediatr 1971;1:137.
suctioning requirements 4. Emerson JH. The Evolution of Iron Lungs: 1928-78. J.H.
New onset of worsening cough, dyspnea, or tachypnea Emerson Company; 1978.
Rales or bronchial breath sounds 5. Magill IW. Endotracheal Anaesthesia. Proc R Soc Med 1928;22:
Worsening gas exchange (PaO2/FiO2240, increased 838.
oxygen requirements, or increased ventilation demand) 6. Rowbotham S. Intratracheal anaesthesia by the nasal route for
Two or more abnormal chest radiographs (can be one if no operations on the mouth and lips. BMJ 1920;2:5901.
7. Eckman M, Barach B. An appraisal of intermittent pressure
pulmonary or cardiac disease) with one of the following:
breathing as a method of increasing altitude tolerance. J Aviat Med
New or progressive and persistent infiltrate 1947;18:56576.
Consolidation 8. Stahlman MT, Young WC, Payne G. Studies of ventilatory
Cavitation aids in hyaline membrane disease. Am J Dis Child 1962;104:
Pneumatoceles (in infants 1 year) 526.
9. Cassani VL 3rd. Weve come a long way baby! Mechanical ventila-
From NNIS/CDCNational Nosocomial Infections Surveillance System/ tion of the newborn. Neonatal Netw 1994;13:638.
Centers for Disease Control. 10. Avery ME, Mead J. Surface properties in relation to atelectasis
and hyaline membrane disease. Am J Dis Child 1959;97:
51723.
11. Thomas DV, Fletcher G, Sunshine P, et al. Prolonged respirator
Broad-spectrum, early empirical antibiotics, when appro- use in pulmonary insufficiency of newborn. JAMA 1965;193:
priately chosen, have been shown to decrease mortality 18390.
in adults, but overuse can increase antibiotic resist- 12. Gregory GA, Kitterman JA, Phibbs RH, et al. Treatment of the
ance.208,209 Risk factors for multidrug-resistant pathogens idiopathic respiratory-distress syndrome with continuous positive
airway pressure. N Engl J Med 1971;284:133340.
in pediatric patients include younger age, increasing risk 13. Kssel H, Versmold H. 25 years of respiratory support of newborn
of mortality score, previous PICU admissions, exposure infants. Perinat Med 1997;25:42132.
to household contacts hospitalized over the past year, 14. Bartlett RH. Use of Mechanical Ventilation. In: Holcroft J, editor.
intravenous antibiotic use in the past 12 months, and Care of the Surgical Patient. New York: Scientific American
exposure to chronic care facilities.210,211 Once final cul- Medicine; 1989.
15. West JB. Pulmonary PathophysiologyThe Essentials. Balti-
tures are available, it is important to target therapy to more: Williams & Wilkins; 1990.
prevent overuse of antibiotics and the breeding of 16. Gattinoni L, Mascheroni D, Basilico E, et al. Volume/pressure
multidrug-resistant organisms. The optimal duration of curve of total respiratory system in paralysed patients: Artefacts
therapy in adults was addressed in a multicenter, rand- and correction factors. Intensive Care Med 1987;13:1925.
17. Gama AM, Meyer EC, Gaudncio AM, et al. Different low con-
omized, controlled trial comparing eight days of antibiot- stant flows can equally determine the lower inflection point in
ics versus 15 days.212 There was no difference in the acute respiratory distress syndrome patients. Artif Organs
mortality rates. Patients infected with nonfermenting 2001;25:8829.
7 Mechanical Ventilation in Pediatric Surgical Disease 111
18. Kondili E, Prinianakis G, Hoeing S, et al. Low flow inflation Augmentation of CO2 elimination by an intratracheal catheter.
pressure-time curve in patients with acute respiratory distress Am Rev Respir Dis 1992;146:96573.
syndrome. Intensive Care Med 2000;26:175663. 43. Kirby RR. Intermittent mandatory ventilation in the neonate. Crit
19. Harris RS, Hess DR, Venegas JG. An objective analysis of the Care Med 1977;5:1822.
pressure-volume curve in the acute respiratory distress syndrome. 44. Bernstein G, Mannino FL, Heldt GP, et al. Randomized multi-
Am J Respir Crit Care Med 2000;161:4329. center trial comparing synchronized and conventional intermit-
20. Putensen C, Baum M, Hrmann C. Selecting ventilator settings tent mandatory ventilation in neonates. J Pediatr 1996;128:
according to variables derived from the quasi-static pressure/ 45363.
volume relationship in patients with acute lung injury. Anesth 45. Cleary JP, Bernstein G, Mannino FL, et al. Improved oxygenation
Analg 1993;77:43647. during synchronized intermittent mandatory ventilation in
21. Bartel LP, Bazik JR, Powner DJ. Compression volume during neonates with respiratory distress syndrome: a randomized, cross-
mechanical ventilation: Comparison of ventilators and tubing cir- over study. J Pediatr 1995;126:40711.
cuits. Crit Care Med 1985;13:8514. 46. Chen JY, Ling UP, Chen JH. Comparison of synchronized and
22. Gattinoni L, Pesenti A, Mascheroni D, et al. Low-frequency conventional intermittent mandatory ventilation in neonates. Acta
positive-pressure ventilation with extracorporeal CO2 removal in Paediatr Jpn 1997;39:57883.
severe acute respiratory failure. JAMA 1986;256:8816. 47. Greenough A, Milner AD, Dimitriou G. Synchronized mechani-
23. Zwischenberger JB, Wang D, Lick SD. The paracorporeal artifi- cal ventilation for respiratory support in newborn infants.
cial lung improves 5-day outcomes from lethal smoke/burn- Cochrane Database Syst Rev 2001:CD000456.
induced acute respiratory distress syndrome in sheep. Ann Thorac 48. Leung P, Jubran A, Tobin MJ. Comparison of assisted ventilator
Surg 2002;74:101118. modes on triggering, patient effort, and dyspnea. Am J Respir Crit
24. Gattinoni L, DAndrea L, Pelosi P, et al. Regional effects and Care Med 1997;155:19408.
mechanism of positive end-expiratory pressure in early adult res- 49. Jarreau PH, Moriette G, Mussat P, et al. Patient-triggered ventila-
piratory distress syndrome. JAMA 1993;269:21227. tion decreases the work of breathing in neonates. Am J Respir Crit
25. Maunder RJ, Shuman WP, McHugh JW, et al. Preservation Care Med 1996;153:117681.
of normal lung regions in the adult respiratory distress 50. Dekel B, Segal E, Perel A. Pressure support ventilation. Arch
syndrome. Analysis by computed tomography. JAMA 1986;255: Intern Med 1996;156:36973.
24635. 51. Banner MJ, Kirby RR, Blanch PB, et al. Decreasing imposed work
26. White KM. Completing the hemodynamic picture: SvO2. Heart of the breathing apparatus to zero using pressure-support ventila-
Lung 1985;14:27280. tion. Crit Care Med 1993;21:13338.
27. Nelson LD. Continuous venous oximetry in surgical patients. Ann 52. Kacmarek RM. The role of pressure support ventilation in reduc-
Surg 1986;203:32933. ing the work of breathing. Respir Care 1988;33:99120.
28. Rivers EP, Ander DS, Powell D. Central venous oxygen saturation 53. Brochard L, Pluskwa F, Lemaire F. Improved efficacy of spontane-
monitoring in the critically ill patient. Curr Opin Crit Care ous breathing with inspiratory pressure support. Am Rev Respir
2001;7:20411. Dis 1987;136:41115.
29. Jan K, Usami S, Smith JA. Effects of transfusion on rheological 54. Gullberg N, Winberg P, Selldn H. Pressure support ventilation
properties of blood in sickle cell anemia. Transfusion 1982;22: increases cardiac output in neonates and infants. Paediatr Anaesth
1720. 1996;6:31115.
30. Ranieri VM, Mascia L, Fiore T, et al. Cardiorespiratory effects of 55. Tokioka H, Kinjo M, Hirakawa M. The effectiveness of pressure
positive end-expiratory pressure during progressive tidal volume support ventilation for mechanical ventilatory support in children.
reduction (permissive hypercapnia) in patients with acute respira- Anesthesiology 1993;78:8804.
tory distress syndrome. Anesthesiology 1995;83:71020. 56. Marraro GA. Innovative practices of ventilatory support with
31. Michaels AJ, Wanek SM, Dreifuss BA, et al. A protocolized pediatric patients. Pediatr Crit Care Med 2003;4:820.
approach to pulmonary failure and the role of intermittent prone 57. Randolph AG, Wypij D, Venkataraman ST, et al. Effect of
positioning. J Trauma 2002;52:103747. mechanical ventilator weaning protocols on respiratory outcomes
32. Marini JJ. Pressure-targeted, lung-protective ventilatory support in infants and children: A randomized controlled trial. JAMA
in acute lung injury. Chest 1994;105:S10915. 2002;288:25618.
33. Parker JC, Townsley MI, Rippe B, et al. Increased microvascular 58. Amato MB, Barbas CS, Bonassa J, et al. Volume-assured pressure
permeability in dog lungs due to high peak airway pressures. support ventilation (VAPSV). A new approach for reducing
J Appl Physiol 1984;57:180916. muscle workload during acute respiratory failure. Chest
34. Palmisano BW, Fisher DM, Willis M, et al. The effect of paralysis 1992;102:122534.
on oxygen consumption in normoxic children after cardiac 59. Younes M. Proportional assist ventilation, a new approach to
surgery. Anesthesiology 1984;61:51822. ventilatory support. Theory. Am Rev Respir Dis 1992;145:
35. Coggeshall JW, Marini JJ, Newman JH. Improved oxygenation 11420.
after muscle relaxation in adult respiratory distress syndrome. 60. Younes M. Proportional assist ventilation and pressure support
Arch Intern Med 1985;145:171820. ventilation: Similarities and differences. In: Ventilatory Failure
36. Ganong WF. Ganongs Review of Medical Physiology. New York: (Update in Intensive Care and Emergency Medicine) 1st edition
Appleton & Lange; 1979. by Marini, JJ, ed. Springer; 1991. p. 36180.
37. Kacmarek RM, Hess D. Basic principles of ventilator machinery. 61. Younes M, Puddy A, Roberts D, et al. Proportional assist ventila-
In: Tobin MJ, editor. Principles and Practice of Mechanical Ven- tion. Results of an initial clinical trial. Am Rev Respir Dis
tilation. New York: McGraw-Hill Professional Publishing; 1994. 1992;145:1219.
p. 65110. 62. Bigatello LM, Nishimura M, Imanaka H, et al. Unloading of the
38. Pilbeam SP. Physical aspects of mechanical ventilators. In: Russell work of breathing by proportional assist ventilation in a lung
J, editor. Mechanical Ventilation: Physiological and Clinical model. Crit Care Med 1997;25:26772.
Applications. St. Louis: Mosby; 1998. p. 6291. 63. Schulze A, Bancalari E. Proportional assist ventilation in infants.
39. Piotrowski A, Sobala W, Kawczyski P. Patient-initiated, pressure- Clin Perinatol 2001;28:56178.
regulated, volume-controlled ventilation compared with intermit- 64. Schulze A, Gerhardt T, Musante G, et al. Proportional assist
tent mandatory ventilation in neonates: A prospective, randomised ventilation in low birth weight infants with acute respiratory
study. Intensive Care Med 1997;23:97581. disease: A comparison to assist/control and conventional mechani-
40. Sinha SK, Donn SM. Volume-controlled ventilation. Variations cal ventilation. J Pediatr 1999;135:33944.
on a theme. Clin Perinatol 2001;28:54760. 65. Musante G, Schulze A, Gerhardt T, et al. Proportional assist
41. Abraham E, Yoshihara G. Cardiorespiratory effects of pressure ventilation decreases thoracoabdominal asynchrony and chest wall
controlled ventilation in severe respiratory failure. Chest distortion in preterm infants. Pediatr Res 2001;49:17580.
1990;98:14459. 66. Verbrugghe W, Jorens PG. Neurally adjusted ventilatory assist:
42. Nahum A, Burke WC, Ravenscraft SA, et al. Lung mechanics and A ventilation tool or a ventilation toy? Respir Care 2011;56:
gas exchange during pressure-control ventilation in dogs. 32735.
112 SECTION I General
67. Breatnach C, Conlon NP, Stack M, et al. A prospective crossover pressure release ventilation. Intensive Care Med 2002;28:
comparison of neurally adjusted ventilatory assist and pressure- 17429.
support ventilation in a pediatric and neonatal intensive care unit 89. Hering R, Peters D, Zinserling J, et al. Effects of spontaneous
population. Pediatr Crit Care Med 2010;11:711. breathing during airway pressure release ventilation on renal per-
68. Gittermann MK, Fusch C, Gittermann AR, et al. Early nasal fusion and function in patients with acute lung injury. Intensive
continuous positive airway pressure treatment reduces the need Care Med 2002;28:142633.
for intubation in very low birth weight infants. Eur J Pediatr 90. Cane RD, Peruzzi WT, Shapiro BA. Airway pressure release ven-
1997;156:3848. tilation in severe acute respiratory failure. Chest 1991;100:
69. Padman R, Lawless ST, Kettrick RG. Noninvasive ventilation via 4603.
bilevel positive airway pressure support in pediatric practice. Crit 91. Valentine DD, Hammond MD, Downs JB, et al. Distribution of
Care Med 1998;26:16973. ventilation perfusion with different modes of mechanical ventila-
70. Lofaso F, Brochard L, Hang T, et al. Home versus intensive care tion. Am Rev Respir Dis 1991;143:12626.
pressure support devices. Experimental and clinical comparison. 92. Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventila-
Am J Respir Crit Care Med 1996;153:15919. tion increases cardiac performance in patients with acute lung
71. Yaez LJ, Yunge M, Emilfork M, et al. A prospective, randomized, injury/adult respiratory distress syndrome. Crit Care (Lond)
controlled trial of noninvasive ventilation in pediatric acute respi- 2001;5:2216.
ratory failure. Pediatr Crit Care Med 2008;9:4849. 93. Walsh MA, Merat M, La Rotta G, et al. Airway pressure release
72. Finer NN, Carlo WA, Walsh MC, et al. Early CPAP versus ventilation improves pulmonary blood flow in infants after cardiac
surfactant in extremely preterm infants. N Engl J Med 2010; surgery. Crit Care Med 2011;39:2599604.
362:19709. 94. Martin LD, Wetzel RC, Bilenki AL. Airway pressure release ven-
73. Lain DC, DiBenedetto R, Morris SL, et al. Pressure control tilation in a neonatal lamb model of acute lung injury. Crit Care
inverse ratio ventilation as a method to reduce peak inspiratory Med 1991;19:3738.
pressure and provide adequate ventilation and oxygenation. Chest 95. Foland JA, Martin J, Novotny T, et al. Airway pressure release
1989;95:10818. ventilation with a short release time in a child with acute respira-
74. Tharratt RS, Allen RP, Albertson TE. Pressure controlled inverse tory distress syndrome. Respir Care 2001;46:101923.
ratio ventilation in severe adult respiratory failure. Chest 96. Hollinger IB. Postoperative management: Ventilation. Int Anesth
1988;94:75562. Clin 1980;18:20516.
75. Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Ration- 97. Jenkinson SG. Oxygen toxicity. New Horiz 1993;1:50411.
ale and implementation. Chest 1991;100:494504. 98. Wolfe WG, DeVries WC. Oxygen toxicity. Annu Rev Med
76. Porembka DT. Inverse ratio ventilation. Probl Respir Care 1975;26:20317.
1989;2:6976. 99. Gladstone IM Jr, Levine RL. Oxidation of proteins in neonatal
77. McCarthy MC, Cline AL, Lemmon GW, et al. Pressure control lungs. Pediatrics 1994;93:7648.
inverse ratio ventilation in the treatment of adult respiratory dis- 100. Wung JT, James LS, Kilchevsky E, et al. Management of infants
tress syndrome in patients with blunt chest trauma. Am Surg with severe respiratory failure and persistence of the fetal circula-
1999;65:102730. tion without hyperventilation. Pediatrics 1985;76:488.
78. Mercat A, Titiriga M, Anguel N, et al. Inverse ratio ventilation 101. Webb HH, Tierney DF. Experimental pulmonary edema due to
(I/E=2/1) in acute respiratory distress syndrome: A six-hour con- intermittent positive pressure ventilation with high inflation pres-
trolled study. AM J Resp Crit Care Med 1997;155:163742. sures: Protection by positive end-expiratory pressure. Am Rev
79. Armstrong BW Jr, MacIntyre NR. Pressure-controlled, inverse Respir Dis 1974;110:55665.
ratio ventilation that avoids air trapping in the adult respiratory 102. Fu Z, Costello ML, Tsukimoto K, et al. High lung volume
distress syndrome. Crit Care Med 1995;23:27985. increases stress failure in pulmonary capillaries. J Appl Physiol
80. Mancebo J, Vallverd I, Bak E, et al. Volume-controlled ventila- 1992;73:12333.
tion and pressure-controlled inverse ratio ventilation: A compari- 103. Kolobow T, Moretti MP, Fumagalli R, et al. Severe impairment
son of their effects in ARDS patients. Monaldi Arch Chest Dis in lung function induced by high peak airway pressure during
1994;49:2017. mechanical ventilation. Am Rev Respir Dis 1987;135:312
81. Lessard MR, Gurot E, Lorino H, et al. Effects of pressure- 15.
controlled with different I:E ratios versus volume-controlled ven- 104. Dreyfuss D, Basset G, Soler P, et al. Intermittent positive-pressure
tilation on respiratory mechanics, gas exchange, and hemodynamics hyperventilation with high inflation pressures produces pulmo-
in patients with adult respiratory distress syndrome. Anesthesiol- nary microvascular injury in rats. Am Rev Respir Dis
ogy 1994;80:98391. 1985;132:8804.
82. Goldstein B, Papadakos PJ. Pressure-controlled inverse-ratio ven- 105. Hernandez LA, Peevy K, Moise AA, et al. Chest wall restriction
tilation in children with acute respiratory failure. AM J Crit Care limits high airway pressure-induced lung injury in young rabbits.
1994;3:1115. J Appl Physiol 1989;66:23648.
83. Wang SH, Wei TS. The outcome of early pressure-controlled 106. Savel R, Yao E, Gropper M. Protective effects of low tidal volume
inverse ratio ventilation on patients with severe acute respiratory ventilation in a rabbit model of Pseudomonas aeruginosa-induced
distress syndrome in surgical intensive care unit. Am J Surg acute lung injury. Crit Care Med 2001;29:3928.
2002;183:1515. 107. Rich PB, Reickert CA, Sawada S, et al. Effect of rate and inspira-
84. Huang CC, Shih MJ, Tsai YH, et al. Effects of inverse ratio ven- tory flow on ventilator induced lung injury. J Trauma
tilation versus positive end-expiratory pressure on gas exchange 2000;49:90311.
and gastric intramucosal PCO(2) and pH under constant mean 108. Nahum A, Hoyt J, Schmitz L, et al. Effect of mechanical ventila-
airway pressure in acute respiratory distress syndrome. Anesthe- tion strategy on dissemination of intratracheally instilled
siology 2001;95:11828. Escherichia coli in dogs. Crit Care Med 1997;25:173343.
85. McIntyre RC Jr, Pulido EJ, Bensard DD, et al. Thirty years of 109. Stewart TE, Meade M, Cook DJ, et al. Evaluation of a ventilation
clinical trials in acute respiratory distress syndrome. Crit Care strategy to prevent barotrauma in patients at high risk for acute
Med 2000;28:331431. respiratory distress syndrome. N Engl J Med 1998;338:35561.
86. Chiang AA, Steinfeld A, Gropper C, et al. Demand-flow airway 110. Brochard L. Low versus high tidal volumes. In: Vincent JL, editor.
pressure release ventilation as a partial ventilatory support mode: Acute Lung Injury. Brussels: Springer-Verlag; 1998. p. 27681.
Comparison with synchronized intermittent mandatory ventila- 111. Amato MB, Barbas CS, Mederios DM, et al. Effect of a protective-
tion and pressure support ventilation. Crit Care Med 1994;22: ventilation strategy on mortality in the acute respiratory distress
14317. syndrome. N Engl J Med 1998;338:34754.
87. Rasanen J, Cane RD, Downs JV, et al. Airway pressure release 112. Ranieri VM, Suter PM, Tortoralla T, et al. Effect of mechanical
ventilation during acute lung injury: A prospective multicenter ventilation on inflammatory mediators in patients with acute res-
trial. Crit Care Med 1991;19:123441. piratory distress syndrome. JAMA 1999;282:5461.
88. Neumann P, Golisch W, Strohmeyer A, et al. Influence of differ- 113. The Acute Respiratory Distress Syndrome Network. Ventilation
ent release times on spontaneous breathing pattern during airway with lower tidal volumes as compared with traditional tidal
7 Mechanical Ventilation in Pediatric Surgical Disease 113
volumes for acute lung injury and the acute respiratory distress oleic-acid-induced acute lung injury. Am Rev Respir Dis 1987;
syndrome. N Engl J Med 2000;342:13018. 135:62833.
114. Hickling KG. Low volume ventilation with permissive hypercap- 138. Wiener CM, Kirk W, Albert RK. Prone position reverses gravi-
nea in the adult respiratory distress syndrome. Clin Intensive Care tational distribution of perfusion in dog lungs with oleic acid-
1992;3:6778. induced injury. J Appl Physiol 1990;68:138692.
115. Hickling KG, Walsh J, Henderson S, et al. Low mortality rate in 139. Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone position-
adult respiratory distress syndrome using low-volume, pressure- ing on the survival of patients with acute respiratory failure. N
limited ventilation with permissive hypercapnia: A prospective Engl J Med 2001;345:56873.
study. Crit Care Med 1994;22:156878. 140. Baltopoulos G, Zakynthinos S, Dimpoulos A, et al. Effects of
116. Sheridan R, Kacmarek R, McEttrick M, et al. Permissive hyper- furosemide on pulmonary shunts. Chest 1989;96:4948.
capnia as a ventilatory strategy in burned children: Effect on 141. Gattinoni L. Decreasing edema results in improved pulmonary
barotrauma, pneumonia, and mortality. J Trauma 1995;39: function and survival in patients with ARDS. Intensive Care Med
8549. 1986;12:137.
117. Paulson TE, Spear RM, Silva PD, et al. High-frequency pressure- 142. Simmons RS, Berdine GG, Seidenfeld JJ, et al. Fluid balance
control ventilation with high positive end-expiratory pressure in in the respiratory distress syndrome. Am Rev Respir Dis 1987;
children with acute respiratory distress syndrome. J Pediatr 135:9249.
1996;129:56673. 143. Schuster DP. The case for and against fluid restriction and occlu-
118. McCulloch PR, Forkert PG, Forese AB. Lung volume mainte- sion pressure reduction in adult respiratory distress syndrome.
nance prevents lung injury during high frequency oscillatory New Horiz 1993;1:47888.
ventilation in surfactant-deficient rabbits. Am Rev Respir Dis 144. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of
1988;137:118592. two fluid-management strategies in acute lung injury. N Engl J
119. Dreyfuss D, Sjoer P, Basset G, et al. High inflation pressure pul- Med 2006;354:256475.
monary edema: Respective effects of high airway pressure, high 145. McIntyre RC Jr, Haenel JB, Moore FA, et al. Cardiopulmonary
tidal volume, and positive end-expiratory pressure. Am Rev Respir effects of permissive hypercapnia in the management of adult
Dis 1988;137:115964. respiratory distress syndrome. J Trauma 1994;37:4338.
120. Lachmann B. Open up the lung and keep the lung open. Intensive 146. Brochard L, Rauss A, Benito SM, et al. Comparison of three
Care Med 1992;18:31921. methods of gradual withdrawal from ventilation support during
121. Mancebo J. PEEP, ARDS, and alveolar recruitment. Intensive weaning from mechanical ventilation. AJRCCM 1995;150:
Care Med 1992;18:3835. 896903.
122. Gattinoni L, Pesenti A, Avalli L, et al. Pressure-volume curve of 147. Leitch EA, Moran JL, Grealy B. Weaning and extubation in the
total respiratory system in acute respiratory failure. Am Rev intensive care unit. Clinical or index-driven approach? Intensive
Respir Dis 1987;136:7306. Care Med 1996;22:7529.
123. Roupie E, Dambrosio M, Servillo G, et al. Titration of tidal 148. Esteban A, Frutos F, Tobin MJ, et al. A comparison of four
volume and induced hypercapnia in acute respiratory distress syn- methods of weaning patients from mechanical ventilation. N Engl
drome. AJRCCM 1995;152:1218. J Med 1995;332:34550.
124. Gattinoni L, Caironi P, Pelosi P, et al. What has computed tom- 149. Ferrara TB, Georgieff MK, Ebert J, et al. Routine use of dexam-
ography taught us about the acute respiratory distress syndrome? ethasone for the prevention of postextubation respiratory distress.
Am J Respir Crit Care Med 2001;164:170111. J Perinatol 1989;9:28790.
125. Crotti S, Mascheroni D, Caironi P, et al. Recruitment and dere- 150. Couser RJ, Ferrera B, Falde B, et al. Effectiveness of dexametha-
cruitment during acute respiratory failure: A clinical study. Am J sone in preventing extubation failure in preterm infants at
Respir Crit Care Med 2001;164:13140. increased risk for airway edema. J Pediatr 1992;121:5916.
126. Desai SR, Wells AU, Suntharalingam G, et al. Acute respiratory 151. Dries DJ. Weaning from mechanical ventilation. J Trauma
distress syndrome caused by pulmonary and extrapulmonary 1997;43:37284.
injury: A comparative CT study. Radiology 2001;218:68993. 152. Holdgaard HO, Pedersen J, Jensen RH, et al. Percutaneous dila-
127. DiRusso SM, Nelson LD, Safcsak K, et al. Survival in patients tational tracheostomy versus conventional surgical tracheostomy:
with severe adult respiratory distress syndrome treated with A clinical randomised study. Acta Anaesth Scand 1988;42:
high-level positive end-expiratory pressure. Crit Care Med 1995; 54550.
23:148596. 153. Rosenbower TJ, Morris JA Jr, Eddy VA, et al. The long-term
128. Nagano O, Tokioka H, Ohta Y, et al. Inspiratory pressure-volume complications of percutaneous dilatational tracheostomy. Am
curves at different positive end-expiratory pressure levels in Surg 1998;64:827.
patients with ALI/ARDS. Acta Anaesth Scand 2001;45:125561. 154. Citta-Pietrolungo TJ, Alexander MA, Cook SP, et al. Complica-
129. Valente Barbas CS. Lung recruitment maneuvers in acute respira- tions of tracheostomy and decannulation in pediatric and young
tory distress syndrome and facilitating resolution. Crit Care Med patients with traumatic brain injury. Arch Phys Med Rehab
2003;31:26571. 1993;74:9059.
130. Witte MK, Galli SA, Ghatburn RL, et al. Optimal positive end- 155. Biarent D. New tools in ventilatory support: High frequency
expiratory pressure therapy in infants and children with acute ventilation, nitric oxide, tracheal gas insufflation, non-invasive
respiratory failure. Pediatr Res 1988;24:21721. ventilation. Pediatr Pulmonol Suppl 1999;18:17881.
131. Bartlett R, Roloff DW, Custer J, et al. Extracorporeal life support: 156. Clark RH. High-frequency ventilation. J Pediatr 1994;124:
The University of Michigan experience. JAMA 2000;283:9048. 66170.
132. Sjostrand UH, Lichtwarch-Aschoff M, Nielsen JB, et al. Different 157. Froese AB, Bryan AC. High frequency ventilation. Am Rev Respir
ventilatory approaches to keep the lung open. Intensive Care Med Dis 1987;135:136374.
1995;21:31018. 158. Krishnan JA, Brower RG. High-frequency ventilation for acute
133. Papadakos PJ, Halloran W, Hessney JI, et al. The use of pressure- lung injury and ARDS. Chest 2000;118:795807.
controlled inverse ratio ventilation in the surgical intensive care 159. Rouby JJ, Simonneau G, Benhamou D, et al. Factors influencing
unit. J Trauma 1991;31:121114. pulmonary volumes and CO2 elimination during high-frequency
134. Pappert D, Rossaint R, Slama K, et al. Influence of positioning jet ventilation. Anesthesiology 1985;63:47382.
on ventilation-perfusion relationships in severe adult respiratory 160. Baumann MH, Sahn SA. Medical management and therapy of
distress syndrome. Chest 1994;106:151116. bronchopleural fistulas in the mechanically ventilated patient.
135. Fridrich P, Krafft P, Hochleuthner H, et al. The effects of long- Chest 1991;97:7218.
term prone positioning in patients with trauma-induced adult 161. High-frequency oscillatory ventilation compared with conven-
respiratory distress syndrome. Anesth Analg 1996;83:120611. tional mechanical ventilation in the treatment of respiratory
136. Langer M, Mascheroni D, Marcolin R, et al. The prone position failure in preterm infants. The HIFI Study Group. N Engl J Med
in ARDS patients: A clinical study. Chest 1988;94:1037. 1989;320:8893.
137. Albert RK, Leasa D, Sanderson M, et al. The prone 162. Clark RH, Gerstmann DR, Null DMJ, et al. Prospective
position improves arterial oxygenation and reduces shunt in randomized comparison of high-frequency oscillatory and
114 SECTION I General
conventional ventilation in respiratory distress syndrome. Pediat- randomized, controlled trial nitric oxide for persistent pulmonary
rics 1992;89:512. hypertension of the newborn. Pediatrics 2001;107:13516.
163. Keszler M, Donn SM, Bucciarelli RL, et al. Multicenter control 184. Inhaled nitric oxide and hypoxic respiratory failure in infants
trial comparing high frequency jet ventilation and conventional with congenital diaphragmatic hernia. The Neonatal Inhaled
ventilation in newborn patients with pulmonary interstitial Nitric Oxide Study Group (NINOS). Pediatrics 1997;99:
emphysema. J Pediatr 1991;119:8593. 83845.
164. Gerstmann DR, Minton SD, Stoddard RA, et al. The Provo 185. Karamanoukian HL, Glick PL, Wilcox DT, et al. Pathophysiol-
multicenter early high-frequency oscillatory ventilation trial: ogy of congenital diaphragmatic hernia. VIII: Inhaled nitric
Improved pulmonary and clinical outcome in respiratory distress oxide requires exogenous surfactant therapy in the lamb model
syndrome. Pediatrics 1996;98:104457. of congenital diaphragmatic hernia. J Pediatr Surg 1995;30:
165. Moriette G, Paris-Llado J, Walti H, et al. Prospective randomized 14.
multicenter comparison of high-frequency oscillatory ventilation 186. Van Meurs KP, Rhine WD, Asselin JM, et al. Response of
and conventional ventilation in preterm infants of less than 30 premature infants with severe respiratory failure to inhaled nitric
weeks with respiratory distress syndrome. Pediatrics 2001;107: oxide. Preemie NO Collaborative Group. Pediatr Pulmonol
36372. 1997;24:31923.
166. Courtney SE, Durand DJ, Asselin JM, et al. High-frequency oscil- 187. Hoehn T, Krause M, Buhrer C. Inhaled nitric oxide in premature
latory ventilation versus conventional mechanical ventilation for infants: A meta-analysis. J Perinat Med 2000;28:713.
very-low-birth-weight infants. N Engl J Med 2002;347:64352. 188. Haddad IY, Ischiropoulos H, Holm BA, et al. Mechanisms of
167. Durand DJ, Asselin LM, Hudak HL, et al. Early high-frequency peroxynitrite-induced injury to pulmonary surfactants. Am J
oscillatory ventilation versus synchronized intermittent manda- Physiol 1993;265:L55564.
tory ventilation in very low birth weight infants: A pilot study of 189. Beckman JS, Beckman T, Chen J, et al. Apparent hydroxyl radical
two ventilation protocols. J Perinatol 2001;21:2219. production by peroxynitrite: Implications for endothelial injury
168. Gerstmann DR, Wood K, Miller A, et al. Childhood outcome from nitric oxide and superoxide. Proc Natl Acad Sci U S A
after early high-frequency oscillatory ventilation for neonatal res- 1990;87:16204.
piratory distress syndrome. Pediatrics 2001;108:61723. 190. Jobe AH. Pulmonary surfactant therapy. N Engl J Med
169. Clark RH, Yoder BA, Sell MS. Prospective, randomized compari- 1993;328:8618.
son of high-frequency oscillation and conventional ventilation in 191. Hallman M, Merritt TA, Jarvenpaa AL, et al. Exogenous human
candidates for extracorporeal membrane oxygenation. J Pediatr surfactant for treatment of severe respiratory distress syndrome:
1994;124:44754. A randomized prospective clinical trial. J Pediatr 1985;106:
170. Arnold JH, Hanson JH, Toro-Figuero LO, et al. Prospective, 9639.
randomized comparison of high-frequency oscillatory ventilation 192. Long W, Corbet A, Cotton R, et al. A controlled trial of synthetic
and conventional mechanical ventilation in pediatric respiratory surfactant in infants weighing 1250g or more with respiratory
failure. Crit Care Med 1994;22:15309. distress syndrome: The American Exosurf Neonatal Study Group
171. Rosenberg RB, Broner CW, Peters KJ, et al. High-frequency I, and the Canadian Exosurf Neonatal Study Group. N Engl J
ventilation for acute pediatric respiratory failure. Chest Med 1991;325:1696703.
1994;104:121621. 193. Lotze A, Mitchell BR, Bulas DI, et al. Multicenter study of sur-
172. Dobyns EL, Anas NG, Fortenberry JD, et al. Interactive effects factant (beractant) use in the treatment of term infants with severe
of high-frequency oscillatory ventilation and inhaled nitric oxide respiratory failure. Survanta in Term Infants Study Group.
in acute hypoxemic respiratory failure in pediatrics. Crit Care J Pediatr 1998;132:407.
Med 2002;30:24259. 194. Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement
173. Bhuta T, Clark RH, Henderson-Smart DJ. Rescue high frequency therapy for meconium aspiration syndrome. Pediatrics
oscillatory ventilation vs conventional ventilation for infants with 1996;97:4852.
severe pulmonary dysfunction born at or near term. Cochrane 195. Hentschel R, Dittrich F, Hilgendorff A, et al. Neurodevelopmen-
Database Syst Rev 2001;CD002974-CD002974. tal outcome and pulmonary morbidity two years after early versus
174. Cools F, Henderson-Smart DJ, Offringa M, et al. Elective high late surfactant treatment: Does it really differ? Acta Paediatr
frequency oscillatory ventilation versus conventional ventilation 2009;98:6549.
for acute pulmonary dysfunction in preterm infants. Cochrane 196. Stevens TP, Harrington EW, Blennow M, et al. Early surfactant
Database Syst Rev 2009;(8):CD000104-CD000104. administration with brief ventilation vs. selective surfactant and
175. Murad F. Cyclic guanosine monophosphate as a mediator of continued mechanical ventilation for preterm infants with or at
vasodilation. J Clin Invest 1986;78:15. risk for respiratory distress syndrome. Cochrane Database Syst
176. Abman SH, Griebel JL, Parker DK, et al. Acute effects of inhaled Rev (Online) 2007:CD003063-CD003063.
nitric oxide in children with severe hypoxemic respiratory failure. 197. Lotze A, Knight GR, Anderson KD, et al. Surfactant (beractant)
J Pediatr 1994;124:8818. therapy for infants with congenital diaphragmatic hernia on
177. Day RW, Allen EM, Witte MK. A randomized, controlled study ECMO: Evidence of persistent surfactant deficiency. J Pediatr
of the 1-hour and 24-hour effects of inhaled nitric oxide therapy Surg 1994;29:40712.
in children with acute hypoxemic respiratory failure. Chest 198. Cogo PE, Zimmermann LJ, Rosso F, et al. Surfactant synthesis
1997;112:132431. and kinetics in infants with congenital diaphragmatic hernia. Am
178. Roberts JJ, Fineman J, Morin F. Inhaled nitric oxide and persistent J Respir Crit Care Med 2002;166:1548.
pulmonary hypertension of the newborn: The Inhaled Nitric 199. IJsselstijn H, Zimmermann LJ, Bunt JE, et al. Prospective evalu-
Oxide Study Group. N Engl J Med 1997;336:60510. ation of surfactant composition in bronchoalveolar lavage fluid of
179. Clark R, Kueser T, Walker M, et al. Low-dose nitric oxide therapy infants with congenital diaphragmatic hernia and of age-matched
for persistent pulmonary hypertension of the newborn. N Engl J controls. Crit Care Med 1998;26:57380.
Med 2000;342:46974. 200. Wilcox DT, Glick PL, Karamanoukian H, et al. Pathophysiology
180. Christou H, Van Marter L, Wessel D, et al. Inhaled nitric oxide of congenital diaphragmatic hernia, V: Effect of exogenous
reduces the need for extracorporeal membrane oxygenation in surfactant therapy on gas exchange and lung mechanics in the
infants with persistent pulmonary hypertension of the newborn. lamb congenital diaphragmatic hernia model. J Pediatr
Crit Care Med 2000;28:37227. 1994;124:28993.
181. The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric 201. Glick PL, Leach CL, Besner GE, et al. Pathophysiology of con-
oxide in full-term and nearly full-term infants with hypoxic res- genital diaphragmatic hernia, III: Exogenous surfactant therapy
piratory failure. N Engl J Med 1997;336:597604. for the high-risk neonate with CDH. J Pediatr Surg 1992;
182. Inhaled nitric oxide in term and near-term infants: Neurodevel- 27:8669.
opmental follow-up of the neonatal inhaled nitric oxide study 202. Ullrich R, Lorber C, Rder G, et al. Controlled airway pressure
group (NINOS). J Pediatr 2000;136:61117. therapy, nitric oxide inhalation, prone position, and extracorporeal
183. Ellington MJ, OReilly D, Allred E, et al. Child health status, membrane oxygenation (ECMO) as components of an integrated
neurodevelopmental outcome, and parental satisfaction in a approach to ARDS. Anesthesiology 1999;91:157786.
7 Mechanical Ventilation in Pediatric Surgical Disease 115
203. Priestley MA, Helfaer MA. Approaches in the management of America Joint Committee on the Prevention of Antimicrobial
acute respiratory failure in children. Curr Opin Pediatr 2004 Resistance: Guidelines for the prevention of antimicrobial resist-
16:2938. ance in hospitals. Clin Infect Dis 1997;25:58499.
204. Foglia E, Meier MD, Elward A. Ventilator-associated pneumonia 210. Toltzis P, Hoyen C, Spinner-Block S, et al. Factors that predict
in neonatal and pediatric intensive care unit patients. Clin Micro- preexisting colonization with antibiotic-resistant gram-negative
biol Rev 2007;20:40925. bacilli in patients admitted to a pediatric intensive care unit. Pedi-
205. Muscedere J, Dodek P, Keenan S, et al. Comprehensive evidence- atrics 1999;103:71923.
based clinical practice guidelines for ventilator-associated pneu- 211. Toltzis P, Yamashita T, Vilt L, et al. Colonization with antibiotic-
monia: Prevention. J Crit Care 2008;23:12637. resistant gram-negative organisms in a pediatric intensive care
206. Principi N, Esposito S. Ventilator-associated pneumonia (VAP) unit. Crit Care Med 1997;25:53844.
in pediatric intensive care units. Pediatr Infect Dis J 2007; 212. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days
26:8414. of antibiotic therapy for ventilator-associated pneumonia in
207. Gauvin F, Dassa C, Chaibou M, et al. Ventilator-associated pneu- adults: A randomized trial. JAMA 2003;290:258898.
monia in intubated children: Comparison of different diagnostic 213. Dodek P, Keenan S, Cook D, et al. Evidence-based clinical prac-
methods. Pediatr Crit Care Med 2003;4:43743. tice guideline for the prevention of ventilator-associated pneumo-
208. Iregui M, Ward S, Sherman G, et al. Clinical importance of delays nia. Ann Int Med 2004;141:30513.
in the initiation of appropriate antibiotic treatment for ventilator- 214. Curley MA, Schwalenstocker E, Deshpande JK, et al. Tailoring
associated pneumonia. Chest 2002;122:2628. the Institute for Health Care Improvement 100,000 Lives Cam-
209. Shlaes DM, Gerding DN, John JF, et al. Society for Healthcare paign to pediatric settings: The example of ventilator-associated
Epidemiology of America and Infectious Diseases Society of pneumonia. Pediatr Clin North Am 2006;53:123151.
C H A P T E R 8
Vascular Access
Ravindra K. Vegunta
A peripheral intravenous (PIV) cannula is the most com- infections can be prevented with appropriate education
monly used device for venous access in children. Although and training utilizing insertion and maintenance
venous access is often achieved in adults with minimal bundles.3,5,6
distress, placement of an intravenous catheter in children
can be quite traumatic to the child, the parents, and the
attendant health care providers. In some situations, it can PERIPHERAL VENOUS ACCESS
be a fairly frustrating and time-consuming procedure.1
Particular circumstances of each child may demand spe- Peripheral intravenous catheter placement is the most
cific solutions for vascular access, namely the choice of frequently used method of gaining vascular access. In
device and the site chosen for its placement (Table 8-1). infants and children, PIV access is usually achieved by
Clinicians must be aware of the limitations and potential using the veins on the dorsum of the hand, forearm,
adverse effects of the various vascular access devices dorsum of the foot, medial aspect of the ankle, and the
(VADs) that are available. scalp. In infants, the median vein tributaries on
In an emergency, other options should promptly be the ventral aspect of the distal forearm and wrist, and the
considered after a few failed attempts at PIV cannula lateral tributaries of the dorsal venous arch on the dorsum
placement. Historically, the only available options were of the foot, may be available, but typically allow cannula-
a venous cutdown or an emergency central venous cath- tion of only the finest-diameter catheters. The location
eter (CVC) placement. These options take considerable of the distal long saphenous vein (anterior to the medial
time and frequently require the services of a pediatric malleolus) is fairly constant and is frequently palpable,
surgeon. Intraosseous (IO) needle placement has become making it one of the most popular veins used for PIV
the most common contingency method of emergency access, particularly in infants. It allows a larger size cath-
vascular access in children. The newer mechanical devices eter and excellent stabilization of the catheter as well.
allow easier training of emergency medical personnel and Scalp veins can be readily visible and accessible but it can
have improved the success rate of IO placement in the be difficult to maintain access for any length of time.
prehospital setting. In fact, with appropriate training, an Similarly, external jugular vein catheters tend to get dis-
IO needle can be placed more quickly than a PIV cannula.2 lodged promptly in a moving patient and may only be
In sick neonates, umbilical vessels are frequently cannu- useful for a short time.
lated, but can only be used for a finite period [maximum Several techniques have been shown to be beneficial
of 5 days for an umbilical artery catheter (UAC)] and 14 in cannulating a peripheral vein, including warming the
days for an umbilical venous catheter (UVC).3 Early extremity, transillumination, and epidermal vasodilators.7
placement of a peripherally introduced CVC (PICC) is Ultrasound (US) guidance has been used to obtain access
preferable in these infants. Persistence with using PIV to basilic and brachial veins in the emergency depart-
cannulas leads to higher complication rates and reduces ment.8 Devices utilizing near-infrared imaging of the
the number of future PICC placement sites. veins up to a depth of 10mm are being used routinely in
In choosing the appropriate VAD for an oncology the hospitals, as well as by emergency medical personnel
patient, the requirements of the oncologist, the patients in the field, to find and access peripheral veins in all age
age, expected activity level, expected chance of cure, groups.9 Unlike ultrasound, there is no physical contact
number of previous VADs placed, and patency of the with the overlying skin and hence there is no compres-
central veins should all be considered. The number of sion or distortion of the veins. Significant complications
lumens, size of the catheter, type of catheter, and its loca- associated with PIV catheters include phlebitis, throm-
tion can all be tailored to the specific patient.4 Long-term bosis, and extravasation with chemical burn or necrosis
maintenance of central venous access in patients suffering of surrounding soft tissue.
from intestinal malabsorption is particularly challenging.
Once the six conventional sites of central venous access
bilateral internal jugular, subclavian, and femoral veins UMBILICAL VEIN AND ARTERY ACCESS
are exhausted, one must become more creative in gaining
central access. Neonates are often managed with catheters placed either
Complications that are common to all types of VADs in the umbilical vein and/or one of the umbilical arteries.
are extravasation of infusate, hemorrhage, phlebitis, sep- They can be used for monitoring central venous or arte-
ticemia, thrombosis, and thromboembolism. Multiple rial pressure, blood sampling, fluid resuscitation, medica-
studies have shown that catheter-related blood stream tion administration, and total parenteral nutrition (TPN).
116
8 Vascular Access 117
TABLE 8-1 Indications for Vascular Access in Infants and Children and the Recommended Devices
CVC
Indications PIV PICC IO NONTUNNELED TUNNELED SUBCUTANEOUS PORT
Emergency venous access X X X
Short-term venous access X X
Medium-term venous access X X X
Long-term venous access X X X
CVC, central venous catheter; IO, intraosseous needle; PICC, peripherally introduced central venous catheter; PIV, peripheral intravenous
catheter.
routine basis have developed special teams and protocols central veins accessed for placement of CVCs are the
for placement of PICC lines to reduce variations in prac- bilateral internal jugular veins, subclavian veins, and
tice and increase availability.20 The modified Seldinger femoral veins. In older children and full-term neonates,
technique is used most frequently. A small peripheral the percutaneous Seldinger technique is used. In prema-
intravenous catheter (about 24 gauge) is first placed, pref- ture neonates and occasionally in older children, the rel-
erably with ultrasound guidance, in a suitable extremity evant central vein or one of its tributaries (i.e., common
vein such as the basilic, cephalic, or long saphenous vein. facial vein or external jugular vein in the neck, cephalic
A fine guide wire is advanced through the vein, the initial vein in the deltopectoral groove, or the long saphenous
catheter is removed, the track is dilated, and a peel-away vein at the groin [Fig. 8-3]), is dissected and cannulated.2628
PICC introducer sheath is advanced over the guide wire. In some emergency situations, percutaneous femoral vein
The guide wire is then removed, and the PICC line is access may be preferred as the insertion site is away from
introduced through the sheath (Fig. 8-2).21,22 The tip of the activity centered around the head, neck, and chest.
the PICC should be placed at the superior vena cava The tip of a CVC placed from the lower body should be
(SVC)/RA junction or the IVC/RA junction. Locations positioned at the junction of the IVC and RA, which will
peripheral to these are considered non-central and are ensure prompt dilution of the infusate and likely has a
associated with higher complications.23 PICC lines are lower chance of thrombosis. Again, the xiphoid process
also eminently suitable for short- to medium-term is a good surface landmark to estimate the length of
(weeks) home intravenous therapy of antibiotics or catheter needed. Radiographically, the tip should be posi-
TPN.24 The most common complications associated with tioned just above the diaphragm.
PICC lines are infections, occlusion, and dislodgement A CVC placed through an upper body vein should be
of the catheter.25 positioned such that the tip is at the junction of the SVC
and RA. Surface landmarks for this location are less reli-
able. A point about 1cm caudal to the manubriosternal
CENTRAL VENOUS CATHETERS junction, at the right sternal border, gives a close estimate
to the SVC/RA junction in toddlers and older children.
With the development of PICC teams and the increasing The lower margin of the third right costosternal junction
use of PICC lines, there has been a decline in the use of has been shown to be the best surface landmark in adults
CVCs in neonates and older children.20 Nontunneled for placement of the CVC tip at the SVC/RA junction.29
CVCs are used for short- and medium-term indications, Length recommendations have been made based on a
whereas surgically placed tunneled CVCs are used for childs weight for placement of right internal jugular and
medium- and long-term indications. In premature right subclavian CVCs.30 On a chest radiograph, the tip
neonates, if PICC placement is not successful, tunneled of the catheter should project about two vertebral bodies
CVCs are preferentially used because of their smaller size caudal to the carina. A tunneled CVC can be left in place
and durability as opposed to nontunneled CVCs. The for several months to years. The Broviac and Hickman
catheters (Bard Access Systems, Salt Lake City, UT) are catheter days.28 Urgent CVCs placed in 289 pediatric
made of silicone and are available in various sizes, the burn unit patients also resulted in higher infection rates
smallest being a 2.7 French single-lumen catheter. These associated with subclavian and internal jugular CVCs
catheters have a Dacron cuff that promotes tissue compared with the femoral CVCs (10 and 13.6 versus 8.2
ingrowth, resulting in anchoring of the catheter within per 1000 catheter days).38 This is thought to be due to
the subcutaneous tunnel. The cuff can be placed close to the higher nursing and respiratory therapy activity around
the exit site of the catheter to facilitate removal by dis- the head and neck in these patients requiring intensive
section through the exit site. Placement of the Dacron burn care. Ethanol lock, in addition to antibiotic therapy,
cuff midway between the venotomy site and the exit site has been shown to be beneficial in salvaging CVCs that
has the advantage of reducing the chance of unintended become infected.39 Ethanol lock has also been shown to
removal of the catheter. be superior to heparin lock in preventing catheter infec-
Use of ultrasound guidance for percutaneous central tion and loss in children with intestinal failure.40 Retained
venous access is becoming standard of care. The benefits fragments of CVCs after attempted removal has been
of ultrasound assistance include higher success rate, faster reported to occur at a rate of 2%. Leaving a ligated frag-
access, fewer needle passes, and fewer arterial ment of the catheter within the blood vessel is felt to be
punctures.3136 Real-time 2D ultrasound guidance is rec- safer than the alternative, which involves interventional
ommended as the preferred method when placing a CVC or operative removal.41
into the internal jugular vein (IJV) in adults and children
in elective situations.31,32,36 In a randomized controlled
trial, ultrasound was shown to be beneficial in IJV cath- TOTALLY IMPLANTED CENTRAL
eterization in infants weighing less than 7.5kg when VENOUS CATHETERS
compared with a ultrasound image-based skin surface
marking.33 During insertion, the ultrasound transducer is Totally implantable intravascular devices (ports) are sub-
wrapped in a sterile sleeve, and sterile gel is used to obtain cutaneous reservoirs attached to CVCs. The reservoirs
real-time images of the vessel being accessed. Either a are made of a metal or hard plastic shell with a central
short-axis view across the diameter of the vessel (Fig. 8-4) silicone septum that is penetrated for access. They
or the long axis view along the length of the vessel is used provide a reliable, long-lasting solution for patients who
to visualize the needle approaching and entering the need intermittent access to their central venous system.
vessel. A guide wire is then passed into the vessel, fol- They are ideal for patients who desire to be involved in
lowed by the Seldinger technique for placement of the aquatic sports and other physical activities. They are
CVC.36 Because of the proximity of the clavicle, visualiza- most useful for patients with malignancies, coagulopa-
tion of the subclavian vein is poor with ultrasound. Infra- thies, hemolytic syndromes, and renal failure, all of which
clavicular axillary vein cannulation has been performed require recurrent vascular access. Low profile ports with
with 96% success with ultrasound guidance for tunneled 5 or 6 French catheters are available for use in infants.
CVC placement into the subclavian vein.37 Larger ports are available with dual lumens. High-flow
The majority of bloodstream infections in children are ports are available (PowerPort-Bard Access Systems, Salt
associated with the use of a vascular access device. Tun- Lake City, UT) that allow high-pressure injection of
neled CVCs inserted in the neck veins in neonates in the intravenous contrast for radiologic imaging. Ports require
NICU have been associated with a higher rate of com- special noncoring needles to keep the septum from
plications than those placed in the inguinal region. Infec- leaking. The reservoir should be implanted in a subcuta-
tion rates were 5.8 (neck) versus 0.7 (groin) per 1000 neous pocket, over a firm base such as the chest wall.
Preferred sites for port placement include the pectoral
area, parasternal area, (above and medial to the areola)
and the subclavicular area (medial to the anterior axillary
fold). In females with a concern for cosmesis, the low
presternum area and the lateral chest wall are locations
that hide the scar when the port is eventually removed.
IJV In determining port placement, consideration should be
CA given to the age of the patient, the intended activities, as
well as the convenience of the caregivers. Subclavicular
placement will make it easy to access the port with
minimal disrobing; in obese girls and young women, it is
less likely to get displaced by the highly mobile breast
tissue. The presternal location will provide a very stable
A B C
foundation for the port, even in the obese child. When
FIGURE 8-4 Ultrasound short-axis image of the right internal placed over the lower sternum, it can be accessed with
jugular vein and carotid artery obtained with SonoSite S Series opening the front of a button-down top or shirt. Com-
using a 136MHz transducer (SonoSite Inc., Bothell, Washing- plications that are unique to a port include an inability to
ton) in a child. (A) The internal jugular vein (IJV) and the carotid access the port, disconnection of the catheter from the
artery (CA). (B) The yellow arrow is pointing to the needle
indenting the IJV. (C) The red arrow points to the target sign
reservoir with extravasation, flipping of the port, fracture
caused by the needle in the middle of the IJV confirming correct and embolization of the catheter, and breakdown of the
placement. overlying skin.42
120 SECTION I General
arterial cutdown can be performed. Digital ischemia can 11. Ramasethu J. Complications of vascular catheters in the neonatal
result from radial artery catheters. Thromboembolism intensive care unit. Clin Perinatol 2008;35:199222.
12. Sritipsukho S, Sritipsukho P. Simple and accurate formula to esti-
can result in limb loss if the axillary, brachial, or femoral mate umbilical arterial catheter length of high placement. J Med
artery is catheterized. Local infections can occur when Assoc Thai 2007;90:17937.
the catheters are left for several days. A pseudoaneurysm 13. Lin MS, Lim YJ, Ho NK. A quicker simpler method of pre-
can result from injury to the adjacent vein during determination of the length of umbilical artery catheter insertion
in Asian babies. J Singapore Paediatr Soc 1989;31:7981.
placement. 14. Green C, Yohannan MD. Umbilical arterial and venous catheters:
Placement, use, and complications. Neonatal Netw 1998;17:238.
15. Barrington KJ. Umbilical artery catheters in the newborn: Effects
HEMODIALYSIS CATHETERS of position of the catheter tip. Cochrane Database Syst Rev
2000:000505.
16. Kim JH, Lee YS, Kim SH, et al. Does umbilical vein catheteriza-
The current recommendation is to use an autologous tion lead to portal venous thrombosis? Prospective ultrasound
arteriovenous fistula (AVF) as the route of choice for evaluation in 100 neonates. Radiology 2001;219:64550.
hemodialysis.59 AVFs permit high-flow rates that facili- 17. Edwards JR, Peterson KD, Andrus ML, et al. National Healthcare
tate effective dialysis. They also are reliable, durable, and, Safety Network (NHSN) Report, data summary for 2006, issued
June 2007. Am J Infect Control 2007;35:290301.
once established, have low complication rates. Because 18. Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare
patients are often referred late, and AVFs take time to Safety Network (NHSN) report, data summary for 2009, device-
mature, there is frequently a need for CVCs for immedi- associated module. Am J Infect Control 2011;39:34967.
ate dialysis. Temporary and tunneled long-term double- 19. Dudeck MA, Horan TC, Peterson KD, et al. National Healthcare
lumen hemodialysis catheters are placed preferentially Safety Network (NHSN) Report, data summary for 2010, device-
associated module. Am J Infect Control 2011;39:798816.
through the right IJV, either percutaneously or by 20. Linck DA, Donze A, Hamvas A. Neonatal peripherally inserted
cutdown. The larger size of the vein and the straight central catheter team. Evolution and outcomes of a bedside-nurse-
internal path of the catheter allow a larger catheter to be designed program. Adv Neonat Care 2007;7:229.
placed safely through the right IJV. Additionally, use of 21. Pettit J. Technological advances for PICC placement and manage-
ment. Adv Neonat Care 2007;7:12231.
the IJV avoids possible injury or thrombosis to the SCV 22. Braswell LE. Peripherally inserted central catheter placement in
which must be patent to develop a functioning AVF at infants and children. Tech Vasc Interv Radiol 2011;14:20411.
the wrist. The long-term, cuffed hemodialysis catheters 23. Racadio JM, Doellman DA, Johnson ND, et al. Pediatric peripher-
are precurved to allow right internal jugular placement ally inserted central catheters: Complication rates related to cath-
with tunneling to the pectoral area. Flow rates achieved eter tip location. Pediatrics 2001;107:E28.
24. Earhart A, Jorgensen C, Kaminski D. Assessing pediatric patients
through hemodialysis catheters tend to be lower and for vascular access and sedation. J Infus Nurs 2007;30:22631.
they last a relatively short time. AVF is also an option 25. Pettit J. Assessment of infants with peripherally inserted central
for management of young children with severe catheters: Part 1. Detecting the most frequently occurring compli-
hemophilia.60 cations. Adv Neonat Care 2002;2:30415.
26. Zumbro GL Jr, Mullin MJ, Nelson TG. Catheter placement in
infants needing total parenteral nutrition utilizing common facial
REFERENCES vein. Arch Surg 1971;102:713.
1. Stovroff M, Teague WG. Intravenous access in infants and chil- 27. Meland NB, Wilson W, Soontharotoke CY, et al. Saphenofemoral
dren. Pediatr Clin North Am 1998;45:137393. venous cutdowns in the premature infant. J Pediatr Surg
2. de Caen A. Venous access in the critically ill child: When the 1986;21:3413.
peripheral intravenous fails! Pediatr Emerg Care 2007;23:4224. 28. Vegunta RK, Loethen P, Wallace LJ, et al. Differences in the
3. OGrady N, Alexander M, Burns LA, et al. Healthcare Infection outcome of surgically placed long-term central venous catheters
Control Practices Advisory Committee (HICPAC) (Appendix 1). in neonates: Neck vs. groin placement. J Pediatr Surg 2005;40:
Summary of recommendations: Guidelines for the Prevention 4751.
of Intravascular Catheter-related Infections. Clin Inf Dis 29. Hsu JH, Wang SS, Lu DV, et al. Optimal skin surface landmark
2011;52:108799. for the SVC-RA junction in cancer patients requiring the implanta-
4. Alexander N. Question 3. Do Portacaths or Hickman lines have a tion of permanent central venous catheters. Anaesthesia
higher risk of catheter-related bloodstream infections in children 2007;62:81823.
with leukaemia? Arch Dis Child 2010;95:23941. 30. Andropoulos DB, Bent ST, Skjonsby B, et al. The optimal length
5. Stevens TP, Schulman J. Evidence-based approach to preventing of insertion of central venous catheters for pediatric patients.
central line-associated bloodstream infection in the NICU. Acta Anesth Analg 2001;93:8836.
Paediatrica Supplement 2012;101:1116. 31. Hind D, Calvert N, McWilliams R, et al. Ultrasonic locating
6. Holzmann-Pazgal G, Kubanda A, Davis K, et al. Utilizing a line devices for central venous cannulation: Meta-analysis. BMJ 2003;
maintenance team to reduce central-line-associated bloodstream 16:327361.
infections in a neonatal intensive care unit. J Perinatol 2012;32: 32. Abboud PA, Kendall JL. Ultrasound guidance for vascular access.
2816. Emerg Med Clin North Am 2004;22:74973.
7. Haas NA. Clinical review: Vascular access for fluid infusion in 33. Hosokawa K, Shime N, Kato Y, et al. A randomized trial of ultra-
children. Crit Care 2004;8:47884. sound image-based skin surface marking versus real-time
8. Keyes LE, Frazee BW, Snoey ER, et al. Ultrasound-guided ultrasound-guided internal jugular vein catheterization in infants.
brachial and basilic vein cannulation in emergency department Anesthesiology 2007;107:7204.
patients with difficult intravenous access. Ann Emerg Med 1999;34: 34. Maecken T, Grau T. Ultrasound imaging in vascular access. Crit
71114. Care Med 2007;35:S17885.
9. Miyake RK, Zeman HD, Duarte FH, et al. Vein imaging: A new 35. Wigmore TJ, Smythe JF, Hacking MB, et al. Effect of the imple-
method of near infrared imaging, where a processed image is mentation of NICE guidelines for ultrasound guidance on the
projected onto the skin for the enhancement of vein treatment. complication rates associated with central venous catheter place-
Dermatol Surg 2006;32:10318. ment in patients presenting for routine surgery in a tertiary referral
10. Butler-OHara M, Buzzard CJ, Reubens L, et al. A randomized trial centre. Br J Anaesth 2007;99:6625.
comparing long-term and short term use of umbilical venous cath- 36. Pirotte T. Ultrasound-guided vascular access in adults and children:
eters in premature infants with birth weights of less than 1251 Beyond the internal jugular vein puncture. Acta Anaesthesiol Belg
grams. Pediatrics 2006;118:e2535. 2008;59:15766.
122 SECTION I General
37. Sharma A, Bodenham AR, Mallick A. Ultrasound-guided infracla- 50. Gupta H, Araki Y, Davidoff AM, et al. Evaluation of pediatric
vicular axillary vein cannulation for central venous access. Br J oncology patients with previous multiple central catheters for vas-
Anaesth 2004;93:18892. cular access: Is Doppler ultrasound needed? Pediatr Blood Cancer
38. Sheridan RL, Weber JM. Mechanical and infectious complications 2007;48:52731.
of central venous cannulation in children: Lessons learned from a 51. Azizkhan RG, Taylor LA, Jaques PF, et al. Percutaneous translum-
10-year experience placing more than 1000 catheters. J Burn Care bar and transhepatic inferior vena caval catheters for prolonged
Res 2006;27:71318. vascular access in children. J Pediatr Surg 1992;27:1659.
39. Valentine KM. Ethanol lock therapy for catheter-associated blood 52. Mortell A, Said H, Doodnath R, et al. Transhepatic central venous
stream infections in a pediatric intensive care unit. Pediatr Crit catheter for long-term access in paediatric patients. J Pediatr Surg
Care Med 2011;12:e2926. 2008;43:3447.
40. Oliveira C, Nasr A, Brindle M, et al. Ethanol locks to prevent 53. Rodrigues AF, van Mourik ID, Sharif K, et al. Management of
catheter-related bloodstream infections in parenteral nutrition: A end-stage central venous access in children referred for possible
meta-analysis. Pediatrics 2012;129:31829. small bowel transplantation. J Pediatr Gastroenterol Nutr
41. Milbrandt K, Beaudry P, Anderson R, et al. A multiinstitutional 2006;42:42733.
review of central venous line complications: Retained intravascular 54. Solomon BA, Solomon J, Shlansky-Goldberg R. Percutaneous
fragments. J Pediatr Surg 2009;44:9726. placement of an intercostal central venous catheter for chronic
42. Dillon PA, Foglia RP. Complications associated with an implant- hyperalimentation guided by transhepatic venography. JPEN J
able vascular access device. J Pediatr Surg 2006;41:15827. Parenter Enteral Nutr 2001;25:424.
43. DeBoer S, Russell T, Seaver M, et al. Infant intraosseous infusion. 55. Tannuri U, Tannuri AC, Maksoud JG. The second and third right
Neonatal Netw 2008;27:2532. posterior intercostal veins: An alternate route for central venous
44. Engle WA. Intraosseous access for administration of medications access with an implantable port in children. J Pediatr Surg
in neonates. Clin Perinatol 2006;33:1618. 2005;40:e2730.
45. Calkins MD, Fitzgerald G, Bentley TB, et al. Intraosseous infusion 56. Sola JE, Thompson WR. Thoracoscopic-assisted placement of
devices: A comparison for potential use in special operations. azygos vein central venous catheter in a child. Am J Transplant
J Trauma 2000;48:106874. 2008;8:71518.
46. Buck ML, Wiggins BS, Sesler JM. Intraosseous drug administra- 57. Oram-Smith JC, Mullen JL, Harken AH, et al. Direct right atrial
tion in children and adults during cardiopulmonary resuscitation. catheterization for total parenteral nutrition. Surgery 1978;
Ann Pharmacother 2007;41:167986. 83:2746.
47. Blumberg SM, Gorn M, Crain EF. Intraosseous infusion: A review 58. Kohonen M, Teerenhovi O, Terho T, et al. Is the Allen test reliable
of methods and novel devices. Pediatr Emerg Care 2008 quiz enough? Eur J Cardiothorac Surg 2007;32:9025.
57-8;24:506. 59. DCunha PT, Besarab A. Vascular access for hemodialysis: 2004
48. de Caen AR, Kleinman ME, Chameides L, et al. Part 10: Paediatric and beyond. Curr Opin Nephrol Hypertens 2004;13:6239.
basic and advanced life support: 2010 International Consensus on 60. Mancuso ME, Berardinelli L. Arteriovenous fistula as stable venous
Cardiopulmonary Resuscitation and Emergency Cardiovascular access in children with severe haemophilia. Haemophilia
Care Science with Treatment Recommendations. Resuscitation 2010;16:258.
2010;81:e21359.
49. Boon JM, Gorry DL, Meiring JH. Finding an ideal site for intraos-
seous infusion of the tibia: An anatomical study. Clin Anat
2003;16:1518.
C H A P T E R 9
Despite improvements in antimicrobial therapy, surgical component of any clinical infection. Accumulation of
technique, and postoperative intensive care, infection necrotic tissue, hematoma, and foreign matter is an excel-
continues to be a significant source of mortality and mor- lent nutrient medium for continued organism growth and
bidity for pediatric patients. Widespread antibiotic use spread. Of special importance to the surgeon is the
has brought with it the complication of resistant organ- concept of necrotic tissue and infection.6 This tissue
isms, and the selection of the appropriate antibiotic has often needs to be debrided to restore the hostbacterial
become increasingly complex as newer antibiotics are balance and lead to effective wound healing.7 Neutrophils,
continually developed.1,2 In addition, infections with macrophages and cytokines accumulate in necrotic tissue
uncommon organisms are becoming more frequent with initiating an inflammatory secondary response.8
diminished host resistance from immunosuppressive Finally, for a clinical infection to arise, the bodys
states such as immaturity, cancer, systemic diseases, and defenses must be overcome. Even highly virulent organ-
medications after transplant procedures. Surgical infec- isms can be eradicated before clinical infection occurs if
tions generally require some operative intervention, such resistance is intact. Evolution has equipped humans with
as drainage of an abscess or removal of necrotic tissue, numerous mechanisms of defense, both anatomic and
and seldom respond to antibiotics alone. systemic.
Two broad classes of infectious disease processes affect
a surgical practice: those infectious conditions brought to
the pediatric surgeon for treatment and cure, and those DEFENSE AGAINST INFECTION
that arise in the postoperative period as a complication
of an operation.3 Anatomic Barriers
Intact skin and mucous membranes provide an effective
COMPONENTS OF INFECTION surface barrier to infection.9 These tissues are not merely
a mechanical obstacle. The physiologic aspects of skin
The pathogenesis of infection involves a complex interac- and mucous membranes provide additional protection. In
tion between the host and infectious agent. Four compo- the skin, the constant turnover of keratinocytes, tempera-
nents are important: virulence of the organism, size of ture of the skin, and acid secretion from sebaceous glands
inoculum, presence of nutrient source for the organism, inhibits bacterial cell growth. The mucosal surfaces also
and a breakdown in the hosts defense. have developed advanced defense mechanisms to prevent
The virulence of any microorganism depends on its and combat microbial invasion. Specialized epithelial
ability to cause damage to the host. Exotoxins, such as layers provide resistance to infection. In addition, mecha-
streptococcal hyaluronidase, are digestive enzymes nisms such as the mucociliary transport system in the
released locally that allow the spread of infection by respiratory tract and normal colonic flora in the gastroin-
breaking down host extracellular matrix proteins. Endo- testinal tract prevent invasion of organisms. Anything
toxins, such as lipopolysaccharides, are components of that affects the normal function of these anatomic barri-
gram-negative cell walls that are released only after bac- ers increases the hosts susceptibility to infection. A skin
terial cell death. Once systemically absorbed, endotoxins injury or a burn provides open access to the soft tissues,
trigger a severe and rapid systemic inflammatory response and antibiotic use disrupts normal colonic flora.10 Such
by releasing various endogenous mediators such as breakdowns in surface barriers are dealt with by the
cytokines, bradykinin, and prostaglandins.4 Surgical second line of defenses, the immune system.
infections are often polymicrobial, involving various
interactions among the microorganisms. Immune Response
The size of the inoculum is the second component of
an infection. The number of colonies of microorganisms The immune system involves complex pathways and
per gram of tissue is a key determinant. Predictably, any many specialized effector responses. The first line of
decrease in host resistance decreases the absolute number defense is the more primitive and nonspecific innate
of colonies necessary to cause clinical disease. In general, system, which consists primarily of phagocytic cells and
if the bacterial population in a wound exceeds 100,000 the complement system. The neutrophil is able to rapidly
organisms per gram of tissue, invasive infection is present.5 migrate to the source of the infection and engulf and
For any inoculum, the presence of suitable nutrients destroy the infecting organisms by phagocytosis.
for the organism is essential and comprises the third Cytokines, low molecular weight proteins including
123
124 SECTION I General
tumor necrosis factor (TNF), and many interleukins recurrent, and unusual infections often occur in diabetic
attract and activate neutrophils, and play a significant role patients.16 In addition, malignancy and other conditions
in mediating the inflammatory response. In addition, the that impair hematopoiesis lead to alterations in phagocy-
complement system, when activated, initiates a sequential tosis, resulting in an increased predilection for infection.
cascade that also enhances phagocytosis and leads to lysis Human immunodeficiency virus (HIV) infection in chil-
of pathogens. Neonates, particularly premature infants, dren is another major source of immunodeficiency. Verti-
have an immature immune system and are helped by the cal transmission from mother to child is the dominant
protective agents in human breast milk.11,12 The more mode of HIV acquisition among infants and children.
specialized, adaptive immune system involves a highly Finally, poor nutritional status has adverse effects on
specific response to antigens as well as the eventual pro- immune function owing to a wide variety of negative
duction of a variety of humoral mediators.13 influences on specific defense mechanisms, including
decreased production of antibodies and phagocytic
function.17
Humoral and Cell-Mediated Immunity
In patients with a primary immune defect, susceptibil-
Specific, adaptive immunity has two major components. ity to a specific infection is based on whether the defect
The humoral mechanism (B-cell system) is based on is humoral, cellular, or a combination. Primary immuno-
bursa cell lymphocytes and plasma cells. The cellular deficiencies are rare but important because prompt rec-
mechanism (T-cell system) consists of the thymic- ognition can lead to life-saving treatment or significant
dependent lymphocytes.14 The adaptive immune system improvement in the quality of life.18 B-cell deficiencies
is an antigen-specific system that is regulated by the are associated with sepsis from encapsulated bacteria,
lymphocytes. A myriad of receptors on the T-cells especially pneumococcus, Haemophilus influenzae, and
that are matched to particular individual antigens meningococcus. Often a fulminating course rapidly
create these specific responses. Furthermore, antibody ends in death, despite timely therapeutic measures.
production from B-cells enhances the antigen-specific Although congenital agammaglobulinemia or dysgam-
interaction. maglobulinemia has been widely recognized, other causes
B-cell immunity is provided by antibodies. The first of humoral defects include radiation, corticosteroid and
exposure of an antigen leads to the production of IgM antimetabolite therapy, sepsis, splenectomy, and starva-
antibodies, whereas subsequent exposure to the same tion. Chronic granulomatous disease is caused by a defi-
antigen results in rapid production of IgG antibodies. ciency in the respiratory burst action of phagocytes that
Humoral antibodies may neutralize toxins, tag foreign leads to severe and recurrent bacterial and fungal infec-
matter to aid phagocytosis (opsonization), or lyse invad- tions in early childhood. Children with chronic granulo-
ing cellular pathogens. Plasma cells and non-thymic- matous disease are prone to develop hepatic abscesses as
dependent lymphocytes that reside in the bone marrow well as suppurative adenitis of a single node or multiple
and in the germinal centers and medullary cords of lymph nodes, both of which may require surgical drainage or
nodes produce the reactive components of this humoral excision.19
system. These agents account for most of the human T-cell deficiencies are responsible for many viral,
immunity against extracellular bacterial species. fungal, and bacterial infections. Cutaneous candidiasis
The cellular or T-cell component of immunity is is a good example of a common infection seen with a
based on sensitized lymphocytes located in the subcorti- T-cell deficiency. DiGeorge syndrome is a developmental
cal regions of lymph nodes and in the periarterial spaces anomaly in which both the thymus and the parathyroid
of the spleen. T-cells are specifically responsible for glands are deficient, thus increasing the risk for infection
immunity to viruses, most fungi, and intracellular bacte- and hypocalcemic tetany during infancy.
ria. They produce a variety of lymphokines, such as trans-
fer factors, that further activate lymphocytes, chemotactic
factors, leukotrienes, and interferons. ANTIBIOTICS
The several classes of antibiotics are based on their
Immunodeficiencies
molecular structure and site of action. The varying classes
Susceptibility to infection is increased when one of the of antibiotics may be divided into bacteriostatic, which
components of the host defense mechanism is absent, inhibit bacterial growth, and bacteriocidal, which destroy
reduced in numbers, or curtailed in function. Some of bacteria. The early initiation and correct choice of anti-
these derangements may be congenital, although the biotics is essential for timely and successful treatment of
majority are acquired as a direct result of medications, infections. In addition, it is important to have knowledge
radiation, endocrine disease, surgical ablation, tumors, or of the specific susceptibility patterns in a particular hos-
bacterial toxins. Immunodeficiencies from any cause sig- pital or intensive care unit to direct initial empirical anti-
nificantly increase the risk of infection both in hospital- biotic therapy. Finally, awareness of interactions and
ized and postoperative patients. Mycotic infections are an adverse reactions in children from commonly used medi-
increasing problem in immunocompromised pediatric cations is critical.
patients.15 The pharmacokinetics and monitoring of drug dosages
Systemic diseases lead to diminished host resistance. in infants and children is also important when treating
For example, in diabetes mellitus, leukocytes often fail to them with antibiotics. The efficacy and safety of many
respond normally to chemotaxis. Therefore, more severe, drugs have not been established in the pediatric patient,
9 Surgical Infectious Disease 125
hypothermia can potentially lead to serious complica- Prophylaxis accounts for nearly 75% of antibiotic use
tions, including coagulopathy, SSIs, and cardiac compli- on pediatric surgical services. As such, prophylaxis is the
cations. A prospective randomized trial of 200 adult major cause of the inappropriate use of antimicrobials in
patients undergoing colorectal surgery showed that intra- children. In one study of children younger than 6 years
operative hypothermia caused delayed wound healing of age undergoing surgical procedures, prophylactic anti-
and a greater incidence of infections.32 A number of tech- biotics were administered inappropriately to 42% of chil-
niques are available to warm infants and children during dren receiving preoperative antibiotics.40 A more recent
surgery, including warming intravenous fluids or using study demonstrated that 82% of patients received pro-
forced-air warming systems. In addition, supplemental phylactic antibiotics when indicated and that 40% of
oxygen given during the perioperative period in adults patients received antibiotics when there was no indica-
has been shown to decrease the rate of wound infection tion.41 In pediatric surgery, it is clear that antibiotic
by as much as 4050%.33,34 Finally, adequate control of coverage is required during clean-contaminated, con-
glucose levels perioperatively has also been demonstrated taminated, or dirty cases. Antibiotic prophylaxis in a clean
to decrease morbidity and mortality in both adult and case in the pediatric population is now at the discretion
pediatric surgical patients, particularly in those patients of the operating surgeon.
undergoing cardiac surgery.35,36
Bowel Preparation
Antibiotic Prophylaxis The efficacy of bowel preparation before an elective
Operative procedures can be classified into one of four colon operation is well documented.42,43 Bowel prepara-
types, as outlined in Table 9-1. In adults, several well- tion includes mechanical irrigation and flushing of the
designed prospective trials have documented a decreased colon to remove stool, oral antibiotics against colonic
incidence of infection for all types of operative proce- aerobes and anaerobes, and preoperative intravenous
dures with established antibiotic recommendations.37 antibiotics that cover both common skin and colonic
Important points for preoperative antibiotic prophylaxis flora.44 The preparation can be started on an outpatient
include using agents that cover the most probable intra- basis the day before the operation, and the parenteral
operative contaminants for the operation, optimal timing drugs are added to the regimen just before the procedure.
for the initial dose of antibiotic so that bactericidal con- Recently, there has been debate in the adult literature
centrations are reached at the time of incision, and main- regarding the necessity of mechanical bowel preparation.
taining the contribution levels throughout the operation.38 In infants and children, protocols for bowel preparation
Timing of the perioperative antibiotic coverage is crucial. have largely been extrapolated from the adult colorectal
The first dose is generally given 30 minutes to one hour literature. It appears that the majority of pediatric sur-
before the start of the operation. In operations that take geons use bowel preparations for elective colorectal
more than the half-life of the administered drug, a second surgery.45 Recently, others have proposed that omitting
dose of prophylactic antibiotics is indicated to re-achieve mechanical bowel preparation carries no increased risk of
adequate serum levels.39 infectious or anastomotic complications.46 If bowel prep-
aration is used in the pediatric population, care must be
taken to avoid dehydration.
TABLE 9-1 Wound Classification
Class Definition TYPES OF INFECTION
Clean An uninfected operative wound in
which no inflammation is Postoperative Surgical Site Infection
encountered and the respiratory,
alimentary, genital, or infected Despite meticulous technique and perioperative antibiot-
urinary tract is not entered. In ics, infectious complications still occur. Postoperative
addition, clean wounds are closed
primarily and, if necessary,
wound infections can be divided into superficial or deep.47
drained with closed drainage Early diagnosis and prompt intervention help to avoid
Cleancontaminated An operative wound in which the morbidity and occasional mortality. Erythema, fever, leu-
respiratory, alimentary, genital, or kocytosis, tenderness, crepitus, and suppuration are diag-
urinary tract is entered under nostic signs but are not always present. When confronted
controlled conditions and without
unusual contamination with one or more of these signs, clinical judgment is
Contaminated Open, fresh, accidental wounds. important. Treatment may include oral or intravenous
This includes operations with antibiotics, simple incision and drainage, or extensive
major breaks in sterile technique surgical debridement.
or gross spillage from the
gastrointestinal tract and incisions
An abscess is a localized collection of pus in a cavity
in which acute, nonpurulent formed by an expanding infectious process (Fig. 9-1A)
inflammation is encountered Pus is a combination of leukocytes, necrotic material,
Dirty Old traumatic wounds with retained bacteria, and extracellular fluid. The usual cause is the
devitalized tissue and those that staphylococcal species in combination with one or more
involve existing clinical infection
or perforated viscera organisms. The treatment is incision and drainage (Fig.
9-1B), followed by antibiotic therapy if associated with
9 Surgical Infectious Disease 127
A B
FIGURE 9-1 (A) This young boy developed a large expanding right inguino-femoral abscess. (B) The abscess has been drained and
the purulent fluid is seen draining from the abscess.
localized cellulitis or an immunocompromised patient. Pneumonia can be a lethal nosocomial infection, with
Drainage must be complete, or the abscess will reform. mortality ranging from 2070% and accounting for
A phlegmon is an area of diffuse inflammation with little 1015% of all pediatric hospital-acquired infections.52
pus and some necrotic tissue. A phlegmon can often be The mortality rate is dependent on the causative organ-
treated with antibiotics, although it can progress to an ism. The risk factors for nosocomial pneumonia in the
abscess. pediatric population include serious underlying illness,
Streptococcal soft tissue infections are probably the immunosuppression, and length of time on a ventilator.53
most virulent and can arise within a few hours after surgi- Measures to prevent ventilator-associated pneumonia
cal procedures. High fever, delirium, leukocytosis, and in children include elevating the head of the bed, daily
severe pain are hallmarks of the patients presentation. assessment of readiness for extubation, and age-
Bacillus infections are the next most virulent infections. appropriate mouth care.54
Inspection of the wound will show dark, mottled areas, Clostridium difficile is a well-recognized cause of infec-
as opposed to the bright pink of a streptococcal cellulitis. tious diarrhea that develops after antibiotic therapy in
Less than half of the patients with Bacillus infections have many patients, although it likely only accounts for 20%
detectable gas crepitation. Severe pain is the most telling of antibiotic-associated diarrhea. It is a very common
clinical symptom of this type of infection. High doses of cause of nosocomial infection, and its incidence is increas-
penicillin and operative debridement of necrotic tissue ing in frequency with associated increasing mortality.55,56
are the hallmarks of treatment for these patients. The best method of prevention is the judicious and
appropriate use of antibiotics.
To decrease nosocomial infections in hospitals, the
Nosocomial Infection Centers for Medicare and Medicaid Services (CMS)
Nosocomial infections are defined as those infections released a proposal in 2008 to expand the list of hospital-
that are hospital acquired.48 As such, they are a potential acquired conditions that will not be reimbursed by Medi-
threat to all hospitalized patients and increase morbidity care. These have been termed Never Events and include
and mortality significantly. Their incidence appears to be SSIs after specific elective surgeries, extreme glycemic
increasing as surgical care becomes more advanced and aberrancies, ventilator-associated pneumonia, and C.
patients survive longer. Recent focus on patient safety has difficile-associated diseases, among others. Under this
made prevention of nosocomial infections increasingly proposal, CMS will not reimburse hospitals for treatment
important. One report describing 676 operative proce- (medical or surgical treatment) of these nosocomial
dures in 608 pediatric patients showed a nosocomial entities.
infection rate of 6.2%.48 The infectious complications
included septicemia, pulmonary, urinary tract, abdomi-
nal, and diarrhea. The highest overall occurrence of
Catheter Infections
infection was in the infant group. The most common Central venous catheters (CVCs) are essential for manag-
isolates were Staphylococcus epidermidis from septic patients ing critically ill patients. The use of CVCs in infants
and gram-negative enteric bacteria from organ and and children has increased as prolonged vascular access
wound infections. Infection was associated with impaired has become increasingly necessary to provide parenteral
nutrition, multiple disease processes, and multiple opera- nutrition, chemotherapy, antimicrobial therapy, and
tions. In addition, ECMO use has been shown to cor- hemodynamic monitoring. However, catheter-related
relate with an increased incidence of nosocomial infection infections are common, despite considerable effort to
as does length of the preoperative stay and exposure to reduce their occurrence, and are associated with increased
invasive medical devices.4951 hospital costs and length of stay. Infection is manifested as
128 SECTION I General
erythema at the site of insertion, tachycardia, and/or leu- Necrotizing Soft Tissue Infection
kocytosis. Rates of infection are influenced by patient-
related factors, by type and severity of illness, and by Necrotizing fasciitis is a rapidly progressing infection of
catheter-related parameters (catheter type, purpose, and the fascial tissues and overlying skin. Although it can
conditions under which it was placed).57 Coagulase- occur as a postoperative complication or as a primary
negative staphylococci, followed by enterococci, were infection, necrotizing fasciitis is more likely in immuno-
the most frequently isolated causes of hospital-acquired compromised patients.70 However, in the pediatric popu-
bloodstream infections in a report from the National lation, necrotizing fasciitis often affects previously healthy
Nosocomial Infections Surveillance System.58 A number children and infants.71 Because the diagnosis is often not
of factors are associated with the development of catheter- obvious, the clinician must look for clinical clues such as
related infections, including the sterility of the insertion edema beyond the area of erythema, crepitus, skin vesi-
technique, type of solution being administered through cles, or cellulitis refractory to intravenous antibiotics.
the line, care of the catheter once inserted, proximity of Skin necrosis is generally a late sign and is indicative of
the catheter to another wound, and the presence of another thrombosis of vessels in the subcutaneous tissue. Necro-
infection elsewhere. Updated guidelines for the preven- tizing fasciitis often occurs in the truncal region in
tion of intravascular catheter-related infections were pub- children as opposed to adults where infection in the
lished in 2011.59 For catheters that will remain for a long extremities is most common (Figs 9-2 and 9-3).72
time, tunneling the catheter has been shown to signifi- Although infections with a single organism often occur
cantly reduce the risk of catheter-related infection.60,61 in adults with necrotizing fasciitis, polymicrobial infec-
Absolute sterile techniques should be maintained in all tions predominate in children.73 Prompt surgical inter-
instances of line insertion whenever possible. Emergency vention, including wide excision of all necrotic and
situations may necessitate less-than-sterile technique. infected tissue, along with the institution of antibiotics
The use of maximal sterile barriers, including sterile including penicillin, is mandatory to avoid progression
gown and gloves and a large sterile sheet, has been shown and mortality. Necrotizing fasciitis can also occur as a
in adults to greatly reduce the risk of catheter-related complication of chickenpox.74 In neonates, necrotizing
infection.62 Studies suggest that chlorhexidine signifi- fasciitis can occur as a secondary infection of omphalitis,
cantly reduces the incidence of microbial colonization balanitis, and fetal monitoring.75
compared with povidone-iodine, and 0.5% chlorhexidine
preparations with alcohol is now recommend for skin
Sepsis
antisepsis.63 The safety and efficacy of chlorhexidine is
unknown in infants < 2 months. Sepsis, by contemporary definition, defines the systemic
The skin and catheter hub are the most common derangements that are caused by the infectious organisms
sources of colonization and infection. Thus, various and their byproducts as opposed to those derangements
methods have been used to combat these risks. Silver that are caused by the host-systemic inflammatory
ions have broad antimicrobial activity, and the use of response. In 1992, the Society of Critical Care Medicine
silver-impregnated cuffs have been tried as a preventive published the results of a consensus conference to define
measure.64,65 In addition, antimicrobial and antiseptic accurately the terms regarding sepsis and the inflamma-
catheters and cuffs may decrease the incidence of catheter- tory response to injury and infection.76 These definitions
related infections.66,67 Catheters have been coated with were updated in the 2001 Consensus Conference.77
chlorhexidine/silver sulfadiazine as well as minocycline/ Although there has been a significant decrease in the
rifampin along with other agents. The use of these coated mortality rate among children with sepsis, severe sepsis
catheters has been approved by the ultrasound Food and remains one of the leading causes of death in the pediatric
Drug Administration for use in patients weighing more population. In 2002, a group of experts gathered to focus
than 3kg. It is likely that the efficacy for reducing infec- specifically on pediatric sepsis.78 Systemic inflammatory
tion decreases after being in place for longer than three response syndrome (SIRS) has previously been defined in
weeks because of a decrease in the antimicrobial activity.67 adults as the nonspecific inflammatory process after a
These impregnated catheters and sponge dressings can variety of insults with sepsis specifically occurring from
be used if the infection rate is not decreasing with other infection.79 The main pediatric modifications include the
measures. Of note, no studies in adults have demon- inclusion of temperature or leukocyte abnormalities in
strated a benefit for systemic antibiotic prophylaxis after addition to tachycardia and tachypnea because these last
insertion of a CVC. Studies in high-risk neonates and two indices are common in many pediatric disease proc-
children have demonstrated conflicting results. However, esses. Another difference is that hypotension is not neces-
concern exists for the emergence of resistance with the sary for the diagnosis of septic shock, but cardiovascular
routine use of antimicrobial prophylaxis.68,69 dysfunction must be present. SIRS may progress to
multi-organ dysfunction and death. Gram-negative
Other Infections Requiring Surgical organisms possess a lipopolysaccharide moiety on the cell
Care and Treatment wall that has been shown to incite most, if not all, of the
toxic effects of end-organ failure.
Although the infections discussed previously are possibly Neonatal sepsis is defined as a generalized bacterial
preventable and occur after operations or hospitalization, infection accompanied by a positive blood culture within
some infections are seen by the pediatric surgeon for the the first month of life.80 Neonatal sepsis occurring during
first time. the first week of life is caused primarily by maternal
9 Surgical Infectious Disease 129
A B
FIGURE 9-2 This 15-year-old was ill for two weeks with perforated appendicitis and presented in shock. After a midline incision
for exploration for a rigid abdomen, his appendix was removed. The peritoneal cavity was extensively and copiously irrigated and
the abdominal incision was left open. He returned to the operating room two days later for evaluation and was found to have
necrotizing fasciitis of the rectus abdominis muscles bilaterally. Eventually, despite aggressive surgical debridement, this process
spread to the retroperitoneum and down the left inguinal canal through a patent processus vaginalis. One week postoperatively,
he was found to have edema and erythema of the left leg that prompted exploration. The necrotizing fasciitis had progressed down
all compartments of the left thigh and the lateral compartment of the left lower leg. In the upper thigh, the semimembranosus and
semitendinosus muscles had to be excised due to necrotic musculature. These photographs were taken on his ninth postoperative
day. (A) The abdomen is seen to be open and the medial aspect of the left thigh is visualized. (B) The incisions in the left buttock
area, the left lateral thigh, and the left lateral lower leg are seen.
Peritonitis
Peritonitis is defined as inflammation of the peritoneum.82
It is divided into primary, secondary, and tertiary. Spon-
taneous primary peritonitis is a bacterial infection without
enteric perforation. Primary peritonitis is usually caused
by a single organism. An infant with primary peritonitis
usually does not exhibit signs of peritonitis but may have
poor feeding, lethargy, distention, vomiting, and mild to
severe abdominal tenderness. Definitive treatment may
FIGURE 9-3 This photomicrograph depicts the histologic find- require only a course of broad-spectrum antibiotics. Sec-
ings of necrotizing fasciitis in the patient shown in Figure 9-2.
Note the inflammatory infiltrate on both sides of the fascia. The
ondary peritonitis is associated with gastrointestinal tract
fascial cultures grew Escherichia coli. disruption. This can be caused directly by intestinal per-
foration, bowel wall necrosis, trauma, or postoperatively
as a result of iatrogenic injury or an anastomotic leak.
organisms transferred during delivery. Maternal contam- In addition, secondary peritonitis also may result from
ination can be transmitted through the placenta to the an indwelling dialysis catheter or ventriculoperitoneal
newborn via the birth canal or by direct contamination shunt.83 These infections are generally polymicrobial.
of the amniotic fluid. The mortality of this early onset Treatment of secondary peritonitis is a combination of
sepsis approaches 50%. Late-onset neonatal sepsis is pri- operative intervention, removal of any prosthetic device,
marily nosocomial and is most often secondary to ind- and antibiotics. Tertiary peritonitis, also called recurrent
welling catheters or bacterial translocation from the gut. peritonitis, is characterized by organ dysfunction and sys-
In the surgical neonate, three factors promote bacterial temic inflammation in association with recurrent infec-
translocation and sepsis: (1) intestinal bacterial coloniza- tion. The mortality rate is very high, and management is
tion and overgrowth; (2) compromised host defenses; and difficult.84 Treatment consists of broad-spectrum antibi-
(3) disruption of the mucosal epithelial barrier.81 The otics because the infection often includes nosocomial
mortality of late-onset sepsis approaches 20%. The organisms and multidrug-resistant bacteria.
130 SECTION I General
56. Nylund CM, Goudie A, Garza JM, et al. Clostridium difficile infec- 68. Kacica MA, Horgan MJ, Ochoa L, et al. Prevention of gram-
tion in hospitalized children in the United States. Arch Pediatr positive sepsis in neonates weighing less than 1500 grams. J Pediatr
Adoles Med 2011;165:4517. 1994;125:2538.
57. OGrady NP, Alexander M, Dellinger EP, et al. Guidelines for 69. Spafford PS, Sinkin RA, Cox C, et al. Prevention of central venous
the prevention of intravascular catheter-related infections. catheter-related coagulase-negative staphylococcal sepsis in
The Hospital Infection Control Practices Advisory Committee, neonates. J Pediatr 1994;125:25963.
Center for Disease Control and Prevention. Pediatrics 2002;110: 70. Farrell LD, Karl SR, Davis PK, et al. Postoperative necrotizing
e51. fasciitis in children. Pediatrics 1988;82:8749.
58. System ArftN. National Nosocomial Infections Surveillance 71. Bingol-Kologlu M, Yildiz RV, Alper B, et al. Necrotizing fasciitis
(NNIS) System Report, data summary from January 1992 through in children: Diagnostic and therapeutic aspects. J Pediatr Surg
June 2004, issued October 2004. Am J Infect Control 2004; 2007;42:18927.
32:47085. 72. Murphy JJ, Granger R, Blair GK, et al. Necrotizing fasciitis in
59. OGrady NP, Alexander M, Burns LA, et al. Summary of recom- childhood. J Pediatr Surg 1995;30:11314.
mendations: Guidelines for the Prevention of Intravascular 73. Moss RL, Musemeche CA, Kosloske AM. Necrotizing fasciitis in
Catheter-related Infections. Clin Infect Dis 2011;52:108799. children: Prompt recognition and aggressive therapy improve sur-
60. Randolph AG, Cook DJ, Gonzales CA, et al. Tunneling short-term vival. J Pediatr Surg 1996;31:11426.
central venous catheters to prevent catheter-related infection: A 74. Waldhausen JH, Holterman MJ, Sawin RS. Surgical implications
meta-analysis of randomized, controlled trials. Crit Care Med of necrotizing fasciitis in children with chickenpox. J Pediatr Surg
1998;26:14527. 1996;31:113841.
61. Timsit JF, Sebille V, Farkas JC, et al. Effect of subcutaneous tun- 75. Hsieh W-S, Yang P-H, Chao H-C, et al. Neonatal necrotizing
neling on internal jugular catheter-related sepsis in critically ill fasciitis: A report of three cases and review of the literature. Pedi-
patients: A prospective randomized multicenter study. JAMA atrics 1999;103:e53.
1996;276:141620. 76. American College of Chest Physicians/Society of Critical Care
62. Raad II, Hohn DC, Gilbreath BJ, et al. Prevention of central Medicine Consensus Conference. Definitions for sepsis and organ
venous catheter-related infections by using maximal sterile barrier failure and guidelines for the use of innovative therapies in sepsis.
precautions during insertion. Infect Control Hosp Epidemiol Crit Care Med 1992;20:86474.
1994;15:2318. 77. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/
63. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of ACCP/ATS/SIS International Sepsis Definitions Conference.
povidone-iodine, alcohol, and chlorhexidine for prevention of Intensive Care Med 2003;29:5308.
infection associated with central venous and arterial catheters. The 78. Goldstein B, Giroir B, Randolph A. International pediatric sepsis
Lancet 1991;338:33943. consensus conference: Definitions for sepsis and organ dysfunction
64. Dahlberg PJ, Agger WA, Singer JR, et al. Subclavian hemodialysis in pediatrics. Pediatr Crit Care Med 2005;6:28.
catheter infections: A prospective, randomized trial of an attachable 79. Bone RC, Sprung CL, Sibbald WJ. Definitions for sepsis and organ
silver-impregnated cuff for prevention of catheter-related infec- failure. Crit Care Med 1992;20:7246.
tions. Infect Control Hosp Epidemiol 1995;16:50611. 80. Wolach B. Neonatal sepsis: Pathogenesis and supportive therapy.
65. Groeger JS, Lucas AB, Coit D, et al. A prospective, randomized Semin Perinatol 1997;21:2838.
evaluation of the effect of silver impregnated subcutaneous cuffs 81. Jackson RJ, Smith SD, Wadowsky RM, et al. The effect of E coli
for preventing tunneled chronic venous access catheter infections virulence on bacterial translocation and systemic sepsis in the neo-
in cancer patients. Ann Surg 1993;218:20610. natal rabbit model. J Pediatr Surg 1991;26:4835.
66. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters 82. Heemken R, Gandawidjaja L, Hau T. Peritonitis: Pathophysiology
coated with minocycline and rifampin for the prevention of and local defense mechanisms. Hepato-gastroenterology 1997;
catheter-related colonization and bloodstream infections. A rand- 44:92736.
omized, double-blind trial. The Texas Medical Center Catheter 83. Levy M, Balfe JW, Geary D, et al. Exit-site infection during con-
Study Group. Ann Intern Med 1997;127:26774. tinuous and cycling peritoneal dialysis in children. Perit Dial Int
67. Veenstra DL, Saint S, Saha S, et al. Efficacy of antiseptic- 1990;10:315.
impregnated central venous catheters in preventing catheter- 84. Nathens AB, Rotstein OD, Marshall JC. Tertiary peritonitis: Clini-
related bloodstream infection: A meta-analysis. JAMA 1999;281: cal features of a complex nosocomial infection. World J Surg
2617. 1998;22:15863.
C H A P T E R 1 0
Fetal Therapy
Corey W. Iqbal Shinjiro Hirose Hanmin Lee
A heightened awareness of fetal anomalies coupled with The primary morbidity following fetal surgery
advances in imaging techniques have allowed clinicians has been, and remains, preterm labor resulting in prema-
to make early and accurate diagnoses of fetal anomalies. ture delivery, usually between 25 and 35 gestational
These advances in prenatal diagnosis have led to the weeks. Preventing preterm labor after fetal intervention
identification of measurable parameters that now allow remains problematic. Complications can also arise from
the clinician to prognosticate and counsel families on the endotracheal intubation, general anesthesia, epidural and
likely outcomes for several prenatally diagnosed anoma- spinal anesthesia, blood transfusion, premature rupture
lies. In cases that carry a grim prognosis, the question is of membranes, chorioamniotic separation, chorioamnio-
often asked: is in utero fetal intervention feasible and will nitis, and placental abruption. Long-term morbidity
it positively impact the outcome? from the hysterotomy includes infertility, uterine rupture
Most prenatally diagnosed anomalies are best treated with the current and future pregnancies, and mandatory
expectantly, with definitive therapy performed after birth. cesarean section with future pregnancies. Notably, in
If a condition poses a threat to the fetus (or mother) and reviewing our experience, subsequent fertility following
the fetus has reached a viable gestational age, then early fetal intervention has been good.2
delivery can be performed. However, when a condition A crucial component contributing to the success of a
progresses to a life-threatening stage at a nonviable ges- fetal treatment program is a multidisciplinary approach.
tational age, then the only options become expectant In addition, specific subspecialists are involved for certain
management with a high likelihood of intrauterine fetal cases, such as the pediatric neurosurgeon for fetal MMC
demise (IUFD) or fetal intervention, which does not repair. Multidisciplinary meetings not only cover the
carry the guarantee of a positive outcome and puts the medical and surgical aspects of the patients care, but also
mother at risk. include the ethical and social considerations specific to
The first open fetal surgical procedure was performed each case. Finally, at UCSF, a special institutional fetal
at the University of California, San Francisco (UCSF) in treatment oversight committee reviews all fetal interven-
1982.1 Since then, more than 515 fetal interventions tions on a monthly basis. This group serves as a quality
have been performed at UCSF over the past 30 years control mechanism as well as an ethical review board.
without maternal mortality. Over the past 30 years,
a number of advances have been developed to allow
a broader application of fetal intervention. These FETAL ACCESS
techniques, including maternal hysterotomy, minimal-
access fetoscopy, and percutaneous fetal access, were There are three general methods for accessing the fetus:
initially tested and validated in animal models. More percutaneous, fetoscopy, and open hysterotomy. In all
recently, in utero therapy has shown to be beneficial for three approaches, preoperative and intraoperative ultra-
non-life-threatening conditions such as myelomenin- sound (US) is crucial for defining the anomaly or anoma-
gocele (MMC). In this chapter, we will present an over- lies, delineating the placental anatomy, determining the
view of the current state of fetal surgery and will review position of the fetus, detecting the location of the mater-
specific fetal problems outlining current management nal blood vessels, and monitoring the fetal heart rate
strategies. during the procedure. With percutaneous and fetoscopic
procedures, ultrasound is particularly important due to
the lack of visualization of the fetus, placenta, and uterus
GENERAL PRINCIPLES during the procedure.
The mother is positioned supine with her left side
Fetal intervention is complicated, not only by the risk to down to minimize compression of the inferior vena cava
the unborn patient, but by the risk to the mother as well. by the gravid uterus. Maternal anesthesia can be either
Fetal intervention does not impart a health benefit to the spinal or general, depending on the nature and duration
mother, yet she is at a significant risk for morbidity and of the intervention. In addition, fetal anesthesia is needed
potential mortality with any fetal surgical intervention. when operating on the fetus. An intramuscular injection
In this light, fetal surgery should be considered only of an opiate and a non-depolarizing neuromuscular
when there is a clear benefit to the fetus. To date, there blocking agent are usually utilized.
have been no reported maternal deaths from fetal surgery, Ultrasound-guided percutaneous procedures are per-
although significant short- and long-term maternal mor- formed through small skin incisions on the mothers
bidity is possible. abdominal wall. During these operations, real-time
132
10 Fetal Therapy 133
ultrasound is needed to visualize the fetal and maternal prevent injury and minimize bleeding. Premature rupture
anatomy.3 Catheters and shunts can be inserted into the of membranes and preterm labor remain a common
fetus to drain cystic masses, ascites, or pleural fluid into problem complicating fetal surgery. These problems
the amniotic space. In addition, radio frequency ablation are often the result of inadequate membrane closure,
(RFA) probes can be deployed into the amniotic space to chorioamnionitis, chorioamniotic separation, and uterine
treat various twin gestational anomalies. The needles contractions.
used to place these catheters, as well as the RFA device,
are approximately 1.52mm in diameter, minimizing
morbidity to the mother and irritation of the uterus.4,5 ANOMALIES AMENABLE
Fetoscopic procedures are generally performed using
a 3mm fetoscope and instruments. Occasionally, stand-
TO FETAL SURGERY
ard 5mm laparoscopic telescopes and instruments are Congenital Diaphragmatic Hernia
used. For many fetoscopic procedures, a 3mm fetoscope
with a 1mm working channel is sufficient. It is important Despite significant advances in neonatal respiratory
to identify a window in the uterus that is devoid of the support, survival for children born with congenital
placenta to reduce the risk of maternal bleeding, placen- diaphragmatic hernia (CDH) remains only 6070%
tal abruption, and fetal morbidity. Occasionally, the throughout the USA. Additionally, survival for prenatally
amniotic fluid is not clear enough for good visualization diagnosed CDH may be as low as 25% due to IUFD and
with the small endoscopes. In such cases, we perform stillborns that are not included in conventional postnatal
amnio-exchange, using warmed crystalloid solutions to survival data.911 This high mortality rate has made CDH
provide a clear operative view. a primary area of interest for the development of effective
Open fetal procedures require general anesthesia with prenatal intervention. In fact, improving outcomes spe-
a combination of preoperative indomethacin and high cifically for CDH was a significant driving force in the
mean alveolar concentration of inhalational agents to genesis of fetal surgery at UCSF.
maintain uterine relaxation.68 An epidural is also inserted
for postoperative analgesia. Prognostic Criteria
A low, transverse maternal incision is usually used with
a vertical or transverse fascial incision, depending on the One of the key elements in developing fetal intervention
exposure needed. Preoperative and intraoperative ultra- for CDH has been identifying what factors will identify
sound are crucial to map out the placenta and avoid those fetuses at the greatest risk for a poor outcome. The
iatrogenic injury. Uterine staplers with absorbable staples factors most consistently associated with a poor outcome
have been developed specifically for fetal surgery and on prenatal ultrasound are (1) the presence of liver her-
allow a hemostatic hysterotomy with minimal blood loss. niation into the chest; and (2) a low lung-to-head ratio
Absorbable staples prevent infertility as nonabsorbable (LHR). In our experience, survival has been 100% in
materials can act as an intrauterine device and prevent fetuses with CDH that do not have liver herniation on
future pregnancies. The uterus is stabilized within the prenatal ultrasound and 56% in fetuses with CDH and
maternal abdomen. Care is taken to minimize tension on liver herniation into the chest.12 The LHR is calculated
the uterine blood vessels, which would decrease placental as the area of the contralateral lung at the level of the
flow. Also, fetal exposure is limited to the specific body cardiac atria divided by the head circumference. This
part in question. Most of the fetus is left inside the uterus, LHR value has been shown to statistically correlate with
and great care is taken not to handle or stretch the umbil- survival: 100% survival with an LHR greater than 1.35,
ical cord as this can cause fetal ischemia from injury or 61% survival with an LHR between 0.6 and 1.35, and 0%
vasospasm. Amniotic fluid volume is maintained using survival with an LHR less than 0.6.12
warmed, isotonic crystalloid solution. After the fetal pro- While the LHR has been a reliable predictor of out-
cedure is completed, the fetus is returned to the uterus, comes at our center, other institutions have suggested the
the amniotic fluid is completely restored, and the uterus LHR does not account for discrepant growth rates
is closed in multiple layers using absorbable sutures. between the head and lung during gestation and there-
Postoperatively, the mother and fetus are monitored con- fore may not be reliable at certain gestational ages.13,14 To
tinuously for uterine contractions and heart rate, respec- account for this, the observed to expected LHR (OE
tively. Often, the uterus is irritable and contractions LHR) has been proposed. The OE LHR is represented
require control with tocolytic agents. as a percentage of what the expected LHR would be in a
Open fetal surgery requires cesarean section for future normal fetus of the same gestational age. For left-sided
pregnancies due to the potential for uterine rupture with defects, an OE LHR <25% is associated with an 18%
subsequent births. While vaginal delivery after cesarean survival whereas an OE LHR >45% correlates with 89%
section (VBAC) can be considered for routine, lower survival.13,15
uterine segment hysterotomy, VBAC is not an option Magnetic resonance imaging (MRI) for volumetric
after hysterotomy for fetal surgery. measurement of the lungs is a promising modality for
As previously mentioned, complications can occur prognosis with CDH.16 MRI can be used to calculate the
after any fetal intervention. Bleeding can originate percent-predicted lung volume (PPLV). Results for PPLV
from the fetus, the placenta, the uterine wall, or the have varied. In one study, a PPLV >20% was associated
maternal abdominal wall despite identifying the uterine with 100% survival whereas survival was only 40% when
vessels with ultrasound and specifically avoiding them to PPLV was <15%.17 In another study, a PPLV <25% was
134 SECTION I General
Fetal Interventions
CDH and its effect on fetal lung development has been
studied in animal models.19,20 In the fetal lamb model,
compression of the lungs, either with an intrathoracic
balloon or by creation of a diaphragmatic hernia, results
in uniformly fatal pulmonary hypoplasia. However, in
utero correction of the compressing lesion leads to suf-
ficient lung growth and development, which improves
postnatal survival.20
This concept of early, in utero correction of CDH has
been studied and applied in humans.21,22 Fetal surgery for
CDH initially involved open repair of the diaphragmatic
defect. The first successful case was reported in 1990
which demonstrated the feasibility of open fetal repair
using a two-step approach which involved creation of
an abdominal silo to accommodate the reduced viscera
and prevent compression of the umbilical vessels.23 This
initial success was followed by a prospective trial at UCSF
comparing open fetal surgery to postnatal repair in severe
cases of prenatally diagnosed CDH. However, in this
study, there was no difference in survival or in the need
for extracorporeal membranous oxygenation (ECMO) FIGURE 10-1 This schematic diagram shows the method of
fetoscopic tracheal occlusion. A fetoscope is placed into the
between fetal repair and postnatal repair.22,24 Concordant fetal mouth, the airway is identified, and a balloon is inserted
with this effort, investigators at UCSF observed that into the trachea by using both fetoscopic and ultrasonographic
fetuses with congenital high airway obstruction syndrome visualization.
(CHAOS) had pulmonary hyperplasia.25 Also, fetal tra-
cheal occlusion had been shown to cause pulmonary
hyperplasia.26 In this condition, the lung parenchyma
creates fluid that is exhaled by the fetus. Occluding the These early results led to an National Institutes of
trachea causes a build-up of this fluid and subsequent Health (NIH) funded, prospective randomized trial com-
pulmonary hyperplasia.27,28 The inability to improve out- paring in utero fetoscopic tracheal occlusion to standard
comes with open fetal repair for severe cases of CDH led postnatal care for fetuses diagnosed with severe left-sided
to an interest in this physiologic process.29 CDH (liver up and LHR <1.4) and no other detectable
The first eight patients were treated with open hyster- anomalies. However, results of the trial showed no dif-
otomy and tracheal occlusion with a metallic clip.30 This ference in survival between the tracheal occlusion group
approach proved to be problematic for several reasons. and the standard postnatal care group (73% vs 77%,
First, the open hysterotomy led to significant prematurity respectively).33 Unexpectedly, the survival in the postna-
due to premature labor. Second, the use of clips was tal repair group was considerably greater when compared
associated with tracheal stenosis and also required a to historical controls. Although this study did not dem-
stringent delivery planwhich was later described as the onstrate a difference in survival between the prenatal
ex utero intrapartum treatment (EXIT) procedure intervention group and the postnatal group, the results
whereby the fetus was exposed through a hysterotomy of this trial demonstrate the tremendous importance of
and maintained on uteroplacental circulation while the proper randomized controlled trials for novel fetal surgi-
clip was removed and a patent airway established prior cal procedures.
to delivering the baby.31 However, outcomes with this Further data regarding fetal tracheal occlusion have
approach were poor with only a 15% survival rate.30 suggested that temporary, short-term reversible tracheal
Ongoing advancements in fetal surgery led to feto- occlusion may be preferable to a longer duration of
scopic balloon placement for tracheal occlusion (Fig. occlusion. Animal models of fetal tracheal occlusion have
10-1). This technique has the advantages of being less demonstrated that long-term tracheal occlusion can be
invasive, a lower risk of tracheal stenosis, and the balloon deleterious to type II pneumocytes (the cells that secrete
being much easier to remove, although still necessitating surfactant) and that this adverse effect is not seen with
an EXIT procedure. Results in the first eight cases were a shorter duration of tracheal occlusion.34 To test the
favorable with a 75% survival rate compared to a 38% hypothesis that temporary fetal tracheal occlusion is
survival rate in historical, case-matched controls managed better, Deprest etal. studied patients undergoing fetal
with postnatal repair.32 tracheal balloon occlusion who also had the balloon
10 Fetal Therapy 135
removed prenatally to limit the duration of occlusion.35 (CVR), defined as the product of the three longest meas-
In this group of patients, improved lung growth was urements of the lesion on ultrasound multiplied by the
evident on fetal MRI and was also associated with constant 0.52, and then divided by the head circumfer-
improved postnatal survival. While reversal of the tra- ence. Crombleholme and colleagues identified a CVR of
cheal occlusion requires a second maternal and fetal 1.6 as a cut-off for an increased likelihood of developing
intervention for balloon removal, it obviates the need for hydrops.45 When the CVR is <1.6, there is only a 2% risk
an EXIT procedure at birth. Early results have been of developing hydrops. When the CVR is >1.6, there is
favorable.31,36 an 80% chance of developing hydrops.
These promising findings with temporary tracheal CCAMs that are predominantly microcystic have a
occlusion have led to its current application in Europe. more predictable course than the macrocystic ones.
The European FETO consortium has reported a 48% Microcystic or solid CCAMs undergo steady growth that
survival rate among 210 cases of severe CDH treated tends to plateau at 26 to 28 weeks gestation. At this point,
with temporary fetal tracheal occlusion, and the Euro fetal growth exceeds that of the CCAM. For this reason,
fetus group is currently sponsoring a prospective fetal patients with microcystic or solid CCAMs should be fol-
tracheal occlusion trial that seeks to determine the ideal lowed closely up to 26 to 28 weeks gestation at which
time and duration for tracheal occlusion.37 Our group at point the interval between ultrasound examinations can
UCSF is currently offering reversible, fetal tracheal be lengthened if the pregnancy has been otherwise
balloon occlusion for fetuses with liver herniation in the uncomplicated. In contrast, macrocystic CCAMs undergo
chest and an LHR of <1.0, as these babies continue to abrupt enlargement due to rapid fluid accumulation in a
have a very high mortality.38 This study has Food and dominant cyst. Therefore, macrocystic CCAMs require
Drug Administration oversight, and involves percutane- close follow-up with serial ultrasound throughout the
ous placement of a fetoscopic tracheal balloon between duration of the pregnancy.42,46
26 and 28 weeks gestation, with removal of the balloon If a fetus develops hydrops at a viable gestational age,
via a second percutaneous fetoscopic procedure between early delivery should be considered. Hydropic fetuses
32 and 34 weeks. who are not yet viable outside the uterus, and have a
dominant macrocystic lesion, are appropriate candidates
for a thoracoamniotic shunt.47 Needle drainage alone has
Neoplasms not been found to be an effective therapy as rapid
Fortunately, fetal neoplasms are rare. When they do re-accumulation of fluid in the cyst necessitates repeat
occur, most are benign. However, if they become large intervention. In the largest single-center experience with
enough, they can impede venous return to the heart or thoracoamniotic shunts, shunting led to a mean 51%
cause high-output heart failure via arteriovenous shunt- volume reduction in the size of the lesion and a 70%
ing. Such shunting can lead to non-immune fetal hydropic survival rate.48 Other institutions have reported similar
changes such as polyhydramnios, placentomegaly, skin survival rates.49 Despite shunting, these babies can still
and scalp edema, and pleural, pericardial, and peritoneal have significant respiratory distress at birth and should
fluid accumulation. When only one compartment is be delivered at a tertiary referral center.
involved, this is considered early fetal hydrops; when two Open fetal thoracotomy and CCAM resection is an
or more compartments are affected, then true hydrops option in the pre-viable fetus with a microcystic or solid
is present. If left untreated, hydrops is nearly always lesion. This is performed through an open hysterotomy.
fatal.3940 The two most common prenatally diagnosed A thoracotomy is made through the fifth intercostal
neoplasms that cause nonimmune fetal hydrops are con- space, and the lobe containing the CCAM is identified
genital pulmonary airway malformations (CPAM) and and exteriorized through the incision (Fig. 10-2). The
sacrococcygeal teratomas (SCT). pulmonary hilar structures are then mass ligated using an
endoloop or endoscopic stapler. The thoracotomy is then
closed in layers.5051
Congenital Pulmonary Airway Malformations
In a group of 120 patients with the prenatal diagnosis
CPAMs are pulmonary lesions with a broad range of of CPAM from UCSF and Childrens Hospital of Phila-
clinical presentations. This new terminology includes delphia (CHOP), 79 had no evidence of hydrops.51 Of
congenital cystic adenomatoid malformations (CCAM) these, 76 were followed expectantly and all survived.
and bronchopulmonary sequestrations. CCAMs are Three fetuses without evidence of hydrops and with large
much more likely than sequestrations to cause nonim- dominant cysts underwent thoracoamniotic shunting. All
mune fetal hydrops. CCAMs are characterized by an three fetuses survived. Twenty-five hydropic fetuses were
overgrowth of respiratory bronchioles with the formation followed with no intervention. All mothers delivered pre-
of cysts of various sizes.4144 Most fetuses diagnosed with maturely and all fetuses died perinatally. Sixteen fetuses
a CCAM develop normally, and can be followed with with hydrops underwent intervention: 13 underwent
serial ultrasound studies. These asymptomatic patients open fetal surgery while three underwent thoracoamni-
then undergo standard, postnatal resection. A small per- otic shunting. Two of the three survived in the group that
centage of patients with the prenatal diagnosis of CCAM underwent shunt insertion and eight of 13 survived in the
will develop non-immune hydrops.43,44 open fetal surgery group.
Various measurements have been developed to predict Despite positive results with open fetal resection in
which fetuses are at risk for developing hydrops. The the hydropic fetus, there has been a shift away from
most accepted measurement is the CCAM volume ratio this therapy in the last five years due to the efficacy of
136 SECTION I General
A B
C D
FIGURE 10-2 These photographs depict an infant with a large left upper lobe CCAM undergoing in utero left lobectomy. (A) The
infants left arm is visualized. Note the maternal hysterotomy and the left fetal thoracotomy (with retractors inserted) through the
fifth intercostal space. (B) The left upper lobe containing the CCAM has been identified and exteriorized through the thoracotomy
incision. The pulmonary hilar structures were mass ligated using an endoloop. (C) The fetal thoracotomy incision (arrow) has been
closed. (D) The left upper lobe specimen containing the CCAM is seen.
Myelomeningocele
MMC, or spina bifida, is characterized by an open neural
tube and exposed spinal canal elements. MMC can occur
anywhere along the spine, but most commonly occurs in
the lumbar or cervical vertebral levels. Complications
include neurologic deficits with motor and somatosen-
sory abnormalities which correspond to the level of the
spinal defect. In addition, autonomic function is com-
monly affected with an inability to control bladder or
bowel function. Also, nearly all patients with MMC
develop the ArnoldChiari II malformation of the hind-
brain and most will require ventriculoperitoneal (VP)
shunting for hydrocephalus. Unlike patients that have
historically been considered for fetal intervention, fetuses
FIGURE 10-4 The myelomeningocele is exposed after maternal
with MMC are generally born alive and healthy. However, hysterectomy. The defect is closed by pediatric neurosurgeons
the attendant morbidity from the neurologic abnormali- using an operating microscope.
ties is severe. Up to 30% of patients die before reaching
adulthood due to respiratory, urinary, or central nervous
system complications. Standard current therapy for There was a 10% rate of uterine dehiscence, and fetal
MMC is postnatal repair of the spinal defect followed by death occurred in 3% of the prenatal repair group.85 For
extensive rehabilitation.77 these reasons, families require extensive counseling to
The rationale for fetal intervention in MMC is the ensure that they fully understand the risks and benefits.
two-hit hypothesis, where the first hit is the original Currently, less invasive methods for the treatment of
neural tube defect that results in an open spinal canal. MMC are being pursued to minimize morbidity. One
The second hit is postulated to be trauma to the exposed promising area may be fetoscopic coverage of the defect
neural elements while the fetus is in utero.78,79 It is this for temporary protection followed by definitive closure
second hit that may be ameliorated by fetal intervention postnatally.90
and early closure.80 The results of animal and preliminary
human studies showed improved neurologic outcomes Hydronephrosis and Low Urinary
and a decreased need for VP shunting with prenatal Tract Obstruction
closure.79,8184 These promising findings prompted a
multi-institutional prospective randomized trial known Hydronephrosis is a common prenatal diagnosis. In most
as the management of myelomeningocele study (MOMS) cases of minimal hydronephrosis, there will be complete
that compared open fetal repair with postnatal repair.85 resolution. However, 10% will have progression and
Fetal repair in the MOMS trial was performed using require postnatal evaluation.91 Therefore, in the setting
an open hysterotomy (Fig. 10-4) with primary repair or of minimal hydronephrosis, an ultrasound should be
the use of skin allografts for large defects as had been obtained in the third trimester to determine if there has
previously described.8689 The studys power analysis indi- been resolution or progression which will help guide the
cated 200 patients were required. However the study was need for postnatal evaluation.
terminated early, after 183 patients, because of the clear More severe cases of hydronephrosis suggest a ure-
advantage to prenatal repair compared to postnatal repair teropelvic junction (UPJ) obstruction, a ureterovesical
for the primary outcome variable which was need for VP junction obstruction, or an obstructing ureterocele. In
shunting. At 12 months, only 68% of the prenatally these scenarios, when unilateral, there is no indication for
repaired group met study criteria for VP shunt placement fetal intervention. Bilateral hydronephrosis is a more sig-
compared to 98% in the postnatal group. Furthermore, nificant problem which can be complicated by oligohy-
neurologic function favored the prenatal repair group, dramnios which leads to fatal pulmonary hypoplasia.
with 42% walking without assistance at 30 months com- Fortunately, bilateral UPJ obstruction rarely leads to oli-
pared to 21% in the postnatal repair cohort.85 Not only gohydramnios and the need for fetal intervention with
were these results a milestone in the evolving treatment shunting.92
of MMC, but this was the first nonlethal anomaly for Lower urinary tract obstruction (LUTO) can be due
which fetal surgery has been shown to be beneficial. to urethral atresia or, most commonly, posterior urethral
The benefit of prenatal MMC repair is associated with valves (PUV). The fetus presents with a classic constel-
risks. In the MOMS trial, there was a 38% incidence of lation of three ultrasound findings: a dilated, keyhole
preterm labor. Also, the mean gestational age in the pre- shaped bladder; bilateral megaureters; and bilateral
natal repair group was 34 weeks compared to 37 weeks hydronephrosis.93 The fetus with LUTO is at high risk
in the postnatal group. Additionally, 46% had premature for the development of oligohydramnios and subsequent
rupture of membranes contributing to earlier delivery. pulmonary hypoplasia that is fatal in the immediate
140 SECTION I General
possible pre-immune status of the fetus, making fetuses improved survival with fetal intervention. NIH funded,
potentially more receptive to exogenous genes or cells. prospective trials have been performed for CDH, TTTS,
Several investigators have utilized hematopoietic stem and MMC which have helped clearly define the roles of
cells (HSC) as a vector in an attempt to induce chimerism fetal therapy in these cases. Current clinical trials include
to treat the diseases.109111 Others have investigated the evaluations for the efficacy of reversible tracheal occlu-
use of retroviral vectors to insert genetic material into the sion for CDH, shunting for LUTO in the absence of
fetus.112,113 This approach reduces the problem of obtain- oligohydramnios, balloon valvuloplasty for critical aortic
ing the large numbers of stem cells needed to create even valve stenosis, and stem cell therapies. Historically, in
a modest amount of chimerism. Other approaches include order to maximize the benefit to the fetus balanced with
using maternal stem cells or genetic material as studies minimizing the risk to the mother, fetal interventions
have demonstrated early cross-trafficking of maternal have been reserved for fetuses with lethal anomalies.
cells in the fetus. MMC represents the first non-lethal anomaly that has
Diseases that are a candidate for this approach include been evaluated. It is not known if the outcomes for other
hematologic, immunologic, metabolic, and neurologic non-lethal anomalies can be improved through fetal
abnormalities (Box 10-1). To date, there have been over intervention.
30 reports of in utero therapy utilizing HSCs with limited As minimal-access techniques improve, and the mater-
success. Until recently, the only durable treatment nal risks are further reduced, indications for fetal inter-
has been in patients with preexisting immunologic vention will continue to expand. New areas of investigation
defects.114,115 However a recent study from UCSF applied include tissue engineering, stem cell therapy, and gene
HSCs in the treatment of four patients with Pelizaeus therapy. Maternal safety must remain paramount, and the
Merzbacher disease, a demyelinating leukodystrophy, risk to the mother should be minimized at all times.
with promising results in three of the patients who have
demonstrated modest improvements in neurologic func- REFERENCES
tion as well as durable engraftment.116 1. Harrison MR, Golbus MS, Filly RA, et al. Fetal surgery for con-
genital hydronephrosis. New Engl J Med 1982;306:5913.
2. Farrell JA, Albanese CT, Jennings RW, et al. Maternal fertility is
THE FUTURE not affected by fetal surgery. Fetal Diagn Ther 1999;14:1902.
3. VanderWall KJ, Meuli M, Szabo Z, et al. Percutaneous access to
the uterus for fetal surgery. J Laparoendosc Surg 1996;6:S657.
Fetal surgery has progressed from an investigational 4. Sydorak RM, Feldstein V, Machin G, et al. Fetoscopic treatment
approach to an accepted mode of therapy for select fetal for discordant twins. J Pediatr Surg 2002;37:17369.
diseases. Multidisciplinary teams are critical for the 5. Lee H, Wagner AJ, Sy E, et al. Efficacy of radiofrequency ablation
success of any fetal program. Some diseases that histori- for twin-reversed arterial perfusion sequence. Am J Obstet
Gynecol 2007;196:459e14.
cally have had a high perinatal mortality rate have shown 6. De Buck F, Deprest J, Van de Velde M. Anesthesia for fetal
surgery. Curr Opin Anaesthesiol 2008;21:2937.
7. Harrison MR, Anderson J, Rosen MA, et al. Fetal surgery in the
Diseases for which in Utero primate I. Anesthetic, surgical, and tocolytic management to
BOX 10-1 Stem Cell or Gene Therapy maximize fetal-neonatal survival. J Pediatr Surg 1982;17:11522.
may be Applicable 8. Rosen MA. Anesthesia for fetal procedures and surgery. Yonsei
Med J 2001;42:66980.
HEMATOLOGIC 9. Logan JW, Rice HE, Goldberg RN, et al. Congenital diaphrag-
matic hernia: A systematic review and summary of best-evidence
-Thalassemia
practice strategies. J Perinatol 2007;27:53549.
Fanconi anemia 10. Moya FR, Lally KP. Evidence-based management of infants with
Chronic granulomatous disease congenital diaphragmatic hernia. Semin Perinatol 2005;29:
Hemophilia A 11217.
11. Doyle NM, Lally KP. The CDH Study Group and advances in
IMMUNOLOGIC the clinical care of the patient with congenital diaphragmatic
Severe combined immunodeficiency (SCID) syndrome hernia. Semin Perinatol 2004;28:17484.
WiskottAldrich syndrome 12. Metkus AP, Filly RA, Stringer MD, et al. Sonographic predictors
of survival in fetal diaphragmatic hernia. J Pediatr Surg
METABOLIC 1996;31:14852.
13. Jani J, Nicolaides KH, Keller RL, et al. Observed to expected lung
Wolman disease area to head circumference ratio in the prediction of survival in
Type II Gaucher disease fetuses with isolated diaphragmatic hernia. Ultrasound Obstet
Pompe disease Gynecol 2007;30:6771.
Osteogenesis imperfecta 14. Cruz-Martinez R, Castanon M, Moreno-Alvarez O, et al. Useful-
Cystic fibrosis ness of lung-to-head ratio and intrapulmonary Doppler in pre-
dicting neonatal morbidity in fetuses with congenital diaphragmatic
NEUROLOGIC hernia treated with fetoscopic tracheal occlusion. Ultrasound
LeschNyhan syndrome Obstet Gynecol 2012;41:5965.
15. Jani JC, Benachi A, Nicolaides KH, et al. Prenatal prediction of
TaySachs disease
neonatal morbidity in survivors with congenital diaphragmatic
Sandhoff disease hernia: A multicenter study. Ultrasound Obstet Gynecol
NiemannPick disease 2009;33:649.
Leukodystrophies 16. Coakley FV, Lopoo JB, Lu Y, et al. Normal and hypoplastic fetal
Generalized gangliosidosis lungs: Volumetric assessment with prenatal single-shot rapid
Leigh disease acquisition with relaxation enhancement MR imaging. Radiology
2000;216:10711.
142 SECTION I General
17. Barnewolt CE, Kunisaki SM, Fauza DO, et al. Percent predicted 40. Adzick NS. Open fetal surgery for life-threatening fetal anoma-
lung volumes as measured on fetal magnetic resonance imaging: lies. Semin Fetal Neonatal Med 2010;15:18.
A useful biometric parameter for risk stratification. J Pediatr Surg 41. Schott S, Mackensen-Haen S, Wallwiener M, et al. Cystic adeno-
2007;42:1937. matoid malformation of the lung causing hydrops fetalis: Case
18. Victoria T, Bebbington MW, Danzer E, et al. Use of magnetic report and review of the literature. Arch Gynecol Obstet
resonance imaging in prenatal prognosis of the fetus with isolated 2009;280:2936.
left congenital diaphragmatic hernia. Prenatal Diagnosis 42. Kunisaki SM, Barnewolt CE, Estroff JA, et al. Large fetal con-
2012;32:71523. genital cystic adenomatoid malformations: Growth trends and
19. Adzick NS, Harrison MR, Flake AW. Experimental studies on patient survival. J Pediatr Surg 2007;42:40410.
prenatal treatment of congenital anomalies. Br J Hosp Med 43. Ierullo AM, Ganapathy R, Crowley S, et al. Neonatal outcome of
1985;34:1549. antenatally diagnosed congenital cystic adenomatoid malforma-
20. Adzick NS, Outwater KM, Harrison MR, et al. Correction of tions. Ultrasound Obstet Gynecol 2005;26:1503.
congenital diaphragmatic hernia in-utero. IV. An early gestational 44. Hsieh CC, Chao AS, Chang YL, et al. Outcome of congenital
fetal lamb model for pulmonary vascular morphometric analysis. cystic adenomatoid malformation of the lung after antenatal diag-
J Pediatr Surg 1985;20:67380. nosis. Int J Gynaecol Obstet 2005;89:99102.
21. Adzick NS, Harrison MR, Glick PL, et al. Diaphragmatic hernia 45. Crombleholme TM, Coleman B, Hedrick HL, et al. Cystic ade-
in the fetus: Prenatal diagnosis and outcome in 94 cases. J Pediatr nomatoid malformation volume ratio predicts outcome in prena-
Surg 1985;20:35761. tally diagnosed cystic adenomatoid malformation of the lung.
22. Harrison MR, Adzick NS, Flake AW, et al. Correction of con- J Pediatr Surg 2002;37:3318.
genital diaphragmatic hernia in-utero. VI. Hard-earned lessons. 46. Miller JA, Corteville JE, Langer JC. Congenital cystic adenoma-
J Pediatr Surg 1993;28:141118. toid malformation in the fetus: Natural history and predictors of
23. Harrison MR, Adzick NS, Longaker MT, et al. Successful outcome. J Pediatr Surg 1996;31:8058.
repair in utero of a fetal diaphragmatic hernia after removal of 47. Wilson RD, Baxter JK, Johnson MP, et al. Thoracoamniotic
herniated viscera from the left thorax. New Eng J Med 1990;322: shunts: Fetal treatment of pleural effusions and congenital
15824. cystic adenomatoid malformations. Fetal Diagn Ther 2004;19:
24. Harrison MR, Adzick NS, Bullard KM, et al. Correction of con- 41320.
genital diaphragmatic hernia in utero VII: A prospective trial. 48. Wilson RD, Baxter JK, Johnson MP, et al. Thoracoamniotic
J Pediatr Surg 1997;32:163742. shunts: Fetal treatment of pleural effusions and congenital
25. Hedrick MH, Ferro MM, Filly RA, et al. Congenital high airway cystic adenomatoid malformations. Fetal Diagn Ther 2004;19:
obstruction syndrome (CHAOS): A potential for perinatal inter- 41320.
vention. J Pediatr Surg 1994;29:2714. 49. Hedrick HL, Flake AW, Crombleholme TM, et al. History of fetal
26. Carmel JA, Friedman F, Adams FH, et al. Fetal tracheal ligation diagnosis and therapy: Childrens Hospital of Philadelphia experi-
and lung development. Am J Dis Child 1965;109:4527. ence. Fetal Diagn Ther 2003;18:6582.
27. DiFiore JW, Fauza DO, Slavin R, et al. Experimental fetal tracheal 50. Adzick NS, Harrison MR. Management of the fetus with a cystic
ligation and congenital diaphragmatic hernia: A pulmonary vas- adenomatoid malformation. World J Surg 1993;17:3429.
cular morphometric analysis. J Pediatr Surg 1995;30:91724. 51. Adzick NS, Harrison MR, Flake AW, et al. Fetal surgery for cystic
28. DiFiore JW, Fauza DO, Slavin R, et al. Experimental fetal tracheal adenomatoid malformation of the lung. J Pediatr Surg
ligation reverses the structural and physiological effects of pulmo- 1993;28:80612.
nary hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg 52. Tsao K, Hawgood S, Vu L, et al. Resolution of hydrops fetalis in
1994;29:24857. congenital cystic adenomatoid malformation after prenatal steroid
29. Hedrick MH, Estes JM, Sullivan KM, et al. Plug the lung until it therapy. J Pediatr Surg 2003;38:50810.
grows (PLUG): A new method to treat congenital diaphragmatic 53. Curran PF, Jelin EB, Rand L, et al. Prenatal steroids for micro-
hernia in-utero. J Pediatr Surg 1994;29:61217. cystic congenital cystic adenomatoid malformations. J Pediatr
30. Harrison MR, Adzick NS, Flake AW, et al. Correction of Surg 2010;45:14550.
congenital diaphragmatic hernia in utero VIII: Response of the 54. Peranteau WH, Wilson RD, Liechty KW, et al. Effect of maternal
hypoplastic lung to tracheal occlusion. J Pediatr Surg betamethasone administration on prenatal congenital cystic ade-
1996;31:133946. nomatoid malformation growth and fetal survival. Fetal Diagn
31. Hirose S, Harrison MR. The ex-utero intrapartum treatment Ther 2007;22:36571.
(EXIT) procedure. Semin Neonatol 2003;8:20714. 55. French NP, Hagan R, Evans SF, et al. Repeated antenatal corti-
32. Harrison MR, Mychaliska GB, Albanese CT, et al. Correction of costeroids: Size at birth and subsequent development. Am J
congenital diaphragmatic hernia in utero IX: Fetuses with poor Obstet Gynecol 1999;180:11421.
prognosis (liver herniation and lung-to-head ratio) can be saved 56. Rodriguez MA, Cass DL, Lazar DA, et al. Tumor volume to fetal
by fetoscopic temporary tracheal occlusion. J Pediatr Surg weight ratio as an early prognostic classification in fetal sacrococ-
1998;33:101723. cygeal teratoma. J Pediatr Surg 2011;46:11825.
33. Harrison MR, Keller RL, Hawgood SB, et al. A randomized trial 57. Shue EH, Bolouri MS, Jelin EB, et al. Tumor metrics and mor-
of fetal endoscopic tracheal occlusion for severe fetal congenital phology predict poor outcome in prenatally diagnosed sacrococ-
diaphragmatic hernia. New Engl J Med 2003;349:191624. cygeal teratoma. J Pediatr Surg. In Press.
34. Saddiq WB, Piedboeuf B, Laberge JM, et al. The effects of tra- 58. Westerburg B, Feldstein VA, Sandberg PL, et al. Sonographic
cheal occlusion and release on type II pneumocytes in fetal lambs. prognostic factors in fetuses with sacrococcygeal teratoma.
J Pediatr Surg 1997;32:8348. J Pediatr Surg 2000;35:3226.
35. Cannie MM, Jani JC, De Keyzer F, et al. Evidence and patterns 59. Hedrick HL, Flake AW, Crombleholme TM, et al. Sacrococcy-
in lung response after fetal tracheal occlusion: Clinical controlled geal teratoma: Prenatal assessment, fetal intervention, and
study. Radiology 2009;252:52633. outcome. J Pediatr Surg 2003;39:4308.
36. Hirose S, Farmer DL, Lee H, et al. The ex-utero intrapartum 60. Ruano R, Duarte S, Zugaib M. Percutaneous laser ablation of
treatment procedure: Looking back at the EXIT. J Pediatr Surg sacrococcygeal teratoma in a hydropic fetus with severe heart
2004;39:37580. failuretoo late for a surgical procedure? Fetal Diagn Ther
37. Jani JC, Nicolaides KH, Gratacos E, et al. Severe diaphragmatic 2009;25:2630.
hernia treated by fetal endoscopic tracheal occlusion. Ultrasound 61. Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality
Obstet Gynecol 2009;34:30410. of monochorionic twin pregnancies. Br J Obstet Gynaecol
38. Jelin E, Lee H. Tracheal occlusion for fetal congenital diaphrag- 1997;104:12037.
matic hernia: The ultrasound experience. Clin Perinatol 2009;36: 62. Quintero R, Morales W, Allen M, et al. Staging of twin-twin
34961. transfusion syndrome. J Perinatol 1999;19:5505.
39. Adzick NS, Harrison MR, Glick PL, et al. Fetal cystic adenoma- 63. Fusi L, Gordon H. Twin pregnancy complicated by single intrau-
toid malformation: Prenatal diagnosis and natural history. terine death. Problems and outcome with conservative manage-
J Pediatr Surg 1985;20:4838. ment. Br J Obstet Gynaecol 1990;97:51116.
10 Fetal Therapy 143
64. Fusi L, McParland P, Fisk N, et al. Acute twin-twin transfusion: 88. Bruner JP, Tulipan NE, Richards WO. Endoscopic coverage of
A possible mechanism for brain-damaged survivors after intrau- fetal open myelomeningocele in-utero. Am J Obstet Gynecol
terine death of a monochorionic twin. Obstet Gynecol 1991; 1997;176:2567.
78:51720. 89. Bruner JP, Tulipan NB, Richards WO, et al. In-utero repair of
65. Berghella V, Kaufmann M. Natural history of twin-twin transfu- myelomeningocele: A comparison of endoscopy and hysterotomy.
sion syndrome. J Reprod Med 2001;46:4804. Fetal Diagn Ther 2000;15:838.
66. Roberts D, Gates S, Kilby M, et al. Interventions for twin-twin 90. Fontecha CG, Peiro SL, Sevilla JJ, et al. Fetoscopic coverage of
transfusion syndrome: A Cochrane review. Ultrasound Obstet experimental myelomeningocele in sheep using a patch with sur-
Gynecol 2008;31:70111. gical sealant. Eur J Obstet Gynecol Reprod Biol 2011;156:
67. Senat MV, Deprest J, Boulvain M, et al. Endoscopic laser surgery 1716.
versus serial amnioreduction for severe twin-to-twin transfusion 91. Morin L, Cendron M, Crombleholme TM, et al. Minimal
syndrome. New Engl J Med 2004;351:13644. hydronephrosis in the fetus: Clinical significance and implications
68. Crombleholme TM, Shera D, Lee H, et al. A prospective, rand- for management. J Urol 1996;155:20479.
omized, multicenter trial of amnioreduction vs. selective feto- 92. Flake AW, Adzick NS, Harrison MR, et al. Ureteropelvic junction
scopic laser photocoagulation for the treatment of severe twin-twin obstruction. J Pediatr Surg 1986;21:105864.
transfusion syndrome. Am J Obstet Gynecol 2007;197:396 e19. 93. Mahoney BS, Callen PW, Filly RA. Sonographic evaluation of
69. Rossi AC, DAddario V. Laser therapy and serial amnioreduction renal dysplasia. Radiology 1984;152:1439.
as therapy for twin-twin transfusion syndrome: A metaanalysis and 94. Heikkla J, Holmberg C, Kyllonen L, et al. Long-term risk of
review of literature. Am J Obstet Gynecol 2008;198:14752. end-stage renal disease in patients with posterior urethral valves.
70. Rand L, Lee H. Complicated monochorionic twin pregnancies: J Urol 2011;186:23926.
Updates in fetal diagnosis and treatment. Clin Perinatol 95. Caione P, Nappo SG. Posterior urethral valves: Long-term
2009;36:41730. outcome. Pediatr Surg Int 2011;27:102735.
71. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial 96. Biard JM, Johnson MP, Carr MC, et al. Long-term outcomes in
perfusion (TRAP) sequence: A study of 14 twin pregnancies with children treated by prenatal vesicoamniotic shunting for lower
acardius. Semin Perinatol 1983;7:28593. urinary tract obstruction. Obstet Gynecol 2005;106:5038.
72. Goh A, Loke HL, Tan KW. The TRAP sequencelife threaten- 97. Nicolini U, Fisk NM, Rodeck CH, et al. Fetal urine biochemistry:
ing consequences to the pump twin. Singapore Med J An index of renal maturation and dysfunction. Br J Obstet
1994;35:32931. Gynaecol 1992;99:4650.
73. Quintero R, Munoz H, Hasbun J, et al. [Fetal endoscopic surgery 98. Carroll SG, Kuo PY, Kyle PM, et al. Fetal protein loss in gastro-
in a case of twin pregnancy complicated by reversed arterial per- schisis as an explanation of associated morbidity. Am J Obstet
fusion sequence (TRAP sequence)]. Rev Chil Obstet Ginecol Gynecol 2001;184:1297301.
1995;60:11217. 99. Bond SJ, Harrison MR, Filly RA, et al. Severity of fetal midgut
74. Hecher K, Hackeloer BJ, Ville Y. Umbilical cord coagulation by herniation: Normal size criteria and correlation with crown-rump
operative microendoscopy at 16 weeks gestation in an acardiac length. J Ultrasound Med 1993;12:2514.
twin. Ultrasound Obstet Gynecol 1997;10:1302. 100. Lenke RR, Persutte WH, Nemes J. Ultrasonographic assessment
75. Tan TY, Sepulveda W. Acardiac twin: A systematic review of of intestinal damage in fetuses with gastroschisis: Is it of clinical
minimally invasive treatment modalities. Ultrasound Obstet value? Am J Obstet Gynecol 1990;163:9958.
Gynecol 2003;22:40919. 101. Sipes SL, Weiner CP, Williamson RA, et al. Fetal gastroschisis
76. Tsao K, Feldstein VA, Albanese CT, et al. Selective reduction of complicated by bowel dilatation: An indication for imminent
acardiac twin by radiofrequency ablation. Am J Obstet Gynecol delivery? Fetal Diagn Ther 1990;5:1003.
2002;187:63540. 102. Alsulyman OM, Monteiro H, Ouzounian JG, et al. Clinical sig-
77. Hirose S, Farmer DL. Fetal surgery for myelomeningocele. Clin nificance of prenatal ultrasonographic intestinal dilatation in
Perinatol 2009;36:4318. fetuses with gastroschisis. Am J Obstet Gynecol 1996;175:
78. Heffez DS, Aryanpur J, Hutchins GM, et al. The paralysis associ- 9824.
ated with myelomeningocele: Clinical and experimental data 103. Crawford RAF, Ryan G, Wright VM, et al. The importance of
implicating a preventable spinal cord injury. Neurosurgery serial biophysical assessment of fetal wellbeing in gastroschisis.
1990;26:98792. Br J Obstet Gynaecol 1992;99:899902.
79. Meuli M, Meuli-Simmen C, Yingling CD, et al. Creation of 104. Langer JC. Abdominal wall defects. World J Surg 2003;27:
myelomeningocele in-utero: A model of functional damage from 11724.
spinal cord exposure in fetal sheep. J Pediatr Surg 1995;30: 105. Aktug T, Erdag G, Kargi A, et al. Amnio-allantoic fluid exchange
102833. for the prevention of intestinal damage in gastroschisis: An
80. Walsh DS, Adzick NS, Sutton LN, et al. The rationale for experimental study on chick embryos. J Pediatr Surg 1995;30:
in-utero repair of myelomeningocele. Fetal Diagn Ther 3847.
2001;16:31222. 106. Kohl T, Tchatcheva K, Stressiq R, et al. Is there a therapeutic role
81. Meuli M, Meuli-Simmen C, Yingling CD, et al. In-utero repair for fetoscopic surgery in the prenatal treatment of gastroschisis?
of experimental myelomeningocele saves neurological function at A feasibility study in sheep. Surg Endosc 2009;23:1499505.
birth. J Pediatr Surg 1996;31:397402. 107. Koivusalo A, Lindahl H, Rintala RJ. Morbidity and quality of life
82. Bruner JP, Tulipan N, Paschall RL, et al. Fetal surgery for mye- in adult patients with a congenital abdominal wall defect: A ques-
lomeningocele and the incidence of shunt-dependent hydroceph- tionnaire survey. J Pediatr Surg 2002;37:1594601.
alus. JAMA 1999;282:181925. 108. Wagner AM, Schoeberlein A, Surbek D. Fetal gene therapy:
83. Sutton LN, Adzick NS, Bilaniuk LT, et al. Improvement in hind- Opportunities and risks. Adv Drug Deliv 2009;61:81321.
brain herniation demonstrated by serial fetal magnetic resonance 109. Burt R, Testor A, Craig R, et al. Hematopoietic stem cell trans-
imaging following fetal surgery for myelomeningocele. JAMA plantation for autoimmune disease: What have we learned?
1999;282:182631. J Autoimmun 2008;30:11620.
84. Farmer DL, von Koch CS, Peacock WJ, et al. In-utero repair of 110. Verda L, Kim D, Ikehara S, et al. Hematopoietic mixed chimerism
myelomeningocele: Experimental pathophysiology, initial clinical derived from allogeneic embryonic stems cells prevents
experience, and outcomes. Arch Surg 2003;138:8728. autoimmune diabetes mellitus in NOD mice. Stem Cells
85. Adzick NS, Thom EA, Spong CY, et al. A randomized trial of 2008;26:3816.
prenatal versus postnatal repair of myelomeningocele. N Engl J 111. Shizuru J, Weissman I, Kernoff R, et al. Purified hematopoietic
Med 2011;364:9931004. stem cell grafts induce tolerance to alloantigens and can mediate
86. Hirose S, Meuli-Simmen C, Meuli M. Fetal surgery for myelom- positive and negative T cell selection. Proc Natl Acad Sci
eningocele: Panacea or peril? World J Surg 2003;27:8794. 2000;97:955560.
87. Johnson MP, Sutton LN, Rintoul N, et al. Fetal myelomenin- 112. Moreno R, Rosal M, Cabero L, et al. Feasibility of retroviral
gocele repair: Short-term clinical outcomes. Am J Obstet Gynecol vector-mediated in-utero gene transfer to the fetal rabbit. Fetal
2003;189:4827. Diagn Ther 2005;20:48593.
144 SECTION I General
113. Ekhterae D, Crumbleholme T, Karson E, et al. Retroviral vector- 115. Shaaban AF, Flake AW. Fetal hematopoietic stem cell transplanta-
mediated transfer of the bacterial neomycin resistance gene into tion. Semin Perinatol 1999;23:51523.
fetal and adult sheep and human hematopoietic progenitors in 116. Gupta N, Henry RG, Strober J, et al. Neural stem cell engraft-
vitro. Blood 1990;75:3659. ment and myelination in the human brain. Sci Transl Med
114. Hayashi S, Flake AW. In-utero hematopoietic stem cell therapy. 2012;4:155ra137.
Yonsei Med J 2001;42:61529.
C H A P T E R 1 1
ESOPHAGEAL FOREIGN BODIES The most common round, smooth object ingested that
is amenable to extraction or advancement techniques is a
Foreign body (FB) ingestions are a common occurrence coin. The majority of esophageal coins will appear en face
in infants and young children. The exact incidence is in the anteroposterior view, and from the side on the
unknown since many cases are not reported. In 2010, the lateral radiograph (see Fig. 11-2). On occasion, more
Annual Report of the American Association of Poison than one coin will have been ingested (Fig. 11-4).
Control Centers noted over 116,000 cases of FB inges- The location of the object on the radiograph is impor-
tion. More than 86,000 occurred in children 5 years of tant in determining the treatment options. Approximately
age.1 The vast majority of ingestions in children are acci- 6070% of FB impactions are located in the proximal
dental.2 The most common type of FB varies by geo- esophagus at the level of the upper esophageal sphincter
graphic region. In the USA and Europe, coins are the or thoracic inlet.57 The majority of FB impactions found
most common.2,3 Other commonly ingested objects in the upper or mid-esophagus will remain entrapped and
include toys, batteries, needles, straight pins, safety pins require retrieval. Options for retrieval include nonemer-
(Fig. 11-1), screws, earrings, pencils, erasers, glass, fish gent endoscopy (rigid or flexible) (Fig. 11-5) and Foley
and chicken bones, and meat. However, in areas of the balloon extraction with fluoroscopy (Fig. 11-6). The
world where fish contributes a significant portion of the Foley balloon extraction technique should be limited to
diet, such as in Asia, a fish bone may be the most common round, smooth objects that have been impacted for less
FB ingested in children.2,4 than one week in appropriately selected children without
FB ingestions usually present after a witnessed event any evidence of complications.8 This technique has been
or disappearance of an object. Also, there may be height- shown to have a success rate of 80% while significantly
ened suspicion for an ingestion by a caregiver based on lowering costs. Objects that are impacted in the lower
the childs description. The initial presentation can vary esophagus often spontaneously pass into the stomach.
from the child being completely asymptomatic to a For this reason, certain lower esophageal impactions may
variety of symptoms including drooling, neck and throat be observed for a brief duration of time, or attempted
pain, dysphagia, emesis, wheezing, respiratory distress, to be advanced into the stomach with bougienage or a
abdominal pain, or distention. The majority of patients nasogastric tube in the emergency department without
will have a normal physical exam; however, the child anesthesia.9 Rarely, a chronic esophageal coin can cause
should be evaluated for signs of complications. Physical esophageal perforation, but this will usually be contained
exam findings that raise suspicion of a potential complica- (Fig. 11-7).
tion include oropharyngeal abrasions, crepitus, or signs
of peritonitis.
The esophagus is the narrowest portion of the alimen-
tary tract and is thus a common site for FB impaction.
Within the esophagus itself, there are three areas of ana-
tomical narrowing that are potential areas of impaction:
the upper esophageal sphincter, the level of the aortic
arch, and the lower esophageal sphincter. Other areas of
potential impaction may be found in the esophagus of
children who have underlying esophageal pathology (i.e.,
strictures or eosinophilic esophagitis), or prior esopha-
geal surgery (i.e., esophageal atresia).
Symptoms of esophageal FB impaction are nonspecific
and include drooling, poor feeding, neck and throat
pain, vomiting, or wheezing. Radiopaque objects can be
detected on the anteroposterior (AP) and lateral neck and
chest radiographs (Fig. 11-2), while radiolucent objects
may require further workup with a gastrografin esopha-
gram or esophagoscopy depending on the symptoms and FIGURE 11-1 This child accidentally ingested this open safety
level of suspicion (Fig. 11-3). pin which was able to be extracted with esophagoscopy.
147
148 SECTION II Trauma
A B
FIGURE 11-2 This 3-year-old child presented with dysphagia and drooling. (A) The anteroposterior radiograph shows a coin that
appears en face in the upper esophagus. (B) The lateral view shows that the coin is posterior to the trachea, confirming its esopha-
geal location.
A B
FIGURE 11-5 This coin was lodged in the esophagus of a 2-year-old child. It was unclear how long the coin had been in the esopha-
gus. Rigid esophagoscopy was performed. (A) The coin is seen through the esophagoscope. (B) The optical graspers are being used
to grasp the coin and remove it. The safety and success rate for rigid esophagoscopy and coin removal approaches 100% with
minimal complications. This is usually a safe and successful way to remove a coin in the esophagus of children in whom the Foley
catheter technique is not appropriate.
A B
FIGURE 11-7 (A) This child was found to have an esophageal leak after uneventful extraction of a coin. (B) As the leak appeared to
be contained, the patient was managed conservatively, and a repeat study two weeks later showed no evidence of a leak. A central
line was placed for total parenteral nutrition.
A B C
FIGURE 11-8 This child began to complain of abdominal pain and the (A) plain film was obtained. Due to the fact that it was unclear
how long ago the sewing needle was ingested and because she was exhibiting new symptoms, diagnostic laparoscopy was per-
formed. (B) At laparoscopy, the sewing needle was seen to have penetrated the proximal jejunum and (C) was able to be extracted.
A water soluble contrast study was performed a few days later. The study was unremarkable, her diet was advanced, and she
recovered uneventfully.
FIGURE 11-9 This child presented within 12 hours of swallow- FIGURE 11-10 This infant accidentally swallowed a lithium
ing an unknown foreign body. However, the double contour rim battery. The battery was removed within a few hours of its
raised suspicion of ingestion of a button battery. This was ingestion. However, 1 week later, the patient developed respira-
confirmed upon emergency removal of the battery via rigid tory distress and bronchoscopy revealed this tracheoesopha-
esophagoscopy. geal fistula (arrow).
11 Ingestion of Foreign Bodies 151
A B
FIGURE 11-11 This 11-year-old child swallowed two small magnets 24 hours prior to presentation to the emergency department.
(A) The abdominal radiograph demonstrates an inability to detect if the two magnets are within a single intestinal lumen or attached
across the bowel wall in two separate lumens. (B) This child underwent exploratory laparotomy for obstructive signs. The two magnets
were found to be in two separate bowel lumens causing the bowel obstruction and fistulization between the two intestinal
segments.
Bezoars
A bezoar is a tight collection of undigested material that
may often present as a gastric outlet or intestinal obstruc-
tion. These can include lactobezoars, phytobezoars, or
trichobezoars. Presenting symptoms often include nausea,
vomiting, weight loss, and abdominal distention. The
diagnosis may be confirmed on plain radiographs, upper
gastrointestinal contrast studies, or endoscopy. Often due
to the size and density of the bezoar, medical manage-
ment and endoscopic removal are unsuccessful, and oper-
ation is necessary (Fig. 11-12). See Chapter 29 for more
information about bezoars.
FIGURE 11-12 This was a gastric bezoar with extension into the
proximal duodenum found in a 12-year-old child that presented
AIRWAY FOREIGN BODIES to the hospital with obstructive signs and symptoms. The size
and density of the trichobezoar necessitated a laparotomy for
Most episodes of aspirated FBs occur while eating or removal. The scale bar is 15cm.
playing. Proposed explanations include the fact that
young children are still in the oral exploration phase of
development when everything tends to go into the mouth. TABLE 11-1 Commonly Aspirated Foreign
Additionally, children often will cry or run with objects in Bodies in Pediatric Patients
their mouth. Overall, these young patients tend to have (19682010)
immature coordination of swallowing and less developed
airway protection. The average age for fatal events is 15 United States International
Type of Foreign Body (%) (%)
months, and 75% of aspiration events occur in those less
than 4 years.13 A high index of suspicion is required to Nuts 41 37
make the diagnosis in these young children and especially Seeds 8 29
Vegetables 5
in those who are debilitated. The annual death rates Beans 8
from aspiration of foreign bodies range from 3502000 in Popcorn 4
the USA.13 Bones 2 2
Boys are affected twice as often as girls. Like esopha- Nonfood 25 12
geal FBs, geographical differences have been noted (Table
Adapted from Kaushal, P, Brown D, Lander L, etal. Aspirated
11-1). For example, sunflower seeds are the most common foreign bodies in pediatric patients, 19682010: A
seed aspirated in the USA, yet watermelon seeds are much comparison between the United States and other countries.
more common internationally.14 A recent publication of Int J Pediatr Otorhinolaryngol 2011;75:13226.
152 SECTION II Trauma
A B
FIGURE 11-13 (A) The anteroposterior chest radiograph shows slight hyperexpansion of the right lung in a four year old who aspi-
rated a peanut. (B) On the expiratory film, note the increased lucency of the right lung compared to the left. This hyper-lucency on
the right is due to air trapping from obstruction of the right main stem bronchus.
132 cases noted a high incidence of food aspirations, espe- dependent position. Interestingly, up to 56% of patients
cially nuts, in children from non-English speaking back- may have a normal chest film within 24 hours of aspira-
grounds.15 Therefore, there may be a role for public tion.19 Radiopaque foreign bodies are easily identified
education in targeted communities. Victims of child abuse (Fig. 11-14A), but radiolucent FBs become clinically
represent another community that is at higher risk. Car- diagnosed through indirect radiographically clues such as
egivers should be on alert when tending to a young child hyperexpansion. Foreign bodies lodged in the larynx or
with multiple FBs or multiple episodes of aspiration.16,17 trachea tend to have a higher radiographic detection rate
Several anatomical differences are found in the airway (90%) than those in the bronchus (70%).1822 A multi-
of children compared to older patients. Children have a institutional review of 1269 FB events revealed that 85%
shorter airway which is smaller in caliber. The anterior were correctly diagnosed following a single physician
position of a childs larynx can increase the difficulty with encounter.23 Therefore, a negative bronchoscopy rate of
oral intubation. Additionally, the subglottic region is the 1015% is considered acceptable in order to
narrowest part of a childs airway. The proclivity for FBs avoid a delay in treatment with subsequent morbidity.24
to find the right main stem bronchus is well known. Not Radiographic imaging remains helpful in children with a
only is the diameter of the right bronchus larger than the history of choking, yet definitive diagnosis still requires
left and airflow generally greater to the right lung, but bronchoscopy.
also the right bronchus has a smaller angle of divergence Emergent management of airway FBs can be a dra-
from the trachea. This important anatomical feature matic experience. An accurate history remains important,
directs the aspirated FB down into the right bronchus. yet sometimes is hard to obtain from small children
Common presenting symptoms include respiratory who are unreliable historians. The use of the flexible
distress, stridor, and/or wheezing. Dysphonia may also be bronchoscope to diagnose a FB followed by a rigid
observed. A subtle change in voice or cry may be noted, bronchoscopy for removal is a common approach utilized
yet many children will be asymptomatic. Many aspiration by pediatric surgeons. General anesthesia in the operat-
events go unwitnessed. Laryngeal pathology usually will ing room using spontaneous ventilation offers the best
manifest as inspiratory stridor while tracheal FBs cause chance for safe and successful removal. Positive pressure
expiratory stridor. Albeit rare, FBs may completely ventilation may be required, but this technique runs the
obstruct the larynx or trachea producing sudden death. risk for further propagating the FB into the more distal
Chronic FBs often masquerade as respiratory illnesses passages of the airway. With severely ill children, where
with persistent cough and atelectasis, recurrent pneumo- transportation presents a logistical risk, rigid bronchos-
nia, or hoarseness. Other late findings include the devel- copy has been performed safely in the intensive care
opment of granulation tissue, strictures, perforation, and setting.25
bronchiectasis.
Following a detailed history, investigation usually Bronchoscopy
turns to AP and lateral films of the neck and chest. If the
child is cooperative, inspiratory and expiratory films are We recommend positioning the head in the sniffing
beneficial (Fig. 11-13). Review of the radiograph may position with a folded towel under the shoulders. The
reveal hyperinflation or air trapping in up to 60% of eyes are taped and protected. Precautions to minimize
children as the FB is acting as a one-way valve producing secretions, laryngospasm, and hypoxia are employed.
obstructive emphysema.18 In time, mediastinal shift may Careful laryngoscopy may reveal a FB that can be
develop. Decubitus views may also prove helpful since retrieved with McGill forceps. More distal evaluation
the obstructed lung will not deflate, even while in a requires direct instrumentation of the airway. Special
11 Ingestion of Foreign Bodies 153
A B C
FIGURE 11-14 (A) This young child accidentally aspirated this nail which was found to be in the left main stem bronchus on chest
radiography. (B) At bronchoscopy, with the bronchoscope in the trachea, the nail is seen to be peering out of the left main stem
bronchus. (C) The nail was removed, and the child recovered uneventfully. Note the size of the nail relative to the childs face and
mouth.
precautions must be considered to avoid injuries to the periods of time. A face mask adapter can be used to
lips, tongue, and most importantly the teeth. Once the reduce the risk of hypoxia. The ultrathin scope (noodle
bronchoscopy starts, the operative team must be ready scope) can be inserted through smaller caliber endotra-
for emergent intubation, or rarely, tracheostomy. Liberal cheal or tracheostomy tubes while maintaining ventila-
use of lidocaine (4mg/kg) applied to the glottic area may tion. However, these scopes have very limited, if any,
minimize laryngospasm. working channels and suction capability. Overall compli-
There are several commercial available rigid broncho- cations of rigid or flexible endoscopy include bleeding
scopes. Instruments vary in size between 2.5cm 20cm from local inflammation, laryngospasm, pneumothorax,
and 6 30cm. Length and diameter of the bronchoscope and hypoxia with the more serious complications being
will be determined by the age and size of the child. The found in the youngest patients.29,30
DoeselHuzly bronchoscope with Hopkins rod-lens tel- A lack of experience, poor visualization, and inade-
escope or Holinger ventilating bronchoscope are com- quate instrumentation contribute to failure of a successful
monly used. Exposure is excellent with both, and the examination. Many of these cases are seen at night, and
caliber of the scope allows the FB to be retracted into the operating room personnel frequently struggle to find the
scope during removal, thereby decreasing the risk of required instruments. The surgeon performing the pro-
inadvertently dropping the FB during extraction (Fig. cedure must ensure that all of the needed instruments are
11-14B,C). Equipment combining optics and illumina- in working order before the child is brought to the oper-
tion while allowing the introduction of working forceps ating room. A preoperative game plan between nursing,
are favored in most childrens hospitals. anesthesia, and surgical staff is also important. Bleeding
The larynx and cords are visualized and the broncho- that obscures visualization is common, and the introduc-
scope is advanced to the right of the laryngoscope and tion of a small suction catheter through the working
into the trachea. Inspection of the right or left main stem channel may be helpful. In other cases, partial FB removal
bronchus can be facilitated by turning the head to the is recommended with a plan to return to the operating
opposite side. Angled scopes are generally not needed. room the next day. Rarely a thoracotomy with bron-
The operative side channel allows passage of suction and chotomy or lobectomy is required. Following successful
retrieval instruments as well as instillation of fluids to removal, attention to proper cleaning of the instruments
help clear a bloody airway. The ventilation side port is important, given that inadequate cleaning and storage
allows continuous ventilation during the procedure. may predispose to cracks in the equipment that could
Loose connections from any of these sites can lead to lead to bacterial contamination.31
hypoventilation. Furthermore, if ventilation is impaired, Maintaining bronchoscopic skills remains necessary to
the telescope can be removed, leaving the unobstructed effectively manage these difficult cases. Across under-
bronchoscope for ventilation. In difficult cases, especially graduate and graduate medical education, simulation
with FBs lodged distal to the main bronchus, a Fogarty continues to gain momentum. Several institutions have
catheter may be helpful to wedge the FB between the developed simulation courses for residents to improve
bronchoscope and Fogarty balloon. Partial FB removal psychomotor skills associated with airway FBs. Objec-
will at times be necessary, especially with chronic foreign tives include an understanding of the tracheobronchial
bodies associated with significant bleeding or airway anatomy, ability to adequately visualize the larynx with
edema. Prior to the second endoscopy,26 the childs condi- laryngoscopy, proficiency in rigid bronchoscopy, and
tion can be optimized with inhaled epinephrine and familiarity with FB instrumentation. Of note, in one
intravenous corticosteroids.27,28 institution, success in assembling the needed instruments
Flexible bronchoscopy remains an option, especially and completing assigned tasks increased after completing
for diagnostic purposes. The standard pediatric flexible the course on average 81% and 43%, respectively.32 One
bronchoscope has a two way deflection tip with a range would expect further development of simulation exercises
between 180220 and a side port to allow passage of to be useful for initial credentialing and continued profi-
suction catheters and working instruments. Most new- ciency for both trainees and faculty.
borns can breathe normally around this scope for brief
154 SECTION II Trauma
Bites
Gary S. Wasserman Jennifer A. Lowry D. Adam Algren
A wide variety of bites are seen in children. It is estimated intramuscularly. Some experts recommend that children
that more than 1 million children are treated annually for receive 500 units to decrease the discomfort from injec-
bites (Table 12-1).1 In this chapter we concentrate on tion.5 Infiltrating part of the dose locally is controversial.
bites of interest to the surgeon. The reader is referred Tetanus prevention in a potentially exposed patient
elsewhere for discussions of management of venomous depends on the nature of the wound and history of immu-
stings and injuries from marine life and general details of nization with tetanus toxoid (Table 12-2).
wound management.
CAT, DOG, HUMAN, AND OTHER
TETANUS MAMMALIAN BITES
The Gram-positive anaerobic organism Clostridium tetani Children are frequent victims of mammalian bites. The
is the causative agent for tetanus, a severe and often fatal most common complication from bites is infection: cats,
disease. In 2009, there were a total of 18 cases (zero under 1650%; dogs, 130%, and humans, 918%.6 When the
14 years of age) reported in the USA.2 bite is from a cat, dog, or other mammal, the most common
There has been a low incidence rate of tetanus since infectious organisms are Streptococcus, Staphylococcus,
a peak of 102 cases in 1975. Mortality from tetanus is Actinomycetes, Pasteurella species, Capnocytophaga species,
associated with co-morbid conditions such as diabetes, Moraxella species, Corynebacterium species, Neisseria
intravenous drug use, and old age, especially when vac- species, Eikenella corrodens, Haemophilus species, anaer-
cination status is unknown. Infection can occur weeks obes, Fusobacterium nucleatum, and Prevotella melanino-
after a break in the skin, even after a wound has seemed genica.5,7,8 Human bites are a potential source not only for
to heal. The ideal anaerobic surroundings allow spores bacterial contamination but also for hepatitis B and, pos-
to germinate into mature organisms producing two neu- sibly, human immunodeficiency virus (HIV) infection.9
rotoxins: tetanolysin and tetanospasmin.3 The latter is Recommendations for bite wound management are
able to enter peripheral nerves and travel to the brain, presented in Box 12-1. Evidence-based medicine studies
causing the clinical manifestations of uncontrolled muscle concerning whether to close wounds are not conclusive.
spasms and autonomic instability. The incubation period Distal extremity wounds, especially hand/fist to teeth,
varies from as short as two days to several months, with are at higher risk for infection. Whether minimal risk
most cases occurring within 14 days.4 In general, the wounds require prophylactic antimicrobial therapy
shorter the incubation period, the more severe the disease is also controversial. Antibiotics started within eight to
and the higher the fatality risk. 12 hours of the bite and continued for two to three days
Initially, the diagnosis is made clinically because cul- may decrease infection rate.5 The oral drug of choice is
tures are often negative and serology for antitoxin anti- amoxicillin-clavulanate. For penicillin-allergic patients,
bodies has a long turn-around time. So-called dirty an extended-spectrum cephalosporin or trimethoprim-
wounds (lacerations treated after 24 hours, abscesses, sulfamethoxazole plus clindamycin should be used.5
ulcers, gangrene, and wounds with nonviable tissue) are
the most common injuries that become infected with
tetanus. However, a history of trauma is not necessary for RABIES AND POSTEXPOSURE PROPHYLAXIS
infection.
All wounds should be cleaned and debrided. Sympto- Rabies is a viral disease usually transmitted through the
matic and supportive care includes medications such as saliva of a sick mammal (e.g., dogs, cats, ferrets, raccoons,
benzodiazepines to control tetanic spasms and antimicro- skunks, foxes, bats, and most other carnivores). The
bials for infection. Metronidazole (oral or intravenous, majority of reported cases in the USA are caused by rac-
30mg/kg/day, divided into four daily doses, maximum coons, skunks, foxes, mongooses, and bats. Small rodents
4g/day) is the preferred antibiotic because it decreases such as rats, mice, squirrels, chipmunks, hamsters, guinea
the number of vegetative forms of C. tetani.5 An alternate pigs, rabbits and gerbils are almost never infected with
choice is parenteral treatment with penicillin G rabies. Over the past decade, cats have been the most
(100,000U/kg/day every four to six hours, not to exceed common domestic animal with rabies. Rabies-related
12 million units/day) for ten to 14 days. Human tetanus human deaths in the USA occur one to seven times per
immune globulin (TIG) is administered to adults and year since 1975. Modern prophylaxis has proven nearly
adolescents as a one-time dose of 30006000 units 100% successful. Worldwide, fatalities are about
155
156 SECTION II Trauma
TABLE 12-1 Bites and Envenomations to Humans: Calls to Poison Centers in 2010
Animal Total Calls Age <6 Years Age >619 Years All Ages Treated at Facility Severe Outcome/Death
Bat 663 85 120 335 0/0
Cat 814 65 136 485 2/0
Dog 2292 367 689 1704 5/1
Fox 26 0 4 21 0/0
Human 42 5 4 22 0/0
Insects 38446 6499 6499 4595 63/2
Other Mammals 929 119 189 516 1/0
Raccoon 146 10 24 112 2/0
Rodent/lagomorphs 1397 269 381 409 1/0
Skunks 12 0 2 5 0/0
Snakes 7013 398 1567 7392 189/2
Spiders 10394 1059 1488 2704 32/1
n = 2,384,825 total human poisoning calls; n = 61,854 (2.6% total) in the category of bites and envenomations.
Data from Bronstein AC, Spyker DA, Cantilena LR, etal, editors. 2010 Annual Report of the American Association of Poison
Control Centers National Poison Data System (NPDS): 28th Report. Clin Toxicol 2011;49:91041, Appendix.
natural habitat but rarely cause arachnidism in nonen- The prevalence of brown recluse spider envenoma-
demic areas. L. reclusa is tan to brown with a characteristic tions is unknown. The victim may not feel the bite or
dark, violin-shaped marking on its dorsal cephalothorax, may only feel a mild pinprick sensation. Many victims are
giving it the nickname fiddleback or violin spider. The bitten while they sleep and may be unaware of the enven-
spider can measure up to 1cm in total body length with omation until a wound develops. The majority of victims
a 3cm or longer leg span (Fig. 12-1). These spiders do not see the spider at the time of the bite.22 Typically,
only have three pairs of eyes whereas most spiders have the bite progressively begins to itch, tingle, and become
four pairs. ecchymotic, indurated, and edematous within several
The incidence of L. reclusa bites predominantly occurs hours.23 Often within hours, a characteristic bleb or
from April through October in the USA. The venom of bullae will form. The tissue under a blister is likely to
the brown recluse spider contains at least 11 protein become necrotic, but the extent of necrosis is not predict-
components. Most are enzymes with cytotoxic activity.16 able. As the ischemia and inflammation progresses, the
Sphingomyelinase D is believed to be the enzyme respon- wound becomes painful and may blanch or become ery-
sible for dermonecrosis and activity on red blood cell thematous, forming a target or halo design. Inflamma-
membranes.1719 In addition to the local effects, the venom tion, ischemia, and pain increase over the first few days
has activity against neutrophils and the complement after the bite as enzymes spread. Over hours to weeks, an
pathway that induces an immunologic response.1921 The eschar forms at the site of the bite. Eventually, this eschar
resulting effect is a necrotic dermal lesion and the pos- sloughs, revealing an underlying ulcer that may require
sibility that a systemic response will be life threatening. months to heal, usually by secondary intention (Fig.
12-2). On very rare occasions, the ulcer does not heal and
may require surgical intervention.
The need for hospitalization occurs if the patient
develops systemic symptoms. Two studies documented
that 14% to more than 50% of patients developed sys-
temic symptoms, with fever being the most common
symptom.10 Other common symptoms include a maculo-
papular rash, nausea and vomiting, headache, malaise,
muscle/joint pain, hepatitis, pancreatitis, and other organ
toxicity. Life-threatening systemic effects include hemo-
lysis (intravascular and/or extravascular), coagulopathy,
and multiple organ system failure. Secondary effects
include sepsis, necrotizing fasciitis, and shock.2426 Hemo-
lysis usually manifests within the first 96 hours. However,
late presentations can occur. When hemolysis does
develop, it can take four to seven days (or longer) to
resolve. Complications such as cardiac dysrhythmias,
FIGURE 12-1 Loxosceles reclusa (brown recluse, fiddleback) coma, respiratory compromise, pulmonary edema, con-
spider showing the classic violin-shaped marking on the back gestive heart failure, renal failure, and seizures can occur.
(dorsal side) of the cephalothorax. Note the long slender legs
and oval body segment with short hairs. The arrow is pointing The diagnosis of a brown recluse spider envenomation
toward the classic violin marking. (From Ford M, Delaney K, Ling is largely one of exclusion as it is rare to see or identify
L, etal. Clinical Toxicology. Philadelphia: Elsevier; 2001.) the spider. While the wound can look classic for an
A B C
FIGURE 12-2 (A) A 3-year-old girl hospitalized on the third day after a brown recluse spider bite for severe hemolytic anemia,
hemoglobinuria, and ecchymosis (note the vast expansion of the ecchymosis secondary to hyaluronidase spreading factor in the
venom). There is no necrosis or ischemia, but a small bleb/blister is present over the right clavicle that, although not pathognomonic,
is often present early in lesion progression. Also note that the cutaneous lesion is mild in comparison with this patients systemic
presentation. (B) On the 15th day after envenomation, the lesion measures 5cm 2cm. Multiple small areas of necrosis have
become apparent in the past week. The largest area indicates the original bite size. The lesions edges have begun to involute with
healing, and the ischemia is fading. (C) Nine months after the bite, the necrotic wound has healed with no significant scarring.
158 SECTION II Trauma
envenomation, other etiologies must be considered (Box Neither dapsone, HBO, nor the combination treatment
12-2). Certain laboratory findings can be consistent with reduced necrosis compared with controls. A second study
a brown recluse spider envenomation but are not specific compared the use of HBO, dapsone, or cyproheptadine
in making the diagnosis (Box 12-3). against no treatment in decreasing the necrotic wound
Controversy surrounds the treatment of dermal and after envenomation with L. deserta venom. No statistical
systemic symptoms of loxoscelism. Medications such as difference was seen with respect to lesion size, ulcer size,
dapsone, nitroglycerin, and tetracycline have been used. or histopathologic ranking.32 In addition, the use of
Also, hyperbaric oxygen (HBO) therapy has been advo- dapsone is not without risk, especially hypersensitivity
cated as has excision of the necrotic wound. However, reactions.33 Therapeutic doses of dapsone are associated
none of these has proven to be effective in treating or with hemolytic anemia, methemoglobinemia, and other
preventing the ulcer development. In South America, an hematologic effects in patients with and without glucose-
antivenom has been developed and used in the treatment 6-phosphate dehydrogenase deficiency.
of Loxosceles envenomations. Unfortunately, the usual Topically applied nitroglycerin as a vasodilator had
long delay in seeking medical care often leads to ineffec- been advocated but is not effective in preventing necro-
tive use of this antivenom.27 An antivenom is not available sis.34 Tetracycline has been shown to be effective. Rabbits
in North America. were inoculated with Loxosceles venom and randomized
The use of dapsone, a leukocyte inhibitor, has been to receive topical doxycycline, topical tetracycline, or
advocated in case reports and animal studies.2830 However, placebo.35 Those who received topical tetracycline had
other animal studies have shown no benefit from this reduced progression of the dermal lesion. However,
treatment. In an animal study,31 piglets received venom treatment was started at six hours after envenomation,
and were randomized to receive one of four treatments: which may not be realistic after a human bite. In addition,
no treatment, HBO, dapsone, or dapsone with HBO. the agents used for this research study are not commer-
cially available in the United States. Further studies need
to be performed before topical tetracycline can be
Differential Diagnosis of Brown recommended.
BOX 12-2
Recluse Spider Envenomations HBO has been advocated for treatment to prevent
Acquired hemolytic anemias progression of the necrotic wound. The initial use of
Bites from other creatures (e.g., snakes, spiders, insects) HBO was based on the belief that tissue hypoxia was
that can result in cutaneous lesions partially responsible for the subsequent necrosis seen
Dermatologic conditions (e.g., pyoderma gangrenosum) after a bite. As mentioned previously, no statistical differ-
Hereditary hemolytic anemias ences were noted in animal studies that compared dapsone
Infectious causes (e.g., Lyme disease, infection with and HBO.31,32 Similar results have been seen in animal
Streptococcus, Staphylococcus, or Clostridium species) studies assessing the effect of HBO alone.36,37 However,
Medical conditions causing necrotic lesions: a randomized, controlled trial of HBO in a rabbit model
Emboli in which standard HBO was used showed a significantly
Frostbite or thermal injuries
reduced wound diameter at ten days.38 No significant
Ischemic injuries
Neoplastic wounds (e.g., ecthyma gangrenosum) change in blood flow at the wound center or 12cm from
Trauma the wound center was seen. HBO is expensive and not
without complications. At the present time, much of the
literature contradicts the benefit of HBO for brown
recluse spider envenomations. As such, it is not currently
Laboratory Findings Consistent recommended as a therapy for these bites, but may be
BOX 12-3 with Systemic Effects of Loxosceles helpful in patients with underlying/preexisting vascular
Envenomations compromise such as sickle cell anemia or diabetes.
Early surgical intervention is not helpful because the
Hemoglobinemia venom diffuses rapidly throughout the soft tissues sur-
Hemoglobinuria or hematuria, elevated urobilinogen rounding the bite.39 In addition, patients may be more at
Elevated plasma free hemoglobin or decreased free
risk for delayed wound healing and excessive scarring if
haptoglobin
Leukocytosis operation occurs within the first 72 hours of the bite.40,41
Anemia Debridement of enlarging blebs is proposed with the
Thrombocytopenia theory that toxins exist within the blister fluid. However,
Coagulopathy (elevated prothrombin time, decreased necrosis almost always occurs beneath the blisters.42 The
fibrinogen, elevated d-dimer, decreased antithrombin question is whether surgical intervention should be advo-
III) cated late after envenomations? The wound from the
Inflammatory markers (elevated C-reactive protein, brown recluse spider may take two to three months to
elevated erythrocyte sedimentation rate, elevated heal. Thus, skin grafting of a non-healing necrotic area
liver and/or pancreatic enzymes), elevated lactate should be delayed up to 12 weeks to allow for neovascu-
dehydrogenase
larization of the demarcated area.43
Immunology (positive antiglobulin tests: direct or indi-
rect Coombs; decreased total serum complement or Treatment of systemic symptoms largely involves
components; interference with blood screening or supportive care. Patients should be monitored closely
crossmatching) for hemolysis (and children hospitalized) if systemic
symptoms such as fever and rash develop. Systemic
12 Bites 159
corticosteroids seem to suppress hemolysis and may be symptoms or for pain that is not relieved by opioids and
needed for five to ten days with a subsequent tapering benzodiazepines.
dose.43 Methylprednisolone can be administered as a
1.02.0mg/kg intravenous loading dose (no maximum)
followed by a 0.51.0mg/kg maintenance dose every six CROTALID SNAKE ENVENOMATIONS
hours. Hydration to maintain good urine output is
required to prevent acute renal tubular necrosis if hemo- In the USA, there are two major classes of poisonous
lysis or hematuria occurs. Antibiotics are not generally snakes: crotalids and elapids. Crotalids, otherwise known
required early in the care of these patients because the as pit vipers, are indigenous to almost every state and
spider does not inoculate humans with bacteria. However, account for the vast majority of poisonous snake bites in
secondary infections can occur and lead to sepsis, toxic the USA annually. Most snake bites occur during the
shock syndrome, and necrotizing fasciitis. These compli- warm summer months when both snakes and humans are
cations require close observation and antibiotic therapy more active and thus more likely to come into contact
to cover anaerobic, staphylococcal, and streptococcal with each other. It is thought that up to 20% of snake bites
infections. are dry bites and do not result in envenomation.47
Crotalids can be classified into three major groups:
rattlesnakes, cottonmouths (water moccasins), and cop-
Black Widow Spider perheads. Copperheads are responsible for the majority
Black widow spiders (Latrodectus mactans) are found of crotalid envenomations. In general, these bites are less
throughout North America.44 They can usually be found severe and rarely result in systemic toxicity.48,49 Rattle-
outdoors in warm, dark places, or in a garage or base- snake envenomations more commonly produce coagu-
ment. They are web-making spiders and usually strike lopathy and systemic toxicity.
when their web is disturbed. The female spider is readily Crotalids have several physical features that help dis-
recognized as she is a black spider with a red marking on tinguish them from nonpoisonous snakes (Fig. 12-3).
her abdomen in the shape of an hourglass. Widow spiders Crotalids have triangular heads and elliptical pupils.
have a neurotoxic venom that is responsible for their Nonpoisonous snakes have round heads and pupils. Cro-
clinical effects. The venom, -latrotoxin, acts on the neu- talids have a single row of subcaudal plates/scales distal
romuscular junction to cause depletion of acetylcholine to the anal plate, whereas nonpoisonous snakes have a
at motor endings and catecholamines at the postgangli- double row of subcaudal plates. Most importantly, crota-
onic sympathetic synaptic sites, which is followed by lids have two retractable fangs and the characteristic
complete blockade of the neuromediator release.45 heat-seeking pit located between the nostril and the eye.
In the majority of cases, a pinprick sensation may be Nonpoisonous snakes have short, pointy teeth, but
felt at the time of a bite. A halo lesion may develop, but no fangs.
this tends to disappear within 12 hours of envenomation.
A few hours after the bite, the regional lymph nodes and Crotalid Venom Pharmacology/
affected extremity may become tender. Depending on
where the bite occurs, pain usually migrates to the large
Pathophysiology
muscle groups in the thigh, buttock, abdomen or chest. Crotalid venom is a complex mixture of proteins, includ-
The most common presenting complaint is intractable ing metalloproteinases, collagenase, hyaluronidase, and
abdominal, chest, back, or leg pain, depending on the site phospholipase.50 These enzymes act to destroy tissue at
of the bite.46 Board-like rigidity of the abdomen, shoul- the site of envenomation. Damage to the vascular
ders, and back may develop that may lead to misdiagnosis endothelium and basement membranes leads to edema,
of a surgical abdomen or other etiology. The pain ecchymosis, and bullae formation. Concurrently with
generally peaks at two to three hours, but can last up to local tissue destruction, venom is absorbed systemically
72 hours. and can result in shock and coagulopathy. The potency
Because the venom affects the autonomic nervous of venom varies with the snakes age, species, diet, and
system, patients can present with symptoms of dysau- time of year.47 Even for the same snake, the composition
tonomia that include hypertension (sometimes severe), and potency of venom can vary substantially based on
tachycardia, weakness, ptosis, eyelid edema, pruritus, these factors.
nausea and vomiting, diaphoresis, hyperreflexia, difficulty
breathing, and excessive salivation. Fatalities are rare, but Clinical Effects
have been reported. Children are more at risk for devel-
oping systemic symptoms. In questioning the patient, one should ascertain the cir-
Management is largely symptomatic and supportive. cumstance and timing of the bite as well as any first aid
For the most part, treatment is focused on analgesia. methods that were used. Knowing what prehospital
For those with mild pain, oral medications are appropri- measures were instituted can be extremely helpful.
ate. Patients may present with severe pain requiring Certain therapies such as incision, excision, and suction
opioids and benzodiazepines as adjunctive therapy. may result in significant local trauma and act to confound
Calcium gluconate was advocated in the past, but is not the assessment of local injury. The clinician should deter-
recommended now because of lack of consistent effects mine if the patient has previously received antivenom
in alleviating the symptoms. Antivenom is available and because sensitization can occur, thereby placing the
generally reserved for patients who have life-threatening patient at higher risk for an allergic reaction. Health care
160 SECTION II Trauma
PIT VIPERS
TABLE 12-3 Clinical Grading of Snake
Elliptical pupil
Envenomations
Nostril
Pit Grading Comments
Fangs Minimal Mild local swelling without progression;
no systemic or hematologic toxicity
Moderate Local swelling with proximal progression
and/or mildly abnormal laboratory
parameters (e.g., decreased platelets,
prolonged coagulation studies)
Severe Marked swelling with progression and/or
NONPOISONOUS significant systemic toxicity (shock,
compartment syndrome) or
Round pupil laboratory abnormalities (severe
thrombocytopenia/coagulopathy)
Nostril
Adapted from Gold BS, Dart RC, Barish RA. Bite of Venomous
Snakes. N Engl J Med 2002;347:34756.
Teeth
PIT VIPERS
Rattles present
(Crotalus &
Sistrurus)
Single row
Anal plate
subcaudal plates
Rattles present
(Crotalus &
Sistrurus)
NONPOISONOUS
Double row
Anal plate
subcaudal plates
FIGURE 12-3 Identifying characteristics of pit vipers and non- FIGURE 12-4 A 15-year-old boy was bitten on his right hand by
poisonous snakes. The presence or absence of a single row of a timber rattlesnake. Note the significant swelling of the arm.
subcaudal plates may be the only identifying feature in a decapi- Serial limb circumference measurements were documented;
tated snake. (From Ford M, Delaney K, Ling L, etal. Clinical Toxicol- the lines mark the progression of the swelling. The patient did
ogy. Philadelphia: Elsevier; 2001.) well after treatment with Fab antivenom.
providers should be cautious regarding the reliability of Serial measurements of the extremity are required to
the victims identification of the snake. It is often assumed detect progression of the swelling. The local effects have
that rattlesnakes will rattle their tails before biting. traditionally been documented by drawing a line demar-
However, this is not always the case. Also, rattles may be cating the progression of the swelling. Unfortunately,
absent from rattlesnakes due to shedding or trauma. this method requires subjective interpretation and can
Victims occasionally trap or kill the snake and bring it to result in measurement variability. Measurement of the
the emergency department. Vigilance is necessary when limb circumference is more objective and can be easily
examining these snakes because they are capable of biting repeated to determine any progression (Fig. 12-4). These
again. Even dead snakes have been known to bite reflex- measurements should be recorded every 15 minutes for
ively for up to an hour after they have been killed.47 the first two hours and then less frequently (every 30-60
Envenomations can result in significant local pain and minutes). In addition to measuring the limb circumfer-
swelling. The patient typically has two fang marks at the ence, serial neurovascular examinations can identify
location of the bite. Often, there is mild bleeding or ischemia or evidence of compartment syndrome.
oozing from the wound. Swelling typically develops Compartment syndrome is rare (<12%) after snake
within one to two hours, and ecchymosis or bullae (some envenomation because it is unusual for a snakes fangs to
hemorrhagic) may appear. Several different grading penetrate the muscle fascia.52 The true incidence is dif-
systems have been developed to grade the severity of ficult to ascertain from the literature because many of the
snake bites.47,51 The minimal, moderate, severe model is older case series report the use of prophylactic fascioto-
a simple tool that can help assess severity and determine mies without measuring the compartment pressure.5254
the need for antivenom (Table 12-3). Although swelling may be severe, it is almost always
12 Bites 161
localized to the subcutaneous tissue. If there is concern may decrease venom absorption into the systemic circula-
for compartment syndrome in the setting of severe pain tion. Rings, jewelry, and other constrictive clothing
and swelling, measurement of compartment pressures is should be removed. Most importantly, the victim should
needed. Even if elevated compartment pressures are be rapidly transported to the nearest emergency
found, treatment with antivenom is usually sufficient to department.
reduce the elevated pressures and reverse the compart- Historically, different procedures and therapies have
ment syndrome.5256 Given the efficacy and safety of the been advocated in the prehospital and in-hospital man-
current crotalid antivenom, prophylactic fasciotomies are agement of snake bites. Treatments such as cryotherapy
not routinely indicated in the setting of an envenoma- and electric shock are associated with significant compli-
tion.57 Recent evidence has shown that prophylactic fas- cations and are not recommended.63 It is commonly
ciotomies worsen local effects and do not improve clinical thought that tourniquets should be applied to the affected
outcomes.58,59 If compartment pressures are elevated, extremity. However, their use has not been found to
they should be re-measured after antivenom administra- improve outcomes and evidence suggests they may
tion and repeat antivenom should be given, if needed. If worsen local toxicity.6466 Therefore, their use should be
the pressures remain elevated for more than 4 hours discouraged. Given the short transport times of most
despite antivenom, then fasciotomy is indicated (Fig. patients, the morbidity associated with tourniquet appli-
12-5). Measurement of finger compartment pressures is cation (limb ischemia) outweighs any potential benefit.
not possible. If significant concern exists about the viabil- In those situations in which the victim is in a remote
ity of the finger, a digit dermotomy is indicated.59 location that is hours away from an emergency depart-
Systemic manifestations present in a variable fashion ment, the use of a constriction band should be consid-
after envenomation. Nonspecific symptoms and signs ered. There are limited data to suggest that constriction
include nausea, vomiting, diaphoresis, and metallic taste. bands decrease the rate of systemic venom absorption.64
Hypotension and shock can develop in severe cases. Constriction bands differ from venous tourniquets in that
Severe rattlesnake envenomations often cause coagulopa- they serve to impede lymphatic return rather than blood
thy with a disseminated intravascular coagulation-like flow. When placed correctly, two fingers should easily slip
syndrome. Thrombocytopenia has been noted to be under a constriction band.
severe and prolonged after timber rattlesnake envenoma- Pressure immobilization is another modality com-
tions.60 Canebrake rattlesnake envenomations have been monly recommended for snake bites. It involves wrap-
associated with significant rhabdomyolysis.61 Rarely, fol- ping the entire limb in an elastic compression bandage
lowing envenomation, patients have been noted to have and then immobilizing the limb in extension with a splint.
extremely rapid decompensation. In these cases, it is Although likely effective in cases of elapid envenoma-
thought that the patient experiences either an immediate tions,67 their use in cases of crotalid envenomation should
anaphylactoid-like reaction or receives a significant intra- be discouraged despite a recent position statement
vascular venom load.62 supporting their use.68 Animal models of crotalid enveno-
mation demonstrated pressure immobilization slightly
Management prolonged the time to death but was associated with a
significant increase in extremity compartment pres-
After a crotalid bite, the victim should avoid exertion and sures.69,70 Additionally, it has been shown that pressure
have the involved extremity immobilized. These actions immobilization bandages are often applied incorrectly
and can act as a tourniquet.71
Suction using a commercially available extractor
device has been previously suggested. The concept is that
the suction would pull the venom out of the wound if
applied shortly after the bite. However, it has been dem-
onstrated that these devices are not efficacious and
remove less than 1% of injected venom.72 Also, these
devices may actually increase the amount of local tissue
destruction.73 Therefore, use of extractor devices in the
prehospital or hospital setting is not recommended.
Incision therapy, often combined with suction, gained
favor in the early 20th century. This procedure entailed
making several parallel incisions longitudinally along the
affected extremity. While early animal models demon-
strated some survival improvement, subsequent human
studies have failed to show any change in clinical out-
FIGURE 12-5 The need for fasciotomy for compartment syn-
drome may be suggested by excessive swelling in the soft comes.74 Incising the wound also risks injury to underly-
tissue, but compartment pressures are rarely elevated signifi- ing tendons, nerves, and blood vessels, and increases
cantly. Prophylactic fasciotomy is based on the belief that it infection rates.7476
protects against compartment syndrome. Such practices are In-hospital management should initially focus on
unnecessary and can be catastrophic in venom-defibrinated
patients. (From Brent J, Wallace K, Burkhart K, etal. Critical Care
assessing and supporting the airway, breathing, and cir-
Toxicology: Diagnosis and Management of the Critically Poisoned culation. Anaphylactic reactions have been reported after
Patient. Philadelphia: Elsevier; 2005.) envenomation.77 The initial evaluation should assess the
162 SECTION II Trauma
BOX 12-4 Indications for Crotalid Antivenom Fortunately, a new polyvalent immune Fab antivenom
(CroFab, Protherics, Inc., Brentwood, TN) is available
Shock that is much safer and associated with significantly fewer
Coagulopathy and/or thrombocytopenia adverse reactions. It is a highly purified product that
Compartment syndrome contains the Fab fragments of IgG antibodies. The
Significant swelling/progression of local effects product is sheep-derived and is effective against all North
Neurotoxicity (Mojave rattlesnake) American crotalid species. The incidence of immediate
hypersensitivity reactions is less than 5% to 10%.8084
Many of the hypersensitivity reactions are mild (urticaria)
and do not prevent further antivenom administration.
patient for shock and hypoperfusion. Hypotension man- Anaphylaxis is uncommon. Likewise, the incidence of
dates aggressive resuscitation with crystalloid, antivenom serum sickness is also less than 5%.83,84 The dosing of
(see later), and possibly vasopressors. If the patient arrives polyvalent immune Fab is based on the clinical severity
in the emergency department with a tourniquet on the and response of the patient to the antivenom (Fig. 12-6).
extremity, it should be slowly loosened and removed over The dosing is not weight based. Therefore, the dosing in
20 to 30 minutes. Rapid removal of the tourniquet could children is the same as in adults. Skin testing is not
result in a bolus of the venom into the central circulation, required. Clinical trials have demonstrated improved
resulting in decompensation of the patient.64 Intravenous outcomes when regular follow-up doses of antivenom
access should be obtained in the noninjured extremity, were given for recurrence (see later) of local and systemic
with placement of a second access line in those with toxicity in those who received a single dose of antivenom.
significant envenomation. Opioids are often required for This resulted in the development of the currently recom-
management of pain. The patients tetanus should be mended dosing schedule. Multiple studies have demon-
updated as needed. Prophylactic antibiotics are not war- strated that the polyvalent immune Fab antivenom is
ranted because the risk of infection resulting from snake efficacious in ameliorating the local and systemic venom
bites is less than 5%.78 Although snakes carry pathogenic toxicity. Recent analysis of pediatric data also demon-
bacteria in their mouths, the majority of infections are strates excellent efficacy and safety in treating children as
secondary to the victims normal skin flora. young as 18 months of age. There were no cases of ana-
The antivenom supplies of the hospital should be phylaxis in pediatric patients (>100 cases) reported in five
assessed in all cases of snake bites, even those cases in
which antivenom administration does not appear to be
indicated. This is prudent because the patients clinical
condition can change rapidly in the first several hours
Patient with indication for
after envenomation. It is important for the clinician to antivenom administration
arrange for procurement of antivenom or hospital trans-
fer while the patient is stable and not in immediate need
of antivenom. A complete blood cell count, chemistries,
Establish initial control
coagulation studies, fibrinogen, and creatinine kinase are of envenomation by
indicated in all cases of snake bites to assess systemic administering 4-6 vials of
toxicity. Medical toxicologists and regional poison centers Crotalid Fab Antivenom Fab
(1-800-222-1222) can serve as valuable resources to clini-
cians who are unfamiliar with the management of snake
envenomations. Initial control
Antivenom is indicated for envenomations displaying achieved?
more than minimal local effects (Box 12-4). The older
Wyeth (Collegeville, PA) polyvalent antivenom that was
introduced in the USA in 1954 is no longer manufac-
YES NO
tured. This product was a crudely purified, equine-
derived IgG antibody directed against the venom of
several crotalids. As it contained foreign proteins and was Administer additional
highly immunogenic, the incidence of immediate hyper- 4-6 vials of Fab
sensitivity reactions was high. Approximately 50% of Antivenom
recipients developed urticaria or signs of anaphylactic
shock.79 Serum sickness, a delayed immunologic reaction
to the foreign proteins, was much more commonly asso- Control
achieved?
ciated with this antivenom (approximately 50% of cases
treated with more than five vials of the Wyeth
antivenom).79 It typically occurs one to three weeks after
antivenom administration and manifests clinically as a Infuse additional 2
fever, rash, arthralgias, myalgias, and occasionally vials at 6, 12, and 18 YES NO
hours after initial control
glomerulonephritis and pericarditis. It is generally self-
limited and can be treated with corticosteroids and FIGURE 12-6 This schematic depicts management of the patient
antihistamines. who needs crotalid polyvalent immune Fab antivenom.
12 Bites 163
case series.8589 Liberal use should be considered for bites All patients with suspected coral snake bites should be
involving the hands or feet because these envenomations admitted for observation. Treatment is supportive with
are associated with significant morbidity and prolonged close monitoring for respiratory compromise. Tradition-
recovery.90 ally it had been recommended to administer antivenom
Recurrence is defined as worsening of local and/or to any patient in whom there was a significant likelihood
systemic toxicity after a period of improvement with of envenomation (even if the patient was asymptomatic
antivenom therapy. This results from the pharmacoki- as the antivenom is less effective after the onset of symp-
netic differences between the antivenom and venom.91 toms due to its neurotoxicity). More recently, it has been
The Fab components have a low molecular weight and recommended to administer antivenom only if symptoms
are small enough to be freely filtered by the kidney. This develop. The initial dose is three to five vials with subse-
results in an elimination half-life of Fab antivenom of quent antivenom administration based on worsening of
about 15 to 20 hours versus venom that has a half-life of symptoms.
approximately 40 hours.91,92 Multiple reports have docu- Coral snake antivenom is an equine-derived IgG. In
mented progression of swelling or worsening hemato- the largest series describing USA coral snake envenoma-
logic toxicity after antivenom therapy.80,83,93 Those tions, immediate hypersensitivity reactions occurred in
patients who develop hematologic toxicity during initial 15% of patients, whereas serum sickness was reported
treatment are at highest risk for recurrence. Administra- in 10%.96
tion of antivenom is usually effective in treating further
local progression. Although hematologic toxicity does REFERENCES
not typically result in clinically significant bleeding, 1. Bronstein AC, Spyker DA, Cantilena LR, et al. 2010 Annual
further antivenom administration is not effective in com- Report of the American Association of Poison Control Centers
pletely normalizing hematologic abnormalities.83,94 Close National Poison Data System (NPDS). Clin Toxicol 2011;49:910
monitoring is indicated, and treatment can be resumed 1011 and Appendix.
2. Centers for Disease Control and Prevention. Summary of Notifi-
in those with bleeding or markedly abnormal laboratory able DiseasesUnited States, 2009. MMWR 2011;58:33, 36.
parameters.94 3. Wu DT. Tetanus. In: Wolfson AB, Hendey GW, Hendry PL, et al,
The disposition of patients who are bitten is depend- editors. Harwood-Nuss Clinical Practice of Emergency Medicine.
ent on the severity of the envenomation. Discharge after Philadelphia: Lippincott Williams & Wilkins; 2005. p. 71820.
4. Loscalzo LI, Ryan J, Loscalzo J, et al. Tetanus: A clinical diagnosis.
eight to 12 hours of observation can be considered in Am J Emerg Med 1995;13:48890.
those circumstances in which it is thought that no signifi- 5. American Academy of Pediatrics. Tetanus (lockjaw), Bite Wounds.
cant envenomation occurred (dry bite).95 There should In: Pickering LK, Baker CJ, Kimberlin DW, et al, editors. Redbook:
be no appreciable local swelling, and results of initial 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk
laboratory studies and repeat laboratory studies before Grove Village, IL: American Academy of Pediatrics; 2009. p. 187
91, 65560.
discharge should be normal. Patients with local swelling 6. Capellan O, Hollander JE. Management of lacerations in the emer-
or evidence of systemic toxicity should be admitted for gency department. In: Peth HA, editor. High Risk Presentations.
further evaluation and management. Rattlesnake bite Emerg Med Clin North Am 2003;21:20531.
victims from those areas in which the Mojave rattlesnake 7. Talan DA, Citron DM, Abrahamian EM, et al. Bacteriologic analy-
sis of infected dog and cat bites. N Engl J Med 1999;340:8592.
is endemic should be monitored for neurotoxicity. 8. Talan DA, Abrahamian EM, Moran GJ, et al. Clinical presentation
and bacteriologic analysis of infected human bites in patients
presenting to emergency departments. Clin Infect Dis 2003;37:
CORAL SNAKE ENVENOMATION 14819.
9. Pretty IA, Anderson GS, Sweet DJ. Human bites and risk of human
immunodeficiency virus transmission. Am J Forens Med Pathol
The coral snake is the only poisonous elapid snake native 1999;20:2329.
to the USA. While there are several species of coral 10. Human rabies prevention. United States, 1999. Recommendation
snakes in the USA, the species of greatest concern is of the Advisory Committee on Immunization Practices (ACIP).
found in Florida and southern Georgia. These snakes are Morb Mortal wkly Rep 1999;48(No. RR-1):121.
11. World Health Organization. WHO expert committee on rabies.
brightly colored and have bands in a distinctive pattern World Health Organ Tech Rep Ser 2005;931:1121.
(black, yellow, red). This order gives rise to the common 12. Rabies Prevention Policy Update. New Reduced-Dose Schedule.
phrases, red on yellow, kill a fellow and red on black, Committee on Infectious Diseases. Pediatrics 2001;127:7857.
venom lack, that can help to differentiate a coral snake 13. Coddington JA, Levi HW. Systematics and evolution of spiders
from the nonpoisonous king snake. Unlike crotalids, (Araneae). Annu Rev Ecol Syst 1991;22:56592.
14. Sams HH, Dunnick CA, Smith ML, et al. Necrotic arachnidism.
coral snakes have round heads and pupils. Instead of J Am Acad Dermatol 2001;44:56173.
fangs, they have short teeth. Up to 25% of bites result in 15. Vetter RS. Spiders of the genus Loxosceles (Araneae, Sicariidae): A
no significant envenomation.96 review of biological, medical, and psychological aspects regarding
Unlike crotalids that produce local tissue destruction envenomations. J Arachnol 2008;36:15063.
16. Forrester LJ, Barrett JT, Campbell BJ. Red blood cell lysis induced
and coagulopathy, venom from elapids is associated with by the venom of the brown recluse spider: The role of sphingomy-
neurotoxicity. After a bite, local effects tend to be mild. elinase D. Arch Biochem Biophys 1978;187:35565.
Of greater concern is the risk of progressive weakness 17. Rees RS, Nanney LB, Yates RA, et al. Interaction of brown recluse
and resulting respiratory failure. Neurologic symptoms spider venom on cell membranes: The inciting mechanism? J Invest
(cranial nerve palsies, weakness) typically develop within Dermatol 1984;83:2705.
18. Tambourgi DV, Magnoli FC, van den Berg CW, et al. Sphingomy-
two hours but may be delayed up to 13 hours.96 Given elinases in the venom of the spider Loxosceles intermedia are
the lack of significant local effects, surgical management responsible for both dermonecrosis and complement-dependent
is not indicated. hemolysis. Biochem Biophys Res Commun 1998;251:36673.
164 SECTION II Trauma
19. Majeski JA, Stinnett JD, Alexander JW, et al. Action of venom from 45. Kunkel DB. The sting of the arthropod. Emerg Med 1996;
the brown recluse spider (Lososceles reclusa) on human neu- 28:13641.
trophils. Toxicon 1977;15:4237. 46. Clark RF, Wethern-Kestner S, Vance MV, et al. Clinical presenta-
20. Futrell JM, Morgan PN. Inhibition of human complement com- tion and treatment of black widow spider envenomation: A review
ponents by Loxosceles reclusa venom. Int Arch Allergy Appl of 163 cases. Ann Emerg Med 1992;21:7827.
Immunol 1978;57:2758. 47. Russell FE. Snake Venom Poisoning. Great Neck, NY: Scholium
21. Kurpiewski G, Campbell JF, Forrester LJ, et al. Alternate comple- International; 1983.
ment pathway activation by recluse spider venom. Int J Tissue 48. Scharman EJ, Noffsinger NJ. Copperhead snakebites: Clinical
React 1981;3:3945. severity of local effects. Ann Emerg Med 2001;38:5561.
22. Wright SW, Wrenn KD, Murray L, et al. Clinical presentation and 49. Thorson A, Lavonas EJ, Rouse AM, et al. Copperhead envenoma-
outcome of brown recluse spider bite. Ann Emerg Med tions in the Carolinas. J Tox Clin Toxicol 2003;41:2935.
1997;30:2832. 50. Gold BS, Dart RC, Barish RA. Bite of venomous snakes. N Engl J
23. Wasserman GS. Brown recluse and other necrotizing spiders. In: Med 2002;347:34756.
Ford MD, Delaney KA, Ling LJ, et al, editors. Clinical Toxicology. 51. Dart RC, Hurlbut KM, Garcia R, et al. Validation of a severity
Philadelphia: WB Saunders; 2001. p. 87884. score for the assessment of Crotalid snakebite. Ann Emerg Med
24. Williams ST, Khare VK, Johnston GA, et al. Severe intravascular 1996;27:3216.
hemolysis associated with brown recluse spider envenomation. Am 52. Cumpston KL. Is there a role for fasciotomy in crotaline enveno-
J Clin Pathol 1995;104:4637. mations in North America. Clin Toxicol 2011;49:35165.
25. Berger RS, Adelstein EH, Anderson PC. Intravascular coagulation: 53. Shaw BA, Hosalkar HS. Rattlesnake bites in children: Antivenin
The cause of necrotic arachnidism. J Invest Dermatol 1973;61: treatment and surgical indications. J Bone Joint Surg Am
14250. 2002;84:16249.
26. de Souza AL, Malague CM, Sztajnbok J, et al. Loxosceles venom 54. Corneille MG, Larson S, Stewart RM, et al. A large single center
induced cytokine activation, hemolysis and acute kidney injury. experience with treatment of patients with Crotalid envenoma-
Toxicon 2008;51:1516. tions: Outcomes with and evolution of antivenin therapy. Am J Surg
27. Pauli I, Puka J, Gubert IC, et al. The efficacy of antivenom in 2006;192:84852.
loxoscelism treatment. Toxicon 2006;48:12337. 55. Tanen DA, Danish DC, Clark RF. Crotalid polyvalent immune Fab
28. King LE, Rees RS. Dapsone treatment of a brown recluse bite. antivenom limits the decrease in perfusion pressure of the anterior
JAMA 1983;250:648. leg compartment in a porcine crotaline envenomation model. Ann
29. Wesley RE, Close LW, Ballinger WH, et al. Dapsone in the Emerg Med 2003;41:38490.
treatment of presumed brown recluse spider bite of the eyelid. 56. Gold BS, Barish RA, Dart RC, et al. Resolution of compartment
Ophthalmic Surg 1985;16:1167, 120. syndrome after rattlesnake envenomation utilizing noninvasive
30. Barrett SM, Romine-Jenkins M, Fisher DE. Dapsone or electric measures. J Emerg Med 2003;24:2858.
shock therapy of brown recluse spider envenomation? Ann Emerg 57. Tanen DA, Danish DC, Grice GA. Fasciotomy worsens the amount
Med 1994;24:215. of myonecrosis in a porcine model of crotaline envenomation. Ann
31. Hobbs GD, Anderson AR, Greene TJ, et al. Comparison of hyper- Emerg Med 2004;44:99104.
baric oxygen and dapsone therapy for Loxosceles envenomation. 58. Stewart RM, Page CP, Schwesinger WH, et al. Antivenin and
Acad Emerg Med 1996;3:75861. fasciotomy/debridement in the treatment of severe rattlesnake bite.
32. Phillips S, Kohn M, Baker D, et al. Therapy of brown spider Am J Surg 1989;158:5437.
envenomation: A controlled trial of hyperbaric oxygen, dapsone 59. Hall EL. Role of surgical intervention in the management of cro-
and cyproheptadine. Ann Emerg Med 1995;25:3638. taline snake envenomation. Ann Emerg Med 2001;37:17580.
33. Wille RC, Morrow JD. Case report: Dapsone hypersensitivity syn- 60. Bond GR, Burkhart KK. Thrombocytopenia following timber rat-
drome associated with treatment of the bite of a brown recluse tlesnake envenomation. Ann Emerg Med 1997;30:404.
spider. Am J Med Sci 1988;296:2701. 61. Carroll RR, Hall EL, Kitchens CS. Canebrake rattlesnake enveno-
34. Lowry BP, Bradfield JF, Carroll RG, et al. A controlled trial of mation. Ann Emerg Med 1997;30:458.
topical nitroglycerin in a New Zealand white rabbit model of 62. Curry SC, OConnor AD, Ruha AM. Rapid-onset shock and/or
brown recluse spider envenomation. Ann Emerg Med anaphylactoid reactions from rattlesnake bites in central Arizona
2001;37:1615. [abstract]. J Med Toxicol 2010;6:241.
35. Paixao-Cavalcante D, van den Berg CW, Goncalves-de-Andrade 63. McKinney PE. Out-of-hospital and interhospital management of
RM, et al. Tetracycline protects against dermanecrosis induced by. crotaline snakebite. Ann Emerg Med 2001;37:16874.
Loxosceles spider venom. J Invest Dermatol 2007;127:141018. 64. Burgess JL, Dart RC, Egen NB, et al. Effects of constriction bands
36. Strain GM, Snider TG, Tedford BL, et al. Hyperbaric oxygen on rattlesnake venom absorption: A pharmacokinetic study. Ann
effect on brown recluse spider (Loxosceles reclusa) envenomation Emerg Med 1992;21:108693.
in rabbits. Toxicon 1991;29:98896. 65. Sutherland SK, Coulter AR. Early management of bites by eastern
37. Merchant ML, Hinton JF, Geren CR. Effect of hyperbaric oxygen diamondback rattlesnake (Crotalus adamanteus) studies in monkeys
on sphingomyelinase D activity of brown recluse spider (Loxosceles (Macaca fascicularis). Am J Trop Med Hyg 1981;30:497500.
reclusa) venom as studied by 31P nuclear magnetic resonance spec- 66. Straight RC, Glenn JL. Effects of pressure/immobilization on the
troscopy. Am J Trop Med Hyg 1997;56:3358. systemic and local action of venoms in a mouse tail model [abstract].
38. Maynor ML, Moon RE, Klitzman B, et al. Brown recluse spider Toxicon 1985;23:40.
envenomation: A prospective trial of hyperbaric oxygen therapy. 67. German BT, Hack JB, Brewer K, et al. Pressure-immobilization
Acad Emerg Med 1997;4:18492. bandages delay toxicity in a porcine model of eastern coral snake
39. Gomez HF, Greenfield DM, Miller MJ, et al. Direct correlation (Micrurus fulvius fulvius) envenomation. Ann Emerg Med
between diffusion of Loxosceles reclusa venom and extent of 2005;45:6038.
dermal inflammation. Acad Emerg Med 2001;8:30914. 68. Markenson D, Ferguson JD, Chameides L, et al. Part 17: First Aid:
40. Rees R, Shack B, Withers E, et al. Management of the brown 2010 American Heart Association and American Red Cross Guide-
recluse spider bite. Plast Reconstr Surg 1981;68:76873. lines for First Aid. Circulation 2010;122(18 Suppl 3):S93446.
41. Rees R, Altenbern DP, Lynch JB, et al. Brown recluse spider bites: 69. Bush SP, Green SM, Laack TA, et al. Pressure immobilization
A comparison of early surgical excision versus dapsone and delayed delays mortality and increases intracompartmental pressure after
surgical excision. Ann Surg 1985;202:65963. artificial intramuscular rattlesnake envenomation in a porcine
42. Wasserman GS, Lowry JA. Loxosceles spiders. In: Brent J, model. Ann Emerg Med 2004;44:599604.
Wallace KL, Burkhart KK, et al, editors. Critical Care Toxicology: 70. Meggs WJ, Courtney C, ORourke D, et al. Pilot studies of
Diagnosis and Management of the Critically Poisoned Patient. pressure-immobilization bandages for rattlesnake envenomations.
Philadelphia: Elsevier Mosby; 2005. p. 1195203. Clin Toxicol 2010;48:613.
43. Wasserman GS, Anderson PC. Loxoscelism and necrotic arach- 71. American College of Medical Toxicology, American Academy of
nidism. Clin Toxicol 1983-1984;21:45172. Clinical Toxicology, American Association of Poison Control
44. Bond GR. Snake, spider, and scorpion envenomation in North Centers, European Association of Poison Control Centers and
America. Pediatr Rev 1999;20:14751. Clinical Toxicologists, International Society on Toxinology, Asia
12 Bites 165
Pacific Association of Medical Toxicology. Pressure immobilization 85. Pizon AF, Riley BD, LoVecchio F, et al. Safety and efficacy of
after North American Crotalinae snake envenomation. Clin Toxicol Crotalidae Polyvalent Immune Fab in pediatric crotaline enveno-
2011;49:8812. mations. Acad Emerg Med 2007;14:3736.
72. Alberts MB, Shalit M, LoGolbo F. Suction for venomous snakebite: 86. Offerman SR, Bush SP, Moynihan JA, et al. Crotaline Fab
A study of mock venom extraction in a human model. Ann Emerg antivenom for the treatment of children with rattlesnake enveno-
Med 2004;43:1816. mation. Pediatrics 2002;110:96871.
73. Bush SP, Hegewald KG, Green SM, et al. Effects of a negative 87. Rowden AK, Holstege CP, Kirk MA. Pediatric copperhead enveno-
pressure venom extraction device (extractor) on local tissue injury mations [abstract]. Clin Toxicol 2007;45:644.
after artificial rattlesnake envenomation in a porcine model. Wil- 88. Rowden AK, Boylan VV, Wiley SH, et al. Crofab use for copper-
derness Environ Med 2000;11:1808. head envenomation in the young [abstract]. Clin Toxicol
74. Wingert WA, Chan L. Rattlesnake bites in southern California and 2006;44:6967.
rationale for recommended treatment. West J Med 1988;148: 89. Feng S, Stephan M. What a biteReview of snakebites in children
3744. [abstract]. Clin Toxicol 2005;43:712.
75. Tokish JT, Benjamin J, Walter F. Crotalid envenomation: The 90. Spiller HA, Bosse GM. Prospective study of morbidity associated
southern Arizona experience. J Orthop Trauma 2001;15:59. with snakebite envenomation. J Tox Clin Toxicol 2003;41:
76. Arnold RE. Results of treatment of Crotalus envenomation. Am 12530.
Surg 1975;41:6437. 91. Seifert SA, Boyer LV. Recurrence phenomena after immunoglobu-
77. Brooks DE, Graeme KA, Ruha AM, et al. Respiratory compromise lin therapy for snake envenomations: I. Pharmacokinetics and
in patients with rattlesnake envenomation. J Emerg Med pharmacodynamics of immunoglobulin antivenoms and related
2002;23:32932. antibodies. Ann Emerg Med 2001;37:18995.
78. LoVecchio F, Klemens J, Welch S, et al. Antibiotics after rattle- 92. Seifert SA, Boyer LV, Dart RC, et al. Relationship of venom effects
snake envenomation. J Emerg Med 2002;23:3278. to venom antigen and antivenom serum concentrations in a patient
79. Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms with Crotalus atrox envenomation treated with a Fab antivenom.
in the United States. Ann Emerg Med 2001;37:1818. Ann Emerg Med 1997;30:4953.
80. Dart RC, Seifert SA, Boyer LV, et al. A randomized multicenter 93. Bogdan GM, Dart RC, Falbo SC, et al. Recurrent coagulopathy
trial of Crotalidae Polyvalent Immune Fab (ovine) antivenom for after antivenom treatment of Crotalid snakebite. South Med J
the treatment of crotaline snakebite in the United States. Arch 2000;93:5626.
Intern Med 2001;161:20306. 94. Boyer LV, Seifert SA, Cain JS. Recurrence phenomena after immu-
81. Lavonas EJ, Gerardo CJ, OMalley G, et al. Initial experience with noglobulin therapy for snake envenomations: II. Guidelines for
Crotalidae Polyvalent Immune Fab (ovine) antivenom in the treat- clinical management with Crotaline Fab antivenom. Ann Emerg
ment of copperhead snakebite. Ann Emerg Med 2004;43:2006. Med 2001;37:196201.
82. Dart RC, Seifert SA, Carroll L, et al. Affinity-purified, mixed 95. Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algo-
monospecific crotalid antivenom ovine Fab for the treatment of rithm for the management of crotaline snakebite in the United
crotalid venom poisoning. Ann Emerg Med 1997;30:339. States: Results of an evidence-informed consensus workshop. BMC
83. Ruha AM, Curry SC, Beuhler M, et al. Initial postmarketing expe- Emerg Med 2011;11:2.
rience with Crotalidae Polyvalent Immune Fab for the treatment 96. Kitchens CS, Van Mierop LHS. Envenomation by the eastern coral
of rattlesnake envenomation. Ann Emerg Med 2002;39:60915. snake (Micrurus fulvius fulvius). JAMA 1987;258:161518.
84. Cannon R, Ruha AM, Kashani J. Acute hypersensitivity reactions
associated with administration of Crotalidae Polyvalent Immune
Fab antivenom. Ann Emerg Med 2008;51:40711.
C H A P T E R 1 3
Burns
E. Marty Knott Daniel J. Ostlie David Juang
Over the past several decades, burn-related hospital zone of stasis surrounds this area and has decreased tissue
admissions and deaths have decreased by 50% in large perfusion, but remains salvageable with aggressive resus-
part due to advancements in burn care, introduction citation. Outside the zone of stasis is the zone of hyper-
of topical antimicrobial agents, and a better under- emia where tissue perfusion is increased and often survives
standing of fluid resuscitation and aggressive surgical unless faced with infection or hypotension.
management.13 Despite these advances, nearly 100,000 The systemic response to burn injury is mediated
children age 14 years and under were treated for burns by the release of inflammatory mediators such as throm-
in hospital emergency rooms in 2007. Of these, 20% boxane A2, bradyknin, oxidants, and cytokines which
occurred in children less than 4 years old.4 Thus, burns can impair flow to the zone of stasis through thrombosis,
remain a leading cause of morbidity and mortality in vasoconstriction, and capillary blockage.6 The adminis-
children. Optimal management requires a team of health tration of antioxidants, bradykinin antagonists, and
care providers, therapists, and social workers. thromboxane A2 inhibitors can improve blood flow
and mitigate injury.79 In addition, the administration
of -glucan, through its immunomodulatory effects,
PATHOPHYSIOLOGY antioxidant properties, and ability to reduce the
inflammatory response, has been shown to improve
Skin is a complex, multilayer organ with a surface area re-epithelialization in a rat model of burn injury.10
ranging from 0.20.3m2 in the newborn to 1.52.0m2 in The systemic effects of burn injury extend beyond
the adult. An understanding of its basic structure and these three zones and can potentially lead to multiorgan
regenerating ability is critical to burn management. The dysfunction. The cardiovascular system can experience
skin provides protection, participates in thermoregula- myocardial depression and hypovolemia. Pulmonary
tion and vitamin D production, and is involved in sensa- vasoconstriction and edema lead to respiratory failure.11
tion. The epidermis is the avascular and aneural superficial Splanchnic vasoconstriction can result in gut dysmotility
layer made up of keratinocytes (95%), melanocytes, and malabsorption by causing epithelial apoptosis and
Langerhans cells, and Merkel cells. Desquamation of decreased epithelial proliferation.1214 This results in
cells formed at the basal layer takes 2 to 4 weeks. The atrophy of small bowel mucosa, increased intestinal per-
entire epidermis is replaced by new cells every 48 days. meability, bacterial translocation, and sepsis.15 Splanchnic
The dermis has a deep reticular layer and a superficial vasoconstriction and activation of stress-induced hor-
papillary region that are connected to the epidermis via mones and mediators, such as angiotensin, aldosterone,
the basement membrane. Composed primarily of colla- and vasopressin, leads to a decrease in renal perfusion
gen and elastin from fibroblasts, the dermis provides that can lead to oliguria.16 When unrecognized, this
support for the skin. can progress to acute tubular necrosis, renal failure,
The mechanism of any burn plays an important role and, ultimately, death.17,18 Finally, there is a systemic
in how deep and severe the injury will extend as well as decrease in immune function due to impaired production
how it is treated. The extent of injury is determined by and function of neutrophils, macrophages and T-
the temperature, duration of exposure, skin thickness, lymphocytes, placing the patient at risk for infectious
and specific heat of the causative agent. Grease burns complications.19,20
result in deeper injury than water of the same tempera-
ture, since lipid has a higher specific heat. Scald burns
constitute 70% of pediatric burns with the majority INITIAL MANAGEMENT
occurring in toddlers. Whether due to spilling hot drinks
or hot tap water, they tend to be superficial dermal burns. The majority of pediatric burns are minor, often resulting
Flame burns are more common in adolescents and can from scald accidents and affecting less than 10% total
result in deep injury. Contact burns are also common in body surface area (TBSA), or from thermal injuries iso-
children and may be caused by touching a hot oven door, lated to the hands. Such burns are usually limited to
an iron, or even hot pavement. partial-thickness injury of the skin and can be managed
In 1953, Jackson described the zones of burn injury on an outpatient basis, which is beyond the scope of this
that remain important to the understanding and manage- chapter. Unfortunately, larger burns require inpatient
ment of burns today (Fig. 13-1).5 The zone of coagulation treatment and special attention. The initial step is com-
occurs at the site of maximal damage and is defined by pletion of the primary and secondary surveys.21 Issues
irreversible tissue loss due to protein coagulation. The with airway, breathing, and circulation should be
166
13 Burns 167
Epidermis
Zone of
Dermis coagulation
Zone of
Subcutaneous stasis
tissue Zone of
hyperemia
FIGURE 13-1 Three zones of burn injury: coagulation, stasis, and hyperemia.
addressed immediately. Signs and symptoms including Major Burn Injury Criteria
increased respiratory effort, wheezing, stridor, and tachy BOX 13-1
(American Burn Association)
pnea should raise concern for impending loss of the
airway. The decision to intubate a patient with a tenuous Second-degree burns >10% TBSA in patients younger
airway should be made early. Inhalation injury can result than 10 years of age
in edema that may worsen over the first few hours, so Third-degree burns >5% TBSA
repeated evaluations of the airway are important. Burn Burns involving the face, hands, feet, genitalia, perineum,
injuries can have a negative effect on breathing mechan- and major joints
ics through smoke inhalation, a blast injury causing blunt Chemical burns
Electrical burns including lightning injury
chest trauma, and the restrictive effects of a burn eschar
Inhalation injury
that limits full chest expansion. Escharotomy should be Burns with significant concomitant trauma
performed for the latter. Patients need support with Burns with significant preexisting medical disorders
100% supplemental oxygen. If inhalation injury is sus-
pected, arterial blood gas analysis and carboxyhemo- TBSA, total body surface area.
globin level are needed. Two large bore IVs should be
placed and aggressive fluid resuscitation is important.
When extremity burns limit peripheral IV access or if and the anterior and posterior trunks are 18% each. The
there is difficulty obtaining central venous access, intra- perineum, genitalia, and neck each measures 1%. Due to
osseus access should be utilized as a temporary (<24 differences in body proportions for infants and children,
hours) alternate route for fluid administration. A urinary the rule of nines has been modified to more accurately
catheter should be inserted, and heart rate, blood pres- determine burn area in these patients. In this modifica-
sure and urine output should be monitored as tachycardia tion, the head represents 18% of the TBSA and each leg
and low urine output signal a low intravascular volume is 13.5%. Other modifications have been proposed to
state. better estimate TBSA burn in obese patients.24 The
The source of thermal injury needs to be removed Lund and Browder chart may provide more accurate
from the patient as quickly as possible, even during the determination of burn area in children as it compensates
primary survey, if not done before. Active cooling may for variations in body shape and proportions (Fig. 13-2).
limit the depth of the burn but can result in hypothermia. For a rapid estimation of burn size, the palmar method
Chemicals need to be removed from the skin and the area can be used. The palmar surface is approximately 1% of
should be thoroughly irrigated with water. Neutralization the TBSA and is best used for estimating small surface
of chemicals is not needed and may produce additional area burns. First-degree burns should not be included in
heat that could lead to a deeper burn. Care should be burn size calculations using any of these techniques. A
taken to keep the patient warm as the risk of hypothermia recent study found that estimates of burn area are inac-
increases with increasing burn area. curate in approximately 80% of children with the major-
A decision should be made after initial evaluation, ity being overestimated.25 The authors concluded that
resuscitation, and wound dressing as to whether or not this may be due to the variety of techniques used, or
the patient needs to be transferred to a burn center. The inclusion of first-degree burns in the calculation. This
American Burn Association and American College of can also lead to unnecessary transfer of patients to burn
Surgeons have clear recommendation regarding which care centers as discussed previously.
patients should be referred to these centers (Box 13-1).22 A key component to the initial management of the
However, a recent study raises concern that resources are severely burned patient includes escharotomy when indi-
often wasted by transferring less severe injuries to burn cated (Fig. 13-3). Full-thickness circumferential burns on
centers.23 the extremities can produce a constricting eschar which,
There are several techniques to estimate the TBSA of together with the associated edema, can impede venous
the burn. The Wallace rule of nines estimates burn area outflow and impair arterial flow. If pulses are absent, a
fairly well for adolescents. Each upper extremity and the bedside escharotomy should be performed with a scalpel
head represent 9% of the TBSA. The lower extremities or electrocautery along the lateral and medial aspects of
168 SECTION II Trauma
B B B B
FLUID RESUSCITATION
Once adequate intravenous or intraosseous access is
obtained, fluid resuscitation is initiated. There are several
formulas available to guide this resuscitation (Table 13-1).
The Parkland formula is the most widely used, but is not
as applicable in young children because children have
greater TBSA relative to their body weight than adults. As
a result, weight-based formulas can under-resuscitate
children with minor burns and can grossly over-resuscitate
children with extensive burns.26 TBSA-based formulas,
such as the ShrinersGalveston formula, are therefore
better at estimating fluid requirements in children less
than 20kg.27 TBSA is assessed from height and weight
using standard nomograms or calculated using formulas
(Table 13-2). Dextrose-containing solutions, such as 5%
dextrose with 0.25 to 0.5 normal saline, are used as the
primary solution. Children younger than 2 years of age
are susceptible to hypoglycemia due to limited glycogen
stores. Therefore, lactated Ringers solution with 5% dex-
trose is given during the first 24 hours in these patients.
Regardless of which formula is utilized, there must be
close monitoring of the patients physiologic response to
the fluid administration. Urine output should be main-
FIGURE 13-3 Escharatomies. The incisions are made on the
medial and lateral aspects of the extremity. Hand escharotomies
tained at 1mL/kg/h. Inadequate resuscitation can result
are performed on the medial and lateral digits and on the in hypoperfusion to the zone of stasis, with subsequent
dorsum of the hand. (From Eichelberger MR [ed]; Pediatric Trauma: deepening of the burn, as well as hypoperfusion of major
Prevention, Acute Care, Rehabilitation. St Louis, Mosby, 1993.) organs. During the first six to 12 hours, capillary perme-
ability is increased and fluid moves from the intravascular
space to the interstitial tissues with worsening edema.
the affected extremity. Incisions can be carried onto the Overly aggressive fluid administration can result in sig-
hypothenar and thenar eminences and dorsolateral nificant tissue edema, tissue hypoxia, and elevated com-
aspects of the digits if the hands or fingers are involved partment pressures.28
(Fig. 13-4). The resulting ischemia reperfusion injury Several authors have shown that the addition of
and edema can cause significant increases in fascial colloid solutions such as albumin can reduce crystalloid
13 Burns 169
A B
C D
FIGURE 13-4 A 3-year-old male transferred after being rescued from a house fire. He required extensive escharotomies of the
(A,B) chest and (C) distal extremities during the initial resuscitation. (D) Incisions should be carried onto the hypothenar and thenar
eminences and dorsolateral aspects of the digits if the hands or fingers are involved.
requirements and more rapidly establish a balanced fluid aggressive fluid resuscitation, and correction is required
intake to output ratio.29,30 However, a 2011 Cochrane to avoid severe electrolyte imbalance.
database review found that albumin does not lower mor- An increased incidence of pneumonia, bloodstream
tality in adults with major burns.31 Thus, the benefit of infection, acute respiratory distress syndrome (ARDS),
the more expensive albumin instead of standard crystal- multiple-organ failure, and death may be associated with
loid solutions is questionable. Other solutions, such as over-resuscitation during the first 24 hours postburn.33
hypertonic saline, have been used in an effort to provide Interestingly, permissive hypovolemia helps avoid these
a high osmotic pressure which is thought to keep more complications and has been shown to decrease multiple-
volume in the intravascular space. Hypertonic saline also organ dysfunction.34
may have anti-inflammatory effects. However, it should
be used with caution as it causes hypernatremia, and has
not been shown to improve outcomes for hypotensive
Inhalation Injury
trauma patients.32 While inhalation injury is less common in children than
Unlike adults, children do not show hemodynamic adults, the mortality increases to nearly 40% when it
changes reflecting hypovolemia until they are signifi- occurs.35 The heat of inhaled gas causes upper airway
cantly volume depleted. Tachycardia may be a sign of injury. Inhaled toxins can result in upper airway injury in
compensation for a low volume state or stress response addition to causing tracheobronchial irritation and bron-
to injury. Signs of inadequate perfusion include lethargy choconstriction. Damaged epithelium releases vasoactive
and decreased capillary refill with cool, clammy extremi- substances (thromboxanes A2, C3a, and C5a) that lead to
ties. Laboratory tests should be performed along with hypoxia, increased airway resistance, decreased pulmo-
serial clinical exams to follow the response to resuscita- nary compliance, increased alveolar epithelial permeabil-
tion. Resolving acidosis, for example, may serve as an ity, and increased pulmonary vascular resistance.36 Carbon
objective marker of improvement. Hyponatremia is a monoxide (CO) is produced during combustion and can
frequent complication in pediatric burn patients after contribute to the inhalational injury by displacing oxygen
170 SECTION II Trauma
from hemoglobin-binding sites. The oxyhemoglobin dis- consisting of chest physiotherapy, frequent suctioning,
sociation curve is shifted to the left as the ability of and early mobilization of the patient should be started.
hemoglobin to unload oxygen in the tissues is decreased. Bronchodilators and racemic epinephrine are used to
Secondary injury is due to impaired ciliary clearance of treat bronchospasm. Clearance of secretions can be
airway debris. Neutrophil infiltration occurs, macro- assisted with inhalation treatments composed of heparin
phages are destroyed, and bacteria accumulate leading to and acetylcysteine. Human autopsy and animal models
pneumonia. have shown nebulized heparin (500010,000 units/3mL
An inhalation injury should be recognized early of NS q5 hours) to reduce tracheobronchial cast forma-
through a detailed history of the burn and the initial tion improves minute ventilation and decreases peak
evaluation. On examination, patients may be found to inspiratory pressures after smoke inhalation.4143 The
have facial burns, singed hairs in the nose, eyebrows or addition of 20% acetylcysteine (3mL q4 hours) also
head, and/or carbonaceous sputum. Patients with inhala- improves the clearance of tracheobronchial secretions
tion injury who are obtunded are likely to have a carboxy- and minimizes bronchospasm. Pediatric and adult studies
hemoglobin level greater than 10%. Additional signs of have shown this combination of medications to decrease
significant injury are an altered voice along with hoarse- reintubation rates and reduce mortality.4446
ness and stridor. Airway security in these patients is
imperative. Fiberoptic bronchoscopy continues to be the
preferred technique for documenting inhalation injury. ASSESSMENT OF BURN DEPTH
Inflammatory changes in the tracheal mucosa such as
edema, hyperemia, mucosal ulceration, and sloughing Burn injury may involve one or both layers of the skin and
can be visualized. A ventilation scan with xenon-133 can may even extend to the subcutaneous fat, muscle, and
also identify regions of inhalation injury by assessing bone.47 First-degree burns involve the epidermis. They
respiratory exchange and excretion of xenon-133 from are erythematous and very painful. Most sunburns fit this
the lungs.37 When combined, bronchoscopy and xenon- category of superficial, epidermal injury. For first-degree
133 scanning are over 90% accurate in the diagnosis of burns, topical ointments may be used for symptom relief
inhalation injury. However, the clinical applicability of and the involved areas should be kept out of the sunlight.
xenon-133 scans remains unclear due to false positives in Superficial second-degree burns (superficial dermal
children with pulmonary disease.38,39 They may also be burns) extend into the papillary dermis. They character-
potentially dangerous due to the need to transport a criti- istically form blisters, but these blisters may not imme-
cally ill burn patient to a nuclear medicine suite. Chest diately follow the injury, making determination of depth
radiographs are not useful as they are often normal difficult (Fig. 13-5). These wounds are painful when
immediately following injury.38,40 Bedside bronchoscopy uncovered. The wound blanches with pressure due to
and a heightened clinical suspicion remain paramount in increased vascularity secondary to vasodilatation. Super-
the diagnosis and treatment of these injuries. ficial second-degree burns are managed with daily dress-
After the airway is secured, an inhalation treatment ing changes with topical antimicrobials. They may also
protocol is utilized in the intensive care unit that focuses be treated with application of petroleum gauze or a
on the clearance of secretions and control of bronchos- synthetic dressing to allow for rapid spontaneous
pasm. One hundred per cent high flow, humidified re-epithelialization. With appropriate care, these wounds
oxygen should be administered to displace CO from will heal spontaneously within two to three weeks without
hemoglobin. Early and aggressive pulmonary therapy the need for excision and grafting.
A B C
FIGURE 13-5 A superficial second-degree burn of the lower extremity is shown. (A) The characteristic blisters seen with this degree
of burn injury. (B) After removal of the blister, the wounds are painful and blanch when pressure is applied. (C) The progress of
healing after several days of daily dressing changes with topical antimicrobials.
13 Burns 171
Antimicrobial Soaks
0.5% Silver nitrate Painless; broad spectrum; rare sensitivity No eschar penetration; discolors
contacted areas; electrolyte imbalance;
methemoglobinemia
Povidone-iodine (Betadine) Broad-spectrum antimicrobial Painful; potential systemic absorption;
hypersensitivity
5% Mafenide acetate Broad-spectrum antimicrobial Painful; no fungal coverage; metabolic
acidosis
0.025% Sodium hypochlorite Effective against most organisms Mildly inhibits epithelialization
(Dakins solution)
0.25% Acetic acid Effective against most organisms Mildly inhibits epithelialization
Silver Impregnated
Aquacel, Acticoat Broad-spectrum antimicrobial; no dressing Cost
changes
Synthetic Dressings
Biobrane Provides wound barrier; minimizes pain; useful Exudate accumulation risks invasive
for outpatient burns, hands (gloves) wound infection; no antimicrobial
property
OpSite, Tegaderm Provides moisture barrier; minimizes pain; Exudate accumulation risks invasive
useful for outpatient burns; inexpensive wound infection; no antimicrobial
property
Transcyte Provides wound barrier; accelerates wound Exudate accumulation risks invasive
healing wound infection; no antimicrobial
property
Integra, Alloderm Complete wound closure, including dermal No antimicrobial property; expensive;
substitute requires training, experience
Biologic Dressings
Allograft (cadaver skin), Temporary biologic dressings Requires access to skin bank; cost
Xenograft (pig skin)
Amniotic membrane Minimizes dressing changes Not widely used
painful which limits its practical use in the outpatient (Aquacel, ConvaTec Ltd., UK; Acticoat, Smith & Nephew,
setting. Sulfamylon is a potent carbonic anhydrase inhibi- London, UK) hold promise for retaining the effectiveness
tor and can therefore cause metabolic acidosis.70 This side of silver nitrate but without its side effects. Several favo-
effect can usually be avoided by limiting its use to only rable clinical trials utilizing these products have been
20% TBSA at any given time, and rotating application conducted and have found these products to be as effec-
sites every several hours with another topical antimicro- tive as traditional dressings utilizing silver nitrate. The
bial agent. products were also noted to be less painful than traditional
Silver nitrate (0.5%) was also introduced in the mid- dressings when applied and removed, and also were asso-
1960s. It is typically used to soak gauze dressings thereby ciated with decreased burn wound cellulitis.7173
avoiding frequent dressing changes with the potential loss Facial burns, small areas of partial-thickness burns,
of grafts or healing cells. Silver nitrate is painless on appli- and healing donor sites require special mention. On
cation and has broad coverage. Unfortunately, the com- superficial facial wounds, silver sulfadiazine may retard
pound can cause hyponatremia and hypochloremia while epithelialization and is not usually placed on the face.74
also creating dark gray or black stains. Another important An alternative is petroleum-based antimicrobial oint-
but infrequent complication is methemoglobinemia, ments. These include polymyxin B, bacitracin, and
which occurs as a result of nitrate reduction by wound polysporin. Their application is painless and transparent
bacteria followed by the systemic absorption of the toxic which allows for easier monitoring. These agents are
nitrite. Dressings containing biologically active silver ions mostly effective against Gram-positive organisms.
13 Burns 173
Proteolytic enzymatic agents have been utilized to aspirated if needed. However, if a foul-smelling exudate
debride wounds, including proteases (sultilains) elabo- is detected, the Biobrane should be removed and an anti-
rated from Bacillus subtilis, collagenase, and papaine-urea. microbial dressing applied. Biobrane is now widely used
Collagen is a protein that is found normally in skin (~75% in the management of superficial second-degree burns as
of dry weight of skin) and is the dominant protein that it reduces pain, fluid, and electrolyte loss. These advan-
must be lysed to allow for eschar separation. Collagenase tages make it an ideal dressing for use in the outpatient
is an exogenous enzyme that breaks down denatured col- setting.79
lagen but does not lyse healthy, normal collagen. Colla- Dressings that are commonly utilized for coverage of
genase Santyl ointment (Healthpoint Biotherapeutics, postoperative incisions may also be used as small super-
Fort Worth, TX) is used in many burn units for the treat- ficial second-degree burn dressings. These alternatives
ment of partial-thickness burns. A multicenter trial of 79 include Duoderm (ER Squibb & Sons, Inc. Princeton
patients ranging in age from 5 to 60 years suggested a NJ), Opsite (Smith & Nephew, London, UK), and Tega-
slight acceleration of wound closure compared to silver derm (3M Pharmaceuticals, St Paul MN). Despite lacking
sulfadiazine.75 A recent prospective randomized study in special biological factors (collagen and growth factors),
children comparing collagenase to silver sulfadiazine these dressings provide a cheap and transparent alterna-
showed equivalent outcomes with regards to skin graft tive to more expensive dressings. Also, Duoderm has
rates, hospitalization, and hospital charges.76 been found to be less expensive than Biobrane and there-
fore could be a first-line treatment option for intermedi-
ate thickness burn wounds in children.80
Burn Wound Dressings The disfigurement resulting from full-thickness burns
The concept of an optimal environment is derived from has been decreased with the advent of combined syn-
the work carried out by Winter in 1962.77 In young pigs, thetic and biologic materials. Integra (Integra LifeSci-
he found that partial-thickness wounds that were kept ences Corp, Plainsboro NJ) has an inner layer composed
moistened with polyethylene film epithelialized twice as of a porous matrix of bovine collagen and the gly-
fast as those left exposed to air. Hinman and Maiback cosaminoglycan chrondroitin-6-sulfate which facilitates
confirmed this observation with a series of human volun- fibrovascular ingrowth.81 The outer layer is a polysiloxane
teers.78 Therefore, for 50 years, it has been felt that a burn polymer with vapor transmission characteristics similar
dressing should provide an optimal environment while to normal epithelium. Integra acts as a dermal replace-
also possessing bacterial inhibition. Typically, burn dress- ment. It provides a matrix for the infiltration of fibro
ings consist of mesh that either contains or are placed blasts, macrophages, lymphocytes, and capillaries from
over antimicrobial compounds. Nonadherent dressings the wound bed, and promotes rapid neo-dermis forma-
such as Telfa (Tyco Healthcare Group LP, Mansfield, tion. Approximately two weeks after engraftment, the
MA), Xeroform (Tyco Healthcare Group LP, Mansfield, outer silicone layer is removed and is replaced with an
MA), Adaptic (Johnson & Johnson, New Brunswick, NJ), epidermal split thickness autograft (Fig. 13-8). Integra
or Mepitel (Molnlycke Health Care AB Gothenburg, covered wounds have less scarring, but are susceptible to
Sweden) can be placed directly on the wound to help infection and must be monitored carefully. Its advantages
reduce both the pain associated with dressing changes were validated in a randomized study in children with
and the friction associated damage to the wound or skin large TBSA burns.82 Children treated with Integra dem-
graft. The nonadherent dressing and antimicrobial com- onstrated significantly decreased resting energy expendi-
pound serve to provide the optimal environment for ture as well as increased bone mineral content and density.
re-epithelialization. Also, improved scarring was found at 24 months after
Further advancements with burn dressings have burn injury.
recently led to a number of synthetic mesh products Biological dressings include xenografts from swine and
designed to adhere to wounds until epithelialization allografts from cadaver donors, such as Alloderm (Life-
has occurred. The benefits of these dressings include less Cell Corp., Branchburg, NJ). They are especially useful
pain related to fewer dressing changes. These dressings for coverage of large full-thickness burns. The dressings
are very effective for superficial partial-thickness wounds. are eventually rejected by the patients immune system
Deep wounds and those with excessive drainage do not and slough. The wound beds become excellent recipient
allow adherence, and therefore, negate the benefits of beds for subsequent autografts. Although extremely rare,
these synthetic dressings. the transmission of viral diseases from the allograft is a
An example of a synthetic mesh product is Biobrane potential concern. These dressings are useful adjuncts
(UCL Laboratories, Rockford IL). It is a bilaminate thin when autografts are not available or time is needed for
membrane composed of thin semipermeable silicone donor sites to heal before being used again for grafting.
bonded to a layer of nylon mesh, which is coated with a
monomolecular layer of type I collagen of porcine origin. Excision and Grafting
This dressing provides a hydrophilic coating for fibrin
ingrowth which promotes wound adherence. The dress- Prompt burn excision and grafting has been shown to
ing is placed on a clean fresh superficial second-degree improve survival, decrease length of hospitalization, and
burn wound and can be secured using steri-strips and/or reduce costs in burn patients of all ages. Children par-
bandages. This dressing is easily removed from the ticularly have benefited from more timely and extensive
wound bed as the wound epithelializes underneath it. operative management.8186 Once a burn is considered
Fluid can accumulate under the dressing and can be deep or fails to heal with topical care, tangential excision
174 SECTION II Trauma
A B
FIGURE 13-8 The use of Integra for a superior cosmetic result in a child with facial burns is depicted. (A) The application of the
Integra with the silicone layer in place. Approximately two weeks after placement, the silicone layer is removed and split thickness
skin grafts are placed. (B) The same child after skin grafting over the Integra.
is needed. This technique was originally described by material should be flushed from the skin with copious
Janzekovic in 1970.87 The eschar is sequentially shaved amounts of water. Chemicals are classified as either
using a dermatome, knife blade or, more recently, a Ver- alkali or acid. Alkalis, such as lime, potassium hydroxide,
sajet (Smith & Nephew, Inc., London, UK) water dissec- sodium hydroxide, and bleach are the common agents
tor until a viable tissue bed is obtained.88 In a prospective involved in chemical injury and cause liquification necro-
randomized trial, the Versajet technique was shown to sis in deep burns. Acid burns are less common and cause
produce a more precise and faster excision than hand- coagulation necrosis. Formic acid injuries are rare but can
held dermatome escharectomy.89 result in multiple systemic organ failure with metabolic
After excision, coverage is ideally completed with an acidosis, renal failure, intravascular hemolysis, and ARDS.
autograph. Split-thickness autografts (0.0080.010 inch Hydrofluoric acid burns are managed with copious water
thickness) are harvested and utilized as a sheet (unmeshed) irrigation and neutralization of the fluoride ion using
or meshed graft. Sheet grafts provide better long-term topical 2.5% calcium gluconate gel. Without this man-
aesthetic outcomes, but are complicated by the develop- agement, free fluoride ion causes liquefaction necrosis of
ment of a seroma or hematoma and also limited coverage. the affected soft tissues, including bones. Because of
Narrow meshed autografts (1:1 or 1:2) have the advan- potential hypocalcemia, patients should be closely moni-
tages of limiting the total surface area of donor harvest tored for prolonged QT intervals.
and allowing better drainage of fluid under the grafted
sites. In larger burns (>2030%), coverage may require a
combination of meshed autograft and allografts. The
Electrical Burns
meshed autografts (4:1 to 6:1) can be covered with Three to 9% of all admitted burn patients are injured
meshed allograft (2:1) overlays.90 Alternatively, grafting from electrical contact.91 Electrical burns are categorized
with sequential harvesting of split-thickness autograft into low- and high-voltage injuries. Low voltage
from limited donor sites until the entire burn wound is (<1000V) injuries typically occur at home where electri-
covered may be needed. The use of a widely meshed graft cal cords are bitten especially by younger children (Fig.
is avoided on the face and functionally important parts of 13-9). High-voltage (>1000V) injuries may result from
the hand. Full-thickness grafts that include both dermal power lines or lightning strikes, and are characterized by
and epidermal components are commonly obtained from a varying degree of local burn with destruction of deep
the lower abdomen, groin, or upper arm. These grafts tissues.92 The electrical current enters the body and
provide the best outcome for wound coverage with travels preferentially through the low resistance tissues
diminished contracture and a better pigment match, but (nerves, blood vessels, and muscles). As skin has high
their use is generally limited due to the lack of donor resistance, it is mostly spared leaving little visible evi-
sites. dence of injury. Primary and secondary surveys, including
electrocardiography, are very important. If the initial
electrocardiogram is normal, further cardiac monitoring
NONTHERMAL INJURIES is not needed. However, any abnormal findings require
Chemical Burns continued monitoring for 48 hours and appropriate man-
agement of dysrhythmias if detected.93 Injuries to deep
Cleaning products pose a risk for accidental exposure and tissues and organs must be identified and treated. As
chemical burns. The chemical agent responsible for the tissue edema worsens, patients may develop compart-
injury should be identified. Contacting poison control is ment syndromes requiring fasciotomy to avoid limb loss.
often necessary. During the initial evaluation, all caustic Myoglobinuria can lead to renal failure and should be
13 Burns 175
44. Saliba MJ Jr. Heparin in the treatment of burns: A review. Burns 69. Lindberg RB, Moncrief JA, Mason AD Jr. Control of experimental
2001;27:34958. and clinical burn wounds sepsis by topical application of sulfamylon
45. Desai MH, Micak R, Richardson J, et al. Reduction in mortality in compounds. Ann N Y Acad Sci 1968;150:95060.
pediatric patients with inhalation injury with aerosolized heparin/ 70. Asch MJ, White MG, Pruitt BA Jr. Acid base changes associated
N-acetylcystine [correction of acetylcysteine] therapy. J Burn Care with topical Sulfamylon therapy: Retrospective study of 100 burn
Rehabil 1998;19:21012. patients. Ann Surg 1970;172:94650.
46. Brown M, Desai M, Traber LD, et al. Dimethylsulfoxide with 71. Fong J, Wood F, Fowler B. A silver coated dressing reduces the
heparin in the treatment of smoke inhalation injury. J Burn Care incidence of early burn wound cellulitis and associated costs of
Rehabil 1988;9:225. inpatient treatment: Comparative patient care audits. Burns
47. Forage AV. The history of the classification of burns (diagnosis of 2005;31:5627.
depth). Br J Plastic Surg 1963;16:23942. 72. Tredget EE, Shankowsky HA, Groeneveld A, et al. A matched-pair,
48. Engrav LH, Heimbach DM, Reus JL, et al. Early excision and randomized study evaluating the efficacy and safety of Acticoat
grafting vs. nonoperative treatment of burns of indeterminate silver-coated dressing for the treatment of burn wounds. J Burn
depth: A randomized prospective study. J Trauma 1983;11: Care Rehabil 1998;19:5317.
10014. 73. Varas RP, OKeeffe T, Namias N, et al. A prospective, randomized
49. Hlava P, Moserov J, Knigov R. Validity of clinical assessment of trial of Acticoat versus silver sulfadiazine in the treatment of partial-
the depth of a thermal injury. Acta Chir Plas 1983;25:2028. thickness burns: Which method is less painful? J Burn Care Rehabil
50. Niazi ZB, Essex TJ, Papini R, et al. New laser Doppler scanner, 2005;26:3447.
a valuable adjunct in burn depth assessment. Burns 1993;19: 74. Muller MJ, Hollyoak MA, Moaveni Z, et al. Retardation of wound
4859. healing by silver sulfadiazine is reversed by Aloe vera and nystatin.
51. Yeong EK, Mann R, Goldberg M, et al. Improved accuracy of burn Burns 2003;29:8346.
wound assessment using laser Doppler. J Trauma 1996;40: 75. Hansbrough JF, Achauer B, Dawson J, et al. Wound healing in
95661. partial-thickness burn wounds treated with collagenase ointment
52. Ho-Asjoe M, Chronnell CM, Frame JD, et al. Immunohistochemi- versus silver sulfadiazine cream. J Burn Care Rehabil 1995;
cal analysis of burn depth. J Burn Care Rehabil 1999;20:20711. 16:2417.
53. Moserov J, Hlava P, Malnsk J. Scope for ultrasound diagnosis of 76. Ostlie DJ, Juang D, Aguayo P, et al. Topical silver sulfadiazine vs
the depth of thermal damage. Preliminary report. Acta Chir Plast collagenase ointment for the treatment of partial thickness burns
1982;24:23542. in children: A prospective randomized trial. J Pediatr Surg
54. Cantrell JH Jr. Can ultrasound assist an experienced surgeon in 2012;47:12047.
estimating burn depth? J Trauma 1984;24:S6470. 77. Winter GD. Formation of the scab and the rate of epithelization
55. Kaufman T, Hurwitz DJ, Heggers JP. The india ink injection tech- of superficial wounds in the skin of the young domestic pig. Nature
nique to assess the depth of experimental burn wounds. Burns Incl 1962;193:2934.
Therm Inj 1984;10:4058. 78. Hinman CD, Maibach H. Effect of air exposure and occlusion on
56. Black KS, Hewitt CW, Miller DM, et al. Burn depth evaluation experimental human skin wounds. Nature 1963;200:3778.
with fluorometry: Is it really definitive? J Burn Care Rehabil 79. Paddock HN, Fabia R, Giles S, et al. A silver-impregnated antimi-
1986;7:31317. crobial dressing reduces hospital length of stay for pediatric patients
57. Pape SA, Skouras CA, Byrne PO. An audit of the use of laser with burns. J Burn Care Res 2007;28:40911.
Doppler imaging (LDI) in the assessment of burns of intermediate 80. Cassidy C, St Peter SD, Lacey S, et al. Biobrane versus duoderm
depth. Burns 2001;27:2339. for the treatment of intermediate thickness burns in children:
58. Hackett ME. The use of thermography in the assessment of depth A prospective, randomized trial. Burns 2005;31:8903.
of burn and blood supply of flaps, with preliminary reports on its 81. Tompkins RG, Burke JF. Progress in burn treatment and the use
use in Dupuytrens contracture and treatment of varicose ulcers. Br of artificial skin. World J Surg 1990;14:81924.
J Plast Surg 1974;27:31117. 82. Branski LK, Herndon DN, Pereira C, et al. Longitudinal assess-
59. Erba P, Espinoza D, Koch N, et al. FluxEXPLORER: A new high- ment of Integra in primary burn management: A randomized pedi-
speed laser Doppler imaging system for the assessment of burn atric clinical trial. Crit Care Med 2007;35:261523.
injuries. Skin Res Technol 2012;18:45661. 83. Herndon DN, Parks DH. Comparison of serial debridement and
60. Mihara K, Shindo H, Ohtani M, et al. Early depth assessment of autografting and early massive excision with cadaver skin overlay
local burns by videomicroscopy: 24h after injury is a critical time in the treatment of large burns in children. J Trauma
point. Burns 2011;37:98693. 1986;26:14952.
61. Desai MH, Rutan RL, Herndon DN. Conservative treatment of 84. Herndon DN, Gore D, Cole M, et al. Determinants of mortality
scald burns is superior to early excision. J Burn Care Rehabil in pediatric patients with greater than 70% full-thickness total body
1991;12:4824. surface area thermal injury treated by early total excision and graft-
62. Kumar RJ, Kimble RM, Boots R, et al. Treatment of partial- ing. J Trauma 1987;27:20812.
thickness burns: A prospective, randomized trial using Transcyte. 85. Muller MJ, Herndon DN. The challenge of burns. Lancet
ANZ J Surg 2004;74:6226. 1994;343:21620.
63. Costagliola M, Agros M. Second-degree burns: A comparative, 86. Bull JP, Fisher AJ. A study of mortality in a burns unit: A revised
multicenter, randomized trial of hyaluronic acid plus silver estimate. Ann Surg 1954;139:26974.
sulfadiazine vs. silver sulfadiazine alone. Curr Med Res Opin 87. Janzekovic Z. A new concept in the early excision and immediate
2005;21:123540. grafting of burns. J Trauma 1970;10:11038.
64. Soroff HS, Sasvary DH. Collagenase ointment and polymyxin B 88. Klein MB, Hunter S, Heimbach DM, et al. The Versajet water
sulfate/bacitracin spray versus silver sulfadiazine cream in partial- dissector: A new tool for tangential excision. J Burn Care Rehabil
thickness burns: A pilot study. J Burn Care Rehabil 1994;15: 2005;26:4837.
1317. 89. Gravante G, Delogu D, Esposito G, et al. Versajet hydrosurgery
65. Fox CL Jr. Silver sulfadiazinea new topical therapy for Pseu- versus classic escharectomy for burn debridment: A prospective
domonas in burns. Therapy of Pseudomonas infection in burns. randomized trial. J Burn Care Res 2007;28:7204.
Arch Surg 1968;96:1848. 90. Alexander JW, MacMillan BG, Law E, et al. Treatment of severe
66. Desai MH, Rutan RL, Heggers JP, et al. Candida infection with burns with widely meshed skin autograft and meshed skin allograft
and without nystatin prophylaxis. A 11-year experience with overlay. J Trauma 1981;21:4338.
patients with burn injury. Arch Surg 1992;127:15962. 91. Celik A, Ergun O, Ozok G. Pediatric electrical injuries: A review
67. Jarrett F, Ellerbe S, Demling R. Acute leukopenia during topical of 38 consecutive patients. J Pediatr Surg 2004;39:12337.
burn therapy with silver sulfadiazine. Am J Surg 1978;135: 92. Laberge LC, Ballard PA, Daniel RK. Experimental electrical burns:
81819. Low voltage. Ann Plast Surg 1984;13:18590.
68. Choban PS, Marshall WJ. Leukopenia secondary to silver sulfadi- 93. Robson MC, Smith DJ. Care of the thermal injured victim. In:
azine: frequency, characteristics and clinical consequences. Am Jurkiewicz MJ, Krizek TJ, Mathes SJ, Ariyan S, editors. Plastic
Surg 1987;53:51517. Surgery: Principles and Practice. St. Louis, CV: Mosby; 1990.
C H A P T E R 1 4
Trauma is the leading cause of morbidity and mortality responsible for approximately 75% of all childhood
in children from ages 1 to 14 years. It results in more deaths, which are evenly split between those due to
disability and death than all other childhood diseases pedestrian trauma and those resulting from occupant
combined.1 More than 10,000 pediatric patients die from injuries (Table 14-1).
trauma in the USA each year.1 Approximately 10% of
pediatric hospitalizations,2 15% of pediatric intensive
care unit (PICU) admissions,3 25% of pediatric emer- INJURY RISKS
gency department visits,4 and 50% or more of pediatric
ambulance runs are due to trauma.5 Moreover, it also The lack of adequate supervision of children during play
represents nearly 20% of hospitalizations for serious involving possible injury hazards is recognized as a major
injury among all age groups combined.6 risk factor for unintentional injury in pediatric patients.
However, drug and alcohol use, obesity, poverty, and race
also influence injury frequency. Toxicology screens are
TRAUMA EPIDEMIOLOGY reportedly positive in 1040% of injured adolescents,
while obese children and adolescents appear to have
Several injury severity scales exist in practice and in the more complications and require longer stays in the inten-
literature. The large number of injury severity scales sive care unit.1013 Socioeconomic status has also been
arises from the markedly different perspectives used in associated with increased hospitalization and mortality
the application of the scales. The Abbreviated Injury following major trauma, owing to a higher frequency and
Scale (AIS), primarily an anatomical measure of injury more lethal mechanisms of injury, rather than injury
severity, was the first widely implemented scale used in severity.14 Race and ethnicity affect injury risk independ-
practice. Criticism of the AIS included the inability to ent of socioeconomic status, particularly among African-
take into account multiple injuries to the same body American children, whose rate of death from preventable
region and the poor correlation of the AIS with severity injuries, head injuries, and child abuse is three to six times
and survival. The Injury Severity Score (ISS), New Injury higher than that of white children.1518 Improper use of
Severity Score (NISS) and Pediatric Trauma Score (PTS) restraints may contribute to the increased fatality rates
are just some examples of scoring systems developed to observed in African-American children, who are half as
overcome the issues described. Despite the controversies likely to be restrained as white children when involved in
in these scales, it is commonly accepted that injuries motor vehicle crashes (MVCs) and one-third as likely to
whose severity are a threat to life correspond to an ISS be placed in car seats during MVCs.19
of 10 or higher, or a PTS of 8 or lower.2 Analysis of the Crash Injury Research Engineering
The incidence of serious traumatic injury is approxi- Network (CIREN) database has recently yielded valuable
mately 420/100,000.7 Although the hospital-based fatal- information about the pattern of childhood injuries after
ity rate is 2.4/100,000, the population-based mortality MVCs: (1) child victims in frontal crashes are more likely
rate is 11.8/100,000, indicating that 78% of lethally to suffer severe spine and musculoskeletal injuries; (2)
injured children die before hospital admission and dem- those in lateral crashes are more likely to suffer head and
onstrating the need for effective injury prevention and chest injuries; (3) those in front seats sustain more inju-
prehospital care.8 ries to the chest, abdomen, pelvis, and axial skeleton than
Blunt injuries outnumber penetrating injuries in chil- those in the rear seats; (4) seat belts are especially protec-
dren by a ratio of 12:1, a ratio that has decreased some- tive against pelvic and musculoskeletal injuries; (5) chil-
what in recent years. While blunt injuries are more dren involved in high-severity, lateral-impact crashes
common, penetrating injuries are more lethal. However, typically sustain injuries characterized by higher ISS
despite the decline in penetrating injuries, firearm related and lower Glasgow Coma Scale (GCS) scores.20,21
deaths continue as one of the top three causes of death Restraint devices have also been subjected to careful
in the American youth. Most blunt trauma in childhood analysis in recent years: (1) they do not appear to protect
is sustained unintentionally, but between 510% of young victims of MVCs as well as older victims; (2) car
serious injuries are due to intentional physical assault (of seats may not significantly affect injury outcome; (3)
which half are due to physical abuse).9 Still, the leading improper application may predispose to abdominal inju-
cause of death in children is the motor vehicle, ries, even in low-severity crashes; (4) the presence of
177
178 SECTION II Trauma
Economics
Education
Engineering
the Major Categories of
Enforcement
Pediatric Trauma
Host Agent Environment
By Injury Mechanism Incidence (%) Mortality (%)
Blunt 92 3
Fall 32 0.3 Pre-event
Motor vehicle traffic 25 3 (primary
Struck by, against 11 0.5 prevention)
Pedal cyclist, other 3.7 0.25
Penetrating 8
Gunshot wound 4.5 12 Event
Stabbing 3.5 1.3 (secondary
prevention)
Data from the American College of Surgeons, National
Trauma Data Bank 2012. Post-event
(tertiary
prevention)
abdominal wall bruising in restrained children, although
not commonly observed, is frequently indicative of intra- FIGURE 14-1 The Haddon Factor Phase Matrix, as modified and
abdominal injury.2227 refined to include a third strategic dimension, integrates all
phases of injury control into a single system. (Adapted from
Haddon W. Advances in the epidemiology of injuries as a basis for
public policy. Public Health Rep 1980;95:41121; and Runyan CW.
INJURY OUTCOMES Using the Haddon Matrix: Introducing the third dimension. Inj Prev
1998;4:3027.)
In recent years, much effort has been devoted to out-
comes research in pediatric trauma with the hope that engineering, education, and economics as techniques to
benchmarking of treatment results may lead to better limit the adverse impact of each factor.
care for injured children. Both historical studies and con- Effective injury-prevention programs are community-
temporary investigations indicate that children survive based and require extensive collaboration with civic
more frequently and recover more fully in hospitals that leaders, governmental agencies, community-based organ-
specialize in pediatric trauma than in other hospitals.2845 izations, and neighborhood coalitions. Programs such
No less important than survival outcome is functional as the National Safe Kids Campaign (http://www
outcome, for which numerous studies now indicate .safekids.org) and the Injury Free Coalition for Kids
improved outcomes in hospitals that specialize in pediat- (http://www.injuryfree.org) have proven highly successful
ric trauma care.3246 However, these studies also suggest in reducing the burden of childhood injury in many
that whereas children may recover from injury more communities.
quickly than adults, physical function may not fully nor-
malize. Even so, self-perceived long-term quality of life
among seriously injured children may not be adversely INJURY PATTERNS
affected, justifying an aggressive approach to their
resuscitation.47 Injury mechanism is the main predictor of injury pattern.
Perhaps the most important recent development for The body regions most frequently injured in major child-
outcomes research in pediatric trauma has been the hood trauma are the lower extremities, head and neck,
expansion of the National Trauma Data BankTM and abdomen. In minor childhood injury, soft tissue and
(NTDBTM) of the American College of Surgeons (ACS) upper extremity injuries predominate. Motor vehicle
to include children. Initially designed as a simple case versus pedestrian trauma results in the Waddell triad of
repository, efforts continue to analyze submitted cases to injuries to the head, torso, and lower extremity (pelvis,
provide population estimates of severe pediatric injury femur, or tibia; Fig. 14-2). Motor vehicle accidents may
and develop quality benchmarks for pediatric trauma cause head, face, and neck injuries in unrestrained pas-
care. Preliminary data suggest that these benchmarks sengers. Cervical spine injuries, bowel disruption or
perform as well as existing measures.48 hematoma, and Chance fractures occur in restrained pas-
sengers (Fig. 14-3). Bicycle trauma results in head injury
in the unhelmeted riders as well as upper extremity and
INJURY PREVENTION upper abdominal injuries, the latter the result of contact
with the handlebar (Fig. 14-4 and Table 14-2). Direct
Injuries are not accidents, but rather predictable events impact from a bicycle handlebar remains highly predic-
that respond to harm-reduction strategies similar to tive of the need for operation.27
those applied for other diseases. The Haddon Factor
Phase Matrix neatly depicts these in graphic form (Fig.
14-1).49 Strategies to lessen the burden of injury are
Head
applied to the host, agent, and environment before, Head injuries are potentially more dangerous in children
during, and after the traumatic event using enforcement, than in adults for several reasons. First, developing neural
14 Early Assessment and Management of Trauma 179
Bowel injury FIGURE 14-4 Children riding bicycles can sustain blunt abdomi-
nal trauma after contact with handlebars or head trauma from
falling off the bicycle. (From Foltin G, Tunik M, Cooper A, etal,
editors. Teaching Resource for Instructors of Prehospital Pediatrics.
Vertebral New York: Center for Pediatric Emergency Medicine; 1998.)
fracture
Abdomen Skeleton
Serious intra-abdominal injuries occur in 8% of pediatric Although they are the leading cause of disability, fractures
blunt trauma victims and are caused by crushing the solid are rarely an immediate cause of death from blunt trauma.
14 Early Assessment and Management of Trauma 181
They are reported to occur in 26% of serious blunt- achieved without placing an approximate 2.5cm layer of
injury cases and constitute the principal anatomic diag- padding beneath the torso from shoulders to hips) and
nosis in 22%.9 Upper extremity fractures outnumber careful strapping (because forced vital capacity may be
lower extremity fractures by 7:1, although, in serious decreased by up to 60%).69,70 One study suggested that
blunt trauma, this ratio is 2:3. The most common long cervical spine immobilization can be safely avoided in
bone fractures sustained during pedestrian/MVCs in most pediatric trauma patients with minor injuries, but
children are fractures of the femur and tibia. Falls are caution was urged in view of the known risks of
typically associated with both upper and lower extremity SCIWORA and atlanto-axial instability.71 Advanced life
fractures if the fall height is significant (from the window support of the pediatric trauma patient theoretically adds
of a high-rise dwelling or the top of a bunk bed, but not endotracheal intubation and volume resuscitation to this
from falls from standard beds or down stairs).6265 Because armamentarium, but neither intervention has been shown
isolated long bone and stable pelvic fractures are infre- to improve outcome.7276
quently associated with significant hemorrhage, a diligent Field triage of pediatric trauma patients to pediatric
search must be made for another source of bleeding if trauma centers is now well established. Regional proto-
signs of shock are observed.66,67 Unstable pelvic fractures cols should direct ambulance transports to such centers
are an uncommon feature of childhood injury, but uni- where available. The use of scoring systems to assist in
lateral (type III) or bilateral (type IV) anterior and pos- predicting the need for specialty pediatric trauma care,
terior disruptions are those most often associated with such as the PTS and the Revised Trauma Score (RTS),
major hemorrhage and must be recognized early and may reliably predict the need for specialty pediatric
treated.68 trauma care but neither is optimally sensitive nor specific
The pediatric skeleton is susceptible to fractures (Table 14-4).77,78 The most sensitive and specific indica-
because cortical bone in childhood is highly porous tors for the need for specialty pediatric trauma care are:
whereas the periosteum is more resilient, elastic, and a score of 1 in best motor response in the calculation of
vascular. This results in higher percentages both of the GCS or a selection of unresponsive/unconscious in
incomplete (torus and greenstick) fractures and complete, the calculation of an AVPU Score.79 Good results also
but nondisplaced fractures. Long-term growth distur- have been achieved by using checklists to identify ana-
bances also may complicate childhood fractures. Diaphy- tomic, physiologic, and mechanistic criteria (Box 14-1)
seal fractures of the long bones cause significant rather than calculated scores. These checklists are cur-
overgrowth whereas physeal (growth plate) fractures rently advocated by the ACS Committee on Trauma,
cause significant undergrowth. Both result in limb length based upon the advice of an expert panel convened in
discrepancies unless treated. 2011 by the United States Centers for Disease Control
and Prevention (CDC).80
Secondary Survey
History and physical: SAMPLE history, complete
examination
identifies a pelvic fracture. If a pelvic fracture is suspected
Imaging studies: plain radiographs,c special studiesd on physical examination, a computed tomography (CT)
scan should be obtained.83,84
a
Meatal blood, scrotal hematoma, high-riding prostate.
b
CSF oto-rhinorrhea, basilar skull fracture, midface instability.
c
Chest, pelvis, lateral cervical spine; others as indicated. Resuscitation
d
FAST, CT as indicated.
GCS, Glasgow Coma Scale; CSF, cerebrospinal fluid; FAST, focused Any child initially seen with major trauma should receive
assessment by sonography in trauma; CT, computed tomography. breathing support with high-concentration oxygen by the
Adapted from American College of Surgeons Committee on Trauma. Advanced most appropriate means. For the child with respiratory
Trauma Life Support ATLS Student Course Manual. 9th ed. Chicago:
American College of Surgeons; 2012.
distress (increased work of breathing), a nonrebreather
mask normally will suffice, provided the airway is open
and breathing is spontaneous. For the child with signifi-
cant respiratory distress (labored or inadequate work of
BOX 14-2 Disability/Mental Status breathing), assisted ventilation via face-mask or an
Pupils: symmetry, reaction
endotracheal tube (ETT) attached to a bag-valve device
LOC: GCS should be immediately available. Endotracheal intuba-
Track and trend as a vital sign tion with rapid-sequence induction techniques is neces-
Significant change, 2 points sary in respiratory failure.
Intubate for coma, GCS 8 The first step in management of the circulation is
Motor: strength, symmetry control of bleeding. Direct pressure using sterile dress-
Abnormality/deterioration: call neurosurgeon ings is applied to all actively bleeding external wounds.
Traumatic Brain Injury Blind clamping is avoided, owing to the potential risk of
Mild (GCS 13-15): observe, consider CT for history of injury to neurovascular bundles. Military experience sug-
LOC gests that commercial arterial tourniquets, and topical
Moderate (GCS 9-12): admit, obtain CT, repeat CT
1224hr
hemostatic agents such as chitosan granules or powder,
Severe (GCS 3-8): intubate, ventilate, obtain CT, repeat zeolite granules, and kaolin clay, are effective in stopping
CT 1224hr major arterial hemorrhage, and massive arteriolar,
venular, and capillary oozing from large open wounds.
CT, computed tomography; GCS, Glasgow Coma Scale; LOC, loss of Recent data suggests equivalent effectiveness for tourni-
consciousness. quets in children.85 However, because no reports of
Adapted from American College of Surgeons Committee on Trauma. Advanced
Trauma Life Support ATLS Student Course Manual. 9th ed. Chicago:
topical hemostatic agent use in children have been pub-
American College of Surgeons; 2012. lished to date, no recommendation can be made regard-
ing its applicability in civilian pediatric trauma.
The child with significant trauma will require volume
be completed to identify and correct deficits that pose an resuscitation if signs of hypovolemic shock are present.
immediate threat to life. The primary survey continues Intraosseous access should be used if conventional intra-
with complete exposure of the patient to ensure that no venous access with peripheral large bore catheters is not
injuries are missed, taking care to avoid hypothermia. rapidly obtainable. Central venous catheter insertion,
The placement of therapeutic adjuncts, such as a urinary except in cases when venous access cannot otherwise
and gastric catheter (unless contraindicated), is also com- readily be obtained, is not warranted. Simple hypovo-
pleted during this initial survey. Diagnostic adjuncts, such lemia usually responds to 2040mL/kg of warmed
as pulse oximetry, radiographs, and focused assessment lactated Ringers solution. However, frank hypotension
by sonography in trauma (FAST), facilitate the early rec- (defined clinically by a systolic blood pressure less
ognition and treatment of immediate threats to vital than 70mmHg plus twice the age in years) typically
functions (Box 14-3). The complete trauma series of requires 4060mL/kg of warmed lactated Ringers
radiographs obtained as an adjunct to the primary survey solution followed by 1020mL/kg of warmed packed
in adults may not always be necessary in children, since red blood cells. To avoid the greater mortality associated
the lateral cervical spine radiograph will not detect with coagulopathy and shock on hospital admission, a
SCIWORA, and the screening pelvic radiograph seldom 1:1:1 or 2:1:1 ratio with fresh frozen plasma and
14 Early Assessment and Management of Trauma 183
platelet concentrates should be instituted when massive in serum levels of transaminases or amylase and lipase
uncontrolled hemorrhage is present and a massive trans- suggest injury to the liver or pancreas, but the infre-
fusion protocol is invoked.8688 Urinary output should be quency of pancreatic injury makes the latter cost ineffec-
measured in all seriously injured children as an indication tive versus the former.99,100 Urine that is grossly bloody
of tissue perfusion. The minimum urinary output that or is positive for blood by dipstick or microscopy (>50
indicates adequate renal perfusion is 2mL/kg/h in red blood cells per high-power field) suggests kidney
infants, 1mL/kg/h in children, and 0.5mL/kg/h in trauma.101
adolescents. Selective radiologic evaluation is another important
Due to the ability of a childs blood vessels to compen- part of the secondary survey. CT of the head (without
sate vigorously for hypovolemia by intense vasoconstric- contrast) and abdomen (intravenous and oral) should be
tion, systolic hypotension is a late sign of shock and may obtained as indicated. However, CT should be employed
not develop until 3035% of circulating blood volume is only when the short-term benefit of accurate diagnosis is
lost.89 Thus, any child who cannot be stabilized after felt to outweigh the long-term risk of late malignancy,
infusion of 4060mL/kg of lactated Ringers solution particularly for body regions such as the cervical spine
and 1020mL/kg of packed red blood cells likely has and the thorax for which conventional imaging is ade-
internal bleeding and needs an operation. If a child ini- quate. When utilized, the CT should be performed using
tially is in shock, has no signs of intrathoracic, intra- radiation doses as low as reasonably achievable (ALARA),
abdominal, or intrapelvic bleeding, but fails to improve consistent with the image gently protocols advocated
despite seemingly adequate volume resuscitation, other by The Alliance for Radiation Safety in Pediatric
forms of shock (obstructive, cardiogenic, neurogenic) Imaging.102108
should be considered. Most children in hypotensive CT of the head should be performed whenever loss of
shock are victims of unrecognized hemorrhage that can consciousness has occurred, or if the GCS score is <15.109
be reversed only if promptly recognized and appropri- It can be safely avoided in children <2 years of age with:
ately treated by means of rapid blood transfusion and (1) normal mental status; (2) no scalp hematoma except
immediate intervention, particularly if major intratho- frontal; (3) no loss of consciousness or loss of conscious-
racic or intra-abdominal vessels are injured.9093 ness for less than five seconds; (4) nonsevere injury mech-
anism; (5) no palpable skull fracture; and (6) normal
activity according to parents. Recommendations for not
Secondary Survey obtaining a head CT in children 2 years of age and older
Once the primary survey has been performed, and the include: (1) normal mental status; (2) no loss of conscious-
resuscitation phase is ongoing, a secondary survey is ness; (3) no vomiting; (4) nonsevere injury mechanism;
undertaken. This consists of a SAMPLE history (symp- (5) no signs of basilar skull fracture; and (6) no severe
toms, allergies, medications, past illnesses, last meal, headache.110 CT of the chest adds little to what is already
events, and environment) and a complete head-to-toe known from the chest radiograph obtained during the
physical examination (including all body regions and primary survey, since the incidental pulmonary contu-
organ systems). The physicians chief responsibility is to sions identified by CT of the chest do not correlate with
identify life-threatening injuries that may have been increased fatality.111,112 CT of the cervical spine may facili-
overlooked during the primary survey, such as a tension tate earlier identification of vertebral injury, but does so at
pneumothorax. Physical findings will also assist in deter- the cost of increased radiation dose.113 CT of the abdomen
mining other injuries that are not readily apparent. For should be obtained: (1) in intubated patients; (2) with
example, drainage from the nose or ears, or any evidence signs of internal bleeding (abdominal tenderness, disten-
of midface instability, suggests a basilar skull fracture tion, bruising, or gross hematuria), a history of hypoten-
(which precludes passage of a nasogastric tube) or an sive shock (which has responded to volume resuscitation),
oromaxillofacial fracture (which may threaten the airway). or a hematocrit <30%; (3) if a femur fracture is evident;
All skeletal components should be palpated for evidence (4) if serum transaminase levels are elevated; (5) if signifi-
of instability or discontinuity, especially bony promi- cant microscopic hematuria is present, or (6) if the mecha-
nences such as the anterior superior iliac crests, which nism of injury is deemed significant.114,115
commonly are injured in major blunt trauma. In the Sonography serves an adjunctive role in the imaging
absence of obvious deformities, fractures should be sus- of pediatric trauma. FAST itself is most useful in detect-
pected if bony point tenderness, hematoma, spasm of ing intra-abdominal blood, but is not sufficiently reliable
overlying muscles, an unstable pelvic girdle, or perineal to exclude blunt abdominal injury, although it does have
swelling or discoloration is found. the advantage that such injuries can be detected by
Selective laboratory evaluation is an integral part of repeated examination.116123 Therefore, like its historical
the secondary survey, although routine trauma laboratory predecessor diagnostic peritoneal lavage, FAST adds
panels are of limited utility owing to their relatively low relatively little to the management of pediatric abdominal
sensitivity and specificity.9496 Arterial blood gases are trauma, since unstable patients with presumed intra-
important in determining the adequacy of ventilation abdominal injuries need immediate operation, while
(PsCO2), oxygenation (PsO2), and perfusion (base stable patients are managed nonoperatively without
deficit).97,98 However, the critically important determi- regard to the presence of intra-abdominal blood.124128
nant of blood oxygen content is the blood hemoglobin However, diagnostic sonography has been successfully
concentration. Serial hemoglobin values better reflect the used in screening for intra-abdominal injuries when
extent of blood loss than does the initial value. Elevations abdominal CT is unavailable or contraindicated.129
184 SECTION II Trauma
development of lead poisoning (especially those in contact receiving hospital to the pediatric trauma center is
with bone or joint fluid).143 Thoracotomy is usually not needed. Transport providers must be capable of critical
required except for massive hemothorax (20mL/kg) or pediatric assessment and monitoring, and skilled in the
ongoing hemorrhage (24mL/kg/h) from the chest tube, techniques of endotracheal intubation and vascular access,
persistent massive air leak, or food or salivary drainage as well as drug and fluid administration in children.162,163
from the chest tube. Laparotomy is nearly always required Specialized pediatric transport teams, staffed by physi-
for gunshot wounds as well as stab wounds associated cians and nurses with advanced training in pediatric
with hemorrhagic shock, peritonitis, or evisceration, trauma and critical care treatment and transport, should
although nonoperative management may be employed be used whenever possible, as complications related to
in carefully selected cases.144 Thoracoabdominal injury endotracheal intubation and vascular access are the
should be suspected whenever the torso is penetrated leading causes of adverse events during transport, which
between the nipple line and the costal margin. A dia- occur twice as often as in the PICU and ten times more
phragmatic injury should be suspected if peritoneal irrita- often without a specialized team.164,165
tion develops after thoracic penetration, food or chyle is
recovered from the chest tube, or if injury-trajectory or
imaging studies suggest the possibility of diaphragmatic
Hospital Preparedness
penetration. Tube thoracostomy, followed by laparotomy Regional pediatric trauma centers should be located in
for repair of the diaphragm and/or damaged organs, trauma hospitals with comprehensive pediatric services (a
is mandated with such signs, although laparoscopy is full-service general, university, or childrens hospital) that
being used with increasing frequency.145148 demonstrate an institutional commitment to pediatric
trauma care, including child abuse.2847,150 Adult trauma
centers can achieve results comparable to those of pedi-
Systems Issues atric trauma centers if pediatric subspecialty and nursing
Pediatric patients, at significant risk for death from mul- support (pediatric emergency, acute care, and critical
tiple and severe injuries, are best served by a fully inclu- care medicine) are available.3847,150 Finally, an organized
sive trauma system that incorporates all appropriate pediatric trauma service must be available within the
health care facilities and personnel to the level of their regional pediatric trauma center that, in addition to
resources and capabilities.149,150 Unfortunately, access to exemplary patient care, provides education and research
specialty pediatric trauma care, including pediatric inten- in pediatric trauma, and leadership in pediatric trauma
sive care, remains highly variable.151,152 Moreover, col- system coordination.
laboration with local public health agencies (in programs
for injury prevention and control), as well as local public REFERENCES
health, public safety, and emergency-management agen- 1. National Center for Injury Prevention and Control. CDC Injury
cies (in regional disaster-planning efforts) is neces- Fact Book. Atlanta: Centers for Disease Control and Prevention;
sary.149,150 Although the regional trauma center is at the 2006.
hub of the system, area trauma centers may be needed in 2. Buie VC, Owings MF, DeFrances CJ, et al. National Hospital
Discharge Survey: 2006 Summary. National Center for Health
localities distant from the regional trauma center. All Statistics. Vital Health Stat 2010;13(168).
trauma centers, whether adult or pediatric, must be 3. Klem SA, Pollack MM, Glass NL, et al. Resource use, efficiency,
capable of the initial management of the injured child or and outcome prediction in pediatric intensive care of trauma
infant. This requires the immediate availability of a resus- patients. J Trauma 1990;30:326.
citation team trained and credentialed for the manage- 4. Krauss BS, Harakal T, Fleisher GR. The spectrum and frequency
of illness presenting to a pediatric emergency department. Pediatr
ment of pediatric trauma, for which structured review Emerg Care 1991;7:6771.
and simulation training have been shown to improve 5. Tsai A, Kallsen G. Epidemiology of pediatric prehospital care.
team performance, while family presence during resusci- Ann Emerg Med 1987;16:28492.
tation rarely hinders it.153158 All other hospitals in the 6. Hale GC, Caudill SA, Hicks-Waller CM, et al. The New York
State Trauma System: A Special Report on Pediatric Trauma.
region should participate as they are able, and must be Albany, NY: New York State Department of Health; 2002.
fully capable of initial resuscitation, stabilization, and 7. Tepas JJ, Ramenofsky ML, Mollitt DL, et al. The pediatric trauma
transfer of pediatric trauma patients. Finally, a regional score as a predictor of injury severity: An objective assessment.
trauma advisory committee should include pediatric rep- J Trauma 1988;28:4259.
resentation that has the authority to develop and imple- 8. Cooper A, Barlow B, Davidson L, et al. Epidemiology of pediatric
trauma: Importance of population-based statistics. J Pediatr Surg
ment guidelines for triage of pediatric trauma within the 1992;27:14954.
system to verified pediatric-capable trauma centers.159,160 9. DiScala C. National Pediatric Trauma Registry Annual Report.
Mature systems should expect that seriously injured pedi- Boston: Tufts University Rehabilitation and Childhood Trauma
atric patients will be primarily transported to pediatric Research and Training Center; 2002.
10. Ehrlich PF, Brown JK, Drogonowski R. Characterization of the
trauma centers.161 drug-positive adolescent trauma population: Should we, do we,
and does it make a difference if we test? J Pediatr Surg 2006;
Transport Issues 41:92730.
11. Draus JM, Santos AP, Franklin GA, et al. Drug and alcohol use
Pediatric victims of multisystem trauma should undergo among adolescent blunt trauma patients: Dying to get high?
J Pediatr Surg 2007;43:20811.
direct primary transport from the injury scene to a 12. Ehrlich PF, Drogonowski A, Swisher-McClure S, et al. The
pediatric-capable trauma center.2847,82,150 If this is not importance of a preclinical trial: A selected intervention program
possible, additional secondary transport from the initial for pediatric trauma centers. J Trauma 2008;65:18995.
186 SECTION II Trauma
13. Brown CVR, Nevill AL, Salim A, et al. The impact of obesity on 36. Densmore JC, Lim HJ, Oldham KT, et al. Outcomes and delivery
severely injured children and adolescents. J Pediatr Surg of care in pediatric injury. J Pediatr Surg 2006;41:928.
2006;41:8891. 37. Pracht EE, Tepas JJ, Langland-Orban B, et al. Do pediatric
14. Marcin JP, Schembri MS, Jingsong H, et al. A population-based patients with trauma in Florida have reduced mortality rates when
analysis of socioeconomic status and insurance status and their treated in designated trauma centers? J Pediatr Surg 2008;
relationship with pediatric trauma hospitalization and mortality 43:21221.
rates. Am J Publ Health 2003;93:4616. 38. Knudson MM, Shagoury C, Lewis FR. Can adult trauma surgeons
15. Falcone RA, Brown RL, Garcia VF. The epidemiology of infant care for injured children? J Trauma 1992;32:72939.
injuries and alarming health disparities. J Pediatr Surg 39. Fortune JM, Sanchez J, Graca L, et al. A pediatric trauma center
2007;42:1727. without a pediatric surgeon: A four year outcome analysis.
16. Haider AH, Efron DT, Haut ER, et al. Black children experience J Trauma 1992;33:1309.
worse clinical and functional outcomes after traumatic brain 40. Rhodes M, Smith S, Boorse D. Pediatric trauma patients in an
injury: An analysis of the National Pediatric Trauma Registry. adult trauma center. J Trauma 1993;35:38493.
J Trauma 2007;62:125963. 41. Bensard DD, McIntyre RC, Moore EE, et al. A critical analysis
17. Falcone RA, Martin F, Brown RL, et al. Despite overall low pedi- of acutely injured children managed in an adult level I trauma
atric head injury mortality, disparities exist between races. center. J Pediatr Surg 1994;29:1118.
J Pediatr Surg 2008;43:185864. 42. DAmelio LF, Hammond JS, Thomasseau J, et al. Adult trauma
18. Falcone RA, Brown RL, Garcia VF. Disparities in child abuse surgeons with pediatric commitment: A logical solution to the
mortality are not explained by injury severity. J Pediatr Surg pediatric trauma manpower problem. Am Surg 1995;61:96874.
2007;42:10317. 43. Partrick DA, Moore EE, Bensard DD, et al. Operative manage-
19. Rangel SJ, Martin CA, Brown RL, et al. Alarming trends in the ment of injured children at an adult level I trauma center.
improper use of motor vehicle restraints in children: Implications J Trauma 2000;48:894901.
for public policy and the development of race-based strategies for 44. Sherman HF, Landry VL, Jones LM. Should level I trauma
improving compliance. J Pediatr Surg 2008;43:2007. centers be rated NC-17? J Trauma 2001;50:78491.
20. Brown JK, Ying Y, Wang S, et al. Patterns of severe injury in 45. Aaland MO, Hlaing T. Pediatric trauma deaths: A three-part
pediatric car crash victims: Crash Injury Research Engineering analysis from a nonacademic trauma center. Am Surg 2006;72:
Network database. J Pediatr Surg 2006;41:3627. 24959.
21. Ehrlich PF, Brown JK, Sochor MR, et al. Factors influencing 46. Winthrop AL, Brasel KJ, Stahovic L, et al. Quality of life and
pediatric Injury Severity Score and Glasgow Coma Scale in pedi- functional outcome after pediatric trauma. J Trauma 2005;58:
atric automobile crashes: Results from the Crash Injury Research 46874.
Engineering Network. J Pediatr Surg 2006;41:18548. 47. vanderSluis CK, Kingma J, Eisma WH, et al. Pediatric poly-
22. Zuckerbraun BS, Morrison K, Gaines B, et al. Effect of age on trauma: Short-term and long-term outcomes. J Trauma 1997;43:
cervical spine injuries in children after motor vehicle collisions: 5016.
Effectiveness of restraint devices. J Pediatr Surg 2004;39:4836. 48. Burd RS, Jang TS, Nair SS. Predicting hospital mortality among
23. Hayes JR, Groner JI. Using multiple imputation and propensity injured children using a national trauma database. J Trauma
scores to test the effect of car seats and seat belt usage on injury 2006;60:792801.
severity from trauma registry data. J Pediatr Surg 2008;43: 49. Haddon W. Advances in the epidemiology of injuries as a basis
9247. for public policy. Public Health Rep 1980;95:41121.
24. Arbogast KB, Kent RW, Menon RA, et al. Mechanisms of abdom- 50. Kokoska ER, Keller MS, Rallo MC, et al. Characteristics of pedi-
inal organ injury in seat-belt restrained children. J Trauma atric cervical spine injuries. J Pediatr Surg 2001;36:1005.
2007;62:147380. 51. Patel JC, Tepas JJ, Mollitt DL, et al. Pediatric cervical spine
25. Lutz N, Nance ML, Kallan MJ, et al. Incidence and clinical sig- injuries: defining the disease. J Pediatr Surg 2001;36:3736.
nificance of abdominal wall bruising in restrained children 52. Kewalramani LS, Kraus JF, Sterling HM, et al. Acute spinal-cord
involved in motor vehicle crashes. J Pediatr Surg 2004;39:9725. lesions in a pediatric population: Epidemiological and clinical
26. Chidester S, Rana A, Lowell W, et al. Is the seat belt sign associ- features. Paraplegia 1980;18:20619.
ated with serious abdominal injuries in pediatric trauma? J Trauma 53. Pang D, Wilberger E. Spinal cord injury without radiographic
2009;67:s3436. abnormality in children. J Neurosurg 1982;57:11429.
27. Nadler EP, Potoka DA, Shultz BL, et al. The high morbidity 54. Bohn D, Armstrong A, Becker L, et al. Cervical spine injuries in
associated with handlebar injuries in children. J Trauma 2005; children. J Trauma 1990;30:4639.
58:11714. 55. Bosch PP, Vogt MT, Ward WT. Pediatric spinal cord injury
28. Pollack MM, Alexander SR, Clarke N, et al. Improved outcomes without radiographic abnormality: The absence of occult instabil-
from tertiary center pediatric intensive care: A statewide compari- ity and lack of indication for bracing. Spine 2002;27:2788
son of tertiary and nontertiary care facilities. Crit Care Med 800.
1991;19:1509. 56. Cooper A, Barlow B, DiScala C. Mortality and truncal injury: The
29. Nakayama DK, Copes WS, Sacco WJ. Differences in pediatric pediatric perspective. J Pediatr Surg 1994;29:338.
trauma care among pediatric and nonpediatric centers. J Pediatr 57. Peclet MH, Newman KD, Eichelberger MR, et al. Thoracic
Surg 1992;27:42731. trauma in children: An indicator of increased mortality. J Pediatr
30. Cooper A, Barlow B, DiScala C, et al. Efficacy of pediatric trauma Surg 1990;25:9616.
care: Results of a population-based study. J Pediatr Surg 58. Haller JA. Injuries of the gastrointestinal tract in children: Notes
1993;28:299305. on recognition and management. Clin Pediatr 1966;5:47680.
31. Hall JR, Reyes HM, Meller JT, et al. Outcome for blunt trauma 59. Rogers CG, Knight V, MacUra KJ. High-grade renal injuries in
is best at a pediatric trauma center. J Pediatr Surg 1996;31:727. childrenis conservative management possible? Urology
32. Hulka F, Mullins RJ, Mann NC, et al. Influence of a statewide 2004;64:5749.
trauma system on pediatric hospitalization and outcome. J Trauma 60. Pearl RH, Wesson DE, Spence LJ, et al. Splenic injury: A 5-year
1997;42:51419. update with improved results and changing criteria for conserva-
33. Potoka DA, Schall LC, Gardner MJ, et al. Impact of pediatric tive management. J Pediatr Surg 1989;24:1215.
trauma centers on mortality in a statewide system. J Trauma 61. Galat JA, Grisoni ER, Gauderer MWL. Pediatric blunt liver
2000;49:23745. injury: Establishment of criteria for appropriate management.
34. Potoka DA, Schall LC, Ford HR. Improved functional outcome J Pediatr Surg 1990;25:11625.
for severely injured children treated at pediatric trauma centers. 62. Barlow B, Niemirska M, Gandhi R. Ten years of experience with
J Trauma 2001;51:82434. falls from a height in children. J Pediatr Surg 1983;18:50911.
35. Farrell LS, Hannan EL, Cooper A. Severity of injury and mortal- 63. Selbst SM, Baker MD, Shames M. Bunk bed injuries. Am J Dis
ity associated with pediatric blunt injuries: Hospitals with pediat- Child 1990;144:7213.
ric intensive care units vs. other hospitals. Pediatr Crit Care Med 64. Helfer RE, Slovis TL, Black M. Injuries resulting when small
2004;5:59. children fall out of bed. Pediatrics 1977;60:5335.
14 Early Assessment and Management of Trauma 187
65. Joffe M, Ludwig S. Stairway injuries in children. Pediatrics 89. Schwaitzberg SD, Bergman KS, Harris BH. A pediatric model of
1988;82:45761. continuous hemorrhage. J Pediatr Surg 1988;23:6059.
66. Barlow B, Niemirska M, Gandhi R, et al. Response to injury 90. Klinker DB, Arca MJ, Lewis BD, et al. Pediatric vascular injuries:
in children with closed femur fractures. J Trauma 1987;27: Patterns of injury, morbidity, and mortality. J Pediatr Surg
42930. 2007;42:17883.
67. Ismail N, Bellemare JF, Mollitt D, et al. Death from pelvic frac- 91. Hammer CE, Groner JI, Caniano DA, et al. Blunt intraabdominal
ture: Children are different. J Pediatr Surg 1996;31:825. arterial injury in pediatric trauma patients: Injury distribution and
68. McIntyre RR, Bensard DD, Moore EE, et al. Pelvic fracture markers of outcome. J Pediatr Surg 2008;34:91623.
geometry predicts risk of life-threatening hemorrhage in children. 92. Anderson SA, Day M, Chen NK, et al. Traumatic aortic
J Trauma 1993;35:4239. injuries in the pediatric population. J Pediatr Surg 2008;43:
69. Herzenberg JE, Hensinger RN, Dedrick DK, et al. Emergency 107781.
transport and positioning of young children who have an injury 93. Heckman SR, Trooskin SZ, Burd RS. Risk factors for blunt tho-
of the cervical spine. J Bone Joint Surg Am 1989;71:1522. racic injury in children. J Pediatr Surg 2005;40:98102.
70. Schafermeyer RW, Ribbeck BM, Gaskins J, et al. Respiratory 94. Isaacman DJ, Scarfone RJ, Kost SI, et al. Utility of routine labora-
effects of spinal immobilization in children. Ann Emerg Med tory testing for detecting intraabdominal injury in the pediatric
1991;20:101719. trauma patient. Pediatrics 1993;92:6914.
71. Viccellio P, Simon H, Pressman BD, et al. A prospective multi- 95. Keller MS, Coln CE, Trimble JA, et al. The utility of routine
center study of cervical spine injury in children. Pediatrics trauma laboratories in pediatric trauma resuscitations. Am J Surg
2001;108:e20. 2004;188:6718.
72. Gausche M, Lewis RJ, Stratton SJ, et al. Effect of out-of- 96. Capraro AJ, Mooney D, Waltzman ML. The use of routine labo-
hospital pediatric endotracheal intubation on survival and neuro- ratory studies as screening tools in pediatric abdominal trauma.
logical outcome: A controlled clinical trial. JAMA 2000;283: Pediatr Emerg Care 2006;22:4804.
78390. 97. Kincaid EH, Chang MC, Letton RW, et al. Admission base deficit
73. Cooper A, DiScala C, Foltin G, et al. Prehospital endotracheal in pediatric trauma: A study using the National Trauma Data
intubation for severe head injury in children: A reappraisal. Semin Bank. J Trauma 2001;51:3325.
Pediatr Surg 2001;10:36. 98. Randolph LC, Takacs M, Davis KA. Resuscitation in the pediatric
74. Ehrlich PF, Seidman PS, Atallah O, et al. Endotracheal intuba- trauma population: Admission base deficit remains an important
tions in rural pediatric trauma patients. J Pediatr Surg prognostic indicator. J Trauma 2002;53:83842.
2004;39:137680. 99. Oldham KT, Guice KS, Kaufman RA, et al. Blunt hepatic injury
75. Cooper A, Barlow B, DiScala C, et al. Efficacy of prehospital and elevated hepatic enzymes: A clinical correlation in children.
volume resuscitation in children who present in hypotensive J Pediatr Surg 1984;19:45761.
shock. J Trauma 1993;35:160. 100. Adamson WT, Hebra A, Thomas PB, et al. Serum amylase and
76. Teach SJ, Antosia RE, Lund DP, et al. Prehospital fluid lipase alone are not cost-effective screening methods for pediatric
therapy in pediatric trauma patients. Pediatr Emerg Care 1995;11: pancreatic trauma. J Pediatr Surg 2003;38:3547.
58. 101. Lieu TA, Fleisher GR, Mahboubi S, et al. Hematuria and clinical
77. Tepas JJ, Mollitt DL, Talbert JL, et al. The pediatric trauma score findings as indications for intravenous pyelography in pediatric
as a predictor of injury severity in the injured child. J Pediatr Surg blunt renal trauma. Pediatrics 1988;82:21622.
1987;22:1418. 102. Brenner DJ, Elliston CD, Berdon WE. Estimated risks of
78. Champion HR, Sacco WJ, Copes WS, et al. A revision of the radiation-induced fatal cancer from pediatric CT. Am J Roentge-
trauma score. J Trauma 1989;29:6239. nol 2001;176:28996.
79. Hannan EL, Farrell LS, Meaker PS, et al. Predicting inpatient 103. Fenton SJ, Hansen KW, Meyers RL, et al. CT scan and the
mortality for pediatric blunt trauma patients: A better alternative. pediatric trauma patient: are we overdoing it? J Pediatr Surg
J Pediatr Surg 2000;35:1559. 2004;39:187781.
80. Sasser SM, Hunt RC, Faul M, et al. Recommendations of the 104. Kim PK, Zhu X, Houseknecht E, et al. Effective radiation dose
National Expert Panel on Field Triage, 2011. MMWR from radiologic studies in pediatric trauma patients. World J Surg
2012;61(RR-1):121. 2005;29: 155762.
81. Prehospital Trauma Life Support Committee of the National 105. Brody AS, Frush DP, Huda W, et al. Radiation risk to
Association of Emergency Medical Technicians in cooperation children from computed tomography. Pediatrics 2007;120:
with the Committee on Trauma of the American College of Sur- 67782.
geons. PHTLS: Prehospital Trauma Life Support. 7th ed. St. 106. Chwals WJ, Robinson AV, Sivit CJ, et al. Computed tomography
Louis: Mosby Elsevier; 2010. before transfer to a level I pediatric trauma center risks duplication
82. American College of Surgeons Committee on Trauma. Advanced with associated increased radiation exposure. J Pediatr Surg
Trauma Life Support ATLS Student Course Manual. 9th ed. 2008;43:226872.
Chicago: American College of Surgeons; 2012. 107. Cook SH, Fielding JR, Phillips JD. Repeat abdominal computed
83. Rees MJ, Aickin R, Kolbe A, et al. The screening pelvic tomography after pediatric blunt trauma: missed injuries, extra
radiograph in pediatric trauma. Pediatr Radiol 2001;31:497 costs, and unnecessary radiation exposure. J Pediatr Surg
500. 2010;45:201924.
84. Junkins EP, Stotts A, Santiago R, et al. The clinical presentation 108. Brunetti MA, Mahadevappa M, Nabaweesi R, et al. Diagnostic
of pediatric thoracolumbar fractures: A prospective study. radiation exposure in pediatric trauma patients. J Trauma
J Trauma 2008;65:106671. 2011;70:E248.
85. Kragh JF, Cooper A, Aden JK, et al. Survey of trauma registry 109. Wang MY, Griffith PR, Sterling J, et al. A prospective population-
data on tourniquet use in pediatric war casualties. Pediatr Emerg based study of pediatric trauma patients with mild alterations in
Care 2012;28:13615. consciousness (Glasgow Coma Scale score of 1314). Neurosurg
86. Holcomb JB, Wade CE, Michalek JE, et al. Increased plasma and 2000;46:10939.
platelet to red cell ratios improves outcome in 466 massively 110. Kuppermann N, Holmes JF, Dayan PS, et al. Identification of
transfused civilian trauma patients. Ann Surg 2008;248(3); children at very low risk of clinically-important brain injuries after
44758. head trauma: A prospective cohort study. Lancet 2009;374:
87. Dressler AM, Finck CM, Carroll CL, et al. Use of a massive 116070.
transfusion protocol with hemostatic resuscitation for severe 111. Renton J, Kincaid S, Ehrlich PF. Should helical CT scanning of
intraoperative bleeding in a child. J Pediatr Surg 2010;45: the thoracic cavity replace the conventional chest x-ray as a
15303. primary assessment tool in pediatric trauma? An efficacy and cost
88. Patregnani JT, Borgman MA, Maegele M, et al. Coagulopathy and analysis. J Pediatr Surg 2003;38:7937.
shock on admission is associated with mortality for children with 112. Kwon A, Sorrells DL, Kurkchubaske AG, et al. Isolated computed
traumatic injuries at combat support hospitals. Pediatr Crit Care tomography diagnosis of pulmonary contusion does not correlate
Med 2012;13:2737. with increased morbidity. J Pediatr Surg 2006;41:7882.
188 SECTION II Trauma
113. Keenan HT, Hollingshead MC, Chung CJ, et al. Using CT of the 136. Roaten JB, Partrick DA, Nydam TL, et al. Nonaccidental trauma
cervical spine for early evaluation of pediatric patients with head is a major cause of morbidity and mortality among patients at a
trauma. Am J Roentgenol 2001;177:14059. regional level 1 pediatric trauma center. J Pediatr Surg 2006;41:
114. Flood RG, Mooney DP. Rate and prediction of traumatic injuries 201315.
detected by abdominal computed tomography scan in intubated 137. Cooper A, Floyd T, Barlow B, et al. Fifteen years experience with
children. J Trauma 2006;61:3405. major blunt abdominal trauma due to child abuse. J Trauma
115. Taylor GA, Eichelberger MR, ODonnel R, et al. Indications for 1988;28:14837.
computed tomography in children with blunt abdominal trauma. 138. Wood J, Rubin DM, Nance ML, et al. Distinguishing inflicted
Ann Surg 1991;213:21218. versus accidental abdominal injuries in young children. J Trauma
116. Patel JC, Tepas JJ. The efficacy of focused abdominal sonography 2005;59:12038.
for trauma (FAST) as a screening tool in the assessment of injured 139. Duhaime A-C, Gennarelli TA, Thibault LE, et al. The shaken
children. J Pediatr Surg 1999;34:447. baby syndrome: A clinical, pathological, and biomechanical study.
117. Mutabagani KH, Coley BD, Zumberge N, et al. Preliminary J Neurosurg 1987;66:40915.
experience with focused abdominal sonography for trauma (FAST) 140. Christian CW, Block R, and the Committee on Child Abuse and
in children: Is it useful? J Pediatr Surg 1999;34:4854. Neglect. Abusive head trauma in infants and children. Pediatrics
118. Pershad J, Gilmore B. Serial bedside emergency ultrasound in a 2009;123:140911.
case of pediatric blunt abdominal trauma with severe abdominal 141. Chang DC, Knight V, Ziegfeld S, et al. The tip of the iceberg for
pain. Pediatr Emerg Care 2000;16:3756. child abuse: The critical roles of the pediatric trauma service and
119. Corbett SW, Andrews HG, Baker EM, et al. ED evaluation of the its registry. J Trauma 2004;57:118998.
pediatric trauma patient by ultrasonography. Am J Emerg Med 142. Boyce MC, Melhorn KJ, Vargo G. Pediatric trauma documenta-
2000;18:2449. tion: Adequacy for assessment of child abuse. Arch Pediatr Adolesc
120. Coley BD, Mutabagani KH, Martin LC, et al. Focused abdominal Med 1996;150:7302.
sonography for trauma (FAST) in children with blunt abdominal 143. Selbst SM, Henretig F, Fee MA, et al. Lead poisoning in a child
trauma. J Trauma 2000;48:9026. with a gunshot wound. Pediatrics 1986;77:41316.
121. Soudack M, Epelman M, Maor R, et al. Experience with focused 144. Cigdem MK, Onen A, Siga M, et al. Selective nonoperative man-
abdominal sonography for trauma (FAST) in 313 pediatric agement of penetrating abdominal injuries in children. J Trauma
patients. J Clin Ultrasound 2004;32:5361. 2009;67:12847.
122. Suthers SE, Albrecht R, Foley D, et al. Surgeon-directed ultra- 145. Chen MK, Schropp KP, Lobe TE. The use of minimal access
sound for trauma is a predictor of intraabdominal injury in chil- surgery in pediatric trauma: a preliminary report. J Laparoendo-
dren. Am Surg 2004;70:1648. scop Surg 1995;5:295301.
123. Soundappan SV, Holland AJ, Cass DT, et al. Accuracy of surgeon- 146. Gandhi RR, Stringel G. Laparoscopy in pediatric abdominal
performed focused abdominal sonography (FAST) in blunt pae- trauma. J Soc Laparoendoscop Surg 1997;1:34951.
diatric trauma. Injury 2005;36:9705. 147. Feliz A, Shultz B, McKenna C, et al. Diagnostic and therapeutic
124. Emery KH, McAneney CM, Racadio JM, et al. Absent peritoneal laparoscopy in pediatric abdominal trauma. J Pediatr Surg
fluid on screening trauma ultrasonography in children: A prospec- 2006;41:727.
tive comparison with computed tomography. J Pediatr Surg 148. Marwan A, Harmon CM, Georgeson KE. Use of laparoscopy in
2001;36:5659. the management of pediatric abdominal trauma. J Trauma
125. Holmes JF, London KL, Brant WE. Isolated intraperitoneal fluid 2010;69:7614.
on abdominal computed tomography in children with blunt 149. Committee on Trauma. American College of Surgeons: Resources
trauma. Acad Emerg Med 2000;7:33541. for Optimal Care of the Injured Patient. Chicago: American
126. Rathaus V, Zissin R, Werner M, et al. Minimal pelvic fluid in blunt College of Surgeons; 2006.
abdominal trauma: The significance of this sonographic finding. 150. Committee on Trauma. American College of Surgeons: Regional
J Pediatr Surg 2001;36:13879. Trauma Systems: Optimal Elements, Integration, and Assessment-
127. Holmes JF, Brant WE, Bond WF, et al. Emergency department Systems Consultation Guide. Chicago: American College of Sur-
ultrasonography in the evaluation of hypotensive and normoten- geons; 2008.
sive children with blunt abdominal trauma. J Pediatr Surg 151. Nance ML, Carr BG, Branas CC. Access to pediatric trauma care
2001;36:96873. in the United States. Arch Pediatr Adolesc Med 2009;163:
128. Venkatesh KR, McQuay N. Outcomes of management in stable 51218.
children with intra-abdominal free fluid without solid organ injury 152. Odetola FO, Miller WC, Davis MM, et al. The relationship
after blunt abdominal injury. J Trauma 2007;62:21620. between the location of pediatric intensive care unit facilities and
129. Filiatrault D, Longpre D, Patriquin H, et al. Investigation of child death from trauma: A county-level ecologic study. J Pediatr
childhood blunt abdominal trauma: A practical approach using 2005;147:747.
ultrasound as the initial diagnostic modality. Pediatr Radiol 153. Hunt EA, Hohenhaus SM, Luo X, et al. Simulation of pediatric
1987;17:3739. trauma stabilization in 35 North Carolina emergency depart-
130. Baxt C, Kassam-Adams N, Nance ML, et al. Assessment of pain ments: Identification of targets for performance improvement.
after injury in the pediatric patient: Child and parent perceptions. Pediatrics 2006;117:6418.
J Pediatr Surg 2004;39:97983. 154. Mikrogianakis A, Osmond MH, Nuth JE, et al. Evaluation of a
131. Winthrop AL, Wesson DE, Pencharz PB, et al. Injury severity, multidisciplinary pediatric mock trauma code educational initia-
whole body protein turnover, and energy expenditure in pediatric tive; A pilot study. J Trauma 2008;64:7617.
trauma. J Pediatr Surg 1987;22:5347. 155. Falcone RA, Daugherty M, Schweer L, et al. Multidisciplinary
132. Oliver RC, Sturtevant JP, Scheetz JP, et al. Beneficial effects of a trauma team training using high-fidelity trauma simulation.
hospital bereavement intervention program after traumatic child- J Pediatr Surg 2008;43:106571.
hood death. J Trauma 2001;50:4408. 156. Popp J, Yochum L, Spinella P, et al. Simulation training for surgi-
133. Winston FK, Kassam-Adams N, Vivarelli-ONeill C, et al. Acute cal residents in pediatric trauma scenarios. Connecticut Med
stress disorder symptoms in children and their parents after pedi- 2012;76:15962.
atric traffic injury. Pediatrics 2002;109:e90. 157. OConnell KJ, Farah MM, Spandorfer P, et al. Family presence
134. Schreier H, Ladakokos C, Morabito D, et al. Posttrauma during pediatric trauma team activation: An assessment of a struc-
stress symptoms in children after mild to moderate pediatric tured program. Pediatrics 2007;120:e56574.
trauma: A longitudinal examination of symptom prevalence, cor- 158. Dudley NC, Hansen KW, Furnival RA, et al. The effect of family
relates, and parent-child symptom reporting. J Trauma 2005; presence on the efficiency of pediatric trauma resuscitation. Ann
58:35363. Emerg Med 2009;53:77784.
135. Han PP, Holbrook TL, Sise MJ, et al. Postinjury depression is a 159. Osler TM, Vane DW, Tepas JJ, et al. Do pediatric trauma centers
serious complication in adolescents after major trauma: Injury have better survival rates than adult trauma centers? An examina-
severity and injury-event factors predict depression and long-term tion of the National Pediatric Trauma Registry. J Trauma
quality of life deficits. J Trauma 2011;70:92330. 2001;50:96101.
14 Early Assessment and Management of Trauma 189
160. Ehrlich PF, McClellan WT, Wesson DE. Monitoring perform- 163. MacNab AJ. Optimal escort for interhospital transport of pediat-
ance: Long-term impact of trauma verification and review. J Am ric emergencies. J Trauma 1991;31:2059.
Coll Surg 2005;200:16672. 164. Kanter RK, Boeing NM, Hannan WP, et al. Excess morbidity
161. Vavilala MS, Cummings P, Sharar SR, et al. Association of hospital associated with interhospital transport. Pediatrics 1992;90:
trauma designation with admission patterns of injured children. 8938.
J Trauma 2004;54:11924. 165. Edge WE, Kanter RK, Weigle CGM, et al. Reduction of morbid-
162. Smith DF, Hackel A. Selection criteria for pediatric critical care ity in interhospital transport by specialized pediatric staff. Crit
transport teams. Crit Care Med 1983;11:1012. Care Med 1994;22:118691.
C H A P T E R 1 5
Thoracic Trauma
Alejandro R. Ruiz-Elizalde David W. Tuggle
Trauma is an important cause of morbidity and mortality for easier transmission of breath sounds, which may
in children. Although it accounts for a minority of trauma obscure the diagnosis of a hemothorax or pneumothorax.
injuries (425%), thoracic trauma is associated with a Children are also at an increased risk for hypoxia owing
20-fold increase in mortality when compared with injured to their higher oxygen consumption per unit body mass
children without thoracic trauma.110 Isolated thoracic and their lower functional residual capacity to total lung
trauma in a child is associated with a mortality rate of volume ratio.
approximately 5%, which is largely due to penetrating When assessing circulation, it is important to note that
trauma.1 However, children with head trauma, thoracic the mediastinum is more mobile in children than in older
trauma, and abdominal trauma can have a mortality rate patients. This is particularly true in young children. Uni-
that approaches 40%. lateral changes in thoracic pressure, as occurs from a
Epidemiologic studies have reported a two to three- pneumothorax, can lead to a tension pneumothorax. This
fold higher incidence of thoracic trauma in boys as com- can shift the mediastinum such that venous return is
pared with girls.915 Most injuries (8095%) are the result markedly reduced. The pathophysiologic effect is similar
of blunt trauma, typically resulting from a traffic accident to hypovolemic shock, and this response is more pro-
in which the child is a passenger or pedestrian.2,10 Not nounced than is typically seen in an adult.
surprisingly, many children will have involvement of Children compensate for a decrease in cardiac output
other organ systems with a high injury severity score by increasing their heart rate. In infants, improvement in
(ISS). When penetrating trauma occurs, older children stroke volume provides little in the way of compensation
and adolescents are more likely to be the victims and for hypotension. Infants and children also have a higher
there is a higher mortality rate.5 body surface area to weight ratio than adults, which pre-
Contusion or laceration of the pulmonary parenchyma disposes them to hypothermia. This, in turn, may com-
is the most common thoracic injury and may be associ- plicate the assessment of perfusion.
ated with rib fractures and pneumothorax or hemothorax.
Injuries to other organs such as the tracheobronchial tree
(<1%), esophagus (<1%), aorta (<1%), diaphragm (4%), SPECIFIC INJURIES AND MANAGEMENT
and heart (6%) are uncommon, but not insignificant.12
Thoracic injuries in children can be categorized by loca-
tion as seen in Box 15-1.
ANATOMY AND PHYSIOLOGY
Children have unique anatomic and physiologic proper- Chest Wall
ties that are salient to the diagnosis and management of Rib Fractures
chest injuries. As in any trauma patient, sequential man-
agement of the airway, breathing, and circulation is of Young children have a compliant thorax and do not begin
primary importance. The pediatric airway may be com- to resemble adults until around 8 to 10 years of age. As
plicated by numerous factors. The head of an infant is a consequence, rib fractures are relatively uncommon in
proportionally much larger than that of an adult, thus young children and occur more frequently in adolescents.
predisposing to neck flexion and occlusion of the airway Rib fractures are often suspected on physical examination
in the supine position. The larger tongue and soft palate, and are identified on a chest radiograph (CXR) during
as well as the more anterior glottis, can make the airway the initial assessment. Independently, rib fractures are
difficult to visualize. The childs trachea is shorter relative infrequently a cause of major morbidity or mortality, but
to body size, and narrower and more easily compressed are indicators of significant energy transfer.16 If a rib
compared with an adult. The subglottic region is the fracture is found in a child younger than 3 years, nonac-
narrowest part of the trachea in children. Because of its cidental trauma (NAT) should be considered.17,18 Bone
small cross-sectional diameter, the pediatric airway is scans and bone surveys are useful in diagnosing remote
more susceptible to plugging with mucus or minimal fractures of the bony thorax in abused children, and
airway edema. follow-up studies improve identification of these inju-
The chest wall is more compliant in children, with less ries.19 In older children, rib fractures should draw atten-
muscle mass for soft tissue protection. This allows a tion to the risk of an associated underlying injury.
greater transmission of energy to underlying organs Fractures and dislocations of the bony thorax and joints
when injury occurs. The thinner chest wall also allows may cause significant long-term pain. In addition to
190
15 Thoracic Trauma 191
atrium, excludes blood return from the superior vena and cardiovascular collapse.40 If the clinician suspects a
cava, and results in rupture of venules and capillaries tension pneumothorax in a patient with appropriate signs
about the face and head.31 Patients will exhibit conjunc- and symptoms, it is reasonable to proceed with decom-
tival hemorrhages, facial swelling, and petechial hemor- pression without waiting for a CXR. If rapid drainage of
rhages on the face and upper chest. Although severe cases intrapleural air cannot be accomplished with a needle,
may result in loss of vision or other permanent neuro- insertion of a pigtail catheter or a chest tube should be
logic sequelae, the morbidity and mortality associated performed. A tension pneumothorax treated initially with
with traumatic asphyxia is generally related to the associ- needle decompression will require chest tube or pigtail
ated injuries. The majority of children who survive have catheter insertion due to the continuing collection of air
good outcomes.32,33 under pressure in the involved hemithorax. If one or both
lungs have been compressed for a long time, re-expansion
pulmonary edema may develop.41
Pleural Cavity and Pulmonary Parenchyma Systemic air embolism can occur with any pulmonary
parenchymal injury and increased intrabronchial pres-
PneumothoraxPulmonary Lacerations
sure, creating a bronchopulmonary venous fistula.42 This
Pneumothorax may occur with a penetrating injury to the is most often seen when positive-pressure ventilation is
chest wall or air leak into the pleural space from a pul- required to support the injured patient. Sudden neuro-
monary laceration or disruption of the proximal airway. logic findings or cardiovascular decompensation may be
It is a relatively common finding in children with blunt the initial sign that air has embolized to the coronary or
and penetrating thoracic trauma. The air leak may dissect cerebral vessels. If this complication is recognized, steps
under the pleura to cause pneumomediastinum and sub- should be taken to prevent further air embolism. If pos-
cutaneous emphysema. A simple pneumothorax is often sible, the removal of the intravascular air should be con-
asymptomatic because the lack of increased intrathoracic sidered. Treatment options include tube thoracostomy,
pressure limits the recognition of symptoms. For this but more often an emergency thoracotomy will provide
reason, a screening CXR is an important component immediate reversal of the physiology promoting the air
in the evaluation of thoracic injury in children. Air within embolism. The hilum of the lung should be occluded to
the pleural cavity can layer anteriorly, posteriorly, or in prevent further escape of air into the venous system, and
the subpulmonic space. A simple pneumothorax can be operative control of the bronchialvenous interface
easily missed on chest film, but can be found on a subse- should be obtained. The mortality associated with this
quent computed tomographic (CT) scan.34 However, a complication is high.
recent study analyzing the utility of CT scan as a screen-
ing modality to replace initial CXR concluded that Hemothorax
although a CT scan is highly sensitive, it should not be
used as a primary imaging tool given its cost and the Hemothorax can result from blunt or penetrating injury
acceptable sensitivity of routine CXR.35 Ultrasonography to any of the intrathoracic vessels, the chest wall vessels,
(US) is another diagnostic modality that has been shown the pleura, or the pulmonary parenchyma. Occasionally,
to be nearly as sensitive as CT in determining the pres- a rib fracture can lacerate an intercostal vessel or the lung.
ence of an occult pneumothorax and has gained wide Rarely, the aorta or vena cava may be injured by pressure
acceptance as a screening tool.36,37 or shearing. Unless the volume of blood is large, a hemot-
The need for intervention in the presence of a simple horax may be asymptomatic. Smaller volumes may be
pneumothorax will depend on its severity and the childs more easily detected on CT scan, which also allows for
clinical condition. Some authors have suggested that if measurement of Hounsfield density to aid in the diagno-
the volume of the pneumothorax is greater than 20% of sis.43 Each hemithorax can hold approximately 40% of a
the pleural space, then drainage is needed.38 Although childs blood volume and it is difficult to estimate the
insertion of a chest tube can be considered appropriate amount of blood loss on a CXR.44 Prompt chest tube
in almost every circumstance of traumatic pneumothorax, placement allows for evacuation of the blood from the
there are alternatives to conventional chest tubes, such as pleural space and re-expansion of the lung. It also allows
pigtail catheters.39 Additionally, there may be a benefit in the surgeon to assess the volume of blood loss and
treating with supplemental oxygen alone. The rationale whether the hemorrhage is ongoing.
for this therapy is that atmospheric gas (78% nitrogen) There are instances in which an operation may be
comprises the majority of the entrapped air collection. If needed to stop ongoing intrathoracic bleeding. After
the nitrogen level in the blood is washed out by increased tube thoracostomy, the immediate blood return of
inspired oxygen, a nitrogen gradient will be created that 15mL/kg, or ongoing losses of 23mL/kg/h for 3
will cause accelerated absorption of the air. Oxygen can or more hours, are indicators for thoracic exploration.45,46
be delivered by way of nasal cannula, a hood, or a mask. If undrained, the hemothorax can become organized with
Treatment with supplemental oxygen may be required for the development of a fibrothorax that can cause a restric-
24 to 48 hours. tive lung defect. This predisposes to atelectasis,
In contrast, a tension pneumothorax is a life- ventilationperfusion mismatching, and subsequent
threatening condition that requires expeditious decom- pneumonia.
pression. A tension pneumothorax likely causes symptoms Residual blood is also an excellent culture medium,
initially from hypoxemia and later from increased intra- and empyema and sepsis can result from infection of an
pleural pressure with subsequent decreased venous return undrained hemothorax. Tube thoracostomy may not
15 Thoracic Trauma 193
adequately evacuate an organizing post-traumatic hemo ARDS.55 Children with pulmonary contusions can have
thorax in up to 12% of patients.47 In this situation, tho- prolonged changes in respiratory function and radio-
racoscopy may be useful to evacuate the residual clot. graphic abnormalities. These changes may persist for an
Patients who undergo early thoracoscopy may experience extended period of time after resolution of the symp-
less morbidity.48,49 However, there are also data to suggest toms.56 However, these children do not appear to suffer
that thrombolytic therapy is equally effective in treating any significant long-term sequelae.15
a chronic hemothorax.47 The use of intrapleural tissue
plasminogen activator (tPA) has also been used for the Diaphragmatic Injuries
treatment of traumatic residual hemothoraces and other
parapneumonic processes with good results.50,51 Blunt diaphragmatic rupture is an uncommon occur-
rence. The left diaphragm is involved more often because
of the protective effect of the right lobe of the liver.
Chylothorax
There have been occasional reports of bilateral diaphrag-
Chylothorax caused by injury to thoracic lymphatic chan- matic injury (Fig. 15-2).57,58 The frequency of associated
nels is an uncommon complication from thoracic trauma. injuries, especially liver and spleen injuries, is very high.58
Chylothorax usually becomes evident three to seven days Blunt injury to the diaphragm can have several manifesta-
after injury. The diagnosis is made by obtaining a sample tions, but usually include chest pain that radiates to the
of the pleural fluid and identifying the lymphocyte and shoulder, shortness of breath, or abdominal pain. Breath
lipid content. Treatment includes drainage and either sounds may be diminished and bowel sounds may be
enteral feedings with medium-chain triglycerides or heard on the ipsilateral side.59
parenteral nutrition. On imaging studies, an abnormal diaphragm contour,
a high-riding diaphragm, or a questionable overlap of
Pulmonary Contusion abdominal visceral shadows may suggest injury. Visceral
herniation or the abnormal placement of a nasogastric
One of the most common thoracic injuries in children is tube into the left hemithorax should be considered diag-
a pulmonary contusion, which can occur with blunt or nostic. Many diaphragmatic ruptures are not identified in
penetrating trauma.1 The flexible chest wall of a child the first few days after injury, and may not be detected
allows for contusion of the lung without rib fracture, for a considerable period of time (Fig. 15-3).60 CXR find-
resulting in areas of lung consolidation and chest ings may be obscured by associated contusion or atelecta-
wall contusion. Microscopically, pulmonary contusions sis in the lung bases. In patients requiring intubation,
show alveolar hemorrhage, consolidation, and edema. herniation of abdominal viscera through the injury may
The presence of a pulmonary contusion contributes to not occur until after the patient is off positive-pressure
decreased pulmonary compliance, hypoxia, hypoventila- ventilation.61 CT has been used to establish the diagnosis,
tion, and a ventilationperfusion mismatch. A CXR taken but the CT may appear normal in some patients. A
during the initial assessment may demonstrate the pul- heightened awareness of this injury should be present to
monary contusion. However, because this is invariably a avoid the late complications of visceral herniation or
supine film, it is sometimes difficult to differentiate fluid/ bowel complications.
blood in the pleural space from a lung contusion. To this When penetrating trauma is sustained below the
end, a chest CT scan can show areas of pulmonary contu- nipple line, a diaphragmatic injury needs to be
sion not appreciated on the chest radiograph and can
differentiate a parenchymal process (contusion) from free
fluid.52 However, when a contusion is seen on CXR, these
children typically have a larger parenchymal volume that
has been injured with a higher degree of impaired oxy-
genation.53 Also, a significant percentage will require
ventilatory support. When a pulmonary contusion is seen
only on CT, the morbidity of the injured child does not
appear to be affected when compared with children
with normal CT findings.54 The overall injury severity,
associated injuries, and outcomes in these patients are
similar to those seen in adults.52 Treatment includes
appropriate fluid resuscitation, supplemental oxygen,
pain management, and strategies to prevent atelectasis
and pneumonia.
A significant percentage of patients may develop pneu-
monia or acute respiratory distress syndrome (ARDS)
after pulmonary contusion.13 Occasionally, the pulmo-
nary contusion can cause life-threatening hypoxia that
cannot be supported with conventional ventilation,
including high-frequency oscillation. Extracorporeal life FIGURE 15-2 Bilateral diaphragmatic rupture after blunt
support has been used in extreme circumstances to abdominal trauma. The hemostats have been placed on the
support patients with severe pulmonary contusions or lower rim of the diaphragmatic rupture.
194 SECTION II Trauma
A B
C D
FIGURE 15-3 This 16-year-old was initially admitted to another hospital following a motor vehicle accident that necessitated inser-
tion of a left chest tube. Six weeks later, he began to develop left-sided chest discomfort and vomiting. (A) The patients chest radio-
graph. Note the tip of the nasogastric tube in the left thoracic cavity (arrow). (B) A CT scan was performed at the outlying hospital
which shows an air-fluid level in the stomach which is located in the left side chest cavity. The solid contents in the stomach are
marked with an asterisk. (C) At laparoscopic exploration, the diaphragmatic defect is seen. (D) This defect was able to be closed
laparoscopically and he was discharged two days later. He has recovered uneventfully and has not developed any postoperative
problems with more than a one year follow-up.
considered. Imaging evaluation is often unreliable in this include a persistent large air leak from a chest tube, medi-
setting. Therefore after determining whether other life- astinal air, cervical subcutaneous emphysema without
threatening injuries to the heart, lung, liver, spleen, or pneumothorax, or florid respiratory compromise. Rarely,
gastrointestinal tract exist, operative exploration and complete transection of a distal main-stem bronchus will
repair may be needed.59 If exploration is undertaken, appear on CXR with total lung collapse and mediastinal
laparoscopy, thoracoscopy, thoracotomy, or laparotomy displacement.63 Persistent pneumomediastinum and
have all been used with success (see Fig. 15-3C,D). pneumothoraces on CXR after adequate tube thoracos-
tomy should alert the clinician to consider an injury to
the tracheobronchial tree (Fig. 15-4).
Mediastinum Once recognized, these injuries require prompt diag-
nosis and treatment. Pleural air or fluid collections should
Airway Injury
be drained until an accurate evaluation and diagnosis of
Injuries to the tracheobronchial tree are infrequent in the airway injury is made. Mechanical ventilation may be
children. Airway disruption may occur with penetrating necessary because of respiratory failure in this setting.
injury or with blunt injury such as high-energy accelera- Fiberoptic bronchoscopy allows for evaluation of the
tion or deceleration. Up to three-quarters of these inju- airway and may improve the probability of successful
ries are noted within 2cm of the carina and almost half intubation. Many airway injuries are diagnosed by rigid
occur within the first 2cm of the right main-stem bron- or flexible bronchoscopy. Chest CT with a multiple-array
chus.62 Most patients with tracheal injuries have medias- scanner may have a role in visualizing tracheal or bron-
tinal air on CXR. More distal injuries may rupture into chial injuries, especially if three-dimensional reconstruc-
the pleural space and present as a tension pneumothorax. tions of the airway are used (virtual bronchoscopy)
Other findings associated with a major airway injury (Fig. 15-5).64,65
15 Thoracic Trauma 195
There are no large collective studies of children with than 5% of children with blunt thoracic trauma.86,87 Pen-
aortic injuries. However, of those who survive until diag- etrating trauma is more often a cause of cardiac and aortic
nosis, more than 70% will live to discharge.71,72 Spinal injury in this age group. Cardiac contusion accounts for
cord ischemia is a complication that can occur and may 95% of blunt cardiac injuries in the child, followed by
be associated with preoperative cardiovascular instabil- valvular dysfunction and ventricular septal defect.87 Clini-
ity.76 Although urgent operative repair is thought to be cal manifestations of cardiac injury after blunt thoracic
the best treatment option in most patients, recent experi- trauma include arrhythmia, new-onset murmur, and
ence has demonstrated the ability to delay operative heart failure. However, these findings may be absent in
intervention by using beta-adrenergic blockers while children, and CXR and electrocardiographic findings are
other injuries are managed.70,76,77 This trend in manage- generally nonspecific.87
ment has raised the possibility of using a less invasive The management of a cardiac contusion is supportive.
endovascular approach when dealing with these injuries. Children with a cardiac contusion who are hemodynami-
In adults, studies have demonstrated that it is feasible to cally stable on presentation rarely have deterioration in
treat aortic injuries with endovascular stents.78 Extrapola- their cardiac rhythm. Patients should be monitored with
tion of this approach to children has shown that endovas- continuous electrocardiography and frequent blood
cular treatment in children from the ages 12 to 14 years pressure determinations. Echocardiography should be
has been successful; however, the endovascular grafts performed early in the evaluation of children with a sig-
were constructed from smaller adult stent grafts.77,79,80 In nificant cardiac contusion. In patients with a suspected
the elective setting, such as endovascular treatment of cardiac contusion, serum cardiac troponin I levels may be
aortic coarctation, infants and teenagers alike have been useful to confirm the diagnosis.88
managed with larger adult stents.8183 Currently, the Inotropic agents are occasionally needed to provide
youngest reported person with a traumatic aortic disrup- cardiac support in the presence of a cardiac contusion.
tion treated with an endovascular stent is an 11-year-old Although blunt cardiac injury with heart rupture and
child.84 The long-term sequelae of permanent stents in cardiac tamponade is very rare, only immediate diagnosis
children with growing aortas has not been evaluated. and treatment will be life-saving. This is also true for
However, newer expandable stents may allow for multi- penetrating cardiac trauma. A delayed diagnosis of cardiac
ple interventions in a given patient.85 rupture in children has been described.89,90 Immediate
ultrasound in the emergency department may provide the
clinical information necessary to identify this injury.91
Cardiac Contusion
Pericardiocentesis in this setting may provide a tempo-
Blunt cardiac injury such as myocardial contusion, cardiac rary solution while operative intervention is organized. If
laceration, or cardiac rupture is rare, occurring in less urgent pericardiocentesis is required in a child, it should
A B
FIGURE 15-6 An 8-year-old patient presented with injuries from being an unrestrained passenger in a motor vehicle accident.
(A) On the chest radiograph, note the widened mediastinum and loss of definition of the aortic knob (arrow). There is also a right
pneumothorax that was treated with tube thoracostomy. (B) An aortogram shows a pseudoaneurysm (arrow) at the location of
the ligamentum arteriosum just distal to the left subclavian artery, representing the partial transection of the descending aorta at
this point.
15 Thoracic Trauma 197
be remembered that the distance from the skin to the endoscopy. Nonoperative management is based on the
pericardium is significantly reduced in younger patients clinical status of the patient and the injury seen on
relative to adults. Undercompensating or overcompen- imaging studies. For example, a patient might have a
sating for chest wall thickness may lead to inadequate small leak identified, manifested by mediastinal air or
decompression or iatrogenic cardiac injury. Once stabi- pneumothorax. If there is no fever, no effusion, and the
lized, children with a blunt cardiac injury should be fol- patient looks well, nonoperative treatment with TPN and
lowed closely and monitored for sequelae such as valvular intravenous antibiotics, along with serial examinations,
insufficiency or a ventricular septal defect.87 Rarely, extra- may be reasonable. See Chapter 26 for more information
corporeal life support may be needed to manage a child about esophageal injuries.
with a severe blunt cardiac injury.
Commotio cordis has become a widely recognized REFERENCES
problem in pediatric thoracic trauma.92 Typically, a young 1. Peclet MH, Newman KD, Eichelberger MR, et al. Thoracic
baseball player is struck in the chest with a hit or thrown trauma in children: An indicator of increased mortality. J Pediatr
ball and collapses suddenly. Commotio cordis is charac- Surg 1990;25:9616.
2. Peterson RJ, Tepas JJ, Edwards FH, et al. Pediatric and adult tho-
terized by the absence of cardiac contusion, coronary racic trauma: Age-related impact on presentation and outcome.
artery abnormalities, structural abnormalities, or conduc- Ann Thorac Surg 1994;58:1418.
tion system pathology. It is thought that a sudden blow 3. Stafford PW, Harmon CM. Thoracic trauma in children. Curr
to the chest will result in a disorganized cardiac rhythm Opin Pediatr 1993;5:32532.
4. Holmes JF, Sokolove PE, Brant WE, et al. A clinical decision rule
followed by rapid cardiovascular collapse. Although chest for identifying children with thoracic injuries after blunt torso
protective devices seem useful, they do not provide total trauma. Ann Emerg Med 2002;39:4929.
protection against asystole.93 Automatic electrical defi- 5. Black TL, Snyder CL, Miller JP, et al. Significance of chest trauma
brillators may be life-saving for this rare sports-related in children. South Med J 1996;89:4946.
injury. 6. Mayer T, Matlak ME, Johnson DG, et al. The modified injury
severity scale in pediatric multiple trauma patients. J Pediatr Surg
1980;15:71926.
Esophagus 7. Reynolds M. Pulmonary, esophageal and diaphragmatic injuries.
In: Buntain WL, editor. Management of Paediatric Trauma. Phila-
Pediatric esophageal injuries are uncommon, occurring delphia, PA: WB Saunders; 1995. p. 23847.
8. Woosley CR, Mayes TC. The pediatric patient and thoracic
in less than 1% of children sustaining either blunt or trauma. Semin Thorac Cardiovasc Surg 2008;20:5863.
penetrating thoracic trauma.12,94,95 The esophagus is a 9. Smyth BT. Chest trauma in children. J Pediatr Surg 1979;
relatively elastic, mediastinal structure that is largely pro- 14:417.
tected by the bony thorax. This mobility is helpful when 10. Nakayama DK, Ramenofsky ML, Rowe MI. Chest injuries in
blunt force is applied as the esophagus can move, which childhood. Ann Surg 1989;210:7705.
11. Roux P, Fisher RM. Chest injuries in children: An analysis of 100
limits the likelihood of rupture. Penetrating injuries are cases of blunt chest trauma from motor vehicle accidents. J Pediatr
more likely to cause esophageal trauma. Esophageal dis- Surg 1992;27:5515.
ruption may manifest as dyspnea, dysphagia, cyanosis, 12. Cooper A, Barlow B, DiScala C, et al. Mortality and truncal injury:
mediastinal air, subcutaneous emphysema, pleural effu- The pediatric perspective. J Pediatr Surg 1994;29:338.
13. Allen GS, Cox CS Jr. Pulmonary contusion in children: Diagnosis
sion, chest or epigastric pain, fever, or sepsis.96 Initial and management. South Med J 1998;91:1099106.
symptoms, however, may be vague and nonspecific. 14. Balci AE, Kazez A, Eren S, et al. Blunt thoracic trauma in children:
Esophagography with a water-soluble contrast agent and Review of 137 cases. Eur J Cardiothorac Surg 2004;26:38792.
esophagoscopy are typically the studies that will best 15. Haxhija EQ, Nres H, Schober P, et al. Lung contusion-lacerations
identify an esophageal injury. after blunt thoracic trauma in children. Pediatr Surg Int
2004;20:41214.
If the esophagus is ruptured or perforated, conven- 16. Bliss D, Silen M. Pediatric thoracic trauma. Crit Care Med
tional management is operative repair. This is performed 2002;30:S40915.
for the purpose of drainage and/or repair. Treatment is 17. Cadzow SP, Armstrong KL. Rib fractures in infants: Red alert! The
initiated with fluid resuscitation and parenteral antibiot- clinical features, investigations and child protection outcomes.
J Paediatr Child Health 2000;36:3226.
ics.97 Operative repair consists of direct suture closure of 18. Bulloch B, Schubert CJ, Brophy PD, et al. Cause and clinical
the injury. If possible, pleural flap coverage and tube characteristics of rib fractures in infants. Pediatrics 2000;105:E48.
thoracostomy are performed. If an operation is under- 19. Kleinman PK, Nimkin K, Spevak MR, et al. Follow-up skeletal
taken early after injury, this treatment strategy, along surveys in suspected child abuse. AJR Am J Roentgenol
with no oral intake and total parenteral nutrition (TPN), 1996;167:8936.
20. Harris GJ, Soper RT. Pediatric first rib fractures. J Trauma
has good success. If the perforation is not identified early, 1990;30:3435.
treatment becomes more difficult. In perforations of 21. Garcia VF, Gotschall CS, Eichelberger MR, et al. Rib fractures in
more than 24 hours duration, operative closure becomes children: A marker of severe trauma. J Trauma 1990;30:695700.
technically much more demanding owing to the degree 22. Lee RB, Bass SM, Morris JA Jr, et al. Three or more rib fractures
as an indicator for transfer to a Level I trauma center: A population-
of inflammation and the amount of contamination. Tech- based study. J Trauma 1990;30:68994.
niques used in this circumstance include attempted suture 23. Gipson CL, Tobias JD. Flail chest in a neonate resulting from
repair, esophageal isolation, multiple drain placement, nonaccidental trauma. South Med J 2006;99:5368.
gastrostomy, and TPN. 24. Cannon RM, Smith JW, Franklin GA, et al. Flail chest injury: Are
In selected cases of esophageal perforation, nonopera- we making any progress? Am Surg 2012;78:398402.
25. Tanaka H, Yukioka T, Yamaguti Y, et al. Surgical stabilization of
tive management may be successful.96 This may be the internal pneumatic stabilization? A prospective randomized study
case with certain types of blunt trauma and with iatro- of management of severe flail chest patients. J Trauma 2002;52:
genic injury such as a perforation at the time of 72732.
198 SECTION II Trauma
26. Pettiford BL, Luketich JD, Landreneau RJ. The management of 53. Mizushima Y, Hiraide A, Shimazu T, et al. Changes in contused
flail chest. Thorac Surg Clin 2007;17:2533. lung volume and oxygenation in patients with pulmonary paren-
27. Voggenreiter G, Neudeck F, Aufmkolk M, et al. Operative chest chymal injury after blunt chest trauma. Am J Emerg Med
wall stabilization in flail chestoutcomes of patients with or without 2000;18:3859.
pulmonary contusion. J Am Coll Surg 1998;187:1308. 54. Kwon A, Sorrells DL, Kurkchubasche AG, et al. Isolated computed
28. Slater MS, Mayberry JC, Trunkey DD. Operative stabilization of tomography diagnosis of pulmonary contusion does not correlate
a flail chest six years after injury. Ann Thorac Surg with increased morbidity. J Pediatr Surg 2006;41:7882.
2001;72:6001. 55. Weber TR, Kountzman B. Extracorporeal membrane oxygenation
29. Fitzpatrick DC, Denard PJ, Phelan D, et al. Operative stabilization for nonneonatal pulmonary and multiple-organ failure. J Pediatr
of flail chest injuries: Review of literature and fixation options. Eur Surg 1998;33:16059.
J Trauma Emerg Surg 2010;36:42733. 56. Davis SL, Furman DP, Costarino AT Jr. Adult respiratory distress
30. Mayberry JC, Terhes JT, Ellis TJ, et al. Absorbable plates for rib syndrome in children: Associated disease, clinical course, and pre-
fracture repair: Preliminary experience. J Trauma 2003;55:8359. dictors of death. J Pediatr 1993;123:3545.
31. Thompson A Jr, Illescas FF, Chiu RC. Why is the lower torso 57. Karnak I, Senocak ME, Tanyel FC, et al. Diaphragmatic injuries
protected in traumatic asphyxia? A new hypothesis. Ann Thorac in childhood. Surg Today 2001;31:511.
Surg 1989;47:2479. 58. Koplewitz BZ, Ramos C, Manson DE, et al. Traumatic diaphrag-
32. Gorenstein L, Blair GK, Shandling B. The prognosis of traumatic matic injuries in infants and children: Imaging findings. Pediatr
asphyxia in childhood. J Pediatr Surg 1986;21:7536. Radiol 2000;30:4719.
33. Hurtado TR, Della-Giustina DA. Traumatic asphyxia in a 6-year- 59. Brandt ML, Luks FI, Spigland NA, et al. Diaphragmatic injury in
old boy. Pediatr Emerg Care 2003;19:1678. children. J Trauma 1992;32:298301.
34. Holmes JF, Brant WE, Bogren HG, et al. Prevalence and 60. Guth AA, Pachter HL, Kim U. Pitfalls in the diagnosis of blunt
importance of pneumothoraces visualized on abdominal computed diaphragmatic injury. Am J Surg 1995;170:59.
tomographic scan in children with blunt trauma. J Trauma 61. Westra SJ, Wallace EC. Imaging evaluation of pediatric chest
2001;50:51620. trauma. Radiol Clin North Am 2005;43:26781.
35. Renton J, Kincaid S, Ehrlich PF. Should helical CT scanning of 62. Kiser AC, OBrien SM, Detterbeck FC. Blunt tracheobronchial
the thoracic cavity replace the conventional chest x-ray as a primary injuries: Treatment and outcomes. Ann Thorac Surg 2001;71:
assessment tool in pediatric trauma? An efficacy and cost analysis. 205965.
J Pediatr Surg 2003;38:7937. 63. Nishiumi N, Maitani F, Yamada S, et al. Chest radiography assess-
36. Dente CJ, Ustin J, Feliciano DV, et al. The accuracy of thoracic ment of tracheobronchial disruption associated with blunt chest
ultrasound for detection of pneumothorax is not sustained over trauma. J Trauma 2002;53:3727.
time: A preliminary study. J Trauma 2007;62:13849. 64. Lomoschitz FM, Eisenhuber E, Linnau KF, et al. Imaging of chest
37. Soldati G, Testa A, Sher S, et al. Occult traumatic pneumothorax: trauma: Radiological patterns of injury and diagnostic algorithms.
Diagnostic accuracy of lung ultrasonography in the emergency Eur J Radiol 2003;48:6170.
department. Chest 2008;133:20411. 65. Wan YL, Tsai KT, Yeow KM, et al. CT findings of bronchial
38. Weissberg D, Refaely Y. Pneumothorax: Experience with 1,199 transection. Am J Emerg Med 1997;15:1767.
patients. Chest 2000;117:127985. 66. Ozdulger A, Cetin G, Erkmen Gulhan S, et al. A review of
39. Dull KE, Fleisher GR. Pigtail catheters versus large-bore chest 24 patients with bronchial ruptures: Is delay in diagnosis
tubes for pneumothoraces in children treated in the emergency more common in children? Eur J Cardiothorac Surg 2003;23:
department. Pediatr Emerg Care 2002;18:2657. 37983.
40. Barton ED, Rhee P, Hutton KC, et al. The pathophysiology of 67. Slimane MA, Becmeur F, Aubert D, et al. Tracheobronchial rup-
tension pneumothorax in ventilated swine. J Emerg Med tures from blunt thoracic trauma in children. J Pediatr Surg
1997;15:14753. 1999;34:184750.
41. Ozlu O, Kilic A, Cengizlier R. Bilateral re-expansion pulmonary 68. Reed WJ, Doyle SE, Aprahamian C. Tracheoesophageal fistula
edema in a child: A reminder. Acta Anaesthesiol Scand after blunt chest trauma. Ann Thorac Surg 1995;59:12516.
2000;44:8845. 69. Heckman SR, Trooskin SZ, Burd RS. Risk factors for blunt
42. Rawlins R, Momin A, Platts D, et al. Traumatic cardiogenic shock thoracic aortic injury in children. J Pediatr Surg 2005;40:
due to massive air embolism. A possible role for cardiopulmonary 98102.
bypass. Eur J Cardiothorac Surg 2002;22:8456. 70. Dornhofer T, Dinkel HP, Carrel T, et al. Complex, traumatic
43. Rivas LA, Fishman JE, Mnera F, et al. Multislice CT in thoracic rupture of the thoracic aorta in a child: Diagnostic findings and
trauma. Radiol Clin North Am 2003;41:599616. delayed surgery. Eur Radiol 2002;12:145962.
44. Grisoni ER, Volsko TA. Thoracic injuries in children. Respir Care 71. Lowe LH, Bulas DI, Eichelberger MD, et al. Traumatic aortic
Clin N Am 2001;7:2538. injuries in children: Radiologic evaluation. AJR Am J Roentgenol
45. Rielly JP, Brandt ML, Mattox KL, et al. Thoracic trauma in chil- 1998;170:3942.
dren. J Trauma 1993;34:32931. 72. Eddy AC, Rusch VW, Fligner CL, et al. The epidemiology of
46. Peterson RJ, Tiwary AD, Kissoon N, et al. Pediatric penetrating traumatic rupture of the thoracic aorta in children: A 13-year
thoracic trauma: A five-year experience. Pediatr Emerg Care review. J Trauma 1990;30:98991.
1994;10:12931. 73. Hall A, Johnson K. The imaging of paediatric thoracic trauma.
47. Kimbrell BJ, Yamzon J, Petrone P, et al. Intrapleural thrombolysis Paediatr Respir Rev 2002;3:2417.
for the management of undrained traumatic hemothorax: A pro- 74. Pearson GD, Karr SS, Trachiotis GD, et al. A retrospective review
spective observational study. J Trauma 2007;62:11759. of the role of transesophageal echocardiography in aortic and
48. Uribe RA, Pachon CE, Frame SB, et al. A prospective evaluation cardiac trauma in a level I Pediatric Trauma Center. J Am Soc
of thoracoscopy for the diagnosis of penetrating thoracoabdominal Echocardiogr 1997;10:94655.
trauma. J Trauma 1994;37:6504. 75. Mirvis SE, Shanmuganathan K. Diagnosis of blunt traumatic aortic
49. Fabbrucci P, Nocentini L, Secci S, et al. Video-assisted thoracos- injury 2007: Still a nemesis. Eur J Radiol 2007;64:2740.
copy in the early diagnosis and management of post-traumatic 76. Karmy-Jones R, Carter YM, Nathens A, et al. Impact of presenting
pneumothorax and hemothorax. Surg Endosc 2008;22:122731. physiology and associated injuries on outcome following traumatic
50. Skeete DA, Rutherford EJ, Schlidt SA, et al. Intrapleural tissue rupture of the thoracic aorta. Am Surg 2001;67:616.
plasminogen activator for complicated pleural effusions. J Trauma 77. Karmy-Jones R, Hoffer E, Meissner M, et al. Management of
2004;57:117883. traumatic rupture of the thoracic aorta in pediatric patients. Ann
51. St. Peter SD, Tsao K, Harrison C, et al. Thoracoscopic decortica- Thorac Surg 2003;75:151317.
tion vs. tube thoracostomy with fibrinolysis for empyema in 78. Wellons ED, Milner R, Solis M, et al. Stent-graft repair of trau-
children: A prospective, randomized trial. J Pediatr Surg 2009;44: matic thoracic aortic disruptions. J Vasc Surg 2004;40:1095100.
10611. 79. Hoffer EK, Karmy-Jones R, Bloch RD, et al. Treatment of acute
52. Allen GS, Cox CS, Moore FA, et al. Pulmonary contusion in chil- thoracic aortic injury with commercially available abdominal aortic
dren: Are children different? J Am Coll Surg 1997;185:22933. stent-grafts. J Vasc Interv Radiol 2002;13:103741.
15 Thoracic Trauma 199
80. Milas ZL, Milner R, Chaikoff E, et al. Endograft stenting in the 88. Hirsch R, Landt Y, Porter S, et al. Cardiac troponin I in pediatrics:
adolescent population for traumatic aortic injuries. J Pediatr Surg Normal values and potential use in the assessment of cardiac injury.
2006;41:e2730. J Pediatr 1997;130:8727.
81. Lee ML. Endovascular stent for the aortic coarctation in a 1.7-kg 89. Murillo CA, Owens-Stovall SK, Kim S, et al. Delayed cardiac
premie presenting intractable heart failure. Int J Cardiol tamponade after blunt chest trauma in a child. J Trauma 2002;
2006;113:2368. 52:5735.
82. Takawira FF, Sinyangwe G, Mooloo R. Endovascular covered stent 90. Rezende Neto JB, Diniz HO, Filho CS, et al. Blunt traumatic
treatment for descending aorta pseudoaneurysm following coarcta- rupture of the heart in a child: Case report and review of the litera-
tion of the aorta repair in an infant. Heart Lung Circ ture. J Trauma 2001;50:7469.
2010;19:7458. 91. Symbas NP, Bongiorno PF, Symbas PN. Blunt cardiac rupture: The
83. Patnaik AN, Srinivas B, Rao DS. Endovascular stenting for utility of emergency department ultrasound. Ann Thorac Surg
native coarctation in older children and adolescents using adult 1999;67:12746.
self-expanding (Nitinol) iliac stents. Indian Heart J 2009;61: 92. Perron AD, Brady WJ, Erling BF. Commodio cordis: An underap-
3537. preciated cause of sudden cardiac death in young patients: Assess-
84. Gunabushanam V, Mishra N, Calderin J, et al. Endovascular stent- ment and management in the ED. Am J Emerg Med 2001;
ing of blunt thoracic aortic injury in an 11-year-old. J Pediatr Surg 19:4069.
2010;45:E1518. 93. Maron BJ, Gohman TE, Kyle SB. Clinical profile and spectrum of
85. Chakrabarti S, Kenny D, Morgan G, et al. Balloon expandable commotio cordis. JAMA 2002;287:11426.
stent implantation for native and recurrent coarctation of the 94. Sartorelli KH, McBride WJ, Vane DW. Perforation of the intratho-
aortaprospective computed tomography assessment of stent integ- racic esophagus from blunt trauma in a child: Case report and
rity, aneurysm formation and stenosis relief. Heart 2010;96: review of the literature. J Pediatr Surg 1999;34:4957.
121216. 95. Cotton BA, Nance ML. Penetrating trauma in children. Semin
86. Tiao GM, Griffith PM, Szmuszkovicz JR, et al. Cardiac and great Pediatr Surg 2004;13:8797.
vessel injuries in children after blunt trauma: An institutional 96. Engum SA, Grosfeld JL, West KW, et al. Improved survival in
review. J Pediatr Surg 2000;35:165660. children with esophageal perforation. Arch Surg 1996;131:
87. Dowd MD, Krug S. Pediatric blunt cardiac injury: Epidemiology, 60411.
clinical features, and diagnosis. Pediatric Emergency Medicine 97. Asensio JA, Chahwan S, Forno W, et al. Penetrating esophageal
Collaborative Research Committee: Working Group on Blunt injuries: Multicenter study of the American Association for the
Cardiac Injury. J Trauma 1996;40:617. Surgery of Trauma. J Trauma 2001;50:28996.
C H A P T E R 1 6
While head injuries are responsible for the majority of development of irreversible shock. Complicating the
pediatric trauma deaths, intra-abdominal and retroperi- evaluation of injured children is the normal variability of
toneal injuries can still result in significant morbidity and vital signs depending on age.
mortality. Diagnostic uncertainty and delays in diagnosis
can lead to long-term complications and adversely impact
quality of life. Injuries to intra-abdominal organs occur INITIAL EVALUATION AND DIAGNOSIS
in 1015% of injured children.1 The spleen is the most OF ABDOMINAL INJURIES
frequently injured organ, and low velocity mechanisms,
such as falls, is the most frequent mechanism of injury. As the number of children with significant abdominal
The combination of the unique anatomic and physiologic injuries is relatively low, but the consequences of a missed
features of children and differences in mechanism result injury are high, accurate diagnosis is important. Initial
in patterns of injury unique to the pediatric population. assessment begins before the child arrives at the hospital.
As just mentioned, falls are the most frequent mecha- Important information from the first responders includes
nism of injury in children. However, motor vehicle mechanism of injury, use of protective or restraint devices,
crashes (MVC) are the most deadly, and are the leading condition of the child in the field, and, in the case of
cause of death for all children after the age of 1 year.2 MVC, damage to vehicle. Once in the emergency depart-
From the perspective of abdominal trauma, and using the ment (ED), a thorough history and physical examination
spleen as a marker for intra-abdominal injury, pediatric is essential. In most statistical models regarding the diag-
injuries tend to be the result of lower-velocity mecha- nosis of intra-abdominal injury, an abnormal physical
nisms when compared to adults. In a study that compared examination is the highest variable.58 While the exami-
splenic injuries at an adult level one trauma center and a nation can be challenging given the developmental level
pediatric level one trauma center, MVC accounted for of the child, use of comfort strategies and distraction can
66.9% of adult injuries but only 23.7% of pediatric inju- calm an initially distraught child to a degree that he/she
ries.3 On the other hand, sports mishaps resulted in only can reliably participate in the evaluation. Important phys-
2.3% of the adult injuries, but 17% of injuries involving ical findings include vital signs (particularly the presence
children. Even in the MVC population, pediatric injuries of persistent tachycardia), abdominal contusions or abra-
tend to differ from those suffered by adults. Children are sions, tenderness, or distention. Particular physical find-
less likely to be in the drivers seat (and hence less likely ings, such as the seat belt sign and handle bar mark,
to suffer injuries to the thorax from the steering wheel), are suspicious for the presence of intra-abdominal injury
and are more likely to be victims of poorly fitted restraint (and potential spine fracture in the case of the seat belt
systems. It is an important part of the initial history to mark) (Fig. 16-1).9
ascertain whether the pediatric victims in an MVC were
restrained, and the type and appropriateness of that
restraint for the childs age.
Laboratory Testing
Anatomically, the smaller size of children, as compared Laboratory testing for the purpose of diagnosing intra-
to adults, results in a closer proximity of organs. The abdominal injuries has generated considerable interest
abdominal wall, rib cage, and pelvic girdle are underde- and conflicting results. One study reported that the com-
veloped and provide less protection to the abdominal bination of an abnormal physical examination and >50
contents. In addition, children have less body fat, and red blood cells per high power field on urinalysis was a
hence, less padding to absorb and diffuse external highly sensitive screen for the presence of intra-abdominal
force.4 From the physiologic perspective, children injury.5 The study, limited by the low number of children
are generally healthy and have fewer underlying who actually had a documented injury (14 out of the total
medical problems than adults. It is uncommon for chil- study population of 285), also concluded that laboratory
dren to be on medications, particularly those that poten- abnormalities in this trauma population were relatively
tially affect hemodynamics or hemostasis. Therefore, uncommon. The conclusion that routine laboratory
injured pediatric patients are better able to effectively studies add little to the evaluation has also been replicated
compensate for physiologic insults such as acute blood in more recent studies.6,7 Conversely, studies using
loss. It is generally accepted that children can lose up sophisticated regression analyses have demonstrated that
to 45% of their circulating blood volume, and exhibit elevations of aspartate aminotransferase (AST) and/or
tachycardia as the only abnormal vital sign.4 Persistent alamine aminotransferase (ALT), in combination with an
hypotension is an ominous finding, suggesting the abnormal physical examination, correlate with the pres-
failure of compensatory mechanisms and the potential ence of an intra-abdominal injury, although the tests are
200
16 Abdominal and Renal Trauma 201
not diagnostic for a particular injured organ.8,1012 A clini- of intra-abdominal injuries in hemodynamically stable
cal prediction model using a combination of physical children.4 Newer generation scanners have excellent sen-
examination findings (hypotension and abnormal exami- sitivity and specificity, especially for the evaluation of
nation findings) and laboratory studies (AST, amylase, solid organ injuries. Upwards of 95% of liver, spleen, and
hematocrit, heme-positive urinalysis) successfully pre- renal injuries can be diagnosed and staged by CT (Fig.
dicted the presence of intra-abdominal injury in a 16-2). Injuries to the intestine and pancreas are more
small, single center study.13 Interestingly, routine amylase difficult to definitively diagnose by CT. However, with
and lipase determinations do not appear to be very reli- the addition of coronal reconstructions, CT provides sig-
able or cost effective screening tools.14 In the special nificant information to guide the clinician regarding
population of children suspected of abuse, elevations in these injuries. Similarly, the risk of a missed intra-
AST or ALT, or abnormal physical examination findings abdominal injury in a child with a completely negative
(such as bruising, distention, or tenderness), may indicate CT is very low, leading some to advocate using CT as a
the need for further abdominal imaging looking for means to decrease the need for in-patient observation
occult injury.15 after blunt abdominal trauma.16
In summary, it appears that laboratory panels in the It has been suggested that in young children who lack
evaluation of children at risk for intra-abdominal injuries visceral fat, the addition of oral contrast to the standard
are best utilized in conjunction with physical examination IV contrast may be helpful, especially in evaluating the
findings and as a screen to determine those children who duodenum and pancreatic head.17 The use of oral con-
might require further diagnostic testing, particularly trast, however, remains controversial due to concerns
imaging. regarding aspiration, and may not provide significant
additional information with current, multi-detector CT
imaging. Intravenous contrast, however, is essential for
Computed Tomography the evaluation of traumatic injuries. If IV contrast is con-
Computed tomography (CT) with intravenous contrast traindicated, alternative methods of abdominal evalua-
(IV) is the preferred modality for the diagnosis tion should be considered.
A B
FIGURE 16-2 CT scans are highly accurate in demonstrating solid organ injuries. (A) Hemoperitoneum with a liver laceration (arrow)
and a shattered spleen is seen. (B) Hemoperitoneum and a left renal laceration (arrow) is shown.
202 SECTION II Trauma
The radiation exposure during CT imaging has in developing algorithms that incorporate ultrasound
become an area of major concern in children. The use of into the evaluation of abdominal trauma.29,30 The ulti-
CT has been rapidly increasing over the past decade, with mate goal is to limit the number of CT scans. In the less
over seven million scans performed on children, mostly common scenario of the hemodynamically unstable child,
for the evaluation of trauma and appendicitis.18 Using a positive FAST examination supports the decision to
models extrapolated from radiation exposure from the rapidly proceed to the operating room.
atomic bomb explosions, a risk of one fatal cancer per
1000CT scans performed in young children (above the
baseline cancer risk of approximately one in four adults
Laparoscopy
in the USA) has been estimated.19 A recently published Minimally invasive approaches are now well incorporated
longitudinal, population-based study in Great Britain in pediatric surgical practice so it is not surprising that
demonstrated an increased incidence of leukemia and laparoscopy for the evaluation of abdominal trauma is
brain cancer after repeated CT scans in children.20 Infants being utilized. Despite the excellent anatomic definition
and children are more sensitive than adults to the effects provided by multi-detector CT, there remain areas of
of radiation given their small size (larger absorbed dose diagnostic uncertainty. The child with free fluid without
per unit area) and growing organs.21 In response, the evidence of solid organ injury, particularly with physical
pediatric radiology community has developed an Image examination findings of a seat belt or handlebar mark, is
Gently campaign to address the publics concerns.21 In one example. Another scenario is the child with signifi-
addition, two recent position papers, authored by the cant abdominal tenderness with a nondiagnostic CT
APSA Education Committee and the American Academy scan. If the findings at laparoscopy indicate the need for
of Pediatrics (AAP) Radiology Committee, have addressed a formal laparotomy, an open approach can be targeted
the issue of CT scans in children.22,23 Both endorse the to the specific injury. In two relatively large reviews,
ALARA principle (as low as reasonably achievable) and laparoscopy was found to be safe and beneficial by avoid-
advocate for the use of scanners with pediatric dose ing laparotomy in a significant number of patients.31,32
reduction software, employing alternative imaging Also, a number of injuries were amenable to laparoscopic
modalities (if available), limiting the number or phases of repair. CT and laparoscopy now provide complementary
scans (for example with and without contrast or arterial information, with CT defining areas, such as the retro-
and venous phases), and the use of limited scans. Other peritoneum, kidneys, and pancreas, which are difficult to
concepts include limiting the number of repeat scans and assess using laparoscopy. On the other hand, laparoscopy
developing relationships with referring adult institutions allows for direct visualization of the bowel, mesentery,
to limit the number of scans performed on children prior and diaphragmatic surfaces, regions that CT has tradi-
to transfer. tionally not been as accurate (Fig. 16-3).
Ultrasound
As concerns regarding CT have increased, there has been
MANAGEMENT
a renewed interest in the use of ultrasound (US) in the Liver and Spleen
evaluation of pediatric abdominal trauma. The original
descriptions about ultrasound in trauma centered on the Close to 9095% of injuries to the liver and spleen in
rapid evaluation of the unstable adult trauma patient to children can be managed nonoperatively. It is rare for
determine the presence and source of life-threatening isolated low grade injuries to these organs to require
hemorrhage. The FAST (focused assessment with sonog- blood transfusion.33 Nonoperative management (NOM)
raphy in trauma) examination was developed to assess the is dependent upon the accurate diagnosis and staging of
presence of intra-abdominal free fluid (with examination the injured organ, usually by CT imaging at present.
of Morrisons pouch, the pouch of Douglas, and the left Injuries are graded according to the American Associa-
flank) or fluid within the pericardial sac (subxiphoid tion for the Surgery of Trauma (AAST) organ injury
view), and thus indicate the need for operative explora- scale, with grade I injuries representing small lacerations
tion. In multiple studies, the traditional FAST examina- or hematomas and grade V injuries indicating complete
tion has been found to have a low sensitivity and specificity vascular disruption or massive parenchymal injury (Table
for the diagnosis of injury in children.2427 A recently 16-1).34 In order to be a candidate for NOM, the child
published large series directly comparing FAST examina- should have normal hemodynamics, and be monitored
tion in children to CT or laparotomy for the presence of closely for signs of ongoing hemorrhage. Most children
free fluid concluded that a positive FAST suggested who fail NOM do so within four hours of injury as a
hemoperitoneum and associated abdominal injury, but a result of shock, peritonitis, or persistent bleeding.35 Late
negative FAST adds little in decision making.28 In addi- failures are often the result of peritonitis due to an evolv-
tion, since the majority of pediatric solid organ injuries, ing intestinal injury. There are published, evidence-based
even those with significant free fluid (hemoperitoneum), guidelines for NOM in a child with a liver or spleen
can be managed nonoperatively, a positive FAST exami- injury.36,37 Essentially, these guidelines recommend hos-
nation may not be very helpful in directing clinical care. pitalization for grade of injury plus one days, and note
On the other hand, the use of provider-performed ultra- that children with higher grade injuries may benefit from
sound has increased dramatically over the past several intensive care unit observation. Routine follow-up
years in the pediatric ED, and there is significant interest imaging is not indicated, and children can return to
16 Abdominal and Renal Trauma 203
A B
FIGURE 16-3 In some patients it is not always clear whether a significant intestinal injury has occurred from either blunt or penetrat-
ing trauma. Diagnostic laparoscopy is a useful technique in these patients. (A) Perforation of the bowel from penetrating trauma is
seen at laparoscopy. This was closed primarily. (B) Full-thickness injury to the colon (arrow) in a patient with blunt trauma is shown.
The laparoscopic approach was converted to an open operation for treatment of this injury.
regular activity after grade of injury plus two weeks from abdomen, and to have access to the femoral vessels. Upon
the time of injury. More recent work challenges these entrance to the abdomen, the four quadrants are packed
recommendations, finding that more abbreviated periods to tamponade the bleeding and allow the anesthesiolo-
of bed rest and hospitalization does not result in delayed gists to catch-up. The peritoneal contents are then
bleeding or return to the hospital.38 Fortunately, most explored in a systematic fashion. The goal of initial oper-
splenic and hepatic injuries in children will resolve ative exploration is to stop bleeding and control the fecal
without the need for operative intervention with excel- stream (damage control).
lent long-term outcomes. Splenectomy easily controls bleeding in the hemody-
While bleeding from most solid organ injuries in chil- namically unstable patient with active exsanguination
dren will stop, there are a small number in which the from a massively damaged spleen, although at the theo-
bleeding is significant. Tachycardia, not responsive to retical cost of a long-term risk of postsplenectomy sepsis.
fluid resuscitation, is the initial sign of shock in these Children with splenic injuries who have ongoing bleed-
children. Hypotension is often a late finding and suggests ing, but are not in shock, are potential candidates for
significant hemorrhage. Evidence of ongoing bleeding splenic sparing operations. Partial splenectomy and mesh
with an abnormal abdominal examination or a positive splenorrhaphy are techniques that can successfully save
abdominal FAST examination necessitates urgent opera- splenic parenchyma, although they may be time consum-
tive exploration. Rapid transfusion protocols, while not ing, and are therefore not appropriate in the unstable
formally validated in children, are utilized with the goal patient.40
of 1:1:1 transfusion of packed red blood cells (PRBC), Postsplenectomy sepsis is a rare, but potentially fatal
fresh frozen plasma (FFP), and platelets. In infants and consequence of splenectomy due to overwhelming
children, this translates to 20mL/kg of PRBC, FFP and infection by encapsulated organisms. The reported
platelets.39 In the operating room, a rapid transfusion incidence is around 0.23% a year, with an increased
device and cell saver should be available in the event of incidence in children less than 2 years of age, and those
rapid blood loss. The patient is prepped from neck to that underwent splenectomy for hematologic reasons.41
knees to allow for entrance into either the chest or Vaccination with the 23-valent pneumococcal vaccine, as
Vascular Juxtahepatic venous injuries: i.e., retrohepatic vena cava/central major hepatic veins
Vascular Couinauds segments within single lobe
Hepatic avulsion
From Tinkoff G, Esposito TJ, Reed J, etal. American Association for the Surgery of Trauma Organ Injury Scale I: spleen, liver,
and kidney, validation based on the National Trauma Data Bank. J Am Coll Surg 2008;207:64655.
204 SECTION II Trauma
well as vaccinations against Haemophilus influenzae type B causes reduced perfusion to the intra-abdominal organs.
and meningococcus, should be administered after The result is ischemia and refractory metabolic acidosis
splenectomy. With high grade splenic injuries managed along with interference with cardiopulmonary function
nonoperatively, assessment of splenic function may also secondary to reduced preload from decreased central
be indicated. venous return to the heart, decreased respiratory compli-
A major hepatic injury is considerably more difficult ance, and decreased functional residual capacity.45 ACS is
to control in the operating room. The segmental anatomy associated with a 4060% mortality in children.4648
of the liver and the location of important arterial, venous, As IAH in children is different from adults, the current
and portal structures is very important. Peitzman and proposed working definition for ACS in children is an
Marsh recently reviewed operative techniques for the elevated intra-abdominal pressure (IAP) of 10mmHg or
management of complex liver injury.42 Key components greater with the development of new or worsening mul-
of operative control of hepatic parenchymal injury include tiorgan failure.44 There are three different types of ACS:
adequate exposure, an experienced co-surgeon, good (1) primary ACS refers to ACS that occurs due to a
anesthesia support, and supradiaphragmatic intravenous primary intra-abdominal cause such as abdominal trauma;
access. They recommend initial management of deep (2) secondary ACS or extra-abdominal compartment syn-
parenchymal fractures with compression, followed by drome occurs as a result of massive bowel edema second-
suture ligation of bleeding vessels, and the avoidance of ary to sepsis, capillary leak, and other conditions requiring
deep liver sutures. The Pringle maneuver can help dif- massive fluid resuscitation; and (3) tertiary ACS or recur-
ferentiate between hepatic arterial bleeding (decreases rent ACS in which ACS recurs after resolution of an
when the clamp is engaged) and hepatic venous bleeding. earlier episode of either primary or secondary ACS.49 IAP
Ideally, intermittent clamping of the porta hepatis should can be measured by using the bladder pressure. If IAH is
be performed to decrease the degree of hepatic ischemia. detected, serial IAP measurements are needed. It is
Large fractures are best treated with anatomic or non- important to note that clinical examination is an inac-
anatomic resection, assuming enough residual liver curate predictor of IAP and should not be substituted for
remains. Resection can be efficiently performed using IAP measurement.50
mechanical staplers. While the definitive operation must Initial management strategies in the trauma patient
control bleeding and bile leak, debride nonviable tissue, include improving abdominal wall compliance via ade-
and adequately drain the resected margin, control of quate sedation and paralysis, evacuation of intralumenal
hemorrhage is the primary concern in an emergency intestinal contents, evacuation of large abdominal fluid
operation. Temporizing maneuvers, such as packing with collections, optimization of fluid administration by goal-
control of bleeding, are performed and a temporary directed therapies and correcting positive fluid balance,
abdominal closure is created to allow for ongoing resus- and optimization of abdominal perfusion pressure.51 Over
citation and to prevent abdominal compartment syn- the last ten years, three major changes have led to signifi-
drome. Vacuum dressings have been developed specifically cant reductions in the incidence and mortality from ACS
for this purpose, but techniques such as the Bogota bag in adult trauma patients. These are adoption of massive
are still viable alternatives. Multiple trips to the operating transfusion protocols and 1:1 blood to plasma transfu-
room for wash-out, packing removal, and treatment of sion strategies in trauma, the widespread use of damage
other injuries may be required before the patient is ready control and open abdomen approaches to the polytrau-
for formal abdominal closure. matized abdominal cavity, and an increased use of plasma
and colloids in the resuscitation of burn patients.51 Similar
strategies and an increased awareness of ACS in pediatric
Abdominal Compartment Syndrome trauma patients may also result in improved outcomes.
Abdominal compartment syndrome (ACS) is defined as In the unstable trauma patient who requires an emer-
sustained intra-abdominal hypertension (IAH) that is gent laparotomy and massive fluid resuscitation, main-
associated with new onset organ dysfunction or failure.43,44 taining an open abdomen with planned staged closure
It is an uncommon, but potentially lethal condition that may prevent the development of ACS but often needs to
occurs when abdominal distension associated with IAH be performed prophylactically (Fig. 16-4A). In patients
A B
FIGURE 16-4 (A) Abdominal wall expansion was performed in this patient with a bowel bag. (B) Abdominal wall expansion in this
patient was accomplished with a polytetrafluoroethylene patch.
16 Abdominal and Renal Trauma 205
Diaphragmatic Injury
Blunt traumatic rupture of the diaphragm via massive
compressive forces to the abdomen accounts for 8090%
of diaphragmatic injury in the pediatric population.73
This injury rarely occurs in isolation, but is often associ-
ated with multiple organ injury and a high index of sever-
ity scores.74 Abdominal contents may herniate into the
thoracic cavity due to the pressure gradient between the
pleura and peritoneal cavities. Right and left sided rup-
FIGURE 16-6 This abdominal CT scan demonstrates blunt tures occur with equal frequency.75 Plain radiographs may
transection of the pancreas (arrow). suggest the diagnosis of traumatic diaphragm rupture via
an obscured or elevated hemidiaphragm, gas in herniated
viscus above the diaphragm (Fig. 16-8A), tip of nasogas-
tric tube in the thorax, the presence of an atypical pneu-
mothorax, and plate-like atelectasis adjacent to the
diaphragm.73
Emergent operative exploration in patients with dia-
phragm injury is indicated in the hemodynamically
unstable patient with multiple organ injury. A thorough
and systematic exploration of the entire abdomen and
palpation of retroperitoneal structures is required due to
the frequency of multiple organ injury. Repair of the
diaphragmatic defect is typically possible after debride-
ment of any compromised tissue. If large defects are
found, a prosthetic patch may be needed to minimize the
tension. Successful laparoscopic or thoracoscopic repair
of diaphragmatic injuries can be performed in hemody-
namically stable children and in cases with delayed diag-
nosis (Fig. 16-8B, C).7678
A B C
FIGURE 16-8 This teenager developed respiratory symptoms several weeks after a motor vehicle accident. (A) The chest radiograph
shows air in either the stomach or the intestine in the left chest. (B) At laparoscopic exploration, the traumatic diaphragmatic hernia
is seen after reduction of the stomach and several loops of small intestine. (C) The traumatic diaphragmatic hernia was repaired
laparoscopically and the patient recovered uneventfully.
Laparoscopy may be needed to evaluate for intra- handlebars, collisions involving ejection, or ATV rollo-
peritoneal extension.106 Most vaginal, anal, and superficial ver. Increased awareness and use of proper safety equip-
perineal body injuries can be treated with primary repair. ment may contribute to decreased prevalence and severity,
Historically, rectal trauma was managed with a diverting including abdominal or flank padding, to reduce blunt
colostomy, drainage of the perineal wound, and rectal force and handlebar intrusion.119
irrigation.113 Currently, selective diversion has been advo- Patients with renal trauma typically present with gross
cated for both pediatric and adult patients with good hematuria and flank pain. The diagnosis is confirmed by
results.7,106 abdominal CT scan which is highly sensitive. Renal inju-
ries have also been classified by the AAST (Table 16-3).
This classification system has been useful in standardiz-
Gallbladder Injury ing and validating treatment strategies.125 Management
The gallbladder is rarely injured in children. However, goals involve maximizing functional renal parenchyma
associated injuries are common.114,115 Predisposing factors while minimizing patient morbidity.126 Expectant
for gallbladder trauma are a thin-walled normal gallblad- NOM is widely accepted for hemodynamically stable
der, a distended gallbladder after a meal, and alcohol grade I-III renal injuries which do not have urinary
ingestion. If identified, a cholecystectomy is usually per- extravasation.127
formed. This may be performed via laparoscopy or Treatment for children with high grade renal injury
laparotomy. (grade IV and grade V) remains controversial (Fig.
16-13). Urinary extravasation and urinoma continue to
be relative indications for exploration in some centers.128
Urinary Bladder Historically, patients with higher grade injury were also
The bladder is the second most common genitourinary more likely to undergo endourologic interventions such
(GU) injury in children.116,117 Bladder injuries range from as nephrostomies or ureteral stents.129,130 Most current
grade I contusions to grade V extraperitoneal or intra- pediatric series report successful nonoperative manage-
peritoneal ruptures involving the bladder neck or ureteral ment for grade IV and V injuries.127 Endourologic inter-
orifices.118 It is hypothesized that the bladders rostral ventions are reserved primarily for persistent extravasation
location in relation to the pelvis increases the risk of or symptomatic urinomas rather than all injuries with
injury in children.119 CT cystography is used to evaluate disrupted collecting systems.127 Selective angioemboliza-
a suspected bladder injury. Prompt repair is required for tion of renal artery branches has been successful in nearly
intraperitoneal ruptures as incomplete drainage of intra- 80% of cases with delayed hemorrhage.131 Using indi-
abdominal urine can lead to infection, peritonitis, and vidualized selective management, several studies have
even death.120 Typically, a two layered closure with documented renal preservation in over 95% of chil-
absorbable suture material is performed, and either dren.127,132,133 The main indications for immediate explo-
transurethral or suprapubic drains are used for temporary ration in a child with a renal injury are hemodynamic
decompression. Urethral catheter drainage is considered
sufficient for uncomplicated extraperitoneal ruptures.120
REFERENCES
FIGURE 16-13 This child developed a grade III injury to the right
kidney. There is a deep laceration through the central aspect of 1. Gaines BA. Intra-abdominal solid organ injury in children: Diag-
the kidney (arrow), but no evidence of urinary extravasation or nosis and treatment. J Trauma 2009;67:S135139.
development of a urinoma. This patient was managed nonop- 2. WISQARS. Centers for Disease Control and Prevention, 2008.
eratively and recovered uneventfully. 3. Powell M, Courcoulas A, Gardner M, et al. Management of blunt
splenic trauma: Significant differences between adults and chil-
dren. Surgery 1997;122:65460.
4. Trauma AcoSCo. Advanced Trauma Life Support for Doctors,
instability, penetrating mechanism, and associated non- Student Course Manual. In: American College of Surgeons Com-
renal injuries.132 mittee on Trauma. Chicago; 2004. p. 251.
5. Isaacman DJ, Scarfone RJ, Kost SI, et al. Utility of routine labora-
Stable patients with high grade injury are typically tory testing for detecting intra-abdominal injury in the pediatric
placed at bed rest with serial exams, blood counts, and trauma patient. Pediatrics 1993;92:6914.
close hemodynamic monitoring until the gross hematuria 6. Capraro AJ, Mooney D, Waltzman ML. The use of routine labo-
resolves. However, there are no evidence-based guide- ratory studies as screening tools in pediatric abdominal trauma.
lines regarding length of activity restriction in these Pediatr Emerg Care 2006;22:4804.
7. Haut ER, Nance ML, Keller MS, et al. Management of penetrat-
patients.134 A multi-institutional prospective study allow- ing colon and rectal injuries in the pediatric patient. Dis Colon
ing for immediate ambulation and discharge based on Rectum 2004;2004:47:152632.
standard criteria, rather than resolution of gross hematu- 8. Holmes JF, Sokolove PE, Brant WE, et al. Identification of chil-
ria, is currently underway to address possible dren with intra-abdominal injuries after blunt trauma. Ann Emerg
Med 2002;39:5009.
guidelines. 9. Sokolove PE, Kuppermann N, Holmes JF. Association between
the seat belt sign and intra-abdominal injury in children with
Penetrating Renal Injury blunt torso trauma. Acad Emerg Med 2005;12:80813.
10. Holmes JF, Sokolove PE, Land C, et al. Identification of intra-
Penetrating renal injury in children is rare, but typically abdominal injuries in children hospitalized following blunt torso
trauma. Acad Emerg Med 1999;6:799806.
requires exploration for management. Selective observa- 11. Cotton BA, Beckert BW, Smith MK, et al. The utility of clinical
tion for penetrating renal trauma, however, is also being and laboratory data for predicting intraabdominal injury among
applied and can be done safely.135,136 Hemodynamically children. J Trauma 2004;56:106874.
unstable patients with penetrating injury or patients with 12. Flood RG, Mooney DP. Rate and prediction of traumatic injuries
detected by abdominal computed tomography scan in intubated
an expanding retroperitoneal hematoma require renal children. J Trauma 2006;61:3405.
exploration. During exploration, a one-shot IVP may be 13. Streck CJ Jr, Jewett BM, Wahlquist AH, et al. Evaluation for
helpful to identify the injured area and confirm the pres- intra-abdominal injury in children after blunt torso trauma: Can
ence of a functioning contralateral kidney. we reduce unnecessary abdominal computed tomography by uti-
lizing a clinical prediction model? J Trauma Acute Care Surg
2012;73:3716.
Risk of Injury for Solitary Normal Kidney 14. Adamson WT, Hebra A, Thomas PB, et al. Serum amylase and
lipase alone are not cost-effective screening methods for pediatric
It is not uncommon for patients with a single, normal pancreatic trauma. J Pediatr Surg 2003;38:3547.
kidney and their family to seek advice from physicians 15. Lindberg D, Makoroff K, Harper N, et al. Utility of hepatic
transaminases to recognize abuse in children. Pediatrics
regarding the safety of participating in contact sports. As 2009;124:50916.
kidney injuries from sports are rare, the AAP recom- 16. Hom J. The risk of intra-abdominal injuries in pediatric patients
mends a qualified yes for participation in contact or with stable blunt abdominal trauma and negative abdominal com-
collision sports for young athletes with a single kidney.137 puted tomography. Acad Emerg Med 2010;17:46975.
Still, many physicians are reluctant to give approval.138 17. Nastanski F, Cohen A, Lush SP, et al. The role of oral contrast
administration immediately prior to the computed tomographic
A recent prospective study, analyzing more than 4.4 evaluation of the blunt trauma victim. Injury 2001;32:5459.
million high school athlete exposures, discovered that 18. Brenner DJ, Hall EJ. Computed tomographyan increasing
sport-related renal injuries are very rare.139 Out of the source of radiation exposure. N Engl J Med 2007;357:227784.
212 SECTION II Trauma
19. Brenner D, Elliston C, Hall E, et al. Estimated risks of radiation- 44. Ejike JC, Newcombe J, Baerg J, et al. Understanding of abdominal
induced fatal cancer from pediatric CT. AJR Am J Roentgenol, compartment syndrome among pediatric healthcare providers.
2001;176:28996. Crit Care Res Pract 2010; Article ID 876013, 6 pages.
20. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from 45. Vidal MG, Ruiz Weisser J, Gonzalez F, et al. Incidence and clinical
CT scans in childhood and subsequent risk of leukaemia and brain effects of intra-abdominal hypertension in critically ill patients.
tumours: A retrospective cohort study. Lancet 2012;380: Crit Care Med 2008;36:182331.
499505. 46. Beck R, Halberthal M, Zonis Z, et al. Abdominal compartment
21. Image Gently. www.pedrad.org/associations/5364/1g. syndrome in children. Pediatr Crit Care Med 2001;2:516.
22. Rice HE, Frush DP, Farmer D, et al. Review of radiation risks 47. Diaz FJ, Fernandez Sein A, Gotay F. Identification and manage-
from computed tomography: Essentials for the pediatric surgeon. ment of abdominal compartment syndrome in the pediatric inten-
J Pediatr Surg 2007;42:6037. sive care unit. P R Health Sci J 2006;25:1722.
23. Brody AS, Frush DP, Huda W, et al. Radiation risk to children 48. Pearson EG, Rollins MD, Vogler SA, et al. Decompressive
from computed tomography. Pediatrics 2007;120:67782. laparotomy for abdominal compartment syndrome in children:
24. Benya EC, Lim-Dunham JE, Landrum O, et al. Abdominal Before it is too late. J Pediatr Surg 2010;45:13249.
sonography in examination of children with blunt abdominal 49. Cheatham ML, Malbrain ML, Kirkpatrick A, et al. Results from
trauma. AJR Am J Roentgenol 2000;174:6131616. the International Conference of Experts on intra-abdominal
25. Coley BD, Mutabagani KH, Martin LC, et al. Focused abdominal hypertension and abdominal compartment syndrome. II. Recom-
sonography for trauma (FAST) in children with blunt abdominal mendations. Intensive Care Med 2007;33:95162.
trauma. J Trauma 2000;48:9026. 50. Sugrue M, Bauman A, Jones F, et al. Clinical examination is an
26. Emery KH, McAneney CM, Racadio JM, et al. Absent peritoneal inaccurate predictor of intraabdominal pressure. World J Surg
fluid on screening trauma ultrasonography in children: A prospec- 2002;26:142831.
tive comparison with computed tomography. J Pediatr Surg 51. Carr JA. Abdominal compartment syndrome: A decade of
2001;36:5659. progress. J Am Coll Surg 2013;216:13546.
27. Holmes JF, Gladman A, Chang CH. Performance of abdominal 52. Gutierrez IM, Gollin G. Negative pressure wound therapy for
ultrasonography in pediatric blunt trauma patients: A meta- children with an open abdomen. Langenbecks Arch Surg
analysis. J Pediatr Surg 2007;42:158894. 2012;397:13537.
28. Fox JC, Boysen M, Gharahbaghian L, et al. Test characteristics of 53. Suliburk JW, Ware DN, Balogh Z, et al. Vacuum-assisted wound
focused assessment of sonography for trauma for clinically signifi- closure achieves early fascial closure of open abdomens after
cant abdominal free fluid in pediatric blunt abdominal trauma. severe trauma. J Trauma 2003;55:115561.
Acad Emerg Med 2011;18:47782. 54. Nwomeh BC, Nadler EP, Meza MP, et al. Contrast extravasation
29. Cardamore R, Nemeth J, Meyers C. Bedside emergency predicts the need for operative intervention in children with blunt
department ultrasonography availability and use for blunt abdom- splenic trauma. J Trauma 2004;56:53741.
inal trauma in Canadian pediatric centres. CJEM 2012;14: 55. Lutz N, Mahboubi S, Nance ML, et al. The significance of con-
1419. trast blush on computed tomography in children with splenic
30. Noble VE, Blaivas M, Blankenship R, et al. Decision rule for injuries. J Pediatr Surg 2004;39:4914.
imaging utilization in blunt abdominal traumawhere is ultra- 56. Davies DA, Ein SH, Pearl R, et al. What is the significance of
sound? Ann Emerg Med 2010;55:4879. contrast blush in pediatric blunt splenic trauma? J Pediatr Surg
31. Feliz A, Shultz B, McKenna C, et al. Diagnostic and therapeutic 2010;45:91620.
laparoscopy in pediatric abdominal trauma. J Pediatr Surg 57. Puapong D, Brown CV, Katz M, et al. Angiography and the
2006;41:727. pediatric trauma patient: A 10-year review. J Pediatr Surg 2006;41:
32. Marwan A, Harmon CM, Georgeson KE, et al. Use of laparos- 185963.
copy in the management of pediatric abdominal trauma. J Trauma 58. Kiankhooy A, Sartorelli KH, Vane DW, et al. Angiographic
2010;69:7614. embolization is safe and effective therapy for blunt abdominal
33. Gaines BA, Ford HR. Abdominal and pelvic trauma in children. solid organ injury in children. J Trauma 2010;68:52631.
Crit Care Med 2002;30:S416423. 59. Graham GP, Haan JM. Splenic artery embolization in a 7-year-old
34. Tinkoff G, Esposito TJ, Reed J, et al. American Association for with blunt traumatic splenic rupture. Am Surg 2012;78:E2978.
the Surgery of Trauma Organ Injury Scale I: spleen, liver, and 60. Yi IK, Miao FL, Wong J, et al. Prophylactic embolization of
kidney, validation based on the National Trauma Data Bank. J Am hepatic artery pseudoaneurysm after blunt abdominal trauma in a
Coll Surg 2008;207:64655. child. J Pediatr Surg 2010;45:8379.
35. Holmes JH 4th, Wiebe DJ, Tataria M, et al. The failure of non- 61. Stylianos S, Hicks BA. Abdominal and Renal Trauma. Ashcrafts
operative management in pediatric solid organ injury: A multi- Pediatric Surgery. 5th ed. Elsevier Inc.; 2010. p. 190208.
institutional experience. J Trauma 2005;59:130913. 62. Giss SR, Dobrilovic N, Brown RL, et al. Complications of non-
36. Stylianos S. Evidence-based guidelines for resource utilization in operative management of pediatric blunt hepatic injury: Diagno-
children with isolated spleen or liver injury. The APSA Trauma sis, management, and outcomes. J Trauma 2006;61:3349.
Committee. J Pediatr Surg 2000;35:1649. 63. Almaramhi H, Al-Qahtani AR. Traumatic pediatric bile duct
37. Stylianos S. Compliance with evidence-based guidelines in chil- injury: Nonoperative intervention as an alternative to surgical
dren with isolated spleen or liver injury: A prospective study. intervention. J Pediatr Surg 2006;41:9435.
J Pediatr Surg 2002;37:4536. 64. Ulitsky A, Werlin S, Dua KS. Role of ERCP in the management
38. St Peter SD, Sharp SW, Snyder CL, et al. Prospective validation of non-iatrogenic traumatic bile duct injuries in the pediatric
of an abbreviated bedrest protocol in the management of blunt population. Gastrointest Endosc 2011;73:8237.
spleen and liver injury in children. J Pediatr Surg 2011;46: 65. Wood JH, Partrick DA, Bruny JL, et al. Operative vs nonoperative
1737. management of blunt pancreatic trauma in children. J Pediatr
39. Dehmer JJ, Adamson WT. Massive transfusion and blood product Surg 2010;45:4016.
use in the pediatric trauma patient. Semin Pediatr Surg 2010;19: 66. Herman R, Guire KE, Burd RS, et al. Utility of amylase and lipase
28691. as predictors of grade of injury or outcomes in pediatric patients
40. Jacobs LM. Splenorrhaphy. In: Jacobs LM, editor. Advanced with pancreatic trauma. J Pediatr Surg 2011;46:9236.
Trauma Operative Management. Woodbury, CT; 2004. p 7883. 67. Rutkoski JD, Segura BJ, Kane TD. Experience with totally
41. Morgan TL, Tomich EB. Overwhelming post-splenectomy infec- laparoscopic distal pancreatectomy with splenic preservation
tion (OPSI): A case report and review of the literature. J Emerg for pediatric trauma2 techniques. J Pediatr Surg 2011;46:
Med 2012;43:75863. 58893.
42. Peitzman AB, Marsh JW. Advanced operative techniques in the 68. Iqbal CW, Levy SM, Tsao K, et al. Laparoscopic versus open distal
management of complex liver injury. J Trauma Acute Care Surg pancreatectomy in the management of traumatic pancreatic dis-
2012;73:76570. ruption. J Laparoendosc Adv Surg Tech A 2012;22:5958.
43. Saggi BH, Sugerman HJ, Ivatury RR, et al. Abdominal compart- 69. Borkon MJ, Morrow SE, Koehler EA, et al. Operative interven-
ment syndrome. J Trauma 1998;45:597609. tion for complete pancreatic transection in children sustaining
16 Abdominal and Renal Trauma 213
blunt abdominal trauma: Revisiting an organ salvage technique. 97. Cone JB, Eidt JF. Delayed diagnosis of duodenal rupture. Am J
Am Surg 2011;77:61220. Surg 1994;168:6769.
70. Ramesh J, Bang JY, Trevino J, et al. Endoscopic ultrasound-guided 98. Cogbill TH, Moore EE, Feliciano DV, et al. Conservative man-
drainage of pancreatic fluid collections in children. J Pediatr Gas- agement of duodenal trauma: A multicenter perspective. J Trauma
troenterol Nutr 2012; Epub ahead of print. 1990;30:146975.
71. de Blaauw I, Winkelhorst JT, Rieu PN, et al. Pancreatic injury in 99. Clendenon JN, Meyers RL, Nance ML, et al. Management of
children: Good outcome of nonoperative treatment. J Pediatr duodenal injuries in children. J Pediatr Surg 2004;39:9648.
Surg 2008;43:16403. 100. Pokorny WJ, Brandt ML, Harberg FJ. Major duodenal injuries
72. Paul MD, Mooney DP. The management of pancreatic injuries in in children: Diagnosis, operative management, and outcome.
children: Operate or observe. J Pediatr Surg 2011;46:11403. J Pediatr Surg 1986;21:61316.
73. Simpson J, Lobo DN, Shah AB, et al. Traumatic diaphragmatic 101. Dokucu A, Oztrk H, Yamur Y, et al. Colon injuries in children.
rupture: Associated injuries and outcome. Ann R Coll Surg Engl J Pediatr Surg 2000;35:1799804.
2000;82:97100. 102. Nelson R, Singer M. Primary repair for penetrating colon injuries.
74. Koplewitz BZ, Ramos C, Manson DE, et al. Traumatic diaphrag- Cochrane Database Syst Rev 2003:CD002247.
matic injuries in infants and children: Imaging findings. Pediatr 103. Weinberg JA, Griffin RL, Vandromme MJ, et al. Management of
Radiol 2000;30:4719. colon wounds in the setting of damage control laparotomy: A
75. Ramos CT, Koplewitz BZ, Babyn PS, et al. What have we learned cautionary tale. J Trauma 2009;67:92935.
about traumatic diaphragmatic hernias in children? J Pediatr Surg 104. Ordoez CA, Pino LF, Badiel M, et al. Safety of performing a
2000;35:6014. delayed anastomosis during damage control laparotomy in patients
76. Meyer G, Httl TP, Hatz RA, et al. Laparoscopic repair of trau- with destructive colon injuries. J Trauma 2011;71:151218.
matic diaphragmatic hernias. Surg Endosc 2000;14:101014. 105. Kadish HA, Schunk JE, Britton H. Pediatric male rectal and
77. Pitcher G. Fiber-endoscopic thoracoscopy for diaphragmatic genital trauma: Accidental and nonaccidental injuries. Pediatr
injury in children. Semin Pediatr Surg 2001;10:1719. Emerg Care 1998;14:958.
78. Shehata SM, Shabaan BS. Diaphragmatic injuries in children after 106. Bonnard A, Zamakhshary M, Wales PW. Outcomes and manage-
blunt abdominal trauma. J Pediatr Surg 2006;41:172731. ment of rectal injuries in children. Pediatr Surg Int 2007;23:
79. Sharma OP, Oswanski MF, Kaminski BP, et al. Clinical implica- 10716.
tions of the seat belt sign in blunt trauma. Am Surg 2009;75: 107. Rubin LE, Stein PB, DiScala C, et al. Pediatric trauma caused by
8227. personal watercraft: A ten-year retrospective. J Pediatr Surg
80. Chandler CF, Lane JS, Waxman KS. Seatbelt sign following blunt 2003;38:15259.
trauma is associated with increased incidence of abdominal injury. 108. Kapur SS, Frei LW. Colorectal and vaginal injuries in personal
Am Surg 1997;63:8858. watercraft passengers. J Trauma 2007;63:11614.
81. Nance ML, Lutz N, Arbogast KB, et al. Optimal restraint reduces 109. Gill RS, Mangat H, Al-Adra DP, et al. Hydrostatic rectosigmoid
the risk of abdominal injury in children involved in motor vehicle perforation: A rare personal watercraft injury. J Pediatr Surg
crashes. Ann Surg 2004;239:12731. 2011;46:4024.
82. Ciftci AO, Tanyel FC, Salman AB, et al. Gastrointestinal tract 110. Esposito TJ, Ingraham A, Luchette FA, et al. Reasons to omit
perforation due to blunt abdominal trauma. Pediatr Surg Int digital rectal exam in trauma patients: No fingers, no rectum, no
1998;13:25964. useful additional information. J Trauma 2005;59:131419.
83. Moss RL, Musemeche CA. Clinical judgment is superior to diag- 111. Leaphart CL, Danko M, Cassidy L, et al. An analysis of proctos-
nostic tests in the management of pediatric small bowel injury. copy vs computed tomography scanning in the diagnosis of rectal
J Pediatr Surg 1996;31:117882. injuries in children: Which is better? J Pediatr Surg 2006;41:
84. Jerby BL, Attorri RJ, Morton D Jr. Blunt intestinal injury in 7003.
children: The role of the physical examination. J Pediatr Surg 112. Reinberg O, Yazbeck S. Major perineal trauma in children.
1997;32:5804. J Pediatr Surg 1989;24:9824.
85. Letton RW, Worrell V, APSA Committee on Trauma Blunt Intes- 113. Tuggle D, Huber PJ Jr. Management of rectal trauma. Am J Surg
tinal Injury Study Group. Delay in diagnosis and treatment of 1984;148:8068.
blunt intestinal injury does not adversely affect prognosis in the 114. Sharma O. Blunt gallbladder injuries: Presentation of twenty-
pediatric trauma patient. J Pediatr Surg 2010;45:1616. two cases with review of the literature. J Trauma 1995;39:
86. Gaines BA, Rutkoski JD. The role of laparoscopy in pediatric 57680.
trauma. Semin Pediatr Surg 2010;19:3003. 115. Jaggard MK, Johal NS, Choudhry M. Blunt abdominal trauma
87. Garg N, St Peter SD, Tsao K, et al. Minimally invasive manage- resulting in gallbladder injury: A review with emphasis on pediat-
ment of thoracoabdominal penetrating trauma in a child. J Trauma rics. J Trauma 2011;70:100510.
2006;61:21112. 116. McAleer IM, Kaplan GW, Scherz HC, et al. Genitourinary
88. Tejerina Alvarez EE, Holanda MS, Lpez-Espadas F, et al. Gastric trauma in the pediatric patient. Urology 1993;42:5638.
rupture from blunt abdominal trauma. Injury 2004;35:22831. 117. Deibert CM, Spencer BA. The association between operative
89. Begossi G, Danielson PD, Hirsh MP. Transection of the stomach repair of bladder injury and improved survival: Results from the
after blunt injury in the pediatric population. J Pediatr Surg National Trauma Data Bank. J Urol 2011;186:1515.
2007;42:16047. 118. Moore EE, Cogbill TH, Jurkovich GJ, et al. Organ injury scaling.
90. Asensio JA, Feliciano DV, Britt LD, et al. Management of duo- III: Chest wall, abdominal vascular, ureter, bladder, and urethra.
denal injuries. Curr Probl Surg 1993;30:102393. J Trauma 1992;33:3379.
91. Ladd AP, West KW, Rouse TM, et al. Surgical management of 119. Kluemper C, Rogers A, Fallat M, et al. Genitourinary injuries in
duodenal injuries in children. Surgery 2002;132:74853. pediatric all-terrain vehicle traumaa mechanistic relationship?
92. Gaines BA, Shultz BS, Morrison K, et al. Duodenal injuries in Urology 2010;75:11624.
children: Beware of child abuse. J Pediatr Surg 2004;39:6002. 120. Gomez RG, Ceballos L, Coburn M, et al. Consensus statement
93. Vaughan GD 3rd, Frazier OH, Graham DY, et al. The use of on bladder injuries. BJU Int, 2004;94:2732.
pyloric exclusion in the management of severe duodenal injuries. 121. Peclet MH, Newman KD, Eichelberger MR, et al. Patterns of
Am J Surg 1977;134:78590. injury in children. J Pediatr Surg 1990;25:8591.
94. Moore EE, Cogbill TH, Malangoni MA, et al. Organ injury 122. Brown SL, Elder JS, Spirnak JP. Are pediatric patients more sus-
scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. ceptible to major renal injury from blunt trauma? A comparative
J Trauma 1990;30:14279. study. J Urol 1998;160:13840.
95. Shilyansky J, Pearl RH, Kreller M, et al. Diagnosis and manage- 123. Wu HY, Gaines BA. Dirt bikes and all-terrain vehicles: The real
ment of duodenal injuries in children. J Pediatr Surg 1997;32: threat to pediatric kidneys. J Urol 2007;178:16724.
8806. 124. McAleer IM, Kaplan GW. Pediatric genitourinary trauma. Urol
96. Fang JF, Chen RJ, Lin BC. Surgical treatment and outcome after Clin North Am 1995;22:17788.
delayed diagnosis of blunt duodenal injury. Eur J Surg 1999;165: 125. Moore EE, Shackford SR, Pachter HL, et al. Organ injury scaling:
1339. spleen, liver, and kidney. J Trauma 1989;29:16646.
214 SECTION II Trauma
126. Santucci RA, Fisher MB. The literature increasingly supports 133. Broghammer JA, Fisher MB, Santucci RA. Conservative manage-
expectant (conservative) management of renal traumaa system- ment of renal trauma: A review. Urology 2007;70:6239.
atic review. J Trauma 2005;59:493503. 134. Aguayo P, Fraser JD, Sharp S, et al. Nonoperative management
127. Umbreit EC, Routh JC, Husmann DA. Nonoperative manage- of blunt renal injury: A need for further study. J Pediatr Surg
ment of nonvascular grade IV blunt renal trauma in children: 2010;45:131114.
Meta-analysis and systematic review. Urology 2009;74: 135. Navsaria PH, Nicol AJ. Selective nonoperative management of
57982. kidney gunshot injuries. World J Surg 2009;33:5537.
128. Wessel LM, Scholz S, Jester I, et al. Management of kidney inju- 136. Wessells H, McAninch JW, Meyer A, et al. Criteria for nonopera-
ries in children with blunt abdominal trauma. J Pediatr Surg tive treatment of significant penetrating renal lacerations. J Urol
2000;35:132630. 1997;157:247.
129. Russell RS, Gomelsky A, McMahon DR, et al. Management 137. Rice SG. Medical conditions affecting sports participation. Pedi-
of grade IV renal injury in children. J Urol 2001;166: atrics 2008;121:8418.
104950. 138. Grinsell MM, Showalter S, Gordon KA, et al. Single kidney and
130. Philpott JM, Nance ML, Carr MC, et al. Ureteral stenting in the sports participation: Perception versus reality. Pediatrics
management of urinoma after severe blunt renal trauma in chil- 2006;118:101927.
dren. J Pediatr Surg 2003;38:10968. 139. Grinsell MM, Butz K, Gurka MJ, et al. Sport-related kidney
131. Goffette PP, Laterre PF. Traumatic injuries: Imaging and inter- injury among high school athletes. Pediatrics 2012;130:e405.
vention in post-traumatic complications (delayed intervention). 140. Psooy K. Sports and the solitary kidney: How to counsel parents.
Eur Radiol 2002;12:9941021. Can J Urol 2006;13:31206.
132. Nerli RB, Metgud T, Patil S, et al. Severe renal injuries in children 141. Johnson B, Christensen C, Dirusso S, et al. A need for reevalua-
following blunt abdominal trauma: Selective management and tion of sports participation recommendations for children with a
outcome. Pediatr Surg Int 2011;27:121316. solitary kidney. J Urol 2005;174:6869.
C H A P T E R 1 7
Pathophysiology 100
The intracranial contents include the brain parenchymal
tissue, cerebrospinal fluid (CSF), and blood. The brain 80
parenchyma accounts for approximately 80% of the When ICP is
high, small
intracranial contents, with the remainder being evenly 60 ICP does not rise initially volume
due to compensatory
distributed between CSF and blood. The majority of the mechanisms
increases
CSF is in the subarachnoid spaces, and the remainder is marked ICP
40
in the ventricles, with the postcapillary circulation con-
taining most of the intracranial blood. 20
The immature brain has some structural differences
from its adult counterpart that may explain the different 0
responses to injury often seen in children after TBI. The
brain doubles in size in the first 6 months of life and Volume
reaches approximately 80% of adult size by age 2. The FIGURE 17-2 Intracranial pressure (ICP)volume relationship.
Small increases in brain volume do not lead to immediate
developing brain has a higher water content and incom- increase in ICP because of the ability of the cerebrospinal fluid
plete neuronal synapse formation and arborization. In to be displaced into the spinal canal as well as the ability the
addition, incomplete myelinization and neurochemical falx cerebri to stretch slightly between the hemispheres and the
changes result in neuronal plasticity after birth. The sub- tentorium between the hemispheres and the cerebellum.
arachnoid space is generally smaller and offers less pro- However, once the ICP has reached around 25mmHg, small
increases in brain volume can lead to marked elevations in ICP.
tection than the mature brain, owing to less buoyancy,
and thereby provides less protection to the brain paren-
chyma during changes in head momentum. The result is
a higher incidence of diffuse cerebral edema and paren- The MonroKellie doctrine is an important concept
chymal injuries in children. In children with distensible relating to the understanding of ICP dynamics (Fig.
skulls, some argue that the open fontanelle allows for 17-1). The MonroKellie doctrine uses a simple hydrau-
expansion of the intracranial contents and therefore lic approach to the cerebral circulation. Given that the
affords increased protection from elevation of ICP. cranium is a rigid, nonexpansile container, it states that
However, studies have indicated that the smaller neural the total volume of the intracranial contents must remain
axis of infants and young children results in a less compli- constant and any increase in the volume of one compo-
ant pressurevolume relationship with an increased risk nent must be at the expense of the others, assuming the
of intracranial hypertension.8,9 intracranial volume remains constant. Thus, very early
after injury, a mass such as an expanding hematoma may
be enlarging while the ICP remains normal. Once the
limit of displacement of CSF and intravascular blood has
been reached, ICP rapidly increases (Fig. 17-2). Further
work has shown that the relationship between ICP and
cerebral blood flow (CBF) is much more complex
and variable. Whereas simultaneous measurement of ICP
and CBF would be most helpful in optimizing therapeu-
tic strategies, the MonroKellie doctrine provides a rea-
sonable basic explanation of intracranial dynamics.
CBF is defined as the velocity of blood through the
cerebral circulation. In adults, the normal CBF is
5055mL/100g of brain tissue/minute. In children, CBF
may be much higher depending on their age. At 1 year
of age, it approximates adult levels, but at 5 years of age,
normal CBF is approximately 90mL/100g/min and
then gradually declines to adult levels by the mid-late
teens. Brain injury severe enough to cause coma can
result in a 50% reduction in CBF during the first 6 to 12
hours after injury.10,11 It usually increases over the next 2
to 3 days, but for those patients who remain comatose,
CBF remains below normal for days or weeks after injury.
There is increasing evidence that such low levels of CBF
are inadequate to meet the metabolic demands of the
FIGURE 17-1 MonroKellie doctrine. The MonroKellie doctrine brain early after injury and that regional, if not global,
states that the cranial compartment is incompressible and that cerebral ischemia results.1214
the volume inside the cranium is a fixed volume. The cranium Cerebral perfusion pressure (CPP) is the differential
and its constituents (blood, cerebrospinal fluid [CSF], and brain
tissue) create a state of volume equilibrium such that any
pressure of arterial flow into and venous flow out of
increase in volume of one of the cranial constituents must be the brain. CPP may be defined by the difference
compensated by a decrease in volume of another. between mean arterial pressure (MAP) and ICP. CPP is
17 Head Injury and Facial Trauma 217
considered the transmural pressure gradient that is ulti- Primary Brain Injury
mately the driving force required for supplying cerebral
metabolic needs. As ICP increases following head injury, Primary brain injury occurs as a result of direct injury to
CPP decreases and blood flow to the brain eventually the brain parenchyma due to shear forces at the time of
declines. At a CPP of 10mmHg, blood vessels collapse impact. Both cortical disruption and axonal injury can
and blood flow ceases. occur, resulting in a cascade of events contributing to
Current techniques available to measure CBF, such as secondary brain injury, which will be discussed later. Cor-
transcranial Doppler and Xenon-enhanced CT imaging, tical disruption, if occurring within minutes to hours, is
are still considered experimental in the management of not likely to be amenable to resuscitation.
severe TBI. Because CPP is easily determined by ICP Skull fractures occur commonly with head injury and
monitoring, it has become a critical parameter for defin- are readily diagnosed with CT. In children, a skull frac-
ing treatment options. Studies have shown a good cor- ture should prompt an evaluation of the underlying brain
relation between CPP and CBF in patients with intact parenchyma given the significant impact it takes to injure
cerebral autoregulation.13 However, cerebral autoregula- the skull. Fractures of the skull vault can occur in either
tion is often disrupted after severe TBI and measures of a linear or a stellate fashion. Fractures involving the skull
cerebral vascular resistance may be more useful in guiding base are typically associated with a greater force than
therapy.15,16 simple cranial vault fractures. The classic signs of basilar
Cerebral autoregulation refers to a homeostatic skull fractures include Battles sign (ecchymoses over the
process that allows CBF to remain constant over a wide mastoid process associated with an ipsilateral skull frac-
range of MAPs. Arterial vessels can dilate or constrict in ture), raccoon eyes and CSF rhinorrhea (associated with
response to various physiologic changes, including a cribriform plate fracture), and otorrhea (associated with
ICP and systemic arterial pressure, to maintain normal fracture of the mastoid air cells or temporal bone frac-
flow and normal brain metabolism. In healthy adult ture). Meningitis associated with a basilar skull fracture
patients, CBF remains constant with a MAP between occurs in up to 10% of patients.20 Despite the risk of
60160mmHg, or a CPP between 50150mmHg.17 infection, the routine use of prophylactic antibiotics is
Normally, with elevated systemic blood pressure, reflex- not recommended as they have not been shown to prevent
ive vasoconstriction will occur to prevent intracranial meningitis from occurring, and tend to select out for
hypertension. In contrast, a moderate decrease in sys- resistant organisms.2123 Vaccination against Streptococcus
temic blood pressure will paradoxically result in increased pneumoniae should be considered for all patients with a
ICP because compensatory reflex vasodilatation will basilar skull fracture and CSF leak due to the increased
occur. When perfusion pressure falls below 50mmHg, risk of pneumococcal-associated meningitis.24
cerebral ischemia develops and compensatory cerebral Post-traumatic intracranial hemorrhage includes epi-
arteriole vasodilatation is exhausted. When perfusion dural hematomas, subdural hematomas, and subarach-
pressure exceeds 150mmHg, cerebral arteriolar imped- noid hemorrhages. Epidural hematomas usually occur in
ance is overcome, the affected vessels passively dilate, and the middle fossa and are often associated with an injury
fluid is forced through a damaged endothelium into the to the middle meningeal artery, although they can occur
brain, causing diffuse vasogenic edema. Impaired cerebral in the anterior or posterior fossa. The classic CT descrip-
autoregulation after TBI and age-related changes in CBF tion is a lenticular hematoma, bound by suture lines,
make the immature brain susceptible to secondary injury, because of the tightly bound dura (Fig. 17-3). Clot for-
both from diminished and excess CBF, and are both asso- mation under the calvaria compresses the dura and can
ciated with a poor neurologic outcome.18 cause rapid neurologic deterioration as the brain becomes
Historically, treatment protocols were principally
directed toward reducing ICP. Hyperventilation and fluid
restriction were important components in these older
protocols. Sustained elevations in ICP above 20mmHg
are poorly tolerated by the injured brain and have been
associated with poor neurologic outcome and increased *
mortality in pediatric patients.19 Sustained elevation in
ICP may result in cerebral ischemia if cerebral perfusion
is impaired, and ultimately may result in cerebral hernia-
tion. Current treatment strategies seek to optimize CPP
while reducing ICP, with little reliance on hyperventila-
tion or fluid restriction. CPP is likely an age-related con-
tinuum, thus making it problematic to develop treatment
protocols based on a single number for all age groups. To
date, no study has demonstrated that active maintenance
of CPP above any target threshold in infants and children
following TBI improves mortality or morbidity. However,
there seems to be a threshold of less than 40mmHg that
is associated with increased mortality; therefore, most
treatment guidelines recommend a minimum CPP of FIGURE 17-3 CT scan shows an epidural hematoma (asterisk)
40mmHg. in a 14-year-old patient. (Courtesy of Dr Lisa Lowe.)
218 SECTION II Trauma
symptomatic amelioration of chemical meningitis, men- The release of excitatory amino acids, such as gluta-
ingismus, and photophobia. SAH can result in hydro- mate, results in neuronal injury after TBI. Glutamate
cephalus and may require ventricular shunting to relieve is the most abundant neurotransmitter in the brain.
the increased ICP. In patients with severe TBI, SAH is However, toxic levels cause neuronal cell death.30,31 After
associated with a poor outcome and may also be associ- TBI, glutamate and other excitatory amino acids are
ated with cerebral vasospasm. Transcranial Doppler released, resulting in neuronal swelling, calcium influx,
imaging can be utilized to identify vasospasm. Therapy and release of cytotoxic enzymes leading to cell death.
for vasospasm in adults include calcium channel blockers Studies have failed to demonstrate efficacy of anti-
and neurointerventional techniques; however, these are excitotoxic therapies, perhaps owing to their application
not well studied in children and not commonly used.25,26 in all patients with TBI rather than those with excitotox-
icity, and because treatment may have been initiated too
late.32
Secondary Brain Injury
Oxidative stress with free radical formation is an
The cornerstone of TBI management is the prevention important mechanism leading to secondary injury. Free
of secondary injuries. Secondary brain injury includes radicals damage endothelial cells and injure the brain
both the evolution of damage within the brain related to parenchyma. This results in disruption of the blood-brain
a cascade of macroscopic and microscopic events, and the barrier and resultant vasogenic and cytotoxic edema. Free
effects of secondary insults, including hypoxia and hypo- radical scavengers, such as vitamin E, ascorbic acid, and
tension. Endogenous secondary brain injury involves the superoxide dismutase, attempt to minimize injury by
macroscopic cascade of edema, ischemia, necrosis, ele- binding with the free radicals. However, these mecha-
vated ICP, and inadequate CPP. nisms often become overwhelmed and the process
Brain swelling traditionally has been described as becomes self-perpetuating. Clinical studies are ongoing
either vasogenic or cytotoxic. The time course of brain to identify pharmacologic free radical scavenging agents.
edema is variable. It is thought, however, that vasogenic Apoptosis requires a cascade of intracellular events for
edema occurs early after injury and cytotoxic edema completion of cell death and is thus termed programmed
occurs in a more delayed fashion. Vasogenic swelling cell death. Calcium influx into the cell, oxidative stress,
results from the disruption of the bloodbrain barrier. and energy depletion all appear to be important intracel-
The bloodbrain barrier is maintained by tight junctions lular triggers of apoptosis. As our understanding of
between endothelial cells that line the vessels of the brain. the complex biochemical, cellular, and molecular
Injury to these cells allows extravasation of fluid and responses to TBI progresses, application of therapeutic
proteins into the interstitial space of the brain paren- strategies and agents may help halt the secondary injury
chyma. Disruption of these cells can occur from the processes.
primary injury or from free radical formation, cytokines,
and other secondary mechanisms of brain injury. Cyto- Initial Evaluation and Management
toxic edema is edema of the cells themselves, resulting
from a failure of cellular ion homeostasis and membrane
of Head Injury
function. The key principles of management after TBI rest on the
Edema of the brain is an important marker for injury foundation of the MonroKellie doctrine and the avoid-
and is also a cause of secondary injury. In early (<24 ance of secondary brain injury. Interventions that decrease
hours) fatal closed-head injuries in children, CT scans CSF and hyperemia, while ensuring adequate oxygena-
often demonstrate little or no significant parenchymal tion and blood flow, form the basis for all management
bleeding. However, in children, rapid development of strategies discussed here.
edema is commonly seen on serial CT scans and the As with any trauma, the initial management and resus-
diffuse brain swelling causes the obliteration of the ven- citation begins with an assessment of circulation, airway
tricles and loss of the basilar cisterns and subarachnoid and breathing (CAB). Ensuring adequate oxygenation
space. As swelling progresses and the compensatory and ventilation and promptly addressing sources of
mechanisms of the brain are exhausted, ICP increases ongoing blood loss serve as the basic principles in the
markedly with small changes in intracranial volume (see management of persons suspected or confirmed to have
Fig. 17-2). Cerebral edema typically develops early after head injury. Hypotension and hypoxia in the field are
injury, peaking at 72 to 96 hours, and then gradually proven secondary insults that are associated with poor
resolves over the next week in survivors.27 outcomes, with hypotension being considerably more
Studies in adults utilizing xenon CT have shown a detrimental than hypoxia.28,33 There has been no docu-
reduction in CBF early after severe TBI.10,12 This hypo mented advantage to endotracheal intubation over effec-
perfusion may be further exacerbated by hypotension and tive bag-valve-mask ventilation in the field.34,35 Providers
hypoxia. It is clear that this early hypoperfusion or inexperienced in pediatric airway management should
ischemia after severe TBI is associated with a poor defer endotracheal intubation. Efforts should be made to
outcome.28,29 Proposed mediators involved in early post- control bleeding, including scalp lacerations, which may
traumatic ischemia include direct vascular disruption, be a source of shock in the child. The administration of
production of endothelin-1 (a potent vasoconstrictor), isotonic crystalloid solution should be utilized to promptly
loss of endogenous vasodilators (endogenous nitric oxide restore the intravascular volume. Colloid solutions should
synthase), and likely many other complex, interrelated, be avoided. The withholding of fluid because of concerns
cellular and metabolic events. of concomitant head injury is unjustified and may
220 SECTION II Trauma
ICP monitor
Maintain CPP > 40-65 mmHg (age appropriate)
ICP
Neuromuscular blockade
ICP
ICP
Hyperosmolar therapy
1. Hypertonic saline (3% NaCl)Maintain at < 360 mOsm/L
2. MannitolMaintain at < 320 mOsm/L
ICP
ICP
FIGURE 17-6 This algorithm provides an evidence-based approach for treatment of pediatric patients with severe head trauma.
NS, normal saline; LR, lactated Ringers; ICP, intracranial pressure; CSF, cerebrospinal fluid.
222 SECTION II Trauma
flow. The immediate effect of hyperventilation is a reduc- pediatric TBI patient. First, there is strong evidence that
tion of ICP, although this response is neither universal supports the association between intracranial hyperten-
nor sustained. Hyperventilation reduces ICP by causing sion and poor neurologic outcome.41 Second, ICP
cerebral vasoconstriction, with a subsequent reduction in monitoring and aggressive treatment of intracranial
CBF in reactive vascular beds. Hyperventilation should hypertension are associated with the best reported clini-
be reserved for those patients with obvious signs of brain cal outcomes.42 The presence of open fontanelles and/or
stem herniation, often heralded by Cushings triad sutures in an infant does not preclude the development
(abnormal respiratory pattern, hypertension, and brady- of intracranial hypertension or negate the utility of ICP
cardia), and nonreactive, dilated pupils. monitoring.7
The treatment threshold for intracranial hypertension
is typically defined as an ICP greater than 20mmHg.
Patient Positioning Age-specific and injury mechanismspecific ICP thresh-
The bed should be elevated at 1530 and the patients olds have yet to be defined. In more recent years, the
head maintained in the midline position to facilitate focus has switched from ICP-directed therapy to
venous drainage from the head, thus allowing mainte- multimodal-directed therapy. Support for this change has
nance of cerebral perfusion. been bolstered by a recent multicenter randomized
prospective trial comparing two groups of patients ages
13 years and older. Patients were randomized into a
Acute Surgical Management guidelines-based management in which a protocol for
monitoring intraparenchymal intracranial pressure was
A CT scan should be obtained in all patients with severe
used (pressure-monitoring group) or a protocol in which
TBI after initial resuscitation and stabilization. Patients
treatment was based on imaging and clinical examination
with intracerebral hematomas causing a mass effect
(imaging-clinical examination group).43 The study failed
need immediate neurosurgical evacuation. The tradi-
to find superiority with either method in the both short
tional definition of a significant mass effect can be deter-
and long-term outcomes of patients with severe TBI.
mined from the axial views of a noncontrasted CT scan.
The study authors clearly state that this study does not
A line is drawn at the midline of the skull in the sagittal
argue against the use of ICP monitoring, but rather indi-
plane and then a perpendicular line is extended to the
cates that more work needs to be done on interpreting
septum pellucidum. The basilar cisterns are also evalu-
and utilizing this tool in the treatment and management
ated for compression. Greater than 5mm of midline shift
of TBI.
is considered to be significant.
Although there is no single ICP monitoring device
that is superior to the others, intraventricular devices
Sedation and Analgesia are effective monitors that allow CSF drainage as part
of the treatment for elevated ICP. However, if not
Sedation and analgesia are commonly used in the man- inserted early after injury, placement may be difficult
agement of TBI. The maintenance of the airway, place- when damaged brain and cerebral edema have effaced
ment of invasive catheters or other monitoring devices, the normal ventricle. Intraparenchymal monitors have
and the safe transport of the patient for diagnostic or fiberoptic or strain-gauge transducers that provide con-
therapeutic procedures are examples of some aspects of tinuous pressure readings, and can be placed in any
patient care facilitated by these medications. Sedation region of the brain. Newer monitors can measure brain
and analgesia may also be useful in maintaining or tissue oxygen levels and permit manipulations to opti-
decreasing ICP by decreasing the metabolic rate and mize regional oxygenation, including adjustments in the
thereby decreasing CBF. Studies have demonstrated a fraction of inspired oxygen (FiO2) and blood transfusion.
two- to threefold increase in basal metabolic rate result- Coagulation abnormalities are a relative contraindication
ing from painful or stressful stimuli. Noxious stimuli, to the insertion of these devices. Therefore, prompt cor-
such as suctioning, can increase ICP. Painful and noxious rection using plasma or activated factor VIIa should be
stimuli and stress can also increase sympathetic tone, considered before insertion.44
resulting in hypertension and bleeding from operative The optimal CPP for a given individual is not clear.
sites.39,40 However, these medications must be used Global and/or regional cerebral ischemia commonly
with caution, because sedative or narcotic related vasodila complicates brain injury. Studies have consistently shown
tion may decrease CBF with resulting hypotension, that a CPP less than 40mmHg is associated with increased
or conversely may increase CBF by causing cerebral mortality.41,45 A CPP between 4065mmHg likely repre-
vasodilatation. sents an age-related continuum with inter-individual
variability. Studies have suggested that avoidance of
hypotension, rather than elevation of CPP, is more ben-
Intracranial Pressure Monitoring
eficial.41 Efforts to increase CPP in adults to a supernor-
and Management
mal level with the use of fluids and vasoactive infusions
Despite the absence of prospective, randomized clinical are associated with significant risks, including pulmonary
trials to establish efficacy in improving outcome, the use complications, fluid overload, pressor toxicity, and renal
of ICP devices has become standard in the USA for the insufficiency. Furthermore, in cases of disrupted autoreg-
treatment of severe head injury. There are two lines of ulation, exacerbation of intracranial hypertension can
thinking to support the use of ICP monitoring in the result.
17 Head Injury and Facial Trauma 223
TABLE 17-2 A Comparison of Mannitol and Hypertonic Saline (For Hyperosmolar Therapy)
Mannitol 3% Hypertonic Saline
Bolus dosing guidelines 0.251.0g/kg rapid bolus 35mL/kg
Infusion guidelines None 0.11.0mL/kg/h
Effectiveness May wane with repeated administration Effective after repeated administration; effective
when mannitol efficacy has waned
Augmentation of MAP Moderate Greater, more prolonged
Rheologic properties Yes Yes
Diuretic effect Osmotic diuretic, may necessitate volume Diuresis through action of atrial natriuretic
replacement to avoid hypovolemia peptide
Maximum serum osmolarity 320mOsm/L 360mOsm/L
Adverse effects Renal failure, hypotension, rebound Rebound elevation in ICP, central pontine
elevation in ICP myelinolysis, bleeding, electrolyte abnormal
Proposed beneficial effects Antioxidant effects Restoration of resting membrane potential and
cell volume, inhibition of inflammation
is no longer routinely recommended. Hyperosmolar fluids and inotropic infusions. It is important that
therapy should be reserved for those patients with docu- barbiturates are used in the setting of systemic monitor-
mented intracranial hypertension or those with signs of ing with the ability to rapidly detect hemodynamic
impending herniation to avoid secondary injury and com- instability.
plications associated with hyperosmolar therapy.
Hyperventilation
Anticonvulsant Prophylaxis
Hyperventilation has been a mainstay in the management
Anticonvulsants are often administered to patients with of severe TBI, but more recent concerns about its role in
TBI. Current clinical evidence supports their use to cerebral ischemia have lessened its use. As discussed pre-
prevent early post-traumatic seizures which are typically viously, the cerebral vasculature is sensitive to changes in
defined as seizures occurring within the first 7 days after PaCO2, with hypocarbia producing cerebral vasocon-
injury. Early post-traumatic seizures may further increase striction and a decrease in CBF. Historically, hyperemia,
brain metabolic demands, increase ICP, and lead to sec- or excessive CBF, was thought to be the primary mecha-
ondary brain injury. Prophylactic anticonvulsants do not nism resulting in cerebral edema after TBI, thus making
prevent late (occurring longer than seven days from hyperventilation a reasonable approach in the manage-
injury) post-traumatic seizures. ment of the patient with severe TBI. More recent studies
have demonstrated that hyperemia is uncommon after
severe TBI. Hyperventilation may decrease cerebral oxy-
Medically Refractory Intracranial
genation, resulting in secondary brain ischemia.55,56 The
Hypertension
use of aggressive hyperventilation (PaCO2 <30mmHg)
It is estimated that 2142% of children with severe TBI should be reserved for refractory intracranial hyperten-
will develop refractory intracranial hypertension despite sion. Monitoring of CBF, jugular venous oxygen satura-
medical and surgical management.7 In these patients, tion, or brain tissue oxygenation may help identify
therapies and interventions with higher risk profiles cerebral ischemia in this setting.
may need to be considered. Decompressive craniectomy,
high-dose barbiturate therapy, hyperventilation, lumbar Lumbar Drain
drain placement, and the use of moderate hypothermia
should be considered in the patient with medically refrac- Placement of a lumbar drain may be helpful in patients
tory intracranial hypertension. with refractory intracranial hypertension that is unre-
sponsive to the first-line therapies. It is recommended
that the patient has a working ventriculostomy or docu-
Decompressive Craniectomy
mentation of open basilar cisterns on CT.
Children are more likely than adults to have diffuse brain
swelling after TBI and may be more amenable to a treat- Therapeutic Hypothermia
ment strategy utilizing early decompressive craniectomy.
Decompressive craniectomy should be considered in The avoidance of hyperthermia and use of therapeutic
children with severe TBI and infants with abusive head hypothermia after TBI is based on the rationale that
trauma and medically refractory intracranial hyperten- temperature plays an important role in mechanisms con-
sion. The main goal of decompressive craniectomy is to tributing to secondary brain injury (excitotoxicity, free
control ICP, thereby maintaining CPP and cerebral oxy- radical formation). Despite evidence in animal models
genation. Improved outcomes have been demonstrated in demonstrating efficacy of therapeutic moderate hypo-
several small single-center studies, and appears to be thermia (3234C), large randomized clinical studies in
most effective when done early, before the development both adults and children have not proven the effective-
of extensive secondary brain injury.5052 ness of hypothermia on improved outcomes after TBI.57
61
Studies extrapolated from the adult literature indicate
Barbiturate Therapy that hyperthermia adversely affects outcome so it may be
advisable to consider passive re-warming of the mild to
High doses of barbiturates are known to reduce ICP and moderately hypothermic trauma patient with isolated
have been used in the management of increased ICP for head injury.62
decades. Their side effects limit their current use to those
patients with injuries refractory to first-line therapies.
Barbiturates are effective in lowering ICP by suppressing FACIAL TRAUMA
brain metabolism and altering vascular tone. In addition
to the ICP-lowering benefits, barbiturates also inhibit The same mechanisms of injury associated with TBI
free radicalmediated lipid peroxidation and have (sports, motor vehicle accidents, and falls) also lead to
membrane-stabilizing effects. Small case series of chil- facial trauma in infants and children. The elasticity of the
dren with severe TBI suggest that barbiturates may be facial skeleton, the enhanced facial soft tissue padding,
effective in lowering ICP in the setting of refractory the lack of sinuses that thin the surrounding bone, and
intracranial hypertension.53,54 Their use is associated with the prominence of the skull protect the younger childs
myocardial depression, increased risk of hypotension, and face from injury, resulting in a lower incidence of trau-
the need for blood pressure support with intravascular matic injury. As children age, develop, and become more
17 Head Injury and Facial Trauma 225
active, the frequency of injury increases. No matter the Third, the infant and childs mandible is relatively retru-
age, the reconstructive principles remain the same: res- sive compared to its adult counterpart, diminishing the
toration of function, maximization of aesthetic results, incidence of impact and mandibular fracture. Fourth,
limited visible incisions for repair, avoidance of complica- pediatric facial bones are more elastic, leading to either
tions, and minimal effect on later growth and develop- no fracture or a greenstick fracture that does not require
ment from both the trauma and the operative repair. further treatment. Fifth, the bones still have open sutures
Except for the last principle, these goals are the same as and are more cartilaginous, decreasing the fracture rate.
repair of facial trauma in adults. The last principle, Lastly, the lack of sinuses strengthens the bones as com-
related to later growth and development, must be under- pared to the adult facial structure.
stood by both the surgical team and the family as it can As children grow, facial fracture patterns change. The
alter the treatment plan. Furthermore, the treatment face becomes relatively more prominent as craniofacial
plan can often be different for a given fracture that occurs proportions change. Mixed dentition accords more teeth
during infancy versus childhood versus adolescence. in the midface and less bone. The sinuses pneumatize,
The aims of this portion of the chapter include an further weakening the bone. The facial skeleton begins
understanding of facial growth, the causes of significant to calcify, diminishing its elasticity. Thus, frontal, skull,
facial trauma, the diagnosis and age-dependent treatment and periorbital fractures are more common in the pre-
of facial injuries, and the long-term concerns and seque- kindergarten years while midface and mandible fractures
lae of the trauma and its repair. Because soft tissue inju- increase in frequency as children mature. Because of its
ries are touched on in other chapters, this discussion will prominent anterior position, nasal fractures are the most
focus on facial skeletal trauma and fractures. common facial fracture, followed by mandible fractures.
The most common causes of pediatric facial fractures
include MVCs, falls, and sports. As children age, assaults
Craniofacial Growth And Development begin to play a causative role. The advent of air bags,
One cannot appropriately treat pediatric craniofacial mandatory use of seat belts and harnesses, mandatory use
fractures without a comprehensive understanding of of car seats, mandatory helmeting of minors on motor-
facial growth and development. All infants start out top- cycles, and enforcement of driving under the influence
heavy with a cranial to facial proportion of 78:1. The laws have decreased the incidence and sequelae of MVCs.
skull and cranial vault grow rapidly, dictated by growth Protective helmeting and faceguards for sporting activi-
of the brain. The brain expands 300% in the first couple ties and bicycling have also diminished facial trauma.
of years of life, and acts like a balloon to expand the Safety initiatives, such as the American Academy of Pedi-
overlying skull. The skull bones are connected by sutures atrics push to deter trampoline use, should also have a
and are not fused, allowing for this rapid growth to occur positive effect on public health.
unimpeded. Rapid growth of the skull continues for the The recent popularity of extreme sports increases the
first four years of life. By the time children enter kinder- susceptibility to facial trauma, especially when not appro-
garten, their skull is about 90 % of adult size. priately protected. More significantly, the popularity of
Facial growth follows a different path and pattern, and all-terrain vehicles has provided a new high-velocity
varies anatomically. The upper facial bone growth is mechanism for facial trauma in minors without some of
stimulated by growth of the brain and orbit. The perior- the protective features seen in an MVC.
bital bones are 90% of adult size by age 4 to 5 years. The
frontal sinuses begin to pneumatize at age 3 to 4 years,
but complete aeration is not noted until the later teenage
Evaluation and Diagnosis
years. Midfacial growth in the transverse, vertical, and Both evaluation and diagnosis of pediatric facial fractures
anteroposterior planes is stimulated by dental develop- can be difficult. A comprehensive understanding of the
ment. The maxillary sinuses pneumatize around 12 years mechanism of injury is essential. The injuries may be
of age, corresponding with the eruption of permanent unwitnessed, and the child may be a poor historian or too
teeth. On the other hand, the lower facial skeleton devel- young to communicate. The child may not be able to
ops more slowly. The main growth centers are the bilat- specifically tell you what hurts, and may not be able to
eral condyles. The mandible has both membranous and follow commands. Either because of age, pain, or non-
endochondral bone, the only major bone of the facial compliance, the child may not be able to or does not want
skeleton with that composition. to participate in the examination. This is most limiting
in the orbital and visual examination. The child may have
an associated TBI further diminishing the ability to com-
Incidence and Epidemiology municate or participate in a comprehensive evaluation.
Although facial trauma is more common in children, Therefore, a history of the traumatic event must often be
facial fractures are less common in children, although obtained from the parents and/or the emergency medical
they are likely under-diagnosed due to several factors. transport team who accompany the patient.
First, the family provides infants and younger children As the mechanisms of injury leading to facial fractures
with a protective environment, minimizing their expo- mirror those of multisystem trauma, the plastic surgeon
sure to trauma. Second, as discussed previously, these must work in tandem with the trauma team. Special
children have a proportionally larger and protrusive skull attention must be given to the cervical spine, as there is
and forehead, which protects the face by absorbing the an 8 to 10% incidence of spinal injury with significant
impact at the expense of exposing the child to TBI. craniofacial injury.
226 SECTION II Trauma
Cranial vault and cranial base injuries/fracture as well development occurs at the expense of bony weakening.
as intracranial trauma must be excluded. Dental trauma Treatment of maxillary fractures again center around
or intraoral bleeding can lead to aspiration. Cervical reestablishment of occlusion. Fractures with no or minor
spine injuries are increased in all high-impact trauma occlusal abnormalities can be treated with soft diet, and
etiology, especially with mandible fractures. orthodontic intervention if necessary. As the degree of
malocclusion worsens, the necessity for intermaxillary
fixation and/or open reduction and internal fixation
Treatment increases. Again, in the growing facial skeleton, the most
successful conservative approach is advocated. In teenag-
Nasal Fractures
ers, the approach is similar to adult trauma.
Nasal fractures are one of the two most common pediat- Isolated displaced zygoma fractures require open
ric facial fractures, due to the prominence and projection reduction with fixation (Fig. 17-8). As the zygoma is a
of the nose from the facial skeleton. Nasal fractures bone that constitutes part of the orbital walls and floor,
increase in incidence with advancing age. The fractures the orbital floor needs to be explored and repaired at the
not only involve the bone, but often the cartilage, most time of zygoma fracture repair. Orbital sequelae of inad-
notably the septal cartilage. Septal hematomas should be equately repaired zygoma fractures include enopthalmos,
drained acutely. Fracture repair can be deferred until the orbital dystopia, and diplopia.
swelling subsists. Treatment most commonly consists of
closed reduction. Even with adequate reduction, the frac- Periorbital Fractures
ture may lead to long-term growth restriction and/or
distortion, which can then be addressed at skeletal Orbital fractures can occur in combination with zygo-
maturity. matic fractures or as an isolated injury. The lack of sinuses
and the presence of higher maxillary tooth buds give
support to the orbital bones in the young. Trapdoor frac-
Mandible Fractures
tures can occur in the floor, leading to muscle entrap-
Mandible fractures are the other of the two most common ment, limited orbital movement, and diplopia. The goals
pediatric facial fractures. Treatment of mandible frac- of repair include restoration of orbital volume, restora-
tures varies by patient age, dental development, site of tion of globe position and height, and elimination of any
the fracture, and number of mandible fractures. In the entrapment.
young, condylar injuries are the most common. In late
adolescence, fractures of the mandibular angle and body
predominate. Different stages of dental development
Unique Pediatric Concerns
allow for different types of fixation techniques to be Pediatric facial fractures and their repair pose long-term
employed. concerns distinct from adult trauma. The fractures them-
The goals of mandible fracture treatment are reestab- selves may inhibit long-term growth of the involved bony
lishment of occlusion, bony union, and avoidance of structures leading not only to distortion, but to asym-
complications including infection. Nondisplaced or min- metry as well. Fracture repair techniques, including sub-
imally displaced fractures with normal occlusion can be periosteal exposure of the involved bones, may further
treated with a soft diet and close observation. Often impede long-term growth. Bony fixation with permanent
minor malocclusions can be treated the same. For patients metallic plates also can result in growth restriction. The
with more than minor malocclusion, an operative recent development of resorbable plates which function
approach is necessary. In younger patients with a single during the period of bony healing, and then resorb, is an
mandible fracture, closed reduction should be attempted. attempt to eliminate this long-term concern. To date,
If reduction is successful, treatment should proceed with these plates have shown great efficacy in nonweight-
intermaxillary fixation (IMF). IMF can be difficult in the bearing bones, but are more limited in bones involved in
younger patients and often requires adjuvant occlusal
splints and suspension wires for support. For nonreduc-
ible single fractures, an open approach with internal fixa-
tion is usually necessary. An open approach with fixation
is also often needed for the treatment of multiple man-
dible fractures. Avoidance of open reduction with subpe-
riosteal undermining and avoidance of internal fixation
are goals of repair in the growing facial skeleton if
possible.
Midfacial Fractures
Isolated midfacial fractures are rare in the young patient,
The maxilla is protected by the prominence of the
upper face (forehead) and the lower face (mandible/chin). FIGURE 17-8 This 7-year-old was hit by a baseball and sus-
The maxilla and zygoma are also fortified in the young tained this left zygomatic fracture (arrow). He underwent open
because the midfacial sinuses have not developed. Sinus reduction and internal fixation of this displaced fracture.
228 SECTION II Trauma
mastication. Because of these concerns, because of the 21. Rathore MH. Do prophylactic antibiotics prevent meningitis after
differences in anatomy including tooth buds and develop- basilar skull fracture? Pediatr Infect Dis J 1991;10:878.
22. Villalobos T, Arango C, Kubilis P, et al. Antibiotic prophylaxis after
ment, and because of bony elasticity and the absence of basilar skull fractures: A meta-analysis. Clin Infect Dis 1998;
sinuses, pediatric fractures are different than adult frac- 27:3649.
tures as are the philosophies for pediatric fracture repair. 23. O RB, Joo C, Cristina S, et al. Antibiotic prophylaxis for prevent-
In addition, the fracture type and repair varies by age in ing meningitis in patients with basilar skull fractures. John Wiley
& Sons, Ltd; 2011.
this growing population. 24. Venetz I, Schopfer K, Muhlemann K. Paediatric, invasive pneumo-
coccal disease in Switzerland, 19851994. Swiss Pneumococcal
Study Group. Int J Epidem 1998;27:11014.
REFERENCES 25. Harders A, Kakarieka A, Braakman R. Traumatic subarachnoid
1. Adekoya N, Thurman DJ, White DD, et al. Surveillance for trau- hemorrhage and its treatment with nimodipine. German TSAH
matic brain injury deathsUnited States, 19891998. Morbidity & Study Group. J Neurosurg 1996;85:829.
Mortality Weekly Report Surveillance Summaries 2002;51:114. 26. Romner B, Bellner J, Kongstad P, et al. Elevated transcranial
2. Langlois JA, Rutland-Brown W, Thomas KE. The incidence of Doppler flow velocities after severe head injury: Cerebral vasos-
traumatic brain injury among children in the United States: Dif- pasm or hyperemia? J Neurosurg 1996;85:907.
ferences by race. J Head Trauma Rehab 2005;20:22938. 27. Bareyre F, Wahl F, McIntosh TK, et al. Time course of cerebral
3. Billmire ME, Myers PA. Serious head injury in infants: Accident edema aftertraumatic brain injury in rats: Effects of riluzole and
or abuse? Pediatr 1985;75:3402. mannitol. J Neurotrauma 1997;14:83989.
4. Bruce DA, Zimmerman RA. Shaken impact syndrome. Pediatr Ann 28. Chestnut R, Marshall LF, Klauber MR, et al. The role of secondary
1989;18:4824. brain injury in determining outcome from severe head injury.
5. Child Maltreatment Prevention. Center for Disease Control and J Trauma 1993;34:21622.
Prevention; 2008 [cited 2008 May 7]; Available from: http:// 29. Gopinath SP, Robertson CS, Contant CF, et al. Jugular venous
www.cdc.gov/ncipc/dvp/CMP/CMP-prvt-strat.htm. desaturation and outcome after head injury. J Neurol Psychiatry
6. Tilford JM, Aitken ME, Anand KJ, et al. Hospitalizations for criti- 1994;57:71723.
cally ill children with traumatic brain injuries: A longitudinal analy- 30. Choi DW. Excitotoxic cell death. J Neurobiol 1992;23:126176.
sis. Crit Care Med 2005;33:207481. 31. Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neuro-
7. Kochanek PM, Carney N, Adelson PD, et al. Guidelines for the toxicity in cortical cell culture. J Neurosci 1987;7:35768.
acute medical management of severe traumatic brain injury in 32. Koh JY, Choi DW. Selective blockade of non-NMDA receptors
infants, children, and adolescentssecond edition. Pediatric Critical does not block rapidly triggered glutamate-induced neuronal
Care Medicine: A Journal of the Society of Critical Care Medicine death. Brain Res 1991;548:31821.
and the World Federation of Pediatric Intensive and Critical Care 33. Stocchetti N, Furlan A, Volta F. Hypoxemia and arterial hypoten-
Societies 2012;13(Suppl 1):S182. Epub 2012/01/11. sion at the accident scene in head injury. J Trauma 1996;40:
8. Muizelaar JP, Marmarou A, DeSalles AA, et al. Cerebral blood flow 7647.
and metabolism in severely head-injured children. Part 1: Relation- 34. Cooper A, DiScala C, Foltin G, et al. Prehospital endotracheal
ship with GCS score, outcome, ICP, and PVI. J Neurosurg intubation for severe head injury in children: A reaapraisal. Semin
1989;71:6371. Pediatr Surg 2001;10:36.
9. Shapiro K, Marmarou A. Clinical applications of the pressure- 35. Gausche M, Lewis R, Stratton S, et al. Effect of out-of-hospital
volume index in treatment of pediatric head injuries. J Neurosurg pediatric endotracheal intubation on survival and neurological
1982;56:81925. outcome: A controlled clinical trial. JAMA 2000;283:78390.
10. Bouma GJ, Muizelaar JP. Evaluation of regional cerebral blood 36. Gabriel E, Ghajar J, Jagoda A, et al. Guidelines for pre-hospital
flow in acute head injury by stable xenon-enhanced computerized management of traumatic brain injury. New York: Brain Trauma
tomography. Acta Neur S 1993;59:3440. Foundation; 2000.
11. Bouma GJ, Muizelaar JP. Cerebral blood flow in severe clinical 37. Advanced Trauma Life Support (ATLS). 7th ed. Chicago, IL:
head injury. New Horizons 1995;3:38494. American College of Surgeons; 2004.
12. Bouma GJ, Muizelaar JP, Choi SC, et al. Cerebral circulation and 38. Teasdale G, Jennett B. Assessment of coma and impaired con-
metabolism after severe traumatic brain injury: the elusive role of sciousness: A practical scale. Lancet 1974;2:814.
ischemia. J Neurosurg 1991;75:68593. 39. Kerr ME, Weber BB, Sereika SM, et al. Effect of endotracheal
13. Cold GE. Cerebral blood flow in the acute phase after head injury. suctioning on cerebral oxygenation in traumatic brain-injured
Part 2: Correlation to intraventricular pressure (IVP), cerebral per- patients. Crit Care Med 1999;27:277681.
fusion pressure (CPP), PaCO2, ventricular fluid lactate, lactate/ 40. Raju TN, Vidyasagar D, Torres C, et al. Intracranial pressure
pyruvate ratio and pH. Acta Anaesthesiologica Scandinavica during intubation and anesthesia in infants. J Pediatr 1980;96:
1981;25:3325. 8602.
14. Jaggi J, Obrist W, Gennarelli T, et al. Relationship of early cerebral 41. Downard C, Hulka F, Mullins RJ, et al. Relationship of cerebral
blood flow and metabolism to outcome in acute head injury. perfusion pressure and survival in pediatric brain-injured patients.
J Neurosurg 1990;72:17682. J Trauma 2000;49:6548.
15. Cruz J, Jaggi JL, Hoffstad OJ. Cerebral blood flow, vascular resist- 42. Tilford J, Aitken M, Anand K, et al. Hospitalizations for critically
ance, and oxygen metabolism in acute brain trauma: Redefining ill children with traumatic brain injuries: A longitudinal analysis.
the role of cerebral perfusion pressure? Crit Care Med 1995;23: Crit Care Med 2005;33:207481.
141217. 43. Chestnut RM, Temkin N, Carney N, et al. A trial of intracranial-
16. Lang EW, Lagopoulos J, Griffith J, et al. Cerebral vasomotor pressure monitoring in traumatic brain injury. N Engl J Med
reactivity testing in head injury: The link between pressure and 2012;367:247181.
flow. J Neurol Psychiatry 2003;74:10539. 44. Morenski JD, Tobias JD, Jimenez DF. Recombinant activated
17. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. factor VII for cerebral injury-induced coagulopathy in pediatric
Cerebrovas Brain Met 1990;2:16192. patients. Report of three cases and review of the literature. J Neu-
18. Vavilala MS, Muangman S, Tontisirin N, et al. Impaired cerebral rosurg 2003;98:61116.
autoregulation and 6-month outcome in children with severe trau- 45. Elias-Jones AC, Punt JA, Turnbull AE, et al. Management and
matic brain injury: Preliminary findings. Dev Neurosci 2006;28: outcome of severe head injuries in the Trent region 198590. Arch
34853. Dis Child 1992;67:14305.
19. Pfenninger J, Kaiser G, Lutschg J, et al. Treatment and outcome 46. Hsiang JK, Chesnut RM, Crisp CB, et al. Early, routine paralysis
of the severely head injured child. Intens Care Med 1983;9: for intracranial pressure control in severe head injury: is it neces-
1316. sary? Crit Care Med 1994;22:14716.
20. Dagi TF, Meyer FB, Poletti CA. The incidence and prevention of 47. Muizelaar JP, Wei EP, Kontos HA, et al. Mannitol causes compen-
meningitis after basilar skull fracture. Am J Emer Med 1983;1: satory cerebral vasoconstriction and vasodilation in response to
2958. blood viscosity changes. J Neurosurg 1983;59:8228.
17 Head Injury and Facial Trauma 229
48. Khanna S, Davis D, Peterson B, et al. Use of hypertonic saline in 56. Stringer WA, Hasso AN, Thompson JR, et al. Hyperventilation-
the treatment of severe refractory posttraumatic intracranial hyper- induced cerebral ischemia in patients with acute brain lesions:
tension in pediatric traumatic brain injury. Crit Care Med Demonstration by xenon-enhanced CT. Am J Neuroradiol
2000;28:114451. 1993;14:47584.
49. Peterson B, Khanna S, Fisher B, et al. Prolonged hypernatremia 57. Adelson PD. Hypothermia following pediatric traumatic brain
controls elevated intracranial pressure in head-injured pediatric injury. J Neurotraum 2009;26:42936.
patients. Crit Care Med 2000;28:113643. 58. Adelson PD, Ragheb J, Kanev P, et al. Phase II clinical trial of
50. Guresir E, Schuss P, Seifert V, et al. Decompressive craniectomy moderate hypothermia after severe traumatic brain injury in chil-
in children: Single-center series and systematic review. Neurosurg. dren. Neurosurg 2005;56:74054.
2012;70:8819. 59. Biswas AK, Bruce DA, Sklar FH, et al. Treatment of acute trau-
51. Oluigbo CO, Wilkinson CC, Stence NV, et al. Comparison of matic brain injury in children with moderate hypothermia improves
outcomes following decompressive craniectomy in children with intracranial hypertension. Crit Care Med 2002;30:274251.
accidental and nonaccidental blunt cranial trauma. J Neuros- 60. Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia Pediatric
Pediatr 2012;9:12532. Head Injury Trial Investigators and the Canadian Critical Care
52. Prez Surez E. Decompressive craniectomy in 14 children with Trials Group. Hypothermia therapy after traumatic brain injury in
severe head injury: Clinical results with long-term follow-up and children. N Engl J Med 2008;358:244756.
review of the literature. J Trauma 2011;71:13340. 61. Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic
53. Kasoff SS, Lansen TA, Holder D, et al. Aggressive physiologic brain injury with moderate hypothermia. N Engl J Med
monitoring of pediatric head trauma patients with elevated intrac- 1997;336:5406.
ranial pressure. Pediatr Neurosci 1988;14:2419. 62. Jones PA, Andrews PJ, Midgley S, et al. Measuring the burden of
54. Pittman T, Bucholz R, Williams D. Efficacy of barbiturates in the secondary insults in head-injured patients during intensive care.
treatment of resistant intracranial hypertension in severely head- J Neurosurg Anesth 1994;6:414.
injured children. Pediatr Neurosci 1989;15:1317.
55. Skippen P, Seear M, Poskitt K, et al. Effect of hyperventilation on
regional cerebral blood flow in head-injured children. Crit Care
Med 1997;25:14029.
C H A P T E R 1 8
Musculoskeletal trauma is the most common medical and reporting is essential because children who return
emergency in children.1 In children ages 1 to 14 years, home after hospitalization with unrecognized abuse have
accidents are the leading cause of death.2 However, not a 25% risk of serious injury and a 5% risk of death.17
all orthopedic injuries sustained by children are life Children at highest risk for abuse are first-born children,
threatening. The chance of a child sustaining a fracture premature infants, stepchildren, and handicapped chil-
before age 16 is 42% for boys and 27% for girls.3 It has dren.18 Most cases of child abuse involve children younger
been estimated that between 12% of children present than 3 years of age. Any child presenting with fractures,
with a fracture each year.4 As participation in sports and particularly if they involve the long bones, should be
other recreational activities increases, the number of frac- viewed with circumspection as to cause (Table 18-1).19,20
tures is likely to increase. A study in 2006 looking at the
impact of trauma on an urban pediatric orthopedic prac-
tice demonstrated that fracture management (both oper- PATHOPHYSIOLOGY
ative and nonoperative) accounted for approximately
one-third of the total work-related relative value units. In the immature skeleton, longitudinal and appositional
The most common fracture-related operations were per- growth takes place through the physes (growth plates)
formed on the elbow (23%), tibia (12%), femur (9.8%), that are located at the ends of the long bones, in the
forearm (5.5%), and the distal aspect of the radius (5%).5 endplates of the vertebral bodies, or at the periphery of
The same practice reported that trauma care comprised the round bones in the feet and hands. Thus, the physis
44% of their operative volume in 2006 and 2007.6 is essential for normal skeletal growth, but is also the
Patient gender, age, climate, time of day, and social weakest portion of the bone in children. It is estimated
situation in the home have been shown to impact the that approximately 30% of fractures of the long bones
frequency of orthopedic injuries. In children, boys sustain include an injury to the physis.2123 Most fractures that
fractures at 2.7 times the rate of girls.7 However, as girls involve the growth plates heal without consequence.
become involved in more athletic events, this margin may However, some injuries can result in permanent damage
narrow. It has been shown that fracture location varies with significant sequelae such as angular deformity or
with chronologic age, a finding that is probably due to a complete cessation of growth.
combination of the anatomic maturation of the child and The ends of every long bone consist of an epiphysis
the age-specific activities of childhood.3 Several authors (near the joint), physis, and metaphysis (area of newly
have shown that fractures are more common during the formed bone). At the time of skeletal maturity, the physis
summer months when children are out of school.4,7,8 It closes, which means there is no more longitudinal growth.
has also been shown that there is also a strong association Fracture healing in children is rapid and the potential for
between sunshine and fractures, and a negative associa- remodeling is great due to the growth potential and
tion between rain and fractures.9 Likewise, two studies dynamism of the immature skeleton. These characteris-
have proven that the afternoon is the most frequent time tics allow for nonoperative treatment of some fractures
for fractures to occur.10,11 This correlates with the time in children that demand operative treatment in skeletally
of peak activity for children. Injuries in the home during mature patients. Remodeling of fractures predictably
the late afternoon and evening account for more than occurs in the plane of primary motion of the adjacent
83% of all injuries to children.12 Moreover, the overall joint (usually flexion/extension) and, to a lesser degree,
incidence of fractures occurring at home increases with in the coronal plane (varus and valgus deformities).
the age of the child.4,13 In a Swedish study, fracture inci- Remodeling is virtually nonexistent in the transverse
dence was correlated with the degree of social handicaps plane with rotational malalignment.24
such as welfare or alcoholism in the family.14 Similarly, a Physeal fractures are classified to predict outcome and
study from Manitoba elicited the social situation at home guide treatment. Currently, most orthopedic surgeons
as a major influence of childrens injuries.15 use the Salter Harris classification (Fig. 18-1).25 Classic
No discussion of pediatric orthopedic trauma is com- teaching states that type I and II injuries heal without
plete that does not include a discussion of nonaccidental growth abnormalities if reduced appropriately. However,
trauma. The incidence of physical abuse to children is some reports dispute some of this dogma.2628 Types III
estimated to be 4.9 per 1,000. Of those abused, 1 of every and IV injuries usually occur in older children and require
1,000 will ultimately die as a result.16 Early recognition anatomic realignment via open reduction to restore
230
18 Pediatric Orthopedic Trauma 231
TABLE 18-1 Specificity of Musculoskeletal TABLE 18-2 Severity Classification for Open
Radiologic Findings in Fractures
Nonaccidental Trauma
Grade Description
Specificity Radiologic Finding I Wound <1cm
High Metaphyseal corner lesions II Transitional wound (110cm)
Posterior rib fractures III Wound >10cm
IIIA Extensive soft tissue injury
Scapular fractures IIIB Reconstructive soft tissue injury
Spinous process fractures IIIC Vascular injury
Sternal fractures
Moderate Multiple fractures From Gustilo RB, Mendoza RM, Williams DN. Problems in the
Fractures of different ages management of type III (severe) open fractures: A new
classification of type III open fractures. J Trauma
Epiphyseal separations 1984;24:74796; Gustilo RB, Anderson T. Prevention of
Vertebral body fractures infection in the treatment of 1025 open fractures of long
Digital fractures bones: Retrospective and prospective analyses. J Bone Joint
Complex skull fractures Surg Am 1976;50:45358.
Lowa Clavicular fractures
Long bone shaft fractures (humerus, femur,
tibia) COMPLEX INJURIES
Linear skull fractures
a
Children sustain injuries that are different from adults
Low specificity, but these findings are commonly seen in
nonaccidental trauma.
due to their size and activities. A common example is a
Adapted from OConnor JF, Cohen J. Dating fractures. In: pedestrian struck by a car. An adult will frequently sustain
Kleinman PK, editor. Diagnostic Imaging of Child Abuse. an injury to the tibia or knee from the cars bumper.
Baltimore: Williams & Wilkins, 1987. p. 6. However, the same mechanism will result in a fracture of
the femur or pelvis in conjunction with a chest or head
injury in a small child.30 Motor vehicle accidents (MVAs)
Type I Type II Type III are the most common cause of multiple injuries to chil-
dren, both as occupants and pedestrians.30,31
Open fractures are considered one of the true ortho-
pedic emergencies in children.32 These injuries usually
result from high-energy mechanisms and are often seen
in the setting of multiple trauma. Open fractures in chil-
dren and adults are classified according to the system of
GustiloAnderson (Table 18-2).3335 The four goals of
Type IV
treatment of open fractures are: prevention of infection,
bony union, prevention of malunion, and return to func-
tion of limb and patient.32,36 To attain these goals, open
fractures must be treated by early irrigation and debride-
ment along with broad-spectrum antibiotics. 3335 Kinds-
fater and colleagues found that early treatment of tibial
shaft fractures in children resulted in fewer cases of
osteomyelitis when compared to those treated later.37 As
Type V Type VI a counterpoint, data from our institution demonstrated
no difference in infection or nonunion rates with delayed
debridement in 390 open fractures of the lower extremi-
ties in adults.38 Additionally, in a study of 554 pediatric
open fractures, there was no difference in infection rates
when debridement was within 6 hours of injury as com-
pared to seven to 24 hours.39 There is no consensus on
the effect of delayed operative treatment of open frac-
FIGURE 18-1 Salter Harris classification of physeal injuries tures in regards to rates of infection and need for second-
with Rang modification. (Adapted from Rang ML, editor. The ary surgical procedures to promote bone healing.32,3945
Growth Plate and Its Disorders. Edinburgh: E&S Livingstone; 1969. Our practice is to debride open fractures within 24 hours
p 139.)
of presentation and more urgently if there is severe
contamination.
Push and riding lawn mowers produce complex
congruity of the joint to minimize the risk of arthritis. wounds and open fractures in children with an annual
Reduction also restores continuity of the physis to incidence of approximately 11 per 100,000.46 These inju-
decrease the risk of growth disturbance. Type V are crush ries frequently require serial debridement, internal or
injuries that are not usually recognized at presentation, external fixation, and reconstruction of soft tissue defects.
but have a high risk of growth arrest.29 Unfortunately, amputation is often needed.
232 SECTION II Trauma
FRACTURES OF THE LOWER EXTREMITY spiral fractures in preambulatory children are pathogno-
monic for abuse. However, studies have demonstrated
Due to the high energy required, fractures of the pelvis that any fracture pattern can occur as the result of abuse.68
and proximal femur are rare but serious injuries in chil- Falls are the leading cause of femur fractures in children
dren. Approximately two-thirds of patients with pelvic age 2 to 3 years, and MVAs are the most common cause
fractures have associated injuries, and approximately one- in older children.67 Although bleeding following a femur
third have residual, long-term morbidity.47,48 Pelvic frac- fracture can be fairly extensive, transfusion in isolated,
tures rank second to head injuries in terms of complications, closed injuries is rarely needed. Therefore, other causes
including life-threatening visceral injuries. The mortality of blood loss must be considered if there is hemodynamic
rate of pelvic fractures is between 918%.47 Children instability or a falling hematocrit at 24 hours after injury
with multiple injuries should be checked carefully to in a patient with a femur fracture, especially in the setting
exclude fractures of the pelvis. Some common findings of of multiple trauma.70
fractures of the pelvis are the presence of a hematoma Treatment of femur fractures also varies with age.69
beneath the inguinal ligament (Desot sign); decreased Younger children (<4 to 5 years) are usually treated non-
distance between the greater trochanter and anterior operatively by closed reduction and immediate spica cast
superior iliac spine on the affected side in lateral com- immobilization.7174 Older children (4 to 10 years) are
pression injuries (Roux sign); the presence of a bony managed with flexible nails7582 or plates.8385 Adolescents
prominence or hematoma on rectal exam (Earl sign). An (>10 years or >100 pounds) may be treated as adults with
anteroposterior pelvis radiograph is usually sufficient as solid, reamed, femoral nails, which should be introduced
the initial screening study, although increasingly these through the tip of the greater trochanter rather than
injuries are diagnosed by computed tomography (CT) as through the piriformis fossa to avoid injury to the vascu-
part of the initial trauma evaluation.49 Most pediatric lar supply to the femoral head (Fig. 18-3). A recent review
pelvic fractures, even those in which the pelvic ring is of rigid nails for older children and adolescents noted no
disrupted, can be treated nonoperatively with good cases of osteonecrosis with nail entry via the lateral aspect
outcomes.48 of the greater trochanter.86 In contrast to adults, the
Fractures of the femoral neck are serious injuries that timing of femur fracture stabilization in children, even in
typically require operative treatment.5059 Osteonecrosis the setting of multiple trauma, does not appear to have
caused by disruption of the blood supply to the femoral an effect on the development of pulmonary complica-
epiphysis is a dreaded complication of this fracture that tions.87 The implications are that operation can be
occurs in up to 75% of children after this injury.5055,5962 deferred until the general medical condition of the child
The risk of developing osteonecrosis correlates with a permits, with the caveat that expeditious stabilization of
higher anatomic location of the fracture in the femoral femur (as well as other long bone) fracture(s) will facili-
neck, extent of displacement, and delay in reducing tate mobilization and nursing care in the overall manage-
the fracture. Accordingly, fractures and dislocations of ment of the child.
the proximal femur are orthopedic emergencies. They Knee injuries in children differ from those in adults.
require immediate anatomic reduction, which may be In children, the cartilage of the physes, apophyses,
achieved by closed or open techniques, and internal fixa- menisci, and articular surface are weaker than the knee
tion (Fig. 18-2).52,56,59,6366 ligaments and are thus more prone to injury.88 Therefore,
Femoral shaft fractures are common injuries in chil- fractures about the knee occur more commonly than liga-
dren. The incidence and mechanism of these fractures mentous injuries in skeletally immature individuals.89
varies with patient age and gender. Child abuse accounts The distal femoral physis is the largest and fastest growing
for up to 67% of femur fractures in children younger physis. It is often injured as a result of a direct blow and
than age 1, but only 11% of fractures in children between is a common injury in American football players. Most
ages 1 and 2 years old.6769 Classic teaching states that fractures are Salter Harris type I or II injuries. These
A B C
FIGURE 18-2 (A) Anteroposterior radiograph of the pelvis of a 12-year-old female injured from a fall showing a displaced transcervi-
cal fracture of the left femoral neck (arrow). The fracture was treated emergently by closed reduction and internal fixation with two
cannulated screws. (B,C) Radiographs one year later show healing of the fracture and no evidence of osteonecrosis.
18 Pediatric Orthopedic Trauma 233
A B C D
FIGURE 18-3 Four methods for treatment of femoral shaft fractures in children and adolescents are shown: (A) spica cast in a
24-month-old; (B) flexible intramedullary nails in a 7-year-old; (C) submuscular plating in an 8-year-old with severe head injury;
(D) rigid locked intramedullary nail in an 11-year-old.
fractures can usually be treated by closed reduction and injury, impending compartment syndrome, unacceptable
percutaneous, cross-pin stabilization. Fractures extend- alignment following closed reduction, and fractures
ing into the articular surface (type III and IV injuries) occurring in the setting of multiple trauma.
require open reduction and internal fixation if displace- Ankle fractures are typically caused by indirect, tor-
ment of the articular surface is greater than 2mm. sional forces. Injuries to the distal tibial and fibular physes
Because of the size of this growth plate, its complex, account for 25% to 38% of all childrens physeal inju-
undulating anatomy, and the forces required for displace- ries.94,95 Sports injuries account for up to 60% of physeal
ment, fractures of the distal femoral physis, even type I fractures about the ankle.96 Nonoperative management
and II injuries, may result in permanent growth distur- has historically been the preferred approach, except for
bance in up to 50% of cases.90 All of these fractures intra-articular fractures and those unable to be adequately
should be followed for a minimum of 1 year to evaluate reduced by closed techniques. Newer data suggests
for sequelae of growth arrest. improved results with open reduction of distal tibial
Proximal tibial physeal injuries are uncommon due to physeal injuries.26 CT is very useful in defining the patho-
the reinforcement provided by the knee joint capsular anatomy of fractures with intra-articular involvement or
attachments and collateral ligaments. Vascular compro- unusual patterns, and is useful in making management
mise of the lower leg due to popliteal artery injury is decisions and in preoperative planning.97 Foot fractures
possible, particularly with extension-type injuries in are uncommon and most can be treated nonoperatively
which the proximal portion of the tibial metaphysis is with immobilization and restricted weight bearing. More
displaced posteriorly. Such injuries tent the popliteal complex problems that require operative intervention
artery at the level of the physis and proximal to the tri- include fractures of the talar neck and calcaneus, fractures
furcation, where it is relatively tethered by the peroneal or dislocations of the tarsometarsal (Lisfranc) joint, open
branch as it courses thru the fascia entering the anterior fractures, and lawn mower injuries.97
compartment of the leg (Fig. 18-4). Close attention to
the vascular examination of the lower extremity is critical
following injuries to the proximal tibia. Intra-articular
knee injuries typically present with a hemarthrosis and
SPINE INJURIES
include patellar fractures or dislocations, tibial spine/
plateau fractures, osteochondral fractures, and
Cervical Spine Injuries
ligamentous/meniscal injuries. These injuries are typi- Cervical spine injuries in children are relatively uncom-
cally not emergencies and can be splinted with delayed mon but potentially catastrophic. Accurate diagnosis
definitive treatment. requires an awareness of the injury patterns, anatomic
Nonphyseal fractures of the tibia and fibula are among characteristics, and radiographic variants of the immature
the most common injuries involving the lower extremity cervical spine.98 These injuries account for approxi-
in children.91,92 Fortunately, most of these injuries are low mately 1% of all pediatric fractures and only 2% of all
energy and can be treated nonoperatively. However, one spine fractures.99101 Pediatric cervical spine injuries are
must always be cognizant of the possibility of compart- fundamentally different from their adult counterparts
ment syndrome following closed or open fractures of the due to the anatomic characteristics of the immature spine
tibial shaft.93 Indications for operative treatment of tibial and, and to a lesser extent, the differences in the mecha-
shaft fractures include: open fractures, neurovascular nisms of injury.102 The cervical spine in children is
234 SECTION II Trauma
Popliteal
artery
A B C D
FIGURE 18-4 (A) Anteroposterior and lateral radiographs of a 13-year-old male showing a Salter Harris type I fracture of the proximal
tibial physis with posterior displacement of the distal fragment following an extension-type injury. (B) Distal pulses were diminished
prior to and following closed reduction and stabilization of the fracture. (C) Arteriogram shows occlusion of the popliteal artery
(arrow) at the level of the fracture. Vascular repair with an interposition graft was performed successfully. (D) Drawing shows the
relationship of the popliteal artery to the proximal tibial physis and mechanism of vascular injury (arrow) in this fracture. (D, Adapted
from Zionts LE: Fractures and Dislocations about the Knee. In Green NE, Swiontkowski MF [eds]: Skeletal Trauma in Children, 3rd Edition.
Philadelphia, Saunders, 2003. 3:460)
inherently mobile because of the presence of generalized injuries may be associated with other signs of nonacci-
laxity of the interspinous ligaments and joint capsules, dental trauma including fractures of the skull, rib, or long
underdeveloped neck musculature, thick cartilaginous bones, and superficial ecchymoses. In older children (up
end plates, incomplete vertebral ossification (wedge- to about age 10), the most common causes are pedestrian-
shaped vertebral bodies), and shallow-angled facet joints, MVAs and falls. In children over 10 years of age, the most
particularly between the occiput and C4.102 common etiologies are passenger-related MVAs, sports-
In infants and young children, injuries to the upper related injuries, and diving accidents.
cervical spine (above C3) predominate because the head Appropriate methods of immobilizing children for
is disproportionately large and creates a large bending transport and proper clinical and radiographic evaluation
moment in the upper cervical spine. In an 11-year experi- are crucial to avoid detrimental outcomes. The goal of
ence with 122 pediatric neck injuries, none of the 21 immobilization during transport of the injured child with
patients age 8 years or less had evidence of injury below potential spine trauma is to avoid excessive angulation of
C3.103 Also, multiple level spinal injuries are common, the spinal column so as to avoid causing or exacerbating
occurring in approximately 25% of children with cervical spinal cord injury. Immobilization of children less than 8
spine fractures.103106 Spinal cord injury without radio- years of age on a standard spine board during emergency
graphic abnormality (SCIWORA) occurs more fre- transportation will cause excessive flexion of the cervical
quently in children than in adults.100,102 After age 8 to 10 spine due to the disproportionately large diameter of the
years, the anatomical and biomechanical characteristics head relative to the torso. It has been recommended that
of the cervical spine are more like an adult, and injuries the childs spine board be modified by building up the
to the cervical spine are much more likely to occur in the area under the torso with padding to allow the head to
subaxial region (below C3). Evaluation and treatment of fall back slightly or cutting out the area under the occiput
these injuries is essentially the same as in an adult.98,100,102,107 to recess the skull (Fig. 18-5).112 In addition to proper
Mechanisms of injury vary somewhat with age. In spine-board immobilization, an appropriately fitting cer-
neonates, birth trauma is the most common cause of vical collar is necessary to achieve neutral alignment of
cervical spine injury and occult spinal cord injury has the cervical spine after injury.113
been demonstrated at necropsy in 30% to 50% of still- Clinical evaluation of a child suspected of having an
borns. Excessive distraction and/or hyperextension of the injury to the cervical spine is often hampered by an ina-
cervical spine are thought to be the most common mech- bility to obtain an accurate history and the unreliability
anisms of injury, and may be associated with abnormal of the physical examination.98,100,107,114116 Historically,
intrauterine position (transverse lie) or a difficult cephalic overt or occult injury to the cervical spine is more likely
or breech delivery.108,109 In infants and young children, to occur as a result of falls from a height of more than
nonaccidental trauma is a significant cause of injury to four feet, pedestrian or cyclist MVAs, and unrestrained
the cervical spine. Avulsion fractures of the spinous proc- occupant MVAs. Head or facial trauma, altered mental
esses, fractures of the pars or pedicles (most commonly status and/or loss of consciousness are also risk factors.
C2), or compression fractures of multiple vertebral bodies Neck pain, guarding, and torticollis are the most reliable
are the most common patterns of injury and are thought signs of an injury to the cervical spine in children.
to result from severe shaking or battering.110,111 These Extremity weakness, sensory changes, bowel and bladder
18 Pediatric Orthopedic Trauma 235
A B
FIGURE 18-5 (A) Drawings of an adult and a child on a normal spine board contrasting the differences in position of the head and
neck during emergency transport. Because of the disproportionate head-to-body ratio in children, the childs cervical spine is flexed.
(B) Two methods of modifying the traditional spine board for pediatric patient transport are shown. In the upper illustration, a cutout
in the board allows the occiput to be recessed. In the lower illustration, the area under the thorax is built up with padding. Both
methods effectively allow the head to translate posteriorly, creating more normal alignment of the cervical spine. (Adapted from
Herzenberg JE, Hensiger RN, Dedrick DK. Emergency transport and positioning of young children who have an injury to the cervical spine.
J Bone Joint Surg Am 1989;71:1521.)
dysfunction, and, less frequently, headaches, seizures, cervical spine is necessary before immobilization is dis-
syncope, and respiratory distress are signs of injury to the continued.115 In general, the cervical spine may be cleared
spinal cord.98,99,104,117126 When these conditions present, based on clinical examination alone if the child is awake,
the cervical spine should be immobilized until imaging alert, and cooperative; if there are no signs of cervical
studies can be completed and the spine cleared.98 injury; and if the mechanism of injury is not consistent
Radiographic evaluation of the cervical spine in chil- with cervical trauma.98,115 For children under age 8 to 10
dren is hampered by the presence of normal anatomic years who are obtunded or otherwise unable to be exam-
variants that can be mistaken for trauma. Synchondroses ined, and all those with a profile suggestive of injury to
and incompletely ossified, wedged-shaped vertebral the cervical spine, clearance may be based on a five-view
bodies can simulate fractures.127130 Anterior angulation of cervical spine radiographic series, consisting of antero-
the odontoid is a normal variant in approximately 5% of posterior, lateral, open mouth odontoid, and two oblique
children and may be mistaken for a Salter Harris type I views, and a CT of the axial region of the spine, from
fracture of the dens. Physiologic subluxation of C2 on C3 occiput to C2. In a study at our institution in which this
or C3 on C4 of up to 3mm is a normal variant (pseudo- protocol was followed, eight of 112 children were diag-
subluxation) in about 40% of children younger than age 8 nosed with cervical spine injuries. Two of six children
years and is often misinterpreted as pathologic instabil- with bony injuries (33%) were diagnosed only by CT
ity.129,131 Focal kyphosis of the mid-cervical spine is a scan. No injuries were missed and cervical immobiliza-
normal variant in about 15% of children under age 16 tion was discontinued in a timely fashion.135 The ration-
years that can also be misinterpreted as pathologic. ale for CT include the predisposition for injuries to occur
Initial radiographic evaluation should include cross- in the upper cervical region in children younger than 8
table lateral and anteroposterior radiographs. On the years old and the technical difficulty imaging this area
lateral view, it is essential to see the C7T1 disc space. with plain radiographs.98 In a subsequent study from our
Oblique radiographs provide detail of the pedicles and institution, helical CT was shown to be have higher spe-
facet joints.127 Open mouth odontoid radiographs are cificity, sensitivity and negative predictive value than con-
technically difficult to perform and rarely helpful.132 CT ventional radiographs in evaluating the cervical spine in
is a much better way to image the upper cervical spine children with blunt trauma.134
and also provides excellent definition of known fractures, Others have advocated for the definitive role of MRI,
confirmation of suspicious areas, and excellent visualiza- particularly in identifying soft tissue injury.136138 In a
tion of the cervicothoracic level, which can be difficult to study of 79 children, MRI revealed injuries in 15 patients
adequately image on plain radiography. CT has been with normal radiographs and excluded injuries suspected
shown to be more efficacious than conventional images on plain radiographs and CT scans in 7 and 2 patients,
in evaluating the cervical spine in adult and pediatric respectively. In 25 obtunded or uncooperative children,
trauma and to lower institutional costs and complications MRI demonstrated three with significant injuries.136
in urban trauma centers.124,133,134 Magnetic resonance Halo vest immobilization is being used with increasing
imaging (MRI) is the preferred study to evaluate the frequency in children with cervical spine injuries. It
spinal cord and soft tissue structures including ligaments, affords superior immobilization to a rigid cervical collar
cartilage, and intervertebral discs. and is easier to apply and more versatile than a Minerva
Once a cervical collar has been placed on a child or cast. It permits access for skin and wound care while
the neck immobilized, either at the scene of an accident avoiding the skin problems (maceration, ulceration) typi-
or in the emergency department, formal clearance of the cally associated with both hard collars and casts. However,
236 SECTION II Trauma
complication rates up to 70% have been reported with cord.146 Injury may be complete or incomplete and may
use of halo vests in children.139 Pin site infections are the occur at more than one level.148 Partial spinal cord syn-
most common problems, but skull perforation, cerebro- dromes reported in SCIWORA include BrownSequard,
spinal fluid leaks, and brain abscesses have also been anterior, and central cord syndromes, as well as mixed
described.107,139 In children younger than age 6 years, a patterns of injury.142144,146
CT scan of the skull to measure calvarial thickness can Prognosis following SCIWORA is correlated to MRI
be helpful in determining optimal sites for pin place- findings, if any are present, and to the severity of neuro-
ment.140 In children older than 6 years, the standard adult logical injury.142144,149 Effective management demands
halo construct utilizing four pins (two anterolaterally, two careful evaluation of the cervical spine to exclude osseous
posterolaterally) inserted at standard torques of 68 inch- or cartilaginous injury or mechanical instability. In addi-
pounds generally works well (Fig. 18-6A). In younger tion, immobilization with a rigid cervical collar for two
children, more pins (up to 12) placed with lower inser- to three months has been recommended to prevent
tional torques (24 inch-pounds) have been advocated recurrent injury.142145 However, the need for prolonged
(Fig. 18-6B) .139,140 Standard pediatric halo rings fit most immobilization in the absence of radiographic or MRI
children, but infants and toddlers may require custom evidence of instability has been challenged. In a 34-year
rings. Although standard pediatric halo vests are availa- review of SCIWORA at a single institution, recurrent
ble, custom vests or body casts generally provide better injury was uncommon and of uncertain etiology. Immo-
immobilization.141 bilization did not prevent recurrent symptoms or improve
The possibility of SCIWORA should be considered in outcomes. A full recovery occurred in all cases of recur-
children, particularly in those younger than 8 years old. rent SCIWORA.149 Surgery is occasionally necessary for
SCIWORA is defined as spinal cord injury in a patient unstable injury patterns. The prevalence of scoliosis fol-
in whom there is no visible fracture on plain radiographs lowing infantile quadriplegia is over 90%. Therefore,
or CT scan.142145 MRI may be diagnostic in demonstrat- long-term follow-up is necessary to monitor for vertebral
ing spinal cord edema or hemorrhage, soft tissue or column deformity. Administration of high-dose corticos-
ligamentous injury, or apophyseal or disc disruption, but teroids within the first eight hours of spinal cord injury
is completely normal in approximately 25% of cases. has been shown to improve the chances of neurologic
SCIWORA is the cause of paralysis in approximately recovery in adults.150153 According to guidelines from the
2030% of children with injuries of the spinal cord. third National Acute Spinal Cord Injury Study (NASCIS),
Potential mechanisms of SCIWORA include hyperex- when treatment is initiated within 3 hours of injury,
tension of the cervical spine, which can cause compres- methylprednisolone should be administered as an intra-
sion of the spinal cord by the ligamentum flavum, followed venous bolus of 30mg/kg over 15 minutes followed by a
by flexion, which can cause longitudinal traction. Other continuous infusion of 5.4mg/kg/h over the next 23
mechanisms include transient subluxation without gross hours. Also, if treatment cannot be started until more
failure or unrecognized cartilaginous end plate failure than 3 to 8 hours after injury, the corticosteroids should
(Salter Harris type I fracture). be given for 48 hours. After 8 hours, there is no benefit
Regardless of the specific mechanism, injury to the and corticosteroids should not be administered.152,153 As
spinal cord occurs because of the variable elasticity of the the effect on younger children (<13 years old) is not
elements of the spinal column in children.146 Experimen- known, this protocol is not universally followed at all
tally, it has been shown that the bone, cartilage and soft institutions.
tissue in the spinal column can stretch about two inches
without disruption but that the spinal cord ruptures after
one-quarter inch.109,145,147 Spinal cord injury occurs when
Thoracic, Lumbar, and Sacral Fractures
deformation of the musculoskeletal structures of the Thoracic, lumbar and sacral fractures are also relatively
spinal column exceeds the physiologic limits of the spinal uncommon in children. MVAs or falls causes the majority
of these injuries. Child abuse should be considered in patterns of extension into the middle and anterior columns
younger children.120,154158 The most common injuries are (Chance fracture). These injuries may be missed on axial
compression fractures and flexiondistraction injuries. CT because of the transverse plane of orientation of the
Compression fractures are caused by a combination of fracture. Widening of the interspinous distance on a
hyperflexion and axial compression. Because the disc in lateral radiograph or CT with sagittal reconstruction are
children is stronger than cancellous bone, the vertebral the most helpful studies in diagnosing this fracture (Fig.
body is the first structure to fail. It is common for children 18-7). Approximately two-thirds of patients have injury to
to sustain multiple compression fractures. Compression a hollow viscus, a solid organ injury, or even injury to the
rarely exceeds more than 20% of the vertebral body. In abdominal aorta. These injuries often result in greater
the multiply injured patient, CT has become the pre- morbidity than the spine fracture and may be life-
ferred imaging modality to diagnose and characterize threatening, particularly if unrecognized initially.165,169,170
these fractures.49,159 These fractures are managed con- Fortunately, neurologic injury is unusual. Lap belt inju-
servatively with rest, analgesics and bracing.158 ries with mostly bony involvement and kyphosis less than
Flexion/distraction injuries (seat-belt injuries) occur 20 can be treated with hyperextension casting. Those
in the upper lumbar spine in children wearing a lap with posterior ligamentous disruption and significant
belt.160168 With sudden deceleration, the seat belt slides intra-abdominal injury require surgical stabilization with
up on the abdomen where it provides an axis about which compression instrumentation and posterior arthrodesis.
the spine rotates. As a result, the torso is forcibly flexed Fracturedislocations of the spine are unstable injuries
and the spinal column fails in tension, resulting primarily that usually occur at the thoracolumbar junction and
in disruption of the posterior column with variable often are associated with neurologic deficits. These are
A B
C D
FIGURE 18-7 (A) A 12-year-old female involved in a motor vehicle accident with ecchymosis (arrow) in the lower abdomen caused
by the lap belt portion of a three-point restraint. (B) This child had a laceration of the mesentery discovered at laparotomy and a
(C,D) flexiondistraction fracture of L1 (arrow) with disruption of all three columns of the spine that required operative
stabilization.
238 SECTION II Trauma
However, we now recognize that this fracture does not shown by follow-up studies that vein grafts of vascular
need immediate operative stabilization unless there are injuries will frequently clot because of the excellent col-
other extenuating circumstances, such as vascular injury, lateral circulation about the elbow.196 The only true indi-
compartment syndrome, or an open wound. Currently, cation for vascular exploration is the pulseless, ischemic
the general policy is to delay treatment until the next day. extremity which is a true surgical emergency. In this
Initially, the elbow is splinted in less than 90 of flexion instance, the fracture should be reduced and stabilized
with a loose bandage over a posterior splint.193,194 These with crossed pins before vascular repair.197,198
fractures can usually be reduced by closed manipulation Compartment syndrome is a feared complication that
and stabilized by percutaneous pins (Fig. 18-9). is uncommon in the modern era. Stabilizing the fracture
There has long been a controversy as to the treatment with internal fixation avoids the need to immobilize the
of the pulseless extremity in patients who have sustained elbow in hyperflexion, which has been shown to increase
a supracondylar fracture. Absence of the pulse with this the risk of vascular compression and forearm compart-
fracture is not uncommon. It is believed that the absence ment swelling.192
of the pulse may either be the result of vascular spasm The signs of compartment syndrome are well known,
and/or direct vascular injury. However, the collateral cir- but the main one is pain that is out of proportion to
culation about the elbow is so rich that the circulation to the fracture itself. Once this fracture is stabilized, the
the forearm and hand usually remains normal. Treatment child should be comfortable and not have significant
of the vascular injury has been debated for decades in the pain. Passive extension of the fingers should be possible to
orthopedic and vascular surgery literature. The current a neutral position. If not, it suggests the need for investi-
practice is observation as long as circulation to the hand gation of a compartment syndrome by removal of the
and forearm is clinically normal.192,193,195 It has been splint, palpation of the forearm compartment, and pres-
A B
C D
FIGURE 18-9 A 6-year-old fell while horseback riding and landed on his outstretched left arm. (A) Anteroposterior and (B) lateral
radiographs show a completely displaced (type III) supracondylar humerus fracture. Neurovascular status of the extremity was intact.
(C,D) The child was treated with closed reduction and percutaneous fixation with smooth Steinmann pins.
240 SECTION II Trauma
sure measurements, if necessary. If the pressures are ele- Forearm and wrist fractures have traditionally been
vated, then fasciotomy should be urgently performed. treated with closed manipulation and casting. Our prefer-
Salter Harris type I fractures of the distal humerus are ence is to perform closed reduction of these fractures in
less common than other injuries about the elbow and are the emergency department with conscious sedation.203,204
frequently misdiagnosed. In very young children, this The use of a portable fluoroscopy unit is essential, both
fracture often occurs as the result of nonaccidental trauma to guide reduction of the fracture and to confirm align-
and should trigger investigation into the possibility of ment following immobilization. Use of a mini-C-arm
abuse.199 This fracture may also occur in newborns as a improves reduction quality, decreases need for repeat
result of birth trauma.192 Unfortunately, especially in reduction, and results in less overall radiation exposure.205
instances of nonaccidental trauma, the child is commonly After manipulation of the fracture, the extremity is
seen a significant time after this injury has already begun immobilized in a sugar tong splint that will allow for
to heal, and manipulation of the fracture is either not swelling. When swelling is no longer a concern, the sugar
possible or ill advised (Fig. 18-10). tong splint is incorporated into a long-arm, fiberglass
Fractures of the lateral condyle of the humerus must cast. In general, the child should be seen weekly for the
also be distinguished from the Salter Harris type I frac- first three weeks to be certain that the alignment of the
tures of the distal humeral physis (Fig. 18-11). If the fracture is maintained. After 3 weeks, a short arm cast is
condylar fracture is displaced at all, it requires open applied for another 3 weeks after which progressive use
reduction and pin fixation because the risk of nonunion and motion is started.
is high when it is treated nonoperatively. Nonunion will Fractures of the shaft of both bones of the forearm
result in a progressive valgus deformity of the elbow with have a limited range of acceptable residual deformity to
an ulnar nerve palsy.200202 avoid loss of motion, particularly in children older than
A B C D
FIGURE 18-10 An 11-month-old infant, ultimately determined to have been the victim of abuse, presented with a swollen arm.
(A) On the anteroposterior radiograph of the elbow, the capitellum, the proximal radius, and the ulna are displaced from their normal
positions relative to the distal humerus (arrows), consistent with a fracture-separation of the distal humeral epiphysis. In an elbow
dislocation, the radius and ulna are displaced relative to the distal humerus but the capitellum is not displaced from its normal
position in the distal humerus. (B) The lateral radiograph of the elbow shows a small metaphyseal fragment (arrow), also consistent
with a fracture of the distal humeral physis and not with dislocation of the elbow. This fracture was treated with cast immobilization.
(C,D) Note the exuberant fracture callus 3 weeks after the injury.
A B C D
FIGURE 18-11 A 7-year-old child fell from a bunk bed, resulting in a fracture of the lateral condyle of the humerus. (A) Anteropos-
terior and (B) lateral radiographs show displacement of the capitellum (arrow), whereas the radius and ulna remain aligned with
the humerus. Even if they were minimally displaced, the risk of joint incongruity and nonunion is high after nonoperative treatment
of this fracture. (C) Anteroposterior and (D) lateral radiographs of the elbow after open reduction and pin fixation show anatomic
alignment.
18 Pediatric Orthopedic Trauma 241
A B C D
FIGURE 18-12 (A) Anteroposterior and (B) lateral radiographs show grade 1 open forearm fractures in an 8-year-old. (C,D) Following
debridement, the fracture was stabilized with flexible titanium nails inserted via 1cm incisions, distally in the radius and proximally
in the ulna, and advanced across the fracture under fluoroscopy.
the age of 8 or 9 years. It may be difficult to maintain 8. Reed MH. Fractures and dislocations of the extremities in chil-
reduction of these fractures in a cast or splint. For this dren. J Trauma 1977;17:351.
9. Masterson E, Borton D, Foster BK. Victims of our climate. Injury
reason, fractures of the shafts of the radius and ulna are 1993;24:247.
being treated by internal fixation using flexible titanium 10. Shank LP, Bagg RJ, Wagnon J, editors. Etiology of pediatric
nails with increasing frequency.172,173,176,206214 These frac- fractures: The fatigue factors in childrens fractures. Indianapolis:
tures can be reduced by closed manipulation and stabi- National Conference of Pediatric Trauma; 1992.
11. Westfelt JARN. Environmental factors in childhood accidents: A
lized by percutaneous insertion of titanium or stainless prospective study in Goteborg, Sweden. Acta Paediatr Scand
steel intramedullary nails, although open reduction may 1982(Suppl. 291).
be required approximately in 2944% of closed fractures 12. Izant RJ, Hubay CA. The annual injury of 15,000,000 children:
(Fig. 18-12).172,173,176 A limited study of childhood accidental injury and death. J Trauma
The vast majority of wrist and hand fractures in chil- 1966;6:65.
13. Ong ME, Ooi SB, Manning PG. A review of 2,517 childhood
dren can be managed nonoperatively. Exceptions include injuries seen in a Singapore emergency department in 1999
open fractures or fractures that cannot be maintained in mechanisms and injury prevention suggestions. Singapore Med
acceptable rotational or angular alignment. Phalangeal J 2003;44:1219.
neck fractures are unstable injuries that frequently benefit 14. Wilkins KE. The Incidence of Fractures in Children. In: Rock-
wood CE Jr, Wilkins KE, Beaty JH, editors. Fractures in Chil-
from pin fixation to prevent malunion with loss of digital dren. Philadelphia: Lippincott-Raven; 1996. p. 117.
motion. 15. Brownell M, Friesen D, Mayer T. Childhood injury rates in
Manitoba: socioeconomic influences. Can J Public Health 2002;
93(Suppl 2):S506.
REFERENCES 16. Johnson CF. Inflicted injury versus accidental injury. Pediatr Clin
1. Smith MD, Burrington JD, Woolf AD. Injuries in children sus- North Am 1990;37:791814.
tained in free falls: An analysis of 66 cases. J Trauma 1975;15:987. 17. Schmitt BD, Gray JD, Britton HL. Child Abuse. In: Green M,
2. Starfield B. Childhood Morbidity: Comparisons, Clusters, and Haggerty RJ, editors. Ambulatory. Pediatrics III: W.B. Saunders;
Trends. Pediatrics 1991;88:519. 1984.
3. Landin LA. Fracture patterns in children. Acta Orthop Scand 18. Akbarnia BA, Akbarnia NO. The role of the orthopedist in child
1983;54(Suppl. 202):1. abuse and neglect. Orthop Clin North Am 1976;7:73342.
4. Worlock P, Stower M. Fracture patterns in Nottingham children. 19. Galleno H, Oppenheim WL. The battered child syndrome revis-
J Pediatr Orthop 1986;6:656. ited. Clin Orthop 1982;62:1119.
5. Ward WT, Rihn JA. The impact of trauma in an urban pediatric 20. OConnor JF, Cohen J. Dating Fractures. In: Kleinman PK,
orthopaedic practice. J Bone Joint Surg Am 2006;88:275964. editor. Diagnostic Imaging of Child Abuse. Baltimore: Williams
6. Tuason D, Hohl JB, Levicoff E, et al. Urban pediatric orthopaedic & Wilkins; 1987. p. 6.
surgical practice audit: Implications for the future of this subspe- 21. Mann DC, Rajmatra S. Distribution of physeal and non-physeal
cialty. J Bone Joint Surg Am 2009;91:29928. fractures of long bones in children aged 0 to 16 years. J Pediatr
7. Cheng JC, Shen WY. Limb fracture pattern in different Orthop 1990;10:713.
pediatric age groups: A study of 3350 children. J Orthop Trauma 22. Marcus RE, Mills MF, Thompson GH. Multiple injury in chil-
1993;7:15. dren. JBJS 1983;65:1290.
242 SECTION II Trauma
23. Ogden J. Skeletal Injury in the Child. 2nd ed. Philadelphia: Lea 48. Grisoni N, Connor S, Marsh E, et al. Pelvic fractures in a pediatric
& Feibeger; 1990. level I trauma center. J Orthop Trauma 2002;16:45863.
24. Ogden J. Complications of Fractures. Philadelphia: J.B. Lippin- 49. Stewart BG, Rhea JT, Sheridan RL, et al. Is the screening portable
cott; 1995. pelvis film clinically useful in multiple trauma patients who will
25. Salter RB, Harris WR. Injuries involving the epiphyseal plate. be examined by abdominopelvic CT? Experience with 397
JBJS Am 1963;45:587. patients. Emerg Radiol 2002;9:26671.
26. Barmada A, Gaynor T, Mubarak S. Premature physeal closure 50. Azouz EM, Karamitsos C. Types and complications of femoral
following distal tibia physeal fractures: A new radiographic predic- neck fractures in children. Pediatr Radiol 1993;23:41520.
tor. J Pediatr Orthop 2003;23:7339. 51. Bagatur AE, Zorer G. Complications associated with surgically
27. Kling TFJ, Bright RW, Hensinger RN. Distal tibial physeal frac- treated hip fractures in children. J Pediatr Orthop B
tures in children that may require open reduction. J Pediatr 2002;11:21928.
Orthop 1984;66:64757. 52. Canale ST. Fractures of the hip in children and adolescents.
28. Spiegel PG, Mast JW, Cooperman DR, et al. Epiphyseal fractures Orthop Clin North Am 1990;21:34152.
of the distal ends of the tibia and fibula. A retrospective study of 53. Maeda S, Kita A, Fujii G, et al. Avascular necrosis associated
two hundred and thirty-seven cases in children. JBJS Am with fractures of the femoral neck in children: Histological evalu-
1978;60:104650. ation of core biopsies of the femoral head. Injury 2003;34:
29. Mendez AA, Bartal E, Grillot MB, et al. Compression (Salter 2836.
Harris type V) physeal fracture: An experimental model in the rat. 54. Moon ES, Mehlman CT. Risk factors for avascular necrosis after
J Pediatr Orthop 1992;12:29. femoral neck fractures in children: 25 Cincinnati cases and meta-
30. Wilber JH, Thompson GH. The Multiply Injured Child. In: analysis of 360 cases. J Orthop Trauma 2006;20:3239.
Green NE, Swiontkowski MF, editors. Skeletal Trauma in Chil- 55. Morsy HA. Complications of fracture of the neck of the femur in
dren. 3rd ed. Philadelphia: Saunders; 2003. p. 73101. children. A long-term follow-up study. Injury 2001;32:4551.
31. Morrison A, Stone DH, Redpath A, et al. Childhood injury 56. Ng GP, Cole WG. Effect of early hip decompression on the
mortality in Scotland, 1981-95. Health Bull (Edinb) 1999;57: frequency of avascular necrosis in children with fractures of the
2416. neck of the femur. Injury 1996;26:41921.
32. Stewart DG Jr, Kay RM, Skaggs DL. Open fractures in children. 57. Pape H, Kretteck C, Friedrich A, et al. Long-term outcome in
Principles of evaluation and management. J Bone Joint Surg Am children with fractures of the proximal femur after high energy
2005;87:278498. trauma. J Trauma 1999;46:5864.
33. Gustillo R, Mendoza R, Williams D. Problems in the manage- 58. Ratliff A. Fractures of the neck of the femur in children. J Bone
ment of type III (severe) open fractures: A new classification of Joint Surg Br 1962;44:52854.
Type III open fractures. J Trauma 1984;24:74796. 59. Shrader MW, Jacofsky DJ, Stans AA, et al. Femoral neck fractures
34. Gustilo RB, Anderson JT. Prevention of infection in treatment of in pediatric patients: 30 years experience at a level 1 trauma
1025 open fractures of long bones: Retrospective and prospective center. Clin Orthop Relat Res 2007;454:16973.
analysis. JBJS Am 1976;58:4538. 60. Mirdad T. Fractures of the neck of femur in children: An experi-
35. Gustilo RB, Merkow RL, Templeman D. Current Concepts ence at the Aseer Central Hospital, Abha, Saudi Arabia. Injury
Review: The Management of Open Fractures. JBJS Am 2002;33:8237.
1990;72:299304. 61. Theruvil B, Kapoor V. Avascular necrosis associated with fractures
36. Chapman MW. The use of immediate internal fixation in open of the femoral neck in children: Histological evaluation of core
fractures. Orthop Clin North Am 1980;11:57991. biopsies of the femoral head. Injury 2005;36:2301.
37. Kindsfater K, Jonassen EA. Osteomyelitis in grade II and III open 62. Togrul E, Bayram H, Gulsen M, et al. Fractures of the femoral
tibia fractures with late debridement. J Orthop Trauma 1995;9: neck in children: Long-term follow-up in 62 hip fractures. Injury
1217. 2005;36:12330.
38. Rohmiller MT, Kusuma S, Blanchard GM, et al, editors. Manage- 63. Dhammi IK, Singh S. Displaced femoral neck fracture in children
ment of Open Fractures of the Lower Extremity: Does Time to and adolescents: Closed versus open reductiona preliminary
Debridement and Primary Wound Closure Really Matter? OTA; study. J Orthop Sci 2005;10:1739.
2002; Toronto, Ontario, Canada. 64. Flynn JM, Wong KL. Displaced fractures of the hip in children.
39. Skaggs DL, Friend L, Alman B, et al. The effect of surgical delay Management by early operation and immobilization in a hip spica
on acute infection following 554 open fractures in children. J Bone cast. J Bone Joint Surg Br 2002;84:10812.
Joint Surg Am 2005;87:812. 65. Forster N, Ramseier L. Undisplaced femoral neck fractures in
40. Charalambous CP, Siddique I, Zenios M, et al. Early versus children have a high risk of secondary displacement. J Pediatr
delayed surgical treatment of open tibial fractures: Effect on the Orthop 2006;15:1313.
rates of infection and need of secondary surgical procedures to 66. Song KS, Kim YS, Sohn SW, et al. Arthrotomy and open reduc-
promote bone union. Injury 2005;36:65661. tion of the displaced fracture of the femoral neck in children. J
41. Iobst CA, Tidwell MA, King WF. Nonoperative management Pediatr Orthop B 2001;10:20510.
of pediatric type I open fractures. J Pediatr Orthop 2005; 67. Nork SE, Bellig GJ, Woll JP, et al. Overgrowth and outcome after
25:51317. femoral shaft fracture in children younger than 2 years. Clin
42. Khatod M, Botte MJ, Hoyt DB, et al. Outcomes in open tibia Orthop 1998(357):18691.
fractures: relationship between delay in treatment and infection. 68. Scherl SA, Miller L, Lively N, et al. Accidental and nonaccidental
J Trauma 2003;55:94954. femur fractures in children. Clin Orthop 2000(376):96105.
43. Skaggs DL, Kautz SM, Kay RM, et al. Effect of delay of surgical 69. Solga P. Pediatric femur fractures: Treatment in the year 2007.
treatment on rate of infection in open fractures in children. Med Health R I 2007;90:1226.
J Pediatr Orthop 2000;20:1922. 70. Lynch JM, Gardner MJ, Gains B. Hemodynamic significance of
44. Spencer J, Smith A, Woods D. The effect of time delay on infec- pediatric femur fractures. J Pediatr Surg 1996;31:135861.
tion in open long-bone fractures: a 5-year prospective audit from 71. Cassinelli EH, Young B, Vogt M, et al. Spica cast application in
a district general hospital. Ann R Coll Surg Engl 2004;86: the emergency room for select pediatric femur fractures. J Orthop
10812. Trauma 2005;19:70916.
45. Yang EC, Eisler J. Treatment of isolated type I open fractures: is 72. Czertak DJ, Hennrikus WL. The treatment of pediatric femur
emergent operative debridement necessary? Clin Orthop Relat fractures with early 90-90 spica casting. J Pediatr Orthop
Res 2003(410):28994. 1999;19:22932.
46. Vollman D, Smith GA. Epidemiology of lawn-mower-related 73. Hughes BF, Sponseller PD, Thompson JD. Pediatric femur frac-
injuries to children in the United States, 1990-2004. Pediatrics tures: effects of spica cast treatment on family and community.
2006;118:e2738. J Pediatr Orthop 1995;15:45760.
47. Demetriades D, Karaiskakis M, Velmahos GC, et al. Pelvic frac- 74. Infante AF Jr, Albert MC, Jennings WB, et al. Immediate hip spica
tures in pediatric and adult trauma patients: Are they different casting for femur fractures in pediatric patients. A review of 175
injuries? J Trauma 2003;54:114651; discussion 51. patients. Clin Orthop Relat Res 2000(376):10612.
18 Pediatric Orthopedic Trauma 243
75. Flynn JM, Hresko T, Reynolds RA, et al. Titanium elastic nails 103. Hill S, Miller C, Kosnik E. Pediatric neck injuries: A clinical study.
for pediatric femur fractures: A multicenter study of early results J Neurosurg 1984;60:700.
with analysis of complications. J Pediatr Orthop 2001;21:48. 104. Brown RL, Brunn MA, Garcia VF. Cervical spine injuries in
76. Flynn JM, Luedtke L, Ganley TJ, et al. Titanium elastic nails for children: A review of 103 patients treated consecutively at a level
pediatric femur fractures: Lessons from the learning curve. Am J 1 pediatric trauma center. J Pediatr Surg 2001;36:110714.
Orthop 2002;31:714. 105. Hadden W, Gillepsie W. Multiple level injuries of the cervical
77. Heinrich SD, Drvaric D, Darr K, et al. Stabilization of pediatric spine. Injury 1985;16:62833.
diaphyseal femur fractures with flexible intramedullary nails (a 106. Heilman CB, Riesenburger RI. Simultaneous noncontiguous
technique paper). J Orthop Trauma 1992;6:4529. cervical spine injuries in a pediatric patient. Neurosurg 2001;
78. Ho CA, Skaggs DL, Tang CW, et al. Use of flexible intramedul- 49:101720.
lary nails in pediatric femur fractures. J Pediatr Orthop 107. Jones E, Hensinger R. Injuries of the cervical spine. In: Rockwood
2006;26:497504. W, Beaty, editor. Fractures in Children. Philadelphia: Lippincott-
79. Kraus R, Schiefer U, Schafer C, et al. Elastic stable intramedullary Raven; 1996. p. 102462.
nailing in pediatric femur and lower leg shaft fractures: Intraop- 108. Bresnam J, Adams F. Neonatal spinal cord transection secondary
erative radiation load. J Pediatr Orthop 2008;28:1416. to intrauterine neck hyperextension in breech presentation. Fatal
80. Lee SS, Mahar AT, Newton PO. Ender nail fixation of pediatric Neonat Med. 1971;84:734.
femur fractures: A biomechanical analysis. J Pediatr Orthop 109. Leventhal H. Birth injuries of the spinal cord. J Pediatr Orthop
2001;21:4425. 1960;56:44753.
81. Mehlman CT, Nemeth NM, Glos DL. Antegrade versus retro- 110. Caffey J. The whiplash shaken infant syndrome. Pediatrics
grade titanium elastic nail fixation of pediatric distal-third femoral 1974;54:396.
shaft fractures: A mechanical study. J Orthop Trauma 2006;20: 111. Swischuck L. Spinal cord trauma in the battered child syndrome.
60812. Radiology 1977;92:733.
82. Sink EL, Gralla J, Repine M. Complications of pediatric femur 112. Herzenberg J, Hensiger R, Dedrick D, et al. Emergency transport
fractures treated with titanium elastic nails: A comparison of frac- and positioning of young children who have an injury to the cervi-
ture types. J Pediatr Orthop 2005;25:57780. cal spine. J Bone Joint Surg [Am] 1989;71:15.
83. Hedequist D, Bishop J, Hresko T. Locking plate fixation for 113. Curran C, Dietrich A, Bowman M, et al. Pediatric cervical spine
pediatric femur fractures. J Pediatr Orthop 2008;28:69. immobilization: Achieving neutral position? J Trauma 1995;
84. Hedequist DJ, Sink E. Technical aspects of bridge plating for 39:72932.
pediatric femur fractures. J Orthop Trauma 2005;19:2769. 114. Jaffe DM, Binns H, Radkowski MA, et al. Developing a clinical
85. Kanlic EM, Anglen JO, Smith DG, et al. Advantages of submus- algorithm for early management of cervical spine injury in child
cular bridge plating for complex pediatric femur fractures. Clin trauma victims. Ann Emerg Med 1987;16:2706.
Orthop Relat Res 2004(426):24451. 115. Lee SL, Sena M, Greenholz SK, et al. A multidisciplinary
86. MacNeil JA, Francis A, El-Hawary R. A systematic review of rigid, approach to the development of a cervical spine clearance proto-
locked, intramedullary nail insertion sites and avascular necrosis col: process, rationale, and initial results. J Pediatr Surg
of the femoral head in the skeletally immature. J Pediatr Orthop 2003;38:35862; discussion -62.
2011;31:37780. 116. Viccellio P, Simon H, Pressman BD, et al. A prospective multi-
87. Hedequist D, Starr AJ, Wilson P, et al. Early versus delayed sta- center study of cervical spine injury in children. Pediatrics
bilization of pediatric femur fractures: Analysis of 387 patients. 2001;108:E20.
J Orthop Trauma 1999;13:4903. 117. Anderson RC, Kan P, Hansen KW, et al. Cervical spine clearance
88. Zobel MS, Borrello JA, Siegel MJ, et al. Pediatric knee MR after trauma in children. Neurosurg Focus 2006;20:E3.
imaging: pattern of injuries in the immature skeleton. Radiology 118. Avellino AM, Mann FA, Grady MS, et al. The misdiagnosis of
1994;190:397401. acute cervical spine injuries and fractures in infants and children:
89. Close BJ, Strouse PJ. MR of physeal fractures of the adolescent The 12-year experience of a level I pediatric and adult trauma
knee. Pediatr Radiol 2000;30:75662. center. Childs Nerv Syst 2005;21:1227.
90. Riseborough EJ, Barrett IR, Shapiro F. Growth disturbances fol- 119. Bayless P, Ray VG. Incidence of cervical spine injuries in
lowing distal femora physeal fracture-separation. JBJS Am association with blunt head trauma. Am J Emerg Med 1989;7:
1983;65:88593. 13942.
91. Karholm J, Hansson LI, Svensonn K. Incidence of tibio-fibular 120. dAmato C. Pediatric spinal trauma: Injuries in very young chil-
shaft and ankle fractures in children. J Pediatr Orthop dren. Clin Orthop Relat Res 2005(432):3440.
1982;2:38692. 121. Davis J, Phreaner D, Hoyt D, et al. The etiology of missed cervi-
92. Shannak AO. Tibial fractures in children: Follow-up study. cal spine injuries. J Trauma 1993;34:3426.
J Pediatr Orthop 1988;8:30610. 122. Evans D, Bethem D. Cervical spine injuries in children. J Pediatr
93. Hope PG, Cole WG. Open fractures of the tibia in children. Orthop 1989;9:5638.
J Bone Joint Surg [Br] 1992;74:54653. 123. Finch G, Barnes M. Major cervical spine injuries in children and
94. Hynes D, OBrien T. Growth disturbance lines after injury to the adolescents. J Pediatr Orthop 1998;18:81114.
distal tibial physis. J Bone Joint Surg [Br] 1988;70:231. 124. Grogan EL, Morris JA Jr, Dittus RS, et al. Cervical spine evalu-
95. Rogers LF. The radiography of epiphyseal injuries. Radiology ation in urban trauma centers: Lowering institutional costs and
1970;96:289. complications through helical CT scan. J Am Coll Surg
96. Goldberg VM, Aadalen R. Distal tibial epiphyseal injuries: The 2005;200:1605.
role of athletics in fifty-three cases. Am J Sports Med 1978;6: 125. Lewis VL, Manson PN, Morgan RF. Facial injuries associated
263. with cervical fractures: Recognition patterns and management.
97. Vanhoenacke FM, Bernaerts A, Gielen J, et al. Trauma of the J Trauma 1985;25:903.
pediatric ankle and foot. J Bone Joint Surg [Br] 2002;85:21218. 126. Patel JC, Tepas JJ 3rd, Mollitt DL, et al. Pediatric cervical spine
98. Weiser ER, Mencio GA. Pediatric cervical spine injuries: Assess- injuries: Defining the disease. J Pediatr Surg 2001;36:3736.
ment and treatment. Semin Spine Surg 2001;13:14251. 127. Lally KP, Senac M, Hardin WD Jr, et al. Utility of the cervical
99. Eleraky M, Theodore N, Adams M, et al. Pediatric cervical spine spine radiograph in pediatric trauma. Am J Surg 1989;158:5401;
injuries: Report of 102 cases and review of the literature. J Neu- discussion 12.
rosurg 2000;92(1 Suppl):1217. 128. Smith T, Skinner S, Shonnard N. Persistent synchondrosis of the
100. Jones E, Haid R. Injuries to the pediatric subaxial cervical spine. second cervical vertebra simulating a hangmans fracture in a
W.B. Saunders Company; 1991. child. J Bone Joint Surg [Am] 1993;75:8923.
101. McGrory B, Klassen R, Chao E, et al. Acute fractures and disloca- 129. Swischuck L. Anterior displacement of C2 in children. Physio-
tions of the cervical spine in children and adolescents. J Bone Joint logic or pathologic? Radiology 1977;122(Suppl 2):75963.
Surg [Am] 1993;75:98895. 130. Swischuck L, Swischuck P, SD J. Wedging of C3 in infants and
102. Givens T, Polley K, Smith G, et al. Pediatric cervical spine injury: children: Usually a normal finding not a fracture. Radiology
A three-year experience. J Trauma 1996;41:31014. 1993;188:5236.
244 SECTION II Trauma
131. Cattell H, Filtzer D. Pseudosubluxation and other normal varia- 154. Cirak B, Ziegfeld S, Knight V, et al. Spinal injuries in children.
tions of the cervical spine in children. J Bone Joint Surg [Am] J Pediatr Surg 2004;39:60712.
1965;47:1295309. 155. Clark CR, White AA. Fractures of the dens. J Bone Joint Surg
132. Buhs C, Cullen M, Klein M, et al. The pediatric trauma C-spine: 1985;67:1340.
is the odontoid view necessary. J Pediatr Surg 2000;35:9947. 156. Diamond P, Hansen CM, Christofersen MR. Child abuse present-
133. Adelgais KM, Grossman DC, Langer SG, et al. Use of helical ing as a thoracolumbar spinal fracture dislocation: a case report.
computed tomography for imaging the pediatric cervical spine. Pediatr Emerg Care 1994;10:836.
Acad Emerg Med 2004;11:22836. 157. Reynolds R. Pediatric spinal injury. Curr Opin Pediatr
134. Carlan D, Bradbury T, Green N, Mencio GA, editors. The effi- 2000;12:6771.
cacy of helical CT versus conventional radiography of the cervical 158. Santiago R, Guenther E, Carroll K, et al. The clinical presenta-
spine in pediatric trauma. Pediatric Orthopaedic Society of North tion of pediatric thoracolumbar fractures. J Trauma
America, Annual Meeting; 2008 May 1, 2008; Albuquerque, NM. 2006;60:18792.
135. Hartley W, Mencio G, Green N. Clinical and radiographic algo- 159. Hauser CJ, Visvikis G, Hinrichs C, et al. Prospective validation
rithm for acute management of pediatric cervical spine trauma. of computed tomographic screening of the thoracolumbar spine
Scoliosis Research Society, 32nd Annual Meeting. St. Louis, Mis- in trauma. J Trauma 2003;55:22835.
souri 1997. p. 138. 160. Akbarnia BA. Pediatric spine fractures. Orthop Clin North Am
136. Dormans J, editor. The role of MRI in the assessment of pediatric 1999;30:52136, x.
cervical spine injuries in Evaluation and Management of Pediatric 161. Banerian KG, Wang AM, Samberg LC, et al. Association of ver-
Spine Trauma. American Academy of Orthopaedic Surgeons, 67th tebral end plate fracture with pediatric lumbar intervertebral disk
Annual Meeting Instructional Course Lecture 321; 2000; Orlando, herniation: value of CT and MR imaging. Radiology
Florida. 1990;177:7635.
137. Flynn JM, Closkey RF, Mahboubi S, et al. Role of magnetic reso- 162. Greenwald TA, Mann DC. Pediatric seatbelt injuries: Diagnosis
nance imaging in the assessment of pediatric cervical spine inju- and treatment of lumbar flexion-distraction injuries. Paraplegia
ries. J Pediatr Orthop 2002;22:5737. 1994;32:74351.
138. Frank JB, Lim CK, Flynn JM, et al. The Efficacy of Magnetic 163. Griffet J, Bastiani-Griffet F, El-Hayek T, et al. Management of
Resonance Imaging in Pediatric Cervical Spine Clearance. Spine seat-belt syndrome in children. Gravity of 2-point seat-belt. Eur
2002;27:11769. J Pediatr Surg 2002;12:636.
139. Dormans J, Criscitiello A, Drummond D, et al. Complications in 164. Johnson DL, Falci S. The diagnosis and treatment of pediatric
children managed with immobilization in a halo vest. J Bone Joint lumbar spine injuries caused by rear seat lap belts. Neurosurgery
Surg [Am] 1995;77:13703. 1990;26:43441.
140. Letts M, Kaylor D, Gouw G. A biomechanical analysis of halo 165. Newman KD, Bowman LM, Eichelberger MR, et al. The lap belt
fixation in children. J Bone Joint Surg [Am] 1988;70B:2779. complex: intestinal and lumbar spine injury in children. J Trauma
141. Mubarak S, Camp J, Vueltich W, et al. Halo application in the 1990;30:11338; discussion 840.
infant. J Pediatr Orthop 1989;9:612. 166. Raney EM, Bennett JT. Pediatric Chance fracture. Spine
142. Pang D. Spinal cord injury without radiographic abnormality in 1992;17:15224.
children, 2 decades later. Neurosurg 2004;55:132542. 167. Reid AB, Letts RM, Black GB. Pediatric Chance fractures: Asso-
143. Pang D, Pollack I. Spinal cord injury without radiographic ciation with intra-abdominal injuries and seatbelt use. J Trauma
abnormality in childrenthe SCIWORA syndrome. J Trauma 1990;30:38491.
1989;29:65464. 168. Smith MD 2nd, Camp E 3rd, James H, Kelley HG. Pediatric seat
144. Pang D, Wilberger J. Spinal cord injury without radiographic belt injuries. Am Surg 1997;63:2948.
abnormalities in children. J Neurosurg 1982;57:11429. 169. Choit RL, Tredwell SJ, Leblanc JG, et al. Abdominal aortic inju-
145. Sullivan A. Fractures of the Spine in Children. In: Green N, ries associated with chance fractures in pediatric patients. J Pediatr
Swiontowski M, editors. Skeletal Trauma in Children. 2nd ed. Surg 2006;41:118490.
Philadelphia: Saunders; 2003. p. 34471. 170. Letts M, Davidson D, Fleuriau-Chateau P, et al.. Seat belt fracture
146. Kriss V, Kriss T. SCIWORA (Spinal Cord Injury Without Radio- with late development of an enterocolic fistula in a child. A case
graphic Abnormality) in infants and children. Clin Pediatr report. Spine 1999;24:11515.
1996;35:11924. 171. Lalonde F, Letts M, Yang JP, et al. An analysis of burst fractures
147. Copley L, Dormans J. Pediatric cervical spine problems: Devel- of the spine in adolescents. Am J Orthop 2001;30:11520.
opmental evaluation and congenital anomalies. J Am Acad Orthop 172. Hill JM, McGuire MH, Crosby LA. Closed treatment of displaced
Surg 1998;6:20414. middle-third fractures of the clavicle gives poor results. J Bone
148. Pollina J, Li V. Tandem spinal cord injuries without radiographic Joint Surg Br 1997;79:5379.
abnormalities in a young child. Pediatr Neurosurg 1999;30: 173. Lazarides S, Zafiropoulos G. Conservative treatment of fractures
2636. at the middle third of the clavicle: the relevance of shortening and
149. Bosch PP, Vogt MT, Ward WT. Pediatric spinal cord injury clinical outcome. J Shoulder Elbow Surg 2006;15:1914.
without radiographic abnormality (SCIWORA): The absence of 174. McKee MD, Pedersen EM, Jones C, et al. Deficits following
occult instability and lack of indication for bracing. Spine (Phila nonoperative treatment of displaced midshaft clavicular fractures.
Pa 1976). 2002;27:2788800. J Bone Joint Surg Am 2006;88:3540.
150. Bracken M, Shepard M, Collins W, et al. A randomized, control- 175. Wick M, Muller EJ, Kollig E, et al. Midshaft fractures of the
led trial of methylprednisolone or naloxone in the treatment of clavicle with a shortening of more than 2cm predispose to non-
acute spinal cord injury: Results of the second national spinal cord union. Arch Orthop Trauma Surg 2001;121:20711.
injury study. New England J Med 1990;322:140511. 176. Zlowodzki M, Zelle BA, Cole PA, et al. Treatment of acute mid-
151. Bracken MB, Shepard MJ. Treatment of acute spinal cord injury shaft clavicle fractures: systematic review of 2144 fractures: on
with methylprednisolone: Results of a multicenter randomized behalf of the Evidence-Based Orthopaedic Trauma Working
clinical trial. J Neurtrauma 1991;8 (Suppl):4750. Group. J Orthop Trauma 2005;19:5047.
152. Bracken MB, Shepard MJ, Holford TR. Administration of meth- 177. Canadian Orthopaedic Trauma Society. Nonoperative treatment
ylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 compared with plate fixation of displaced midshaft clavicular frac-
hours in the treatment of acute spinal cord injury: Results of the tures. A multicenter, randomized clinical trial. J Bone Joint Surg
third national acute spinal cord injury randomized controlled Am 2007;89:110.
trial- National Acute Spinal Cord Injury Study. J Am Med Assoc 178. Golthamer C. Duplication of the clavicle (os claviculare). Radi-
1997;277:1597604. ology 1957;68:5768.
153. Bracken MB, Shepard MJ, Holford TR, et al. Methylprednisolone 179. Twigg HL. Duplication of the clavicle. Skeletal Radiol
or tirilazad mesylate administration after acute spinal cord injury: 1981;6:2813.
1-year follow-up: Results of the Third National Acute Spinal 180. Webb LX, Mooney JF. Fractures and dislocations about the shoul-
Cord Injury Randomized Controlled Trial. J Neurosurg der In: Green NE, Swiontkowski MF, editors. Skeletal Trauma in
1998;1998:699706. Children. Philadelphia: Saunders; 2003. p. 32244.
18 Pediatric Orthopedic Trauma 245
181. Gray H. Anatomy of the Human Body. Philadelphia: Lea and 198. Schoenecker PL, Delgado E, Rotman M. Pulseless arm in associa-
Febiger; 1985. tion with totally displaced supracondylar fracture. J Orthop
182. Groh GI, Wirth MA, Rockwood CA Jr. Treatment of traumatic Trauma 1996;10:41015.
posterior sternoclavicular dislocations. J Shoulder Elbow Surg 199. DeLee JC, Wilkins KE, Rogers LF. Fracture separation of the
2011;20:10713. distal humerus epiphysis. J Bone Joint Surg [Am]
183. Laffosse JM, Espie A, Bonnevialle N, et al. Posterior dislocation 1980;62:4651.
of the sternoclavicular joint and epiphyseal disruption of the 200. Jakob R, Fowles JV, Rang M. Observations concerning fractures
medial clavicle with posterior displacement in sports participants. of the lateral condyle in children. J Bone Joint Surg Br
J Bone Joint Surg Br 2010;92:1039. 1975;57:4306.
184. Waters PM, Bae DS, Kadiyala RK. Short-term outcomes after 201. Jeffrey C. Nonunion of epiphysis of the lateral condyle of the
surgical treatment of traumatic posterior sternoclavicular fracture- humerus. J Bone Joint Surg Am 1958;40:396405.
dislocations in children and adolescents. J Pediatr Orthop 202. Rutherford A. Fractures of the lateral humeral condyle in chil-
2003;23:4649. dren. J Bone Joint Surg Am 1995;67:8516, 1985:8516.
185. Baxter MP, Wiley JJ. Fractures of the proximal humeral epiphysis: 203. McCarty EC, Mencio GA, Green NE. Ketamine sedation for the
Their influence on humeral growth. J Bone Joint Surg [Br] reduction of childrens fractures in the emergency department.
1986;68:5703. J Bone Joint Surg Am 2000;82:91218.
186. Beaty JH. Fractures of the proximal humerus and shaft in chil- 204. McCarty EC, Mencio GA, Green NE. Anesthesia and analgesia
dren. Instr Course Lect 1992;41:36972. for the ambulatory management of fractures in children. J Am
187. Dameron TB, Reibel DB. Fractures involving the proximal Acad Orthop Surg 1999;2:8191.
humeral epiphyseal plate. J Bone Joint Surg [Am] 1969;51: 205. Lee MC, Stone NE 3rd, Ritting AW, et al. Mini-C-arm fluoros-
28997. copy for emergency-department reduction of pediatric forearm
188. Smith FM. Fracture-separation of the proximal humeral epiphy- fractures. J Bone Joint Surg Am 2011;93:14427.
sis. Am J Surg 1956;91:62735. 206. Agarwal A. Treatment of pediatric both bone forearm fractures: a
189. Beebe A, Bell DF. Management of severely displaced fractures of comparison of operative techniques. J Pediatr Orthop 2007;27:480
the proximal humerus in children. Tech Orthop 1989;4:14. 1; author reply 1.
190. Loder RT. Pediatric polytrauma. Orthopaedic care and hospital 207. Flynn JM, Waters PM. Single bone fixation of both bone forearm
course. J Orthop Trauma 1987;1:4854. fractures. . J Pediatr Orthop 1996;16:6559.
191. Haraldsson S. On osteochondritis deformans juvenilis capituli 208. Garg NK, Ballal MS, Malek IA, et al. Use of elastic stable
humeri including investigation of intra-osseous vasculature in intramedullary nailing for treating unstable forearm fractures in
distal humerus. Acta Orthop Scand Suppl 1959;38. children. J Trauma 2008;65:10915.
192. Green NE. Fractures and dislocations about the elbow. In: Green 209. Griffet J, FeHayek T, Baby M. Intramedullary nailing of forearm
NE, Swiontkowski MF, editors. Skeletal Trauma in Children. fractures in children. J Pediatr Orthop Br 1999;8:889.
Philadelphia: Saunders; 2003. p. 257322. 210. Kanellopoulos AD, Yiannakopoulos CK, Soucacos PN. Flexible
193. Green NE. Overnight delay in the reduction of supracondylar intramedullary nailing of pediatric unstable forearm fractures. Am
fractures of the humerus in children. J Bone Joint Surg [Am] J Orthop 2005;34:4204.
2001;93:3212. 211. Lascombes P, Haumont T, Journeau P. Use and abuse of flexible
194. Mehlman CT, Strub WM, Roy DR. The effect of surgical timing intramedullary nailing in children and adolescents. J Pediatr
on the perioperative complications of treatment of supracondylar Orthop 2006;26:82734.
humeral fractures in children. J Bone Joint Surg [Am] 212. Lee S, Nicol RO, Stott NS. Intramedullary fixation for pediatric
2001;83:3237. unstable forearm fractures. Clin Orthop Relat Res
195. Sabharwal S, Tredwell SJ, Beauchamp RD. Management of pulse- 2002(402):24550.
less pink hand in pediatric supracondylar fractures of the humerus. 213. Luhmann SJ, Gordon JE, Schoenecker PL. Intramedullary fixa-
J Pediatr Orthop 1997;17:30310. tion of unstable both bone forearm fractures in children. J Pediatr
196. Sabharwal S. Role of Ilizarov external fixator in the management Orthop 1998;18:4516.
of proximal/distal metadiaphyseal pediatric femur fractures. 214. Muensterer OJ, Regauer MP. Closed reduction of forearm refrac-
J Orthop Trauma 2005;19:5639. tures with flexible intramedullary nails in situ. J Bone Joint Surg
197. Copley LA, Dormans JP, Davidson RS. Vascular injuries and their Am 2003;85-A:21525.
sequelae in pediatric supracondylar humerus fractures: Toward a
goal of prevention. J Pediatr Orthop 1996;16:99103.
C H A P T E R 1 9
Neurosurgical Conditions
Gregory W. Hornig Clarence Greene
FIGURE 19-1 MR image of a posterior fossa ependymoma. The tumor involves the lateral aspect of the posterior fossa and contains
calcifications typical of ependymomas. The brain stem is severely distorted by the mass effect of the tumor. The tumor also com-
presses cranial nerves on the right side, making complete tumor removal problematic. This patient had right facial weakness,
diplopia, and mild left hemiparesis postoperatively.
probability of new or worsening neurologic deficits as a locations that are believed to have derived from progeni-
result of the operative dissection. There is a correlation tor subependymal neuroepithelial cells undergoing
between postoperative residual tumor and tumor recur- malignant transformation. Nearly half of medulloblasto-
rence and/or progression. In the 30% of children where mas have chromosomal abnormalities, particularly the
the tumor is totally resected, there is still a 20% to 40% deletion of 17p chromosome that contains the tumor
possibility of recurrence, even after conventional radio- suppressor gene TP53.10
therapy.7 In cases of near-total resection, the rate of Hydrocephalus often occurs with medulloblastomas
progression-free survival falls to 30%.8 Most of the because of their location within the cerebellar vermis (a
recurrences are local and radiation therapy has become midline structure), often filling the fourth ventricle (Fig.
the mainstay of treatment, even with complete resection. 19-2). Children with this tumor often have symptoms of
Very small children, usually younger than age 3 years, are elevated intracranial pressure (ICP) (obtundation, head-
faced with comparatively greater morbidity from conven- ache, nausea/vomiting, irritability) and have signs sugges-
tional radiotherapy, and radiation therapy is often tive of posterior fossa compression (dysmetria, ataxia,
deferred. Chemotherapy has been used with some success diplopia, head tilt, and papilledema). Lumbar puncture
in this group of patients. The role of chemotherapy should not be done after computed tomography (CT) or
without irradiation has generally not been favorable in magnetic resonance imaging (MRI) has established the
older age groups. Retrospective studies have failed to presence of a posterior fossa tumor and obstructive
prove substantial benefit in survival when chemotherapy hydrocephalus. CSF diversion (usually via an external
is added to surgery and radiation therapy for newly diag- drain) is usually done either before or in conjunction with
nosed ependymomas. craniotomy. Conversion of these temporary devices to
Treatment of ependymomas has remained problem- permanent ventriculoperitoneal shunts is not uncommon
atic. Large, invasive tumors are clearly difficult to remove in children with large tumors and marked preoperative
without significant risk to the patient, and residual tumors ventriculomegaly.
are largely refractory to chemotherapy and radiation. Complete resection of medulloblastomas is often pos-
Some surgeons have suggested a staged operative sible, although permanent postoperative deficits can
approach with an initial subtotal debulking followed by a occur.6 The posterior fossa syndrome can occur postop-
second aggressive operative exploration after chemother- eratively in 1015% of children and is characterized by
apy. Whether this approach provides improved outcomes mutism, drooling and swallowing difficulties, ocular
has not been established. Surveillance of treated patients palsies, and increasing ataxia.11 These problems resolve
with ependymomas must continue for many years, inde- entirely in most patients after several months. Improve-
pendent of histologic grading and extent of resection. ment is thought to occur with resolution of swelling
Radiosurgery is also being used to treat focal areas of within the inferior vermis.
recurrent or unresectable tumor. Staging is important with medulloblastomas because
patients have a predictable outcome depending on age,
metastases, pathology, and extent of surgical resection.
Medulloblastomas Poor survival is correlated with age younger than 4 years,
Medulloblastomas are the most common malignant solid residual tumor measuring more than 1.5cm,2 and tumor
tumor in children and constitute 20% of pediatric brain dissemination, particularly drop metastasis along the
tumors.9 They are usually located in the posterior fossa spinal column. After craniospinal radiation in eligible
and they are also referred to as PNETs because they patients, survival occurs in 5070% of patients with
are histologically identical to tumors (pineoblastomas, standard or low-risk medulloblastomas. Newer treatment
neuroblastomas, and retinoblastomas) located in other protocols include chemotherapy first, which is followed
248 SECTION II Trauma
I:Integral
Cho
I:8.24
1.5
1.0
0.0
ppm
4 3 2 1
FIGURE 19-2 MRI and MRS (magnetic resonance spectroscopy) of a posterior fossa medulloblastoma, with compression of fourth
ventricle. The MRS profile shows a choline peak with depression of N-acetyl aspartate (NAA) typical of aggressive tumors.
by radiotherapy consisting of lowered cumulative cranio predominantly. Germ cells tumors often metastasize and
spinal doses (2436Gy to the entire brain) with hyper- cannot be surgically cured. Therefore, they are often best
fractionated delivery, usually 1Gy twice daily. Survival in treated with radiation and chemotherapy. This combina-
these good risk patients is nearly 90% after five years. tion of therapies is often quite successful with the major-
Survival in high-risk patients is 6065% with current ity of germ cell neoplasms.
multimodality therapy, with the worst outcomes in Ependymomas that occur in the cerebral hemispheres
affected infants. Children younger than 3 years of age are remain problematic in terms of treatment, although hem-
usually treated first with chemotherapy, with irradiation ispheric tumors generally have comparatively better out-
deferred for 1 to 2 years. Radiation is sometimes avoided comes. Incomplete resection (often because of diffuse
altogether in the 40% with progression-free survival.12 involvement within critical brain regions) and leptome-
Recurrent medulloblastoma after surgery and radio- ningeal spread are significant adverse risk factors. Age is
therapy is not amenable to cure, but a combination of also a factor. Children younger than 3 years of age have
aggressive therapies can allow remission of disease. These significantly diminished progression-free survival (10
treatments include reoperation, radiosurgery, and high- 15%) compared with older children.13
dose chemotherapy with autologous stem cell rescue. As with medulloblastoma, glial and nonglial tumors
Each of these treatments carries significant morbidity, often have genetic abnormalities, with chromosomal
including loss of cognitive skills, growth retardation, abnormalities and gene mutations. Many low-grade
endocrine problems, and the risk of second tumors and lesions progress to become more malignant. The pathway
vascular malformations in previously irradiated areas. to this malignant progression is complex. Chromosomal
translocations and mutations occur as initiating events
before the amplification of deleterious genes that support
Supratentorial Nonglial and Glial Neoplasms tumor progression.1416
There are multiple nonglial tumors involving the cerebral With most benign tumors, there exists a strong asso-
hemisphere. Supratentorial tumors are fairly common, ciation between extent of resection and outcome. From
and the majority of these are glial in origin, usually desig- the neurosurgical viewpoint, maximal resection should be
nated in ascending order of malignancy as astrocytomas, attempted without inordinate surgical morbidity. The
anaplastic astrocytomas, or glioblastoma multiforme. advent of frameless stereotaxy for precise tumor localiza-
Nonastrocytic tumors include PNETs (including cerebral tion, functional localization with intraoperative moni-
neuroblastomas), choroid plexus tumors (papillomas and toring (e.g., somatosensory evoked potential mapping to
carcinomas), and teratomas (including dysembryoplastic determine the location of the motor cortex), presurgical
neuroepithelial tumors [DNETs]), germinomas, oli- functional MRI to determine location of speech areas,
godendrogliomas, meningiomas, and gangliogliomas. In and intraoperative scanning (via real-time ultrasonogra-
this latter grouping, operative resection is the requisite phy [US], CT, or MRI) have each added considerably to
initial treatment. In the last three tumors, adjunctive ther- the safety of the operation. Nonetheless, the operative
apies are not recommended after gross total resection if approach can only achieve resection of targeted areas.
tumor histology is benign. Infiltrative tumors (which typically extend well beyond
Seizures are much more common with supratentorial the target borders) cannot be ablated using current surgi-
tumors because they affect the eloquent neocortex, par- cal technology. The roles of chemotherapy, molecular
ticularly tumors in the medial or lateral temporal cortex. manipulation, and conformal radiation therapy remain
Older individuals are afflicted with these tumors and can essential to the goal of controlling high-grade brain neo-
present with personality changes, cognitive difficulties, plasms partially treated with operation. Unfortunately,
headache, and growth deficits. high-grade brain lesions remain stubbornly resistant to
Germ cell tumors are composed of germinomas and the intensive multimodality treatments that follow surgi-
teratomas, and arise in pineal and suprasellar regions cal resection. Survival curves for highly malignant brain
19 Neurosurgical Conditions 249
lesions have not changed substantially in the past several with the precision and control of SRS. Tumors typically
decades. treated in this manner are craniopharyngiomas, optic
system tumors, and pituitary adenomas.
Radiotherapy for Pediatric CNS Tumors
The target for radiation therapy is cellular DNA. Ioniz- TREATMENT OF SPASTICITY AND
ing radiation damages double-stranded DNA, leading to MOVEMENT DISORDERS
cell death. Unlike normal cells, which have a preserved
ability to repair radiation damage, neoplastic cells often Spasticity is defined as an abnormal response to passive
are replicating at abnormally high rates and radiation muscle stretch. As the velocity of passive movement
interferes with their mitotic or proliferative ability. With of a joint is increased, increased resistance develops.
slowly growing tumors such as craniopharyngiomas, the During examination of an affected extremity, there can
response to radiation is subtle and such tumors may take be as little as a catch to passive movement or, in more
many months to show a clinical response. The critical severe cases, no movement at all. Children with spastic
sublethal dose required to preserve normal tissue but conditions often have muscle stiffness, fatigue, and pain.
damage brain tumors, the so-called therapeutic window, If the condition is severe and chronic, muscle contrac-
is quite well understood and depends on a number of tures and joint dislocation can occur, particularly in the
factors, including vulnerability of affected tissue (which flexor muscles and internal rotator muscles. In children
can depend on the age of the patient and locale of the with spastic quadriparesis, the typical stance is one of
target; optic nerve radiation, as an example, is poorly flexed elbows and wrists, with standing and walking on
tolerated), tumor vulnerability, volume irradiated, total toes, the knees and hips flexed, and the legs internally
dose, fraction size, and interfraction interval. As total rotated.
volume of irradiation increases, the cumulative radiation Spasticity occurs because of an imbalance of excitatory
dose must necessarily decrease to reduce the morbidity Ia afferent nerves from muscle spindles into the spinal
of treatment. The conventional cumulative radiation cord and inhibitory descending impulses from the basal
dose for most pediatric CNS tumors is in the 5060Gy ganglia and cerebellum. In most children, the inhibitory
range, although some tumors (e.g., germinomas) are impulses are diminished because of early CNS injury or
much more sensitive to radiation and can respond to injury to the spinal cord, which conducts the descending
treatment in the 3050Gy range.17 Tumor type is there- inhibitory impulses. Hence, treatment is directed toward
fore an important determinant of the effectiveness of either increasing the inhibitory neurotransmitters (usually
radiation therapy, and biopsy is often a prerequisite for -aminobutyric acid [GABA]) or reducing the afferent
treatment. excitatory transmission from muscle spindles. Baclofen
Radiotherapy has enjoyed significant technologic achieves the former, and dorsal rhizotomy (via cutting
advances with the advent of improved radiologic defini- afferent nerve roots) interrupts the reflex transmission
tion of tumors and sophisticated computer-assisted from muscle spindles.18,19
planning in three-dimensional systems. Stereotactic radi- The children most susceptible to spasticity are those
osurgery (SRS) has become routine in the USA, and with low birth weight due to prematurity who have suf-
single high-dose fractions can be delivered with great fered a variety of cerebral insults, particularly hypoxic
precision using high-energy photons produced either by ischemic encephalopathy with its predilection for causing
linear accelerators or cobalt sources (gamma knife). periventricular white matter loss. Other affected infants
Proton-beam therapy utilizes charged nuclear particles to have antepartum or intrapartum insults that lead to spe-
deliver energy in discrete target points after the proton cific brain injuries that interrupt pyramidal pathways that
has nearly come to rest. As such, the proton can traverse mediate the inhibitory spinal pathways.
normal brain without losing energy. As it comes to rest, Treatment of spasticity should aim to improve func-
it gives off most of its energy in less than 1cm in the tion and facilitate care. Multidisciplinary clinics usually
form of a Bragg peak, providing a distinctively sharp rise assess the potential candidate for surgical treatment. The
in absorbed energy at the targeted tissue. best candidates for lumbosacral rhizotomy are motivated,
All these stereotactic methods are very precise and older children (age 5 to 6 years) with spastic diplegia
ideal for small targets, which are usually noninfiltrative (affecting the legs predominantly) who lack severe con-
lesions with well-delineated borders. The complications tractures and have relatively good leg strength. Children
arising from targeting structures larger than 3.5cm limit with weak legs and spasticity can lose function with rhizo-
the radiosurgical approach. As such, the utility of treating tomy because they depend on their increased tone to
small noninfiltrative tumors is optimal with single- maintain marginal ambulatory function. Rhizotomy can
fraction radiosurgery. For larger lesions in vulnerable produce, to their detriment, a nonadjustable and perma-
areas of the brain (e.g., brain stem, retina, or cranial nent decrease in spasticity. Oral baclofen can be most
nerves), fractionation can be used with either repeat head useful in these very young children. Baclofen pumps are
fixation or localization systems to minimize complica- advantageous in children with severe spasticity that inter-
tions of SRS therapy. In pediatric patients, SRS is mainly feres with their care and in children with quadriplegia,
used as a boost to tumors that have recurred or persisted often with a greater reduction of spasticity in the legs
after conventional fractionated radiation therapy. than the arms. The treatment is not permanent and non-
Finally, so-called conformal radiation provides the ablative, and the dosing is amenable to adjustments. It is
radiobiologic advantages of hyperfractionation along particularly useful in children with spinal cord insult from
250 SECTION II Trauma
trauma or inflammatory processes (transverse myelitis), fact, be relatively diffuse and involve eloquent cortex.
and in patients with familial spastic paraparesis. Nonetheless, some series show excellent results in more
Botulinum toxin produces neuromuscular blockade than 50% of patients, particularly if there is complete
and thereby reduces muscle contractions and spasticity. resection of an epileptogenic focus, including the focal
It is typically injected into spastic muscles, and for a area of interictal abnormality.22 Intelligence quotient
period of several months, will decrease spasticity and scores tend to be stable or improved in the majority of
increase range of motion. These injections are often used children selected for surgery.
to extend the period of time until a definitive procedure In some patients, seizures can be lateralized to one
can be performed in very young children, often decreas- hemisphere by preoperative studies but not precisely
ing the risk of developing muscle contractures that localized. These patients may be considered for hemi-
become fixed deformities which are not amenable to spherectomy if there is significant unilateral dysfunction.
treatment.20 As radical as such operative resection would appear, the
improvement of hemisphere disconnection procedures is
in the 70% range for seizure freedom, with likely hemi-
EPILEPSY SURGERY paresis and hemianopia found postoperatively (although
these deficits are often present before surgery). Newer
Epilepsy affects about 1% of the population and starts techniques involve a disconnection of the hemisphere
commonly in the first decade of life. Surgical manage- without anatomic removal of the affected hemisphere,
ment is a well-established therapy when medical treat- thereby reducing some of the complications associated
ment has not been successful. Temporal lobectomy has with volumetric removal of large portions of the brain.23
been a mainstay of operative care for more than 40 years, Corpus callosum sectioning is a palliative approach in
and temporal resections constitute more than half of patients who have seizures without focal onset. In patients
the epilepsy operations performed in children. In a with drop attacks, division of all or part of the corpus
randomized, controlled trial of operation versus medical callosum can result in improvement in about 60% of
therapy, 64% of patients were free of disabling seizures patients by reducing the severity of their seizures and
after operation compared with only 8% of those in the decreasing the likelihood of severe injury from falling.24
medical group.21 In addition, surgery may curtail the cog- Vagal nerve stimulation (VNS) is useful for the treat-
nitive and psychosocial disabilities that can occur with ment of partial seizures, providing about a 50% reduction
medically intractable seizures, particularly in remediable in seizure frequency in patients with intractable seizures
syndromes that begin in infancy before the acquisition of who are not candidates for resection. The morbidity of
language and social skills. The quality of life for patients implantation of the vagal nerve stimulator is extremely
with epilepsy is unambiguously related to the recurrence small, and the efficacy of the device rivals that of new
of seizures, and uncontrolled seizures carry a substantial antiepileptic medications. As opposed to medications,
risk of disability and death. there is no toxicity and no issues of compliance.25
Drug-resistant epilepsy is thought to be reasonably
predicted after two antiepileptic medications have proven
ineffective. After the failure of a third medication, the HYDROCEPHALUS
probability of being seizure free is less than 10%. There-
fore, despite the invasiveness of surgery, it is highly rea- Other than trauma, hydrocephalus is the single most
sonable to consider operative intervention one or two common entity pediatric neurosurgeons are called on to
years after the onset of disabling epileptic seizures, par- manage. This disorder of CSF circulation and absorption
ticularly in the 30% of epileptic children who have accounts for 0.6% of all pediatric hospital admissions,
complex partial seizures emanating (unilaterally) from 1.8% of all pediatric hospital days, and 3.1% of all pedi-
the temporal area. Surgery requires comprehensive pre- atric hospital charges.2629 The care of hydrocephalic
operative evaluation by epilepsy specialists, along with patients is a major health care expenditure, hovering near
multiple imaging and monitoring studies. Invasive moni- $1 billion in the USA per year.30 Although hydrocephalus
toring is fairly common in pediatric patients, who tend can afflict individuals at any age, the range of causes and
to have seizures that are multilobar. Newer noninvasive manifestations are larger and often more complex in
modalities such as magnetoencephalography are rapidly children.
achieving success in determining the source of the CSF is a clear fluid, which is primarily secreted within
seizures. the ventricles of the brain by the choroid plexus. A con-
The success of temporal lobe surgery has led to more siderable volume may be formed by interstitial fluid from
aggressive approaches to control epilepsy originating the intercellular clefts in the brain and spinal cord.3133
elsewhere in the brain. The pathologic substrates of The total production of CSF has been calculated at about
pediatric extratemporal epilepsies are quite diverse, 500mL/day.34 The volume in the system turns over
including cortical dysplasia, developmental abnormalities nearly four times per day.
of neuronal migration, gliosis, tumors, neurocutaneous The circulation of CSF is complex. CSF exits the brain
disorders (e.g., SturgeWeber syndrome, tuberous scle- through the fourth ventricle and has a pulsatile course
rosis), and inflammatory lesions. These entities are often through the subarachnoid space over the convexities of
intensely epileptogenic from an early age. In such lesions, the brain, the basal cisterns, the spinal subarachnoid
the MRI abnormality does not strictly correlate with the space, and ultimately back intracranially to the vertex
source of seizures and the epileptogenic focus may, in of the brain. There, the CSF transits through midline
19 Neurosurgical Conditions 251
arachnoid granulations into the venous system at the spinal dysraphism of myelomeningocele or meningocele.
superior sagittal sinus. This transfer is passive from a Chiari II malformation interrupts the egress of CSF from
high-pressure system into a low-pressure environment. the fourth ventricle and disrupts the pulsatile flow of CSF
Escape of the CSF through alternative routes exists, around the confines of the posterior fossa. Children with
although none is adequate to maintain normal nervous untreated or undertreated hydrocephalus and Chiari mal-
system function. Many mothers have observed that their formation are at risk for the development of hydromyelia
children look puffy around the eyes when their shunt is or syrinx.
malfunctioning. There is perhaps escape of CSF through The DandyWalker malformation is next in frequency
the craniofacial lymphatics that might account for this for causing hydrocephalus. In the fullest expression of
observation. This transit of CSF has been confirmed in this anomaly, one finds a retrocerebellar cyst, which can
other mammals, and there is advancing evidence of this be quite sizable with a cleft or defect in the vermis of the
in humans.3537 cerebellum, agenesis of the corpus callosum, and extrac-
ranial anomalies such as cardiac septal defects and syn-
Congenital Hydrocephalus dactyly. These children are at higher risk for developmental
delays and epilepsy.
Hydrocephalus may be an isolated development or In DandyWalker malformations, the hydrocephalus
be associated with many syndromes and brain malde- is due to an alternation in CSF flow at the exit of the
velopment conditions such as holoprosencephaly and fourth ventricle. A DandyWalker malformation may be
schizencephaly. further complicated by a double compartment hydro-
The most common genetic hydrocephalus is X-linked cephalus. The cyst formation may block escape of the
hydrocephalus. It occurs in 1:30,000 male births and CSF at the distal end of the aqueduct of Sylvius with
represents 25% of nonsyndromal cases of hydrocepha- resultant dilation of the third and lateral ventricles. In
lus. The aqueduct of Sylvius is narrowed, causing subse- addition, the choroid plexus within the fourth ventricle
quent dilation of the third and lateral ventricles, sparing will create CSF with no access to the subarachnoid space
the fourth ventricle (Figs 19-3 to 19-5). In its fullest and subsequent enlargement of the cyst. In infants, this
expression, other neurologic abnormalities can occur. may lead to an unsightly distortion of the cranium and
Twenty-five percent of males with clear aqueduct stenosis signs and symptoms of hindbrain compression. Not
will have X-linked hydrocephalus, which is very impor- infrequently, additional surgical attention must be
tant in advising couples about future pregnancies.38 Other directed to the cyst, usually a CSF shunt catheter, either
causes of aqueduct stenosis can be thickening of the joined with a ventriculoperitoneal shunt or a separate
tectum of the midbrain from hamartoma, glioma forma- shunt entirely (see Figs 19-3 and 19-4).40,41
tion, or from intrauterine infections.39
The Chiari II malformation includes alternation in the
size and shape of the posterior fossa, descent of the
Acquired Hydrocephalus
midline cerebellar tonsils through the foramen magnum, In the USA, there are more than 50,000 very low birth
and straightening of the brain stem along with a beaking weight infants born each year. Almost 20% of these
appearance of the tectum or dorsal midbrain. This is the neonates suffer some degree of intraventricular hemor-
next most common etiology of hydrocephalus and is rhage, most related to bleeding within the germinal
always present to some degree in children who have the matrix adjacent to the ventricles of the brain (see
A B
FIGURE 19-3 (A) Sagittal MR image showing aqueduct stenosis and dilated third and lateral ventricles. (B) Axial CT after ventricu-
loperitoneal shunt (arrow).
252 SECTION II Trauma
A B
FIGURE 19-4 (A) Axial CT scan of DandyWalker malformation. (B) The axial CT scan shows supratentorial and posterior fossa shunt
catheters. The posterior fossa shunt was required after the cyst continued to expand.
Diagnosis
Imaging for communicating hydrocephalus typically
demonstrates dilation of all the ventricles of the brain and
occasionally the subarachnoid space. Patients with post-
meningitic hydrocephalus are a typical example. The
signs and symptoms of hydrocephalus are age dependent
and often relate to the rapidity of the ventricular expan-
sion. In the neonate and young infant, there are typically
few symptoms. The child often feeds well and is attentive
and happy, and the only clue may be an accelerated rate
of head growth.
In older children with firmer calvaria, hydrocephalus
usually creates a more pronounced increase in ICP and
the increased pressure will generate more symptoms.
Most commonly, there is head pain or excessive irritabil-
ity in the nonverbal child. Vomiting, detachment, or dis-
interest in play is common. Other common observations
are poor school performance and easy fatigability. Visual
changes such as blurriness or change in color perception
can be noted by older children. Recumbence increases
ICP, and therefore typically the headaches and vomiting
are more pronounced in the morning. Seizures may
occur, but not usually as a presenting or solitary event.
Physical findings commonly include a large head, a full
FIGURE 19-6 Axial CT scan shows mildly dilated lateral ventri-
but not tense anterior fontanelle, and prominent scalp cles and a generous subarachnoid space in the frontal and
veins. Peculiar to infants is the sunset eye appearance. frontoparietal areas (arrows).
This downward and outward deviation of the eyes is a
response to pressure on the superior colliculus of the
midbrain by a dilated third ventricle. After treatment, this
disturbance regresses. Older children may demonstrate a Shunt occlusions and infections are still vexing in our
Parinaud sign: the failure of upward gaze, pupil unrespon- efforts to have these children lead a normal life. Nearly
siveness to light, and impairment of accommodation. half of all shunt operations are revisions for occlusion or
Papilledema and altered visual fields often are evident. infection. Perioperative antibiotic usage, although not
Suspicions are to be confirmed by brain imaging without controversy, has reduced the shunt infection rate
studies. Ultrasonography in infants with an open fonta- to 8% or less in busy pediatric centers.50 There is no
nelle is a good screening study, but even if hydrocephalus consensus as to which antimicrobial agents are most
is diagnosed with that technique, MRI or CT is required efficacious.51
to more fully understand the etiology (Fig. 19-6). Alternatives to ventriculoperitoneal shunts are still
useful, if not required in some complex cases. Lum-
boperitoneal shunts have regained some popularity
Treatment among pediatric neurosurgeons in selected patients with
The first reproducibly successful treatment for hydro- communication of CSF from the intracranial compart-
cephalus of any type occurred in the early 1950s. Lum- ment to the spinal subarachnoid space. The development
boureteral shunts were successfully employed in patients of a Chiari I malformation from chronic CSF drainage
with communicating hydrocephalus.46 Success was then that draws the cerebellar tonsils downward has given
reported with ventricular to jugular vein shunts incorpo- many neurosurgeons pause before considering this shunt
rating a miniaturized spring and ball valve.47 As silicone in young patients.5254 When circumstances make the
replaced the earlier stiffer plastics, the ventriculoperito- peritoneum inhospitable to CSF absorption, alternate
neal shunt became and remains the mainstay of hydro- termini for the tube include the venous system, pleural
cephalus therapy.48 space, and even the gallbladder.55
Development of shunt hardware has matured. The An alternative to CSF shunting has re-emerged with
quality of the silicone has improved, making the tubing the miniaturization of endoscopic equipment. Creating
more pliable and less hazardous to abdominal organs. an opening in the floor of the third ventricle to look
Valves can be adjusted to various opening pressures with around an obstruction at the aqueduct or the outlet of
external magnets. Tubing that incorporates antibiotics the fourth ventricle is very appealing. The concept dates
within or coating it is available. With these mechanical from 1922 but was a failure. New technology for mini-
advances, life expectancy of the shunt itself has improved mally invasive surgery has given a rebirth to the idea and,
and the complications have diminished, although only today, endoscopic third ventriculostomy (ETV) is selec-
slightly. Realistically, there is little difference in the per- tively done in lieu of CSF shunts (Fig. 19-7). When suc-
formance of one brand of shunt over another, despite the cessful, the hydrocephalus is managed without the need
claims of the multiple vendors.49 for foreign body implant and without the inherent risks
254 SECTION II Trauma
of infection or valve or catheter failure. This approach whereas older children may quickly become dreadfully ill
has been found to be successful in 60% of properly as the ICP increases. Headache, vomiting, and altered
selected children.56 The potential complications, such as mental status predominate as symptoms. The clinical
uncontrollable hemorrhage, neuroendocrine dysfunc- assessment typically includes a brain imaging study, a
tion, and short-term memory loss, are severe, more so shunt survey (plain films of the shunt) to look for a frac-
than with shunting. Nevertheless, there is great appeal ture of the tube, a shortened end, or a migration. Although
in having hydrocephalus treated effectively without a change in the ventricular size noted on imaging is a
implanted hardware. strong clue to the diagnosis, normal ventricular size can
often be a falsely reassuring sign. It is not uncommon for
symptomatic children to have no dilation of their ventri-
Shunt Malfunctions cles, presumably related to loss of brain compliance.57,58
Despite the progress in shunt design and materials, Often a percutaneous needle tap of the shunt reservoir
shunts will fail, and at a surprisingly high rate. Forty or valve will be needed to measure pressure. Some sur-
percent fail within the first year of implant. At 15 years, geons use radioisotope or contrast flow studies (shunto-
there is an 80% likelihood of failure. Again, the signs and grams). When in doubt, surgical exploration of the shunt
symptoms will be age dependent. Infants may have is the best option.59
minimal symptoms because of the expandable cranium,
SPINAL DYSRAPHISM
There are multiple types of spinal dysraphism, or
neural tube defects, in children. The most common
are myelomeningocele, lipomyelomeningocele, and
ETV approach meningocele.
Myelomeningocele
Myelomeningocele is the most frequently encountered
spinal neural tube defect. In the USA, the incidence is
0.3 per 1,000 live births, a decrease of nearly 50% since
the widespread use of folic acid in women planning preg-
nancy or begun in the first trimester.60 It is rarely a diag-
nostic problem and is now frequently discovered with
fetal ultrasound or MRI.
Essentially, these are defects in the skin, fascia, poste-
rior elements of the spine, and the conus medullaris of
the cord, along with a failure in neurulation during the
26th to 28th weeks of gestation. Myelomeningocele is
most frequent in the lumbar and lumbosacral area (Fig.
19-8). Often of considerable size, it might be confused
with a sacral teratoma. The neonatal assessment may
require MRI of the entire spinal canal to exclude concur-
FIGURE 19-7 Sagittal MRI of patient with a large tumor in the rent anomalies. Cranial ultrasound is usually sufficient to
posterior third ventricle causing aqueduct occlusion. The arrow
depicts the approach for an endoscopic third ventriculostomy
evaluate for hydrocephalus. The surgical challenge is not
(ETV) to bypass the obstruction and relieve the hydrocephalus. so much in closing the exposed nervous system but in
At the same operation, the tumor was sampled. obtaining a tension-free cutaneous closure. At operation,
A B
FIGURE 19-8 (A) A typical myelomeningocele shows a small neural placode at the dome with a large CSF-filled sack and little useful
skin. (B) A meningocele with common surrounding port-wine stains is seen.
19 Neurosurgical Conditions 255
the exposed end of the incompletely fused spinal cord is often require tedious micro dissection with release of any
separated from the cutaneous attachments, and a pseudo- tethering effect on the spinal cord to prevent neurologic
dural layer is closed over it. Not infrequently, the skin (weakness, sensory loss), urologic (neurogenic bladder),
closure is the more complex segment of the operation, or orthopedic (scoliosis, leg-length discrepancies) conse-
and plastic surgical techniques (relaxing flank incisions, quences. These children do not have Chiari malforma-
skin grafts, rotational flaps) may be required to accom- tion, sparing them the burden of hydrocephalus.
plish this closure. Whether to correct the asymptomatic infant with a
The more rostral the defect, the more severe the neu- lipomyelomeningocele is not without controversy. Unfor-
rologic deficit, and the more severe the challenges pre- tunately, the natural history of these anomalies is
sented to the patient throughout his or her lifetime. To unknown. The rationale for early operation in these
some degree, all of these children have a concurrent patients is to release any tethering on the spinal cord and
Chiari II malformation, which will lead to hydrocephalus prevent neurologic, urologic, or orthopedic consequences
in most patients. of spinal cord injury. However, a significant number of
Prenatal closure of the myelomeningocele defect at patients have suffered the same deficits postoperatively
three designated centers has confirmed the efficacy of this that the surgery was planned to prevent.62,63
intervention in highly selected patients in a recently com-
pleted trial (Management of myelomeningocele study
[MOMS]).61 The incidence of CSF shunts at one year was
Meningocele
40% in the prenatal surgery group vs 80% in those babies The least common of the neural tube defects is the sim-
managed after birth (p < 0.001). Prenatal intervention plest one. A meningocele consists of a defect in the skin,
also resulted in improvement in the composite score for fascia, posterior spine, and meninges but not the nervous
mental development and motor function at 30 months system. When this anomaly occurs, it has a predilection
(p = 0.007). Independent walking at 3 years was 42% in for the lumbosacral area, although it can develop any-
the prenatal group vs 21% in the postnatal surgery group where along the neural axis. Unlike the myelomenin-
(p = 0.01). However, prenatal operation was associated gocele, these lesions are almost always covered by nearly
with higher rates of preterm birth, intraoperative com- normal skin. Operative repair must be vigilant for cord
plications, and uterine-scar defects apparent at delivery tethering; dorsal untethering may be needed along with
as well as a higher rate of maternal transfusion at primary dural closure.
delivery.
Tethered Spinal Cord Syndrome
Lipomyelomeningocele With any of the spinal dysraphisms, there is a high prob-
Lipomyelomeningocele is a complex anomaly that con- ability the conus medullaris lies below the L2 disc space
sists of a subcutaneous meningocele, fascia and bony and is deemed to be tethered by radiographic imaging.
defects, and a lipoma interfacing with the spinal cord, When constricted from free excursion, stretching of the
which is located dorsally, dorsolateral, or terminally. neurons and microvascular ischemia will lead to neuro-
Externally, these lesions appear in the midline and can logic dysfunction. This chronic injury leads to a plethora
range from tiny subtle fatty lumps to large masses often of signs and symptoms, most commonly neurogenic
accompanied by skin tags, port-wine stains, and an altered bladder, motor weakness or increasing tone in the lower
intragluteal fold (Fig. 19-9). Before the availability of CT, extremities, sensory loss, and skeletal growth anomalies,
the connection with the spinal canal was often missed and including scoliosis. Operative exploration for lysis of
cosmetic removal of the subcutaneous fat was performed, adhesions is required. Unfortunately, the process may be
often with significant negative sequelae. These lesions recurrent throughout the childs growing years. All chil-
dren with spinal dysraphism are at risk for tethered cord
syndrome, and long-term follow-up is essential.
REFERENCES
1. Janisch W, Haas JF, Schreiber D, et al. Primary central nervous
system tumors in stillborns and infants: Epidemiological considera-
tion. J Neurooncol 1984;2:11316.
2. Grabb PA, Albright AL. Brain tumors of congenital and develop-
mental origin in infants and children: Clinical features and natural
history. In: Tindall GT, Cooper PR, Barrow DL, editor. The Prac-
tice of Neurosurgery, vol. 1. Baltimore: Williams & Wilkins; 1996.
p. 82131.
3. Carmel PW. Brain tumors of disordered embryogenesis. In:
Youmans JR, editor. Neurological Surgery, vol. 4. Philadelphia:
WB Saunders; 1996. p. 276181.
4. Lieberman DM, Russo CL, Berger MS. Brain tumors during the
first 2 years of life. In: Albright AL, Pollack IF, Adelson PD, editor.
Principles and Practice of Pediatric Neurosurgery. New York:
Thieme; 1999. p. 46390.
5. Steinbok P, Mutat A. Cerebellar astrocytomas. In: Albright AL,
FIGURE 19-9 A sizable lipomyelomeningocele is seen with Pollack IF, Adelson PD, editor. Principles and Practice of Pediatric
cutaneous port-wine stains. Neurosurgery. New York: Thieme; 1999. p. 64162.
256 SECTION II Trauma
6. Cochrane DD, Gustavsson B, Poskitt KP, et al. The surgical and 33. Milhorat TH, Hammock MK, Fenstermacher JD, et al. CSF pro-
natural morbidity of aggressive resection for posterior fossa tumors duction by the choroid plexus and brain. Science 1971;173:3302.
in childhood. Pediatr Neurosurg 1994;20:1929. 34. Rekate HL. The treatment of hydrocephalus. In: Albright AL,
7. Pollack I. Brain tumors in children. N Engl J Med 1994;331: Pollack EF, Adelson PD, editor. Principles and Practice of Pediatric
15007. Neurosurgery. 2nd ed. New York: Thieme; 2008. p. 1035.
8. Sutton L, Goldwein J, Perilongo G, et al. Prognostic factors in 35. Boulton M, Flessner M, Armstrong D, et al. Determination of
childhood ependymomas. Pediatr Neurosurg 1990-1991;16:57 volumetric CSF absorption into extracranial lymphatics in sheep.
65. Am J Physiol 1998;274:8896.
9. Roberts RO, Lynch CF, Jones MP, et al. Medulloblastoma: A 36. Erlich SS, McComb JG, Hyman S, et al. Ultrastructure of the
population-based study of 532 cases. J Neuro-pathol Exp Neurol orbital pathways for CSF drainage in rabbits. J Neurosurg
1991;50:13444. 1989;70:92631.
10. Raffel C, Thomas GA, Tishler DM, et al. Absence of p53 mutations 37. Johnston M, Zakharov A, Papaiconomou C, et al. Evidence of
in childhood central nervous system primitive neuroectodermal connections between CSF and nasal lymphatic vessels in humans,
tumors. Neurosurgery 1993;33:3016. non-human primates and other mammalian species. CSF Res
11. Pollack IF, Polinko P, Albright AL, et al. Mutism and pseudobulbar 2004;1:2.
symptoms after resection of posterior fossa tumors in children: 38. Dirks P. Genetics of hydrocephalus. In: Cinalli G, Maixner WJ,
Incidence and pathophysiology. Neurosurgery 1995;37:88593. Sainte-Rose C, editor. Pediatric Hydrocephalus. New York:
12. Duffner PK, Horowitz ME, Krischer JP, et al. Postoperative chem- Springer-Verlag; 2005.
otherapy and delayed radiation in children less than 3 years of age 39. Barkovich AJ, Newton TH. MR of aqueductal stenosis: Evidence
with malignant brain tumors. N Engl J Med 1993;328:172531. of a broad spectrum of tectal distortion. AJNR Am J Neuroradiol
13. Pollack IF, Gerszten PC, Martinez AJ, et al. Intracranial ependy- 1989;10:4716.
momas of childhood: Long-term outcome and prognostic factors. 40. Mohanty A, Biswas A, Satish S, et al. Treatment options for
Neurosurgery 1995;37:65567. Dandy-Walker malformation. J Neurosurg 2006;105(5 Suppl
14. Sanai N, Alvarez-Buylia A, Berger M. Neural stem cells and the Pediatrics):34856.
origin of gliomas. N Engl J Med 2005;353:81122. 41. Yceer N, Mertol T, Arda N. Surgical treatment of 13 pediatric
15. Croce CM. Oncogenes and Cancer. N Engl J Med 2008;358: patients with Dandy-Walker syndrome. Pediatr Neurosurg
50211. 2007;43:35863.
16. Esteller M. Epigenetics in cancer. N Engl J Med 2008;358: 42. Boop FA. Posthemorrhagic hydrocephalus of prematurity. In:
114859. Cinalli G, Maixner WJ, Sainte-Rose C, editor. Pediatric Hydro-
17. Tarbell N, Loeffler JS. Radiotherapy for pediatric brain tumors. In: cephalus. New York: Springer-Verlag; 2005. p. 1216.
Albright AL, Pollack IF, Adelson PD, editor. Principles and Prac- 43. Fritsch M, Mehdorn M. Endoscopic intraventricular surgery for
tice of Pediatric Neurosurgery. New York: Thieme; 1999. treatment of hydrocephalus and loculated CSF spaces in children
p. 76578. less than one year of age. Pediatr Neurosurg 2002;36:1838.
18. Albright AL, Barron WB, Faick MP, et al. Continuous intrathecal 44. Rekate HL. The treatment of hydrocephalus. In: Albright AL,
baclofen infusion for spasticity of cerebral origin. JAMA Pollack EF, Adelson PD, editor. Principles and Practice of Pediatric
1993;270:24757. Neurosurgery. 2nd ed. New York: Thieme; 2008. p. 1035.
19. Peacock WJ, Arens LJ, Berman B. Cerebral palsy spasticity: Selec- 45. Rekate HL, Nulsen FE, Mack H, et al. Establishing the diagnosis
tive posterior rhizotomy. Pediatr Neurosci 1987;13:616. of shunt independence. Monogr Neural Sci 1982;8:2236.
20. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl 46. Matson DD. A new operation for treatment of communicating
J Med 1991;324:118694. hydrocephalus. J Neurosurg 1949;6:23847.
21. Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled 47. Nulsen FE, Spitz EB. Treatment of hydrocephalus by direct shunt
trial of surgery for temporal-lobe epilepsy. N Engl J Med from ventricle to jugular vein. Surg Forum (Am Coll Surg)
2001;345:31118. 1952;2:399403.
22. Morrison G. Extratemporal epilepsy surgery in children. In: 48. Ames RH. Ventricular peritoneal shunts in the management of
Albright AL, Pollack IF, Adelson PD, editor. Principles and Prac- hydrocephalus. J Neurosurg 1967;27:5259.
tice of Pediatric Neurosurgery. New York: Thieme; 1999. p. 49. Drake JM, Kestle JR, Milner R, et al. Randomized trial of CSF
112746. shunt valve design in pediatric hydrocephalus. Neurosurgery
23. Schramm J, Kral T, Clusmann H. Transsylvian keyhole functional 1998;43:294305.
hemispherectomy. Neurosurgery 2001;49:891901. 50. Piatt JH, Carlson CV. A search of determinates of cerebrospinal
24. Black PM, Holmes G, Lombroso C. Corpus callosum section for fluid shunt survival: Retrospective analysis of a 14-year institutional
intractable epilepsy in children. Pediatr Neurosurg experience. Pediatr Neurosurg 1993;19:23342.
1992;18:298304. 51. Biyani N, Grisaru-Soen G, Steinbok P, et al. Prophylactic
25. Murphy JV. Left vagal nerve stimulation in children with epilepsy. antibiotics in pediatric shunt surgery. Childs Nerv Syst 2006;22:
J Pediatr 1999;134:5636. 146571.
26. Simon TD, Riva-Cambrin Srivastaua R, et al. or the hydrocephalus 52. Welch K, Shillito J, Strand R, et al. Chiari I malformation: An
clinical network: Hospital care for children with hydrocephalus in acquired disorder? J Neurosurg 1981;55:6049.
the United States: Utilization, charges, comorbidities and deaths. 53. Wang V, Barbaro N, Lauton M, et al. Complications of lumbar
J Neurosurg Pediatr 2008;1:1318. peritoneal shunts. Neurosurgery 2007;60:10459.
27. Cochrane DD, Kestle J. Ventricular shunting for hydrocephalus in 54. Dagnew E, van Loveren H, Tew J Jr. Acute foramen magnum
children: Patients, procedures, surgeons, and institutions in English syndrome caused by an acquired Chiari malformation after lumbar
Canada, 1989-2001. Eur J Pediatr Surg 2002;12(1 Suppl):S6S11. drainage of cerebral spinal fluid: Report of three cases. Neurosur-
28. Smith ER, Butler WE, Barker FG II. In-hospital mortality rates gery 2002;51:8239.
after ventricular peritoneal shunt procedures in the United States, 55. Aldana P, James H, Postlethwait R. Ventriculogallbladder shunts in
1998-2002: Relation to hospital and surgeon volume of care. pediatric patients. J Neurosurg Pediatr 2008;1:2847.
J Neurosurg 2004;100(2 Suppl Pediatrics):907. 56. Kadrian D, van Gelder J, Florida D, et al. Long-term reliability
29. Berry JG, Hall MA, Sharma V, et al. A multi-institutional five year of endoscopic third ventriculostomy. Neurosurgery 2005;56:
analysis of initial and multiple shunt revisions in children. Neuro- 12718.
surgery 2008;62:44553. 57. McNatt SA, Kim A, Hohuan D, et al. Pediatric shunt malfunction
30. Patwardham RV, Nanda A. Implanted ventricular shunts in the without ventricular dilation. Pediatr Neurosurg 2008;44:
United States: The billion-dollar-a-year cost of hydrocephalus 12832.
treatment. Neurosurgery 2005;56:13945. 58. Winston KR, Lopez JA, Freeman J. CSF shunt failure with stable
31. Milhorat TH. Cerebral Spinal Fluid and the Brain Edemas. Neu- normal ventricular size. Pediatr Neurosurg 2006;42:1515.
roscience Society of New York; 1987. p. 467. 59. Vinchon M, Fichten A, Delestret I, et al. Shunt revision for asymp-
32. Milhorat TH. Choroid plexus and CSF production. Science tomatic failures: Surgical and clinical results. Neurosurgery
1969;166:151416. 2003;52:34756.
19 Neurosurgical Conditions 257
60. Diaz M, McLone D. Myelomeningocele. In: Albright AL, Pollack 62. Cochrane DD, Finley C, Kestle J, et al. The patterns of late dete-
IF, Adelson PD, editor. Principles and Practice of Pediatric Neu- rioration in patients with transitional lipomyelomeningocele. Eur
rosurgery. 2nd ed. New York: Thieme; 2008. p. 33866. J Pediatr Surg 2000;10(Suppl 1):1317.
61. Adzick NS, Tom E, Spong CY, et al. A randomized trial of prenatal 63. Cochrane DD. Occult spinal dysraphism. In: Albright AL, Pollack
versus postnatal repair of myelomeningocele. N Engl J Med IF, Adelson PD, editor. Principles and Practice of Pediatric Neu-
2011;364:9931004. rosurgery. 2nd ed. New York: Thieme; 2008. p. 36793.
C H A P T E R 2 0
Congenital chest wall deformities fall into two groups: This chest wall deformity may be noted at birth and
those with overgrowth of the cartilages causing either a usually progresses with age and growth. With rapid
depression or protuberance, and those with varying growth at puberty, the progression may become espe-
degrees of either aplasia or dysplasia. cially pronounced, a fact apparently unknown to many
Pectus excavatum, also known as an excavated, sunken, pediatricians, who mistakenly advise families of younger
or funnel chest, is the most common chest wall anomaly, patients that the condition will resolve spontaneously. We
constituting about 80% of deformities seen at our hospi- have seen many families who were given this advice and
tal (Table 20-1). Pectus carinatum, a chest wall protuber- missed the opportunity to have the deformity repaired
ance, comprises approximately 12% of chest wall before puberty while the chest was still soft and malleable
deformities, whereas combined excavatum/carinatum and before it interfered with physical performance.
deformities are found in about 5%. Jeune syndrome, or
asphyxiating chondrodystrophy, is an extreme form of
mixed pectus excavatum/carinatum and is very rare.
History
Poland syndrome and bifid sternum represent differ- Pectus excavatum was recognized as early as the 16th
ent forms of aplasia of the anterior chest wall. Poland century. Johan Schenck collected literature on the
syndrome consists of varying degrees of dysplasia of the subject.1 In 1594, Bauhinus described the clinical features
breast, the pectoralis muscles, and ribs. In bifid sternum, of pectus excavatum in a patient who had pulmonary
partial or complete failure of the midline fusion of the compression with dyspnea and paroxysmal cough, both
sternum is seen. This may result in ectopia cordis or attributed to the severe pectus excavatum.2 The familial
varying degrees of sternal dysplasia and deficiencies of predisposition was first noted by Coulson in 1820, who
associated structures such as the heart, pericardium, dia- cited a family of three brothers with pectus excavatum.3
phragm, and anterior abdominal wall (pentalogy of In 1872, Williams described a 17-year-old patient who
Cantrell). was born with a pectus excavatum, and whose father and
Many of these deformities are present at birth. Some brother also had the condition.4
cases, such as ectopia cordis, are incompatible with life Numerous other case reports appeared in the 19th
and have rarely been successfully repaired. Chest wall century, including a five-case report by Ebstein in 1882
deformities are frequently associated with a systemic that covered the clinical spectrum of this condition.5
weakness of the connective tissues and with poor muscu- Treatment at that time was limited to fresh air, breathing
lar development of the abdominal region, thorax, and exercises, aerobic activities, and lateral pressure.6,7
spine. An association with Marfan syndrome, Ehlers Thoracic surgery remained forbidden territory until
Danlos syndrome, and scoliosis, as well as with ompha- the early years of the 20th century. The first attempt at
locele in the case of bifid sternum, have been identified, correction was a tentative approach in 1911 by Meyer
all of which complicate the management of these patients who removed the second and third costal cartilages on
(see Table 20-1). the right side without improvement.8 Sauerbruch, one of
the pioneers of thoracic surgery, used a more aggressive
approach in 1913 by excising a section of the anterior
PECTUS EXCAVATUM chest wall, which included the left fifth to ninth costal
cartilages as well as a segment of the adjacent sternum.7
Pectus excavatum is a depression of the anterior chest Before his operation, the patient was incapacitated by
wall of variable severity and can usually be characterized severe dyspnea and palpitations, even at rest, and was
as mild, moderate, or severe. The deformity may be unable to work in his fathers watch factory. After recov-
localized and deep (cup-shaped; Fig. 20-1A), or diffuse ery, the heart could be seen to pulsate under the muscle
and shallow (saucer-shaped; see Fig. 20-1B), or flap, but the patient was able to work without dyspnea
asymmetric (see Fig. 20-1C). The depth and extent of and was married three years later.
the depression determine the degree of cardiac and pul- In the 1920s, Sauerbruch performed the first pectus
monary compression, which, in turn, determines the repair that used the bilateral costal cartilage resection and
degree of physiologic effect. Only one-third of patients sternal osteotomy technique later popularized by Ravitch.9
referred from our own region had a deformity severe He also advocated external traction to hold the sternum
enough to require surgical correction. Even with referral in its corrected position for six postoperative weeks. His
of patients with a severe deformity from other centers, technique was soon adapted by others in Europe and
our ratio of operative correction has been only about rapidly gained popularity in the USA. In 1939, Ochsner
60% (Box 20-1). and DeBakey published their experience with this
261
262 SECTION III Thoracic
A B C
FIGURE 20-1 (A) Localized or cup-shaped pectus excavatum. (B) Diffuse or saucer-shaped deformity. (C) Eccentric deformity.
20 Congenital Chest Wall Deformities 263
cause severe sternal retraction. Trauma rarely cardiac and pulmonary reserve and their chest wall is still
causes rib fractures and flail chest because the chest very pliable, the majority of young children are asymp-
is so soft and malleable.2123 Thus, the American tomatic. However, as they become older, the deformity
Heart Association recommends using only two becomes more severe and the chest wall becomes more
fingers when performing cardiac resuscitation in rigid. Eventually, they find that they have difficulty
young children and only one hand in older chil- keeping up with their peers when playing aerobic sports.
dren for fear of crushing the heart. A vicious cycle may develop as patients stop participating
2. Chest reconfiguration. In middle-aged and older in aerobic activities because of their inability to keep up.
adults, a barrel-shaped chest configuration devel- Subsequently, their exercise capacity diminishes further.
ops in response to chronic obstructive respiratory The downward spiral is further promoted by the fact that
diseases such as emphysema. If older adults are able these patients, already embarrassed by their deformity,
to reconfigure the chest wall, children and teenag- will avoid situations in which they have to remove their
ers should be able to remodel as well, especially shirts in front of other children, inhibiting participation
with the increased malleability of their anterior in school and team activities.
chest wall. By withdrawing from participation in activities with
3. Bracing. The role of braces and serial casting in their peers, they also become depressed, which may
successfully correcting skeletal anomalies such as affect their schoolwork. Most pectus patients have a
scoliosis, clubfoot, and maxillomandibular maloc- typical geriatric or pectus posture that includes
clusion by orthopedic and orthodontic surgeons is thoracic kyphosis, forward-sloping shoulders, and a
well established. The anterior chest wall, being protuberant abdomen (Fig. 20-2). A sedentary couch
even more malleable than the previously mentioned potato lifestyle may aggravate this posture, and the
skeletal structures, is ideally suited for this type of poor posture depresses the sternum even farther. For this
correction. reason, we always recommend an aggressive pectus
posture exercise and breathing program, both preopera-
tively and postoperatively.
INCIDENCE AND ETIOLOGY Many patients have a relatively mild deformity during
childhood. Because pediatricians are unaware of the
Pectus excavatum occurs in approximately 1 in 1000 chil- potential for marked progression of the deformity as the
dren and constitutes 80% of all chest wall deformities in child grows, they reassure the parents that it will resolve
our center (see Table 20-1). However, this is not the case spontaneously or even improve. Although the deformity
in all countries. In Argentina, pectus carinatum is more may not always increase in severity, it is unlikely that it
common than pectus excavatum.24 Pectus excavatum also will spontaneously resolve. When the patients grow
is rare in African-Americans and in Africans. A genetic rapidly during puberty, the deformity often suddenly
predisposition, already noted in the 19th century, has been accelerates. A mild deformity may become severe in as
found in almost 40% of our patients. We have seen fami- little as six to 12 months. These patients give a history
lies with three siblings, as well as cousins and other family that my chest suddenly caved in. It is the rapid progres-
members, who had a pectus deformity severe enough to sion that alarms parents and stimulates them to seek
require correction. We also have seen patients whose consultation with a surgeon. Patients with a rapid pro-
fathers and grandfathers have the deformity. The male-to- gression of their deformity exhibit the most pronounced
female ratio of 4:1 in our series of pectus excavatum symptom-complex.
patients is similar to that of other large series.25 Female
patients have an increased risk of associated scoliosis.
Inheritance is autosomal dominant, autosomal recessive,
X-linked, and multifactorial in different families.26, 27
The association with a connective tissue disorder is
higher than in the normal population. The vast majority
of our patients have an asthenic build and a definitive
diagnosis of Marfan syndrome has been found in 2.7%
of our patients. An additional 17% have had clinical fea-
tures suggestive of Marfan syndrome. EhlersDanlos
syndrome was present in another 0.7%. Mild scoliosis
was noted in 20% of our patients. In our experience,
severely asymmetric pectus excavatum tends to aggravate
the postural abnormality of scoliosis. Early correction of
the pectus excavatum has improved the mild scoliosis in
many patients.
Clinical Features
Pectus excavatum is noted in infancy in approximately
one-third of patients,25 and usually progresses slowly as FIGURE 20-2 Classic pectus posture with thoracic kyphosis,
the child grows. Because young children have significant forward-sloping shoulders, and lumbar lordosis.
264 SECTION III Thoracic
and a cardiac evaluation that includes an electrocardio- asymmetry of the chest, sternal torsion, compensatory
gram (ECG) and an echocardiogram. development of a barrel-chest deformity in long-standing
CT scans are very helpful because they clearly show deformities, and ossification of the cartilages in patients
the degree of cardiac compression and displacement, the with previous repairs (Fig. 20-4A, B). They also are used
degree of pulmonary compression and atelectasis, to calculate the CT index, which gives an objective meas-
urement for comparing the severity among patients. The
CT index is calculated by dividing the transverse diam-
eter by the anteroposterior diameter (see Fig. 20-4C).42
Physical We have recently utilized MRI of the chest instead of
examination CT scan to diminish radiation exposure. However, MRI
History
does not give as clear a picture of the bony structures
which are the central issue, and cardiac MRI, which
should be able to provide the same information as echocar-
diography and CT scan, remains in development.
Mild or Severe
moderate Determination of a severe pectus excavatum and the
need for repair include two or more of the following
criteria: (1) a CT index greater than 3.2; (2) pulmonary
Exercise PFT function studies that indicate restrictive airway disease;
Moderate
program CT scan (3) a cardiology evaluation in which compression is
Cardiac evaluation causing murmurs, mitral valve prolapse, cardiac displace-
Evaluation ment, or conduction abnormalities on the echocardio-
gram or ECG tracings; (4) documentation of progression
Q 6 month Severe of the deformity with associated physical symptoms other
follow-up than isolated concerns of body image; (5) a failed Ravitch
procedure; or (6) a failed minimally invasive procedure.
Minimally With these criteria, only about 60% of patients referred
invasive
repair to us are found to have a deformity severe enough to
warrant correction.20,43
FIGURE 20-3 Algorithm for evaluation and treatment of patients The age parameters for surgical correction depend on
with pectus deformities. the type of repair selected. Unlike the more invasive
A B
procedures (e.g., Ravitch procedure, sternal turnover), withdrawn. The pectus support bar is then attached to
there is no interference with growth plates with the mini- the umbilical tape and is slowly guided through the sub-
mally invasive approach. Therefore, it can be done at any sternal tunnel with its convexity facing posteriorly until
age, as evidenced by the fact that we have successfully it emerges on the contralateral side. All the maneuvers
operated on patients from ages 13 months through to 31 are performed using thoracoscopy to see inside the chest.
years (Fig. 20-5). However, the concern with patients The length of the bar is determined by measuring the
younger than 11 years is that if the procedure is per- distance from midaxillary line to midaxillary line and
formed at too young an age, many years of subsequent subtracting 2.5cm (1 inch). The bar is bent to the desired
growth remain during which the excavatum can recur. configuration using a bar bender. Once the bar is posi-
Our experience suggests that the optimal age for repair tioned inside the chest with the convexity facing posteri-
is 11 to 14 years. At this age, the patient is prepubertal, orly, it is turned over by using specially designed bar
the chest is still soft and malleable, there is a quick recov- flippers, resulting in correction of the excavatum. The
ery with a rapid return to normal activities, and results bar is secured with a stabilizer on one side and sutures
are excellent. After puberty, the flexibility of the chest around the bar and underlying ribs on the other side.
wall is decreased, sometimes requiring the insertion of Alternatively, stabilizers can be used on both sides to
two bars, which makes the operation more difficult. It secure the bar as well. These sutures can be placed with
also takes patients longer to recover. However, patients an EndoClose needle (Covidien, Mansfield NJ) using
older than 20 years have been uniformly pleased with thoracoscopy. It is essential that the bar is well stabilized
their results. Several other centers have reported success or it will become displaced. Once the bar is secure, the
with patients up to age 44 years.34,44,45 incisions are closed. The thoracoscope is removed, and
the pneumothorax is evacuated.
The patient is discharged from the hospital, usually on
Operative Approaches the fourth or fifth day. Patients are instructed to refrain
from sports or other similar activities for six weeks after
Minimally Invasive Pectus Repair
operation. All patients are restarted on an exercise and
The minimally invasive pectus repair (Fig. 20-6) involves posture program to facilitate chest expansion and main-
making incisions on each side of the chest and creating a tain a good posture.
subcutaneous tunnel from the lateral thoracic incision to Pain management for both the open and closed
the top of the pectus ridge on each side. At the top of the pectus repairs is similar and designed to pre-empt the
ridge, bilateral thoracostomy incisions are bluntly created, pain cascade. This is accomplished by the use of intrave-
and a large introducer is inserted into the chest cavity nous narcotics, benzodiazapenes, and nonsteroidal anti-
under thoracoscopic visualization. Very carefully, the inflammatory agents, which are started immediately
pleura and pericardium are dissected off the undersurface before operation and continued postoperatively for three
of the sternum and the introducer is slowly advanced days until transition to oral medications can be accom-
across the mediastinum and exteriorized through the tho- plished. When patients are discharged, they are given
racostomy incision on the contralateral side. When the prescriptions for nonsteroidal anti-inflammatory
introducer is in place, the sternum is lifted out of its medications, muscle relaxants, and narcotic medication.
depressed position by the introducer. Once the sternal Patients less than 13 years of age are generally able to
depression has been corrected, an umbilical tape is stop all pain medications after 7 to 10 days while patients
attached to the introducer, and the introducer is slowly 13 and over may require pain medication for 10 to 14
days postoperatively.
A recent prospective randomized trial evaluated the
use of a thoracic epidural catheter vs patient-controlled
analgesia (PCA) with intravenous narcotics for postop-
170
160 erative pain management after the minimally invasive
150 pectus repair. One hundred and ten patients were rand-
140 omized with fixed protocols for each arm. The primary
130
120 outcome variable was length of postoperative hospitaliza-
110 tion with a power of 0.8 and an alpha of 0.05. No differ-
100
Frequency
A B
D E
FIGURE 20-6 (A) To calculate the length of the pectus bar, measure the distance from right to left midaxillary line and subtract
12cm (1 inch). (B) Bend the Lorenz pectus support bar to conform to the desired chest wall curvature. (C) Mark the deepest point
of the pectus excavatum with a circle by using a marking pen. If this point is inferior to the sternum, then move the circle superiorly
to the lower end of the sternum just above the xiphoid. This point sets the horizontal plane bar for insertion. (D) After confirming
by thoracoscopy that the internal and external anatomy match up well, make lateral thoracic skin incisions and raise skin flaps
anteriorly toward the X marked on the external skin at the top of the pectus ridge. (E) Retract skin incision anteriorly to allow visu-
alization of the intercostal space previously marked with an X. Under thoracoscopic control, insert the appropriate size Lorenz
introducer through the right intercostal space at the top of the pectus ridge and at the previously marked X.
Continued
268 SECTION III Thoracic
F G
H I
FIGURE 20-6, Contd (F) When the substernal tunnel has been completed, gently push the tip of the introducer through the contra
lateral intercostal space at the previously marked X, medial to the top of the pectus ridge on the left side. (G) Use the introducer
to elevate the sternum. The surgeon lifts on the right side, and the assistant lifts the left side of the introducer. (H) Attach the previ-
ously prepared pectus bar to the umbilical tape and slowly guide the bar through the tunnel by using the umbilical tape for traction.
(I) The bar is inserted with the convexity facing posteriorly. (J) When the bar is in position, use the specially designed Lorenz bar
rotational instrument (bar flipper) to turn the bar over.
minimally invasive technique. However, because of the asymmetric or eccentric deformities, and patients with
risk of interference with growth plates in young children mixed pectus carinatum/excavatum deformities.
and the development of asphyxiating chondrodystrophy, The open technique involves making an anterior tho-
the procedure should be reserved for patients who have racic incision and elevating skin and muscle flaps until all
completed their growth.18,19 The open procedure is best the costal cartilages from T3 to T6 are exposed. The
suited for the older patients, especially those who have perichondrium is then incised longitudinally, and the
20 Congenital Chest Wall Deformities 269
deformed cartilages are either partially or completely loss in most patients was minimal (10mL), with the
removed. Most surgeons now advocate removing only a exception of 6 (0.4%) patients in whom a hemothorax
small section (12cm) of the deformed cartilages, as was formed. Thirteen (0.9%) pleural effusions required treat-
originally advocated by Sauerbruch and Gross.9,17 An ment with either a chest tube or aspiration (Table 20-3).
anterior table, wedge-shaped, sternal osteotomy is per- Pericarditis requiring treatment with indomethacin
formed at the angle of Louis. The sternum is elevated, occurred after 9 (0.6%) repairs. One patient required
and the osteotomy is closed with nonabsorbable sutures. pericardiocentesis. Pneumonia developed after 13 (0.9%)
Some surgeons insert a metal strut under the sternum to procedures, and medication reactions have occurred after
bridge the gap between the ribs and the sternum 36 (3.6%) operations. Wound infections developed in 22
to prevent the sternum from sinking back into the patients (1.5%). These resulted in eventual early bar
chest. The perichondrial sleeves are approximated with removal in 2 (0.02%) patients.
absorbable sutures, drains are left, the muscle flaps are
sutured back into position, and the incisions are closed. Late Complications
Postoperative management is similar to that for the mini-
mally invasive technique except that patients are required Eighty-four (5.7%) bars have become displaced, and 54
to refrain from contact sports for at least three months. (3.7%) have required repositioning. In the 54 cases in
which patients required repositioning of the bar, 16
occurred before stabilizers were available, a time period
Results
covering our first 105 repairs. After the introduction of
The minimally invasive approach received rapid accept- stabilizers, the incidence of bar displacement decreased
ance by the surgical community because the technique from 15.2% to 6.5%. When the bar and stabilizers were
requires neither rib incision nor resection nor sternal wired together, the incidence of bar displacement
osteotomy. The blood loss is minimal, the operating time decreased to 4.3%. Since we combined placing a stabi-
is short, and the patient rapidly returns to regular lizer on the left and polydioxanone (PDS, Ethicon, Inc.,
activity.4753 Somerville NJ) sutures around the bar and underlying rib
Although our initial report in 1998 presented a ten- on the right, the incidence of bar displacement has
year experience, the numbers were limited (42 patients) dropped to 1.5%.
and the long-term results were affected by the early In two patients, a late hemothorax developed second-
learning curve of using a support bar that was too soft.20 ary to trauma. Both underwent thoracoscopy with drain-
Moreover, in some of these patients, the bar was removed age of the hemothorax. At the time of thoracoscopy, no
too soon. From 1988 through December 2011, 1463 active bleeding was found. Therefore, an injury to an
patients have had their initial operation at our institution intercostal vessel was presumed. Whether hemothoraces
(see Box 20-1). Since the original presentation, numerous would have developed in these patients as a result of their
important modifications have been made, both to the thoracic trauma if they had not had a bar placed in situ
operative technique (e.g., routine use of thoracoscopy) is unknown. We have several patients who have been
and instruments, to minimize the risks of the procedure involved in major automobile accidents who sustained
and facilitate insertion and stabilization of the support head and musculoskeletal trauma but no chest injuries.
bar. These modifications have markedly reduced the risks Thirty-nine (2.7%) of 1463 patients have had unsus-
and complications and have been previously reported.43,45 pected allergies to the metal in the bar. These allergies
In our series of 1463 patients with pectus excavatum, initially presented as rashes in the area of the bar or
only seven (0.48%) had a mixed pectus excavatum and
carinatum. One (0.07%) patient had Poland syndrome,
and one (0.1%) had an associated complex cardiac TABLE 20-3 Complications after Initial Pectus
anomaly (atrioventricular canal). The male-to-female Excavatum Repair at Childrens
ratio in patients undergoing repair was more than 4:1. Hospital of the Kings Daughters
The median age was 15 years, with a range from 13
months to 32 years. Preoperative evaluation included CT Complication Percentage (Number)
scan with a median CT index of 4.6 (range, 2.4 to 21). Pneumothorax w/spontaneous 55.7% (815)
Cardiac compression was noted on echocardiography or resolution
CT scan, or both, in 1,301 of 1,450 patients (89.72%). Pneumothorax w/chest tube 3.8% (56)
Bar displacement requiring revision 3.7% (54)
Results of PFTs are shown in Table 20-2. Overcorrection 3.1% (47)
In 68% of our patients, a single bar was used. Two bars Bar allergy 2.9% (39)
were needed in 32% of the patients. The median length Suture site infection 1.2% (18)
of stay has been five days. Pneumonia 0.9% (13)
Hemothorax 0.36% (6)
Hemothorax (post-traumatic) 0.1% (2)
Pericarditis 0.6% (9)
Complications Pleural effusion (requiring drainage) 0.9% (13)
Temporary paralysis <0.1% (2)
Early Complications Death 0%
Cardiac perforation 0%
No deaths or cardiac perforations occurred during the Recurrence 0.9% (13)
1463 repairs at our institution. Pneumothorax requiring
chest tube drainage developed in 56 (3.8%) repairs. Blood Data collected from 5/18/1987 through to 1/1/2012; n = 1463.
270 SECTION III Thoracic
Percentage
Overall Results and Long-Term Follow-up
40
Patients are evaluated six months following the operation Excellent
and then yearly until the bar is removed. Long-term Good
assessment has allowed classification of the results into
excellent, good, fair, or failed categories. 20 Fair
An excellent repair indicates that the patient experi- Poor
enced complete repair of the pectus deformity and reso-
lution of associated symptoms. A good repair is 0 Failed
distinguished by a markedly improved but not completely <1 year >1 year
normal chest wall appearance and resolution of associated
symptoms. A fair result indicates a mild residual pectus FIGURE 20-7 The authors outcomes evaluated by the length of
time since bar removal.
excavatum without complete resolution of symptoms. A
failed repair is defined as a recurrence of the pectus
deformity and associated symptoms, or the need for addi-
tional surgery (or both) after final removal of the bar.
In addition, patients with ECG conduction abnor- PECTUS CARINATUM
malities or mitral valve prolapse had follow-up assess-
ments. Patients old enough to have pulmonary function Pectus carinatum, or protrusion deformity of the chest,
studies preoperatively were reassessed with repeated occurs less frequently than does pectus excavatum
studies. in most countries. It comprises about 5% of patients
It is our observation that patients who are sedentary with chest wall deformities.54 The prominence may be
and who do not perform the pectus breathing exercises in the upper manubrium of the sternum, which is called
tend to have mild recurrences over time. Therefore, we a chondromanubrial deformity. The most common pro-
strongly emphasize these aerobic activities and deep trusion is found in the lower segment or body of the
breathing exercises. sternum (the gladiolus) and is called chondrogladiolar
As of December 2010, there were 972 primary repair (Fig. 20-8). The protrusion may be unilateral, bilateral, or
patients who have undergone bar removal. Results were mixed.55 About 80% of patients who develop pectus cari-
deemed excellent in 85%, good in 12%, fair in 1.1%, and natum are boys. Although the etiology is unknown, a
failed in 1.7%. The long-term results are affected by the genetic component of causation is suggested by the
length of time the bar was left in place. approximately 25% of patients with a family history of a
chest wall defect.53,56,57 Pectus carinatum has also been
Bar Removal reported to occur after treatment for pectus excavatum.58
Pectus carinatum is usually noted in adolescence and
We advise the pectus bar be left in place for two to three is seen most commonly around the time of a growth
years. We evaluate patients on an annual basis and spurt, rather than at birth as is often seen with pectus
monitor their growth, activity level, and PFT results, excavatum. Symptoms of dyspnea, reduced endurance, or
and encourage them to perform their pectus exercises and tachypnea with exertion were noted in all 260 patients in
participate in aerobic sports. Patients between the ages one study.59 Associated mitral valve disease has been
of 6 and 10 years often do not grow rapidly. Therefore, reported as well.60,61 Other associations include Marfan
they tolerate the bar well for three or even four years. syndrome and scoliosis (in 15%53).
Conversely, we have had teenagers who have undergone Orthotic bracing has been applied successfully in some
a massive growth spurt, completely outgrowing the bar, patients with pectus carinatum. Reports have described
and requiring bar removal after 2 years. We consider the correction or improvement in this condition by means
exercise programs to be as important as the operation. of a brace analogous to that used for treatment of scol-
Many children and adults lead sedentary lifestyles and iosis but that exerts pressure in the anteroposterior
never perform aerobic activities. Therefore, their lungs direction.24,62
never expand beyond the resting tidal volume (approxi- Following adoption of a new brace in 2009, we have
mately 10% of total lung capacity). Deep breathing with seen marked improvement in success with brace treatment
breath holding for ten to 15 seconds and aerobic activi- (Fig. 20-9). About 85% of our brace patients have been
ties, such as running (e.g., soccer, basketball) and swim- successfully treated without operation.62 In the remainder,
ming, are strongly encouraged. We have seen a mild minimally invasive or open operation is performed.25,55,6266
recurrence over the long term in patients who do not Postoperative complications are uncommon, and recur-
follow our exercise protocol (Fig. 20-7). rence rates are low in centers with a large experience.
20 Congenital Chest Wall Deformities 271
An unusual form of pectus carinatum occurs with a wedge-shaped osteotomy through the anterior cortex of
short nonsegmented sternum and marked posterior the sternum at the point of maximal angularization. The
angulation at the site of the normal chondromanubrial lower sternum is then displaced anteriorly with sutures
junction (CurrarinoSilverman syndrome).60 Also, con- while the costal cartilages regenerate.69 The confusing
genital heart disease is often present. Although its etiol- part about this anomaly is that it may appear to be a
ogy is unclear, early fusion of the sternal plates is pectus excavatum deformity when, in fact, it is an uncom-
postulated as the cause of this deformity.67 In a large mon variant of pectus carinatum (Fig. 20-10).
review from our hospital, we found about 1% of pectus
patients had this anomaly.68 Repair is best performed
using an open technique with subparachondral resection POLAND SYNDROME
of the second to seventh costal cartilages and a broad
Poland syndrome affects 1 in 30,000 live births and is
sporadic in occurrence.70 It is a constellation of anomalies
that present in a variety of ways. Clinical manifestations
can include any or all of the following: absence of the
pectoralis major, pectoralis minor, serratus anterior,
rectus abdominis, and latissimus dorsi muscles (Fig.
20-11). Athelia or amastia, nipple deformities, limb
deformities (syndactyly, brachydactyly), absent axillary
hair, and limited subcutaneous fat can also be found.
In 1841, Alfred Poland, an English medical student,
published a partial description of the deformity.71
However, the syndrome had been initially described in
the French and German literature in 1826 and 1839.72,73
Poland syndrome does not appear to be genetic,
although occasional occurrences within families have
occurred. The right side is more commonly affected and
is present in boys 70% of the time.74 Approximately 15%
of patients with breast hypoplasia/aplasia have Poland
syndrome. The etiology is unclear, but theories include
abnormal migration of the embryonic tissues forming the
pectoralis muscles, hypoplasia of the subclavian artery, or
in utero trauma.
No correlation has been identified between the extent
of hand deformities and the chest wall anomalies. Varying
degrees of either can occur with mild hypoplasia to total
aplasia of muscles, ribs, and cartilage. The latter can lead
to major chest wall depression and paradoxical respira-
FIGURE 20-8 This teenager has a chondrogladiolar pectus cari-
natum. This is the most common form of pectus carinatum and
tory motion.
involves protrusion of the lower portion of the sternum (the Repair is rarely required, except in those patients with
gladiolus). In this patient, the protrusion is fairly symmetrical. aplasia of the ribs or a major depression deformity.74,75
A B
FIGURE 20-9 A patient being treated with dynamic compression bracing for a prominent pectus carinatum. The advantage of this
brace is that it allows a preset pressure to be used to compress the carinatum.
272 SECTION III Thoracic
STERNAL DEFECTS
Sternal defects are found in the midline of the upper
THORACIC INSUFFICIENCY
torso and range from the relatively benign sternal cleft SYNDROME ASSOCIATED WITH
(sternal defect without displacement of the heart) to the DIFFUSE SKELETAL DISORDERS
very rare and almost uniformly fatal thoracic ectopia
cordis (the heart is out of the chest without a skin Thoracic insufficiency syndrome may be defined as any
covering). disorder that produces the inability of the thorax to
20 Congenital Chest Wall Deformities 273
CI
1 1 1 1
2 2
2 2
3 3
3 c 3
Skin incision raci
4 ndotho
4 E ia
4
fasc 4
5
5 5 5
6
6 6
6 7
7
7 7
A B C
OSTEOTOMY 1 1
1
2
2 2
3 3 Rib 3
Notch for rib graft 4
grafts
Rotate 4 4
5
5
6 5
6 Harvest rib from
7 6 contralateral side
7
7 and split for grafts
D E
FIGURE 20-12 (A) The transverse incision is placed below and within the nipples. In girls, it is placed in the future inframammary
crease. (B) A schematic depiction of the deformity with rotation of the sternum, depression of the cartilages of the involved side,
and carinate protrusion of the contralateral side. (C) In cases with aplasia of the ribs, the endothoracic fascia is encountered directly
below the attenuated subcutaneous tissue and pectoral fascia. The pectoral muscle flap is elevated on the contralateral side, with
the pectoral fascia, if present, on the involved side. Subperichondrial resection of the costal cartilages is carried out as shown
(dashed line), preserving the costochondral junction. Rarely this resection must be carried to the level of the second costal cartilage.
(D) A transverse, offset, wedge-shaped sternal osteotomy is created below the second costal cartilage. Closure of this defect with
heavy silk sutures or elevation of the sternum with a strut corrects both the posterior displacement and the rotation of the sternum.
(E) In cases with rib aplasia, rib grafts are harvested from the contralateral fifth or sixth ribs, split, and secured medially with wire
sutures into notches created in the sternum and with wire to the native ribs laterally. Ribs are split as shown, along their short axes,
to maintain maximal mechanical strength. (Adapted from Shamberger RC, Welch KJ, Upton J III. Surgical treatment of thoracic deformity
in Polands syndrome. J Pediatr Surg 1989;24:7606.)
support normal respiration or lung growth.83 It includes wall configuration produces a rigid chest with very little
a spectrum of disorders including asphyxiating thoracic intercostal excursion for normal respiration, leading to
dystrophy (Jeune syndrome), acquired asphyxiating tho- ventilator dependence and eventual death from respira-
racic dystrophy (after open pectus excavatum repair), tory failure.85,86 The presence or absence of intrinsic pul-
spondylothoracic dysplasia (JarchoLevin syndrome), monary abnormalities varies among patients. However,
congenital scoliosis with multiple vertebral anomalies most have normal bronchial development with variable
and fused or absent ribs (jumbled spine), and severe alveolar density.87,88 This suggests that the extrinsic chest
kyphoscoliosis. These disorders have been viewed and wall plays a significant role in the underlying hypoplasia.
treated as separate entities, with little coordinated Other associated skeletal abnormalities in Jeune syn-
effort between specialties. However, they are best drome include short stubby extremities, fixed elevated
addressed with a unified approach integrating pediatric clavicles, hypoplastic iliac wings, and a high incidence of
general and orthopedic surgeons as well as pediatric C1 spinal stenosis.8991 These patients also have varying
pulmonologists. degrees of renal dysplasia.92
Jeune syndrome is an autosomal recessive inherited Spondylothoracic dysplasia (JarchoLevin) syndrome
osteochondrodystrophy with variable expression.84 In occurs in two forms with different inheritance patterns.
mild forms, the chest may support adequate respiration. Type I is an autosomal recessive deformity characterized
In more severe cases, the thorax is narrowed both trans- by multiple vertebral hemivertebrae and posterior rib
versely and vertically, with short, wide horizontal ribs and fusions.93 This produces a marked shortening of the tho-
irregular costochondral junctions (Fig. 20-16). This chest racic spine and a crab-like appearance of the chest on a
274 SECTION III Thoracic
Pericardium and
endothoracic fascia
Midline incision Sternal bar
Cla
v
A Bifid sternum B
Tevdek or
PDS sutures
FIGURE 20-13 (A) Repair of a bifid sternum is best
Undermine performed through a longitudinal incision extending
the length of the defect. These defects are charac-
teristically cleft superiorly, as shown. (B) Directly
beneath the subcutaneous tissues, the sternal bars
are encountered, with the origin of the pectoral
muscles on the lateral aspect of the bars. The endo
thoracic fascia and pericardium are just below these
structures. (C) The endothoracic fascia is mobilized
off the sternal bars posteriorly with blunt dissection
to allow safe placement of the sutures. Approxima-
tion of the sternal bars may be facilitated by excising
a wedge of cartilage inferiorly. Repair is best accom-
plished in the neonatal period because of the flexi-
bility of the chest wall. (D) Closure of the defect is
achieved with 2-0 Tevdek or polydioxanone sutures.
C D (Adapted from Shamberger RC, Welch KJ. Sternal
wedge defects. Pediatr Surg Int 1990;5:15664.)
FIGURE 20-14 An infant with thoracic ectopia cordis with no FIGURE 20-15 A newborn with the external features of Cantrell
significant abdominal wall defect present. Note the characteris- pentalogy is seen. Flaring of the lower thoracic cavity is present,
tic high insertion of the umbilicus and anterior projection of the with a large epigastric omphalocele. The transverse septum of
apex of the heart. the diaphragm and the inferior portion of the pericardium are
absent. The patient also has tetralogy of Fallot.
chest radiograph (Fig. 20-17).94 Associated malforma- with near-normal longevity. It is seen most commonly in
tions are noted in 30% of patients and include cardiac white children.91
and renal anomalies. This form is often fatal by age 15 Thoracic insufficiency also may arise secondary
months, and a high incidence is reported in Puerto Rican to over-extensive Ravitch-type pectus excavation repairs
families.95 Type II spondylothoracic dysplasia has an or repairs performed too early in life.19 Complex
autosomal dominant inheritance pattern and is associated spine anomalies producing the so-called jumbled spine,
20 Congenital Chest Wall Deformities 275
FIGURE 20-18 Bilateral vertical expandable prosthetic titanium FIGURE 20-20 Bilateral VEPTRs were placed in the patient in
rib (VEPTR) fixed with titanium rings to ribs of the patient with Figure 20-17 with JarchoLevin syndrome.
Jeunes asphyxiating thoracic dystrophy seen in Figure 20-16A.
21. Kelley SW. Surgical Diseases of Children: Dislocations, Congeni- 47. Azizkhan RG. Whats new in pediatric surgery? J Am Coll Surg
tal and Acquired. 3rd ed. St. Louis: CV Mosby; 1929. vol 1, p 537. 1998;186:20311.
22. Haller JA Jr. Thoracic injuries. In: Welch KJ, Randolph JG, 48. Adzick NS, Nance ML. Pediatric surgery. N Engl J Med
Ravitch MM, et al, editor. Pediatric Surgery, vol. 1. 4th ed. 2000;342:16517.
Chicago: Year Book Medical Publishers; 1986. p. 147. 49. Hebra A, Swoveland B, Egbert M, et al. Outcome analysis of
23. Wesson DE, et al. Thoracic injuries. In: ONeill JA Jr, Rowe MI, minimally invasive repair of pectus excavatum: Review of 251
Grosfeld JL, editor. Pediatric Surgery, vol. 1. 5th ed. St. Louis: cases. J Pediatr Surg 2000;35:2528.
Mosby Grosfeld; 1998. p. 245. 50. Miller KA, Woods RK, Sharp RJ, et al. Minimally invasive repair
24. Martinez-Ferro M, Fraire C, Bernard S. Dynamic compression of pectus excavatum: A single institutions experience. Surgery
system for the correction of pectus carinatum. Semin Pediatr Surg 2001;130:6529.
2008;17:194200. 51. Molik KA, Engum SA, Rescoda FJ, et al. Pectus excavatum repair:
25. Shamberger RC. Congenital chest wall deformities. In: Grosfeld Experience with standard and minimally invasive techniques.
JL, ONeill JA Jr, Fonkalsrud EW, Coran AG, editor. Pediatric J Pediatr Surg 2001;36:3248.
Surgery. 5th ed. Philadelphia: Elsevier; 1998. p. 787817. 52. Wu PC, Knauer EM, McGowan GE, et al. Repair of pectus
26. Creswick HA, Stacey MW, Kelly RE, et al. Family study of the excavatum deformities in children: A new perspective of treatment
inheritance of pectus excavatum. J Pediatr Surg 2006;41: using minimal access surgical technique. Arch Surg 2001;136:
1699703. 41924.
27. Horth L, Stacey M, Kelly RE Jr, et al. Advancing our understand- 53. Hosie S, Sitkiewicz T, Peterson C, et al. Minimally invasive repair
ing of the inheritance and transmission of pectus excavatum of pectus excavatum: The Nuss procedure: A European Multi-
Inheritance of pectus exavatum. J Pediatr Genetics. 2012: center Experience. Eur J Pediatr Surg 2002;12:2358.
16173. 54. Shamberger RC, Welch KJ. Surgical correction of pectus carina-
28. Lawson ML, Cash TF, Akers RA, et al. A pilot study of the impact tum. J Pediatr Surg 1987;22:4853.
of surgical repair on disease-specific quality of life among patients 55. Chin EF. Surgery of funnel chest and congenital sternal promi-
with pectus excavatum. J Pediatr Surg 2003;38:91618. nence. Br J Surg 1957;44:36076.
29. Shamberger RC. Cardiopulmonary effects of anterior chest wall 56. Robisek F, Cook JW, Daugherty HK, et al. Pectus carinatum.
deformities. Chest Surg Clin North Am 2000;10:24551. J Thorac Cardiovasc Surg 1979;78:5261.
30. Haller JA Jr, Peters GN, Mazur D, et al. Pectus excavatum: 57. Pena A, Perez L, Nurka S, et al. Pectus carinatum and pectus
A 20-year surgical experience. J Thorac Cardiovasc Surg excavatum: Are they the same disease? Am Surg 1981;47:
1970;60:37583. 21518.
31. Zhao L, Feinberg MS, Gaides M, et al. Why is exercise capacity 58. Hebra A, Thomas PB, Tagge EP, et al. Pectus carinatum as a
reduced in subjects with pectus excavatum? J Pediatr sequela of minimally invasive pectus excavatum repair. Pediatr
2000;136:1637. Endosurg Innovat Techn 2002;6:414.
32. Mocchegiani R, Badano L, Lestuzzi C, et al. Relation of right 59. Fonkalsrud EW. Surgical correction of pectus carinatum: Lessons
ventricular morphology and function in pectus excavatum to the learned from 260 patients. J Pediatr Surg 2008;43:123543.
severity of the chest wall deformity. Am J Cardiol 1995;76: 60. Currarino G, Silverman FN. Premature obliteration of the
9416. sternal sutures and pigeon breast deformity. Radiology 1958
33. Sigalet DL, Montgomery M, Harder J, et al. Long-term cardiop- ;70:53240.
ulmonary effects of closed repair of pectus excavatum. Pediatr 61. Chidambaram B, Mehta AV. Currarino-Silverman syndrome
Surg Int 2007;23:4937. (pectus carinatum type 2 deformity) and mitral valve disease.
34. Coln D, Gunning T, Ramsay M, et al. Early experience with the Chest 1992;102:7802.
Nuss minimally invasive correction of pectus excavatum in adults. 62. Cohee A, Lin JR, Frantz FW, et al. Staged management of pectus
World J Surg 2002;26:121721. carinatum. Eur J Pediatr Surg 2013;48(2):31520.
35. Malek MH, Berger DE, Housh TJ. Cardiovascular function fol- 63. Haje SA, Bowen JR. Preliminary results of orthotic treatment of
lowing surgical repair of pectus excavatum: A meta-analysis. Chest pectus deformities in children and adolescents. J Pediatr Orthop
2006;130:50616. 1992;12:795800.
36. Shamberger RC, Welch KJ, Sanders SP. Mitral valve prolapse 64. Ravitch MM. The operative correction of pectus carinatum
associated with pectus excavatum. J Pediatr 1987;111:4047. (pigeon breast). Ann Surg 1960;151:70514.
37. Saint-Mezard G, Duret JC, Chanudet X, et al. Mitral valve pro- 65. Welch KJ, Vos A. Surgical correction of pectus carinatum (pigeon
lapse and pectus excavatum. Presse Med 1986;15:439. breast). J Pediatr Surg 1973;8:65967.
38. Warth DC, King ME, Cohen JM, et al. Prevalence of mitral valve 66. Abramson H, DAgostino JD, Wuscovi S. A 5-year experience
prolapse in normal children. J Am Coll Cardiol 1985;5:11737. with a minimally invasive technique for pectus carinatum repair.
39. Park JM, Farmer AR. Wolff-Parkinson-White syndrome in chil- J Pediatr Surg 2009;44:11824.
dren with pectus excavatum. J Pediatr Surg 1988;112:9268. 67. Allwyn JS, Shetty L, Pare VS, et al. Chondro-manubrial deformity
40. Redlinger RE Jr, Wootton A, Kelly RE, et al. Optoelectronic and bifid rib, rare variations seen in pectus carinatum: A radiologi-
plethysmography demonstrates abrogation of regional chest wall cal finding. Surg Radiol Anat 2012: Epub ahead of print.
motion dysfunction in patients with pectus excavatum after Nuss 68. Kelly RE Jr, Quinn A, Varela P, et al. Dysmorphology of chest
repair. J Pediatr Surg 2012;47:1604. wall deformities: Frequency distribution of subtypes of typical
41. Haller JA Jr, Loughlin GM. Cardiorespiratory function is signifi- pectus excavatum and rare subtypes. Arch Bronconeumol 2012
cantly improved following corrective surgery for severe pectus Epub ahead of print.
excavatum. J Cardiovasc Surg 2000;41:12530. 69. Shamberger RC, Welch KJ. Surgical correction of chondromanu-
42. Haller JA Jr, Kramer SS, Lietman SA. Use of CT scans in selec- brial deformity (Currarino Silverman syndrome). J Pediatr Surg
tion of patients for pectus excavatum surgery: A preliminary 1988;23:31922.
report. J Pediatr Surg 1987;22:9048. 70. Freire-Maia N, Chautard EA, Opitz JM. The Poland syndrome:
43. Croitoru DP, Kelly RE Jr, Nuss D, et al. Experience and modifica- Clinical and genealogical data, dermatoglyphic analysis, and inci-
tion update for the minimally invasive Nuss technique for pectus dence. Hum Hered 1973;23:97104.
excavatum repair in 303 patients. J Pediatr Surg 2002;37:43745. 71. Poland A. Deficiency of the pectoralis muscles. Guys Hosp Rep
44. Columbani P. Personal communication. 1841;6:1913.
45. Park HJ, Lee SY, Lee CS, et al. The Nuss procedure for pectus 72. Froriep R. Beobachtung eines Falles Von Mangel der Brustdrse.
excavatum: An evolution of techniques and results on 322 patients. Notizen aus dem Gebiete der Naturund Heilkinde 1839;10:
Presented at the 39th annual meeting of the Society of Thoracic 914.
Surgeons, San Diego, CA, January 31 to February 2, 2003. 73. Lallemand LM. Ephermerides. Medicales de Montpellier.
46. St Peter SD, Weesner KA, Weissend EE, et al. Epidural vs. 1826;1:1447.
patient-controlled analgesia for postoperative pain after pectus 74. Seyfer AE, Icochea R, Graber GM. Polands anomaly: Natural
excavatum repair: A prospective, randomized trial. J Pediatr Surg history and long-term results of chest wall reconstruction in 33
2012;47:14853. patients. Ann Surg 1988;208:77682.
278 SECTION III Thoracic
75. Shamberger RC, Welch KJ, Upton J III. Surgical treatment of 94. Roberts AP, Conner AN, Tolmie JL, et al. Spondylothoracic and
thoracic deformity in Polands syndrome. J Pediatr Surg spondylocostal dysostosis: Hereditary forms of spinal deformity.
1989;24:7605. J Bone Joint Surg Br 1988;70:1236.
76. Samarrai AR, Charmockley HA, Attr AA. Complete cleft sternum: 95. Heilbronner DM, Renshaw TS. Spondylothoracic dysplasia.
Classification and surgical repair. Int Surg 1985;70:713. J Bone Joint Surg Am 1984;66:3023.
77. Shamberger RC, Welch KJ. Sternal defects. Pediatr Surg Int 96. McMaster MJ. Congenital scoliosis. In: Weinstein SL, editor. The
1990;5:15664. Pediatric Spine: Principles and Practice. New York: Raven Press;
78. Knox L, Tuggle D, Knott-Craig CJ. Repair of congenital sternal 1994.
clefts in adolescence and infancy. J Pediatr Surg 1994;29: 97. McMaster MJ. Congenital scoliosis caused by unilateral failure of
151316. vertebral segmentation with contralateral hemivertebrae. Spine
79. Amato J, Douglas W, Desai U, et al. Ectopia cordis. Chest Surg 1998;23:9981005.
Clin N Am 2000;10:297316. 98. McMaster MJ, David C. Hemivertebrae as a cause of scoliosis: A
80. Groner JI. Ectopia cordis and sternal defects. In: Zeigler MM, study of 104 patients. J Bone Joint Surg Br 1986;68:58895.
Azizkhan RG, Weber TR, editor. Operative Pediatric Surgery. 99. Campbell RM. Congenital scoliosis due to multiple vertebrae
New York: McGraw-Hill; 2003. p. 27993. anomalies associated with thoracic insufficiency syndrome. Spine
81. Amato U, Zelen J, Talwalker NG. Single-stage repair of thoracic 2000;14:20918.
ectopia cordis. Ann Thorac Surg 1995;59:51820. 100. Campbell RM, Smith MD, Mayes T, et al. The characteristics of
82. Engum SA. Embryology, sternal clefts, ectopia cordis, and Can- thoracic insufficiency syndrome associated with fused ribs and
trells pentalogy. Semin Pediatr Surg 2008;17:15460. congenital scoliosis. J Bone Joint Surg 2003;85:399408.
83. Campbell RM, Smith MD, Mayes TC, et al. The characteristics 101. Todd DW, Tinguely ST, Norberg WJ. A thoracic expansion tech-
of thoracic insufficiency syndrome associated with fused ribs and nique for Jeunes asphyxiating thoracic dystrophy. J Pediatr Surg
congenital scoliosis. J Bone Joint Surg Am 2003;85:399408. 1986;21:1613.
84. Jeune M, Carron R, Beraud C, et al. Polychondrodystrophie 102. Barnes ND, Hall D, Milner AD, et al. Chest reconstruction
avec blocage thoracique devolution fatale. Pediatrie 1954;9: in asphyxiating thoracic dystrophy. Arch Dis Child 1971;46:
3902. 8337.
85. Borland LM. Anesthesia for children with Jeunes syndrome 103. Weber TR, Kurkchubasche AG. Operative management of
(asphyxiating thoracic dystrophy). Anesthesiology 1987;66: asphyxiating thoracic dystrophy after pectus repair. J Pediatr Surg
868. 1998;33:2625.
86. Tahernia AC, Stamps P. Jeunes syndrome (asphyxiating thoracic 104. Sharoni E, Erez E, Chorer G, et al. Chest reconstruction in
dystrophy). Chin Pediatr 1977;16:9037. asphyxiating thoracic dystrophy. J Pediatr Surg 1998;33:
87. Williams AJ, Vawter G, Reid LM. Lung structure in asphyxiating 157881.
thoracic dystrophy. Arch Pathol Lab Med 1984;108:65861. 105. Davis JT, Heistein JB, Castile RG, et al. Lateral thoracic expan-
88. Finegold J, Katzew H, Genieser NB, et al. Lung structure in sion for Jeunes syndrome: Mid-term results. Ann Thorac Surg
thoracic dystrophy. Am J Dis Child 1971;122:1539. 2001;72:8728.
89. Langer LO. Thoracic pelvic phalangeal dystrophy: Asphyxiating 106. Campbell RM, Hell-Vocke AK. Growth of the thoracic spine in
thoracic dystrophy of the newborn, infantile thoracic dystrophy. congenital scoliosis after expansion thoracoplasty. J Bone Joint
Radiology 1968;91:44756. Surg Am 2003;85:40919.
90. Oberklaid F, Danks DM, Mayne V, et al. Asphyxiating thoracic 107. Phillips JD, van Aalst JA. Jeunes syndrome (asphyxiating thoracic
dysplasia. Arch Dis Child 1977;52:75865. dystrophy): Congenital and acquired. Semin Pediatr Surg
91. Campbell RM. The incidence of proximal cervical spine stenosis 2008;17:16772.
in Jeunes asphyxiating dystrophy. Paper presented at the Scoliosis 108. Ramirez N, Flynn JM, Emans JB. Vertical expandable prosthetic
Research Society 2001. titanium rib as treatment of thoracic insufficiency syndrome in
92. Herdman RC, Langer LO. The thoracic asphyxiant dystrophy spondylocostal dysplasia. J Pediatr Orthop 2010;30:5216.
and renal disease. Am J Dis Child 1977;52:192201. 109. Gadepalli SK, Hirschl RB, Tsai WC, et al. Vertical expandable
93. Jarcho S, Levin PM. Hereditary malformations of the vertebral prosthetic titanium rib device insertion: Does it improve pulmo-
bodies. Bull Johns Hopkins Hosp 1938;62:21626. nary function? J Pediatr Surg 2011;46:7780.
C H A P T E R 2 1
Management of Laryngotracheal
Obstruction in Children
David R. White H. Biemann Othersen, Jr. Andr Hebra
Pediatric surgeons are often involved in the management When compared with an adult, the anatomy of the
of acute and chronic airway obstruction. Moreover, iatro- trachea and larynx of a child differs in several ways (Fig.
genic injury to the pediatric airway occasionally occurs. 21-3). The childs epiglottis is short and small, and the
The large number of operative techniques for the treat- valleculae are shallow. Also, the larynx points posteriorly,
ment of laryngotracheal stenosis shows that no single and the arytenoid apparatus is large in relation to the
procedure or technique is universally applicable and suc- lumen of the larynx. Finally, the narrowest point of the
cessful. Prevention of, or prompt therapy for, injury is all normal pediatric airway is the subglottis. In the adult, it
important.1,2 is the glottis.
In the normal trachea, the cartilaginous rings are
horseshoe-shaped, with the posterior wall composed of
PRACTICAL EMBRYOLOGY AND ANATOMY connective tissue and the trachealis muscle. Thus, the
lumen may change as the trachea expands or contracts with
A working knowledge of the embryonic development of respiration. Long congenital stenotic segments in the
the mediastinal structures aids in understanding the etiol- trachea are usually the result of complete cartilaginous
ogy and associated anomalies of tracheal obstruction. tracheal rings. When complete cartilaginous rings are
Malformations of the great vessels (vascular rings) should present, the lumen is rigid and much smaller than the
be suspected and investigated when evaluating a child normal trachea. If it does not produce early respiratory
with complete tracheal rings. The most common vascular distress, complete cartilaginous rings may be detected
malformation associated with complete tracheal rings is when an inflammatory process within the trachea produces
a pulmonary vascular sling. This anomaly occurs when mucosal edema, which further compromises the lumen and
the left pulmonary artery arises to the right of the trachea, results in acute airway obstruction. Occasionally, tracheal
around which it curves and compresses just above the intubation for an elective operative procedure may be dif-
carina, and then passes between the trachea and esopha- ficult and the narrowed segment is discovered.
gus before reaching the left lung (Fig. 21-1).3 Other vas-
cular ring malformations may produce varying degrees of
tracheal, bronchial, and esophageal compression.
Acquired Subglottic and Tracheal Stenosis
Acquired airway malformations usually result from
intrinsic injury with subsequent inflammation, ulcera-
SUBGLOTTIC AND TRACHEAL tion, and scarring, leading to subglottic or tracheal scar-
ring and narrowing. Occasionally, trauma is the initiating
MALFORMATIONS event but an iatrogenic event can exacerbate an unstable
Congenital Subglottic and Tracheal Stenosis situation.2 For example, a child with a congenitally small
airway might be asymptomatic until an endotracheal tube
The anatomy of the pediatric airway has been compared is inserted. The tube may be appropriate in size but,
to an inverted cone, with the trachea fitting telescopically because of the congenital stenosis, it will fit tightly and
into the cricoid above it, the cricoid into the thyroid can lead to ulceration and stricture. Particularly difficult
cartilage, and then the thyroid into the hyoid space (Fig. to treat are those injuries that occur well below the
21-2).4 Congenital subglottic stenosis is the most common subglottic region, usually produced by an endotracheal
morphologic abnormality and presents as a narrowing of balloon that caused compression and ulceration in the
the airway at the distal end of the larynx, just at the begin- trachea. Frequently, these areas of injury are below the
ning of the trachea. The subglottic region lies at the level usual site for a tracheostomy. The cuff may even erode
of the cricoid cartilage, which is normally the only com- into overlying vessels (Fig. 21-4).
plete cartilaginous ring in the airway. Congenital sub-
glottic abnormalities result in elliptical narrowing of the
cricoid cartilage, the etiology of which is not known. VASCULAR COMPRESSION
Subglottic stenosis is exceeded only by laryngomalacia
and vocal cord paralysis in the frequency of congenital Compression and partial obstruction of the trachea may
airway anomalies. be caused by abnormalities of the aortic arch that impinge
279
280 SECTION III Thoracic
Vocal cords
CRICOID
Cricoid cartilage
2 CHILD
3
NARROWEST POINT
ADULT
Cricoid cartilage
Vocal cords
GLOTTIS
Ep Vef
Hy
Th
Vof
Cr
Tr
A B Destruction of
cartilages
FIGURE 21-2 (A) Ventral area of the larynx in the neonate
viewed from behind. The ventricle, or third cavity, is bounded Cuff
above by the ventricular folds (Vef) and below by the vocal folds Innominate artery
(Vof). Ep, epiglottis. (B) Laryngeal cartilages (without aryten-
oids). Th, thyroid; Cr, cricoid; Tr, trachea; and Hy, hyoid viewed
from behind. Inner dashed lines show telescopic configuration
in the neonate as opposed to the rectangular shape in the adult
(outer dashed lines). (Adapted from Othersen HB Jr, editor. The
Pediatric Airway. Philadelphia: WB Saunders; 1991.)
Swallowing
Esophagus
Trachea
Anterior
compression
by artery
A B
FIGURE 21-6 A lateral view shows how the dilated proximal FIGURE 21-7 An enlarged diagram of Figure 21-6 illustrates
esophagus displaces the trachea and compresses it against the how the compression is increased by ingestion of food. (Adapted
overlying innominate artery. (Adapted from Othersen HB Jr, from Othersen HB Jr, editor. The Pediatric Airway. Philadelphia: WB
editor. The Pediatric Airway. Philadelphia: WB Saunders; 1991.) Saunders; 1991.)
Incision
A B C
FIGURE 21-8 The operative technique for aortopexy. (A) Anterior left thoracotomy in the third interspace. (B) Sutures placed into
the wall of the innominate artery and the aortic arch. (C) Sutures passed through the sternum and tied to elevate the compressing
vessels. Tracheal attachments pull the anterior wall of the trachea forward. (Adapted from Othersen HB Jr, editor. The Pediatric Airway.
Philadelphia: WB Saunders; 1991.)
282 SECTION III Thoracic
intravenous administration of a contrast agent allows may sustain pressure necrosis. Erosion into the aortic
excellent visualization of the trachea and vessels as well. arch can produce an aortoesophageal fistula that may not
Occasionally, a child will appear with acute airway be manifest until either the endotracheal or the esopha-
obstruction or other medical problems requiring inten- geal tube is removed. A sentinel hemorrhage may occur
sive care, during which endotracheal intubation and a before a massive, and often fatal, hemorrhage occurs into
concomitant nasogastric tube are inserted. The presence the esophagus. The passage of a SengstakenBlakemore
of tubes in both airway and esophagus makes detection tube with inflation of the esophageal balloon can be life-
of a vascular ring difficult and can generate complica- saving by tamponading the fistula.14 Because no reliable
tions. In a child who is already intubated, performance of diagnostic study is available to demonstrate an aor-
contrast radiographic procedures may not be possible. toesophageal fistula, the observation of a sentinel hemor-
Ultrasonography (US), or CT, or contrast-enhanced rhage in such a patient with ultrasound confirmation of
MRI may delineate the vascular abnormality. When both a double aortic arch is a clear indication for urgent car-
tracheal and esophageal intubations are necessary in a diopulmonary bypass and repair.14
patient with a double aortic arch, the encircling vessels Vascular rings cause airway constriction and not vas-
cular problems. Thus, simple division of the vascular ring
is often not enough to relieve tracheal compression. Fol-
lowing division of a vascular ring, if part of the ring
continues to compress the airway, it should not be dis-
sected away from the trachea but suspended anteriorly,
often to the back of the sternum. The vascular-tracheal
attachments will lift the anterior tracheal wall and enlarge
the lumen (see Fig. 21-8). Traditionally, an open opera-
tion has been used for vascular ring repair. Significant
numbers of patients are now being treated by the thora-
coscopic approach.15 Regardless of the approach, whether
from the right or from the left,16 or other technical vari-
ations,17 the recurrent laryngeal and phrenic nerves need
to be identified and protected. Flexible endoscopic obser-
vation of the trachea during these maneuvers can cor-
roborate relief of the compression.6
TRACHEOMALACIA
Often, tracheomalacia is produced by constant pressure
from a cardiovascular structure. Thus it is almost always
necessary to suspend the offending vessel and utilize its
attachments to the trachea to expand the tracheal lumen.
FIGURE 21-9 Both trachea and esophagus are compressed by
Tracheomalacia can be primary in nature without evi-
a double aortic arch. (Adapted from Othersen HB Jr, editor. The dence of compression. In these cases, suspension of the
Pediatric Airway. Philadelphia: WB Saunders; 1991.) large mediastinal vessels may enlarge the tracheal lumen,
A B
FIGURE 21-10 This infant presented with stridor. There was a suggestion of tracheal indentation on the chest radiograph. Therefore,
a barium esophagogram was performed (A) and shows the double indentations diagnostic of a double aortic arch. (B) A CT scan
shows contrast in the double arch that is encircling the trachea and esophagus (collapsed).
21 Management of Laryngotracheal Obstruction in Children 283
or the peritracheal fascia can be suspended to the sternum without the need for operation. Treatment includes
to overcome collapse of the airway.1821 In the UK oxygen with increased humidification and inhalation of
(Scotland), guidelines have been promulgated for the use racemic epinephrine. Endotracheal intubation is well tol-
of thoracoscopic aortopexy to treat severe primary tra- erated in epiglottitis. However, in cases of viral or bacte-
cheomalacia. Interestingly, the National Health Service rial tracheitis, even brief (2448 hours) intubation may
believed that these guidelines were necessary because cause ulceration in a trachea that is already acutely
individual surgeons would operate infrequently on infants inflamed and swollen. Croup is more easily treated
and children who are good candidates for operative without intubation using racemic epinephrine inhalation
correction. combined with dexamethasone.
ENDOTRACHEAL INTUBATION
Endotracheal intubation may be difficult in small chil-
dren. The preferred laryngoscopic blade for infants and
children is a straight blade, such as the Miller or the
WisHipple. Otolaryngologic laryngoscopes, such as the
Parsons and BenjaminLindholm laryngoscopes, provide
even better exposure. The childs head should be in the
neutral position and not extended. With the infants head
in the neutral, or sniffing, position, the laryngoscope
FIGURE 21-11 Mechanism of head injury. With a padded dash- blade is introduced and the tongue and floor of the mouth
board, external evidence of injury is minimal. (Adapted from lifted to expose the epiglottis. Once the epiglottis is seen,
Othersen HB Jr. Cardiothoracic injuries. In: Touloukian RJ, editor. extension or flexion of the head and neck may be needed.
Pediatric Trauma. New York: John Wiley & Sons; 1978.)
For infants and children, a commonly applied formula
to determine the correct endotracheal tube size is (age +
16)/4 or age/4 + 4. If a child needs to be rapidly intubated
with a tube that fits snugly and allows no air leak, this
fact should be noted and documented. At the earliest
possible opportunity, the snugly fitting tube should be
changed to a smaller size. If intubation is required for a
long period (usually longer than two to three weeks),
tracheostomy may be considered. An air leak is generally
an indication that the tube is not too snug.
Usually a cuffed endotracheal tube is not necessary in
children because compensation for air leaks can be accom-
plished by increasing the volume of air delivered by the
ventilator. However, with massive craniofacial injuries
and bleeding, or with significant gastroesophageal reflux,
a cuff may be necessary to prevent aspiration of blood or
gastric contents. Otherwise, it is best not to use a cuff to
prevent damage to the subglottic trachea.29,30 Indications
for tracheostomy are summarized in Table 21-2.
A B C
FIGURE 21-15 An autogenous costal cartilage graft reconstruction. (A) Expose the larynx and upper trachea. (B) Incise the afore-
mentioned region, remaining superior to the tracheostomy stoma if the stenosis does not involve this site. (C) Sew the costal cartilage
to the incised edges of the larynx and trachea, placing the perichondrium internally. (Adapted from Othersen HB Jr, editor. The Pediatric
Airway. Philadelphia: WB Saunders; 1991.)
open procedure can be done with or without cardiopul- the airway lumen.51 Another option is resection of the
monary bypass.42 Recently, there has been a tendency to stenotic tracheal segment and primary end-to-end anas-
avoid bypass and use only endotracheal anesthesia. tomosis.52 A slide tracheoplasty technique can also be
Second, the repair can be performed with or without an used.53,54
augmentation graft. Possible graft options include tra- A fifth option for repair of tracheal stenosis utilizes an
cheal allografts or autografts, costal cartilage, cartilage anterior tracheal incision with closure of the defect
from other sites such as thyroid or alar cartilage, autolo- using pericardium. These pericardial patch operations
gous or allogeneic pericardium, or skin. Third, a stent are performed with cardiopulmonary bypass.55 However,
can be used to maintain the lumen and can remain for experience at some centers has not been as favorable
hours, days, months, or years. because of complications secondary to patch collapse.56
The anterior cricoid split procedure is useful in treat- The original proponents of pericardial patching have
ing moderate subglottic stenosis in neonates and now reported improved results with a free tracheal
young infants.43,44 Infants selected for this procedure autograft in which the excised stenotic segment is flat-
should weigh more than 1500g and require assisted ven- tened and used as a free anterior autograft to expand the
tilation or inspired oxygen of more than 35%. They tracheal lumen.57
should also not be in cardiac failure. This technique is Silicone T-tubes can be used as an internal stents to
illustrated in Figure 21-14.45 Proper selection of patients maintain the tracheal lumen and allow tracheal remod-
for the anterior cricoid split is crucial. After undergoing eling following tracheoplasty.58 These tubes can be placed
the anterior cricoid split, infants who can be successfully temporarily to maintain the airway lumen while the
extubated have excellent long-term outcomes, while airway heals following tracheoplasty. Alternatively,
those who continue to need intubation usually require T-tubes can be effective as a permanent stent for the dif-
tracheostomy. ficult airway stenosis or in cases of failed tracheoplasty.
The classic laryngotracheoplasty utilizes a cartilage In very complicated and difficult cases, we have utilized
graft (Fig. 21-15).46,47 An omental flap may help a long custom-made T-tubes. One such custom T-tube is shown
cartilaginous graft survive.48 The cartilage is inserted in Figure 21-16. This tube was necessary for the treat-
anteriorly after incising the stenotic segment.49,50 Carti- ment of tracheomalacia at the carina. As a bifurcated
lage inserts also can be placed posteriorly and laterally as Y-tube is difficult to insert, in this case, a bronchial arm
well. Ciliated mucosa has been found on the surface of a extended into one bronchus and a hole allowed aeration
mature costal cartilage graft if the perichondrium faces of the other lung.
288 SECTION III Thoracic
41. Matute JA, Villafruela MA, Delgado MD, et al. Surgery of subglot- 50. Gustafson LM, Hartley BE, Liu JH, et al. Single-stage laryngotra-
tic stenosis in neonates and children. Eur J Pediatr Surg cheal reconstruction in children: A review of 200 cases. Otolaryngol
2000;10:28690. Head Neck Surg 2000;123:4304.
42. Loukanov T, Sebening C, Springer W, et al. Simultaneous manage- 51. Oue T, Kamata S, Usui N, et al. Histopathologic changes after
ment of congenital tracheal stenosis and cardiac anomalies in tracheobronchial reconstruction with costal cartilage graft for con-
infants. J Thorac Cardiovasc Surg 2005;130:153741. genital tracheal stenosis. J Pediatr Surg 2001;36:32933.
43. Cotton RT, Seid AB. Management of the extubation problem in 52. Har-El G, Shaha A, Chaudry R, et al. Resection of tracheal stenosis
the premature child. Anterior cricoid split as an alternative to with end-to-end anastomosis. Ann Otol Rhinol Laryngol
tracheotomy. Ann Otol Rhinol Laryngol 1980;89:50811. 1993;102:6704.
44. Silver FM, Myer CM 3rd, Cotton RT. Anterior cricoid split. 53. Lipshutz GS, Jennings RW, Lopoo JB, et al. Slide tracheoplasty for
Update 1991. Am J Otolaryngol 1991;12:3436. congenital tracheal stenosis: A case report. J Pediatr Surg
45. Myer CM 3rd, Cotton RT. Cricoid split and cartilage tracheoplasty. 2000;35:25961.
In: Othersen HB Jr, editor. The Pediatric Airway. Philadelphia: 54. Lang FJ, Hurni M, Monnier P. Long-segment congenital tracheal
WB Saunders; 1991. p. 11724. stenosis: Treatment by slide-tracheoplasty. J Pediatr Surg
46. Kimura K, Mukohara N, Tsugawa C, et al. Tracheoplasty for 1999;34:121622.
congenital stenosis of the entire trachea. J Pediatr Surg 1982; 55. Backer CL, Mavroudis C, Gerber ME, et al. Tracheal surgery in
17:86971. children: An 18-year review of four techniques. Eur J Cardiothorac
47. Tsugawa C, Kimura K, Muraji T, et al. Congenital stenosis involv- Surg 2001;19:77784.
ing a long segment of the trachea: Further experience in recon- 56. Houel R, Serraf A, Macchiarini P, et al. Tracheoplasty in congenital
structive surgery. J Pediatr Surg 1988;23:4715. tracheal stenosis. Int J Pediatr Otorhinolaryngol 1998;44:318.
48. Tsugawa C, Nishijima E, Muraji T, et al. The use of omental 57. Backer CL, Mavroudis C, Dunham ME, et al. Repair of congenital
pedicle flap for tracheobronchial reconstruction in infants and chil- tracheal stenosis with a free tracheal autograft. J Thorac Cardiovasc
dren. J Pediatr Surg 1991;26:7625. Surg 1998;115:86974.
49. Forsen JW Jr, Lusk RP, Huddleston CB. Costal cartilage tracheo- 58. Huang CJ. Use of the silicone T-tube to treat tracheal stenosis or
plasty for congenital long-segment tracheal stenosis. Arch tracheal injury. Ann Thorac Cardiovasc Surg 2001;7:1926.
Otolaryngol Head Neck Surg 2002;128:116571.
C H A P T E R 2 2
Congenital Bronchopulmonary
Malformations
Erik G. Pearson Alan W. Flake
Congenital bronchopulmonary malformations (BPMs) maturation. During this complex process, the timing of
represent a continuum of abnormalities of the broncho congenital BPMs and their pathogenesis can be related
pulmonary unit for which classification and management to specific time points in each of the six developmental
remain in evolution. An improved understanding of stages (Fig. 22-1).
the molecular mechanisms underlying the embryologic
development of the lung and the pathogenesis of BPMs
suggests that these lesions may have similar mechanistic PRENATAL DIAGNOSIS AND
origins that differ in developmental timing or location in
the bronchopulmonary tree.1 From a clinical perspective, CLASSIFICATION OF CONGENITAL
improvements in prenatal imaging and increasing obser BRONCHOPULMONARY
vational experience have resulted in a better understand MALFORMATIONS
ing of the natural history of these anomalies, and a better
predictive capacity for pre-, peri-, and postnatal events. Malformations
Finally, postnatal treatment for the majority of lesions has
improved with advances in neonatal care, and the devel Prenatal diagnosis and fetal therapy for congenital lung
opment of thoracoscopic surgery. This chapter discusses malformations have evolved significantly since Adzick
the prenatal and postnatal management of the major con etal. described the near universal mortality of congenital
genital BPMs with an emphasis on utilizing the thoraco pulmonary airway malformation (CPAM)-induced fetal
scopic approach for management. hydrops almost three decades ago.4 Congenital BPMs
represent 90% of lung lesions seen in clinical practice and
include CPAMs, (formally called congenital cystic adeno
EMBRYOLOGY AND DEVELOPMENT matoid malformation or CCAM), bronchopulmonary
OF THE BRONCHOPULMONARY TREE sequestration (BPS), and congenital lobar emphysema
(CLE).5 Other less common malformations are varied
Embryological development of the human lung transi and are included in the classification system described by
tions through six separate stages to form a bronchial tree Langston etal.6 (Box 22-1), but will not be discussed in
with greater than 1 105 conducting and 1 107 respira this chapter.
tory airways.2 These stages include embryonic, pseudo Prenatal ultrasonography (US) functions as a window
glandular, canalicular, saccular, alveolar, and microvascular. into fetal development and is the most common mode of
The progression of each stage is a highly coordinated prenatal diagnosis of congenital thoracic abnormalities
process guided by mesenchymalepithelial interactions (Box 22-2). We routinely supplement ultrasound with
under the influence of a number of regulatory growth magnetic resonance imaging (MRI) as a complementary
factors. method to further define the anatomy of the lesion
Briefly, the embryonic phase of lung development and overall fetal morphology.7,8 In combination, the
begins with the formation of the laryngotracheal bud two modalities allow accurate prenatal diagnosis of
from the anterior portion of the primitive gut. Beginning the different types of BPMs and exclude other anatomic
at week 5 in the pseudoglandular phase, the preacinar anomalies.
airways and blood vessels develop, followed by growth of
the bronchial tree until all bronchial divisions are com Congenital Pulmonary Airway
pleted by 16 weeks gestation.3 The cannalicular stage
follows, and is characterized by capillary growth towards Malformation
the respiratory epithelium which marks the future blood CPAMs are the most commonly diagnosed BPM. The
air interface.2 The transition to the saccular stage at best estimate of the incidence of CPAM is 0.66 per 10,000
24 weeks is marked by the widening of peripheral air live births, but better studies are needed based on high
spaces distal to the terminal bronchioles with septa for quality prenatal imaging of all pregnancies in a study
mation. The final stages of lung development include the population.9 This heterogeneous group of congenital
alveolar stage, defined by the formation of secondary cystic and noncystic lung masses is characterized by an
septa and budding alveoli, and followed by the microvas extensive overgrowth of immature primary bronchioles
cular stage with significant alveolar development and localized to a segment of the bronchial tree (Fig. 22-2).10
290
22 Congenital Bronchopulmonary Malformations 291
Type IV CPAM
Saccular
Pulmonary Agenesis
Lobar Agenesis Canalicular
Pseudogandular
Embryonic
0 5 10 15 20 25 30 35 40 1y 2y 3y
Weeks
FIGURE 22-1 This graphic depicts milestones in fetal lung development and the timing for development of congenital bronchopul-
monary malformations. CPAM, congenital pulmonary airway malformation; BPS, bronchopulmonary sequestration; CHAOS, con-
genital high airway obstruction syndrome.
0
Classification of Congenital
BOX 22-1
Lung Lesions
Bronchopulmonary malformation
Bronchogenic cyst 1
Bronchial atresia 2
Congenital pulmonary airway malformation (Stocker 3
4
type 1 and 2)
Bronchopulmonary sequestration
Pulmonary hyperplasia and related lesions
Laryngeal atresia
Congenital pulmonary airway malformation (Stocker
type 3)
Polyalveolar lobe
Congenital lobar emphysema
Other cystic lesions
Lymphatic/lymphangiomatous cysts
Enteric cysts
Mesothelial cysts FIGURE 22-2 This CPAM classification schematic is based on
Simple parenchymal cysts the location of the development of the malformation. Type 0,
Low-grade cystic pleuropulmonary blastoma tracheobronchial; 1, bronchial/bronchiolar; 2, bronchiolar; 3,
bronchiolar/alveolar; 4, distal acinar. Adapted from Stocker
Adapted from Langston C. New concepts in the pathology of congenital lung (2009).63
malformations. Semin Pediatr Surg 2003;12:1737.
based on prenatal ultrasound findings: (1) macrocystic
lesions containing a single or multiple cysts that are
Benefits of Prenatal Ultrasonogra- 5.0mm in diameter or greater; and (2) microcystic lesions
BOX 22-2 phy in the Evaluation of Broncho presenting as a solid echogenic mass on prenatal ultra
pulmonary Malformations sound (Fig. 22-3).4
Early diagnosis of the entire spectrum of congenital lung In the prenatal period, ultrasound will usually demon
lesions strate an area of hyperechogenic tissue with or without
Serial monitoring of the size and secondary effects of the hypoechoic cysts that vary in number and size. Signs of
mass (polyhydramnios, mediastinal shift, and hydrops) mass effect may be seen, such as mediastinal shift, dia
Planning for prenatal and perinatal treatment and deliv phragmatic eversion, and polyhydramnios. With very
ery strategies large lesions, heart failure (hydrops) due to mediastinal
shift and cardiac compression can occur.11 CPAMs receive
their blood supply from the pulmonary artery and have
The current classification system defined by Stocker pulmonary venous drainage. However, there is a subset
classifies CPAMs into five types that differ by location, of CPAMs, known as hybrid lesions, where the blood
cystic structure, size, and epithelial lining (Table 22-1). supply also includes an anomalous systemic artery.12
However, from a practical perspective, the prenatal These lesions demonstrate anatomic and histologic fea
classification of CPAMs is divided into two categories tures of both CPAMs and BPS.
292 SECTION III Thoracic
From Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and
morphologic spectrum. Hum Pathol 1977;8:15571.
A B
FIGURE 22-4 (A) The CT scan demonstrates an extralobar sequestration in the typical basilar location of the left chest (arrow).
(B) In a different patient, the chest radiograph shows a large transdiaphragmatic extralobar sequestration (arrow).
A B
FIGURE 22-5 This 9-month-old developed an upper respiratory infection and a chest radiograph was performed. (A) The chest
radiograph shows a left apical mediastinal mass. (B) After her infection resolved, she was found to have this extrapulmonary mass
at thoracoscopy, along with a feeding vessel (arrow). The vessel was ligated and the mass removed, and she recovered unevent-
fully. Histologic examination showed the mass to an extralobar sequestration associated with a microcystic congenital pulmonary
airway malformation.
contain visible cysts that ultimately are shown to have pulmonary vein. The subtleties of prenatal diagnosis of
CPAM histology (Fig. 22-5). In addition, an ELS can these lesions are consistent with a continuum of develop
occasionally have venous drainage via a large venous mental pathogenesis. It should be emphasized that post
channel draining directly into a pulmonary vein that is natal computed tomography (CT) should be obtained in
usually identified as aberrant venous drainage by imaging all patients to confirm the anatomy and to aid in manage
studies. ment. The final diagnosis will depend on the anatomy
In contrast to ELS, ILS routinely has pulmonary found at postnatal resection as well as the histologic anal
venous drainage and has variable degrees of hyperecho ysis, and is frequently a combination of the classifications
genicity by ultrasound or MRI. They are uniformly asso previously described.
ciated with the lower lobes and are distinguishable from
the microcystic hybrid lesions described previously only
by the absence of pulmonary arterial inflow. Careful
Congenital Lobar Emphysema
Doppler ultrasound identification of the arterial inflow CLE is a condition characterized by overinflation and
to these lesions is required to definitively distinguish distension of one or more pulmonary lobes with com
between a microcystic hybrid CPAM and an ILS prena pression of the adjacent lung. In 50% of cases, the cause
tally. Finally, an ILS can be difficult to distinguish from is unknown. In the remaining 50%, it may result from
a systemic to pulmonary vascular malformation where dysplastic bronchial cartilage, endobronchial obstruction,
the bronchial anatomy and pulmonary parenchyma are extrinsic compression from aberrant cardiopulmonary
relatively normal, but there is an aberrant systemic blood vasculature, or diffuse bronchial abnormalities related to
supply coursing through a vascular network within infection.16 In the fetus, amniotic fluid trapping is analo
normal parenchyma with venous drainage into the gous to air trapping and can lead to lobar expansion. The
294 SECTION III Thoracic
left upper lobe is the most frequently affected, followed CPAM (length height width 0.52) by the head
by right middle and upper lobes, with rare bilateral or circumference. In addition, the CVR has proven on ret
multifocal involvement. CLE is most commonly diag rospective and prospective assessment to be the most
nosed in the neonate or infant presenting with respira useful predictor for the development of hydrops.20 A
tory distress. CVR of <1.6 in a CPAM without a dominant cyst predicts
Prenatal discrimination between CLE and CPAM or a risk of developing hydrops of less than 3%. If the CVR
bronchial atresia may be difficult, but the absence of a is >1.6, the risk of hydrops is around 75%. We have found
systemic vascular supply differentiates this lesion from an the CVR very useful in counseling parents, determining
ELS. Although complications such as polyhydramnios the intensity of serial follow-up, and determining which
and hydrops have not been reported with CLE, perinatal patients to preemptively treat with steroids. Other param
respiratory distress correlates with the prenatal size of the eters such a massthorax ratio, cystic predominance of
lesion as manifest by mediastinal shift or compression of the lesion, and eventration of the diaphragm, while asso
adjacent lung parenchyma.17 ciated with large lesions, do not add independent predic
tive value to the CVR.21
Bronchogenic Cysts and Bronchial Based on the type of CPAM, the prenatal CVR, and
gestational age, a management strategy can be formu
Atresia/Stenosis lated to optimize outcome. In recent years, the prenatal
Bronchogenic cysts develop from abnormal budding of treatment of large microcystic CPAMs with a CVR of
the tracheal diverticulum or the ventral aspect of the >1.6 and/or the presence of hydrops at less than 32 weeks
primitive foregut, which is not followed by bronchial gestation has changed. Whereas open fetal surgery and
development or branching. The result is a cavity that may lobectomy were once the primary option at fetal treat
or may not communicate with the airway and can be ment centers, the majority of these patients will respond
found in a variety of locations depending on the location to steroid treatment, with inhibition of further CPAM
of abnormal budding during foregut development. His growth and/or regression of hydrops. The mechanism for
tologically, these lesions are thin walled and have a bron the steroid effect is speculative, but the phenomenon has
chial epithelial lining, and are filled with mucus.18 Prenatal been documented by multiple fetal treatment centers
diagnosis of these lesions is usually made by ultrasound with very few open resections performed since this strat
where they may be seen as an isolated cystic structure in egy was implemented.2225 In a recent study at our institu
the mediastinum, or causing bronchial obstruction with tion, we were able to achieve 100% survival in fetuses
findings of bronchial dilation and lung hyperplasia distal either with hydrops (5/5) or a CVR >1.6 at the time of
to the point of obstruction. Bronchial atresia without a steroid administration.27 This compares to a mortality
bronchogenic cyst also results in hyperplasia distal to the rate of 100% in fetuses with hydrops and a 56% mortality
level of obstruction and is frequently associated with rate in fetuses with a CVR >1.6 among historical con
mucocele formation. The presence of dilated bronchi trols. In contrast to microcystic CPAMs, macrocystic
indicates a diagnosis of atresia rather than microcystic CPAMs do not consistently respond to steroid treatment.
CPAM. The more proximal the atresia, the greater the Also, if hydrops is evolving, the fetus is best treated by
potential for mass effect manifest by mediastinal shift, thoracoamniotic shunting (Fig. 22-6).
and ultimately, fetal hydrops. Segmental bronchial Our algorithm for the prenatal management of CPAM
stenosis/atresia is a relatively recently recognized abnor at the Childrens Hospital of Philadelphia (CHOP) is
mality characterized by an echogenic segment of lung on shown in Figure 22-7. Three common clinical scenarios
ultrasound that is indistinguishable from and usually in the management of CPAM are generally apparent by
diagnosed as a microcystic CPAM.19 32 to 34 weeks gestation (Table 22- 3) and guide recom
mendations for site and mode of delivery. As gestation
proceeds, it is not unusual for previously hyperechoic
PRENATAL AND PERINATAL lesions to become isoechoic with surrounding lung
parenchyma (the so called disappearing CPAM). This is
MANAGEMENT OF due to increasing echogenicity of the surrounding lung
BRONCHOPULMONARY tissue and rib shadowing that occurs during the third
MALFORMATIONS trimester. However, it is important to realize that, in
essentially all such cases, a postnatal CT scan will confirm
Congenital Pulmonary Airway persistence of the lesion.
Future options for treatment of CPAM in the hydropic
Malformation fetus may include minimally invasive ablative or vascular
Experience with serial imaging of large numbers of occlusion therapy. Thus far, however, techniques such as
fetuses with CPAMs has clarified the pre- and perinatal radiofrequency or laser thermal ablation have been asso
natural history of this anomaly. There is a typical pattern ciated with excessive collateral damage due to the diffi
of growth of a CPAM with a period of growth relative to culty with controlling the energy dispersion in the high
the size of the fetus until approximately 26 weeks gesta fluid content fetus. Sclerotherapy has been described but
tion at which time growth plateaus. After 28 weeks, the the patient selection must be questioned and the advis
CPAM typically gets smaller relative to the size of the ability of injecting highly caustic agents into the fetal
fetus as measured by the CPAM volume ratio or CVR. bloodstream is concerning and needs further research
The CVR is calculated by dividing the volume of the investigation.2628
22 Congenital Bronchopulmonary Malformations 295
Thoracoamniotic shunt
placement for macrocystic CCAM
with associated fetal hydrops
B C
Detailed sonography
Isolated CPAM
Associated Ultrafast MRI
without fetal
anomalies Fetal echocardiogram
hydrops
(amniocentesis)
Low risk
Counsel Isolated CPAM
CVR 1.6
Follow up with
High risk serial ultrasound
CVR>1.6
Trial of steroids
Hydrops No hydrops
FIGURE 22-7 This algorithm depicts our current management strategy at Childrens Hospital of Philadelphia for a fetus with a con-
genital pulmonary airway malformation (CPAM). CHOP, Childrens Hospital of Philadelphia; CVR, CPAM volume ratio; MRI, magnetic
resonance imaging; US, ultrasound.
of bronchial stenosis or atresia. CLE and segmental bronchial atresia can be treated in the early postnatal
bronchial stenosis are not associated with significant pre period.
natal pathophysiology. CLE can enlarge prenatally due
to fluid trapping, presumably by a similar mechanism to
postnatal air trapping, though at most this has been found POSTNATAL MANAGEMENT
to cause moderate mediastinal shift. Bronchial atresia, OF BRONCHOPULMONARY
also known as bronchial mucocele, is a condition result MALFORMATIONS
ing from focal obliteration or stenosis of a segmental,
subsegmental, or lobar bronchus at or near its origin.30 Congenital Pulmonary Airway
Bronchial atresia can result in hydrops and fetal or neo Malformation
natal death when located proximally. This is due to the
hyperplastic growth response induced by the bronchial The postnatal clinical spectrum of CPAM ranges from
obstruction that can lead to massive lung or lobar expan the neonate requiring mechanical ventilation, to the child
sion. Findings of severe mediastinal shift with diaphrag presenting with an infected CPAM, to the asymptomatic
matic eversion and evolution of hydrops have been adult. The treatment of the neonate with a symptomatic
uniformly fatal in cases of main stem bronchial atresia CPAM is immediate resection of the involved lobe by an
due to either fetal demise or neonatal death due to the open or thoracoscopic approach. Lobectomy is preferred
inability to ventilate the infant. Fetuses with lobar hyper over attempts at lung preserving surgery, such as segmen
plasia resulting in fetal hydrops prior to 30 weeks gesta tal or wedge resection, due to the inability to accurately
tion may be offered open fetal surgery and lobectomy. ascertain the borders of the lesion, the higher complica
After 30 weeks gestation, delivery utilizing the ex-utero tion rate related to segmentectomy, and the compensa
intrapartum treatment (EXIT) approach followed by tory lung growth that occurs in the remaining lobe or
resection is performed. In our experience, these lesions lobes that results in normal long-term pulmonary func
have not been responsive to steroid therapy. An interest tion following infant lobectomy.32 When multiple lobes
ing recent case of fetal bronchoscopic decompression of are involved (1% of CPAMs), segmentectomy should be
a right bronchus intermedius obstruction has been considered if anatomically feasible. As noted previously,
described which may be applicable to a subset of proximal very large lesions with significant mediastinal shift and
bronchial obstructions.31 Fortunately, cases requiring diaphragmatic displacement should be delivered using
fetal intervention are rare, and most infants with lobar the EXIT procedure and resected on placental support.
22 Congenital Bronchopulmonary Malformations 297
With these very large masses, care must be exercised to As the frequency of malignant transformation of a CPAM
avoid rupturing the CPAM or tearing the fragile hilar is unknown, it is not possible to predict which patients
vessels during attempts at exposure when retracting the will develop cancer. Moreover, there is no imaging
CPAM. A thoracoabdominal incision can be helpful with modality that can be safely used to serially image patients
large CPAMs to aid in the safe delivery of the lobe and during a lifetime. This risk of malignancy may represent
to provide additional space for the hilar dissection. In the strongest argument for resection of asymptomatic
contrast to CDH, extracorporeal membrane oxygenation lesions.
(ECMO) is rarely required for CPAM-related pulmonary At CHOP, we strongly advocate early resection of an
hypoplasia, presumably because of the lesions slow asymptomatic CPAM due to the considerations outlined,
growth and the relatively late onset of pulmonary com the extremely low rate of complications of resection at
pression. Outside the neonatal period, a symptomatic our center, and the negligible impact on long-term pul
CPAM should be treated by lobectomy when recognized. monary function associated with infant lobectomy. We
Babies may present with air trapping in the first few see no surgical or anesthetic benefit to waiting and feel
months of life, infection of the CPAM in the first several that resection, whether thoracoscopic or open, is easier
years of life, and occasionally spontaneous pneumothorax at an early age (less adenopathy, perihilar fat, and inflam
related to the lesion.33,34 Infection in CPAMs may be dif mation related adhesion) than later in life. In addition,
ficult to clear with antibiotics and resection should be recovery, and the potential for compensatory lung growth
performed once the patient has improved following anti and restoration of normal pulmonary function is likely
biotic therapy. higher in younger infants. With this policy, we have had
In contrast to large and symptomatic CPAMs, there is no major complications and a combined minor complica
controversy regarding the treatment of the asymptomatic tion (persistent air leak, need for transfusion, late pneu
CPAM. In the era of prenatal diagnosis, the majority of mothorax, chylothorax) rate under 10% following either
patients are asymptomatic. The arguments for resection open or thoracoscopic resection of asymptomatic CPAMs.
are that CPAMs do not completely regress and that they While a nonoperative approach to CPAMs was evalu
put the patient at risk for future infection, pneumothorax, ated in a small number of patients demonstrating a low
and malignancy. There is also the risk that the mass is risk of adverse events, the mean follow-up was only three
really a pleuropulmonary blastoma (PPB), a lesion that is years.40 In addition, a nonoperative approach requires
rare, but indistinguishable from CPAM on pre- and post serial surveillance by CT scanning and exposes the patient
natal imaging studies.35 The controversy is related to the to a significant risk of cumulative radiation with signifi
belief by some that many lesions regress and disappear, cant long-term consequences.41 Waiting until the lesion
as well as the unknown frequency of infection and malig becomes symptomatic places the patient at risk for devel
nant deterioration in the asymptomatic patient. Infection oping complications when operating in an inflammatory
in CPAMs is well documented, particularly before the or infectious field. Our data supports lobectomy between
era of prenatal diagnosis. CPAMs can develop infection the ages of 13 months as the optimal management for
anytime between a few weeks of age until adulthood. the asymptomatic CPAM.42,43 We prefer the thoraco
Infections can be severe and life threatening, difficult to scopic approach, but this recommendation is dependent
clear with antibiotics, associated with complications of on an experienced surgeon. If that is not the case, then
abscess, empyema, and other secondary complications, open lobectomy using a muscle sparing thoracotomy is
and in neglected or unrecognized cases, may increase the recommended.
risk of lobectomy. There are no well-designed prospec
tive studies that provide an accurate assessment of the risk
of infection in a CPAM during ones lifetime, much less
Bronchopulmonary Sequestration
in the first 10 years of life. In a long-term retrospective An increasing number of BPS are prenatally diagnosed
study in which 21 patients were initially diagnosed as and postnatal therapy can be planned based on the antici
asymptomatic (including eight that were prenatally diag pated risk of postnatal complications. For ELS, the treat
nosed) and followed, 18 developed symptoms (median ment depends on the size of the lesion, blood flow,
age 2 years, range 1 month13 years) and required opera associated pleural effusion, and location. Our indications
tion. Symptoms included pneumonia with or without an for resection of ELS are defined in Box 22-3. In both an
infected CPAM (43%), respiratory distress (14%), and ELS and ILS that has large systemic feeding vessels,
spontaneous pneumothorax (14%). Eight patients under vascular flow can be anticipated to increase, not decrease,
went multiple hospital encounters with complications over time due to the low resistance of the vascular bed
related to the CPAM.36 with the end result being high flow cardiac physiology
There is also a clear association between CPAM and and ultimately cardiac failure as the child grows. Ana
malignancy. A review of children with lung neoplasms tomical BPS with cystic areas on imaging likely contain
demonstrated that 9% had a history of cystic lung mal CPAM elements within the BPS,44 and this may be
formations.37 The mucinous cells in a type I CPAM responsible for the sporadic reports of malignancy occur
produce gastric mucins that are important in the patho ring in both ILS and ELS, but more frequently in ELS.
genesis of bronchioloalveolar carcinoma.38 The associa The malignancies that have been reported in association
tion with PPB is also clear, although resection of a CPAM with ELS include lymphoepithelial carcinoma, PPB,
does not preclude the development of PPB.39 Type II squamous cell carcinoma, carcinoid, and mesothelioma.4548
CPAM has been demonstrated to exhibit skeletal muscle Within ILS, benign sclerosing hemangioma can be
differentiation as found in PPB and rhabdomyosarcoma. found. Because ELS do not communicate with the
298 SECTION III Thoracic
tracheobronchial tree, infection is rare. However, in ILS, are usually able to be discharged the next day. Percutane
air enters by tracking through the pores of Kohn. Thus, ous coil embolization of the feeding systemic artery to
with stasis of mucous and the absence of bronchial clear ELS has been performed in children and adults. In most
ance, infection is a frequent complication. cases there is little reason to favor this approach over
The differential diagnosis of subdiaphragmatic ELS in resection.51 In contrast to resection, embolization carries
the fetus or neonate includes neuroblastoma and adrenal the potential for vascular injury at the catheter insertion
hemorrhage, and these lesions can be differentiated on site, embolic occlusion of other vessels, and the potential
serial ultrasound imaging. Finally, an ELS in close prox for dysplastic residual tissue that may persist with possi
imity to the esophagus, particularly if difficult to separate, ble future malignant transformation.
may have an esophageal bronchus that needs to be identi In our opinion, all cases of ILS should be resected,
fied and closed during excision. There is debate regard because of the risk of infection and evolution of high
ing the postnatal management of a small intrathoracic or output physiology. Thoracoscopic lobectomy is our
subdiaphragmatic ELS. A small ELS can remain asymp preferred approach. Segmentectomy for ILS has been
tomatic throughout life, have been reported to spontane reported in the literature with success.52,53 However,
ously regress, and carry a low risk of infection or trying to avoid performing a lobectomy may carry a
malignancy. This has led some surgeons to observe these higher risk as these lesions usually do not have normal
lesions if the lesion is not visible on plain radiography, or segmental anatomy, share pleural investment, can have
if it is small, or does not have a significant systemic arte significant internal blood flow, and can be difficult to
rial blood supply.49,50 We feel that the ELS treatment distinguish from adjacent lung tissue which risks leaving
should be individualized with specific indications for residual disease.
resection as shown in Box 22-3.
The surgical management of ELS involves division of Congenital Lobar Emphysema
the systemic blood supply and removal of the mass (see
Fig. 22-5). This must be done with care as systemic Asymptomatic children with CLE or those with only
vessels arising from the abdominal aorta may cross the mild symptoms can be safely managed without resec
diaphragm and lead to difficult-to-control bleeding if not tion.54 In neonates or infants presenting with respiratory
adequately ligated. However, ELS are generally straight distress and pulmonary lobar hyperinflation, open lobec
forward lesions for thoracoscopic resection and patients tomy is our preferred option (Fig. 22-8). These patients
have unique and difficult anesthetic challenges from air
trapping and cardiovascular compromise that may prevent
successful single lung ventilation. Therefore, considera
Indications for Resection of tion for thoracoscopic resection should be highly selec
BOX 22-3 Extralobar Bronchupulmonary tive and requires careful preoperative review by the
Sequestration anesthetic and surgical team.55 Symptomatic patients
usually present with respiratory distress within the first
Large systemic vascular supply 6 months of life with 25% of patients presenting at
Large lesions with significant compression of surround birth and 50% presenting prior to one month of age.
ing lung parenchyma or mediastinal shift The severity of disease is dependent on the size of the
Lesions with cystic abnormality on prenatal ultrasound affected lobe and compression of adjacent lung tissue.
or postnatal CT scan as this likely represents CPAM
elements within BPS
The mainstay of management for CLE is resection of the
Growth of an ELS on serial imaging affected lobe. However, whether pre- or intraoperatively,
Lesions in or under the diaphragm near the esophageal care must be taken to avoid progressive air trapping with
hiatus causing obstructive symptoms resulting lobar tension emphysema from positive pres
sure ventilation.16
A B C
FIGURE 22-8 (A) Chest radiograph demonstrates the characteristic changes in an infant with congenital lobar emphysema (CLE).
Marked overdistention of the left upper lobe caused the mediastinal shift, flattening of the left diaphragm, and likely subsequent
respiratory distress. (B) Bronchogram shows the absence or occlusion of the left upper lobe bronchus, producing the typical findings
in CLE. (C) Operative photograph demonstrates the dramatic herniation of an emphysematous lobe through the thoracotomy
incision.
22 Congenital Bronchopulmonary Malformations 299
THORACOSCOPIC LOBECTOMY
The benefits of thoracoscopy include less postoperative
pain, more rapid recovery, less hospitalization, and an
improved functional and cosmetic result compared to
traditional thoracotomy.59,60 However, despite these
obvious advantages and the development of appropriate
instrumentation for infants, the use of thoracoscopy for
congenital lung lesions has been relatively limited. This
is likely due to the infrequency of these anomalies, and
the technical challenges inherent in learning the tech
nique. Nevertheless, adequate experience has been accu
mulated in a number of centers to validate the approach
and demonstrate safety and efficacy that mimics tradi
tional thoracotomy.59,61
The challenges unique to infant thoracoscopic lobec Lower lobe
tomy can be separated into anesthesia, anatomic, and
technical. The anesthetic challenges relate to single lung Heart
ventilation in infants and require a committed anesthesia FIGURE 22-9 This is the anatomy seen by the surgeon when
staff. Main stem bronchial intubation can be easily the contents of the fissure between the left upper and lower
achieved by the use of a 3-0 micro-cuffed tube introduced lobes are exposed at thoracoscopy. The arteries are visualized
using fluoroscopy.62 This approach is much faster than first within the fissure and the bronchial structures are behind
the arteries. The pulmonary veins exit from the inferior portion
using bronchoscopy to correctly position the endotra of these lobes and drain into the heart. (From Holcomb GW III,
cheal tube. For left-sided lobectomies in particular, it is Georgeson KE, Rothenberg SS. Atlas of Pediatric Laparoscopy and
important to introduce the tube deep enough in the right Thoracoscopy. Philadelphia: Elsevier; 2008.)
300 SECTION III Thoracic
30. Keswani SG, Crombleholme TM, Pawel BR, et al. Prenatal diag 46. Olgac G, Peirovi F, Yilmaz A, et al. Giant carcinoid tumor
nosis and management of mainstem bronchial atresia. Fetal Diagn mimicking pulmonary sequestration. Ann Thorac Surg 2007;84:
Ther 2005;20:748. 13756.
31. Martinez JM, Prat J, Gomez O, et al. Decompression through 47. Priest JR, McDermott MB, Bhatia S, et al. Pleuropulmonary blas
tracheobronchial endoscopy of bronchial atresia presenting as toma: A clinicopathologic study of 50 cases. Cancer 1997;80:
massive pulmonary tumor: A new indication for fetoscopic surgery. 14761.
Fetal Diagn Ther 2012. 48. Westphal FL, Lima LC, Lima Netto JC, et al. Carcinoid
32. Muller CO, Berrebi D, Kheniche A, et al. Is radical lobectomy tumor and pulmonary sequestration. J Bras Pneumol 2012;38:
required in congenital cystic adenomatoid malformation? J Pediatr 1337.
Surg 2012;47:6425. 49. Laberge JM, Puligandla P, Flageole H. Asymptomatic congenital
33. Choudhury SR, Chadha R, Mishra A, et al. Lung resections in lung malformations. Semin Pediatr Surg 2005;14:1633.
children for congenital and acquired lesions. Pediatr Surg Int 50. Samuel M, Burge DM. Management of antenatally diagnosed pul
2007;23:8519. monary sequestration associated with congenital cystic adenoma
34. Lujan M, Bosque M, Mirapeix RM, et al. Late-onset congenital toid malformation. Thorax 1999;54:7016.
cystic adenomatoid malformation of the lung. Embryology, clinical 51. Chien KJ, Huang TC, Lin CC, et al. Early and late outcomes of
symptomatology, diagnostic procedures, therapeutic approach and coil embolization of pulmonary sequestration in children. Circ J
clinical follow-up. Respiration 2002;69:14854. 2009;73:93842.
35. Oliveira C, Himidan S, Pastor AC, et al. Discriminating preopera 52. Johnson SM, Grace N, Edwards MJ, et al. Thoracoscopic segmen
tive features of pleuropulmonary blastomas (PPB) from congenital tectomy for treatment of congenital lung malformations. J Pediatr
cystic adenomatoid malformations (CCAM): A retrospective, age- Surg 2011;46:22659.
matched study. Eur J Pediatr Surg 2011;21:27. 53. Peiry B, De Buys Roessingh A, Francini K, et al. Thoracoscopic
36. Wong A, Vieten D, Singh S, et al. Long-term outcome of asymp segmentectomy: One vessel may hide a second one. J Pediatr Surg
tomatic patients with congenital cystic adenomatoid malformation. 2012;47:e1113.
Pediatr Surg Int 2009;25:47985. 54. Mei-Zahav M, Konen O, Manson D, et al. Is congenital lobar
37. Hancock BJ, Di Lorenzo M, Youssef S, et al. Childhood primary emphysema a surgical disease? J Pediatr Surg 2006;41:105861.
pulmonary neoplasms. J Pediatr Surg 1993;28:11336. 55. Tempe DK, Virmani S, Javetkar S, et al. Congenital lobar emphy
38. Lantuejoul S, Nicholson AG, Sartori G, et al. Mucinous cells in sema: Pitfalls and management. Ann Card Anaesth 2010;13:
type 1 pulmonary congenital cystic adenomatoid malformation as 538.
mucinous bronchioloalveolar carcinoma precursors. Am J Surg 56. Laje P, Liechty KW. Postnatal management and outcome of pre
Pathol 2007;31:9619. natally diagnosed lung lesions. Prenat Diagn 2008;28:61218.
39. Papagiannopoulos KA, Sheppard M, Bush AP, et al. Pleuropulmo 57. Tolg C, Abelin K, Laudenbach V, et al. Open vs. thoracoscopic
nary blastoma: Is prophylactic resection of congenital lung cysts surgical management of bronchogenic cysts. Surg Endosc
effective? Ann Thorac Surg 2001;72:6045. 2005;19:7780.
40. Aziz D, Langer JC, Tuuha SE, et al. Perinatally diagnosed asymp 58. Calzada AP, Wu W, Salvado AR, et al. Poorly differentiated adeno
tomatic congenital cystic adenomatoid malformation: To resect or carcinoma arising from a cervical bronchial cyst. Laryngoscope
not? J Pediatr Surg 2004;39:32934. 2011;121:14468.
41. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from 59. Rothenberg SS. First decades experience with thoracoscopic lobec
CT scans in childhood and subsequent risk of leukaemia and brain tomy in infants and children. J Pediatr Surg 2008;43:405.
tumours: A retrospective cohort study. Lancet 2012;380:499505. 60. Rothenberg SS, Kuenzler KA, Middlesworth W, et al. Thoraco
42. Adzick NS, Flake AW, Crombleholme TM. Management of con scopic lobectomy in infants less than 10kg with prenatally diag
genital lung lesions. Semin Pediatr Surg 2003;12:1016. nosed cystic lung disease. J Laparoendosc Adv Surg Tech A 2011;21:
43. Tsai AY, Liechty KW, Hedrick HL, et al. Outcomes after postnatal 1814.
resection of prenatally diagnosed asymptomatic cystic lung lesions. 61. Vu LT, Farmer DL, Nobuhara KK, et al. Thoracoscopic versus
J Pediatr Surg 2008;43:51317. open resection for congenital cystic adenomatoid malformations of
44. Conran RM, Stocker JT. Extralobar sequestration with frequently the lung. J Pediatr Surg 2008;43:359.
associated congenital cystic adenomatoid malformation, type 2: 62. Cohen DE, McCloskey JJ, Motas D, et al. Fluoroscopic-assisted
Report of 50 cases. Pediatr Dev Pathol 1999;2:45463. endobronchial intubation for single-lung ventilation in infants.
45. Hekelaar N, van Uffelen R, van Vliet AC, et al. Primary Paediatr Anaesth 2011;21:6814.
lymphoepithelioma-like carcinoma within an intralobular pulmo 63. Stocker JT. Cystic lung disease in infants and children. Fetal
nary sequestration. Eur Respir J 2000;16:10257. Pediatr Pathol 2009;28(4):15584.
C H A P T E R 2 3
*
A B
FIGURE 23-2 Ultrasonography and/or CT of the chest are helpful during the initial evaluation of children with a pleural effusion and
possible empyema. (A) In the ultrasound study, note the loculations identified in the pleural fluid. (B) On the CT scan, a large pleural
effusion (asterisk) is noted. Also there is collapse of the underlying lung parenchyma as well as septations (arrow).
be performed effectively with the use of automatic dose group, but similar length of stay.32 While this approach
modulation software that limit the radiation dose.25 may be reasonable in an older child who can tolerate the
Despite this ability to limit radiation exposure with CT procedure with local anesthesia, it would likely not be
scan, consensus statements are clear in their recommen- appropriate in younger children. The British Thoracic
dations for performing CT only when needed, such as Society guidelines recommend a chest tube for cases in
preoperative planning in some cases.6,7 which the first thoracentesis fails to adequately drain the
effusion in order to avoid multiple thoracentesis attempts.6
A retrospective series compared 33 children who under-
Management went chest tube placement on the basis of effusion size
and/or thoracentesis fluid analysis vs 32 who were treated
Parapneumonic Effusion
conservatively with tube thoracostomy only for progres-
After the diagnosis of PPE is made, the first branch in sive symptoms or mediastinal shift.33 The authors found
the management algorithm depends on the nature of the no difference in duration of hospitalization and suggested
fluid. With a free-flowing effusion and no solid compo- frugal use of chest tubes.3 In a series of 405 adult patients,
nents or signs of frank pus, the nature of the intervention 266 had a chest tube smaller than 14 French compared
will depend on the size of the effusion and the symptoms. to 139 with larger tubes.34 There was no difference in the
Classifying the size is difficult to define precisely. ability to drain the effusion. Furthermore, smaller caliber
However, in general, small effusions are defined as having tubes did not hinder the use of fibrinolytics. In a retro-
1cm rim of fluid, moderate effusions have a 12cm spective series of 20 children treated with standard chest
rim, and large effusions have 2cm rim on decubitus tubes compared to 12 treated with pigtail tubes, no
films. A recently published twelve year retrospective outcome differences were found.35 In patients with pleural
study in children classified small effusions as less than a effusions or empyema, we exclusively use 12 French
quarter hemithorax opacification, moderate effusions as Thal-Quick chest tubes (Cook Critical Care, Blooming-
a quarter to a half opacification, and large effusions as ton, Indiana, USA) that are inserted using the Seldinger
more than half opacification based on upright films.30 In technique (Fig. 23-3). We have not felt it necessary to use
this study, the authors found that small and most moder- image guidance in the majority of patients.
ately sized effusions could be effectively managed without
drainage and without an increase in the length of hospi- Empyema
talization or other complications. The authors suggest
that interventions should be based on symptoms, not the Empyema is diagnosed by identifying solid components
size of the effusion alone. in the pleural fluid on imaging studies or pus during
Symptoms leading to intervention generally are thoracentesis or tube catheter placement. The definitive
feeding intolerance, tachypnea, and an increasing oxygen management for empyema has traditionally been opera-
requirement. A retrospective case series in children found tive debridement, which is currently performed via video-
respiratory distress on presentation was related to pro- assisted thoracoscopy surgery (VATS).3640 VATS has
longed stay and a higher likelihood for intervention.31 resulted in earlier and more complete resolution of
After deciding to drain the effusion, options include empyema than chest tube drainage alone in both retro-
single or multiple thoracentesis versus tube thoracostomy spective and prospective studies, translating into shorter
or catheter drainage. A prospective, nonrandomized hospitalization with VATS as the initial therapy.4144 A
pediatric series compared treatment with repeated ultra- retrospective series of 89 children undergoing primary
sound-guided needle aspirations vs tube thoracostomy. thoracoscopic debridement/decortication found a 12%
There was a mean 2.4 drainages/patient in the aspiration risk for needing another procedure to address ongoing
23 Acquired Lesions of the Lung and Pleura 305
disease or a complication.45 However, the superiority of over a 48-hour period. The results were highly concord-
operative mechanical debridement as a definitive man- ant as both studies found no difference in duration of
agement strategy has been increasingly challenged by hospitalization between the two interventions. The
chemical debridement with fibrinolysis. common parameters between the two studies are outlined
Examples of fibrinolytics include urokinase, streptoki- in Table 23-2. The USA study found no difference in days
nase, and tissue plasminogen activator (tPA). Since fibrin of tube drainage, days of fever, doses of analgesics, or
is a predominant component of the extracellular matrix oxygen requirements.54 Both studies documented thora-
upon which septations and solid debris develop, fibri- coscopic debridement was more expensive and both uti-
nolysis has been shown to be superior to tube thoracos- lized an intention-to-treat analysis so the length of stay
tomy alone in retrospective and prospective studies.4652 and total charges included the patients who failed fibri-
These studies include direct comparisons between the nolysis and subsequently required VATS. The failure rate
two treatment options as well as the use of fibrinolytic for fibrinolysis was 16.6% in both studies. This failure
therapy after failure of tube thoracostomy. rate was similar to previous studies investigating the utility
Two prospective, randomized trials have been con- of fibrinolysis.48,5559 An example of a first-line fibrinolytic
ducted independently comparing fibrinolysis to VATS for approach is outlined Figure 23-4. A similar algorithm has
empyema in children.53,54 The studies were conducted been proposed based on a review of the literature.60
in the UK and USA in 60 and 36 patients, respectively. One of the groups that performed the prospective
Both studies compared the instillation of three intratho- randomized trial comparing fibrinolysis to thoracoscopic
racic doses of fibrinolytic agents to thoracoscopy as the debridement recently reported their data using an
initial therapy for empyema. The first fibrinolytic dose in evidence-based algorithm with primary fibrinolytic
both studies was given at the time of diagnosis and/or therapy. One hundred and two consecutive patients were
chest tube insertion followed by two additional doses in treated with fibrinolysis following completion of the
24-hour increments to complete the fibrinolytic course prospective randomized trial and 16 patients (15.7%)
EMPYEMA
(Loculations or > 10,000 WBC/L)
Ultrasound or CT
TABLE 23-2 Common Outcome Variables Reported between the Two Prospective Trials Comparing
Fibrinolysis to VATS in Children
Study United Kingdom 200653 United States 200954
Study variable Urokinase VATS P value tPA VATS P value
Mean length of stay (days) 6 6 0.33 6.8 6.9 0.96
Mean procedure chargesa 9.1K 11.3K <0.001 7.5K 11.6K 0.01
Failure rate for fibrinolysis 16.6% 16.6%
a
Charges are in thousands of British pounds and thousands of ultrasound dollars.
VATS, video-assisted thoracoscopic surgery; tPA, tissue plasminogen activator.
306 SECTION III Thoracic
LUNG ABSCESS
Pulmonary abscess is often assumed to develop as a
primary process in a previously normal lung, usually as a
result of a necrotizing pneumonia. However, a pulmo-
nary abscess in a child without an antecedent history
ought to be considered as a secondary abscess which
arises in an infected pulmonary anomaly such as a cystic
pulmonary adenomatoid malformation, bronchogenic
cyst, or foreign body. Most primary lung abscesses are
located in the posterior segment of the right upper lobe
and the superior segments of the right and left lower
lobes (Fig. 23-5). In contrast, secondary and/or recurrent
collections may be found in multiple locations with no B
specific anatomic predilection.
In the patient with known pneumonia, the non- FIGURE 23-5 (A) This young infant was found to have this lung
responding patient who develops a suspicious lesion on abscess in the right lower lobe on chest radiograph. Note the
chest film should undergo CT to evaluate for an abscess. air-fluid level (arrow). (B) The lesion is seen on the CT as well.
Workup did not reveal an associated congenital pulmonary
The treatment of a lung abscess in an infant or child airway malformation and she recovered with antibiotic therapy.
follows the same basic principles of postural drainage and
pulmonary toilet used in adults, but it is more often inef-
fective, secondary to the small size of the airway.62,63 PNEUMATOCELE
In general, an operation should be avoided as abscesses
can usually be successfully treated with antibiotics Pneumatoceles are thin-walled, air-filled, intraparenchy-
alone.64,65 CT-guided drainage or catheter placement is mal pulmonary cysts. They typically occur secondary to
usually needed if the lesion is peripheral and not con- an underlying bacterial pneumonia, a treated abscess, or
nected to the airway, .6668 Retrospective data suggests as a result of trauma. Pneumatoceles are the result of a
that drainage shortens hospitalization and facilitates severe inflammatory reaction and the subsequent destruc-
earlier recovery.69 A recent series of 11 children with tion of the alveolar and interstitial architecture. With an
pulmonary abscess treated with thoracoscopic drainage infectious etiology, the release of bacterial exotoxins has
fared well without complications which may be a good been postulated.72 Although pneumatoceles have been
option when less invasive maneuvers fail.70 Alternatively, associated with a variety of underlying bacterial organ-
pulmonary resection may be required for abscesses that isms, the majority appear to be the result of staphylococ-
are more centrally located and resistant to medical man- cal pneumonia.7274 Other pathogens that have been
agement.62,71 Patients with fungal isolates and immuno- identified as being associated with pneumatocele forma-
compromised patients generally require early and tion include Streptococcus, Haemophilus influenzae,
aggressive pulmonary resection. However, as a general Klebsiella, Escherichia coli, and Pseudomonas. In addition,
statement, patience should be employed in managing pneumatoceles have been found in cases of pulmonary
pulmonary abscesses. tuberculosis and measles.73
23 Acquired Lesions of the Lung and Pleura 307
A B
FIGURE 23-6 (A) Chest radiograph demonstrating the classic appearance of bronchiectasis in a pediatric patient with cystic fibrosis.
(B) Magnified view of the patient demonstrating honeycombed appearance.
the most common cause is an injury to the thoracic duct the diaphragm has been shown to be a useful technique
or a major tributary. The incidence of chyle leak has been in patients with a traumatic leak.100,101 Others have
reported as high as 1% after cardiac operations in infants described direct suture of the area of chylous leak fol-
and children.92 lowed by the application of fibrin glue.102 In adults, a
minimally invasive technique of percutaneous injection
of the cisterna chyli with platinum coil embolization of
Presentation and Diagnosis the thoracic duct has been shown to be successful in over
As with any pleural effusion, chylothorax can present two-thirds of patients with high-output chylothorax in
with respiratory symptoms. Congenital cases may be whom nonoperative management has failed.103,104 In cases
suspected during routine prenatal ultrasound. In postop- that are refractory after an operation, use of a pleuro-
erative patients, it will present with milky drainage from peritoneal shunt has been described (Fig. 23-8).105 In
the chest drain/tube. The drainage may seem like normal these patients, the chyle in the pleural space is manually
pleural fluid until enteral nutrition is resumed and the pumped into the peritoneal cavity where it is absorbed,
drainage becomes chylous. Analysis of the fluid confirms presumably into the venous system. These shunts can
the diagnosis. Chyle typically demonstrates a total fat remain open for several months until the chylous leak
content greater than 400mg/dL, triglycerides greater seals.
than 200mg/dL, or a specific gravity greater than 1.012.
In addition, Gram stain demonstrates the presence of
more than 90% lymphocytes and Sudan red staining may DIFFUSE INTERSTITIAL DISEASE
reveal the presence of chylomicrons.93
Pseudochylothorax (also termed cholesterol pleurisy The interstitium of the lung is the tissue around and
or chyliform effusion) is a rare condition that is charac- between the airway and vascular system. A persistent lung
terized by a cholesterol-rich pleural effusion and is com- injury results in a reparative process which causes scar-
monly associated with chronic inflammatory disorders ring and inflammation. The lung may be permanently
such as tuberculosis or rheumatoid arthritis. These are damaged, with inflamed interstitial tissue replacing the
often long-standing effusions which are distinguished normal capillaries, alveoli, and healthy interstitium. This
from chylothorax by the lack of triglycerides and condition is known as chronic interstitial lung disease
chylomicrons. (ILD). It may be the result of myriad processes, some of
which are listed in Table 23-4.106108 The clinical conse-
quence is restrictive lung physiology and abnormal gas
Management exchange which produces considerable morbidity and
There are physiologic consequences from the chylotho- mortality. The clinical disease patterns range from a
rax. Protein and fat losses can result in acute malnutri- chronic, slowly progressive picture in a relatively stable
tion. Lymphocyte losses result in immunosuppression. patient to one of acute pulmonary decompensation,
The net fluid losses can cause dehydration. Therefore, it requiring emergency life-saving maneuvers.
is important to understand these losses so vigorous moni- The role of the surgeon is to help establish the
toring and replacement can occur concomitant with diagnosis, usually with a lung biopsy, after imaging
maneuvers to stop the leak. Initially, nonoperative maneu- demonstrates a diffuse pulmonary process (Fig. 23-9).
vers should be attempted based on the goals of reducing
the amount of chyle produced while still providing ade-
quate nutrition. This begins with limiting fat intake. As
medium-chain fatty acids are carried through the portal TABLE 23-4 Infectious and Noninfectious
venous system (as opposed to the intestinal lymphatic Processes Associated with
network), it is reasonable to start with a fat-restricted diet the Development of Chronic
rich in medium-chain fatty acids. The next step would be Interstitial Lung Disease
to stop oral intake and begin total parenteral nutrition.
Infectious Noninfectious
As many as 80% of patients respond to this management
strategy.92 Pneumocystis Hypersensitivity pneumonitis
In addition to dietary manipulations, several authors Cryptococcus Sarcoidosis
have reported success with the use of somatostatin Aspergillus Neoplasms
analogs, such as octreotide, whether the chyle leak is Streptococcus Systemic lupus erythematosus
spontaneous or post-traumatic.9498 Some authors recom- Chlamydia Graft-vs.-host disease
mend utilizing octreotide early in the plan of care.97 Mycoplasma pneumoniae Radiation pneumonitis
Nonoperative therapy is typically recommended for Rickettsia Adult respiratory distress
one to two weeks prior to considering operative options.93 Adenovirus syndrome
The goal of the operation begins with stopping the leak. Parainfluenzavirus Aspiration pneumonitis
(gastroesophageal reflux
This is straightforward if the leak is visualized and can be Respiratory syncytial virus
disease)
closed or obliterated. Thoracic duct ligation proximal to Cytomegalovirus
Chemotherapeutic agents
the leak is usually curative. If neither of these options can Varicella-zoster virus
Fat embolism
be accomplished, pleurodesis can be attempted.99 These Herpes simplex virus
Allergic alveolitis
cases can be approached with thoracoscopy. Right thora- Pulmonary hemosiderosis
coscopy with occlusion of the thoracic duct as it crosses
310 SECTION III Thoracic
30
2
1
A B
C D
E F
G H
FIGURE 23-8 Insertion of pleuroperitoneal shunt. (A) The affected hemithorax is elevated 30. The two incisions are planned to allow
the pump chamber to rest on the costal margin. (B) A small incision is made over the rib in the anterior axillary line, and a deep
subcutaneous pocket is created inferiorly. (C) Insertion of pleuroperitoneal shunt into the pleural space is done with a large curved
clamp. The pleural catheter is tunneled 23cm and bluntly passed through the intercostal space. The catheter must be carefully
passed through the intercostal muscle at an angle to avoid kinking. (D) A second small incision is made overlying the rectus muscle,
and the peritoneal catheter is tunneled through this incision. The distal end of the shunt device is delivered to the second incision,
as shown. The pumping chamber is drawn into the subcutaneous pocket by traction on the peritoneal catheter. (E) The flow of chyle
is confirmed before the distal catheter is inserted into the peritoneum. (F,G) A purse-string suture is used to secure the peritoneal
catheter at the level of the posterior rectus fascia. (H) Both incisions should be closed with an absorbable suture, leaving a totally
implanted system. (Adapted from Murphy M, Newman B, Rodgers B. Pleuroperitoneal shunts in the management of persistent chylothorax.
Ann Thorac Surg 1989;48:195200.)
23 Acquired Lesions of the Lung and Pleura 311
20. Schultz KD, Fan L, Pinsky J, et al. The changing face of pleural 45. Freitas S, Fraga JC, Canani F. Thoracoscopy in children with
empyemas in children: Epidemiology and management. Pediatrics complicated parapneumonic pleural effusion at the fibrinopuru-
2004;113:173540. lent stage: A multi-institutional study. J Bras Pneumol 2009;35:
21. King S, Thomson A. Radiological perspectives in empyema. Br 6608.
Med Bull 2002;61:20314. 46. Yao CT, Wu JM, Liu CC, et al. Treatment of complicated para-
22. Brixey AG, Luo Y, Skouras V, et al. The efficacy of chest radio- pneumonic pleural effusion with intrapleural streptokinase in
graphs in detecting parapneumonic effusions. Respirology children. Chest 2004;125:56671.
2011;16:10004. 47. Ekingen G, Guvenc BH, Sozubir S, et al. Fibrinolytic treatment
23. Balik M, Plasil P, Waldauf P, et al. Ultrasound estimation of of complicated pediatric thoracic empyemas with intrapleural
volume of pleural fluid in mechanically ventilated patients. Inten- streptokinase. Eur J Cardiothorac Surg 2004;26:5037.
sive Care Med 2006;32:31821. 48. Misthos P, Sepsas E, Konstantinou M, et al. Early use of intrap-
24. Eibenberger KL, Dock WI, Ammann ME, et al. Quantification leural fibrinolytics in the management of postpneumonic
of pleural effusions: Sonography versus radiography. Radiology empyema. A prospective study. Eur J Cardiothorac Surg
1994;191:6814. 2005;28:599603.
25. Calder A, Owens CM. Imaging of parapneumonic pleural effu- 49. Kili N, Celebi S, Grpinar A, et al. Management of thoracic
sions and empyema in children. Pediatr Radiol 2009;39:52737. empyema in children. Pediatr Surg Int 2002;18:213.
26. Kurian J, Levin TL, Han BK, et al. Comparison of ultrasound 50. Cochran JB, Tecklenburg FW, Turner RB. Intrapleural instillation
and CT in the evaluation of pneumonia complicated by parapneu- of fibrinolytic agents for treatment of pleural empyema. Pediatr
monic effusion in children. AJR Am J Roentgenol 2009;193: Crit Care Med 2003;4:3943.
164854. 51. Ulku R, Onat S, Kili N. Intrapleural fibrinolytic treatment of
27. Pillai D, Song X, Pastor W, et al. Implementation and impact of multiloculated pediatric empyemas. Minerva Pediatr 2004;56:
a consensus diagnostic and management algorithm for compli- 41923.
cated pneumonia in children. J Investig Med 2011;59:12217. 52. Bouros D, Antoniou KM, Chalkiadakis G, et al. The role of video-
28. Shomaker KL, Weiner T, Esther CR Jr. Impact of an evidence- assisted thoracoscopic surgery in the treatment of parapneumonic
based algorithm on quality of care in pediatric parapneumonic empyema after the failure of fibrinolytics. Surg Endosc 2002;16:
effusion and empyema. Pediatr Pulmonol 2011;46:7228. 1514.
29. Brenner DJ, Hall EJ. Computed tomographyan increasing 53. Sonnappa S, Cohen G, Owens CM, et al. Comparison of uroki-
source of radiation exposure. N Engl J Med 2007;357:227784. nase and video-assisted thoracoscopic surgery for treatment of
30. Carter E, Waldhausen J, Zhang W, et al. Management of children childhood empyema. Am J Respir Crit Care Med 2006;174:
with empyema: Pleural drainage is not always necessary. Pediatr 2217.
Pulmonol 2010;45:47580. 54. St. Peter SD, Tsao K, Spilde TL, et al. Thoracoscopic decortica-
31. Soares P, Barreira J, Pissarra S, et al. Pediatric parapneumonic tion vs tube thoracostomy with fibrinolysis for empyema in
pleural effusions: Experience in a university central hospital. Rev children: A prospective, randomized trial. J Pediatr Surg 2009;
Port Pneumol 2009;15: 24159. 44:10611.
32. Shoseyov D, Bibi H, Shatzberg G, et al. Short-term course and 55. Zuckerman DA, Reed MF, Howington JA, et al. Efficacy of intra-
outcome of treatments of pleural empyema in pediatric patients: pleural tissue-type plasminogen activator in the treatment of locu-
Repeated ultrasound-guided needle thoracocentesis vs chest tube lated parapneumonic effusions. J Vasc Interv Radiol
drainage. Chest 2002;121:83640. 2009;20:10669.
33. Epaud R, Aubertin G, Larroquet M, et al. Conservative use of 56. Cohen E, Weinstein M, Fisman DN. Cost-effectiveness of com-
chest tube insertion in children with pleural effusion. Pediatr Surg peting strategies for the treatment of pediatric empyema. Pediat-
Int 2006;22:35762. rics 2008;121:e12501257.
34. Rahman NM, Maskell NA, Davies CW, et al. The relationship 57. Kalfa N, Allal H, Lopez M, et al. Thoracoscopy in pediatric
between chest tube size and clinical outcome in pleural infection. pleural empyema: A prospective study of prognostic factors. J
Chest 2010;137:53643. Pediatr Surg 2006;41:17327.
35. Lin CH, Lin WC, Chang JS. Comparison of pigtail catheter with 58. Bouros D, Schiza S, Tzanakis N, et al. Intraplerual urokinase
chest tube for drainage of parapneumonic effusion in children. versus normal saline in the treatment of complicated parapneu-
Pediatr Neonatol 2011;52:33741. monic effusions and empyema. A randomized, double-blind study.
36. Wurnig PN, Wittmer V, Pridun NS, et al. Video-assisted thoracic Am J Respir Crit Care Med 1999;159:3742.
surgery for pleural empyema. Ann Thorac Surg 2006;81: 59. Diacon AH, Theron J, Schuurmans MM, et al. Intrapleural strep-
30913. tokinase for empyema and complicated parapneumonic effusions.
37. Hope WW, Bolton WD, Stephenson JE. The utility and timing Am J Respir Crit Care Med 2004;170:4953.
of surgical intervention for parapneumonic empyema in the era 60. Proesmans M, De Boeck K. Clinical practice: Treatment of child-
of video-assisted thoracoscopy. Am Surg 2005;71:51214. hood empyema. Eur J Pediatr 2009;168:63945.
38. Olgac G, Fazlioglu M, Kutlu CA. VATS decortication in patients 61. Gasior AC, Knott EM, Sharp SW, et al. Experience with an
with stage 3 empyema. Thorac Cardiovasc Surg 2005;53:1820. evidence-based protocol using fibrinolysis as first-line treatment
39. Cheng G, Vintch JR. A retrospective analysis of the management for empyema in children. J Pediatr Surg 2013;48:131215.
of parapneumonic empyemas in a county teaching facility from 62. Kosloske AM, Ball WS, Butler C, et al. Drainage of pediatric lung
1992 to 2004. Chest 2005;128:328490. abscess by cough, catheter or complete resection. J Pediatr Surg
40. Tsao K, St Peter SD, Sharp SW, et al. Current application of 1986;21:596600.
thoracoscopy in children. J Laparoendosc Adv Surg Tech A 63. Tseng Y, Wu M, Lin M. Surgery for lung abscess in immunocom-
2008;18:1315. petent and immunocompromised children. J Pediatr Surg
41. Kurt BA, Winterhalter KM, Connors RH, et al. Therapy of para- 2001;36:4703.
pneumonic effusions in children: Video assisted thoracoscopic 64. Estera AS, Platt MR, Mills LJ, et al. Primary lung abscess.
surgery versus conventional thoracostomy drainage. Pediatrics J Thorac Cardiovasc Surg 1980;79: 27582.
2006;118:e547553. 65. Chidi CC, Mendelsohn HJ. Lung abscess. A study of the results
42. Gates RL, Hogan M, Weinstein S, et al. Drainage, fibrinolytics, of treatment based on 90 consecutive cases. J Thorac Cardiovasc
or surgery: A comparison of treatment options in pediatric Surg 1974;68:16872.
empyema. J Pediatr Surg 2004;39:163842. 66. Lorenzo RL, Bradford BF, Black J, et al. Lung abscesses in chil-
43. Aziz A, Healey JM, Qureshi F, et al. Comparative analysis of chest dren: Diagnostic and therapeutic needle aspiration. Radiology
tube thoracostomy and video-assisted thoracoscopic surgery in 1985;157: 7980.
empyema and parapneumonic effusion associated with pneumonia 67. Ball BS, Bisset GS, Towbin RB. Percutaneous drainage of chest
in children. Surg Infect (Larchmt) 2008;9:31723 abscesses in children. Radiology 1989;171: 4314.
44. Chiu CY, Wong KS, Huang YC, et al. Echo-guided management 68. Hoffer FA, Bloom DA, Colin AA, et al. Lung abscess versus
of complicated parapneumonic effusion in children. Pediatr Pul- necrotizing pneumonia: Implications for interventional therapy.
monol 2006;41:122632. Pediatr Radiol 1999;29:8791.
314 SECTION III Thoracic
69. Patradoon-Ho P, Fitzgerald DA. Lung abscesses in children. Pae- 95. Luca R, Bini R, Chessa M, et al. The effectiveness of octreotide
diatr Respir Rev 2007;8:7784. in the treatment of postoperative chylothorax. Eur J Pediatr
70. Nagasawa KK, Johnson SM. Thoracoscopic treatment of pediat- 2002;161:14950.
ric lung abscesses J Pediatr Surg 2010;45:5748. 96. Rodgers B, Michalsky MP, Kattwinkel J. The use of octreotide to
71. Ayed AK, Al-Rowayeh A. Lung resection in children for infectious treat congenital chylothorax. J Pediatr Surg 2006;41:8457.
pulmonary diseases. Pediatr Surg Int 2005;21:6048. 97. Au M, Weber TR, Flemmin RE. Successful use of octreotide
72. Quigley MJ, Fraser RS. Pulmonary pneumatocele: Pathology and in a case of neonatal chylothorax. J Pediatr Surg 2003;38:
pathogenesis. AJR Am J Roentgenol 1988;150:12757. 11067.
73. Oviawe O, Ogundipe O. Pneumatoceles associated with pneumo- 98. Benedix F, Schulz HU, Scheidbach H, et al. Successful conserva-
nia: Incidence and clinical course in Nigerian children. Trop tive treatment of chylothorax following oesophagectomy - a clini-
Geogr Med 1985;37:2649. cal algorithm. S Afr J Surg 2010;48:868.
74. Glustein JZ, Kaplan M. Enterobacter cloacae causing pneuma- 99. Valentine VG, Raffin TA. The management of chylothorax. Chest
tocele in a neonate. Acta Pediatr 1994;83:9901. 1992;102:58691.
75. Zuhdi MK, Bradley JS, Spear RM, et al. Fatal air embolism as a 100. Buchan K, Amir-Reza H, Ritchie A. Thoracoscopic thoracic duct
complication of staphylococcal pneumonia with pneumatoceles. ligation for traumatic chylothorax. Ann Thorac Surg 2001;
Pediatr Infect Dis J 1995;14:81112. 72:13667.
76. Zuhdi MK, Spear R, Worthen M, et al. Percutaneous catheter 101. Graham DD, McGahren ED, Tribble CG, et al. Use of video-
drainage of tension pneumatocele, secondarily infected pneuma- assisted thoracic surgery in the treatment of chylothorax. Ann
tocele and lung abscess in children. Crit Care Med 1996;42: Thorac Surg 1994;57:150711.
3303. 102. Fahimi H, Casselman F, Mariani M, et al. Current management
77. Kogutt M, Lutrell C, Pulau F, et al. Decompression of pneuma- of postoperative chylothorax. Ann Thorac Surg 2001;71:44851.
tocele in a neonate by percutaneous catheter placement. Pediatr 103. Cope C. Management of chylothorax via percutaneous emboliza-
Radiol 1999;29:4889. tion. Curr Opin Pulmon Med 2004;10:31114.
78. Lannec RTH. De lAuscultation Mdiat on Traite du Diagnos- 104. Cope C, Kaiser LR. Management of unremitting chylothorax by
tic des Maladies des Poumons et du Coeur, Fond Principalement percutaneous embolization and blockage of retroperitoneal lym-
sur ce Noveau Moyer dExploration. Paris: Brosson et Claude; phatic vessels in 42 patients. J Vasc Interv Radiol 2002;13:
1819. 113948.
79. Reid LM. Reduction in bronchial subdivision in bronchiectasis. 105. Wolff AB, Silen ML, Kokoska ER, et al. Treatment of refractory
Thorax 1950;5:23347. chylothorax with externalized pleuroperitoneal shunts in children.
80. Rademacher J, Welte T. Bronchiectasis-Diagnosis and Treatment. Ann Thorac Surg 1999;68:10537.
Dtsch Arztebl Int 2011;108: 80915 106. Turner-Warwick M. Interstitial lung disease. Semin Respir Med
81. McGuinnea G, Naidich DP. CT of airways disease and bron- 1984;6:1102.
chiectasis. Radiol Clin North Am 2002;40:119. 107. Fan L, Langston C. Chronic interstitial lung disease in children.
82. Agasthian T, Deschamps C, Trastek VF, et al. Surgical manage- Pediatr Pulmonol 1993;16:18496.
ment of bronchiectasis. Ann Thorac Surg 1996;62:97680. 108. Bokulic RE, Hilman BC. Interstitial lung disease in children.
83. Goeminne P, Dupont L. Non-cystic fibrosis bronchiectasis: Diag- Pediatr Clin North Am 1994;41:54367.
nosis and management in 21st century. Postgrad Med J 2010;86: 109. Langston C, Patterson K, Dishop MK, et al. Child Pathology
493501. Co-operative Group. A protocol for the handling of tissue
84. Kumar NA, Nguyen B, Maki D. Bronchiectasis: Current clinical obtained by operative lung biopsy: Recommendations of the child
and imaging concepts. Semin Roentgenol 2001;36:4150. pathology co-operative group. Pediatr Dev Pathol 2006;9:
85. Smevik B. Complementary investigations in bronchiectasis in 17380.
children. Monaldi Arch Chest Dis 2000;55:4206. 110. Wagner RB, Johnston MR. Middle lobe syndrome. Ann Thorac
86. Ashour M, Al-Kattan K, Rafay MA, et al. Current surgical therapy Surg 1983;35:67986.
for bronchiectasis. World J Surg 1999;23:10961104. 111. Saha SP, Mayo P, Long GA, et al. Middle lobe syndrome: Diag-
87. Haciibrahimoglu G, Fazliogu M, Olcmen A, et al. Surgical man- nosis and management. Ann Thorac Surg 1982;33:2831.
agement of childhood bronchiectasis due to infectious disease. 112. Yung K, Aspestrand F, Kolbenstvedt A. High-resolution CT and
Gen Thorac Surg 2004;127:13615. bronchography in the assessment of bronchiectasis. Acta Radiol
88. Otgn I, Karnak I, Tanyel FC, et al. Surgical treatment of bron- 1991;32:43941.
chiectasis in children. J Pediatr Surg 2004;39:15326. 113. Sehitoqullari A, Sayir F, Cobanaglu U, et al. Surgical treatment
89. Rothenberg SS, Kuenzler KA, Middlesworth W. Thoracoscopic of right middle lobe syndrome in children. Ann Thorac Med
lobectomy for severe bronchiectasis in children. J Laparoendosc 2012;7:811.
Adv Surg Tech A 2009;19:5557. 114. Healthcare Cost and Utilization Project (HCUP). Kids Inpatient
90. Dubin P, King I, Gallagher P. Congenital chylothorax. Curr Opin Database (KID). 1997, 2000, 2003, 2006. Available at: http://
Pediatr 2000;12:5059. www.hcup-us.ahrq.gov/kidoverview.jsp. Accessed October 15,
91. Beghatti M, La Scala G, Belli D, et al. Etiology and management 2010.
of pediatric chylothorax. J Pediatr 2000;8:1368. 115. United States Census Bureau. Your Gateway to Census 2000.
92. Allen EM, Van Heeckeren DW, Spector ML, et al. Management Available at http://www.census.gov/main/www/cen2000.html.
of nutritional and infectious complications of postoperative chy- Accessed October 15, 2010.
lothorax in children. J Pediatr Surg 1991;26:116974. 116. Laituri CA, Valusek PA, Rivard DC, et al. The utility of computed
93. Bond SJ, Guzzetta PC, Snyder ML, et al. Management of pedi- tomography in the management of patients with spontaneous
atric postoperative chylothorax. Ann Thoracic Surg 1993;56: pneumothorax. J Pediatr Surg 2011;46:15235.
46973. 117. Cardillo G, Carleo F, Giunti R, et al. Videothoracoscopic talc
94. Sharkey AJ, Rao JN. The successful use of octreotide in the treat- poudrage in primary spontaneous pneumothorax: A single-
ment of traumatic chylothorax. Tex Heart Inst J 2012;39: institution experience in 861 cases. J Thorac Cardiovasc Surg
42830. 2006;131:3228.
C H A P T E R 2 4
The management and treatment of congenital dia- types of structural chromosomal abnormalities including
phragmatic hernia (CDH) remains a challenge. Despite deletions, translocations, and trisomies have been
advances in prenatal diagnosis, operative management, identified.1621 In addition, a gene distal to the 15q21
and neonatal critical care, infants born with CDH still locus has been identified for the normal development of
have a significant mortality and long-term disability. The the diaphragm.17,18
relatively rare incidence of the disease and wide spectrum CDH has been associated with over 70 syndromes.19
of disease severity results in clinical challenges for indi- In some cases, the diaphragmatic malformation is the
vidual practitioners and institutions. The large majority predominant defect, as in Fryns and DonnaiBarrow syn-
of centers will treat less than 10 CDH infants per year.1 dromes.20,21 In other syndromes, CDH only occurs in a
Thus, broad clinical experience, especially in cases of the small percentage, but still greater than the general popu-
most severe disease, is difficult to achieve. lation, as in SimpsonGolabiBehmel and Beckwith
The morbidity and mortality associated with CDH is Wiedermann syndromes. The inheritance patterns for
largely due to pulmonary hypoplasia and pulmonary vas- these syndromes include dominant and recessive as well
cular hypertension (PHTN).2,3 Over the last 25 years, as autosomal and X-linked variants.22 Identifying the
clinical efforts to avoid lung injury, including extracor- patterns of non-hernia-related anomalies associated with
poreal membrane oxygenation (ECMO), high-frequency CDH and recognizing genetic syndromes help determine
oscillating ventilation (HFOV), and permissive hyper- the prognosis, treatments, counseling, and outcomes.16 If
capnia, have improved overall survival, but significant the antenatal diagnosis of CDH is made, amniocentesis
variation remains amongst institutions.2,4 Reported sur- with karyotype and chromosomal analysis is indicated.
vival ranges from 5090%.3,5
Associated Anomalies
EPIDEMIOLOGY The posterolateral Bochdalek hernia accounts for 90%
of all diaphragmatic hernia cases.23 The remainder are
The incidence of CDH has been reported as high as 1 in the anterior Morgagni hernia along with defects of the
2000 births.6 In the USA, approximately 1,000 CDH central septum transversum. The majority of posterola-
infants are born with a prevalence of 2.4 per 10,000 live teral CDH are left sided (85%), with right sided (13%)
births.6,7 One-third of infants with CDH die as stillbirths, and bilateral (2%) accounting for the rest.2325
often associated with other congenital anomalies.8 Approximately 50% of CDH are isolated defects with
However, the overall incidence of CDH may be under- the others associated with anomalies of the cardiovascular
estimated. Proportions of fetuses are prenatally diag- (27.5%), urogenital (17.7%), musculoskeletal (15.7%),
nosed with CDH and will die in utero or shortly after and central nervous (9.8%) systems (CNS).26 Many con-
birth. Thus, many may never been seen or accounted for ditions, such as lung hypoplasia, intestinal malrotation,
in a tertiary referral center. Presumed to be the most some cardiac malformations, and patent ductus arteriosus
severe of all CDH infants, these patients contribute to (PDA) are considered to be consequences of the dia-
the hidden mortality of CDH.912 phragmatic defect. Non-CDH-related defects are esti-
Infants with isolated CDH are typically male and one- mated to occur in 4060% of cases and can involve the
third are associated with a major congenital anomaly.7 cardiovascular, CNS, gastrointestinal, and genitourinary
Approximately 80% are left sided. Bilateral defects are systems, and may be a consequence of an underlying field
rare and are associated with other major anomalies.13 defect of unknown etiology.27,28
Although the exact etiology remains unknown, mothers The impact of associated anomalies on prognosis and
that are thin or underweight may have an increased risk outcome cannot be overstated. Ninety-five per cent of
of bearing an infant with CDH.14 stillborn infants with CDH have an associated major
anomaly.29 Greater than 60% of infants who do not
survive the immediate neonatal period have associated
Genetics anomalies.30 In contrast, infants that survive preoperative
CDH is no longer thought of as a sporadic isolated stabilization and come to operative repair have less than
anomaly in all cases. A first-degree relative has an 10% additional anomalies.30 Although the severity of
expected occurrence rate of approximately 2%.15 All pulmonary hypoplasia and hypertension are the major
315
316 SECTION III Thoracic
determinants of overall survival, there is a significant have documented expenses as high as $250,000 per CDH
survival advantage for infants with isolated CDH (43.7% case with an estimated annual cost of $230 million, and
vs 7.1%).27 Due to this dismal outcome, the emphasis on estimated cost of $98,000 for non-ECMO survivors com-
detailed and accurate prenatal diagnosis has influenced pared with $365,000 for ECMO survivors.35
the management and treatment of CDH. Twenty per
cent of prenatally diagnosed CDH infants have chromo-
somal anomalies, with 70% having an associated struc- EMBRYOLOGY
tural malformation. In contrast, only 35% of postnatally
diagnosed CDH infants have an associated anomaly.27 Diaphragm development and
This difference may be the result of lethal chromosomal CDH pathogenesis
anomalies and/or may reflect parental decisions for ter-
mination in high-risk infants with anomalies that portend The development of the human diaphragm is a complex,
significant morbidity. multicellular, multi-tissue interaction that is poorly
Common cardiac defects include atrial septal defects understood. Precursors to the diaphragm begin to form
(ASDs), ventricular septal defects (VSDs), and other during the fourth week of gestation. Historically, the
outflow tract anomalies (transposition of the great vessels, diaphragm was thought to develop from the fusion of
tetralogy of Fallot, double-outlet right ventricle, and four embryonic components: anteriorly by the septum
aortic coarctation).3032 In a review of 4,268 infants with transversum, dorsolaterally by the pleuroperitoneal
CDH, approximately 18% of infants had an associated folds (PPF), dorsally by the crura from the esophageal
cardiac defect. Major cardiac lesions (excluding patent mesentery, and posteriorly by the body wall mesoderm
foramen ovale, atrial septal defects, PDA) was 8% with (Fig. 24-1).36,37 As the embryo begins to form, the septum
an overall survival of 36% compared to infants with transversum migrates dorsally and separates the pleuro-
minor anomalies (67% survival) and those without cardiac pericardial cavity from the peritoneal cavity. At this point,
defects (73% survival).33 the pleural and peritoneal cavities still communicate. The
septum transversum interacts with the PPF and mesoder-
mal tissue surrounding the developing esophagus and
Cost other foregut structures, resulting in the formation of
Despite improvements in outcomes and advances in primitive diaphragmatic structures. Bound by pericardial,
treatment, the cost of caring for CDH infants continues pleural, and peritoneal folds, the paired PPFs now sepa-
to increase. Data from the Kids Inpatient Database has rate the pleuropericardial and peritoneal cavities. Even-
projected the annual national costs to range between tually, the septum transversum develops into the central
$264 and $400 million based on 60% overall survival.34 tendon.36,37 As the PPF develops during the sixth week
The utilization of ECMO was the highest single factor of gestation, concurrently, the pleuroperitoneal mem-
associated with cost with a 2.4-fold increase in expendi- branes close and separate the pleural and abdominal cavi-
tures from 1997 to 2006. The highest median cost were ties by the eighth week of gestation. Typically, the right
ECMO patients at $156,499.90/patient, constituting side closes before the left. Ultimately, the phrenic axons
28.5% of the total national costs.34 Single-center reports and myogenic cells destined for neuromuscularization
Pleural canals
Foregut
Aorta
Sinus
venosus
Mesentery of
esophagus
Septum
Esophagus
transversum
Liver Pleuro-
cords peritoneal
membrane
Vitelline
duct
Inferior
Allantois vena cava
Muscular ingrowth
Cloaca Septum transversum
Body wall from body wall
FIGURE 24-1 Historically, the diaphragm has been thought to develop from fusion of its four embryologic components. According
to this theory, the septum transversum fuses posteriorly with the mediastinal mesenchyme. The pleuroperitoneal canals (arrow)
allow free communication between the pleural and peritoneal cavities. Closure of these canals is completed as the pleuroperitoneal
membranes develop. The four embryologic components of the developing diaphragm are shown in cross section. (From Skandalakis
IJ, Colborn GL, Skandalakis JE. In: Nyhus LM, Baker RJ, Fischer JE, editors. Mastery of Surgery. 3rd ed. Boston: Little, Brown; 1996.)
24 Congenital Diaphragmatic Hernia and Eventration 317
alveolar stage begins after birth with a continued increase growth, proper alveolar development, and normal lung
and development of functional alveoli. growth.71
Concomittantly, fetal pulmonary vascular develop- Utilizing fetal Doppler ultrasound (US), fetuses with
ment occurs in concordance with the associated lung CDH exhibit a decrease in the overall pulmonary blood
development and follows the pattern of airway and alveo- flow and vascularity.72 The modified McGoon Index, a
lar maturation. A functional unit known as the acinus ratio of the combined diameter of the proximal pulmo-
consists of the alveolus, alveolar ducts, and respiratory nary arteries to the descending aorta, may help predict the
bronchioles. The pulmonary vasculature develops as degree of PHTN that correlates with death. A modified
these acinar units multiply and evolve during the canal- McGoon Index of 1.3 has an 85% sensitivity and 100%
icular stage. The preacinar structures consist of the specificity for mortality.73 An index <1.25 and birth weight
trachea, major bronchi, lobar bronchi, and terminal <2755g has been shown to result in 80% mortality, with
bronchioles. The pulmonary vascular development a sensitivity of 73% and a specificity of 78%.74 The arte-
for the preacinus is typically completed by end of the rial adventitia and medial wall thickness are increased in
pseudoglandular stage.5759 In theory, any impedance to postmortem CDH infants compared to controls.75,76 In
normal pulmonary development will concurrently hinder addition, the adventitial thickness and area were greater
pulmonary vascular development. in CDH stillborns and newborns when compared to live
Pulmonary hypoplasia is characterized by a decrease born non-CDH infants, suggesting that increased muscu-
in bronchial divisions, bronchioles, and alveoli. The larization of the pulmonary vasculature occurs in utero
alveoli and terminal saccules exhibit abnormal septations and fails to appropriately remodel after birth.
that impair the aircapillary interface limiting gas In a retrospective study, CDH infants who developed
exchange.60 At birth, the alveoli are thick-walled with normal pulmonary artery pressures during the first 3
intra-alveolar septations. These immature alveoli have weeks of life were found to have a 100% survival rate.77
increased glycogen content leading to thickened secre- In this same study, an intermediate reduction in elevated
tions which further limit gas exchange. Animal models of pulmonary pressures after birth were seen in 34% of
CDH have demonstrated pulmonary hypoplasia with infants with a 75% survival. Mortality was 100% in CDH
decreased levels of total lung DNA and protein. In infants that failed to normalize their pulmonary pressures
addition, the pulmonary vasculature appears to be less despite therapy. Although contemporary outcomes for
compliant with abnormally thick-walled arterioles.61 Sur- infants with pulmonary hypertension have improved,
factant levels are also decreased which may result in these data underscore the importance of PHTN in CDH.
immature functioning lungs.62 Endogenous surfactant
synthesis has been found to be decreased in CDH infants
that required ECMO compared with non-CDH venti-
lated neonates without significant lung disease.63 Inter-
DIAGNOSIS
estingly, the contralateral lung also exhibits the structural Prenatal Diagnosis
abnormalities of pulmonary hypoplasia.
Due to the wide discrepancy of disease severity and
Pulmonary Vascular Development potential fetal therapies, accurate and timely prenatal
diagnosis of CDH is important. The differential diagno-
and Pulmonary Hypertension sis for CDH include other pulmonary anomalies, such as
Normal fetal cardiopulmonary circulation transitions to congenital pulmonary airway malformations (CPAM),
it postnatal state rapidly with a tenfold increase in pul- bronchogenic cysts, bronchial atresia, or bronchopulmo-
monary blood flow shortly after birth. Fetal pulmonary nary sequestrations, as well as mediastinal lesions, includ-
blood flow is characterized as a low-flow, high-resistance ing enteric, neuroenteric, or thymic cysts. In these
circuit due to medial and adventitial hypertrophy of the conditions, the normal intra-abdominal anatomy is not
vasculature.64 Normally, the pulmonary vascular resist- disturbed. In addition, diaphragmatic eventration can be
ance quickly decreases as the distal small pulmonary misinterpreted for CDH. Although this differentiation
arteries and arterioles remodel over the first few months from CDH can be difficult, this distinction is important
of life, resulting in a low-resistance, high-flow postnatal as diaphragmatic eventration portends a much better
circulation.65,66 However, this process appears to be prognosis and requires different management. Eventra-
arrested in CDH newborns, and the fetal circulation per- tion are typically isolated lesions, but may be associated
sists resulting in PHTN. In fact, the abnormal fetal pul- with pleural and/or pericardial effusions.78
monary circulation in CDH fetuses appears to occur in The diagnosis of CDH can be made by ultrasound as
early gestation. The pulmonary arteries exhibit a decrease early as 11 weeks gestation, although most are not seen
in density per unit of lung parenchyma as well as an until after 16 weeks (Fig. 24-3).79 Although most CDH
increase in muscularization that extends to the vascula- can be detected during the second trimester, some sono-
ture at the acinar level.67 In fetal lamb models of surgi- graphic features may not manifest until later in preg-
cally created CDH as well as human fetuses with CDH, nancy.80 Approximately 5070% of CDH are diagnosed
there is a relative decrease in lung parenchyma.68,69 during pregnancy.79,81 However, for some tertiary centers,
This impaired lung growth and development has 90% of CDH newborns may have been diagnosed in
been speculated to be related to impaired vascular utero.82 Fetal ultrasound features include polyhydram-
development.70 As a result, PHTN appears to develop in nios, bowel loops within the chest, an echogenic chest
utero, which may cause a reduction in pulmonary artery mass, and/or an intrathoracic stomach. Left-sided CDH
24 Congenital Diaphragmatic Hernia and Eventration 319
A B
FIGURE 24-5 (A) Anteroposterior chest radiograph in a neonate with a CDH demonstrating air-filled loops of bowel within the left
chest. The heart and mediastinum are shifted to the right, and the hypoplastic left lung can be seen medially. (B) Postoperative
radiograph demonstrating hyperexpansion of the right lung with shift of the mediastinum to the left. The edge of the severely
hypoplastic left lung is again easily visualized (arrow).
glucocorticoids demonstrated a reduction in alveolar These inotropic agents can augment left ventricular
septal thickness, increased DNA synthesis, and increased output and increase systemic pressures in order to amel-
total lung protein production.106,107 Initial results from iorate right-to-left ductal shunting.
small patient series seemed promising in that antenatal
administration of glucocorticoids suggested improved
lung function.108,109 However, a prospective randomized
Mechanical Ventilation
trial failed to demonstrate any benefit for CDH.110 At this Mechanical ventilation is a critical component in the care
point, no data exist on proper dosing or timing of steroid of infants with respiratory failure secondary to CDH.
administration in the setting of CDH. As such, prenatal However, the physiologic limits of the hypoplastic lung
steroids are not currently recommended for CDH. make mechanical ventilation a challenge. Hypoplastic
lungs in CDH infants are characterized by a decreased
number of airways and smaller airspaces. Also, the pul-
Resuscitation and Stabilization monary vasculature exhibits decreased vascular branching
After confirming the diagnosis, initial postnatal therapy as well as increased adventitia and medial wall thick-
is targeted at resuscitation and stabilization of the infant ness.111,112 This combination results in varying degrees of
in cardiopulmonary distress. A rapid overall assessment respiratory failure and PHTN. Fortunately, pulmonary
is important to determine hemodynamic stability and the and vascular development continues after birth and these
severity of disease. In severe cases, prompt endotracheal pulmonary sequelae of CDH can improve.113,114 Because
intubation and mechanical ventilatory support is likely to of this ongoing maturation, mechanical ventilation strat-
be required. A nasogastric tube should be inserted to egies have trended towards less aggressive approaches
avoid gastric and intestinal distention. Arterial and venous with the goal of maintaining oxygenation while limiting
catheters assist in resuscitative maneuvers. Acidbase the risks of ventilator-induced lung injury, a major con-
balance and oxygenation-ventilation status should be tributor to mortality.115
carefully monitored. The optimal type of mechanical ventilation in infants
Invasive monitoring is important in accurately assess- with CDH is individual clinician preference, but most
ing the infants overall perfusion and the severity of pul- cases of CDH can be managed using a pressure-cycled
monary hypertension and hypoplasia. Umbilical venous mode. A fractional inspired oxygen (FiO2) of 1.0 is
catheters may be helpful and, if possible, should be posi- initially utilized to maintain adequate SaO2. Typically,
tioned in the right atrium to measure central venous higher respiratory rates and lower peak airway pressures
pressures. In addition, an approximation of cerebral per- (1822cmH2O) are employed while titrating the FiO2 to
fusion should be available using preductal oxygen content a preductal PaO2 greater than 60mmHg, or the preduc-
and/or saturation via either a right radial arterial catheter tal SaO2>85% and a PaCO2 less than 60mmHg. Main-
or a transcutaneous saturation probe. taining an acceptable pH and PaCO2 are important in
Targets for initial resuscitation include preductal managing PHTN.116,117 The ventilation strategy of
arterial saturation (SaO2) between 8595% with a induced respiratory alkalosis with hyperventilation to
minimal amount of positive airway pressures. In order to reduce ductal shunting has been abandoned in most
maintain lower peak inspiratory pressures (PIP), a centers.118121 Initial conventional mechanical ventilation
moderate level of hypercarbia (PaCO2, 4560mmHg) settings should include pressure-limited ventilation rates
is accepted without a compensatory acidosis and lactate between 4060 breaths per minute with PIP<25cmH2O
of 35mmol/L. Occasionally, higher levels of PaCO2 to minimize barotrauma.118,122 The initial PIP can be
are tolerated as long as the pH>7.2 is maintained. weaned to minimal settings, but should be done with
Failure to provide adequate tissue oxygenation can result caution. While targeting a PaCO2<45mmHg, rapid
in metabolic acidosis which may exacerbate the PHTN. reduction in mechanical support may allow transient
Pulmonary vascular resistance (PVR) is increased by periods of stability, but may also produce potential refrac-
hypoxia and acidosis, which should be avoided or cor- tory exacerbations of PHTN. Spontaneous respirations
rected. If severe ductal shunting develops, iNO can be are maintained by avoiding neuromuscular paralysis and
tried, although PHTN in association with CDH is less minimal ventilation rates. This combination of spontane-
responsive to iNO than other causes of PHTN. ous respiration and permissive hypercapnia has been a
Depending on the degree of PHTN and associated well-documented preoperative stabilization strategy in
cardiac anomalies, hemodynamic stability can be difficult some centers with survival rates of almost 90% in patients
to achieve. PHTN may be exhibited by a different pre- with isolated CDH.118120
and postductal SaO2. However, echocardiography can If conventional ventilation fails to reverse hypercapnia
better characterize the degree of PHTN. Sonographic and hypoxemia, HFOV strategies can be tried to avoid
findings of PHTN include poor contractility of the right ventilatory-induced lung injury by preserving end-
ventricle, flattening of the interventricular septum, expiratory lung volume without overdistending the lung
enlarged right heart chambers, and tricuspid valve regur- parenchyma. As the understanding of the CDH lungs
gitation. There may be right-to-left or bidirectional continues to evolve, HFOV strategies have also changed.
shunting across the ductus arteriosus. Initially used in a high-pressure, lung recruitment mode,
Almost all infants with CDH and severe PHTN this strategy demonstrated no benefit due to the nonre-
exhibit some left ventricular dysfunction. Vasopressor cruitable nature of these hypoplastic lungs.123,124
agents such as dopamine, dobutamine, and milrinone High-frequency strategies as a rescue therapy for infants
may be needed in hemodynamically unstable patients. with profound hypoxia and refractory hypercapnia on
322 SECTION III Thoracic
conventional ventilators have also not been successful.4,125 newborn is directed at reducing PVR. With increased
As the concept of preoperative stabilization became PVR, patients often display super-systemic pressures
better defined, HFOV began to be used as means to avoid leading to right-to-left shunting in both the pre- and
barotrauma early in the treatment course prior to refrac- postductal circulations. This can cause right heart failure
tory respiratory failure. In fact, some institutions have with increases in preductal desaturation, narrowing of the
utilized HFOV as primary therapy.5,126,127 These strate- pre- and postductal SaO2, and, ultimately, systemic hypo-
gies of preoperative stabilization to prevent lung injury tension and decreased perfusion. In previously stable
along with delayed operation, regardless of ventilator neonates, signs of poor perfusion may indicate closure of
modalities, have resulted in improved survival.5,115,126128 a PDA. In response, prostaglandin E1 (PGE1) can be
In order to achieve lower peak airway pressures, HFOV instituted to re-open the ductus and improve right ven-
should be considered when PIP exceeds 25cmH2O with tricle (RV) pressures.122 In infants that demonstrate
conventional ventilation. Initial HFOV settings include a significant PHTN and RV dysfunction, left ventricular
mean airway pressure between 1315cmH2O, 1012Hz, filling/function and overall perfusion may improve by
amplitude between 3050cmH2O, and inspiration to off-loading the RV to improve the geometry of the inter-
expiration ratio of 50%. The initial PaCO2 should be ventricular septum.137 Preductal SaO2>85% should be
maintained in the range of 4055mmHg and can be maintained to ensure adequate cerebral perfusion.118 As
weaned by decreasing the amplitude. Eight rib expansion the RV is unloaded, systolic blood pressure may decrease,
of the contralateral hemithorax can be used as a guide to especially in the setting of left ventricular dysfunction.
achieve optimal lung expansion without overdisten- Adequate preload should be maintained with volume
tion.126,127 Tidal volumes are directly related to the ampli- loading or vasopressor support, such as epinephrine, to
tude and inversely related to frequency. As such, significant ensure ventricular function and coronary artery per-
increases in tidal volume can be seen when frequencies fusion. Increasing the systemic pressure may decrease the
are below 10Hz. This can result in hyperinflation degree of right-to-left shunting. In a small study, CDH
which, in turn, may adversely affect the pulmonary infants with persistent PHTN and right-to-left shunting
vasculature by impeding venous return. Constant assess- through the ductus, despite PGE1 use, had an 80%
ment of acid-base status and end-organ perfusion is neces- mortality.138
sary as lung compliance can change before and after CDH iNO is a potent pulmonary vasodilator that has been
repair. shown to have tremendous benefit in the treatment
of persistent pulmonary hypertension of the neonate
(PPHN).4,139142 Typically, iNO is utilized in the setting
Surfactant of echocardiographic evidence of right-to-left shunting
and RV pressures greater than two-thirds systemic pres-
Animal studies of CDH have demonstrated altered sur-
sures. In clinical studies, iNO has been shown to improve
factant levels and composition.129,130 Experimentally, sur-
oxygenation and decrease the need for ECMO in infants
factant decreases PVR, improves pulmonary blood flow,
with respiratory failure secondary to PPHN.142,143
and reduces ductal shunting.131 However, supporting data
However, the efficacy of iNO as a rescue therapy for
are not definite.62 Initial reports demonstrated surfactant
PHTN secondary to CDH by either decreasing the need
administration augmented iNO delivery and improved
for ECMO or a reduction in mortality has not been sup-
gas exchange, leading to its empiric utilization.132
ported.144 In the Neonatal Inhaled Nitric Oxide Study
However, clinical evidence in term and preterm infants
Group trial, the CDH subgroup had a greater likelihood
with CDH has not shown benefit.133 Van Meurs etal.
for ECMO or death.145 The response to iNO is variable
suggested that surfactant therapy in term infants with
and unpredictable in infants with CDH. The initial
CDH was associated with an increased use of ECMO,
improvement in oxygenation in CDH infants suggest
increased incidence of chronic lung disease, and higher
that iNO could be utilized as a bridge for transport
mortality.134 Similar findings were found in preterm
or until ECMO can be initiated.122 Some infants may
infants despite adjusting for Apgar scores and gestational
demonstrate a rebound PHTN that is more difficult
age.133 Even as a rescue therapy in CDH infants on
to control than the initial disease.146,147 Also, the effect
ECMO, surfactant failed to demonstrate a survival advan-
appears to be transient and does not obviate the need for
tage.135,136 Despite the lack of proven efficacy, exogenous
ECMO.77,148 A meta-analysis of iNO utilization for per-
surfactant therapy continues to be used with unclear risks
sistent PHTN did not show benefit in CDH infants, and
and benefits. Proponents of this therapy argue that the
recommended its use only in hypoxic respiratory failure
clinical evidence is based on a heterogeneous population
infants without CDH.149
of disease severity, and that the lack of clinical evidence
Phosphodiesterase (PDE) inhibitors are cyclic guano-
to support its efficacy is due to its use in the most severe
sine monophosphate (cGMP) modulators that target
CDH infants. Given the current clinical data, surfactant
vascular remodeling by limiting smooth muscle cell pro-
therapy should only be used in the setting of clinical
lifeation.150 Type 5 PDEs (dipyridamole and sildenafil)
research.
are the most active on visceral and vascular smooth
muscle and have been utilized with iNO for the treat-
ment of PHTN in patients with and without CDH. In
Pulmonary Vasodilators limited case reports, dipyridamole produces a transient
PHTN is a common consequence in CDH infants. Even improvement in oxygenation which may allow weaning
if asymptomatic, the initial management in the CDH of ventilatory support and may avoid escalation of therapy
24 Congenital Diaphragmatic Hernia and Eventration 323
to ECMO.151153 Sildenafil has been shown to improve procedure. However, the optimal timing for repair
oxygenation and decrease PVR when used independently remains unclear. Historically, early repair was thought to
or in combination with iNO.146,154,155 Sildenafil has been improve ventilation by reducing intrathoracic pressures
used in oral or intravenous forms for congenital heart after reduction of the herniated viscera. However, this
disease and CDH-associated PHTN.146,148,156,157 Similar strategy often led to urgent procedures being performed
to dipyridamole, utilization of sildenafil may have benefit on unstable infants.193 A paradigm shift in management
in improving oxygenation and avoiding ECMO in the to delay the operative repair until the infant is stable
setting of refractory iNO.146,158 However, despite its became widely adopted in the early 1990s.121,122,194 Several
approval for use in adults, the USA Food and Drug studies have shown no difference in mortality rate or the
Administration has warned against using sildenafil for need for ECMO in infants undergoing early vs late
pediatric pulmonary hypertension between ages 1 and 17 repairs,195197 including two randomized trials of early
years due to a potential increase in mortality during long- (<12 hours) versus delayed repair (after 24 hours197 and
term therapy.159 Other vasodilators have been utilized in after 96 hours195). Today, repair of CDH is usually delayed
infants with CDH, but the experience to date is until cardiopulmonary stability is achieved, although the
limited.160174 definition of physiologic stability remains highly variable
and inconsistent amongst centers.127,194,196200
In 1995, Wung etal. reported advantages with a
Extracorporeal Membrane Oxygenation delayed repair strategy for CDH.121 Comparing three
CDH accounts for approximately one-quarter of all eras of treatment strategies, the study contrasted an early
infants requiring ECMO for respiratory failure.175178 period of emergency surgery to the most recent era of
ECMO utilization for CDH was first introduced as a delayed repair and gentle ventilation, where infants with
rescue therapy for infants who had severe ventilator- CDH were managed with a lung-preserving ventilation
associated lung injury.179 Prior to the era of preoperative strategy. Repair was not performed until the pre- and
stabilization, ECMO was associated with only a modest postductal SpO2 gradient equalized and right-to-left
improvement in survival in high-risk CDH infants.180182 shunting on echocardiogram had resolved. With an
Since then, ECMO has evolved as a treatment modality average of 4.2 days after birth before operation, survival
to prevent ventilator-induced barotrauma.183,184 In com- was 94% with only one patient requiring ECMO. From
bination with other adjunctive treatments such as HFOV, the same institution in 2002, 120 consecutive patients
ECMO is now routinely used for preoperative stabiliza- were treated with permissive hypercapnia, spontaneous
tion.185 The strategy of stabilization with ECMO and respiration, and elective repair after 36 hours of life with
delay in operative correction has been shown to be an overall survival of 84%.118 Of note, only 13.3% of
beneficial with a reported survival of 67% in high-risk patients needed ECMO and only 7% of infants required
patients.8,186 a prosthetic patch, suggesting a relatively small propor-
Although results are dependent on patient selection tion of infants with large diaphragmatic defects. A differ-
and disease severity, survival has been reported between ent group reported similar results from a center that
6090% for CDH patients requiring ECMO.5,118,139,175,187 did not offer ECMO.201 In this study, all high-risk
Without ECMO, the predicted mortality in the high-risk patients (defined as assisted ventilation within two hours
cohort reaches 80%.175 Despite these data, the benefits of life) were divided in three historical cohorts with the
of ECMO for CDH are not universally accepted. Some most recent group being managed by permissive hyper-
authors report no survival advantage with ECMO,188,189 capnia, gentle ventilation, and delayed repair until hemo-
while others report as high as 80% survival without using dynamic stability was achieved (PaCO2<60mmHg,
ECMO.190,191 PaO2>40mmHg, SaO2>85% with a FiO2<50%) for
Initially, strict criteria were established as indications at least 48 consecutive hours. Overall survival in this
for ECMO use in CDH. These included an oxygenation recent cohort was 90%. Despite the benefits of preopera-
index >40 and persistent alveolararterial O2 gradient tive stabilization and delayed repair, the specific param-
>610mmHg.177,192 Today, those criteria have eased and eters that define hemodynamic stability and timing of
the most common indication for ECMO is a failure to operation remain unanswered.
respond to other therapy. In efforts to maintain lung- According to data from the Congenital Diaphragmatic
protective ventilation, clinicians have opted for ECMO Hernia Registry (CDHR) and Extracorporeal Life
rather than escalation of positive airway pressures. Support Organization (ELSO) over a recent 15 year
Relative contraindications include significant congenital period, one-third of infants with CDH required ECMO
anomalies, lethal chromosomal anomalies, intracranial during their initial hospitalization, during which 85% of
hemorrhage, birth weight <2kg, and gestational age <34 these infants underwent early CDH repair on ECMO.202
weeks. See Chapter 6 for more information about ECMO. In this study, survival was 71% with only 9% requiring
operative intervention for bleeding complications follow-
ing CDH repair on ECMO compared to survival of 49%
SURGERY and a 14.7% bleeding complication rate from the CDH
and ELSO registries. The authors attributed the better
Timing of Operation outcomes after early repair on ECMO to less body wall
edema and a quicker recovery following operation which
With an improved understanding of its pathophysiology, led to fewer total days on ECMO (11.7 vs 13.3 days). In
repair of CDH is no longer considered an emergency another study, among infants who underwent repair of a
324 SECTION III Thoracic
unilateral CDH, 47.6% were repaired on ECMO, 45.8% especially if connected to suction. The thoracic space will
were repaired after ECMO, and only 6.6% were repaired eventually fill with fluid, and the lung will gradually grow.
before ECMO.203 Tube thoracostomy should only be used for postoperative
Bleeding remains the most significant complication chylothorax or pleural fluid causing hemodynamic com-
following CDH repair on ECMO including both surgical promise.212 If a chest tube is needed, it is positioned in
site bleeding and intracranial hemorrhage. These risks the thoracic cavity prior to final closure of the diaphragm.
may be minimized with early repair on ECMO prior Chest tubes should be placed to water seal rather than
to the development of a coagulopathy and significant suction. Symptomatic pleural fluid can be treated with
edema,177,202 as well as repair when PHTN has resolved, repeated thoracentesis. If used, chest tubes should be
but prior to decannulation to allow reinstitution of removed early to avoid infectious complications.
ECMO if respiratory failure and/or PHTN recur.204
Although rare, recurrent PHTN can develop after repair Minimally Invasive Techniques
requiring a second ECMO run.205 In addition, use of
aminocaproic acid (Amicar), a fibrinolysis inhibitor, The respiratory sequelae and other morbidity seen after
has significantly decreased bleeding complications. One open CDH repair has prompted surgeons to adopt mini-
group reported no changes in intracranial hemorrhage mally invasive surgical (MIS) approaches. Both thoraco-
rates, but a significant decrease in surgical site bleeding scopic and laparoscopic repairs have been
from 12% to 7% (P<0.05) with Amicar.176Amicar performed.207,213216 Data from the CDHR show that
should be used prior to operation and for two to three laparoscopic and thoracoscopic strategies are being used
days after repair. Additional strategies include ECMO worldwide, and have been utilized in 20% of centers since
without heparinization, fresh ECMO circuits, minimal 1995.207 MIS techniques have been used for primary
diaphragmatic muscular dissection, fibrin or thrombin repair as well as prosthetic patch closure with suggested
sealants, and utilization of recombinant factor VII for advantages of less postoperative pain, avoidance of
established bleeding. thoracotomy-associated complications, and an overall
reduction of surgical stress.216,217
The sensitivity of CDH infants to hypercapnia and
Operative Approach acidosis has drawn concerns regarding the utilization of
Open repair of CDH can be performed using a thoracic or MIS. The overall benefits of MIS are questioned because:
abdominal approach. Advantages to laparotomy include (1) CDH neonates may absorb the CO2 insufflation;218,219
easier reduction of intrathoracic viscera, the ability to and (2) insufflation with CO2 can raise intracavity pres-
mobilize the posterior rim of diaphragm, easier manage- sures that may limit venous return, end-organ perfusion,
ment of intestinal rotational anomalies, and avoidance of and tidal volume. The combination of CDH-related pul-
thoracotomy-associated musculoskeletal sequelae. The monary hypoplasia, PHTN, and labile pulmonary vascu-
vast majority of neonatal repairs for CDH are through a lar reactivity may be detrimental during MIS operations.
subcostal incision (91%).206,207 Less than 10% are per- Although increases in CO2 absorption during MIS are
formed via a thoracotomy. The intra-abdominal contents generally well tolerated in infants, CDH neonates spe-
should be reduced out of the thorax with careful attention cifically demonstrate greater changes in end-tidal CO2
to the spleen that can be caught and lacerated on the rudi- (ETCO2) and impaired elimination of CO2 during tho-
mentary rim of diaphragm. A true hernia sac, which is racoscopy and laparoscopy.220,221 Hypercapnia and the
present less than 20% of the time, should be excised.208 associated acidosis may result in increased pulmonary
The thoracic and abdominal cavities should be inspected shunting.
for an associated pulmonary sequestration. Patient selection is paramount for successful comple-
Despite this gold standard abdominal approach, the tion of an MIS repair as well as for minimizing operative
morbidity and respiratory sequelae of open CDH repair morbidity. Historically, MIS was reserved for stable
remain a concern. In addition to pulmonary hypoplasia infants with anticipated small defects. Utilizing anatomic
and hypertension, respiratory compliance is significantly markers such as stomach herniation, surgeons have
reduced after open repair. Mortality significantly increases attempted to predict which defects might be amenable to
when compliance decreases by >50% which can occur as MIS repairs.215 Initially, the radiographic presence of the
a result of a tight abdominal wall closure.193,209 Careful nasogastric tube within the abdomen and minimal respi-
attention should be paid to the peak airway pressures as ratory compromise (PIP<24mmHg) were thought to
the abdominal fascia is closed. Respiratory compromise predict a successful thoracoscopic repair. One group
should alert the surgeon to leave the abdomen open. This reported 95% success rates with thoracoscopic repairs
approach is more often needed in CDH infants on when patients did not have a significant congenital cardiac
ECMO.210 Temporary closure can be achieved using just anomaly or the need for preoperative ECMO, and had a
the skin or a prosthetic silo. Delayed closure, especially PIP26cmH2O, and an oxygenation index 5 on the
in those infants on ECMO, should be attempted after the day of surgery.222 Another group has advocated for
generalized edema has resolved or the intra-abdominal strict preoperative selection criteria for thoracoscopic
domain has enlarged.211 repair, including minimal ventilatory support (PIP<
The routine use of chest tubes after CDH repair to 24mmHg), no clinical or sonographic evidence of
drain pleural fluid has been abandoned.118,121,201 One PHTN, and an intra-abdominal stomach.215 On the other
concern is that the chest tube can cause ipsi- and contra hand, infants requiring preoperative ECMO have under-
lateral lung injury secondary to mediastinal shift, gone successful repair with an MIS approach.218,223 Large
24 Congenital Diaphragmatic Hernia and Eventration 325
defects that require patch repairs218,222,224 and right-sided studies, patch repair has been utilized as a surrogate
defects are no longer contraindications to MIS.225 for defect size and disease severity (i.e., larger the
However, patients undergoing MIS repair of CDH defect=increased severity of disease).
should have stringent intraoperative monitoring of
ETCO2 and PaCO2.226 Nonabsorbable Synthetic Patches
Although success with laparoscopic216,227 and thoraco-
Synthetic patches such as polytetrafluoroethylene (PTFE
scopic213,224 repairs have been reported, comparative
or Gore-Tex) or composite polypropylene (Marlex)
evidence between MIS and open approaches has been
represent the majority of the mesh replacements used in
limited to single-institution experiences or retrospective
neonates with a large CDH.236 Advantages to synthetic
analyses.213,228,229 A recent single-institution review of
patches include: (1) immediate availability; (2) minimal
54 neonates undergoing unilateral CDH repair between
preparation time; (3) easily cut to fit the diaphragmatic
20062010 was published.228 Thirty-five neonates under-
defect; and (4) less tissue dissection, reducing the risk
went attempted thoracoscopic repair with 26 being suc-
of hemorrhage, especially during repair on ECMO.
cessfully completed. During the same time interval, 19
However, there are several disadvantages to synthetic
open CDH repairs were performed. Recurrence was
patches for CDH repair. PTFE, anchored to the chest
higher after the thoracoscopic repair (23% vs 0%). There
wall, can potentially produce a tethering point for creat-
were no individual factors that were found to be predic-
ing a pectus-type deformity.237 There is an increased
tive of recurrence with the thoracoscopic approach. In
incidence of bowel obstruction, need for splenectomy,
another report, a systematic review and meta-analysis of
patch infections, and abdominal wall deformities.236,238
neonatal endosurgical CDH repairs identified only three
The overall recurrence rate has been reported to be as
eligible studies comparing open to endosurgical repair.230
high as 50% with a bimodal distribution showing early
The cumulative risk ratio for death was 0.33 (95%
recurrence in the first months after repair and late recur-
CI:0.101.13) in favor of the MIS approach and recur-
rence years later.236 Early recurrences for defects requir-
rence was 3.21 (95% CI:1.119.29) in favor of the open
ing a patch are most likely due to lack of tissue adhesion
repair. The overall survival rate for MIS patients was
or scarring and an incomplete muscular rim which then
significantly higher compared with patients undergoing
requires anchoring the patch to the ribs or esophagus.
open repair (82.9% open and 98.7% MIS, P<0.01) with
PTFE tends to scar and retract over time, which may lead
a risk-adjusted odds ratio (OR) of survival for MIS repairs
to late recurrences in the growing child. In an effort to
of 5.57 (95%CI:1.3423.14).222 These results suggest a
prevent CDH recurrence, one group described a cone-
significant survival advantage for the MIS approach, even
shaped, double-fixed PTFE patch to allow expansion
after risk-adjustment. However, the data are more likely
over time.239 The recurrence rate decreased from 46% to
the result of selection bias based on surgeon preference
9% at one year after repair. Similar results have been seen
regarding which patients were good candidates for MIS.
with a mesh plug and patch technique in the setting of a
Although the ability to perform MIS repair of CDH
recurrent CDH.240 Another group described a double-
has been shown, the short- and long-term outcomes
sided composite patch consisting of PTFE and type-1
regarding the durability and recurrence rates for an MIS
monofilament, macroporous Marlex. Utilizing a pledg-
approach are less clear. The reported overall recurrence
eted, nonabsorbable running suture, the recurrence rate
rates for MIS repair range from 523.1%,218,222,224,225 with
was 2.2% with a mean follow-up of 49 months.241
early recurrences as high as 2333%.228,229 In another
study, MIS repairs were performed in only 3.4% infants Absorbable Biosynthetic Patches
with CDH, but had a significantly higher in-hospital
recurrence rate compared to open (7.9% vs 2.7%, Absorbable biosynthetic materials have been utilized as
P<0.05).207 The true risks and benefits of the MIS an alternative replacement to synthetic patches. They
approach for CDH repair, including the impact of have been reported to decrease complications by offering
re-operations, remain unclear. At the very least, recur- a lower risk of infection and the ability of the patch to
rence seems to be higher. grow with the patient. Surgisis (SIS) is an acellular,
Robotic CDH repair has been demonstrated to be bioengineered porcine intestinal submucosal matrix that
feasible and safe.231233 Proponents of robotic CDH repair consists of a type I collagen lattice with embedded growth
tout the increased degrees of freedom of the articulating factors. This non-crosslinked biological matrix promotes
instruments for suturing. fibroblast migration and cellular differentiation.242 First
described for repair of incisional, inguinal, and
paraesophageal hernias,243245 SIS has also been utilized
Diaphragmatic Replacements for CDH repair.216,246 Permacol is an acellular porcine
Repair of large diaphragmatic defects is a challenge, dermal collagen patch consisting of collagen fibers with
usually requiring diaphragmatic replacement with a pros- cross-linked lysine and hydroxylysine. By promoting an
thetic patch or autologous tissue. In one large study, inflammatory response in a manner similar to wound
48.3% of infants undergoing CDH repair required dia- healing, the neodiaphragm is more pliable and, subse-
phragmatic replacement.207 Comparative studies between quently, less prone to recurrence. One group reported
patch and primary repairs have consistently shown no recurrences observed with a median follow-up of 20
increased morbidity and mortality in the patch groups, months, while recurrences were noted in 2% of patients
most likely due to the large defect size and the associated with primary repair and 28% with PTFE.247 AlloDerm
severity of the pulmonary hypoplasia.234,235 In many is an acellular human cadaveric dermal patch that is
326 SECTION III Thoracic
The concept of tracheal occlusion originated from analysis, overall survival was 50% in the fetal tracheal
the observation that infants with congenital high airway occlusion group compared to 4.8% in controls (RR
obstructions developed hyperplastic lungs. Several groups 10.5;95%CI:1.574.7). The mean gestational age at
have demonstrated increases in total lung protein and delivery was 35.62.4 weeks in the treated group and
DNA, alveolar space, overall lung weight, and cross- 37.41.9 weeks in controls (P<0.01). Despite these
sectional area of the pulmonary vasculature as well as positive results, one limitation of this study was that it
better lung compliance following prenatally placed tra- did not utilize some of the currently accepted prenatal
cheal balloons in sheep.269272 However, it has been noted and postnatal treatment strategies. Tracheal balloons
that long-term tracheal occlusion decreases the number were removed at the time of delivery through an EXIT
of type 2 pneumocytes and surfactant production. This procedure, thus discarding the temporary tracheal occlu-
finding has led to the concept of temporary in utero sion concept. In addition, ECMO was not available in the
tracheal occlusion for CDH.131,273 study institution for postnatal care in both arms.
It is known that liver herniation and LHR<1.0 are Currently, the European FETO group is conducting
fetal parameters that portend the worst outcomes.274 a multicenter randomized trial for severe, isolated CDH
Current in utero techniques involve endoscopic insertion cases in patients with O/E LHR<25% and liver in the
of an occlusive balloon in the fetal trachea without mater- chest. Short-term tracheal occlusion is performed with
nal laparotomy or general anesthesia.275 These balloons balloon insertion between 27 and 30 weeks gestation and
are inserted percutaneously with ultrasound guidance removal at 34 weeks. There is a standardized postnatal
between 2428 weeks gestations and are deflated at 34 management protocol as well as a standardized technique
weeks. This strategy of temporary tracheal occlusion for emergent and elective balloon removal. Until defini-
avoids the need for an ex-utero intrapartum treatment tive evidence-based practice is established, fetal tracheal
(EXIT) procedure at delivery, although emergent airway occlusion for CDH remains an unproven therapy.
access may be needed at delivery for any patient who
undergoes in utero tracheal occlusion.
In 2003, an NIH-sponsored randomized trial compar- OUTCOMES
ing fetal tracheal occlusion versus standard postnatal
care was reported.276 Criteria for randomization was Clinical outcomes for the treatment and management of
LHR<1.4 and liver in the chest. After 24 cases (11 with infants with CDH have traditionally been difficult to
tracheal occlusion), the study was terminated early due generalize due to the low incidence of disease and single
to comparable survival outcomes (77% by postnatal care, institutions reports. Patient characteristics and clinical
73% by tracheal occlusion). The hazard ratio (HR) for practices are different, and each institutions ability to
mortality associated with tracheal occlusion, as compared offer state-of-the-art neonatal critical care is highly vari-
to conventional postnatal therapy, was 1.2 (95% CI:0.29 able. Survival analyses for CDH remain difficult to inter-
4.67). However, when stratified based on LHR, survival pret due to variations in patient disease, management
was significantly better for LHR greater than 0.9 with a strategies, and operative techniques. Unique to individual
HR for death with tracheal occlusion being 0.13 (95% institutions are differences in ventilation strategies, avail-
CI:0.030.64). ability and entry criteria for ECMO, and operative
In 2004, the European Fetal Endoscopic Tracheal timing. As a result, survival rates for CDH vary between
Occlusion (FETO) task group reported on 21 fetuses institutions, even when risk adjusted, and range from
undergoing tracheal occlusion.277 This nonrandomized 2583%.6 In an attempt to ameliorate these difference,
study of fetuses with a severe CDH (liver up and LHR<1) the CDH Study Group (CDHSG) was the first to publish
showed improved survival (64%) in the last 11 patients risk-stratified outcomes.280 Multivariate analysis demon-
compared to the first 10 (30%). In 2009, the FETO group strated birth weight and 5-minute Apgar scores to be the
reported their results in 210 patients utilizing a minimal most significant predictors of outcome.
access approach under regional and local anesthesia.278
This FETO study also included fetuses with liver hernia-
tion and an O/E LHR<1.0. The median time to insert
Volume-Based Outcomes for CDH
the balloon was 10 minutes. Successful balloon placement Outcomes for CDH appear better in centers that treat a
was achieved in 97% at the first procedure. Ninety-seven higher volume of CDH infants. The Canadian Pediatric
per cent of the babies were live born and the overall sur- Surgery Network (CAPSNet) grouped centers into low
vival until discharge was 48%. The mean gestational age (<12 cases/year) and high (12 cases/year) volume.281
at birth was 35.3 weeks. When these outcomes were com- Low volume centers had a higher mortality (23% vs
pared to the CDH registry, fetuses with a left-sided CDH, 10%). In a recent follow-up report, CAPSNet found
liver up, and an O/E LHR<1, who were treated with that significant differences between centers was found at
fetal tracheal occlusion, had a survival of 49.1% vs 24.1% six cases per year.282 After risk-adjustment, low-volume
in the registry. Survival increased from 0% in the registry centers demonstrated 33% mortality compared to 15%
to 35% in similar fetuses with a right CDH who under- in high-volume centers. Recent data from the Pediatric
went fetal tracheal occlusion.278 Health Information System (PHIS) administrative data-
In 2012, Ruano etal. reported on a randomized con- base showed the average yearly hospital CDH volume
trolled trial between FETO and conventional postnatal varies from 1.4 to 17.5 cases per year among the 42 insti-
care for isolated, severe CDH (LHR<1.0 and liver up) tutions.283 After being grouped into low (6 cases/year),
between 22 and 26 weeks.279 With an intention-to-treat medium (610 cases), and high volume (>10 cases)
328 SECTION III Thoracic
centers, medium and high volume centers were found to Follow-Up Guidelines
have a significant lower mortality compared to low
volume hospitals. Although many survive to discharge, the sequelae and
ongoing health needs of CDH infants that require
medical care after discharge is significant. Despite many
Risk Stratification for CDH single institution reports, the standard follow-up care for
infants with CDH has not been established.290,291 Pulmo-
Congenital heart defects occur in 1035% of CDH nary, neurological, gastrointestinal, and musculoskeletal
infants.33,284,285 Categorized into major (hemodynamically complications necessitate a multidisciplinary team of sur-
significant) and minor lesions (such asymptomatic ASD, gical, medical, and developmental specialists. In 2008,
VSD, or PDA), in one study, the overall survival was 73% the Section on Surgery and Committee on Fetus and
without any cardiac anomalies, 67% with minor defects, Newborn for the American Academy of Pediatrics estab-
and 36% with major anomalies.33 When compared to lished follow-up guidelines for the care of infants with
infants without structural cardiac anomalies, the adjusted CDH.292 The recommendations begin before discharge
risk in-hospital mortality was 2.2 times higher in infants and extend through age 16 years (Table 24-1).
with major heart defects while there was no statistical
difference among infants with minor lesions.
Defined as delivery <38 weeks gestation, preterm
Pulmonary Outcomes
birth occurs in approximately 30% of infants with Prior to the era of ECMO and lung-protective ventila-
CDH.286,287 The overall survival is approximately 53% for tion, long-term survivors were usually reported as
all preterm CDH infants.286 However, mortality signifi- healthy children without any respiratory disease.59,293
cantly increases with younger gestational age. In a recent However, with improved care, more severely affected
study, infants born less than 28 weeks gestational age CDH infants are surviving and exhibiting functional and
were found to have a survival rate of 31.6%, while sur- radiographic evidence of chronic lung disease.291,294 Pul-
vival increased to 73.1% for those born at 37 weeks.286 monary function has been reported to be normal in
After adjusting for comorbidities and disease severity, 5070% of CDH survivors with the remainder exhibiting
prematurity had an increased OR of 1.68 for death. some form of restrictive or obstructive respiratory symp-
Risk stratification by defect size appears to correlate toms.295,296 Approximately 25% of children beyond the
with disease severity. In two reviews, the overall mortality age of 5 have signs of obstructive airway disease. In a
for patients with agenesis of the diaphragm was 43% with review of 100 consecutive CDH survivors, disease sever-
an OR of 14.07 compared to defects that could be repaired ity (defined as the need for ECMO and patch repair) was
primarily.288,289 The association between defect size and found to be predictive of pulmonary outcome.295 While
disease severity has prompted development of a universal only 16% of the infants required oxygen at discharge,
grading system to define CDH defect size.1 Based on 53% required at least transient usage of bronchodilators
intraoperative findings, the four classifications range within the first year. Similarly, 41% were either depend-
from small defects which could be repaired primarily to ent on or intermittently needing steroids during their
total diaphragmatic agenesis (Fig. 24-8). Utilizing other first year.
variables of comorbidity and disease severity, the CDHSG Respiratory infections appear to have a higher preva-
is attempting to provide an evidence-based risk- lence in children with CDH.295,297,298 Respiratory syncy-
stratification classification for CDH. tial virus (RSV) is the most common pathogen seen in
A B
Neurodevelopmental Testing
Head computed If abnormal finding on If indicated If indicated If indicated If indicated If indicated
tomography or MRI head ultrasound,
seizures, abnormal
neurologic findings, or
ECMO, or patch repair
Hearing evaluation Auditory brainstem X X X X Every 6 months to
evoked response or 3 years of age,
otoacoustic emissions then annually to
screen 5 years of age
Developmental X X X X Annually to 5 years
screening evaluation of age
Neurodevelopmental X Annually to 5 years
evaluation of age
Gastrointestinal testing
Oral aversion screening X X If oral feeding If oral feeding If oral feeding If oral feeding
problems persist problems persist problems persist problems persist
Upper gastrointestinal Consider for all patients If symptomatic If symptomatic Consider for all If symptomatic If symptomatic
study, pH probe, and/ patients
or gastric scintiscan
Esophagoscopy If symptomatic If symptomatic If symptoms or if If symptomatic If symptomatic
abnormal
gastrointestinal
evaluations
Cardiac Testing
Echocardiogram and X If previously If previously If previously If previously If previously
cardiology follow-up abnormal or if on abnormal or if abnormal or if on abnormal or if on abnormal or if on
supplemental on supplemental supplemental supplemental supplemental
oxygen oxygen oxygen oxygen oxygen
Pulmonary Testing
Chest radiograph X If patched If patched If patched If patched If patched
Pulmonary function tests If patched If patched If patched
Musculoskeletal Testing
24 Congenital Diaphragmatic Hernia and Eventration
Adapted from Lally KP, Engle W. Post-discharge follow-up of infants with CDH. Pediatrics 2008;121:62732.
330 SECTION III Thoracic
children less than 3 years of age, suggesting a need for one study showed normal, mildly delayed, and severely
RSV prophylaxis.295 Recurrent pneumonias have been delayed neuromotor testing in 58%, 29%, and 13%,
reported in 2639% of CDH survivors with at least 10 respectively.308 In a prospective cohort of ECMO survi-
years of follow-up.114,297 vors, only 38% of preschool children scored in the normal
Obstructive pulmonary disease is commonly reported range.309 Thirty-four per cent demonstrated mild motor
in surviving children with CDH. Asthma and general delays only, 6% showed mild delay in motor, cognitive,
symptoms of bronchospasm and wheezing are well docu- and/or behavior development, while 16% were severely
mented.183,298,299 Although symptoms appear to improve delayed in at least two of the three domains.
with age, most CDH children will exhibit some combina- Neurological delays may continue beyond preshool
tion of obstructive and restrictive pulmonary function as age. An age-matched controlled study that compared
well as increased reactivity to pharmacological agents.298,299 CDH and normal children for neurocognitive, visual,
This reduced pulmonary function is most likely due to and fine motor outcomes found significant differences.310
lower functional volumes rather than primary obstruc- With an average age of 13 years, the mean score for full
tion of the airways.299 IQ, verbal IQ, and performance IQ were similar between
Although lung development begins early in gestation, groups. However, 13% of CDH children were signifi-
alveolar maturation continues after birth. In CDH, cantly delayed, with 15% scoring below average for
lung hypoplasia affects both lungs with a reduction in Full-IQ and Verbal-IQ while 23% were delayed for
airway and pulmonary artery branching.49,300 Based on performance-IQ. In addition, the CDH cohort had a
ventilation/perfusion (V /Q ) radionuclide scans, pulmo- significantly higher proportion with oral-motor pro-
nary hypoplasia will persist despite continued lung gramming and visual-motor deficits compared to normal
growth.299,301 These V /Q mismatches are due to abnor- controls. Furthermore, approximately 45% of CDH chil-
mal lung perfusion. Although increases in lung volume dren had below average IQ scores at 10 years of age.311
continues during early childhood, there is not an associ- ECMO use, disease severity with prolonged hypoxia,
ated increase in lung perfusion. In a review of 137 and prolonged hospitalizations have all been implicated
CDH infants, 61% had V /Q mismatching with the in the poor neurologic outcomes. In a study of 82 CDH
strongest correlation in children that underwent patch children that required ECMO, developmental delay at 1
repair and ECMO. 302 Even though V /Q scans in CDH year post-repair was significantly more prevalent com-
children have provided valuable information, its predic- pared to children needing ECMO for other indications.303
tive value for chronic lung disease in CDH survivors Abnormal neuroimaging in CDH children with neurode-
remains to be determined. velopmental delays that underwent ECMO has also been
found.312 However, ECMO has not been a significant risk
factor for neurological deficits in other studies.313,314 Cer-
Neurological Outcomes tainly, other comorbidities, such as low socio-economic
Although most children with CDH may resolve their status and prematurity, may contribute to the poor neu-
pulmonary or gastrointestinal conditions, residual neuro- rological outcomes as well.315317
logic morbidities may be harder to detect. Complications Hearing impairment is a recognized sequelae of CDH
associated with the disease and initial treatment, such as with an overall incidence exceeding those of other neo-
seizure disorders, cerebral palsy, and hemorrhagic or natal intensive care infants (2%) and the general popula-
ischemic strokes, occur with a very low prevelance.303,304 tion (0.10.2%).183,318 The prevalence of sensorineural
However, neurodevelopmental conditions, such as learn- hearing loss (SNHL) ranges from none in some series to
ing disabilities, fine and gross motor skill deficits, behav- 100% in others.304,318 SNHL has been detected in as
ior problems, and visual-motor coordination may be many as 50% of CDH children that initially tested as
more common than initially prevalence.290,305,306 normal.318 The etiology of SNHL is unclear. One study
Most longitudinal data have been limited to early suggested a relationship between SNHL and ECMO and
development (<3 years of age). Overall, only 5458% of hyperventilation.291 While several studies have suggested
CDH children demonstrate normal neurodevelopment a causal relationship between ECMO and SNHL,183,318,319
with 2325% demonstrating suspected delays, and others have suggested that SNHL occurs regardless of
1723% showing marked delays.305,307 Utilizing the ECMO use.317,320 Several ototoxic medications, including
Bayley Scales of Infant Development (BSID)-II, some diuretics, antibiotics, and muscle relaxants, are routinely
neuromotor delay was seen in 77% of infants with a 19 used in the acute and chronic care of infants with CDH.319
month median follow-up.305 The severity of neurological Another study suggested that severe hypoxia and acidosis
problems seem to be related to the severity of disease may be linked to SNHL.317 Most likely, SNHL is due to
with mild to moderate developmental delay in 37% of a combination of treatments and severity of disease.
CDH survivors, including 72% that had undergone Because of the increased risk of SNHL in CDH children,
ECMO.291 The largest series of CDH survivors (41 audiological testing is warranted as early as 6 months
patients) demonstrated mild and severely delayed cogni- of age.292
tive and language skills in 17% and 15%, respectively.306
With a median age at 24 months, psychomotor skills were
normal, mildly delayed, and severely delayed in 46%,
Gastrointestinal Outcomes
23%, and 31%, respectively. Gastroesophageal reflux disease (GERD) occurs in two-
Neurodevelopment outcomes beyond 3 years of age thirds of all CDH survivors with approximately half
are limited. Among preshool children born with CDH, requiring fundoplication.320322 Long-term symptoms can
24 Congenital Diaphragmatic Hernia and Eventration 331
persist with 63% of patients requiring GERD medica- the diaphragm. These are usually large anterior midline
tions after 2 years in one study.323 The etiology of CDH- defects. Typically, a hernia sac is present containing
association GERD is unclear. Certainly, anatomical omentum, small intestine, and/or colon. Rarely these
changes following CDH repair can contribute to GERD. hernias will contain liver and/or spleen. The majority of
Esophageal ectasia may occur due to the mediastinal shift children with a Morgagni hernia are asymptomatic and
which results in an abnormal lower esophageal sphinc- are rarely diagnosed during the neonatal period. Symp-
ter.324 An intrathoracic stomach due to herniation can toms typically include general epigastric discomfort or
cause loss of the angle of His.325,326 The CDH may also sometimes vomiting and coughing due to intermittent
cause a differential growth pattern and a shortening of obstruction.328,329 An acute presentation may be due to
the intra-abdominal esophagus.327 Distortion of the intestinal ischemia with necrosis and perforation as well
esophageal hiatus and increased intra-abdominal pressure as gastric volvulus. Herniation into the pericardium
from reducing the viscera have also been implicated as causing tamponade has also been described.330
post-surgical causes of GERD.314 Due to the frequency The chest radiograph may exhibit a well-defined air-
of symptomatic GERD, fundoplication has been recom- fluid level in the midline of the chest and visceral hernia-
mended at the time of CDH repair by some surgeons, tion in the retrosternal space (Fig. 24-9). Small hernias
especially in patients with large diaphragmatic defects, may require a contrast radiograph or CT scan to confirm
but without proven benefit.304 the diagnosis. Operative repair usually entails reduction
of the herniated viscera, excision of the hernia sac, and
approximation of the diaphragm to the posterior rectus
Musculoskeletal Outcomes sheath at the costal margin. These repairs can be per-
Musculoskeletal development and chest wall deformities, formed laparoscopically (Fig. 24-10).331,332 Although
such as pectus deformities, chest asymmetry, and scolio- most defects can be repaired primarily, large defects
sis, are common in CDH children with an estimated may require patch closure.213,216 The long-term outcome
incidence between 2148%.291,296 Scoliosis can be severe regarding recurrence is yet to be defined.
and can progress until adulthood. These musculoskeletal An anterior diaphragmatic hernia may be found in
abnormalities may be due to tension on the diaphragm association with a pentalogy of Cantrell due to a failure
after repair, or result from a thoracotomy without muscle in the development of the septum transversum.333 Pental-
sparing techniques, or result from a small hemithorax due ogy of Cantrell is a rare cluster of congenital anomalies
to hypoplastic lungs.11,296 Most patients are asymptomatic which includes omphalocele, cardiac defects, ectopic
and do not require operative intervention. cordis, and an anterior diaphragmatic defect extending
into the pericardium. The cardiac defect is the most
severe problem and is the main cause of mortality.
ANTERIOR HERNIAS OF MORGAGNI
An anterior diaphragmatic Morgagni hernia accounts for DIAPHRAGMATIC EVENTRATION
less than 2% of all CDH. The foramen of Morgagni
hernia results from failure of fusion of the crural and Eventration is an abnormal elevation of the diaphragm
sternal portions of the diaphragm. This can occur on which results in a paradoxical motion during respiration
either side at the junction of the septum transversum and interferes with normal pulmonary mechanics and
and thoracic wall where the superior epigastric artery function.334,335 Congenital eventration results from the
(internal mammary artery, intrathoracically) traverses incomplete development of the central tendon or
9. Ontario Congenital Anomalies Study Group. Apparent truth 35. Metkus AP, Esserman L, Sola A, et al. Cost per anomaly: What
about congenital diaphragmatic hernia: A population-based data- does a diaphragmatic hernia cost? J Pediatr Surg 1995;30:
base is needed to establish benchmarking for clinical outcomes for 22630.
CDH. J Pediatr Surg 2004;39:6615. 36. Iritani I. Experimental study on embryogenesis of congenital dia-
10. Harrison MR, Adzick NS, Estes JM, et al. A prospective study phragmatic hernia. Anat Embryol (Berl) 1984;169:1339.
of the outcome for fetuses with diaphragmatic hernia. Jama 37. Kluth D, Keijzer R, Hertl M, et al. Embryology of congenital
1994;271:3824. diaphragmatic hernia. Semin Pediatr Surg 1996;5:22433.
11. Lund DP, Mitchell J, Kharasch V, et al. Congenital diaphragmatic 38. Babiuk RP, Zhang W, Clugston R, et al. Embryological origins
hernia: The hidden morbidity. J Pediatr Surg 1994;29:25862. and development of the rat diaphragm. J Comp Neurol 2003;455:
12. Stege G, Fenton A, Jaffray B. Nihilism in the 1990s: The true 47787.
mortality of congenital diaphragmatic hernia. Pediatrics 2003;112: 39. Skandalakis JE, Gray SE, Ricketts RR. The Diaphragm. In:
5325. Skandalakis JE, Gray SE, editors. Embryology for Surgeons.
13. Neville HL, Jaksic T, Wilson JM, et al. Bilateral congenital dia- Baltimore, MD: Williams and Wilkens; 1994. p. 491539.
phragmatic hernia. J Pediatr Surg 2003;38:5224. 40. Jenkinson EL. Absence of half of the diaphragm (thoracic stomach;
14. Waller DK, Tita AT, Werler MM, et al. Association between diaphragmatic hernia). Am J Roentgenol 1931;26:899.
prepregnancy maternal body mass index and the risk of having an 41. Bremer JL. The diaphragm and diaphragmatic hernia. Arch
infant with a congenital diaphragmatic hernia. Birth Defects Res Pathol 1943;36:539.
A Clin Mol Teratol 2003;67:736. 42. Greer JJ, Allan DW, Babiuk RP, et al. Recent advances in under-
15. Lipson AH, Williams G. Congenital diaphragmatic hernia in half standing the pathogenesis of nitrofen-induced congenital dia-
sibs. J Med Genet 1985;22:1457. phragmatic hernia. Pediatr Pulmonol 2000;29:3949.
16. Witters I, Legius E, Moerman P, et al. Associated malformations 43. Wiseman NE, MacPherson RI. Acquired congenital diaphrag-
and chromosomal anomalies in 42 cases of prenatally diagnosed matic hernia. J Pediatr Surg 1977;12:65765.
diaphragmatic hernia. Am J Med Genet 2001;103:27882. 44. Noble BR, Babiuk RP, Clugston RD, et al. Mechanisms of action
17. Schlembach D, Zenker M, Trautmann U, et al. Deletion 15q24- of the congenital diaphragmatic hernia-inducing teratogen nitro-
26 in prenatally detected diaphragmatic hernia: Increasing fen. Am J Physiol Lung Cell Mol Physiol 2007;293:L107987.
evidence of a candidate region for diaphragmatic development. 45. Migliazza L, Otten C, Xia H, et al. Cardiovascular malformations
Prenat Diagn 2001;21:28992. in congenital diaphragmatic hernia: Human and experimental
18. Aviram-Goldring A, Daniely M, Frydman M, et al. Congenital studies. J Pediatr Surg 1999;34:13528.
diaphragmatic hernia in a family segregating a reciprocal translo- 46. Migliazza L, Xia H, Diez-Pardo JA, et al. Skeletal malformations
cation t(5;15)(p15.3;q24). Am J Med Genet 2000;90:1202. associated with congenital diaphragmatic hernia: Experimental
19. Slavotinek AM. Single gene disorders associated with congenital and human studies. J Pediatr Surg 1999;34:16249.
diaphragmatic hernia. Am J Med Genet C Semin Med Genet 47. Clugston RD, Klattig J, Englert C, et al. Teratogen-induced,
2007;145C:17283. dietary and genetic models of congenital diaphragmatic hernia
20. Langer JC, Winthrop AL, Whelan D. Fryns syndrome: A rare share a common mechanism of pathogenesis. Am J Pathol 2006;
familial cause of congenital diaphragmatic hernia. J Pediatr Surg 169:15419.
1994;29:12667. 48. Allan DW, Greer JJ. Pathogenesis of nitrofen-induced congenital
21. Neville HL, Jaksic T, Wilson JM, et al. Fryns syndrome in diaphragmatic hernia in fetal rats. J Appl Physiol 1997;83:
children with congenital diaphragmatic hernia. J Pediatr Surg 33847.
2002;37:16857. 49. Chinoy MR. Pulmonary hypoplasia and congenital diaphragmatic
22. Scott DA. Genetics of congenital diaphragmatic hernia. Semin hernia: Advances in the pathogenetics and regulation of lung
Pediatr Surg 2007;16:8893. development. J Surg Res 2002;106:20923.
23. Torfs CP, Curry CJ, Bateson TF, et al. A population-based 50. Chinoy MR. Lung growth and development. Front Biosci
study of congenital diaphragmatic hernia. Teratology 1992;46:555 2003;8:d392415.
65. 51. Mey J, Babiuk RP, Clugston R, et al. Retinal dehydrogenase-2 is
24. Pober BR. Genetic aspects of human congenital diaphragmatic inhibited by compounds that induce congenital diaphragmatic
hernia. Clin Genet 2008;74:115. hernias in rodents. Am J Pathol 2003;162:6739.
25. van Loenhout RB, Tibboel D, Post M, et al. Congenital diaphrag- 52. Wilson JG, Roth CB, Warkany J. An analysis of the syndrome of
matic hernia: Comparison of animal models and relevance to the malformations induced by maternal vitamin A deficiency. Effects
human situation. Neonatology 2009;96:13749. of restoration of vitamin A at various times during gestation. Am
26. Stoll C, Alembik Y, Dott B, et al. Associated malformations in J Anat 1953;92:189217.
cases with congenital diaphragmatic hernia. Genet Couns 2008; 53. Mendelsohn C, Lohnes D, Decimo D, et al. Function of the
19:3319. retinoic acid receptors (RARs) during development (II). Multiple
27. Bollmann R, Kalache K, Mau H, et al. Associated malformations abnormalities at various stages of organogenesis in RAR double
and chromosomal defects in congenital diaphragmatic hernia. mutants. Development 1994;120:274971.
Fetal Diagn Ther 1995;10:529. 54. Major D, Cadenas M, Fournier L, et al. Retinol status of newborn
28. Tibboel D, Gaag AV. Etiologic and genetic factors in congenital infants with congenital diaphragmatic hernia. Pediatr Surg Int
diaphragmatic hernia. Clin Perinatol 1996;23:68999. 1998;13:5479.
29. Butler N, Claireaux AE. Congenital diaphragmatic hernia as a 55. Miniati D. Pulmonary vascular remodeling. Semin Pediatr Surg
cause of perinatal mortality. Lancet 1962;1:65963. 2007;16:807.
30. Sweed Y, Puri P. Congenital diaphragmatic hernia: Influence of 56. Weibel ER, Gomez DM. A principle for counting tissue structures
associated malformations on survival. Arch Dis Child 1993;69: on random sections. J Appl Physiol 1962;17:3438.
6870. 57. Hislop A, Reid L. Intra-pulmonary arterial development during
31. Eghtesady P, Skarsgard ED, Smith BM, et al. Congenital dia- fetal life-branching pattern and structure. J Anat 1972;113:
phragmatic hernia associated with aortic coarctation. J Pediatr 3548.
Surg 1998;33:9435. 58. Hislop A, Reid L. Pulmonary arterial development during child-
32. Migliazza L, Xia H, Alvarez JI, et al. Heart hypoplasia in experi- hood: branching pattern and structure. Thorax 1973;28:12935.
mental congenital diaphragmatic hernia. J Pediatr Surg 1999;34: 59. Reid IS, Hutcherson RJ. Long-term follow-up of patients with
70610. congenital diaphragmatic hernia. J Pediatr Surg 1976;11:
33. Menon SC, Tani LY, Weng HY, et al. Clinical characteristics and 93942.
outcomes of patients with cardiac defects and congenital dia- 60. Dibbins AW. Congenital diaphragmatic hernia: Hypoplastic lung
phragmatic hernia. J Pediatr 2013;162:1149. and pulmonary vasoconstriction. Clin Perinatol 1978;5:93
34. Raval MV, Wang X, Reynolds M, et al. Costs of congenital dia- 104.
phragmatic hernia repair in the United States-extracorporeal 61. Suen HC, Catlin EA, Ryan DP, et al. Biochemical immaturity of
membrane oxygenation foots the bill. J Pediatr Surg 2011;46: lungs in congenital diaphragmatic hernia. J Pediatr Surg 1993;
61724. 28:4715.
334 SECTION III Thoracic
62. Moya FR, Thomas VL, Romaguera J, et al. Fetal lung maturation 85. Metkus AP, Filly RA, Stringer MD, et al. Sonographic predictors
in congenital diaphragmatic hernia. Am J Obstet Gynecol 1995; of survival in fetal diaphragmatic hernia. J Pediatr Surg
173:14015. 1996;31:14851.
63. Janssen DJ, Zimmermann LJ, Cogo P, et al. Decreased surfactant 86. Harrison MR, Adzick NS, Flake AW, et al. Correction of con-
phosphatidylcholine synthesis in neonates with congenital dia- genital diaphragmatic hernia in utero: VI. Hard-earned lessons.
phragmatic hernia during extracorporeal membrane oxygenation. J Pediatr Surg 1993;28:14117.
Intensive Care Med 2009;35:175460. 87. Keller RL, Glidden DV, Paek BW, et al. The lung-to-head ratio
64. Wagenvoort CA, Neufeld HN, Edwards JE. The structure of the and fetoscopic temporary tracheal occlusion: Prediction of sur-
pulmonary arterial tree in fetal and early postnatal life. Lab Invest vival in severe left congenital diaphragmatic hernia. Ultrasound
1961;10:75162. Obstet Gynecol 2003;21:2449.
65. Allen K, Haworth SG. Human postnatal pulmonary arterial 88. Laudy JA, Van Gucht M, Van Dooren MF, et al. Congenital
remodeling. Ultrastructural studies of smooth muscle cell and diaphragmatic hernia: An evaluation of the prognostic value of the
connective tissue maturation. Lab Invest 1988;59:7029. lung-to-head ratio and other prenatal parameters. Prenat Diagn
66. Haworth SG. Pulmonary vascular remodeling in neonatal pulmo- 2003;23:6349.
nary hypertension. State of the art. Chest 1988;93:S1338. 89. Lipshutz GS, Albanese CT, Feldstein VA, et al. Prospective analy-
67. Roubliova X, Verbeken E, Wu J, et al. Pulmonary vascular mor- sis of lung-to-head ratio predicts survival for patients with prena-
phology in a fetal rabbit model for congenital diaphragmatic tally diagnosed congenital diaphragmatic hernia. J Pediatr Surg
hernia. J Pediatr Surg 2004;39:106672. 1997;32:16346.
68. Lipsett J, Cool JC, Runciman SI, et al. Morphometric analysis of 90. Baath ME, Jesudason EC, Losty PD. How useful is the lung-to-
preterm fetal pulmonary development in the sheep model of con- head ratio in predicting outcome in the fetus with congenital
genital diaphragmatic hernia. Pediatr Dev Pathol 2000;3:1728. diaphragmatic hernia? A systematic review and meta-analysis.
69. Sokol J, Bohn D, Lacro RV, et al. Fetal pulmonary artery diam- Ultrasound Obstet Gynecol 2007;30:897906.
eters and their association with lung hypoplasia and postnatal 91. Heling KS, Wauer RR, Hammer H, et al. Reliability of the lung-
outcome in congenital diaphragmatic hernia. Am J Obstet Gynecol to-head ratio in predicting outcome and neonatal ventilation
2002;186:108590. parameters in fetuses with congenital diaphragmatic hernia.
70. Jakkula M, Le Cras TD, Gebb S, et al. Inhibition of angiogenesis Ultrasound Obstet Gynecol 2005;25:1128.
decreases alveolarization in the developing rat lung. Am J Physiol 92. Deprest JA, Flemmer AW, Gratacos E, et al. Antenatal prediction
Lung Cell Mol Physiol 2000;279:L6007. of lung volume and in-utero treatment by fetal endoscopic tra-
71. Grover TR, Parker TA, Balasubramaniam V, et al. Pulmonary cheal occlusion in severe isolated congenital diaphragmatic hernia.
hypertension impairs alveolarization and reduces lung growth in Semin Fetal Neonatal Med 2009;14:813.
the ovine fetus. Am J Physiol Lung Cell Mol Physiol 2005;288: 93. Peralta CF, Cavoretto P, Csapo B, et al. Lung and heart
L64854. volumes by three-dimensional ultrasound in normal fetuses at
72. Ruano R, Aubry MC, Barthe B, et al. Quantitative analysis of fetal 1232 weeks gestation. Ultrasound Obstet Gynecol 2006;27:
pulmonary vasculature by 3-dimensional power Doppler ultra- 12833.
sonography in isolated congenital diaphragmatic hernia. Am J 94. Ruano R, Benachi A, Martinovic J, et al. Can three-dimensional
Obstet Gynecol 2006;195:17208. ultrasound be used for the assessment of the fetal lung volume in
73. Suda K, Bigras JL, Bohn D, et al. Echocardiographic predictors cases of congenital diaphragmatic hernia? Fetal Diagn Ther
of outcome in newborns with congenital diaphragmatic hernia. 2004;19:8791.
Pediatrics 2000;105:11069. 95. Ruano R, Martinovic J, Dommergues M, et al. Accuracy of fetal
74. Casaccia G, Crescenzi F, Dotta A, et al. Birth weight and McGoon lung volume assessed by three-dimensional sonography. Ultra-
Index predict mortality in newborn infants with congenital dia- sound Obstet Gynecol 2005;26:72530.
phragmatic hernia. J Pediatr Surg 2006;41:258. 96. Cannie MM, Jani JC, Van Kerkhove F, et al. Fetal body volume
75. Taira Y, Yamataka T, Miyazaki E, et al. Comparison of the pul- at MR imaging to quantify total fetal lung volume: Normal ranges.
monary vasculature in newborns and stillborns with congenital Radiology 2008;247:197203.
diaphragmatic hernia. Pediatr Surg Int 1998;14:305. 97. Coakley FV, Lopoo JB, Lu Y, et al. Normal and hypoplastic fetal
76. Taira Y, Yamataka T, Miyazaki E, et al. Adventitial changes in lungs: Volumetric assessment with prenatal single-shot rapid
pulmonary vasculature in congenital diaphragmatic hernia com- acquisition with relaxation enhancement MR imaging. Radiology
plicated by pulmonary hypertension. J Pediatr Surg 1998;33: 2000;216:10711.
3827. 98. Rypens F, Metens T, Rocourt N, et al. Fetal lung volume: Estima-
77. Dillon PW, Cilley RE, Mauger D, et al. The relationship of pul- tion at MR imaging-initial results. Radiology 2001;219:236
monary artery pressure and survival in congenital diaphragmatic 41.
hernia. J Pediatr Surg 2004;39:30712. 99. Cannie M, Jani J, Meersschaert J, et al. Prenatal prediction of
78. Jeanty C, Nien JK, Espinoza J, et al. Pleural and pericardial effu- survival in isolated diaphragmatic hernia using observed to
sion: A potential ultrasonographic marker for the prenatal dif- expected total fetal lung volume determined by magnetic reso-
ferential diagnosis between congenital diaphragmatic eventration nance imaging based on either gestational age or fetal body
and congenital diaphragmatic hernia. Ultrasound Obstet Gynecol volume. Ultrasound Obstet Gynecol 2008;32:6339.
2007;29:37887. 100. Gorincour G, Bouvenot J, Mourot MG, et al. Prenatal prognosis
79. Garne E, Haeusler M, Barisic I, et al. Congenital diaphragmatic of congenital diaphragmatic hernia using magnetic resonance
hernia: Evaluation of prenatal diagnosis in 20 European regions. imaging measurement of fetal lung volume. Ultrasound Obstet
Ultrasound Obstet Gynecol 2002;19:32933. Gynecol 2005;26:73844.
80. Vettraino IM, Lee W, Comstock CH. The evolving appearance 101. Jani J, Cannie M, Done E, et al. Relationship between lung area
of a congenital diaphragmatic hernia. J Ultrasound Med at ultrasound examination and lung volume assessment with
2002;21:859. magnetic resonance imaging in isolated congenital diaphragmatic
81. Dillon E, Renwick M, Wright C. Congenital diaphragmatic her- hernia. Ultrasound Obstet Gynecol 2007;30:85560.
niation: Antenatal detection and outcome. Br J Radiol 2000;73: 102. Sandaite I, Claus F, De Keyzer F, et al. Examining the relationship
3605. between the lung-to-head ratio measured on ultrasound and lung
82. Benjamin DR, Juul S, Siebert JR. Congenital posterolateral volumetry by magnetic resonance in fetuses with isolated congeni-
diaphragmatic hernia: Associated malformations. J Pediatr Surg tal diaphragmatic hernia. Fetal Diagn Ther 2011;29:807.
1988;23:899903. 103. Manning PB, Murphy JP, Raynor SC, et al. Congenital diaphrag-
83. DeVore GR, Horenstein J, Platt LD. Fetal echocardiography. VI. matic hernia presenting due to gastrointestinal complications.
Assessment of cardiothoracic disproportiona new technique J Pediatr Surg 1992;27:12258.
for the diagnosis of thoracic hypoplasia. Am J Obstet Gynecol 104. Paut O, Mely L, Viard L, et al. Acute presentation of congenital
1986;155:106671. diaphragmatic hernia past the neonatal period: A life threatening
84. Wilcox DT, Irish MS, Holm BA, et al. Prenatal diagnosis of emergency. Can J Anaesth 1996;43:6215.
congenital diaphragmatic hernia with predictors of mortality. Clin 105. Weber TR, Tracy T Jr, Bailey PV, et al. Congenital diaphragmatic
Perinatol 1996;23:7019. hernia beyond infancy. Am J Surg 1991;162:6436.
24 Congenital Diaphragmatic Hernia and Eventration 335
106. Losty PD, Suen HC, Manganaro TF, et al. Prenatal hormonal 129. Cogo PE, Simonato M, Danhaive O, et al. Impaired surfactant
therapy improves pulmonary compliance in the nitrofen-induced protein b synthesis in infants with congenital diaphragmatic
CDH rat model. J Pediatr Surg 1995;30:4206. hernia. Eur Respir J 2012;Epub ahead of print.
107. Oue T, Shima H, Guarino N, et al. Antenatal dexamethasone 130. Cogo PE, Zimmermann LJ, Rosso F, et al. Surfactant synthesis
administration increases fetal lung DNA synthesis and RNA and kinetics in infants with congenital diaphragmatic hernia. Am
and protein content in nitrofen-induced congenital diaphragmatic J Respir Crit Care Med 2002;166:1548.
hernia in rats. Pediatr Res 2000;48:78993. 131. OToole SJ, Karamanoukian HL, Morin FC 3rd, et al. Surfactant
108. Kay HH, Bird IM, Coe CL, et al. Antenatal steroid treatment and decreases pulmonary vascular resistance and increases pulmonary
adverse fetal effects: What is the evidence? J Soc Gynecol Investig blood flow in the fetal lamb model of congenital diaphragmatic
2000;7:26978. hernia. J Pediatr Surg 1996;31:50711.
109. Smith GN, Kingdom JC, Penning DH, et al. Antenatal corticos- 132. Karamanoukian HL, Glick PL, Wilcox DT, et al. Pathophysiol-
teroids: Is more better? Lancet 2000;355:2512. ogy of congenital diaphragmatic hernia. VIII: Inhaled nitric oxide
110. Lally KP, Bagolan P, Hosie S, et al. Corticosteroids for fetuses requires exogenous surfactant therapy in the lamb model of con-
with congenital diaphragmatic hernia: Can we show benefit? genital diaphragmatic hernia. J Pediatr Surg 1995;30:14.
J Pediatr Surg 2006;41:66874. 133. Lally KP, Lally PA, Langham MR, et al. Surfactant does not
111. Levin DL. Morphologic analysis of the pulmonary vascular bed improve survival rate in preterm infants with congenital diaphrag-
in congenital left-sided diaphragmatic hernia. J Pediatr 1978;92: matic hernia. J Pediatr Surg 2004;39:82933.
8059. 134. Van Meurs K. Is surfactant therapy beneficial in the treatment of
112. Shehata SM, Sharma HS, van der Staak FH, et al. Remodeling of the term newborn infant with congenital diaphragmatic hernia?
pulmonary arteries in human congenital diaphragmatic hernia J Pediatr 2004;145:3126.
with or without extracorporeal membrane oxygenation. J Pediatr 135. Colby CE, Lally KP, Hintz SR, et al. Surfactant replacement
Surg 2000;35:20815. therapy on ECMO does not improve outcome in neonates
113. Beals DA, Schloo BL, Vacanti JP, et al. Pulmonary growth and with congenital diaphragmatic hernia. J Pediatr Surg 2004;39:
remodeling in infants with high-risk congenital diaphragmatic 16327.
hernia. J Pediatr Surg 1992;27:9971002. 136. Lotze A, Knight GR, Anderson KD, et al. Surfactant (beractant)
114. Okuyama H, Kubota A, Kawahara H, et al. Correlation between therapy for infants with congenital diaphragmatic hernia on
lung scintigraphy and long-term outcome in survivors of congeni- ECMO: Evidence of persistent surfactant deficiency. J Pediatr
tal diaphragmatic hernia. Pediatr Pulmonol 2006;41:8826. Surg 1994;29:40712.
115. Sakurai Y, Azarow K, Cutz E, et al. Pulmonary barotrauma in 137. Buss M, Williams G, Dilley A, et al. Prevention of heart failure
congenital diaphragmatic hernia: A clinicopathological correla- in the management of congenital diaphragmatic hernia by main-
tion. J Pediatr Surg 1999;34:18137. taining ductal patency. A case report. J Pediatr Surg 2006;41:
116. Drummond WH, Gregory GA, Heymann MA, et al. The inde- e911.
pendent effects of hyperventilation, tolazoline, and dopamine 138. Tanabe M, Yoshida H, Iwai J, et al. Doppler flow patterns through
on infants with persistent pulmonary hypertension. J Pediatr the ductus arteriosus in patients with congenital diaphragmatic
1981;98:60311. hernia. Eur J Pediatr Surg 2000;10:925.
117. Rudolph AM, Yuan S. Response of the pulmonary vasculature 139. Finer NN, Barrington KJ. Nitric oxide in respiratory failure in
to hypoxia and H+ ion concentration changes. J Clin Invest the newborn infant. Semin Perinatol 1997;21:42640.
1966;45:399411. 140. Kinsella JP, Abman SH. Inhalational nitric oxide therapy for per-
118. Boloker J, Bateman DA, Wung JT, et al. Congenital diaphrag- sistent pulmonary hypertension of the newborn. Pediatrics 1993;
matic hernia in 120 infants treated consecutively with permissive 91:9978.
hypercapnea/spontaneous respiration/elective repair. J Pediatr 141. Kinsella JP, Ivy DD, Abman SH. Inhaled nitric oxide improves
Surg 2002;37:35766. gas exchange and lowers pulmonary vascular resistance in severe
119. Kays DW, Langham MR Jr, Ledbetter DJ, et al. Detrimental experimental hyaline membrane disease. Pediatr Res 1994;
effects of standard medical therapy in congenital diaphragmatic 36:4028.
hernia. Ann Surg 1999;230:3408. 142. Roberts JD, Polaner DM, Lang P, et al. Inhaled nitric oxide in
120. Langham MR Jr, Kays DW, Beierle EA, et al. Twenty years of persistent pulmonary hypertension of the newborn. Lancet
progress in congenital diaphragmatic hernia at the University of 1992;340:8189.
Florida. Am Surg 2003;69:4552. 143. Kinsella JP, Neish SR, Shaffer E, et al. Low-dose inhalation nitric
121. Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic oxide in persistent pulmonary hypertension of the newborn.
hernia: Survival treated with very delayed surgery, spontaneous Lancet 1992;340:81920.
respiration, and no chest tube. J Pediatr Surg 1995;30:4069. 144. Clark RH, Kueser TJ, Walker MW, et al. Low-dose nitric oxide
122. Bohn D. Congenital diaphragmatic hernia. Am J Respir Crit Care therapy for persistent pulmonary hypertension of the newborn.
Med 2002;166:91115. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med
123. Azarow K, Messineo A, Pearl R, et al. Congenital diaphragmatic 2000;342:46974.
herniaa tale of two cities: The Toronto experience. J Pediatr Surg 145. The Neonatal Inhaled Nitric Oxide Study Group (NINOS).
1997;32:395400. Inhaled nitric oxide and hypoxic respiratory failure in infants
124. Paranka MS, Clark RH, Yoder BA, et al. Predictors of failure of with congenital diaphragmatic hernia. The Neonatal Inhaled
high-frequency oscillatory ventilation in term infants with severe Nitric Oxide Study Group (NINOS). Pediatrics 1997;99:
respiratory failure. Pediatrics 1995;95:4004. 83845.
125. Hirschl RB. Innovative therapies in the management of newborns 146. Keller RL, Hamrick SE, Kitterman JA, et al. Treatment of
with congenital diaphragmatic hernia. Semin Pediatr Surg rebound and chronic pulmonary hypertension with oral sildenafil
1996;5:25665. in an infant with congenital diaphragmatic hernia. Pediatr Crit
126. Desfrere L, Jarreau PH, Dommergues M, et al. Impact of delayed Care Med 2004;5:1847.
repair and elective high-frequency oscillatory ventilation on sur- 147. Ivy DD, Kinsella JP, Ziegler JW, et al. Dipyridamole attenuates
vival of antenatally diagnosed congenital diaphragmatic hernia: rebound pulmonary hypertension after inhaled nitric oxide with-
First application of these strategies in the more severe subgroup drawal in postoperative congenital heart disease. J Thorac Cardio-
of antenatally diagnosed newborns. Intensive Care Med 2000; vasc Surg 1998;115:87582.
26:93441. 148. Kinsella JP, Ivy DD, Abman SH. Pulmonary vasodilator therapy
127. Reyes C, Chang LK, Waffarn F, et al. Delayed repair of congenital in congenital diaphragmatic hernia: Acute, late, and chronic pul-
diaphragmatic hernia with early high-frequency oscillatory venti- monary hypertension. Semin Perinatol 2005;29:1238.
lation during preoperative stabilization. J Pediatr Surg 1998;33: 149. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in
10106. infants born at or near term. Cochrane Database Syst Rev (Online)
128. Cacciari A, Ruggeri G, Mordenti M, et al. High-frequency oscil- 2006;CD000399.
latory ventilation versus conventional mechanical ventilation in 150. Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases:
congenital diaphragmatic hernia. Eur J Pediatr Surg 2001;11: Molecular regulation to clinical use. Pharmacol Rev 2006;58:
37. 488520.
336 SECTION III Thoracic
151. Buysse C, Fonteyne C, Dessy H, et al. The use of dipyridamole with congenital diaphragmatic hernia? J Pediatr Surg 1999;34:
to wean from inhaled nitric oxide in congenital diaphragmatic 7205.
hernia. J Pediatr Surg 2001;36:18645. 176. Downard, C. Impact of Amicar on hemorrhagic complications of
152. Kinsella JP, Torielli F, Ziegler JW, et al. Dipyridamole augmenta- ECMO: A ten-year review. J Pediatr Surg 2003;38:12126.
tion of response to nitric oxide. Lancet 1995;346:6478. 177. Lally KP. Extracorporeal membrane oxygenation in patients with
153. Thebaud B, Saizou C, Farnoux C, et al. Dypiridamole, a cGMP congenital diaphragmatic hernia. Semin Pediatr Surg 1996;5:
phosphodiesterase inhibitor, transiently improves the response to 24955.
inhaled nitric oxide in two newborns with congenital diaphrag- 178. Somaschini M, Locatelli G, Salvoni L, et al. Impact of new treat-
matic hernia. Intensive Care Med 1999;25:3003. ments for respiratory failure on outcome of infants with congeni-
154. Filan PM, McDougall PN, Shekerdemian LS. Combination tal diaphragmatic hernia. Eur J Pediatr 1999;158:7804.
pharmacotherapy for severe neonatal pulmonary hypertension. 179. German JC, Gazzaniga AB, Amlie R, et al. Management of pul-
J Paediatr Child Health 2006;42:21920. monary insufficiency in diaphragmatic hernia using extracorpor-
155. Noori S, Friedlich P, Wong P, et al. Cardiovascular effects of eal circulation with a membrane oxygenator (ECMO). J Pediatr
sildenafil in neonates and infants with congenital diaphragmatic Surg 1977;12:90512.
hernia and pulmonary hypertension. Neonatology 2007;91: 180. Heiss K, Manning P, Oldham KT, et al. Reversal of mortality for
92100. congenital diaphragmatic hernia with ECMO. Ann Surg 1989;
156. De Luca D, Zecca E, Vento G, et al. Transient effect of epopros- 209:22530.
tenol and sildenafil combined with iNO for pulmonary hyperten- 181. Sawyer SF, Falterman KW, Goldsmith JP, et al. Improving sur-
sion in congenital diaphragmatic hernia. Paediatr Anaesth vival in the treatment of congenital diaphragmatic hernia. Ann
2006;16:5978. Thorac Surg 1986;41:758.
157. Steinhorn RH, Kinsella JP, Pierce C, et al. Intravenous sildenafil 182. Weber TR, Connors RH, Pennington DG, et al. Neonatal dia-
in the treatment of neonates with persistent pulmonary hyperten- phragmatic hernia. An improving outlook with extracorporeal
sion. J Pediatr 2009;155:8417. membrane oxygenation. Arch Surg 1987;122:6158.
158. Hunter L, Richens T, Davis C, et al. Sildenafil use in congenital 183. Davis PJ, Firmin RK, Manktelow B, et al. Long-term outcome
diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed following extracorporeal membrane oxygenation for congenital
2009;94:F467. diaphragmatic hernia: The UK experience. J Pediatr 2004;
159. Abman SH, Kinsella JP, Rosenzweig EB, et al. Implications of the 144:30915.
FDA warning against the use of Sildenafil for the treatment of 184. Langham MR Jr, Krummel TM, Greenfield LJ, et al. Extracor-
pediatric pulmonary hypertension. Am J Respir Crit Care Med poreal membrane oxygenation following repair of congenital dia-
2013;187:5725. phragmatic hernias. Ann Thorac Surg 1987;44:24752.
160. Barst RJ. Recent advances in the treatment of pediatric pulmonary 185. Lally KP, Lally PA, Van Meurs KP, et al. Treatment evolution in
artery hypertension. Pediatr Clin North Am 1999;46:33145. high-risk congenital diaphragmatic hernia: Ten years experience
161. Barst RJ, Ivy D, Dingemanse J, et al. Pharmacokinetics, safety, with diaphragmatic agenesis. Ann Surg 2006;244:50513.
and efficacy of bosentan in pediatric patients with pulmonary 186. Lally KP, Paranka MS, Roden J, et al. Congenital diaphragmatic
arterial hypertension. Clin Pharmacol Ther 2003;73:37282. hernia. Stabilization and repair on ECMO. Ann Surg 1992;
162. Rosenzweig EB, Barst RJ. Pulmonary arterial hypertension in 216:56973.
children: A medical update. Curr Opin Pediatr 2008;20:28893. 187. Reickert CA, Hirschl RB, Atkinson JB, et al. Congenital diaphrag-
163. Terragno NA, Terragno A. Prostaglandin metabolism in the fetal matic hernia survival and use of extracorporeal life support at
and maternal vasculature. Fed Proc 1979;38:757. selected level III nurseries with multimodality support. Surgery
164. Leffler CW, Hessler JR, Green RS. Mechanism of stimulation of 1998;123:30510.
pulmonary prostacyclin synthesis at birth. Prostaglandins 1984; 188. Keshen TH, Gursoy M, Shew SB, et al. Does extracorporeal
28:87787. membrane oxygenation benefit neonates with congenital dia-
165. Leffler CW, Hessler JR, Green RS. The onset of breathing at phragmatic hernia? Application of a predictive equation. J Pediatr
birth stimulates pulmonary vascular prostacyclin synthesis. Pediatr Surg 1997;32:81822.
Res 1984;18:93842. 189. ORourke PP, Lillehei CW, Crone RK, et al. The effect of extra-
166. Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vaso- corporeal membrane oxygenation on the survival of neonates with
constrictor peptide produced by vascular endothelial cells. Nature high-risk congenital diaphragmatic hernia: 45 cases from a single
1988;332:4115. institution. J Pediatr Surg 1991;26:14752.
167. Buchan KW, Magnusson H, Rabe KF, et al. Characterisation of 190. Al-Shanafey S, Giacomantonio M, Henteleff H. Congenital dia-
the endothelin receptor mediating contraction of human pulmo- phragmatic hernia: Experience without extracoporeal membrane
nary artery using BQ123 and Ro 46-2005. Eur J Pharmacol 1994; oxygenation. Pediatr Surg Int 2002;18:2831.
260:2216. 191. Pusic AL, Giacomantonio M, Pippus K, et al. Survival in neonatal
168. Ziegler JW, Ivy DD, Kinsella JP, et al. The role of nitric oxide, congenital hernia without extracorporeal membrane oxygenation
endothelin, and prostaglandins in the transition of the pulmonary support. J Pediatr Surg 1995;30:118890.
circulation. Clin Perinatol 1995;22:387403. 192. Skarsgard ED, Harrison MR. Congenital diaphragmatic hernia:
169. Ivy DD, Kinsella JP, Abman SH. Physiologic characterization of The surgeons perspective. Pediatr Rev 1999;20:e718.
endothelin A and B receptor activity in the ovine fetal pulmonary 193. Harting M. Surgical management of neonates with congenital
circulation. J Clin Invest 1994;93:21418. diaphragmatic hernia. Semin Pediatr Surg 2007;16:10914.
170. de Lagausie P, de Buys-Roessingh A, Ferkdadji L, et al. Endothe- 194. Sakai H, Tamura M, Hosokawa Y, et al. Effect of surgical repair
lin receptor expression in human lungs of newborns with congeni- on respiratory mechanics in congenital diaphragmatic hernia.
tal diaphragmatic hernia. J Pathol 2005;205:1128. J Pediatr 1987;111:4328.
171. Keller RL, Tacy TA, Hendricks-Munoz K, et al. Congenital dia- 195. de la Hunt MN, Madden N, Scott JE, et al. Is delayed
phragmatic hernia: Endothelin-1, pulmonary hypertension, and surgery really better for congenital diaphragmatic hernia?: A
disease severity. Am J Respir Crit Care Med 2010;182:55561. prospective randomized clinical trial. J Pediatr Surg 1996;31:
172. Kobayashi H, Puri P. Plasma endothelin levels in congenital dia- 15546.
phragmatic hernia. J Pediatr Surg 1994;29:125861. 196. Langer JC, Filler RM, Bohn DJ, et al. Timing of surgery for
173. Ivy DD, Rosenzweig EB, Lemarie JC, et al. Long-term outcomes congenital diaphragmatic hernia: Is emergency operation neces-
in children with pulmonary arterial hypertension treated with sary? J Pediatr Surg 1988;23:7314.
bosentan in real-world clinical settings. Am J Cardiol 2010; 197. Nio M, Haase G, Kennaugh J, et al. A prospective randomized
106:13328. trial of delayed versus immediate repair of congenital diaphrag-
174. Rosenzweig EB, Ivy DD, Widlitz A, et al. Effects of long-term matic hernia. J Pediatr Surg 1994;29:61821.
bosentan in children with pulmonary arterial hypertension. J Am 198. Al-Hathal M, Crankson SJ, Al-Harbi F, et al. Congenital dia-
Coll Cardiol 2005;46:697704. phragmatic hernia: Experience with preoperative stabilization and
175. The Congenital Diaphragmatic Hernia Study Group. Does extra- delayed surgery without ECMO and inhaled nitric oxide. Am J
corporeal membrane oxygenation improve survival in neonates Perinatol 1998;15:48790.
24 Congenital Diaphragmatic Hernia and Eventration 337
199. Breaux CW Jr, Rouse TM, Cain WS, et al. Improvement in 223. Kim AC, Bryner BS, Akay B, et al. Thoracoscopic repair of
survival of patients with congenital diaphragmatic hernia utilizing congenital diaphragmatic hernia in neonates: Lessons learned.
a strategy of delayed repair after medical and/or extracorporeal J Laparoendosc Adv Surg Tech A 2009;19:57580.
membrane oxygenation stabilization. J Pediatr Surg 1991;26: 224. Cho SD, Krishnaswami S, McKee JC, et al. Analysis of 29 con-
3338. secutive thoracoscopic repairs of congenital diaphragmatic hernia
200. West KW, Bengston K, Rescorla FJ, et al. Delayed surgical repair in neonates compared to historical controls. J Pediatr Surg
and ECMO improves survival in congenital diaphragmatic hernia. 2009;44:806; discussion 6.
Ann Surg 1992;216:45462. 225. Shah SR, Wishnew J, Barsness K, et al. Minimally invasive con-
201. Bagolan P, Casaccia G, Crescenzi F, et al. Impact of a current genital diaphragmatic hernia repair: A 7-year review of one insti-
treatment protocol on outcome of high-risk congenital diaphrag- tutions experience. Surg Endosc 2009;23:126571.
matic hernia. J Pediatr Surg 2004;39:3138. 226. McHoney MC, Corizia L, Eaton S, et al. Laparoscopic surgery in
202. Dassinger MS, Copeland DR, Gossett J, et al. Early repair of children is associated with an intraoperative hypermetabolic
congenital diaphragmatic hernia on extracorporeal membrane response. Surg Endosc 2006;20:4527.
oxygenation. J Pediatr Surg 2010;45:6937. 227. Taskin M, Zengin K, Unal E, et al. Laparoscopic repair of con-
203. Levy SM, Lally PA, Lally KP, et al. The impact of chylothorax genital diaphragmatic hernias. Surg Endosc 2002;16:869.
on neonates with repaired congenital diaphragmatic hernia. 228. Gander JW, Fisher JC, Gross ER, et al. Early recurrence of con-
J Pediatr Surg 2013;48:7249. genital diaphragmatic hernia is higher after thoracoscopic than
204. Sigalet DL, Tierney A, Adolph V, et al. Timing of repair of con- open repair: A single institutional study. J Pediatr Surg 2011;
genital diaphragmatic hernia requiring extracorporeal membrane 46:13038.
oxygenation support. J Pediatr Surg 1995;30:11837. 229. Keijzer R, van de Ven C, Vlot J, et al. Thoracoscopic repair in
205. Meehan JJ, Haney BM, Snyder CL, et al. Outcome following congenital diaphragmatic hernia: patching is safe and reduces the
recannulation and a second ECMO course. J Pediatr Surg recurrence rate. J Pediatr Surg 2010;45:9537.
2002;37:84550. 230. Lansdale N, Alam S, Losty PD, et al. Neonatal endosurgical
206. Clark RH, Hardin WD Jr, Hirschl RB, et al. Current surgical congenital diaphragmatic hernia repair: a systematic review and
management of congenital diaphragmatic hernia: a report from meta-analysis. Ann Surg 2010;252:206.
the Congenital Diaphragmatic Hernia Study Group. J Pediatr 231. Knight CG, Gidell KM, Lanning D, et al. Laparoscopic Morgagni
Surg 1998;33:10049. hernia repair in children using robotic instruments. J Laparoen-
207. Tsao K, Lally PA, Lally KP. Minimally invasive repair of congeni- dosc Adv Surg Tech A 2005;15:4826.
tal diaphragmatic hernia. J Pediatr Surg 2011;46:115864. 232. Meehan JJ, Sandler A. Robotic repair of a Bochdalek congenital
208. Puri P. Congenital diaphragmatic hernia. Curr Probl Surg diaphragmatic hernia in a small neonate: Robotic advantages and
1994;31:787846. limitations. J Pediatr Surg 2007;42:175760.
209. Kyzer S, Sirota L, Chaimoff C. Abdominal wall closure with a 233. Slater BJ, Meehan JJ. Robotic repair of congenital diaphragmatic
silastic patch after repair of congenital diaphragmatic hernia. Arch anomalies. J Laparoendosc Adv Surg Tech A 2009;19 (Suppl. 1):
Surg 2004;139:2968. S1237.
210. Schnitzer JJ, Kikiros CS, Short BL, et al. Experience with abdomi- 234. Grethel E, Cortes R, Wagner A, et al. Prosthetic patches for
nal wall closure for patients with congenital diaphragmatic hernia congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex.
repaired on ECMO. J Pediatr Surg 1995;30:1922. J Pediatr Surg 2006;41:2933.
211. Rana AR, Khouri JS, Teitelbaum DH, et al. Salvaging the severe 235. Hajer GF, vd Staak FH, de Haan AF, et al. Recurrent congenital
congenital diaphragmatic hernia patient: Is a silo the solution? diaphragmatic hernia; which factors are involved? Eur J Pediatr
J Pediatr Surg 2008;43:78891. Surg 1998;8:32933.
212. Cheah FC, Noraida MH, Boo NY, et al. Chylothorax after repair 236. Moss RL, Chen CM, Harrison MR. Prosthetic patch durability
of congenital diaphragmatic herniaa case report. Singapore Med in congenital diaphragmatic hernia: A long-term follow-up study.
J 2000;41:5489. J Pediatr Surg 2001;36:1524.
213. Arca MJ, Barnhart DC, Lelli JL Jr, et al. Early experience with 237. Lally KP, Cheu HW, Vazquez WD. Prosthetic diaphragm
minimally invasive repair of congenital diaphragmatic hernias: reconstruction in the growing animal. J Pediatr Surg 1993;28:
Results and lessons learned. J Pediatr Surg 2003;38:15638. 457.
214. Nguyen TL, Le AD. Thoracoscopic repair for congenital dia- 238. St Peter SD, Valusek PA, Tsao K, et al. Abdominal complications
phragmatic hernia: Lessons from 45 cases. J Pediatr Surg related to type of repair for congenital diaphragmatic hernia.
2006;41:17135. J Surg Res 2007;140:2346.
215. Yang EY, Allmendinger N, Johnson SM, et al. Neonatal thoraco- 239. Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped
scopic repair of congenital diaphragmatic hernia: Selection crite- double-fixed patch increases abdominal space and prevents recur-
ria for successful outcome. J Pediatr Surg 2005;40:136975. rence of large defects in congenital diaphragmatic hernia. J Pediatr
216. Holcomb GW III, Ostlie DJ, Miller KA. Laparoscopic patch Surg 2005;40:17015.
repair of diaphragmatic hernia with Surgisis. J Pediatr Surg 240. Saltzman DA, Ennis JS, Mehall JR, et al. Recurrent congenital
2005;40:E17. diaphragmatic hernia: A novel repair. J Pediatr Surg 2001;36:
217. Shah SR, Gittes GK, Barsness KA, et al. Thoracoscopic patch 17689.
repair of a right-sided congenital diaphragmatic hernia in a 241. St Peter SD, Shah SR, Little DC, et al. Bilateral congenital dia-
neonate. Surg Endosc 2008;23:215. phragmatic hernia with absent pleura and pericardium. Birth
218. McHoney M, Giacomello L, Nah SA, et al. Thoracoscopic repair Defects Res A Clin Mol Teratol 2005;73:6247.
of congenital diaphragmatic hernia: Intraoperative ventilation and 242. Sandusky GE Jr, Badylak SF, Morff RJ, et al. Histologic findings
recurrence. J Pediatr Surg 2010;45:3559. after in vivo placement of small intestine submucosal vascular
219. Pacilli M, Pierro A, Kingsley C, et al. Absorption of carbon grafts and saphenous vein grafts in the carotid artery in dogs. Am
dioxide during laparoscopy in children measured using a novel J Pathol 1992;140:31724.
mass spectrometric technique. Br J Anaesth 2006;97:2159. 243. Oelschlager BK, Barreca M, Chang L, et al. The use of small
220. Bliss D, Matar M, Krishnaswami S. Should intraoperative hyper- intestine submucosa in the repair of paraesophageal hernias: Initial
capnea or hypercarbia raise concern in neonates undergoing observations of a new technique. Am J Surg 2003;186:48.
thoracoscopic repair of diaphragmatic hernia of Bochdalek? 244. Franklin ME Jr, Gonzalez JJ Jr, Michaelson RP, et al. Preliminary
J Laparoendosc Adv Surg Tech A 2009;19 (Suppl. 1):S558. experience with new bioactive prosthetic material for repair of
221. McHoney M, Corizia L, Eaton S, et al. Carbon dioxide elimina- hernias in infected fields. Hernia 2002;6:1714.
tion during laparoscopy in children is age dependent. J Pediatr 245. St. Peter SD, Holcomb GW III. The use of biosynthetic mesh to
Surg 2003;38:10510. enhance hiatal repair at the time of re-do Nissen fundoplication.
222. Gourlay DM, Cassidy LD, Sato TT, et al. Beyond feasibility: A J Pediatr Surg 2007;42:1298301.
comparison of newborns undergoing thoracoscopic and open 246. Smith MJ, Paran TS, Quinn F, et al. The SIS extracellular matrix
repair of congenital diaphragmatic hernias. J Pediatr Surg scaffold-preliminary results of use in congenital diaphragmatic
2009;44:17027. hernia (CDH) repair. Pediatr Surg Int 2004;20:85962.
338 SECTION III Thoracic
247. Mitchell IC, Garcia NM, Barber R, et al. Permacol: A potential 270. DiFiore JW, Fauza DO, Slavin R, et al. Experimental fetal tracheal
biologic patch alternative in congenital diaphragmatic hernia ligation reverses the structural and physiological effects of pulmo-
repair. J Pediatr Surg 2008;43:21614. nary hypoplasia in congenital diaphragmatic hernia. J Pediatr Surg
248. Menon NG, Rodriguez ED, Byrnes CK, et al. Revascularization 1994;29:24856; discussion 5657.
of human acellular dermis in full-thickness abdominal wall recon- 271. Hedrick MH, Estes JM, Sullivan KM, et al. Plug the lung until it
struction in the rabbit model. Ann Plast Surg 2003;50:5237. grows (PLUG): A new method to treat congenital diaphragmatic
249. Urita Y, Komuro H, Chen G, et al. Evaluation of diaphragmatic hernia in utero. J Pediatr Surg 1994;29:6127.
hernia repair using PLGA mesh-collagen sponge hybrid scaffold: 272. Lipsett J, Cool JC, Runciman SI, et al. Effect of antenatal
An experimental study in a rat model. Pediatr Surg Int 2008;24: tracheal occlusion on lung development in the sheep model of
10415. congenital diaphragmatic hernia: A morphometric analysis of
250. Sandoval JA, Lou D, Engum SA, et al. The whole truth: Com- pulmonary structure and maturity. Pediatr Pulmonol 1998;25:
parative analysis of diaphragmatic hernia repair using 4-ply vs 25769.
8-ply small intestinal submucosa in a growing animal model. J 273. Bin Saddiq W, Piedboeuf B, Laberge JM, et al. The effects of
Pediatr Surg 2006;41:51823. tracheal occlusion and release on type II pneumocytes in fetal
251. Laituri CA, Garey CL, Valusek PA, et al. Outcome of congenital lambs. J Pediatr Surg 1997;32:8348.
diaphragmatic hernia repair depending on patch type. Eur J 274. Jani JC, Nicolaides KH, Gratacos E, et al. Fetal lung-to-head ratio
Pediatr Surg 2010;5. in the prediction of survival in severe left-sided diaphragmatic
252. Kimber CP, Dunkley MP, Haddock G, et al. Patch incorporation hernia treated by fetal endoscopic tracheal occlusion (FETO). Am
in diaphragmatic hernia. J Pediatr Surg 2000;35:1203. J Obstet Gynecol 2006;195:164650.
253. Simpson JS, Gossage JD. Use of abdominal wall muscle flap in 275. Deprest J, Jani J, Van Schoubroeck D, et al. Current consequences
repair of large congenital diaphragmatic hernia. J Pediatr Surg of prenatal diagnosis of congenital diaphragmatic hernia. J Pediatr
1971;6:424. Surg 2006;41:42330.
254. Scaife ER, Johnson DG, Meyers RL, et al. The split abdominal 276. Harrison MR, Keller RL, Hawgood SB, et al. A randomized trial
wall muscle flapa simple, mesh-free approach to repair large of fetal endoscopic tracheal occlusion for severe fetal congenital
diaphragmatic hernia. J Pediatr Surg 2003;38:174851. diaphragmatic hernia. N Engl J Med 2003;349:191624.
255. Brant-Zawadzki PB, Fenton SJ, Nichol PF, et al. The split abdom- 277. Deprest J, Gratacos E, Nicolaides KH. Fetoscopic tracheal occlu-
inal wall muscle flap repair for large congenital diaphragmatic sion (FETO) for severe congenital diaphragmatic hernia: Evolu-
hernias on extracorporeal membrane oxygenation. J Pediatr Surg tion of a technique and preliminary results. Ultrasound Obstet
2007;42:104750. Gynecol 2004;24:1216.
256. Barnhart DC, Jacques E, Scaife ER, et al. Split abdominal wall 278. Jani JC, Nicolaides KH, Gratacos E, et al. Severe diaphragmatic
muscle flap repair vs patch repair of large congenital diaphrag- hernia treated by fetal endoscopic tracheal occlusion. Ultrasound
matic hernias. J Pediatr Surg 2012;47:816. Obstet Gynecol 2009;34:30410.
257. Bianchi A, Doig CM, Cohen SJ. The reverse latissimus dorsi 279. Ruano R, Yoshisaki CT, da Silva MM, et al. A randomized control-
flap for congenital diaphragmatic hernia repair. J Pediatr Surg led trial of fetal endoscopic tracheal occlusion versus postnatal
1983;18:5603. management of severe isolated congenital diaphragmatic hernia.
258. Samarakkody U, Klaassen M, Nye B. Reconstruction of congeni- Ultrasound Obstet Gynecol 2012;39:207.
tal agenesis of hemidiaphragm by combined reverse latissimus 280. The Congenital Diaphragmatic Hernia Study Group. Estimating
dorsi and serratus anterior muscle flaps. J Pediatr Surg 2001;36: disease severity of congenital diaphragmatic hernia in the first 5
163740. minutes of life. J Pediatr Surg 2001;36:1415.
259. Meeker IA Jr, Snyder WH Jr. Surgical management of diaphrag- 281. Javid PJ, Jaksic T, Skarsgard ED, et al. Survival rate in congenital
matic defects in the newborn infant. A report of twenty infants diaphragmatic hernia: The experience of the Canadian Neonatal
each less than one week old (19561961). Am J Surg 1962;104: Network. J Pediatr Surg 2004;39:65760.
196203. 282. Grushka JR, Laberge JM, Puligandla P, et al. Effect of hospital
260. Sydorak, R. Reversed latissimus dorsi muscle flap for repair of case volume on outcome in congenital diaphragmatic hernia: The
recurrent congenital diaphragmatic hernia. J Pediatr Surg experience of the Canadian Pediatric Surgery Network. J Pediatr
2003;38:296300. Surg 2009;44:8736.
261. Bekdash B, Singh B, Lakhoo K. Recurrent late complications fol- 283. Bucher BT, Guth RM, Saito JM, et al. Impact of hospital volume
lowing congenital diaphragmatic hernia repair with prosthetic on in-hospital mortality of infants undergoing repair of congenital
patches: a case series. J Med Case Reports 2009;3:7237. diaphragmatic hernia. Ann Surg 2010;252:63542.
262. Barbosa RF, Rodrigues J, Correia-Pinto J, et al. Repair of a large 284. Cohen MS, Rychik J, Bush DM, et al. Influence of congenital
congenital diaphragmatic defect with a reverse latissimus dorsi heart disease on survival in children with congenital diaphrag-
muscle flap. Microsurgery 2008;28:858. matic hernia. J Pediatr 2002;141:2530.
263. Ferrari G, Cusella-De Angelis G, Coletta M, et al. Muscle regen- 285. Graziano JN. Cardiac anomalies in patients with congenital
eration by bone marrow-derived myogenic progenitors. Science diaphragmatic hernia and their prognosis: A report from the
1998;279:152830. Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg
264. Rossi CA, Pozzobon M, Ditadi A, et al. Clonal characterization 2005;40:10459; discussion 950.
of rat muscle satellite cells: Proliferation, metabolism and differ- 286. Tsao K, Allison ND, Harting MT, et al. Congenital diaphragmatic
entiation define an intrinsic heterogeneity. PLoS One 2010;5: hernia in the preterm infant. Surgery 2010;148:40410.
e8523. 287. Levison J, Halliday R, Holland AJ, et al. A population-based
265. De Coppi P, Bartsch G Jr, Siddiqui MM, et al. Isolation of amni- study of congenital diaphragmatic hernia outcome in New South
otic stem cell lines with potential for therapy. Nat Biotechnol Wales and the Australian Capital Territory, Australia, 19922001.
2007;25:1006. J Pediatr Surg 2006;41:104953.
266. Fuchs JR, Kaviani A, Oh JT, et al. Diaphragmatic reconstruction 288. Rygl M, Pycha K, Stranak Z, et al. Congenital diaphragmatic
with autologous tendon engineered from mesenchymal amnio- hernia: onset of respiratory distress and size of the defect: Analysis
cytes. J Pediatr Surg 2004;39:8348; discussion 8. of the outcome in 104 neonates. Pediatr Surg Int 2007;23:
267. Turner CG, Klein JD, Steigman SA, et al. Preclinical regulatory 2731.
validation of an engineered diaphragmatic tendon made with 289. Lally KP, Lally PA, Lasky RE, et al. Defect size determines sur-
amniotic mesenchymal stem cells. J Pediatr Surg 2011;46:5761. vival in infants with congenital diaphragmatic hernia. Pediatrics
268. Harrison MR, Adzick NS, Bullard KM, et al. Correction of con- 2007;120:e6517.
genital diaphragmatic hernia in utero VII: A prospective trial. 290. Danzer E, Hedrick HL. Neurodevelopmental and neurofunc-
J Pediatr Surg 1997;32:163742. tional outcomes in children with congenital diaphragmatic hernia.
269. Harrison MR, Bressack MA, Churg AM, et al. Correction of Early Hum Dev 2011;87:62532.
congenital diaphragmatic hernia in utero. II. Simulated correction 291. Nobuhara KK, Lund DP, Mitchell J, et al. Long-term outlook
permits fetal lung growth with survival at birth. Surgery for survivors of congenital diaphragmatic hernia. Clin Perinatol
1980;88:2608. 1996;23:87387.
24 Congenital Diaphragmatic Hernia and Eventration 339
292. Lally KP, Engle W. Postdischarge follow-up of infants with con- 314. Qi B, Soto C, Diez-Pardo JA, et al. An experimental study on the
genital diaphragmatic hernia. Pediatrics 2008;121:62732. pathogenesis of gastroesophageal reflux after repair of diaphrag-
293. Wohl ME, Griscom NT, Strieder DJ, et al. The lung following matic hernia. J Pediatr Surg 1997;32:13103.
repair of congenital diaphragmatic hernia. J Pediatr 1977;90: 315. Stolar CJ, Crisafi MA, Driscoll YT. Neurocognitive outcome for
40514. neonates treated with extracorporeal membrane oxygenation: Are
294. Falconer AR, Brown RA, Helms P, et al. Pulmonary sequelae in infants with congenital diaphragmatic hernia different? J Pediatr
survivors of congenital diaphragmatic hernia. Thorax 1990;45: Surg 1995;30:36671; discussion 7172.
1269. 316. Colvin J, Bower C, Dickinson JE, et al. Outcomes of congenital
295. Muratore CS, Kharasch V, Lund DP, et al. Pulmonary diaphragmatic hernia: A population-based study in Western Aus-
morbidity in 100 survivors of congenital diaphragmatic hernia tralia. Pediatrics 2005;116:e356363.
monitored in a multidisciplinary clinic. J Pediatr Surg 2001;36: 317. Nield TA, Langenbacher D, Poulsen MK, et al. Neurodevelop-
13340. mental outcome at 3.5 years of age in children treated with extra-
296. Vanamo K, Rintala R, Sovijarvi A, et al. Long-term pulmonary corporeal life support: Relationship to primary diagnosis. J Pediatr
sequelae in survivors of congenital diaphragmatic defects. 2000;136:33844.
J Pediatr Surg 1996;31:10969; discussion 9100. 318. Robertson CM, Tyebkhan JM, Hagler ME, et al. Late-onset,
297. Kamata S, Usui N, Kamiyama M, et al. Long-term follow-up of progressive sensorineural hearing loss after severe neonatal respi-
patients with high-risk congenital diaphragmatic hernia. J Pediatr ratory failure. Otol Neurotol 2002;23:3536.
Surg 2005;40:18338. 319. Fligor BJ, Neault MW, Mullen CH, et al. Factors associated with
298. Trachsel D, Selvadurai H, Bohn D, et al. Long-term pulmonary sensorineural hearing loss among survivors of extracorporeal
morbidity in survivors of congenital diaphragmatic hernia. Pediatr membrane oxygenation therapy. Pediatrics 2005;115:151928.
Pulmonol 2005;39:4339. 320. Bagolan P, Morini F. Long-term follow up of infants with
299. Marven SS, Smith CM, Claxton D, et al. Pulmonary function, congenital diaphragmatic hernia. Semin Pediatr Surg 2007;16:
exercise performance, and growth in survivors of congenital dia- 13444.
phragmatic hernia. Arch Dis Child 1998;78:13742. 321. Muratore CS, Utter S, Jaksic T, et al. Nutritional morbidity in
300. Bargy F, Beaudoin S, Barbet P. Fetal lung growth in congenital survivors of congenital diaphragmatic hernia. J Pediatr Surg
diaphragmatic hernia. Fetal Diagn Ther 2006;21:3944. 2001;36:11716.
301. Arena F, Baldari S, Centorrino A, et al. Mid- and long-term effects 322. Vanamo K, Rintala RJ, Lindahl H, et al. Long-term gastrointes-
on pulmonary perfusion, anatomy and diaphragmatic motility in tinal morbidity in patients with congenital diaphragmatic defects.
survivors of congenital diaphragmatic hernia. Pediatr Surg Int J Pediatr Surg 1996;31:5514.
2005;21:9549. 323. Cortes RA, Keller RL, Townsend T, et al. Survival of severe con-
302. Hayward MJ, Kharasch V, Sheils C, et al. Predicting inadequate genital diaphragmatic hernia has morbid consequences. J Pediatr
long-term lung development in children with congenital dia- Surg 2005;40:3645; discussion-6.
phragmatic hernia: An analysis of longitudinal changes in ventila- 324. Stolar CJ, Levy JP, Dillon PW, et al. Anatomic and functional
tion and perfusion. J Pediatr Surg 2007;42:1126. abnormalities of the esophagus in infants surviving congenital
303. Bernbaum J, Schwartz IP, Gerdes M, et al. Survivors of extracor- diaphragmatic hernia. Am J Surg 1990;159:2047.
poreal membrane oxygenation at 1 year of age: The relationship 325. Kieffer J, Sapin E, Berg A, et al. Gastroesophageal reflux after
of primary diagnosis with health and neurodevelopmental seque- repair of congenital diaphragmatic hernia. J Pediatr Surg
lae. Pediatrics 1995;96:90713. 1995;30:13303.
304. Jaillard SM, Pierrat V, Dubois A, et al. Outcome at 2 years of 326. Koot VC, Bergmeijer JH, Bos AP, et al. Incidence and manage-
infants with congenital diaphragmatic hernia: A population-based ment of gastroesophageal reflux after repair of congenital dia-
study. Ann Thorac Surg 2003;75:2506. phragmatic hernia. J Pediatr Surg 1993;28:4852.
305. Chen C, Jeruss S, Chapman JS, et al. Long-term functional impact 327. Nagaya M, Akatsuka H, Kato J. Gastroesophageal reflux occur-
of congenital diaphragmatic hernia repair on children. J Pediatr ring after repair of congenital diaphragmatic hernia. J Pediatr
Surg 2007;42:65765. Surg 1994;29:144751.
306. Danzer E, Gerdes M, Bernbaum J, et al. Neurodevelopmental 328. Kimmelstiel FM, Holgersen LO, Hilfer C. Retrosternal
outcome of infants with congenital diaphragmatic hernia prospec- (Morgagni) hernia with small bowel obstruction secondary to a
tively enrolled in an interdisciplinary follow-up program. J Pediatr Richters incarceration. J Pediatr Surg 1987;22:9981000.
Surg 2010;45:175966. 329. Sarihan H, Imamoglu M, Abes M, et al. Pediatric Morgagni
307. Van Meurs KP, Robbins ST, Reed VL, et al. Congenital hernia. Report of two cases. J Cardiovasc Surg (Torino)
diaphragmatic hernia: Long-term outcome in neonates treated 1996;37:1957.
with extracorporeal membrane oxygenation. J Pediatr 1993;122: 330. de Fonseca JM, Davies MR, Bolton KD. Congenital hydroperi-
8939. cardium associated with the herniation of part of the liver into the
308. van der Cammen-van Zijp MH, Gischler SJ, Mazer P, et al. pericardial sac. J Pediatr Surg 1987;22:8513.
Motor-function and exercise capacity in children with major ana- 331. Dutta S, Albanese CT. Use of a prosthetic patch for laparoscopic
tomical congenital anomalies: An evaluation at 5 years of age. repair of Morgagni diaphragmatic hernia in children. J Laparoen-
Early Hum Dev 2010;86:5238. dosc Adv Surg Tech A 2007;17:3914.
309. Nijhuis-van der Sanden MW, van der Cammen-van Zijp MH, 332. Ponsky TA, Lukish JR, Nobuhara K, et al. Laparoscopy is useful in
Janssen AJ, et al. Motor performance in five-year-old extracorpor- the diagnosis and management of foramen of Morgagni hernia in
eal membrane oxygenation survivors: A population-based study. children. Surg Laparosc Endosc Percutan Tech 2002;12:3757.
Crit Care 2009;13:R47. 333. Cantrell JR, Haller JA, Ravitch MM. A syndrome of congenital
310. Jakobson LS, Frisk V, Trachsel D, et al. Visual and fine-motor defects involving the abdominal wall, sternum, diaphragm, peri-
outcomes in adolescent survivors of high-risk congenital dia- cardium, and heart. Surg Gynecol Obstet 1958;107:60214.
phragmatic hernia who did not receive extracorporeal membrane 334. Symbas PN, Hatcher CR Jr, Waldo W. Diaphragmatic eventra-
oxygenation. J Perinatol 2009;29:6306. tion in infancy and childhood. Ann Thorac Surg 1977;24:1139.
311. Bouman NH, Koot HM, Tibboel D, et al. Children with congeni- 335. Wayne ER, Campbell JB, Burrington JD, et al. Eventration of the
tal diaphragmatic hernia are at risk for lower levels of cognitive diaphragm. J Pediatr Surg 1974;9:64351.
functioning and increased emotional and behavioral problems. 336. Elberg JJ, Brok KE, Pedersen SA, et al. Congenital bilateral even-
Eur J Pediatr Surg 2000;10:37. tration of the diaphragm in a pair of male twins. J Pediatr Surg
312. McGahren ED, Mallik K, Rodgers BM. Neurological outcome is 1989;24:11401.
diminished in survivors of congenital diaphragmatic hernia 337. Akay TH, Ozkan S, Gultekin B, et al. Diaphragmatic paralysis
requiring extracorporeal membrane oxygenation. J Pediatr Surg after cardiac surgery in children: Incidence, prognosis and surgical
1997;32:121620. management. Pediatr Surg Int 2006;22:3416.
313. Masumoto K, Nagata K, Uesugi T, et al. Risk factors for sen- 338. Joho-Arreola AL, Bauersfeld U, Stauffer UG, et al. Incidence
sorineural hearing loss in survivors with severe congenital dia- and treatment of diaphragmatic paralysis after cardiac surgery in
phragmatic hernia. Eur J Pediatr 2007;166:60712. children. Eur J Cardiothorac Surg 2005;27:537.
340 SECTION III Thoracic
339. Yazici M, Karaca I, Arikan A, et al. Congenital eventration of the 342. Guvenc BH, Korkmaz M, Avtan L, et al. Thoracoscopic dia-
diaphragm in children: 25 years experience in three pediatric phragm plication in children and indications for conversion to
surgery centers. Eur J Pediatr Surg 2003;13:298301. open thoracotomy. J Laparoendosc Adv Surg Tech A 2004;
340. Smith CD, Sade RM, Crawford FA, et al. Diaphragmatic paralysis 14:3025.
and eventration in infants. J Thorac Cardiovasc Surg 343. Huttl TP, Wichmann MW, Reichart B, et al. Laparoscopic
1986;91:4907. diaphragmatic plication: Long-term results of a novel surgical
341. Becmeur F, Talon I, Schaarschmidt K, et al. Thoracoscopic dia- technique for postoperative phrenic nerve palsy. Surg Endosc
phragmatic eventration repair in children: About 10 cases. 2004;18:54751.
J Pediatr Surg 2005;40:17125.
C H A P T E R 2 5
Mediastinal Tumors
Juan A. Tovar
The mediastinum can be divided into three compart- For many tumors, histology, cell markers, and molecu-
ments (Fig. 25-1). The anterior one contains the thymus, lar biology features can be identified before undertaking
vessels, lymphoid structures, and nerves. The middle one operative therapy. Cells can be obtained by biopsy of
contains the trachea, main-stem bronchi, the heart and cervical or suprasternal lymph nodes, by fine needle
great vessels, and the hilar lymph nodes. The posterior aspiration (FNA), or by pleural or pericardial fluid
mediastinum accommodates the aorta, the thoracic aspiration.911 When this is not feasible, operative biopsy
esophagus, and the sympathetic nerve chains. or excision is required. Thoracoscopy12,13 or anterior
The tracheobronchial tree derives from the embryonic mini-thoracotomy through the bed of the second or third
foregut that is innervated by neural crest cells that form rib (the Chamberlain approach)14,15 may provide material
the sympathetic chains. Embryonal germ cells migrate for biopsy or for complete removal. Mediastinoscopy is
toward their final settlement in the gonads through the rarely used in children.16
anterior mediastinum. The thymus primordia from the
third pharyngeal pouches migrate into the anterior medi-
astinum and fuse to form a single organ. Finally, huge PRINCIPLES OF MANAGEMENT
vascular structures develop in the mediastinum. All these
embryonal events explain the nature of the tumors located Children with anterior mediastinal masses can undergo
in each compartment. Their most frequent location is respiratory collapse after induction of anesthesia. Ventila-
summarized in Table 25-1. tion can be critically difficult, particularly in children
with lymphoma. Cross-sectional surfaces of the tracheal
lumen decreased by 50% or more on CT scan carry a
CLINICAL FEATURES high anesthetic risk.14 These patients also have marked
reductions in the maximum expiratory flow rates, and
Mediastinal tumors and cysts are occasionally diagnosed special modalities of anesthesia (e.g., spontaneous venti-
before birth and may even benefit from prenatal instru- lation, laryngeal mask, rigid tubes) may be necessary.6
mentation.1 However, most of them remain silent during Except for lymphomas that respond to chemotherapy
infancy and are discovered serendipitously. Respiratory and/or radiotherapy and in which surgery is usually adju-
embarrassment, orthopnea, stridor, wheezing, severe dis- vant, mediastinal tumors should be removed. Median
tress, and superior vena cava syndrome are occasionally sternotomy17 or standard thoracotomy are the preferred
seen. Large anterior tumors may cause sternal bulging. approaches. Sternotomy extended to the neck allows safe
Recurrent laryngeal or phrenic nerve palsies or Horner approach for large cervicothoracic masses (Fig. 25-2).18
syndrome may also lead to diagnosis. Sudden paraplegia Thoracoscopy is an alternative approach, and should
can occur in dumbbell tumors involving the spinal cord. respect the principles of oncologic surgery, avoiding spill-
Finally, secretion of catecholamines, -fetoprotein, or age of tumor cells or fluids (particularly true for germ cell
gonadotropins may also uncover the tumor. tumors).17,19,20 Robotic surgery has also been described.21
A B C
FIGURE 25-2 (A,B) Coronal and sagittal views from an MRI of a 5-year-old girl with a high mediastinal ganglioneuroma (asterisk)
extending from the hilum of the lung to the neck and involving the vessels and nerves of this area. (C) This was safely excised
through a cervico-transternal approach seen after removal of the mass. Ao, aorta; LCA, left carotid artery; LSA, left subclavian artery;
LVA, left vertebral artery; LJV, left jugular vein.
25 Mediastinal Tumors 343
Rapid growth of mediastinal lymphomas may cause Arbor classification of four stages with subgroups, accord-
respiratory distress, wheezing, orthopnea, cervicofacial ing to the presence or absence of systemic symptoms,
edema, and jugular ingurgitation. Systemic symptoms are remains the most widely used system, but mapping of the
possible, and bone marrow invasion causes hematologic involved organs or lymph node groups requires refined
disturbances. Enlarged lymph nodes may become palpa- imaging tools.
ble in the neck, axillae, and supraclavicular or supraster- Hodgkin lymphoma may be localized primarily in the
nal regions. mediastinum and may cause the same compressive effects
Imaging depicts an enlarged mediastinum and airway as NHL (Fig. 25-3). Biopsies of extrathoracic nodes are
involvement. Pleural or pericardial fluid can often be sometimes possible. If not, the Chamberlain operation or
obtained for cytologic analysis.11 If neither peripheral thoracoscopy should be used. The preference for chemo-
lymph nodes nor fluids are available for biopsy or cytol- therapy over radiotherapy has limited the use of staging
ogy, FNA or biopsy by thoracoscopy or the anterior laparotomy in children. This should be reserved for cases
Chamberlain approach may be necessary. In all cases, the with thoracic stage II cases in which localized radio-
anesthetic risks and precautions should be emphasized.24 therapy as the sole treatment requires excluding transdia-
Mediastinal NHL cases are stage III except when bone phragmatic involvement.30 PET/CT seems promising as
marrow and/or central nervous system are involved (stage a noninvasive staging modality.29,31
IV).25 Gallium-67 isotopic scanning may be helpful for Surgery is not usually the primary treatment of
staging.26,27 The role of combined positron emission tom- Hodgkin lymphoma, except in very localized cases.
ography (PET) and CT in children is still undefined. However, it may occasionally be needed in children.32
Mediastinal NHL respond well to chemotherapy and
corticosteroids, and the contribution of surgery is limited
to retrieval of biopsy material for cytologic assessment. GERM CELL TUMORS
Chemotherapy leads to long-term survival in more than
80% of these children.25,28 The primitive germ cells may produce various types of
tumors. Gonadal germ cells cause seminoma or dysger-
minoma whereas totipotential cells can cause yolk sac
Hodgkin Lymphoma tumors and choriocarcinoma (extraembryonic) or terato-
Mediastinal Hodgkin lymphoma is less frequent and mas (embryonic). In fact, these different components can
occurs more often in adolescents. The main feature is the be found in the same tumor.
ReedSternberg cell, the malignant counterpart of the
dendritic interdigitating cell that has a role in antigen
presentation. These cells are embedded in lymph nodes
Teratomas
in which the proportions of fibrous stroma, lymphocytes, These comprise only 816% of the tumors in this region
and plasma cells are variable, allowing classification into and are uncommon in children.33,34 They consist of
lymphocyte predominant, lymphocyte depleted, mixed solid or organoid masses containing tissues derived
cellularity, and nodular sclerosis types. Most children from all three blastodermic layers. Their histologic
with Hodgkin lymphoma have the nodular sclerosis type, features are heterogeneous and may include cystic or
but the youngest ones may have lymphocyte predomi- solid areas as well as mature and immature components.
nant or mixed cellularity varieties.29 Hodgkin lymphoma Their incidence is higher in individuals with Klinefelter
originates in one group of lymph nodes and spreads to syndrome.35,36
contiguous or distant nodes. Accurate staging is impera- Mediastinal teratomas originate most often from the
tive before selection of the treatment protocol. The Ann thymus or pericardium and are therefore anterior. They
A B
FIGURE 25-3 Imaging studies in an 11-year-old boy with Hodgkin lymphoma. (A) Widening of the mediastinum is accompanied by
compression of the upper trachea that is seen on the chest radiograph. (B) Transverse section on a CT scan of the upper mediasti-
num shows the extent of this tracheal compression by adenopathy that displaces the vessels laterally.
344 SECTION III Thoracic
are as frequent in girls as in boys, in contrast to the situa- anterior mediastinum. These are malignant and require
tion in adults in whom there is a clear male predomi- complete removal and chemotherapy, as explained earlier
nance.37,38 They develop relatively early in fetal life, and for the malignant components of teratomas.35,44
may cause hydrops and fetal demise.1,39 These masses can
be diagnosed prenatally (Fig. 25-4), but they are more
often detected after birth because of respiratory distress TUMORS AND CYSTS OF THE THYMUS
or later in life because of vague symptoms (thoracic or
cervical pain, dyspnea). The diagnosis is often incidental. During their migration, the thymic primordia leave
Mediastinal teratomas should be suspected whenever a behind thymopharyngeal ducts that progressively obliter-
mass with or without calcifications is detected in the ante- ate. Epithelial tumors and cysts are therefore possible in
rior mediastinal compartment. However, this diagnosis this organ along with lymphocytic and mesenchymal
often is not made until the operation. Most mediastinal tumors.
teratomas are benign in children, but the prognosis is
definitely worse if they contain elements of yolk sac,
embryonal carcinoma, seminoma, germinoma, or chorio
Thymic Hyperplasia
carcinoma.35,40,41 Some of these lesions may induce preco- The thymus participates in the development of cellular
cious puberty or detectable pancreatic secretions.35,42 immunity during infancy. Therefore, it is larger at this
Operative excision is the treatment of choice. Median age and subsequently shrinks. Thymic hyperplasia may
sternotomy allows excellent exposure, but lateral thora- be confounded with a tumor. However, the absence of
cotomies may be preferred when the tumor extends into symptoms and some radiologic features (e.g., the absence
either hemithorax. Thoracoscopy has also been used.43 of compression of the airway or the boat sail shape of
Chemotherapy with carboplatin, bleomycin, and etopo- the inferior boundaries of the organ) rule out this suspi-
side may allow for complete removal after tumor shrink- cion. Treatment with corticosteroids achieves thymic
age in cases that cannot be initially excised.35 Although regression, and observation may be enough.
wide adherence to adjacent tissues usually makes a com-
plete resection difficult, it is essential to avoid recurrence.
In fact, these tumors have an excellent prognosis when
Thymic Cysts
resection is complete. -Fetoprotein is a good tumor Cysts derived from the thymopharyngeal ducts may
marker because it is usually elevated in malignant and appear in the anterior mediastinum and/or in the neck.
immature tumors and very seldom in mature ones.44 They are lined by pharyngeal or ciliated epithelium.
They have secretory and thymic elements (Hassalls cor-
puscles) and may be inflamed or infected. When they
Nonteratomatous Germ Cell Tumors reach a certain size, they become palpable (in the neck)
Very rarely, pure extraembryonal germ cell tumors or detected on imaging of the mediastinum.4547 They
(seminoma/dysgerminoma, embryonal carcinoma, yolk may also cause respiratory symptoms by compression.48
sac tumor, or choriocarcinoma) may develop in the Thymic cysts can also be found in rare instances of malig-
nant lymphoma and in patients with human immunode-
ficiency virus (HIV) infection in whom they can be
multilocular.32,49
Vascular Tumors
Most hemangiomas located in the anterior mediastinum A
are in continuity with cervicofacial components that
sometimes cause respiratory compromise when they
extend into the airway. If they are asymptomatic, they
should not be treated because they tend to regress over
time. However, if airway compression is present, active
anti-angiogenic treatment with corticosteroids and/or
interferon-2 or vincristine have been used. Interferon-
2 has been found to cause severe neurologic complica-
tions.53 Propranolol, which induces rapid regression of
hemangiomas, has also been used with success in medi-
astinal locations.55 B
Kaposiform hemangioendothelioma may be accompa-
nied by a KasabachMerritt syndrome with massive
platelet trapping and risks of hemorrhage. These tumors
involve the thoracic wall and often the mediastinum. Full
anti-angiogenic therapy together with close hematologic
monitoring and eventually surgery are required. This
tumor has a mortality rate close to 20%.53
Vascular Malformations
Venous and arteriovenous malformations, and particu-
larly lymphangiomas, are occasionally located near the
confluences of large venous and lymphatic collectors in
the mediastinum.56,57 The tumor may extend into either C
hemithorax and eventually into the neck and the base of
the mouth. Lymphangiomas are usually multicystic and
infiltrate the anatomic structures. Reaction to local
infections may make the mass swell or even suppurate.
Respiratory symptoms may arise in cases with airway
compromise.58 MRI in the best imaging method for
diagnosis.
Mediastinal lymphangiomas do not tend to involute.
Treatment strategies must take into account that they are
benign, that total removal is often impossible, and that a
too radical operation may endanger nerve trunks or other
structures (Fig. 25-5).59,60 Sclerosis with OK-432 or bleo-
mycin is an alternative or a complement in cases in which
incomplete removal has already reduced the volume of
the tumor.53 Only in cases of single, wide cysts is the
result of sclerosing procedures generally satisfactory.61
For masses with multiple infiltrating cysts of small size,
partial debulking may be needed to reduce symptoms.60
D
A B
FIGURE 25-6 This newborn with the prenatal diagnosis of an upper mediastinal cyst had respiratory distress at birth. These T2-
weighted MR images show a large prevertebral mucus cyst that (A) displaces the trachea forward and (B) extends to both sides. In
A, deformation of the anterior vertebral bodies due to prolonged prenatal compression can be seen. This bronchogenic cyst was
successfully removed thoracoscopically.
mucosa. These cysts are in close contact with either the contact or within the wall of the esophagus are lined by
trachea and main-stem bronchi or the esophagus. The esophageal or mixed epithelium and are known as
secreting mucosa progressively enlarges the cysts, which esophageal duplication cysts.
can then become symptomatic. In rare instances, the Plain chest radiographs may show paramediastinal
foregut malformation is more extensive and involves both round opacities, and esophagrams depict external esopha-
the respiratory and digestive tracts, and combines esopha- geal compression or intraluminal imprinting by the cyst.
geal duplications with airway malformations.62,63 When the CT and/or MRI demonstrate the size and location of the
foregut cyst is due to a persistence of the embryonic neu- cysts and the nature of their content. Endoscopy may be
roenteric communication, it involves both the foregut and useful when the cyst is within the wall of the esophagus, and
the neural tube. It splits the notochord and, as a conse- it can demonstrate external compression in other cases.
quence, is accompanied by split vertebral bodies. This rare Foregut cysts and duplications should be excised
variety is termed a neuroenteric cyst.6466 because of their secretory nature. Prenatal diagnosis may
Prenatal detection of mediastinal cysts is possible.67 allow intrauterine treatment.70 Thoracoscopy has become
However, most cases are diagnosed at birth or later in life the preferred approach.7174 Most esophageal duplications
because of symptoms of respiratory or gastrointestinal and bronchogenic cysts can be removed by this approach.
compression (Fig. 25-6). Very seldom, mediastinal cysts Dissection from the esophageal wall may be delicate, but
may bleed due to mucosal ulceration. because these cysts generally do not communicate with
The cysts located close to the trachea and main-stem the esophageal lumen, they can be mobilized without
bronchi are lined by ciliated epithelium and are termed damage to the mucosa. As in other duplications, it is
bronchogenic cysts (Fig. 25-7).68,69 Those located in essential to completely remove the secreting mucosa to
$ % &
FIGURE 25-7 (A) This 12-year-old developed some respiratory distress that prompted the chest radiograph that shows a right bron-
chogenic cyst (arrows). (B) The lesion (asterisk) is seen at thoracoscopy. (C) After removal of the cyst, the esophagus (arrow) is seen
to lie in the posterior bed of the resection. The cyst was intimately adherent to the right main-stem bronchus (asterisk).
25 Mediastinal Tumors 347
$ %
FIGURE 25-8 A 16-year-old presented with Horner syndrome and was found to have a right superior mediastinal mass. (A) MR image
of the mass showing the ganglioneuroma (asterisk). (B) At thoracoscopy, the mass (asterisk) can be visualized cephalad to the azygous
vein and just lateral to the superior vena cava (arrow). This ganglioneuroma was able to be removed thoracoscopically.
prevent recurrence or cancer later in adulthood.68 (See All tests required for neuroblastoma workup
Chapter 39 for more information about duplications.) (e.g., meta-iodine-benzyl-guanidine scan, catecholamine
metabolite excretion) should be used for tumors in this
location.
NEURAL TUMORS In cases with paraplegia, emergency laminectomy or
laminotomy with removal of the intraspinal extension is
These tumors originate from the sympathetic chains generally preferred, although some groups advise chemo-
located on both sides of the spine and may exhibit differ- therapy initially.8385 Except in very extensive tumors and
ent degrees of differentiation, ranging from malignant in those with bone metastases in which chemotherapy
neuroblastomas to mature ganglioneuromas that may should precede surgical removal, mediastinal neural
appear intermixed in the same tumor (Fig. 25-8). For tumors are primarily excised.86 This operation can be dif-
unknown reasons, thoracic neural tumors are less malig- ficult, particularly when the tumor extends beyond the
nant than abdominal ones and tend to behave less aggres- midline or into the neck, the spinal canal, or below the
sively.75 The proportion of stages 1 and 2 and the favorable diaphragm. Mobilization of the aorta with division of
histologic patterns are definitely higher than in other several intercostal vessels may be required. Clearance of
locations. Moreover, these tumors often have less MYCN the tumor should be as complete as possible, although in
amplification.7578 The tumors involve the sympathetic many cases minimal macroscopic residual disease is una-
trunks, and can extend into the spinal canal through voidable. In cases of thoracoabdominal tumors, splitting
one or several foramina (dumbbell- or hourglass-shaped the diaphragm and dissecting the retroperitoneal mass
tumors).79,80 The upper or apical tumors may extend to from above at the same operative setting is advantageous.
the neck and often involve the stellate ganglion. The Thoracoscopic excision is being increasingly
lower ones can extend into the abdomen through the utilized.19,20,87
posterior diaphragmatic insertions and/or the aortic Irrespective of their histology, the survival of patients
hiatus. The aorta and the esophagus on the left side and with thoracic neuroblastoma is encouraging and always
the azygos vein on the right may be in close contact with better than that of abdominal primaries. Some sequelae
the tumor, which sometimes passes across the midline. are unavoidable. Paraplegia may persist when the cord
Intercostal arteries and veins are often intratumoral. has been permanently damaged (this happens in tumors
Horner syndrome and/or heterochromia of the iris that cause prenatal compression).88,89
may lead to the diagnosis.81,82 Paraplegia due to spinal Permanent paraplegia may rarely occur due to intra-
cord compression can occur suddenly.83 However, most operative spinal cord ischemia.90 Division of the segmen-
cases are silent and are discovered by imaging procedures tal vessels may cause localized paralysis of upper
for concurrent conditions or vague symptoms. Secreting abdominal or thoracic muscles. Removal of the stellate
tumors and paraneoplastic symptoms such as hyperten- ganglion usually leads to permanent Horner syndrome.
sion and diarrhea are rare in this location. A limited Finally, scoliosis can develop after laminectomies.
number of malignant tumors spread from the primary
site and metastasize to distant regions such as the bone
marrow or the bones.78 OTHER RARE MEDIASTINAL TUMORS
Imaging reveals a round or fusiform mass with some-
times hemorrhagic, necrotic, or calcified areas. The ribs Rarely, other mediastinal tumors have been reported in
and the spinal pedicles may be distorted and the foramina children. These include pseudoinflammatory tumor,
enlarged. In dumbbell tumors, the intraspinal component Langerhans cell histiocytosis with calcification, thymo
is better depicted by MRI (Fig. 25-9).79 lipoma, sarcoma, and liposarcoma.9195
348 SECTION III Thoracic
A B
C D
FIGURE 25-9 This 7-year-old patient had a long-standing history of neuroblastoma that was treated with chemotherapy but the
lesion was not resected. The tumor is seen as a fusiform mass extending to both sides of the thorax on the (A) plain radiograph
and (B) and MR image. (C) CT scan shows rib and vertebral body deformations with widening of the foramina and displacement of
the great vessels. (D) MR image depicts the dumbbell-shaped nature of the tumor, which invaded the spinal canal, although without
paraplegia. Combined spinal and right thoracotomy approaches allowed complete resection of the mass.
11. Chaignaud BE, Bonsack TA, Kozakewich HP, et al. Pleural effu-
REFERENCES sions in lymphoblastic lymphoma: A diagnostic alternative.
1. Sbragia L, Paek BW, Feldstein VA, et al. Outcome of prenatally J Pediatr Surg 1998;33:13557.
diagnosed solid fetal tumors. J Pediatr Surg 2001;36:12447. 12. Rothenberg SS. Thoracoscopy in infants and children. Semin
2. Lemaitre L, Leclerc F, Marconi V, et al. Ultrasonographic findings Pediatr Surg 1998;7:194201.
in thymic lymphoma in children. Eur J Radiol 1987;7:1259. 13. Tsao K, St Peter SD, Sharp SW, et al. Current application of
3. Borecky N, Gudinchet F, Laurini R, et al. Imaging of cervico- thoracoscopy in children. J Laparoendosc Adv Surg Tech A
thoracic lymphangiomas in children. Pediatr Radiol 1995;25: 2008;18:1315.
12730. 14. Shamberger RC. Preanesthetic evaluation of children with anterior
4. Ichikawa T, Ohtomo K, Araki T, et al. Ganglioneuroma: Computed mediastinal masses. Semin Pediatr Surg 1999;8:618.
tomography and magnetic resonance features. Br J Radiol 1996; 15. Glick RD, Pearse IA, Trippett T, et al. Diagnosis of mediastinal
69:11421. masses in pediatric patients using mediastinoscopy and the Cham-
5. Wyttenbach R, Vock P, Tschappeler H. Cross-sectional imaging berlain procedure. J Pediatr Surg 1999;34:55964.
with CT and/or MRI of pediatric chest tumors. Eur Radiol 16. Gun F, Toker A, Kaya S, et al. Cervical mediastinoscopy for
1998;8:10406. paratracheal masses in pediatric patients. Pediatr Hematol Oncol
6. Shamberger RC, Holzman RS, Griscom NT, et al. CT quantitation 2008;25:3937.
of tracheal cross-sectional area as a guide to the surgical and anes- 17. Koga H, Yamataka A, Kobayashi H, et al. Median sternotomy
thetic management of children with anterior mediastinal masses. provides excellent exposure for excising anterior mediastinal
J Pediatr Surg 1991;26:13842. tumors in children. Pediatr Surg Int 2005;21:8647.
7. Castellote A, Vazquez E, Vera J, et al. Cervicothoracic lesions in 18. Grosfeld JL, Weber TR, Vane DW. One-stage resection for
infants and children. Radiographics 1999;19:583600. massive cervicomediastinal hygroma. Surgery 1982;92:6939.
8. Zhang Y, Nishimura H, Kato S, et al. MRI of ganglioneuroma: 19. Partrick DA, Rothenberg SS. Thoracoscopic resection of medias-
Histologic correlation study. J Comput Assist Tomogr 2001;25: tinal masses in infants and children: An evaluation of technique and
61723. results. J Pediatr Surg 2001;36:11657.
9. Motoyama T, Yamamoto O, Iwamoto H, et al. Fine needle aspira- 20. Petty JK, Bensard DD, Partrick DA, et al. Resection of neurogenic
tion cytology of primary mediastinal germ cell tumors. Acta Cytol tumors in children: Is thoracoscopy superior to thoracotomy? J Am
1995;39:72532. Coll Surg 2006;203:699703.
10. Shabb NS, Fahl M, Shabb B, et al. Fine-needle aspiration of the 21. Meehan JJ, Sandler AD. Robotic resection of mediastinal
mediastinum: A clinical, radiologic, cytologic, and histologic study masses in children. J Laparoendosc Adv Surg Tech A 2008;18:
of 42 cases. Diagn Cytopathol 1998;19:42836. 11419.
25 Mediastinal Tumors 349
22. Long JC, McCaffrey RP, Aisenberg AC, et al. Terminal deoxynu- 47. De Caluwe D, Ahmed M, Puri P. Cervical thymic cysts. Pediatr
cleotidyl transferase positive lymphoblastic lymphoma: A study of Surg Int 2002;18:4779.
15 cases. Cancer 1979;44:212739. 48. Wagner CW, Vinocur CD, Weintraub WH, et al. Respiratory
23. Kaneko Y, Variakojis D, Kluskens L, et al. Lymphoblastic lym- complications in cervical thymic cysts. J Pediatr Surg 1988;23:
phoma: Cytogenetic, pathologic, and immunologic studies. Int J 65760.
Cancer 1982;30:2739. 49. Kontny HU, Sleasman JW, Kingma DW, et al. Multilocular thymic
24. Ricketts RR. Clinical management of anterior mediastinal tumors cysts in children with human immunodeficiency virus infection:
in children. Semin Pediatr Surg 2001;10:1618. Clinical and pathologic aspects. J Pediatr 1997;131:26470.
25. Marky I, Bjork O, Forestier E, et al. Intensive chemotherapy 50. Takeda S, Miyoshi S, Akashi A, et al. Clinical spectrum of primary
without radiotherapy gives more than 85% event-free survival for mediastinal tumors: A comparison of adult and pediatric popula-
non-Hodgkin lymphoma without central nervous involvement: A tions at a single Japanese institution. J Surg Oncol 2003;83:
6-year population-based study from the Nordic Society of Pediatric 2430.
Hematology and Oncology. J Pediatr Hematol Oncol 2004;26: 51. Yaris N, Nas Y, Cobanoglu U, et al. Thymic carcinoma in children.
55560. Pediatr Blood Cancer 2006;47:2247.
26. Drossman SR, Schiff RG, Kronfeld GD, et al. Lymphoma of the 52. Stachowicz-Stencel T, Bien E, Balcerska A, et al. Thymic carci-
mediastinum and neck: Evaluation with Ga-67 imaging and CT noma in children: A report from the Polish Pediatric Rare Tumors
correlation. Radiology 1990;174:1715. Study. Pediatr Blood Cancer 2010;54:91620.
27. Hamrick-Turner JE, Saif MF, Powers CI, et al. Imaging of child- 53. Fishman SJ. Vascular anomalies of the mediastinum. Semin Pediatr
hood non-Hodgkin lymphoma: Assessment by histologic subtype. Surg 1999;8:928.
Radiographics 1994;14:1128. 54. Moran CA, Suster S. Mediastinal hemangiomas: A study of 18 cases
28. Goubin A, Auclerc MF, Auvrignon A, et al. Survival in France after with emphasis on the spectrum of morphological features. Hum
childhood acute leukaemia and non-Hodgkins lymphoma (1990 Pathol 1995;26:41621.
2000). Eur J Cancer 2006;42:53441. 55. Fulkerson DH, Agim NG, Al-Shamy G, et al. Emergent medical
29. Donaldson SS. Pediatric Hodgkins diseaseup, up, and beyond. Int and surgical management of mediastinal infantile hemangioma
J Radiat Oncol Biol Phys 2002;54:18. with symptomatic spinal cord compression: Case report and litera-
30. Tebbi CK, Mendenhall N, London WB, et al. Treatment of stage ture review. Childs Nerv Syst 2010;26:1799805.
I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomy- 56. Ratan J, Bhatnagar V, Mitra DK. Mediastinal cystic hygroma in
cin, vincristine and etoposide (DBVE) and radiation: A Pediatric infancy and childhood. Pediatr Surg Int 1992;7:3801.
Oncology Group (POG) study. Pediatr Blood Cancer 2006;46: 57. Wright CC, Cohen DM, Vegunta RK, et al. Intrathoracic cystic
198202. hygroma: A report of three cases. J Pediatr Surg 1996;31:
31. Metwally H, Courbon F, David I, et al. Coregistration of preche- 14302.
motherapy PET-CT for planning pediatric Hodgkins disease 58. Sumner TE, Volberg FM, Kiser PE, et al. Mediastinal cystic
radiotherapy significantly diminishes interobserver variability of hygroma in children. Pediatr Radiol 1981;11:1602.
clinical target volume definition. Int J Radiat Oncol Biol Phys 59. Glasson MJ, Taylor SF. Cervical, cervicomediastinal and intratho-
2011;80:7939. racic lymphangioma. Prog Pediatr Surg 1991;27:6283.
32. Nogues A, Tovar JA, Sunol M, et al. Hodgkins disease of the 60. Alqahtani A, Nguyen LT, Flageole H, et al. 25 years experience
thymus: A rare mediastinal cystic mass. J Pediatr Surg 1987;22: with lymphangiomas in children. J Pediatr Surg 1999;34:11648.
9967. 61. Okazaki T, Iwatani S, Yanai T, et al. Treatment of lymphangioma
33. Weidner N. Germ-cell tumors of the mediastinum. Semin Diagn in children: Our experience of 128 cases. J Pediatr Surg 2007;42:
Pathol 1999;16:4250. 3869.
34. Takeda S, Miyoshi S, Ohta M, et al. Primary germ cell tumors in 62. Kitano Y, Iwanaka T, Tsuchida Y, et al. Esophageal duplication cyst
the mediastinum: A 50-year experience at a single Japanese institu- associated with pulmonary cystic malformations. J Pediatr Surg
tion. Cancer 2003;97:36776. 1995;30:17247.
35. Billmire D, Vinocur C, Rescorla F, et al. Malignant mediastinal 63. Horwitz JR, Lally KP. Bronchogenic and esophageal duplication
germ cell tumors: An intergroup study. J Pediatr Surg 2001;36: cyst in a single mediastinal mass in a child. Pediatr Pathol Lab Med
1824. 1996;16:11318.
36. Beresford L, Fernandez CV, Cummings E, et al. Mediastinal poly- 64. Almog B, Leibovitch L, Achiron R. Split notochord syndrome
embryoma associated with Klinefelter syndrome. J Pediatr Hematol prenatal ultrasonographic diagnosis. Prenat Diagn 2001;21:
Oncol 2003;25:3213. 115962.
37. Grosfeld JL, Billmire DF. Teratomas in infancy and childhood. 65. Schurink M, van Herwaarden-Lindeboom MY, Coppes MH, et al.
Curr Probl Cancer 1985;9:153. Neurenteric cysta case report of this rare disorder. J Pediatr Surg
38. Moran CA, Suster S. Primary germ cell tumors of the mediastinum: 2007;42:E57.
I. Analysis of 322 cases with special emphasis on teratomatous 66. Kumakura A, Takahara T, Asada J, et al. Split notochord syndrome
lesions and a proposal for histopathologic classification and clinical with congenital unilateral Horners sign. Pediatr Neurol 2008;38:
staging. Cancer 1997;80:68190. 479.
39. Froberg MK, Brown RE, Maylock J, et al. In utero development 67. Kawahara H, Kamata S, Nose K, et al. Congenital mediastinal
of a mediastinal teratoma: A second-trimester event. Prenat Diagn cystic abnormalities detected in utero: Report of two cases.
1994;14:8847. J Pediatr Gastroenterol Nutr 2001;33:2025.
40. Lakhoo K, Boyle M, Drake DP. Mediastinal teratomas: Review of 68. Suen HC, Mathisen DJ, Grillo HC, et al. Surgical management
15 pediatric cases. J Pediatr Surg 1993;28:11614. and radiological characteristics of bronchogenic cysts. Ann Thorac
41. De Backer A, Madern GC, Hakvoort-Cammel FG, et al. Medias- Surg 1993;55:47681.
tinal germ cell tumors: Clinical aspects and outcomes in 7 children. 69. Ribet ME, Copin MC, Gosselin B. Bronchogenic cysts of the
Eur J Pediatr Surg 2006;16:31822. mediastinum. J Thorac Cardiovasc Surg 1995;109:100310.
42. Kallis P, Treasure T, Holmes SJ, et al. Exocrine pancreatic function 70. Martinez Ferro M, Milner R, Voto L, et al. Intrathoracic alimen-
in mediastinal teratomata: An aid to preoperative diagnosis? Ann tary tract duplication cysts treated in utero by thoracoamniotic
Thorac Surg 1992;54:7413. shunting. Fetal Diagn Ther 1998;13:3437.
43. Feo CF, Chironi G, Porcu A, et al. Videothoracoscopic removal of 71. Schier F, Waldschmidt J. Thoracoscopy in children. J Pediatr Surg
a mediastinal teratoma. Am Surg 1997;63:45961. 1996;31:16403.
44. Dehner LP. Germ cell tumors of the mediastinum. Semin Diagn 72. Michel JL, Revillon Y, Montupet P, et al. Thoracoscopic treatment
Pathol 1990;7:26684. of mediastinal cysts in children. J Pediatr Surg 1998;33:17458.
45. Samuel M, Spitz L, Deleval M, et al. Mediastinal thymic cysts in 73. Merry C, Spurbeck W, Lobe TE. Resection of foregut-derived
children. Pediatr Surg Int 1995;10:1467. duplications by minimal-access surgery. Pediatr Surg Int 1999;15:
46. Sturm-OBrien AK, Salazar JD, Byrd RH, et al. Cervical thymic 2246.
anomaliesthe Texas Childrens Hospital experience. Laryngo- 74. Engum SA. Minimal access thoracic surgery in the pediatric popu-
scope 2009;119:198893. lation. Semin Pediatr Surg 2007;16:1426.
350 SECTION III Thoracic
75. Suita S, Tajiri T, Sera Y, et al. The characteristics of mediastinal surgical removal of residual disease. A prospective study of 42
neuroblastoma. Eur J Pediatr Surg 2000;10:3539. patientsresults of the NBL 90 Study of the French Society of
76. Morris JA, Shcochat SJ, Smith EI, et al. Biological variables in Pediatric Oncology. Cancer 1996;78:31119.
thoracic neuroblastoma: A Pediatric Oncology Group study. 86. Kang CH, Kim YT, Jeon SH, et al. Surgical treatment of malignant
J Pediatr Surg 1995;30:296302. mediastinal neurogenic tumors in children. Eur J Cardiothorac
77. La Quaglia MP, Kushner BH, Su W, et al. The impact of gross Surg 2007;31:72530.
total resection on local control and survival in high-risk neuroblas- 87. Sue K, Yamanaka K, Nakamura M. Thoracoscopic resection of a
toma. J Pediatr Surg 2004;39:41217. ganglioneuroma in the posterior mediastinum of 3-year-old boy.
78. Escobar MA, Grosfeld JL, Powell RL, et al. Long-term outcomes Pediatr Surg Int 1998;14:151.
in patients with stage IV neuroblastoma. J Pediatr Surg 2006;41: 88. Rothner AD. Congenital dumbbell neuroblastoma with paraple-
37781. gia. Clin Pediatr (Phila) 1971;10:2356.
79. Shadmehr MB, Gaissert HA, Wain JC, et al. The surgical approach 89. Shimada Y, Sato K, Abe E, et al. Congenital dumbbell neuroblas-
to dumbbell tumors of the mediastinum. Ann Thorac Surg 2003; toma. Spine 1995;20:1295300.
76:16504. 90. Boglino C, Martins AG, Ciprandi G, et al. Spinal cord vascular
80. Takeda S, Miyoshi S, Minami M, et al. Intrathoracic neurogenic injuries following surgery of advanced thoracic neuroblastoma: An
tumors50 years experience in a Japanese institution. Eur J Car- unusual catastrophic complication. Med Pediatr Oncol 1999;32:
diothorac Surg 2004;26:80712. 34952.
81. Jaffe N, Cassady R, Petersen R, et al. Heterochromia and Horner 91. Gorospe L, Fernandez-Gil MA, Torres I, et al. Misleading lead:
syndrome associated with cervical and mediastinal neuroblastoma. Inflammatory pseudotumor of the mediastinum with digital club-
J Pediatr 1975;87:757. bing. Med Pediatr Oncol 2000;35:4847.
82. McRae D Jr, Shaw A. Ganglioneuroma, heterochromia iridis, and 92. Lee BH, George S, Kutok JL. Langerhans cell histiocytosis involv-
Horners syndrome. J Pediatr Surg 1979;14:61214. ing the thymus. A case report and review of the literature. Arch
83. Mam MK, Mathew S, Prabhakar BR, et al. Mediastinal enterogenic Pathol Lab Med 2003;127:e2947.
cyst presenting as paraplegiaa case report. Indian J Med Sci 93. Moran CA, Rosado-de-Christenson M, Suster S. Thymolipoma:
1996;50:3379. Clinicopathologic review of 33 cases. Mod Pathol 1995;8:7414.
84. Akwari OE, Payne WS, Onofrio BM, et al. Dumbbell neurogenic 94. Burt M, Ihde JK, Hajdu SI, et al. Primary sarcomas of the
tumors of the mediastinum. Diagnosis and management. Mayo mediastinum: Results of therapy. J Thorac Cardiovasc Surg 1998;
Clin Proc 1978;53:3538. 115:67180.
85. Plantaz D, Rubie H, Michon J, et al. The treatment of neuroblas- 95. Plukker JT, Joosten HJ, Rensing JB, et al. Primary liposarcoma of
toma with intraspinal extension with chemotherapy followed by the mediastinum in a child. J Surg Oncol 1988;37:25763.
C H A P T E R 2 6
The Esophagus
Nicole M. Chandler Paul M. Colombani
The esophagus is a hollow muscular tube connecting the gives rise to the subclavian artery and its branches, includ-
pharynx to the stomach. It is positioned in the posterior ing the inferior thyroid artery, which supplies the cervical
mediastinum and travels through the esophageal hiatus esophagus. The thoracic esophagus is supplied directly
to the cardia of the stomach. Two sphincters control from branches of the aorta. The abdominal esophagus
passage of contents into the gastrointestinal tract: an ana- has a generous blood supply from the phrenic branches
tomic upper esophageal sphincter (UES) and a physio- and gastric vessels. The excellent submucosal plexus of
logic lower esophageal sphincter (LES). The UES the proximal esophagus allows for extensive mobilization
consists of the cricopharyngeus and inferior pharyngeal without compromise to the blood supply, whereas caution
constrictors. The LES is histologically similar to the should be taken distally because of the segmental lower
muscular component of the esophagus. esophageal blood supply.
Embryologically, the trachea and esophagus are Lesions of the upper esophagus are best approached
intimately related. The trachea and esophagus both through the right chest to avoid problems with the aortic
develop from the foregut as a median ventral diverticu- arch. The azygos vein should be ligated and divided
lum. Familiarity with the embryologic development of where it crosses the esophagus. As long as the superior
the esophagus and trachea is important to understand the vena cava is patent, the azygos vein can be divided without
congenital abnormalities that arise from these structures. consequence. Lesions of the lower esophagus can be
The classic description of these malformations proposes explored through either the right or left chest. To expose
impairment in the process of septation of the trachea and the distal esophagus via the left chest, the inferior pul-
esophagus.1 monary ligament must be divided, taking care not to
In humans, normal development of the foregut begins injure the inferior pulmonary vein that runs in the upper
during the fourth week of gestation. At 22 days gestation, aspect of the pulmonary ligament.
the foregut endoderm differentiates into a ventral respi-
ratory part and a dorsal esophageal part. The separation
of the respiratory part from the esophageal part is ENDOSCOPY
achieved by the formation of lateral longitudinal tra-
cheoesophageal folds. The trachea and esophagus elon- In current pediatric practice, diagnostic esophagoscopy is
gate first distally and then proximally. At 6 to 7 weeks frequently used to evaluate dysphagia and gastroesopha-
gestation, the separation of the esophagus and trachea is geal reflux (GER). Therapeutic esophagoscopy is used to
complete. At birth, the esophagus is 810cm in length.2 dilate esophageal strictures, evaluate for trauma, aid in
The length of the esophagus will double in the first few sclerotherapy for bleeding esophageal varices, and place
years of life. gastrostomy tubes. Both rigid and flexible esophago-
The esophageal wall is composed of mucosa, submu- scopes are available for use in children of all ages.
cosa, muscularis propria, and adventia. The esophagus Flexible endoscopy is the technique of choice for
lacks a distinct serosa. The mucosa is lined by nonkerati- routine diagnostic esophagoscopy. The rigid esophago-
nizing, stratified squamous epithelium. The muscularis scope is more versatile and provides a larger diameter
mucosa is the deepest layer of the mucosa and contains that allows for better visualization and a larger channel
longitudinal smooth muscle fibers. The submucosa con- for biopsies. It also does not require air insufflation of the
tains the venous and lymphatic plexuses. The muscularis esophagus, which is important in the setting of trauma
propria contains the internal circular and external longi- because air will not be forced through a perforation into
tudinal muscle layers. The upper third of the esophagus the mediastinum.
is composed primarily of striated muscle fibers under The main value of rigid esophagoscopy in current
voluntary control. The middle third is mixed striated and pediatric practice is for therapeutic procedures such as
smooth muscle fibers, and the lower third of the esopha- dilation of an esophageal stricture or removal of a foreign
gus contains only smooth muscle fibers. These two lower body. Rigid esophagoscopy requires general anesthesia
segments are under anatomic control. The mucosa is the with endotracheal intubation and muscle relaxation. The
strongest layer of the esophageal wall. When the esopha- child is positioned supine with a roll under the shoulders
gus is divided, the mucosa will retract proximally and to extend the neck. With care taken to protect the teeth,
distally. Meticulous approximation of the esophageal the esophagoscope, with its bevel up, is introduced
mucosa is essential for a technically sound anastomosis. into the oral cavity along the hard and soft palates to
The blood supply to the proximal esophagus is derived identify the cricopharyngeus muscle and enter the
from the fourth brachial arch. The fourth brachial arch esophagus. Once the most distal aspect of evaluation is
351
352 SECTION III Thoracic
reached, it is easy to examine the esophagus fully when bronchus; and (4) the LES. The cricopharyngeus is the
withdrawing the scope to identify any lesions or foreign narrowest point in the gastrointestinal tract. Endoscopic
bodies missed on insertion. removal has been the preferred approach in many referral
Flexible endoscopes are now available for upper centers and has been highly successful with low complica-
endoscopy in premature infants all the way to adolescents tion rates.
in a reliable, safe, and efficient manner. Endoscopy with Key principles of endoscopic management of esopha-
a flexible scope can be performed under sedation or geal foreign bodies are to protect the airway, maintain
general anesthesia. The endoscope is passed though the control of the object during extraction, and avoid causing
pharynx and cricopharynx into the upper esophagus. This additional damage. Children are more likely than adults
is most safely done under direct vision. The scope should to be asymptomatic and have an increased frequency of
be advanced down the esophagus carefully, making sure respiratory symptoms. There should be a high suspicion
to always maintain visualization of the esophageal lumen. of foreign body ingestion in infants with excessive drool-
The endoscope should never be advanced blindly. If the ing, refusal of food, and unexplained coughing or gagging.
lumen is not apparent, the scope should be withdrawn Anteroposterior and lateral chest radiographs are the best
slightly with gentle insufflation until the lumen is identi- diagnostic tests for radiopaque objects. The flat surface
fied. Once the stomach is entered, it should be insufflated of a coin is best seen on the anteroposterior view when
to allow inspection of the mucosa. In small infants, it is lodged in the esophagus, whereas the lateral view
over-distention of the stomach may lead to respiratory will show the flat surface when it is lodged in the trachea
distress. (Fig. 26-1).
Complications related to passage of a rigid or flexible Rigid esophagoscopy has long been considered the
endoscope are typically at the level of the cricopharyn- gold standard for removal of retained foreign bodies.
geus muscle. Perforation of the cricopharyngeus occurs This procedure has been proven to be highly successful
in about 0.093% with flexible endoscopy and 0.074% in with low complication rates. Other approaches have been
rigid esophagoscopy.3 Perforation during diagnostic described to treat esophageal coins including flexible
esophagoscopy is exceedingly rare. endoscopy,15 bougienage,16, 17 Foley balloon extraction
A more thorough description of pediatric esophagos- under fluoroscopy,8 and brief observation trials.17,18
copy and emerging therapeutic endoscopic techniques There is much more concern for serious injury with
can be found elsewhere.47 the ingestion of button batteries. There are four mecha-
nisms of injury caused by batteries: (1) the toxic effect
due to absorption of substances, particularly batteries
FOREIGN BODY ESOPHAGEAL INJURY containing mercuric oxide; (2) electrical discharge and
mucosal burn; (3) pressure necrosis; and (4) caustic injury
Coins are the most frequently ingested foreign body.8,9 from leakage. Severe esophageal damage may occur in as
When foreign bodies become lodged in the esophagus, little as four hours after ingestion and perforation in as
they may cause serious complications. Between 1020% little as six hours after ingestion.19 Emetics should not be
of foreign bodies may lodge in the esophagus and place given, owing to their ineffectiveness and possible reflux
the patient at risk for developing complications such of a battery back into the esophagus.
as aortoesophageal fistula,10 esophageal perforation,11 There were 20 reported cases of esophageal injury
esophageal stricture,12 tracheoesophageal fistula,13 and from ingested button batteries from 1979 to 2004.19
respiratory distress.14 There are four sites of physiologic Undoubtedly, there are many more unreported incidents.
narrowing in the esophagus: (1) the cricopharyngeus of Complications from the ingestion of button batteries
the UES; (2) the aortic notch; (3) the left main-stem include death from vascular invasion and uncontrollable
A B
FIGURE 26-1 (A) Anteroposterior and (B) lateral radiographs demonstrate a coin lodged at the cricopharyngeus muscle. Note that
coins will most often orient with the flat surface facing anteroposteriorly.
26 The Esophagus 353
hemorrhage,20 esophageal perforation,21 tracheoesopha- erythema. The esophageal mucosa will slough, but no
geal fistula (see Fig. 11-4),22,23 and bilateral vocal cord stricture will form. Second-degree injuries involve the
paralysis.24 mucosa, submucosa, and muscle layers. They result in
Further information about esophageal foreign bodies deep ulceration and granulation tissue after which col-
can be found in Chapter 11. lagen deposition and contraction occur. If there is cir-
cumferential injury, a stricture may develop. Third-degree
injuries are transmural with deep ulcerations that result
CHEMICAL ESOPHAGEAL INJURIES in a black appearance to the lining of the esophagus.
These injuries can result in esophageal perforation.
In 2010, the American Association of Poison Control Patients with grade 2b or 3 will develop strictures in
Centers reported that 50% of all human exposures 70100% of cases.27,28 Endoscopic grading of mucosal
occurred in children under the age of 6 years.25 House- injury directly predicts risk of complications with a nine-
hold cleaning substances are the third most frequent fold increase in morbidity with each incremental increase
exposure in children, accounting for 116,000 ingestions in injury grade.29 Patients who present with peritonitis,
per year. In children, ingestions are primarily accidental. mediastinitis, disseminated intravascular coagulation, or
The mean age for ingestions is 3.7 years, and 60% of shock may require emergency resection of the damaged
patients are male.26 esophageal tissue.
The extent of injury is dependent on several factors Following a corrosive ingestion, patients may be
including the composition of the substance, volume, con- asymptomatic or may present with nausea, vomiting, dys-
centration, and duration of contact. Acidic injury results phagia, odynophagia, drooling, abdominal pain, chest
in immediate pain and coagulative necrosis with eschar pain, or stridor. There are no conclusive data to correlate
formation, which likely limits tissue penetration and laboratory values or symptoms with degree of injury. The
injury depth. Acidic ingestions most commonly cause absence of symptoms or oropharyngeal lesions does not
gastric injury. Alkali ingestions more commonly result in exclude esophageal injury. In fact, 12% of patients who
esophageal injury. Alkalis combine with tissue proteins to are asymptomatic and 61% of patients without oral injury
cause liquefactive necrosis and saponification, and gener- will be found to have esophageal injury at endoscopy.26,30,31
ally penetrate deeper into tissues, potentially leading to In symptomatic patients, the presence of three or more
full-thickness damage to the esophageal wall. Alkali symptoms is an important predictor of severe esophageal
absorption leads to vascular thrombosis, further imped- injury.28
ing blood flow to damaged tissues. Ingestion of granular Initial management of these patients should focus on
products may result in more serious injuries due to pro- airway management and volume resuscitation. Direct
longed contact time with the esophageal mucosa. laryngoscopy can be useful for identifying laryngeal
Alkali ingestions have three phases of injury: liquefac- edema. Inducing emesis should be discouraged because
tive necrosis, reparative phase, and scar retraction. In additional exposure to the substance can cause increased
liquefactive necrosis, the injury rapidly penetrates the mucosal damage. A chest and abdominal radiograph
deep layers of the esophagus until the alkali is buffered should be obtained to look for signs of perforation. Com-
by tissue fluids. Between five days and two weeks is con- puted tomography (CT) of the chest can also be used in
sidered the reparative phase. Sloughing of the necrotic selected cases.
debris is followed by the development of granulation Endoscopic evaluation should be carried out in the
tissue and collagen deposition. The esophageal wall is first 24 to 48 hours after ingestion. Contraindications to
thinnest during this subacute phase and at highest risk endoscopy include shock, respiratory distress, peritonitis,
for perforation. Scar formation begins after two weeks. mediastinitis, or evidence of perforation. Endoscopy
During this time, there is deposition of collagen, result- should not be performed after five days, once the repara-
ing in possible esophageal stricture formation. tive phase has begun, because the esophagus is at its
Caustic injuries are classified similar to burns (Table thinnest and the risk of perforation is highest. Once the
26-1). The classification of injury is based on endoscopic degree of injury is identified, further evaluation of the
evaluation and is used clinically to help predict subse- distal esophagus also increases the risk of perforation.
quent clinical outcomes and course. First-degree caustic There is some controversy regarding whether all
injuries are superficial and will result in edema and patients with a history of corrosive ingestion need to
undergo endoscopy. Some authors advocate that all
patients with suspected corrosive ingestion undergo
TABLE 26-1 Classification of Caustic endoscopy as part of the medical evaluation because even
Esophageal Injuries asymptomatic patients may have esophageal injury.27,32
However, these injuries are typically mild, require no
Grade Endoscopic Findings further acute treatment, and are at low risk for long-term
1 Mucosal edema and erythema
complications. There is some evidence that asympto-
2a Friability, hemorrhage, blisters, erosions, matic patients may not benefit from routine endos-
erythema, white exudate copy.28,33 Certainly all patients who are symptomatic
2b Findings of grade 2a plus deep or circumferential require endoscopic evaluation of the esophagus.
ulceration Patients found to have grade 1 or 2a injury on endos-
3a Small and scattered area of necrosis
3b Extensive necrosis copy can be allowed oral intake and are discharged once
symptoms have resolved. Patients with grade 2b and 3
354 SECTION III Thoracic
GER-associated strictures are treated with a combina- perforation in children is the thoracic esophagus. Typi-
tion of preoperative dilations and antireflux procedures.39 cally, a perforation in the upper thoracic esophagus will
Preoperative management includes proton pump inhibi- result in findings in the left thorax, whereas perforations
tors, maximal nutritional support, and optimization of in the distal thoracic esophagus will present with right-
respiratory status. Fundoplication is delayed until nutri- sided thoracic findings. This is in contrast to the neonate,
tional optimization is met, esophagitis has resolved, and where the pharyngoesophgeal junction is the most
the stricture has been dilated. Most patients undergo common site of perforation. This is likely due to the fact
three to five dilations prior to fundoplication. Postopera- this region is the narrowest area of the esophagus.
tive dilations are then performed until the stricture is Patients with thoracic esophageal perforations may
resolved. Almost 90% of patients have complete resolu- present with respiratory distress, dysphagia, fever, chest
tion of the stricture and the associated GER with this pain, or subcutaneous emphysema. It is important that
management protocol. any child who is symptomatic following an endoscopic or
esophageal dilation be evaluated for esophageal perfora-
tion. The initial study is a chest radiograph in the antero-
ESOPHAGEAL PERFORATION posterior and lateral views. Findings suggestive of
esophageal perforation include pneumothorax, pleural
Esophageal perforation is a rare but life-threatening effusion, subcutaneous emphysema, pneumopericardium,
event in children. Iatrogenic injuries, as a result of or pneumomediastinum. A contrast esophagram is the
nasogastric tube placement, stricture dilations, and preferred diagnostic study to determine the presence of
endotracheal intubation are the most common reasons an esophageal perforation. Frequently, water-soluble
found in infants and children. Due to the fact the esopha- contrast is used initially and followed by barium if no leak
gus lacks a serosal layer, a perforation allows bacteria and is initially seen. There is a 10% false-negative rate with
digestive enzymes to leak into the mediastinum. The esophogography.44 Chest CT can also suggest esophageal
surrounding loose areolar connective tissue is unable to perforation, with findings such as mediastinal air, fluid,
contain the spread of infection and inflammation, and or esophageal thickening.
may lead to mediastinitis, empyema, abscess, and sepsis.40 Treatment is guided by the type and extent of injury
Esophageal perforations may be iatrogenic, or result as well as the clinical status of the child. Most patients
from ingestion of a foreign body, caustic substances, with esophageal perforation can be successfully managed
spontaneous, infectious, or traumatic. In the pediatric with an aggressive conservative approach (Fig. 26-4).
literature, nearly 80% of esophageal perforations are Patients are started on broad-spectrum antibiotics. If fea-
attributable to iatrogenic causes.4143 In children, the sible, a nasogastric tube is inserted beyond the perfora-
most common cause of iatrogenic esophageal perforation tion into the stomach. This allows enteral alimentation
is from stricture dilation. The most common location of during the healing process. Otherwise, parenteral
triple A syndrome (achalasia, alacrima, and adrenocorti- applicability in children. Because of the limited success
cotropic hormone [ACTH] insensitivity). of these therapies, they not used for primary therapy but
Data obtained from the Healthcare Cost and Utiliza- they may be considered in children unable to undergo
tion Project (HCUP) from 1997 to 2006 found an annual general anesthesia.
hospitalization rate of 0.25/100,000 for patients with Forceful dilation of the LES is accomplished with a
achalasia under the age of 18 years.56 Symptoms of acha- balloon dilator specifically designed for the treatment of
lasia are age dependent. Infants present with frequent achalasia. Pneumatic dilation reduces the LES pressure
regurgitation, choking, pneumonia, and failure to thrive. by partially disrupting the sphincter muscle complex.
Symptoms in older children are similar to those seen in Immediate relief of symptoms can be expected in the
adults and include dysphagia, vomiting, and weight loss. majority of patients following pneumatic dilation but
The presenting symptoms are often attributed to recurrence of symptoms can be as high as 100%.58 Sec-
GER; however, symptoms persist following initiation of ondary procedures, such as repeat pneumatic dilation or
antireflux medication. A barium esophagogram will surgical esophagomytomy, may be required in 8093%
show aperistalsis of the esophagus, a dilated esophagus, of patients.58,59 Approximately half of these patients
and no or minimal opening of the LES, known as the choose to undergo additional dilations and half proceed
birds beak sign (Fig. 26-6). Esophageal manometry is to surgical repair.58,59 The perforation rate with pneu-
the standard diagnostic test for achalasia and typical find- matic dilation is about 5%60, 61 and may be managed
ings include an elevated LES pressure, failure of the conservatively, or with immediate myotomy based on the
sphincter to relax with swallowing, and low-amplitude, patients clinical status.
nonprogressive, or absent peristaltic contractions in the A large, multicenter, prospective, randomized trial
esophageal body. comparing serial pneumatic dilation to primary laparo-
There is no cure for the underlying pathology. The scopic esophagomyotomy with Dor fundoplication in
aims of therapy are to reduce the LES pressure to facili- adults was recently conducted.62 A minimal two-year
tate esophageal emptying, and improve symptoms. Treat- follow-up (mean 43 months) was attained in 95 patients
ment has utilized several approaches: pharmacologic who underwent dilation and 106 who underwent
agents, mechanical dilation, and esophagomyotomy. myotomy. At two years, there was no difference in lower
Pharmacologic treatment with nitrates or calcium- esophageal pressure, esophageal emptying, abnormal
channel blockers can result in a decrease in the LES esophageal acid exposure, or quality of life. The authors
pressure, but the response is temporary. The need for concluded that myotomy did not offer superior therapeu-
long-term medicine limits its usefulness in children. tic success and thus dilation could be considered as first-
Intersphincteric injection of Botulinum toxin (Botox) has line treatment. These data may represent a paradigm
been used in recent years for the treatment of achalasia.57 shift in the treatment for achalasia, although longer
Botox is a neurotoxin that binds to presynaptic choliner- follow-up is needed as are data in children.
gic terminals in skeletal muscle, inhibiting the release of The goal of esophagomyotomy is to disrupt the LES
acetylcholine at the neuromuscular junction, which enough to eliminate dysphagia without causing complica-
creates a chemical denervation. While initially effective, tions of excessive reflux. This can be accomplished with
there is a high recurrence rate that also limits its a thoracic or abdominal approach, open or minimally
invasively, with or without a concomitant antireflux pro-
cedure. Excellent results have been reported in 7093%
patients at more than five years of follow-up, either
with59,63 or without64,65 a fundoplication. In long-term
follow-up studies, manometry has shown low LES pres-
sures, but no significant increase in the amplitude of the
esophageal contractions.66
Two areas of controversy in the operative management
of achalasia include the length of the myotomy and per-
formance of a concomitant antireflux procedure. It is
believed that an extended myotomy past the LES results
in postoperative GER. Surgeons who do not routinely
perform an antireflux procedure advocate for a shorter
distal myotomy, extending approximately 5mm past the
gastroesophageal junction to maintain a higher pressure
at the LES to prevent GER.65 However, in patients
treated with myotomy alone, the postoperative occur-
rence of GER can be as high as 47%.61,66 In addition,
postoperative dysphagia occurs in 25%.63,64 These find-
ings may indicate that not only does a limited myotomy
not prevent postoperative GER, but also suggest it may
FIGURE 26-6 This barium swallow was performed in a 16-year- not always relieve the symptoms.
old patient with dysphagia secondary to achalasia. The classic
birds beak narrowing of the distal esophagus at the level of
In adults, there is good evidence to support a longer
the spastic, contracted esophagus is seen. Also, note the dilated myotomy combined with a partial fundoplication. A pro-
esophagus proximal to the lower esophageal sphincter. spective randomized controlled study in adults showed a
358 SECTION III Thoracic
fundoplication decreases the incidence of postoperative shortest and straightest route. Third, the prevention of
reflux from 47% to 9.1%.66 In addition to an antireflux reflux into any conduit is important. An interposition
procedure, it has been recognized in adults that a longer procedure that incorporates the distal normal esophagus
myotomy, extending for 2.53cm onto the gastric wall, with its gastroesophageal junction may have an advantage
reduces postoperative dysphagia from 17% to 5%.67 in preventing reflux complications. Fourth, persistence is
There has also been good success reported in children exceedingly important. Anastomotic dilatations should
undergoing an extended myotomy with partial fundopli- not be necessary except during the healing phase. Stric-
cation.68 As a result of these findings, the most commonly tures should be revised (Fig. 26-7). Complex interposi-
utilized operation is the laparoscopic esophagomyotomy tions that do not function well should be revised to provide
with Dor fundoplication with extension of the esophageal the straightest, lowest resistance conduit possible.
myotomy 46cm above and 23cm distal to the gastro-
esophageal junction.
Persistence or recurrence of dysphagia following
Gastric Tube Esophageal Replacement
myotomy is thought to be the result of incomplete dis- Gastric tubes have become popular because they can be
ruption of the muscle fibers of the distal esophagus. created rapidly with a stapling device. The gastric tube is
Adjunctive techniques to improve the adequacy of the constructed from the greater curve of the stomach with
myotomy have included intraoperative endoscopy and the blood supply based on the left gastroepiploic artery.
intraoperative mamometry.69,70 Intraoperative endoscopy These tubes can be created from the antrum up, or from
correctly identifies the squamocolumnar transition at the the fundus down, and can be constructed so that there is
esophagogastric junction to determine the distal extent enough gastric tube to reach the neck (Fig. 26-8). The
of myotomy. Intraoperative manometery has been used advantages of a gastric tube are its reliable blood supply,
to confirm reduction of LES pressures following its resistance to ulceration from gastric acid reflux, and its
myotomy. In one study, intraoperative manometry fol- ability to bridge long gaps. The tube is also resilient and
lowing myotomy showed residual high pressure in 34%, does not become tortuous or dilated over time. Theoreti-
prompting extension of the myotomy.69 The use of intra- cal disadvantages are a long suture line, continued acid
operative manometry in children has been shown to production by the tube, and reduced stomach capacity.
reduce recurrence of symptoms at one year to 0%.70 Complications include anastomotic leak, stricture for-
It is important to remember that achalasia is a chronic mation requiring dilation, temporary dumping syndrome,
condition. Even following operation for achalasia, chil- and the development of Barrett esophagus above the
dren have significantly lower quality of life (QOL) scores anastamosis.73,74 Control studies have shown normal
than children with inflammatory bowel disease and have swallowing and manometry has shown mass contractions
QOL scores that are comparable to children with chronic
constipation.71 Population-based studies have found a
16-fold risk of development of esophageal cancer follow-
ing treatment for achalasia.72 However, the absolute risk
of esophageal cancer remains relatively low, and there is
no consensus regarding the need for routine surveillance
in patients with achalasia.
ESOPHAGEAL REPLACEMENT
The most common indications for esophageal replace-
ment in infants and children are long-gap esophageal
atresia, failed primary repair of esophageal atresia, and
strictures related to reflux or corrosive injury.7375 The
colon was the first conduit used as an esophageal replace-
ment and remains the most commonly used technique in
practice today. Other alternatives that have been used
with success include gastric tube, gastric transposition,
and jejunal interposition graft. Which conduit is best for
any given patient depends on multiple factors, including
the location and length of the native remaining esopha-
gus, the original diagnosis, the patients size and age, and
previous procedures on the esophagus, stomach, or colon.
Regardless of the conduit used, there are several impor-
tant principles. First, the esophagus is the optimal conduit,
provided it functions relatively normally and has no
malignant potential (e.g., Barrett esophagus). Second, a
FIGURE 26-7 Barium swallow of a 28-year-old patient after suc-
short straight tract is best because almost all conduits cessful left colon interposition for isolated esophageal atresia.
function as passive tubes rather than by means of intrinsic The patient developed bleeding and dysphagia from peptic
peristaltic activity. The posterior mediastinum is often the ulceration at the distal anastomosis, requiring revision.
26 The Esophagus 359
A B C
FIGURE 26-8 Graphic depiction of the technique to create a reversed gastric tube for esophageal replacement. (A) Inspection of the
blood supply to the stomach and preservation of the gastroepiploic artery for creating the tube. (B) The use of a stapler to create
the tube along the greater curvature of the stomach. (C) The completed reversed tube is brought up to the chest for the esophageal
anastomosis.
Gastric Transposition
The gastric transposition (or pull-up procedure) is per-
formed by mobilizing the entire stomach on a vascular
pedicle, relocating the entire stomach into the mediasti-
num, and creating an anastomosis to the cervical esopha-
gus in the neck. In addition, many surgeons will perform
a pyloroplasty to prevent gastroparesis. The advantages
of this approach include that it is technically straightfor-
ward, the stomach has an excellent blood supply, only one
anastomosis is needed, and that the entire esophagus can
be replaced with a low risk of necrosis, leak, or stricture.
Complications following gastric transposition have
included anastomotic leak, stricture, and significant swal-
lowing problems. Mortality has been reported to be
4.6%.75 Death following gastric transposition is typically
due to respiratory failure. Gastric transposition may not
be the ideal substitution in patients with borderline res-
piratory function as a bulky stomach in the chest may
contribute to further respiratory compromise. Figure
26-9 depicts a postoperative barium study after a gastric
pull-up procedure for an extensive stricture following lye
ingestion.
The long-term outcome is considered good to excel- FIGURE 26-9 This infant underwent a gastric pull-up after a
lent in 90%, although many patients prefer eating small failed colonic interposition for isolated esophageal atresia. The
native esophagus is identified by the arrow, and the gastric
frequent meals. There has been no documented evidence pull-up is marked with an asterisk.
of deterioration in the function of the gastric transposi-
tion in 72 patients who were observed for longer than ten
years.75 create the additional stomach length required to reach
In older patients who have had multiple procedures, the neck.
the blood supply to the stomach may be compromised
and a long gastric tube is not advised. These patients
also may not have adequate stomach length to reach
Colon Interposition
the cervical esophagus. In such patients, a gastric pull- The right, transverse, or left colon on its vascular pedicle
up, combined with a short gastric tube, may be used to has been used as an esophageal replacement, either in an
360 SECTION III Thoracic
isoperistaltic or an antiperistaltic direction. It can be with a right colon interposition for esophageal atresia
placed retrosternal or in a transhiatal posterior mediasti- are seen in Figure 26-10, and the operative steps for
nal location. The left colon and its vascular pedicle, based a left or transverse colon interposition are seen in
on the left colic artery, is most commonly used.76 The Figure 26-11.
colon is pulled up into the neck, and an end-to-side or A colon interposition is a relatively straightforward
end-to-end esophagocolic anastomosis is performed. procedure, and the colon is readily positioned into the
The gastrocolic anastomosis is then performed, followed thorax without causing respiratory compromise. Disad-
by a fundoplication and pyloroplasty. The steps involved vantages of this approach include the need for
A B
C D
FIGURE 26-10 (A) For any esophageal lesion in which a substitution procedure may be anticipated, the gastrostomy should be
placed on the lesser curve at about the level of the incisura, so that a right or left colon or gastric tube interposition can be carried
out without compromising the blood supply. (B) The right colon and terminal ileum are isolated, based on blood supply from the
arcades and from the middle colic artery. (C) The colon on its pedicle is brought up through the lesser sac and positioned subster-
nally in an isoperistaltic fashion. (D) Most frequently, excision of the terminal ileum and cecum is accomplished. Careful tailoring
of the distal end allows a straight conduit to be anastomosed to the antrum. Pyloroplasty may or may not be added to the procedure.
The incidence of significant gastrocolic reflux is reduced by a drainage procedure.
26 The Esophagus 361
three anastomoses, an increased risk for anastomotic leak, the newborn period. Several authors report performing
strictures at the esophagocolic anastomosis, and tortuos- colonic interposition once the patient is 3 months of age
ity or redundancy of the graft over time. or 5kg in weight.7779 Many pediatric surgeons, however,
Graft necrosis or ischemia can be prevented by metic- prefer a cervical esophagoscopy and gastrostomy, and
ulous attention to the blood supply. Assuring that the wait to perform the colon interposition when the patient
graft has a dual blood supply from the left colic artery is walking, usually over the age of 1 year. Both approaches
and from the marginal arcade will help prevent ischemia have theoretical and practical advantages. Most reported
or necrosis. Careful attention not to disrupt the vascular experience has been in patients who are 12 to 18 months
supply to the cervical esophagus and performing a wide of age and are walking to allow the upright position to
anastamosis will help avoid anastomotic leak and stenosis. counteract reflux into the graft and allow for passive
The addition of a partial fundoplication may decrease the emptying of the neoesophagus.80 During the period from
incidence of GER into the graft and resultant ulceration. esophagostomy to colon interposition, it is important to
An accurate measurement of the graft length and excision provide sham feedings to develop oralmotor coordina-
of excess length before anastamosis should prevent tion. If sham oral feedings accompany gastrostomy feed-
redundancy. ings, the patient may then associate a full stomach with
swallowing.
Timing of Colon Interposition
In those patients in whom esophageal atresia has devel-
Jejunal Substitution
oped without a distal fistula, and in whom attempts at The jejunum has been used as an esophageal substitute
stretching are successful, the colon can be interposed in much more commonly in adults than in children.
A B C
D E
FIGURE 26-11 The left colon or transverse colon substitution described by Waterston is illustrated in this patient with isolated
esophageal atresia. However, it works equally well for other lesions requiring esophageal replacement. (A) A standard posterolateral
left thoracotomy at about the sixth intercostal space. (B) Incision of the diaphragm peripherally. (C) A section of colon is isolated
and its vascular pedicle is developed, usually based on the left colic artery. It may be necessary to base it on the middle colic artery,
in which case, this interposed colon is placed in an antiperistaltic manner. (D) The colon and its vascular pedicle are delivered behind
the spleen and pancreas and through a separate posterior opening in the diaphragm, so that the abdominal viscera do not stretch
or otherwise obstruct the blood supply to this colon segment. (E) The distal anastomosis may be made to the remnant of the distal
esophagus (as is depicted) or to the posterior aspect of the stomach.
362 SECTION III Thoracic
FIGURE 26-11, Contd (F) The upper anastomosis is made to the esophagus either within the mediastinum or within the neck. Ade-
quate drainage of the pleura is necessary to prevent empyema. A fundoplication after the method of Thal also may be added to
this procedure, if the distal esophagus is used. This technique reduces the amount of reflux that can interfere with the healing or
that can produce ulcers in the colon. (G) A lateral view of an alternative method of cologastrostomy with Waterstons procedure.
(H) The segment of colon is shown within the abdominal cavity, which may possibly reduce the incidence of gastrocolic reflux.
Advantages to using jejunum include a diameter that is necrosis of the interposition. This complication is most
similar to the esophagus and does not occupy much space commonly seen when using the jejunum or colon and is
in the thoracic cavity. Also, the jejunum retains its peri- recognized at the time of interposition as a blue, pulseless
staltic activity. Significant disadvantages include the pre- graft. Adjustment of the graft to relieve tension or
carious vascular supply of a pedicled jejunal graft. Also, a twisting of the pedicle may be effective in improving
tension-free anastomosis may be difficult to achieve. the blood supply. Intraoperative hypotension may result
Esophageal substitution with free and pedicled jejunal in the graft taking on the appearance of vascular insuf-
grafts has resulted in significant perioperative morbidity, ficiency. If the geometry of the graft and the patients
including intraoperative repeat interpositions for imme- blood pressure are both satisfactory, the graft must be
diate graft loss, early postoperative graft loss, anastomotic abandoned because its vascularity will rarely improve
leaks, late anastomotic strictures, and graft redun- after completion of the operation.
dancy.81,82 Less than 50% of patients are able to achieve Interposition of a well-vascularized graft is sometimes
a completely oral diet without reliance on gastrostomy followed several days later by fever, increased leukocyto-
feeds.81 In spite of technically sound outcomes, it is sis, and drainage from the proximal anastomosis. An
known that significant complications exist, including anastomotic leak from tension or mild ischemia can be
death, graft necrosis, ischemia, and strictures. managed expectantly if the conduit appears viable. A con-
trast study, however, may demonstrate that the mucosal
pattern of the interposed segment is ischemic. The inter-
Complications of Esophageal Substitution position must be inspected and removed if it is necrotic.
Regardless of the conduit used, substitution of the In this case, a cervical esophagostomy should be estab-
esophagus carries a number of predictable complications. lished and a different form of substitution planned. Many
The most serious one is vascular insufficiency with investigators have reported using the left colon after
26 The Esophagus 363
28. BetallI P, Falchetti D, Giuliani S, et al. Caustic ingestion in chil- 56. Sonnenberg A. Hospitalization for achalasia in the United States
dren: is endoscopy always indicated? The results of an Italian mul- 19972006. Dig Dis Sci 2009;54:16805.
ticenter observational study. Gastrointest Endosc 2008;68:4349. 57. Walton JM, Tougas G. Botulinum toxin use in pediatric achalasia:
29. Poley JW, Steyerberg EW, Kuipers EJ, et al. Ingestions of acid and A case report. J Pediatr Surg 1997;32:91617.
alkaline agents: Outcome and prognostic value of early upper 58. Lee CW, Kays DW, Chen MK, et al. Outcomes of treatment of
endoscopy. Gastrointest Endosc 2004;60:3723. childhood achalasia. J Pediatr Surg 2010;45:11737.
30. Gaudreault P, Parent M, McGuigan MA, et al. Predictability of 59. Pastor AC, Mills J, Marcon MA, et al. A single center 26-year
esophageal injury from signs and symptoms: A study of caustic experience with treatment of esophageal achalasia: Is there an
ingestion in 378 children. Pediatrics 1983;71:76770. optimal method? J Pediatr Surg 2009;44:134954.
31. Riffat F, Cheng A. Pediatric caustic ingestion: 50 consecutive cases 60. Speiss AE, Kahrilas PJ. Treating achalasia. From whalebone to
and a review of the literature. Dis Esophagus 2009;22:8994. laparoscope. JAMA 1998;280:63842.
32. Broto J, Asensio M, Soler C, et al. Conservative treatment of 61. Csendes A, Braghetto I, Henriques A, et al. Late results of a pro-
caustic esophageal injuries in children: 20 years of experience. spective randomized study comparing forceful dilatation and
Pediatr Surg Int 1999;15:32325. oesophagomyotomy in patients with achalasia. Gut 1989;30:
33. Gupta SK, Croffie JM, Fitzgerald JF. Is esophagogastroduodenos- 299304.
copy necessary in all caustic ingestions? JPGN 2001;32:503. 62. Boeckxstaens GE, Annese V, Bruley des Varannes S, et al. Pneu-
34. Anderson KD, Rouse TM, Randolph KG. A controlled trial of matic dilation versus laparoscopic Hellers myotomy for idiopathic
corticosteroids in children with corrosive injury of the esophagus. achalasia. N Engl J Med 2011;364:180716
N Engl J Med 1990;323:63740. 63. Morris-Stiff G, Foster M E, Khan R, et al. Long-term results of
35. Kay M, Wyllie R. Caustic ingestions in children. Curr Opin Pediatr surgery for childhood achalasia Ann R Coll Surg Engl 1997;79:
2009;21:6514. 4324.
36. ONeill AJ, Betts J, Ziegler MM, et al. Surgical management of 64. Karnak J, Senocak ME, Tanyet FC, et al. Achalasia in childhood:
reflux strictures of the esophagus in childhood. Ann Surg Surgical treatment and outcome. Eur J Pediatr Surg 2001;11:
1982;196:45360. 2239.
37. Lan LC, Wong KK, Lin SC, et al. Endoscopic balloon dilation of 65. Vaos G, Demetriou L, Velaoras C, et al. Evaluating long-term
esophageal strictures in infants and children: 17 years experience results of modified Heller limited esophagomyotomy in children
and a literature review. J Pediatr Surg 2003;38:171215. with esophageal achalasia. J Pediatr Surg 2008;43:12629.
38. Said M, Mekki M, Golli M, et al. Balloon dilatation of anastomotic 66. Richards WO, Torquati A, Holzman MD, et al. Heller myotomy
structures secondary to surgical repair of oesophageal atresia. Br J versus Heller myotomy with Dor fundoplication for achalasia. A
Radiol 2003;76:2631. prospective randomized double-blind clinical trial. Ann Surg
39. Numanoglu A, Millar AJ, Brown RA, et al. Gastroesophageal reflux 2004;240:40515.
strictures in children, management and outcome. Pediatr Surg Int 67. Wright AS, Williams CW, Pellegrini CA, et al. Long-term out-
2005;21:6314. comes confirm the superior efficacy of extended Heller myotomy
40. Panieri E, Millar AJ, Rode RA, et al. Iatrogenic esophageal perfora- with Toupet fundoplication for achalasia. Surg Endosc 2007;
tions in children: Patterns of injury, presentation, management and 21:71318.
outcome. J Pediatr Surg 1996;31:8905. 68. Patti MG, Albanese C, Holcomb GW III, et al. Laparoscopic
41. Peng L, Quan X, Zongzheng J, et al. Videothoracoscopic drainage Heller myotomy and Dor fundoplication for esophageal achalasia
for esophageal perforation with mediastinitis in children. J Pediatr in children. J Pediatr Surg 2001;36:124851.
Surg 2006;41:51417. 69. Chapman JR, Joehl RJ, Murayama KM, et al. Achalasia treatment.
42. Engum SA, Gosfeld JL, West KW, et al. Improved survival in Improved outcome of laparoscopic myotomy with operative man-
children with esophageal perforation. Arch Surg 1996;31:60411. ometry. Arch Surg 2004;139:50813.
43. Martinez L, Rivas S, Hernandez F, et al. Aggressive conservative 70. Jafri M, Alonso M, Kaul A, et al. Intraoperative manometry during
treatment of esophageal perforations in children. J Pediatr Surg laparoscopic Heller myotomy improves outcome in pediatric acha-
2003;38:6859. lasia. J Pediatr Surg 2008;43:6670.
44. Gander JW, Berdon WE, Cowls RA. Iatrogenic esophageal perfo- 71. Marlais M, Fishman JR, Fell JM, et al. Health-related quality
ration in children. Pediatr Surg Int 2009;25:395401. of life in children with achalasia. J Paediatr Child Health 2011;
45. Amae S, Nio M, Kamiyama T, et al. Clinical characteristics and 47:1821.
management of congenital esophageal stenosis: A report on 14 72. Sandler RS, Nyren O, Ekbom A, et al. The risk of esophageal
cases. J Pediatr Surg 2003;38:56570. cancer in patients with achalasia. A population-based study. JAMA
46. Vasudevan SA, Kerendi F, Lee H, et al. Management of congenital 1995;274:135962.
esophageal stenosis. J Pediatr Surg 2002;37:10246. 73. Borgnon J, Tounian P, Auber F, et al. Esophageal replacement in
47. Ibrahim AHM, Al Malki TA, Hamaza AF, et al. Congenital esopha- children by an isoperistaltic gastric tube: A 12-year experience.
geal stenosis associated with esophageal atresia: New concepts. Pediatr Surg Int 2004;20:82933.
Pediatr Surg Int 2007;23:5337. 74. Gupta L, Bhatnagar V, Gupta AK, et al. Long-term follow-up of
48. Martinez-Ferro M, Rubio M, Piaggio L, et al. Thoracoscopic patients with esophageal replacement by reversed gastric tube. Eur
approach for congenital esophageal stenosis. J Pediatr Surg J Pediatr Surg 2011;21:8893.
2006;41:E5E7. 75. Spitz L. Gastric transposition in children. Semin Pediatr Surg
49. Murphy SG, Yazbeck S, Russo P. Isolated congenital esophageal 2009;18:303.
stenosis. J Pediatr Surg 1995;30:123841. 76. Burgos L, Barrena S, Andres AM, et al. Colonic interposition
50. Takamizawa S, Tsugawa C, Mouri N, et al. Congenital esophageal for esophageal replacement in children remains a good choice:
stenosis: Therapeutic strategy based on etiology. J Pediatr Surg 33-year median follow-up of 65 patients. J Pediatr Surg 2010;45:
2002;37:197201. 3415.
51. Sneed WF, LaGarde DC, Kogutt MS, et al. Esophageal stenosis 77. Arul GS, Parikh D. Oesophageal replacement in children. Ann R
due to cartilaginous tracheobronchial remnants. J Pediatr Surg Coll Surg Engl 2008;90:712.
1979;14:7868. 78. Cowles RA, Coran AG Gastric transposition in infants and chil-
52. Kouchi K, Yoshida H, Matsunaga T, et al. Endosonographic evalu- dren. Pediatr Surg Int 2010;26:112934.
ation in two children with esophageal stenosis. J Pediatr Surg 79. Hamza AF Colonic replacement in cases of esophageal atresia.
2002;37:9346. Semin Pediatr Surg 2009;18:403.
53. Usui N, Kamata S, Kawahara H, et al. Usefulness of endoscopic 80. Tannuri U, Tannuri CA Should patients with esophageal atresia be
ultrasonography in the diagnosis of congenital esophageal stenosis. submitted to esophageal substitution before they start walking? Dis
J Pediatr Surg 2002;37:17446. Esophagus 2011;24:259.
54. Chao H, Chen S, Kong M. Successful treatment of congenital 81. Cauchi JA, Buick RG, Gornall P, et al. Oesophageal substitution
esophageal web by endoscopic electrocauterization and balloon with free and pedicled jejunum: Short- and long-term outcomes.
dilation. J Pediatr Surg 2008;43:E1315. Pediatr Surg Int 2007;23:1119.
55. Achildi O, Grewal H. Congenital anomalies of the esophagus. 82. Bax KM. Jejunum for bridging long-gap esophageal atresia. Semin
Otolaryngol Clin North Am 2007;40:21944. Pediatr Surg 2009;18:349.
C H A P T E R 2 7
Esophageal atresia (EA) and tracheoesophageal fistula This theory of longitudinal tracheoesophageal folds
(TEF) anomalies present the pediatric surgeon with a merging to form a septum has been challenged.12,13 In
unique and complex congenital disease, which tests both chick embryo studies, these folds could not be demon-
the diagnostic and technical skill of the surgeon. Most strated. Instead, cranial and caudal folds were found in
pediatric surgeons consider the surgical correction of the region of tracheoesophageal separation. According to
these malformations to be the height of neonatal surgical this theory, EA/TEF would then be due to an imbalance
care. In 1959, Dr Willis Potts wrote, To anastomose the in the growth of these folds. Furthermore, rat studies
ends of an infants esophagus, the surgeon must be as suggest that EA/TEF results from disturbances in either
delicate and precise as a skilled watchmaker. No other epithelial proliferation or apoptosis.14
operation offers a greater opportunity for pure technical More recent studies show that ectopic expression of
artistry.1 While this statement still remains true, improve- sonic hedgehog occurs in the tissues between the noto-
ments in anesthetic and neonatal intensive care chord and the gut. Knockout mice models have helped
have made repair of these anomalies and their postopera- elucidate the functions of different genes in the develop-
tive management much more routine so that a good ment of the foregut aberrations such as EA/TEF.15 Also,
outcome can be achieved in most cases. Technical the relationship between BMP4 (bone morphogenic
advances, including the application of the minimally protein) and Nog, the gene encoding noggin (which is a
invasive approach, have also decreased the morbidity BMP antagonist), may also have an impact on the devel-
from these operations. opment of TEF.1618
The first report of EA was by Durston in 1670,2 who
found a blind upper pouch in one of a pair of thoracopa-
gus conjoined twins, but the initial classic description was EPIDEMIOLOGY
by Thomas Gibson in 1697.3 However, it was not until
1939 when a baby with EA/TEF survived following suc- The birth incidence of EA/TEF varies between 1 in 2500
cessful staged repairs described separately by Leven and to 3000 live births.1921 There is a slight male preponder-
Ladd.4,5 In 1940, Haight described the first survival fol- ance of 1.26:1. There is no evidence for a link between
lowing primary anastomosis.6 By the mid-1980s, most EA/TEF and maternal age when chromosomal cases are
neonatal centers were performing primary repair and excluded.22 The risk for a second child with EA/TEF
reporting successful outcomes in up to 90%.710 among parents of one affected child is 0.52%, increasing
to 20% when more than one child is affected. The empir-
ical risk of an affected child born to an affected person is
EMBRYOLOGY 34%.23 The relative risk for EA/TEF in twins is 2.56
when compared with singletons.24 The concordance rate
The embryology of the foregut is still subject to contro- in twins is low, but the risk among twins of the same
versy.11 What is known, however, is that during the fourth gender is high.25
week of gestation the foregut starts to differentiate into Environmental factors that have been implicated
a ventral respiratory part and a dorsal esophageal part. include the use of methimazole in early pregnancy,
The laryngotracheal diverticulum then invaginates ven- prolonged use of contraceptive pills, progesterone and
trally into the mesenchyme. The traditional theory pos- estrogen exposure, maternal diabetes, and thalidomide
tulates that the ventral respiratory system separates from exposure.2630 EA is occasionally seen in the fetal alcohol
the esophagus by the formation of lateral tracheoesopha- syndrome and in maternal phenylketonuria.31,32
geal folds that fuse in the midline and create the tra- Chromosomal anomalies are found in 610% of the
cheoesophageal septum. At 6 to 7 weeks of gestation, the patients.3335 The total number of trisomy 18 cases exceeds
separation between trachea and esophagus is complete. the total number of trisomy 21 cases. As the incidence of
Incomplete fusion of the folds results in a defective trisomy 18 is higher, it would seem to indicate that
tracheoesophageal septum and abnormal connection trisomy 18 is a greater risk for EA development. Three
between the trachea and esophagus. separate genes have been associated with EA/TEF:
365
366 SECTION III Thoracic
MYCN haploinsufficiency in Feingold syndrome, CHD7 chromosomal defect or a syndrome without a known
in CHARGE syndrome, and SOX2 in the anophthalmia genetic defect. Interestingly, as many as 70% of the
esophagealgenital (AEG) syndrome.3437 remaining 90 patients had additional defects other than
EA may occasionally be part of the Opitz G/BB syn- VACTERL anomalies.
drome, Fanconi anemia, oculo-auriculo-vertebral syn-
drome, BartsocasPapas syndrome, or Frijns syndrome.38
CLASSIFICATION
ASSOCIATED ANOMALIES EA and TEF present in many forms and various classifi-
cation systems have been used to describe them. It is clear
The factor or factors responsible for the early disturbance that EA should be thought of as a spectrum of anomalies
in organogenesis causing EA may affect other organs or (Fig. 27-1).42 The original classification system was
systems that are developing at the same time. EA can be devised by Vogt in 1929.43 Ladd put forth his own clas-
divided clinically into isolated EA and syndromic EA, sification in 19455 and Gross revised this in 1953.44 These
occurring at roughly the same rate.38 classifications tend to be confusing, as the same subclasses
The most frequent associated malformations encoun- are named differently. For clarity, it seems much better
tered in syndromic EA are: to give descriptive names to the major subtypes.
Cardiac (1334%)
Vertebral (621%) Esophageal Atresia with Distal Fistula
Limb (519%) (Gross Type C)
Anorectal (1016%)
Renal (514%). This is the most common subtype, accounting for about
Vertebral anomalies are confined mainly to the thoracic 85% of EA anomalies.45 The very dilated proximal
region. An earlier claim that the presence of 13 pairs of esophagus has a thickened wall and descends into the
ribs is a good indicator of long-gap EA has not been superior mediastinum usually to the third or fourth tho-
substantiated.39 racic vertebrae. The distal esophagus is slender and has
Nonrandom associations have been documented as a thin wall. It enters the trachea posteriorly either at the
well. Two of these are the VACTERL association (verte- level of the carina or 12cm higher. The distance between
bral, anorectal, cardiac, tracheo-esophageal, renal, and the esophageal ends varies from very small to quite wide.
limb abnormalities) and the CHARGE association (colo- Very rarely, the distal fistula may be occluded, leading to
boma, heart defects, atresia of the choanae, developmen- the misdiagnosis of EA without distal fistula.46
tal retardation, genital hypoplasia, and ear deformities).
In 1973, VACTERL was originally described as VATER, Pure Esophageal Atresia without
an acronym made up of vertebral defects, anal atresia, TEF (Gross Type A)
tracheo-esophageal fistula with EA, and radial dysplasia.40
It was later extended with the C for cardiac anomalies Pure EA has an incidence of about 7%. The proximal and
and the L for limb anomalies. In a cohort of 463 distal esophagus end blindly in the posterior mediasti-
patients with EA, 107 (23%) had at least two additional num. The proximal end is dilated and has a thickened
VACTERL defects.41 Seventeen of these patients had a wall as in the more common EA/TEF. If there is no
A B C D E
FIGURE 27-1 Classification of EA and/or TEF: (A) esophageal atresia with distal tracheoesophageal fistula: Vogt IIIb, Ladd III, Gross
C; (B) esophageal atresia without fistula: Vogt II, Ladd I, Gross A; (C) esophageal atresia with proximal fistula: Vogt IIIa, Ladd II,
Gross B; (D) esophageal atresia with proximal and distal fistulas: Vogt IIIc, Ladd V, Gross D; (E) tracheoesophageal fistula (H-type)
without atresia: Vogt IV, Gross E.
27 Esophageal Atresia and Tracheoesophageal Fistula Malformations 367
concomitant proximal fistula, the upper esophagus ends Current ultrasound technology does not allow for the
at the level of the azygos vein. The distal esophagus is certain diagnosis of EA/TEF. Therefore, definitive coun-
short and often suspended by a fibrotic band. The dis- seling of the parents should be guarded.54 The application
tance between the two segments is considerable, usually of 3D power Doppler imaging seems promising, both
precluding immediate anastomosis. antenatally and postnatally. Aortic arch anomalies, for
example, have been diagnosed using this modality.55,56
H-type Fistula without Esophageal Magnetic resonance imaging (MRI) has been used to
identify other fetal thoracic lesions, and may be beneficial
Atresia (Gross Type E) in patients deemed to be at risk on prenatal ultrasound.
H-type TEF without atresia is usually discussed together Sensitivity in various studies is between 60100% and the
with EA because it may be part of the VACTERL associa- diagnosis is made by the lack of visualization of the tho-
tion. It occurs with an incidence of about 4%. The fistula racic esophagus.5759
starts from the membranous trachea and runs caudad to
enter the esophagus. Normally it is short, although the
diameter may be variable. The fistula is usually situated at
Postnatal Diagnosis
the thoracic aperture or higher in the neck.47 If pregnancy was complicated by polyhydramnios, passage
of a tube or catheter into the stomach should be per-
Esophageal Atresia with Proximal formed to assess esophageal patency. The same holds true
when the child presents with anomalies that fit the
Fistula (Gross Type B) VACTERL association (e.g., radial aplasia).
The association of a proximal fistula in a patient with As EA prevents the passage of saliva down the esopha-
pure EA is generally thought to be about 2%, but may gus, saliva accumulates in the proximal esophagus and
be higher than is generally appreciated. In a recent series mouth, and feeding should be withheld until esophageal
of 13 children without distal fistula, a proximal fistula was continuity is confirmed. This is best done with a stiff 10
found in seven.48 An upper esophageal fistula is usually French catheter inserted either through the nose or
not found at the end of the pouch. This fistula is similar mouth. A chest film is then obtained with downward
to the H-type starting proximally on the trachea and pressure on the tube. With EA, the tip of the tube is
ending distally in the dilated proximal esophagus. Usually, found to be slightly curled in the blind upper pouch
there is only one proximal fistula, but two or three have around T2T4 (Fig. 27-2). This technique not only
been described.49 The fistula is usually located at the
thoracic aperture or higher in the neck. Although limited
in length, its diameter may vary from tiny to large. If not
diagnosed preoperatively, it may be suspected during
operative repair when bubbles are seen when opening the
proximal esophagus.
DIAGNOSIS
Antenatal Diagnosis
The prenatal diagnosis of EA/TEF relies, in principle, on
two nonspecific signs: polyhydramnios and an absent or
small stomach bubble. Polyhydramnios is associated with
a wide range of fetal abnormalities and is nonspecific.
Similarly, the ultrasonographic (US) absence of a stomach
bubble may point to a variety of fetal anomalies. The
combination of a small stomach together with a dilated FIGURE 27-2 This plain radiograph depicts the classic features
seen in an infant with EA and TEF. A nasoesophageal tube is
cervical esophagus (the pouch sign) has been confirmed to seen in the upper pouch and has kinked a little at the end of the
be diagnostic for pure EA in a number of patients.5153 pouch. There is air in the stomach and bowel, which signifies
Nevertheless, it is encountered in only a few patients. the presence of a distal TEF.
368 SECTION III Thoracic
A B
FIGURE 27-3 These two radiographs depict less common presentations of EA. (A) Isolated EA. The nasoesophageal tube (arrow)
is seen in the proximal pouch. There is no air in the gastrointestinal tract. (B) This patient has EA with distal TEF and
duodenal atresia and has been endotracheally intubated. A nasoesophageal catheter (arrow) sits in the upper esophageal pouch.
An endotracheal tube is also seen. The stomach and bulbous duodenum are distended with air but no air is seen distal to the
duodenum.
identifies the atresia but gives some clue to the length of will affect the measurement of the gap between the two
the upper pouch. Often, the dilated upper esophageal esophageal segments and may under- or over-estimate
pouch is visualized by air within it. Air in the stomach the gap length. In one report by an experienced surgeon,
signifies the presence of a distal TEF. If the tip of the operative management was linked to the measured
catheter passes beyond the level of the carina, then the gap length: less than two vertebrae, then primary anasto-
diagnosis of EA should be questioned. Esophageal steno- mosis; two to six vertebrae, then delayed primary anasto-
sis, tracheal rings, and iatrogenic perforation of the mosis; more than six vertebrae, then esophageal
esophagus can be confused with EA.60,61 If there is any replacement.64 In the era of thoracoscopy, an initial tho-
question about the diagnosis, a small amount of contrast racic exploration can be considered if the upper pouch
can be dripped into the upper pouch, but this needs to appears fairly long. If the lower pouch is identified and
be done with fluoroscopy and under direction of the seen to be of adequate length, a primary repair can be
surgeon to assure that the contrast is not aspirated. attempted. If not, then a gastrostomy can be placed and
Radiographs may reveal associated anomalies such as delayed repair planned.65
vertebral and rib anomalies, or other problems such as In EA/TEF, a longer gap between the two esophageal
duodenal atresia (Fig. 27-3). The absence of air in the ends should be expected when the distal fistula is found
stomach points to EA without distal fistula (see Fig. at the carina.66 Combined with a short upper pouch, this
27-3A). Mediastinal ultrasound has been suggested as a can mean a long gap exists between the two esophageal
helpful adjunct in the diagnosis of pure EA.62 segments and may not be amenable to an initial primary
The length of the esophageal gap is usually not known repair. Unfortunately this may not fully be appreciated
preoperatively. Absence of air in the stomach has been until the time of exploration. However since it is usually
linked with a long gap, but has also been described in necessary to ligate the fistula in the early postnatal period,
association with a distal fistula occluded with mucus.46 the gap length can be assessed at that time. A thoraco-
Even in true long-gap EA (atresia without distal fistula), scopic approach in this scenario allows for minimal
the gap length varies. In newborns with isolated EA, the morbidity if the decision is to ligate the fistula only
first procedure is generally a gastrostomy, which allows without reconstruction. Bronchoscopy can also be per-
for enteral feeding and also allows for assessment of the formed prior to exploration, not only to assess the site of
length and location of the lower pouch. It can be identi- the distal fistula, but to also look for an upper pouch
fied radiologically, either with metal bougies, a small fistula. Echocardiography should be performed prior to
gastroscope, or with a contrast injected through the gas- operation as it may reveal cardiac and/or aortic arch
trosomy.63 This can be done at the time of the initial anomalies. A right descending aorta, which occurs in
gastrostomy or more routinely seven to ten days later. If about 2.5% of the cases, may make a left-sided thoracic
bougies or a telescope are introduced into the distal approach preferable.67 Renal ultrasound and spine radio-
esophagus, the amount of pressure on these instruments graphs should be obtained as well. Because EA may be
27 Esophageal Atresia and Tracheoesophageal Fistula Malformations 369
OPERATIVE REPAIR
Esophageal Atresia with Distal Fistula
The operation is performed with the patient under
general anesthesia and with adequate venous access. An
arterial line is occasionally beneficial depending on the
FIGURE 27-4 This preoperative CT scan reconstruction shows babys clinical status. Generally, a pulse oximeter and end
EA with a distal TEF. The distal TEF (arrow) originates at the tidal CO2 monitor are adequate. The operation can be
carina. The upper esophageal pouch is very dilated (asterisk). performed through a thoracotomy or using a thoraco-
The distance between the upper pouch and lower esophagus is scopic approach. The side of entrance into the chest is
relatively short.
opposite the turn of the aortic arch: right for a left
descending aorta, left for a right descending aorta. If a
right-sided aortic arch is not detected until the operation
part of a syndrome, consultation by a geneticist is recom- has begun, change to the left side is appropriate if the
mended at some point. thoracoscopic approach was initially chosen. If a thora-
There is little doubt that better preoperative imaging cotomy has been performed, an anastomosis from the
of the neck and chest allows for better preoperative plan- right chest should be attempted, but there is a higher
ning. At present, the two best imaging modalities are CT morbidity in this setting.67
and MRI. Although MRI would certainly be preferable
for its absence of radiation exposure, it requires general Preoperative Bronchoscopy
anesthesia. On the other hand, MRI is better for diagnos-
ing cardiac and aortic arch anomalies.68 CT has also been The value of routine preoperative rigid bronchoscopy is
performed in children with EA/TEF (Fig. 27-4).6972 much debated because the incidence of a simultaneous
proximal and distal fistula is less than 1%.63 With the
availability of small-diameter flexible fiberscopes, tra-
cheobronchoscopy can now be performed after intuba-
MANAGEMENT tion through the endotracheal tube.79,80 Forceful
ventilation must be avoided, not only to avoid lung
Preoperative damage,81 but also to prevent gastric distention and
Once the diagnosis of EA has been established, the baby, gastric perforation with insufflation through the distal
if not delivered in a maternal/fetal/neonatal center, fistula. Bronchoscopy may reveal abnormalities such as a
should be transferred to a pediatric surgical center. A 10 second proximal fistula, a laryngotracheoesophageal cleft,
French Replogle tube is placed in the upper esophagus tracheal stenosis, or a tracheal bronchus to the right
and set to continuous suction.73 The child is positioned upper lobe.8284 The entrance of the distal fistula is usually
head-up and on his or her side. Intravenous access is well seen (Fig. 27-5). Its distance to the carina provides
important, and the vital signs are monitored. a clue as to the gap between the esophageal segments: the
If the child is in respiratory distress, endotracheal intu- closer the fistula is to the carina, the longer the distance.
bation and ventilation may be needed. Forceful ventila- An indication of the severity of tracheomalacia is only
tion will over distend the stomach, possibly causing possible when the child is breathing spontaneously. The
diaphragmatic splinting and even gastric rupture.74,75 problem with bronchoscopy is that it may prolong the
Gentle low-pressure ventilation is therefore essential. In procedure and the infant can decompensate prior to liga-
these cases, some feel high-frequency ventilation is tion of the fistula.8588 The surgeon and the anesthesiolo-
advantageous. However, on occasion, emergency ligation gist should discuss the advantages/disadvantages in each
of the fistula may be needed as a life-saving maneu- individual case. Following intubation, it may be helpful
ver.64,7476 After ligation of the fistula, a delayed primary to position the endotracheal tube distal to the fistula,
repair can be performed when the infant is more stable. assuming the fistula is not at the carina.
370 SECTION III Thoracic
A
A
B B
FIGURE 27-7 (A) Ligation of the azygos vein. (B) The distal FIGURE 27-8 The distal esophagus is identified, looped, and
fistula is being mobilized from its insertion in the trachea. carefully dissected up to its junction with the trachea, meticu-
lously sparing the segmental vessels from the aorta. (A) Trac-
tion sutures may be placed for gentle handling of the segments.
Attention is then turned to the proximal esophagus The fistula is divided close to the trachea without narrowing its
lumen. (B) The tracheal end of the tracheoesophageal fistula is
which can be identified by asking the anesthesiologist to closed with continuous or interrupted sutures. Adjacent tissue,
push on the Replogle tube. A traction suture, taking a if available, is tacked over the closure. (From Holder TM, Manning
good bite of the muscular wall, is placed in the most distal PB. Esophageal atresia and tracheoesophageal fistula. Surg Rounds
part of the proximal pouch. Using the traction suture, the 1991;14:492502.)
proximal pouch can be freed posteriorly and laterally by
blunt dissection. Anteriorly, however, the pouch may be Before finishing the anastomosis, an 8 French or 10
adherent to the membranous trachea. Usually, it can be French tube is passed into the stomach. This protects
dissected sharply, staying on the esophageal side to avoid from inadvertent closure of the lumen and for gastric
entrance into the membranos trachea. Extensive dissec- decompression. Others feel the placement of an intralu-
tion is not warranted, unless there is a long gap, because menal tube or stent causes an increased risk of stricture
the dissection can damage the tracheal or esophageal or leak, and choose not to use it.
walls and may interfere with innervation to the upper The use of a chest drain is also optional.98,99 We use
esophagus.97 Extensive dissection of the proximal pouch one until a contrast study is obtained on day 4 or 5. The
searching for a proximal fistula should not be performed chest incision is then closed in layers. The ribs should be
routinely because the incidence of a proximal fistula in approximated with one 3-0 absorbable suture. This
combination with a distal one is only about 1%. If a suture should be tied gently so that the intercostal space
proximal fistula is present, it is usually of the H-type. If is not obliterated. If a muscle-sparing approach was used,
missed at birth and diagnosed after repair of the EA, it the muscles are allowed to fall back into their normal
can usually be repaired through the neck at a later date. position and the skin is closed with a 5-0 absorbable
If the trachea is entered during the dissection of the subcuticular suture.
proximal pouch, one should be wary that a proximal
fistula may have been opened as well. There should not Thoracoscopic Repair
be a common wall between the trachea and esophagus.
After mobilization of the proximal pouch, the tip is The first successful repair was reported in 2000 and the
now amputated so that the lumen and mucosa become first series reported in 2002.100,101 Since then, there have
visible. An end-to-end anastomosis is performed with 5-0 been several retrospective reports describing experience
absorbable sutures starting in the middle of the back wall with the thoracoscopic approach.102105 During this early
of each esophageal segment (Fig. 27-9). It is important experience, attempts were made to obtain single lung
to include both the mucosa and the muscular wall with ventilation by intubating the left mainstem bronchus.
each suture. The sutures in the back wall of the anasto- However, this proved time consuming and often unsuc-
mosis are tied intralumenally. Then, the front part of the cessful so now the endotracheal tube is usually left in the
anastomosis is performed with sutures tied on the outside. trachea just above the carina and right lung collapse is
372 SECTION III Thoracic
A
SA/C
SN
Replogle tube. If the child has persistent respiratory optimal. If a delayed primary anastomosis with or without
problems, a proximal fistula should again be considered. lengthening is not feasible, an alternative procedure
Cervical esophagostomy should be avoided as this will should be considered, such as a gastric pull-up or a
likely jeopardize the ability to perform a primary jejunal, ileal, or colonic interposition. An alternative
esophago-esophagostomy in the future. Home care option is to attempt esophageal growth and lengthening
during the waiting period has been advocated, but most by placing trans-thoracic traction sutures, but the results
of the reported patients have required a long time in the are variable.140,141
hospital before they were sent home.111,112 Thoracoscopy is ideal to evaluate the gap length to be
The gap between the esophageal segments should be bridged (Fig. 27-14). Moreover, the ends can be dissected
periodically measured and is usually expressed in terms and mobilized as well. An anastomosis can also be per-
of the number of vertebral bodies, thus taking the childs formed thoracoscopically. In one series, all long gaps
length into account. This can be done with a simultane- were successfully closed.142 Also, a thoracoscopic Foker
ous contrast study of the upper and lower esophagus, or procedure can be performed.
by insertion of a metal bougie transorally into the upper
esophagus and through the gastrostomy into the lower Postoperative Management
esophagus. The metal bougie ends should overlap before
attempting a primary anastomosis. Mechanical ventilation with muscle relaxation for five
At the time of definite repair, several techniques to days has been advocated after an anastomosis is per-
lengthen the native esophagus have been described, formed under considerable tension.143145 Evidence for
including esophageal myotomy or extensive mobilization the effectiveness of this approach is lacking.146 A chest
of the proximal and distal esophagus (see Box 27-1). drain is optional and feedings can be started early through
There is little doubt that all these maneuvers damage the the nasogastric tube if there is no evidence of a leak or
esophagus and that the long-term results may be less than concern about significant gastroesophageal reflux (GER).
27 Esophageal Atresia and Tracheoesophageal Fistula Malformations 375
COMPLICATIONS
Anastomotic Leaks
An overall leak rate of 3.517% has been reported by
several authors.9,147,148 Major leaks which require active
intervention occur much less frequently3.5% in the
first study and 4.5% in the more recent one, which con-
firms the statement that most leaks will close spontane-
ously. In the largest thoracoscopic report, the leak rate
was 7.6%,103 but this was an multi-institutional study and
early in each institutions experience. Published reports
often include all types of EA and do not always mention
whether the leak was detected at routine esophagography
or how it was identified.
Anastomotic Stricture
As with anastomotic leaks, no uniform definition is used
for an anastomotic stricture. It has been defined as a nar-
rowing of more than 50% of the lumen149 or as a narrow-
ing detected on a contrast study, or at esophagoscopy in
combination with symptoms.150 Reported incidences
range from 1760%.150152 Four of 104 patients (3.8%)
undergoing thoracoscopic repair developed a stricture,
which was defined on the initial esophagogram.103
Routine dilatation is not indicated because many patients FIGURE 27-15 On this water-soluble contrast study, a recurrent
never require dilatation. Anastomotic tension, anasto- TEF (arrow) is seen.
motic leakage, and GER have been implicated as risk
factors.153155 Strictures usually respond well to dilation.
Resection of the stricture is rarely required. Balloon dila- Treatment of a recurrent TEF can be difficult. Thus,
tation seems superior, but there is no hard evidence. attempts at prevention have been described. Interposition
of a biosynthetic patch between the tracheal closure and
esophageal anastomosis has been described for this
Recurrent Tracheoesophageal Fistula purpose (Fig. 27-16).156 Native tissue such as pleura, peri-
The reported incidence of a recurrent TEF varies cardium, or intercostal muscle can also be used.
between 315%. In one study, the 10% incidence in the Once developed, attempts at endoscopic management
period 1986 to 1995 had dropped to 5% in the period with cautery, fibrin glue, and small intestine submucosa
1996 to 2005.7 In the large multi-institution study of have been described (Fig. 27-17).157159 The results are
thoracoscopic repairs, the incidence was 1.9%.103 The mixed with success rates reported between 2080%.
etiology of a recurrent fistula is almost certainly second-
ary to an anastomotic leak. Tracheomalacia
A recurrent fistula is suspected when the child starts
to cough during feeding, has apneic or cyanotic episodes, Tracheomalacia is a generalized or localized weakness of
or has repeat respiratory infections. The diagnosis can the trachea that allows the anterior and posterior walls to
sometimes be made by an esophagram using a water- come together during expiration or coughing.15 The area
soluble contrast medium (Fig. 27-15) but bronchoscopy of collapse is usually in the region of the fistula.160 The
is usually needed to confirm the diagnosis. cartilage of the rings is softened, and the length of the
376 SECTION III Thoracic
Disordered Peristalsis/
Gastroesophageal Reflux/
Esophageal Cancer
Disturbed motility of the esophagus in EA patients has
been recognized for a long time.173176 Symptoms included
dysphagia, episodes of foreign body impaction, heart-
burn, vomiting, and various respiratory disorders.177179
The oral phase of swallowing is normal, but the pharyn-
geal and esophageal phases are abnormal in all patients,
both on video-fluoroscopy180,181 and with manometry.182187
FIGURE 27-16 After thoracoscopic repair of esophageal atresia Whether the cause of these disturbed motility prob-
and distal fistula in this infant, Surgisis was interposed between
the tracheal closure and esophageal anastomosis to help lems is congenital or acquired has been a long-standing
prevent a recurrent TEF. (From St. Peter SD, Calkins CM, Holcomb debate. Whatever the cause, it brings with it several prob-
GW III. The use of biosynthetic mesh to separate the anastomoses lems, not the least of which is GER. While GER tends
during the thoracoscopic repair of esophageal atresia and tra- to improve during the first year of life in most infants,
cheoesophageal fistula. J Laparoendosc Adv Surg Tech 2007;17:380
2. Reprinted with permission.)
this is not the case in infants with EA. The incidence of
significant reflux in patients with EA has been stated to
be up to 50%, and about half of these will require antire-
flux surgery.103,188190 A considerable number of patients
with EA have complaints in adult life pointing toward
GER as the etiology including Barretts esophagitis.189
Early normal pH values in the esophagus do not exclude
significant reflux on follow-up.190 Antireflux medication,
including gastric acid suppression, is successful in only
about half of the cases.191 Antireflux operations in patients
with repaired EA have a higher failure rate than in
non-EA patients,192 but there seems to be no other alter-
native. While some surgeons have advocated partial
wraps because of concerns over dysmotility,193 there is
* little evidence to support this practice. The question
remains whether adults with repaired EA as an infant
should be screened as there may be a higher incidence of
squamous cell carcinoma.194
Thoracotomy-Related Morbidity
Thoracotomy, especially in the newborn, can lead to
significant morbidity, such as winged scapula, elevation
or fixation of the shoulder, asymmetry of the chest wall,
rib fusion, scoliosis, and breast and pectoral muscle
maldevelopment.200207 Moreover, chronic pain after tho-
racic surgery is a serious problem, at least in adults, and
has been reported in more than 50% of patients.208,209
These negative consequences of a thoracotomy can be
alleviated by using the thoracoscopic approach.
H-TYPE FISTULA FIGURE 27-18 Imaging for an H-type TEF. A contrast swallow is
performed using a low osmolar, water-soluble medium. The
The incidence of H-type TEF is about 4%.14,15 Isolated fistula (arrow) is clearly seen on the lateral chest film. The fistula
TEF is associated with the same anomalies as seen in EA, is at the level of the thoracic inlet. Contrast material entered the
trachea and bronchial tree.
although at lower incidences.210 The fistula runs from the
trachea downward to the esophagus, typically intramu-
rally, and is short (see Fig. 27-1). In a series of 20 chil-
dren, the fistula was at C5C6 in two, C6C7 in three, fistula, which is transected close to the esophagus. The
C7T1 in eight, T1T2 in three, and T2T3 in one.47 trachea is closed longitudinally and the esophagus trans-
Rarely, there is a second fistula.211 versely with interrupted absorbable sutures. To eliminate
Respiratory symptoms, especially choking, often occur a recurrent fistula, the sternal head of the sternocleido-
immediately after birth with feeding. Sometimes, there mastoid muscle can be interposed between the cut ends
are unexplained cyanotic spells. Symptoms subside when of the fistula.
the child is fed by a nasogastric tube. Often the abdomen It is evident that less trauma is inflicted when a thora-
is distended with air, and flatulence may be present. cotomy can be avoided. The availability of thoracoscopy
Older children can present with recurrent pneumonia. obviates the need for a thoracotomy, thus making a cervi-
Symptoms can often be traced back to the neonatal cal approach for the extremely low H-fistulas less impera-
period. On occasion, symptoms develop later in life.212,213 tive. Several reports of thoracoscopically repaired
It can be difficult to diagnose an H-type fistula even H-fistulas have been described.219221 Whether a fistula
if there is a high degree of suspicion. A water-soluble, low should be approached from the neck or the chest depends
osmolar contrast study seems to be the best initial inves- on the location of the fistula based on preoperative
tigation and demonstrates the fistula in many cases (Fig. imaging, and the surgeon and patient preference.
27-18). Bronchoscopy (usually rigid) is another diagnos-
tic modality, but even then, the fistula can be missed.214
CT esophagography is another option but has the disad- LARYNGEAL AND
vantage of radiation exposure.215 LARYNGOTRACHEOESOPHAGEAL CLEFT
A cervical approach can be used in most (80%) cases.216
With the use of a small feeding tube or guide wire placed Laryngeal and laryngotracheoesophageal clefts are rare
through the fistula at tracheoscopy and pulled out of the congenital anomalies with an incidence of approximately
esophagus, most lower H-type fistulas can be pulled up 1 in 10,000 to 20,000 live births.222 The cleft consists of
and approached through the neck as well.217,218 The classic a midline communication of the larynx, trachea, and
approach is through a small low right cervical incision rarely bronchus with the pharynx and upper esophagus.
(Fig. 27-19). The sternal head of the sternocleidomastoid Its embryology is poorly understood. Originally, it was
muscle may need transection. The esophagus is easily thought to be the consequence of a failure of the tra-
identified and separated from the trachea, taking care not cheoesophageal septum to fuse in the caudocranial direc-
to injure the recurrent laryngeal nerve. The left recurrent tion. However, as previously mentioned, this theory of
laryngeal nerve is vulnerable as well. The proximal tracheoesophageal separation by fusion of a tra-
esophagus, as well as the fistula, is encircled with separate cheoesophageal septum has been challenged.1118
vessel loops and so is the distal esophagus. Traction Many congenital malformations can coexist, includ-
sutures are placed at the upper and lower ends of the ing congenital heart disease, gastrointestinal and
378 SECTION III Thoracic
* *
A B
Comment: The classification of Myer and colleagues seems best suited because it is more specific regarding the anatomic region
involved. Extension into the bronchus, however, is not part of this classification. It could be added as LTEIII.
A B
FIGURE 27-21 This newborn began to have respiratory distress shortly after birth. Clinically, it was felt that the baby might have a
tracheoesophageal fistula without esophageal atresia as a small nasogastric tube was able to be passed into the stomach. The
bronchoscopic examination is shown. In both figures, the trachea is identified with the asterisk. (A) The laryngotracheoesophageal
cleft is visualized. The esophagus is marked with the arrow. (B) The distal end of the laryngotracheoesophageal cleft is easily seen
with the trachea anteriorly (asterisk) and the esophagus posteriorly. According to the classification of laryngotracheoesophageal
clefts described by Meyer, this would be an LTE1 (see Fig. 27-20E).
This is a rare anomaly, and reported series are small. 11. Felix JF, Keijzer R, van Dooren MF, et al. Genetics and develop-
Tracheal instability, tracheomalacia, and GER with recur- mental biology of oesophageal atresia and tracheo-oesophageal
fistula: Lessons from mice relevant for paediatric surgeons. Pediatr
rent aspiration have been noted. The anastomotic leak Surg Int 2004;20:7316.
rate is high, and hospitalization is often prolonged. 12. Zaw-Tun HA. The tracheo-esophageal septumfact or fantasy?
Origin and development of the respiratory primordium and
esophagus. Acta Anat (Basel) 1982;114:121.
REFERENCES 13. Kluth D, Fiegel H. The embryology of the foregut. Semin Pediatr
1. Potts WJ. The Surgeon and the Child. W. B. Saunders Co; 1959. Surg 2003;12:39.
2. Durston W. A Narrative of a Monstrous Birth in Plymouth, Oct. 14. Qi BQ, Beasley SW. Stages of normal tracheo-bronchial develop-
22, 1670; together with the Anatomical Observations, taken there- ment in rat embryos: Resolution of a controversy. Dev Growth
upon by William Durston Doctor in Physick, and communicated Differ 2000;42:14553.
to Dr. Tim. Clerk. Philos Trans (London) 1670;5:20968. 15. Felix JF, Keijzer R, van Dooren MF, et al. Genetics and develop-
3. Gibson T. Anatomy of Humane bodies Epitomized. 5th ed. mental biology of oesophageal atresia and tracheo-oesophageal
London: printed by TW for Awnsham and John Churchill, at the fistula: Lessons from mice relevant for paediatric surgeons. Pediatr
Black Swan in Pater-Noster-Row, and sold by Timothy Childe, at Surg Int 2004;20:7316.
the White-Hart, the West end of St. Pauls Church Yard; 1697. 16. Que, J Choi M, Zeil JW, et al. Morphogenesis of the trachea and
4. Levin NL. Congenital atresia of the esophagus with tracheo- esophagus; current players and new roles for Noggin and BMPS.
esophageal fistula. J Thorac Cardiovasc Surg 1941;10:64857. Differentiation 2006;74:42237.
5. Ladd WE. The surgical treatment of esophageal atresia and tra- 17. Que J, Okinbo T, Goldenring JR, et al. Multiple dose-dependent
cheoesophageal fistulas. N Engl J Med 1944;230:62537. roles for Sox2 in pathway and differentiation of the anterior
6. Haight C, Towsley HA. Congenital atresia of the esophagus with foregut endoderm. Development 2009;134:252131.
tracheoesophageal fistula: Extrapleural ligation of fistula and end- 18. Jacobs J, Ku WY, Que J. Genetic and cellular mechanisms regulat-
to-end anastomosis. Surg Gynecol Obstet 1943;76:67288. ing anterior foregut and esophageal development. Dev Biol
7. Lilja HE, Wester T. Outcome in neonates with esophageal atresia 2012;1:5464.
treated over the last 20 years. Pediatr Surg Int 2008;24:5316. 19. Depaepe A, Dolk H, Lechat MF. The epidemiology of tracheo-
8. Spitz L, Kiely EM, Morecroft JA, et al. Oesophageal atresia: oesophageal fistula and oesophageal atresia in Europe. EUROCAT
At-risk groups for the 1990s. J Pediatr Surg 1994;29:7235. Working Group. Arch Dis Child 1993;68:7438.
9. Tonz M, Kohli S, Kaiser G. Oesophageal atresia: What has 20. Robert E, Mutchinick O, Mastroiacovo P, et al. An international
changed in the last 3 decades? Pediatr Surg Int 2004;20:76872. collaborative study of the epidemiology of esophageal atresia or
10. Orford J, Cass DT, Glasson MJ. Advances in the treatment of stenosis. Reprod Toxicol 1993;7:40521.
oesophageal atresia over three decades: The 1970s and the 1990s. 21. Harris J, Kallen B, Robert E. Descriptive epidemiology of alimen-
Pediatr Surg Int 2004;20:4027. tary tract atresia. Teratology 1995;52:1529.
380 SECTION III Thoracic
22. Shaw-Smith C. Oesophageal atresia, tracheo-oesophageal fistula, 46. Goh DW, Brereton RJ, Spitz L. Esophageal atresia with obstructed
and the VACTERL association: Review of genetics and epidemi- tracheoesophageal fistula and gasless abdomen. J Pediatr Surg
ology. J Med Genet 2006;43:54554. 1991;26:1602.
23. Pletcher BA, Friedes JS, Breg WR, et al. Familial occurrence of 47. Laffan EE, Daneman A, Ein SH, et al. Tracheoesophageal
esophageal atresia with and without tracheoesophageal fistula: fistula without esophageal atresia: Are pull-back tube esophago-
Report of two unusual kindreds. Am J Med Genet 1991;39: grams needed for diagnosis? Pediatr Radiol 2006;36:1141
3804. 7.
24. Mastroiacovo P, Castilla EE, Arpino C, et al. Congenital malfor- 48. Bax KN, Roskott AM, van der Zee DC. Esophageal atresia
mations in twins: An international study. Am J Med Genet without distal tracheoesophageal fistula: High incidence of proxi-
1999;83:11724. mal fistula. J Pediatr Surg 2008;43:5225.
25. Robert E, Mutchinick O, Mastroiacovo P, et al. An international 49. Kane T, Atri P, Potoka DA. Triple fistula: Management of a
collaborative study of the epidemiology of esophageal atresia or double tracheoesophageal fistula with a third H-type proximal
stenosis. Reprod Toxicol 1993;7:40521. fistula. J Pediatr Surg 2007;42:e1e3.
26. Clementi M, Di Gianantonio E, Pelo E, et al. Methimazole 50. Touloukian RJ. Membranous esophageal obstruction simulating
embryopathy: Delineation of the phenotype. Am J Med Genet atresia with a double tracheoesophageal fistula in a neonate.
1999;83:436. J Thorac Cardiovasc Surg 1973;65:1914.
27. Ramirez A, Espinosa de los Monteros A, Parra A, et al. Esophageal 51. Centini G, Rosignoli L, Kenanidis A, et al. Prenatal diagnosis of
atresia and tracheoesophageal fistula in two infants born to hyper- esophageal atresia with the pouch sign. Ultrasound Obstet
thyroid women receiving methimazole (Tapazol) during preg- Gynecol 2003;21:4947.
nancy. Am J Med Genet 1992;44:2002. 52. Has R, Gunay S. Upper neck pouch sign in prenatal diagnosis of
28. Szendrey T, Danyi G, Czeizel A. Etiological study on isolated esophageal atresia. Arch Gynecol Obstet 2004;270:568.
esophageal atresia. Hum Genet 1985;70:518. 53. Kalache KD, Chaoui R, Mau H, et al. The upper neck pouch sign:
29. Nora AH, Nora JJ. A syndrome of multiple congenital anomalies A prenatal sonographic marker for esophageal atresia. Ultrasound
associated with teratogenic exposure. Arch Environ Health Obstet Gynecol 1998;11:13840.
1975;30:1721. 54. Houben CH, Curry JI. Current status of prenatal diagnosis,
30. Chen H, Goei GS, Hertzler JH, et al. Family studies in congenital operative management and outcome of esophageal atresia/
esophageal atresia with and without tracheoesophageal fistula. In: tracheoesophageal fistula. Prenat Diagn 2008;28:66775.
Epstein CJ, Curry CJR, Packman S, editors. Risks, Communica- 55. Chaoui R, Schneider MB, Kalache KD. Right aortic arch with
tion, and Decision Making in Genetic Counseling. New York: vascular ring and aberrant left subclavian artery: Prenatal diagno-
Alan R. Liss for the National Foundation March-of-Dimes; sis assisted by three-dimensional power Doppler ultrasound.
1979. Ultrasound Obstet Gynecol 2003;22:6613.
31. Martinez-Frias ML, Rodriguez-Pinilla E. Tracheoesophageal and 56. Sivaprakasam MC, Vettukattil JJ. 3-D echocardiographic imaging
anal atresia in prenatal children exposed to a high dose of alcohol. of double aortic arch. Eur J Echocardiogr 2006;7:4767.
Am J Med Genet 1991;40:128. 57. Levine D, Barnewolt CE, Mehta TS, et al. Fetal thoracic abnor-
32. Lipson A, Beuhler B, Bartley J, et al. Maternal hyperphenyla- malities: MR imaging. Radiology 2003;228:37988.
laninemia fetal effects. J Pediatr 1984;104:21620. 58. Matsuoka S, Takeuchi K, Yamanaka Y, et al. Comparison of mag-
33. Depaepe A, Dolk H, Lechat MF. The epidemiology of tracheo- netic resonance imaging and ultrasonography in the prenatal diag-
oesophageal fistula and oesophageal atresia in Europe. EUROCAT nosis of congenital thoracic abnormalities. Fetal Diagn Ther
Working Group. Arch Dis Child 1993;68:7438. 2003;18:44753.
34. Torfs CP, Curry CJ, Bateson TF. Population-based study of tra- 59. Langer JC, Hussain H, Khan A, et al. Prenatal diagnosis of
cheoesophageal fistula and esophageal atresia. Teratology 1995;52: esophageal atresia using sonography and magnetic resonance
22032. imaging. J Pediatr Surg 2001;36:8047.
35. van Bokhoven H, Celli J, van Reeuwijk J, et al. MYCN haploinsuf- 60. Eklof O, Lohr G, Okmian L. Submucosal perforation of the
ficiency is associated with reduced brain size and intestinal atresias esophagus in the neonate. Acta Radiol Diagn (Stockh) 1969;8:
in Feingold syndrome. Nat Genet 2005;37:4657. 18792.
36. Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in 61. Sapin E, Gumpert L, Bonnard A, et al. Iatrogenic pharyn-
a new member of the chromodomain gene family cause CHARGE goesophageal perforation in premature infants. Eur J Pediatr Surg
syndrome. Nat Genet 2004;36:9557. 2000;10:837.
37. FitzPatrick DR, Magee A, Friedler Z, et al. Mutations in SOX2 62. Gassner I, Geley TE. Sonographic evaluation of oesophageal
cause Rogers syndrome (anophthalmia, tracheoesophageal fistula, atresia and tracheoesophageal fistula. Pediatr Radiol 2005;35:
and genitourinary anomalies). Presented before the American 15964.
Society of Human Genetics annual meeting, 2004(session 54), 63. Gross ER, Reichstein A, Gander JW, et al. The role of fiberoptic
p 190. endoscopy in the evaluation and management of long gap esopha-
38. Genevieve D, de Pontual L, Amiel J, et al. An overview of isolated geal atresia. Pediatr Surg Int 2010;45:12237.
and syndromic oesophageal atresia. Clin Genet 2007;71:3929. 64. Spitz L. Esophageal atresia: Lessons I have learned in a 40-year
39. Kulkarni B, Rao RS, Oak S, et al. 13 pairs of ribsa predictor of experience. J Pediatr Surg 2006;41:163540.
long gap atresia in tracheoesophageal fistula. J Pediatr Surg 65. Rothenberg SS. Thoracoscopic repair of tracheoesophageal
1997;32:14534. fistula. Semin Pediatr Surg 2005;14:27.
40. Quan L, Smith DW. The VATER association: Vertebral defects, 66. Gupta DK, Arora M, Srinivas M. Azygos vein anomaly: The best
Anal atresia, T-E fistula with esophageal atresia, Radial and Renal predictor of a long gap in esophageal atresia and tracheoesopha-
dysplasia: A spectrum of associated defects. J Pediatr 1973; geal fistula. Pediatr Surg Int 2001;17:1013.
82:1047. 67. Babu R, Pierro A, Spitz L, et al. The management of oesophageal
41. de Jong EM, Felix JF, Deurloo JA, et al. NonVACTERL-type atresia in neonates with right-sided aortic arch. J Pediatr Surg
anomalies are frequent in patients with esophageal atresia/ 2000;35:568.
tracheo-esophageal fistula and full or partial VACTERL associa- 68. Cantinotti M, Hedge S, Bell A, et al. Diagnostic role of magnetic
tion. Birth Defects Res A Clin Mol Teratol 2008;82:927. resonance imaging in identifying aortic arch anomalies. Congent
42. Kluth D. Atlas of esophageal atresia. J Pediatr Surg 1976;11: Heart Dis 2008;3:11723.
90119. 69. Tam PK, Chan FL, Saing H. Diagnosis and evaluation of esopha-
43. Vogt EC. Congenital esophageal atresia. Am J Roentgenol 1929; geal atresia by direct sagittal CT. Pediatr Radiol 1987;17:
22:4635. 6870.
44. Gross RE. The Surgery of Infancy and Childhood. Philadelphia: 70. Ratan SK, Varshney A, Mullick S, et al. Evaluation of neonates
WB Saunders; 1953. with esophageal atresia using chest CT scan. Pediatr Surg Int
45. Harmon C, Coran GC. Congenital anomalies of the esophagus. 2004;20:75761.
In: Grosfeld J, ONeill JA, Coran AG, editors. Pediatric Surgery. 71. Ou P, Seror E, Layouss W, et al. Definitive diagnosis and surgical
6th ed. Philadelphia: Mosby; 2006. p. 105181. planning of H-type tracheoesophageal fistula in a critically ill
27 Esophageal Atresia and Tracheoesophageal Fistula Malformations 381
neonate: First experience using air distension of the esophagus 96. Poenaru D, Laberge JM, Neilson IR, et al. A more than 25-year
during high-resolution computed tomography acquisition. experience with end-to-end versus end-to-side repair for esopha-
J Thorac Cardiovasc Surg 2007;133:111617. geal atresia. J Pediatr Surg 1991;26:4727.
72. Islam S, Cavanaugh E, Honeke R, et al. Diagnosis of a proximal 97. Davies MR. Anatomy of the extrinsic motor nerve supply to mobi-
tracheoesophageal fistula using three-dimensional CT scan: A lized segments of the oesophagus disrupted by dissection during
case report. J Pediatr Surg 2004;39:1002. repair of oesophageal atresia with distal fistula. Br J Surg
73. Replogle RL. Esophageal atresia: Plastic sump catheter for drain- 1996;83:126870.
age of the proximal pouch. Surgery 1963;54:2967. 98. McCallion WA, Hannon RJ, Boston VE. Prophylactic extrapleu-
74. Holcomb GW 3rd. Survival after gastrointestinal perforation ral chest drainage following repair of esophageal atresia: Is it
from esophageal atresia and tracheoesophageal fistula. J Pediatr necessary? J Pediatr Surg 1992;27:561.
Surg 1993;28:15325. 99. Kay S, Shaw K. Revisiting the role of routine retropleural drain-
75. Maoate K, Myers NA, Beasley SW. Gastric perforation in infants age after repair of esophageal atresia with distal tracheoesophageal
with esophageal atresia and distal tracheo-oesophageal fistula. fistula. J Pediatr Surg 1999;34:10825.
Pediatr Surg Int 1999;15:247. 100. Rothenberg SS. Thoracoscopic repair of tracheoesophageal fistula
76. Beasley SW, Myers NA, Auldist AW. Management of the prema- in a newborn. Ped Endosurg Innovative Tech 2000;28994.
ture infant with esophageal atresia and hyaline membrane disease. 101. Rothenberg SS. Thoracoscopic repair of tracheoesophageal fistula
J Pediatr Surg 1992;27:235. in newborns. J Pediatr Surg 2002;37:86972.
77. Holmes S, Keily EM, Spitz L. Tracheo-oesophageal atresia and 102. Bax KM, van Der Zee DC. Feasibility of thoracoscopic repair of
the respiratory distress syndrome. Pediatr Surg Int 1987;2: esophageal atresia with distal fistula. J Pediatr Surg 2002;37:
1618. 1926.
78. Malone PS, Kiely EM, Brain AJ, et al. Tracheo-oesophageal fistula 103. Holcomb GW 3rd, Rothenberg SS, Bax KM, et al. Thoracoscopic
and pre-operative mechanical ventilation. Aust N Z J Surg repair of esophageal atresia and tracheoesophageal fistula: A
1990;60:5257. multi-institutional analysis. Ann Surg 2005;242:42230.
79. Atzori P, Iacobelli BD, Bottero S, et al. Preoperative tracheobron- 104. van der Zee DC, Bax NM. Thoracoscopic repair of esophageal
choscopy in newborns with esophageal atresia: Does it matter? atresia with distal fistula. Surg Endosc 2003;17:10657.
J Pediatr Surg 2006;41:10547. 105. Bax N, van der Zee DC, et al. The thoracoscopic approach to
80. Usui N, Kamata S, Ishikawa S, et al. Anomalies of the tracheo- esophageal atresia with distal fistula. In: Bax N, Georgeson KE,
bronchial tree in patients with esophageal atresia. J Pediatr Surg Rothenberg SS, editors. Endoscopic Surgery in Infants and Chil-
1996;31:25862. dren. Heidelberg: Springer; 2008. p. 199205.
81. Iannoli ED, Litman RS. Tension pneumothorax during flexible 106. Rothenberg SS. Thoracoscopic repair of esophageal atresia and
fiberoptic bronchoscopy in a newborn. Anesth Analg 2002;94: tracheoesophageal fistula in neonates: Evolution of a technique.
51213. J Laparoendosc Adv Surg Tech A 2012;1959.
82. Holzki J. Bronchoscopic findings and treatment in congenital 107. Mortellaro VE, Fike FB, Adibe OO, et al. The use of high-
tracheoesophageal fistula. Paediatr Anaesth 1992;2:297303. frequency oscillating ventilation to facilitate stability during neo-
83. Johnson AM, Rodgers BM, Alford B, et al. Esophageal atresia natal thoracoscopic operations. J Laparoendosc Adv Surg Tech
with double fistula: The missed anomaly. Ann Thorac Surg 2011;A 21:8779.
1984;38:195200. 108. Puri P, Blake N, ODonnell B, et al. Delayed primary anastomosis
84. Katsura S, Shono T, Yamanouchi T, et al. Esophageal atresia with following spontaneous growth of esophageal segments in esopha-
double tracheoesophageal fistulaa case report and review of the geal atresia. J Pediatr Surg 1981;16:1803.
literature. Eur J Pediatr Surg 2005;15:3547. 109. Puri P, Ninan GK, Blake NS, et al. Delayed primary anastomosis
85. Bikhazi G, Davis PJ. Anesthesia for neonates and premature for esophageal atresia: 18 months to 11 years follow-up. J Pediatr
infants. In: Motoyama E, editor. Anesthesia for Infants and Chil- Surg 1992;27:112730.
dren. St. Louis: Mosby; 1990. p. 4503. 110. Spitz L, Kiely E, Brereton RJ, et al. Management of esophageal
86. Salem MR, Wong AY, Lin YH, et al. Prevention of gastric disten- atresia. World J Surg 1993;17:296300.
tion during anesthesia for newborns with tracheoesophageal fis- 111. Aziz D, Schiller D, Gerstle JT, et al. Can long-gap esophageal
tulas. Anesthesiology 1973;38:823. atresia be safely managed at home while awaiting anastomosis?
87. Schwartz N, Eisenkraft JB. Positioning the endotracheal tube in J Pediatr Surg 2003;38:7058.
an infant with tracheoesophageal fistula. Anesthesiology 1988;69: 112. Hollands CM, Lankau CA Jr, Burnweit CA. Preoperative home
28990. care for esophageal atresiaa survey. J Pediatr Surg 2000;
88. Alabbad SI, Shaw K, Puligandla PS, et al. The pitfalls of endotra- 35:27982.
cheal intubation beyond the fistula in babies with type C esopha- 113. Howard R, Myers NA. Esophageal atresia: A technique for elon-
geal atresia. Semin Pediatr Surg 2009;18(2):11618. gating the upper pouch. Surgery 1965;58:7257.
89. Soucy P, Bass J, Evans M. The muscle-sparing thoracotomy in 114. Mahour GH, Woolley MM, Gwinn JL. Elongation of the upper
infants and children. J Pediatr Surg 1990;27:12578. pouch and delayed anatomic reconstruction in esophageal atresia.
90. Rothenberg SS, Pokorny WJ. Experience with a total muscle J Pediatr Surg 1974;9:37383.
sparing approach for thoracotomies in neonates, infants and chil- 115. Hays DM, Woolley MM, Snyder WH Jr. Changing techniques in
dren. J Ped Surg 1992;27:115760. the management of esophageal atresia. Arch Surg 1966;92:
91. McKinnon LJ, Kosloske AM. Prediction and prevention of anas- 61116.
tomotic complications of esophageal atresia and tracheoesopha- 116. Hendren WH, Hale JR. Electromagnetic bougienage to lengthen
geal fistula. J Pediatr Surg 1990;25:77881. esophageal segments in congenital esophageal atresia. N Engl J
92. Bishop PJ, Klein MD, Philippart AI, et al. Transpleural repair Med 1975;293:42832.
of esophageal atresia without a primary gastrostomy: 240 117. Livaditis A, Radberg L, Odensjo G. Esophageal end-to-end anas-
patients treated between 1951 and 1983. J Pediatr Surg tomosis: Reduction of anastomotic tension by circular myotomy.
1985;20:8238. Scand J Thorac Cardiovasc Surg 1972;6:20614.
93. Sharma S, Sinha SK, Rawat JD, et al. Azygos vein preservation in 118. Kate JT. Method of suturing operations for congenital oesopha-
primary repair of esophageal atresia with tracheoesophageal geal atresia. Arch Chir Neerland 1952;4:437.
fistula. Pediatr Surg Int 2007;23:121518. 119. Gough MH. Esophageal atresiause of an anterior flap in the
94. Upadhyaya VD, Gangopadhyaya AN, Gopal SC, et al. Is ligation difficult anastomosis. J Pediatr Surg 1980;15:31011.
of azygos vein necessary in primary repair of tracheoesophageal 120. Kimura K, Soper RT. Multistaged extrathoracic esophageal
fistula with esophageal atresia? Eur J Pediatr Surg 2007; elongation for long gap esophageal atresia. J Pediatr Surg
17:23640. 1994;29:5668.
95. Touloukian RJ, Pickett LK, Spackman T, et al. Repair of esopha- 121. Martinez-Ferro M, et al. Thoracoscopic repair of esophageal
geal atresia by end-to-side anastomosis and ligation of the tra- atresia without fistula. In: Bax N, Georgeson KE, Rothenberg SS,
cheoesophageal fistula: A critical review of 18 cases. J Pediatr Surg editors. Endoscopic surgery in infants and children. Heidelberg:
1974;9:30510. Springer; 2008. p. 20719.
382 SECTION III Thoracic
122. Davison P, Poenaru D, Kamal I. Esophageal atresia: Primary 149. Said M, Mekki M, Golli M, et al. Balloon dilatation of anasto-
repair of a rare long gap variant involving distal pouch mobiliza- motic strictures secondary to surgical repair of oesophageal
tion. J Pediatr Surg 1999;34:18813. atresia. Br J Radiol 2003;76:2631.
123. Lessin MS, Wesselhoeft CW, Luks FI, et al. Primary repair of 150. Spitz L, et al. Oesophageal atresia and tracheoesophageal fistula.
long-gap esophageal atresia by mobilization of the distal esopha- In: Freeman NV, editor. Surgery of the Newborn. New York:
gus. Eur J Pediatr Surg 1999;9:36972. Churchill Livingstone; 1994. p. 35373.
124. Lai JY, Sheu JC, Chang PY, et al. Experience with distal circular 151. Chittmittrapap S, Spitz L, Kiely EM, et al. Anastomotic stricture
myotomy for long-gap esophageal atresia. J Pediatr Surg 1996;31: following repair of esophageal atresia. J Pediatr Surg 1990;25:
15038. 50811.
125. Giacomoni MA, Tresoldi M, Zamana C, et al. Circular myotomy 152. Koivusalo A, Turunen P, Rintala RJ, et al. Is routine dilatation
of the distal esophageal stump for long gap esophageal atresia. after repair of esophageal atresia with distal fistula better than
J Pediatr Surg 2001;36:8557. dilatation when symptoms arise? Comparison of results of two
126. Rehbein F, Schweder N. Reconstruction of the esophagus without European pediatric surgical centers. J Pediatr Surg 2004;39:
colon transplantation in cases of atresia. J Pediatr Surg 1971;6: 16437.
74652. 153. Ashcraft KW, Goodwin C, Amoury RA, et al. Early recognition
127. Okmian L, Booss D, Ekelund L. An endoscopic technique for and aggressive treatment of gastroesophageal reflux following
Rehbeins silver olive method. Z Kinderchir 1975;16:21215. repair of esophageal atresia. J Pediatr Surg 1977;12:31721.
128. Vogel AM, Yang EY, Fishman SJ. Hydrostatic stretch-induced 154. Fonkalsrud EW. Gastroesophageal fundoplication for reflux fol-
growth facilitating primary anastomosis in long-gap esophageal lowing repair of esophageal atresia: Experience with nine patients.
atresia. J Pediatr Surg 2006;41:11702. Arch Surg 1979;114:4851.
129. Schaerli A. Esophageal reconstruction in very long atresia by 155. Pieretti R, Shandling B, Stephens CA. Resistant esophageal steno-
elongation of the lesser curvature. Pediatr Surg Int 1992;7: sis associated with reflux after repair of esophageal atresia: A
1015. therapeutic approach. J Pediatr Surg 1974;9:3557.
130. Rao KL, Menon P, Samujh R, et al. Fundal tube esophagoplasty 156. St. Peter SD, Calkins CM, Holcomb GW III. The use of biosyn-
for esophageal reconstruction in atresia. J Pediatr Surg 2003;38: thetic mesh to separate the anastomoses during the thoracoscopic
17235. repair of esophageal atresia and tracheoesophageal fistula.
131. Waterston D. Colonic replacement of the esophagus (intratho- J Laparoendosc Adv Surg Tech 2007;17:3802.
racic). Surg Clin North Am 1994;44:. 157. Richter GT, Ryckman F, Brown RL, et al. Endoscopic manage-
132. Anderson KD, Randolph JG. The gastric tube for esophageal ment of recurrent tracheoesophageal fistula. J Pediatr Surg
replacement in children. J Thorac Cardiovasc Surg 1973;66: 2008;43:23845.
33342. 158. Keckler SJ, St. Peter SD, Calkins CM, et al. Occlusion of a
133. Heimlich HJ, Winfield JM. The use of a gastric tube to replace recurrent tracheoesophageal fistula. J Pediatr Surg 2008;18:
or by-pass the esophagus. Surgery 1955;37:54959. 4658.
134. Spitz L, Kiely E, Pierro A. Gastric transposition in childrena 159. Meier JD, Sulman CG, Almond PS, et al. Endoscopic manage-
21-year experience. J Pediatr Surg 2004;39:27681. ment of recurrent congenital tracheoesophageal fistula: A review
135. Ure BM, Jesch NK, Sumpelmann R, et al. Laparoscopically of techniques and result. Int J Pediatr Otorhinolaryngol
assisted gastric pull-up for long gap esophageal atresia. J Pediatr 2007;71:6917.
Surg 2003;38:16612. 160. Wailoo MP, Emery JL. The trachea in children with tra-
136. Bax NM, van der Zee DC. Jejunal pedicle grafts for reconstruc- cheooesophageal fistula. Histopathology 1979;3:32938.
tion of the esophagus in children. J Pediatr Surg 2007;42:3639. 161. Cohen B, Glasson M. Tracheomalacia in association with con-
137. Ring WS, Varco RL, LHeureux PR, et al. Esophageal replace- genital tracheoesophageal fistula. Surgery 1978;79:5048.
ment with jejunum in children: An 18 to 33 year follow-up. 162. Rideout DT, Hayashi AH, Gillis DA, et al. The absence of clini-
J Thorac Cardiovasc Surg 1982;83:91827. cally significant tracheomalacia in patients having esophageal
138. Saitua F, Madrid A, Capdeville F, et al. Pharyngoesophageal atresia without tracheoesophageal fistula. J Pediatr Surg 1991;
reconstruction by free jejunal graft and microvascular anastomosis 26:13035.
in a 10-year-old girl. J Pediatr Surg 2004;39:e1012. 163. Delius RE, Wheatley MJ, Coran AG. Etiology and management
139. Bax NM, Van Renterghem KM. Ileal pedicle grafting for esopha- of respiratory complications after repair of esophageal atresia with
geal replacement in children. Pediatr Surg Int 2005;21:36972. tracheoesophageal fistula. Surgery 1992;112:52732.
140. Foker JE, Linden BC, Boyle EM Jr, Marquardt C. Development 164. Gross RE, Neuhauser EBD. Compression of the trachea by an
of a true primary repair for the full spectrum of esophageal atresia. anomalous innominate artery: An operation for its relief. Am J Dis
Ann Surg 1997;226:53341. Child 1948;75:5704.
141. Foker JE, Kendall Krosch TC, Catton K, et al. A flexible approach 165. Schwartz MZ, Filler RM. Tracheal compression as a cause of
to achieve a true primary repair for all infants with esophageal apnea following repair of tracheoesophageal fistula: Treatment by
atresia. Semin Pediatr Surg 2009;18:239. aortopexy. J Pediatr Surg 1980;15:8428.
142. van der Zee DC, Vieirra-Travassos D, Kramer WL, et al. Thora- 166. Applebaum H, Woolley MM. Pericardial flap aortopexy for tra-
coscopic elongation of the esophagus in long gap esophageal cheomalacia. J Pediatr Surg 1990;25:302.
atresia. J Pediatr Surg 2007;42:17858. 167. Koyluoglu G, Gunay I, Ceran C, et al. Pericardial flap aortopexy:
143. Spitz L, Kiely E, Brereton RJ, et al. Management of esophageal An easy and safe technique in the treatment of tracheomalacia.
atresia. World J Surg 1993;17:296300. J Cardiovasc Surg (Torino) 2002;43:2957.
144. MacKinlay G, Burlles R. Oesophageal atresia: Paralysis and ven- 168. Blair GK, Cohen R, Filler RM. Treatment of tracheomalacia:
tilation management of the wide gap. Pediatr Surg Int 1987;2: Eight years experience. J Pediatr Surg 1986;21:7815.
1012. 169. Vaishnav A, MacKinnon AE. New cervical approach for trache-
145. Lyall P, Bao-Quan Q, Beasley S. The effect of neck flexion on opexy. Br J Surg 1986;73:4412.
oesophageal tension in the pig and its relevance to repaired 170. DeCou JM, Parsons DS, Gauderer MWL. Thoracoscopic aor-
oesophageal atresia. Pediatr Surg Int 2001;17:1935. topexy for severe tracheomalacia. Pediatr Endosurg Innov Tech
146. Beasley SW. Does postoperative ventilation have an effect on the 2001;5:2058.
integrity of the anastomosis in repaired oesophageal atresia? 171. Bax N, van der Zee DC, et al. Aortosternopexy for tracheomala-
J Paediatr Child Health 1999;35:1202. cia. In: Bax N, Georgeson KE, Rothenberg SS, editors. Endo-
147. Chittmittrapap S, Spitz L, Kiely EM, et al. Anastomotic leakage scopic Surgery in Infants and Children. Heidelberg: Springer;
following surgery for esophageal atresia. J Pediatr Surg 1992;27: 2008. p. 15762.
2932. 172. Kane T, Nadler EP, Potoka DA. Thoracoscopic aortopexy for
148. Yanchar NL, Gordon R, Cooper M, et al. Significance of the vascular compression of the trachea: Approach from the right.
clinical course and early upper gastrointestinal studies in predict- J Laparoendosc Adv Surg Tech A 2008;18:31316.
ing complications associated with repair of esophageal atresia. 173. Kirkpatrick JA, Cresson SL, Pilling GP 4th. The motor activity
J Pediatr Surg 2001;36:81522. of the esophagus in association with esophageal atresia and tra-
27 Esophageal Atresia and Tracheoesophageal Fistula Malformations 383
cheoesophageal fistula. Am J Roentgenol Radium Ther Nucl Med 197. Chetcuti P, Phelan PD. Respiratory morbidity after repair of
1961;86:8847. esophageal atresia and tracheoesophageal fistula. Arch Dis Child
174. Lind JF, Blanchard RJ, Guyda H. Esophageal motility in tra- 1993;68:16770.
cheoesophageal fistula and esophageal atresia. Surg Gynecol 198. Malmstrm K, Lohi J, Lindahl H, et al. Longitudinal
Obstet 1966;123:55764. follow-up of bronchial inflammation, respiratory symptoms,
175. Shermeta DW, Whitington PF, Seto DS, et al. Lower esophageal and pulmonary function in adolescents after repair of esophageal
sphincter dysfunction in esophageal atresia: Nocturnal regurgita- atresia with tracheoesophageal fistula. J Pediatr Surg 2008;
tion and aspiration pneumonia. J Pediatr Surg 1977;12:8716. 153:396401.
176. Tovar JA, Diez Pardo JA, Murcia J, et al. Ambulatory 24-hour 199. Vazquez-Jimenez JF, Sachweh JS, Liakopoulos OJ, et al. Aor-
manometric and pH metric evidence of permanent impairment of topexy in severe tracheal instability: Short-term and long-term
clearance capacity in patients with esophageal atresia. J Pediatr outcome in 29 infants and children. Ann Thorac Surg 2001;72:
Surg 1995;30:122431. 1898901.
177. Deurloo JA, Ekkelkamp S, Bartelsman JF, et al. Gastroesophageal 200. Durning RP, Scoles PV, Fox OD. Scoliosis after thoracotomy in
reflux: Prevalence in adults older than 28 years after correction of tracheoesophageal fistula patients: A follow-up study. J Bone Joint
esophageal atresia. Ann Surg 2003;238:6869. Surg Am 1980;62:11569.
178. Zigman A, Yazbeck S. Esophageal foreign body obstruction after 201. Jaureguizar E, Vazquez J, Murcia J, et al. Morbid musculoskeletal
esophageal atresia repair. J Pediatr Surg 2002;37:7768. sequelae of thoracotomy for tracheoesophageal fistula. J Pediatr
179. Hormann M, Pokieser P, Scharitzer M, et al. Videofluoroscopy of Surg 1985;20:51114.
deglutition in children after repair of esophageal atresia. Acta 202. Cherup LL, Siewers RD, Futrell JW. Breast and pectoral muscle
Radiol 2002;43:50710. maldevelopment after anterolateral and posterolateral thoracoto-
180. Dutta HK, Rajani M, Bhatnagar V. Cineradiographic evaluation mies in children. Ann Thorac Surg 1986;41:4927.
of postoperative patients with esophageal atresia and tra- 203. Westfelt JN, Nordwall A. Thoracotomy and scoliosis. Spine
cheoesophageal fistula. Pediatr Surg Int 2000;16:3225. 1991;16:11245.
181. Montgomery M, Witt H, Kuylenstierna R, et al. Swallowing dis- 204. Chetcuti P, Dickens DR, Phelan PD. Spinal deformity in patients
orders after esophageal atresia evaluated with videomanometry. born with oesophageal atresia and tracheo-oesophageal fistula.
J Pediatr Surg 1998;33:121923. Arch Dis Child 1989;64:142730.
182. Dutta HK, Grover VP, Dwivedi SN, et al. Manometric evaluation 205. Chetcuti P, Myers NA, Phelan PD, et al. Chest wall deformity in
of postoperative patients of esophageal atresia and tracheo- patients with repaired esophageal atresia. J Pediatr Surg
esophageal fistula. Eur J Pediatr Surg 2001;11:3716. 1989;24:2447.
183. Kawahara H, Kubota A, Hasegawa T, et al. Lack of distal esopha- 206. Emmel M, Ulbach P, Herse B, et al. Neurogenic lesions after
geal contractions is a key determinant of gastroesophageal reflux posterolateral thoracotomy in young children. Thorac Cardiovasc
disease after repair of esophageal atresia. J Pediatr Surg 2007;42: Surg 1996;44:8691.
201721. 207. Schier F, Korn S, Michel E. Experiences of a parent support group
184. Shono T, Suita S, Arima T, et al. Motility function of the esopha- with the long-term consequences of esophageal atresia. J Pediatr
gus before primary anastomosis in esophageal atresia. J Pediatr Surg 2001;36:60510.
Surg 1993;28:6736. 208. Perttunen K, Tasmuth T, Kalso E. Chronic pain after thoracic
185. Shono T, Suita S. Motility studies of the esophagus in a case of surgery: A follow-up study. Acta Anaesthesiol Scand 1999;43:
esophageal atresia before primary anastomosis and in experimen- 5637.
tal models. Eur J Pediatr Surg 1997;7:13842. 209. Rogers ML, Duffy JP. Surgical aspects of chronic post-thoracotomy
186. Cheng W, Poon KH, Lui VC, et al. Esophageal atresia and pain. Eur J Cardiothorac Surg 2000;18:71116.
achalasia-like esophageal dysmotility. J Pediatr Surg 2004;39: 210. Haller JO, Berdon WE, Levin TL, et al. Tracheoesophageal
15813. fistula (H-type) in neonates with imperforate anus and the VATER
187. Tibboel D, Pattenier JW, Van Krutgen RJ, et al. Prospective association. Pediatr Radiol 2004;34:835.
evaluation of postoperative morbidity in patients with esophageal 211. Fordham LA. Imaging of the esophagus in children. Radiol Clin
atresia. Pediatr Surg Int 1988;4:2525. North Am 2005;43:283302.
188. Koch A, Rohr S, Plaschkes J, et al. Incidence of gastroesophageal 212. Azoulay D, Regnard JF, Magdeleinat P, et al. Congenital
reflux following repair of esophageal atresia. Progr Pediatr Surg respiratory-esophageal fistula in the adult: Report of nine cases
1986;19:10313. and review of the literature. J Thorac Cardiovasc Surg 1992;104:
189. Koivusalo A, Pakarinen MP, Rintala RJ. The cumulative incidence 3814.
of significant gastroesophageal reflux in patients with oesophageal 213. Garand SA, Kareti LR, Dumont TM, et al. Thoracoscopic repair
atresia with a distal fistulaa systematic clinical, pH-metric, and of tracheoesophageal fistula in a septuagenarian. Ann Thorac Surg
endoscopic follow-up study. J Pediatr Surg 2007;42:3704. 2006;81:1899901.
190. Koivusalo A, Pakarinen M, Rintala RJ, et al. Does postoperative 214. Crabbe DC. Isolated tracheo-oesophageal fistula. Paediatr Respir
pH monitoring predict complicated gastroesophageal reflux in Rev 2003;4:748.
patients with esophageal atresia? Pediatr Surg Int 2004;20: 215. Nagata K, Kamio Y, Ichikawa T, et al. Congenital tracheoesopha-
6704. geal fistula successfully diagnosed by CT esophagography. World
191. Van Biervliet S, Van Winckel M, Robberecht E, et al. High-dose J Gastroenterol 2006;12:14768.
omeprazole in esophagitis with stenosis after surgical treatment 216. LaSalle AJ, Andrassy RJ, Ver Steeg K, et al. Congenital tra-
of esophageal atresia. J Pediatr Surg 2001;36:141618. cheoesophageal fistula without esophageal atresia. J Thorac Car-
192. Wheatley MJ, Coran AG, Wesley JR. Efficacy of the Nissen diovasc Surg 1979;78:5838.
fundoplication in the management of gastroesophageal reflux 217. Garcia NM, Thompson JW, Shaul DB. Definitive localization of
following esophageal atresia repair. J Pediatr Surg 1993;28: isolated tracheoesophageal fistula using bronchoscopy and
535. esophagoscopy for guide wire placement. J Pediatr Surg 1998;33:
193. Snyder CL, Ramachandran V, Kennedy AP, et al. Efficacy of 16457.
partial wrap fundoplication for gastroesophageal reflux after 218. Ko BA, Frederic R, DiTirro PA, et al. Simplified access for divi-
repair of esophageal atresia. J Pediatr Surg 1997;32:108992. sion of the low cervical/high thoracic H-type tracheoesophageal
194. Sistonen SJ, Koivusalo A, Lindahl H, et al. Cancer after repair of fistula. J Pediatr Surg 2000;35:16212.
esophageal atresia: Population-based long-term follow-up. 219. Rothenberg SS. Experience with thoracoscopic tracheal surgery
J Pediatr Surg 2008;43:6025. in infants and children. J Laparoendosc Adv Surg Tech A
195. Mortellaro VE, Pettiford JN, St. Peter SD, et al. Incidence, diag- 2009;19:6714.
nosis and outcomes of vocal fold immobility after esophageal 220. Allal H, Montes-Tapia F, Andina G, et al. Thoracoscopic repair
atresia (EA) and/or tracheoesophageal fistula (TEF) repair. Eur J of H-type tracheoesophageal fistula in the newborn: A technical
Pediatr Surg 2011;21:3868. case report. J Pediatr Surg 2004;39:156870.
196. Robertson JR, Birck HG. Laryngeal problems following infant 221. Aziz GA, Schier F. Thoracoscopic ligation of a tracheoesophageal
esophageal surgery. Laryngoscope 1976;86:96570. H-type fistula in a newborn. J Pediatr Surg 2005;40:e35e36.
384 SECTION III Thoracic
222. Roth B, Rose KG, Benz-Bohm G, et al. Laryngo-tracheo- 228. Myer CM 3rd, Cotton RT, Holmes DK, et al. Laryngeal and
oesophageal cleft: Clinical features, diagnosis and therapy. Eur J laryngotracheoesophageal clefts: Role of early surgical repair. Ann
Pediatr 1983;140:416. Otol Rhinol Laryngol 1990;99:98104.
223. Walner DL, Stern Y, Collins M, et al. Does the presence of a 229. Donahoe PK, Gee PE. Complete laryngotracheoesophageal cleft:
tracheoesophageal fistula predict the outcome of laryngeal cleft Management and repair. J Pediatr Surg 1984;19:1438.
repair? Arch Otolaryngol Head Neck Surg 1999;125:7824. 230. Mathur NN, Peek GJ, Bailey CM, et al. Strategies for managing
224. Phelan PD, Stocks JG, Williams HE, et al. Familial occurrence Type IV laryngotracheoesophageal clefts at Great Ormond Street
of congenital laryngeal clefts. Arch Dis Child 1973;48:2758. Hospital for Children. Int J Pediatr Otorhinolaryngol
225. Tyler DC. Laryngeal cleft: Report of eight patients and a review 2006;70:190110.
of the literature. Am J Med Genet 1985;21:6175. 231. Moukheiber AK, Camboulives J, Guys JM, et al. Repair of a type
226. Pettersson G. Inhibited separation of larynx and the upper part of IV laryngotracheoesophageal cleft with cardiopulmonary bypass.
trachea from oesophagus in a newborn: Report of a case success- Ann Otol Rhinol Laryngol 2002;111:107680.
fully operated upon. Acta Chir Scand 1955;110:2504. 232. Geiduschek JM, Inglis AF Jr, ORourke PP, et al. Repair of a
227. Ryan DP, Muehrcke DD, Doody DP, et al. Laryngotracheoesopha- laryngotracheoesophageal cleft in an infant by means of extracor-
geal cleft (type IV): Management and repair of lesions beyond the poreal membrane oxygenation. Ann Otol Rhinol Laryngol
carina. J Pediatr Surg 1991;26:9629. 1993;102:82733.
C H A P T E R 2 8
Gastroesophageal Reflux
Corey W. Iqbal George W. Holcomb III
When a normal angle of His is present, there is a convo- have the dual effect of increasing the gastric pH while
luted fold of mucosa present at the gastroesophageal simultaneously decreasing the acid volume.5254 However,
junction. This mucosa creates a rosette-like configuration it is now recognized that some children with GERD have
that collapses on itself with increases in intragastric pres- normal pH probe studies and acid reflux with esophageal
sure or negative pressure in the thoracic esophagus, thus injury is not as big an issue for this subset of patients
acting as an additional weak antireflux valve.29,30 as is poor nutrition and pulmonary complications.
Patients with increased abdominal pressure as a result Other substances that increase esophageal mucosal injury
of neurologically related retching, physiologic effects include bile salts, pepsin, and trypsin. When combined
(obesity, ascites, peritoneal dialysis), or anatomic abnor- with acid, bile salts are injurious to the esophageal mucosa
malities (gastroschisis, omphalocele, CDH) are at by increasing the permeability of the esophageal mucosa
increased risk for developing GERD owing to the to existing acid, thus further potentiating injury.55,56
effects of chronic pressure from the abdomen into the Pepsin and trypsin are both proteolytic enzymes that can
thorax.3137 Finally, certain congenital defects such as con- injure the esophageal mucosa. Both of these enzymes are
genital short esophagus, congenital hiatal hernia, and more toxic at lower pH levels and, hence, are more injuri-
EA/TEF predispose to GERD. In patients with EA/TEF, ous in the presence of acid.57,58
the esophagus has abnormal peristalsis and the LES is
incompetent. It has been reported that up to 30% of
these patients will require antireflux surgery after repair CLINICAL MANIFESTATIONS
of their EA/TEF.3840 Regarding CDH, anatomic abnor-
malities of the esophageal hiatus and the esophagus pre- The presentation of GERD in infants and children is
dispose to GERD, with 1520% of surviving patients variable and depends on the patients age and overall
undergoing an antireflux operation for GERD.3537 medical condition. The surgeon must consider both this
Once the barrier to GER has been overcome (or variability and the patient characteristics when evaluating
failed), mechanisms for esophageal clearance become a child with symptoms for possible GERD. Although the
important in preventing damage associated with exposure symptoms of GERD are variable for each patient, the
of the esophageal mucosa to the gastric refluxate. The actual frequency of symptoms seen in infants who have
primary mechanism for esophageal clearance remains required surgical intervention for GERD has been
esophageal motility. However, gravity and saliva contrib- reported (Table 28-2).59
ute to the ability of the esophagus to clear the reflux- When considering the symptoms associated with
ate.41,42 There are three types of esophageal contractions: GERD, persistent regurgitation is the most common
primary, secondary, and tertiary. Primary contraction complaint reported by parents of children with GERD.60
waves are initiated with swallowing and are responsible However, in infants, vomiting is often physiologic and
for the clearance of refluxed contents in 8090% of reflux can be normal. This type of vomiting is termed chalasia
episodes. Secondary waves occur when material is refluxed of infancy and is seen early in life, usually during burping,
into the esophagus and clearance is required, especially after feeding, or when placed in the recumbent position.61
when the reflux occurs during sleep.43,44 Tertiary waves Chalasia does not interfere with normal growth or devel-
have nothing to do with esophageal clearance and are opment and rarely leads to other complications. It is a
sporadic, non-propagating contractions. When impaired self-limited process with most infants transitioning to
esophageal motility is present as a result of abnormal being asymptomatic by 2 years of age or near the time of
smooth muscle function, impaired vagal stimulation, or initiating solid foods.1 No treatment is necessary in
obstruction, refluxed gastric contents are not moved patients who have chalasia, and no diagnostic evaluation
caudad into the stomach in a timely manner. This pro- should be pursued. However, when persistent regurgita-
longed exposure can lead to esophageal mucosal injury tion is the result of GER, it can lead to complications,
and can potentiate the motility disturbance due to vagal including significant malnutrition and growth failure due
and/or smooth muscle inflammation or injury. Saliva to insufficient caloric intake.
neutralizes refluxed material, and patients with GERD In infants, another presenting symptom is irritability
have been found to have decreased salivary function. It due to pain. Painful esophagitis can be the result of the
has also been shown that positional effects of GERD acid refluxate. Discomfort leads to crying despite consol-
treatment may be related to gravity assisting in the clear- ing measures.62,63 Occasionally, small volumes of feeds
ance of esophageal refluxate.4548
The final element for prevention of esophageal injury
related to GERD is the ability to limit injury once TABLE 28-2 Frequency of Symptoms in Patients
refluxed contents have reached the esophagus. In addi- with Gastroesophageal Reflux
tion to functioning as a neutralizing agent, saliva also aids
in lubricating the esophageal contents, thus making it Symptom Frequency (%)
easier to clear any retained refluxate. Acid exposure has Regurgitation/vomiting 81
traditionally been postulated to cause the most significant Pulmonary symptoms 41
injury, but more recent data has also implicated alkaline Dysphagia/pain 30
bile reflux as well.20,49 Some pediatric patients with docu- Hemorrhage 7
mented GERD have been shown to have increased acid Adapted from Tovar JA, Olivares P, Diaz M, etal. Functional
secretion.50,51 To this end, the role of PPIs in controlling results of laparoscopic fundoplication in children. J Pediatr
GERD in this population is very important because they Gastroenterol Nutr 1998;26:42931.
390 SECTION IV Abdomen
briefly assist in alleviating pain. However, this is generally GERD and determining the need for antireflux therapy.
not a lasting effect.24,25 In contrast to infants, children Once the concern for GER as the etiologic cause of the
with GERD more often present with complaints of pain. patients complaints has been raised, diagnostic evalua-
As in adults, the pain is retrosternal in nature, and often tion should be initiated. The aim is not only to determine
described as heartburn. Long-standing GERD with the presence or absence of GERD, but to also ensure that
esophagitis can lead to chronic inflammation or even there are no other etiologies such as oropharyngeal dys-
ulcer formation with eventual scarring and stricture. Dys- motility, esophageal dysmotility, esophageal web, gastric
phagia develops as a result of a narrowed esophageal outlet obstruction, or food allergies.
lumen, as well as possible esophageal dysmotility second- Upper gastrointestinal radiography is the most fre-
ary to long-standing mucosal inflammation. Obstructive quent initial study employed. Evidence for reflux is seen
symptoms and pain are the two most common associated in up to 50% of the examinations.78,79 However, the
complaints when an esophageal stricture is present.64,65 absence of reflux is an extremely poor indicator of GERD
Barrett esophagitis is a premalignant condition that is as a cause of the patients symptoms. Furthermore, the
associated with prolonged GERD. It occurs when meta- presence of reflux on an upper gastrointestinal series does
plasia develops in the esophageal squamous epithelium not necessarily indicate pathologic GER. The contrast
that is replaced with columnar epithelium. In adults, it is study is most useful for delineating the anatomy of the
thought to be the result of chronic esophageal injury. esophagus and esophagogastric junction. It also evaluates
Whether it develops from gastric acid injury or exposure esophageal clearance and assesses esophageal and gastric
to alkaline bile reflux is currently a controversial topic.6668 motility. The contrast study can identify the presence of
Although uncommon in infants and children, when it does esophageal strictures, webs, or distal obstructions, such
develop, serious complications often result. In addition to as duodenal obstruction, antral web, or malrotation, as
the increased risk for adenocarcinoma, approximately the cause of the reflux symptomswhich may be the case
50% of these patients will develop stricture and many in 4% of patients.80 These correctable, anatomic causes
patients will develop ulcers.69,70 Aggressive GERD man- for GER are critical to rule out before pursuing further
agement, along with vigilant long-term surveillance via studies.
yearly esophagogastroscopy, must be pursued to minimize Twenty-four hour pH probe monitoring has been con-
these often difficult and possibly fatal complications. sidered the gold standard in diagnosing GERD since the
Respiratory symptoms are commonly seen in infants 1980s when DeMeester established scores that correlated
and children. Delineating the role of GER as an etiologic with the presence or absence of GERD.8183 Boix-Ochoa
agent for ongoing respiratory complaints can be difficult later proposed a revised score that was applicable to pedi-
because of the similarity of the symptoms that are seen atric patients aged 2 months to 3 years old that is still
with other pulmonary diseases and the fact that primary used today.84 Currently, the 24-hour pH probe monitor-
aspiration from oropharyngeal dysmotility may be the ing study is recommended in infants with respiratory
inciting factor not GER. Chronic cough, wheezing, symptoms, especially ALTE spells or apneic events;
choking, apnea, or near sudden infant death syndrome infants who are irritable with intractable crying and ano-
(SIDS) can all be symptoms attributable to GER. Recur- rexia; infants and children with reactive airway disease
rent bronchitis or pneumonia can occur from aspiration or recurrent pneumonia; and children unresponsive
of the refluxate.71 Esophageal stimulation via acidification to medical measures in whom GER is suspected. Special
of the esophageal mucosa causes vagally mediated laryn- considerations should be given to those children who
gospasm and bronchospasm, which clinically presents as become symptomatic after fundoplication. Conversely,
apnea or choking or mistakenly as asthma.72,73 Esophageal the study generally is not useful or necessary for infants
inflammation, as seen with esophagitis, likely enhances with uncomplicated regurgitation, children with esophag-
this mechanism.74,75 The effects of GER on premature itis already diagnosed by endoscopy and biopsy, and chil-
infants with respiratory problems have been studied.76 dren with dysphagia or heartburn thought to be caused
Most of these infants were intubated for varying periods by GER.
owing to respiratory distress syndrome or bronchopul- The pH study is performed by placing an electrode
monary dysplasia. In the former group, GERD was 23cm proximal to the gastroesophageal junction and
responsible for a deteriorating pulmonary status requir- measuring the pH in the distal esophagus. The accuracy
ing intubation. In the latter, deterioration of pulmonary of the pH examination is dependent on the cessation of
status plus failure to thrive and anorexia led to the diag- all antireflux medication: PPIs should be withheld for
nosis of GERD. All improved with correction of the seven days, and histamine receptor blockers are stopped
GERD.77 48 hours before the study. A reflux episode is considered
Although uncommon, hemorrhage can be a present- to have occurred if the esophageal pH is recorded as less
ing symptom of GERD. Esophagitis, gastritis, and ulcer than 4. Ideally, the examination should occur over an
formation can lead to hematochezia or melena in a small uninterrupted 24-hour period. The pH is continuously
percentage of infants or children.59 monitored via the esophageal electrode while the patients
position (upright, supine, prone) and activities (awake,
asleep, eating) are simultaneously recorded. The final
DIAGNOSTIC EVALUATION score is calculated based on the percent of total time that
the pH was less than 4, the total number of reflux epi-
As noted in the previous section, the clinical history is sodes, the number of episodes lasting longer than 5
an invaluable asset when evaluating for the presence of minutes, and the longest reflux episode.85,86
28 Gastroesophageal Reflux 391
Data from the pH probe monitoring has increased our independent of the pH of the refluxate or the esophageal
understanding of GER and taught us that not all GER is lumen. The second is multichannel intraluminal imped-
acidic. Three patterns of reflux have been described in ance (MII), a method that recognizes the flow of gastric
symptomatic infants, as determined by extended esopha- contents into the esophagus by detecting decreases in
geal pH monitoring: continuous, discontinuous, and impedance from high (the esophagus) to low (the stomach)
mixed.87 Those infants with the discontinuous type rarely values across electrode pairs placed throughout the
required an antireflux operation, whereas approximately esophagus and in the stomach. The presence of acid,
half of those with the other two types did. One should therefore, is also completely irrelevant with this diagnos-
keep in mind that medical treatment at the time of this tic tool which can be performed at the same time as pH
study was much less effective than it is currently. None- probe monitoring. Furthermore, MII also can distinguish
theless, this study indicates that pH monitoring can be liquid from gas refluxate.9597
useful in sorting out infants with GER who may or may Recent studies using MII support the concept that
not require an antireflux procedure.88,89 Incidentally, all measuring acid reflux (pH study) may not be the best
of the infants in this study, including the normal con- method of evaluating GERD.98101 These studies reaffirm
trols, experienced reflux frequently in the first two hours that the pH probe does not simultaneously detect the
after being given apple juice. majority of reflux events as defined by impedance moni-
It has been assumed that the retrograde flow of acid/ toring, presumably because the re-reflux boluses are not
pepsin material from the stomach into the esophagus is acidic. When MII and pH monitoring are used simulta-
the basic pathologic event of reflux disease. It is becoming neously, there are significant reflux episodes that are not
clear that the situation is not this straightforward which identified with pH monitoring alone because the epi-
suggests that pH probe monitoring may not be diagnostic sodes are actually non-acid reflux episodes with a pH
in all cases of GERD. Attempts to correlate symptoms greater than 4.99 These nonacid reflux episodes are less
(other than spitting up and vomiting) to pH probe- common in untreated GERD patients than in normal
detected reflux episodes have been particularly problem- patients. MII has shown that GERD patients more com-
atic. For example, in infants with spells of choking or monly have liquid-type reflux events, whereas non-
colic, a close association between pH probe-detected acid GERD patients generally have more gas-type reflux
reflux and these symptoms cannot be routinely demon- events.100 Additionally, MII data suggest that treatment
strated. Some spells coincide with reflux episodes, but with PPIs does not decrease the amount of reflux but
many do not. Similar questions can be raised when rather converts the reflux to non-acid or weakly acidic in
looking at pH probe data on the relation between acid nature.101
reflux episodes and apnea/bradycardia spells of prema- Although essential in adults, esophageal manometry is
ture infants or between wheezing, coughing, dental infrequently utilized in the pediatric population. When
erosion, sleep disturbance, and all the other myriad employed, the study measures the motility of the esopha-
symptoms attributed to reflux. gus and the pressure at the LES via a multiple-port pres-
The etiology for this non-acid reflux is likely to be due sure transducer placed in the esophagus and traversing
to the infant diet and buffering. The infant is not capable the LES. The clinical data accumulated in adult patients
of acidifying their gastric secretions to the extent that have revealed several important points that are likely
older children and adults are.90,91 Probe data from infants applicable to infants and children with GERD. First, it
showed that gastric pH was <4 for 15% of the time in has been shown that pharyngeal swallowing and primary
infants compared to a pH <4 for 42% of the time in older peristaltic contractions are responsible for the majority
children.92 Furthermore, the infants milk-based diet of the esophageal clearance of refluxed gastric contents,
serves as a buffer altering the pH of the gastric contents. rather than by secondary and tertiary peristalsis as previ-
This effect was investigated by measuring gastric pH ously believed.102 Additionally, through the use of a con-
after feeds whereby the gastric pH was >4 for a mean comitant 24-hour pH study and esophageal manometry,
time of 130 minutes post-feeding.93 it has been shown that there is a direct relationship
By using one old diagnostic technique and one new between worsening esophagitis secondary to GERD and
one, some of the disparities between pH probe observa- deterioration of esophageal motility. Manometric evalu-
tions and events may be better understood. This is based ation has been particularly useful in documenting abnor-
on the observation that some reflux of acid into the lower mal distal esophageal motility in infants after repair of
esophagus occurs while the intraesophageal pH is still EA/TEF.103 It is hoped that, as technology continues to
less than 4 due to a traditional acid reflux episode. This provide more appropriately sized instruments for sophis-
is called acid re-reflux (ARR) and will be missed by using ticated manometric studies in infants and children, the
only pH-monitoring techniques.94 ARR is most likely to usefulness and feasibility of such studies will increase our
occur in patients with severe esophagitis, postprandially, knowledge of the physiology and abnormalities associ-
and in the recumbent posture. It is now thought to be a ated with GERD in this population.
common cause of prolonged acid contact. Detecting Endoscopic evaluation of the esophagus and stomach is
ARR provides a better estimation of the incompetence of occasionally needed in the diagnosis of GERD in infants
the antireflux barrier than does traditional pH probe and children. Hematemesis, dysphagia, irritability in
evaluations. infants, or dysphagia with or without heartburn in chil-
Two methods may be used to evaluate ARR. The first dren, should prompt esophagogastroscopy to determine if
is scintigraphy, which directly measures radiolabeled esophagitis is present. Other complications, such as ulcer
liquid gastric contents flowing into the esophagus, formation, esophageal stricture, and Barrett esophagus,
392 SECTION IV Abdomen
can also be diagnosed during the endoscopic examination. decision needs to be individualized based on the patients
Mucosal biopsy should be performed to stage the severity age, anatomic information, disease severity, and social
of esophagitis or to histologically exclude dysplasia or environment (which will affect compliance with a treat-
malignancy in Barrett esophagus.104,105 ment regimen). In the majority of cases, nonoperative
The relationship between delayed gastric emptying treatment is the initial therapy of choice.
(DGE) and GERD in infants and children has been
extensively studied and continues to be one of the more
controversial aspects of antireflux surgery. The evalua- Medical Management
tion for DGE is undertaken using radionuclide scanning Position and Feeding
via a technetium-99-labeled meal. When documented
preoperatively, DGE has not been shown to significantly Nonoperative therapy for GERD in infants and children
improve when an emptying procedure is performed at the has been based on postural changes and dietary modifica-
time of an antireflux procedure.106 In fact, one study tion for many years. It is important to know the caloric
evaluating patients with DGE undergoing fundoplication needs of the patient so that a reduction in feeding volume
showed significantly improved gastric emptying for both in an attempt to limit reflux does not result in caloric dep-
solids and liquids after fundoplication alone.107 Neuro- rivation. Postural and dietary modifications alone will
logically impaired children with GERD have been shown result in clinical improvement in the vast majority of infants
to have DGE more often than neurologically normal with GERD.109,110 In older children, dietary alterations
children. Conflicting data regarding the benefit and com- should include a diet low in fat and the elimination of
plication rates for these patients undergoing emptying chocolate, coffee, tea, carbonated drinks, and spicy foods.
procedures at the time of their fundoplication have been The seated semi-upright position (approximately 45)
reported as well.108 Based on these data, it is not recom- for an infant with reflux has been recommended since the
mended that an emptying procedure be performed for a 1950s. In the 1960s, Carr showed that 60% of children
patient with DGE and GERD unless a second operative with GERD treated in this way improved by approxi-
intervention would place the patient at significant mor- mately 2 years of age and an additional 30% improved
bidity or mortality. by age 4 years.1,111
At our institution, the evaluation for GERD usually Failure of postural therapy may be related to social
includes an upper gastrointestinal contrast study to evalu- problems, chronic infections, or impaired gastric clear-
ate for normal anatomy and no evidence of malrotation. ance. In older patients, postural treatment is impractical
We are moving away from using the pH probe in favor because of the virtual impossibility of maintaining the
of clinical symptoms of GER, even utilizing nasogastric desired semi-sitting posture for sleep. Close attention to
feeding trials with close clinical observation. If there the details of postural therapy by the family members is
is still uncertainty about the diagnosis, a pH probe/ most important to its success.112
impedance study is performed. The main exception is the
baby with significant underlying airway disease in the
Pharmacologic Therapy
neonatal intensive care unit who needs a gastrostomy for
feeding and for whom the intensivists request a fundop- If symptoms persist despite a well-monitored program of
lication to protect the airway from aspiration. The neu- postural therapy and dietary modifications, pharmaco-
rologically impaired infant requiring a gastrostomy may logic measures should be added. Medical therapy includes
be another exception. Esophagogastroscopy and esopha- the administration of one or more drugs that increase
geal manometry are employed only when circumstances esophageal peristalsis, increase LES pressure, increase
suggest that the information they will provide will dictate gastric emptying, or lessen gastric acid production.
changes in the operative management. An example of this
situation is the patient with symptoms of GER but a Prokinetic Agents
normal pH study. When esophagitis or other complica-
tions of GERD are found after esophagogastroscopy or Historically, prokinetic agents have been utilized in an
manometry, surgical intervention is usually recom- attempt to increase LES pressure, enhance esophageal
mended. Preoperative gastric emptying studies are not peristalsis, and accelerate gastric emptying. The use of
performed on a routine basis, primarily owing to the cisapride and, more recently, metoclopramide has been
improvement that has been seen and reported in gastric questioned with regard to their safety.113115 In fact, cis-
emptying after fundoplication.106,107 If symptoms of DGE apride is no longer available due to safety concerns. Both
persist after antireflux surgery, gastric emptying studies randomized controlled trials and meta-analyses have
can be performed with a subsequent emptying procedure, shown no clinically relevant improvement in children
if necessary. However, all patients requiring a second receiving cisapride or metoclopramide.113,114,116,117 There-
fundoplication undergo an emptying study to be sure fore, the current recommendation regarding prokinetic
their recurrent symptoms are not exacerbated by DGE. agents in the management of GERD is that there is no
beneficial effect and their use is not advantageous.
esophagitis.118 Alterations in gastric acid may be accom- Another scenario is the infant who presents with an
plished by neutralization with antacids, by competition ALTE spell and GER is documented but no other etiol-
with histamine-2 (H2)-receptor antagonists, or by PPIs. ogy is identified. This patient may be best served with a
Because of the superiority of PPIs in controlling acid fundoplication as the initial therapy. In a review from our
production, H2-receptor antagonists or antacids are being institution involving 81 infants presenting with ALTE,
utilized less frequently. their symptoms resolved with fundoplication in 78.123
PPIs inhibit the final step of gastric acid secretion by The median follow-up in this study was 1,738 days. Two
blocking proton production by bonding and deactivating required a second fundoplication when their symptoms
H+, K+-ATPase (or proton pump) by traversing the pari- recurred, and one needed a pyloromyotomy. Interest-
etal cell membrane and accumulating in the secretory ingly, 96.3% of these patients had been treated with
canaliculi.119 The PPI omeprazole has been demonstrated antireflux mediation and 87.7% were taking antireflux
to reduce gastric acid production to zero.120122 It is a very medications at the time of their ALTE. Therefore, medical
powerful medicine that affects gastric acid production for management may not be effective in this population.
72 hours after cessation of administration. A prospective Barrett esophagitis and esophageal stricture are the
study determined that, within the therapeutic dose range two other conditions in which initial operative therapy
(0.73.5mg/kg/day), omeprazole was both efficacious is recommended. The changes of Barrett esophagus
and safe for children.121 In this study, omeprazole was will usually resolve in adolescents after fundoplication,
found to be highly effective in severe (grade IV) esophag- although life-long postoperative endoscopic surveillance
itis and patients refractory to other medical therapy. A is still needed. Regarding a stricture, dilation can be per-
dosage of 0.7mg/kg/day healed 45% of patients, and formed at the time of fundoplication. Subsequent dila-
1.4mg/kg/day healed another 30%. On a body weight tions may be needed in severe cases. Finally, children with
basis, the dosages required in children are generally a known hiatal hernia and symptomatic GER are not
higher than those in adults.122 For children unable to likely to respond to medical management. Initial fundop-
swallow the whole capsule, it is suggested to open the lication is a reasonable choice in these patients.
capsule and give the granular contents in a weakly acidic
vehicle such as orange juice, yogurt, or cranberry juice. Laparoscopic Nissen Fundoplication
The granules are stable in acid but are degraded in a
neutral or alkaline pH. Multiple PPIs are now available. The patient is placed at the end of the operating table so
However, the use of PPIs is limited to acid reflux and will that the surgeon can stand at the foot of the bed and the
have no benefit for the patient with non-acid reflux. assistant to his or her right. The scrub nurse stands to
the surgeons left (Fig. 28-2). For infants, the legs should
be placed in a frog-leg position. For older children, the
Operative Management lithotomy position can be used with stirrups. Neurologi-
Operative management usually follows failed medical cally impaired children may have contractures that pre-
management for growth failure (failure to thrive or gain clude lithotomy, and careful consideration should be
weight appropriately), most respiratory symptoms, and given to ensure they have appropriate padding of their
other symptoms such as pain and esophagitis. However, pressure points. Although a single monitor placed over
in selected circumstances, it may be best to proceed with the patients head is usually sufficient, two monitors,
fundoplication without a trial of medical therapy. These placed to the right and the left of the patients head, can
select situations include the previously mentioned patient be used as well. An orogastric tube is introduced by the
in an intensive care unit with underlying respiratory anesthesiologist to decompress the stomach. The bladder
disease who requires gastrostomy and possibly the neu- is usually emptied using a Cred maneuver.
rologically impaired patient with a similar need for gas- After prepping and draping, a 5mm vertical incision
trostomy and concern for aspiration. This latter scenario is made in the center of the umbilicus and carried down
is commonly seen in infants and children, and the deci- through the umbilical fascia. A Step sheath (Covidien,
sion for or against fundoplication at the time of gastros- Mansfield, MA) is gently introduced into the abdominal
tomy should be individualized. For example, in a 2- or cavity, followed by introduction of a cannula with a blunt-
3-year-old (or older) neurologically impaired patient who tipped trocar through the sheath. By using this open
begins to have difficulty with oral intake and requires technique, injury to the underlying viscera should
tube feedings but has no reflux symptoms, gastrostomy be extremely rare. The sheath can be secured to the
alone without fundoplication is very reasonable. On the umbilical skin for stabilization should the surgeon desire.
other hand, a neurologically impaired infant who cannot A pneumoperitoneum is created to a pressure of
swallow and requires tube feedings in the intensive care 1215mmHg, and diagnostic laparoscopy is performed
unit due to respiratory disease probably should have a with a 5mm, 45-angled telescope. Four stab incisions
fundoplication in addition to a gastrostomy. We have are then placed in infants, and three stab incisions and a
found that a trial of nasogastric feeds can be helpful in 5mm port for the ultrasonic scalpel are utilized in chil-
determining which neurologically impaired patient, with dren older than 5 years of age. The arrangement of these
the need for gastrostomy due to poor oral intake, would cannulas is seen in Figure 28-3. A liver retractor is intro-
also benefit from a fundoplication. With the laparoscopic duced through the lateral right port. The two main
placement of gastrostomy buttons, we have not found any working sites are the instruments positioned on either
particular difficulties in performing a laparoscopic fun- side of the midline. The assistants instrument is in the
doplication later if needed. patients left lateral abdomen.
394 SECTION IV Abdomen
A B
FIGURE 28-3 There are a number of ways to orient the instruments when performing a laparoscopic fundoplication. With our tech-
nique, a 45-angled, 5mm telescope is introduced after insertion of the 5mm umbilical cannula. The liver retractor is introduced
in the patients right subcostal region (solid arrow). The two main working ports are in the left and right epigastrium. The main
working port for the surgeon is the one in the patients left epigastric region. It is through this incision that dissecting instruments,
needle holder, and suture are introduced. The instrument utilized by the surgical assistant is in the patients left subcostal region
(dotted arrow). The stab incision technique can be utilized for both (A) infants and (B) adolescents. (From Holcomb GW III. Laparoscopic
Nissen fundoplication. In: Holcomb GW, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadel-
phia: Elsevier; 2008. p. 1520.)
28 Gastroesophageal Reflux 395
A B
FIGURE 28-4 If an adequate length of intra-abdominal esophagus is present, then as little dissection as possible is performed to
help prevent migration of the fundoplication wrap through an enlarged esophageal hiatus. The phrenoesophageal ligament is kept
intact on both the patients (A) right side and (B) left side of the esophagus. Note creation of the retroesophageal window has been
initiated (arrows). (From Holcomb GW III. Laparoscopic Nissen fundoplication. In: Holcomb GW, Georgeson KE, Rothenberg SS, editors.
Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; 2008. p. 1520.)
A B
FIGURE 28-5 Following closure of the esophageal hiatus with a 2-0 silk suture placed posterior to the esophagus, esophagocrural
sutures are placed at the 8, 11, 1, and 5 oclock positions around the esophagus. These photographs show the (A) right and (B) left
sides of the patients esophagus. The purpose of these sutures is to secure the esophagus in the intra-abdominal position to reduce
the incidence of postoperative reflux and also to obliterate the space between the esophagus and crura in an effort to prevent
transmigration of the fundoplication wrap.
of these stitches is not known if the phrenoesophageal TABLE 28-3 Recommended Bougie Size for
membrane is preserved. After placement of these crural Esophageal Calibration in Patients
sutures, the bougie is then introduced. A table describing Weighing Less Than 15kg
the appropriate bougie size for neonates weighing less
than 15kg has been developed and validated (Table Weight (kg) Bougie Size
28-3).124 The fundoplication is then performed using a 2.54.0 2024
standard Nissen technique. Usually, three 2-0 sutures are 4.05.5 2428
utilized to perform the fundoplication. The most supe- 5.57.0 2832
rior suture also incorporates a small portion of the 7.08.5 3234
anterior esophagus to anchor the wrap around the intra- 8.510.0 3436
10.015.0 3640
abdominal esophagus. The length of the fundoplication
is measured. Usually a length of approximately 2cm is From Ostlie DJ, Miller KA, Holcomb GW III. Effective Nissen
desired.124 For older children, 2.53.0cm may be fundoplication length and bougie diameter size in young
appropriate. children undergoing laparoscopic Nissen fundoplication.
J Pediatr Surg 2002;37:16646.
Bupivacaine is instilled in the incisions, and the umbil-
ical fascia and skin are closed. Steri-strips are usually
utilized for closure of the stab incisions. one utilized for exteriorization of the gastrostomy button.
If a fundoplication has not been performed, then the
Gastrostomy same site is used for locating the button. In either event,
this site is marked before insufflation so as not to distort
If a gastrostomy is also needed, the stab incision or its location when the abdomen is distended with CO2 to
cannula site in the patients left mid-epigastric area is the keep the gastrostomy off of the costal margin.
396 SECTION IV Abdomen
A red rubber catheter is introduced by the anesthesi- stomach and not external to the stomach (Fig. 28-7). This
ologist into the stomach which is then insufflated with can also be confirmed with the angled telescope by
3060mL of air to prevent incorporating the back wall looking around each side of the stomach with the button
of the stomach with the suture utilized to secure the in place. The PDS sutures are then secured over the
stomach to the anterior abdominal wall. The anterior button to prevent its dislodgement. Our protocol is to
wall of the stomach is grasped with a locking grasper and cut these sutures in five days. Others may cut them
brought toward the anterior abdominal wall. The tech- sooner. This technique was initially described by George-
nique for laparoscopic gastrostomy is seen in Figure 28-6. son and Owings, and details about complications have
Two 2-0 PDS sutures (Ethicon, Inc., Somerville, NJ) are been published.130,131
placed through the anterior abdominal wall cephalad to
the grasper, through the stomach, and out through the Postoperative Care
anterior abdominal wall inferior to the instrument that
has been used to grasp the stomach. Next, a needle fol- Postoperatively, if a gastrostomy button was placed with
lowed by a guide wire is introduced through the abdomi- the fundoplication (or if a button was placed primarily),
nal wall and stomach in the center of the square formed feedings are usually started several hours later and
by the two PDS sutures. Dilators from a Cook Vascular advanced over the evening and the next morning. Most
Dilator Set (Cook, Inc., Bloomington, IN) are used to (90%) patients are ready for discharge the day after the
serially dilate the anterior abdominal wall and gastrot- operation. The parents will have been instructed on the
omy. In infants, a 16 French dilator is usually the largest use of the gastrostomy during the patients 24-hour hos-
needed. In older children, the 20 French dilator may be pitalization and can advance the feedings as needed. The
required. The gastrostomy button is then placed over the patient can also be seen in the clinic should further ques-
guide wire and into the stomach. Under visualization, the tions or issues arise.
balloon on the Mic-Key (Ballard Medical Products, If the patient did not need a gastrostomy, then liquids
Draper, UT) gastrostomy button is inflated. Attention are allowed several hours after the procedure. It is very
must be paid to be sure that the button is, in fact, in the important to mention to the family that there is initial
A B
C D
FIGURE 28-6 (A) After approximation of the stomach to the anterior abdominal wall, two sutures of 2-0 or 0 PDS (depending on
the patients age) are placed extracorporeally through the abdominal wall, through the stomach, and out through the abdominal
wall inferior to the gastrostomy. (B) After placing the extracorporeal sutures, an 18 gauge needle is introduced through the left
epigastric incision and into the stomach under direct visualization. Following a rush of air through the needle, a guide wire is inserted
through the needle and the needle is removed. With the guide wire in place, the tract is serially dilated using the Cook Vascular
Dilator Set (Cook, Inc., Bloomington IN). These dilators come in 8, 12, 16, and 20 French sizes. (C) After dilating the tract and gas-
trostomy with the 20 French dilator, the 8 French dilator is placed through the Mic-Key gastrostomy button and is introduced over
the guide wire and into the stomach. (D) After placement of the button within the stomach, the balloon on the button is inflated,
the guide wire and dilator are removed, and the extracorporeal sutures are tied over the button to secure it to the anterior abdominal
wall. (From Holcomb GW III. Gastroesophageal reflux in infants and children. In: Fischer JE, editor. Mastery of Surgery. 5th ed. Philadelphia:
Lippincott Williams & Wilkins; 2007. p. 6501.)
28 Gastroesophageal Reflux 397
edema around the fundoplication. Therefore, for the first during that time, the incidence of repeat fundoplication
three weeks, especially in older children, the diet should was 12%. All patients who required a repeat operation
be a mechanical soft diet that has the consistency of had transmigration of the fundoplication wrap. During
pudding, apple sauce, mashed potatoes, and so on. Essen- that time period, the esophagus was being extensively
tially, meats and pizza should not be allowed because mobilized to try to create at least a 2cm length of intra-
these food substances can become lodged above the fun- abdominal esophagus. Moreover, there was no attempt to
doplication wrap. After three weeks, the edema usually obliterate the space between the esophagus and the crura.
resolves and small portions of meats and pizza can be These principles derived from prior training as well as
added to the diet. literature reports in adults.22,23 Although the operations
Patients are seen 2 weeks, 3 months, 6 months, and proceeded nicely and no conversions were needed, this
1 year after the operation. An upper gastrointestinal 12% incidence of re-do procedures seemed high.
contrast study is performed at 1 year to evaluate for However, historical reports for the open operation have
transmigration of the wrap or any other abnormalities. also documented a relatively high incidence of repeat
fundoplications from 612% (Table 28-4).60,143146
In an attempt to reduce the incidence of postoperative
Outcomes
transmigration of the wrap, two modifications were made
Our group has been interested in the efficacy of laparo- in our operative technique beginning in April, 2002.
scopic fundoplication for the past 12 years. A number First, there was minimal mobilization of the esophagus.
of articles have been published from our institution It was believed that the main reason for wrap transmigra-
detailing our thoughts about indications, complications, tion was that the esophagus was being mobilized and a
the operative technique, and ways to improve our space was being created between the esophagus and crura
results.123-129,132137 Also, there have been several articles to allow for the transmigration to occur. Therefore, the
published in the last few years looking at long-term phrenoesophageal membrane was kept intact to obliter-
outcomes.138142 ate this space. Second, to further reinforce this space,
In early 2002, in looking at our outcomes from January sutures were placed between the esophagus and crura.
2000, through March 2002, we believed that the need for Initially, only two sutures were used, but eventually four
repeat fundoplication was higher than desired.127 In 130 sutures have come to be placed for the purpose of further
patients undergoing laparoscopic Nissen fundoplication obliterating this space (see Fig. 28-5). No other modifica-
tions in the operative technique were made. In looking
at the results from April, 2002, through December, 2004,
the incidence of transmigration was reduced to 5%.121
This was actually reduced even further when looking at
the patients in whom four esophageal crural sutures were
utilized rather than two or three.
In 2005, conversations with Georgeson and colleagues
at the University of AlabamaBirmingham, prompted a
prospective, randomized trial looking at the operative
technique.27 It was believed that the efficacy of esopha-
geal mobilization should be evaluated. The primary end-
point was transmigration of the wrap. A power analysis
based on the difference between the 12% and 5% repeat
fundoplication rate previously mentioned was made, and
FIGURE 28-7 After the button is introduced into the stomach the study was powered at 360 patients. The patients were
and inflated, it is very important to insure that the button is, in randomized on the day of the surgery. One group was
fact, in the gastric lumen. Often, it is helpful to take an angled randomized to receive minimal esophageal mobilization
telescope (70) to look around the portion of the stomach that with placement of four esophagocrural sutures. The
is adherent to the anterior abdominal wall so that one can feel
secure that the button is not outside the stomach. In this patient, other group was randomized to extensive esophageal
the button was deflated and removed, and then reinserted mobilization to create a 2cm length of intra-abdominal
correctly. esophagus along with the four esophagocrural sutures.
TABLE 28-4 Operative Results after Open Operations for Management of GERD
Study Number of Patients % Reoperation Herniation Wrap Dehiscence Other
143
Dedinsky etal. (Indiana) 429 6.7% (29) 29 0 0
19751985
Caniano etal. (Ohio State)144 358 6% (21) 16 2 3
19761988
Wheatley etal. (Michigan)145 242 12% (29) 3 14 3
19741989
Fonkalsrud etal. (UCLA)146 7467 7.1% Not mentioned Not mentioned Not mentioned
19761996
398 SECTION IV Abdomen
A B
FIGURE 28-8 In 510% of patients undergoing laparoscopic fundoplication, reoperation becomes necessary. (A) In our experience,
almost all reoperations are due to transmigration of the fundoplication wrap, which is seen on this upper gastrointestinal study.
(B) The intraoperative photograph shows a large esophageal hiatus (arrows) with transmigration of the fundoplication wrap and
upper stomach into the lower mediastinum. Note the significant lack of adhesions after the initial laparoscopic fundoplication. (From
Ostlie DJ, Holcomb GW III. Reiterative surgery for gastroesophageal reflux. Semin Pediatr Surg 2007;16:2528.)
large paraesophageal hernia defect to help prevent recur- 21. Liebermann-Meffert D, Allgower M, Schmid P, et al. Muscular
rence. This trial also closed early because of the marked equivalent of the lower esophageal sphincter. Gastroenterology
1979;76:318.
disparity in results favoring the use of Surgisis to 22. DeMeester TR, Wernly JA, Bryant GH, et al. Clinical and in vitro
help close the large diaphragmatic defect. The primary analysis of determinants of gastroesophageal competence. Am J
outcome variable was recurrence of the paraesophageal Surg 1979;137:3946.
hernia. The study closed at 108 total patients because, at 23. Branton SA, Hinder RA, Floch NR, et al. Surgical treatment of
gastroesophageal reflux disease. In: Castell DO, Richter JE,
the time of interim review, 12 patients (24%) had devel- editors. The Esophagus. 3rd ed. Philadelphia: Lippincott Wil-
oped a recurrence in the arm in which Surgisis was not liams & Wilkins; 1999. p. 51125.
used, and only four patients (9%) had a recurrent 24. Werlin SL, Dodds WJ, Hogan WJ, et al. Mechanisms of GER in
paraesophageal hernia in the Surgisis arm. children. J Pediatr 1980;97:2449.
Laparoscopic fundoplication has evolved into the pre- 25. Cucchiara S, Bartolotti M, Minella R, et al. Fasting and postpran-
dial mechanisms of GER in children with GERD. Dig Dis Sci
ferred technique for surgical management of GERD. 1993;38:8692.
Although the Nissen operation is generally performed, 26. Winans CS, Harris LD. Quantitation of lower esophageal sphinc-
similar results have been noted with the Thal ter competence. Gastroenterology 1967;52:7738.
operation.150153 It is only through critical evaluation of 27. StPeter SD, Barnhart DC, Ostlie DJ, et al. Minimal vs extensive
esophageal mobilization during laparoscopic fundoplication: A
ones experience that advances are made in improving the prospective randomized trial. J Pediatr Surg 2011;46:1638.
results. There is no doubt that patients have less discom- 28. Thor KB, Hill LD, Mercer DD, et al. Reappraisal of the flap valve
fort and earlier discharge from the hospital after the mechanism in the gastroesophageal junction. Acta Chir Scand
laparoscopic operation.136 Moreover, there is a faster 1987;153:258.
return to regular activities as well. However, the opera- 29. Altschuler SM, Boyle JT, Nixon TE, et al. Simultaneous reflex
inhibition of lower esophageal sphincter and crural diaphragm in
tive technique continues to need ongoing evaluation with cats. Am J Physiol 1985;249:58691.
proper data collection and critical analysis to improve 30. Roussos C, Macklem PT. The respiratory muscles. N Engl J Med
these results. 1982;307:78697.
31. Barak N, Ehrenpreis ED, Harrison JR, et al. Gastro-oesophageal
reflux disease in obesity: Pathophysiological and therapeutic con-
REFERENCES siderations. Obes Rev 2002;3:915.
1. Carr IJ. The natural history of the partial thoracic stomach in 32. Min F, Tarlo SM, Bargman J, et al. Prevalence and causes of cough
children. Arch Dis Child 1959;34:34453. in chronic dialysis patients. Adv Perit Dial 2000;16:12933.
2. Fonkalsrud EW, Foglia RP, Ament ME, et al. Operative treatment 33. Navarro-Rodriguez T, Hashimoto CL, Carrilho FJ, et al. Reduc-
for the gastroesophageal syndrome in children. J Pediatr Surg tion of abdominal pressure in patients with ascites reduces gastro-
1989;24:5259. esophageal reflux. Dis Esophagus 2003;16:7782.
3. Billard P. Maladie des Enfants Nouveau-Ns. Pars; 1828. 34. Koivusalo A, Rintala R, Lindahl H. Gastroesophageal reflux in
4. Allison PR, Johnston AS, Royce GB. Short esophagus with simple children with a congenital abdominal wall defect. J Pediatr Surg
peptic ulceration. J Thorac Cardiovasc Surg 1943;12:432. 1999;34:11279.
5. Tileston W. Peptic ulcer of the esophagus. Am J Med Sci 35. Jaillard SM, Pierrat V, Dubois A, et al. Outcome at 2 years of
1906;132:240. infants with congenital diaphragmatic hernia: A population-based
6. Winkelstein A. Peptic esophagitis: A new clinical entity. JAMA study. Ann Thorac Surg 2003;75:2506.
1935;104:906. 36. Kamiyama M, Kawahara H, Okuyama H, et al. Gastroesophageal
7. Thal AP. A unified approach to surgical problems of the esoph- reflux after repair of congenital diaphragmatic hernia. J Pediatr
agogastric junction. Ann Surg 1968;168:5429. Surg 2002;37:16814.
8. Lortat-Jacob JL. Le traitment chirurgical des maladies du reflux 37. Fasching G, Huber A, Uray E, et al. Gastroesophageal reflux and
gastroesophagienne. Presse Med 1957;65:457. diaphragmatic motility after repair of congenital diaphragmatic
9. Hill LD. An effective operation for hiatal hernia: An eight-year hernia. Eur J Pediatr Surg 2000;10:3604.
appraisal. Ann Surg 1967;166:681. 38. Bergmeijer JH, Tibboel D, Hazebroek FW. Nissen fundoplica-
10. Hill LD. Surgery and gastroesophageal reflux. Gastroenterology tion in the management of gastroesophageal reflux occurring after
1972;63:183. repair of esophageal atresia. J Pediatr Surg 2000;35:5736.
11. Belsey R. Surgery of the diaphragm. In: Brown JM, editor. Surgery 39. Kubiak R, Spitz L, Kiely EM, et al. Effectiveness of fundoplication
of Children. Baltimore: Williams & Wilkins; 1963:762. in early infancy. J Pediatr Surg 1999;34:2959.
12. Belsey R. Gastroesophageal Reflux and Hiatal Hernia. Boston: 40. Schalamon J, Lindahl H, Saarikoski H, et al. Endoscopic follow-up
Little, Brown; 1972. in esophageal atresiafor how long is it necessary? J Pediatr Surg
13. Nissen R, Rossetti M. Die Behandlung von Hiatushernie und 2003;38:7024.
Reflux-oesophagitis mit Gastropexie und Fundoplication. 41. Cadiot G, Bruhat A, Rigaud D, et al. Multivariate analysis of
Stuttgart:Georg Thieme Verlag; 1959. pathophysiological factors in reflux oesophagitis. Gut 1997;
14. Nissen R. Gastropexy and fundoplication in surgical treatment of 40:16774.
hiatal hernia. Am J Dig Dis 1961;6:95461. 42. Ho SC, Chang CS, Wu CY, et al. Ineffective esophageal motility
15. Boix-Ochoa J. The physiologic approach to the management of is a primary motility disorder in gastroesophageal reflux disease.
gastric esophageal reflux. J Pediatr Surg 1986;21:10329. Dig Dis Sci 2002;47:6526.
16. Dallemagne B, Weerts JM, Jehaes C, et al. Laparoscopic Nissen 43. Holloway RH. Esophageal body motor response to reflux events:
fundoplication: Preliminary report. Surg Laparosc En dosc Secondary peristalsis. Am J Med 2000;108(Suppl):20565.
1991;1:13843. 44. Jeffery HE, Ius D, Page M. The role of swallowing during active
17. Georgeson KE. Laparoscopic gastrostomy and fundoplication. sleep in the clearance of reflux in term and preterm infants.
Pediatr Ann 1993;92:6757. J Pediatr 2000;137:54558.
18. Lobe TE, Schropp KP, Lunsford K. Laparoscopic Nissen fundop- 45. Allen ML, Zamani S, Dimarino AJ Jr. The effect of gravity on
lication in childhood. J Pediatr Surg 1993;28:35861. esophageal peristalsis in humans. Neurogastroenterol Motil
19. Fike FB, Mortellaro VE, Pettiford JN, et al. Diagnosis of gastro- 1997;9:716.
esophageal reflux disease in infants. Pediatr Surg Int 2011; 46. Orenstein SR. Effects on behavior state of prone versus seated
27:7917. positioning for infants with gastroesophageal reflux disease. Pedi-
20. Yen CJ, Izzo JG, Lee DF, et al. Bile acid exposure up-regulates atrics 1990;85:7657.
tuberous sclerosis complex 1/mammalian target of rapamycin 47. Vandenplas Y, Hassall E. Mechanisms of gastroesophageal reflux
pathway in Barretts-associated esophageal adenocarcinoma. and gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr
Cancer Res 2008;68:263240. 2002;35:11936.
400 SECTION IV Abdomen
48. Vandenplas Y, Sacre-Smits L. Seventeen-hour continuous esopha- 75. Jolley SG, Herbst JJ, Johnson DG, et al. Esophageal pH monitor-
geal pH monitoring in the newborn: Evaluation of the influence ing during sleep identifies children with respiratory symptoms
of position in asymptomatic and symptomatic babies. J Pediatr from gastroesophageal reflux. Gastroenterology 1981;80:15016.
Gastroenterol Nutr 1985;4:35661. 76. Hrabovsky EE, Mullett MD. Gastroesophageal reflux and the
49. Richter JE. Importance of bile reflux in Barretts esophagus. Dig premature infant. J Pediatr Surg 1986;21:5837.
Dis Sci 2001;18:20816. 77. Orenstein SA. An overview of reflux-associated disorders in
50. Collen MJ, Ciarleglio CA, Stanczak VJ, et al. Basal gastric acid infants: Apnea, laryngospasm, and aspiration. Am J Med 2001;
secretion in children with atypical epigastric pain. Am J Gastro- 111:60S63S.
enterol 1988;83:9236. 78. Suwandhi E, Ton MN, Schwarz TS. Gastroesophageal reflux in
51. Kalach N, Badran AM, Jaffray P, et al. Correlation between gastric infancy and childhood. Pediatr Ann 2008;35:25966.
acid secretion and severity of acid reflux in children. Turk J Pediatr 79. Ramenofsky ML, Powell RW, Curreri PW. Gastroesophageal
2003;45:610. reflux: pH probe-directed therapy. Ann Surg 1986;203:5315.
52. Boyle JT. Acid secretion from birth to adulthood. J Pediatr Gas- 80. Valusek PA, St. Peter SD, Keckler SJ, et al. Does an upper gas-
troenterol Nutr 2003;37:S1216. trointestinal study change operative management for gastro-
53. Gibbons TE, Gold BD. The use of proton pump inhibitors in esophageal reflux? J Pediatr Surg 2010;45:116972.
children: A comprehensive review. Paediatr Drugs 2003;5: 81. Spencer J. Prolonged pH recording in the study of gastroesopha-
2540. geal reflux. Br J Surg 1969;56:91214.
54. Gold BD, Freston JW. Gastroesophageal reflux in children: 82. Johnson LF, DeMeester TR. Twenty-four hour pH monitoring
Pathogenesis, prevalence, diagnosis, and role of proton pump of the distal esophagus. A quantitative measure of gastroesopha-
inhibitors in treatment. Paediatr Drugs 2002;4:67385. geal reflux. Am J Gastroenterol 1974;62:32532.
55. Penagini R. Bile reflux and oesophagitis. Eur J Gastroenterol 83. DeMeester TR, Johnson LF, Joseph GJ, et al. Patterns of gastro-
Hepatol 2001;13:13. esophageal reflux in health and disease. Ann Surg 1976;
56. Todd JAQ, de Caestecker J, Jankowski J. Gastro-esophageal reflux 184:45969.
disease and bile acids. J Pediatr Gastroenterol Nutr 2003;36: 84. Boix-Ochoa J, Lafuente JM, Gil-Vernet JM. Twenty-four hour
1724. esophageal pH monitoring in gastroesophageal reflux. J Pediatr
57. Richter JE. Duodenogastric reflux-induced (alkaline) esophagitis. Surg 1980;15:748.
Curr Treat Options Gastroenterol 2004;7:5358. 85. Koch A, Gass R. Continuous 2024 hour esophageal pH monitor-
58. Vaezi MF, Singh S, Richter JE. Role of acid and duodenogastric ing in infancy. J Pediatr Surg 1981;16:10913.
reflux in esophageal mucosal injury: A review of animal and 86. Stein HJ, DeMeester TR. Indications, technique, and clinical use
human studies. Gastroenterology 1995;108:1897907. of ambulatory 24-hour esophageal motility monitoring in a surgi-
59. Tovar JA, Olivares P, Diaz M, et al. Functional results of laparo- cal practice. Ann Surg 1993;217:12837.
scopic fundoplication in children. J Pediatr Gastroenterol Nutr 87. Jolley SG, Herbst JJ, Johnson DG, et al. Patterns of postcibal
1998;26:42931. gastroesophageal reflux in symptomatic infants. Am J Surg
60. Fonkalsrud EW, Ashcraft KW, Coran AG, et al. Surgical treat- 1979;138:94650.
ment of gastroesophageal reflux in children: A combined hospital 88. Jamieson JR, Stein HJ, DeMeester TR, et al. Ambulatory 24-hour
study of 7,467 patients. Pediatrics 1998;101:41922. esophageal pH monitoring: Normal values, optimal thresholds,
61. Neuhauser EBD, Berenberg W. Cardio-esophageal relaxation as specificity, sensitivity, and reproducibility. Am J Gastroenterol
cause of vomiting in infants. Radiology 1947;48:4803. 1992;87:110211.
62. Luostarinen M. Nissen fundoplication for reflux esophagitis: 89. Colletti RB, Christie DL, Orenstein SR. Indications for pediatric
Long-term clinical and endoscopic results in 109 of 127 consecu- esophageal pH monitoring. J Pediatr Gastroenterol Nutr 1995;
tive patients. Ann Surg 1993;217:32937. 21:25362.
63. Richardson JD, Kuhns JG, Richardson RL, et al. Properly con- 90. Harada T, Hyman PE, Everett S, et al. Meal-stimulated gastric
ducted fundoplication reverses histologic evidence of esophagitis. acid secretion in infants. J Pediatr 1984;104:5348.
Ann Surg 1983;197:76370. 91. Kelly EJ, Newell SJ, Brownlee KG, et al. Gastric acid secretion
64. ONeill JA Jr, Betts J, Ziegler MM, et al. Surgical management of in preterm infants. Early Hum Dev 1993;35:21520.
reflux strictures of the esophagus in childhood. Ann Surg 92. Sondheimer JM, Clark DA, Gervaise EP. Continuous gastric pH
1982;196:45360. measurement in young and older healthy preterm infants receiv-
65. Hyman PE. Gastroesophageal reflux: One reason why baby wont ing formula and clear liquid feedings. J Pediatr Gastroenterol
eat. J Pediatr 1994;125(Suppl):S1039. Nutr 1985;4:3525.
66. Kountourakis P, Ajani JA, Davila M, et al. Barretts esophagus: A 93. Mitchell DJ, McClure BG, Tubman TRJ. Simultaneous monitor-
review of biology and therapeutic approaches. Gastrointest ing of gastric and oesophageal pH reveals limitations of conven-
Cancer Res 2012;5:4957. tional oesophageal pH monitoring in milk fed infants. Arch Dis
67. Wiseman EF, Ang YS. Risk factors for neoplastic progression Child 2001;84:2736.
in Barretts esophagus. World J Gastroenterol 2011;17: 94. Shay SS, Johnson LF, Richter JE. Acid rereflux. Dig Dis Sci
367283. 2003;48:19.
68. Quante M, Bhagat G, Abrams JA, et al. Bile acid and inflammation 95. Wenzl TC, Moroder C, Trachterna M, et al. Esophageal pH
activate gastric cardia stem cells in a mouse model of Barrett-like monitoring and impedance measurement: A comparison of two
metaplasia. Cancer Cell 2012;21:3651. diagnostic tests for gastroesophageal reflux. J Pediatr Gastroen-
69. Hassall E, Weinstein WM, Ament ME. Barretts esophagus in terol Nutr 2002;34:51923.
childhood. Gastroenterology 1985;89:13317. 96. Vela MF, Camacho-Lobato L, Srinivasan R, et al. Simultaneous
70. Othersen HB Jr, Ocampo RJ, Parker EF, et al. Barretts esophagus intraesophageal impedance and pH measurement of acid and non-
in children. Ann Surg 1993;217:67681. acid gastroesophageal reflux: Effect of omeprazole. Gastroenter-
71. Lundell L, Myers JC, Jamieson GG. The effect of antireflux ology 2001;120:1599606.
operations on lower oesophageal sphincter tone and postprandial 97. Sifrim D, Holloway RH, Silny J, et al. Acid, non-acid and gas
symptoms. Scand J Gastroenterol 1993;28:72531. reflux in patients with gastroesophageal reflux disease during
72. Halper LM, Jolley SG, Tunnell WP, et al. The mean duration of 24-hr ambulatory pH-impedance recordings. Gastroenterology
gastroesophageal reflux during sleep as an indicator of respiratory 2001;120:158898.
symptoms from gastroesophageal reflux in children. J Pediatr Surg 98. Kahrilas P. Will impedance testing rewrite the book on GERD?
1991;26:68690. Gastroenterology 2001;120:186264.
73. Foglia RP, Fonkalsrud EW, Ament ME, et al. Gastroesophageal 99. Vela MF. Multichannel intraluminal impedance and pH monitor-
fundoplication for the management of chronic pulmonary disease ing in gastroesophageal reflux disease. Expert Rev Gastroenterol
in children. Am J Surg 1980;140:729. Hepatol 2008;2:66572.
74. del Rosario JF, Orenstein SR. Evaluation and management of 100. Lopez-Alonso M, Moya MJ, Cabo JA, et al. Twenty-four-hour
gastroesophageal reflux and pulmonary disease. Curr Opin Pediatr esophageal impedance-pH monitoring in healthy preterm
1996;8:20915. neonates: Rate and characteristics of acid, weakly acidic, and
28 Gastroesophageal Reflux 401
weakly alkaline gastroesophageal reflux. Pediatrics 2006;118: undergoing laparoscopic Nissen fundoplication. J Pediatr Surg
e299308. 2002;37:16646.
101. Wise JL, Murray JA. Utilising multichannel intraluminal imped- 125. Ostlie DJ, Miller KA, Woods RK, et al. Single cannula technique
ance for diagnosing GERD: A review. Dis Esophagus 2007; and robotic telescopic assistance in infants and children who
20:838. require laparoscopic Nissen fundoplication. J Pediatr Surg
102. Bremner RM, Hoeft SF, Costantini MD, et al. Pharyngeal swal- 2003;38:11115.
lowing. Ann Surg 1993;218:36470. 126. Ostlie DJ, Holcomb GW III. Laparoscopic fundoplication in
103. Shepard R, Fenn S, Seiber WK. Evaluation of esophageal function infants and children. In: Langer JC, Albanese CT, editors. Pedi-
in postoperative esophageal atresia and tracheoesophageal fistula. atric Minimal Access Surgery: A Principle and Evidence Based
Surgery 1966;59:60817. Approach. New York: Marcel Dekker; 2005. p. 16790.
104. Biller JA, Winter HS, Grand RJ, et al. Are endoscopic changes 127. St. Peter SD, Valusek PA, Calkins CM, et al. Use of esophagocru-
predictive of histologic esophagitis in children? J Pediatr ral sutures and minimal esophageal dissection reduces the inci-
1983;103:21518. dence of postoperative transmigration of laparoscopic Nissen
105. Meyers WF, Roberts CC, Johnson DG, et al. Value of tests for fundoplication wrap. J Pediatr Surg 2007;42:2530.
evaluation of gastroesophageal reflux in children. J Pediatr Surg 128. Holcomb GW III. Gastroesophageal reflux in infants and chil-
1985;20:51520. dren. In: Fischer JE, editor. Mastery of Surgery. 6th ed. Philadel-
106. Brown RA, Wynchank S, Rode H, et al. Is a gastric drainage phia: Lippincott Williams & Wilkins; 2012. p. 76980.
procedure necessary at the time of antireflux surgery? J Pediatr 129. Holcomb GW III. Laparoscopic Nissen fundoplication. In:
Gastroenterol Nutr 1997;25:37780. Holcomb GW III, Rothenberg SS, Georgeson KW III, editors.
107. Maddern GJ, Jamieson GG. Fundoplication enhances gastric Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia:
emptying. Ann Surg 1985;201:2969. Elsevier; 2008. p. 1520.
108. Maxson RT, Harp S, Jackson RL, et al. Delayed gastric emptying 130. Aprahamian CJ, Morgan TL, Harmon CM, et al. U-stitch
in neurologically impaired children with gastroesophageal reflux: laparoscopic gastrostomy technique has a low rate of complica-
The role of pyloroplasty. J Pediatr Surg 1994;29:7269. tions and allows primary button placement: Experience with 461
109. Katz PO. Treatment of gastroesophageal reflux disease: Use of pediatric procedures. J Laparoendosc Adv Surg Tech A 2006;16:
algorithms to aid in management. Am J Gastroenterol 1999; 6439.
94:310. 131. Georgeson K, Owings E. Surgical and laparoscopic techniques for
110. Orenstein SR, Whitington PF, Orestein DM. The infant seat as feeding tube placement. Gastrointest Endosc Clin North Am
a treatment for gastroesophageal reflux. N Engl J Med 1983;309: 1998;8:58192.
7603. 132. Ostlie DJ, Holcomb GW III, et al. Clinical principles of abdomi-
111. Carr IJ. Postural treatment of children with a partial thoracic nal surgery. In: Oldham KT, Colombani PM, Foglia RP, editors.
stomach (hiatus hernia). Arch Dis Child 1960;35:56980. Surgery of Infants and Children. 2nd ed. Philadelphia: Lippincott
112. Ponsonby AL, Dwyer T, Gibbons LE, et al. Factors potentiating Williams & Wilkins; 2005. p. 106786.
the risk of sudden infant death syndrome associated with the 133. Ostlie DJ, Holcomb GW III. Laparoscopic fundoplication with
prone position. N Engl J Med 1993;329:37782. gastrostomy. Semin Pediatr Surg 2002;11:196204.
113. Augood C, MacLennan S, Gilbert R, et al. Cisapride treatment 134. Holcomb GW III. Laparoscopic fundoplication in an infant. Surg
for gastro-oesophageal reflux in children. Cochrane Database Syst Endosc 2003;17:1319.
Rev 2003;(4):CD002300. 135. St. Peter SD, Holcomb GW III. Gastroesophageal reflux disease
114. Dalby-Payne JR, Morris AM, Craig JC. Meta-analysis of rand- and fundoplication in infants and children. Ann Pediatr Surg
omized controlled trials on the benefits and risks of using cisapride 2007;3:110.
for the treatment of gastroesophageal reflux in children. J Gastro- 136. Ostlie DJ, St. Peter SD, Snyder CL, et al. A financial analysis of
enterol Hepatol 2003;18:196202. pediatric laparoscopic versus open fundoplication. J Laparoendosc
115. Enger C, Cali C, Walker AM. Serious ventricular arrhythmias Adv Surg Tech 2007;17:4936.
among users of cisapride and other QT-prolonging agents in the 137. Barsness KA, St. Peter SD, Holcomb GW 3rd, et al. Laparoscopic
United States. Pharmacoepidemiol Drug Saf 2002;11:47786. fundoplication after previous open abdominal operations in
116. Machida HM, Forbes DA, Gall DG, et al. Metoclopramide in infants and children. J Laparoendosc Adv Surg Tech A 2009;1:
gastroesophageal reflux of infancy. J Pediatr 1988;112:4837. S479.
117. Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evalua- 138. Davis CS, Baldea A, Johns JR, et al. The evolution and long-term
tion and treatment of gastroesophageal reflux in infants and chil- results of laparoscopic antireflux surgery for the treatment of
dren. Recommendations of the North American Society for gastroesophageal reflux disease. JSLS 2010;14:33241.
Pediatric Gastroenterology and Nutrition. J Pediatr Gastroen- 139. Rhee D, Zhang Y, Chang DC, et al. Population-based comparison
terol Nutr 2001;32:S131. of open vs laparoscopic esophagogastric fundoplication in chil-
118. Dimand RJ. Use of H2-receptor antagonists in children. Ann dren: Application of the Agency for Healthcare Research and
Pharmacother 1990;24(Suppl):426. Quality pediatric quality indicators. J Pediatr Surg 2011;46:
119. Wolfe MM, Sachs G. Acid suppression: Optimizing therapy for 64854.
gastroduodenal ulcer healing, gastroesophageal reflux disease, and 140. Mauritz FA, van Herwaarden-Lindeboom MY, Stomp W, et al.
stress-related erosive syndrome. Gastroenterology 2000;118: The effects and efficacy of antireflux surgery in children with
S931. gastroesophageal reflux disease: A systematic review. J Gastroin-
120. Zimmermann AE, Walters JK, Katoma BG, et al. A review of test Surg 2011;15:18728.
omeprazole use in the treatment of acid-related disorders in chil- 141. Esposito C, De Luca C, Alicchio F, et al. Long-term outcome of
dren. Clin Ther 2001;2385:66079. laparoscopic Nissen Procedure in pediatric patients with gastro-
121. Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment esophageal reflux disease measured using the modified QOSG
of chronic erosive esophagitis in children: A multicenter study Roma III European Society for Pediatric Gastroenterology and
of efficacy, safety, tolerability and dose requirements. Interna- Hepatology and Nutritions Questionnaire. J Laparoendosc Adv
tional Pediatric Omeprazole Study Group. J Pediatr 2000;137: Surg Tech 2012;22:93740.
8007. 142. Kubiak R, Andrews J, Grant HW. Long-term outcome of laparo-
122. Andersson T, Hassall E, Lundborg P, et al. Pharmacokinetics of scopic Nissen fundoplication compared with laparoscopic Thal
orally administered omeprazole in children. International Pediat- fundoplication in children: A prospective, randomized study. Ann
ric Omeprazole Pharmacokinetic Group. Am J Gastroenterol Surg 2011;253:449.
2000;95:31016. 143. Dedinsky GK, Vane DW, Black T, et al. Complications and reop-
123. Valusek PA, St. Peter SD, Tsao K, et al. The use of fundoplication eration after Nissen fundoplication in childhood. Am J Surg
for prevention of apparent life-threatening events. J Pediatr Surg 1987;153:17783.
2007;42:10225. 144. Caniano DA, Ginn-Pease ME, King DR. The failed antireflux
124. Ostlie DJ, Miller KA, Holcomb GW III. Effective Nissen fun- procedure: Analysis of risk factors and morbidity. J Pediatr Surg
doplication length and bougie diameter size in young children 1990;25:10225.
402 SECTION IV Abdomen
145. Wheatley MJ, Coran AG, Wesley JR, et al. Redo fundoplication 150. Esposito C, Montupet P, van der Zee D, et al. Long-term outcome
in infants and children with recurrent gastroesophageal reflux. of laparoscopic Nissen, Toupet, and Thal antireflux procedures
J Pediatr Surg 1991;26:75861. for neurologically normal children with gastroesophageal reflux
146. Fonkalsrud WE, Ashcraft KW, Coran AG, et al. Surgical treat- disease. Surg Endosc 2006;20:8558.
ment of gastroesophageal reflux in children: A combined hospital 151. van der Zee DC, Bax KN, Ure BM, et al. Long-term results after
study of 7467 patients. Pediatrics 1998;101:41922. laparoscopic Thal procedure in children. Semin Laparosc Surg
147. Ostlie DJ, Holcomb GW III. Reiterative laparoscopic surgery 2002;9:16871.
for recurrent gastroesophageal reflux. Semin Pediatr Surg 2007; 152. Esposito C, Becmeur F, Centonze A, et al. Laparoscopic reopera-
16:2528. tion following unsuccessful antireflux surgery in childhood. Semin
148. St. Peter SD, Ostlie DJ, Holcomb GW III. The use of biosyn- Laparosc Surg 2002;9:1779.
thetic mesh to enhance hiatal repair at the time of redo Nissen 153. Esposito C, van der Zee DC, Settimi A, et al. Risks and benefits
fundoplication. J Pediatr Surg 2007;42:1298301. of surgical management of gastroesophageal reflux in neurologi-
149. Oelschlager BK, Pellegrini CA, Hunter J, et al. Biologic prosthesis cally impaired children. Surg Endosc 2003;17:70810.
reduces recurrence after laparoscopic paraesophageal hernia
repair. Ann Surg 2006;244:48190.
C H A P T E R 2 9
The stomach forms from the foregut and is recognizable weeks old. Initially, the emesis is infrequent and may
by the fifth week of gestation. It then elongates, descends, appear to be gastroesophageal reflux disease. However,
and dilates to form its familiar structure by the seventh over a short period of time, the emesis occurs with every
week of gestation. The vascular supply to the stomach is feeding and becomes forceful (i.e., projectile). The
very robust, and ischemia of the stomach is rare. The contents of the emesis are usually the recent feedings,
stomach is supplied by the right and left gastric arteries but signs of gastritis are not uncommon (coffee-ground
along the lesser curvature, the right and left gastroepi emesis). On physical examination, the neonate usually
ploic arteries along the greater curvature, and the short appears well if the diagnosis is made early. However,
gastric vessels from the spleen. There is also contribution depending on the duration of symptoms and degree of
from the posterior gastric artery, which is a branch of the dehydration, the neonate may be gaunt and somnolent.
splenic artery, as well as the phrenic arteries. Visible peristaltic waves may be present in the mid to left
In this chapter, we discuss common and unusual con upper abdomen. The pylorus may be palpable in 7289%
ditions of the stomach that are treated surgically. Some of patients.11,12 To palpate the hypertrophied pylorus, the
topics relevant to the stomach, such as gastroesophageal baby must be relaxed. Techniques for relaxing the infant
reflux and obesity, are covered elsewhere. include bending the knees and flexing the hips, and using
a pacifier with sugar water. These techniques should be
attempted after the stomach has been decompressed with
HYPERTROPHIC PYLORIC STENOSIS a 10 French to 12 French orogastric tube. After palpating
the liver edge, the examiners fingertips should slide
Hypertrophic pyloric stenosis (HPS) is one of the most underneath the liver in the midline. Slowly, the fingers
common surgical conditions of the newborn.19 It occurs are pulled back and down, trying to trap the olive. Pal
at a rate of 1 to 4 per 1,000 live births in Caucasian pating the hypertrophied pylorus requires patience and
infants, but is seen less often in non-Caucasian children.14 an optimal examination setting. If palpated, no further
Males are affected more often with a 4:1 male-to-female studies are needed. If the pylorus cannot be palpated,
ratio. Risk factors for HPS include family history, gender, ultrasound (US) should be performed.
younger maternal age, being a first-born infant, and Ultrasound has become the standard technique for
maternal feeding patterns.4,9,10 Premature infants are diagnosing HPS and has supplanted the physical exami
diagnosed with HPS later than term or post-term infants.4 nation at most institutions. The diagnostic criteria for
pyloric stenosis is a muscle thickness greater than or
equal to 4mm and a pyloric channel length greater than
Etiology or equal to 16mm (Fig. 29-1).12 A thickness of more than
The cause of HPS is unknown, but genetic and environ 3mm is considered positive if the neonate is younger
mental factors appear to play a large role in the than 30 days of age.13 The study is dependent on the
pathophysiology. Circumstantial evidence for a genetic expertise of the ultrasound technician and radiologist.
predisposition includes race discrepancies, the increased There are reports of non-radiologists performing
frequency in males, and the birth order (first-born infants ultrasound for HPS, which would obviously reduce the
with a positive family history). Environmental factors need for the ultrasound technician.14,15 If the ultrasound
associated with HPS include the method of feeding findings are equivocal, then an upper gastrointestinal
(breast vs formula), seasonal variability, exposure to series can be helpful in confirming the diagnosis (Fig.
erythromycin, and transpyloric feeding in premature 29-2).
infants.57 Additionally, there has been interest in several In the past, the diagnosis was often delayed and pro
gastrointestinal peptides or growth factors that may facil found dehydration with metabolic derangements was
itate pyloric hypertrophy. Some of these include excessive common. Today, however, primary care physicians are
substance P, decreased neurotrophins, deficient nitric more aware of the problem and the availability of ultra
oxide synthase, and gastrin hypersecretion.8,9 Thus, the sound facilitates an earlier diagnosis and treatment.
etiology of HPS is likely multifactorial with environmen However, the complete differential diagnosis for nonbil
tal influences. ious vomiting should be considered. This includes medical
causes such as gastroesophageal reflux, gastroenteritis,
increased intracranial pressure, and metabolic disorders.
Diagnosis Anatomic causes include an antral web, foregut duplica
The classic presentation of HPS is nonbilious, projectile tion cyst, gastric tumors, or a tumor causing extrinsic
vomiting in a full-term neonate who is between 2 and 8 gastric compression.
403
404 SECTION IV Abdomen
A B
FIGURE 29-1 Ultrasonography has become the standard imaging study for diagnosing pyloric stenosis and has supplanted physical
examination at most institutions. The (A) transverse and (B) longitudinal views of hypertrophic pyloric stenosis are seen here. Muscle
thickness greater than or equal to 4mm on the transverse view or a length greater than or equal to 16mm on the longitudinal view
is diagnostic of pyloric stenosis. On this study, the pyloric wall thickness was 5mm and the length (arrows) was 20mm.
Postoperative Care
Postoperative care is similar for both operative approaches,
assuming the mucosal integrity of the stomach is intact.
Complicated feeding regimens have been advocated in
the past. However, more recent studies support the use
of ad libitum feedings in the early postoperative period.
This results in a faster time to full feeding and earlier
discharge.24,25 In many centers, if postoperative emesis is
A encountered, it is suggested to feed through it. At our
institution, we limit the feedings to a maximum of 3oz
every three hours. There are data to suggest that the
degree and duration of preoperative metabolic derange
ment affects the postoperative feeding schedule. Babies
who required more complicated resuscitation tend to
take longer to reach full feeding and discharge.26
A survey about postoperative feeding regimens in
pediatric surgery residency training centers in North
America was recently performed. Thirty-two of the 47
institutions responded to the survey. The average time
from operation to initiation of feedings was 4.3 hours.
There was a wide variability in responses, but 26 of the
32 responding programs employ a protocol-based feeding
regimen.27
A prospective randomized trial recently compared a
B
protocol-based feeding regimen to ad libitum feeding
FIGURE 29-4 Laparoscopic pyloromyotomy has become a
after laparoscopic pyloromyotomy.28 Feeding was begun
common approach for pyloric stenosis in infants. In the USA, two hours after laparoscopic pyloromyotomy in both
the sheathed arthrotomy knife is no longer available. Therefore, groups. The ad libitum group was allowed formula or
other techniques are now utilized. (A) The atraumatic grasper breast milk two hours after the operation and was con
that is holding the duodenum is seen on the patients right (solid sidered ready for discharge after tolerating three
arrow). In the patients left upper abdomen, a spatula tipped
cautery (dotted arrow) has been introduced to incise the serosa consecutive feeds without emesis. The babies who
of the stomach . The 5mm cannula has been placed in the underwent feeding via protocol were given Pedialyte two
umbilicus through which an angled telescope is introduced for hours after the operation followed by another round of
visualization. (B) The stab incisions have been closed with Pedialyte, which was followed by two rounds of half
steri-strips.
strength formula or breast milk, followed by two rounds
of full strength formula or breast milk, followed by the
home feeding regimen. The baby was discharged on the
home feeding regimen if doing well. With a power of 0.9
A B C D
FIGURE 29-5 These intraoperative photographs depict a laparoscopic pyloromyotomy. (A) The spatula tipped cautery is being used
to incise the serosa and outer muscular layer of the hypertrophied pylorus. (B) The tip of the cautery is introduced into the hyper-
trophied muscle and twisted to break up the muscle fibers and create a space for insertion of the pyloric spreader. (C) The pyloric
spreader is introduced into the muscle and gently opened to split the hypertrophied muscle fibers. The submucosa is visualized
through the myotomy. (D) Air is introduced into the stomach to assess the integrity of the mucosa.
29 Lesions of the Stomach 407
and an alpha of 0.05, a sample size of 150 patients was Wound infections also occur in 12% of cases.22,23
calculated. There were no differences in patient charac There are no data to support the use of prophylactic
teristics at presentation. The ad libitum group reached perioperative antibiotics because a pyloromyotomy is
goal feeding sooner than the group who were fed via considered a clean procedure. Local wound care is usually
protocol (Table 29-1). However, this did not translate sufficient to treat these infections.
into a difference in length of postoperative hospitaliza Incisional hernias and wound dehiscence occurs in
tion. There were more patients with emesis in the ad approximately 1% of cases.22 Most hernias require repair
libitum group after reaching goal feedings. There was no at some point. Laparoscopically, port site hernias usually
difference in readmission rates, as two patients in each involve omentum protruding through the incision. This
group were readmitted after discharge.28 can sometimes be managed at the bedside by cleansing
Postoperatively, pain is usually controlled with aceta the area with povidone-iodine, ligating and trimming the
minophen. Most infants are ready for discharge on the extracorporeal omentum, elevating the abdominal wall to
first postoperative day. get the omentum back into the peritoneal cavity, and
using fine absorbable suture to close the skin.
Postoperative emesis is common, occurring in most
Complications infants to some degree. Prolonged emesis is less common
The major complications of pyloromyotomy include and ranges in incidence from 226%. Most commonly,
mucosal perforation, wound infection, incisional hernia, this is due to gastroesophageal reflux but can occur sec
prolonged postoperative emesis, incomplete myotomy, ondary to an incomplete myotomy. It has been suggested
and duodenal injury. There are prospective randomized that the laparoscopic approach may be a risk factor for
trials that do not show any difference in complication inadequate myotomy, but this is likely related to the sur
rates between the laparoscopic and open techniques.22,23 geons experience with this technique.24
Mucosal perforation occurs in 12% of cases.22,23 If the
disruption occurs at the duodenopyloric junction, a
simple interrupted absorbable suture can be used to close
Outcomes
the defect and a patch of omentum can be positioned over In the past, the mortality from pyloric stenosis was con
the closure. This can be accomplished laparoscopically siderable and approached 50%. Today, however, mortal
depending on the surgeons experience. Otherwise, the ity is nearly zero with improvement in neonatal
laparoscopic procedure should be converted to open. If resuscitation and anesthesia as well as surgical techniques.
the perforation is large or in the middle of the myotomy, Morbidity is also significantly lower than in the past, with
then the myotomy should be closed with absorbable an overall complication rate between 12%. Additionally,
suture. A new myotomy can then be made 90180 from with more pyloromyotomies being performed laparo
the original incision. Feedings should be held for 24 scopically, the cosmetic advantage of the minimally inva
hours and then restarted. A water-soluble contrast study sive technique cannot be overemphasized.
can be performed if desired.
Duodenal injuries also can occur with either the lapar
oscopic or open approach. In a 25-year retrospective PYLORIC ATRESIA
review of 901 open pyloromyotomies performed between
1969 and 1994, there were 39 duodenal perforations that Pyloric atresia is a rare disease (1:100,000 live births) and
were recognized intraoperatively and repaired. There presents with symptoms of gastric outlet obstruction. The
were no unrecognized duodenal perforations that devel disease is difficult to characterize because it is so rare.
oped after the operation.29 However, several generalizations can be made from looking
TABLE 29-1 Preoperative and Postoperative Data from a Prospective Randomized Trial Comparing Ad
Libitum Feeding to Feeding Using a Standardized Protocol after Laparoscopic
Pyloromyotomy28
Ad lib fed (n = 75; Mean Protocol fed (n = 75; Mean
Variable Standard Deviation) Standard Deviation) P value
Age (days) 39.9 19.08 39.75 14.90 0.93
Pre-op pyloric thickness (mm) 4.44 0.84 4.43 0.89 0.93
Pre-op pyloric length (mm) 19.56 3.44 19.97 3.64 0.48
Operating time (minutes) 20.63 10.64 18.19 7.99 0.11
Postoperative emesis pre-goal feed (number) 1.04 2.16 0.57 0.99 0.09
Number of patients with pre-goal feed emesis 45 (60%) 51 (68%) 0.40
Post-goal feed emesis (number) 1.05 2.26 0.47 2.79 0.16
Number of patients with post-goal feed emesis 31 (41%) 11 (14.6%) 0.0000
Doses of analgesia (number) 1.47 1.38 1.56 1.40 0.68
Time to goal feeds (hours) 9.15 7.02 16.58 7.86 0.0000
Length of stay after goal (hours) 16.18 14.65 9.20 6.15 0.0002
Length of stay after operation (hours) 25.39 15.41 25.78 10.05 0.85
Readmission for emesis 2 (2.6%) 2 (2.6%) 1.0
408 SECTION IV Abdomen
at relatively large series. Other congenital anomalies are The operative management depends on the type of
found in up to 40% of patients with pyloric atresia.3032 The atresia. Excision of the web or membrane with Heinecke
most common associated condition is epidermolysis Mikulicz pyloroplasty is usually possible for a type I
bullosa.3336 There is a suggestion of autosomal recessive atresia. However, for types II or III, often a Billroth I
transmission in patients with familial disease.30 gastroduodenostomy is needed if the solid core or gap is
Three anatomic variants have been described. With long (see Fig 29-6). There is also a report of successful
type I, there is a mucosal membrane or web. In type II, treatment with gastroduodenal mucosal advancement for
the pyloric channel is a solid cord (Fig. 29-6). In type III, this condition.39 Gastrojejunostomy is not recommended
there is a gap between the stomach and the duodenum.31 as there is a reported 60% failure rate and mortality rate
These babies present with nonbilious emesis and have of 50%.40 Laparoscopic repair for a type II atresia was
similar electrolyte abnormalities to infants with HPS. A recently described.41
single bubble is usually found on an abdominal radio Generally, long-term outcomes are very good. Mor
graph (see Figure 29-6). If necessary, the diagnosis can bidity and mortality are usually related to the associated
be confirmed with a contrast study. The differential diag anomalies. Patients with pyloric atresia and epidermolysis
nosis includes malrotation with volvulus, proximal duo bullosa often die due to septicemia, electrolyte imbal
denal atresia, gastric volvulus, pyloric duplication, ance, protein loss, or failure to thrive due to the exuda
retrograde duodenal gastric intussusception, and aber tive skin lesions. However, there are reports of long-term
rant pancreatic tissue plugging the pylorus.37,38 survival in neonates with pyloric atresia and
A B
C D
FIGURE 29-6 This baby developed nonbilious emesis shortly after birth. (A) An abdominal film shows a single bubble. This is classic
for pyloric atresia. (B) The baby underwent laparoscopic repair and the position of the instruments is shown. (C) At operation, the
pylorus was a solid core (type II). On close inspection, note a gastric duplication in the superior aspect of the greater curve of the
stomach (arrow). This gastric duplication is better seen in (D) and was resected. The baby has recovered nicely and has not devel-
oped any problems two years later.
29 Lesions of the Stomach 409
GASTRIC PERFORATION
The causes of gastric perforation include spontaneous
perforation in the newborn, iatrogenic perforation from
instrumentation, peptic ulcer disease, and trauma. Gastric
perforation usually presents with abdominal distention
and signs of sepsis or shock. The diagnosis is suspected
when a large amount of extraluminal air is seen on an
abdominal radiograph.
Neonatal gastric perforations most commonly occur
in premature infants. About half of neonatal perforations
are spontaneous, and the other half are iatrogenic from
instrumentation.43 Prematurity is associated with an
increased mortality.44 The perforations are usually
managed with laparotomy or laparoscopy. The perfora
tion can usually be closed primarily with or without an
omental patch.
Gastric perforation due to peptic ulcer disease in
infants and children is very rare. Typically, perforation
occurs at the site of a prepyloric ulcer. Again, this may FIGURE 29-7 A 10-year-old presented with abdominal pain and
be repaired primarily via laparotomy or laparoscopy with vomiting. She was found to have a prepyloric ulcer (arrow) on
or without an omental patch.45 the upper gastrointestinal study. In addition, there was evidence
of gastric outlet obstruction. She underwent antrectomy and
Billroth I reconstruction.
Gastrophrenic ligament
Gastrohepatic Gastrosplenic
ligament ligament
Stomach
A B
Esophagus
Esophagus
Greater Greater
curvature Esophagus curvature
Pylorus
Posterior
stomach
surface
Lesser
curvature Pylorus
Posterior
C Pylorus D E stomach
surface
FIGURE 29-10 These drawings depict the development of a gastric volvulus. (A) Normal anatomy. (B) The axis of rotation for an
organoaxial volvulus is seen on the left and a mesoaxial volvulus is on the right. (C) Demonstration of an organoaxial volvulus.
(D) Demonstration of a mesoaxial volvulus. (E) Combined mesoaxial and organoaxial volvulus. (Adapted from Cribbs RK, Gow KW,
Wulkan ML. Gastric volvulus in infants and children. Pediatrics 2008;122:e75262.)
Pylorus
Gastroesophageal
Duodenum junction
A B
FIGURE 29-11 These two contrast studies depict a gastric volvulus. (A) This contrast study depicts an organoaxial volvulus in which
the stomach has rotated on its long axis. Note the relatively normal position of the pylorus (arrow). (B) This contrast study shows
a mesoaxial volvulus. In this study, the pylorus is in the left upper abdomen due to rotation around the short axis of the stomach.
In both studies, the gastroesophageal junction is in a relatively normal position.
412 SECTION IV Abdomen
10. White MC, Langer JC, Don S, et al. Sensitivity and cost minimiza
tion analysis of radiology versus olive palpation for the diagnosis
of hypertrophic pyloric stenosis. J Pediatr Surg 1998;33:91317.
11. Breaux CW Jr, Georgeson KE, Royal SA, et al. Changing patterns
in the diagnosis of hypertrophic pyloric stenosis. Pediatrics
1988;81:21317.
12. Keller H, Waldmann D, Greiner P. Comparison of preoperative
sonography with intraoperative findings in congenital hypertrophic
pyloric stenosis. J Pediatr Surg 1987;22:9502.
13. Lamki N, Athey PA, Round ME, et al. Hypertrophic pyloric steno
sis in the neonatediagnostic criteria revisited. Can Assoc Radiol
J 1993;44:214.
14. Malcom GE 3rd, Raio CC, Del Rios M, et al. Feasibility of emer
gency physician diagnosis of hypertrophic pyloric stenosis using
point-of-care ultrasound: A multi-center case series. J Emerg Med
2009;37:2836.
15. Boneti C, McVay MR, Kokoska ER, et al. Ultrasound as a diag
nostic tool used by surgeons in pyloric stenosis. J Pediatr Surg
2008;43:8791.
16. Meissner PE, Engelmann G, Troeger J, et al. Conservative treat
ment of infantile hypertrophic pyloric stenosis with intravenous
atropine sulfate does not replace pyloromyotomy. Pediatr Surg Int
2006;12:10214.
17. Kawahara H, Takama Y, Yoshida H, et al. Medical treatment of
infantile hypertrophic pyloric stenosis: Should we always slice the
olive? J Pediatr Surg 2005;40:184851.
18. Kawahara H, Imura K, Nishikawa M, et al. Intravenous atropine
treatment in infantile hypertrophic pyloric stenosis. Arch Dis Child
2002;87:714.
19. Ogawa Y, Higashimoto Y, Nishijima E, et al. Successful endoscopic
FIGURE 29-12 A young girl presented with gastric outlet
balloon dilatation for hypertrophic pyloric stenosis. J Pediatr Surg
obstruction and was found to have a trichobezoar. The preop-
1996;31:171214.
erative radiograph shows the outline of the bezoar in the
20. Yusuf TE, Brugge WR. Endoscopic therapy of benign pyloric ste
stomach. Inset, The bezoar after removal.
nosis and gastric outlet obstruction. Curr Opin Gastroenterol
2006;22:5703.
21. Alain JL, Grousseau D, Terrier G. Extramucosal pylorotomy by
laparoscopy. J Pediatr Surg 1991;26:11912.
usually fills the stomach and extends into the duodenum. 22. St. Peter SD, Holcomb GW, Calkins CM, et al. Open versus
However, it can extend to the ileum. Attempts at gastro laparoscopic pyloromyotomy for pyloric stenosis: A prospective,
scopic removal are usually futile, except in cases of small randomized trial. Ann Surg 2006;244:36370.
23. Leclair MD, Plattner V, Mirallie E, et al. Laparoscopic pyloromyo
bezoars. The bezoar has been typically removed through tomy for hypertrophic pyloric stenosis: A prospective, randomized
a gastrotomy at laparotomy. However, there are recent controlled trial. J Pediatr Surg 2007;42:6928.
reports of laparoscopic removal.65,66 At our institution, we 24. Adibe OO, Nichol PF, Lim FY, et al. Ad libitum feeds after laparo
recently removed a large gastric trichobezoar laparoscop scopic pyloromyotomy: A retrospective comparison with a stand
ically with the aid of an endoscopic bag (Fig. 29-12). ardized feeding regimen in 227 infants. J Laparoendosc Adv Surg
Tech A 2007;17:2357.
25. Georgeson KE, Corbin TJ, Griffen JW, et al. An analysis of feeding
REFERENCES regimens after pyloromyotomy for hypertrophic pyloric stenosis.
1. Pedersen RN, Garne E, Loane M, et al. Infantile hypertrophic J Pediatr Surg 1993;28:147880.
pyloric stenosis: A comparative study of incidence and other epi 26. St. Peter SD, Tsao K, Sharp SW, et al. Predictors of emesis and
demiological characteristics in seven European regions. J Matern time to goal intake after pyloromyotomy: Analysis from a prospec
Fetal Neonatal Med 2008;21:599604. tive trial. J Pediatr Surg 2008;43:203841.
2. Sommerfield T, Chalmers J, Youngson G, et al. The changing 27. Juang D, Adibe OO, Laituri CA, et al. Distribution of feeding styles
epidemiology of infantile hypertrophic pyloric stenosis in Scotland. after pyloromyotomy among pediatric surgical training programs
Arch Dis Child 2008;93:100711. in North America. Eur J Pediatr Surg 2012;22:40911.
3. Persson S, Ekbom A, Granath F, et al. Parallel incidences of sudden 28. Adibe OO, Iqbal CS, Sharp SW, et al. Protocol versus ad lib feeds
infant death syndrome and infantile hypertrophic pyloric stenosis: after laparoscopic pyloromyotomy: A prospective randomized trial.
A common cause? Pediatrics 2001;108:E70. 2012 (accepted for publication).
4. Schechter R, Torfs CP, Bateson TF. The epidemiology of infantile 29. Hulka F, Harrison MW, Campbell TJ, et al. Complications of
hypertrophic pyloric stenosis. Paediatr Perinat Epidemiol 1997; pyloromyotomy for infantile hypertrophic pyloric stenosis. Am J
11:40727. Surg 1997;173:4502.
5. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hyper 30. Ilce Z, Erdogan E, Kara C, et al. Pyloric atresia: 15-year review
trophic pyloric stenosis after pertussis prophylaxis with erythromy from a single institution. J Pediatr Surg 2003;38:15814.
cin: A case review and cohort study. Lancet 1999;354:21015. 31. Okoye BO, Parikh DH, Buick RG, et al. Pyloric atresia: Five new
6. Mitchell LE, Risch N. The genetics of infantile hypertrophic cases, a new association, and a review of the literature with guide
pyloric stenosis: A re-analysis. Am J Dis Child 1993;147:120311. lines. J Pediatr Surg 2000;35:12425.
7. Rasmussen L, Green A, Hansen LP. The epidemiology of infantile 32. Al-Salem AH. Congenital pyloric stenosis and associated anoma
hypertrophic pyloric stenosis in a Danish population, 1950-84. Int lies. Pediatr Surg Int 2007;23:55963.
J Epidemiol 1989;18:41317. 33. Almaani N, Liu L, Dopping-Hepenstal PJ, et al. Autosomal domi
8. Spitz L, Zail SS. Serum gastrin levels in congenital hypertrophic nant junctional epidermolysis bullosa. Br J Dermatol
pyloric stenosis. J Pediatr Surg 1976;11:335. 2009;160:10947.
9. Vanderwinden JM, Mailleux P, Schiffmann SN, et al. Nitric oxide 34. Birnhaum RY, Landau D, Elbedour K, et al. Deletion of the first
synthase activity in infantile hypertrophic pyloric stenosis. N Engl pair of fibronectin type III repeats of the integrin beta-4 gene is
J Med 1992;327:51115. associated with epidermolysis bullosa, pyloric atresia and aplasia
29 Lesions of the Stomach 413
cutis congenita in the original Carmi syndrome patients. Am J Med 49. Cooper S, Abrams RS, Carbaugh RA. Pyloric duplications: Review
Genet A 2008;146:10636. and case study. Am Surg 1995;61:10924.
35. Nakamura H, Sawamura D, Goto M, et al. Epidermolysis bullosa 50. Muraoka A, Tsuruno M, Katsuno G, et al. A gastric duplication
simplex associated with pyloric atresia is a novel clinical subtype cyst with an aberrant pancreatic ductal system: Report of a case.
caused by mutations in the plectin gene (PLEC1). J Mol Diagn Surg Today 2002;32:5315.
2005;7:2835. 51. Jones VS, Cohen RC. An eighteen-year follow-up after surgery for
36. Samad L, Siddiqui EF, Arain MA, et al. Pyloric atresia associated congenital microgastriacase report and review of literature.
with epidermolysis bullosa: Three cases presenting in three months. J Pediatr Surg 2007;42:195760.
J Pediatr Surg 2004;39:12679. 52. Kroes EJ, Festen C. Congenital microgastria: A case report and
37. Moore CC. Congenital gastric outlet obstruction. J Pediatr Surg review of literature. Pediatr Surg Int 1998;13:41618.
1989;24:12416. 53. Velasco AL, Holcomb GW, Templeton JM, et al. Management of
38. Bronsther B, Nadeau MR, Abrams MW. Congenital pyloric atresia: congenital microgastria. J Pediatr Surg 1990;25:1927.
A report of three cases and a review of the literature. Surgery 54. Neifeld JP, Berman WF, Lawrence W, et al. Management of con
1971;69:1306. genital microgastria with a jejunal reservoir pouch. J Pediatr Surg
39. Dessanti A, Iannuccelli M, Dore A, et al. Pyloric atresia: An attempt 1980;15:8825.
at anatomic pyloric sphincter reconstruction. J Pediatr Surg 55. Banks PA, Waye JD. The gastroscopic appearance of antral web.
2000;35:13724. Gastrointest Endosc 1969;15:2289.
40. Kourolinka CW, Steward JR. Pyloric atresia. Am J Dis Child 56. Hait G, Esselstyn CB Jr, Rankin GB. Prepyloric mucosal dia
1978;132:9035. phragm (antral web): Report of a case and review of the literature.
41. Juang D, Holcomb GW III. Laparoscopic repair of pyloric atresia. Arch Surg 1972;105:48690.
Video presentation, 2012 American College of Surgeons meeting. 57. Campbell DP, Vanhoutte JJ, Smith EI. Partially obstructing antral
42. Hayashi AH, Galliani CA, Gilis DA. Congenital pyloric atresia and weba distinct clinical entity. J Pediatr Surg 1973;8:7238.
junctional epidermolysis bullosa: A report of long-term survival and 58. Patnaik DN, Sun S, Groff DB. Newborn gastric outlet obstruction
a review of the literature. J Pediatr Surg 1991;26:13415. caused by an antral web. J Med Soc N J 1976;73:7367.
43. Abadir J, Emil S, Nguyen N. Abdominal foregut perforations in 59. Bell MJ, Ternberg JL, McAlister W, et al. Antral diaphragma
children: A 10-year experience. J Pediatr Surg 2005;40:19037. cause of gastric outlet obstruction in infants and children. J Pediatr
44. Lin CM, Lee HC, Kao HA, et al. Neonatal gastric perforation: 1977;90:196202.
Report of 15 cases and review of the literature. Pediatr Neonatol 60. Huggins MJ, Friedman AC, Lichtenstein JE, et al. Adult acquired
2008;49:6570. antral web. Dig Dis Sci 1982;27:803.
45. Edwards MJ, Kollenberg SJ, Brandt ML, et al. Surgery for peptic 61. Miller DL, Pasquale MD, Seneca RP, et al. Gastric volvulus in the
ulcer disease in children in the post-histamine2-blocker era. pediatric population. Arch Surg 1991;126:11469.
J Pediatr Surg 2005;40:8504. 62. Heldrich FJ, Kumarasena D, Hakim J, et al. Acute gastric volvulus
46. Wong BP, Chao NS, Leung MW, et al. Complications of peptic in children: A rare disorder. Pediatr Emerg Care 1993;9:2213.
ulcer disease in children and adolescents: Minimally invasive treat 63. Cribbs RK, Gow KW, Wulkan ML. Gastric volvulus in infants and
ments offer feasible surgical options. J Pediatr Surg 2006;41: children. Pediatrics 2008;122:e75262.
20735. 64. Naik S, Gupta V, Naik S, et al. Rapunzel syndrome reviewed and
47. Hua MC, Kong MS, Lai MW, et al. Perforated peptic ulcer in redefined. Dig Surg 2007;24:15761.
children: A 20-year experience. J Pediatr Gastroenterol Nutr 65. Shami SB, Jararaa AA, Hamade A, et al. Laparoscopic removal of
2007;45:714. a huge gastric trichobezoar in a patient with trichotillomania. Surg
48. Kato S, Konno M, Maisawa S, et al. Results of triple eradication Laparosc Endosc Percutan Tech 2007;17:197200.
therapy in Japanese children: A retrospective multicenter study. 66. Nirasawa Y, Mori T, Ito Y, et al. Laparoscopic removal of a large
J Gastroenterol 2004;39:83843. gastric trichobezoar. J Pediatr Surg 1998;33:6635.
C H A P T E R 3 0
Congenital intestinal obstruction occurs in approximately underlying atresia or stenosis.16 Between the fourth and
1:2000 live births and is a common cause of admission eighth week of gestation, the pancreatic buds merge. In
to a neonatal surgical unit, accounting for up to one-third annular pancreas, the tip of the ventral pancreas becomes
of all admissions.1 Morphologically, congenital defects fixed to the duodenal wall forming a nondistensible, ring-
related to continuity of the intestine can be divided into like or annular portion of pancreatic tissue surrounding
either atresia or stenosis. Together, they constitute one the descending part of the duodenum.13 In annular pan-
of the most common etiologies of neonatal intestinal creas associated with duodenal obstruction, the distal
obstruction.24 See Chapter 29 for information about biliary tree is often abnormal and may open proximal or
pyloric atresia. distal to the atresia or stenosis.17,18 Other reported biliary
abnormalities associated with duodenal obstruction
include biliary atresia, gallbladder agenesis, stenosis of
DUODENAL ATRESIA AND STENOSIS the common bile duct, choledochal cyst, and immune
deficiency.1924
Congenital duodenal atresia and stenosis is a frequent
cause of intestinal obstruction and occurs in 1 per 5000
to 10,000 live births, affecting boys more commonly than
Classification
girls.5 More than 50% of affected patients have associated Anatomically, duodenal obstructions are classified as
congenital anomalies, with trisomy 21 occurring in either atresias or stenoses. An incomplete obstruction,
approximately 30% of patients.6,7 Operative correction is due to a fenestrated web or diaphragm, is considered a
accomplished via a duodenoduodenostomy, with or stenosis. Most stenoses involve the third and/or fourth
without tapering duodenoplasty. This can be performed part of the duodenum. Atresias, or complete obstruction,
either laparoscopically or open. Early postoperative sur- are further classified into three morphologic types (Fig.
vival rates of greater than 90% should be expected.711 30-1). Type I atresias account for more than 90% of all
duodenal obstructions and contain a lumenal diaphragm
that includes mucosal and submucosal layers. A dia-
Etiology phragm that has ballooned distally (windsock) is a type I
Congenital duodenal obstruction can occur due to an atresia.25,26 It is important to understand that the anatomy
intrinsic or extrinsic lesion.12 The most common cause of of the windsock may lead to a portion of the dilated
duodenal obstruction is atresia.7 This intrinsic lesion is duodenum actually being distal to the actual obstruction
most commonly believed to be caused by a failure of (Fig. 30-2). Type II atresias are characterized by a dilated
recanalization of the fetal duodenum resulting in com- proximal and collapsed distal segment connected by a
plete obstruction. Early in the fourth week of gestation, fibrous cord. Type III atresias have an obvious gap sepa-
the duodenum begins to develop from the distal foregut rating the proximal and distal duodenal segments.27
and the proximal midgut. During the fifth and sixth More than 50% of affected patients with duodenal
weeks of gestation, the duodenal lumen temporarily atresia have associated congenital anomalies.28 Approxi-
obliterates due to proliferation of its epithelial cells. Vac- mately 30% are associated with trisomy 21, 30% with
uolation due to degeneration of the epithelial cells during isolated cardiac defects, and 25% with other gastrointes-
the 11th week of gestation then leads to duodenal reca- tinal (GI) anomalies.29,30 Approximately 45% of patients
nalization.13 An embryologic insult during this period can are premature, and about one-third exhibit growth
lead to an intrinsic web, atresia, or stenosis. The extrinsic retardation.6,7
form of duodenal obstruction is due to defects in the
development of neighboring structures such as the pan-
creas, a preduodenal portal vein, or malrotation and
Pathology
Ladds bands.14,15 The obstruction can be classified as either preampullary
Annular pancreas as an etiology for duodenal obstruc- or postampullary, with approximately 85% of obstruc-
tion warrants special mention as this form of obstruction tions located distal to the ampulla.30 With complete or
is likely due to failure of duodenal development rather almost complete obstruction, the stomach and proximal
than a true constricting lesion. Thus, the presence of an duodenum become significantly dilated. The pylorus is
annular pancreas is simply a visible indication of an usually distended and hypertrophic. The bowel distal to
414
30 Duodenal and Intestinal Atresia and Stenosis 415
I II III
A B C
FIGURE 30-1 Duodenal atresia (and stenosis) is depicted. In type I (A), either a membrane (B) or web (C) causes the intrinsic duo-
denal obstruction. There is no fibrous cord and the duodenum remains in continuity. Type II is characterized by complete obliteration
of a segment of the duodenum with the proximal and distal portions attached via a fibrous cord. Type III is associated with complete
separation of the dilated proximal duodenum from the collapsed distal duodenum.
FIGURE 30-4 This schematic depicts several of the variations in biliary ductal anatomy seen in babies with duodenal atresia.
30 Duodenal and Intestinal Atresia and Stenosis 417
A B
FIGURE 30-7 Two approaches to placement of the instruments for a laparoscopic duodenal atresia repair. (A) The two right-sided
instruments are the primary working sites for the surgeon. The liver retractor (arrow) has been placed in the left midepigastric
region. The falciform ligament has been elevated by a suture placed under it and tied over the red rubber catheter, which is used
as a bolster. The suture (dotted arrow) exteriorized in the infants left upper abdomen was placed in the dilated proximal duodenum
so that it could be easily manipulated. (B) This is a similar configuration except the instrument elevating the liver (arrow) is placed
in the infants right upper abdomen rather than the left upper abdomen. The suture that was placed through the proximal dilated
duodenum in A was not needed in this particular case.
418 SECTION IV Abdomen
A B
FIGURE 30-8 (A) Laparoscopic view of a completed duodenoduodenostomy using the Nitinol U-clips. (B) A postoperative contrast
study at five days showed no evidence of obstruction or leak at the anastomosis. The U-clips (arrow) can be seen marking the
anastomosis.
upp o u s
End
a ri
arteries
ly
ec
Vessel
JEJUNOILEAL ATRESIA AND STENOSIS
Pr
Pr
a ri
ec
ou thrombosed
B lo
ds
ds s
Bl
o
oo
Etiology up
ply N o bl o o d s u p pl y
its occurrence later in fetal life and the localized nature Pathology
of the vascular insult.69 Rarely, jejunoileal atresia has been
found in patients with Hirschsprung disease, cystic fibro- The Grosfeld classification system separates these defects
sis, malrotation, Down syndrome, anorectal and vertebral into four groups, with an additional consideration for
anomalies, neural tube defects, congenital heart disease, type III(b) (Fig. 30-10).4 This classification has significant
and other GI atresias.56,69,70 Methylene blue, previously prognostic and therapeutic value as it emphasizes the
used for amniocentesis in twin pregnancies, has been importance of associated loss of intestinal length, abnor-
implicated in causing small bowel atresia.71 mal collateral intestinal blood supply, and concomitant
Although jejunoileal atresias are usually not heredi- atresia or stenosis.75 Regarding classification, the most
tary, there is a well-documented autosomal recessive proximal atresia determines whether the atresia is classi-
pattern of inheritance of multiple atresias.72 In these fied as jejunal or ileal atresia. Multiple atresias are found
cases, intestinal rotation was normal, mesenteric defects in up to 30% of patients.56,76
were never observed, and lanugo hairs and squamous
cells were not identified distal to the most proximal Stenosis
atresia. All these findings suggest an early intrauterine
event. Survival is poor in these infants, even with success- Stenosis is defined as a localized narrowing of the intes-
ful bowel resection. tinal lumen without disruption in the intestinal wall or a
No correlations have been found between jejunoileal defect in the mesentery (see Fig. 30-10A). At the stenotic
atresia and parental or maternal disease. However, the site, a short, narrow, somewhat rigid segment of intestine
use of maternal vasoconstrictive medications, as well as with a small lumen is found. Often the muscularis is
maternal cigarette smoking in the first trimester of preg- irregular and the submucosa is thickened. Stenosis may
nancy, has been shown to increase the risk of small bowel also take the form of a type I atresia with a fenestrated
atresia.73 Chromosomal abnormalities are seen in less web. Patients with jejunoileal stenosis usually have a
than 1% of the patients with jejunoileal atresia.74 normal length of small intestine.
A Stenosis B Type I
$ % &
FIGURE 30-12 This baby was suspected of having a proximal jejunal atresia based on symptoms of bilious emesis and the abdominal
film. (A, B) At operation, this type III(a) jejunal atresia was found. Note the V-shaped mesenteric defect between the dilated proximal
atretic bowel and the distal decompressed bowel. Due to the size discrepancy between the two ends of the intestine, the proximal
dilated bowel was resected at the arrow and an end-to-side anastomosis was performed. (C) The operation was performed through
a slightly extended umbilical incision. The baby recovered nicely and no complications developed.
30 Duodenal and Intestinal Atresia and Stenosis 421
$ %
FIGURE 30-13 (A) The operative findings in neonate with a type III(b) intestinal atresia are seen. Note the classic apple-core or
Christmas tree deformity as well as the wide mesenteric gap between the proximal dilated bowel and distal decompressed ileum.
Also, the colon and distal small bowel are perfused through a single artery (arrow) running through the mesentery of the distal
bowel. (B) This operation was performed through a small umbilical incision. This baby recovered nicely and has not developed any
complications.
overall recurrence rate of 18%.78,81,82 Infants with this and large bowel has been described.72,88 It is associated
anomaly are often premature, and up to 50% may have with prematurity and shortened bowel length. To date, it
malrotation. Short bowel syndrome is present in nearly has been uniformly fatal. It is associated with type I and
75% of cases. Accordingly, there is increased morbidity II atresias, with type II predominating. An autosomal
(63%) and mortality (54%) in this population.78,83 Type recessive mode of transmission has been suggested for
III(b) atresias are most likely the result of a proximal this familial condition because it is unlikely that an iso-
superior mesenteric arterial occlusion with extensive lated prenatal vascular accident is responsible for such
infarction of the proximal segment of the midgut. Also, extensive involvement of the GI tract. In addition, infants
it can develop from a midgut volvulus.58,84 Primary failure affected with this familial form are found to have long
of development of the distal superior mesenteric artery segments of completely occluded small or large intestine
has also been suggested as an etiologic factor. However, without a recognizable lumen.8890 Another pathogno-
this is unlikely because meconium is usually found in the monic feature seen in FMIA is the sieve-like appearance
bowel distal to the atresia. This finding indicates that the of the intestine on histologic examination where multiple
atresia develops after bile secretion begins, which occurs lumina are surrounded by epithelial cells and muscularis
around week 12 of intrauterine life. The superior mucosa.88
mesenteric artery develops much earlier than 12 weeks.85
Pathophysiology
Type IV atresia
The vascular and subsequent ischemic insult not only
Multiple-segment atresias or a combination of types I to causes morphologic abnormalities but also adversely
III are classified as type IV (see Fig. 30-10F). Twenty to influences the structure and subsequent function of the
35% of infants affected with jejunoileal atresia present remaining proximal and distal bowel.58,59,91 The blind-
with multiple atresias.56,76 The majority of cases of ended proximal bowel is dilated and hypertrophied
multiple-segment atresias are sporadic with no other with histologically normal villi, but without effective
family history of intestinal abnormalities. They are likely peristaltic activity. A deficiency of mucosal enzymes and
a result of multiple vascular insults to the mesentery, muscular adenosine triphosphatase has also been found.92
intrauterine inflammatory processes, or a malformation At the level of the atresia, the ganglia of the enteric
of the GI tract occurring during embryonic develop- nervous system are atrophic with minimal acetylcho-
ment.76,86 Embolic material from a nonviable fetus to a linesterase activity. These changes are most likely sec-
living monochorionic twin through placental vascular ondary to local ischemia. Obstruction alone can elicit
connections could also account for single or multiple similar, but less severe, morphologic and functional
intestinal atresias.87 Associated defects, particularly abnor- abnormalities.92
malities of the central nervous system, have been noted in Experimental studies showing that the intestinal
approximately 25% of nonfamilial multiple intestinal atresia results from ischemic necrosis of the intestine also
atresia patients.76 Multiple atresias have also been seen in imply that there is a precarious blood supply to the proxi-
association with severe immunodeficiency.23 mally dilated bowel. This has been confirmed with post-
A familial form of multiple intestinal atresia (FMIA) mortem injection of barium sulfate into the mesenteric
involving the stomach, duodenum, and both the small vessels.58,59,85 However, it has also been postulated that the
422 SECTION IV Abdomen
intestine is not ischemic at birth, but rather becomes so the meconium may appear normal, it is more common to
only with swallowing air. Distention and increased intra- see gray plugs of mucus passed via the rectum. Occasion-
luminal pressure or torsion can then occur. The good ally, if the distal bowel in type III(b) atresia is ischemic,
results obtained with tapering procedures without resec- blood may be passed through the rectum.
tion of the bulbous portion would support the contention Intestinal stenosis is more likely to create diagnostic
that the blood and nerve supply to the bowel adjacent to difficulty when compared to intestinal atresia. Intermit-
the atresia is normal.58 However, this ischemic insult may tent partial obstruction or malabsorption may improve
interfere with mucosal and neural function. Defective without treatment. Clinical investigations can initially be
peristalsis is commonly noticed in the atretic area, thus normal. However, these babies usually develop failure to
supporting resection of the dilated bulbous proximal end thrive and ultimately progress to complete intestinal
for better function.93 Because the proximal end of the obstruction and require exploration.
distal atretic bowel has been subjected to a similar insult,
a small portion of it should be resected at the time of
operative correction as well.
Diagnosis
The diagnosis of jejunoileal atresia can usually be made
by radiographic examination of the abdomen using swal-
Clinical Manifestations lowed air as contrast. Swallowed air reaches the proximal
Prompt recognition of intestinal obstruction in the bowel by one hour and the distal small bowel by three
neonate is paramount due to the possibility of midgut hours in a normal vigorous infant in whom its passage is
volvulus or an internal hernia with subsequent ischemia. blocked, but this pattern may be delayed in premature or
Although prenatal ultrasound is more reliable at detect- sick infants with poor sucking.94,95 Jejunal atresia patients
ing duodenal atresia, in recent years it has become useful can have a few gas-filled and fluid-filled loops of small
in diagnosing jejunoileal atresia as well. The ultrasound bowel, but the remainder of the abdomen is gasless (Fig.
findings include dilated loops of bowel and polyhydram- 30-14). When the atresia is associated with cystic fibrosis,
nios, which may not be present early in gestation or only fewer air-fluid levels are evident, and the typical ground-
with very distal obstructions. A fetus with these abnormal glass appearance of inspissated meconium is seen. A
findings should elicit a search for familial GI abnormali- limited-contrast study may be useful if intestinal stenosis
ties as well as referral for prenatal evaluation. The vast is suspected.
majority of patients with jejunoileal atresia will not be As haustral markings are rarely seen in neonates, distal
diagnosed prenatally. ileal atresia may be difficult to differentiate from colonic
In neonates with atresia or stenosis, the presenting atresia (Fig. 30-15). A contrast enema will reveal an
symptoms are consistent with bowel obstruction, includ- unused appearance to the colon. Reliance on intraopera-
ing bilious emesis and abdominal distention. Although tive injection of saline into the large bowel to confirm
FIGURE 30-14 (A) The abdominal radiograph in this neonate shows several proximally dilated intestinal loops consistent with jejunal
atresia. (B) A type III(a) distal atresia was found at operation.
30 Duodenal and Intestinal Atresia and Stenosis 423
Management
Delay in diagnosis may lead to impairment of intestinal
viability (50%), frank necrosis and perforation (1020%),
fluid and electrolyte abnormalities, and sepsis. Preopera-
tive management should include gastric decompression
and fluid resuscitation to correct electrolyte abnormali-
ties and hypovolemia. Antibiotics should be initiated if
there is suspicion for perforation or infection.
Surgical Considerations
The operative management of intestinal atresias is
based on the location of the lesion, anatomic findings,
associated conditions noted at operation, and the length
of the remaining instestine.56 Resection of the dilated
and hypertrophied proximal bowel (see Fig. 30-12B),
with primary end-to-end anastomosis with or without
tapering of the proximal bowel, is the most common
FIGURE 30-15 The diagnosis of colonic atresia can be difficult
technique.4, 77,100
on the plain abdominal radiograph. This radiograph shows mul- As recently as the 1950s, the surgical mortality for
tiple dilated intestinal loops and appears similar to the findings newborns with intestinal atresia was 80% to 90%.56,99
shown in Figure 30-14. At operation, the infant was found to This high mortality rate was mostly related to late pres-
have atresia of the transverse colon (see Fig. 30-16). entation and dysmotility of the proximal dilated bowel
which led to complications related to chronic obstruction
distal bowel patency may fail to identify an associated and inanition. Fortunately, the current survival rate is
colonic or rectal atresia.96,97 If the small bowel atresia greater than 90%.56 The understanding that the proximal
occurred late in gestation, the bowel distal to the atresia bowel is dysfunctional, improvements in the anastomotic
may have a more normal caliber. Occasionally, air and technique and suture material, and the development of
meconium can accumulate proximal to an atresia, mim- total parenteral nutrition (TPN) are the primary reasons
icking the radiologic appearance of meconium ileus. for this significantly improved survival in recent years.
Additionally, total colonic aganglionosis may be difficult Currently, only infants with severe associated congenital
to differentiate from small bowel atresia. abnormalities or short bowel syndrome should not have
Ten per cent of babies with jejunoileal atresia present a good prognosis.
with meconium peritonitis.4 The intestinal perforation
usually occurs proximal to the obstruction, near the
bulbous blind end. The radiologic appearance of a meco-
Operative Considerations
nium pseudocyst containing a large air/fluid level is The repair of small intestinal atresia can be undertaken
related to the late intrauterine bowel perforation. Intra- via several approaches. One option is to evaluate using a
luminal calcification of meconium or intramural calcifica- laparoscopic approach, with subsequent resection and
tion in the form of diffuse punctate or rounded anastomosis performed in an extra-corporeal fashion.
aggregations have been reported with intestinal stenosis Although this approach seems attractive, it can be diffi-
or atresia.98 Meconium calcification in patients with cult to identify the atresia due to the markedly dilated
hereditary FMIA produces a string of pearls, which is small intestine and the small working space of the
pathognomonic of this condition.72,88 neonates abdominal cavity. To overcome these limita-
The clinical and radiologic picture of jejunoileal ste- tions, we explore the abdomen through the umbilicus.
nosis is determined by the level and degree of stenosis, With this technique, the umbilical skin is incised and the
and the diagnosis may be delayed for years. Morphologic fascia is opened vertically in the midline to the extent
and functional changes in the proximal obstructed intes- allowed by the umbilical skin incision. The small intes-
tine vary depending on the degree of obstruction. tine can be exteriorized relatively easy through the
umbilical incision (see Figs 30-12C and 30-13B). In a
retrospective report, a circumumbilical incision for neo-
Differential Diagnosis natal surgery was found to as effective as the transverse
Diseases that mimic jejunoileal atresia include colonic abdominal incision with less morbidity and better cos-
atresia, midgut volvulus, meconium ileus, duplication metic results.102 The traditional transverse supra- or
cysts, internal hernias, ileus due to sepsis, birth trauma, infraumbilical incision is also appropriate. Regardless of
424 SECTION IV Abdomen
the approach, access to the entire intestine and peritoneal gut syndrome, previous estimates that a small bowel
cavity is necessary. Careful inspection of the entire bowel length of 100cm or more is necessary to sustain oral
is performed and the site and type of obstruction should intake and survival may no longer be applicable. Preser-
be noted as well as any other abnormalities. In addition, vation of bowel length at the expense of a poorly func-
the length of bowel should be assessed. The most distal tioning anastomosis should be avoided.
limb of the atretic bowel can then be cannulated with a If proximal resection will lead to significant, or unac-
red rubber catheter and irrigated with warm saline to ceptable bowel loss, tapering or plication of the dilated
evaluate for distal obstruction. Continuity of the colon bowel is a useful technique.104,107 Tapering enteroplasty as
can be established preoperatively by a contrast enema or far proximal as the second portion of the duodenum can
with a prepositioned transrectal catheter placed prior to be accomplished by resecting an antimesenteric strip of
prepping.103 Failure to adequately evaluate for distal the dilated proximal bowel.108 During tapering duodeno-
obstruction or stenosis can lead to postoperative compli- jejunoplasty, particularly with type III atresias, the duo-
cations, including an anastomotic leak. If present, malro- denum is de-rotated, thus allowing a direct caudal descent
tation should be corrected with a Ladd procedure. from the stomach which decreases the risk for obstruc-
Because the length of functional bowel has important tion. Additionally, the mesentery should be maximally
prognostic significance, and determines the most appro- opened, while meticulously protecting the small bowel
priate method of repair, the length of functional bowel blood supply. During this process, the cecum can be
should be carefully measured along the antimesenteric mobilized to the left which results in a broader mesentery
border and documented in the operative report. and also allows the anastomosis to lie in manner that will
Delayed intestinal function in the blind proximal help avoid kinking.109 The tapering can be safely per-
atretic segment as well as functional obstruction after formed up to 35cm.107 The tapered bowel may then be
performance of a side-to-side anastomosis without resec- anastomosed to the distal bowel or exteriorized as a
tion of the dilated proximal atretic bowel have been stoma.
described.100 Therefore, if the length of functional bowel A primary anastomosis may be contraindicated in cases
is adequate, the bulbous hypertrophied proximal bowel of peritonitis, volvulus with vascular compromise, meco-
should be resected to approximately normal caliber nium ileus, or type III(b) atresia.110,111 Under these cir-
bowel. Ultimately, the goal is to restore bowel continuity cumstances, exteriorization of both ends of the atresia
while maintaining both intestinal function and length. may be needed.
Intestinal imbrication has also been shown to be an effec- Intestinal atresia encountered in a baby with gastro-
tive method to reduce the caliber of the dilated bowel schisis may be single or multiple, and may be located in
while maintaining mucosal absorptive surface.104 Regard- either the small or large bowel. In a series from our
ing the distal segment, a short length (45cm) of bowel institution, 12.6% of 199 patients with gastroschisis had
is obliquely resected, leaving the mesenteric side longer an associated atresia.112 The most common location for
than the antimesenteric aspect. An incision along the the atresia was jejunoileal and most were type III(a). Our
antimesenteric border to create a fish mouth may be current management algorithm for patients with gastro-
needed to create an adequate distal enterotomy for the schisis and atresia is to first assess the extent of reactive
anastomosis. change (peel) on the intestine. If there is minimal peel,
Although there are multiple techniques for the anas- primary anastomosis may be an option. This is rare and
tomosis, we generally perform a one-layer modification should be considered only in the most optimal situations.
of the end-to-back technique using 5-0 or 6-0 sutures. In nearly all instances, the atresia should be left undis-
Once the anastomosis is completed, the suture line is turbed at the initial operation. After fascial closure is
tested for leaks, and reinforcing sutures are placed as accomplished, management should include gastric
needed. The mesenteric defect is repaired with careful decompression and TPN support with subsequent atresia
attention to avoid rotation or kinking of the anastomosis, repair four to six weeks later.
or injury to the blood supply. A temporary enterostomy With type III(b) atresia, restricting bands along the
should be performed if there is a question of bowel viabil- free edge of the distal coiled and narrow mesentery
ity.56 However, neither decompressive gastrostomy nor should be divided to optimize the blood supply. The
transanastomotic stents are usually needed.105,106 bowel should be returned to the abdomen with careful
Similar techniques are used for stenosis and jejunoileal inspection of the mesentery to prevent torsing the single
membranes. Procedures such as transverse enteroplasty, marginal artery and vein. In cases of questionable intes-
excision of the membrane, and bypassing techniques are tinal viability, improved long-term results have been
not recommended primarily because they fail to remove achieved with resection and tapering of the dilated proxi-
the abnormal segments of bowel, and may produce blind- mal bowel with limited resection of the distal bowel.113,114
loop syndromes. Bowel-length conservation methods, such as multiple
anastomoses for multiple atresias, may result in increased
morbidity. A silicone (Silastic) catheter stent can be used
Prognostic Factors with multiple primary anastomoses and serves as a conduit
for radiologic evidence of anastomotic integrity, luminal
The normal small bowel length in term neonates is patency, and enteral feeding.115 If multiple atresias are
approximately 250cm. In preterm infants, it ranges from grouped closely together and there is adequate bowel
160240cm. With the development of TPN, special length, a single resection and anastomosis can be
enteral diets and pharmacologic management of short performed.
30 Duodenal and Intestinal Atresia and Stenosis 425
No attempt at any bowel lengthening procedures types. Type I consists of mucosal atresia with an intact
should be entertained at the initial operation. However, bowel wall and mesentery. In type II, the atretic ends are
such procedures may ultimately obviate the need for pro- separated by a fibrous cord. In type III, the atretic ends
longed TPN in patients with short gut syndrome. are separated by a V-shaped mesenteric gap (Fig. 30-16).
Type III lesions are the most commonly occurring lesions
overall, while types I and II are seen more commonly
Postoperative Care distal to the splenic flexure.122,127
Parenteral nutrition is mandatory and should begin as The rate of associated anomalies with CA is much
soon as possible, and should continue until the infant is smaller when compared to other atresias. CAs have been
tolerating full enteral feeds. found in approximately 2.5% of neonates with gastro-
Enteral feedings can be initiated when the gastric aspi- schisis.112 There are less than 25 published cases of CA
rate is clear, output is minimal, and the infant is stooling. and Hirschsprung disease (HD).126 Complex urologic
At our institution, enteral feeding is usually started abnormalities, multiple small intestinal atresias, an
through a feeding tube at a rate of 20mL/kg/day of unfixed mesentery, and skeletal anomalies have also been
breast milk or formula in a continuous fashion. The feeds reported with CA.122,127129 Similar to small bowel atresias,
are increased by 2030mL/kg/day. Oral intake is started a vascular insult to the colon continues to be the accepted
when the baby is alert, able to suck, and tolerating at least etiology for all types of CA.130,131
8mL of tube feeds per hour. The characteristic clinical features of CA are abdomi-
Transient GI dysfunction is frequently observed in nal distention, bilious emesis, and failure to pass meco-
infants with jejunal and ileal atresia, and its etiology is nium. On plain radiographs, air-fluid levels are usually
multifactorial.4,116 Lactose intolerance, malabsorption appreciated as well as dilated intestinal loops of large
(owing to stasis with bacterial overgrowth), and diarrhea bowel often associated with a ground-glass appearance
may be significant in infants who have undergone repair of meconium mixed with air. Occasionally, the dilation
of type III(b) atresia, or in those with short bowel syn- can be so massive that it mimics pneumoperitoneum
drome after surgery for multiple atresias. Regular moni- (Fig. 30-17). The diagnosis is made with a contrast enema
toring for clinical signs of intestinal overload or showing a small diameter distal colon that comes to an
intolerance is required. Water-loss stools, increasing fre- abrupt halt at the level of the obstruction (Fig. 30-18).
quency of stooling, hematochezia, fecal-reducing sub- The diagnosis of CA is an indication for urgent opera-
stances, or a decreased stool pH warrant biochemical tive management as the risk for perforation is higher than
evaluation of the stool for disaccharide or monosaccha- is seen in jejunoileal atresias. The operative approach
ride intolerance.117 Unintentional injury to the mucosa depends on the clinical status of the patient, the level of
can be caused by sugars, high-osmolarity feeds, oral med-
ications, and bacterial or viral infections. Pharmacologic
control of altered GI function may hasten adaptation.
Loperamide hydrochloride decreases intestinal peristaltic
activity and cholestyramine is effective in binding bile
salts.117,118 Cholestyramine should not be given unless
water-loss stools are evident. Vitamin B12 and folic acid
should be given regularly to the patient without a termi-
nal ileum to prevent megaloblastic anemia.
Functional outcome ultimately depends on the follow-
ing factors: (1) the location of the atresia (the ileum
adapts to a greater degree than the jejunum); (2) the
maturity of the intestine (the small intestine in a prema-
ture infant still has time for maturation and growth); and
(3) the length of the small intestine, which can be difficult
to determine accurately after birth.119 The ileocecal valve
is critically important as it allows for more rapid intestinal
adaptation when the residual small bowel length is short.
COLONIC ATRESIA
Colonic atresia (CA) is a rare cause of intestinal obstruc-
tion and comprises 1.815% of all GI atresias.120,121 The
reported incidence of CA varies greatly from 1:5000 to
1:60,000 live births.122125 The accepted incidence is
approximately 1 in 20,000 live births. Although it is most
commonly reported as an isolated anomaly, approxi- FIGURE 30-16 A type III colonic atresia was found at operation
in this infant with intestinal obstruction. Note the cecum and
mately one-third of babies have associated congenital appendix and the very dilated right colon. Also, note the
lesions.123,124,126 There are various classifications of CA, extremely small distal colon (arrow). A colostomy was per-
but the one most commonly used divides CA into three formed as the initial procedure in this infant.
426 SECTION IV Abdomen
FIGURE 30-18 The contrast enema on the right in a patient with a distal intestinal obstruction (left) shows a small colon and failure
of the contrast to move proximally past the mid-transverse colon.
30 Duodenal and Intestinal Atresia and Stenosis 427
the atresia, any associated small intestinal atresias, and the 13. Moore KL, Persaud TVN. The digestive system. In: The Devel-
patency of the bowel distal to the atresia. It is important oping Human. 8th ed. Philadelphia: WB Saunders; 2007. p. 218,
233.
to exclude other intestinal atresias and stenoses at the time 14. Schnaufer L. Duodenal atresia, stenosis and annular pancreas. In:
of operation as they occur with some frequency.132 A diag- Welch RJ, Randolph JG, et al, editors. Pediatric Surgery. Chicago:
nosis of associated HD, although rare, must be made by Year Book Medical; 1986. p. 929.
frozen section analysis of rectal biopsies during the initial 15. Shawis R, Antao B. Prenatal bowel dilatation and the subsequent
postnatal management. Early Hum Dev 2006;82:297303.
surgery as unrecognized HD can lead to an anastomotic 16. Elliot GB, Kliman R, Elliot KA. Pancreatic annulus: A sign or a
leak or functional obstruction. cause of duodenal obstruction? Can J Surg 1968;11:357.
A staged approach consisting of colostomy with 17. Gourevitch A. Duodenal atresia in the newborn. Ann R Coll Surg
mucous fistula is generally preferred for CA. Because the Engl 1971;48:14158.
proximal and distal ends adjacent to the atresia are abnor- 18. Jona JZ, Belin RP. Duodenal anomalies and the ampulla of Vater.
Surg Gynecol Obstet 1976;143:5659.
mal in both innervation and vascularity, resection of the 19. Irving IM, Rickham PP. Duodenal atresia and stenosis: Annular
bulbous proximal colon as well as a portion of the distal pancreas. In: Rickham PP, Lister J, Irving IM, editors. Neonatal
microcolon is suggested.133,134 Primary resection with Surgery. 2nd ed. Boston: Butterworths; 1978. p. 355.
anastomosis has a higher incidence of complications, 20. Brereton RJ, Cudmore RE, Bouton JM. Double atresia of the
duodenum. Z Kinderchir 1980;31:605.
usually due to undiagnosed distal pathology.124,135 21. Coughlin JP, Rector FE, Klein MD. Agenesis of the gallbladder
A recent report of a small case series of rectal and in duodenal atresia: Two case reports. J Pediatr Surg 1992;27:
sigmoid atresias described a transanal approach for the 1304.
repair of the atresias.136 An initial colostomy at birth was 22. Davenport M, Saxena R, Howard E. Acquired biliary atresia.
performed followed by a transanal approach three to six J Pediatr Surg 1996;31:17213.
23. Moore SW, de Jongh G, Bouic P, et al. Immune deficiency in
months later. Closure of the colostomy was then carried familial duodenal atresia. J Pediatr Surg 1996;31:17335.
out one to two months later. 24. Mali V, Wagener S, Sharif K, et al. Foregut atresias and bile duct
In the absence of other serious co-morbidities, the anomalies: Rare, infrequent or common?! Pediatr Surg Int
prognosis in CA is excellent. If diagnosed early, the 2007;23:88995.
25. Bill AH Jr, Pope WM. Congenital duodenal diaphragm. Surgery
overall mortality is less than 10%.126 A delay in diagnosis 1954;35:4826.
beyond 72 hours, however, may result in a mortality of 26. Rowe M, Buckner D, Clatworthy HW Jr. Wind sock web of the
greater than 60%.129 This high mortality is due, in part, duodenum. Am J Surg 1968;116:4449.
to the formation of a closed loop obstruction between an 27. Magnuson DK, Schwartz MZ. Stomach and duodenum. In:
intact ileocecal valve and the atresia, leading to massive Oldham KT, Colombani PM, Foglia RP, et al, editors. Principles
and Practice of Pediatric Surgery. Philadelphia: Lippincott
colonic distention and perforation. Williams & Wilkins; 2004. p. 1149.
28. Kimble RM, Harding J, Kolbe A. Additional congenital anomalies
in babies with gut atresia or stenosis: When to investigate, and
REFERENCES which investigation. Pediatr Surg Int 1997;12:56570.
1. Irving IM. Duodenal atresia and stenosis: Annular pancreas. In: 29. Mustafawi AR, Hassan ME. Congenital duodenal obstruction in
Lister J, Irving IM, editors. Neonatal Surgery. 3rd ed. London: children: A decades experience. Eur J Pediatr Surg 2008;
Buttersworths; 1990. p. 424. 18:937.
2. Adeyemi D. Neonatal intestinal obstruction in a developing tropi- 30. Escobar MA, Ladd AP, Grosfeld JL, et al. Duodenal atresia and
cal country: Patterns, problems, and prognosis. J Trop Pediatr stenosis: Long-term follow-up over 30 years. J Pediatr Surg
1989;35:6670. 2004;39:86771.
3. Cywes S, Davies MRQ, Rode H. Congenital jejuno-ileal atresia 31. Fonkalsrud EW, DeLorimier AA, Hays DM. Congenital atresia
and stenosis. S Afr Med J 1980;57:6309. and stenosis of the duodenum: A review compiled from the
4. Grosfeld JL. Jejunoileal atresia and stenosis, section 3: The small members of the Surgical Section of the American Academy of
intestine. In: Ravitch MM, Welch KJ, Benson CD, et al, editors. Pediatrics. Pediatrics 1969;43:7983.
Pediatric Surgery. Chicago: Year Book Medical; 1986. p. 838. 32. al-Salem AH, Khwaja S, Grant C, et al. Congenital intrinsic duo-
5. Kimura K, Loening-Baucke V. Bilious vomiting in the newborn: denal obstruction: Problems in the diagnosis and management.
Rapid diagnosis of intestinal obstruction. Am Fam Physician J Pediatr Surg 1989;24:12479.
2000;61:27918. 33. Longo MF, Lynn HB. Congenital duodenal obstruction: Review
6. Chhabra R, Suresh BR, Weinberg G, et al. Duodenal atresia of 29 cases encountered in a 30-year period. Mayo Clin Proc
presenting as hematemesis in a premature infant with Down syn- 1967;42:42330.
drome. Case report and review of the literature. J Perinatol 34. Kimble RM, Harding JE, Kolbe A. Does gut atresia cause poly-
1992;12:257. hydramnios? Pediatr Surg Int 1998;13:11517.
7. Grosfeld JL, Rescorla FJ. Duodenal atresia and stenosis: Reassess- 35. Stubbs TM, Horger EO. Sonographic detection of fetal duodenal
ment of treatment and outcome based on antenatal diagnosis, atresia [Letter]. Obstet Gynecol 1989;73:146.
pathologic variance, and long-term follow-up. World J Surg 36. Akhtar J, Guiney EJ. Congenital duodenal obstruction. Br J Surg
1993;17:301309. 1992;79:1335.
8. Adzick NS, Harrison MR, de Lorimier AA. Tapering duodeno- 37. Bittnecourt DG, Barini R, Marba S, et al. Congenital duodenal
plasty for megaduodenum associated with duodenal atresia. obstruction: Does prenatal diagnosis improve the outcome?
J Pediatr Surg 1986;21:31112. Pediatr Surg Int 2004;20:5825.
9. Rothenberg SS. Laparoscopic duodenoduodenostomy for duo 38. Lawrence MJ, Ford WD, Furness ME, et al. Congenital duodenal
denal obstruction in infants and children. J Pediatr Surg obstruction: Early antenatal ultrasound diagnosis. Pediatr Surg
2002;37:10889. Int 2000;16:3425.
10. Valusek PA, Spilde TL, Tsao K, et al. Laparoscopic duodenal 39. Dumont RC, Rudolph CD. Development of gastrointestinal
atresia repair using surgical U-clips: A novel technique. Surg motility in the infant and child. Gastroenterol Clin North Am
Endosc 2007;21:10234. 1994;23:65571.
11. Spilde TL, St Peter SD, Keckler SJ, et al. Open vs. laparoscopic 40. Berseth CL. Gestational evolution of small intestinal motility in
repair of congenital duodenal obstructions: A concurrent series. preterm and term infants. J Pediatr 1989;115:64651.
J Pediatr Surg 2008;43:10025. 41. Britton JR, Britton HL. Gastric aspirate volume at birth as an
12. Ladd WE. Congenital obstruction of the duodenum in children. indicator of congenital intestinal obstruction. Acta Paediatr
N Engl J Med 1931;206:27783. 1995;84:9456.
428 SECTION IV Abdomen
42. Traubici J. The double bubble sign. Radiology 2001;220:4634. 71. Nicolini U, Monni G. Intestinal obstruction in babies exposed
43. Kassner EG, Sutton A, De Groot TJ. Bile duct anomalies associ- in-utero to methylene blue. Lancet 1990;336:12589.
ated with duodenal atresia: Paradoxical presence of small bowel 72. Guttman FM, Braun P, Garance PH, et al. Multiple atresias and
gas. Am J Roentgenol Radium Ther Nucl Med 1972;116: a new syndrome of hereditary multiple atresias involving the gas-
57783. trointestinal tract from stomach to rectum. J Pediatr Surg
44. Kimura K, Mukohara N, Nishijima E, et al. Diamond-shaped 1973;8:63340.
anastomosis for duodenal atresia: An experience with 44 patients 73. Werler MM, Sheehan JE, Mitchell AA. Association of vasocon-
over 15 years. J Pediatr Surg 1990;25:9779. strictive exposures with risks of gastroschisis and small intestinal
45. Weber TR, Lewis JE, Mooney D, et al. Duodenal atresia: A atresia. Epidemiology 2003;14:34954.
comparison of techniques of repair. J Pediatr Surg 1986;21: 74. Cywes S, Davies MR, Rode H. Congenital jejuno-ileal atresia and
11336. stenosis. S Afr Med J 1980;57:6309.
46. Singh SJ, Dickson R, Baskaranathan S, et al. Excision duodeno- 75. Davies MR, Louw JH, Cywes S, et al. The classification of con-
plasty: A new technique for congenital duodenal obstruction. genital intestinal atresias [letter]. J Pediatr Surg 1982;17:224.
Pediatr Surg Int 2002;18:758. 76. Baglaj M, Carachi R, Lawther S. Multiple atresia of the small
47. Rescorla FJ, Grosfeld JL. Duodenal atresia in infancy and child- intestine: A 20-year review. Eur J Pediatr Surg 2008;18:1318.
hood: Improved survival and long-term follow-up. Contemp Surg 77. Louw JH. Congenital intestinal atresia and severe stenosis in the
1988;33:227. newborn. S Afr J Clin Sci 1952;3:10929.
48. Takayashi Y, Tajiri T, Masumoto K, et al. Umbilical crease incision 78. Seashore JH, Collins FS, Markowitz RI, et al. Familial apple peel
for duodenal atresia achieves excellent cosmetic results. Pediatr jejunal atresia: Surgical, genetic, and radiographic aspects. Pedi-
Surg Int 2010;26:9636. atrics 1987;80:5404.
49. Ein SH, Kim PC, Miller HA. The late nonfunctioning duodenal 79. Mishalany HG, Der Kaloustian VM. Familial multiple-level intes-
atresia repair-A second look. J Pediatr Surg 2000;35:6901. tinal atresias: Report of two siblings. J Pediatr 1971;79:1245.
50. Kimura K, Tsugawa C, Ogawa K, et al. Diamond-shaped anasto- 80. Weitzman JJ, Vanderhoof RS. Jejunal atresia with agenesis of the
mosis for congenital duodenal obstruction. Arch Surg 1977;112: dorsal mesentery with Christmas tree deformity of the small
12623. intestine. Am J Surg 1966;111:4439.
51. Richardson WR, Martin LW. Pitfalls in the surgical management 81. Zerella JT, Martin LW. Jejunal atresia with absent mesentery and
of the incomplete duodenal diaphragm. J Pediatr Surg 1969;4: a helical ileum. Surgery 1976;80:5503.
30312. 82. Smith MB, Smith L, Wells JW, et al. Concurrent jejunal atresia
52. St. Peter SD, Little DC, Barsness KS, et al. Should we be con- with apple peel deformity in premature twins. Pediatr Surg Int
cerned about jejunoileal atresia during repair of duodenal atresia? 1991;6:4258.
J Laparoendoscopic Adv Surg Tech 2010;20:7735. 83. DeLorimier AA, Fonkalsrud EW, Hays DM. Congenital atresia
53. Feggetter S. A review of the long-term results of operations for and stenosis of the jejunum and ileum. Surgery 1969;65:81927.
duodenal atresia. Br J Surg 1969;56:6872. 84. Dickson JA. Apple peel small bowel: An uncommon variant of
54. Stauffer UG, Irving I. Duodenal atresia and stenosislong-term duodenal and jejunal atresia. J Pediatr Surg 1970;5:595600.
results. Prog Pediatr Surg 1977;10:4960. 85. Jimenez FA, Reiner L. Arteriographic findings in congenital
55. Kokkonen ML, Kalima T, Jaaskelainen J, et al. Duodenal atresia: abnormalities of the mesentery and intestines. Surg Gynecol
Late follow-up. J Pediatr Surg 1988;23:21620. Obstet 1961;113:34652.
56. Dalla Vecchia LK, Grosfeld JL, West KW, et al. Intestinal atresia 86. Tsujimoto K, Sherman FE, Ravitch MM. Experimental intestinal
and stenosis: A 25-year experience with 277 cases. Arch Surg atresia in the rabbit fetus. Sequential pathological studies. Johns
1998;133:4906. Hopkins Med J 1972;131:28797.
57. Kumaran N, Shankar KR, Lloyd DA, et al. Trends in the manage- 87. Komuro H, Amagai T, Hori T, et al. Placental vascular compro-
ment and outcome of jejuno-ileal atresia. Eur J Pediatr Surg mise in jejunoileal atresia. J Pediatr Surg 2004;39:17015.
2002;12:1637. 88. Bilodeau A, Prasil P, Cloutier R, et al. Hereditary multiple intes-
58. Louw JH. Congenital intestinal atresia and stenosis in the tinal atresia: Thirty years later. J Pediatr Surg 2004;39:72630.
newborn. Observations on its pathogenesis and treatment. Ann R 89. Hasegawa T, Sumimura J, Nose K, et al. Congenital multiple
Coll Surg Engl 1959;25:20934. intestinal atresia successfully treated with multiple anastomoses in
59. Louw JH, Barnard CN. Congenital intestinal atresia: Observa- a premature neonate: Report of a case. Surg Today 1996;26:
tions on its origin. Lancet 1955;269:10657. 84951.
60. Abrams JS. Experimental intestinal atresia. Surgery 1968;64: 90. Puri P, Guiney E, Carroll R. Multiple gastrointestinal atresias in
18591. three consecutive siblings: Observations on pathogenesis. J Pediatr
61. Puri P, Fujimoto T. New observations on the pathogenesis of Surg 1985;20:224.
multiple intestinal atresias. J Pediatr Surg 1988;23:2215. 91. Baglaj SM, Czernik J, Koryszko J, et al. Natural history of experi-
62. Koga Y, Hayashida Y, Ikeda K, et al. Intestinal atresia in fetal dogs mental intestinal atresia: Morphologic and ultrastructural study.
produced by localized ligation of mesenteric vessels. J Pediatr J Pediatr Surg 2001;36:142834.
Surg 1975;10:94953. 92. Pickard LR, Santoro S, Wyllie RG, et al. Histochemical studies
63. Tibboel D, van der Kamp AW, Molenaar JC. An experimental of experimental fetal intestinal obstruction. J Pediatr Surg
study of the effect of an intestinal perforation at various develop- 1981;16:25660.
mental stages. Z Kinderchir 1982;37:626. 93. Doolin EJ, Ormsbee HS, Hill JL. Motility abnormalities in intes-
64. Khen N, Jaubert F, Sauvat F, et al. Fetal intestinal obstruction tinal atresia. J Pediatr Surg 1987;22:3204.
induces alteration of enteric nervous system development in 94. Cremin BJ, Cywes S, Louw JH. Small intestine. In: Cremin BJ,
human intestinal atresia. Pediatr Res 2004;56:97580. Cywes S, Louw JH, editors. Radiological Diagnosis of Digestive
65. Amoury RA, Ashcraft KW, Holder TM. Gastroschisis compli- Tract Disorders in the Newborn: A Guide to Radiologists, Sur-
cated by intestinal atresia. Surgery 1977;82:37381. geons, and Paediatricians. London: Butterworths; 1973. p. 62.
66. Grosfeld JL, Clatworthy HW Jr. The nature of ileal atresia 95. Wasch MG, Marck A. The radiographic appearance of the gas-
due to intrauterine intussusception. Arch Surg 1970;100: trointestinal tract during the first day of life. J Pediatr 1948;32:
71417. 47989.
67. Murphy DA. Internal hernias in infancy and childhood. Surgery 96. Benson CD, Lofti MW, Brogh AJ. Congenital atresia and stenosis
1964;55:31116. of the colon. J Pediatr Surg 1968;3:2537.
68. Vassy LE, Boles ET Jr. Iatrogenic ileal atresia secondary to 97. Jackman S, Brereton RJ. A lesson in intestinal atresias. J Pediatr
clamping of an occult omphalocele. J Pediatr Surg 1975;10: Surg 1988;23:8523.
797800. 98. Aharon M, Kleinhaus U, Lichtig C. Neonatal intramural intesti-
69. Sweeney B, Surana R, Puri P. Jejunoileal atresia and associated nal calcifications associated with bowel atresia. AJR Am J Roent-
malformations: Correlation with timing of in-utero insult. genol 1986;130:9991000.
J Pediatr Surg 2001;36:7746. 99. Hays DM. Intestinal atresia and stenosis. In: Ravitch M, editor.
70. Moore SW, Rode H, Millar AJW, et al. Intestinal atresia and Current Problems in Surgery. Chicago: Year Book Medical; 1969.
Hirschsprungs disease. Pediatr Surg Int 1990;5:1824. p. 3.
30 Duodenal and Intestinal Atresia and Stenosis 429
100. Louw JH. Resection and end-to-end anastomosis in the manage- 117. Dowling RH. Small bowel adaptation and its regulation. Scand J
ment of atresia and stenosis of the small bowel. Surgery 1967;62: Gastroenterol Suppl 1982;17:5374.
94050. 118. Remmington M, Malagelada JR, Zinsmeister A, et al. Abnormali-
101. Blanck C, Okmian L, Robbe H. Mucoviscidosis and intestinal ties in gastrointestinal motor activity in patients with short bowels:
atresia. A study of four cases in the same family. Acta Paediatr Effect of a synthetic opiate. Gastroenterology 1983;85:62936.
Scand 1965;54:55765. 119. Rode H, Millar AJW. Jejuno-ileal atresia and stenosis. In: Puri P,
102. Suri M, Langer JC. A comparison of circumbilical and transverse editor. Newborn Surgery. 2nd ed. London: Hodder Arnold; 2003.
abdominal incisions for neonatal abdominal surgery. J Pediatr p. 445.
Surg 2011;46:107680. 120. Boles ET Jr, Vassy LE, Ralston M. Atresia of the colon. J Pediatr
103. McKee MA. Jejunoileal Atresia. In: Oldham KT, Colombani PM, Surg 1976;11:6975.
Foglia RP, et al, edsitors. Principles and Practice of Pediatric 121. Benson CD, Lotfi MW, Brogh AJ. Congenital atresia and stenosis
Surgery. Philadelphia: Lippincott Williams & Wilkins; 2004. of the colon. J Pediatr Surg 1968;3:2537.
p. 1149. 122. Powell RW, Raffensperger JG. Congenital colonic atresia.
104. de Lorimier AA, Harrison MR. Intestinal plication in the treat- J Pediatr Surg 1982;17:16670.
ment of atresia. J Pediatr Surg 1983;18:7347. 123. Croaker GD, Harvey JG, Cass DT. Hirschsprungs disease,
105. Holder TM, Gross RE. Temporary gastrostomy in pediatric colonic atresia, and absent hand: A new triad. J Pediatr Surg
surgery. Experience with 187 cases. Pediatrics 1960;26:3641. 1997;32:136870.
106. Howard ER, Othersen HB. Proximal jejunoplasty in the treat- 124. Kim PC, Superina RA, Ein S. Colonic atresia combined with
ment of jejunoileal atresia. J Pediatr Surg 1973;8:68590. Hirschsprungs disease: A diagnostic and therapeutic challenge.
107. Ramanujan TM. Functional capability of blind small bowel loops J Pediatr Surg 1995;30:121617.
after intestinal remodeling techniques. Aust N Z J Surg 125. Davenport M, Bianchi A, Doig CM, et al. Colonic atresia: Current
1984;54:14550. results of treatment. J R Coll Surg Edinb 1990;35:258.
108. Kimura K, Perdzynski W, Soper RT. Elliptical seromuscular 126. Williams MD, Burrington JD. Hirschsprungs disease complicat-
resection for tapering the proximal dilated bowel in duodenal or ing colon atresia. J Pediatr Surg 1993;28:6379.
jejunal atresia. J Pediatr Surg 1996;31:14056. 127. Karnak I, Ciftci AO, Senocak ME, et al. Colonic atresia: Surgical
109. Kling K, Applebaum H, Dunn J, et al. A novel technique for cor- management and outcome. Pediatr Surg Int 2001;17:6315.
rection of intestinal atresia at the ligament of Treitz. J Pediatr Surg 128. Sui KL, Kwok WK, Lee WY, et al. A male newborn with colonic
2000;35:3535. atresia and total colonic aganglionosis. Pediatr Surg Int
110. Grosfeld JL, Ballantine TV, Shoemaker R. Operative manage- 1999;15:1412.
ment of intestinal atresia and stenosis based on pathologic find- 129. Cox SG, Numanoglu A, Millar AJ, et al. Colonic atresia: Spectrum
ings. J Pediatr Surg 1979;14:36875. of presentation and pitfalls in management. A review of 14 cases.
111. Touloukian RJ. Intestinal atresia. Clin Perinatol 1978;5:318. Pediatr Surg Int 2005;21:81318.
112. Snyder CL, Miller KA, Sharp RJ, et al. Management of intestinal 130. Louw JH. Investigations into the etiology of congenital atresia of
atresia in patients with gastroschisis. J Pediatr Surg 2001;36: the colon. Dis Colon Rectum 1964;7:4718.
15425. 131. Santulli TV, Blanc WA. Congenital atresia of the intestine: Patho-
113. Festen S, Brevoord JC, Goldhoorn GA, et al. Excellent long-term genesis and treatment. Ann Surg 1961;154:93948.
outcome for survivors of apple peel atresia. J Pediatr Surg 132. Rescorla FJ, Grosfeld JL. Intestinal atresia and stenosis: Analysis
2002;37:615. of survival in 120 cases. Surgery 1985;98:66876.
114. Waldhausen JH, Sawin RS. Improved long-term outcome for 133. Watts AC, Sabharwal AJ, Mackinlay GA, et al. Congenital colonic
patients with jejunoileal apple peel atresia. J Pediatr Surg atresia: Should primary anastomosis always be the goal? Pediatr
1997;32:13079. Surg Int 2003;19:1417.
115. Chaet MS, Warner BW, Sheldon CA. Management of multiple 134. DeFore WW, Garcia-Rinaldi R, Mattox KL, et al. Surgical man-
jejunoileal atresias with an intraluminal Silastic stent. J Pediatr agement of colon atresia. Surg Gynecol Obstet 1976;143:7679.
Surg 1994;29:16046. 135. Pohlson EC, Hatch EI Jr, Glick PL, et al. Individualized manage-
116. Haller JA Jr, Tepas JJ, Pickard LR, et al. Intestinal atresia. Current ment of colonic atresia. Am J Surg 1988;155:6902.
concepts of pathogenesis, pathophysiology, and operative man- 136. Hamzaoui M, Ghribi A, Makni W, et al. Rectal and sigmoid
agement. Am Surg 1983;49:38591. atresia: Transanal approach. J Pediatr Surg 2012;47:E414.
C H A P T E R 3 1
Malrotation
M. Sidney Dassinger III Samuel D. Smith
Normal rotation of the intestine requires transformation omphalomesenteric duct at the apex. Due to the dispro-
from a simple, straight alimentary tube into the mature portional growth and elongation of the midgut during
fixed and folded configuration normally present at birth. the fourth gestational week, the intestinal loop herniates
Through precise embryologic events, the duodenojejunal into the extraembryonic coelom. Next, the bowel enters
junction becomes fixed in the left upper abdomen while a critical period of rotation when the prearterial and
the cecum is anchored in the right lower quadrant. The postarterial limbs make three separate 90 turns, all in
midgut, defined as the portion of the intestine supplied the counterclockwise direction around the SMA. The
by the superior mesenteric artery (SMA), is thus sus- first 90 rotation occurs outside the abdomen. The second
pended from a wide mesenteric base. In children with 90 turn commences during the return of the intestine
malrotation, the bowel is not fixed adequately and is thus into the abdominal cavity during the 10th gestational
held by a precariously narrow-based mesentery. Rota- week. The duodenojejunal junction now passes posterior
tional anomalies create a spectrum of anatomic condi- to the SMA. The last rotation occurs in the abdomen.
tions with critical importance to the pediatric surgeon. The primitive intestine has thus completed a 270 coun-
Clinical disorders may arise when intestinal rotation terclockwise rotation, allowing the duodenojejunal limb
either fails to occur or is incomplete. Rotational anoma- to be positioned to the left of the SMA while the ceco-
lies may be isolated or occur as an intrinsic component colic limb is on the right. Fixation of the ascending and
of gastroschisis, omphalocele, or congenital diaphrag- descending colon then occurs. Disruption of any of these
matic hernia. Additionally, malrotation may present as an vital steps leads to the spectrum of malrotation encoun-
incidental, subtle finding discovered during the radio- tered clinically.
graphic evaluation for another diagnosis or with shock The most common forms of rotational disorders
from a catastrophic midgut volvulus. include nonrotation (Fig. 31-2), incomplete rotation
The earliest descriptions of intestinal development (Fig. 31-3), and reversed rotation. Right and left meso-
were from Mall in 1898, and later expanded upon by colic hernias can also occur. In nonrotation, there is
Frazer and Robbins in 1915.1,2 Eight years later, Dott failure of the normal intestinal 270 counterclockwise
translated these preliminary embryologic observations rotation around the SMA. Thus, the duodenojejunal
into problems encountered clinically.3 In his 1932 land- limb lies in the right hemi-abdomen with the cecocolic
mark paper, Ladd described the evaluation and operative limb in the left hemi-abdomen. Midgut volvulus due to
treatment of malrotation.4 He described a relatively a narrow mesenteric pedicle and extrinsic duodenal
simple solution to a complicated problem.5 Over 200 obstruction secondary to abnormally positioned cecal
postmortem studies had been reported previous to Ladds attachments are the most common symptomatic conse-
paper, yet he was the first to emphasize the importance quences. In cases of incomplete rotation, normal rotation
of placing the duodenum along the right abdominal wall, has been arrested at or near 180. The cecum will usually
widening the mesenteric base, and moving the cecum to reside in the right upper abdomen. Obstructing perito-
the left upper abdomen. With the exception of the lapar- neal bands over the duodenum are present. With reversed
oscopic approach, Ladds original technique has remained rotation, an errant 90 clockwise rotation occurs, which
relatively unchanged. leaves a tortuous transverse colon to the right of the
SMA, passing through a retroduodenal tunnel dorsal to
the artery and in the small bowel mesentery.7,8 The duo-
EMBRYOLOGY denum will assume an anterior position. Reverse rotation
with volvulus may occur with obstruction of the trans-
The development of the midgut begins with the differ- verse colon. Paraduodenal hernias are rare and result
entiation of the primitive intestinal tract into the foregut, from failure of the right or left mesocolon to fuse to the
midgut, and hindgut at the fourth week of gestation.6 The posterior body wall. A potential space is created. Subse-
mature alimentary tract and all associated digestive quently, the small intestine may become sequestered and
organs are formed from this primitive tube. The most potentially obstructed.
accepted model of midgut maturation involves four dis-
tinct stages: (1) herniation; (2) rotation; (3) retraction;
and (4) fixation. Normal fixation of the duodenum and PRESENTATION
colon is illustrated in Figure 31-1. The intestinal loop
can be divided into the cephalic (duodenojejunal) limb The incidence of malrotation has been estimated at 1 in
and the caudal (cecocolic) limb, which rotate separately 6000 live births. An increased incidence of 0.2% has been
but in parallel. The SMA serves as the fulcrum with the found in barium swallow studies,9 whereas autopsy studies
430
31 Malrotation 431
Ligament
of Treitz
Ascending
colon Descending
colon
Cecum
A B
A B
FIGURE 31-10 An upper gastrointestinal study was performed in this infant who presented with vomiting. The radiologic interpreta-
tion was that the duodenum was entirely on the patients right side and the ligament of Treitz was at the level of pylorus. Also, the
ligament of Treitz did not cross the midline. There was no evidence of obstruction. This patient underwent diagnostic laparoscopy
and was found to have normal anatomy with correct positioning of the ligament of Treitz and the cecum (see Fig. 31-11).
31 Malrotation 435
A B
FIGURE 31-11 At times, the upper gastrointestinal study can be equivocal for possible malrotation (see Fig. 31-10). In such patients,
diagnostic laparoscopy is a useful technique to ascertain whether the patient actually has malrotation. (A) The ligament of Treitz
(arrow) is seen to be to the left of the patients midline. (B) In addition, the location of the cecum in the right lower quadrant also
helps verify that the patient does not have malrotation.
POSTOPERATIVE MANAGEMENT
In patients without evidence of volvulus or obstruction,
a nasogastric tube is not generally used. Bowel function
generally returns in 1 to 5 days. However, older patients
with chronic obstruction are likely to have a prolonged
ileus, and thus nasogastric drainage and parenteral
support may be required. Antibiotics are not uniformly
needed. Feedings can be advanced per the surgeons dis-
cretion. Patients with extended or subtotal small bowel
resection pose special problems. Total parenteral nutri-
tion is essential to sustain these patients until adaptation
and compensatory growth of the residual bowel can
FIGURE 31-14 When performing a laparoscopic Ladd proce-
occur.37 Small bowel or multiple-viscera transplantation
dure, an extracorporeal appendectomy eliminates the need for should be considered. Postoperative intussusception has
a large port for the endoscopic stapler. The appendix is grasped been noted in 3.1% of all patients who underwent a Ladd
with one of the intracorporeal instruments and brought into procedure, compared with 0.05% following other
view through the umbilical fascial defect, where it is grasped laparotomies.38 The incidence of recurrent volvulus is
and exteriorized. (From Moir CR. Laparoscopic Ladd procedure. In:
Holcomb GW III, Georgeson KE, Rothenberg SS, editors. Atlas of low. At the authors institution, the recurrent volvulus
Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; rate has approximated 1%. Finally, up to 10% of patients
2008. p. 5560.) may develop a postoperative adhesive small bowel
obstruction requiring an operation.23,24,39
Heterotaxy
Rotational disorders are known to coexist with heterotaxy
syndrome (HS).51 Thus, in many institutions, screening
upper gastrointestinal contrast studies are performed.
Patients that are symptomatic from these anomalies
A
should undergo a Ladd operation. However, manage-
ment of the asymptomatic patient remains controversial
with literature available to support either observation or
SMV elective operation. Recently, a retrospective study docu-
mented a higher morbidity rate when heterotaxy patients,
who underwent prophylactic Ladd procedure, were com-
pared to those without heterotaxy. Despite the small
sample size, they concluded that asymptomatic patients
SMA
should be observed.52 Conversely, a group from Boston
noted similar outcomes when HS patients were com-
pared to patients without HS that underwent Ladd pro-
cedures.53 Interestingly, 27% of the HS patients that had
abdominal symptoms were found to have volvulus at
exploration, emphasizing the potential hazards of obser-
vational management. Multi-institutional, prospective
B studies are needed to make more definitive recommenda-
tions for this challenging group of patients.
FIGURE 31-15 This 15-year-old presented with chronic abdomi-
nal pain and underwent a CT scan for diagnosis. (A) On this REFERENCES
coronal view, the small bowel is filled with contrast and most
of it is located along the right paracolic gutter. (B) On transverse 1. Mall FP. Development of the human intestine and its position in
section, note that the superior mesenteric artery (SMA) and the adult. Johns Hopkins Hosp Bull 1898;9:197208.
superior mesenteric vein (SMV) are malpositioned, and are 2. Frazer TE, Robbins RF. On the factors concerned in causing rota-
reversed in orientation to each other. This patient underwent tion of the intestine in man. J Anat Physiol 1915;50:74110.
a laparoscopic Ladd procedure with resolution of her 3. Dott NM. Anomalies of intestinal rotation: Their embryology and
symptoms. surgical aspects, with the report of five cases. Br J Surg 1923;11:
25186.
4. Ladd W. Congenital obstruction of the duodenum in children. N
been suggested.46 However, up to 20% of adult patients Engl J Med 1932;206:27783.
5. Ladd WE, Gross RE. Intestinal obstruction resulting from
undergoing operative repair of malrotation will have an malrotation of the intestines and colon. Abdominal Surgery of
acute volvulus or bowel ischemia, both potentially life- Infancy and Childhood. Philadelphia: WB Saunders; 1941. p.
threatening presentations.47 Furthermore, even in 5370.
patients who are believed to be asymptomatic, preopera- 6. Kluth D, Jaeschke-Melli S, Fiegel H. The embryology of gut rota-
tive symptoms attributable to malrotation have retro- tion. Semin Pediatr Surg 2003;12:2759.
7. Kanazawa T, Kasugai K, Miyata M, et al. Midgut malrotation in
spectively been noted to improve or resolve.31,43,48 Thus, adulthood. Intern Med 2000;39:62631.
operative correction in the asymptomatic older patient is 8. Wang C, Welch CE. Anomalies of intestinal rotation in adolescents
currently recommended. and adults. Surgery 1963;54:82954.
9. Warner BR. Malrotation. In: Oldham KT, Colombani PM, Foglia
RP, editors. Surgery of Infants and Children. Philadelphia:
Atypical Malrotation Lippincott-Raven; 1996. p. 122940.
10. Kapfer SA, Rappold JF. Intestinal malrotationnot just the pedi-
The dilemma arises when an abnormality is discovered atric surgeons problem. J Am Coll Surg 2004;199:62835.
on imaging, and the child is labeled as a malrotation 11. Aiken JJ, Oldham KT. Malrotation. In: Ashcraft KW, Holcomb
variant. To exclude malrotation, the duodenojejunal GW III, Murphy JP, editors. Pediatric Surgery. Philadelphia: Else-
vier Saunders; 2005. p. 43547.
flexure must be located to the left of the spine at the level 12. Gross RE. Malrotation of the intestine and colon. In: Gross R.E.,
of the duodenal bulb. Defined as the ligament of Treitz, editor. The Surgery of Infancy and Childhood. Philadelphia: WB
this flexure can be in an equivocal position. Symptoms Saunders; 1953. p. 192203.
438 SECTION IV Abdomen
13. Ford EG, Senac MO Jr, Srikanth MS, et al. Malrotation of the 33. Martinez-Ferro M, Bignon H, Figueroa M. Ladd laparoscopic pro-
intestine in children. Ann Surg 1992;212:1728. cedure in the neonate. Cir Pediatr 2006;19:1824.
14. Stewart DR, Colodny AL, Daggett WC. Malrotation of the bowel 34. Draus JM Jr, Foley DS, Bond SJ. Laparoscopic Ladd procedure: A
in infants and children: A 15-year review. Surgery 1976;79: minimally invasive approach to malrotation without midgut volvu-
71620. lus. Am Surg 2007;73:6936.
15. Powell DM, Othersen HB, Smith CD. Malrotation of the intestine 35. Waldhausen JH, Sawin RS. Laparoscopic Ladds procedure
in children: The effect of age on presentation and therapy. J Pediatr and assessment of malrotation. J Laparoendosc Surg 1996;6:
Surg 1989;24:77780. S1035.
16. Maxson RT, Franklin PA, Wagner CW. Malrotation in the older 36. Fraser JD, Aguayo P, Sharp SW, et al. The role of laparoscopy in
child: Surgical management, treatment, and outcome. Am Surg the management of malrotation. J Surg Res 2009;156:802.
1995;61:1358. 37. Georgeson KE, Breaux CW Jr. Outcome and intestinal adaptation
17. Sizemore AW, Rabbani KZ, Ladd A, et al. Diagnostic performance in neonatal short-bowel syndrome. J Pediatr Surg 1992;27:
of the upper gastrointestinal series in the evaluation of children 34450.
with clinically suspected malrotation. Pediatr Radiol 2008;38: 38. Kidd J, Jackson R, Wagner C, et al. Intussusception following the
51828. Ladd procedure. Arch Surg 2000;135:71315.
18. Shimanuki Y, Aihara T, Takano H. Clockwise whirlpool sign at 39. Murphy FL, Sparnon AL. Long-term complications following
color Doppler ultrasound: An objective and definite sign of midgut intestinal malrotation and the Ladds procedure: A fifteen-year
volvulus. Radiology 1996;199:2614. review. Pediatr Surg Int 2006;22:3269.
19. Pracros JP, Sann L, Genin G, et al. Ultrasound diagnosis of midgut 40. Hsu SD, Yu JC, Chou SJ, et al. Midgut volvulus in an adult with
volvulus: The whirlpool sign. Pediatr Radiol 1992;22:1820. congenital malrotation. Am J Surg 2008;195:7057.
20. Chao JC, Kong MS, Chen JY, et al. Sonographic features related 41. Gamblin TC, Stephens RE Jr, Johnson RK, et al. Adult malrota-
to volvulus in neonatal intestinal malrotation. J Ultrasound Med tion: A case report and review of the literature. Curr Surg
2000;19:3716. 2003;60:51720.
21. Orzech N, Navarro OM, Langer JC. Is ultrasonography a good 42. von Flue M, Herzog U, Ackermann C, et al. Acute and chronic
screening test for intestinal malrotation? J Pediatr Surg presentation of intestinal nonrotation in adults. Dis Colon Rectum
2006;41:10059. 1994;37:1928.
22. Yousefzadeh DK, Kang L, Tessicini L. Assessment of retrome- 43. Fu T, Tong WD, He YJ, et al. Surgical management of intestinal
senteric position of the third portion of the duodenum: An ultra- malrotation in adults. World J Surg 2007;31:1797803.
sound feasibility study in 33 newborns. Pediatr Radiol 44. Pickhardt PJ, Bhalla S. Intestinal malrotation in adolescents and
2010;40:147684. adults: Spectrum of clinical and imaging features. AJR Am J Roent-
23. Stauffer UG, Herman P. Comparison of late results in patients with genol 2002;179:142935.
corrected intestinal malrotation with and without fixation of the 45. Durkin ET, Lund DP, Shaaban AF, et al. Age-related differences in
mesentery. J Pediatr Surg 1980;15:912. diagnosis and morbidity of intestinal malrotation. J Am Coll Surg
24. Rescorla FJ, Shedd FJ, Grosfeld JL, et al. Anomalies of intestinal 2008;206:65863.
rotation in childhood: Analysis of 447 cases. Surgery 1990; 46. Malek MM, Burd RS. The optimal management of malrotation
108:71015. diagnosed after infancy: A decision analysis. Am J Surg
25. van der Zee DC, Bax NMA. Laparoscopic repair of acute volvulus 2006;191:4551.
in a neonate with malrotation. Surg Endosc 1995;9:11234. 47. Malek NM, Burd RS. Surgical treatment of malrotation after
26. Bax K, van der Zee DC. Intestinal malrotation. In: Klaas N, Bax infancy: A population-based study. J Pediatr Surg 2005;40:
MA, Georgeson KE, et al, editors. Endoscopic Surgery in Infants 2859.
and Children. New York: Springer; 2007. p. 299304. 48. Rao KM, Kiran PR. Midgut malrotation presenting in adult life.
27. Moir CR. Laparoscopic Ladd procedure. In: Holcomb GW III, Br J Surg 1994;81:11734.
Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Lapar- 49. McVay MR, Kokoska ER, Jackson RJ, et al. The changing spectrum
oscopy and Thoracoscopy. Philadelphia: WB Saunders; 2008. of intestinal malrotation: Diagnosis and management. Am J Surg
p. 5560. 2007;194:71217.
28. McLean SE, Minkes RK. Intestinal Rotation Abnormalities. In: 50. Smith SD. Disorders of intestinal rotation and fixation. In:
Langer JC, Albanese CT, editors. Pediatric Minimal Access Grosfeld JL, ONeill JA Jr, Fonkalsrud EW, Coran AG,
Surgery. Boca Raton, FL: Taylor & Francis; 2005. p. 27183. editors. Pediatric Surgery. 6th ed. Philadelphia: Mosby; 2006. p.
29. Bass KD, Rothenberg SS, Chang JH. Laparoscopic Ladds proce- 134257.
dure in infants with malrotation. J Pediatr Surg 1998;33:27981. 51. Chang J, Brueckner M, Touloukian RJ. Intestinal rotation and fixa-
30. Mazziotti MV, Strasberg SM, Langer JC. Intestinal rotation abnor- tion abnormalities in heterotaxia: Early detection and management.
malities without volvulus: The role of laparoscopy. J Am Coll Surg J Pediatr Surg 1993;28:12814.
1997;185:1726. 52. Pockett CR, Dicken B, Rebeyka IM, et al. Heterotaxy Syndrome:
31. Lessin MS, Luks FI. Laparoscopic appendectomy and duodenoco- Is a prophylactic Ladd procedure necessary in asymptomatic
lonic dissociation (Ladd) procedure for malrotation. Pediatr Surg patients? Pediatr Cardiol 2013;34:5963.
Int 1998;13:1845. 53. Yu DC, Thiagarajan RR, Laussen PC, et al. Outcomes after the
32. Gross E, Chen MK, Lobe TE. Laparoscopic evaluation and treat- Ladd procedure in patients with heterotaxy syndrome, congenital
ment of intestinal malrotation in infants. Surg Endosc 1996; heart disease, and intestinal malrotation. J Pediatr Surg 2009;44:
10:9367. 108995.
C H A P T E R 3 2
Meconium Disease
Michael G. Caty Mauricio A. Escobar, Jr.
Intestinal obstruction is one of the most common admit- most common, potentially lethal genetic defect affecting
ting diagnoses to the neonatal intensive care unit, account- Caucasians. Each year 1,200 infants are born with CF
ing for as many as one-third of all admissions.1 Failure to (1:2500 live births), and 30,000 children and young
pass meconium within the first 24 to 48 hours of life, adults live with CF in the USA.4 It is an inherited auto-
feeding intolerance, abdominal distension, and bilious somal recessive disease with a 45% carrier rate.14 The
emesis are hallmarks of intestinal obstruction in the incidence of CF is much lower in non-Caucasian popula-
newborn, and evoke a differential diagnosis of obstruction tions: 1 in 10,500 Native American Aleut (Eskimo) births,
based on anatomic, metabolic, and functional considera- 1 in 13,500 in HispanicCaucasian births, 1 in 15,000
tions. The term meconium disease refers to meconium AfricanAmerican births (much lower in native Africans),
ileus and meconium plug syndrome. These conditions are and 1 in 31,000 in AsianAmerican births.
considered separately from functional or anatomic causes
of neonatal intestinal obstruction, such as Hirschsprung
disease, intestinal atresia, and anorectal malformations.
Genetics
In 1989, the CF locus was localized through linkage
analysis to human chromosome 7q31, and it was discov-
MECONIUM ILEUS ered that mutations in the CF transmembrane (conduct-
ance) regulator (CFTR) gene result in CF.1518 The cell
Meconium ileus (MI) is one of the most common causes membrane protein coded by CFTR is a 35-cyclic ade-
of intestinal obstruction in the newborn, accounting for nosine monophosphate (cAMP)-induced chloride
933% of neonatal intestinal obstructions.2 It is charac- channel, which also regulates the flow of other ions across
terized by extremely viscid, protein-rich, inspissated the apical surface of epithelial cells. The alteration in
meconium causing an intraluminal obstruction in the CFTR results in an abnormal electrolyte content in the
distal ileum, usually at the ileocecal valve. It is often the environment external to the apical surface of epithelial
earliest clinical manifestation of cystic fibrosis (CF), membranes. This leads to desiccation and reduced clear-
occurring in approximately 16% of patients with CF.3 ance of secretions from tubular structures lined by
Although MI can occur with other uncommon conditions affected epithelia.
such as pancreatic aplasia and total colonic aganglionosis, The most common mutation of the CFTR gene,
it is often considered pathognomonic for CF.4,5 MI may F508del (previously known as F508), is a three base-
be an early indication of a more severe phenotype of pair deletion that results in the removal of a phenyl
cystic fibrosis, as suggested by significantly diminished alanine residue at amino acid position 508 of the CFTR.
pulmonary function found in children with a history of Although there are currently 1,903 mutations listed in
MI compared to age- and gender-matched children with the CFTR database, the F508del mutation is responsible
CF who did not have MI.6 for approximately 70% of abnormal CF genes.15,16,18,19 In
Due to abnormalities of exocrine mucus secretion and families with MI, there is a significantly higher occur-
pancreatic enzyme deficiency, the meconium in MI differs rence rate than the expected 25% for an autosomal reces-
from normal meconium. Meconium in MI has less water sive genetic disorder.20,21 In one series, 79% of CF patients
content (65% vs 75%) when compared to normal meco- with the F508del mutation presented with abdominal
nium, lower sucrase and lactase levels, increased albumin, complaints (including MI) rather than pulmonary com-
and decreased pancreatic enzymes.79 Additionally, con- plaints.4 However, there is no evidence of distinct allelic
centrations of sodium, potassium, magnesium, heavy frequencies or haplotypic variants in CF patients with MI
metals, and carbohydrates in MI meconium are reduced compared with those without22 or in CF patients with
in CF. Concentrations of protein nitrogen are increased significant liver disease.23,24
and composed of abnormal mucoproteins.1012 Therefore,
more viscous intestinal mucus in the absence of degrad-
ing enzymes results in thick, dehydrated meconium that
Gastrointestinal Pathophysiology
obstructs the intestine.13 Cystic fibrosis is characterized by mucoviscidosis of exo-
crine secretions throughout the body resulting from
abnormal transport of chloride ions across apical mem-
CYSTIC FIBROSIS branes of epithelial cells.4,2527 Abnormal bicarbonate
transport also affects mucin formation in CF.28 The clini-
An understanding of CF is important for all clinicians cal result is chronic obstruction and infection of the res-
involved in the management of MI patients. CF is the piratory tract, insufficiency of the exocrine pancreas, and
439
440 SECTION IV Abdomen
elevated sweat chloride levels.29 Other clinical variants, this process begins in utero, it occurs variably over time.
such as patients with chronic sinusitis or adult males with Regardless, pancreatic insufficiency is prevalent in young
congenital bilateral absence of the vas deferens (CBAVD), infants with CF and has a significant impact on growth
who typically have little other clinical involvement, have and nutrition.23
been described (Fig. 32-1).3032 In patients with CBAVD, Pancreatic insufficiency plays a central role in the
the CFTR genotype usually includes at least one mild pathogenesis of MI. Congenital stenosis of the pancreatic
mutation not typical of CF patients. The mild-mutation ducts is associated with meconium-induced bowel
allele is frequently associated with a severe mutation on obstruction.36 This is further supported by the fact that
the other allele, such as the F508del mutation.6,33 CBAVD two-thirds of infants found to have CF by neonatal
has been described in a patient with F508del and G551D screening are pancreatic insufficient at birth.37 However,
mutations , both of which were categorized as severe.34 approximately 10% of patients with CF are pancreatic
The allele G551D is the third most common CF-associated sufficient and tend to have a milder course. Also, pancre-
mutation, and patients affected by this mutation may atic lesions are variable at birth and become more severe
have pancreatic insufficiency, pulmonary symptoms, and in CF children older than age 1.38 This finding suggests
an episode of MI equivalent, indicating CBAVD may be that pancreatic insufficiency is not the leading cause of
associated with a more severe CF phenotype.7,35 abnormal meconium in MI. It appears that a prevalence
Development of both the pancreas and intestinal tract of intestinal glandular abnormalities contribute more sig-
in fetuses with CF is abnormal. In patients with CF, nificantly to the production of abnormal meconium.39
abnormal pancreatic secretions obstruct the ductal system The lack of concordance between MI and the severity of
leading to autodigestion of the acinar cells, fatty replace- pancreatic disease and the preponderance of intestinal
ment of pancreatic parenchyma, and fibrosis. Although glandular lesions implies that intraluminal intestinal
factors contribute more to the development of MI than
the absence of pancreatic secretions.9,11,12,3643
Abnormal intestinal motility may also contribute to
Internal ring the development of MI. Some patients with CF have
prolonged small intestinal transit times.44,45 Also, the
Gonadal vessels CFTR ion channel defect results in an exocrine secretion
Absent that is rich in sodium and chloride which can lead to
vas deferens further dehydration of the intraluminal contents, result-
ing in impaired clearance.6 Non-CF diseases associated
with abnormal gut motility, such as Hirschsprung disease
and chronic intestinal pseudo-obstruction, have been
associated with MI-like disease, signifying that decreased
peristalsis may allow for increased reabsorption of water,
thus favoring the development of abnormal meconium.4648
of intrauterine intestinal perforation and meconium peri- sample size. Neonatal CF screening programs using the
tonitis. Radiographic findings of obstruction and a large Guthrie blood spot test for raised concentrations of
dense mass with a rim of calcification imply a pseudocyst immunoreactive trypsinogen is available in many coun-
(Fig. 32-5). These calcium deposits are linear and course tries, but must be confirmed in a two-stage approach
along the parietal peritoneum and serosal surface of the incorporating CFTR mutation analysis.86,87 Genetic
visceral organs.83 Interestingly, one-third of cases of com- testing for CFTR mutations is available, however, com-
plicated MI have no radiologic findings that suggest a mercial assays test for a limited number of mutations.
complication.84 Most regional laboratories will provide the results for the
A contrast enema should be performed in all cases of four or five most common mutations for the relevant
low intestinal obstruction in the newborn. We advocate ethnic group or geographical region in their area using
an initial water-soluble contrast enema for both diagnosis the amplification refractory mutation system (ARMS)
and treatment. In MI, contrast instillation is monitored technique. Stool analyses for albumin, trypsin, and chy-
fluoroscopically and demonstrates a colon of small caliber, motrypsin are available, and abnormal values coupled
described as the microcolon of disuse, often containing with operative findings suggest CF.37
small, inspissated rabbit pellets (scybala) of meconium Neonates with MI who fail to respond to nonoperative
(Fig. 32-6). The enema also identifies cecal position, indi- measures may be treated by appendectomy and irrigation
cating whether malrotation is present. In complicated with water-soluble contrast into the small bowel via the
cases, such as atresia, a microcolon with reflux into a small bowel or appendiceal stump.88 The appendix (or
decompressed terminal ileum may be noted.4 If contrast other intestinal biopsy) may be sent for histologic analy-
cannot be refluxed into the dilated small bowel, operative sis. Pathognomonic findings or histology for CF include
exploration is required for diagnosis and therapy. goblet cell hyperplasia and accumulated secretions within
crypts or lumen.89
Diagnostic Testing
The diagnosis of CF is established with a sweat test. A
Nonoperative Management of Simple
sodium concentration of 60mmol/L in 100mg of sweat Meconium Ileus
is diagnostic of CF with 4060mmol/L being intermedi- Neonates should initially be managed as any other
ate (but more likely to be diagnostic in infants) and less newborn with intestinal obstruction. This management
than 40mmol/L being normal.85 The test is typically
performed at several weeks of life to obtain an adequate
should include volume resuscitation and ventilator Potential causes for late perforation include severe bowel
support as necessary. Gastric decompression to prevent distension by fluid osmotically drawn into the intestine
progressive abdominal distension, aspiration, and pulmo- or by injury to the bowel mucosa by the contrast
nary compromise is important. In addition, correction of medium.94 Lower perforation rates have been reported
any coagulation disorders and empiric broad-spectrum more recently, possibly related to less aggressive enema
antibiotic coverage should be initiated. attempts and isotonic enema agents.4,92 Hypovolemic
The majority of newborns with MI can be managed shock is a risk when delivering hypertonic enemas.
nonoperatively. As noted above, the initial management Ischemia caused by overdistension is worsened by hypo
should include an isotonic water-soluble contrast enema perfusion caused by hypovolemia due to inadequate fluid
under fluoroscopic control. The water-soluble enema resuscitation.95
will also exclude other causes of neonatal intestinal
obstruction. Prior to performing the water-soluble
enema, the neonate should receive adequate intravenous
fluid to correct and avoid hypovolemia, receive appropri- Operative Management
ate electrolyte repletion, and be normothermic. Simple Meconium Ileus
Under fluoroscopic control, the water-soluble contrast
material is slowly infused at low hydrostatic pressure The indications for operative management of simple MI
through a catheter inserted into the rectum. Inflation of are inadequate meconium evacuation or a complication
the catheter balloon should be avoided to minimize the from the contrast enema (e.g., perforation). Failure of
risk of perforation. Upon completion, the catheter is nonoperative treatment with the contrast enema may
withdrawn and an abdominal radiograph is obtained to result from the inability to advance the column of enema
evaluate for perforation. The infant is then returned to fluid into the ileum or from an unsuspected associated
the neonatal care unit for intensive monitoring and fluid intestinal atresia. If the enema fails to promote passage
resuscitation. Usually there is rapid passage of meconium of meconium within 24 to 48 hours, or two attempts
pellets followed by semi-liquid meconium, which contin- at washout are unsuccessful, operative intervention is
ues in the ensuing 2448 hours. Upon instillation of the indicated.
enema, extraluminal fluid is drawn into the intestinal At laparotomy, manual evacuation of the inspissated
lumen, hydrating and softening the meconium mass. meconium can be aided by intraoperative instillation of
Warm saline enemas containing 1% N-acetylcysteine 2% or 4% N-acetylcysteine or saline solutions. These
(Mucomyst; Apothecon, Princeton, New Jersey) may fluids can be passed antegrade through a nasogastric tube,
be given to help complete the evacuation.73 Radiographs retrograde through the appendiceal stump, or directly
should be obtained as clinically indicated to confirm into the meconium through an enterotomy. A purse-
evacuation of the obstruction and to exclude late perfora- string suture is placed in the antimesenteric wall of the
tion. If evacuation is incomplete, or if the first attempt bowel and a red rubber catheter is inserted through a
at contrast enema evacuation does not reflux contrast small incision within the purse-string. This is followed
into dilated bowel, a second enema may be necessary. by gentle instillation of the solution into the proximal
However, if progressive distension, signs of peritonitis, bowel and terminal ileum to avoid perforation. Often the
or clinical deterioration occur, operative exploration is thick tenacious meconium can be removed directly
indicated. After two failed attempts at nonoperative through the enterotomy (Fig. 32-7). The dissolved meco-
water-soluble enemas, operative intervention is likely nium and pellets can be either removed directly or milked
warranted. into the colon. It is important that the surgeon avoids
Following successful evacuation and resuscitation, exposure of the meconium to the peritoneum. Once the
5mL of a 10% N-acetylcysteine solution may be admin- meconium is cleared, the enterotomy or appendiceal
istered every six hours through a nasogastric tube to stump is closed. If necessary, an indwelling intestinal
liquefy the upper gastrointestinal secretions. Feedings catheter or a T-tube may be left through the enterotomy
with supplemental pancreatic enzymes for those infants for the purpose of postoperative bowel irrigation, decom-
confirmed with CF may be initiated when signs of pression, pancreatic enzyme instillation, and/or feeding.96
obstruction have subsided. In the past, the success rate of The enterostomy tube should be positioned at the junc-
patients with uncomplicated MI, treated with Gastro- tion of the proximal dilated bowel and collapsed distal
grafin enemas, has ranged between 6383%.90,91 ileum. The irrigations are begun in the early postopera-
However, more recent reports indicate a much lower tive period and after successful clearance of meconium,
success rate likely secondary to the use of isotonic enema the tubes are removed and the enterocutaneous fistula is
fluid.4,92 allowed to close spontaneously.96100
Several potential complications exist with the use of Although uncommon, resection with primary anasto-
enemas in treating MI. The risk of rectal perforation can mosis is occasionally required and was first described in
be avoided by careful placement of the catheter under 1962.101 Anastomotic leakage complicated early attempts
fluoroscopic guidance and by not inflating the balloon- with this approach, but improved results have been
tipped catheter. A 23% perforation rate has been dem- recently reported.102104 Successful outcome following
onstrated in patients when inflated balloon catheters resection with primary anastomosis depends on adequate
were used, and the risk of perforation increases with resection of compromised bowel, complete proximal and
repeated enemas.93,94 Late perforation, occurring between distal evacuation of meconium, and preservation of an
12 and 48 hours following the enema, can occur as well. adequate blood supply.
32 Meconium Disease 445
Other surgical approaches involve resection, anasto- enterostomy, and the Santulli and Blanc proximal enter-
mosis, and temporary enterostomy through which ostomy.98,104 Disadvantages of these and other procedures
postoperative irrigations can be delivered (Fig. 32-8). employing resection and stoma(s) include potential high-
Several stomas have been used: the Mikulicz double- volume stoma output, bowel length loss due to resection,
barreled enterostomy, the Bishop-Koop distal chimney and the need for a second procedure to re-establish intes-
tinal continuity.
Mikulicz stoma
Bishop-Koop stoma
A B
C D
FIGURE 32-8 There are a number of options for surgical management of a neonate with meconium ileus. Options for creation of
an ileostomy include the (A) double-barrel ileostomy (Mikulicz enterostomy), (B) the Bishop-Koop ileostomy, and (C) the Santulli
ileostomy. Both the Bishop-Koop and Santulli ileostomies require an intra-abdominal anastomosis. (D) Another option is to place
a red rubber catheter into the uninvolved proximal small bowel for postoperative irrigations.
446 SECTION IV Abdomen
discrepancy, anastomotic leak/obstruction, and return of aspartate aminotransferase (AST), and bilirubin should
bowel activity. In cases with pseudocyst formation, decor be monitored weekly. The fluid and nutritional status of
tication of the cyst wall is recommended if possible.74 infants who have had significant bowel resection (greater
Although meconium peritonitis is best managed with than one-third) may be difficult to manage. In addition,
an enterostomy, segmental volvulus and intestinal atresia the presence of an ileostomy may lead to excessive losses
(without peritoneal contamination) in stable patients may of fluid and sodium. If access to the distal, defunctional-
be managed with resection, bowel irrigation, and primary ized bowel is possible, drip feeds of glutamine-enriched
anastomosis depending on the state of the intestine. Ulti- formula or instillation of the effluent from the proximal
mately, the goal of operative management is the relief of stoma may be given at low volumes to enhance bowel
intestinal obstruction and the preservation of maximal growth and help prevent bacterial translocation.
intestinal length. Gastric acid hypersecretion is seen in patients who
have short bowel syndrome.111 An acidic intestinal envi-
ronment inactivates pancreatic enzymes and prevents dis-
Postoperative Management solution of enteric-coated microcapsules. H2-receptor
antagonists or proton pump inhibitors may be used as an
Postoperative management requires ongoing resuscita-
adjunct with pancreatic enzyme therapy in patients
tion, including maintenance fluids and replacement of
who have had significant bowel resections. Patients
insensible and gastrointestinal fluid losses, (nasogastric
with excessive sweat and intestinal sodium losses may
suction and ileostomy). Instillation of 2% or 4% N-
develop a total body sodium deficit. Urine sodium should
acetylcysteine via a nasogastric tube, enterostomy tube,
be measured in infants with ileostomies, especially
or via an ileostomy or mucous fistula will help solubilize
when there is growth failure, even if serum sodium levels
residual meconium. In the patient with fetal or neonatal
are normal. Those with a urine sodium less than
bowel obstruction, diagnostic tests to evaluate for CF
10mEq/L will need sodium (and possibly bicarbonate)
should be performed. Stomas should be closed when pos-
supplementation.107,112
sible (four to six weeks) to avoid prolonged problems with
fluid, electrolyte, nutritional losses, and cholestatic
jaundice. Pulmonary Management
Although clinical lung disease is usually a delayed com-
plication, mucous plugging and atelectasis can be seen.
Nutritional Management Prophylactic pulmonary care with chest physiotherapy
Enteral feeds in infants with uncomplicated MI and CF should be initiated early in the postoperative period. The
may be initiated with breast milk or infant formula, along head-down position should not be used as this increases
with supplemental pancreatic enzymes and vitamins.105,106 the risk of gastroesophageal reflux (GER) and aspiration.
Caution must be used when prescribing enteric enzyme Infants should receive nebulized albuterol twice daily fol-
medication to patients with MI/CF. Treatment failures lowed by chest physiotherapy. Prophylactic antibiotics
and complications include fibrosing colonopathy from are contraindicated, and antibiotic therapy should be
excessive enzyme doses and MI equivalent, or distal intes- directed by respiratory cultures, if needed.
tinal obstruction syndrome (DIOS) from inadequate
enzyme therapy or generic substitutions for proprietary
medications.48,105,107109 Often patients with a complicated
Prognosis
postoperative course will require either continuous The prognosis for infants with MI was uniformly poor,
enteral feeds or total parenteral nutrition (TPN). Dila- despite operative treatment, prior to the mid-1900s.
tion of the small bowel by the obstructing meconium may Early series reported mortality rates of 5067%.98,99 The
lead to mucosal damage that could contribute to poor improved survival in infants with MI can be attributed to
peristalsis or malabsorption. In patients with complicated many factors. Advances in prenatal diagnosis, pulmonary
MI or in those with significant loss of intestinal length, and neonatal intensive care, nutrition, antibiotics,
initiating the enteral feeding with a predigested, diluted anesthesia, operative management, and an improved
formula at low continuous volumes is best. If this is well understanding of the pathophysiology and treatment of
tolerated, the concentration should be increased followed the CF complications have resulted in dramatic prognos-
by the volume. Pancreatic enzymes should be given with tic improvement for infants with both complicated and
enteral feeds (even with predigested formula) starting at simple MI.22,113 Survival rates of 85 to 100% have been
2,0004,000 lipase units per 120mL of full strength reported in uncomplicated MI, and up to 93% in com-
formula. Capsules containing enteric-coated micro- plicated cases.4,84,113
spheres can be opened and the contents mixed with Previously, it was thought that patients with CF pre-
formula or applesauce in older infants. The microcap- senting with MI have worse outcomes than those without
sules should not be crushed as this will expose the enzymes MI. However, it is no longer clear if this is accurate.
to the acid of the stomach where they will be destroyed. Several long-term follow-up studies of patients with MI
Uncrushed pancreatic enzymes should be given even with report pulmonary function at age 13 years to be no dif-
MCT-oil containing formulas.110 ferent between those born with and those without
Infants with MI are at increased risk for cholestasis, MI.114,115 However, a recent prospective study found chil-
particularly if they have had or are receiving TPN. Alka- dren with MI have worse lung function and more obstruc-
line phosphatase, alanine aminotransferase (ALT), tive lung disease than those with CF but without MI.111
32 Meconium Disease 447
Furthermore, comparison of the nutritional status of a Children unresponsive to medical management should
similar population of patients with CF suggests that those undergo evaluation for an antireflux procedure. Our pre-
who presented with MI suffer long-term nutritional com- ferred approach is the laparoscopic Nissen fundoplica-
plications and other problems.116 tion. Recent data suggests that a fundoplication may
improve respiratory function (improved FEV1 slope) in
CF children with mild versus moderate disease.125 Patients
with symptomatic GER requiring an antireflux proce-
MECONIUM PLUG SYNDROME dure may benefit from concurrent placement of a gas-
trostomy if inadequate caloric intake is problematic.
The meconium plug syndrome (MPS) was first described
Barrett esophagus, a rare finding in children, has been
in 1956.117 It was hypothesized initially that either colonic
reported in older children with CF.4,126 Although an
motility or the character of the meconium was altered,
antireflux procedure may halt the advancement of meta-
thereby preventing its normal passage and subsequent
plasia, if dysplasia is present, the malignant potential
decompression of the colon in the newborn period.
remains.127 In cases with metaplasia, endoscopic monitor-
Under normal conditions, the terminal two centimeters
ing is the same for patients with CF as those without.127
of neonatal meconium is firm in texture, forming a
In adults, if high-grade dysplasia is confirmed by two
whitish cap. Most newborns pass this meconium cap
pathologists and aggressive medical therapy fails to elimi-
before, during, or shortly after delivery. One in 500 new-
nate the dysplasia, esophagectomy is recommended.
borns will have a longer, more tenacious obstructive plug.
With so little data available in children with CF, at a
Failure to pass this plug results in MPS, and the term
minimum, it is reasonable that patients who have dysplas-
plugged-up babies was coined.
tic esophageal changes should be evaluated for an antire-
The presentation of MPS is similar to that of MI.
flux procedure.
Signs and symptoms include failure to pass meconium,
bilious vomiting, and abdominal distention with an
obstructive pattern on plain abdominal films. Often, the Biliary Tract Disease
meconium plug becomes dislodged following digital
Multiple macroscopic cysts may replace the pancreas in
stimulation of the anus and rectum. Fortunately, colon
CF.27 Although it has been thought that hepatic and pan-
function is generally preserved and returns to normal
creatic dysfunction occurred together, hepatic dysfunc-
following passage of the plug. Ultimately, most of these
tion may occur in patients with normal pancreatic
infants are found to be healthy.
function.128 The most common hepatic complications of
Pathologic causes of MPS include CF, small left colon
CF are steatosis, fibrosis, biliary cirrhosis, atretic gall-
syndrome, and Hirschsprung disease.117120 Less common
bladder, cholelithiasis, sclerosing cholangitis, and biliary
causes include congenital hypothyroidism, maternal nar-
dyskinesia. Obstruction of intrahepatic biliary ductules
cotic addiction, and neuronal intestinal dysplasia. A con-
by abnormal mucoid secretions or inspissated bile, result-
trast enema may be therapeutic as well as diagnostic.
ing from the absence of functional CFTR in bile duct
Following resolution, a sweat test should be performed
epithelial cells, results in the development of cirrhosis in
to exclude CF and a thryroid-stimulating hormone level
patients with CF.128 When biopsied, the classic liver his-
should be obtained. A rectal biopsy should be performed
tology in CF is focal biliary fibrosis with progression to
to evaluate for Hirschsprung disease if there is a dysfunc-
multilobular, biliary cirrhosis. Prolonged cholestatic liver
tional stooling pattern after resolution of the plug.73,118,119
disease in CF patients may lead to cirrhosis, portal hyper-
tension, and ultimately liver failure and death without
liver transplantation.
COMPLICATIONS OF MECONIUM ILEUS Though more common in older patients with CF, int-
rahepatic cholestasis can be seen in the neonate. In
AND CYSTIC FIBROSIS extreme forms, this process can be associated with a
Gastroesophageal Reflux Disease marked decrease in ductal diameter, varying from hypo-
plasia to atresia. Additionally, these neonates are at
GER occurs with increased prevalence in patients with increased risk for cholestatic jaundice when they are not
CF. Aspiration in CF children may aggravate failure to being fed enterally. Cholestatic jaundice is suggested by
thrive, adversely affect pulmonary function, and may prolonged jaundice unresponsive to choleretics, nondi-
account for the predilection of CF lung disease in the lated bile ducts and gallbladder on ultrasound, absent
right upper lobe.121,122 Pathological reflux with endo- biliary excretion on nuclear scan, and characteristic liver
scopic and histological esophagitis is present in more biopsy.129131
than 50% of CF patients and the incidence of GER in End-stage liver disease (ESLD) is manifest by loss of
patients with CF is approximately 80% in patients synthetic function, growth failure, or portal hypertension
younger than 5 years.123 It is clear that early diagnosis and presenting as variceal hemorrhage.132 Although abnormal
treatment of GER is of prime importance if its complica- liver function tests have been noted in 13% of CF
tions are to be minimized and respiratory function patients, only 4.2% manifest overt liver disease (although
maximized. the prevalence is as high as 37% depending on the defini-
Antireflux medications, modification of chest physio- tion of liver disease).133 Portosystemic shunts, transjugu-
therapy, and eliminating the 30 head-down tilt may all lar intrahepatic portosystemic shunts (TIPS), partial
decrease the incidence of GER in this population.124 splenectomy, and endoscopic injection sclerotherapy
448 SECTION IV Abdomen
have been advocated in treating CF patients with portal to the presence of undigested protein and fat, precipita-
hypertension.134 Other surgical options for these patients tion of undigested protein and bile acids in duodenal fluid
are direct ligation of the varices, esophageal transection, with reduced pH, lower water content of pancreatic and
or the Sugiura procedure (gastric devascularization).135,136 duodenal secretions, hyperviscosity of mucus resulting
These procedures are all palliative, with the only curative from abnormal ion and water transport, abnormal regula-
treatment for portal hypertension and end-stage liver tion of mucin secretion, and altered biochemical proper-
disease being orthotopic liver transplantation (OLT). ties of mucus glycoprotein.152154 Precipitating factors
Liver transplantation has been successfully carried out include sudden withdrawal of (or noncompliance with)
in CF patients with ESLD who did not have respiratory enzyme supplementation, immobilization, dehydration,
failure.137,138 There are several successful reports of com- respiratory tract infections, and recovery from surgery.
bined liver and intestinal transplantation, combined liver However, in the majority of cases, no identifiable cause
and pancreas transplant, kidney transplant after com- will be found.4
bined heart and lung transplants, and triple organ trans- DIOS occurs in 1537% of patients with CF, and is
plant (pancreas, liver and kidney) in patients with exocrine seen particularly in those with associated pancreatic
pancreatic insufficiency and insulin-dependent diabetes insufficiency with malabsorption and severe pulmonary
related to CF.4,139,140 Long-term studies are demonstrat- limitation.148,149,151 One study noted a 12% incidence in
ing preservation or maintenance of respiratory function children with CF, with the majority (63%) having MI as
and nutritional status following OLT in patients with an infant.4 Children with normal fat absorption are rarely
CF.137,138 affected.
Gallbladder disease is prevalent in the CF population, Patients with DIOS present with crampy abdominal
including cholelithiasis in up to 24%, and abnormal pain, often localized to the right lower quadrant, and
cholecystograms in 46%.136,141,142 Other abnormalities decreased frequency of defecation. They may complain
include microgallbladder, atretic cystic duct , and hyper- of insidious, debilitating abdominal pain. Physical exami-
viscous mucus. Many CF patients with gallstones are nation in uncomplicated DIOS usually reveals abdominal
asymptomatic, with the incidence of symptomatic gall- distension and a tender mass in the right lower quadrant
bladder disease in CF reported to be approximately with no evidence of peritonitis. Typically, there is no fecal
4%.143 Because the stones are radiolucent, ultrasound impaction on rectal examination and the stool is guaiac
rather than computed tomography (CT) is recommended negative. Different degrees of obstruction can occur,
in patients with CF.136,144 Bile in patients with CF is not ranging from partial (most common) to complete with
cholesterol supersaturated; hence the stones are com- vomiting, abdominal distension, and obstipation.
posed of protein and calcium bilirubinate.141 A supine and erect abdominal film is the most useful
CF patients with symptomatic gallbladder disease initial investigation when DIOS is suspected (Fig. 32-9).
(symptomatic cholelithiasis and/or acute cholecystitis) This will show distended small bowel with scattered air-
should undergo prompt cholecystectomy.144,145 Although fluid levels and a granular, bubbly pattern of intestinal gas
of historical interest only, the complication rate with representing the mixing of air and inspissated meconium
open cholecystectomy was quite low with aggressive pul- in the right lower quadrant, similar to infants with MI.
monary toilet.146,147 The laparoscopic approach is now the Inspissated material in the right colon and distal ileum
accepted standard.4 Due to the low incidence of common can be demonstrated with a water-soluble contrast enema.
bile duct (CBD) stones in CF patients, routine intraop- With this study, an ileocolic intussusception, which can
erative cholangiograms or preoperative endoscopic ret- also be seen in CF patients, can be excluded, and the
rograde cholangiopancreatography (ERCP) are not contrast study itself may prove therapeutic in some cases.
needed.4,147 In fact, the biliary tract abnormalities often The diagnosis of DIOS should take into consideration
encountered in patients with CF make penetration of other potential causes of abdominal pain and intestinal
radiocontrast dye into the biliary tract during ERCP dif- obstruction in CF patients. This constellation of signs
ficult.136 Intraoperative cholangiography is recommended and symptoms has historically been a diagnostic dilemma
if jaundice, pancreatitis, cholangitis, dilated CBD, or pal- in these patients. Intussusception, mechanical small
pable stones in the CBD are present.4 bowel obstruction due to adhesions, appendicitis, Crohn
disease, and biliary tract disease may present similarly.
In the absence of mechanical small bowel obstruction
Distal Intestinal Obstruction Syndrome due to adhesions, intussusception, or appendiceal disease,
DIOS (formerly called MI equivalent) is a recurrent, a trial of medical management aimed at relieving the
partial or complete intestinal obstruction unique to inspissated distal bowel obstruction is suggested. After
teenage and young adult patients with CF that occurs adequate volume resuscitation and colonic enema
secondary to abnormally viscid mucofeculent material in washout, a balanced polyethylene glycol-electrolyte solu-
the distal ileum and right colon.148151 The etiology of tion, such as GoLytely or Colyte, can be given orally
DIOS is unclear, but these patients are more likely to or by nasogastric tube.155 The dose is 2040mL/kg/h
have a history of steatorrhea from pancreatic exocrine with a maximum of 1200mL/h. Alternatively, ingestion
insufficiency despite adequate enzyme therapy. A number of a nonabsorbable intestinal lavage solution may produce
of aspects particular to gastrointestinal function in the the most striking results.156 Younger patients will usually
CF patient may help to explain this syndrome. In addi- require nasogastric tube placement whereas older chil-
tion to inherently slow intestinal motility, other contrib- dren may be able to ingest sufficient volumes of lavage
uting factors may include thickening of chyme secondary solution to relieve the impacted material.
32 Meconium Disease 449
A B
FIGURE 32-9 This 18-year-old with cystic fibrosis presented with crampy abdominal pain that was localized to the right lower
abdomen. In addition, he also had a decreased frequency of defecation. (A) The ground-glass appearance in the loops of bowel on
the right side are typical findings in a patient with distal intestinal obstruction syndrome. (B) The upright abdominal film shows
air-fluid levels. This patient responded well to a contrast enema with relief of his symptoms.
The passage of stool, resolution of symptoms, and the and interval appendectomy. Appendectomy is required in
disappearance of a previously palpable right iliac fossa acute nonperforated appendicitis. If the diagnosis is still
mass imply successful treatment. Sequential abdominal in doubt, diagnostic laparoscopy can be utilized. Many
radiographs will help to document the resolution of surgeons perform incidental appendectomy during other
DIOS, but if symptoms persist then the differential diag- abdominal operations in CF patients.
nosis must be re-considered. Some authors have recom-
mended DIOS prophylaxis with use of scheduled laxatives Intussusception
and high dietary fiber.148
When there is complete obstruction or evidence of Intussusception occurs in approximately 1% of children
peritonitis, an operation is necessary and oral or rectal with CF with the average age of onset of 9.5 years.151 In
therapies are contraindicated. A nasogastric tube should contrast, the average age of onset in children with idio-
be passed for decompression and adequate resuscitative pathic intussusception in the general pediatric population
measures initiated. At laparotomy, the bowel wall will feel is 618 months.121 Toddlers and older children presenting
thickened and filled with tenacious material. It can be with intussusception and a history of recurrent pulmo-
decompressed and irrigated via a small catheter placed nary infections should be tested for CF. The most
through the appendiceal stump, as previously described common site for intussusception is ileocolic, but it may
for uncomplicated MI. It is also possible to leave an irri- be ileoileal, cecocolic, or colocolic.122 The abnormally
gating tube in situ to irrigate the bowel postoperatively. thick stool adheres to the bowel wall and acts as a lead
Some children may require lysis of adhesions and/or point.157 The appendix may also be a lead point.158 Con-
bowel resections with either primary anastomosis or cre- troversy exists over conservative management of intus-
ation of an ostomy.4 susception in CF patients. Some report high rates of
successful hydrostatic reduction, while others report less
optimal results.157,159 If the intussusception is unable to be
Appendicitis reduced operatively, a bowel resection with anastomosis
Abdominal pain is a common complaint of patients with is required. The appendix should be removed at opera-
CF. As they are often already being treated with antibiot- tion in patients with an intussusception.
ics and steroids, the classical clinical signs and symptoms
of appendicitis are often masked, and the diagnosis can
be missed. This results in an increased incidence of per-
Fibrosing Colonopathy
foration and substantial morbidity in this patient group. Fibrosing colonopathy is a result of colonic strictures,
Despite the blunting of clinical signs, there may still be and presents with signs and symptoms of DIOS.105107,160,161
fever and leukocytosis. Depending on the location of the Histologic findings include colonic strictures with his-
appendix, a contrast enema may show deformity of topathologic changes of post-ischemic ulcer repair,
the cecum with an associated mass effect and lack of erythematous cobblestone appearance to the mucosa,
typical inspissated material features of DIOS. With mucosal and submucosal fibrosis, and destruction of
appendiceal perforation, abdominal ultrasound or CT the muscularis mucosa. A change from conventional
scan will show free fluid or an abscess in the region of enteric-coated pancreatic enzymes to high-strength
the cecum. In cases of perforated appendicitis, initial products 1215 months before presentation has been
treatment should be percutaneous drainage of the abscess described.105 In the largest case-control study reported,
450 SECTION IV Abdomen
the absolute dose of pancreatic enzymes, rather than the develop DIOS and fibrosing colonopathy. Furthermore,
type of enzyme, was the strongest predictor of fibrosing patients may be more prone to develop mechanical bowel
colonopathy.105 obstructions later in life if operated on as an infant for
The diagnosis of fibrosing colonopathy should be con- MI.4 Other late complications of MI such as gallstones,
sidered in CF patients who have been exposed to high cirrhosis, and male sterility may also be viewed as late
doses of pancreatic enzymes and present with symptoms complications of CF in general. Many patients with CF
of abdominal pain, distension, chylous ascites, change in are now surviving into the third and even fourth decades
bowel habit, or failure to thrive. Continued diarrhea may of life. Hence, many of the surgical complications of CF
also be a prominent feature, which unfortunately may occur later in life.
prompt the family to increase supplemental enzymes
further. On occasion, the diarrhea may be bloody. A REFERENCES
barium enema may reveal mucosal irregularity, loss of 1. Lister J. Intestinal obstruction: General considerations. Neonatal
haustral markings with a foreshortened colon, and varying Surgery, vol. 3. London: Butterworth; 1990. p. 4213.
degrees of stricture formation. In some cases, the entire 2. DeLorimier AA, Fonkalsrud EW, Hays DM. Congenital
atresia and stenosis of the jejunum and ileum. Surgery 1969;65:
colon is involved. Colonoscopy may show an erythema- 81927.
tous mucosa with areas of narrowing, from which it is 3. FitzSimmons SC. The changing epidemiology of cystic fibrosis.
advisable to take multiple biopsies.73 J Pediatr 1993;122:19.
Initial management should include reduction of the 4. Escobar MA, Grosfeld JL, Burdick JJ, et al. Surgical considera-
tions in Cystic Fibrosis: A 32-year evaluation of outcomes. Surgery
enzyme dosage to 5002500 lipase units/kg per meal. 2005;138:56072.
This should be accompanied with adequate nutritional 5. Stringer MD, Brereton RJ, Drake DP, et al. Meconium ileus due
supplementation which may be enteral elemental feeding to extensive intestinal aganglionosis. J Pediatr Surg 1994;23:
or even TPN temporarily. Those patients who show 5013.
signs of unrelenting failure to thrive, obstruction, uncon- 6. Evans AK, Fitzgerald DA, McKay KO. The impact of meconium
ileus on the clinical course of children with cystic fibrosis. Eur
trollable diarrhea, or chylous ascites will need operative Respir J 2001;18:7849.
intervention. 7. Antonowicz I, Lebenthal E, Schwachman H. Disaccharidase
When exploration is planned electively for patients activities in small intestinal mucosa in patients with cystic fibrosis.
with intractable symptoms, a gentle bowel preparation J Pediatr 1978;92:21419.
may be given preoperatively. The aim of operative inter- 8. Schwachman H, Antionowicz I. Studies on meconium. In: E Leb-
enthal, editor. Gastroenterology and Nutrition in Infancy. New
vention is to resect the affected bowel and perform a York: Raven Press; 1981. p. 8393.
primary anastomosis. Unfortunately, this is not possible 9. Emery J. Laboratory observations of the viscidity of meconium.
with total colonic or rectal involvement, and the patient Arch Dis Child 1954;29:347.
may require an ileostomy or colostomy. It is also not clear 10. Di SantAgnese PA, Dische Z, Danilczenko A. Physiochemical
differences of mucoproteins in duodenal fluid of patients
if this condition completely resolves by reducing the with cystic fibrosis of the pancreas and controls. Pediatrics
enzyme dosage and resecting the involved colon. There- 1957;19:25260.
fore, these patients also require regular follow-up for 11. Green M, Clarke J, Shwachman H. Studies in cystic fibrosis of
signs of recurrence. the pancreas: Protein pattern in meconium ileus. Pediatrics
1958;21:63541.
12. Stephan U, Busch EW, Kollberg H, et al. Cystic fibrosis detection
by means of a test-strip. Pediatrics 1975;55:358.
OUTLOOK 13. Eggermont E, De Boeck K. Small-intestinal abnormalities in
cystic fibrosis patients. Eur J Pediatr Surg 1991;150:8248.
The operative mortality in patients with CF has decreased 14. American College of Obstetricians and Gynecologists Committee
on Genetics. ACOG Committee Opinion No. 486: Update
considerably in the past three decades. The mortality rate on carrier screening for cystic fibrosis. Obstet Gynecol 2011;117:
for meconium ileus and peritonitis was 55% in the 1960s 102831.
and 1970s.159 Moreover, there was a significant decrease 15. Rommens JM, Iannuzzi MC, Kerem BS, et al. Identification of
in survival in the first year of life for these infants com- the cystic fibrosis gene: Chromosome walking and jumping.
Science 1989;245:105965.
pared to those patients with CF who did not have MI.121 16. Kerem BS, Rommens JM, Buchanan JA, et al. Identification
After the first year of life, survival among infants with MI of the cystic fibrosis gene: Genetic analysis. Science 1989;245:
approached that of other infants with CF. Recently, these 107380.
statistics have improved dramatically. There are now 17. Welsh MJ, Anderson MP, Rich DP, et al. Cystic fibrosis trans-
reports documenting a 100% early survival and 86% late membrane conductance regulator: A chloride channel with novel
regulation. Neuron 1992;8:8219.
survival in patients with MI, and a 91.6% survival for 18. Riordan JR, Rommens JM, Kerem B, et al. Identification of the
uncomplicated MI and 85% for complicated cases at 1 cystic fibrosis gene: Cloning and characterization of complemen-
year.113,114 Recently, survival for patients with simple MI tary DNA [published erratum appears in Science 1989; 245:1437.
was found to be 93% (early 100%, late 93%) and com- Science 1989;245:106673.
19. Cystic fibrosis mutation database statistics [Internet]. Toronto:
plicated 89% (early 96%, late 93%).4 Cystic Fibrosis Centre at the Hospital for Sick Children in
Discussing the long-term needs of the patient with MI Toronto; 2012[cited February 8, 2012]. Available from: http://
means discussing the long-term needs of the patient with www.genet.sickkids.on.ca/StatisticsPage.html.
CF. A multidisciplinary approach to the management of 20. Mornet E, Simon-Bouy B, Serre JL, et al. Genetic differences
the surgical patient with CF including respiratory care, between cystic fibrosis with and without meconium ileus. Lancet
1988;1:3768.
nutrition support, and pancreatic enzyme therapy allows 21. Fanconi G, Uehlinger E, Knauer C. Das Coeliakiesyndrom bei
for a low operative morbidity and mortality. Children angeborener zystischer pancreasfibromatose und bronchiektasien.
with MI need long-term follow-up as they are prone to Wien Med Wochenschr 1936;27/28:7536.
32 Meconium Disease 451
22. Kerem E, Corey M, Kerem B, et al. Clinical and genetic compari- 48. Wilcox DT, Borowitz DS, Stovroff MC, et al. Chronic intestinal
sons of patients with cystic fibrosis, with or without meconium pseudo-obstruction with meconium ileus at onset. J Pediatr
ileus. J Pediatr 1989;114:76773. 1993;123:7512.
23. Bronstein MN, Sokol RJ, Abman SH, et al. Pancreatic insuffi- 49. Irish MS, Gollin Y, Borowitz DS, et al. Meconium Ileus: Antenatal
ciency, growth, and nutrition in infants identified by newborn diagnosis and perinatal care. Fetal Matern Med Rev 1996;8:
screening as having cystic fibrosis. J Pediatr 1992;120:53340. 7983.
24. Duthie A, Doherty DG, Williams C, et al. Genotype analysis for 50. Irish MS, Ragi JM, Karamanoukian H, et al. Prenatal diagnosis
delta F508, G551D and R553X mutations in children and young of the fetus with cystic fibrosis and meconium ileus. Pediatr Surg
adults with cystic fibrosis with and without chronic liver disease. Int 1997;12:4346.
Hepatology 1992;15:6604. 51. Irish M, Boriwitz DS, Glick PL. Meconium Ileus. In: Ziegler
25. Wilmott RW, Tyson SL, Dinwiddie R, et al. Survival rates in MM, Azizkhan RG, Gauderer MWL, Weber TR, editors. Opera-
cystic fibrosis. Arch Dis Child 1983;38:8356. tive Pediatric Surgery. Stamford: Appleton & Lange, Co.; 2003.
26. Rescorla FJ, Grosfeld JL. Contemporary management of meco- 52. Dicke JM, Crane JP. Sonographically detected hyperechoic fetal
nium ileus. World J Surg 1993;17:31825. bowel: Significance and implications for pregnancy management.
27. Westwood ATR, Ireland JD, Bowie MD. Surgery in cystic Obstet Gynecol 1992;80:77882.
fibrosisa 20-year review. S Afr J Surg 1997;35:1814. 53. Denholm TA, Crow HC, Edwards WH, et al. Prenatal sono-
28. Quinton PM. Cystic fibrosis: Impaired bicarbonate secretion and graphic appearance of meconium ileus in twins. AJR Am J Roent-
mucoviscidosis. Lancet 2008;372:41517. genol 1984;143:3712.
29. Boat T, Welsh M, Beaudet A. Cystic Fibrosis. In: Scriver C, 54. Caspi B, Elchalal U, Lancet M, et al. Prenatal diagnosis of cystic
Beaudet A, Sly W, Valle D, editors. The Metabolic Basis of Inher- fibrosis: Ultrasonographic appearance of meconium ileus in the
ited Disease. New York: McGraw-Hill; 1989. p. 264980. fetus. Prenat Diagn 1988;8:37982.
30. Dohle GR, Veeze HJ, Overbeek SE, et al. The complex relation- 55. Benacerraf BR, Chaudhury AK. Echogenic fetal bowel in the third
ships between cystic fibrosis and congenital bilateral absence of trimester associated with meconium ileus secondary to cystic
the vas deferens: Clinical, electrophysiological and genetic data. fibrosis. A case report. J Reprod Med 1989;34:299300.
Hum Reprod 1999;14:3714. 56. Fakhry J, Reiser M, Shapiro LR, et al. Increased echogenicity in
31. Jarvi K, McCallum S, Zielenski J, et al. Heterogeneity of repro- the lower fetal abdomen: A common normal variant in the second
ductive tract abnormalities in men with absence of the vas defer- trimester. J Ultrasound Med 1986;5:48992.
ens: Role of cystic fibrosis transmembrane conductance regulator 57. Lince DM, Pretorius DH, Manco-Johnson ML, et al. The clinical
gene mutations. Fertil Steril 1998;70:7248. significance of increased echogenicity in the fetal abdomen. AJR
32. Shin D, Gilbert F, Goldstein M, et al. Congenital absence of the Am J Roentgenol 1985;145:6836.
vas deferens: Incomplete penetrance of cystic fibrosis gene muta- 58. Goldstein RB, Filly RA, Callen PW. Sonographic diagnosis of
tions. J Urol 1997;158:17949. meconium ileus in utero. J Ultrasound Med 1987;6:6636.
33. Daudin M, Bieth E, Bujan L, et al. Congenital bilateral absence 59. Boue A, Muller F, Nezelof C, et al. Prenatal diagnosis in 200
of the vas deferens: Clinical characteristics, biological parameters, pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet
cystic fibrosis transmembrane conductance regulator gene muta- 1986;74:28897.
tions, and implications for genetic counseling. Fertil Steril 60. Bromley B, Doubilet P, Frigoletto FD, Jr, et al. Is fetal hypere-
2000;74:116474. choic bowel on second-trimester sonogram an indication for
34. Escobar MA, Lau ST, Glick PL. Congenital bilateral absence of amniocentesis? Obstet Gynecol 1994;83:64751.
the vas deferens. J Pediatr Surg 2008;43:12223. 61. Nyberg DA; Resta RG, Luthy DA, et al. Prenatal sonographic
35. Bompadre SG, Sohma Y, Li M, Hwang TC. G551D and G1349D, findings of Down syndrome: Review of 94 cases. Obstet Gynecol
two CF-associated mutations in the signature sequences of CFTR, 1990;76:3707.
exhibit distinct gating defects. J Gen Physiol 2007;129:28598. 62. Gollin Y, Shaffer W, Gollin G, et al. Increased abdominal echo-
36. Farber S. The relation of pancreatic achylia to meconium ileus. genicity in utero: A marker for intestinal obstruction. Am J Obstet
J Pediatr 1944;24:38792. Gynecol 1993;168:349.
37. Kerem E, Corey M, Kerem BS, et al. The relation between geno- 63. Bahado-Singh R, Morotti R, Copel JA, Mahoney MJ. Hypere-
type and phenotype in cystic fibrosisanalysis of the most common choic fetal bowel: The perinatal consequences. Prenat Diagn
mutation (delta F508). N Engl J Med 1990;323:151722. 1994;14:9817.
38. Hinen E. Meconium ileus with no pancreatic abnormality. Arch 64. Forouzan I. Fetal abdominal echogenic mass: An early sign of
Dis Child 1950;25:99100. intrauterine cytomegalovirus infection. Obstet Gynecol
39. Thomaidis TS, Arey JB. The intestinal lesions in cystic fibrosis of 1992;80:5357.
the pancreas. J Pediatr 1963;63:44453. 65. Paulson EK, Hertzberg BS. Hyperechoic meconium in the third
40. Glanzmann E. Dysporia entero-bronco-pancreatica congenita trimester fetus: An uncommon normal variant. J Ultrasound Med
familiaris. Ann Paediat 1946;166:289. 1991;10:67780.
41. Buchanan D, Rapoport S. Chemical comparison of normal meco- 66. De Backer AI, De Schepper AM, Deprettere A, et al. Radio-
nium and meconium from patients with meconium ileus. Pediat- graphic manifestations of intestinal obstruction in the newborn.
rics 1952;9:30410. JBR-BTR 1999;82:15966.
42. Bodian M, editor. Fibrocystic Disease of the Pancrease: Congeni- 67. Duchatel F, Muller F, Oury JF, et al. Prenatal diagnosis of cystic
tal disorder of mucous production-mucosis. New York: Grune and fibrosis: Ultrasonography of the gallbladder at 1719 weeks of
Stratton, Inc.; 1953. gestation. Fetal Diagn Ther 1993;8:2836.
43. Foulkes AG, Harris A. Localization of expression of the cystic 68. Rescorla FJ, Grosfeld JL, West KJ, et al. Changing patterns of
fibrosis gene in human pancreatic development. Pancreas treatment and survival in neonates with meconium ileus. Arch
1993;8:36. Surg 1989;124:83740.
44. Bali A, Stableforth DE, Asquith P. Prolonged small-intestinal 69. Donnison AB, Shwachman H, Gross RE. A review of 164 children
transit time in cystic fibrosis. Br Med J (Clin Res Ed) with meconium ileus seen at the Childrens Hospital Medical
1983;287:101113. Center, Boston. Pediatrics 1966;37:83350.
45. Dalzell AM, Freestone NS, Billington D, et al. Small intestinal 70. Holsclaw DS, Eckstein JB, Nixon HH. Meconium ileus: 20 year
permeability and orocaecal transit time in cystic fibrosis. Arch Dis review of 109 cases. AMA M J Dis Child 1965;109:10113.
Child 1990;65:5858. 71. Leonidas JC, Berdon WE, Baker DH, et al. Meconium ileus and
46. Toyosaka A, Tomimoto Y, Nose K, et al. Immaturity of the its complications. A reappraisal of plain film roentgen diagnostic
myenteric plexus is the aetiology of meconium ileus without criteria. Am J Roentgenol Radium Ther Nucl Med
mucoviscidosis: A histopathologic study. Clin Auton Res 1970;108:598609.
1994;4:17584. 72. Santulli T, Blanc W. Congenital atresia of the intestine: Patho-
47. Emery JL. Colonic retention syndrome (megacolon) associated genesis and treatment. Ann Surg 1961;154:93948.
with immaturity of intestinal intramural plexus. Proc R Soc Med 73. Rescorla FJ, Grosfeld JL. Contemporary management of meco-
1973;66:2223. nium ileus. World J Surg 1993;17:31825.
452 SECTION IV Abdomen
74. Careskey JM, Grosfeld JL, Weber TR, et al. Giant cystic meco- 104. Santulli T. Meconium ileus. In: Holder T, Ashcraft K, editors.
nium peritonitis (GCMP): Improved management based on clini- Pediatric Surgery. Philadelphia: W. B. Saunders; 1980.
cal and laboratory observations. J Pediatr Surg 1982;17:4829. 105. FitzSimmons SC, Burkhart GA, Borowitz D, et al. High-dose
75. Andrassy R, Nirgiotis J. Meconium disease of infancy: Meconium pancreatic-enzyme supplements and fibrosing colonopathy
ileus, meconium plug syndrome,and meconium peritonitis. In: in children with cystic fibrosis. N Engl J Med 1997;336:
Holder T, Ashcraft K, editors. Pediatric Surgery. Philadelphia: W. 12839.
B. Saunders; 1990. p. 33140. 106. Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme
76. Rescorla FJ, Grosfeld JL. Intestinal atresia and stensosis: Analysis supplements for patients with cystic fibrosis in the context
of survival in 120 cases. Surgery 1985;98:66876. of fibrosing colonopathy. Consensus Committee. J Pediatr 1995;
77. Dalla Vecchia LK, Grosfeld JL, West KW, et al. Intestinal atresia 127:6814.
and stenosis: a 25-year experience with 277 cases. Arch Surg 107. Coates AJ, Crofton PM, Marshall T. Evaluation of salt supple-
1998;1333:4907. mentation in CF infants. J Cystic Fibrosis 2009;8:3825.
78. Lloyd D. Meconium ileus. In: Welch K, Randolph J, Ravitch M, 108. Hendeles L. Use bioequivalency rating to select generics [letter].
et al, editors. Pediatric Surgery. 4th ed. Chicago: Year Book Am Pharm 1989;NS29:6.
Medical Publishers, Inc.; 1986. p. 84958. 109. Hendeles L, Dorf A, Stecenko A, et al. Treatment failure after
79. Martin LW. Meconium peritonitis. In: Ravitch MM, Welch KJ, substitution of generic pancrelipase capsules. Correlation with in
Benson CD, et al, editors. Pediatric Surgery. Chicago: Year Book vitro lipase activity. JAMA 1990;263:245961.
Medical Publishers; 1979. p. 9525. 110. Durie PR, Newth CJ, Forstner GG, et al. Malabsorption
80. Speck CR, Moore TC, Stout FE. Antenatal roentgen diagnosis of of medium-chain triglycerides in infants with cystic fibrosis:
meconium peritonitis. Am J Radiol 1962;88:56670. Correction with pancreatic enzyme supplement. J Pediatr 1980;
81. Herson R. Meconium ileus. Radiology 1957;68: 56871. 96:8624.
82. Foster MA, Nyberg DA, Mahony BS, et al. Meconium peritonitis: 111. Li Z, Lai HJ, Kosorok MR, et al. Longitudinal pulmonary status
Prenatal sonographic findings and their clinical significance. Radi- of cystic fibrosis children with meconium ileus. Pediatr Pulmonol
ology 1987;165:6658. 2004;38:27784.
83. White H. Meconium ileus: A new roentgen sign. Radiology 112. Bower TR, Pringle KC, Soper RT. Sodium deficit causing
1956;66:56771. decreased weight gain and metabolic acidosis in infants with ileos-
84. Ziegler MM. Meconium ileus. Curr Probl Surg 1994;31:73177. tomy. J Pediatr Surg 1988;23:56772.
85. Gibson LE, Cooke RE. A test for concentration of electrolytes in 113. McPartlin JF, Dickson JA, Swain VA. Meconium ileus. Immediate
sweat in cystic fibrosis of the pancreas utilizing pilocarpine by and long-term survival. Arch Dis Child 1972;47:20710.
iontophoresis. Pediatrics 1959;23:5459. 114. Efrati O, Nir J, Fraser D, et al. Meconium ileus in patients with
86. Wallis C. Diagnosing cystic fibrosis: Blood, sweat, and tears. Arch cystic fibrosis is not a risk factor for clinical deterioration
Dis Child 1997;76:858. and survival: The Israeli Multicenter Study. JPGN 2010;50:
87. Southern KW, Munck A, Pollitt R, et al. A survey of newborn 1738.
screening for cystic fibrosis in Europe. J Cyst Fibros 115. Johnson J, Bush A, Buchdahl R. Does presenting with meconium
2007;6:5765. ileus affect the prognosis of children with cystic fibrosis? Pediatr
88. Fitzgerald R, Conlon K. Use of the appendix stump in the treat- Pulmonol 2010;45:9518.
ment of meconium ileus. J Pediatr Surg 1989;24:899900. 116. Lai HC, Kosorok MR, Laxova A, et al. Nutritional status of
89. Oppenheimer EH, Easterly JR. Pathological evidence of patients with cystic fibrosis with meconium ileus: A comparison
cystic fibrosis patients with meconium ileus. Pediatr Res 1973;7: with patients without meconium ileus and diagnosed early through
339. neonatal screening. Pediatrics 2000;105:5361.
90. Noblett H. Meconium Ileus. In: Ravtch M, Welch K, Benson C, 117. Clatworthy H, Howard W, Lloyd J. The meconium plug syn-
et al, editors. Pediatric Surgery. 3rd ed. Chicago: Year Book drome. Surgery 1956;39:13142.
Medical Publishers; 1979. p. 94351. 118. Flake AW, Ryckman FC. Meconium plug syndrome. In: Fanaroff
91. Rowe MI, Furst AJ, Altman DH, et al. The neonatal response to AA, Martin RJ, editors. Neonatal-Perinatal Medicine, Disease of
gastrografin enema. Pediatrics 1971;48:2935. the Fetus and Infant. 5th ed. St. Louis: Mosby-Year Book; 1992.
92. Copeland DR, St Peter SD, Sharp SW, et al. Diminishing role of p. 10545.
contrast enema in simple meconium ileus. J Pediatr Surg 119. Keckler SJ, St Peter SD, Spilde TL, et al. Current significance of
2009;44:21302. meconium plug syndrome. J Pediatr Surg 2008;43:8968.
93. Ein S, Shandling B, Reilly B, et al. Bowel perforation 120. Stewart DR, Mixon GW, Johnson DG, et al. Neonatal small left
with nonoperative treatment of meconium ileus. J Pediatr Surg colon syndrome. Ann Surg 1977;186:74195.
1987;22:1467. 121. Gross K, Desanto A, Grosfeld JL, et al. Intra-abdominal compli-
94. Rowe MI, Seagram G, Weinberger M. Gastrografin-induced cations of cystic fibrosis. J Pediatr Surg 1985;20:4315.
hypertonicity. The pathogenesis of a neonatal hazard. Am J Surg 122. Beierle EA, Vinocur CD. Gastrointestinal surgery in cystic
1973;125:1858. fibrosis. Curr Opin Pulm Med 1998;4:31925.
95. Lutzger LG, Factor SM. Effects of some water-soluble contrast 123. Malfroot A, Dab I. New insights on gastro-oesophageal reflux in
media on the colonic mucosa. Radiology 1976;118:5458. cystic fibrosis by longitudinal follow up. Arch Dis Child
96. Steiner Z, Mogilner J, Siplovich L, et al. T-tubes in the manage- 1991;66:133945.
ment of meconium ileus. Pediatr Surg Int 1997;12:1401. 124. Button BM, Heine RG, Catto-Smith AG, et al. Postural drainage
97. Jawaheer J, Khalil B, Plummer T, et al. Primary resection and and gastro-oesophageal reflux in infants with cystic fibrosis. Arch
anastomosis for complicated meconium ileus: A safe procedure? Dis Child 1997;76:14850.
Pediatr Surg Int 2007;23:10913. 125. Boesch RP, Acton JD. Outcomes of fundoplication in children
98. Bishop H, Koop C. Management of meconium ileus: Resection, with cystic fibrosis. J Pediatr Surg 2007;42:13414.
Roux-en-Y anastomosis and ileostomy irrigation with pancreatic 126. Hassall E, Isreal DM, Davidson AG, et al. Barretts esophagus in
enzymes. Ann Surg 1957;145:41014. children with cystic fibrosis: Not a coincidental association. Am J
99. Gross R. The surgery of infants and childhood. Philadelphia: W. Gastroenterol 1993;88:19348.
B. Saunders Co.; 1953. 127. McDonald ML, Trastek VF, Allen MS, et al. Barretts esophagus:
100. Harberg FJ, Senekjian EK, Pokorny WJ. Treatment of uncompli- Does an antireflux procedure reduce the need for endoscopic
cated meconium ileus via T-tube ileostomy. J Pediatr Surg surveillance? J Thorac Cardiovasc Surg 1996;111:11358.
1981;16:613. 128. Cohn JA, Strong TV, Picciotto MR, et al. Localization of
101. Swenson O. Pediatric Surgery. 2nd ed. New York: Appelton- the cystic fibrosis transmembrane conductance regulator in
Century-Crofts; 1962. human bile duct epithelial cells. Gastroenterol 1993;105:
102. Mabogunje OA, Wang CI, Mahour H. Improved survival of 185764.
neonates with meconium ileus. Arch Surg 1982;117:3740. 129. Shapira R, Hadzic N, Francavilla R, et al. Retrospective review of
103. Chappell JS. Management of meconium ileus by resection and cystic fibrosis presenting as infantile liver disease. Arch Dis Child
end-to-end anastomosis. S Afr Med J 1977;52:10934. 1999;81:1258.
32 Meconium Disease 453
130. Greenholz SK, Krishnadasan B, Marr C, et al. Biliary obstruction 146. Anagnostopoulos D, Tsagari N, Noussia-Arvanitaki S, et al. Gall-
in infants with cystic fibrosis requiring Kasai portoenterostomy. J bladder disease in patients with cystic fibrosis. Eur J Pediatr Surg
Pediatr Surg 1997;32:17580. 1993;3:34851.
131. Oppenheimer EH, Esterly JR. Hepatic changes in young infants 147. Saltzman DA, Johnson EM, Feltis BA, et al. Surgical experience
with cystic fibrosis: possible relation to focal biliary cirrhosis. in patients with cystic fibrosis: A 25-year perspective. Pediatr
J Pediatr 1975;86:6839. Pulmonol 2002;33:10610.
132. Scott-Jupp R, Lama M, Tanner MS. Prevalence of liver disease in 148. Hanly JG, Ritzgerald MX. Meconium ileus equivalent in older
cystic fibrosis. Arch Dis Child 1991;66:698701. patients with cystic fibrosis. Br Med J 1983;286:141113.
133. Roy CC, Weber AM, Morin CL, et al. Hepatobiliary disease in 149. Dalzell AM, Heaf DP, Carty H. Pathology mimicking distal intes-
cystic fibrosis: A survey of current issues and concepts. J Pediatr tinal obstruction syndrome in cystic fibrosis. Arch Dis Child
Gastroenterol Nutr 1982;1:46978. 1990;65:5401.
134. Debray D, Lykavieris P, Frdric G, et al. Outcome of cystic 150. Matseshe JW, Go VLW, Dimagno E. Meconium ileus equivalent
fibrosis-associated liver cirrhosis: Management of portal hyper- complicating cystic fibrosis in post-neonatal children and young
tension. J Hepatol 1999;31:7783. adults. Gastroenterology 1972;72:7326.
135. Karrer FM. Portal hypertension. Semin Pediatr Surg 1992;1: 151. Van der Doef HP, Kokke FT, van der Ent CK, et al. Intestinal
13444. obstruction syndromes in cystic fibrosis: Meconium ileus, distal
136. Williams SGJ, Westaby D, Tanner MS, et al. Liver and intestinal obstruction syndrome, and constipation. Curr Gastro-
biliary problems in cystic fibrosis. Br Med Bull 1992;48: enterol Rep 2011;12:26570.
87792. 152. Wilschanski M, Rivlin J, Cohen S, et al. Clinical and genetic risk
137. Dowman JK, Watson D, Loganathan S, et al. Long-term impact factors for cystic fibrosis-related liver disease. Pediatrics
of liver transplantation on respiratory function and nutritional 1999;103:527.
status in children and adults with cystic fibrosis. Am J Transplant 153. Marino CR, Gorelick FS. Scientific advances in cystic fibrosis.
2012;12:95464. Gastroenterology 1992;103:68193.
138. Miller MR, Sokol RJ, Narkewicz MR, et al. Pulmonary function 154. Kopelman H, Corey M, Gaskin K, et al. Impaired chloride secre-
in individuals with cystic fibrosis from the USA cystic fibrosis tion, as well as bicarbonate secretion, underlies the fluid secretory
foundation registry who had undergone liver transplant. Liver defect in the cystic fibrosis pancreas. Gastroenterology
Transpl 2012;18:58593. 1988;95:34955.
139. Fridell JA, Mazariegos GV, Orenstein RS, et al. Liver and intes- 155. OHalloran SM, Gilbert J, McKendrick OM, et al. Gastrografin
tinal transplantation in a child with cystic fibrosis: A case report. in acute meconium ileus equivalent. Arch Dis Child 1986;61:
Pediatr Transplant 2003;7:2402. 112830.
140. Stern RC, Mayes JT, Weber FL Jr. Restoration of exocrine pan- 156. Cleghorn GJ, Forstner GG, Stringer DA, et al. Treatment of
creatic function following pancreas-liver-kidney transplantation distal intestinal obstruction syndrome in cystic fibrosis with a bal-
in a cystic fibrosis patient. Clin Transplant 1994;8:14. anced intestinal lavage solution. Lancet 1986;1:811.
141. Angelico M, Gandin C, Canuzzi P, et al. Gallstones in cystic 157. Holsclaw DS, Rocmans C, Shwachman H. Intussusception in
fibrosis: A critical reappraisal. Hepatology 1991;14:76875. patients with cystic fibrosis. Pediatrics 1971;48:518.
142. Rovsing H, Sloth K. Micro-gallbladder and biliary calculi in 158. Coughlin JP, Gauderer MWL, Stern RC, et al. The spectrum of
mucoviscidosis. Acta Radiol 1973;14:58892. appendiceal disease in cystic fibrosis. J Pediatr Surg 1990;
143. Lheureux PR, Isenberg JN, Sharp HL, et al. Gallbladder disease 25:8359.
in cystic fibrosis. AJR Am J Roentgenol 1977;128:9536. 159. Olsen MM, Gauderer MWL, Girz MK, et al. Surgery in patients
144. Stern RC, Rothstein FC, Doershunk CF. Treatment and progno- with cystic fibrosis. J Pediatr Surg 1987;22:61318.
sis of symptomatic gallbladder disease in patients with cystic fibro- 160. Lloyd-Still JD, Beno DW, Kimura RM. Cystic fibrosis colonopa-
sis. J Pediatr Gastroenterol Nutr 1986;5:3540. thy. Curr Gastroenterol Rep 1999;1:2317.
145. Snyder CL, Ferrell KL, Saltzman DA, et al. Operative therapy of 161. Serban DE, Florescu P, Miu N. Fibrosing colonopathy revealing
gallbladder disease in patients with cystic fibrosis. Am J Surg cystic fibrosis in a neonate before any pancreatic enzyme sup-
1989;157:55761. plementation. J Pediatr Gastroenterol Nutr 2002;35:3569.
C H A P T E R 3 3
Necrotizing Enterocolitis
Kathleen M. Dominguez R. Lawrence Moss
Necrotizing enterocolitis (NEC) is not a new disease. Though over 90% of cases are seen in preterm infants,
Reports of a disease fitting the clinical characteristics of there are occasional reports of NEC developing in full-
NEC date to the 1820s in France.1 The earliest reports term infants. Although the clinical and pathologic find-
in the USA occurred in the early 1960s, when Santulli ings are similar, the initiating factors are likely different.
and colleagues published the first significant surgical Term infants who develop NEC are more likely to have
experience with NEC.2,3 They described a disease of low predisposing risk factors such as congenital heart disease,
birth weight infants with a high mortality rate, which sepsis, respiratory disease, or reported hypoxic events.1720
requires early, aggressive surgical management. Many The common feature of these predisposing conditions is
investigators have devoted careers to better define this reduced mesenteric perfusion.18 The incidence of
challenging disease and improve strategies for treatment NEC in term or near term infants is approximately 0.5
and prevention. Despite these efforts, NEC remains a per 1000 live births.20 The mortality rate for term infants
difficult and elusive disease. It remains unclear which with NEC appears to be similar to that of preterm infants
premature infants are most at risk and what are the with NEC.18
optimal prevention and treatment strategies. Long-term The morbidity associated with NEC translates into
sequelae are easily overlooked in the acute setting, but considerable economic burden. In one study, infants with
contribute substantially to the subsequent morbidity and NEC were hospitalized 60 days longer than unaffected
mortality. preterm infants if operation was needed, and 20 days
longer if medical treatment was successful.21 In this study,
the mean hospital costs were $186,200 greater for surgi-
EPIDEMIOLOGY cally treated patients than controls and $73,700 greater
for medically treated patients. In addition to the high
Several large population-based studies have found the costs associated with the initial hospitalization, these chil-
incidence of NEC to be approximately 1 per 1000 live dren often have significant long-term health care needs.
births. In select populations, such as infants under 1500g, The mean cost of care for a child with short bowel syn-
the incidence rises to between 2.311% (Table 33-1). Both drome over a five-year period exceeds $1.6M.22
the incidence and case fatality rate of NEC are inversely
associated with birth weight.49 Several studies have iden-
tified an increased incidence of NEC in black infants, PATHOPHYSIOLOGY
particularly males, a difference that holds true even when
adjusting for birth weight. Hispanic infants also show an Despite decades of research into the pathogenesis of
increased incidence, though to a lesser degree.4,10 NEC, a complete understanding of its pathophysiology
Despite improvements in other areas of neonatal care, remains elusive. Classic histologic findings include
rates of NEC have remained stable for very low birth inflammation, bacterial overgrowth, and coagulation
weight infants (VLBW) infants.11 Mortality remains necrosis, and are present in over 90% of surgical speci-
high, with rates ranging from 1530%.4,5,9,10,12 Higher mens.23 Radiographic findings provide insight into the
fatality rates are associated with lower birth weight and pathologic process that is unfolding. Pneumatosis intes-
younger gestational age.12,13 In a study summarizing tinalis, or air within the intestinal wall, is thought to be
trends for mortality and NEC in the USA between 1979 due to gas produced by overgrowth of enteric bacteria.24
and 1992, the death rate was 12.4 deaths per 100,000 live Progression to portal venous or lymphatic gas suggests
births.13 The highest mortality rate was seen in VLBW extension of this process along vessels draining the
infants who were black and male.4,10,13 affected intestine. Pneumoperitoneum indicates necrosis
Although most cases of NEC are managed medically, with complete disruption of the intestinal wall.
2040% will require operative intervention.5,7,12,14 Mor- As our understanding of the pathophysiology of NEC
tality increases up to 50% when surgery is necessary, and evolves, a working model of the multifactorial nature of
has not changed significantly over the past 30 years. The this disease has emerged. The unifying concept is that
highest risk for mortality in this subgroup is also in the NEC represents an exaggerated inflammatory response
lowest birth weight and youngest gestational age infants.15 to an insult. The nature of this insult is not well defined,
Long-term outcomes in patients requiring operation and may vary among affected infants. It may be a global
are worse, with increased complications such as neurode- ischemic insult from congenital heart disease, an infec-
velopmental delay, growth delay and chronic gastrointes- tious insult from abnormal bacterial colonization, an
tinal problems.16 insult related to formula feeding or lack of enteral feeding,
454
33 Necrotizing Enterocolitis 455
or simply the response of translocation of normal bacte- An increased ileal bile acid level may play a role in the
rial flora in a genetically predisposed host. pathogenesis of NEC. Bile acids are known to be cyto-
Whatever the insult, it leads to a disruption of the toxic, resulting in the development of mucosal injury.33
intestinal epithelial barrier followed by translocation of In premature infants, levels of ileal bile acid-binding
bacteria. There is an exaggerated or inappropriate protein are lower, leading to increased levels of bile acids
immune response, likely owing to the immature nature in the intestinal lumen and in enterocytes.34 Another risk
of the intestine and immune system. Stress pathways factor which may contribute is formula feeding, which
become activated, and pathways that normally suppress elicits more toxic bile acids than breast feeding.35
the immune system are inhibited. The end result is
activation of the host immune system and release of The Mucous Coat
cytokines, leading to a global, detrimental inflammatory
response. The mucous coat overlying the intestinal epithelium
plays a key role in the barrier function. This layer is
composed of water, mucin, lipids, and peptides.36 Mucin,
The Intestinal Barrier a glycoprotein, is secreted by goblet cells in the epithelial
The pathologic features of NEC suggest that failure of layer and concentrates enzymes near the intestinal
the intestinal barrier is either a cause or result of disease surface.37,38 Mucin aids in lubrication, mechanical protec-
progression. The normal intestinal barrier is composed tion, protection against the acidity of gastric and duode-
of both mechanical and non-mechanical factors. The nal secretions,39 and fixation of pathogens.40 The
mechanical factors include intestinal peristalsis, the effectiveness of mucin is related to maturity.39 Mature
mucous coat, and tight junctions between epithelial cells. mucins have higher viscosity, better pH buffering, and
Non-mechanical factors include immunologic defenses resistance to bacterial breakdown.3941 Mucin production
and cellular homeostasis and regeneration. and composition changes with gestational age, bacterial
challenges, and colonization by commensal organisms.4244
Deficits in the production or composition of mucin may
Intestinal Motility and Digestion
contribute to the ability of bacteria to invade the intesti-
Intestinal motility develops during the third trimester of nal epithelium and thus contribute to the pathogenesis of
pregnancy but may not be fully mature until the eighth NEC.32,36,37,4547
month of gestation.2528 In premature infants, immature
motility leads to increased epithelial exposure to poten- Tight Junctions
tially noxious substances, and poor clearance of bacteria
with subsequent overgrowth. Additionally, the immature Tight junctions create fusion points between epithelial
intestine has decreased digestion and absorption, which cells, forming an intact yet semipermeable barrier. Mature
may lead to direct epithelial injury through a lowered tight junctions are composed of the transmembrane pro-
pH.2931 Newborns have reduced gastric acidity and pan- teins occludin, claudin, and junctional adhesion protein;
creatic enzyme activity, which may further contribute to these normally present a barrier to diffusion of large
impaired digestion of macromolecules and bacterial molecules.32,48 Tight junctions are not static, but may
proliferation.32 be altered by disease processes.49 Immaturity in the
456 SECTION IV Abdomen
composition of tight junctions likely plays a role in the abundant proinflammatory stimuli. LPS is seen in high
increased permeability of the epithelium of the newborn levels in NEC.24 LPS impairs intestinal barrier function
intestine.50 by inhibiting repair and promoting the release of signal-
Cytokines are produced in response to bacteria, and ing molecules and proinflammatory mediators such as
may interfere with tight junctions, promoting the trans- NO, IFN-, cyclooxygenase-2 (COX-2) and RhoA from
location of bacteria.51 Inflammatory mediators such as enterocytes which promote intestinal injury.49,6062 LPS
tumor necrosis factor, interferon (IFN)-, and interleukin causes increased expression and function of integrins on
(IL)-1 further cause epithelial dysfunction by upregulat- the cell surface, resulting in increased cell adhesion to the
ing inducible nitric oxide synthase (iNOS) leading to basement membrane,63 and compounds the effects of
the overproduction of nitric oxide (NO), and the genera- platelet-activating factor (PAF).64,65
tion the reactive nitrogen intermediate peroxynitrite
(ONOO). This process has been associated with Nitric Oxide
increased epithelial cell apoptosis and death.52 NO has
been shown to play a role in mediating the decrease in NO is a key mediator of numerous physiologic and path-
the localization and expression of tight junction pro- ologic systems, but has been shown to have a paradoxical
teins.49,53 Disruption of tight junctions may lead to role in NEC. Low levels of NO are important for main-
increased intestinal permeability, allowing bacterial taining vasodilation; conversely, sustained overproduc-
translocation and activation of the immune system. tion of NO can have profound cytopathic effects. The
cytopathic effects of NO are believed to be due to toxic
Immunologic Defenses of the nitrogen intermediates, such as ONOO.32
NO is a highly reactive free radical formed by the
Gastrointestinal Tract conversion of arginine to citrulline by NO synthase
The gastrointestinal tract contains the largest amount of (NOS) which exists in three forms: the constitutive form
lymphoid tissue in the body and coordinates the immu- (nNOS), the inducible isoform (iNOS), and the constitu-
nologic mechanisms of the adaptive and innate immune tive endothelial isoform (eNOS).66 The presence of the
systems.54 Gut-associated lymphoid tissue consists of constitutive forms of NOS in the gastrointestinal tract
several cell types which work in concert to perform suggests that NO has a normal physiologic role in gut
antigen presentation and processing37,55 function. The eNOS isoform maintains intestinal home-
In neonates, antigen processing and presentation is ostasis by enhancing mucosal blood flow and maintaining
less efficient, reducing the ability of the immune system microvascular tone.67
to respond to pathogenic organisms. Peyer patches are When produced by iNOS under inflammatory condi-
fewer, smaller, and lack germinal centers.36 Paneth cell tions, the NO level increases up to a million fold,67 which
activation by bacteria or components of bacterial cell can lead to cellular damage and failure of the intestinal
walls leads to secretion of a variety of antibacterial sub- barrier. Excess NO overwhelms local scavenging mecha-
stances, including -defensins and lysozyme.56,57 Produc- nisms and reacts with superoxide anion (O2) to produce
tion of these peptides is decreased in premature infants, the highly toxic ONOO.6769 These effects may be com-
and may predispose to bacterial overgrowth, allowing pounded in the presence of high levels of LPS, which
NEC to develop. Following recovery from NEC, Paneth leads to increased iNOS expression and function within
cell hyperplasia occurs, suggesting these cells play an the intestine.6970 Studies have linked NO with the patho-
important role in NEC.56 genesis of NEC. The expression of iNOS has been shown
IgA is normally synthesized by plasma cells of the to be upregulated in critically ill patients and in patients
lamina propria and secreted into the mucin layer where with NEC.52 Conversely, expression is down regulated by
it binds bacteria and viruses, inhibiting attachment to the the anti-inflammatory cytokine interleukin-10.71 Excess
epithelium. The newborn lamina propria is largely devoid NO may also inhibit intestinal restitution by blocking
of the IgA-secreting plasma cells, resulting in deficient enterocyte migration and proliferation.32,49,72
secretion until several weeks of age.58,59 Neonates can
obtain IgA through passive transfer from breast milk,49 Platelet-Activating Factor
but infants who do not receive breast milk lack this
important immunoglobulin and its protective effects. PAF is potent phospholipid inflammatory mediator that
is produced by most cells and tissues.73,74 The cytotoxic
effects of PAF are due to initiation of the inflammatory
Regenerating the Intestinal Barrier cascade. PAF-induced bowel injury is associated with the
The pathologic findings of NEC arise not only from production of oxygen-derived free radicals as well as leu-
alterations in the integrity of the intestinal barrier but kocyte migration, activation, and capillary leakage result-
also from an impaired ability to regenerate.60 Premature ing in apoptosis in affected enterocytes.75
infants have a reduced capacity for intestinal repair, likely Various studies have shown the importance of PAF in
contributing to the pathogenesis of NEC. the pathogenesis of NEC. Higher concentrations of PAF
have been found in NEC patients compared with
controls.7577 PAF-acetylhydrolase (AH) activity has been
Lipopolysaccharide
shown to be deficient in sick infants with NEC, and the
Lipopolysaccharide (LPS) is the endotoxin portion of the administration of PAF-AH or a PAF receptor antagonist
Gram-negative bacterial cell wall, and is one of the most in animal models of NEC reduces the degree of intestinal
33 Necrotizing Enterocolitis 457
injury.74,76,78 PAF-AH is present in maternal breast milk, and released within the intestineone vasoconstrictive
which may contribute to the protective effect against and one vasodilatory.101,102 Endothelin (ET)-1 is the
NEC it provides.74 primary vasoconstrictor stimulus in the newborn intes-
tine and is produced by the endothelium.103,104 Although
constitutively produced, it can also be stimulated by
Maintaining Intestinal Barrier decreased flow, hypoxia, and various inflammatory
Homeostasis cytokines.105107 The production of ET-1 is age specific,
being greater in younger subjects.103
Epidermal Growth Factor
NO is the primary vasodilator stimulus.98,99 eNOS is
Epidermal growth factor (EGF) is a peptide secreted into also continuously produced, but like ET-1 the rate of
the intestinal lumen.79 It plays an important role in the production can be increased in response to a variety of
development, maturation, and maintenance of gut stimuli.101 In the neonate, the balance of these two prod-
homeostasis, being active in processes from intestinal ucts favors vasodilation, generating the characteristic low
repair and adaptation to cell movement and prevention vascular resistance. In disease states, endothelial dysfunc-
of bacterial translocation.8086 EGF has been shown to tion leads to ET-1 mediated vasoconstriction, causing
support maintenance of the intestinal barrier, as well as compromised blood flow, intestinal ischemia, and injury.
being active in the down regulation of inflammatory The vasoconstrictor ET-1 has been linked to intestinal
cytokines.79,86 tissue injury in several studies.103,108 Increased expression
EGF is believed to play an important role in the of ET-1 has been found in intestine removed from infants
pathogenesis of NEC. Decreased levels of EGF have with NEC, and the amount of ET-1 increased propor-
been demonstrated in the saliva and serum of premature tionally to the degree of intestinal injury.102
infants with NEC.87 Furthermore, studies have shown In summary, the intestinal circulation of the newborn
that salivary levels of EGF in the first two weeks of is unique, with a dynamic balance between constrictor
preterm life may have a predictive value for the occur- (ET-1) and dilator (NO) stimuli maintaining basal vascu-
rence of NEC.88 A potentially therapeutic role for EGF lar resistance. Disruption of the intestinal endothelial
was reported in an infant suffering from intestinal necro- function can alter the delicate balance, favoring vasocon-
sis resembling NEC who received a continuous infusion striction over the normal state of vasodilation, leading to
of EGF resulting in complete recovery of the damaged significant intestinal ischemia and tissue injury.
intestine.89 These investigators subsequently treated a
small group of neonates with stage II and III NEC in a
randomized, double-blind, prospective trial with recom-
Bacterial Colonization
binant EGF and found that repair of the intestinal epi- NEC is most commonly diagnosed during the second
thelium was seen at four, seven, and 14 days.90 week of life, after intestinal colonization has been estab-
Heparin-binding EGF (HB-EGF) is a member of this lished. Bacteria likely play a role in the pathogenesis of
family of growth factors, and is found in amniotic fluid NEC, though studies have not identified a single infec-
and breast milk.91 In animal models of NEC, administra- tious agent. NEC likely arises from an unfavorable
tion of HB-EGF has been shown to reduce the incidence balance between commensal and pathogenic bacteria.
of bowel injury by 50%, more than double survival,9295 Abnormal colonization may alter the balance of patho-
and preserve the integrity of the intestinal barrier.96 genic and beneficial bacteria, favoring an increase in
Animals with overexpression of HB-EGF have decreased pathogenic bacteria and resulting in a loss of the benefi-
susceptibility to NEC,97 while animals with deletion of cial role of commensal bacteria. Furthermore, the imma-
the HB-EGF gene have increased susceptibility.86,97 ture immune system of premature infants may not be able
These effects seem to be at least in part due to the cyto- to respond appropriately to normal colonization of bac-
protective effects of HB-EGF, which serves to protect teria, much less abnormal flora.109
intestinal stem cells from injury.86
EGF and HB-EGF have a role as a potential preven-
tive strategy for NEC. These compounds may have a CLINICAL DIAGNOSIS
protective effect by altering the balance of pro- and anti-
inflammatory cytokines in the pathogenesis of NEC, and The diagnosis of NEC is based on clinical and radio-
may also play a role in decreasing bacterial translocation graphic findings. The clinical course can vary from a
from the intestine. Active research is ongoing. slow, indolent process to a rapid fatal progression. Early
signs are nonspecific, including apnea, bradycardia, leth-
Neonatal Vasculature and the argy, and temperature instability. Feeding intolerance,
demonstrated by high gastric residuals, is the most
Pathogenesis of NEC common gastrointestinal symptom of NEC. The most
Newborn intestinal circulation is characterized by a low common presenting sign is abdominal distention. Gross
resting vascular resistance.98,99 This results in increased or occult blood in the stool may be found.
blood flow and oxygen delivery. Control of vascular Gastrointestinal signs progress from abdominal dis-
resistance involves intrinsic and extrinsic control mecha- tention to tenderness suggestive of peritoneal irritation
nisms.100 Extrinsic mechanisms are mediated by the auto- (Fig. 33-1). Palpable loops of intestine may become
nomic nervous system. The intrinsic regulation is evident. Localized disease may progress to generalized
mediated by two vascular effector mechanisms produced peritonitis or may worsen in a focal area, including
458 SECTION IV Abdomen
discoloration of the skin and the development of an avoiding prolonged periods without enteral nutrition as
abdominal mass. When present, the findings of a fixed well as the use of unnecessary tests and antibiotics.115
abdominal mass and erythema of the abdominal wall are Serum acute phase proteins and cytokines have been
strongly predictive of dead bowel; however, these find- investigated for an association between high levels and
ings occur in only 10% of patients with NEC.110 A sudden the severity of NEC. Increased levels of IL-6, IL-10, and
need for increased ventilatory support may also serve as C-reactive protein (CRP) have been documented in pre-
a harbinger of NEC.111 This is due to increased metabolic mature infants with NEC, with the highest levels of
requirements combined with increased intra-abdominal IL-10 in those patients who did not survive.116 CRP has
pressure. also been associated with NEC when the levels rose
Confirmation of the diagnosis of NEC combines signs quickly after the diagnosis was suspected. A failure of the
and symptoms with radiologic findings. These findings levels to return to normal has been found to be associated
have been combined into the clinical staging system pro- with complications, including abscesses, strictures, and
posed by Bell that aids in describing the severity of disease sepsis.117 In a prospective study, CRP levels were elevated
(Table 33-2).112,113 in infants with stage II and III NEC and may be useful
in discriminating between stage II NEC and other gas-
trointestinal disorders.118
Laboratory Studies Multiple other potential markers have been studied
Laboratory studies reveal nonspecific indicators of an gastrointestinal tonometry, urinary d-lactate levels,
inflammatory or infectious process such as leukocytosis exhaled breath hydrogen, endotoxin elevations in stool,
with bandemia. Thrombocytopenia and metabolic acido- plasma intestinal fatty acid-binding proteinsbut none
sis are also common. A rapid fall in platelet count is a of these has yielded the sensitivity or specificity required
poor prognostic factor.114 for a diagnostic tool.61,119121 Currently, no biochemical
Several studies have tried to identify an accurate bio- markers have been adequately predictive of the patients
chemical marker to identify neonates at risk for NEC, clinical course or outcome to be clinically useful.
Radiographic Findings
Plain Films
The cornerstone of the radiographic diagnosis of NEC
relies on plain radiographs. The most specific radio-
graphic finding is pneumatosis intestinalis, as seen in
Figure 33-2. Other radiographic findings include air
fluid levels, gas-filled loops of bowel, persistently dilated
loops of bowel, thickened bowel walls, portal venous gas,
and pneumoperitoneum. Although most commonly seen
in NEC, pneumatosis intestinalis has also been reported
in cases of Hirschsprung enterocolitis, severe diarrhea,
and carbohydrate intolerance. Portal venous gas (Fig.
33-3) is a less common radiographic finding but is gener-
ally considered a poor prognostic sign. This finding is
associated with twice the incidence of diffuse or pan
necrosis and a significantly lower survival rate.122 Never-
FIGURE 33-1 This infant has NEC. Note the abdominal disten- theless, many patients with portal venous gas recover
sion and abdominal wall erythema. fully with medical management.
33 Necrotizing Enterocolitis 459
DIFFERENTIAL DIAGNOSIS
The most clinically relevant differential diagnosis in a
premature infant with abdominal distention is distin-
guishing between NEC and sepsis with ileus. In the
absence of clinical signs of peritonitis or radiographic
signs of NEC, the two conditions may be indistinguish-
able and only differentiated after observing the clinical
course. The differential diagnosis also includes other
conditions that may cause abdominal distention, such as
Hirschsprung disease, ileal atresia, volvulus, meconium
ileus, and intussusception.
A subset of premature infants presents with bowel
perforation while not exhibiting other symptoms of NEC
FIGURE 33-3 Portal venous gas (arrow) is demonstrated on this nor pneumatosis on radiographs. Some investigators have
abdominal radiograph. This finding is considered a poor prog- defined this as spontaneous, isolated, or focal intestinal
nostic sign. This baby also has widespread pneumatosis perforation (FIP). FIP tends to occur in low birth weight
intestinalis. infants, usually the first seven to ten days of life, and is
sometimes associated with indomethacin treatment.134140
Whether these infants have a limited form of NEC or a
Other Imaging Modalities
distinct entity is controversial. Some reports contend that
Studies have examined ultrasonography (US) as an FIP is a different disease than NEC, but definitive evi-
adjunctive measure for the diagnosis and management of dence is lacking.139142 As expected, neonates with an iso-
infants with NEC. Abdominal ultrasound evaluation lated bowel perforation have better outcomes in the
emerged as a potential modality in the treatment of NEC absence of extensive disease.138,143145
after a report in 2005 that assessed bowel viability using
color Doppler imaging in neonates with NEC.123 This
publication established critical data for bowel wall thick- MEDICAL MANAGEMENT
ness, echogenicity, peristalsis, and perfusion in both
normal neonates and those with NEC. Additional studies Medical management of NEC begins with bowel rest,
corroborated the usefulness of ultrasound as a means of gastric decompression, intravenous fluid resuscitation,
diagnosing NEC.124,125 ultrasound offers some potential and broad-spectrum antibiotic therapy, including anaero-
advantages over plain films in that it can depict bowel bic coverage. Blood, urine, and sputum cultures should
wall thickness and echogenicity, free and focal fluid col- be obtained before the initiation of antibiotic therapy. A
lections, peristalsis, and the presence or absence of bowel critical component of medical management is ongoing
wall perfusion by using Doppler imaging.126,127 close observation with serial abdominal examinations and
460 SECTION IV Abdomen
Experimental Medical
Treatments: HB-EGF
Endogenous HB-EGF is increased in response to hypoxia,
stress, and during wound healing.146151 HB-EGF mRNA
is induced after intestinal ischemia/reperfusion injury in
vivo152 and is involved in epithelial cell repair, prolifera-
tion, and regeneration in the early stages after injury.153
Based on these findings, it has been theorized that exog-
enous HB-EGF may also play a role protecting the intes-
tinal mucosa from injury.
Multiple studies have demonstrated that exogenous FIGURE 33-4 Free air (arrows) is seen on this radiograph. This
finding is an indication of perforation, and is considered an
administration of HB-EGF can protect cells and organs absolute indication for intervention, whether drainage or
from injury both in vitro and in vivo. HB-EGF can exploration.
protect enterocytes from proinflammatory cytokine-
induced apoptosis.154 Intestinal epithelial cells pretreated
with HB-EGF before hypoxia showed less necrosis with condition despite maximal medical management. Such
maintenance of the cytoskeletal structure and improved signs can include oliguria, hypotension, worsening meta-
recovery ability.155 HB-EGF also downregulates the pro- bolic acidosis, worsening thrombocytopenia, leukopenia
duction of NO156,157 and blocks NF-B activation in or leukocytosis, and ventilatory failure. Relative radio-
intestinal epithelial cells after cytokine stimulation.157 In graphic indicators for operation include portal venous gas
a neonatal rat model of NEC, the administration of or persistently abnormal fixed loops of bowel on serial
HB-EGF reduced the severity and incidence of NEC radiographs.
with preservation of gut barrier integrity.92 Studies have Ideally, surgical intervention would occur when intes-
also shown that treatment with HB-EGF decreases the tinal gangrene is imminent but before actual perforation
overproduction of IL-18 and increases the production of or necrosis actually occurs. However, this ideal time for
anti-inflammatory IL-10.158 HB-EGF is the only com- intervention is often difficult to identify. One study has
pound with imminent plans for investigation in humans. tried to evaluate the sensitivity and specificity of 12 dif-
A host of other therapeutic agents have shown promise ferent findings to identify early indicators for opera-
but not yet reached the stage of clinical testing. tion.110 Three findings had a specificity and positive
predictive value (PPV) close to 100% with prevalence
greater than 10%. These findings were deemed the best
SURGICAL MANAGEMENT indications and included portal venous gas and a positive
paracentesis (Table 33-3). Three indicators had specifi-
Although many infants can be managed medically, city and PPV close to 100% but prevalence less than 10%
2040% will require operative intervention. In some and were considered good indicators, including a fixed
cases, indication for operation develops during the loop on an abdominal radiograph, erythema of the
medical management, while in others it is found at pres- abdominal wall, and a palpable abdominal mass. One
entation. The only absolute indication for drainage or indicator, severe pneumatosis, was deemed fair because it
exploration is evidence of intestinal perforation either on had a specificity and PPV above 90% and 20% preva-
an abdominal radiograph (Fig. 33-4) or via paracentesis lence. The five remaining indicators were considered
that is positive for stool or bile.159 Relative indications for poor because the specificities were less than 90% and the
operation include deterioration in the infants clinical PPVs less than 80%. This probability analysis may be
TABLE 33-3 Probability Analysis of Various Indications for Operation in Necrotizing Enterocolitis
Indication Sensitivity (%) Specificity (%) Positive predictive Value (%)
Pneumoperitoneum 48 100 100
Portal venous gas 24 100 100
Fixed loop (on radiograph) 12.5 100 100
Fixed abdominal mass 12.5 100 100
Erythema of abdomen 8 100 100
Positive paracentesis 87 100 97
Severe pneumatosis 31 94 91
Clinical deterioration 39 89 78
33 Necrotizing Enterocolitis 461
useful in the complex decision-making process when an element of neurologic impairment at 18 to 22 months.
operation is being considered. The babies in this study were not randomized to their
NEC can affect any segment of the gastrointestinal treatment groups. The treating surgeons and neonatolo-
tract. Most commonly, both large and small bowel are gists chose which therapy to use for each infant. However,
involved.23 Isolated small intestinal lesions occur with the unlike other nonrandomized studies, extensive prospec-
next greatest frequency. It is as common to have a single tive data were collected, allowing for risk-adjusted mul-
affected area as to have multiple-segment disease.23,160,161 tivariable regression analyses. This strategy enabled the
A small subgroup of NEC patients develop massive investigators to account for the differences between the
necrosis of the entire intestine, known as NEC totalis.160 treatment groups. The odds ratio for death after adjust-
Traditional operative management has consisted either ing for differences in the two treatment groups was 0.97
of laparotomy with limited resection of the affected for laparotomy compared with peritoneal drainage (95%
bowel with creation of stomas or of primary peritoneal confidence interval [CI]: 0.432.20). The odds ratio for
drainage. Much of the attention of surgical investigators the combined outcome of death or neurodevelopmental
of NEC has focused on the relative benefits of these impairment at 18 to 22 months was 0.44 for laparotomy
approaches. compared with drainage (95% CI: 0.161.2). Although
Peritoneal drainage was first reported in 1977 as not statistically significant, there is some suggestion
salvage treatment for perforation in VLBW infants in this study that overall outcomes at 18 to 22 months
who were believed to be too unstable for laparotomy of age may be improved by laparotomy rather than
(Fig. 33-5).162 Initially intended as a temporizing proce- drainage.
dure in the sickest and smallest patients, this treatment The first randomized trial evaluating laparotomy
has evolved into a widely utilized option as primary treat- versus peritoneal drainage was the NECSTEPS trial.165
ment of perforated NEC. After many years of conflicting In this trial, 117 VLBW infants at 15 North American
results comparing outcomes of the two approaches, a tertiary care centers were randomized to either treatment
meta-analysis was attempted to synthesize these disparate group. The primary outcome variable was mortality at 90
data. This study found such significant bias in the assign- days. There was no difference in mortality at 90 days
ment of patients to one treatment or another that the two between the two treatment groups (34.5% vs 35.5%).
options could not be adequately compared.163 A need Need for parenteral nutrition at 90 days and the length
existed for a prospective randomized controlled trial. of hospitalization were also similar between the two
Three prospective studies have compared laparotomy groups. This study focused on short-term outcomes;
to peritoneal drainage. The NICHD Neonatal Research within those limits, results suggest that the method of
Network conducted a prospective observational cohort surgical intervention does not impact the outcome.
study at 16 centers.164 This study included 156 infants The second randomized trial comparing laparotomy
with either NEC or FIP. Overall 50% (n = 78) of the and peritoneal drainage in infants with perforated NEC
patients died and 72% (n = 112) either died or had some was the NET trial.166 This trial was a multinational trial
FIGURE 33-5 A micropremature infant with NEC and perforation is shown with her corresponding abdominal radiograph. A percu-
taneous drain (arrows) has been placed in the right lower quadrant for drainage of the intestinal perforation. Note that the drain is
placed at a position below the level of the umbilicus to avoid injury to the lower edge of the right lobe of the liver.
462 SECTION IV Abdomen
conducted at 31 centers in 13 countries. The primary segments are left in the abdomen, and continuity is
outcome variable was mortality at 1 and 6 months. Sixty- restored or ostomies are created on re-exploration in 48
nine patients weighing less than 1000g were enrolled to 72 hours. Proximal diversion alone has also been used
and randomized. There was a trend toward better sur- to treat pan necrosis without reported worsened survival
vival in the laparotomy group (65% survival) compared and with recovery of much of the bowel by the time of
with the drainage group (51%), with a relative risk of ostomy closure.172 None of these approaches has been
mortality of 0.5 (95% CI: 0.21.5). These findings were prospectively evaluated; therefore, no single technique
not statistically significant. The authors concluded that can be strongly advocated.
there was no evidence from the trial to support the benefit
of primary peritoneal drainage in extremely low birth
weight (LBW) infants with intestinal perforation. OUTCOMES
Overall, both of these randomized trials suggest that
the method of surgical management does not affect the Recurrence
ultimate outcome of infants with perforated NEC. The
impact of choice of operation on the outcome of infants, NEC recurs in approximately 5% of cases.173,174 There is
who underwent operation for an indication other than no apparent correlation between the site of disease and
perforation, is not known. Most commonly, these infants the site of recurrence. Usually recurrent disease can be
are treated with laparotomy. managed nonoperatively.159,174179
An additional randomized trial is currently underway.
The NEST trial is designed to compare long-term out- Length of Hospitalization
comes in extremely LBW infants (1000g) with necro-
tizing enterocolitis or isolated intestinal perforation Hospital stays are longer for infants who suffer from
treated by either laparotomy or peritoneal drainage. The NEC when compared with other infants of the same
primary outcome is death or neurodevelopmental impair- gestational age. Furthermore, those who require opera-
ment at 1822 months corrected gestational age. Results tion tend to have even longer hospitalization. Several
are expected in the fall of 2015.167 studies have shown hospitalizations averaging two to
When laparotomy is performed, stomas are usually three months for medically treated NEC and four to five
created. Because of concerns about the high morbidity months for surgically treated NEC.180182 There was no
associated with enterostomies (Box 33-1), a few centers difference in length of hospitalization between the two
have advocated primary anastomosis at the time of initial treatment groups in the NECSTEPS trial.165
laparotomy. The data to support such management are
nonrandomized and retrospective. In actuality, the major- Mortality
ity of stomal complications are easily managed and early
closure is well tolerated.168 One study found that survival Estimates of mortality from NEC have remained steady
was 72% with intestinal diversion but only 48% in those over the past two decades at 1530% despite the fact that
undergoing primary anastomosis.169 the postsurfactant era has led to a rise in the incidence
Diffuse intestinal involvement poses the most difficult of disease.4,5,9,10,12,13,180,181,183,184 Operative mortality has
situation for the surgeon. Those infants who survive may improved with a decline from 70% mortality in the
develop short bowel syndrome and have some level of 1960s185 to more recent rates of 2050%.5,10,13,180,183,186,187
dependency on total parenteral nutrition given the exten- The main predictor of mortality in NEC is gestational
sive amount of affected bowel. Surgical strategies focus age. The highest mortality occurs in the youngest, small-
on trying to preserve as much intestine as possible while est infants, and black male VLBW infants are at greatest
still resecting enough bowel to stabilize the patient. risk. Additionally, infants with a greater extent of bowel
Second-look laparotomies have been proposed as a way affected by the disease tend to also have a higher mortal-
to minimize the amount of bowel resected.170 The clip ity rate.188,189
and drop-back technique is another option with a similar
strategy.171 All nonviable intestine is resected initially but
no ostomies or anastomoses are created. Blind-ending Gastrointestinal Outcomes
Short Bowel Syndrome
NEC is the leading disease responsible for short bowel
BOX 33-1 Enterostomal Complications syndrome (SBS) in children, accounting for half of all
pediatric cases. Furthermore, SBS develops in a fourth of
Prolapse all patients who suffer from NEC.190 SBS develops when
Stricture an infant is left with inadequate functional intestine to
Retraction absorb the nutrients required for growth. This can result
Wound separation or dehiscence from resection at the time of operation or from poor
Wound infection
function of the remaining intestine. Traditional teaching
Parastomal hernia
Intestinal obstruction based on early reports suggests that a minimum of 40cm
Intestinal torsion of small intestine is required for a patient to have a chance
Fistula formation of weaning from total parenteral nutrition.191 Despite
these observations, experience has shown that the
33 Necrotizing Enterocolitis 463
function of the intestine is much more important to this proximal stomas due to fluid and electrolyte losses and
disease than the specific length of intestine. the inability to gain weight. Coexisting medical problems
The portion of intestine resected is also important for must also be considered in determining the optimal time
subsequent gastrointestinal functioning. Patients with for closure.
ileal or jejunal disease have a higher mortality rate than
those with colonic disease.187,188,192,193 Patients with exten- Intestinal Strictures
sive jejunal resection fare better than those with extensive
ileal resection. This is due to the differing abilities of the Intestinal strictures are a common occurrence after NEC.
intestinal regions to undergo adaptation. The ileum has The incidence of stricture has been reported from
the greatest capacity to adapt and increase its absorptive 1235%, and occurs in patients who have been managed
capacity. medically or surgically.131,207,216221 This incidence does
Preservation of the ileocecal valve has been considered not differ between patients treated by primary anastomo-
important for minimizing the risk of SBS.194 Some studies sis or enterostomies.159,186,187,199,206,207,212,215227 In one series
have suggested that dependence on parenteral nutrition of patients treated for severe NEC by proximal diverting
is lessened when the ileocecal valve was preserved,195198 enterostomy, the incidence was 55%.217 Most post-NEC
but others have found no difference.180,199202 It appears strictures occur in the colon, specifically the left colon
that the actual length and functional capacity of the (Fig. 33-6).160,212,219,226,228
remaining ileum is far more important than the presence Resection of strictures is usually needed, although not
of the valve itself. all lesions are symptomatic and spontaneous resolution
has been reported.131,224,229,230 Other approaches have been
proposed, including close radiographic follow-up of
Stoma Complications
asymptomatic patients.131 Balloon dilatation is an option
Creation of a properly constructed stoma can be life- for focal, nonobstructing lesions, but has not been widely
saving in the management of NEC. Stomas are used for utilized.230
both decompression and diversion. Enterostomies can be Patients treated by laparotomy and stoma for NEC
fraught with early and late complications. A number of should undergo routine imaging of the distal intestine
strategies have been proposed for optimal stoma creation, before enterostomy closure to evaluate for a possible
including what type of stoma to create as well as how to stricture. Patients managed medically, by peritoneal
exteriorize the stoma. End stomas, double-barrel (Miku- drainage, or with primary anastomosis may also develop
licz) stomas, and loop enterostomy have all been advo- strictures. Some patients remain asymptomatic and others
cated. Small studies comparing complication rates present acutely in distress due to perforation.219 Thus,
between these various strategies have not found differ- some surgeons advocate contrast studies in all NEC
ences in complications, including retraction, prolapse, patients.131,218,219,221 The potential for false-negative results
hernias, or wound infections.203205 Many surgeons exte- and the invasiveness of the procedure prevent this prac-
riorize the stoma and mucous fistula through the incision, tice from being commonly used.
some at one end, others at opposite ends of the incision. Little is known about the long-term impact of stric-
Others advocate a separate incision, citing concerns ture formation after NEC. Infants who require ostomy
about increased wound infection and difficulties attach- closure may have strictures addressed at that time. For
ing stoma appliances. Another consideration for a sepa- those managed without ostomies, stricture resection
rate incision is whether the stoma needs to remain for a requires a new operation with subsequent prolongation
prolonged period of time. Most surgeons do not recom-
mend maturing a stoma owing to potential interference
with an already tenuous blood supply.203
Stomal complications can lead to significant morbid-
ity. Studies have shown complication rates exceeding
50%.187,206209 The most serious complications include
prolapse, stricture, and retraction, all of which may
require surgical intervention. Proximal jejunostomies can
cause significant electrolyte and fluid losses that can lead
to problems with fluid balance and weight gain.194,210
Fluid losses from jejunostomies can also cause peristomal
skin complications. Despite these problems, with an
aggressive approach to fluid and electrolyte replacement
and meticulous skin care, proximal jejunostomies can be
a viable option for the management of NEC.194,211
The timing of enterostomy closure remains contro-
versial. Recommendations vary from as early as one
month to as late as four months after operation.212215
Most suggest waiting one to two months after the initial FIGURE 33-6 This contrast enema demonstrates a stricture
(arrow) in the ascending colon after nonoperative management
operation, and until a weight of 2000g is reached, as long for NEC. NEC strictures may occur anywhere in the intestinal
as adequate feeding and growth is being main- tract, but are most common in the left colon. These can develop
tained.194,210,213 Earlier closure may be necessary with very whether the baby was treated medically or surgically.
464 SECTION IV Abdomen
of recovery and time to full enteral feeding. Resection of educational classes,231 and delays in locomotor, hearing
additional bowel may also ultimately impact gastrointes- and speech, intellectual performance, and social skills.234
tinal outcomes. A large multicenter cohort study from the NICHD
Neonatal Research Network evaluated neurodevelop-
mental outcomes in 1100 extremely LBW survivors.238
Growth
This study confirmed that NEC is associated with
Several small observational studies have shown that chil- increased odds of having a delayed score on psychomotor
dren treated for NEC fall below the 50th percentile developmental assessment as well as increased odds of
for height and weight even into their grade-school cerebral palsy. This study found that almost all of these
years.231233 This growth retardation seems particularly to abnormalities occurred in patients who required an oper-
affect those who suffered from stage III NEC.234,235 The ation for NEC.239
problem is much more severe in children who develop Two systematic reviews have confirmed the increased
SBS as a result of NEC. Long-term evaluations of growth risk of neurodevelopmental impairment in VLBW infants
are required to evaluate the impact that birth weight, who develop NEC (Fig. 33-7).240,241 The risk for those
NEC severity, operative strategy, and subsequent out- treated surgically is nearly twice the risk for those treated
comes may play in ultimate growth outcomes for these medically. Most infants with NEC who are treated medi-
children. cally develop like age-matched premature infants without
NEC, whereas those requiring an operation have an
increased risk of poor neurodevelopmental outcomes.
Neurodevelopmental Outcomes
In infants surviving NEC, adverse neurodevelopmental
outcomes remain an important challenge. In 1980, a PREVENTION
groundbreaking study reported that less than half of chil-
dren surviving NEC were neurodevelopmentally normal Prevention of NEC has become a major focus of research
at three-year follow-up.236 Subsequently, multiple obser- because management strategies have had little impact on
vational studies have cited intellectual delays,237 moderate- mortality. Prevention has focused on two main aspects of
to-severe developmental delay with speech and motor care: feeding strategies and infectious characteristics of
impairment,183 developmental delay requiring special the gastrointestinal tract.
gastrointestinal tract. Supplementation with arginine has rates, with increased levels of Lactobacillus and decreased
been considered as a potential preventive measure for counts of Enterobacter.277 Another study showed that
avoiding NEC. One randomized controlled trial of 152 administering Bifidobacterium probiotics to preterm
preterm infants found a significant reduction in NEC in infants lowered the levels of pathogenic species such as
those infants receiving this supplementation.254 This Enterobacter and Clostridium in their intestines compared
small study was unable to evaluate stage II and III NEC with controls who did not receive the probiotics.278 These
independently; further research on this possible preven- studies all suggest that the use of probiotic supplementa-
tive measure needs to be performed to confirm these tion can influence intestinal colonization.
results.255 Once it was shown that such changes in intestinal flora
A deficiency of serum glutamine has also been corre- could be manipulated, the next step lay in determining
lated with NEC.256 Glutamine is fuel for enterocytes and what clinical effect this might have on these preterm
promotes the growth and integrity of the intestinal epi- infants. One large prospective cohort study using histori-
thelium. Glutamine has also been postulated as having cal controls evaluated whether newborns given Lactobacil-
protective effects against NEC. Two large multicenter lus acidophilus and Bifidobacterium infantis would have
randomized trials have failed to show a benefit for those reduced rates of NEC.279 They studied 1237 infants over
who received glutamine.257,258 A Cochrane systematic one year with a mean gestational age of 35 weeks and
review of five trials also did not show any benefit to the mean birth weight of 2040g. These infants were treated
infants receiving glutamine.259 with each probiotic daily until discharge. The results
were compared with historical controls from the preced-
ing year. During the treatment year, the incidence
Oral Antibiotics of NEC was 3% compared with 6.6% the year before
Given the role of bacteria in the pathogenesis of NEC, (p < 0.0002). Furthermore, no side effects were noted.
enteral antibiotics have been considered as possible NEC Subsequently, there have been many studies analyzing
prophylaxis. The use of antibiotics also increases the the effects of probiotic supplementation in preterm
potential for the development of resistant bacteria. Five infants. The first meta-analysis in 2007 reviewed seven
randomized trials have examined the effects of prophy- randomized controlled trials involving a total of 690
lactic therapy with enteral antibiotics. No individual infants who received no treatment and 703 who received
study found a significant reduction in NEC; however, probiotics (Table 33-4).280 The relative risk for NEC in
when the five were combined together in a meta-analysis, the group that received probiotics was 0.36 (95% CI:
there was a significant reduction in the incidence of NEC 0.200.65). These results must be considered with caution
in those who received the antibiotics.260 Unfortunately, because this meta-analysis combined studies that had
these studies did not report on the potential harmful many significant differences. This heterogeneity nor-
effects of this use of enteral antibiotics. Without suffi- mally would preclude the method of meta-analysis.291
cient evidence regarding the safety of using enteral anti- Considerable variability among the studies in the demo-
biotics as prophylaxis, an endorsement for this prophylactic graphics of the patients, the age at commencement of
measure cannot be made. treatment, and the type, dose, and duration of probiotic
treatment existed. Though this meta-analysis found no
increased risk of sepsis in the treatment group, side effects
Probiotics of probiotics were not adequately addressed due to lack
Probiotics are live microbial supplements that colonize of power to detect serious infections. Given the high-risk
the gastrointestinal tract. They have been proposed as a population in which these probiotics would be used, the
means of protecting against NEC. These supplements issue of safety is crucial.
contain potentially beneficial bacteria or yeasts, most A 2012 meta-analysis included 20 studies with a total
commonly Lactobacillus, Bifidobacterium, and Streptococcus of 3816 patients. For preterm VLBW patients receiving
strains.261 They can enhance the mucosal barrier by probiotic supplements, the incidence of stage II or higher
reducing permeability, increasing mucus production, NEC was 3% compared to 7.4% in the placebo group,
inhibiting bacterial translocation, and strengthening with a RR of 0.33 (95% CI, .0240.46; p < 0.00001).292
tight junctions.42,262267 Colonization with these organ- Due to differences in the type of probiotics used in the
isms can reduce the ability of pathogenic bacteria to studies, subgroup analysis was performed; the three main
adhere to the intestinal mucosa.268,269 Probiotics have also probiotic agents (Bifidobacteria, Lactobacillus, and Bifido-
been shown to increase the production of mucosal IgA bacteria and Lactobacillus) all showed a significant risk
and short-chain fatty acids that help the immature reduction. Overall mortality was reduced in the group
immune system.270272 Additionally, they decrease intesti- receiving probiotics as well: RR of 0.56 (95% CI 0.43
nal inflammation through the reduction of proinflamma- 0.73; p < 0.0001). In regards to safety of probiotics, four-
tory cytokines, the increase of anti-inflammatory teen of the trials reported data for culture positive sepsis.
cytokines, and the increase of cytokine production by In VLBW infants receiving probiotics, there was no dif-
T-cells.273276 ference in the risk of culture positive sepsis.
Studies have examined the ability of probiotics to nor- These studies suggest that probiotics are safe and
malize intestinal flora and to prevent NEC. One rand- effective in reducing the incidence of NEC and mortality
omized controlled trial showed that administration of without increasing the risk of sepsis. Despite the many
Bifidobacterium breve within the first 24 hours and contin- studies available in the literature, there is heterogeneity
ued for 28 days can change the intestinal colonization in type of probiotic, timing of therapy, and dosing.
33 Necrotizing Enterocolitis 467
TABLE 33-4 Clinical Trials Evaluating Probiotics and The Incidence of Necrotizing Enterocolitisa
Incidence of NEC
Study
(First Author) Population Number Probiotic STUDY GROUP CONTROL p Value Comment
Dani 281
<33 weeks 585 LBG 4/295 (1.4%) 8/290 (2.8%)
or <1500g
Lin282
<1500g 367 LBA, BI 2/180 (1.1%) 10/187 (5.3%) 0.04
BinNun283 1500g 145 BI, BBB, ST 3/72 (4%) 12/73 (16.4%) 0.031
Kitajima284 <1500g 91 BB 0/45 0/46 1 NEC a secondary
outcome measure
Costalos285 2832 weeks 87 SB 5/51 (9.8%) 6/36 (16%) 0.5 NEC a secondary
outcome measure
Manzoni286 <1500g 80 LBC 1/39 3/41 0.51 NEC a secondary
outcome measure
Mohan287 <37 weeks 38 BBL 2/21 1/17 NEC a secondary
outcome measure
Manzoni288 <1500g 319 BLF or BLF 3/153 (1.9%); 10/168 (6%) 0.09; 0.002 NEC a secondary
plus LGG 0/151 (0%) outcome measure
Braga289 <1500g 231 BB, LBC 0/119 4/112
Lin290 <1500g 434 BBB, LBA 4/217 20/217 0.002
BB, Bifidobacterium breve; BBB, Bifidobacterium bifidus; BBL, Bifidobacterium lactis; BI, Bifidobacterium infantis; BLF, bovine lactoferrin;
LBA, Lactobacillus acidophilus; LBC, Lactobacillus casei; LBG, locust bean gum; LGG, Lactobacillus rhamnosus GG; SB, Saccharomyces
boulardii; ST, Streptococcus thermophilus.
a
See references for further information.
Long-term effects are also not well studied. While pro- disease,295 advanced approaches using proteomic and
biotics are a very promising preventative strategy, ques- genomic techniques should be considered to compare
tions still need to be addressed. those who develop NEC with those who do not, as well
as those who progress to severe disease with those who
have a mild course. Novel treatment strategies such as
Epidermal Growth Factor growth factors should be evaluated. Any trial of treatment
As discussed earlier, EGF plays an important role in the should include evaluation of both short- and long-term
pathogenesis of NEC. Premature infants in general, and outcomes. Finally, because no treatment for NEC will be
infants with NEC specifically, have been shown to have uniformly effective once the disease is established,
decreased salivary concentrations of EGF.87 Because EGF research efforts should focus on approaches to prevent
is known to support the maintenance of the intestinal this disease.
barrier and downregulate proinflammatory cytokines,122
its use has been postulated to help prevent NEC. A pre- REFERENCES
liminary study of neonates diagnosed with NEC has 1. Obladen M. Necrotizing enterocolitis150 years of fruitless
shown that administration of EGF will promote the search for the cause. Neonatology 2009;96:20310.
repair of the intestinal epithelium. In animal models, 2. Santulli TV, Schullinger JN, Heird WC, et al. Acute necrotizing
enterocolitis in infancy: A review of 64 cases. Pediatrics
supplementation with EGF has decreased the incidence 1975;55:37687.
of NEC.293 HB-EGF has been shown to have similar 3. Touloukian RJ, Berdon WE, Amoury RA, et al. Surgical experi-
effects. Trials to test both EGF and HB-EGF as preven- ence with necrotizing enterocolitis in the infant. J Pediatr Surg
tive strategies are planned.294 1967;2:389401.
4. Llanos AR, Moss ME, Pinzon MC, et al. Epidemiology of neo-
natal necrotising enterocolitis: A population-based study. Paediatr
Perinat Epidemiol 2002;16:3429.
CONCLUSION 5. Guthrie SO, Gordon PV, Thomas V, et al. Necrotizing entero-
colitis among neonates in the United States. J Perinatol
Despite many advances in the care of premature infants, 2003;23:27885.
6. Horbar JD, Badger GJ, Carpenter JH. Trends in mortality and
NEC remains a challenging disease with a relatively con- morbidity for very low birth weight infants, 1991-1999. Pediatrics
stant incidence rate over the past four decades. The only 2002;110:14351.
clearly established risk factor is prematurity. Insight has 7. Sankaran K, Puckett B, Lee DS, et al. Variations in incidence of
been gained into the pathophysiology of this disease, with necrotizing enterocolitis in Canadian neonatal intensive care
units. J Pediatr Gastroenterol Nutr 2004;39:36672.
a unifying hypothesis emerging: an excessive and uncon- 8. Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of
trolled inflammatory response by the neonatal intestine extremely preterm infants from the NICHD Neonatal Research
after exposure to an inciting event. Future research efforts Network. Pediatrics 2010;126:44356.
will focus on further elucidating the underlying causes 9. Guillet R, Stoll BJ, Cotten CM, et al. Association of H2-blocker
and the molecular mechanisms that occur early in therapy and higher incidence of necrotizing enterocolitis in very
low birth weight infants. Pediatrics 2006;117:e137e42.
this pathogenic process. Because clinical parameters 10. Holman RC, Stoll BJ, Curns AT, et al. Necrotising enterocolitis
alone have not helped identify which children are at risk hospitalisations among neonates in the United States. Paediatr
for developing the disease and progressing to serious Perinat Epidemiol 2006;20:498506.
468 SECTION IV Abdomen
11. Lemons JA, Bauer CR, Oh W, et al. Very low birth weight out- 37. McElroy SJ, Prince LS, Weitkamp JH, et al. Tumor
comes of the National Institute of Child health and human devel- necrosis factor receptor 1-dependent depletion of mucus in imma-
opment neonatal research network, January 1995 through ture small intestine: A potential role in neonatal necrotizing ente-
December 1996. NICHD Neonatal Research Network. Pediatrics rocolitis. Am J Physiol Gastrointest Liver Physiol 2011;301:
2001;107:E1. G65666.
12. Luig M, Lui K, NICUS group, et al. Epidemiology of necrotizing: 38. Strous GJ, Dekker J. Mucin-type glycoproteins. Crit Rev Biochem
enterocolitis: II. Risks and susceptibility of premature infants Mol Biol 1992;27:5792.
during the surfactant era: A regional study. J Pediatr Child Health 39. Allen A, Bell A, Mantle M. The structure and physiology of gas-
2005;41:1749. trointestinal mucus. Adv Exp Med Biol 1982;144:11533.
13. Holman RC, Stoll BJ, Clarke MJ, et al. The epidemiology of 40. Montagne L, Piel C, Lalles JP. Effect of diet on mucin kinetics
necrotizing enterocolitis infant mortality in the United States. Am and composition: Nutrition and health implications. Nutr Rev
J Public Health 1997;87:202631. 2004;62:10514.
14. Sharma R, Hudak ML, Tepas JJ 3rd, et al. Impact of gestational 41. Rhodes JM. Colonic mucus and mucosal glycoproteins: The key
age on the clinical presentation and surgical outcome of necrotiz- to colitis and cancer? Gut 1989;30:16606.
ing enterocolitis. J Perinatol 2006;26:3427. 42. Deplancke B, Gaskins HR. Microbial modulation of innate
15. Blakely ML, Lally KP, McDonald S, et al. Postoperative outcomes defense: Goblet cells and the intestinal mucus layer. Am J Clin
of extremely low birth-weight infants with necrotizing enterocoli- Nutr 2001;73:1131S41S.
tis or isolated intestinal perforation: A prospective cohort study 43. Hackam DJ, Upperman JS, Grishin A, et al. Disordered entero-
by the NICHHD Neonatal Research Network. Ann Surg cyte signaling and intestinal barrier dysfunction in the pathogen-
2005;241:98494. esis of necrotizing enterocolitis. Semin Pediatr Surg
16. Blakely ML, Gupta H, Lally KP. Surgical management of necro- 2005;14:4957.
tizing enterocolitis and isolated intestinal perforation in prema- 44. Ryley HC, Rennie D, Bradley DM. The composition of a mucus
ture neonates. Semin Perinatol 2008;32:1226. glycoprotein from meconium of cystic fibrosis, healthy pre-term
17. Ng S. Necrotizing enterocolitis in the full-term neonate [see and full-term neonates. Clin Chim Acta 1983;135:4956.
comment]. J Paediatr Child Health 2001;37:14. 45. Corfield AP, Myerscough N, Longman R, et al. Mucins and
18. Lambert DK, Christensen RD, Henry E, et al. Necrotizing ente- mucosal protection in the gastrointestinal tract: New prospects
rocolitis in term neonates: Data from a multihospital health-care for mucins in the pathology of gastrointestinal disease. Gut
system [see comment]. J Perinatol 2007;27:43743. 2000;47:58994.
19. Ostlie DJ, Spilde TL, St Peter SD, et al. Necrotizing enterocolitis 46. Kyo K, Muto T, Nagawa H, et al. Associations of distinct variants
in full-term infants. J Pediatr Surg 2003;38:103942. of the intestinal mucin gene MUC3A with ulcerative colitis and
20. Bolisetty S, Lui K. Necrotizing enterocolitis in full-term neonates Crohns disease. J Hum Genet 2001;46:520.
[comment]. J Pediatr Child Health 2001;37:41314. 47. Vieten D, Corfield A, Carroll D, et al. Impaired mucosal regen-
21. Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing ente- eration in neonatal necrotizing enterocolitis. Pediatr Surg Int
rocolitis on length of stay and hospital charges in very low birth 2005;21:15360.
weight infants. Pediatrics 2002;109:4238. 48. Liu Z, Li N, Neu J. Tight junctions, leaky intestines, and pediatric
22. Spencer AU, Kovacevich D, McKinney-Barnett M, et al. Pediatric diseases. Acta Paediatr 2005;94:38693.
short-bowel syndrome: the cost of comprehensive care. Am J Clin 49. Anand RJ, Leaphart CL, Mollen KP, et al. The role of the intes-
Nutr 2008;88:15529. tinal barrier in the pathogenesis of necrotizing enterocolitis.
23. Ballance WA, Dahms BB, Shenker N, et al. Pathology of neonatal Shock 2007;27:12433.
necrotizing enterocolitis: A ten-year experience. J Pediatr 1990; 50. Muresan Z, Paul DL, Goodenough DA. Occludin 1B, a variant
117:S613. of the tight junction protein occludin. Mol Biol Cell
24. Hsueh W, Caplan MS, Qu XW, et al. Neonatal necrotizing ente- 2000;11:62734.
rocolitis: Clinical considerations and pathogenetic concepts. 51. Shen L, Turner JR. Role of epithelial cells in initiation and propa-
Pediatr Dev Pathol 2003;6:623. gation of intestinal inflammation. Eliminating the static: Tight
25. Sanderson I. The physicochemical environment of the neonatal junction dynamics exposed. Am J Physiol Gastrointest Liver
intestine. Am J Clin Nutr 1999;69:10285345. Physiol 2006;290:G577G82.
26. Berseth CL. Gestational evolution of small intestine motility in 52. Ford H, Watkins S, Reblock K, et al. The role of inflammatory
preterm and term infants. J Pediatr 1989;115:64651. cytokines and nitric oxide in the pathogenesis of necrotizing ente-
27. Berseth CL. Gastrointestinal motility in the neonate. Clin Peri- rocolitis. J Pediatr Surg 1997;32:27582.
natol 1996;23:17990. 53. Han X, Fink MP, Delude RL. Proinflammatory cytokines cause
28. Milla PJ. Intestinal motility during ontogeny and intestinal NO-dependent and independent changes in expression and locali-
pseudo-obstruction in children. Pediatr Clin North Am 1996;43: zation of tight junction proteins in intestinal epithelial cells. Shock
51132. 2003;3:22037.
29. Lebenthal A, Lebenthal E. The ontogeny of the small intestinal 54. Mowat AM, Viney JL. The anatomical basis of intestinal immu-
epithelium. J Parenter Enteral Nutr 1999;23(Suppl. 5): nity. Immunol Rev 1997;156:14566.
S36. 55. Neutra MR, Mantis NJ, Kraehenbuhl JP. Collaboration of epithe-
30. Di Lorenzo M, Bass J, Krantis A. An intraluminal model of necro- lial cells with organized mucosal lymphoid tissues. Nat Immunol
tizing enterocolitis in the developing neonatal piglet. J Pediatr 2001.10049.
Surg 1995;30:113842. 56. Puiman PJ, Burger-Van Paassen N, Schaart MW, et al. Paneth
31. Lin J. Too much short chain fatty acids cause neonatal necrotizing cell hyperplasia and metaplasia in necrotizing enterocolitis.
enterocolitis. Med Hypotheses 2004;62:2913. Pediatr Res 2011;69:21723.
32. Ford HR. Mechanism of nitric oxide-mediated intestinal barrier 57. Ayabe T, Satchell DP, Wilson CL, et al. Secretion of microbicidal
failure: Insight into the pathogenesis of necrotizing enterocolitis. alpha-defensins by intestinal Paneth cells in response to bacteria.
J Pediatr Surg 2006;41:2949. Nat Immunol 2000;1:11318.
33. Halpern MD, Holubec H, Saunders TA. Bile acids induce ileal 58. Mayer L. Mucosal immunity. Pediatrics 2003;111:1595600.
damage during experimental necrotizing enterocolitis. Gastroen- 59. Ogra SS, Weintraub D, Ogra PL. Immunologic aspects of human
terology 2006;130:35972. colostrum and milk: III. Fate and absorption of cellular and
34. Halpern MD, Dvorak B. Does abnormal bile acid metabolism soluble components in the gastrointestinal tract of the newborn.
contribute to NEC? Semin Perinatol 2008;32:11421. J Immunol 1977;119:2458.
35. Hammons JL, Jordan WE, Stewart RL. Age and diet effects 60. Cetin S, Ford HR, Sysko LR, et al. Endotoxin inhibits intestinal
on fecal bile acids in infants. J Pediatr Gastroenterol Nutr 1988; epithelial restitution through activation of Rho-GTPase and
7:308. increased focal adhesions. J Biol Chem 2004;279:24592600.
36. Hunter CJ, Upperman JS, Ford HR, et al. Understanding the 61. Duffy LC, Zielezny MA, Carrion V, et al. Concordance of bacte-
susceptibility of the premature infant to necrotizing enterocolitis. rial cultures with endotoxin and interleukin-6 in necrotizing ente-
Pediatr Res 2008;63:11723. rocolitis. Dig Dis Sci 1997;42:35965.
33 Necrotizing Enterocolitis 469
62. Forsythe RM, Xu DZ, Lu Q, et al. Lipopolysaccharide-induced 88. Warner B, Ryan A, Seeger K. Ontogeny of salivary epidermal
enterocyte-derived nitric oxide induces intestinal monolayer per- growth factor and necrotizing enterocolitis. J Pediatr
meability in an autocrine fashion. Shock 2002;17:1804. 2007;150:35863.
63. Grishin A, Wang J, Hackam DJ, et al. p38 MAP kinase mediates 89. Sullivan PB, Brueton MJ, Tabara ZB. Epidermal growth factor in
endotoxin-induced expression of cyclooxygenase-2 in enterocytes. necrotising enteritis. Lancet 1991;338:534.
Surgery 2004;136:32935. 90. Sullivan PB, Lewindon PJ, Cheng C. Intestinal mucosal
64. Gonzalez-Crussi F, Hsueh W. Experimental model of ischemic remodeling by recombinant human EGF in neonates with
bowel necrosis: The role of platelet-activating factor and endo- severe necrotizing enterocolitis. J Pediatr Surg 2007;42
toxin. Am J Pathol 1983;112:12735. :4629.
65. Hsueh W, Gonzalez-Crussi F, Arroyave JL. Platelet-activating 91. Christensen RD, Gordon PV, Besner GE. Can we cut the inci-
factor-induced ischemic bowel necrosis: The effect of PAF antag- dence of necrotizing enterocolitis in halftoday? Fetal Pediatr
onists. Eur J Pharmacol 1986;123:7983. Pathol 2010;29:18598.
66. Levy RM, Prince JM, Billiar TR. Nitric oxide: A clinical primer. 92. Feng J, El-Assal O, Besner GE. Heparin-binding EGF-like
Crit Care Med 2005;33:S492S5. growth factor (HB-EGF) and necrotizing enterocolitis. Semin
67. Chokshi N, Guner Y, Hunter CJ, et al. The role of nitric oxide Pediatr Surg 2005;14:16774.
in intestinal epithelial injury and restitution in neonatal necrotiz- 93. Feng J, Besner GE. Heparin-binding epidermal growth factor-like
ing enterocolitis. Semin Perinatol 2008;32:929. growth factor promotes enterocyte migration and proliferation in
68. Beckman JS. Ischaemic injury mediator. Nature 1990;345:278. neonatal rats with necrotizing enterocolitis. J Pediatr Surg
69. Upperman JS, Potoka DA, Grishin A. Mechanisms of nitric oxide 2007;42:21420.
mediated intestinal barrier failure in necrotizing enterocolitis. 94. Feng J, El-Assal ON, Besner GE. Heparin-binding epidermal
Semin Pediatr Surg 2005;14:15966. growth factor-like growth factor reduces intestinal apoptosis in
70. Hoffman RA, Zhang G, Nussler NC. Constitutive expression of neonatal rats with necrotizing enterocolitis. J Pediatr Surg
inducible nitric oxide synthase in the mouse ileal mucosa. Am J 2006;41:7427.
Physiol 1997;272(2Pt1):G383G92. 95. Feng J, El-Assal ON, Besner GE. Heparin-binding epidermal
71. Emami CN, Chokshi N, Wang J, et al. Role of interleukin-10 in growth factor-like growth factor decreases the incidence of
the pathogenesis of necrotizing enterocolitis. Am J Surg necrotizing enterocolitis in neonatal rats. J Pediatr Surg 2006;
2012;203:42835. 41:1449.
72. Chokshi N, Guner Y, Hunter CJ, et al. The role of nitric oxide 96. Radulescu A, Yu X, Orvets ND, et al. Deletion of the heparin-
in intestinal epithelial injury and restitution in neonatal necrotiz- binding epidermal growth factor-like growth factor gene increases
ing enterocolitis. Semin Perinatol 2008;32:929. susceptibility to necrotizing enterocolitis. J Pediatr Surg
73. Snyder F. Platelet-activating factor and related acetylated lipids as 2010;45:72934.
potent biologically active cellular mediators. Am J Physiol 97. Radulescu A, Zhang HY, Yu X, et al. Heparin-binding epidermal
1990;259:C697C708. growth factor-like growth factor overexpression in transgenic
74. Frost BL, Jilling T, Caplan MS. The importance of proinflamma- mice increases resistance to necrotizing enterocolitis. J Pediatr
tory signaling in neonatal necrotizing enterocolitis. Semin Peri- Surg 2010;45:19339.
natol 2008;32:1006. 98. Nankervis CA, Nowicki P. Role of nitric oxide in regulation of
75. Caplan MS, Simon D, Jilling T. The role of PAF, TLR, and the vascular resistance in postnatal intestine. Am J Physiol
inflammatory response in neonatal necrotizing enterocolitis. 1995;268:G949G58.
Semin Pediatr Surg 2005;14:14551. 99. Reber KM, Mager GM, Miller CE. Relationship between flow
76. Caplan M, Hsueh W, Kelly A, et al. Serum PAF acetylhydrolase rate and NO production in postnatal mesenteric arteries. Am J
increases during neonatal maturation. Prostaglandins 1990; Physiol 2000;280:G43G50.
39:70514. 100. Nowicki P. Intestinal ischemia and necrotizing enterocolitis.
77. Rabinowitz SS, Dzakpasu P, Piecuch S, et al. Platelet-activating J Pediatr 1990;117:S14S19.
factor in infants at risk for necrotizing enterocolitis. J Pediatr 101. Reber KM, Nankervis CA, Nowicki PT. Newborn intestinal cir-
2001;138:816. culation. Physiology and pathophysiology. Clin Perinatol
78. Caplan MS, Lickerman M, Adler L, et al. The role of recombinant 2002;29:2339.
platelet-activating factor acetylhydrolase in a neonatal rat model 102. Nowicki P. Ischemia and necrotizing enterocolitis: Where, when
of necrotizing enterocolitis. Pediatr Res 1997;42:77983. and how. Semin Pediatr Surg 2005;14:1528.
79. Coursodon CF, Dvorak B. Epidermal growth factor and necrotiz- 103. Nankervis CA, Dunaway DJ, Nowicki P. Role of endothelin-1 in
ing enterocolitis. Curr Opin Pediatr 2012;24:1604. regulation of the postnatal intestinal circulation. Am J Physiol
80. Dvorak B, Philips AF, Koldovsky O. Milk-borne growth factors 2000;278:G367G75.
and gut development. In: Zeigler E, Lucas A, Moro G, editors. 104. Yanagisawa M, Kurihara H, Kimura S. A novel potent vasocon-
Nutrition of the Very Low Birthweight Infant. Philadelphia: Lip- strictor peptide produced by vascular endothelial cells. Nature
pincott Williams and Wilkins; 1999. p. 24555. 1998;332:41115.
81. Pollack PF, Goda T, Colony PC. Effects of enterally fed epidermal 105. Kuchan MJ, Frangos JA. Shear stress regulates endothelin-1
growth factor on the small and large intestine of the suckling rat. release via protein kinase C and cGMP in cultured endothelial
Regul Pept 1987;17:12132. cells. Am J Physiol 1993;264:H150H6.
82. Playford R, Wright N. Why is epidermal growth factor present 106. Kourembanas S, Marsden PA, McQuillan LP. Hypoxia induces
in the gut lumen. Gut 1996;38:3035. endothelin gene expression and secretion in cultured human
83. Barnard JA, Beauchamp D, Russel W. Epidermal growth factor- endothelium. J Clin Invest 1991;88:10547.
related peptides and their relevance to gastrointestinal patho- 107. Woods M, Mitchel JA, Wood EG. Endothelin-1 is induced by
physiology. Gastroenterology 1995;108:56480. cytokines in human vascular smooth muscle cells: Evidence for
84. Warner B, Warner B. Role of epidermal growth factor in the intracellular endothelin converting enzyme. Mol Pharmacol
pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr 1999;55:9029.
Surg 2005;14:17580. 108. Ito Y, Doelle S, Clark JA. Intestinal microcirculatory dysfunction
85. Hirai C, Ichiba H, Saito M. Trophic effect of multiple growth during the development of experimental necrotizing enterocolitis.
factors in amniotic fluid or human milk on cultured human Pediatr Res 2007;61:1804.
fetal small intestinal cells. J Pediatr Gastroenterol Nutr 2002; 109. Lin PW, Nasr TR, Stoll BJ. Necrotizing enterocolitis: Recent
34:5248. scientific advances in pathophysiology and prevention. Semin
86. Chen CL, Yu X, James IO, et al. Heparin-binding EGF-like Perinatol 2008;32:7082.
growth factor protects intestinal stem cells from injury in a rat 110. Kosloske AM. Indications for operation in necrotizing enterocoli-
model of necrotizing enterocolitis. Lab Invest 2012;92:33144. tis revisited. J Pediatr Surg 1994;29:6636.
87. Shin CE, Falcone RA Jr, Stuart L, et al. Diminished epidermal 111. Dolgin SE, Shlasko E, Levitt MA, et al. Alterations in respiratory
growth factor levels in infants with necrotizing enterocolitis. status: Early signs of severe necrotizing enterocolitis. J Pediatr
J Pediatr Surg 2000;35:1737. Surg 1998;33:8568.
470 SECTION IV Abdomen
112. Bell MJ. Neonatal necrotizing enterocolitis. N Engl J Med 138. Rovin JD, Rodgers BM, Burns RC, et al. The role of peritoneal
1978;298:2812. drainage for intestinal perforation in infants with and without
113. Kliegman RJ, Walsh MC. Neonatal necrotizing enterocolitis: necrotizing enterocolitis. J Pediatr Surg 1999;34:1437.
Pathogenesis, classification and spectrum of disease. Curr Probl 139. Okuyama H, Kubota A, Oue T, et al. A comparison of the clinical
Pediatr 1987;26:32744. presentation and outcome of focal intestinal perforation and
114. Kafetzis DA, Skevaki C, Costalos C. Neonatal necrotizing necrotizing enterocolitis in very-low-birth-weight neonates.
enterocolitis: An overview. Curr Opin Infect Dis 2003;16: Pediatr Surg Int 2002;18:7046.
34955. 140. Tarrado X, Castanon M, Thio M, et al. Comparative study
115. Noerr B. Current controversies in the understanding of necrotiz- between isolated intestinal perforation and necrotizing enterocoli-
ing enterocolitis: I. Adv Neonatal Care 2003;3:10720. tis. Eur J Pediatr Surg 2005;15:8894.
116. Romagnoli C, Frezza S, Cingolani A, et al. Plasma levels of 141. Pumberger W, Mayr M, Kohlhauser C, et al. Spontaneous local-
interleukin-6 and interleukin-10 in preterm neonates evaluated ized intestinal perforation in very-low-birth-weight infants: A
for sepsis. Eur J Pediatr 2001;160:34550. distinct clinical entity different from necrotizing enterocolitis.
117. Isaacs D, North J, Lindsell D, et al. Serum acute phase reactants J Am Coll Surg 2002;195:796803.
in necrotizing enterocolitis. Acta Paediatr Scand 1987;76:9237. 142. Buchheit JQ, Stewart DL. Clinical comparison of localized intes-
118. Pourcyrous M, Korones S, Yang W, et al. C-reactive protein in tinal perforation and necrotizing enterocolitis in neonates [see
the diagnosis, management, and prognosis of neonatal necrotizing comment]. Pediatrics 1994;93:326.
enterocolitis. Pediatrics 2005;116:10649. 143. Cass DL, Brandt ML, Patel DL, et al. Peritoneal drainage as
119. Edelson MB, Bagwell CE, Rozycki HJ. Circulating pro- and definitive treatment for neonates with isolated intestinal perfora-
counterinflammatory cytokine levels and severity in necrotizing tion. J Pediatr Surg 2000;35:15316.
enterocolitis. Pediatrics 1999;103:76671. 144. Lessin MS, Luks FI, Wesselhoeft CW. Peritoneal drainage
120. Kosloske AM. Epidemiology of necrotizing enterocolitis. Acta as definitive treatment for intestinal perforation in infants
Paediatr Suppl 1994;396:27. with extremely low birth weight (<750gms). J Pediatr Surg 1998
121. Chandler JC, Hebra A. Necrotizing enterocolitis in infants ;33:3702.
with very low birth weight. Semin Pediatr Surg 2000;9:63 145. Gordon PV, Swanson JR, Attridge JT, et al. Emerging trends in
72. acquired neonatal intestinal disease: Is it time to abandon Bells
122. Kennedy J, Holt CL, Ricketts RR. The significance of portal vein criteria. J Perinatol 2007;27:66171.
gas in necrotizing enterocolitis. Am Surg 1987;53:2314. 146. Cribbs RK, Harding PA, Luquette MH. Endogenous production
123. Faingold R, Daneman A, Tomlinson G. Necrotizing enterocolitis: of heparin-binding EGF-like growth factor during murine partial
Assessment of bowel viability with color Doppler ultrasound. thickness burn wound healing. J Burn Care Rehabil
Radiology 2005;235:58794. 2002;23:11625.
124. Kim WY, Kim WS, Kim IO, et al. Sonographic evaluation of 147. Jin K, Mao XO, Sun Y. Heparin-binding epidermal growth factor-
neonates with early-stage necrotizing enterocolitis. Pediatr Radiol like growth factor: Hypoxia-inducible expression in vitro and
2005;35:105661. stimulation of neurogenesis in vitro and in vivo. J Neurosci
125. Kim WY, Kim IO, Kim WS. Bowel sonography in necrotizing 2002;22:536573.
enterocolitis: Histopathologic correlation in experimental studies. 148. Frank GD, Mifune M, Inagami T. Distinct mechanisms of
Pediatr Radiol 2005;35(Suppl):S51. receptor and nonreceptor tyrosine kinase activation by reactive
126. Azarow K, Connolly B, Babyn P, et al. Multidisciplinary evalua- oxygen species in vascular smooth muscle cells: Role of metallo-
tion of the distended abdomen in critically ill infants and children: protease and protein kinase C-delta. Mol Cell Biol 2003;23:
The role of bedside sonography. Pediatr Surg Int 1998;13: 15819.
3559. 149. Kayanoki Y, Higashiyama S, Suzuki K. The requirement of both
127. Silva CT, Daneman A, Navarro OM, et al. Correlation of sono- intracellular reactive oxygen species and intracellular calcium
graphic findings and outcome in necrotizing enterocolitis. Pediatr elevation for the induction of heparin-binding EGF-like growth
Radiol 2007;37:27482. factor in vascular endothelial cells and smooth muscle cells.
128. Epelman M, Daneman A, Navarro OM, et al. Necrotizing ente- Biochem Biophys Res Commun 1999;259:505.
rocolitis: Review of state-of-the-art imaging findings with patho- 150. Marikovsky M, Breuing K, Liu PY. Appearance of heparin-
logic correlation. RadioGraphics 2007;27:285305. binding EGF-like growth factor in wound fluid as a response to
129. Buonomo C. The radiology of necrotizing enterocolitis. Radiol injury. Proc Natl Acad Sci U S A 1993;90:388993.
Clin North Am 1999;37:118798.vii 151. McCarthy DW, Downing MT, Brigstock DR. Production of
130. Kao SC, Smith WL, Franken EA Jr, et al. Contrast enema heparin-binding epidermal growth factor-like growth factor
diagnosis of necrotizing enterocolitis. Pediatr Radiol 1992;22: (HBEGF) at sites of thermal injury in pediatric patients. J Invest
11517. Dermatol 1996;106:4956.
131. Schwartz MZ, Hayden CK, Richardson CJ, et al. A prospective 152. Xia G, Rachfal AW, Martin AE. Upregulation of endogenous
evaluation of intestinal stenosis following necrotizing enterocoli- heparin-binding EGF-like growth factor (HB-EGF) expression
tis. J Pediatr Surg 1982;17:76470. after intestinal ischemia reperfusion injury. J Invest Surg
132. Rencken IO, Sola A, al-Ali F, et al. Necrotizing enterocolitis: 2003;16:5763.
Diagnosis with CT examination of urine after enteral administra- 153. El-Assal O, Besner GE. Heparin-binding epidermal growth
tion of iodinated water-soluble contrast material. Radiology factor-like growth factor and intestinal ischemia-reperfusion
1997;205:8790. injury. Semin Pediatr Surg 2004;13:210.
133. Maalouf EF, Fagbemi A, Duggan PJ, et al. Magnetic resonance 154. Michalsky MP, Kuhn A, Mehta V. Heparin-binding EGF-like
imaging of intestinal necrosis in preterm infants. Pediatrics growth factor decreases apoptosis in intestinal epithelial cells in
2000;105:51014. vitro. J Pediatr Surg 2001;36:11305.
134. Meyer CL, Payne NR, Roback SA. Spontaneous, isolated intesti- 155. Pillai SB, Turman MA, Besner GE. Heparin-binding EGF-like
nal perforations in neonates with birth weight less than 1,000g growth factor is cytoprotective for intestinal epithelial cells
not associated with necrotizing enterocolitis. J Pediatr Surg exposed to hypoxia. J Pediatr Surg 1998;33:9738.
1991;26:71417. 156. Lara-Marquez ML, Mehta V, Michalsky MP. Heparin-binding
135. Mintz AC, Applebaum H. Focal gastrointestinal perforations not EGF-like growth factor down regulates proinflammatory
associated with necrotizing enterocolitis in very low birth weight cytokine-induced nitric oxide and inducible nitric oxide synthase
neonates. J Pediatr Surg 1993;28:85760. production in intestinal epithelial cells. Nitric Oxide
136. Aschner JL, Deluga KS, Metlay LA, et al. Spontaneous focal 2002;6:14252.
gastrointestinal perforation in very low birth weight infants. J 157. Mehta VB, Besner GE. Inhibition of NF-kappa B activation and
Pediatr 1988;113:3647. its target genes by heparin-binding epidermal growth factor-like
137. Azarow KS, Ein SH, Shandling B, et al. Laparotomy or drain for growth factor. J Immunol 2003;171:601422.
perforated necrotizing enterocolitis: Who gets what and why? 158. Halpern M, Dominguez JA, Dvorakova K. Ileal cytokine
Pediatr Surg Int 1997;12:1379. dysregulation in experimental necrotizing enterocolitis is reduced
33 Necrotizing Enterocolitis 471
by epidermal growth factor. J Pediatr Gastroenterol Nutr 185. Touloukian RJ. Neonatal necrotizing enterocolitis: An update
2003;36:12633. on etiology, diagnosis, and treatment. Surg Clin North Am
159. Ricketts RR, Jerles ML. Neonatal necrotizing enterocolitis: Expe- 1976;56:28198.
rience with 100 consecutive surgical patients. World J Surg 186. Kurscheid T, Holschneider AM. Necrotizing enterocolitis
1990;14:6005. (NEC)mortality and long-term results. Eur J Pediatr Surg
160. Albanese CT, Rowe MI. Necrotizing enterocolitis. Semin Pediatr 1993;3:13943.
Surg 1995;4:2006. 187. Horwitz JR, Lally KP, Cheu HW, et al. Complications after surgi-
161. Grosfeld JL, Cheu H, Schlatter M, et al. Changing trends in cal intervention for necrotizing enterocolitis: A multicenter
necrotizing enterocolitis: Experience with 302 cases in two review. J Pediatr Surg 1995;30:9949.
decades. Ann Surg 1991;214:3007. 188. de Souza JC, da Motta UI, Ketzer CR. Prognostic factors of
162. Ein SH, Marshall DG, Girvan D. Peritoneal drainage under local mortality in newborns with necrotizing enterocolitis submitted to
anesthesia for perforations from necrotizing enterocolitis. exploratory laparotomy. J Pediatr Surg 2001;36:4826.
J Pediatr Surg 1977;12:9637. 189. Cikrit D, Mastandrea J, West KW, et al. Necrotizing enterocolitis:
163. Moss RL, Dimmitt RA, Henry MC, et al. A meta-analysis of Factors affecting mortality in 101 surgical cases. Surgery
peritoneal drainage versus laparotomy for perforated necrotizing 1984;96:64855.
enterocolitis. J Pediatr Surg 2001;36:121013. 190. Ricketts RR. Surgical treatment of necrotizing enterocolitis
164. Blakely ML, Tyson JE, Lally KP, et al. Laparotomy versus peri- and the short bowel syndrome. Clin Perinatol 1994;21:365
toneal drainage for necrotizing enterocolitis or isolated intestinal 87.
perforation in extremely low birth weight infants: Outcomes 191. Wilmore DW. Factors correlating with a successful outcome fol-
through 18 months adjusted age. Pediatrics 2006;117:e680e7. lowing extreme intestinal resection in newborn infants. J Pediatr
165. Moss RL, Dimmitt RA, Barnhart DC, et al. Laparotomy versus 1972;80:8895.
peritoneal drainage for necrotizing enterocolitis and perforation 192. Fasching G, Hollwarth ME, Schmidt B, et al. Surgical strategies
[see comment] [erratum appears in N Engl J Med. 2006 Aug in very-low-birthweight neonates with necrotizing enterocolitis.
24;355(8):856]. N Engl J Med 2006;354:222534. Acta Paediatr Suppl 1994;396:624.
166. Rees C M, Eaton S, Khoo AK. Peritoneal drainage or laparotomy 193. Beasley SW, Auldist AW, Ramanjuan TM. The surgical manage-
in neonatal bowel perforation? A randomized controlled trial. ment of neonatal necrotizing enterocolitis: 1975-1984. Pediatr
Presented at the American Pediatric Surgical Association, Surg Int 1994;1:21017.
Orlando, FL, 38th Annual Meeting, May 2007. 194. Albanese CT, Rowe MI, et al. Necrotizing enterocolitis. In:
167. Laparotomy vs. Drainage for Infants With Necrotizing Entero- ONeill JA Jr, Rowe MI, Grosfeld J, editors. Pediatric Surgery. St.
colitis (NEST). 2012; Available at: http://www.clinicaltrial.gov/ Louis: Mosby; 1998. p. 1297320.
ct2/show/NCT01029353. Accessed 06/24, 2012. 195. Thompson JS, Quigley EMM, Adrian TE. Effect of intestinal
168. Nadler EP, Upperman JS, Ford HR. Controversies in the man- tapering and lengthening on intestinal structure and function. Am
agement of necrotizing enterocolitis. Surg Infect 2001;2:11320. J Surg 1995;169:11119.
169. Cooper A, Ross AJ 3rd, ONeill JA Jr, et al. Resection with 196. Goulet OJ, Revillon Y, Jan D, et al. Neonatal short bowel syn-
primary anastomosis for necrotizing enterocolitis: A contrasting drome. J Pediatr 1991;119:1823.
view. J Pediatr Surg 1988;23:648. 197. Georgeson KE, Breaux CW Jr. Outcome and intestinal adaptation
170. Weber TR, Lewis JE. The role of second-look laparotomy in in neonatal short-bowel syndrome. J Pediatr Surg
necrotizing enterocolitis. J Pediatr Surg 1986;21:3235. 1992;27:34450.
171. Vaughan WG, Grosfeld JL, West K, et al. Avoidance of stomas 198. Chaet MS, Farrell MK, Ziegler MM, et al. Intensive nutritional
and delayed anastomosis for bowel necrosis: The clip and drop- support and remedial surgical intervention for extreme short
back technique. J Pediatr Surg 1996;31:5425. bowel syndrome. J Pediatr Gastroenterol Nutr 1994;19:2958.
172. Luzzatto C, Previtera C, Boscolo R, et al. Necrotizing enterocoli- 199. Fasoli L, Turi RA, Spitz L, et al. Necrotizing enterocolitis: Extent
tis: Late surgical results after enterostomy without resection. Eur of disease and surgical treatment. J Pediatr Surg 1999;34:
J Pediatr Surg 1996;6:924. 10969.
173. Lee JS, Polin RA. Treatment and prevention of necrotizing ente- 200. Andorsky DJ, Lund DP, Lillehei CW, et al. Nutritional and other
rocolitis. Semin Neonatol 2003;8:44959. postoperative management of neonates with short bowel syn-
174. Stringer MD, Brereton RJ, Drake DP, et al. Recurrent necrotizing drome correlates with clinical outcomes. J Pediatr 2001;139:
enterocolitis. J Pediatr Surg 1993;28:97981. 2733.
175. Frantz ID 3rd, LHeureux P, Engel RR, et al. Necrotizing ente- 201. Cooper A, Floyd TF, Ross AJ 3rd, et al. Morbidity and mortality
rocolitis. J Pediatr 1975;86:25963. of short-bowel syndrome acquired in infancy: An update. J Pediatr
176. Vollman JH, Smith WL, Tsang RC. Necrotizing enterocolitis Surg 1984;19:71118.
with recurrent hepatic portal venous gas. J Pediatr 1976;88: 202. Weber TR, Tracy T Jr, Connors RH. Short-bowel syndrome in
4867. children: Quality of life in an era of improved survival. Arch Surg
177. Mollitt DL, Golladay ES. Postoperative neonatal necrotizing 1991;126:8416.
enterocolitis. J Pediatr Surg 1982;17:75763. 203. Gauderer MW, et al. Stomas of the small and large intestine. In:
178. Oldham KT, Coran AG, Drongowski RA, et al. The development ONeill JA Jr, Rowe MI, Grosfeld J, editors. Pediatric Surgery. St.
of necrotizing enterocolitis following repair of gastroschisis: A Louis, CV: Mosby; 1998. p. 134959.
surprisingly high incidence. J Pediatr Surg 1988;23:9459. 204. Musemeche CA, Kosloske AM, Ricketts RR. Enterostomy in
179. Shanbhogue LK, Tam PK, Lloyd DA. Necrotizing enterocolitis necrotizing enterocolitis: An analysis of techniques and timing of
following operation in the neonatal period. Br J Surg closure. J Pediatr Surg 1987;22:47983.
1991;78:10457. 205. Alaish SM, Krummel TM, Bagwell CE, et al. Loop enterostomy
180. Ladd AP, Rescorla FJ, West KW, et al. Long-term follow-up after in newborns with necrotizing enterocolitis. J Am Coll Surg
bowel resection for necrotizing enterocolitis: Factors affecting 1996;182:4578.
outcome. J Pediatr Surg 1998;33:96772. 206. OConnor A, Sawin RS. High morbidity of enterostomy and its
181. Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing ente- closure in premature infants with necrotizing enterocolitis. Arch
rocolitis on length of stay and hospital charges in very low birth Surg 1998;133:87580.
weight infants. Pediatrics 2002;109:4238. 207. Lemelle JL, Schmitt M, de Miscault G, et al. Neonatal necrotizing
182. Limpert JN, Limpert PA, Weber TR, et al. The impact of surgery enterocolitis: A retrospective and multicentric review of 331 cases.
on infants born at extremely low birth weight. J Pediatr Surg Acta Paediatr Suppl 1994;396:703.
2003;38:9247. 208. Haberlik A, Hollwarth ME, Windhager U, et al. Problems of
183. Patel JC, Tepas JJ 3rd, Huffman SD, et al. Neonatal necrotizing ileostomy in necrotizing enterocolitis. Acta Paediatr Suppl
enterocolitis: The long-term perspective. Am Surg 1998;64: 1994;396:746.
57580. 209. Cogbill TH, Millikan JS. Reconstitution of intestinal continuity
184. Kliegman RM, Fanaroff AA. Necrotizing enterocolitis. N Engl J after resection for neonatal necrotizing enterocolitis. Surg
Med 1984;310:1093103. Gynecol Obstet 1985;160:3304.
472 SECTION IV Abdomen
210. Gertler JP, Seashore JH, Touloukian RJ. Early ileostomy closure 237. Cikrit D, West KW, Schreiner R, et al. Long-term follow-up after
in necrotizing enterocolitis. J Pediatr Surg 1987;22:1403. surgical management of necrotizing enterocolitis: Sixty-three
211. Sugarman ID, Kiely EM. Is there a role for high jejunostomy in cases. J Pediatr Surg 1986;21:5335.
the management of severe necrotizing enterocolitis? Pediatr Surg 238. Castro L, Yolton K, Haberman B, et al. Bias in reported neurode-
Int 2001;17:1224. velopmental outcomes among extremely low birth weight survi-
212. Ricketts RR. Surgical therapy for necrotizing enterocolitis. Ann vors. Pediatrics 2004;114:40410.
Surg 1984;200:6537. 239. Hintz SR, Kendrick DE, Stoll BJ, et al. Neurodevelopmental and
213. ONeill JA Jr, Holcomb GW Jr. Surgical experience with neonatal growth outcomes of extremely low birth weight infants after
necrotizing enterocolitis (NNE). Ann Surg 1979;189:61219. necrotizing enterocolitis. Pediatrics 2005;115:696703.
214. Rowe MI. Necrotizing enterocolitis. In: Welch KJ, Randolph JG, 240. Schulzke SM, Deshpande GC, Patole SK. Neurodevelopmental
Ravitch MM, editors. Pediatric Surgery. Chicago: Year Book outcomes of very low-birth-weight infants with necrotizing ente-
Medical; 1986. p. 94458. rocolitis: A systematic review of observational studies [review].
215. Gobet R, Sacher P, Schwobel MG. Surgical procedures in colonic Arch Pediatr Adolesc Med 2007;161:58390.
strictures after necrotizing enterocolitis. Acta Paediatr Suppl 241. Rees CM, Pierro A, Eaton S. Neurodevelopmental outcomes
1994;396:779. of neonates with medically and surgically treated necrotizing
216. Schullinger JN, Mollitt DL, Vinocur CD, et al. Neonatal necro- enterocolitis [review]. Arch Dis Child Fetal Neonatal Ed 2007;
tizing enterocolitis: Survival, management, and complications: A 92:F193F8.
25-year study. Am J Dis Child 1981;135:61214. 242. Svenningsen N, Lindroth M, Lindquist B. A comparative study
217. Schimpl G, Hollwarth ME, Fotter R, et al. Late intestinal stric- of varying protein intake in low birth weight infant feeding. Acta
tures following successful treatment of necrotizing enterocolitis. Paediatr Scand Suppl 1982;296:2831.
Acta Paediatr Suppl 1994;396:803. 243. Gross S. Growth and biochemical response of preterm infants
218. Radhakrishnan J, Blechman G, Shrader C, et al. Colonic strictures fed human milk or modified infant formula. N Engl J Med
following successful medical management of necrotizing entero- 1983;308:23741.
colitis: A prospective study evaluating early gastrointestinal con- 244. Tyson JE, Lasky RE, Mize CE. Growth, metabolic response, and
trast studies. J Pediatr Surg 1991;26:10436. development in very-low-birth-weight infants fed banked human
219. Hartman GE, Drugas GT, Shochat SJ. Post-necrotizing entero- milk or enriched formula. J Pediatr 1983;103:95104.
colitis strictures presenting with sepsis or perforation: Risk of 245. Cooper PA, Rothberg AD, Pettifor J. Growth and biochemical
clinical observation. J Pediatr Surg 1988;23:5626. response of premature infants fed pooled preterm milk or special
220. Butter A, Flageole H, Laberge JM. The changing face of surgical formula. J Pediatr Gastroenterol Nutr 1984;3:74954.
indications for necrotizing enterocolitis. J Pediatr Surg 246. Lucas A, Cole T. Breast milk and neonatal necrotising enterocoli-
2002;37:4969. tis. Lancet 1990;336:151923.
221. Kosloske AM, Burstein J, Bartow SA. Intestinal obstruction due 247. Boyd CA, Quigley MA, Brocklehurst P. Donor breast milk versus
to colonic stricture following neonatal necrotizing enterocolitis. infant formula for preterm infants: Systematic review and meta-
Ann Surg 1980;192:2027. analysis [see comment]. Arch Dis Child Fetal Neonatal Ed
222. Weber TR, Tracy TF Jr, Silen ML, et al. Enterostomy and its 2007;92:F169F75.
closure in newborns. Arch Surg 1995;130:5347. 248. McGuire W, Anthony MY. Donor human milk versus formula for
223. Bell MJ, Ternberg JL, Askin FB, et al. Intestinal stricture in necro- preventing necrotizing enterocolitis in preterm infants. Arch Dis
tizing enterocolitis. J Pediatr Surg 1976;11:31927. Child Fetal Neonatal Ed 2003;88:F11F15.
224. Schwartz MZ, Richardson CJ, Hayden CK, et al. Intestinal steno- 249. Sullivan S, Schanler RJ, Kim JH, et al. An exclusively human
sis following successful medical management of necrotizing ente- milk-based diet is associated with a lower rate of necrotizing
rocolitis. J Pediatr Surg 1980;15:8909. enterocolitis than a diet of human milk and bovine milk-based
225. Kosloske AM. Surgery of necrotizing enterocolitis. World J Surg products. J Pediatr 2010;156:5627.
1985;9:27784. 250. Kuschel CA, Harding JE. Multicomponent fortified human milk
226. Janik JS, Ein SH, Mancer K. Intestinal stricture after necrotizing for promoting growth in preterm infants. Cochrane Database Syst
enterocolitis. J Pediatr Surg 1981;16:43843. Rev CD000343, 2002.
227. Robertson JF, Azmy AF, Young DG. Surgery for necrotizing ente- 251. Kennedy KA, Tyson JE. Early versus delayed initiation of progres-
rocolitis. Br J Surg 1987;74:3879. sive enteral feedings for parenterally fed low birth weight or
228. Born M, Holgersen LO, Shahrivar F, et al. Routine contrast preterm infants. Cochrane Database Syst Rev CD001970, 2000
enemas for diagnosing and managing strictures following nonop- 252. Kennedy KA, Tyson JE. Rapid versus slow rate of advancement
erative treatment of necrotizing enterocolitis. J Pediatr Surg of feedings for promoting growth and preventing necrotizing
1985;20:4613. enterocolitis in parenterally fed low-birth-weight infants.
229. Tonkin IL, Bjelland JC, Hunter TB, et al. Spontaneous resolution Cochrane Database Syst Rev CD001241, 1998.
of colonic strictures caused by necrotizing enterocolitis: Thera- 253. Berseth CL, Bisquera JA, Paje VU. Prolonging small feeding
peutic implications. AJR Am J Roentgenol 1978;130:107781. volumes early in life decreases the incidence of necrotizing ente-
230. Ball WS Jr, Kosloske AM, Jewell PF, et al. Balloon catheter dilata- rocolitis in very low birth weight infants [see comment]. Pediatrics
tion of focal intestinal strictures following necrotizing enterocoli- 2003;111:52934.
tis. J Pediatr Surg 1985;20:6379. 254. Amin HJ, Zamora SA, McMillan DD, et al. Arginine supplemen-
231. Stanford A, Upperman JS, Boyle P, et al. Long-term follow-up tation prevents necrotizing enterocolitis in the premature infant
of patients with necrotizing enterocolitis. J Pediatr Surg 2002; [see comment]. J Pediatr 2002;140:42531.
37:104850. 255. Shah P, Shah V. Arginine supplementation for prevention of necr-
232. Orellana CB, Orellana FA, Friesen C. Long-term follow-up: Neu- otising enterocolitis in preterm infants. Cochrane Database Syst
rodevelopmental outcome and gastrointestinal function in infants Rev CD004339, 2011
< 801 grams diagnosed with necrotizing enterocolitis. Pediatr Res 256. Becker RM, Wu G, Galanko JA, et al. Reduced serum amino acid
2003;54:77382. concentrations in infants with necrotizing enterocolitis [see
233. Whiteman L, Wuethrich M, Egan E. Infants who survive necro- comment]. J Pediatr 2000;137:78593.
tizing enterocolitis. Matern Child Nurs J 1985;14:12333. 257. Vaughn P, Thomas P, Clark R. Enteral glutamine supplementation
234. Sonntag J, Grimmer I, Scholz T, et al. Growth and neurodevel- and morbidity in low birth weight infants. J Pediatr 2003;142
opmental outcome of very low birthweight infants with necrotiz- :6628.
ing enterocolitis. Acta Paediatr 2000;89:52832. 258. Poindexter BB, Ehrenkranz RA, Stoll BJ. Parenteral glutamine
235. Walsh MC, Kliegman RM, Hack M. Severity of necrotizing ente- supplementation does not reduce the risk of mortality or late-
rocolitis: Influence on outcome at 2 years of age. Pediatrics onset sepsis in extremely low birth weight infants. Pediatrics
1989;84:80814. 2004;113:120915.
236. Stevenson DK, Kerner JA, Malachowski N, et al. Late morbidity 259. Tubman TRJ, Thompson SW, McGuire W. Glutamine supple-
among survivors of necrotizing enterocolitis. Pediatrics 1980;66: mentation to prevent morbidity and mortality in preterm infants.
9257. Cochrane Database Syst Rev CD001457, 2008.
33 Necrotizing Enterocolitis 473
260. Bury RG, Tudehope D. Enteral antibiotics for preventing necro- 279. Hoyos AB. Reduced incidence of necrotizing enterocolitis associ-
tising enterocolitis in low birthweight or preterm infants. ated with enteral administration of Lactobacillus acidophilus and
Cochrane Database Syst Rev 2001.CD000405, 2001. Bifidobacterium infantis to neonates in an intensive care unit. Int
261. Martin CR, Walker WA. Probiotics: Role in pathophysiology and J Infect Dis 1999;3:197202.
prevention in necrotizing enterocolitis. Semin Perinatol 280. Deshpande G, Rao S, Patole S. Probiotics for prevention of necr-
2008;32:12737. otising enterocolitis in preterm neonates with very low birth-
262. Panigrahi P, Gupta S, Gewolb IH, et al. Occurrence of necrotizing weight: A systematic review of randomised controlled trials.
enterocolitis may be dependent on patterns of bacterial adherence Lancet 2007;369:161420.
and intestinal colonization: Studies in Caco-2 tissue culture and 281. Dani C, Biadaioli R, Bertini G, et al. Probiotics feeding in preven-
weanling rabbit models. Pediatr Res 1994;36:11521. tion of urinary tract infection, bacterial sepsis and necrotizing
263. Mack DR, Michail S, Wei SH. Probiotics inhibit enteropatho- enterocolitis in preterm infants. A prospective double-blind study.
genic E. coli adherence in vitro by inducing intestinal mucin gene Biol Neonate 2002;82:1038.
expression. Am J Physiol 1999;276:G941G50. 282. Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the
264. Madsen KL, Cornish A, Soper P. Probiotic bacteria enhance incidence and severity of necrotizing enterocolitis in very low
murine and human intestinal epithelial barrier function. Gastro- birth weight infants. Pediatrics 2005;115:14.
enterology 2001;121:58091. 283. Bin-Num A, Bromiker R, Wilschanski M, et al. Oral probiotics
265. Kennedy RJ, Kirk SJ, Gardiner K. Mucosal barrier function and prevent necrotizing enterocolitis in very low birth weight neonates.
the commensal flora. Gut 2002;50:4412. J Pediatr 2005;147:1926.
266. Orrhage K, Nord CE. Factors controlling the bacterial coloniza- 284. Kitajima H, Sumida Y, Tanaka R, et al. Early administration of
tion of the intestine in breastfed infants. Acta Paediatr Suppl Bifidobacterium breve to preterm infants: Randomized conrolled
1999;88:4757. trial. Arch Dis Child 1997;76:F1017.
267. Stratiki Z, Costalos C, Sevastiadou S. The effect of a Bifidobacter- 285. Costalos C, Skouteri V, Gounaris A, et al. Enteral feeding of
supplemented bovine milk on intestinal permeability of preterm premature infants with Saccharomyces boulardii. Early Hum Dev
infants. Early Hum Dev 2007;83:5759. 2003;74:8996.
268. Bernet MF, Brassart D, Neeser JR. Lactobacillus acidophilus LA 286. Manzoni P, Mostert M, Leonessa ML, et al. Oral supplementation
1 binds to cultured human intestinal cell lines and inhibits cell with Lactobacillus casei subspecies rhamnosus prevents enteric
attachment and cell invasion by enterovirulent bacteria. Gut colonization by Candida species in preterm neonates: A rand-
1994;35:4839. omized study. Clin Infect Dis 2006;42:173542.
269. Collins MD, Gibson G. Probiotics, prebiotics and synbiotics: 287. Mohan R, Koebnick C, Schildt J, et al. Effects of Bifidobacterium
Approaches for modulating the microbial ecology of the gut. Am lactis Bb12 supplementation on intestinal microbiota of preterm
J Clin Nutr 1999;69:1052S7S. neonates: A double placebo controlled, randomized study. J Clin
270. Sudo N, Sawamura S, Tanaka K. The requirement of intestinal Microbiol 2006;44:402531.
bacterial flora for the development of an IgE production system 288. Manzoni P, Rinaldi M, Cattani S, et al. Bovine lactoferrin sup-
fully susceptible to oral tolerance induction. J Immunol plementation for prevention of late-onset sepsis in very low-
1997;159:173945. birth-weight neonates: A randomized trial. JAMA 2009 7;302:
271. Fukushima Y, Kawata Y, Hara H. Effect of a probiotic formula on 14218.
intestinal immunoglobulin A production in healthy children. Int 289. Braga TD, da Silva GA, de Lira PI, et al. Efficacy of Bifidobacte-
J Food Microbiol 1998;42:3944. rium breve and Lactobacillus casei oral supplementation on
272. Schiffrin EJ, Rochat F, Link-Amster H. Immunomodulation of necrotizing enterocolitis in very-low-birth-weight preterm
human blood cells following the ingestion of lactic acid bacteria. infants: a double-blind, randomized, controlled trial. Am J Clin
J Dairy Sci 1995;78:4917. Nutr 2011;93:816.
273. Marin ML, Tejada-Simon MV, Lee JH. Stimulation of cytokine 290. Lin HC, Hsu CH, Chen HL, et al. Oral probiotics prevent necro-
production in clonal macrophage and T-cell models by Strepto- tizing enterocolitis in very low birth weight preterm infants: a
coccus thermophilus: Comparison with Bifidobacterium sp. and multicenter, randomized, controlled trial. Pediatrics 2008;122:
Lactobacillus bulgaricus. J Food Prot 1998;61:85964. 693700.
274. Murch SH. Toll of allergy reduced by probiotics. Lancet 291. Barclay AR, Stenson B, Simpson JH, et al. Probiotics for necrotiz-
2001;357:10579. ing enterocolitis: A systematic review. J Pediatr Gastroenterol
275. Klinman DM, Yi AK, Beaucage SL. CpG motifs present in bac- Nutr 2007;45:56976.
teria DNA rapidly induce lymphocytes to secrete interleukin 6, 292. Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of
interleukin 12 and interferon gamma. Proc Natl Acad Sci U S A necrotizing enterocolitis and mortality in preterm very low-birth-
1996;93:287983. weight infants: An updated meta-analysis of 20 randomized, con-
276. Fujii T, Ohtsuka Y, Lee T. Bifidobacterium breve enhances trans- trolled trials. J Pediatr Surg 2012;47:2418.
forming growth factor beta1 signaling by regulating Smad7 293. Nair RR, Warner BB, Warner BW. Role of epidermal growth
expression in preterm infants. J Pediatr Gastroenterol Nutr factor and other growth factors in the prevention of necrotizing
2006;43:838. enterocolitis. Semin Perinatol 2008;32:10713.
277. Kitajima H, Sumida Y, Tanaka R. Early administration of Bifido- 294. Grave GD, Nelson SA, Walker WA, et al. New therapies and
bacterium breve to preterm infants: Randomized controlled trial. preventive approaches for necrotizing enterocolitis: Report of a
Arch Dis Child Fetal Neonatal Ed 1997;76:F101F7. research planning workshop. Pediatr Res 2007;62:51014.
278. Mohan R, Koebnick C, Schildt J. Effects of Bifidobacterium lactis 295. Moss RL, Kalish LA, Duggan C, et al. Clinical parameters do not
B12 supplementation on intestinal microbiota of preterm infants: adequately predict outcome in necrotizing enterocolitis: Results
A double-blind, placebo-controlled, randomized study. J Clin from a prospective multi-institutional study. J Perinatol 2008;28:
Microbiol 2006;44:402531. 65764.
C H A P T E R 3 4
Hirschsprung Disease
Jacob C. Langer
Hirschsprung disease (HD), also known as congenital ETIOLOGY AND GENETIC BASIS
megacolon is characterized by the absence of ganglion
cells in the myenteric and submucosal plexuses of the
OF DISEASE
intestine. The first known description of this condition
Ganglion cells are derived from the neural crest. By 13
was by ancient Hindu surgeons in the Shushruta Samheta,1
weeks post-conception, the neural crest cells have
and the first descriptions in the modern medical literature
migrated from proximal to distal through the gastroin-
were from the 17th century.2 In 1887, Harald Hirschs-
testinal tract, after which they differentiate into mature
prung, a pediatrician from Copenhagen, described two
ganglion cells.9 There are two main theories why this
cases of the condition that ultimately bore his name.3 At
process is disturbed in children with HD. The first pos-
that time most children with congenital megacolon died
sibility is that the neural crest cells never reach the distal
from malnutrition and enterocolitis. As the underlying
intestine due to early maturation or differentiation into
pathological basis of the disease was unknown, surgeons
ganglion cells. Data supporting this theory come from
removed the massively dilated proximal bowel and created
animal models showing spontaneous aganglionosis10,11
a colostomy. Attempts at re-anastomosis were uniformly
and from studies of normal neural crest cell migration
unsuccessful.4
performed in chick embryos and human fetuses.12,13 The
Although the absence of ganglion cells in the distal
second possibility is that the neural crest cells reach their
colon of a child with HD was first noted by Tittel in
destination, but fail to survive or differentiate into gan-
19015 and subsequent publications repeated this observa-
glion cells due to an inhospitable microenvironment.14,15
tion, it took many decades for clinicians caring for these
It is likely that HD is actually a heterogeneous group of
children to become aware. The first recognition of agan-
diseases with multiple genetic causes and etiologies.
glionosis by a surgeon as the cause of congenital mega-
A genetic basis for HD has long been suspected
colon was by Ehrenpreis in 1946.6 This was followed in
because of the presence of a family history in many cases
1949 by Swensons first description of a reconstructive
and the known association with trisomy 21 and other
operation for HD.7 Although Swensons operation was
genetically based conditions. Over the past two decades,
originally performed without a colostomy, technical dif-
an increasing number of researchers have made signifi-
ficulties in small infants and the debilitated and malnour-
cant progress in identifying and elucidating the complex
ished state in which many children presented were
array of genetic mutations and mechanisms responsible
reasons most surgeons adopted a multi-staged approach
for this disease.1618 The first and most common gene to
with colostomy as the initial step.8 In recent years,
be identified is the RET proto-oncogene, which encodes
improvements in operative technique and earlier diagno-
a tyrosine kinase receptor. Many mutations of this
sis have resulted in an evolution toward one-stage and
gene and related genes, such as neurturin and glial cell
minimal access procedures. These advances have resulted
line-derived neurotrophic factor (GDNF), have been
in significantly improved morbidity and mortality in
described. It remains unclear how these mutations result
infants with HD.
in aganglionosis, but there is evidence that early neuronal
cell death may be a prominent mechanism.19,20 RET
INCIDENCE AND SPECTRUM abnormalities are most commonly found in patients with
OF DISEASE familial and long-segment involvement. Mutations in the
endothelin family of genes, particularly endothelin-3 and
HD occurs in approximately 1:5,000 live births. Approx- the endothelin-B receptor, are also commonly associated
imately 80% of children have a transition zone in the with HD. Many of these children have other neuro
rectum or rectosigmoid colon. Another 10% have more cristopathies such as dysfunction of melanocytes, con-
proximal colonic involvement, and about 510% have genital deafness, central hypoventilation, and
total colonic aganglionosis with variable involvement of neuroblastoma. From animal models, there is evidence
the distal small intestine. Rarely, babies are afflicted with that mutations in the endothelin and SOX-10 genes may
near-total intestinal aganglionosis. produce early maturation or differentiation of neural
A number of syndromes are associated with HD crest cells, which decreases the number of available pro-
including trisomy 21, congenital central hypoventilation genitor cells and prevents the neural crest cells from
syndrome, GoldbergShprintzen syndrome, Smith migrating any further.21,22 Other genes associated with
LemliOpitz syndrome, neurofibromatosis, and neuro HD include S1P1 (now known as ZFHX1B), Phox2B, and
blastoma (Box 34-1). the Hedgehog/Notch complex.23
474
34 Hirschsprung Disease 475
A B
FIGURE 34-1 These two barium enema examinations in different infants demonstrate Hirschsprung disease. The aganglionic rectum
(arrows) in both studies is small and contracted. The proximal ganglionic colon is dilated. A transition zone between the aganglionic
and ganglionic colon is nicely seen in both studies.
Prenatal diagnosis of HD is rare, and is usually due to transition zone between the normal and aganglionic
total colonic disease resulting in ultrasound (US) findings bowel (Fig. 34-1), although approximately 10% of
of fetal intestinal obstruction.24 Most affected patients neonates with HD may not have a demonstrable radio-
present during the neonatal period with abdominal dis- logical transition zone.26 Occasionally, false positive
tension, bilious vomiting, and feeding intolerance. studies occur.27 It is also important to obtain a plain
Delayed passage of meconium beyond the first 24 hours radiograph 24 hours later. Retention of the contrast is
is present in approximately 90%. Occasionally, cecal or very suggestive for HD (Fig. 34-2). It is also important
appendiceal perforation may be the initial event.25 Plain to use a water-soluble material as the enema potentially
radiographs characteristically show dilated bowel loops may be a definitive treatment for other conditions in the
throughout the abdomen. The next step is a water-soluble differential diagnosis, such as meconium ileus and meco-
contrast enema. The pathognomonic finding of HD is a nium plug syndrome. Once the diagnosis of HD is
476 SECTION IV Abdomen
suspected, the diagnosis must be confirmed by rectal line, the rectal biopsy should be taken at least 1.01.5cm
biopsy, which in the neonate can be done at the bedside above it. However, a biopsy too proximal may miss a
without sedation and using a suction technique. short aganglionic segment. In addition to hematoxylin
Patients presenting later in childhood have chronic and eosin, many pathologists also stain for acetylcho-
severe constipation. As constipation is common in chil- linesterase, which has a characteristic pattern in the sub-
dren, it can be difficult to differentiate HD from more mucosa and mucosa in children with HD (Fig. 34-5).
common causes. Clinical features pointing to the diagno- Recently, it has been shown that immunochemical stain-
sis include delayed passage of meconium at birth, failure ing for calretinin is almost always absent in patients with
to thrive, abdominal distention, and dependence on HD (Fig. 34-6).29
enemas without significant encopresis.28 Although a con-
trast enema usually demonstrates a transition zone in
Rectal
older children, a false negative study may be due to distention
massive rectal distension in combination with a very short
aganglionic segment. Reversal of the usual rectosigmoid
ratio and retention of contrast on a 24-hour postevacua-
mmHg
tion film also support the diagnosis. Anorectal manom-
etry is another useful screening technique, in which the
presence of a recto-anal inhibitory reflex (reflex relaxa-
tion of the internal anal sphincter in response to balloon
distension of the rectum) essentially rules out HD (Fig.
34-3). In older children, the suction rectal biopsy may be
A
less reliable because of a higher risk of sampling error. Time
Full-thickness biopsies, usually under general anesthesia,
may be necessary in these patients.
Approximately 10% of neonates with HD present
with fever, abdominal distention, and diarrhea due to
Hirschsprung-associated enterocolitis (HAEC), which
can be life-threatening. Since HD characteristically
mmHg
causes constipation rather than diarrhea, this presenta-
tion may be confusing and the diagnosis may not be
considered. A careful history, including a history of
delayed passage of meconium and intermittent stooling,
should lead to an investigation for HD.
The gold standard for the diagnosis is the absence of B
Time
ganglion cells in the submucosal and myenteric plexuses FIGURE 34-3 (A) In the child without Hirschsprung disease
on histological examination (Fig. 34-4A). Most patients undergoing anorectal manometry, the recto-anal inhibitory
will also have evidence of hypertrophied nerve trunks reflex is normal. Note the drop in the internal sphincter pressure
(Fig. 34-4B), although this finding is not always present, with rectal distention. (B) A child with Hirschsprung disease is
seen to have abnormally increased contraction of the anal canal
particularly in children with total colonic disease or a very and no relaxation of the internal sphincter with rectal distention.
short aganglionic segment. As there is normally a paucity (The arrow points to the initiation of rectal distention in both A
of ganglion cells in the area 0.51.0cm above the dentate and B.)
Proximal
ganglionated
bowel
Everted
rectosigmoid
stump
A B
FIGURE 34-7 The principles of the Swenson pull-through procedure are seen in these drawings. (A) The proximal ganglionated
bowel is grasped through an incision in the prolapsed rectosigmoid stump. (B) The ganglionated bowel is then sewn to the anus.
34 Hirschsprung Disease 479
A B
FIGURE 34-8 (A) For the Soave operation, there is extramucosal dissection of the rectum after circumferential incision of the rectal
mucosa. (B) The ganglionated colon is pulled through the aganglionic rectal cuff, and a coloanal anastomosis is performed.
SA/C
SN
$ B
FIGURE 34-10 (A) The surgeon (S) and surgical assistant/camera holder (SA/C) stand above the patients head with the monitor (M)
positioned beyond the infants feet. The scrub nurse (SN) can be positioned according to the surgeons preference, although being
positioned at the foot of the operating table appears to be ideal. A, anesthesiologist. (B) The photograph shows port placement for
this operation. Usually three or four ports are required. The umbilical port is inserted using an open technique, and the other ports
are introduced under direct visualization. The telescope (dotted arrow) is placed through the 5mm port in the right upper abdomen.
The surgeons two primary working ports are the umbilical port for the left hand and the right lower abdominal port for the right
hand. A retracting instrument (solid arrow) is often helpful and can be inserted through a stab incision in the infants left upper
abdomen. A urinary catheter has been introduced to help decompress the bladder. (From Morowitz MJ, Georgeson KE. Laparoscopic
assisted pull-through for Hirschsprungs disease. In: Holcomb GW, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy
and Thoracoscopy. Philadelphia: Elsevier; 2008. p. 101108. Reprinted with permission.)
A B
FIGURE 34-11 (A) An intracorporeal biopsy is being performed on the sigmoid colon. A fine-tipped grasping forceps has been used
to grasp the biopsy site, and Metzenbaum scissors are used to obtain the biopsy specimen. (B) This biopsy was performed through
the umbilical incision. One port and another instrument have been introduced through the infants abdominal wall. A site on the
colon for the biopsy was visualized and delivered just under the umbilical cannula. The umbilical cannula was removed, and this
portion of the colon was grasped and exteriorized. An extracorporeal biopsy was obtained and the biopsy site was closed. This is
an alternative means for obtaining the biopsy. (From Morowitz MJ, Georgeson KE. Laparoscopic assisted pull-through for Hirschsprungs
disease. In: Holcomb GW, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier;
2008. p. 101108. Reprinted with permission.)
those without laparoscopic skills, and by pediatric sur- usually also includes some of the distal ileum (Fig. 34-16).
geons in parts of the world where access to laparoscopic In rare cases of near-total intestinal aganglionosis, most
equipment is limited. of the small bowel is aganglionic as well. Most neonates
with long-segment disease present with a distal small
bowel obstruction, although occasionally children with
Long-Segment Aganglionosis long-segment disease may not present until after weaning
Long-segment HD is usually defined as a transition zone from breast milk. The contrast enema typically shows a
which is proximal to the mid-transverse colon. The most shortened, relatively narrow question mark colon (Fig.
common form is total colonic aganglionosis, which 34-17).57 There may also be a transition zone in the small
34 Hirschsprung Disease 481
C B
FIGURE 34-13 (A) The perineal dissection begins with the placement of circumferential 2-0 silk traction sutures from the dentate
line to the perineum 2 to 3 cm outward from the anus. (B, C) A needle-tipped electrocautery is used to circumferentially incise the
rectal mucosa approximately 5mm proximal to the anal columns. Fine silk traction sutures are then placed in the rectal mucosa
to help retract the mucosa during circumferential dissection. (From Morowitz MJ, Georgeson KE. Laparoscopic assisted pull-through
for Hirschsprungs disease. In: Holcomb GW, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy.
Philadelphia: Elsevier; 2008. p. 101108. Reprinted with permission.)
482 SECTION IV Abdomen
A B
C D
FIGURE 34-14 (A) The muscular cuff of the rectum has been divided and the ganglionic colon has been exteriorized through the
anal canal. Note that the anastomosis will be performed proximal to the biopsy site (arrow). (B) The pull-through colon is being
completely transected above the biopsy site and made ready for the coloanal anastomosis. (C) The anastomosis is being performed
with interrupted 4-0 absorbable sutures. (D) The everting stay sutures have been cut, allowing the anastomosis to retract cephalad.
(From Morowitz MJ, Georgeson KE. Laparoscopic assisted pull-through for Hirschsprungs disease. In: Holcomb GW, Georgeson KE, Rothen-
berg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; 2008. p. 101108. Reprinted with permission.)
bowel. The rectal biopsy shows absence of ganglion cells, outcomes following pull-through are better once the
but in many cases there are no hypertrophic nerves or stool has thickened, which usually occurs after the first
abnormalities on acetylcholinesterase staining. few months of life.
The initial operative approach involves sequential There are three types of operations available for chil-
colonic biopsies looking for ganglion cells on frozen dren with long-segment disease: straight pull-through
section. These biopsies can be performed via laparotomy using one of the standard techniques (Swenson, Duhamel,
or laparoscopy, or through an umbilical incision. Using or Soave), colon patch using either the left colon (Martin)
the appendix for the initial biopsy can result in a false (Fig. 34-18) or the right colon (Kimura) (Fig. 34-19), and
positive diagnosis of total colonic aganglionosis as there ileal J-pouch. There are no prospective or well-controlled
may be a paucity of ganglion cells in the appendix in series reporting long-term results of operations for long-
children with shorter segment disease.58 Thus, a biopsy segment HD. Although the colon patch procedures theo-
of the cecum is preferable. Once the level of agangliono- retically result in decreased stool output due to better
sis is identified, most surgeons create a stoma, wait for water absorption, the aganglionic colon tends to dilate
permanent sections, and perform the definitive recon- and many of these patients develop severe enterocolitis,
structive procedure later. Although primary pull-through requiring removal of the patch or a permanent stoma.
without ileostomy for total colonic disease has been per- Children undergoing a straight pull-through tend to
formed, this approach requires a high degree of confi- experience gradually decreasing stool frequency over
dence in the pathologist, since it requires performing a time, with an acceptable quality of life.6062
total colectomy on the basis of frozen section analysis Rarely, almost the entire intestinal tract is aganglionic,
alone. In addition, there are many reports of skip areas usually leaving 1040cm of normally innervated jejunum.
in children with total colonic aganglionosis so that per- These children require total parenteral nutrition (TPN)
manent sections are advisable before considering total from birth. At the time of the first exploration, the goal
colectomy.59 Finally, some surgeons believe that the is to determine the extent of aganglionosis based on
34 Hirschsprung Disease 483
A B
C D
FIGURE 34-15 The salient points for a transanal Soave pull-through are depicted. (A) An umbilical incision is used for a preliminary
biopsy. A Hegar dilator is used to push the sigmoid colon into the umbilical incision. (B) Eversion sutures are placed in the anus,
and a nasal speculum is used to provide exposure to the anal canal. A circumferential incision is made 5 mm above the dentate
line. (C) The submucosal dissection is carried 23cm. (D) The pull-through bowel is divided at least 2 cm above the biopsy site that
has ganglion cells, and the anastomosis is performed. Care must be taken to perform the anastomosis to the rectal mucosa, not to
the transitional epithelium. Otherwise, normal sensation will be lost and the risk of incontinence will be increased.
FIGURE 34-16 This neonate has total colon aganglionosis. The FIGURE 34-17 This contrast enema was performed in a child
solid arrow marks the contracted aganglionic terminal ileum with total colonic aganglionosis. There is no transition zone in
and the transition zone to ganglionated ileum is marked by the the colon, and the colon is foreshortened with a question mark
dotted arrow. configuration.
484 SECTION IV Abdomen
POSTOPERATIVE MANAGEMENT
Most children undergoing a laparoscopic or transanal
pull-through can be fed immediately and discharged
within 2448 hours. The anastomosis is calibrated with
an appropriately sized dilator or finger one to two weeks
after the procedure. Although most surgeons instruct the
parents to perform daily dilatations, a program of weekly
calibration by the surgeon is less traumatic and is associ-
A
ated with similar outcomes.71 The parents should be
instructed to protect the buttocks with barrier cream to
prevent perineal skin breakdown. In addition, the family
and the primary care physician should be educated about
the signs and symptoms of postoperative enterocolitis,
since this can result in rapid severe illness and even death
in a few patients.72
LONG-TERM OUTCOMES
Long-term problems in children with HD include
B
ongoing obstructive symptoms, soiling, and enterocoli-
FIGURE 34-19 These drawings show the salient points with the tis.73 It is important for the surgeon to follow these chil-
Kimura procedure. dren closely, at least until they are through the toilet
training process, in order to identify and provide timely
frozen sections, and to create a stoma either at the most treatment for these problems.40,74,75
distal point that has normally innervated bowel or more
distally with aganglionic bowel.63 A central venous cath-
eter should be inserted for TPN, and a gastrostomy
Obstructive Symptoms
should be considered for continuous feeding of breast Obstructive symptoms may take the form of abdominal
milk or elemental formula. distension, bloating, vomiting, or ongoing severe consti-
These children are best managed by a multidiscipli- pation. There are five major reasons for these symptoms
nary group focused on intestinal failure.64 Strict attention following a pull-through: mechanical obstruction, recur-
to prevention of sepsis, treatment of bacterial overgrowth, rent or acquired aganglionosis, disordered motility in the
use of trophic feedings, and prevention of TPN-related residual colon or small bowel, internal sphincter achala-
cholestasis using a variety of strategies including omega-3 sia, or functional megacolon caused by stool-holding
lipids are all important.65 behavior (Box 34-2). The clinician will have much greater
Subsequent management must be individualized, success in managing these difficult patients if an organ-
depending on the length of normally innervated bowel ized approach is taken. One proposed algorithm is shown
and the clinical status of the child.66 For infants and chil- in Figure 34-20.76
dren who develop significant dilatation of the normally
innervated bowel, tapering, imbrication, or bowel length-
Mechanical Obstruction
ening procedures such as the Bianchi or serial transverse
enteroplasty (STEP) procedure may be helpful.67,68 The The most common cause of mechanical obstruction after
myectomymyotomy procedure popularized by Zeigler a pull-through operation is a stricture. This problem is
34 Hirschsprung Disease 485
more common after a Swenson or Soave operation (Fig. an anastomotic stricture consists of repeated dilatation
34-21A). Patients undergoing a Duhamel procedure may using a finger, dilator, or balloon. For recalcitrant stric-
have a retained spur consisting of the anterior agangli- tures, antegrade dilatation using Tucker dilators,77 intral-
onic bowel, which may fill with stool and obstruct the esional steroid,78 or topical mitomycin C79 can be tried.
pulled-through bowel (Fig. 34-21B). In other cases, there In some cases, revision of the pull-through is necessary.8082
may be obstruction secondary to a twist in the pulled- Duhamel spurs can be resected from above or managed
through bowel (Fig. 34-21C), or narrowing due to a long by extending the staple line from below. Twisted pull-
muscular cuff in children who have had a Soave throughs and narrow muscular cuffs usually require a
operation. repeat pull-through, although a muscular cuff can occa-
Obstruction can be discovered with digital rectal sionally be divided laparoscopically.
examination and a contrast enema. Initial management of
Persistent or Acquired Aganglionosis
Physical exam and barium enema This problem may be due to an error in histological
analysis,83 a transition zone pull-through,84,85 or loss of
No stricture Stricture ganglion cells,86 and can be diagnosed by performing a
biopsy above the colo-anal anastomosis.87 The specimen
from the original operation should be reviewed and
Rectal biopsy Dilate or re-do further sections should be taken circumferentially at the
pull through
resection margin since the transition zone can be asym-
No ganglion cells Ganglion cells present metrical in children with HD.88 In most cases, the best
treatment for persistent or acquired aganglionosis is a
repeat pull-through, which can be accomplished using
Re-do pull through Motility workup either a Soave or a Duhamel approach.81
Motility Disorder
Normal Abnormal focal Abnormal Children with HD often have abnormal motility through-
generalized
out the intestinal tract, including gastroesophageal reflux
Resect
and delayed gastric emptying.89 These abnormalities may
be focal, usually involving the left colon, or may be gen-
eralized, and may or may not be associated with other
Bowel regimen
Try botox No clinical response
or stoma histological abnormalities such as intestinal neuronal dys-
plasia (IND). Techniques for diagnosing motility disor-
ders include radiological shape study90 radionuclide colon
Clinical response
transit study,91 colonic manometry,92 and laparoscopic
biopsies looking for evidence of IND.93 If a focal abnor-
Repeat botox or mality is found, resection with repeat pull-through using
myectomy normal bowel is needed. Diffuse dysmotility is best
FIGURE 34-20 Algorithm for the investigation and management
treated with bowel management, which may include
of the child with obstructive symptoms following a antegrade enemas through a cecostomy,94 and the use of
pull-through. prokinetic agents.
A B C
FIGURE 34-21 Causes of mechanical obstruction after a pull-through are shown. (A) Stricture following a Soave procedure.
(B) Anterior aganglionic spur (asterisk) following a Duhamel procedure. (C) Twisted transanal pull-through.
486 SECTION IV Abdomen
Internal Sphincter Achalasia are amenable to a surgical solution. Most of these chil-
dren are best managed using a bowel routine which may
This term refers to obstructive symptoms caused by the include a constipating diet, stimulant laxatives, and rectal
lack of a normal recto-anal inhibitory reflex which is or antegrade enemas. Biofeedback training has been
found in all children with HD (see Fig. 34-3). Most chil- advocated, especially for those children with sphincter
dren eventually grow out of this problem over time, weakness. In some cases, the child is best served by a
usually by the age of 5 years. The diagnosis can be con- colostomy.
firmed by demonstrating a clinical response to intra If both the sphincter and sensation are intact, the most
sphinteric botulinum toxin.95 The traditional operative likely cause of soiling after a pull-through is pseudo-
approach for internal sphincter achalasia has been inter- incontinence.103 This may be caused by severe obstipa-
nal sphincterotomy or myectomy.96,97 However, since this tion with a massively distended rectum and overflow of
problem may resolve on its own, and there is concern liquid stool. Other patients leak small amounts of stool
about sphincter-cutting operations impacting continence, through the day, creating skid marks in the underwear
we prefer to use chemical sphincterotomy with intras- on a constant basis. Other children can suffer from
phincteric botulinum toxin.98100 In many cases, repeated hyperperistalsis of the pulled-through bowel, which
injection of botulinum toxin, or applications of nitroglyc- results in the inability of the anal sphincter to achieve
erine paste or topical nifedipine, are necessary while control despite normal sphincter function.92
waiting for resolution of the problem. Successful management of soiling in a child with HD
depends on a clear understanding of the reasons for the
Functional Megacolon soiling. Evaluation requires a careful history and physical
examination, and investigations such as abdominal films,
Functional megacolon is the result of stool-holding barium enema, anorectal manometry, and in some cases,
behavior, which is very common in normal children.101 colonic manometry. Children with severe constipation
This behavior may be even more common in children will benefit from laxative therapy. However, if the sphinc-
with HD because of their predisposition to constipa- ter and/or sensation are inadequate, passive laxatives such
tion.102 This problem is best treated with a bowel man- as lactulose or PEG 3300 will make the problem worse,
agement regimen consisting of laxatives and behavior and the child instead should be treated with stimulant
modification strategies. In severe cases, the child may laxatives such as senna, or enemas. On the other hand,
require a cecostomy for antegrade enemas, or even a children with stool-holding behavior who have normal
proximal stoma. In many cases, the cecostomy or stoma sphincter function and sensation will often experience
can be reversed when the child reaches adolescence. exacerbation of the behavioral problem by enemas or any
other kind of anal manipulation. Children without con-
Fecal Soiling stipation who have hyperperistalsis of the pulled-through
bowel or abnormal sphincter function or sensation will
There are three broad causes for soiling after a pull- benefit from a constipating diet and medications such as
through: abnormal sphincter function, abnormal sensa- loperamide. On the other hand, children with slow transit
tion, or pseudo-incontinence (Box 34-3). Abnormal constipation or stool-holding behavior will benefit from
sphincter function may be due to sphincter injury during a high-fiber diet and passive laxative therapy. The treat-
the pull-through or to a previous myectomy or sphinc- ment of soiling must be based on a clear understanding
terotomy, and can usually be identified using anorectal of the childs underlying problem.
manometry or endorectal ultrasound. There are two
forms of abnormal sensation. The first is lack of sensation
of a full rectum, which can also be identified using Enterocolitis
anorectal manometry, and the other is an inability to The etiology of HAEC is unknown, and is probably
detect the difference between gas and stool. This problem multi-factorial. Stasis caused by functional obstruction
is usually due to loss of the transitional epithelium because permits bacterial overgrowth with secondary infection.
the anastomosis was performed below the dentate line. Infectious agents such as Clostridium dificile or rotavirus
This distinction is usually evident on physical examina- have been postulated as being causative, but there are few
tion. Neither sphincter weakness nor abnormal sensation data to support a specific pathogen.104 There is some
evidence implicating alterations in intestinal mucin pro-
duction and the mucosal production of immunoglobu-
Causes of Soiling following Surgery lins, which presumably results in loss of intestinal barrier
BOX 34-3 function and allows bacterial invasion.105,106
for Hirschsprung Disease
Enterocolitis may be present both before and after
Abnormal sensation operative correction, and can range in severity from mild
Inability to feel rectal distension to life-threatening. HAEC is more common in younger
Loss of transitional epithelium children,107 longer segment disease, and trisomy 21. Clin-
Abnormal sphincter function
ical presentation includes fever, abdominal distention,
Pseudo-incontinence
Associated with severe constipation diarrhea, elevated leukocyte count, and evidence of intes-
Associated with hyperperistalsis of the pulled-through tinal edema on an abdominal film. Because there is
bowel overlap between HAEC and other conditions such as
gastroenteritis, the true incidence is unknown. A HAEC
34 Hirschsprung Disease 487
20. Uesaka T, Nagashimada M, Yonemura S, et al. Diminished 45. de Lagausie P, Berrebi D, Geib G, et al. Laparoscopic Duhamel
Ret expression compromises neuronal survival in the colon and procedure. Management of 30 cases. Surg Endosc 1999;13:
causes intestinal aganglionosis in mice. J Clin Invest 2008;118: 9724.
18908. 46. Hoffmann K, Schier F, Waldschmidt J. Laparoscopic Swensons
21. Paratore C, Eichenberger C, Suter U, et al. Sox10 haploinsuffi- procedure in children. Eur J Pediatr Surg 1996;6:157.
ciency affects maintenance of progenitor cells in a mouse model 47. De la Torre-Mondragon L, Ortega-Salgado JA. Transanal
of Hirschsprung disease. Hum Mol Genet 2002;11:307585. endorectal pull-through for Hirschsprungs disease. J Pediatr Surg
22. Gershon MD. Endothelin and the development of the enteric 1998;33:12836.
nervous system. Clin Exp Pharmacol Physiol 1999;26:9858. 48. Langer JC, Minkes RK, Mazziotti MV, et al. Transanal one-stage
23. Ngan ES, Garcia-Barcelo MM, Yip BH, et al. Hedgehog/Notch- Soave procedure for infants with Hirschsprung disease. J Pediatr
induced premature gliogenesis represents a new disease mecha- Surg 1999;34:14852.
nism for Hirschsprung disease in mice and humans. J Clin Invest 49. De La Torre L, Langer JC. Transanal endorectal pull-through for
2011;121:346778. Hirschsprung disease: Technique, controversies, pearls, pitfalls,
24. Belin B, Corteville JE, Langer JC. How accurate is prenatal and an organized approach to the management of postoperative
sonography for the diagnosis of imperforate anus and Hirschs- obstructive symptoms. Semin Pediatr Surg 2010;19:96106.
prungs disease? Pediatr Surg Int 1995;10:302. 50. Nasr A, Langer JC. Evolution of the technique in the transanal
25. Newman B, Nussbaum A, Kirkpatrick JA Jr. Bowel perforation in pull-through for Hirschsprung disease: Effect on outcome.
Hirschsprungs disease. AJR 1987;148:11957. J Pediatr Surg 2007;42:369.
26. Smith GHH, Cass D. Infantile Hirschsprungs diseaseis barium 51. Sookpotarom P, Vejchapipat P. Primary transanal Swenson pull-
enema useful? Pediatr Surg Int 1991;6:31821. through operation for Hirschsprungs disease. Pediatr Surg Int
27. Diamond IR, Casadiego G, Traubici J, et al. The contrast enema 2009;25:76773.
for Hirschsprung disease: Predictors of a false-positive result. 52. Sauer CJE, Langer JC, Wales PW. The versatility of the umbilical
J Pediatr Surg 2007;42:7925. incision in the management of Hirschsprungs disease. J Pediatr
28. Lewis NA, Levitt MA, Zallen GS, et al. Diagnosing Hirschs- Surg 2005;40:3859.
prungs disease: Increasing the odds of a positive rectal biopsy 53. Proctor ML, Traubici J, Langer JC, et al. Correlation between
result. J Pediatr Surg 2003;38:4126. radiographic transition zone and level of aganglionosis in Hirschs-
29. Kapur RP, Reed RC, Finn LS, et al. Calretinin immunohisto- prungs disease: Implications for surgical approach. J Pediatr Surg
chemistry versus acetylcholinesterase histochemistry in the evalu- 2003;38:7758.
ation of suction rectal biopsies for Hirschsprung Disease. Pediatr 54. Muller CO, Mignot C, Belarbi N, et al. Does the radiographic
Dev Pathol 2009;12:615. transition zone correlate with the level of aganglionosis on the
30. Kaymakcioglu N, Yagci G, Can MF, et al. Role of anorectal myec- specimen in Hirschsprungs disease? Pediatr Surg Int 2012;28:
tomy in the treatment of short segment Hirschsprungs disease in 597601.
young adults. Int Surg 2005;90:10912. 55. Langer JC, Durrant AC, de la Torre ML, et al. One-stage transanal
31. Visser R, van de Ven TJ, van Rooij IA, et al. Is the Rehbein pro- Soave pullthrough for Hirschsprung disease: A multicenter expe-
cedure obsolete in the treatment of Hirschsprungs disease? rience with 141 children. Ann Surg 2003;238:56976.
Pediatr Surg Int 2010;26:111720. 56. Kim AC, Langer JC, Pastor AC, et al. Endorectal pull-through
32. Swenson O. Hirschsprungs disease: A review. Pediatrics for Hirschsprungs disease-a multicenter, long-term comparison
2002;109:9148. of results: Transanal vs transabdominal approach. J Pediatr Surg
33. So HS, Schwartz DL, Becker JM, et al. Endorectal pull-through 2010;45:121320.
without preliminary colostomy in neonates with Hirschsprungs 57. Stranzinger E, DiPietro MA, Teitelbaum DH, et al. Imaging of
disease. J Pediatr Surg 1980;15:4701. total colonic Hirschsprung disease. Pediatr Radiol 2008;38:
34. Cass DT. Neonatal one-stage repair of Hirschsprungs disease. 116270.
Pediatr Surg Int 1990;5:3416. 58. Anderson KD, Chandra R. Segmental aganglionosis of the appen-
35. Langer JC, Fitzgerald PG, Winthrop AL, et al. One vs two stage dix. J Pediatr Surg 1986;21:8524.
Soave pull-through for Hirschsprungs disease in the first year of 59. Burjonrappa S, Rankin L. Hop the skip with extended segment
life. J Pediatr Surg 1996;31:337. intestinal biopsy in Hirschsprungs disease. Intern J Surg Case
36. Hackam DJ, Superina RA, Pearl RH. Single-stage repair of Hir- Reports 2012;3:1869.
schsprungs disease: A comparison of 109 patients over 5 years. 60. Shen C, Song Z, Zheng S, et al. A comparison of the effectiveness
J Pediatr Surg 1997;32:102831. of the Soave and Martin procedures for the treatment of total
37. Bufo AJ, Chen MK, Shah R, et al. Analysis of the costs of surgery colonic aganglionosis. J Pediatr Surg 2009;44:23558.
for Hirschsprungs disease: One-stage laparoscopic pull-through 61. Barrena S, Andres AM, Burgos L, et al. Long-term results of the
versus two-stage Duhamel procedure. Clin Pediatr 1999;38: treatment of total colonic aganglionosis with two different tech-
5936. niques. Eur J Pediatr Surg 2008;18:3759.
38. Sherman JO, Snyder ME, Weitzman JJ, et al. A 40-year multina- 62. Marquez TT, Acton RD, Hess DJ, et al. Comprehensive review
tional retrospective study of 880 Swenson procedures. J Pediatr of procedures for total colonic aganglionosis. J Pediatr Surg
Surg 1989;24:8338. 2009;44:25765.
39. Swenson O. Hirschsprungs diseasea complicated therapeutic 63. Travassos DV, van der Zee DC. Is complete resection of the
problem: Some thoughts and solutions based on data and personal aganglionic bowel in extensive total aganglionosis up to the
experience over 56 years. J Pediatr Surg 2004;39:144953. middle ileum always necessary? J Pediatr Surg 2011;46:20549.
40. Moore SW, Albertyn R, Cywes S. Clinical outcome and long-term 64. Diamond IR, de Silva N, Pencharz PB, et al. Neonatal short bowel
quality of life after surgical correction of Hirschsprungs disease. syndrome outcomes after the establishment of the first Canadian
J Pediatr Surg 1996;31:1496502. multidisciplinary intestinal rehabilitation program: Preliminary
41. Giuliani S, Betalli P, Narciso A, et al. Outcome comparison among experience. J Pediatr Surg 2007;42:80611.
laparoscopic Duhamel, laparotomic Duhamel, and transanal 65. Diamond IR, Sterescu A, Pencharz PB, et al. The rationale
endorectal pull-through: A single-center, 18-year experience. for the use of parenteral omega-3 lipids in children with short
J Laparosc Adv Surg Tech 2011;21:85963. bowel syndrome and liver disease. Pediatr Surg Int 2008;24:
42. Gunnarsdottir A, Larsson LT, Arnbjornsson E. Transanal endorec- 7738.
tal vs. Duhamel pull-through for Hirschsprungs disease. Eur J 66. Ruttenstock E, Puri P. A meta-analysis of clinical outcome in
Pediatr Surg 2010;20:2426. patients with total intestinal aganglionosis. Pediatr Surg Int
43. Georgeson KE, Fuenfer MM, Hardin WD. Primary laparoscopic 2009;25:8339.
pull-through for Hirschsprungs disease in infants and children. 67. Wales PW. Surgical therapy for short bowel syndrome. Pediatr
J Pediatr Surg 1995;30:101721. Surg Int 2004;20:64757.
44. Georgeson KE, Cohen RD, Hebra A, et al. Primary laparoscopic- 68. Wales PW, de Silva N, Langer JC, et al. Intermediate outcomes
assisted endorectal colon pull-through for Hirschsprungs disease: after serial transverse enteroplasty in children with short bowel
A new gold standard. Ann Surg 1999;229:67883. syndrome. J Pediatr Surg 2007;42:180410.
490 SECTION IV Abdomen
69. Ziegler MM, Royal RE, Brandt J, et al. Extended myectomy- 93. Mazziottti MV, Langer JC. Laparoscopic full-thickness intestinal
myotomy. A therapeutic alternative for total intestinal agangliono- biopsies in children. J Pediatr Gastroenterol Nutr 2001;33:
sis. Ann Surg 1993;218:5049. 547.
70. Sauvat F, Grimaldi C, Lacaille F, et al. Intestinal transplantation 94. Yagmurlu A, Harmon CM, Georgeson KE. Laparoscopic cecos-
for total intestinal aganglionosis: A series of 12 consecutive chil- tomy button placement for the management of fecal incontinence
dren. J Pediatr Surg 2008;43:18338. in children with Hirschsprungs disease and anorectal anomalies.
71. Temple S, Shawyer AC, Langer JC. Is daily dilatation by parents Surg Endosc 2006;20:6247.
necessary after surgery for Hirschsprung disease and anorectal 95. Minkes RK, Langer JC. A prospective study of botulinum toxin
malformations? J Pediatr Surg 2012;47:20912. for internal anal sphincter hypertonicity in children with Hirschs-
72. Marty TL, Matlak ME, Hendrickson M, et al. Unexpected death prungs disease. J Pediatr Surg 2000;35:17336.
from enterocolitis after surgery for Hirschsprungs disease. Pedi- 96. Abbas Banani S, Forootan H. Role of anorectal myectomy after
atrics 1995;96:11821. failed endorectal pull-through in Hirschsprungs disease. J Pediatr
73. Dasgupta R, Langer JC. Evaluation and management of persistent Surg 1994;29:13079.
problems after surgery for Hirschsprung disease in a child. 97. Wildhaber BE, Pakarinen M, Rintala RJ, et al. Posterior myotomy/
J Pediatr Gastroenterol Nutr 2008;46:139. myectomy for persistent stooling problems in Hirschsprungs
74. Yanchar NL, Soucy P. Long term outcomes of Hirschsprungs disease. J Pediatr Surg 2004;39:9206.
disease: The patients perspective. J Pediatr Surg 1999;34: 98. Koivusalo AI, Pakarinen MP, Rintala RJ. Botox injection treat-
115260. ment for anal outlet obstruction in patients with internal anal
75. Rintala RJ, Pakarinen MP. Outcome of anorectal malformations sphincter achalasia and Hirschsprungs disease. Pediatr Surg Int
and Hirschsprungs disease beyond childhood. Semin Pediatr Surg 2009;25:8736.
2010;19:1607. 99. Jiang da P, Xu CQ, Wu B, et al. Effects of botulinum toxin injec-
76. Langer JC. Persistent obstructive symptoms after surgery for Hir- tion on anal achalasia after pull-through operations for Hirschs-
schsprung disease: Development of a diagnostic and therapeutic prungs disease: A 1-year follow-up study. Inter J Colorectal Dis
algorithm. J Pediatr Surg 2004;39:145862. 2009;24:5978.
77. Langer JC, Winthrop AL. Antegrade dilatation over a string for 100. Patrus B, Nasr A, Langer JC, et al. Intrasphincteric botulinum
the management of anastomotic complications after a pull- toxin decreases the rate of hospitalization for postoperative
through procedure. J Am Coll Surg 1996;183:4112. obstructive symptoms in children with Hirschsprung disease.
78. Lucha PA Jr, Fticsar JE, Francis MJ. The strictured anastomosis: J Pediatr Surg 2011;46:1847.
Successful treatment by corticosteroid injectionsreport of three 101. Di Lorenzo C. Constipation. In: Hyman PE, editor. Pediatric
cases and review of the literature. Dis Colon Rectum Gastrointestinal Motility Disorders. New York, NY: Academy
2005;48:8625. Professional Information Services; 1994. p. 12944.
79. Mueller CM, Beaunoyer M, St-Vil D. Topical mitomycin-C for 102. Blum NJ, Taubman B, Nemeth N. During toilet training, consti-
the treatment of anal stricture. J Pediatr Surg 2010;45:2414. pation occurs before stool toileting refusal. Pediatrics 2004;113:
80. van Leeuwen K, Teitelbaum DH, Elhalaby EA, et al. Long-term e5202.
follow-up of redo pull-through procedures for Hirschsprungs 103. Levitt M, Pena A. Update on pediatric faecal incontinence. Eur J
disease: Efficacy of the endorectal pull-through. J Pediatr Surg Pediatr Surg 2009;19:19.
2000;35:82933. 104. Wilson-Storey D, Scobie WG, McGenity KG. Microbiological
81. Langer JC. Repeat pullthrough surgery for complicated Hirschs- studies of the enterocolitis of Hirschsprungs disease. Arch Dis
prung disease: Indications, techniques, and results. J Pediatr Surg Child 1990;65:13389.
1999;34:113641. 105. Mattar AF, Coran AG, Teitelbaum DH. MUC-2 mucin produc-
82. Pena A, Elicevik M, Levitt MA. Reoperations in Hirschsprung tion in Hirschsprungs disease: Possible association with entero-
disease. J Pediatr Surg 2007;42:100813. colitis development. J Pediatr Surg 2003;38:41721.
83. Shayan K, Smith D, Langer JC. Reliability of intraoperative 106. Imamura A, Puri P, OBriain DS, et al. Mucosal immune defence
frozen sections in the management of Hirschsprung disease. mechanisms in enterocolitis complicating Hirschsprungs disease.
J Pediatr Surg 2004;39:13458. Gut 1992;33:8016.
84. Ghose SI, Squire BR, Stringer MD, et al. Hirschsprungs disease: 107. Haricharan RN, Seo JM, Kelly DR, et al. Older age at diagnosis
Problems with transition-zone pull-through. J Pediatr Surg of Hirschsprung disease decreases risk of postoperative entero-
2000;35:18059. colitis, but resection of additional ganglionated bowel does not.
85. Coe A, Collins MH, Lawal T, et al. Reoperation for Hirschsprung J Pediatr Surg 2008;43:111523.
disease: Pathology of the resected problematic distal pull-through. 108. Pastor AC, Osman F, Teitelbaum DH, et al. Development of a
Pediatr Dev Pathol 2012;15:308. standardized definition for Hirschsprungs-associated enterocoli-
86. West KW, Grosfeld JL, Rescorla FJ, et al. Acquired aganglionosis: tis: A Delphi analysis. J Pediatr Surg 2009;44:2516.
A rare occurrence following pull-through procedures for Hirschs- 109. Marty TL, Seo T, Sullivan JJ, et al. Rectal irrigations for the
prungs disease. J Pediatr Surg 1990;25:1048. prevention of postoperative enterocolitis in Hirschsprungs
87. Friedmacher F, Puri P. Residual aganglionosis after pull-through disease. J Pediatr Surg 1995;30:6524.
operation for Hirschsprungs disease: A systematic review and 110. Menezes M, Corbally M, Puri P. Long-term results of bowel
meta-analysis. Pediatr Surg Int 2011;27:10537. function after treatment for Hirschsprungs disease: A 29-year
88. White FV, Langer JC. Circumferential distribution of ganglion review. Pediatr Surg Int 2006;22:98790.
cells in the transition zone of children with Hirschsprung disease. 111. Caniano DA, Teitelbaum DH, Qualman SJ. Management of
Pediatr Dev Pathol 2000;3:21622. Hirschsprungs disease in children with trisomy 21. Am J Surg
89. Medhus AW, Bjornland K, Emblem R, et al. Liquid and 1990;159:4024.
solid gastric emptying in adults treated for Hirschsprungs 112. Morabito A, Lall A, Gull S, et al. The impact of Downs syndrome
disease during early childhood. Scand J Gastroenterol 2007;42: on the immediate and long-term outcomes of children with Hir-
3440. schsprungs disease. Pediatr Surg Int 2006;22:17981.
90. Zaslavsky C, da Silveira TR, Maguilnik I. Total and segmental 113. Travassos D, van Herwaarden-Lindeboom M, van der Zee DC.
colonic transit time with radio-opaque markers in adolescents Hirschsprungs disease in children with Down syndrome: A com-
with functional constipation. J Pediatr Gastroenterol Nutr parative study. Eur J Pediatr Surg 2011;21:2203.
1998;27:13842. 114. Moore SW, Tshifularo N. Hirschsprungs disease in the neuro-
91. Southwell BR, Clarke MC, Sutcliffe J, et al. Colonic transit logically challenged child. Intern J Adolesc Med Health
studies: Normal values for adults and children with comparison 2011;23:2237.
of radiological and scintigraphic methods. Pediatr Surg Int 115. Puri P. Variant Hirschsprungs disease. J Pediatr Surg 1997;32:
2009;25:55972. 14957.
92. Di Lorenzo C, Solzi GF, Flores AF, et al. Colonic motility after 116. Feichter S, Meier-Ruge WA, Bruder E. The histopathology of
surgery for Hirschsprungs disease. Am J Gastroenterol 2000;95: gastrointestinal motility disorders in children. Sem Pediatr Surg
175964. 2009;18:20611.
34 Hirschsprung Disease 491
117. Meier-Ruge W. Casuistic of colon disorder with symptoms of 128. Millar AJ, Steinberg RM, Raad J, et al. Anal achalasia after pull-
Hirschsprungs disease. Verh Dtsch Ges Pathol 1971;55:50610. through operations for Hirschsprungs diseasepreliminary expe-
118. Ryan DP. Neuronal intestinal dysplasia. Sem Pediatr Surg rience with topical nitric oxide. Eur J Pediatr Surg 2002;12:
1995;4:225. 20711.
119. Csury L, Pena A. Intestinal neuronal dysplasia: Myth or reality? 129. Meier-Ruge W. Ultrashort segment Hirschsprung disease. An
Pediatr Surg Int 1995;10:4416. objective picture of the disease substantiated by biopsy. Z Kinder-
120. Koletzko S, Jesch I, Faus-Kebler T, et al. Rectal biopsy for diag- chir 1985;40:14650.
nosis of intestinal neuronal dysplasia in children: A prospective 130. Osifo OD, Okolo CJ. Outcome of trans-anal posterior anorectal
multicentre study on interobserver variation and clinical outcome. myectomy for the ultrashort segment Hirschsprungs disease
Gut 1999;44:85361. Benin City experience in five years. Niger Postgrad Med J
121. Kapur RP. Neuronal dysplasia: A controversial pathological cor- 2009;16:2137.
relate of intestinal pseudo-obstruction. Am J Med Gen 2003;122A: 131. Meier-Ruge WA, Bruder E, Holschneider AM, et al. Diagnosis
28793. and therapy of ultrashort Hirschsprungs disease. Eur J Pediatr
122. Zhang HY, Feng JX, Huang L, et al. Diagnosis and surgical treat- Surg 2004;14:3927.
ment of isolated hypoganglionosis. World J Pediatr 2008;4: 132. Meier-Ruge WA. Desmosis of the colon: A working hypothesis
295300. of primary chronic constipation. Eur J Pediatr Surg 1998;8:
123. Tatekawa Y, Kanehiro H, Kanokogi H, et al. The evaluation of 209303.
meconium disease by distribution of cathepsin D in intestinal 133. Marshall DG, Meier-Ruge WA, Chakravarti A, Langer JC.
ganglion cells. Pediatr Surg Int 2000;16:535. Chronic constipation due to Hirschsprungs disease and desmosis
124. Davidson M, Bauer CH. Studies of distal colonic motility in coli in a family. Pediatr Surg Int 2002;18:1104.
children IV: Achalasia of the distal rectal segment despite presence 134. Hotta R, Natarajan D, Thapar N. Potential of cell therapy to treat
of ganglia in the myenteric plexuses of this area. Pediatrics pediatric motility disorders. Sem Pediatr Surg 2009;18:26373.
1958;21:74661. 135. Zhang D, Brinas IM, Binder BJ, et al. Neural crest regionalization
125. De Caluwe D, Yoneda A, Akl U, et al. Internal anal sphincter for enteric nervous system formation: Implications for Hirschs-
achalasia: Outcome after internal sphincter myectomy. J Pediatr prungs disease and stem cell therapy. Dev Biol 2010;339:
Surg 2001;36:7368. 28094.
126. Heikkinen M, Lindahl HG, Rintala RJ. Long-term outcome after 136. Tsai YH, Murakami N, Gariepy CE. Postnatal intestinal engraft-
internal sphincter myectomy for internal sphincter achalasia. ment of prospectively selected enteric neural crest stem cells in a
Pediatr Surg Int 2005;21:847. rat model of Hirschsprung disease. Neurogastroenterol Motil
127. Messineo A, Codrich D, Monai M, et al. The treatment of internal 2011;23:3629.
anal sphincter achalasia with botulinum toxin. Pediatr Surg Int
2001;17:5213.
C H A P T E R 3 5
Imperforate anus has been a well-known condition since component but were left with a persistent urogenital
antiquity.13 For many centuries, physicians, as well as sinus.21,23 Additionally, most rectovestibular fistulas were
individuals who practiced medicine, have tried to help erroneously called rectovaginal fistula.21 A rectoblad-
these children by creating an orifice in the perineum. derneck fistula in males is the only true supralevator
Many patients survived, most likely because they suffered malformation and occurs in about 10%.18 As it is the only
from a type of defect that is now recognized as low. malformation in males in which the rectum is unreach-
Those with a high defect did not survive. In 1835, able through a posterior sagittal incision, it requires an
Amussat was the first to suture the rectal wall to the skin abdominal approach (via laparoscopy or a laparotomy) in
edges which was the first actual anoplasty.2 Stephens addition to the perineal approach.
made a significant contribution by performing the first Anorectal malformations represent a wide spectrum of
anatomic studies in human specimens. In 1953, he pro- defects. The terms low, intermediate, and high are arbi-
posed an initial sacral approach followed by an abdomi- trary and not useful in current therapeutic or prognostic
noperineal operation, if needed.4 The purpose of the terminology. A therapeutic and prognostically oriented
sacral stage of this procedure was to preserve the pub- classification is depicted in Box 35-1.24
orectalis sling, considered a key factor in maintaining
fecal incontinence. Over the next 25 years, different sur-
gical techniques were described, with the common MALE ANORECTAL DEFECTS
denominator being the protection and use of the pub-
orectalis sling.58 Rectoperineal Fistulas
The posterior sagittal approach for the treatment of
imperforate anus was performed first in 1980, and its Rectoperineal fistula is the lowest defect. The rectum is
description was published in 1982.9 With this approach, located within most of the sphincter mechanism. Only
the unique opportunity arose to correlate the external the lowest part of the rectum is anteriorly mislocated
appearance of the perineum with the operative findings (Fig. 35-1). Sometimes, the fistula does not open into the
and, subsequently, with the clinical results. perineum but rather follows a subepithelial midline tract,
opening somewhere along the midline perineal raphe,
scrotum, or even at the base of the penis (Fig. 35-2). This
INCIDENCE, TYPES OF DEFECTS, diagnosis is established by perineal inspection. No further
AND TERMINOLOGY investigations are required. Usually, the anal fistula
opening is stenotic. The terms covered anus, anal mem-
An anorectal malformation occurs in one out of every brane, anteriorly mislocated anus, and bucket-handle malfor-
4000 to 5000 newborns and is slightly more common in mations all refer to rectoperineal fistulas.
males.1012 The estimated risk for a couple having a second
child with an anorectal malformation is approximately
1%.1317 The most frequent defect in males is imperforate
Rectourethral Fistulas
anus with a rectourethral fistula.18 In females, it is a rec- Imperforate anus with a rectourethral fistula is the most
tovestibular fistula.18 Imperforate anus without a fistula is common defect in males.18 The fistula may be located at
a rather unusual defect, occurring in about 5% of the the lower (bulbar) (Fig. 35-3A) or the higher (prostatic)
entire group of malformations, and is associated with part of the urethra (Fig. 35-3B).
Down syndrome.18,19 Historically, a cloaca has been con- Immediately above the fistula, the rectum and urethra
sidered an unusual defect, whereas a high incidence of share a common wall. The lower the fistula, the longer
rectovaginal fistula has been reported in the literature.20 is the common wall. This is an important anatomic fact,
In retrospect, we now know that a cloaca is the third most which guides the operation. The rectum is usually dis-
common defect in female patients after vestibular and tended and surrounded laterally and posteriorly by the
perineal fistulas, whereas a rectovaginal fistula is actually levator muscle. Between the rectum and the perineal skin,
a rare defect, present in less than 1% of all cases.21,22 It is a portion of striated voluntary muscle called the muscle
likely that most females with a persistent cloaca complex is present. The contraction of these muscle
were erroneously thought to have a rectovaginal fistula. fibers elevates the skin of the anal dimple. At the level of
Many of these patients underwent repair of the rectal the skin, a group of voluntary muscle fibers, called
492
35 Imperforate Anus and Cloacal Malformations 493
Rectobladderneck Fistulas
B
In this defect, the rectum opens into the bladder neck
(Fig. 35-4). The patient usually has poor prognosis for FIGURE 35-3 Anorectal atresia with rectourethral fistulas.
bowel control because the levator muscles, the striated (A) Rectourethrobulbar fistula; (B) rectourethroprostatic fistula.
494 SECTION IV Abdomen
Rectovestibular Fistulas
Rectovestibular fistula is the most common defect in
females and has an excellent functional prognosis. The
diagnosis is based on clinical examination. A meticulous
inspection of the newborns genitalia allows the clinician
to observe a normal urethral meatus and a normal vagina,
with a third hole in the vestibule, which is the rectoves-
tibular fistula (Fig. 35-7). About 5% of these patients will
have two hemivaginas with a vaginal septum.26
This defect can be repaired without a protective colos-
tomy by experienced surgeons.2729 The advantage of this
approach is that it avoids the potential morbidity of a B
colostomy and reduces the number of operations to one FIGURE 35-7 (A) Schematic drawing of a rectovestibular fistula.
from as many as three (colostomy, main repair, and colos- (B) Female neonate with a rectovestibular fistula is in the prone
tomy closure). Many patients do very well with a primary position. The rectal fistula (arrow) is located in the posterior
aspect of the vestibule.
neonatal operation without a protective colostomy.
However, a perineal infection followed by dehiscence of
the anal anastomosis or perineal body, or recurrence of
the fistula provokes severe fibrosis that may interfere
with the sphincter function. If these complications
Persistent Cloaca
occur, the patient may have lost the best opportunity for This group of defects represents the extreme in the spec-
an optimal functional result because secondary opera- trum of complexity of female malformations. A cloaca is
tions do not render the same prognosis as a successful a defect in which the distal portions of the rectum, vagina,
primary operation.30 Thus, a protective colostomy is still and urinary tract fuse and create a single common peri-
the best way to avoid these complications for most sur- neal channel. The diagnosis of a cloaca is a clinical one.
geons. The decision to perform a colostomy or primary This defect should be suspected in a female born with
repair in these cases must be made individually by the imperforate anus and small-looking genitalia. Careful
surgeon based on experience and the clinical condition separation of the labia discloses a single perineal orifice.
of the patient. At our institution, neonates without sig- The length of the common channel varies from 17cm,
nificant associated defects undergo repair without a and is very important for operative and prognostic impli-
colostomy. cations (Fig. 35-8). A common channel of less than 3cm
usually means that the defect can be repaired with a pos-
Imperforate Anus without Fistula terior sagittal operation without opening the abdomen.
Common channels longer than 3cm are more complex,
This defect in female patients carries the same therapeu- mobilization of the vagina is often difficult, and some
tic and prognostic implications as described for male form of vaginal replacement may be needed during the
patients. definitive repair. When the rectum opens high into the
496 SECTION IV Abdomen
B
FIGURE 35-8 (A) Schematic diagram of a long common channel
in a female with a cloacal anomaly. (B) The more commonly
encountered short common channel cloaca is depicted.
A NEWBORN MANAGEMENT
AB AB
A decision-making algorithm for the initial management
B in male infants is seen in Figure 35-12.
BC BC When asked to evaluate a male newborn with an
C
anorectal malformation, a thorough perineal inspection
must be performed. It is important not to make a decision
about a colostomy or a primary operation before 24 hours
BC
of life. The reason is that significant intraluminal pres-
A Normal ratio: 0.77 B sure is required for the meconium to be forced through
AB
FIGURE 35-11 Drawings with landmarks necessary for the cal- a perineal fistula. If meconium is seen on the perineum,
culation of the sacral ratio. (A) Lateral view. (B) Anteroposterior a rectoperineal fistula is present. If there is meconium in
view. The normal ratio is 0.77. the urine, a rectourinary fistula exists.
498 SECTION IV Abdomen
Radiographic evaluations may not show the correct colostomy. This allows for a future distal colostogram,
anatomy before 24 hours because the rectum is collapsed. which will delineate the distal rectal anatomy. We will
It takes a significant amount of intraluminal pressure to then perform a posterior sagittal anorectoplasty two to
overcome the muscle tone of the sphincters that surround three months later, provided the neonate is gaining
the lower part of the rectum. Therefore, imaging studies weight appropriately.
before 24 hours most likely will show a very high rectum Performing the definitive repair early in life has
and may lead to an incorrect diagnosis. Historically, an important advantages including less time with an abdom-
invertogram was used to identify whether the anomaly is inal stoma, less size discrepancy between the proximal
high or low.58 and distal bowel at the time of colostomy closure, and
During the first 24 hours, the neonate should receive easier anal dilation (because the infant is smaller). In
intravenous fluids, antibiotics, and nasogastric decom- addition, at least theoretically, placing the rectum in the
pression, and be evaluated for associated defects that may right location early in life potentially may represent an
represent a threat to life. These include cardiac malfor- advantage in terms of acquired local sensation.60
mations, esophageal atresia, and urinary defects.34,59 A All of these potential advantages of an early operation
radiograph of the lumbar spine and the sacrum should be must be weighed against the possible disadvantages of an
obtained as well as a spinal ultrasound to evaluate for a inexperienced surgeon who is not familiar with the ana-
tethered cord. Renal/abdominal ultrasound should be tomic structures of an infants pelvis. Operating on
done to evaluate for hydronephrosis. patients with anorectal malformations primarily without
If the neonate has signs of a rectoperineal fistula, an a protective colostomy has been done successfully, but
anoplasty can be performed in the newborn period may have negative consequences if the surgeon does
without a protective colostomy. After 24 hours, if there not have the necessary preoperative evaluation and
is no meconium on the perineum, we recommend obtain- experience.29,61,62
ing a cross-table lateral radiograph with the patient in the A temptation to repair these defects without a protec-
prone position (Fig. 35-13A). If air in the rectum is seen tive colostomy always exists.27,61,62 Repair without a colos-
distal to the coccyx (Fig. 35-13B), and the patient is in tomy does not allow a distal colostogram which may be
good condition with no significant associated defects, one very helpful to the surgeon. The worst complications
may consider performing a posterior sagittal operation involve infants who undergo repair without a colostomy
without a protective colostomy. A more conservative or a properly performed distal colostogram.63 Proceeding
alternative would be to perform the posterior sagittal with the posterior sagittal approach looking blindly for
repair and a protective colostomy at the same stage. the rectum has resulted in a spectrum of serious compli-
Conversely, if the rectal gas does not extend beyond cations, including damage to the urethra, complete divi-
the coccyx, or the patient has meconium in the urine, an sion of the urethra, pull-through of the urethra,
abnormal sacrum, or a flat bottom, we recommend a pull-through of the bladder neck, injury to the ureters,
and division of the vas deferens or seminal vesicles.63
A decision-making algorithm for the initial manage-
ment of newborn females is shown in Figure 35-14. Again,
the perineal inspection is the most important step to guide
diagnosis and decision making. The first 24 hours should
also be used to evaluate for associated defects, as previ-
ously described. Perineal inspection may show the pres-
ence of a single perineal orifice, which establishes the
diagnosis of a cloaca and carries a high risk of an associ-
ated urologic defect. Also, it should prompt a complete
urologic evaluation, including abdominal and pelvic ultra-
sound, to look for hydronephrosis and hydrocolpos.
Patients with a cloaca require a colostomy. It is impor-
A
tant to perform the divided sigmoid colostomy in such a
manner as to leave enough redundant, distal rectosig-
moid colon to allow for the subsequent pull-through
(Fig. 35-15). When performing the colostomy for a
cloaca, it is important to drain a hydrocolpos when
present. This can be achieved with a curled catheter.
Because a significant number of these patients have two
hemivaginas, the surgeon must be certain that both
hemivaginas are drained. Occasionally, a vaginovaginos-
tomy in the vaginal septum needs to be created to drain
B
both hemivaginas with one catheter. At times, the hydro-
colpos is so large that it may produce respiratory distress.
FIGURE 35-13 Technique for a cross-table lateral radiograph. Also, the hydrocolpos can compress the trigone and cause
(A) A roll has been placed beneath the hips of the infant to
elevate the buttocks and allow air to migrate superiorly to the
hydronephrosis, and drainage of the hydrocolpos allows
end of the rectum. (B) Actual cross-table lateral radiograph. Air for decompression of the urologic system. Rarely, if the
is visualized distal to the coccyx (arrow). common channel is very narrow and does not allow the
35 Imperforate Anus and Cloacal Malformations 499
Perineal inspection
B
FIGURE 35-19 This drawing shows a posterior sag-
ittal incision in a male patient with a rectourethral
fistula. Separation of the parasagittal fibers and
C exposure of the muscle complex are shown.
Rectobladderneck Fistulas
B C
In these patients, the rectum enters the bladder neck
FIGURE 35-23 A schematic representation of the separation of approximately 2cm below the peritoneal reflection. A
the rectal fistula from the urethra is shown. (A) Separation of very important anatomic feature is that the higher the
the rectum from the urethra using silk traction stitches in the
rectum. (B) Proximal dissection of the rectum from the urethra.
malformation, the shorter the common wall between the
(C) Depiction of the rectum completely separated from the rectum and the urinary tract. In such cases, this means
underlying urethra. that the rectum joins with the urinary tract at nearly a
504 SECTION IV Abdomen
A B
Rectal Atresia and Rectal Stenosis
FIGURE 35-25 (A) Technique of anoplasty. Four quadrant stay
sutures are placed followed by three sutures between each The approach to these malformations is also posterior
quadrant. (B) Subcuticular skin closure. sagittal. The upper rectal pouch is opened and the distal
35 Imperforate Anus and Cloacal Malformations 505
A B C
FIGURE 35-28 Schematic drawings of the final stages of the repair of a rectovestibular fistula in a female. (A) Reconstruction of the
perineal body. (B) Positioning the rectum in front of the levator muscle complex. (C) Sagittal view of the completed operation.
506 SECTION IV Abdomen
FIGURE 35-31 Total urogenital mobilization. The patient is in FIGURE 35-33 A nearly completed cloacal repair. The urethral
the prone position. Silk sutures have been placed around the meatus (with catheter) and vaginal introitus have been anasto-
vagina (top) and transversely across the dissection plane near mosed to the perineum in their appropriate positions. The
the clitoris (bottom). A catheter has been inserted in the urethra. patient is in the prone position. (From Pea A, Levitt. In Imperfo-
(From Pea A, Levitt, Treatment of Cloacas. In: Anorectal Malforma- rate Anus and Cloacal Malformations. In: Pediaric Surgery. 4th ed.
tions in Children. Ch 22 Holschneider AM, Hutson J, editors. Hei- Ashcraft, Whitfield and Murphy, editors. Philadelphia: Elsevier
delberg: Springer; 2006. p. 30714.) Saunders; 2005. p. 496517.)
R. tube
R. hemiuterus
Vaginal septum
Divide
R. ovary L. ovary
R. giant hemivagina
hydrocolpos Communication with urinary
tract and/or rectum
FIGURE 35-35 Diagram shows the constellation of persistent
cloaca with hydrocolpos in the presence of hemivaginas and
hemiuterus. Bilateral hydrocolpos is present with a very high
vagina. This circumstance is the ideal anatomy for a subsequent
repair via a vaginal switch maneuver. (Adapted from Kiely EM,
Pea A. Anorectal malformations. In: ONeil JA, Rowe MI, Grosfeld
JL, etal, editors: Pediatric Surgery. St. Louis: MosbyYear Book;
A B 1998. p. 1442.)
FIGURE 35-34 Drawings showing the final stages of cloacal
repair. (A) The repaired urethra and vagina and the anoplasty
are being completed. (B) Sagittal depiction of the finished
cloacal repair. (Adapted from Pea A. Atlas of Surgical Manage-
ment of Anorectal Malformations. New York: Springer-Verlag; 1990.
p. 69.) Vaginal Switch Maneuver
There is a specific group of patients who are born with
hydrocolpos and two hemivaginas. The hemivaginas are
the mobilized urogenital complex up into the abdomen very large, and the two hemiuteri are separated (Fig.
allows for enough dissection to get it to reach. If further 35-35). The distance between one hemiuterus and the
dissection does not allow it to reach then the vagina can other is longer than the vertical length of both hemiva-
be separated from the urinary tract and the urethra ginas. In these cases, it is ideal to perform a maneuver
tubularized. called a vaginal switch (Fig. 35-36), whereby one of the
The patency of the Mllerian structures can be checked uteri and its fallopian tube are resected, preserving the
by injecting saline through a 3 French feeding tube ovary and its blood supply. The blood supply of the ipsi-
through the fimbriae of the fallopian tubes. If one of the lateral hemivagina must be sacrificed, but collateral
tubes is not patent, we recommend excising it, along with vessels from the opposite vagina should support both.
its hemiuterus if the system is bifid, and the ovary and its The vaginal septum is resected, creating a single long
blood supply are preserved.26 vagina. The cut end of the ipsilateral vagina is turned
When both Mllerian structures are atretic, we rec- down to the perineum. This is an excellent technique for
ommend leaving both in place, and following the patient. constructing a viable and functional vagina.
Once the patient develops breast buds, menstruation
usually occurs one to two years thereafter and ultrasound
is used to follow the size of these pelvic structures. At
that point, laparoscopic inspection or intervention for
nondraining structures can be done if needed.
Preserved
With the abdomen open, operative decisions are based L. hemiuterus
on the anatomic findings. In the presence of a single (Right hemihisterectomy)
vagina of normal size, the surgeon must separate the Preserved ovary
vagina from the urinary tract, being sure to preserve its
blood supply that comes from the uterine vessels. It is
brought to the perineum, and the introitus is constructed.
When the vagina is found to be too short, the patient Resected vaginal septum Preserved
blood supply
requires some form of vaginal replacement that can be
performed using the rectum, colon, or small bowel.
The presence of a common channel longer than 5cm
R. hemivagina
means that total urogenital mobilization from below will switched down
not be enough to repair the malformation. Therefore in
this scenario, it is advisable to leave the common channel
intact for use as the urethra, which will eventually be used
for intermittent catheterization. The vagina is separated
from the urinary tract, and the posterior wall of the previ- FIGURE 35-36 Technique of vaginal reconstruction using a
vaginal switch maneuver. (Adapted from Kiely EM, Pea A.
ous common channel is closed with interrupted absorb- Anorectal malformations. In: ONeil JA, Rowe MI, Grosfeld JL, etal,
able sutures. This is a very delicate maneuver best started editors. Pediatric Surgery. St. Louis: MosbyYear Book; 1998.
posterosagittally and then continued via laparotomy. p. 1442.)
35 Imperforate Anus and Cloacal Malformations 509
A B C
FIGURE 35-39 Technique of vaginal replacement using small bowel. (A) A segment of small bowel is chosen that has adequate
mesenteric length for transposition to the pelvis. (B) The mesentery has been divided, the segment of small bowel chosen for vaginal
reconstruction is identified, and the blood supply is evaluated to ensure adequate perfusion. (C) The completed anastomosis.
80% of the time. Upon removal of the urinary catheter, stretching of the voluntary muscle. The most
the patient is observed to see if the patient is capable important clinical implication is that liquid or soft
of spontaneous bladder emptying. A kidney and fecal material may not be felt by the patient with
bladder ultrasound can assess this emptying and should anorectal malformations as the rectum is not dis-
be performed two to three weeks after the catheter is tended. Thus, to achieve some degree of sensation
removed and repeated every several months. If she cannot and bowel control, the patient must be able to (or
pass urine, or does not empty her bladder well, the helped to) form solid stool.
parents need to learn how to perform intermittent 3. Bowel motility. Perhaps the most important factor in
catheterization. fecal continence is bowel motility. In a normal indi-
Most patients with persistent cloaca have a flaccid, vidual, the rectosigmoid remains quiet for variable
smooth, large bladder that does not empty completely.75 periods of time (one to several days), depending on
Fortunately, most patients with cloacas have a competent an individuals defecation habits. During that time,
bladder neck. The combination of a competent bladder anorectal sensation and voluntary muscle structures
neck with a flaccid bladder makes these patients ideal are almost unnecessary because the stool remains
candidates for intermittent catheterization, which keeps in the rectosigmoid if it is solid.
them completely dry. Two exceptions to this rule exist. The patient normally feels the rectosigmoids peristaltic
One is the patient with a very long common channel and contraction. Voluntarily, the normal individual can relax
the hemivaginas attached to the bladder neck, leading to the striated muscles, which allows the rectal contents to
bladder neck damage during the reconstruction. The migrate down into the highly sensitive area of the anal
other is the rare baby born with separated pubic bones, canal. There, accurate information is provided concern-
a condition that can be described as a covered exstro- ing the consistency and quality of the stool. The volun-
phy.76,77 These patients have congenital absence of the tary muscles are used to push the rectal contents back up
bladder neck and will eventually require a continent into the rectosigmoid and hold them if desired until the
urinary diversion. appropriate time for evacuation. At the time of defeca-
tion, the voluntary muscle structures relax, allowing the
fecal mass to pass into and through the anorectum.
FUNCTIONAL DISORDERS AFTER The main factor that initiates emptying of the recto
REPAIR OF ANORECTAL sigmoid is an involuntary peristaltic contraction that is
MALFORMATIONS helped sometimes by a Valsalva maneuver. Most patients
with an anorectal malformation have a disturbance of this
Most patients who undergo repair of an anorectal mal- sophisticated bowel motility mechanism. Patients who
formation suffer from some degree of a functional defe- have undergone a posterior sagittal anorectoplasty or any
cating disorder.78,79 other type of sacroperineal approach, in which the
Fecal continence depends on three main factors: most distal part of the bowel was preserved, often show
1. Voluntary muscle structures. These structures are rep- evidence of an overefficient bowel reservoir (megarec-
resented by the levator muscle, the striated muscle tum) (Fig. 35-41). The main clinical manifestation of
complex, and the external sphincter. Normally, this is constipation, which seems to be more severe in
they are used only for brief periods when the rectal patients with lower defects.70 The enormously dilated
fecal mass, pushed by the involuntary peristaltic
contraction of the rectosigmoid, reaches the
anorectal area. This contraction occurs only in the
minutes prior to defecation. The voluntary muscle
structures that close around the anus are used only
occasionally during the rest of the day and night.
Patients with anorectal malformations have abnor-
mal voluntary striated muscles with varying degrees
of hypodevelopment. Voluntary muscles can be
used only when the patient feels that it is necessary
to use them.
2. For that sensation, the patient needs information
that can only be derived from an intact sensory mech-
anism, a mechanism lacking in many patients with
anorectal malformations. Exquisite sensation in
normal individuals resides in the anal canal. Except
for patients with rectal atresia and stenosis, most
patients with anorectal malformations are born
without an anal canal. Therefore, sensation does
not exist or is rudimentary. Distention of the
rectum, however, can be felt in many of these
patients, provided the rectum has been located FIGURE 35-41 A contrast enema is shown in a patient with a
accurately within the muscle structures. This pro- megarectum. Note the markedly dilated rectum in relation to
prioception seems to be a consequence of the more proximal normal-sized colon.
512 SECTION IV Abdomen
TABLE 35-2 Global Functional Results in Patients Undergoing Repair of Anorectal Malformations
Voluntary Bowel Totally
Movements Soiling Continent Constipated
NO. OF NO. OF NO. OF NO. OF
PATIENTS % PATIENTS % PATIENTS % PATIENTS %
Rectal atresia/rectal stenosis 14/14 100 4/10 40 6/10 60 9/12 75
Rectoperineal fistula 62/64 97 10/59 17 44/55 80 43/74 58
Rectovestibular fistula 144/160 90 52/140 37 87/142 61 84/152 55
Imperforate anus without fistula 35/43 81 21/40 53 18/41 44 21/42 50
Rectourethral bulbar fistula 93/117 79 52/107 49 47/108 44 69/114 61
Cloaca: short common channel (< 3cm) 68/101 67 55/92 60 33/94 35 38/97 39
Rectourethral prostatic fistula 74/112 66 84/109 77 19/110 17 47/110 43
Rectovaginal fistula 2/4 50 3/4 75 1/4 25 1/4 25
Cloaca: long common channel (> 3cm) 27/73 37 45/56 80 6/67 9 17/58 29
Rectobladderneck fistula 12/53 23 46/61 90 2/52 4 9/51 18
rectosigmoid has normal ganglion cells, but behaves like consisting of a daily enema and a constipating diet, with
it has a hypomotility disorder. The overflow fecal incon- medications to slow down the colonic motility, is indi-
tinence based on rectosigmoid constipation in patients cated.78 See Chapter 36 for more information on bowel
with potential for bowel control can be managed with the management.
appropriate dose of stimulant laxatives. Those with a
poor sacrum, poor muscles, and thus with no potential
for bowel control are treated with a daily enema.78 EVALUATION OF RESULTS
Those patients treated with older techniques in
which the most distal part of the bowel was resected Each defect described in this chapter has a different prog-
(abdominoperineal pull-through) behave clinically as nosis. The patients with lower defects usually have excel-
individuals without a rectal reservoir (Fig. 35-42). This lent results, except when technical errors have been
is a situation equivalent to a perineal colostomy. Depend- made, or if they have associated sacral or spinal
ing on the amount of colon resected, the patient may problems.
have loose stools. In these cases, medical management Tables 35-2 and 35-3 show our results. The patients
with a sacral ratio of less than 0.3 and flat perineums have
fecal incontinence regardless of the type of malformation
or quality of the repair. Associated spinal anomalies nega-
tively affect progress for bowel control.
As persistent cloacas represent another spectrum of
defects, they must be subclassified on the basis of poten-
tial for bowel and bladder control. The length of the
common channel seems to be the most important prog-
nostic factor.
34. Stoll C, Alembik Y, Dott B. Associated malformations in patients 57. Boemers TM, de Jong TP, van Gool JD, et al. Urologic problems
with anorectal anomalies. Eur J Med Genet 2007;50:28190. in anorectal malformations: II. Functional urologic sequelae.
35. Karrer FM, Flannery AM, Nelson MD Jr, et al. Anorectal malfor- J Pediatr Surg 1996;31:5347.
mations: Evaluation of associated spinal dysraphic syndromes. 58. Wangensteen OH, Rice CO. Imperforate anus: A method of deter-
J Pediatr Surg 1988;23:458. mining the surgical approach. Ann Surg 1930;92:7781.
36. Davidoff AM, Thompson CV, Grimm JK, et al. Occult spinal 59. Shaul DB, Harrison EA. Classification of anorectal malformations
dysraphism in patients with anal agenesis. J Pediatr Surg initial approach, diagnostic tests, and colostomy. Semin Pediatr
1991;26:10015. Surg 1997;6:18795.
37. Daskiewicz P, Barszsc S, Roskowski M, et al. Tethered cord syn- 60. Freeman NV, Burge DM, Soar JS, et al. Anal evoked potentials. Z
drome in childrenimpact of surgical treatment on functional Kinderchir 1980;31:2230.
neurological and urological outcome. Neurol Neurochir Pol 61. Albanese CT, Jennings RW, Lopoo JB, et al. One-stage correction
2007;41:42735. of high imperforate anus in the male neonate. J Pediatr Surg
38. Bui CJ, Tubbs RS, Oakes WJ. Tethered cord syndrome in children: 1999;34:8346.
A review. Neurosurg Focus 2007;23:19. 62. Vick LR, Gosche JR, Boulanger SC, et al. Primary laparoscopic
39. Tsuda T, Iwai N, Kimura O, et al. Bowel function after surgery for repair of high imperforate anus in neonatal males. J Pediatr Surg
anorectal malformations in patients with tethered spinal cord. 2007;42:187781.
Pediatr Surg Int 2007;23:11714. 63. Hong AR, Rosen N, Acua MF, et al. Urological injuries associated
40. Kuo MF, Tsai Y, Hsu WM, et al. Tethered spinal cord and with the repair of anorectal malformations in male patients.
VACTERL association. J Neurosurg 2007;106:2014. J Pediatr Surg 2002;37:33944.
41. Steinbok P, Garton HJ, Gupta N. Occult tethered cord syndrome: 64. Gross GW, Wolfson PJ, Pea A. Augmented-pressure colostogram
A survey of practice patterns. J Neurosurg 2006;104:30913. in imperforate anus with fistula. Pediatr Radiol 1991;21:5603.
42. Drake JM. Occult tethered cord syndrome: Not an indication for 65. Pea A, Migotto-Krieger M, Levitt MA. Colostomy in anorectal
surgery. J Neurosurg 2006;104:3058. malformations: A procedure with serious but preventable complica-
43. Seldon NR. Occult tethered cord syndrome: The case for surgery. tions. J Pediatr Surg 2006;41:74856.
J Neurosurg 2006;104:3024. 66. Wilkins S, Pea A. The role of colostomy in the management of
44. Levitt MA, Patel M, Rodriguez G, et al. The tethered spinal cord anorectal malformations. Pediatr Surg Int 1988;3:1059.
in patients with anorectal malformations. J Pediatr Surg 67. Sydorak RM, Albanese CT. Laparoscopic repair of high imperfo-
1997;32:4628. rate anus. Semin Pediatr Surg 2002;11:21725.
45. Belman BA, King LR. Urinary tract abnormalities associated with 68. Georgeson K. Laparoscopic-assisted anorectal pull-through. Semin
imperforate anus. J Urol 1972;108:8234. Pediatr Surg 2007;16:2669.
46. Hoekstra WJ, Scholtmeijer RJ, Molenar JC, et al. Urogenital tract 69. Georgeson KE, Inge TH, Albanese CT. Laparoscopically assisted
abnormalities associated with congenital anorectal anomalies. anorectal pull-through for high imperforate anus: A new technique.
J Urol 1983;130:9623. J Pediatr Surg 2000;35:92731.
47. Munn R, Schillinger JF. Urologic abnormalities found with imper- 70. Levitt MA, Kant A, Pea A. The morbidity of constipation in
forate anus. Urology 1983;21:2604. patients with anorectal malformations. J Pediatr Surg 2010;
48. Parrott TS. Urologic implications of anorectal malformations. 45:122833.
Urol Clin North Am 1985;12:1321. 71. Belizon A, Levitt MA, Shoshany G, et al. Rectal prolapse following
49. Wiener ES, Kiesewetter WB. Urologic abnormalities associated posterior sagittal anorectoplasty for anorectal malformations.
with imperforate anus. J Pediatr Surg 1973;8:1517. J Pediatr Surg 2005;40:1926.
50. William DI, Grant J. Urological complications of imperforate anus. 72. Levitt MA, Pea A. Reoperations in Anorectal Malformations. In:
Br J Urol 1969;41:6605. Teich S, Caniano D, editors. Reoperative Pediatric Surgery.
51. Rich MA, Brock WA, Pea A. Spectrum of genitourinary malfor- Totowa: Humana Press; 2008. p. 31126.
mations in patients with imperforate anus. Pediatr Surg Int 73. Levitt MA, Pea A. Cloacal malformations: Lessons learned from
1988;3:11013. 490 cases. Semin Pediatr Surg 2010;19:12838.
52. Stephens FD, Smith ED. Incidence, frequency of types, etiology. 74. Pea A. Total urogenital mobilizationAn easier way to repair
In: Stephens FD, Smith ED, editors. Anorectal Malformations in cloacas. J Pediatr Surg 1997;32:2638.
Children. Chicago: Year Book Medical; 1971. p. 28992. 75. Pea A, Levitt MA. Neurogenic bladder and anorectal malforma-
53. Spence HM. Anomalies and complications of the urogenital tions. In: Esposito C, Guys JM, Gough D, et al, editors. Pediatric
tract associated with congenital imperforate anus. J Urol 1954; Neurogenic Bladder Dysfunction. Berlin: Springer; 2006. p. 858.
71:45363. 76. Pea A. New concepts in bowel reconstruction in cloacal exstrophy.
54. Smith ED. Urinary anomalies and complications in imperforate Dialog Pediatr Urol 2000;23:34.
anus and rectum. J Pediatr Surg 1968;3:33742. 77. Levitt MA, Mak GA, Falcone RA, et al. Cloacal exstrophypull
55. Carcassonne M, Monfort G, Isman H. Les problemes urologiques through or permanent stoma? A review of 53 patients. J Pediatr
des malformations ano-rectales. Arch Fr Pediatr 1971;28: Surg 2008;43:16470.
72339. 78. Levitt MA, Pea A. Pediatric fecal incontinence: A surgeons per-
56. Boemers TM. Neurogenic bladder in infants born with anorectal spective. Pediatr Review 2010;31: 91101.
malformations: Comparison with spinal and urologic status. 79. Pea A, Levitt MA. Colonic inertia disorders. Curr Prob Surg
J Pediatr Surg 1999;34:188990. 2002;39:661730.
C H A P T E R 3 6
Fecal Incontinence
and Constipation
Marc A. Levitt Alberto Pea
Fecal incontinence can prevent a person from becoming Voluntary Muscle Structures
socially accepted, which, in turn, provokes serious psy-
chological sequelae. It is a problem that impacts more In the normal continent patient, the voluntary muscle
children than previously thought, affecting those born structures are represented by the levators, the muscle
with anorectal malformations and Hirschsprung disease complex, and the parasagittal fibers. Normally, they are
as well as children with spinal cord problems or spinal used only for brief periods of time when the fecal mass,
injuries. pushed by the involuntary peristaltic contraction of the
True fecal incontinence must be distinguished from rectosigmoid colon, reaches the anorectal area. This vol-
overflow pseudoincontinence. Children with true fecal untary contraction keeps the stool in the rectum by
incontinence can include some surgical patients with closing the anus around the time of defecation. These
anorectal malformations (ARMs), those with Hirschs- muscles are used only occasionally during the rest of the
prung disease, and those with spinal problems, either day and night.
congenital or acquired. In patients with pseudoinconti- Patients with ARMs have abnormal voluntary striated
nence, who have the potential for bowel control but who muscles with different degrees of hypodevelopment.
soil, their problem usually results from severe constipa- Some patients are close to normal whereas some patients
tion (encopresis) and sometimes from hypermotility. do not have any voluntary sphincter muscles. Also,
Most patients who require repair of an ARM suffer patients with Hirschsprung disease may have suffered
from some degree of a functional defecation disorder. All damage to this sphincter mechanism at the time of pull-
have some degree of an abnormality in their fecal conti- through, and patients with spinal abnormalities may have
nence mechanisms. One-quarter of them are deficient deficient innervation of these muscles.
enough to the point that they are fecally incontinent and
cannot have a voluntary bowel movement.1 The majority
are capable of having voluntary bowel movements but
Anal Canal Sensation
may require treatment of an underlying dysmotility dis- Voluntary muscles are used only when the patient has the
order, which most often manifests as constipation.2,3 A sensation that determines that it is necessary to use them.
small, yet significant, number of patients with Hirschs- To appreciate that sensation, the patient needs feedback
prung disease suffer from fecal incontinence because of a that is derived from an intact anal sensory mechanism.
lost anal canal or damaged sphincters that occurred Exquisite sensation in normal individuals resides in the
during operative repair.46 To varying degrees, patients anal canal. Except for patients with rectal atresia, most
with spinal problems7,8 or injuries9 can lack the capacity patients with ARMs are born without an anal canal.
for voluntary bowel movements. Therefore, sensation does not exist or is rudimentary.
Patients with true fecal incontinence require artificial Patients with spinal conditions may lack this anal canal
means to be kept clean. This regimen is termed bowel sensation as well.7,8 Those with Hirschsprung disease are
management and involves a daily enema.10 On the other born with a normal anal canal, but this can be injured if
hand, patients with pseudoincontinence require proper not meticulously preserved at the time of their pull-
medical treatment for either constipation or loose stools. through (Fig. 36-1).5,6 Also, perineal trauma may result
This involves finding the right consistency for the stool in an injured or destroyed anal canal.9
so that they can have a bowel movement that they vol- It seems that most individuals can perceive distention
untarily control. Understanding this major differentia- of the rectum. This point is important for patients under-
tion is the key to deciding the correct bowel management going pull-through procedures for imperforate anus as
program. the distal rectum and anus must be placed precisely
within the sphincter mechanism. This sensation seems to
be a consequence of stretching of the voluntary muscles
MECHANISM OF CONTINENCE (proprioception). The most important clinical implica-
tion of this point is that patients might not feel liquid or
Fecal continence depends on three factors: voluntary soft fecal material because such stool consistency does
sphincter muscles, anal canal sensation, and colonic not distend the rectum. Thus, to achieve some degree of
motility.2 sensation and bowel control, the patient must have the
515
516 SECTION IV Abdomen
FIGURE 36-1 Loss of the anal canal (with no visible dentate line)
is seen after a Soave pull-through operation. In this patient, the
anal dissection was begun too distally.
Laxatives will make such a patient soil more. The and/or quality of the enemas should be modified, as well
program, although simplistic, is ideally implemented by as any changes in diet and/or medication, is made each
trial and error over a period of one week.10 The patient day (Fig. 36-4).10
is seen each day and an abdominal radiograph is obtained
to look for the amount and location of any stool left in
the colon. The presence or absence of stool in the under-
Which Children Have True
wear is also noted. The decision as to whether the type Fecal Incontinence?
In children with ARMs, 75% who have undergone a
correct and successful operation have voluntary bowel
movements after the age of 3 years.1 About half of these
patients occasionally soil their underwear. These episodes
of soiling are usually related to constipation. When the
constipation is treated properly, the soiling frequently
disappears. Thus, approximately 40% overall have volun-
tary bowel movements and no soiling, and behave nor-
mally. Children with good bowel control still may suffer
from temporary episodes of fecal incontinence, especially
when they experience diarrhea.
Some 25% of all patients with ARMs suffer from true
fecal incontinence, and are the patients who need bowel
management to be kept clean. As previously noted,
certain patients with Hirschsprung disease and those with
spinal problems can suffer from true fecal incontinence
as well. For these patients, similar principles of bowel
management learned from treatment of patients with
ARMs can be applied.10
For children with ARMs, the surgeon should be able
to predict in advance which patient will likely have a good
functional prognosis and which child will have a poor
prognosis. Table 36-1 shows the most common indicators
for a good or poor prognosis. After primary repair and
colostomy closure, it is possible to establish a functional
prognosis (Table 36-2). Parents should be given the
information regarding their childs realistic chances for
FIGURE 36-3 This contrast enema was performed in a patient bowel control to avoid needless frustration at the age of
who had resection of the rectosigmoid colon. Often these toilet training.
patients act like they do not have a rectal reservoir. (From Levitt
MA, Pea A. Treatment of chronic constipation and resection of the
Once the diagnosis of the specific anorectal defect is
inert rectosigmoid. In: Anorectal Malformations in Children. Heidel- established, the functional prognosis can be predicted. If
berg: Springer; 2006. p. 417.) the childs defect is associated with a good prognosis such
A B C
FIGURE 36-4 (A,B) This series of abdominal radiographs was obtained during inpatient bowel management showing progression
toward a completely clean colon with daily adjustment of the enema. (C) After five days, a postcontrast abdominal film shows
minimal evidence of retained fecal material.
518 SECTION IV Abdomen
as a vestibular fistula, perineal fistula, rectal atresia, rec- Children with an ARM who have reached the age for
tourethral bulbar fistula, or imperforate anus with no a bowel management program can be divided into two
fistula, one should expect that the child will have volun- well-defined groups that require individualized treatment
tary bowel movements by the age of 3 years provided the plans. The first and larger group has fecal incontinence
sacrum and spine are normal. These children will need and a tendency toward constipation. The second group
careful attention to avoid fecal impaction, constipation, has fecal incontinence with a tendency toward loose
and soiling.3 stools. Patients with fecal incontinence after operations
If the childs defect is associated with a poor prognosis, for Hirschsprung disease and those with spinal disorders
such as a very high cloaca with a common channel longer usually have a tendency toward constipation. A small
than 3cm, a rectobladder neck fistula, an associated group of Hirschsprung patients fall into the hypermotile
myelomeningocele, or a very hypodeveloped sacrum, the group. These patients have multiple daily stools and a
child will most likely need a bowel management program nondilated colon seen on a contrast enema (Fig. 36-5; see
with enemas to remain clean. This should be imple- also Fig. 36-3). Interestingly, because of abnormal inner-
mented at 3 to 4 years of age and before starting school. vation of the colon, patients with spinal diseases can have
Children with a rectoprostatic fistula have a 50% chance severe constipation, yet have a nondilated colon.
of having voluntary bowel movements and continence. In
these children, an attempt should be made to achieve Children with True Fecal Incontinence and
toilet training by the age of 3 years. If this proves unsuc- Constipation (Colonic Hypomotility)
cessful, bowel management should be implemented. The
ability to toilet train can be reassessed each summer after Patients with true fecal incontinence and a tendency
school has ended. toward constipation should not be treated with laxatives,
In patients who have undergone repair of an imperfo- but instead need an enema program. In these children,
rate anus and who have fecal incontinence, reoperation the motility of the colon is slow. The basis of their bowel
to relocate a misplaced rectum or repair a rectal prolapse management program is to clean the colon once a day
should be considered if the child was born with a good with an enema. No special diet or medications are neces-
sacrum, a good sphincter mechanism, and a malforma- sary. The fact that they suffer from constipation (hypo-
tion with good functional prognosis. A repeat PSARP can motility) is useful because it helps them to remain clean
be performed and the rectum relocated within the sphinc- between enemas. The real challenge is to find the appro-
ter mechanism.11 priate enema capable of evacuating the colon. Definitive
36 Fecal Incontinence and Constipation 519
evidence that the rectosigmoid colon is empty after an BOWEL MANAGEMENT: KEY STEPS
enema requires a plain abdominal radiograph (see Fig.
36-4). Soiling episodes or accidents occur when there is The first step is to perform a contrast enema with water-
incomplete colonic evacuation with progressive enlarge- soluble material, never with barium. It is very important
ment of the stool followed by leakage around the stool. to obtain a postevacuation film. This contrast study
shows the type of colon that is present: dilated-constipated
Children with True Fecal Incontinence and (see Fig. 36-2) or nondilated-tendency toward loose stool
Loose Stools (Colonic Hypermotility) (see Figs 36-3 and 36-5). The enema volume and type
can also be estimated from this contrast study.
The great majority of children with ARMs who suffer The bowel management program is then implemented
from this problem were repaired before the introduction according to the patients type of colon, and the results
of the PSARP technique. The older procedures fre- are evaluated daily. Changes in the volume and content
quently included a rectosigmoid resection.12,13 Therefore, of the enema are made until the colon is successfully
these children have an overactive colon because they lack cleaned. For this, an abdominal radiograph that is
a rectal reservoir (see Fig. 36-3). Rapid transit of stool obtained every day is invaluable in determining whether
results in frequent episodes of diarrhea. This means that the colon is empty (see Fig. 36-4).
even when an enema cleans their colon rather easily, stool There are different types of solutions to use for
keeps passing fairly quickly from the cecum to the enemas. Some can be bought in a drugstore. The use of
descending colon and out the anus. To manage this situ- phosphate enemas is convenient because they are avail-
ation, a constipating diet and/or medications (loperamide able in prepared containers. However, saline enemas are
and water-soluble fiber) to slow down the colon are nec- often just as effective, and some families find them easier
essary. Also, eliminating foods that loosen bowel move- and less expensive. A 0.9% saline can be made at home
ments will help the colon slow down (Table 36-3). A by adding 1.5 teaspoons of salt to 1000mL of water.
small subset of patients with Hirschsprung disease Occasionally, children will complain of cramping with
(see Fig. 36-5) behaves like they have hypermotility and the phosphate enema while the saline enemas are usually
can be managed similarly. well tolerated. Children should never receive more than
The keys to the success of a bowel management one phosphate enema a day because of the risk of phos-
program are dedication and sensitivity from the medical phate intoxication, and patients with impaired renal func-
team. The basis of the program is to clean the colon and tion should avoid them entirely. The saline enema
keep it quiet, thus keeping the patient clean for the 24 (350750mL) can be mixed with glycerin (1040mL)
hours after the enema. It is an ongoing process that needs and/or soap (1040mL) to make it more effective.
to be responsive to the individual patient and differs The daily enema should result in a bowel movement
for each child. It is usually successful within a week, within 30 to 45 minutes, followed by a period of 24 hours
during which time the family, patient, physician, and of complete cleanliness. If the chosen enema does not
nurse undergo a process of trial and error, tailoring radiographically clean the colon, or if the child keeps
the regimen to the specific patient. More than 95% of soiling, then a more voluminous or concentrated enema
the children who follow this program are artificially is needed. Administering the enema through a catheter
kept clean for the whole day and can have a completely with a balloon helps prevent leakage (Fig. 36-6). The
normal life.10 right enema is the one that can empty the childs colon
and allow him or her to stay clean for the following 24
hours. This can be only determined by trial and error.
Children with loose stools have an overactive colon,
and usually do not have a rectal reservoir. This means
TABLE 36-3 Food Products and Stool that even when an enema cleans their colon easily, new
Consistency stool passes quickly from the cecum to the descending
Foods that Produce Foods that Promote colon and anus. To prevent this, a constipating diet,
Loose Stools Constipation bulking agents, and/or medications to slow down the
Milk or milk products Apple sauce
colon can be used. Eliminating foods that loosen bowel
Fats Apple without skin
movements will help decrease the colonic motility (see
Fried foods Rice
Table 36-3).
Fruits White bread
Such patients should be provided with a list of consti-
Vegetables Bagels
pating foods and a list of laxative foods to avoid. The
Spices Soft drinks
constipating diet is rigid: banana, apple, baked bread,
Fruit juices Banana
white pasta with no sauce, boiled meat, etc. Fried foods,
French fries Pasta
dairy products and sugary drinks should be avoided (see
Chocolate Pretzels
Table 36-3). Most parents learn which meals provoke
Tea
loose stools and which constipate their child. To deter-
Potato
mine the right combination, treatment is initiated with
Jelly (not jam)
enemas, a very strict diet, loperamide, and a water-soluble
Boiled, broiled, baked meat,
fiber such as pectin. Most children respond to this aggres-
chicken or fish sive management within one to two weeks. The child
should remain on a strict diet until clean for 24 hours for
520 SECTION IV Abdomen
FIGURE 36-8 Some patients are able to have bowel continence with a daily prograde enema administered through an appendicos-
tomy. (Adapted from Levitt MA, Soffer SZ, Pea A. Continent appendicostomy in the bowel management of fecal incontinent children.
J Pediatr Surg 1997;32:1631.)
performing it, the child should be completely clean untreated, constipation can be extremely incapacitating.3
through a bowel management regimen. Although diet affects colonic motility, its therapeutic
value is negligible in the most serious forms of constipa-
tion. While it is true that many patients with severe
CONSIPATION constipation suffer from psychological disorders, a psy-
chological origin for the constipation cannot explain the
Pseudoincontinence occurs when a patient behaves like severe forms, because it is not easy to voluntarily retain
he or she is fecally incontinent but really has severe con- stool when an autonomous rectosigmoid undergoes peri-
stipation and overflow soiling. Once the disimpaction is stalsis. Passage of large, hard pieces of stool may provoke
treated and the patient receives enough laxatives to avoid pain and make the patient behave like a stool retainer.
constipation, he or she starts having voluntary bowel This may complicate the problem of constipation, but it
movements. is not the original cause.
The colon absorbs water from the stool and serves a Constipation is a self-perpetuating disease. A patient
reservoir function. These processes depend on colonic who suffers from a certain degree of constipation and is
motility, which is an area of physiology that is not well not treated adequately will only partially empty the colon,
understood and for which treatments are limited. Every leaving larger and larger amounts of stool inside the rec-
24 to 48 hours, the colon develops active peristaltic tosigmoid. This results in greater degrees of distal colonic
waves, indicating that it is time to empty. A normal indi- enlargement. Dilation of a hollow viscus results in poor
vidual feels this sensation and decides when to tighten peristalsis. This explains why constipation leads to fecal
and relax the voluntary sphincter mechanism. retention culminating in megacolon, which exacerbates
If a child has potential to be fecally continent, then the constipation. In addition, the passage of large, hard
management involves treatment of constipation, using pieces of stool may produce anal fissures, leading to painful
stimulant laxatives to provoke peristalsis and overcome stooling and reluctance to have bowel movements.
the dysmotility. Stool softeners should be avoided as they The clinician must decide which type of patient is
can exacerbate overflow incontinence. Patients who have being treated. Patients with ARMs and Hirschsprung
undergone successful surgery for Hirschsprung disease or disease with good prognosis for bowel control are those
for low ARMs with a normal spine should be fecally more likely to have constipation. In these patients, an
continent. aggressive, proactive treatment of their constipation is
Constipation in children with ARMs is extremely the best approach. Of course, the child must be capable
common, particularly in the more benign types.1,3 It is of being fecally continent and having the capacity for
also common in patients after successful surgery for Hir- voluntary bowel movements before initiating treatment
schsprung disease and occurs in a large group of patients for constipation because laxatives will make an inconti-
considered to have idiopathic constipation.2 When left nent child worse.
522 SECTION IV Abdomen
When children with ARMs and Hirschsprung disease evacuate it. The dosage of the laxative is increased daily
are managed early with aggressive treatment of constipa- until the right amount is reached to completely empty
tion, children with a good prognosis should toilet train the colon every day. Water soluble fiber is added which
without difficulty. When constipation is not managed provides stool bulk and makes the laxative more
properly, they behave much like children with idiopathic efficient.
constipation and may have overflow pseudoincontinence.3 If medical treatment proves to be difficult because the
Because of a hypomotility disorder that interferes with child has a severe megasigmoid and requires an enormous
complete emptying of the rectosigmoid, most of these amount of laxatives to empty, the surgeon can offer a
patients suffer from different degrees of dilation of the segmental resection of the colon (Fig. 36-9). After the
rectum and sigmoid, a condition known as megarecto resection, the amount of laxatives required to treat these
sigmoid (see Fig. 36-2).2 Often, these children were born children can be significantly reduced or even eliminated.
with a good prognosis type of anorectal defect and under- Before performing this operation, however, it is manda-
went a technically correct operation, but did not receive tory to confirm that the child is definitely suffering from
appropriate treatment for constipation. Subsequently overflow pseudoincontinence rather than true fecal
they developed fecal impaction and overflow pseudoin- incontinence with constipation. Failure to make this dis-
continence. These may also be children with severe idi- tinction may lead to an operation in which a fecally
opathic constipation without a prior operation, who have incontinent, constipated child is changed to one with a
a dilated rectosigmoid because of years of constipation. tendency to have loose stool, which will make the patients
First, the impaction needs to be removed with enemas condition much more difficult to manage.
and colonic irrigations to clean the megarectosigmoid. The dysmotility of the colon in patients with Hirschs-
Fecal impaction is a stressful event resulting from retained prung disease, even after a successful operation to remove
stool for several days or weeks, crampy abdominal pain, the aganglionic bowel, is not well understood. These
and sometimes tenesmus. When laxatives are prescribed patients can also benefit from proactive medical treat-
to such a patient, the result is exacerbation of the crampy ment of their constipation.
abdominal pain and sometimes vomiting, a consequence Some clinicians treat these patients with colostomies
of increased colonic peristalsis produced by the laxative or colonic washouts via a catheterized stoma or button
acting against a fecally impacted colon. Therefore, dis- device, and monitor the improvement of colonic dilata-
impaction, proven by radiograph, must precede initiation tion with contrast studies.16 Once the distal colon regains
of laxative therapy. Then, once the colon is clean, the a normal caliber, the physician assumes that the patient
constipation is treated with the administration of large is cured and discontinues the washouts or closes the
doses of stimulant laxatives. Stool softeners should be colostomy. Unfortunately, these patients symptoms
avoided as they only soften the stool, and do not help quickly recur. We have found that washouts are often
A B
FIGURE 36-9 Resection of a dilated sigmoid colon, which can be very effective in select patients with an anorectal malformation
and severe constipation.
36 Fecal Incontinence and Constipation 523
ineffective in such patients because they simply retain the Drugs (containing senna) that are designed to increase
fluid and believe they are really only for patients with true the colonic motility are better when compared with stool
fecal incontinence who are incapable of having voluntary softeners. Softening of the stool without improving the
bowel movements. On the other hand, a patient with colonic motility will likely make the patient worse,
pseudoincontinence is capable of emptying their colon because with soft stool they will no longer have control,
with the help of adequate doses of laxatives and thus does whereas they do reasonably well with solid stool that
not need washouts at all. allows them to feel rectal distention. This is a common
Determining which patient the clinician is managing misconception, and the switch from stool softener to
can be a challenge. If the patient is incontinent, washouts laxative usually makes a significant difference.
with a bowel management regimen are appropriate. If the In many cases, the laxative regimen we employ uses
patient is continent, then aggressive management of the the same medications that have been tried previously, but
constipation after ensuring disimpaction is the optimal were unsuccessful. Success is based on starting with a
treatment. radiographically clean colon and adapting the dosage to
Soiling of the underwear is an ominous sign of severe the patients response. The response is monitored daily
constipation. A patient who is old enough to have bowel with an abdominal radiograph with the laxative dose
control, but soils the underwear day and night and does adjusted, if necessary. The colon is emptied with an
not have spontaneous bowel movements, may have enema whenever 24 hours has passed without a bowel
overflow pseudoincontinence. These patients behave movement. Almost always, the patient previously had
similarly to fecally incontinent individuals. When the received a lower dose than what was really needed.
constipation is treated adequately, the great majority of
these pseudoincontinent children regain bowel control. Disimpaction
Of course, this clinical presentation may also occur in a
patient with true fecal incontinence. When uncertain, the The disimpaction process is a vital and often neglected
clinician can start the 3- to 4-year-old who is having step. This includes the administration of enemas three
trouble with toilet training on a daily enema. Once clean times a day until the patient is radiographically clean. The
with this regimen, and if the child has the potential for contrast enema using water-soluble material not only
bowel control, then an attempt at a laxative program can shows the anatomy, but also is a helpful tool for cleaning
be tried. the colon. If the patient remains impacted after three
A contrast enema with water-soluble material is an days, then he or she is given a balanced electrolyte solu-
extremely valuable study. In the constipated patient, it tion via a nasogastric tube in the hospital and the enema
usually shows a megarectosigmoid with dilation of the regimen is continued. If this is unsuccessful, manual dis-
colon all the way down to the anus (see Fig. 36-2). There impaction under anesthesia may be necessary.
is usually a dramatic size discrepancy between a normal
transverse and descending colon and the dilated megarec- Determining the Laxative Requirement
tosigmoid which is the exact opposite of Hirschsprung
disease. The size of the colon guides the dosing of the Once the patient has been disimpacted, a specific amount
laxatives. It seems that the more localized the dilatation of of senna-based laxative predicted from the contrast study
the rectosigmoid, the better the results of a colonic resec- is begun. An empiric dose is given, and the patient is
tion in reducing or eliminating the laxative requirement. observed for the next 24 hours. If the patient does not
Colonic manometry is sometimes useful in the evalu- have a bowel movement in the 24 hours after giving the
ation of these patients. Manometry is performed by laxative, it means the laxative dose was not strong enough
placing balloons at different levels in the colon and and must be increased. An enema is also required to
recording the waves of contraction or the electrical activ- remove the stool produced during the previous 24 hours.
ity.17,18 Scintigraphy has also been used to assess colonic In these extremely constipated patients, stool should
motility,19 but unfortunately does not yet help guide never remain in the rectosigmoid for more than 24 hours.
therapeutic decisions. The key information the surgeon The routine of increasing the amount of laxatives and
needs to know is if and where a colonic resection would giving an enema, if needed, is continued every night until
prove beneficial to the patient who requires enormous the child has a voluntary bowel movement and empties
doses of laxatives to empty the colon. the colon completely. Ideally, this routine is checked with
Histologic studies of the colon in these patients mainly a daily radiograph. Each day that the patient has a bowel
show hypertrophic smooth muscle in the area of the movement, a radiograph should confirm that the bowel
dilated colon and normal ganglion cells. In the near movement was effective, meaning that the patient com-
future, it is hoped that more sophisticated histopatho- pletely emptied the rectosigmoid. If the patient passed
logic research will enhance our knowledge about colonic stool but did not empty completely, the dose of laxative
dysmotility. should be increased. If the patient passed stool and suc-
cessfully emptied the colon, then that laxative dose should
be continued each day. If the patient passed multiple
Treatment stools and the abdominal film is clean, then the laxative
Patients with ARMs, severe constipation, and the poten- dose can be reduced slightly.
tial for bowel control, as well as those with severe idio- It is important to remember that constipation
pathic constipation in whom dietary measures or gentle covers a wide spectrum and patients may have
laxatives do not work, require a more aggressive regimen. laxative requirements that are much larger than the
524 SECTION IV Abdomen
manufacturers recommendation. Occasionally, in the who have a more localized form of megarectosigmoid.
process of increasing the amount of laxatives, patients Patients with more generalized dilation of the colon do
vomit, or feel nauseated and complain of abdominal not respond as well and may require a more extensive
cramping before reaching any positive effect. In these resection that includes the left and transverse colon,
patients, a different medication can be tried. Some sometimes accompanied by a Malone appendicostomy.
patients vomit all kinds of laxatives and are unable to
tolerate the amount of laxative that produces a bowel REFERENCES
movement that empties the colon. Others empty but have 1. Pea A. Anorectal malformations. Semin Pediatr Surg 1995;4:
significant symptoms from the laxatives. Such a patient is 3547.
2. Pea A, Levitt MA. Colonic inertia disorders. Curr Prob Surg
considered to have an intractable condition and is a can- 2002;39:666730.
didate for an operation. Usually, however, the dosage that 3. Levitt MA, Kant A, Pea A. The morbidity of constipation in
the patient needs to radiographically empty the colon can patients with anorectal malformations. J Pediatr Surg 2010;45:
be achieved. At that dose, the patient stops soiling because 122833.
4. Bax KMA. Duhamel Lecture: The incurability of Hirschsprungs
he or she is successfully emptying the colon each day. disease. Eur J Pediatr Surg 2006;16:3804.
Because the colon is empty, the patient remains clean 5. Levitt MA, Martin C, Olesevich M, et al. Hirschsprungs disease
until the next voluntary bowel movement. and fecal incontinence: Diagnostic and management strategies.
At this point, the patient and parents have the oppor- J Pediatr Surg 2009;44:2717.
tunity to evaluate the quality of life that they have with 6. Levitt MA, Dickie B, Pea A. Evaluation and treatment of the
patient with Hirschsprung disease who is not doing well after a
this treatment, understanding that this treatment will pull-through procedure. Semin Pediatr Surg 2010;19:14653.
most likely be life-long. For many of these patients, a 7. Smith GK. The history of spina bifida, hydrocephalus, paraplegia,
sigmoid or rectosigmoid resection can provide sympto- and incontinence. Pediatr Surg Int 2001;17:42432.
matic improvement leading to significant reduction or 8. Eire PF, Cives RV, Gago MC. Faecal incontinence in children with
complete elimination of laxatives.20 spina bifida: The best conservative treatment. Spinal Cord 1998;36:
7746.
9. Hayden DM, Weiss EG. Fecal incontinence: Etiology, evaluation,
and treatment. Clin Colon Rectal Surg 2011;24:6470.
Rectosigmoid Resection 10. Bischoff A, Levitt MA, Pea A. Bowel management for the treat-
The megarectosigmoid is resected and the descending ment of pediatric fecal incontinence. Pediatr Surg Int 2009;25:
102742.
colon is anastomosed to the rectum (see Fig. 36-9).21 This 11. Levitt MA, Pea A. Reoperations in Anorectal Malformations. In:
can be done laparoscopically and ideally only leaves a Teich S, Caniano D, editors. Reoperative Pediatric Surgery.
small rectal cuff. These patients must be followed closely Totowa: Humana Press; 2008. p. 31126.
because the condition is not cured by the operation. The 12. Kiesewetter WB. Imperforate anus II: The rationale and technique
of the sacro-abdomino-perineal operation. J Pediatr Surg 1967;2:
remaining rectum is most likely abnormal. Without 10610.
careful follow-up and treatment of constipation, the 13. Rehbein F. Imperforate anus: Experiences with abdomino-perineal
colon can re-dilate. and abdomino-sacro-perineal pull-through procedures. J Pediatr
In patients with ARMs, it is particularly vital to keep Surg 1967;2:99105.
the rectum intact because they need it for continence. It 14. Rangel SJ, Lawal TA, Bischoff A, et al. The appendix as a conduit
for antegrade continence enemas in patients with anorectal malfor-
is their reservoir in which they feel the distention of the mations: Lessons learned from 163 cases treated over 18 years.
stool. In contrast, patients with idiopathic constipation J Pediatr Surg 2011;46:123642.
who have not undergone an operation and have a normal 15. Lawal TA, Rangel SJ, Bischoff A, et al. Laparoscopic assisted
anal canal and sphincters, the rectum and sigmoid can be Malone appendicostomy in the management of fecal incontinence
resected with preservation of fecal continence. This is in children. J Laparoendosc Adv Surg Tech A, 2011;21:4559.
16. Marshall J, Hutson JM, Anticich N, et al. Antegrade continence
only done in the rare case that the rectum is significantly enemas in the treatment of slow-transit constipation. J Pediatr Surg
dilated. Resection of the rectosigmoid down to the pec- 2001;36:122730.
tinate line can be performed in a similar manner as used 17. DeLorenzo C, Flores AF, Reddy SN, et al. Use of colonic manom-
for patients with Hirschsprung disease with anastomosis etry to differentiate causes of intractable constipation in children.
J Pediatr 1992;120:6905.
of the nondilated colon to the rectum above the pectinate 18. Sarna SK, Bardakjian BL, Waterfall WE, et al. Human colonic
line.22 It seems that a laparoscopic low anterior resection electric control activity (ECA). Gastroenterology 1980;78:
is best to avoid over-stretching the sphincters, leaving 152636.
behind a small cuff of rectum. Dramatic improvement in 19. Cook BJ, Lim E, Cook D. Radionuclear transit to assess sites of
delay in large bowel transit in children with chronic idiopathic
the patients ability to empty the colon has resulted. constipation. J Pediatr Surg 2005;40:47883.
The most dilated part of the colon is resected because 20. Pea A, El-Behery M. Megasigmoida source of pseudo-
it seems to be the most seriously affected and the nondi- incontinence in children with repaired anorectal malformations.
lated part of the colon is assumed to have a more normal J Pediatr Surg 1993;28:15.
motility. Unfortunately, we lack a more scientific way to 21. Levitt MA, Pena A. Surgery and constipation: When, how, yes, or
no? J Pediatr Gastroenterol Nutr 2005;41(Suppl. 1):S5860.
assess the dysmotile anatomy. Perhaps emerging colonic 22. Levitt MA, Martin CA, Falcone RA, et al. Transanal rectosigmoid
motility technology will help with operative planning. It resection for severe intractable idiopathic constipation. J Pediatr
seems that the patients who improve the most are those Surg 2009;44:128591.
C H A P T E R 3 7
A B C
FIGURE 37-3 (A) At the time of operation, a small, fine, malleable probe is inserted through the fistula and can usually be gently
advanced until it is visualized to exit the base of the involved crypt. (B) An incision is then made along the probe and is deepened
through the superficial portion of the external sphincter. (C) After complete unroofing of the tract, the incision is usually left open,
which may provide some distress on the part of the parents but usually does not cause much discomfort for the child.
downward.2327 We have found submucosal injection of plication or reefing of the posterior rectal wall via a coc-
5% sodium morrhuate to be especially effective in chil- cygectomy incision has been reported to have good
dren with mucosal prolapse unresponsive to nonopera- results, but the morbid potential for a rectocutaneous
tive therapy. An open sclerosing procedure, in which the fistula makes this a technique that we do not routinely
retrorectal space is developed and packed with gauze, is employ.34 Laparoscopic rectopexy is an alternative to
currently not routinely performed.28,29 Endorectal cau- standard open rectopexy and is performed with two oper-
terization or mucosal stripping may be effective; however, ating ports and a port for laparoscopic visualization.35,36
there is little evidence that rectal prolapse is due to The rectum is mobilized and sutured to the periosteum
mucosal overabundance, and we do not recommend this of the sacral promontory in multiple locations with non-
as primary surgical therapy.30,31 absorbable suture. The operation has been successfully
In patients with full-thickness prolapse, or for those completed in children as young as 10 months of age, and
who have failed nonoperative therapy, operative fixation results are encouraging. Open posterior rectopexy is yet
techniques can be used. Transanal suture fixation of another technique for rectal prolapse.37 Through a natal
the rectum (Ekehorn rectopexy) has recently been used cleft incision, the coccyx is removed, the muscular hiatus
in a group of children with good success.32,33 Its benefit is narrowed, and the rectum is suspended from the cut
probably derives from the inflammation and adhesions edge of the sacrum so that it cannot slide downward (Fig.
that are produced by the mattress sutures. An extensive 37-7). This maneuver immediately re-establishes the
A B
C D
FIGURE 37-7 (A) A cut-away sagittal view illustrates the failure of the rectal suspensory mechanism to hold the rectum within
the pelvis. (B) The posterior sagittal incision is depicted. (C) The coccyx has been removed and the posterior rectal wall exposed.
(D) The pelvic diaphragm is closed posterior to the reduced rectum. The rectum is sutured laterally to the pelvic diaphragm. The
rectum is further suspended from the cut edge of the sacrum. (A and D adapted from Ashcraft KW, Amoury RA, Holder TM. Levator
repair and posterior suspension for rectal prolapse. J Pediatr Surg 1977;12:2415; B and C from Ashcraft KW. Atlas of Pediatric Surgery.
Philadelphia: WB Saunders; 1994. p. 217.)
37 Acquired Anorectal Disorders 529
RECTAL TRAUMA
Rectal trauma in pediatric patients generally occurs by
one of two mechanisms. The first is from penetrating
trauma after an accidental impalement injury or, occa-
sionally, a gunshot (Fig. 37-8). The second, and more
common, occurs as the result of sexual abuse. The most
common clinical presentation is that of a chronic stellate
laceration of the anus with edema (Fig. 37-9). Perianal
condylomata are common sequelae in cases of sexual FIGURE 37-9 This male child was the victim of chronic sexual
abuse and shows the typical stellate lacerations of the anal
abuse. Careful questioning may reveal that a male member mucosa and skin.
of the immediate family has penile condylomata.
However, 25% of males who carry papillomavirus in the
urethra have no external evidence of disease.39
The patient with an accidental injury to the anus is otherwise, and should be investigated through the appro-
typically seen immediately after the incident. Sexual priate social service authorities.4042
abuse is suspected when an inconsistent history of the The child who has a traumatic rectal injury is usually
mechanism of injury is elucidated or there is a delay in difficult to examine. An impalement injury often requires
presentation. As with other forms of sexual abuse, diffi- rectal examination and/or sigmoidoscopy under general
culty is often encountered in obtaining an adequate anesthesia (Fig. 37-10). This allows a complete assess-
history from the victim owing to fear, threats of retalia- ment of the injury and also allows appropriate operative
tion, or guilt. Unexplained injuries to the rectum must treatment if necessary. Photographs should be obtained
be considered a manifestation of sexual abuse until proven to document the injury for medicolegal purposes. A ret-
rograde urethrogram and/or voiding cystourethography
should be obtained when there is suspicion of injury to
the lower urinary tract.
Treatment of penetrating rectal injuries often requires
a diverting colostomy.43 However, primary repair without
fecal diversion can be performed safely in select cases.44,45
When in doubt, one should divert the fecal stream to
avoid the consequences of perineal infection. In general,
isolated intraperitoneal rectal injuries can be treated with
primary repair. Inaccessible or severe distal extraperito-
neal rectal injuries should be treated by fecal diversion
and presacral drainage.46 Accessible injuries to the distal Pediatric Surgery. New York: McGraw-Hill Professional; 2003.
rectum and anal canal can be repaired with the intent of p. 7358.
23. Abes M, Sarihan H. Injection sclerotherapy of rectal prolapse in
reapproximating the underlying sphincter muscle mecha- children with 15 percent saline solution. Eur J Pediatr Surg
nism and the overlying mucosa. In the victim who is 2004;14:1002.
found to have an acute laceration extending up the rectal 24. Chan WK, Kay SM, Laberge JM, et al. Injection sclerotherapy in
wall, it is rarely necessary to perform a diverting colos- the treatment of rectal prolapse in infants and children. J Pediatr
Surg 1998;33:2558.
tomy, because these lacerations are not usually full thick- 25. Fahmy MA, Ezzelarab S. Outcome of submucosal injection of dif-
ness. However, patients with full-thickness injury should ferent sclerosing materials for rectal prolapse in children. Pediatr
be managed by repair and diverting colostomy. When Surg Int 2004;20:3536.
present, treatment of condylomata depends on the extent 26. Shah A, Parikh D, Jawaheer G, et al. Persistent rectal prolapse in
of disease. Although small lesions may be responsive to children: Sclerotherapy and surgical management. Pediatr Surg Int
2005;21:2703.
repeated applications of topical agents such as podophyl- 27. Zganjer M, Cizmic A, Cigit I, et al. Treatment of rectal prolapse
lin or imiquimod, more extensive lesions require excision. in children with cow milk injection sclerotherapy: 30-year experi-
Intralesional interferon may be a useful adjunct for recur- ence. World J Gastroenterol 2008;14:73740.
rent disease.47 28. Balde I, Mbumbe-King A, Vinand P. [The Lockhart-Mummery
technique in the treatment of the total rectal prolapse among chil-
Treatment of sexual abuse involves interruption of the dren. Concerning 25 cases (authors transl)]. Chir Pediatr
abuse pattern. Immediate consultation with child protec- 1979;20:3757.
tive services or the local equivalent is mandatory. 29. Scheye T, Marouby D, Vanneuville G. [Total rectal prolapse in
children. Modified Lockhart-Mummery operation]. Presse Med
1987;16:1234.
REFERENCES 30. El-Sibai O, Shafik AA. Cauterization-plication operation in the
1. Fitzgerald RJ, Harding B, Ryan W. Fistula-in-ano in childhood: A treatment of complete rectal prolapse. Tech Coloproctol 2002;
congenital etiology. J Pediatr Surg 1985;20:801. 6:514.
2. Rosen NG, Gibbs DL, Soffer SZ, et al. The nonoperative manage- 31. Hight DW, Hertzler JH, Philippart AI, et al. Linear cauterization
ment of fistula-in-ano. J Pediatr Surg 2000;35:9389. for the treatment of rectal prolapse in infants and children. Surg
3. Murthi GV, Okoye BO, Spicer RD, et al. Perianal abscess in child- Gynecol Obstet 1982;154:4002.
hood. Pediatr Surg Int 2002;18:68991. 32. Sander S, Vural O, Unal M. Management of rectal prolapse in
4. Stites T, Lund DP. Common anorectal problems. Semin Pediatr children: Ekehorns rectosacropexy. Pediatr Surg Int 1999;
Surg 2007;16:718. 15:11114.
5. Poenaru D, Yazbeck S. Anal fistula in infants: Etiology, features, 33. Schepens MA, Verhelst AA. Reappraisal of Ekehorns rectopexy in
management. J Pediatr Surg 1993;28:11945. the management of rectal prolapse in children. J Pediatr Surg
6. Ross ST. Fistula in ano. Surg Clin North Am 1988;68:141726. 1993;28:14947.
7. al-Salem AH, Laing W, Talwalker V. Fistula-in-ano in infancy and 34. Tsugawa C, Matsumoto Y, Nishijima E, et al. Posterior plication
childhood. J Pediatr Surg 1994;29:4368. of the rectum for rectal prolapse in children. J Pediatr Surg
8. Cohen A, Dehn TC. Lateral subcutaneous sphincterotomy 1995;30:6923.
for treatment of anal fissure in children. Br J Surg 1995;82: 35. Koivusalo A, Pakarinen M, Rintala R. Laparoscopic suture rec-
13412. topexy in the treatment of persisting rectal prolapse in children: A
9. Lambe GF, Driver CP, Morton S, et al. Fissurectomy as a treatment preliminary report. Surg Endosc 2006;20:9603.
for anal fissures in children. Ann R Coll Surg Engl 2000;82: 36. Tsugawa K, Sue K, Koyanagi N, et al. Laparoscopic rectopexy for
2547. recurrent rectal prolapse: A safe and simple procedure without a
10. Tankova L, Yoncheva K, Kovatchki D, et al. Topical anal fissure mesh prosthesis. Hepatogastroenterology 2002;49:154951.
treatment: Placebo-controlled study of mononitrate and trinitrate 37. Ashcraft K. Acquired Anorectal Disorders. In: Ashcraft K, Holcomb
therapies. Int J Colorectal Dis 2009;24:4614. GI, Murphy J, editors. Pediatric Surgery. 4th ed. Philadelphia:
11. Sweeney JL, Ritchie JK, Nicholls RJ. Anal fissure in Crohns Elsevier Saunders; 2005.
disease. Br J Surg 1988;75:567. 38. Ashcraft KW, Amoury RA, Holder TM. Levator repair and poste-
12. Buchmann P, Keighley MR, Allan RN, et al. Natural history of rior suspension for rectal prolapse. J Pediatr Surg 1977;12:2415.
perianal Crohns disease. Ten year follow-up: A plea for conserva- 39. Rosemberg SK, Husain M, Herman GE, et al. Sexually transmitted
tism. Am J Surg 1980;140:6424. papillomaviral infection in the male: VI. Simultaneous urethral
13. Strong SA. Perianal Crohns disease. Semin Pediatr Surg 2007; cytology-ViraPap testing of male consorts of women with genital
16:18593. human papillomaviral infection. Urology 1990;36:3841.
14. Hart AL, Plamondon S, Kamm MA. Topical tacrolimus in the 40. Adams JA. Medical evaluation of suspected child sexual abuse: Its
treatment of perianal Crohns disease: Exploratory randomized time for standardized training, referral centers, and routine peer
controlled trial. Inflamm Bowel Dis 2007;13:24553. review. Arch Pediatr Adolesc Med 1999;153:11212.
15. Fleshner PR, Schoetz DJ Jr, Roberts PL, et al. Anal fissure in 41. Geist RF. Sexually related trauma. Emerg Med Clin North Am
Crohns disease: A plea for aggressive management. Dis Colon 1988;6:43966.
Rectum 1995;38:113743. 42. Kadish HA, Schunk JE, Britton H. Pediatric male rectal and genital
16. Severijnen R, Festen C, van der Staak F, et al. Rectal prolapse in trauma: Accidental and nonaccidental injuries. Pediatr Emerg Care
children. Neth J Surg 1989;41:14951. 1998;14:958.
17. Corman ML. Rectal prolapse in children. Dis Colon Rectum 43. Haut ER, Nance ML, Keller MS, et al. Management of penetrating
1985;28:5359. colon and rectal injuries in the pediatric patient. Dis Colon Rectum
18. Park RW, Grand RJ. Gastrointestinal manifestations of cystic fibro- 2004;47:152632.
sis: A review. Gastroenterology 1981;81:114361. 44. Bonnard A, Zamakhshary M, Wales PW. Outcomes and manage-
19. Theuerkauf FJ Jr, Beahrs OH, Hill JR. Rectal prolapse. Causation ment of rectal injuries in children. Pediatr Surg Int 2007;23:
and surgical treatment. Ann Surg 1970;171:81935. 10716.
20. Shwachman H, Redmond A, Khaw KT. Studies in cystic fibrosis. 45. Levine JH, Longo WE, Pruitt C, et al. Management of selected
Report of 130 patients diagnosed under 3 months of age over a rectal injuries by primary repair. Am J Surg 1996;172:5759.
20-year period. Pediatrics 1970;46:33543. 46. Weinberg JA, Fabian TC, Magnotti LJ, et al. Penetrating rectal
21. Zempsky WT, Rosenstein BJ. The cause of rectal prolapse in chil- trauma: Management by anatomic distinction improves outcome.
dren. Am J Dis Child 1988;142:3389. J Trauma 2006;60:50814.
22. Touloukian RJ. Anorectal Prolapse, Abscess, and Fissure. 47. Congilosi SM, Madoff RD. Current therapy for recurrent and
In: Ziegler MM, Azizkhan RG, Weber TR, editors. Operative extensive anal warts. Dis Colon Rectum 1995;38:11017.
C H A P T E R 3 8
Intussusception
Alexandra C. Maki Mary E. Fallat
Intussusception is the most frequent cause of bowel most common lead point is a Meckel diverticulum fol-
obstruction in infants and toddlers. It is an acquired lowed by polyps and duplications. Other benign lead
invagination of the proximal bowel (intussusceptum) into points include the appendix, hemangiomas, carcinoid
the distal bowel (intussuscipiens). It was first described in tumors, foreign bodies, ectopic pancreas or gastric
1674 by Paul Barbette of Amsterdam, defined by Treves mucosa, hamartomas from PeutzJeghers syndrome (Fig.
in 1899, and operated on successfully in 1873 by John 38-1), and lipomas. Malignant causes, although rare,
Hutchinson.1,2 increase in incidence with age and include lymphomas
and small bowel tumors.13 Systemic diseases, including
HenochSchnlein purpura and cystic fibrosis, have been
PATHOPHYSIOLOGY associated with intussusception. Other rare diseases
related to intussusception are celiac disease and Clostrid-
The intussusceptum telescopes into the distal bowel by ium difficile colitis.14
peristaltic activity. There may or may not be a lead point.
As the mesentery of the proximal bowel is drawn into
the distal bowel, it is compressed, resulting in venous INCIDENCE
obstruction and bowel wall edema. If reduction of the
intussusception does not occur, arterial insufficiency Idiopathic intussusception can occur at any age. Most
will ultimately lead to ischemia and bowel wall necrosis. patients are well-nourished, healthy infants, and approxi-
Although spontaneous reduction can occur, the natural mately two-thirds are boys. The highest incidence occurs
history of an intussusception is to progress to bowel in infants between ages 4 and 9 months,15 and it is also
ischemia and necrosis unless the condition is recognized the most common cause of small bowel obstruction in
and treated appropriately. this age group.16 Intussusception is uncommon below 3
months and after 3 years of age. The condition has been
described in premature infants where it has been postu-
Primary Intussusception lated as the cause of small bowel atresia in some cases.17
The vast majority of cases do not have a lead point and are
classified as primary or idiopathic intussusceptions. The
cause is generally attributed to hypertrophied Peyer CLINICAL PRESENTATION
patches within the bowel wall.3 Intussusception occurs
frequently in the wake of an upper respiratory tract infec- The classic presentation is an infant or a young child with
tion or an episode of gastroenteritis, providing an etiology intermittent, crampy abdominal pain associated with
for the hypertrophied lymphoid tissue. Adenoviruses in currant jelly stools and a palpable mass on physical
children older than age two, and to a lesser extent rotavi- examination, although this triad is seen in less than a
ruses, have been implicated in up to 50% of cases.4,5 Other fourth of children.18 The abdominal pain is sudden and
contributing evidence that viruses may play a role in the child may stiffen and pull the legs up to the abdomen.
intussusception includes the rise in cases during seasonal The pain can also be associated with hyperextension,
respiratory viral illnesses and the increased risk associated writhing, breath holding and vomiting. The attack often
with previous rotavirus immunization.6 The newest ceases as suddenly as it started. Between attacks, the child
immunization formulas available in the USA, RotaTeq may appear comfortable but eventually will become
and Rotarix, have not been associated with intussuscep- lethargic. Small or normal bowel movements will stop as
tion in both pre- and post-marketing studies.610 the obstruction progresses and becomes associated with
bilious emesis and increasing abdominal distention.
Stools may be blood tinged as impending ischemia causes
Secondary Intussusception mucosal sloughing and compression of mucous glands
An intussusception may have an identifiable lesion that leading to evacuation of dark, red mucoid clots or currant
serves as a lead point, drawing the proximal bowel into jelly stools. This is often a late sign as are laboratory
the distal bowel by peristaltic activity. The incidence of derangements. A pitfall is to wait for the currant jelly
a lead point varies from 1.5% to 12% and the presence stool, leukocytosis, and electrolyte abnormalities that are
of a lead point increases in proportion with age.11,12 The often hallmarks of ischemic bowel.
531
532 SECTION IV Abdomen
A B C
FIGURE 38-1 (A) Operative view of the outside of the jejunum shows a palpable mass as the lead point of a reduced intussuscep-
tion. (B) A hamartomatous polyp is characteristic of PeutzJeghers syndrome. (C) Mucocutaneous macular lesions are seen in this
patient with PeutzJeghers syndrome. Note extension of the pigmentation beyond the vermilion border.
FIGURE 38-2 This 10-year-old boy has a palpable sausage- FIGURE 38-3 This abdominal radiograph in a patient with intus-
shaped mass (arrows) due to an intussusception. susception shows dilated loops of small bowel in the right lower
quadrant and a right upper quadrant soft tissue mass density
in the vicinity of the transverse colon near the hepatic flexure
PHYSICAL EXAMINATION (arrow).
utilized as a screening tool when one of the abnormal intussusception.21 Equivocal findings using this modality
findings listed above is found.19 should mandate a conventional contrast or air enema.23
A B C
FIGURE 38-6 Concurrent contrast enema and pelvic CT images of an intussusception. (A) Contrast study showing the intussusception
low in pelvis. (B) CT image of the intussusception. (C) CT image of the layered intussuscepted mass. This is the target sign on CT.
534 SECTION IV Abdomen
should be based on clinical findings in symptomatic for younger infants and 110120mmHg for older infants.
patients.25 Laparoscopy is an excellent means to evaluate Potential drawbacks of pneumatic reduction include the
these patients if surgical intervention is needed. possibility of developing tension pneumoperitoneum,
and poor visualization of lead points and/or the intus-
susception reduction process, resulting in false-positive
NONOPERATIVE MANAGEMENT reductions.3234 Rates of perforation range from 0.42.5%
with the most recent publications citing an average rate
If the diagnosis of intussusception is suspected, a nasogas- of 0.8%.16,35
tric tube may be helpful to decompress the stomach. Tension pneumoperitoneum is best treated with
Bowel rest and intravenous fluid resuscitation should be immediate cessation of the procedure and immediate
initiated. A complete blood cell count and serum electro- release of the pneumoperitoneum using a 14, 16, or
lytes are obtained. An air or contrast enema is first-line 18-gauge needle or angiocatheter above or below the
treatment as long as there are no contraindications to umbilicus. This should be followed by immediate opera-
nonoperative reduction. Contraindications include intes- tive exploration.36
tinal perforation (free intra-abdominal air), peritonitis, or For unsuccessful reduction, several studies have shown
persistent hypotension. The advantages of nonoperative improved reduction rates using a second attempt after
reduction are decreased morbidity, cost, and length of waiting between 30 minutes to 24 hours after the initial
hospitalization. attempt.28 In some instances, this is done in the operating
room prior to laparoscopy or in conjunction with laparo-
scopic reduction.37
Hydrostatic and Pneumatic Reduction If nonoperative reduction is successful either by
The methodology for hydrostatic reduction has not hydrostatic or pneumatic technique, the patient should
changed significantly since its first description in 1876.26 be admitted for observation, receive a short period of
Hydrostatic reduction with barium under fluoroscopic bowel rest, and given intravenous fluids. Any clinical
guidance has historically been used.27 More recently, chil- signs of abdominal pain after reduction could be a sign
drens hospitals have transitioned to air or water-soluble of ischemic bowel or recurrent intussusception and repeat
isotonic contrast because of the potential hazard of ultrasound is necessary.
barium peritonitis in patients with intestinal perfora-
tion16,28. Successful reduction (Fig. 38-7) in uncompli-
cated patients is seen in about 85% of cases and ranges
from 42% to 95%.29
OPERATIVE MANAGEMENT
Pneumatic reduction was first described in 1897.30 It Open Approach
gained popularity in the late 1980s. Since then, many
institutions have adopted pneumatic decompression An operation is needed when nonoperative reduction is
because it is quicker, safer, less messy, and decreases the unsuccessful or incomplete, for signs of peritonitis, the
exposure time to radiation.31 The procedure is fluoro- presence of a lead point, or radiographic evidence of
scopically monitored as air is insufflated into the rectum pneumoperitoneum. Preoperative preparation includes
(Fig. 38-8). The maximum safe air pressure is 80mmHg administration of broad-spectrum antibiotics, intravenous
A B C
FIGURE 38-7 Fluoroscopic examination using isotonic contrast for hydrostatic reduction of intussusception. (A) Intussusception
(arrow) seen in midtransverse colon. (B) Reduction has occurred to the hepatic flexure. (C) Complete reduction with reflux of contrast
medium into the terminal ileum. Note the edematous ileocecal valve (arrow).
38 Intussusception 535
AA B C
FIGURE 38-8 Plain radiography and fluoroscopic examination using air for pneumatic reduction of an intussusception. (A) Plain
radiograph showing a mass effect in the right upper quadrant. (B) Pneumatic reduction to the vicinity of the cecum with the intus-
susception still present (arrow). (C) Complete reduction with reflux of air into multiple loops of small intestine. (Courtesy of Charles
Maxfield, MD.)
Laparoscopic Approach
Initially, the use of laparoscopy in the operative manage-
ment of intussusception was strictly diagnostic, or was
FIGURE 38-9 A right lower quadrant muscle-splitting incision
allows delivery of the intussusception through the incision. used in cases with equivocal radiographic studies or in
Gentle and continuous massage from distal to proximal usually patients with suspected lead points, and was associated
results in reduction of the intussusception. with conversion rates in up to 70% of cases.40 More
recently, there has been increased success with laparo-
scopic reduction with some studies showing conversion
fluid resuscitation, insertion of a urinary catheter, and rates as low as 5.4%41 but more in the range of
placement of a nasogastric tube for gastric decompression. 1240%.37,4244
Most commonly, the cecum and terminal ileum are Where laparoscopy fits into a surgeons therapeutic
involved, and can be delivered through the traditional algorithm is a topic frequently discussed. It would be
right lower abdominal incision (Fig. 38-9). It is important beneficial to identify any preoperative risk factors. No
to evaluate the extent of the intussusceptum before deliv- study to date has specifically addressed this topic although
ering it as it can extend into the rectosigmoid region in some have noted an increased conversion rate associated
severe cases which usually requires extension of the with lead points. Recently, a retrospective analysis of
incision. 65 cases found that in patients unable to be reduced
Once the leading edge of the intussusceptum is identi- laparoscopically, 33% had a lead point that necessitated
fied, it is gently manipulated back toward its normal posi- conversion to open (Fig. 38-10).45 Contraindications to
tion in the terminal ileum. Excessive force or pulling is laparoscopy include peritonitis, hemodynamic instability,
avoided to prevent injury or perforation of the bowel. and severe bowel distension that precludes adequate
Inability to manually reduce the intussusception, the visualization.41
536 SECTION IV Abdomen
A B
FIGURE 38-10 (A) This laparoscopic photograph shows an incompletely reduced intussusception with the intussusceptum (white
arrow) telescoping into the intussuscipiens (black arrow). (B) A pathologic lead point due to a Burkitt lymphoma was found requiring
conversion to open.
A B
C D
FIGURE 38-11 Laparoscopic reduction of intussusception with hypertrophied lymph nodes is depicted in these four operative pho-
tographs. (A) Intussusceptum (white arrow) is seen telescoping into the intussuscipiens (black arrow). (B) The intussusception has
almost been completely reduced. (C) This intussusception has been completely reduced and the bowel appears viable. (D) Hyper-
trophied mesenteric lymphadenopathy (arrows) is seen. This lymphadenopathy may reflect a recent viral illness.
38 Intussusception 537
28. Daneman A, Navarro O. Intussusception. Part 1: A review of diag- 42. Kia KF, Mony VK, Drongowski RA, et al. Laparoscopic vs open
nostic approaches. Pediatr Radiol 2003;33:7985. surgical approach for intussusception requiring operative interven-
29. Navarro OM, Daneman A, Chae A. Intussusception: the use of tion. J Pediatr Surg 2005;40:2814.
delayed, repeated reduction attempts and the management of intus- 43. Burjonrappa SC. Laparoscopic reduction of intussusception: An
susceptions due to pathologic lead points in pediatric patients. AJR evolving therapeutic option. JSLS 2007;11:2357.
Am J Roentgenol 2004;182:116976. 44. Bonnard A, Demarche M, Dimitriu C, et al. Indications for lapar-
30. Holt LE. The Diseases of Infancy and Childhood: For the Use of oscopy in the management of intussusception: A multicenter
Students and Practioners of Medicine. New York: Appleton; 1897. retrospective study conducted by the French Study Group for
31. Guo JZ, Ma XY, Zhou QH. Results of air pressure enema reduction Pediatric Laparoscopy (GECI). J Pediatr Surg 2008;43:1249
of intussusception: 6,396 cases in 13 years. J Pediatr Surg 53.
1986;21:12013. 45. Hill SJ, Langness SM, Wulkan ML. Laparoscopic versus Open
32. Kirks DR. Air intussusception reduction: the winds of change. Reduction of Intussusception in Children: Experience Over a
Pediatr Radiol 1995;25:8991. Decade. Poster presented at Southeastern Surgical Congress Feb
33. Peh WC, Khong PL, Chan KL, et al. Sonographically guided 2012 Birmingham, AL, 2012.
hydrostatic reduction of childhood intussusception using Hart- 46. Niramis R, Watanatittan S, Kruatrachue A, et al. Management of
manns solution. AJR Am J Roentgenol 1996;167:123741. recurrent intussusception: Nonoperative or operative reduction?
34. Maoate K, Beasley SW. Perforation during gas reduction of intus- J Pediatr Surg 2010;45:217580.
susception. Pediatr Surg Int 1998;14:16870. 47. Mirza B. Recurrent intussusception: Management options. APSP J
35. Tareen F, Ryan S, Avanzini S, et al. Does the length of the history Case Rep 2011;2:9.
influence the outcome of pneumatic reduction of intussusception 48. Champoux AN, Del Beccaro MA, Nazar-Stewart V. Recurrent
in children? Pediatr Surg Int 2011;27:5879. intussusception. Risks and features. Arch Pediatr Adolesc Med
36. Sohoni A, Wang NE, Dannenberg B. Tension pneumoperitoneum 1994;148:4748.
after intussusception pneumoreduction. Pediatr Emerg Care 49. Navarro O, Dugougeat F, Kornecki A, et al. The impact of imaging
2007;23:5634. in the management of intussusception owing to pathologic lead
37. Kao C, Tseng SH, Chen Y. Laparoscopic reduction of intussuscep- points in children. A review of 43 cases. Pediatr Radiol 2000;30:
tion in children by a single surgeon in comparison with open 594603.
surgery. Minim Invasive Ther Allied Technol 2011;20:1415. 50. Holcomb GW III, Ross AJ III, ONeill JA Jr. Post-operative intus-
38. Waldhausen JH. Intussusception. In: Mattei P, editor. Fundamen- susception: Increasing frequency or increasing awareness? South
tals of Pediatric Surgery. New York: Springer; 2011. Med J 1991;84:13349.
39. Koh CC, Sheu JC, Wang NL, et al. Recurrent ileocolic intussus- 51. Bai YZ, Chen H, Wang WL. A special type of postoperative intus-
ception after different surgical procedures in children. Pediatr Surg susception: Ileoileal intussusception after surgical reduction of ile-
Int 2006;22:7258. ocolic intussusception in infants and children. J Pediatr Surg
40. van der Laan M, Bax NM, van der Zee DC, et al. The role of 2009;44:7558.
laparoscopy in the management of childhood intussusception. Surg 52. Linke F, Eble F, Berger S. Postoperative intussusception in child-
Endosc 2001;15:3736. hood. Pediatr Surg Int 1998;14:1757.
41. Bailey KA, Wales PW, Gerstle JT. Laparoscopic versus open reduc- 53. Laje P, Stanley CA, Adzick NS. Intussusception after pancreatic
tion of intussusception in children: A single-institution comparative surgery in children: A case series. J Pediatr Surg 2010;45:14969.
experience. J Pediatr Surg 2007;42:8458.
C H A P T E R 3 9
Alimentary tract duplications are relatively rare congeni- intestinal atresia suggest a multifactorial process in the
tal anomalies found anywhere from the mouth to the development of alimentary tract duplications.2,13,14 No
anus, and can present with obstruction or be discovered single theory has been described to account for these
incidentally. While most duplications are benign, ectopic heterogeneous malformations.
gastric mucosa and the potential for malignant degenera-
tion remain concerns. Most duplications are discovered
by 2 years of age. However, with the increased use of CLINICAL PRESENTATION
prenatal ultrasound (US), more are being diagnosed in AND DIAGNOSIS
utero.
The goal of operative management is to remove the Alimentary tract duplications present with a wide range
duplication and prevent its recurrence. Since most share of symptoms including abdominal distension and/or
a common blood supply to the native alimentary tract, pain, obstruction, bleeding, respiratory compromise, or
simple resection is usually adequate. Long tubular or a painless mass. Generally, the symptoms are related to
thoracoabdominal duplications may present a more dif- size, location, type of duplication, and presence of het-
ficult scenario as radical resection can carry significant erotopic mucosa. Most (80%) present before 2 years of
morbidity or even mortality. Overall prognosis is gener- age; prenatal ultrasound is detecting duplications as early
ally favorable but associated malformations or the pre- as 16 weeks gestational age.1315 The majority of duplica-
senting illness can factor into the final outcome. tions are cystic and the remaining are tubular (Fig. 39-1).
Alimentary tract duplications have been described for The jejunum/ileum is the most common location fol-
hundreds of years and multiple terms have been used in lowed by the esophagus (Table 39-1). The epithelial
the literature. The current term duplication of the alimen- lining is usually native to the surrounding lesion but
tary tract and a common description of the congenital heterotopic mucosa is found in 2530% of duplications.14
malformation was applied by William Ladd in 1937.1 Gastric tissue is the most common type of ectopic mucosa
Three common findings were described: a well-developed encountered followed by both exocrine and endocrine
smooth muscle coat, an epithelial lining, and attachment pancreatic tissue. Ectopic gastric mucosa may lead to
to the alimentary tract. The first large series to appear in peptic ulceration with subsequent hemorrhage or perfo-
the literature by Gross etal. in 1952 supported these ration (Fig. 39-2).
findings as well.2 Multiple imaging modalities are utilized to make the
diagnosis. Plain radiographs may reveal a mediastinal
mass, suggesting an esophageal duplication. Contrast
EMBRYOLOGY studies may show a mass effect or communication with
the alimentary tract. ultrasound is radiation free and
The incidence of duplications has been reported to be 1 noninvasive, making it a useful test, particularly for
in 4500 births.3 Two types are encountered: cystic and intra-abdominal duplications.16 A typical sonographic
tubular, with cystic being the most common. Duplica- appearance of duplications demonstrates an inner hyper-
tions are considered congenital malformations thought echoic rim of muscosasubmucosa and an outer hypo
to arise from disturbances in embryologic development. echoic muscular layer (Fig. 39-3).17 A history of anemia or
Multiple theories have been postulated to account for bleeding with a suspected duplication suggests ectopic
their development. A persistent embryonic diverticulum gastric mucosa, and technetium-99m (99mTc) scintigraphy
from the alimentary tract was the first theory reported in is a useful imaging modality.18,19 In cases where a com-
the literature4, while a defect in the recanalization of the bined thoracoabdominal duplication is suspected, com-
lumen of the alimentary tract was proposed years later.5 puted tomography (CT) may aid in diagnosis. The
The coincidental finding of colonic and genitourinary presence of vertebral abnormalities and esophageal dupli-
duplications and similar findings in conjoined twins led cations is best investigated with magnetic resonance
to the partial twinning theory.6,7 The split notochord imaging (MRI).20
theory was proposed because of the association of
enteric duplications and spinal anomalies8, and relatively
recent literature supports the notochord as being impor- CLASSIFICATION AND TREATMENT
tant in the development of both foregut and hindgut BY LOCATION
duplications.9,10 Fetal hypoxia has also been implicated in
the development of duplications.11,12 To better understand the wide presentation and surgical
The associated findings of vertebral, spinal cord, and treatment of duplications, they will be discussed accord-
genitourinary malformations as well as malrotation and ing to anatomic location. A compilation of major case
539
540 SECTION IV Abdomen
L R
A B
FIGURE 39-1 (A) Most alimentary tract duplications are cystic. (B) A tubular duplication is seen. Note that the native bowel is bifur-
cated (arrow) into the tubular duplication and native intestine.
Thoracoabdominal Duplications
series reported in the last 60 years from 16 different Extension of an esophageal duplication into the abdomen
institutions is seen in Table 39-1.2,1314,2132 The report is known as a thoracoabdominal duplication. These are
with the largest number of patients described 101 dupli- quite rare accounting for approximately 3% of all dupli-
cations in 96 patients.14 cations. The length of extension can vary from the
stomach to the jejunum, with jejunal connections being
Esophageal Duplications the most common.13,14 These duplications are all tubular
and ectopic gastric mucosa is found in a high percentage.
Approximately 20% of duplications arise from the Clinical presentation can range from asymptomatic to
esophagus. While cervical duplications do occur, the hemorrhage or ulceration from ectopic gastric mucosa. A
A B
FIGURE 39-3 Ultrasonography is a frequent imaging modality for diagnosing abdominal duplications. (A) This ultrasound image
shows a cystic mass (arrow) in an infant with symptoms of intestinal obstruction. (B) The laparoscopic view in this same patient
shows a cystic duplication of the ileum.
A B
FIGURE 39-4 This 16-year-old was found to have a posterior mediastinal mass on a chest radiograph. (A) CT scan shows the dupli-
cation (arrow) to be adjacent to the trachea and the esophagus. (B) View of the duplication as seen at thoracoscopy.
A B C
FIGURE 39-5 A 3-year-old was found to have a right paravertebral mass. (A) A large anterior defect in the vertebral bodies of the
upper thoracic spine (arrow) is seen. (B) This myelogram shows the filling defect caused by a neuroenteric cyst. (C) The contrast
agent from the myelogram is seen in the neuroenteric cyst (upper arrow) with extension subdiaphragmatically (lower arrow) into
the distal small intestine. (From Holcomb GW III, Gheissari A, ONeill JA, etal. Surgical management of alimentary tract duplications. Ann
Surg 1989;209:16774.)
A B
C D
FIGURE 39-6 (A) This patient had nonbilious emesis and was found to have a mass effect on the antrum with extrinsic compression
of the second portion of the duodenum on this contrast study. (B) A gastric duplication (arrow) was found emanating from the
inferior aspect of the greater curvature of the gastric antrum at operation. It was thought best to marsupialize the duplication,
because a significant partial gastrectomy would be required to remove this lesion completely. (C) The duplication has been marsu-
pialized, and the mucosa (arrow) of the duplication lying on the common wall with the stomach is seen. (D) The mucosa has been
stripped, leaving intact the common wall between the duplication and the gastric antrum. (From Holcomb GW III, Gheissari A, ONeill
JA, etal. Surgical management of alimentary tract duplications. Ann Surg 1989;209:16774.)
544 SECTION IV Abdomen
be left intact. Small bowel resection with primary anas- nonspecific. Abdominal ultrasound, CT, or contrast
tomosis is the usual approach. Long tubular duplications enema are helpful based on symptoms. A contrast enema
may pose a challenge because of the intimate blood may demonstrate a communication with the native lumen
supply to the native bowel. Resections of large lengths of if one is present.
bowel increase complications and may lead to short bowel The treatment of colonic duplications will vary
syndrome. In this situation, mucosal stripping through depending on the type and size. As with small cystic
multiple enterotomies will preserve bowel length and duplications, enucleation is possible but resection and
decrease the risk of ulceration or hemorrhage from anastomosis is usually needed. Long tubular duplications
ectopic gastric mucosa.41 present a difficult challenge. If resection is deemed too
aggressive, a distal communication with native bowel can
Colonic Duplications be created to relieve the obstruction (Fig. 39-10). Since
colonic duplications rarely contain ectopic gastric mucosa,
Colonic duplications account for approximately 15% of mucosal stripping is rarely needed. Long tubular duplica-
all duplications. Typically found on the mesenteric side tions with distal communication are often treated con-
of the bowel, most occur in the cecum and are cystic. servatively with stool softeners. If a fistulous tract to the
However tubular duplications are seen, and vary in bladder or uterus is present, it should be excised.
length and complexity (Fig. 39-9). Large bowel obstruc-
tion secondary to compression, intussusceptions, and
volvulus are the usual presenting symptoms. Since colonic
Rectal Duplications
duplications rarely contain ectopic gastric mucosa, gas- Rectal duplications account for approximately 6% of
trointestinal bleeding is infrequent. However a higher duplications, and are commonly found in the presacral
number of associated anomalies are present with long space posterior to the rectum (Fig. 39-11). Chronic con-
tubular duplications. With total colonic tubular duplica- stipation is commonly found secondary to the posterior
tions, other duplicate structures such as bladder, vagina, mass effect. Digital rectal examination may reveal a mass,
and external genitalia are described, supporting the leading to contrast enema for diagnosis. A perineal fistula
partial twinning theory of embryogenesis.42,43 To better should raise the suspicion for a perirectal abscess. Treat-
categorize tubular duplications, a classification system ment of rectal duplications can vary from a transanal
has been described.44 Type I colonic duplications are approach for marsupialization, or division of the septum
limited to the colon, whereas type II have associated between the duplication and the native rectum. A poste-
genital or urinary tract duplications. rior sagittal approach is an alternative for more extensive
Diagnosing colonic duplications can require duplications. Some patients may require an initial colos-
more advanced imaging as plain radiographs may be tomy for large or complicated duplications.
A B
FIGURE 39-9 Ileal and colonic tubular duplications vary in length and complexity. (A) The terminal ileum is seen to bifurcate into
native colon and duplicated colon, which is medial to the native colon. In this scenario the duplicated colon ends blindly in the
upper rectum. (B) In this drawing, the duplicated colon communicates with the native colon and forms a common descending colon.
546 SECTION IV Abdomen
A B
C D
FIGURE 39-10 This female infant was born with high imperforate anus and a duplicate vagina, and underwent initial colostomy. At
the time of the colostomy, it was noted that she had a tubular colonic duplication. (A) Note where the tubular colonic duplication
starts in the transverse colon (arrow). (B) After takedown of the colostomy, the two lumens of the colonic duplication are seen
(asterisk and arrow). (C) A stapler is utilized to create a common channel between the two lumens. Note the dressing on the umbili-
cus as laparoscopy was used to completely mobilize the colon. (D) This end-on view shows a single lumen created after using the
stapler to create the common lumen. This lumen was then anastamosed to the rectum.
A B C
FIGURE 39-11 (A) Radiograph of a neonate with abdominal distention and evidence of a pelvic mass. On rectal examination, a mass
was palpable posterior to the rectum. (B) A contrast study in which an 8-Fr Foley catheter was introduced into the rectum, and the
balloon was inflated with air (solid arrow). Posterior to the rectum and compressing it is a rectal duplication with air (dotted arrow),
indicating communication to the gastrointestinal tract. A colostomy was initially performed because of the rectal obstruction. (C) A
barium enema was performed at age 6 months in this patient. On this lateral radiograph, filling of the posterior rectal mass is seen
(arrow). (From Holcomb GW III, Gheissari A, ONeill JA, etal. Surgical management of alimentary tract duplications. Ann Surg
1989;209:16774.)
39 Alimentary Tract Duplications 547
Meckel Diverticulum
Charles M. Leys
Wilhelm Fabricius Hildanus, a German surgeon, first (614%).810 Other less common signs include a cystic
described the presence of a small bowel diverticulum in abdominal mass11 and a newborn with an umbilical
1598.1 However, the diverticulum is named for Johann fistula resulting from a patent vitelline duct (Fig. 40-3).
Meckel, a German anatomist, who further described the A Littr hernia refers to a Meckel diverticulum found
anatomy and embryology in 1809.2 Meckel diverticulum incarcerated in a hernia which may be located at the
is a remnant of the embryologic vitelline (omphalome- inguinal, femoral, umbilical or Spigelian sites.12 In adults,
senteric) duct that connects the fetal gut with the yolk especially the elderly, neoplasia can develop within the
sac and normally involutes between the fifth and seventh Meckel diverticulum. Carcinoid is the most common
weeks of gestation. Failure of duct regression results in a tumor, but other malignancies include adenocarcinoma,
variety of abnormalities arising from persistence of the leiomyosarcoma, gastrointestinal stromal tumors, and
remnant (Fig. 40-1). The most common anomaly (90%) lymphoma.13 Neonatal presentation of a Meckel diver-
is the classic Meckel diverticulum. It is a true diverticu- ticulum is uncommon and typically is due to perforation
lum, consisting of all normal layers of the bowel wall. or obstruction.14
Clinical symptoms and complications can arise from
small bowel obstruction, bleeding, inflammation, umbili-
cal abnormalities, or neoplasia.
Bleeding
Episodic painless rectal bleeding in a young child is the
classic presentation of a bleeding Meckel diverticulum.
EPIDEMIOLOGY A Meckel accounts for nearly 50% of all lower gastroin-
testinal bleeding in children. The stool may be bright
The true incidence of Meckel diverticulum is unknown, red, dark or maroon red, or less commonly tarry. The
since most patients are asymptomatic. While the inci- bleeding is often associated with anemia, and many chil-
dence is typically estimated at approximately 2%, a recent dren will require transfusion, though life-threatening
systematic review of autopsy studies found an incidence hemorrhage is rare. Physical exam is typically unremark-
of 1.2%.3 The incidence may be increased in patients able. The bleeding may also be slow and not clinically
with major anomalies of the umbilicus, alimentary tract, evident, presenting solely as unexplained anemia. Thus,
nervous system, or cardiovascular system.4 An estimated any child presenting with hemoglobin-positive stools and
4% of patients with Meckel diverticulum will become chronic anemia should be evaluated for a Meckel
symptomatic, and the risk of developing symptoms diverticulum.
decreases with age.5 A recent report based on data from Bleeding is generally attributed to the presence of
the Pediatric Health Information System database found heterotopic mucosa. Gastric mucosa is present in up to
that 53% of Meckel diverticulectomies are performed 80% of Meckel diverticula that bleed.15 Gastric acid pro-
before 4 years of age, with a male:female ratio of 2.3:1 duces mucosal ulceration, typically at the junction of the
overall and 3:1 in symptomatic patients.6 The commonly ectopic mucosa and the normal ileal mucosa. The ulcer
cited rule of 2s regarding the diverticulum is: occurs in may also be located within the ectopic mucosa or even
2% of the population, has a 2:1 male:female ratio, on the mesenteric side of the normal ileum, opposite the
usually discovered by 2 years of age, located 2 feet (60cm) diverticulum. While Helicobacter pylori is associated with
from the ileocecal valve, commonly 2cm in diameter and many ulcers in the duodenum and stomach, studies have
2 inches (5cm) long, and can contain two types of het- shown that H. pylori is rarely present in a bleeding Meckel
erotopic mucosa.7 Gastric is the most common type of diverticulum.16,17
heterotopic mucosa, followed by pancreatic (Fig. 40-2).8
More rarely, it may contain duodenal, colonic, or endome-
trial tissue.
Obstruction
A Meckel diverticulum can cause intestinal obstruction
through several mechanisms, but most commonly intus-
CLINICAL PRESENTATION susception or volvulus. The diverticulum can act as a lead
point for an obstructing ileo-ileal and subsequent ileo-
A variety of symptoms can develop depending on the colic intussusception. A volvulus can occur if bowel twists
configuration of the remnant structure and the presence or kinks around a vitelline remnant with a fibrous cord
of ectopic mucosa. The three most common presenta- between the diverticula and umbilicus (see Fig. 40-1). An
tions in children are intestinal bleeding (3056%), intes- internal hernia can result due to a mesodiverticular artery,
tinal obstruction (1442%), and diverticular inflammation coursing from the base of the mesentery to the
548
40 Meckel Diverticulum 549
Superior mesenteric
Mesentery vessels Umbilicoileal
Fibrous fistula
Meckel cord
diverticulum
Umbilicus
Meckel
diverticulum
A B C
Vitelline
cysts Umbilical
Vitelline
sinus
artery
Fibrous
Fibrous
cord
Anterior cord
abdominal wall
D E F
FIGURE 40-1 Drawings illustrating Meckel diverticulum and other remnants of the yolk sac. (From Moore KL. The Developing Human.
Philadelphia: WB Saunders; 1988.)
Inflammation
Inflammation of the diverticulum is often attributed to
the presence of heterotopic gastric or pancreatic tissue.
Obstruction of the diverticular lumen can also produce
inflammation, similar to the mechanism for appendicitis.
Lumenal obstruction can occur due to stasis of enteric
contents within the diverticulum, the presence of an
enterolith or foreign body, or even parasitic infections.1820
Meckel diverticulitis is often misdiagnosed as appendici-
tis due to similar presenting symptoms, including per-
iumbilical pain that may be associated with nausea,
vomiting, and fever. The point of maximal tenderness on
physical exam may migrate within the abdomen. Given
the possibility of misdiagnosis, the intraoperative finding
of a normal appendix in a child suspected of having
appendicitis should lead to a careful search for a Meckel
FIGURE 40-2 This laparoscopic view shows a long Meckel diverticulum. Due to variability in the location of the
diverticulum emanating from the antimesenteric border of the diverticulum, at least 5 feet of distal small bowel should
ileum. This is a true diverticulum and contains ectopic mucosa be examined, starting at the terminal ileum and working
at the tip of the diverticulum (arrow). proximally. Meckel diverticulitis can also result in perfo-
ration, intra-abdominal abscess, and obstructive signs and
symptoms.
diverticulum, under which the small bowel becomes
entrapped and incarcerated. Other rare obstructing
mechanisms include an incarcerated Littr hernia, and a DIAGNOSIS
long diverticulum that may knot on itself or twist around
its base. In patients presenting with obstruction or inflammation,
Patients presenting with obstruction will usually dem- the diagnosis of a Meckel diverticulum is not typically
onstrate typical signs of crampy abdominal pain, bilious determined preoperatively. On the other hand, in a child
vomiting, and obstipation. In the setting of intussuscep- older than 5 years of age who has not undergone an
tion, the child may pass currant-jelly stools and physical abdominal operation and presents with signs and symp-
exam may demonstrate a palpable abdominal mass. If a toms of small bowel obstruction, a Meckel diverticulum
volvulus progresses to ischemia, the patient will develop should be strongly considered as the etiology. The diag-
signs of peritonitis and may present in-extremis. nosis of intussusception is often confirmed by ultrasound
550 SECTION IV Abdomen
A B C
FIGURE 40-3 This neonate was born with an obvious patent omphalomesenteric duct. (A) Meconium was seen to emanate from
the stoma. (B) A circumumbilical incision was made, and the duct (arrow) was dissected to its connection with the ileum. (C) The
duct was amputated from the ileum and the umbilical incision closed. The patient recovered uneventfully and has not developed
any further problems.
regularly, they may be helpful when all other tests have depending on the appearance of the bowel (Fig. 40-5). In
failed to identify the site of bleeding. cases of bleeding, an ulcer may be present at the base of
the diverticulum or on the mesenteric side of the ileum.
Therefore, segmental resection is typically regarded as
TREATMENT the safest approach to ensure removal of the bleeding
source and avoid the risk of recurrent bleeding. The
The treatment for a symptomatic Meckel diverticulum specimen should be opened after resection to confirm
consists of resection using either an open or laparoscopic that it contains the ulcer.
approach. Preoperative preparation should include rehy- Laparoscopy is now commonly utilized for resection
dration with intravenous fluids, correction of electrolyte of a Meckel diverticulum as it can be both diagnostic and
abnormalities, antibiotics, gastric decompression if the therapeutic.22,25 The diverticulum may be resected with
patient has a bowel obstruction, and transfusion in cases either an intracorporeal technique, or grasped and exte-
of bleeding with significant anemia. riorized through the umbilicus for an extracorporeal
Resection may be accomplished by either simple diverticulectomy or segmental resection (Fig. 40-6). Port
diverticulectomy or segmental ileal resection with anas- placement for the intracorporeal approach is similar to
tomosis. In patients with obstruction, simple diverti- the set-up for laparoscopic appendectomy, with a 12mm
culectomy is often sufficient, but all ectopic tissue should umbilical cannula and two 5mm cannulas in the left
be removed. If a Meckel diverticulum is discovered after lower quadrant. Laparoscopic-assisted extracorporeal
reduction of an intussusception, diverticulectomy may be resection is generally preferred in infants and small chil-
possible, though segmental ileal resection may be safer dren, due to limited intra-abdominal working space,
A B C
FIGURE 40-5 A 4-year-old child presented with an irreducible intussusception and required an operative reduction. (A) Note the
small bowel intussuscepted into the large bowel. (B) After reduction of the ileum, a Meckel diverticulum was found to be the lead
point for the intussusception. (C) The diverticulum was excised with an endoscopic stapler.
A B C
FIGURE 40-6 This is the patient identified in Figure 40-2. (A) When diagnosed, Meckel diverticulum can be managed either totally
intracorporeally or exteriorized through the umbilical incision. (B, C) The diverticulum and a small segment of the ileum just proximal
and distal to the diverticulum were exteriorized through the umbilicus and the diverticulum was excised using the endoscopic
stapler. The excision was done in an oblique direction to avoid narrowing the ileum at the site of the diverticulectomy.
552 SECTION IV Abdomen
which makes the use of staplers cumbersome. Segmental 11. Oguzkurt P, Strlic M, Kayaselcuk F, et al. Cystic Meckel diverticu-
resection is also more easily accomplished extracorpore- lum: A rare cause of cystic pelvic mass presenting with urinary
symptoms. J Pediatr Surg 2001;36:18558.
ally. More recently, reports have described a single- 12. Skandalakis PN, Zoras O, Skandalakis JE, et al. Littre hernia:
incision laparoscopic approach.26,27 Surgical anatomy, embryology, and technique of repair. Am Surg
Management of an asymptomatic incidentally found 2006;72:23843.
diverticulum remains controversial. Operative interven- 13. Thirunavukarasu P, Sathaiah M, Sukumar S, et al. Meckel
DiverticulumA high-risk region for malignancy in the ileum.
tion is not indicated for an asymptomatic diverticulum Ann Surg 2011;253:22330.
discovered incidentally on imaging studies. When a 14. Aguayo P, Fraser JD, St. Peter SD, et al. Perforated Meckel
Meckel diverticulum is found intraoperatively, several diverticulum in a micropremature infant and review of the litera-
reports recommend resection due to the risk of malig- ture. Pediatr Surg Int 2009;25:53941.
nancy or other future complications.9,13,28 However, other 15. Swaniker F, Soldes O, Hirschl RB. The utility of technetium 99m
pertechnetate scintigraphy in the evaluation of Meckel diverticu-
studies conclude that the risk of complications is less than lum. J Pediatr Surg 1999;34:7605.
the risk of complications following resection.2,4 Still 16. Ergun O, Celik A, Akarca US, et al. Does colonization of
others recommend a selective approach, depending on Helicobacter pylori in the heterotopic gastric mucosa play a role
characteristics of the diverticulum, such as length >2cm, in bleeding of Meckel diverticulum? J Pediatr Surg 2002;37:
15402.
presence of ectopic mucosa, male gender, and age younger 17. Tuzun A, Polat Z, Kilciler G, et al. Evaluation for Helicobacter
than 50 years.8 Given the lack of clear consensus, the pylori in Meckel diverticulum by using real-time PCR. Dig Dis Sci
decision to resect an incidentally discovered Meckel 2010;55:196974.
diverticulum should be based on the surgeons clinical 18. Pantongrag-Brown L, Levine MS, Buetow PC, et al. Meckel
judgment. enteroliths: Clinical, radiologic, and pathologic findings. AJR
1996;167:144750.
19. Weissberg D. Foreign bodies within a Meckel diverticulum. Arch
REFERENCES Surg 1992;127:864.
1. Daniels IR. Historical perspectives on health: Johann Friendrich 20. Chirdan LB, Yusufu LM, Ameh EA, et al. Meckel diverticulum due
Meckel the younger and his diverticulum. J R Soc Promot Health to Taenia saginata: Case report. East Afr Med J 2001;78:
2000;120:1256. 1078.
2. Meckel J. Uber die divertikel am darmkanal. Arch Physiol 21. Sfakianakis GN, Conway JJ. Detection of ectopic gastric mucosa
1809;9:421. in Meckel diverticulum and in other aberrations by scintigraphy:
3. Zani A, Eaton S, Rees CM, et al. Incidentally detected Meckel ii. Indications and methodsa 10-year experience. J Nucl Med
diverticulum: To resect or not to resect? Ann Surg 2008;247: 1981;22:7328.
27681. 22. Shalaby RY, Soliman SM, Fawy M, et al. Laparoscopic manage-
4. Simms MH, Corkery JJ. Meckel diverticulum: Its association with ment of Meckel diverticulum in children. J Pediatr Surg
congenital malformation and the significance of atypical morphol- 2005;40:5627.
ogy. Br J Surg 1980;67:21619. 23. Fritscher-Ravens A, Scherbakov P, Bufler P, et al. The feasibility of
5. Soltero MJ, Bill AH. The natural history of Meckel diverticulum wireless capsule endoscopy in detecting small intestinal pathology
and its relation to incidental removal: A study of 202 cases of dis- in children under the age of 8 years: A multicentre European study.
eased Meckel diverticulum found in King County, Washington, Gut 2009;58:146772.
over a fifteen-year period. Am J Surg 1976;132:16873. 24. Uchiyama S, Sannomiya I, Hidaka H, et al. Meckel diverticulum
6. Ruscher KA, Fisher JN, Hughes CD, et al. National trends in the diagnosed by double-balloon enteroscopy and treated laparoscopi-
surgical management of Meckel diverticulum. J Pediatr Surg cally: Case report and review of the literature. Surg Laparosc
2011;46:8936. Endosc Percutan Tech 2010;20:27880.
7. Pepper VK, Stanfill AB, Pearl RH. Diagnosis and management of 25. Chan KW, Lee KH, Mou JWC, et al. Laparoscopic management
pediatric appendicitis, intussusception, and Meckel diverticulum. of complicated Meckel diverticulum in children: A 10-year review.
Surg Clin N Am 2012;92:50526. Surg Endosc 2008;22:150912.
8. Park JJ, Wolff BG, Tollefson MK, et al. Meckel Diverticulum: The 26. Clark J, Koontz C, Smith L, et al. Video-assisted transumbilical
Mayo Clinic experience with 1476 patients (19502002). Ann Surg Meckel diverticulectomy in children. Am Surg 2008;74:3279.
2005;241:52933. 27. Garey CL, Laituri CA, Ostlie DJ, et al. Single-incision laparoscopic
9. St-Vil D, Brandt ML, Panic S, et al. Meckel diverticulum in chil- surgery in children: Initial single-center experience. J Pediatr Surg
dren: A 20-year review. J Pediatr Surg 1991;26:128992. 2011;46:9047.
10. Menezes M, Tareen F, Saeed A, et al. Symptomatic Meckel diver- 28. Onen A, Cigdem MK, Ozturk H, et al. When to resect and when
ticulum in children: A 16-year review. Pediatr Surg Int 2008;24: not to resect an asymptomatic Meckel diverticulum: An ongoing
5757. challenge. Pediatr Surg Int 2003;19:5761.
C H A P T E R 4 1
Inflammatory bowel disease (IBD) is the broad term that cultures and developing countries, although this finding
encompasses Crohn disease (CD), chronic ulcerative seems to be changing recently.7,8
colitis (UC), and indeterminate colitis. Regardless of
which specific disease entity is present, the pediatric Etiology
surgeon and physicians caring for the patient are faced
with difficult medical and surgical challenges. Clinical, While there is much research surrounding UC and
radiographic, and pathologic features typically distin- strides have been made in its underlying mechanisms, the
guish CD from UC. However, in up to 25% of patients exact etiology remains unclear.9,10 Myriad theories have
with IBD, the diagnosis cannot be specified, leading to a been proposed including infectious etiologies, genetic
diagnosis of indeterminant colitis.1 While medical thera- relationships, immunologic disturbances, and psycho-
pies for all variants of IBD share similar strategies, the logic factors. To date, none of these, either independently
surgical care is driven by very different philosophical or in combination, has adequately explained the disease.
foundations. The surgical approach to UC is one of cura- However, each of these factors may account for certain
tive extirpation, rendering the patient free of disease characteristics of the disease. The genetic relationship
through the removal of the affected intestine, generally helps to explain the racial and ethnic distribution of the
with a proctocolectomy. The philosophy directing the disease. For instance, the relative risk for siblings with
operative approach to CD is much more humble, and is disease is 16%,11 and patients with extraintestinal mani-
centered on treating the complications, but without cure. festations have a high incidence of expression of the
The fact that intervention is not curative must be com- major antigen HLA-W27.12 Also, antineutrophil cyto-
municated very clearly to families and patients prior to plasmic antibodies have been associated with UC. Unfor-
operation for CD, as the child will likely remain on tunately, evidence that these are present in unaffected
medical therapy after the procedure and may require family members of UC patients raises doubt about the
further surgical treatment at some point in the future. relationship.13,14 Finally, there are genetic predictors of
disease severity. Recently, NOD-2insC polymorphism
has been linked to worse outcome in patients following
ULCERATIVE COLITIS ileoanal pull-through.15 Additionally, a single nucleotide
polymorphism in chromosome 4q27,16 and mucin abnor-
UC is a mucosal-based inflammatory disease limited to malities have been implicated in poor outcomes in UC
the colon, and has a risk of malignancy.2 The understand- patients.17
ing that UC could be cured by removal of all colonic An infectious etiology for the basis of UC has become
mucosa led to the development of operative treatment a rich area for investigation as evidence increases that the
using total colectomy and proctectomy. The surgical balance of microbial flora plays a key role in the regula-
approach has progressed from proctocolectomy with tion of the normal healthy intestine.18,19 While the balance
permanent ileostomy to restorative proctocolectomy, of bacterial flora may have a critical role in UC, there
and is now routinely performed with minimally invasive does not appear to be a specific infectious agent that is
techniques with or without a protective temporary responsible for causing the disease.
ileostomy.3 Since UC is primarily a disease of autoimmune dys-
regulation, it is logical that investigation would center on
the immune function of those affected. The mucosal
Epidemiology T-cell and its regulation is the primary target of immu-
UC was described first in 1875 by Wilks and Moxon in nologic research. In addition, cytokine expression is
the classic Lectures on Pathologic Anatomy.4 UC is another area of active interest. Interleukin (IL)-1, IL-6
predominantly diagnosed after the second decade of life. and IL-1 receptor agonists all show imbalances in the UC
However, UC is being seen in increasing frequency in population.20
younger patients, with as many as 20% of patients becom-
ing symptomatic before the age of 18 years.5 The inci-
dence of UC has reportedly increased over the past three
Pathology
decades, and is currently reported to occur in 3.1 children UC is a mucosal-based chronic inflammatory process that
per 100,000.6 Males and females are diagnosed with equal involves the rectum and extends proximally to include
frequency. Western and Jewish societies are diagnosed varying amounts of colon, often in a contiguous fashion.21
with UC four times more frequently than Eastern The rectum is essentially always involved, and in cases of
553
554 SECTION IV Abdomen
pancolitis, the rectum is usually the most severely affected. Colorectal carcinoma has been reported to occur in
The characteristic microscopic findings include acute 3% of patients in the first ten years after the initial diag-
inflammation with crypt abscesses, mucosal bridging, and nosis, and the incidence increases to 20% per decade after
pseudopolyp formation. As the disease becomes more the first decade. Quiescent disease does not protect from
chronic in nature, the thin, distended colon becomes the development of cancer. In fact, young age at initial
thickened, stiff, and foreshortened. UC diagnosis may be a risk factor for colorectal
carcinoma.2628
The extraintestinal manifestations of UC are outlined
Clinical Presentation in Box 41-1 and occur in 60% of children.29 Growth
As noted previously, UC is most commonly diagnosed in retardation and delayed bone growth is associated with
young adults, but 4% have onset of symptoms before age the chronicity of inflammation in UC, while delayed
10 years and 17% present between ages 10 and 20 years.22 sexual maturation has been shown to be related to low
The initial presentation is one of persistent diarrhea, gonadotropin levels.30,31 Since chronic inflammation has
progressing to hematochezia with mucus and purulence direct effects on growth and development, adequate
in the stool. Tenesmus, anorexia, weight loss, and growth control of disease can relieve the growth complications
retardation are also common (Box 41-1). As the disease that would otherwise develop.32 Arthralgias occur in
becomes more chronic, children may exhibit signs of about a quarter of UC patients and the knees, ankles and
depression and withdrawal from social and physical activ- wrists are the most commonly affected joints. The joint
ities. Emotional stress has been identified as a precipitat- symptoms often complicate the diagnostic evaluation,
ing factor in patients with relapsing disease.23 Most and may cause the child to be erroneously diagnosed with
patients experience chronic colitis with periods of quies- rheumatoid arthritis before the gastrointestinal symp-
cence and episodic recurring exacerbations. Only a small toms become obvious.
fraction (10%) of patients have a single exacerbation fol- Erythema nodosum occurs primarily on the trunk and
lowed by longstanding remission. Unfortunately, as many manifests as tender, red, subcutaneous nodules. Pyo-
as 80% of children become refractory to medical therapy, derma gangrenosum is usually seen on the lower legs and
and ultimately require colectomy. Fifty per cent of chil- presents as chronic deep ulcerations of the skin. Although
dren diagnosed with UC in childhood will require a much more common in adults, both may occur in chil-
colectomy before age 18 years.24 dren and usually resolve with treatment of the primary
In about 15% of children, the presentation is fulmi- disease.33
nant with profuse bloody diarrhea, severe cramping, and Liver function testing is associated with abnormalities
abdominal pain, fever and sepsis. Aggressive medical in up to 10% of children with UC. When abnormal liver
management will control these symptoms initially in function is identified, the patient requires close observa-
most cases; however, 5% of patients will require urgent tion for the possible manifestations of primary sclerosing
colectomy in the face of toxic megacolon.25 cholangitis.34 Anemia is common and is usually due to
blood loss in the stool, but may also be related to anemia
of chronic disease. Osteoporosis and malacia may be
Clinical Findings in related to decreased calcium absorption associated
BOX 41-1 with poor absorption of fat-soluble vitamins and/or to
Ulcerative Colitis
increased urinary loss from chronic glucocorticoid
SIGNS/SYMPTOMS therapy. Nephrolithiasis can develop and is likely due to
Abdominal pain chronic oliguria related to inadequate intake and increased
Diarrhea water loss in the stool.
Hematochezia The emotional and psychological ramifications of UC
Mucus in stool should not be dismissed. Those caring for these children
Purulent exudates in stool will spend a great deal of time counseling, supporting,
Tenesmus and encouraging them, and the care team should include
Anorexia a mental health care worker.35
Weight loss
EXTRAINTESTINAL MANIFESTATIONS Diagnosis
Chronic fatigue
Growth retardation As diarrhea is usually the initial symptom, evaluation
Delayed sexual maturation begins with investigation for infectious causes of diarrhea
Depression/emotional distress including Salmonella, Shigella, Campylobacter, Clostridium
Arthralgia dificile, and Entamoeba histolytica. Anemia from blood loss,
Pyoderma gangrenosum elevated C-reactive protein, increased sedimentation
Erythema nodosum rate, and hypoalbuminemia are commonly found at the
Oral ulceration initial presentation. Additionally, the prothrombin time
Anemia
may be prolonged.
Liver disease (primary sclerosing cholangitis)
Nephrolithiasis Although work continues on many potential candi-
Osteoporosis dates, serum markers for IBD have not proven to be
Uveitis reliable as yet. Perinuclear antineutrophil cytoplasmic
antibody (pANCA) has been shown to be specific for UC
41 Inflammatory Bowel Disease 555
and absent in controls. However, it is not predictive of can often be controlled with 5-ASA (aminosalicylic acid)
disease severity or course.36 Pancreatic autoantibodies, preparations such as sulfasalazine or mesalamine.
such as NOD2/CARD15 and PAB, have also been shown Although it has not been proven to be beneficial, metro-
to correlate with disease.37 nidazole is frequently added to this regimen.42 Moderate
The improved visualization and characterization of disease requires a more aggressive medical regimen to
disease found on computed tomography (CT) and mag- attain remission. In general, 5-ASA medications are used
netic resonance imaging (MRI) have enhanced their in conjunction with glucocorticoids, with or without
accuracy, and these two imaging modalities have replaced 6-mercaptopurine or azathioprine. The prolonged use of
the contrast enema as a diagnostic standard.3841 Charac- steroids has severe implications, especially for children.
teristic findings have been described as a lead pipe Therefore, alternate forms of therapy are appropriate to
appearance to the colon, loss of haustral markings, and a avoid steroid dependence.43
narrow lumen (Fig. 41-1). Pseudopolyps can develop in Severe exacerbations are treated with bowel rest, intra-
chronic UC and may be seen on both imaging studies. venous fluid resuscitation or nutrition, and antibiotics.
Upper gastrointestinal series are only helpful to assist in Although less frequently seen than mild or moderate
differentiating UC from CD with small bowel disease. disease, a small number of patients will present with
Endoscopy is useful to confirm the diagnosis, and for acute, fulminant colitis that in some cases is associated
surveillance to monitor response to therapy. Typical with pancolitis and sepsis. Toxic megacolon refers to this
endoscopic findings include a friable, inflamed mucosa acute, fulminant, septic colitis with massive distention of
with fibrinous exudate covering the surface. Ulcers may the entire colon. It is usually manifested by a distended
be seen as well. Biopsies may offer histologic proof of air-filled transverse colon on plain films. High dose
diagnosis. However, with severe inflammation, biopsies parenteral steroids are generally started, and cyclosporine
are often nonspecific and experienced endoscopists often and antitumor necrosis factor (TNF) antibodies should
rely on the endoscopic appearance alone. be considered. The approach to these patients is one of
rescue therapy, with the ultimate rescue therapy being
achieved by colectomy.44,45 Perforation is an absolute
Medical Management indication for emergent operation, but failure to improve
Pediatric UC is characterized as mild, moderate, or must be reviewed critically and objectively by the entire
severe based on the number of stools per day, and the team to avoid allowing these children to become too sick
presence of fever, anemia, nutritional depletion, and prior to surgical intervention.
abdominal pain. These classifications are useful to char- A multidisciplinary approach to the care of these
acterize the disease and to monitor the success of thera- children, including medical and surgical specialists, a
pies. Prior to institution of any medical therapy, a psychologist, social worker, and nutrition specialist, is
thorough medication history must be obtained, including valuable in monitoring the course of therapy. Nonopera-
homeopathic remedies, as many of the patients and fami- tive therapy can have morbidity as well as malnutrition,
lies will have sought herbal, dietary, or alternative forms growth failure, delayed sexual maturation, poor control
of treatment prior to diagnosis. of inflammation with persistence of symptoms, and psy-
Maintenance therapy for UC is based on immunosup- chological complications related to frequent stooling,
pressive and anti-inflammatory strategies. Treatment fatigue, and the side effects of medications. Additionally,
algorithms are based on severity of disease. Mild disease the immunomodulating medications that are currently
most effective for controlling IBD carry their own risk of
malignancy, primarily lymphoma.27 A multidisciplinary
team is less likely to become invested in a specific form
of therapy, and more willing to consider alternatives than
a single provider working in isolation.
Surgical Management
The understanding that UC is limited to the colon, and
is cured by removing the colon, has led those caring for
children with this disease to consider earlier operation.
In the past, the morbidity associated with proctocolec-
tomy and permanent ileostomy was responsible for delay
in seeking surgical options until after the child was
severely ill and undernourished, and carried significant
operative risk. As operations have become less morbid
and more refined, and are associated with a better life-
FIGURE 41-1 This 13-year-old child has chronic ulcerative style afterwards, the threshold for colectomy has become
colitis and will undergo proctocolectomy and ileal pouchanal more relaxed. Currently, operative alternatives are con-
anastomosis. This coronal CT image shows a lead pipe appear- sidered safe and effective when compared to medical
ance to the descending colon with diffuse thickening of the
colon wall and a very narrowed lumen (arrow). There is also
therapies. With this in mind, they should be seriously
significant thickening of the wall of the cecum and ascending considered in all children with UC, but especially those
colon (asterisk). that are not responding adequately to the medical
556 SECTION IV Abdomen
therapies. Although already mentioned, it is important to Although this report documented the possibility of a
emphasize that the chronic inflammatory state of the restorative procedure, their results were sufficiently
intestinal mucosa is a risk factor for development of complicated to cause others to search for alternative
cancer, and youth does not protect against this risk.2628 approaches. Hence, various catheterizable pouches and
stomas became the standard form of treatment after total
colectomy, with or without proctectomy, and remained
Preoperative Considerations
so until Martin described an adaptation of Soaves
Once a decision is made for operative intervention, the endorectal pull-through used for Hirschsprung disease.52
preoperative preparation is important. Nutritional defi- The results following Martins adaptation for UC were
ciencies must be addressed and may require a delay in the significantly improved, but were still associated with sig-
operative procedure, assuming an emergency operation nificant issues related to stooling frequency and inconti-
is not needed. A reduction in immunosuppressive medi- nence.53 Subsequent investigators have described differing
cations may be possible, although recent evidence sug- pouch structures in attempt to create a reservoir to reduce
gests that immunosuppression is not necessarily associated stool frequency and continence.5458 The current
with worse surgical outcomes.46 The use of a preoperative operative techniques for restorative proctocolectomy
mechanical bowel preparation was once considered have resulted in significantly improved outcomes, and
standard, but has recently been questioned.4749 Cur- the current debate is centered on the issues outlined in
rently, the need for mechanical bowel prep for colorectal Table 41-1.
surgery is not supported by the literature, although some The surgical options offered to patients with UC are
authors continue to use it as part of their preoperative based on the clinical condition of the patient at the time
preparation. If a mechanical bowel prep is used, careful of consultation. The limitations relate to the emergent
attention must be paid to the fluid and electrolyte status or elective nature of the operation, the comfort and expe-
during the prep, as children are prone to dehydration. rience of the individual surgeon, and the clinical setting
Perioperative intravenous antibiotics are important in which the procedure is being performed. A final con-
and should provide broad-spectrum coverage. The sideration is the preference of the patient and family,
surgeon and anesthesiologist should be mindful of the which is very important if the clinical situation will allow
preoperative use of corticosteroids and prescribe stress flexibility.
dose regimens as appropriate. The placement of a urinary
catheter is helpful for all operations, and consideration Emergency Operation
should be given to the use of regional anesthetics for
perioperative pain management. Prophylaxis for deep When faced with emergent indications for operation
vein thrombosis should be instituted in the IBD patient such as hemorrhage, perforation, or toxic megacolon, the
as the chronic inflammatory state is a known risk for a surgical options are simplified. The standard operative
thromboembolic event. procedure in this situation is total abdominal colectomy
Operative management of UC has undergone tremen- with end ileostomy. This approach is relatively fast,
dous progress over the past 100 years. The earliest treat- avoids the potential complications of creating a pouch,
ment was diversion with sigmoid colostomy. Later, and allows for delayed proctectomy. It is generally
ileostomy alone was advocated. These diversions accom- performed via a laparoscopic approach, and the rectum
plished little for the inflamed colon, and it was not until is controlled by stapling the proximal rectum above
the 1940s that total colectomy was attempted. Unfortu- the peritoneal reflection to simplify the subsequent
nately, there were countless ileostomy stomal complica- proctectomy.
tions until Brooke described the everted stoma that today
bears his name.50 This technical modification allowed Elective Operation
patients to enjoy a functional stoma, although the fluid
and electrolyte derangements associated with an ileos- The goal of all operative interventions for UC is to
tomy continued to pose problems. render the patient free of disease with the best possible
In 1947, Ravitch and Sabiston reported a restorative functional outcome. The quality of the outcome is deter-
procedure that utilized the mucosectomy technique.51 mined by the patient and family, as well as the clinical
41 Inflammatory Bowel Disease 557
TABLE 41-2 Advantages and Disadvantages of a Single Operation Vs a Staged Operative Approach
in Patients with Ulcerative Colitis
Approach Operation Indication Advantages Disadvantages
Three Stage (1) Colectomy with stoma Urgent/emergent Low risk of complications Three operations and multiple
(2) Completion Malnourished Quick initial operation admissions
proctectomy with patient Time to improve clinical
IAPT Infection concerns status prior to pelvic
(3) Stoma closure dissection
Two Stage (1) Proctocolectomy with Elective operation, Standard approach, safe, Two operations, readmission
IAPT and stoma desire to protect allows time for pouch for stoma closure
(2) Stoma closure pouchanal and pouchanal
anastomosiswith anastomosis to heal
proximal ostomy
One Stage (1) Proctocolectomy with Elective operation, Avoids multiple Reports of poor long-term
IAPT good nutritional operations pouch function
status, excellent Pelvic sepsis with leak from
anatomy pouch and pouchanal
anastomosis
situation. However, the goal in most instances is restora- from the pelvic floor. Attention is then turned to the anal
tion of nearly normal anatomy and function. portion of the procedure. The transanal mucosectomy is
While the philosophical goals for the surgical manage- usually performed with a self-retaining, peri-anal retrac-
ment of UC have not changed in the past 50 years, the tor exposing the dentate line. The submucosa can be
operative approaches have continued to be refined. Table injected with an epinephrine solution (1:100,000 units)
41-2 outlines the advantages and disadvantages of a single to help separate the mucosal and submucosal layers, and
operation versus a staged approach. The experience and to assist with hemostasis. A circumferential mucosal inci-
familiarity of the treating surgeon with these various sion approximately 12cm above the anal pillars (dentate
approaches directs much of the decision-making process. line) is created using the fine-point cautery. Multiple fine
The first procedure described to have good functional silk traction sutures are placed circumferentially around
results was the straight ileal pull-through.59 However, the the mucosal flap, decreasing undue trauma, and making
straight pull-through procedure is known to be associ- the specimen easier to handle during the dissection. The
ated with persistent highpressure peristaltic contrac- mucosa is separated from the submucosal layer in a cir-
tions associated with urgency and soiling.60 Due to this cumferential manner from distal to proximal for approxi-
problem, most surgeons have avoided the ileal pull- mately 5cm. At this point, the dissection transitions to
through and have opted for creation of an ileal reservoir, the full-thickness plane, moving outside the rectal wall,
of which the J-pouch is the most common. taking care to stay immediately adjacent to the rectum.
The dissection is continued proximally until the transanal
dissection meets the dissected tissues from the pelvis,
Open Proctocolectomy with Ileoanal
and the rectum and colon are then removed from the
Pull-through Procedure
abdomen.
The most common restorative procedure for children Attention is now turned to creation of the ileal J-pouch.
with UC is currently a proctocolectomy with ileoanal The distal 15cm of ileum is identified and turned back
pull-through. Historically, this operation was performed on itself. The adjacent limbs are secured to one another
via a laparotomy. The patient is positioned in the lithot- and the distal tip (the J limb) is opened. A linear stapling
omy position, with special attention taken to avoid pres- device is used to divide and secure the common wall
sure on the lateral portion of the upper calf where the between the two loops, thus creating the J-pouch. The
peroneal nerve courses around the tibia. Pressure induced pouch is oriented carefully to avoid a twist in its mesen-
injury to this nerve results in foot drop. Thromboembo- tery. In most children, the mesentery will reach easily to
lism prevention is instituted with sequential compression the pelvis if the ileal mesentery is mobilized up to the
devices (SCD) applied to the legs. The abdomen and origin of the superior mesenteric artery. If necessary, the
perineum are prepped into a single field, and a urinary peritoneal leaflets lining the mesentery can be opened,
catheter is inserted on the sterile field. with care taken to avoid injury to the underlying
The abdomen is entered through a vertical midline mesenteric vasculature, to allow more length on the
approach. The ileum is divided at its junction with the mesentery to facilitate the pouch reaching the pelvis. Stay
cecum and the entire colon is mobilized. The posterior sutures are placed on the ileal enterotomy through which
rectal dissection is then performed outside the mesorec- the stapler was fired. These stay sutures are delivered
tum as this plane allows easier dissection. When distal to through the pelvis to the anus. The pouch is positioned
the peritoneal reflection, the anterior dissection should within the rectal muscular cuff, and an end-to-end hand-
be carried out on the rectal wall to avoid injury to the vas sewn, single layer, interrupted pouchanal anastomosis is
deferens, seminal vesicles, or vaginal wall. The dissection completed using absorbable sutures (Fig. 41-2). A con-
proceeds distally along the rectum to approximately 5cm venient loop of ileum is chosen to avoid tension on the
558 SECTION IV Abdomen
A B
FIGURE 41-3 The double-stapled technique for the pouch/anal anastomosis has shown similar results as the hand-sewn technique.
(A) The anvil has been placed into the pouch and is being brought close to the circular stapler, which has been introduced through
the anus. (B) The anus and pouch have been approximated and the circled, stapled anastomosis performed (inset). There is usually
about a 5mm to 1cm cuff of native rectal mucosa remaining that requires lifetime surveillance. (Copyrighted and used with permis-
sion of Mayo Foundation for Medical Education and Research, all rights reserved.)
Outcomes
FIGURE 41-4 This 8-year-old child is undergoing a laparoscopic
proctocolectomy with ileal pouchanal anastomosis and tempo-
Children undergoing operation for UC can be expected
rary ileostomy. This view from the patients left side depicts to have excellent outcomes.7072 The preoperative medical
placement of the ports for the operation. Note a 12mm port is therapies are tapered or discontinued appropriately.
in the umbilicus through which a 10mm, 45 angled telescope These children will predictably have five to eight stools
is inserted. In the right lower quadrant is another 12mm cannula per day until their pouch becomes functional. This stool
(arrow) which will become the site of the temporary ileostomy.
Two 5mm ports are in the left suprapubic area and the left frequency is managed with scheduled loperamide and
mid-abdomen, and are working ports for the surgeon and the diphenoxylate/atropine. Patients are advised to avoid caf-
assistant. feine, high sugar foods, and spicy foods to reduce the
diarrhea. Metamucil, or an equivalent soluble fiber, is
helpful to thicken the stool to make it more controllable,
and to decrease perineal irritation. Additionally, patients
560 SECTION IV Abdomen
may be started on probiotics after continuity is reestab- These patients require close observation and should
lished to decrease the risk of pouchitis. These children be followed annually with pouchoscopy, unless sympto-
should be advised to use the toilet frequently to avoid matic in the interim. Surveillance of the remnant rectal
soiling. The stooling frequency is expected to improve mucosa for dysplasia, and the pouch for evidence of pou-
rapidly over the first six months, but will continue to chitis, should occur yearly, and biopsies should be taken
decrease over the first year. Patients are encouraged to at each occasion. Pouchitis is a common problem after
work on holding the stool at first sensation to improve the ileoanal pull-through procedures, and is reported to
interval between stools, and to strengthen their sphincter some degree in nearly half of patients.70,73 Pouchitis man-
control, which can help decrease nocturnal leakage. Most ifests as lower abdominal pain with increased frequency
children will eventually experience approximately four of watery, foul-smelling stools and fever. It is typically a
bowel movements per day, but some will continue to have clinical diagnosis, but in some cases, pouchoscopy will be
nighttime bowel activity. Night-time soiling is predicta- diagnostic. Contrast studies are usually not helpful.
ble until stool frequency decreases, but unfortunately per- Treatment consists of metronidazole or ciprofloxacin,
sists in a small number of patients. Long-term continence and in some cases, topical steroid applications. Early
rates are over 95%, and the ability to delay a bowel move- recurrence after stopping antibiotics is an indication for
ment reaches 90 minutes in many cases. suppressive therapy with daily metronidazole or cipro-
The restorative proctocolectomy is not without floxacin. Various scoring strategies are available to help
complications. Perioperative complications ranging from with evaluation and management of patients with pou-
wound infection to bowel obstruction occur in as many chitis. The most prominent system is the Heidelberg
40% of patients. Most of these will not require operative Pouchitis Activity Score.74 When pouchitis is severe or
intervention, but in one study, 7% required operation for recurrent, anatomic causes should be considered, includ-
intestinal obstruction, 14% required dilation for an ile- ing technical problems, that can be evaluated by endos-
oanal stricture, and 16% developed pouchitis requiring copy, CT, MRI, or contrast study. Biopsies may also
treatment.72 reveal evidence of CD that has only become evident after
the ileoanal reconstruction. Indeed, of pouches that have
to be abandoned due to poor function, at least half are
diagnosed as CD.72 Although 15% of patients with a
diagnosis of UC who undergo total proctocolectomy and
reconstruction may end up with the subsequent diagnosis
of CD, most of these patients can be managed without
permanent ileostomy.75
CROHN DISEASE
In 1932, Crohn and colleagues described the regional
ileitis that now bears his name.76 It was originally believed
to be isolated to the terminal ileum, but has now been
described as occurring anywhere from mouth to anus.77
CD generally presents before 35 years of age, and is most
common in western countries. There has been a steady
increase in its incidence since the 1950s, most promi-
nently in developing countries and in children.78,79 The
disease occurs equally in males and females, is five times
FIGURE 41-6 After ligation and division of the distal rectum, the more common in Caucasians than African Americans,
colon has been mobilized using the ultrasonic scalpel and has
been exteriorized through the right lower quadrant 12mm port
and has a significantly higher incidence in the Jewish
site (arrow). After the colon is separated from the ileum, the population.80 This relationship between ethnic and racial
J-pouch will be reconstructed extracorporeally (see Fig. 41-7). groups is strong evidence for a genetic predisposition for
41 Inflammatory Bowel Disease 561
A B
FIGURE 41-7 The creation of a J-pouch. (A) The J-pouch is created extracorporeally using the conventional stapler. (B) The J-pouch
has been created and the anvil has been secured into the distal tip of the J-pouch in preparation for a stapled pouchanal
anastomosis.
also be seen in CD, including weight loss, growth retar- Medical Management
dation, delayed puberty, skin lesions, liver disease, uveitis,
arthritis, anemia and stomatitis. The management of CD is neither entirely medical
or surgical. While the mainstay of therapy for CD is
medical, many children will eventually require an opera-
Diagnosis tion and the families should be counseled at an early
The diagnosis of CD may be delayed by the nonspecific stage of disease for this possibility. Surgical intervention
nature of the presentation. Regardless, patients with a does not represent a failure of medical therapy, but
suspicious constellation of gastrointestinal (GI) symp- rather another method of achieving a state of remission.
toms should be evaluated by a pediatrician familiar with These children will require a lifetime of medications,
the diagnosis, or referred to a gastroenterologist. The and psychological support should begin at the outset.
physical findings are typically related to growth failure The goal of medical therapy is to achieve a quiescent state
and abdominal pain and tenderness, many times with a of disease and the Pediatric Crohn Disease Activity Index
mass in the right lower quadrant. Perianal disease is not is a reliable method for following the response to
uncommon and may be quite dramatic. A thorough therapy.90
search for extraintestinal manifestations should be con- The modern approach to medical treatment of CD is
ducted and can help to direct further evaluation. Labora- changing rapidly. The initial therapy still includes gluco-
tory studies reveal a typical microcytic, hypochromic corticoids in an effort to forestall the inflammatory
anemia. Hypoalbuminemia is common, as is an elevated mechanism of the disease. This initial treatment is not
sedimentation rate and C-reactive protein. Similar to used for maintenance therapy, and every attempt should
UC, CD patients will also exhibit abnormalities in be made to wean steroids by 30 days. Of those unable to
pANCA and antibodies to Saccharomyces cerevisiae and to wean in the first 30 days, many require operation to
Escherichia coli outer-membrane porin. achieve disease quiescence.91
As with all patients with IBD, endoscopy is important, Aminosalicylates are used in both UC and CD, and
and a normal rectum is more suspicious of CD than UC. are most effective in colonic disease to decrease mucosal
Children with CD and rectal involvement will have linear inflammation. Unfortunately, due to the fact these medi-
ulcerations that are less friable than those in UC, and cations are most helpful in colonic disease, they are less
biopsy may demonstrate granuloma formation. Both useful in CD than in UC. Azathioprine, 6-mercaptopurine,
upper and lower endoscopy with biopsies is needed in and methotrexate are commonly used as initial therapy
children suspected of CD. These endoscopic findings are when steroids do not induce remission. These drugs are
often very helpful in differentiating CD from UC. known to induce remission and reduce dependence on
Radiographic evaluation can be very helpful in direct- steroids.9294
ing therapy. For example, contrast upper gastrointestinal Metronidazole is commonly used in patients with CD,
series with small bowel follow-through can identify stric- especially patients with rectal or fistulous disease. Also, it
tures, some with proximal dilation (Fig. 41-8). CT with is conceptualized that metronidazole is helpful for
water density contrast (CT enterography) has proven to maintaining remission after resection of involved intes-
be effective at evaluating CD. Recently, MR enterogra- tine. Interestingly, in one study, 75% of adults experi-
phy has become more popular as it avoids radiation and enced relapse after discontinuing this antibiotic.95 Thus,
can detect aperstilatic segments of the midgut inaccessi- many clinicians prefer to continue metronidazole after
ble by endoscopy.88,89 resection.
A B
FIGURE 41-8 (A) This upper gastrointestinal and small bowel follow-through contrast study shows a significant stricture (arrows)
in the terminal ileum in a patient with persistent and symptomatic Crohn disease despite medical therapy. (B) The laparoscopic
view shows active inflammation with creeping fat (arrows) along the terminal ileum in this patient.
41 Inflammatory Bowel Disease 563
Monoclonal antibodies are the newest form of therapy disease is localized, the operative plan can be tailored to
against CD. The most popular monoclonals are directed the site of disease. Options include resection of the dis-
at TNF-. Infliximab (a mouse-human chimeric anti- eased bowel with a primary anastomosis, resection with
body), adalimumab (a human monoclonal antibody), and diversion, or strictureplasty. It is important to note that
certolizumab are available, and are known to control the primary focus of operation in CD is complete resec-
steroid resistant disease. These medications can also be tion while preserving intestinal length, since CD is a
helpful in treating some patients with fistulous disease. common cause of short bowel syndrome in the adult
More recently, agents that are more specific against CD population. The surgeon should approach any operation
have been developed and natalizumab (recognizing in a patient with CD with the goal of removing only
alpha-4 integrin) has shown improved efficacy.96 A top- grossly involved bowel as there is no benefit from attain-
down approach, beginning with infliximab and progress- ing a histologic negative margin.
ing through adalimumab, certolizumab, and natalizumab, The most common operation performed for CD is
has been suggested and is gaining favor with many ileocecectomy due to the distribution of the disease. This
gastroenterologists.97 is typically performed as a laparoscopic-assisted approach
using a 12mm port in the umbilicus and two 5mm ports
in the left lower quadrant (Fig. 41-9A). The ileocecal
Surgical Management junction is identified and the bowel is inspected proxi-
Operative approaches to CD are restricted to the treat- mally to the ligament of Treitz to confirm the affected
ment of complications from the disease. These complica- areas. The cecum is freed from the lateral abdominal wall
tions are primarily perforation, fistula formation, and, if necessary, the hepatic flexure is also mobilized.
obstruction, stricture, bleeding, and failure of medical The umbilical incision can then be enlarged to a suffi-
therapy to achieve quiescence. It is important that the cient extent to exteriorize the ileocecum (Fig. 41-9B).
surgeon is sensitive that persistent disease may be mani- The resection and anastomosis is then performed extra-
fest by protean findings such as growth failure, delayed corporally and the mesenteric defect is closed. The bowel
puberty, complications of medications, compliance, and is returned to the abdomen and the incisions are closed
psychosocial complications. Surgical consultation should (Fig. 41-9C). Many authors prefer a stapled anastomosis,
occur early in the course of the disease and, in many while others feel that end-to-end anastomosis is best.101
cases, can reduce the anxiety that the patient and family Additionally, ileocolectomy has been performed via the
have about the specter of operative intervention. single incision approach with excellent results.102
The operative approach to CD may be either open or Short segment small bowel disease may not require
laparoscopic, although laparoscopy has become the most resection, but can be managed with a bowel-preserving
popular approach since the outcomes are similar with strictureplasty (Fig. 41-10). The operation is conducted
improved cosmesis and perhaps less anxiety for the in a similar fashion to the ileocecectomy previously
patient and family.98100 At operation, the stepwise goal is described, but the area of the small bowel stricture is
to confirm the areas of active disease that were identified identified and exteriorized through the umbilicus. The
by preoperative imaging studies (see Fig. 41-8). If the strictureplasty is performed with a longitudinal incision
A B C
FIGURE 41-9 (A) The port placement for a patient undergoing a laparoscopic ileocecectomy is seen. A 12mm port is placed in the
umbilicus (arrow), and two 5mm ports are introduced in the left lower abdomen and suprapubic area. (B) The diseased small bowel
has been exteriorized through the umbilicus for an extracorporeal resection and anastomosis. Note the inflamed bowel and creeping
fat in the exteriorized portion of the small bowel. (C) The appearance of the incisions after the laparoscopic ileocecectomy. The
intestinal resection and anastomosis was performed extracorporeally through the umbilical incision.
564 SECTION IV Abdomen
Outcomes
through the stricture and then closing the enterotomy The postoperative recovery is usually good although
transversely, creating a wide repair of the stricture. The recurrence rates increase with time and can reach 33%
bowel is then replaced into the abdomen. in long-term followup.107 Perioperative complications
Extensive colonic disease has traditionally been treated are not uncommon, and include wound infection and
with colectomy and permanent ileostomy. Recently, sur- bowel obstruction in as many as 25%.108 Despite the
geons have reported segmental colectomy and anastomo- inability to cure CD, the surgeon should approach the
sis followed by more aggressive medical therapy.103,104 problem with optimism and embrace the opportunity
Pancolitis, or rectal disease, presents fewer options, since to provide the patient with a period free from the
pelvic reconstruction in this setting has been associated symptoms.
with a high risk of complications.103 In those patients with
extensive colitis or with rectal involvement, subtotal
colectomy with Brooke ileostomy may be the least morbid INDETERMINATE COLITIS
approach, and may result in the fastest recovery and
return to a healthy state. In patients with extensive colitis Indeterminate colitis (IC) is a distinct clinical and patho-
and rectal sparing, colectomy and an ileorectal anastomo- logic entity which is diagnosed in approximately 10% of
sis may be reasonable.105,106 Also, if the rectum and colon IBD patients. Over time, these patients will generally be
need to be removed, consideration for anal reconstruc- found to have either UC or CD, with differentiation to
tion using an ileal J-pouch is not unreasonable. CD more likely than to UC.7,109 Not surprisingly, there
Fistulous disease can be managed directly or by diver- is greater morbidity after colectomy and pouchanal
sion in the most severe cases. These lesions may be quite anastomosis in patients with the diagnosis of IC, which
extensive, and CT or MRI are helpful in delineating the is due to the increased likelihood that they will eventually
extent of disease. Perirectal abscesses should be drained, differentiate to CD. Additionally, adults with indetermi-
and fistulas are controlled with fistulotomy for the most nate colitis undergoing colectomy and pouch-anal anas-
simple cases, or a noncutting seton for the more complex tomosis have a two to three times increased risk of serious
(Fig. 41-11). The seton will usually control the recurring postoperative complications compared to patients with
abscesses and provide symptom relief, and may be left for UC, but still less than patients with CD.110,111 The long-
quite some time if it is not causing any discomfort. In term success of colectomy and pouchanal reconstruction
patients with severe perianal manifestations, proctec- for indeterminate colitis is 7385% compared with
tomy, rectosigmoid resection, or proctocolectomy with 89% for UC.112 Although these results support the
41 Inflammatory Bowel Disease 565
consideration of performing colectomy and pouchanal A novel mechanism of chronic intestinal inflammation. J Immunol
anastomosis in the setting of uncontrolled indeterminate 1995;154:243440.
21. Finkelstein SD, Sasatomi E, Regueiro M. Pathologic features of
colitis, the IC patient with features favoring CD may early inflammatory bowel disease. Gastroenterol Clin North Am
benefit from delayed pouchanal reconstruction, six to 12 2002;31:13345.
months after colectomy. Ultimately, operative decisions 22. Coulson WF. Pathological features of inflammatory bowel disease
are based on the age of the patient, severity of disease, in childhood. Semin Pediatr Surg 1994;3:814.
23. Mackner LM, Greenley RN, Szigethy E, et al. Psychosocial Issues
and the urgency of the operation. Children younger than in Pediatric Inflammatory Bowel Disease: A Clinical Report of the
age 8 years with IC should undergo colectomy and the North American Society for Pediatric Gastroenterology, Hepatol-
surgeon should proceed cautiously before reconstruction ogy and Nutrition. J Pediatr Gastroenterol Nutr 2013.
is performed. 24. Falcone RA Jr, Lewis LG, Warner BW. Predicting the need for
colectomy in pediatric patients with ulcerative colitis. J Gastroin-
test Surg 2000;4:2016.
REFERENCES 25. Benchimol EI, Turner D, Mann EH, et al. Toxic megacolon in
1. Malaty HM, Fan X, Opekun AR, et al. Rising incidence of inflam- children with inflammatory bowel disease: Clinical and radio-
matory bowel disease among children: A 12-year study. J Pediatr graphic characteristics. Am J Gastroenterol 2008;103:152431.
Gastroenterol Nutr 2010;50:2731. 26. Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in
2. Pohl C, Hombach A, Kruis W. Chronic inflammatory bowel patients with ulcerative colitis: A meta-analysis of population-
disease and cancer. Hepatogastroenterology 2000;47:5770. based cohort studies. Clin Gastroenterol Hepatol 2012;10:
3. Mattioli G, Buffa P, Martinelli M, et al. Laparoscopic approach 63945.
for children with inflammatory bowel diseases. Pediatr Surg Int 27. Cucchiara S, Escher JC, Hildebrand H, et al. Pediatric inflamma-
2011;27:83946. tory bowel diseases and the risk of lymphoma: Should we revise
4. Wilks S, Moxon W. Lectures on Pathologic Anatomy. Longdon: our treatment strategies? J Pediatr Gastroenterol Nutr 2009;48:
Longmans, Green and Co; 1875. 25767.
5. Mamula P, Telega GW, Markowitz JE, et al. Inflammatory bowel 28. Markowitz JM, McKinley E, Kahn L, et al. Endoscopic screening
disease in children 5 years of age and younger. Am J Gastroenterol for dysplasia and mucosal aneuploidy in adolescents and young
2002;97:200510. adults with childhood onset colitis. Am J Gastroenterol 1997;92:
6. Jakobsen C, Paerregaard A, Munkholm P, et al. Pediatric 20016.
inflammatory bowel disease: increasing incidence, decreasing 29. Lagercrantz R, Winberg J, Zetterstrom R. Extra-colonic manifes-
surgery rate, and compromised nutritional status: A prospective tations in chronic ulcerative colitis. Acta Paediatr 1958;47:
population-based cohort study 20072009. Inflamm Bowel Dis 67587.
2011;17:254150. 30. Brain CE, Savage MO. Growth and puberty in chronic inflamma-
7. Abraham BP, Mehta S, El-Serag HB. Natural history of pediatric- tory bowel disease. Baillieres Clin Gastroenterol 1994;8:83100.
onset inflammatory bowel disease: A systematic review. J Clin 31. Ballinger AB, Savage MO, Sanderson IR. Delayed puberty associ-
Gastroenterol 2012;46:5819. ated with inflammatory bowel disease. Pediatr Res 2003;53:
8. Prideaux L, Kamm MA, De Cruz PP, et al. Inflammatory bowel 20510.
disease in Asia: A systematic review. J Gastroenterol Hepatol 32. Ezri J, Marques-Vidal P, Nydegger A. Impact of disease and treat-
2012;27:126680. ments on growth and puberty of pediatric patients with inflam-
9. Ament ME, Berquist W, Vargas J. Advances in ulcerative colitis. matory bowel disease. Digestion 2012;85:30819.
Pediatrician 1988;15:4557. 33. Tavarela Veloso F. Review article: Skin complications associated
10. Haller C, Markowitz J. A perspective on inflammatory bowel with inflammatory bowel disease. Aliment Pharmacol Ther
disease in the child and adolescent at the turn of the millennium. 2004;20(Suppl 4):503.
Curr Gastroenterol Rep 2001;3:26371. 34. Knight C, Murray KF. Hepatobiliary associations with inflamma-
11. Selby WS, Griffin S, Abraham N, et al. Appendectomy protects tory bowel disease. Expert Rev Gastroenterol Hepatol 2009;3:
against the development of ulcerative colitis but does not affect 68191.
its course. Am J Gastroenterol 2002;97:28348. 35. Szigethy E, McLafferty L, Goyal A. Inflammatory bowel disease.
12. Bouma G, Crusius JB, Garca-Gonzlez MA, et al. Genetic Child Adolesc Psychiatr Clin N Am 2010;19:30118.
markers in clinically well defined patients with ulcerative colitis 36. Ruemmele FM, Lachaux A, Cezard JP, et al. Diagnostic accuracy
(UC). Clin Exp Immunol 1999;115:294300. of serological assays in pediatric inflammatory bowel disease. Gas-
13. Shanahan F, Duerr RH, Rotter I, et al. Neutrophil autoantibodies troenterology 1998;115:8229.
in ulcerative colitis: Familial aggregation and genetic heterogene- 37. Kovacs M, Lakatos PL, Papp M, et al. Pancreatic autoantibodies
ity. Gastroenterology 1992;103:45661. and autoantibodies against goblet cells in pediatric patients with
14. Locht H, Skogh T, Wiik A. Characterisation of autoantibodies to inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2012;
neutrophil granule constituents among patients with reactive 55:42935.
arthritis, rheumatoid arthritis, and ulcerative colitis. Ann Rheum 38. Gore RM, Balthazar EJ, Ghahremani GG, et al. CT features of
Dis 2000;59:898903. ulcerative colitis and Crohns disease. AJR Am J Roentgenol
15. Tyler AD, Milgrom R, Stempak JM, et al. The NOD2insC poly- 1996;167:315.
morphism is associated with worse outcome following ileal pouch- 39. da Luz Moreira A, Vogel JD, Baker M, et al. Does CT influence
anal anastomosis for ulcerative colitis. Gut 2012. the decision to perform colectomy in patients with severe ulcera-
16. Glas J, Stallhofer J, Ripke S, et al. Novel genetic risk markers for tive colitis? J Gastrointest Surg 2009;13:5047.
ulcerative colitis in the IL2/IL21 region are in epistasis with 40. Das CJ, Makharia GK, Kumar R, et al. PET/CT colonography:
IL23R and suggest a common genetic background for ulcerative A novel non-invasive technique for assessment of extent and activ-
colitis and celiac disease. Am J Gastroenterol 2009;104:173744. ity of ulcerative colitis. Eur J Nucl Med Mol Imaging 2010;
17. Tysk C, Riedesel H, Lindberg E, et al. Colonic glycoproteins in 37:71421.
monozygotic twins with inflammatory bowel disease. Gastroen- 41. Kilickesmez O, Soylu A, Yasar N, et al. Is quantitative diffusion-
terology 1991;100:41923. weighted MRI a reliable method in the assessment of the inflam-
18. Zella GC, Hait EJ, Glavan T, et al. Distinct microbiome in matory activity in ulcerative colitis? Diagn Interv Radiol
pouchitis compared to healthy pouches in ulcerative colitis and 2010;16:2938.
familial adenomatous polyposis. Inflamm Bowel Dis 2011;17: 42. Parlak E, Dagli U, Ulker A, et al. Comparison of 5-amino salicylic
1092100. acid plus glucocorticosteroid with metronidazole and cipro-
19. Michail S, Durbin M, Turner D, et al. Alterations in the gut floxacin in patients with active ulcerative colitis. J Clin Gastroen-
microbiome of children with severe ulcerative colitis. Inflamm terol 2001;33:856.
Bowel Dis 2012;18:1799808. 43. Timmer A, McDonald JW, Tsoulis DJ, et al. Azathioprine and
20. Casini-Raggi V, Kam L, Chong YJ, et al. Mucosal imbalance of 6-mercaptopurine for maintenance of remission in ulcerative
IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. colitis. Cochrane Database Syst Rev 2012;(9):CD000478.
566 SECTION IV Abdomen
44. Chang JC, Cohen RD. Medical management of severe ulcerative 69. McLemore EC, Cullen J, Horgan S, et al. Robotic-assisted lapar-
colitis. Gastroenterol Clin North Am 2004;33:23550. oscopic stage II restorative proctectomy for toxic ulcerative colitis.
45. Hart AL, Ng SC. Review article: The optimal medical manage- Int J Med Robot 2012;8:17883.
ment of acute severe ulcerative colitis. Aliment Pharmacol Ther 70. Seetharamaiah R, West BT, Ignash SJ, et al. Outcomes in pediatric
2010;32:61527. patients undergoing straight vs J pouch ileoanal anastomosis: A
46. Schaufler C, Lerer T, Campbell B, et al. Preoperative immuno- multicenter analysis. J Pediatr Surg 2009;44:141017.
suppression is not associated with increased postoperative compli- 71. Durno C, Sherman P, Harris K, et al. Outcome after ileoanal
cations following colectomy in children with colitis. J Pediatr anastomosis in pediatric patients with ulcerative colitis. J Pediatr
Gastroenterol Nutr 2012;55:4214. Gastroenterol Nutr 1998;27:5017.
47. Eskicioglu C, Forbes SS, Fenech DS, et al. Preoperative bowel 72. Fonkalsrud EW, Thakur A, Beanes S. Ileoanal pouch procedures
preparation for patients undergoing elective colorectal surgery: A in children. J Pediatr Surg 2001;36:168992.
clinical practice guideline endorsed by the Canadian Society of 73. Fonkalsrud EW. Long-term results after colectomy and
Colon and Rectal Surgeons. Can J Surg 2010;53:38595. ileoanal pull-through procedure in children. Arch Surg 1996;131:
48. Zmora O, Mahajna A, Bar-Zakai B, et al. Colon and rectal surgery 8816.
without mechanical bowel preparation: A randomized prospective 74. Heuschen UA, Allemeyer EH, Hinz U, et al. Diagnosing pouchi-
trial. Ann Surg 2003;237:3637. tis: Comparative validation of two scoring systems in routine
49. Ram E, Sherman Y, Weil R, et al. Is mechanical bowel preparation follow-up. Dis Colon Rectum 2002;45:77688.
mandatory for elective colon surgery? A prospective randomized 75. Mortellaro VE, Green J, Islam S, et al. Occurrence of Crohns
study. Arch Surg 2005;140:2858. disease in children after total colectomy for ulcerative colitis.
50. Brooke BN. The management of an ileostomy, including its com- J Surg Res 2011;170:3840.
plications. Lancet 1952;2:1024. 76. Crohn BB, Ginzburg L, Oppenheimer GD. Landmark article Oct
51. Ravitch MM, Sabiston DC Jr. Anal ileostomy with preservation 15, 1932. Regional ileitis. A pathological and clinical entity. By
of the sphincter: A proposed operation in patients requiring total Burril B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer.
colectomy for benign lesions. Surg Gynecol Obstet 1947;84: JAMA 1984;251:739.
10959. 77. Brooke BN. Granulomatous diseases of the intestine. Lancet
52. Martin LW, LeCoultre C, Schubert WK. Total colectomy and 1959;2:7459.
mucosal proctectomy with preservation of continence in ulcera- 78. Perminow G, Brackmann S, Lyckander LG, et al. A characteriza-
tive colitis. Ann Surg 1977;186:47780. tion in childhood inflammatory bowel disease, a new population-
53. Martin LW, LeCoultre C. Technical considerations in performing based inception cohort from South-Eastern Norway, 200507,
total colectomy and Soave endorectal anastomosis for ulcerative showing increased incidence in Crohns disease. Scand J Gastro-
colitis. J Pediatr Surg 1978;13:7624. enterol 2009;44:44656.
54. Parks AG, Nicholls RJ, Belliveau P. Proctocolectomy with ileal 79. Benchimol EI, Turner D, Mann EH, et al. Epidemiology of pedi-
reservoir and anal anastomosis. Br J Surg 1980;67:5338. atric inflammatory bowel disease: A systematic review of interna-
55. Utsunomiya J, Yamamura T, Kusunoki M, et al. J-pouch: Change tional trends. Inflamm Bowel Dis 2011;17:42339.
of a method over years. Z Gastroenterol Verh 1989;24:24951. 80. Rogers BH, Clark LM, Kirsner JB. The epidemiologic and demo-
56. Wong WD, Rothenberger DA, Goldberg SM. Ileoanal pouch graphic characteristics of inflammatory bowel disease: An analysis
procedures. Curr Probl Surg 1985;22:178. of a computerized file of 1400 patients. J Chronic Dis 1971;24:
57. Gemlo BT, Wong WD, Rothenberger DA, et al. Ileal pouch-anal 74373.
anastomosis. Patterns of failure. Arch Surg 1992;127:7847. 81. Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and
58. Nicholls RJ, Pezim ME. Restorative proctocolectomy with ileal clinical characteristics of children with newly diagnosed inflam-
reservoir for ulcerative colitis and familial adenomatous polyposis: matory bowel disease in Wisconsin: A statewide population-based
A comparison of three reservoir designs. Br J Surg 1985;72: study. J Pediatr 2003;143:52531.
4704. 82. Fiocchi C. Inflammatory bowel disease: Etiology and pathogen-
59. Morgan RA, Manning PB, Coran AG. Experience with the esis. Gastroenterology 1998;115:182205.
straight endorectal pullthrough for the management of ulcerative 83. Bernstein CN. Why and where to look in the environment with
colitis and familial polyposis in children and adults. Ann Surg regard to the etiology of inflammatory bowel disease. Dig Dis
1987;206:5959. 2012;30(Suppl 3):2832.
60. Fonkalsrud EW, Loar N. Long-term results after colectomy and 84. Rosenstiel P, Sina C, Franke A, et al. Towards a molecular risk
endorectal ileal pullthrough procedure in children. Ann Surg maprecent advances on the etiology of inflammatory bowel
1992;215:5762. disease. Semin Immunol 2009;21:33445.
61. Lane JS, Kwan D, Chandler CF, et al. Diverting loop versus end 85. Heikenen JB, Werlin SL, Brown CW, et al. Presenting symptoms
ileostomy during ileoanal pullthrough procedure for ulcerative and diagnostic lag in children with inflammatory bowel disease.
colitis. Am Surg 1998;64:97982. Inflamm Bowel Dis 1999;5:15860.
62. Mennigen R, Senninger N, Bruwer M, et al. Impact of 86. El Mouzan MI, Al Mofarreh MA, Assiri AM, et al.
defunctioning loop ileostomy on outcome after restorative proc- Presenting features of childhood-onset inflammatory bowel
tocolectomy for ulcerative colitis. Int J Colorectal Dis 2011;26: disease in the central region of Saudi Arabia. Saudi Med J 2012;
62733. 33:4238.
63. Ryan DP, Doody DP. Restorative proctocolectomy with and 87. North American Society for Pediatric Gastroenterology, Hepatol-
without protective ileostomy in a pediatric population. J Pediatr ogy, and Nutrition; Colitis Foundation of America, Bousvaros A,
Surg 2011;46:2003. Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis
64. Mattioli G, Buffa P, Martinelli M, et al. All mechanical low rectal from Crohn disease in children and young adults: Report of a
anastomosis in children. J Pediatr Surg 1998;33:5036. working group of the North American Society for Pediatric Gas-
65. Griffen FD, Knight CD Sr, Knight CD Jr. Results of the double troenterology, Hepatology, and Nutrition and the Crohns and
stapling procedure in pelvic surgery. World J Surg 1992; Colitis Foundation of America. J Pediatr Gastroenterol Nutr
16:86671. 2007;44:65374.
66. Duff SE, Sagar PM, Rao M, et al. Laparoscopic restorative proc- 88. Stuart S, Conner T, Ahmed A, et al. The smaller bowel: Imaging
tocolectomy: Safety and critical level of the ileal pouch anal anas- the small bowel in paediatric Crohns disease. Postgrad Med J
tomosis. Colorectal Dis 2012;14:8836. 2011;87:28897.
67. Fichera A, Zoccali M, Gullo R. Single incision (scarless) laparo- 89. Bruining DH, Siddiki HA, Fletcher JG, et al. Benefit of computed
scopic total abdominal colectomy with end ileostomy for ulcera- tomography enterography in Crohns disease: Effects on patient
tive colitis. J Gastrointest Surg 2011;15:124751. management and physician level of confidence. Inflamm Bowel
68. Pedraza R, Patel CB, Ramos-Valadeza DI, et al. Robotic-assisted Dis 2012;18:21925.
laparoscopic surgery for restorative proctocolectomy with ileal J 90. Otley A, Loonen H, Parekh N, et al. Assessing activity of pediatric
pouch-anal anastomosis. Minim Invasive Ther Allied Technol Crohns disease: Which index to use? Gastroenterology 1999;
2011;20:2349. 116:52731.
41 Inflammatory Bowel Disease 567
91. Faubion WA Jr, Bousvaros A. Medical therapy for refractory pedi- 102. Laituri CA, Fraser JD, Garey CL, et al. Laparoscopic ileocecec-
atric Crohns disease. Clin Gastroenterol Hepatol 2006;4: tomy in pediatric patients with Crohns disease. J Laparoendosc
1199213. Adv Surg Tech A 2011;21:1935.
92. Mahadevan U, Sandborn WJ. Evolving medical therapies for 103. Makowiec F, Paczulla D, Schmidtke C, et al. Long-term follow-up
Crohns disease. Curr Gastroenterol Rep 2001;3:4716. after resectional surgery in patients with Crohns disease involving
93. Mack DR, Young R, Kaufman SS, et al. Methotrexate in patients the colon. Z Gastroenterol 1998;36:61924.
with Crohns disease after 6-mercaptopurine. J Pediatr 1998;132: 104. Tekkis PP, Purkayastha S, Lanitis S, et al. A comparison of seg-
8305. mental vs subtotal/total colectomy for colonic Crohns disease: A
94. Ruemmele FM, Lachaux A, Cezard JP, et al. Efficacy of infliximab meta-analysis. Colorectal Dis 2006;8:8290.
in pediatric Crohns disease: A randomized multicenter open-label 105. Cattan P, Bonhomme N, Panis Y, et al. Fate of the rectum in
trial comparing scheduled to on demand maintenance therapy. patients undergoing total colectomy for Crohns disease. Br J Surg
Inflamm Bowel Dis 2009;15:38894. 2002;89:4549.
95. Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metro- 106. Davies G, Evans CM, Shand WS, et al. Surgery for Crohns
nidazole treatment for prevention of Crohns recurrence after ileal disease in childhood: Influence of site of disease and operative
resection. Gastroenterology 1995;108:161721. procedure on outcome. Br J Surg 1990;77:8914.
96. Bousvaros A. Use of immunomodulators and biologic therapies in 107. Papi C, Spurio FF, Margagnoni G, et al. Randomized controlled
children with inflammatory bowel disease. Expert Rev Clin trials in prevention of postsurgical recurrence in Crohns disease.
Immunol 2010;6:65966. Rev Recent Clin Trials 2012;7:30713.
97. Yang LS, Alex G, Catto-Smith AG. The use of biologic agents in 108. Patel HI, Leichtner AM, Colodny AH, et al. Surgery for Crohns
pediatric inflammatory bowel disease. Curr Opin Pediatr disease in infants and children. J Pediatr Surg 1997;32:10638.
2012;24:60914. 109. Guindi M, Riddell RH. Indeterminate colitis. J Clin Pathol
98. Diamond IR, Gerstle JT, Kim PC, et al. Outcomes after laparo- 2004;57:123344.
scopic surgery in children with inflammatory bowel disease. Surg 110. Prudhomme M, Dehni N, Dozois RR. Causes and outcomes of
Endosc 2010;24:2796802. pouch excision after restorative proctocolectomy. Brit J Surg
99. von Allmen D, Markowitz JE, York A, et al. Laparoscopic-assisted 2006;93:826.
bowel resection offers advantages over open surgery for treatment 111. Yu CS, Pemberton JH, Larson D. Ileal pouch anal anastomosis in
of segmental Crohns disease in children. J Pediatr Surg 2003; patients with indeterminate colitis: Long-term results. Dis Colon
38:9635. Rectum 2000;43:148796.
100. Gardenbroek TJ, Tanis PJ, Buskens CJ, et al. Surgery for Crohns 112. Wolff BG. Is ileoanal the proper operation for indeterminate
disease: New developments. Dig Surg 2012;29:27580. colitis: The case for. Inflam Bowel Dis 2002;8:3629.
101. Resegotti A, Astegiano M, Farina EC, et al. Side-to-side stapled
anastomosis strongly reduces anastomotic leak rates in Crohns
disease surgery. Dis Colon Rectum 2005;48:4648.
C H A P T E R 4 2
Appendicitis
Veronica F. Sullins Steven L. Lee
Appendicitis is one of the most common surgical emer- described and may be the mechanism behind the clinical
gencies in children. Over 70,000 cases are seen in the phenomenon of relapsing or chronic appendicitis.22,23
USA each year.1,2 The lifetime risk of appendicitis is 9% Historically, appendicitis has been considered a some-
in boys and 7% in girls. Unfortunately, there is a lack of what time-sensitive condition such that a significant delay
general consensus regarding its diagnosis and in treatment may lead to an increased risk of perforation.
management.3 It is for this reason that young children have a higher
appendiceal perforation rate compared to older chil-
dren.24 Younger children have less ability to understand
PATHOPHYSIOLOGY or articulate their developing symptoms. As a result, per-
foration rates have been reported to be as high as 82%
The spectrum of appendicitis ranges from simple inflam- in children younger than 5 years and nearly 100% in
mation to gross perforation. This concept was initially 1-year olds.25
described by van Zwalenberg in 1905 and confirmed Age is not the only factor accounting for delays in
in an experimental model by Wangensteen in 1939.4,5 treatment and therefore higher perforation rates. One
Obstruction of the lumen can occur from multiple causes of the biggest concerns contributing to this delay is the
including fecal material (fecalith), lymphoid hyperplasia, lack of access to health care. It follows that patients with
foreign body, or parasites. Fecaliths are present in roughly poor access to health care will have higher perforation
20% of children with acute appendicitis and 3040% of rates. Indeed, children with no insurance or public
children with perforated appendicitis.6,7 Fecaliths and insurance have higher rates of appendiceal perforation
appendicitis are more common in developed countries compared to children with private insurance.2629 Minori-
with low-fiber diets compared to developing countries ties also have higher perforation rates compared to
with high-fiber diets.8 Hyperplasia of the lymphoid tissue whites.2629 Encouragingly, settings in which patients have
near the base of the appendix is also a common cause of equal access to health care or a well-established primary
appendiceal obstruction in children. Interestingly, the care network eliminate these racial, ethnic, and socioeco-
incidence of appendicitis closely resembles the amount of nomic differences.30,31
appendiceal lymphoid follicles present.9 Organisms such
as Yersenia, Salmonella, and Shigella can cause a local or
generalized reaction of the lymphoid tissue leading to CLINICAL PRESENTATION
obstruction. In similar fashion, parasitic infestations from
Entamoeba, Strongyloides, Enterobius, Schistosoma, or Ascaris The clinical presentation of appendicitis closely corre-
species and viral infections such as mumps virus, cox- lates with the pathophysiology of the disease process.
sackie virus B, cytomegalovirus, and adenovirus can The most common initial symptom is vague abdominal
lead to luminal obstruction secondary to lymphoid pain. This pain is due to activation of the visceral pain
hyperplasia.1018 In children with cystic fibrosis, obstruc- fibers from distention of the appendix following obstruc-
tion may be due to abnormal production of mucus leading tion. Pain is vague, nonspecific, and commonly located
to painful distention with or without inflammation.19 in the periumbilical region as with distention of all midgut
Appendicitis in neonates is rare and warrants evaluation derivatives. As the appendiceal distention progresses,
for cystic fibrosis and Hirschsprung disease.20 It is diffi- symptoms of nausea, vomiting, diarrhea, and anorexia
cult to distinguish neonatal appendicitis from necrotizing often follow. The appearance of these symptoms prior to
enterocolitis confined to the appendix.21 the onset of pain makes the diagnosis of appendicitis less
Following obstruction, the appendix becomes dis- likely. Intermittent, crampy pain is also less commonly
tended from the accumulation of mucus and proliferation associated with appendicitis.
of bacteria. As intraluminal pressure increases, lymphatic Fever, tachycardia, and leukocytosis develop as a con-
and venous drainage are impaired resulting in local sequence of systemic inflammatory mediators released by
edema. A further increase in pressure will limit arterial ischemic tissues, white blood cells, and bacteria. The
inflow, thus jeopardizing tissue integrity and ultimately inflamed appendix then irritates the overlying perito-
leading to tissue necrosis and perforation. Although the neum, typically by direct contact. This leads to focal
natural history of untreated appendicitis is usually perfo- peritonitis and localized right lower quadrant pain. This
ration and abscess, not all patients will progress in this process explains the typical migrating pain from the
fashion. Resolution of untreated appendicitis has been umbilicus to the right lower quadrant. Any movement of
568
42 Appendicitis 569
the peritoneum will lead to an exacerbation of the usefulness over clinical judgment.4042 They have, however
pain. Thus, children will often demonstrate voluntary been shown to decrease the use of computed tomography
guarding of the right lower quadrant during the exam. (CT) scans.43 Recent studies have stratified patients into
Furthermore, children will usually resist walking and risk categories based on history, physical examination,
jumping due to the increased pain associated with such and laboratory studies to determine which patients should
movement. have surgical consultation (high risk), additional imaging
The most common finding on physical examination is studies (medium risk), or be discharged (low risk).3842
focal tenderness in the right lower quadrant. Typically in This is the most applicable use of a scoring system or
children, only gentle pressure is required to elicit wincing, clinical pathway at the present time.
moving, or guarding. Applying pressure to a stethoscope
while listening to the abdomen is a subtle way to palpate
the abdomen in frightened children in whom it is difficult IMAGING STUDIES
to obtain an accurate exam. Narcotic analgesics improve
the comfort level of the patient, but do not alter the Misdiagnosing appendicitis can lead to significant delays
inflammatory process. Thus, tenderness will persist in in treatment. Children are often diagnosed with gastro-
patients receiving narcotics. Attempts to illicit rebound enteritis and parents are reassured that their child will
tenderness in children are uncomfortable, inaccurate, and improve, which may delay them from seeking further
should be avoided. An easier and more accurate method care. Epidemiologic data have shown the risk of a missed
for determining the degree of peritoneal irritation is to diagnosis in children to be higher in hospitals with a
ask the patient to walk or jump. Palpating a mass is dif- volume of less than one pediatric appendectomy per
ficult and often impossible due to the level of discomfort week.44 Historically, negative appendectomy rates of 10%
and guarding. Masses are more easily detected after to 20% were not only considered appropriate but advis-
induction of anesthesia. It is important to remember that able to minimize the number of patients with a missed
localized tenderness is dependent on peritoneal irritation. diagnosis and to decrease perforation rates. Some authors
Therefore, obesity, a retrocecal appendix, or an appendix have questioned this philosophy, citing the risk and
that is walled off by omentum, mesentery, or small bowel expense of an avoidable operation.45 Appropriate use of
may not be associated with localized tenderness, making diagnostic imaging can minimize both the negative
the diagnosis more challenging. appendectomy and perforation rates. Currently, the neg-
Laboratory studies often show a mild leukocytosis. A ative appendectomy rate from high-volume childrens
markedly elevated leukocyte count suggests perforation hospitals is 34%.4648 Despite the increased use of
or another diagnosis. Patients with appendicitis will have imaging studies, correctly diagnosing children less than
higher leukocyte counts compared to patients without 5 years of age continues to be challenging with negative
appendicitis.32 However a broad range of sensitivity (52 appendectomy rates ranging from 1317%.48
96%) exists, which limits the usefulness of this laboratory Plain radiography can show fecaliths in 1020% of
value alone. A left-shifted differential count may be a patients and can contribute to the diagnosis if the history
better diagnostic indicator, but a wide range in sensitivity and physical exam findings are consistent. Other helpful
(3996%) also can lead to misinterpretation.3335 Other findings on plain films include lumbar scoliosis and oblit-
inflammatory markers including C-reactive protein eration of the psoas shadow. In general, plain films may
(CRP), procalcitonin, and d-lactate have also been inves- be more useful to evaluate for other disease processes
tigated. Of these markers, only CRP has been shown to when the suspicion for appendicitis is low.
be useful. A value greater than 3mg/dL has been associ- Ultrasonography (US) offers the advantages of being
ated with the definitive diagnosis of appendicitis when an efficient bedside technique that is noninvasive, requires
compared to children with abdominal pain from a differ- no contrast, and emits no radiation. Thus, ultrasound
ent etiology.32 The combination of elevated leukocyte should be the first imaging study utilized in patients with
count and CRP level has the highest correlation of defini- atypical presentations of appendicitis. Common ultra-
tively diagnosing appendicitis.32,36 Although normal sound findings include a fluid-filled, noncompressible
values of both leukocyte count and CRP make the diag- appendix, a diameter greater than 6mm (Fig. 42-1),
nosis of appendicitis less likely, the clinical signs and appendicolith, periappendiceal or pericecal fluid, and
symptoms should be carefully considered as appendicitis increased periappendiceal echogenicity caused by inflam-
cannot be excluded based on normal laboratory values. A mation.49,50 Most studies demonstrate a sensitivity greater
urine analysis is typically obtained and is usually free of than 85% and specificity greater than 90%.51,52 However,
bacteria, but a few or moderate number of red or white ultrasound is operator dependent and results of published
blood cells may be found as the inflammatory process of studies may not be similar to results obtained in many
the appendix may locally affect the bladder or ureter. clinical settings. Patient factors such as bowel gas pattern,
The typical presentation of appendicitis as described obesity, and guarding or movement can affect the accu-
previously is found in roughly 50% of patients.37 Chil- racy. False-positive results may be due to a large appendix
dren with appendicitis often present with wide deviations or another tubular structure being mistaken for the
from this classic picture making for a challenging appendix. When a normal appendix is identified, it is a
diagnosis. In patients with an atypical presentation of reliable study to rule out appendicitis. Unfortunately,
appendicitis, clinical scoring systems have been used only 1050% of children with normal appendices can be
to aid in making the diagnosis.38,39 Accuracy of these identified.5254 When a normal appendix is not seen, there
scoring systems has been inconsistent which limits their is still a risk of appendicitis despite an otherwise normal
570 SECTION IV Abdomen
ultrasound study.55 Graded compression ultrasound These values are significantly lower in diagnosing perfo-
places pressure on the transducer to displace bowel loops rated appendicitis.67 The perceived improved diagnostic
and identify the appendix. The pressure is felt adequate accuracy of CT has led to a dramatic increase in the
if the psoas muscle and the iliac vessels are identified, number of CT scans performed in children even though
which assure the range of view is posterior to the appen- there is not good evidence that supports its routine use
dix. Furthermore, data from a large series employing for the diagnosis of appendicitis.6871
upward graded compression, posterior manual compres- There are, however, several concerns with CT. Some
sion, left oblique lateral decubitus position, and a low protocols require a delay in the emergency department
frequency convex transducer demonstrated that nearly all for contrast administration, and younger children may
appendices could be identified with over 98% accuracy require sedation. Recently, the ease of rapid helical CT
for correctly diagnosing appendicitis.56 Contrast- has led to an estimated 200% increase in pediatric CT
enhanced power Doppler ultrasound imaging demon- scans, significantly increasing radiation exposure in young
strated similar accuracy in a small study.57 patients.72 This has become a growing concern because
When ultrasound is unable to exclude or confirm although no direct connection between CT scan and
appendicitis, additional imaging or observation with malignancy has been made, lifetime radiation exposure
serial examinations is warranted. In order to avoid hos- has been linked to an increased risk of malignancy.73 It
pitalization for observation, many physicians obtain a CT has been estimated that a complete abdominal CT scan
scan. The findings of an enlarged appendix (>6mm), is equivalent to 25.7 months of natural background radia-
appendiceal wall thickening (>1mm), periappendiceal fat tion exposure.74 Developing tissues are more sensitive to
stranding, and appendiceal wall enhancement are useful the effects of radiation as evidenced by an increased risk
diagnostic criteria (Fig. 42-2).58,59 For the most part, the of radiation-induced malignancy in patients exposed at
sensitivity and specificity of CT are around 95%.6066 a younger age.73,75 The risk of a fatal radiation-induced
malignancy is estimated at 0.18% for a 1-year-old child.
In other words, one death due to malignancy would result
from an abdominal CT scan done on 555 1-year-old
patients, whereas about twice as many 15-year-olds would
need to be scanned to equal that risk. Although this esti-
mate seems significant, it represents only a 0.35% increase
in overall risk compared to the risk of cancer mortality
with natural background radiation.76 Use of a staged
imaging protocol, performing CT scan only if ultrasound
findings are equivocal, has shown a reduction in the
number of CT scans performed and therefore overall
radiation exposure without sacrificing diagnostic sensitiv-
ity and specificity.77 In addition, international guidelines
on radiation protection have implemented the ALARA
principle (as low as reasonably achievable), thus decreas-
ing radiation exposure in children by 30-50%.72,75,77
Although the overall increase in risk may be miniscule, it
FIGURE 42-1 This longitudinal view of an ultrasound in a is important to attempt to limit radiation exposure when
patient with acute appendicitis shows an enlarged appendix evaluating children with acute appendicitis.
measuring 11mm. in diameter.
A B C
FIGURE 42-2 These three CT scans show differing presentations for appendicitis. (A) The appendix (arrow) is enlarged and has a
thickened wall. There are no inflammatory changes such as periappendiceal fat stranding seen on this study. (B) The appendix
(arrow) is enlarged and there is free fluid and inflammatory changes medially indicating likely perforation. (C) The patient presented
with a one week history of pain and the appendix has perforated with the development of two abscesses (asterisks). In addition, a
fecalith is seen medially (dotted arrow). This patient was initially managed nonoperatively with drainage of the abscesses and
intravenous antibiotics. She underwent laparoscopic interval appendectomy 10 weeks following the initial admission.
42 Appendicitis 571
Magnetic resonance imaging (MRI) is an intriguing Association members revealed that most surgeons base
nonradiation alternative to CT and is extremely accurate their practice patterns on individual preferences.3 For
in diagnosing appendicitis.78 The current version of this this reason, the literature focusing on perforated appen-
technology makes it impractical for widespread applica- dicitis must be viewed with caution.
tion, but future generations of scanners could allow it to In reality, appendicitis presents as a spectrum of disease
be the preferred diagnostic imaging modality. and it is important to distinguish which patients are at
higher risk of complications. The data comparing out-
comes of nonperforated versus perforated appendicitis is
DIFFERENTIAL DIAGNOSIS extensive, but most studies fail to use a strict definition
of perforation. One prospective study showed that defin-
Acute appendicitis can mimic virtually any intra- ing perforation as a visible hole in the appendix or a feca-
abdominal process and should be high on the differential lith in the abdomen effectively identified those with
diagnosis in children with abdominal pain.79 Causes of greater risk of developing intra-abdominal abscesses (Fig.
acute right lower quadrant pain that are often indistin- 42-3).83 In addition, outcomes in gangrenous appendicitis
guishable from appendicitis include tubo-ovarian patho- are similar to acute appendicitis and many patients may
logic processes, Crohn disease, mesenteric adenitis, cecal actually be over-treated.84 Thus, in the following discus-
diverticulitis, Meckel diverticulitis, constipation, viral sion, the management of uncomplicated appendicitis will
gastroenteritis, and regional bacterial enteritis (Yersinia include acute, suppurative, and gangrenous appendicitis
and Campylobacter in particular). Lower abdominal pain or whereas complicated appendicitis will be synonymous
vague nonfocal pain can result from a urinary tract infec- with perforated appendicitis.
tion, kidney stone, ureteropelvic junction obstruction,
uterine pathologic process, right lower lobe pneumonia,
sigmoid diverticulitis, cholecystitis, pancreatitis, gastro-
Uncomplicated Appendicitis
enteritis, vasculitis, bowel obstruction, and malignancy After intravenous fluids and administration of broad-
(lymphoma). The most common diagnosis made in the spectrum antibiotics, the current standard of care for
presence of missed appendicitis is reported to be gastro- uncomplicated appendicitis is appendectomy. Prophylac-
enteritis.80 Although many of these conditions may seem tic antimicrobial agents should be given for 24 hours or
easily distinguishable, they each possess a spectrum of less. In fact, a single preoperative dose of antibiotics has
presentation that overlaps with appendicitis. shown to decrease the risk of wound infection and
abscess.85,86 Following appendectomy, patients are typi-
cally discharged within 24 hours. Additional postopera-
TREATMENT tive antibiotics for acute appendicitis are not necessary or
recommended.85,87 However, it may be reasonable to
The treatment of appendicitis begins with intravenous administer additional antibiotics for patients with sup-
fluids and broad-spectrum antibiotics to provide coverage purative or gangrenous appendicitis during the first 24
of enteric organisms. Management after initiating anti- hours after appendectomy or longer based on the patients
microbial therapy depends on the severity of inflamma- clinical status.
tion and the discussion must therefore be separated into Recent data in adults suggests that administration of
uncomplicated (nonperforated) and complicated (perfo- antibiotics without appendectomy may be sufficient to
rated appendicitis). This distinction, however, is not treat uncomplicated appendicitis. Multiple prospective
always clear. Diagnostic imaging may help but cannot randomized trials in adults have demonstrated similar
accurately diagnose perforation and many patients will outcomes from acute appendicitis treated with antibiotics
not undergo preoperative imaging.61 Even intraoperative alone with success rates ranging from 44% to 85%.8892
assessment showed high rates of discordance when com- Adults managed nonoperatively demonstrated fewer
pared to histologic evaluation of gangrenous and/or rup- complications and less pain, although recurrence rates
tured appendicitis.81 Surgeons polled with photographs were high, ranging from 14% to 37%.93 There have
showed extreme incongruence on which patients had been no prospective, randomized trials in children com-
perforation,82 and a survey of American Pediatric Surgical paring antibiotics alone to appendectomy. Regardless of
treatment modality, once antibiotics have been initiated, abscess or phlegmon on presentation demonstrated
appendectomy is no longer considered to be an emer- higher rates of overall complications, wound infections,
gency and may even be considered somewhat elec- and intra-abdominal abscesses in those who had immedi-
tive.88,89,9398 Until there is enough prospective randomized ate appendectomy.109
data in pediatric patients proving the efficacy of primary The concept of managing complicated appendicitis
antibiotic treatment, appendectomy remains the standard with antibiotics alone is to decrease the significant local
of care for uncomplicated appendicitis. However, the and regional inflammation that may make an immediate
need for operation may not be as urgent as previously operation very difficult and potentially more dangerous.
thought. Once treated, most surgeons will perform interval appen-
dectomy after six to ten weeks. However, some advocate
that the interval appendectomy is not necessary as recur-
Complicated Appendicitis rence rates are low, ranging from 814%.110,111 One
Patients with perforated appendicitis should receive post- problem with these studies is the relatively short length
operative antibiotics until clinical resolution has occurred. of follow-up. A recent systematic review found a 20.5%
The antibiotic regimen employed for perforated appen- overall risk of recurrent appendicitis with a range of
dicitis has traditionally been triple antibiotic therapy 042%. However, nearly all studies were retrospective
(ampicillin, gentamicin, and clindamycin or metronida- and thus only included patients specifically selected for
zole). However recently there has been a shift towards nonoperative management.112 Some studies showed high
more simple antibiotic regimens. Single agent therapy rates of pathologic findings in interval appendectomy
with piperacillin/tazobactam or cefotaxime, or double specimens.113,114 Although there is a lack of long-term
agent therapy with ceftriaxone and metronidazole, has data to accurately predict the rates of recurrence in both
been shown to be as efficacious as triple antibiotic therapy adults and children, some studies suggest that most recur-
but is more cost effective.99103 Several authors have high- rences will occur within three years and the majority
lighted a decrease in antibiotic expense with once daily within one to six months.110112 For these reasons, most
dosing of ceftriaxone compared with multi-dose mono- pediatric surgeons perform interval appendectomy in
therapeutic agents. In addition, a prospective randomized patients with complicated appendicitis who were initially
study confirmed that single daily dosing of ceftriaxone managed nonoperatively.3
and metronidazole is equal to and more cost effective The majority of patients who present with a well-
than traditional triple antibiotic therapy in the treatment formed abscess on initial imaging are managed nonop-
of perforated appendicitis.103 Therefore, current best evi- eratively (see Fig. 42-2C). Historically, immediate
dence suggests once-a-day dosing with ceftriaxone at appendectomy in this patient population was difficult,
50mg/kg/day and metronidazole at 30mg/kg/day pro- required a larger incision, and had a high morbidity.
vides the simplest and least expensive regimen. Primary treatment of the abscess with antibiotics alone, or
Although the length of antibiotic course for perforated antibiotics and percutaneous drainage with or without
appendicitis is not yet standardized, current findings drain placement for larger fluid collections, is a widely
from multiple systematic reviews recommend continua- accepted treatment strategy. Interval appendectomy is
tion of antibiotics until resolution of clinical symp- then performed after the inflammation has subsided.3,115119
toms.85,102 This includes normalization of leukocyte count Although treatment with percutaneous drainage and
and differential, full return of gastrointestinal function, interval appendectomy has inherent risk of complications,
resolution of fever, and normalization of physical exam. success rates have been reported to be as high as 88%.107 A
In addition, if the duration of intravenous antibiotic recent pilot randomized trial comparing initial laparo-
therapy is less than 5 days, patients can be discharged scopic appendectomy versus antibiotics, percutaneous
safely on oral antibiotics to complete a 7-day course.104 A drainage and subsequent interval laparoscopic appendec-
patient who is clinically well by postoperative day three tomy in patients presenting with perforated appendicitis
is unlikely to develop an abscess.105 However, if a patients and abscess demonstrated no difference in the rate of
clinical symptoms have not resolved, it should raise the recurrent abscess, length of hospital stay, or hospital
suspicion of an intra-abdominal abscess and intravenous charges.120 Patients undergoing immediate appendectomy
antibiotics should be continued. had longer operations and a longer time to return of bowel
After initial intravenous fluid administration and anti- function. Alternately, patients who had interval appendec-
biotics, the management of complicated appendicitis can tomies had more CT scans. Quality of life surveys at pres-
be separated into nonoperative and operative treatment. entation, 2 weeks, and 12 weeks in both groups from this
Choice of treatment depends on identification of patients study showed that families experience significant parent-
at high risk for treatment failure. It is also important to ing distress related to disruption in the childs quality of
consider that many patients will not be diagnosed with life until the appendectomy is performed.121
perforated appendicitis preoperatively. Risk factors for The majority of patients with complicated appendici-
failure of nonoperative management include greater than tis can be safely managed with appendectomy. Specifi-
15% band forms on the white blood cell differential cally, patients with a phlegmonous mass, appendicolith,
count, disease that extends beyond the right lower quad- or absence of a well-formed abscess on imaging have a
rant, absence of a well-defined abscess, or presence of an higher risk of failure of nonoperative management.107,122
appendicolith on imaging.106108 Conversely, a large meta- These patients can safely and reliably undergo immediate
analysis comparing appendectomy versus conservative laparoscopic appendectomy.123,124 In patients with perfo-
treatment for complicated appendicitis as defined by rated appendicitis without abscess, a recent prospective
42 Appendicitis 573
randomized trial demonstrated lower rates of adverse the 12mm umbilical cannula and used to divide the
events, shorter length of hospitalization, and earlier appendix and mesoappendix (Fig. 42-5). The appendix is
return to normal activity with early appendectomy.122 In usually divided first, followed by division of the mesoap-
addition, mean total hospital charges and resource use pendix. On occasion, however, it may be more expedient
were significantly higher in patients undergoing interval to ligate the mesoappendix first. If the appendix can be
appendectomy, likely due to the increased number of delivered through the cannula, an endoscopic bag is not
adverse events.125 used. However, if the appendix is too large for the
The choice of nonoperative versus operative treat- cannula, an endoscopic bag is employed to avoid drag-
ment depends on the preoperative diagnosis of perfora- ging the appendix through the umbilical incision. Drains
tion. As mentioned previously, it is difficult to interpret are not routinely utilized for advanced disease.
data on perforated appendicitis because a strict definition Since the introduction of laparoscopic appendectomy
of perforation has not uniformly been used. Currently, 25 years ago, there has been an abundance of data com-
patients are initially managed operatively or nonopera- paring open and endoscopic techniques. Initial advan-
tively based on disease severity and surgeon preference. tages of the open approach seemed to be a shorter length
Although evidence suggests that the majority of patients of operation and fewer postoperative intra-abdominal
can safely undergo early appendectomy, the optimal man- abscesses.128130 However, as expected, there were higher
agement of complicated appendicitis still remains unclear. rates of wound infections, presumably due to contamina-
tion of the incision when delivering an infected appendix
through the wound (Fig. 42-6). Advantages of the laparo-
Operative Technique scopic approach are multiple. It allows better visualiza-
First described in 1893 by McBurney, the traditional tion of the entire abdomen, which is especially beneficial
method of appendectomy was a muscle-splitting, right in obese patients who would otherwise require a larger
lower quadrant incision.126 The cecum is delivered incision, and fertile females who may have other intra-
through the incision, the mesoappendix is divided, and abdominal pathology.131133 Laparoscopy also allows lysis
the appendix is ligated at its base. In the laparoscopic of interloop abscesses and aspiration of purulent fluid,
approach, both surgeon and first assistant stand on the and it facilitates dissection in obese patients in whom
patients left facing a video monitor positioned on the open appendectomy would be challenging. Use of lapar-
right (Fig. 42-4A).127 The patient is positioned supine on oscopy has been associated with a higher negative appen-
the operating table, and the abdomen is prepped widely. dectomy rate.134 However, this discrepancy may be
After insertion of a 1012mm umbilical cannula, pneu- explained by the increased use of diagnostic laparoscopy
moperitoneum is established. Two 5mm ports are then in patients whose diagnosis is not clear, specifically
placed, one in the left lower quadrant and one in the left teenage females who may have gynecologic findings.
suprapubic area (Fig 42-4B). A 5mm 30 or 45 telescope Open appendectomy may be easier in younger patients
is introduced through the left lower quadrant port, and due to lack of space in the peritoneal cavity relative to
the other two ports are the working ports. This allows the size of the laparoscopic instruments.
effective triangulation of instruments to maximize utility The use of laparoscopy has increased from about 20%
in a small space, a core principle of endoscopic surgery. in 1998 to 70% in 2007.135137 In the past decade, there
Diagnostic laparoscopy is initially performed. If present, have been multiple prospective randomized trials, large
abscesses are opened and purulent fluid is aspirated from retrospective studies, and meta-analyses comparing out-
the pelvis, perihepatic space and paracolic gutters. The comes in open versus the laparoscopic approach. While
appendix is located by following the taenia of the cecum early studies found increased operating times for lapar-
inferiorly. After grasping the appendix and retracting it oscopy, more recent studies have shown no difference in
inferiorly, a window is created in the mesoappendix close length of operation.138142 A few studies actually demon-
to the cecum. The endoscopic stapler is inserted through strated shorter operating times with laparoscopy.139140
A B
FIGURE 42-4 (A) Port positions for a laparoscopic appendectomy. Typically three cannulas are used, with the endoscopic stapler
introduced through the 12mm umbilical port. The appendix is removed through this site as well. (B) Postoperative appearance.
574 SECTION IV Abdomen
A B
FIGURE 42-5 (A) Initially, a window is made in the mesoappendix. (B) Usually, the appendix is ligated and divided with the stapler
first, followed by ligation/division of the mesoappendix.
A B C
FIGURE 42-7 This 10-year-old underwent a transumbilical laparoscopic-assisted appendectomy. (A) A 5mm reusable cannula was
introduced in the cephalad aspect of the umbilical fascia followed by insertion of a 5mm grasping forceps inferior to the cannula
for mobilization of the cecum and appendix..(B) Close-up view of the separate fascial incisions for introduction of the cannula and
instrument. Note the fascial bridge between the instrument and the cannula. This bridge prevents escape of CO2 around the instru-
ments. (C) Following mobilization of the cecum and appendix, an extracorporeal appendectomy was then performed.
laparoscopic appendectomy (SILA), a single transumbili- 5. Wangensteen OH, Dennis C. Experimental proof of obstructive
cal incision is made and a 5mm or 12mm port is placed. origin of appendicitis. Ann Surg 1939;110:62947.
6. Curran TJ, Meunchow SK. The treatment of complicated appen-
One or two additional ports are placed through the same dicitis in children using peritoneal drainage: Results from a public
incision using multi-port devices or separate fascial inci- hospital. J Pediatr Surg 1993;28:2048.
sions. Subsequent dissection and appendectomy are iden- 7. Stringel G. Appendicitis in children: A systematic approach for a
tical to the traditional three-port procedure. Advantages low incidence of complications. Am J Surg 1987;154:6315.
8. Jones BA, Demetriades D, Segal I. The prevalence of appendiceal
of this technique are thought to be shorter length of fecoliths in patients with and without appendicitis: A comparative
hospitalization, better cosmesis, and lower hospital costs. study from Canada and South Africa. Ann Surg 1985;202:
Technically the procedure can be more challenging as 802.
close approximation of instruments limits range of motion 9. Burkitt DP. The aetiology of appendicitis. Br J Surg 1971;58:
and narrows the visual field.172 Theoretically a larger 6959.
10. Attwood SE, Mealy K, Cafferkey MT, et al. Yersinia infection and
fascial incision may result in increased postoperative pain acute abdominal pain. Lancet 1987;1:52933.
and higher rates of incisional hernias although prelimi- 11. Rabau MY, Avigad I, Wolfstein I. Rubella and acute appendicitis.
nary evidence is limited. Hybrid procedures such as Pediatrics 1980;66:813.
laparoscopic-assisted single-port appendectomy (SPA) 12. Rodgers B, Karn G. Yersinia enterocolitis. J Pediatr Surg
1975;10:4979.
and transumbilical laparoscopic-assisted appendectomy 13. Sanders DY, Cort CR, Stubbs AJ. Shigellosis associated with
(TULAA) are other described techniques that combine a appendicitis. J Pediatr Surg 1972;7:31517.
laparoscopic single-incision approach for dissection fol- 14. Adebamowo CA, Akang EE, Ladipo JK, et al. Schistosomiasis of
lowed by extracorporeal removal of the appendix through the appendix. Br J Surg 1991;78:121921.
the umbilicus as in the traditional open procedure 15. Nadler S, Cappell MS, Bhatt B, et al. Appendiceal infection by
Entamoeba histolytica and Strongyloides stercoralis presenting
(Fig. 42-7). Early retrospective reviews have shown no like acute appendicitis. Dig Dis Sci 1990;35:6038.
difference in postoperative complication rates and similar 16. Schnell VL, Yandell R, Van Zandt S, et al. Enterobius vermicularis
or even decreased hospital costs when compared to open salpingitis: A distant episode from precipitating appendicitis.
and other laparoscopic techniques.167,168,170 A recent Obstet Gynecol 1992;80:5535.
17. Kwong MS, Dinner M. Neonatal appendicitis masquerading as
prospective randomized trial comparing single site to necrotizing enterocolitis. J Pediatr 1980;96:91718.
traditional three-port appendectomy in patients with 18. Valerdiz-Casasola S, Pardo-Mindan FJ. Cytomegalovirus infec-
nonperforated appendicitis demonstrated no difference tion of the appendix in patient with the acquired immunodefi-
in postoperative wound infection or abscess rates, length ciency syndrome. Gastroenterology 1991;101:247.
of hospital stay, or hospital charges.164 This particular 19. Coughlin JP, Gauderer MW, Stern RC, et al. The spectrum of
appendiceal disease in cystic fibrosis. J Pediatr Surg 1990;25:
study found a longer operative time (in minutes) for the 8359.
single-incision approach, but this was not clinically 20. Martin LW, Perrin EV. Neonatal perforation of the appendix in
relevant. association with Hirschsprungs disease. Ann Surg 1967;166:
799802.
21. Stiefel D, Stallmach T, Sacher P. Acute appendicitis in neonates:
REFERENCES Complication or morbus sui generis? Pediatr Surg Int 1998;14:
1. Sivit CJ, Siegel MJ, Applegate KE, et al. When appendicitis is 1223.
suspected in children. RadioGraphics 2001;21:24762. 22. Heller MB, Skolnick LM. Ultrasound documentation of sponta-
2. Wagner JM, McKinney WP, Carpenter JL. Does this patient have neously resolving appendicitis. Am J Emerg Med 1993;11:513.
appendicitis? JAMA 1996;276:158994. 23. Mattei P, Sola JE, Yeo CJ. Chronic and recurrent appendicitis are
3. Chen C, Botelho C, Cooper A, et al. Current practice patterns in uncommon entities often misdiagnosed. J Am Coll Surg
the treatment of perforated appendicitis in children. J Am Coll 1994;178:3859.
Surg 2003;196:21221. 24. Lee SL, Stark R, Yaghoubian A, et al. Does age affect the out-
4. van Zwalenburg C. The relation of mechanical distention to the comes and management of pediatric appendicitis? J Pediatr Surg
etiology of appendicitis. Ann Surg 1905;41:43750. 2011;46:23425.
576 SECTION IV Abdomen
25. Nance ML, Adamson WT, Hedrick HL. Appendicitis in the 51. Yacoe ME, Jeffrey RB. Sonography of appendicitis and diverticu-
young child: A continuing diagnostic challenge. Pediatr Emerg litis. Radiol Clin North Am 1994;32:899912.
Care 2000;16:1602. 52. Trout AT, Sanchez R, Ladino-Torres MF, et al. A critical evalua-
26. Jablonski KA, Guagliardo MF. Pediatric appendicitis rupture rate: tion of ultrasound for the diagnosis of pediatric acute appendicitis
A national indicator of disparities in healthcare access. Popul in a real-life setting: How can we improve the diagnostic
Health Metr 2005;3:49. value of sonography? Pediatr Radiol 2012; March 9 Online
27. Ponsky TA, Huang ZJ, Kittle K, et al. Hospital- and patient-level Springer-Verlag.
characteristics and the risk of appendiceal rupture and negative 53. Weyant MJ, Eachempati SR, Maluccio MA, et al. Is imaging
appendectomy in children. JAMA 2004;292:197782. necessary for the diagnosis of acute appendicitis. Adv Surg
28. Gadmonski A, Jenkins P. Ruptured appendicitis among children 2003;37:32745.
as an indicator of access to care. Health Serv Res 2001;36: 54. Sivit CJ, Applegate KE. Imaging of acute appendicitis in children.
12942. Semin Ultrasound CT MR 2003;24:7482.
29. Guagliardo MF, Teach SJ, Huang ZJ, et al. Racial and ethnic 55. Jaremko JL, Crockett A, Rucker D, et al. Incidence and signifi-
disparities in pediatric appendicitis rupture rate. Acad Emerg Med cance of inconclusive results in ultrasound for appendicitis in
2003;10:121827. children and teenagers. Can Assoc Radiol, 2011;62:197202.
30. Lee SL, Shekherdimian S, Chiu VY, et al. Perforated appendicitis 56. Chen SC, Chen KM, Wang SM, et al. Abdominal sonography
in children: Equal access to care eliminates racial and socioeco- screening of clinically diagnosed or suspected appendicitis before
nomic disparities. J Pediatr Surg 2010;45:12037. surgery. World J Surg 1998;22:44952.
31. Nwomeh BC, Chisolm DJ, Caniano DA, et al. Racial and socio- 57. Horton MD, Counter SF, Florence MG, et al. A prospective
economic disparity in perforated appendicitis among children: trial of computed tomography and ultrasonography for diagnos-
Where is the problem? Pediatrics 2006;117:8705. ing appendicitis in the atypical patient. Am J Surg 2000;179:
32. Kwan KY, Nager AL. Diagnosing pediatric appendicitis: 37981.
Usefulness of laboratory markers. Am J Emerg Med 2010;28: 58. Gwynn LK. Appendiceal enlargement as a criterion for clinical
100915. diagnosis of acute appendicitis: Is it reliable and valid? J Emerg
33. Bolton JP, Craven ER, Croft RJ, et al. An assessment of the value Med 2002;23:914.
of the white-cell count in the management of suspected acute 59. Choi D, Park H, Lee YR, et al. The most useful findings for
appendicitis. Br J Surg 1975;62:9068. diagnosing acute appendicitis on contrast-enhanced helical CT.
34. Doraiswany NV. Leucocyte counts in the diagnosis and prognosis Acta Radiol 2003;44:57482.
of acute appendicitis in children. Br J Surg 1979;66:7824. 60. Lowe LH, Penney MW, Stein SM, et al. Unenhanced limited
35. Hoffman J, Rasmussen OO. Aids in the diagnosis of acute appen- CT of the abdomen in the diagnosis of appendicitis in children:
dicitis. Br J Surg 1989;76:7749. Comparison with sonography. AJR Am J Roentgenol 2001;176:
36. Stefanutti G, Ghirado V, Gamba P. Inflammatory markers for 315.
acute appendicitis in children: Are they helpful? J Pediatr Surg 61. Pea BM, Taylor GA, Fishman SJ, et al. Costs and effectiveness
2007;42:7736. of ultrasonography and limited computed tomography for diag-
37. Rothrock SG, Skeoch G, Rush JJ, et al. Clinical features of mis- nosing appendicitis in children. Pediatrics 2000;106:6726.
diagnosed appendicitis in children. Ann Emerg Med 1991;20: 62. Garcia Pea BM, Mandl KD, Kraus SJ, et al. Ultrasonography
4550. and limited computed tomography in the diagnosis and manage-
38. Alvarado A. A practical score for the early diagnosis of acute ment of appendicitis in children. JAMA 1999;282:10416.
appendicitis. Ann Emerg Med 1986;15:55764. 63. Pickuth D, Spielmann RP. Unenhanced spiral CT for evaluating
39. Samuel M. Pediatric appendicitis score. J Pediatr Surg acute appendicitis in daily routine: A prospective study. Hepato-
2002;37:87781. gastroenterology 2001;48:1402.
40. Macklin CP, Radcliffe GS, Merei JM, et al. A prospective evalu- 64. Funaki B, Grosskreutz SR, Funaki CN. Using unenhanced helical
ation of the modified Alvarado score for acute appendicitis in CT with enteric contrast material for suspected appendicitis in
children. Ann R Coll Surg Engl 1997;79:2035. patients treated at a community hospital. AJR Am J Roentgenol
41. McKay R, Shepherd J. The use of the clinical scoring system by 1998;171:9971001.
Alvarado in the decision to perform computed tomography for 65. Weltman DI, Yu J, Krumenacker J Jr, et al. Diagnosis of acute
acute appendicitis in the ED. Am J Emerg Med 2007;25: appendicitis: Comparison of 5- and 10-mm CT sections in the
48993. same patient. Radiology 2000;216:1727.
42. Escriba A, Gamell AM, Fernandez Y, et al. Prospective validation 66. Jacobs JE, Birnbaum BA, Macari M, et al. Acute appendicitis:
of two systems of classification for the diagnosis of acute appen- Comparison of helical CT diagnosis focused technique with oral
dicitis. Pediatr Emer Care 2011;27:1659. contrast material versus nonfocused technique with oral and intra-
43. Rezak A, Hussain MA, Abbas A, et al. Decreased use of computed venous contrast material. Radiology 2001;220:68390.
tomography with a modified clinical scoring system in diagnosis 67. Fraser JD, Aguayo P, Sharp SW, et al. Accuracy of computed
of pediatric acute appendicitis. Arch Surg 2011;146:647. tomography in predicting appendiceal perforation. J Pediatr Surg
44. Smink DS, Finkelstein JA, Kleinman K, et al. The effect of hos- 2010;45:2315.
pital volume of pediatric appendectomies on the misdiagnosis of 68. Brenner DJ. Estimating cancer risks from pediatric CT: Going
appendicitis in children. Pediatrics 2004;113:1823. from the qualitative to the quantitative. Pediatr Radiol 2002;32:
45. Flum DR, Koepsell T. The clinical and economic correlates of 22833.
misdiagnosed appendicitis: Nationwide analysis. Arch Surg 69. Garcia Pena BM, Cook EF, Mandl KD. Selective imaging strate-
2002;137:799804. gies for the diagnosis of appendicitis in children. Pediatrics
46. Newman K, Ponsky T, Kittle K, et al. Appendicitis 2000: Variabil- 2004;113:248.
ity in practice, outcomes, and resource utilization at thirty pedi- 70. Pena BM, Taylor GA, Fishman SJ, et al. Effect of an imaging
atric hospitals. J Pediatr Surg 2003;38:3729. protocol on clinical outcomes among pediatric patients with
47. Smink DS, Finkelstein JA, Garcia Pea BM, et al. Diagnosis of appendicitis. Pediatrics 2002;110:108893.
acute appendicitis in children using a clinical practice guideline. 71. Martin AE, Vollman D, Adler B, et al. CT scans may not reduce
J Pediatr Surg 2004;39:45863. the negative appendectomy rate in children. J Pediatr Surg
48. Bachur RG, Hennelly K, Callahan MJ, et al. Diagnostic imaging 2004;39:88690.
and negative appendectomy rates in children: Effects of age and 72. Linton OW, Mettler FA Jr. National Council on Radiation Pro-
gender. Pediatrics 2012;129:87784. tection and Measurements. National conference on dose reduc-
49. Hayden CK Jr, Kuchelmeister J, Lipscomb TS. Sonography of tion in CT, with an emphasis on pediatric patients. AJR Am J
acute appendicitis in childhood: Perforation versus nonperfora- Roentgenol 2003;181:3219.
tion. J Ultrasound Med 1992;11:20916. 73. Brody AS, Frush DP, Huda W, et al. Radiation risk to children
50. Hahn HB, Hoepner FU, Kalle T, et al. Sonography of acute from computed tomography. Pediatrics 2007;120:67782.
appendicitis in children: 7 years experience. Pediatr Radiol 74. Brennan GD. Pediatric appendicitis: Pathophysiology and appro-
1998;28:14751. priate use of diagnostic imaging. CJEM 2006;8:42532.
42 Appendicitis 577
75. Ware DE, Huda W, Mergo PJ, et al. Radiation effective doses to 97. Yardeni D, Hirschl RB, Drongowski RA, et al. Delayed versus
patients undergoing abdominal CT examinations. Radiology immediate surgery in acute appendicitis: Do we need to operate
1999;210:64550. during the night? J Pediatr Surg 2004;39:4649.
76. Brenner DJ, Elliston CD, Hall EJ, et al. Estimated risks of 98. Stahlfeld K, Hower J, Homitsky S, et al. Is acute appendicitis a
radiation-induced fatal cancer from pediatric CT. Br J Radiol surgical emergency? Am Surg 2007;73:6269.
2008;81:36278. 99. Results of the North American trial of piperacillin/tazobactam
77. Krishnamoorthi R, Ramarajan N, Wang N, et al. Effectiveness of compared with clindamycin and gentamicin in the treatment of
a staged ultrasound and CT protocol for the diagnosis of pediatric severe intra-abdominal infections. Investigators of the Piperacillin/
appendicitis: Reducing radiation exposure in the age of ALARA. Tazobactam Intra-abdominal Infection Study Group. Eur J Surg
Radiology 2011;259:2319. Suppl 1994;573:616.
78. Horman M, Paya K, Eibenberger K, et al. MR imaging in children 100. Nadler EP, Reblock KK, Ford HR, et al. Monotherapy versus
with nonperforated acute appendicitis: Value of unenhanced MR multi-drug therapy for the treatment of perforated appendicitis in
imaging in sonographically selected cases. AJR Am J Roentgenol children. Surg Infect (Larchmt) 2003;4:32733.
1998;171:46770. 101. Maltezou HC, Nikolaidis P, Lebesii E, et al. Piperacillin/
79. Cope Z. Appendicitis and the differential diagnosis of acute tazobactam versus cefotaxime plus metronidazole for treatment of
appendicitis. In: Silen W, editor. Copes Early Diagnosis of children with intra-abdominal infections requiring surgery. Eur J
the Acute Abdomen. New York: Oxford University Press; Clin Microbiol Infect Dis 2001;20:6436.
1991. 102. Lee SL, Islam S, Cassidy LD, et al. Antibiotics and appendicitis
80. Cappendijk VC, Hazebroek FW. The impact of diagnostic delay in the pediatric population: An American Pediatric Surgical Asso-
on the course of acute appendicitis. Arch Dis Child 2000;83: ciation outcomes and clinical trials committee systematic review.
646. J Pediatr Surg 2010;45:21815.
81. Bliss D, McKee J, Cho D, et al. Discordance of the pediatric 103. St Peter SD, Tsao K, Spilde TL, et al. Single daily dosing of
surgeons intraoperative assessment of pediatric appendicitis with ceftriaxone and metronidazole vs. standard triple antibiotic
the pathologists report. J Pediatr Surg 2010;45:1398403. regimen for perforated appendicitis in children: A prospective
82. Ponsky T, Hafi M, Heiss K, et al. Interobserver variation in the randomized trial. J Pediatr Surg 2008;43:9815.
assessment of appendiceal perforation. J Laparoendosc Adv Surg 104. Fraser JD, Aguayo P, Leys CM, et al. A complete course of intra-
Tech A 2009;19(Suppl. 1):S1518. venous antibiotics vs a combination of intravenous and oral anti-
83. St Peter SD, Sharp SW, Holcomb GW, et al. An evidence-based biotics for perforated appendicitis in children: A prospective,
definition for perforated appendicitis derived from a prospective randomized trial. J Pediatr Surg 2010;45:1198202.
randomized trial. J Pediatr Surg 2008;43:22425. 105. Henry MC, Walker A, Silverman BL, et al. Risk factors for the
84. Emil S, Gaied F, Lo A, et al. Gangrenous appendicitis in children: development of abdominal abscess following operation for perfo-
A prospective evaluation of definition, bacteriology, histopathol- rated appendicitis in children: A multicenter case-control study.
ogy, and outcomes. J Surg Res 2012; Accepted. Arch Surg 2007;142:23641.
85. Nadler EP, Gaines BA. Therapeutic Agents Committee of the 106. Kogut KA, Blakely ML, Schropp KP, et al. The association of
Surgical Infection Society: The Surgical Infection Society guide- elevated percent bands on admission with failure and complica-
lines on antimicrobial therapy for children with appendicitis. Surg tions of interval appendectomy. J Pediatr Surg 2001;36:1658.
Infect (Larchmt) 2008;9:7583. 107. Aprahamian CJ, Barnhart DC, Bledsoe SE, et al. Failure in the
86. Andersen BR, Kallehave FL, Andersen HK. Antibiotics versus nonoperative management of pediatric ruptured appendicitis: pre-
placebo for prevention of postoperative complications after dictors and consequences. J Pediatr Surg 2007;42:9348.
appendicectomy. Cochrane Database of Systematic Reviews 2005, 108. Levin T, Whyte C, Borzykowski R, et al. Nonoperative manage-
Issue 3. Art. No.: CD001439. DOI: 10.1002/14651858.CD001439. ment of perforated appendicitis in children: Can CT predict
pub2. outcome? Pediatr Radiol 2007;37:2515.
87. Mui LM, Ng CS, Wong SK, et al. Optimum duration of prophy- 109. Simillis C, Symeonides P, Shorthouse AJ, et al. A meta-analysis
lactic antibiotics in acute non-perforated appendicitis. Aust NZ J comparing conservative treatment versus acute appendectomy for
Surg 2005;75:4258. complicated appendicitis (abscess or phlegmon). Surgery 2010;
88. Eriksson S, Granstrm L. Randomized controlled trial of appen- 147:81829.
dicectomy versus antibiotic therapy for acute appendicitis. Br J 110. Ein SH, Shandling B. Is interval appendectomy necessary
Surg 1995;82:1669. after rupture of an appendiceal mass? J Pediatr Surg 1996;31:
89. Struyd J, Eriksson S, Nilsson I, et al. Appendectomy versus 84950.
antibiotic treatment in acute appendicitis. A prospective multi- 111. Puapong D, Lee SL, Haigh PI, et al. Routine interval appendec-
center randomized controlled trial. World J Surg 2006;30: tomy in children is not indicated. J Pediatr Surg 2007;42:
10337. 15003.
90. Hansson J, Krner U, Khorram-Manesh A, et al. Randomized 112. Hall NJ, Jones CE, Eaton S, et al. Is interval appendectomy justi-
clinical trial of antibiotic therapy versus appendicectomy as fied after successful nonoperative treatment of an appendix mass
primary treatment of acute appendicitis in unselected patients. Br in children? A systematic review. J Pediatr Surg 2011;46:767
J Surg 2009;96:47381. 71.
91. Vons C, Barry C, Maitre S, et al. Amoxicillin plus clavulanic acid 113. Gahukamble DB, Gahukamble LD. Surgical and pathological
versus appendectomy for treatment of acute uncomplicated basis for interval appendectomy after resolution of appendicular
appendicitis: An open-label, non-inferiority, randomised control- mass in children. J Pediatr Surg 2000;35:4247.
led trial. Lancet 2011;377(9777):15739. 114. Mazziotti MV, Marley EF, Winthrop AL, et al. Histopathologic
92. Wilms IM, de Hoog DE, de Visser DC, et al. Appendectomy analysis of interval appendectomy specimens: Support for the role
versus antibiotic treatment for acute appendicitis. Cochrane Data- of interval appendectomy. J Pediatr Surg 1997;32:8069.
base Syst Rev 2011;(11):CD008359. 115. Janik JS, Ein SH, Shandling B, et al. Nonsurgical management of
93. Varadhan KK, Neal KR, Lobo DN. Safety and efficacy of antibi- appendiceal mass in late presenting children. J Pediatr Surg
otics compared with appendicectomy for treatment of uncompli- 1980;15:5746.
cated acute appendicitis: Meta-analysis of randomized controlled 116. Muehlstedt SG, Pham TQ, Schmeling DJ. The management of
trials. BMJ 2012;344:e2156 doi: 10.1136/bmj.e2156. pediatric appendicitis: A survey of North American Pediatric Sur-
94. Liu K, Ahanchi S, Pisaneschi M, et al. Can acute appendicitis be geons. J Pediatr Surg 2004;39:8759.
treated by antibiotics alone? Am Surg 2007;73:11615. 117. Morrow SE, Newman KD. Current management of appendicitis.
95. Friedell ML, Perez-Izquierdo M. Is there a role for interval Semin Pediatr Surg 2007;16:3440.
appendectomy in the management of acute appendicitis? Am Surg 118. Owen A, Moore O, Marven S, et al. Interval laparoscopic appen-
2000;66:115862. dectomy in children. J Laparoendosc Adv Surg Tech 2006;
96. Surana R, Quinn F, Puri P. Is it necessary to perform appendec- 16:30811.
tomy in the middle of the night in children? BMJ 1993;306: 119. Weiner DZ, Katz A, Hirschl RB, et al. Interval appendectomy in
1168. perforated appendicitis. Pediatr Surg Int 1995;10:825.
578 SECTION IV Abdomen
120. St Peter SD, Aguayo P, Fraser JD, et al. Initial laparoscopic appen- 144. Taqi E, Hadher SA, Ryckman J, et al. Outcome of laparoscopic
dectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis in children. J Pediatr
appendectomy for perforated appendicitis with abscess: A pro- Surg 2008;43;8935.
spective, randomized trial. J Pediatr Surg 2010;45:23640. 145. Katkhouda N, Mason RJ, Towfigh S, et al. Laparoscopic versus
121. Schurman JV, Cushing CC, Garey CL, et al. Quality of life assess- open appendectomy: A prospective randomized double-blind
ment between laparoscopic appendectomy at presentation and study. Ann Surg 2005;242:43948.
interval appendectomy for perforated appendicitis with abscess: 146. Garey CL, Laituri CA, Little DC, et al. Outcomes of perforated
Analysis of a prospective, randomized trial. J Pediatr Surg appendicitis in obese and non-obese children. J Pediatr Surg
2011;46:11215. 2011;46:23468.
122. Blakely ML, Williams R, Dassinger MS, et al. Early vs. interval 147. Menezes M, Das L, Alagtal M, et al. Laparoscopic appendectomy
appendectomy for children with perforated appendicitis. Arch is recommended for the treatment of complicated appendicitis in
Surg 2011;146:6605. children. Pediatr Surg Int 2008;24:3035.
123. Goh BK, Chui CH, Yap TL, et al. Is early laparoscopic appen- 148. Paterson HM, Qadan M, de Luca SM, et al. Changing trends in
dectomy feasible in children with acute appendicitis presenting surgery for acute appendicitis. Br J Surg 2008;95:3638.
with an appendiceal mass? A prospective study. J Pediatr Surg 149. Khan MN, Fayyad T, Cecil TD, et al. Laparoscopic versus open
2005;40:11347. appendectomy: The risk of postoperative infectious complica-
124. Senapathi PS, Bhattacharya D, Ammori BJ. Early laparoscopic tions. JSLS 2007;11:3637.
appendectomy for appendicular mass. Surg Endosc 2002;16: 150. Lin HF, Wu JM, Tseng LM, et al. Laparoscopic versus open
17835. appendectomy for perforated appendicitis. J Gastrointest Surg
125. Myers AL, Williams RF, Giles K, et al. Hospital cost analysis of 2006;10:90610.
a prospective randomized trial of early vs interval appendectomy 151. Ikeda H, Ishimaru Y, Takayasu H, et al. Laparoscopic versus open
for perforated appendicitis in children. J Am Coll Surg 2012;214: appendectomy in children with uncomplicated and complicated
42734. appendicitis. J Pediatr Surg 2004;39:16805.
126. McBurney C. The incision made in the abdominal wall in cases 152. Guller U, Hervey S, Purves H, et al. Laparoscopic versus open
of appendicitis, with a description of a new method of operating. appendectomy: Outcomes comparison based on a large adminis-
Ann Surg 1894;20:3843. trative database. Ann Surg 2004;239:4352.
127. Semm K. Endoscopic appendectomy. Endoscopy 1983;15: 153. Marzouk M, Khater M, Elsadek M, et al. Laparoscopic versus
5464. open appendectomy: A prospective comparative study of 227
128. Lintula H, Kokki H, Vanamo K, et al. Laparoscopy in children patients. Surg Endosc 2003;17:7214.
with complicated appendicitis. J Pediatr Surg 2002;37:131720. 154. Nadler EP, Reblock KK, Qureshi FG, et al. Laparoscopic appen-
129. Horwitz JR, Custer MD, May BH, et al. Should laparoscopic dectomy in children with perforated appendicitis. J Laparoendosc
appendectomy be avoided for complicated appendicitis in chil- Adv Surg Tech 2006;16:15963.
dren? J Pediatr Surg 1997;32:16013. 155. Fraser JD, Aguayo P, Sharp SW, et al. Physiologic predictors of
130. Eypasch E, Sauerland S, Lefering R, et al. Laparoscopic versus postoperative abscess in children with perforated appendicitis:
open appendectomy: Between evidence and common sense. Dig Subset analysis from a prospective randomized trial. Surgery
Surg 2002;19:51822. 2010;147:72932.
131. Nataraja RM, Teague WJ, Galea J, et al. Comparison of intraab- 156. Yagmurlu A, Vernon A, Barnhart DC, et al. Laparoscopic appen-
dominal abscess formation after laparoscopic and open appendec- dectomy for perforated appendicitis: A comparison with open
tomies in children. J Pediatr Surg 2012;47:31721. appendectomy. Surg Endosc 2006;20:10514.
132. Varela JE, Hinojosa MW, Nguyen NT. Laparoscopy should be 157. Bilik R, Burnweit C, Shandling B. Is abdominal cavity culture of
the approach of choice for acute appendicitis in the morbidly any value in appendicitis? Am J Surg 1998;175:26770.
obese. Am J Surg 2008;196:21822. 158. Kokoska ER, Silen ML, Tracy TF, et al. The impact of intraopera-
133. Corneille MG, Steigelman MB, Myers JG, et al. Laparoscopic tive culture on treatment and outcome in children with perforated
appendectomy is superior to open appendectomy in obese patients. appendicitis. J Pediatr Surg 1999;34:74953.
Am J Surg 2007;194:87780. 159. Sherman JO, Luck SR, Borger JA. Irrigation of the peritoneal
134. Esposito C, Borzi P, Valla JS, et al. Laparoscopic versus open cavity for appendicitis in children: A double-blind study. J Pediatr
appendectomy in children: A retrospective comparative study of Surg 1976;11:3714.
2,332 cases. World J Surg 2007;31:7505. 160. Kokoska ER, Silen ML, Tracy TF, et al. Perforated appendicitis
135. Jen HC, Shew SB. Laparoscopic versus open appendectomy in in children: Risk factors for the development of complications.
children: Outcomes comparison based on a statewide analysis. Surgery 1998;124:61925.
J Surg Res 2010;161:1317. 161. David IB, Buck JR, Filler RM. Rational use of antibiotics for
136. Lee SL, Yaghoubian A, Kaji A. Laparoscopic versus open appen- perforated appendicitis in childhood. J Pediatr Surg 1982;17:
dectomy in children: Outcomes comparison based on age, sex, and 494500.
perforation status. Arch Surg 2011;146:111821. 162. Kaselas C, Molinaro F, Lacreuse I, et al. Postoperative bowel
137. Masoomi H, Mills S, Dolich MO, et al. Comparison of outcomes obstruction after laparoscopic appendectomy in children: A
of laparoscopic versus open appendectomy in children: Data from 15-year experience. J Pediatr Surg 2009;44:15815.
the nationwide inpatient sample (NIS), 20062008. World J Surg 163. Tsao KJ, St Peter SD, Valusek PA, et al. Adhesive small bowel
2012;36:5738. obstruction after appendectomy in children: Comparison between
138. Aziz O, Athanasiou T, Tekkis PP, et al. Laparoscopic versus open the laparoscopic and open approach. J Pediatr Surg 2007;42:
appendectomy in children: A meta-analysis. Ann Surg 93942.
2006;243:1727. 164. St Peter SD, Adibe OO, Juang D, et al. Single incision versus
139. Yau KK, Siu WT, Tang CN, et al. Laparoscopic versus open standard 3-port laparoscopic appendectomy: A prospective rand-
appendectomy for complicated appendicitis. J Am Coll Surg omized trial. Ann Surg 2011;254:58690.
2007;205:605. 165. Langness SM, Hill SJ, Wulkan ML. Single-site laparoscopic
140. Olmi S, Magnone S, Bertolini A, et al. Laparoscopic versus open appendectomy: A comparison to traditional laparoscopic tech-
appendectomy in acute appendicitis: A randomized prospective nique in children. Am Surg 2011;77:9614.
study. Surg Endosc 2005;19:11935. 166. Muensterer OJ, Puga Nouges C, Adibe OO, et al. Appendectomy
141. Moberg AC, Berndsen F, Palmquist I, et al. Randomized clinical using single-incision pediatric endosurgery for acute and perfo-
trial of laparoscopic versus open appendicectomy for confirmed rated appendicitis. Surg Endosc 2010;24:32014.
appendicitis. Br J Surg 2005;92:298304. 167. Sesia SB, Haecker FM, Kubiak R, et al. Laparoscopy-assisted
142. Carbonell AM, Burns JM, Lincourt AE, et al. Outcomes of laparo- single-port appendectomy in children: Is the postoperative com-
scopic versus open appendectomy. Am Surg 2004;70:75965. plication rate different? J Laparoendosc Adv Surg Tech 2010;20:
143. Sauerland S, Jaschinski T, Neugebauer EA. Laparoscopic versus 86771.
open surgery for suspected appendicitis. Cochrane Databse Syst 168. Shekherdimian S, DeUgarte D. Transumbilical laparoscopic-
Rev 2010:CD001546. assisted appendectomy: An extracorporeal single-incision
42 Appendicitis 579
alternative to conventional laparoscopic techniques. Am Surg invasive technique in pediatric patients. J Laparoendosc Adv Surg
2011;77:55760. Tech 2010;20:8736.
169. Guana R, Gesmundo R, Maiullari E, et al. Treatment of acute 171. Ohno Y, Morimura T, Hayashi S. Transumbilical laparoscopically
appendicitis with one-port transumbilical laparoscopic appendec- assisted appendectomy in children: The results of a single-port,
tomy: A six-year, single-centre experience. Afr J Paediatr Surg single-channel procedure. Surg Endosc 2012;26:5237.
2010;7:16973. 172. Garey CL, Laituri CA, Ostlie DJ, et al. A review of single site
170. Stanfill AB, Matinsky DK, Kalvakuri K, et al. Transumbilical minimally invasive surgery in infants and children. Pediatr Surg
laparoscopically assisted appendectomy: An alternative minimally Int 2010;26:4516.
C H A P T E R 4 3
Biliary Atresia
Atsuyuki Yamataka Joel Cazares Takeshi Miyano
Biliary atresia is a relatively rare obstructive condition of pediatric surgeons around the world is that hepatic por-
the bile ducts causing neonatal jaundice. There is a vari- toenterostomy is the most reasonable first choice.
able incidence around the world (eg, Europe, 1 in 18,000 Recently, the authors had an opportunity to review an
live births; France, 1 in 19,500 live births; the UK and original video of Professor Kasai performing his own
Ireland, 1 in 16,700 live births; Sweden, 1 in 14,000 live portoenterostomy.27 Interestingly, his original portal dis-
births; and Japan, 1 in 9640 live births),16 with the highest section was actually quite shallow and limited, resulting
recorded incidence in French Polynesia (1 in 3124 live in a narrow portoenterostomy anastomosis, with sutures
births).7 There is a slight female predominance. placed shallowly at 2 and 10 oclock where the native
Biliary atresia first appeared as a distinct entity in the right and left bile ducts would have been, probably to
Edinburgh Medical Journal in 1891.8 The concept of minimize microscopic bile duct injury. Although not sup-
correctable and noncorrectable forms was introduced ported by research, the original technique as performed
in 1916.9 Despite the first successful surgical treatment by Kasai may result in superior outcomes as it focuses
for the correctable type being reported in 1928, there specifically on the physiologic and anatomic characteris-
were only a few long-term survivors over the next three tics of the liver in biliary atresia. The authors currently
decades, all with the correctable type.1012 perform a modified version of Kasais original portoen-
In the 1950s and 60s, a variety of procedures for non- terostomy (KOPE) using the minimally invasive approach.
correctable disease were developed, but none provided
consistent biliary decompression.1317 Also, the timing of
operative intervention was controversial, with reports of PATHOGENESIS
spontaneous cures, and second-look explorations for the
rather mystical belief that a totally fibrotic extrahepatic Various etiologic mechanisms for biliary atresia have
ductal system might subsequently become patent.1822 been postulated, including intrauterine or perinatal viral
In 1959, the now common Kasai hepatic portoenter- infection, genetic mutations, abnormal ductal plate
ostomy procedure was first described and ended a long, remodeling, vascular or metabolic insult to the develop-
hopeless era for patients with the noncorrectable-type ing biliary tree, pancreaticobiliary ductal malunion, and
disease.23 Kasais original report was in Japanese and immunologically mediated inflammation. However,
received little attention until it was published in English despite intensive interest and investigation, the cause of
in 1968.24 Although effective bile drainage could be biliary atresia remains unknown and there is no ideal
achieved after portoenterostomy in about 50% of patients, animal model.
early repair was crucial and needed to be performed There are syndromic and nonsyndromic forms of
before the age of 2 months. Conversely, effective bile biliary atresia.28 Syndromic biliary atresia (also known as
drainage was observed in only 7% of patients if correc- the embryonic type) is associated with other congenital
tion was performed after the age of 4 months.25 Kasais anomalies, including interrupted inferior vena cava,
portoenterostomy procedure gradually gained popularity preduodenal portal vein, intestinal malrotation, situs
in the USA, and by the 1990s, more than 90% of infants inversus, cardiac defects, and polysplenia.29 Syndromic
with biliary atresia had undergone this procedure.26 biliary atresia accounts for 1020% of all cases, and is
Since liver transplantation has become a viable treat- likely to be due to a developmental insult occurring
ment option for liver failure in the pediatric population, during differentiation of the hepatic diverticulum from
biliary atresia has become the most common indication the foregut of the embryo. A possible relation between
for liver transplantation in children. Infants whose jaun- syndromic biliary atresia and maternal diabetes has been
dice does not resolve after portoenterostomy, or those reported.28 Nonsyndromic biliary atresia (also known as
with complications associated with end-stage chronic the perinatal type) may have its origins later in gestation,
liver disease related to biliary atresia, will usually require and may have a different clinical course, with biliary
liver transplantation within the first few years of life. obstruction being progressive.
The combination of hepatic portoenterostomy and Reovirus type 3 infection, rotavirus, cytomegalovirus
liver transplantation has transformed a disease that was (CMV), papillomavirus, and EpsteinBarr virus have all
nearly universally fatal in the 1960s into one with an been proposed as possible etiologic agents, but conclusive
overall five-year survival of about 90%. Despite the evidence is lacking. In one report, CMV infection was
debate over whether hepatic portoenterostomy or primary found in four of ten patients with biliary atresia,30 and
liver transplantation should be performed as the initial reovirus infection has been found in the livers of up to
procedure for biliary atresia, the consensus among 55% of biliary atresia patients versus 1020% in a control
580
43 Biliary Atresia 581
group.31 The identification of viruses in children with Interest has also focused on co-stimulatory molecules.
biliary atresia is inconsistent in the literature, and several Two processes are involved in the activation of T lym-
viruses have been used to create animal models that may phocytes by antigen-presenting cells (APC). One relates
be valuable for assessing the pathogenesis and treatment to the expression of major histocompatibility complex
of biliary atresia. class II molecules, which interact directly with T-cell
Generally, biliary atresia is not considered an inherited receptors. The other depends on the expression of B7
disorder. However, genetic mutations that result in defec- antigens on APC, and provides the second (co-stimulatory)
tive morphogenesis may be important in syndromic signal to T-lymphocytes through CD28.44 In postopera-
biliary atresia. Transgenic mice with a recessive deletion tive biliary atresia patients with good liver function,
of the inversin gene have situs inversus and an inter- co-stimulatory antigens (B7-1, B7-2, and CD40) are
rupted extrahepatic biliary tree.32 Mutations of the CFC1 expressed only on bile duct epithelial cells, whereas in
gene, which is involved in leftright axis determination patients with failing livers these markers are found on the
in humans, have been identified in a few patients with surfaces of Kupffer cells, dendritic cells, and sinusoidal
syndromic biliary atresia.33 The importance of the mac- endothelial cells and in the cytoplasm of hepatocytes.45
rophage migration inhibitory factor gene, which is a This suggests that the biliary epithelium and hepato-
pleiotropic lymphocyte and macrophage cytokine in cytes in biliary atresia are susceptible to immune rec-
biliary atresia pathogenesis, has also been reported.34 ognition and destruction. Agents that block or prevent
Other studies have identified abnormalities in laterality co-stimulatory pathways might offer a new therapeutic
genes in a small number of patients with biliary atresia, approach for reducing liver damage.
including the transcription factor ZIC3.35 A high inci- Two studies have involved comprehensive molecular
dence of polymorphic variants in the jagged-1, keratin-8, and cellular surveys of liver biopsies and found a proin-
and keratin-18 genes have also been described in a series flammatory gene expression signature, with increased
of 18 children with biliary atresia.36,37 Taken together, the activation of interferon-, osteopontin, tumor necrosis
increased incidence of nonhepatic anomalies in children factor-, and other inflammatory mediators.46,47 These
with biliary atresia and genetic mutations reported in studies may prove to be helpful in delineating the molec-
subsets of patients with laterality defects suggest that ular networks responsible for the proinflammatory
multiple genes are involved, each affecting a small number response and autoimmunity thought to be involved in the
of patients. pathogenesis of biliary atresia. However, none of these
Intrahepatic bile ducts are derived from primitive mechanisms appears to be mutually exclusive. Moreover,
hepatocytes that form a sleeve (the ductal plate) around it is not clear which signs and symptoms are primary and
the intrahepatic portal vein branches and associated mes- which are secondary.
enchyme early in gestation. Remodeling of the ductal In summary, the etiology of nonsyndromic biliary
plate in fetal life results in the formation of the intrahe- atresia is hypothesized to involve a viral or other toxic
patic biliary system. This is supported by similarities in insult to the bile duct epithelium that induces the expres-
cytokeratin immunostaining between biliary ductules in sion of new antigens on the surfaces of biliary epithelial
biliary atresia and normal first-trimester fetal bile ducts.38 cells.48 Coupled with a genetically predetermined sus-
These findings suggest that nonsyndromic biliary atresia ceptibility that is mediated via histocompatibility anti-
might be caused by a failure of bile duct remodeling at gens, these neoantigens are recognized by circulating
the hepatic hilum, with persistence of fetal bile ducts T-lymphocytes, resulting in an immune cell mediated,
poorly supported by mesenchyme. fibrosclerosing response.
Several studies have investigated whether bile duct
epithelial cells are susceptible to an immune/inflammatory
attack because of abnormal expression of human leuko-
CLASSIFICATION
cyte antigen (HLA) antigens or intracellular adhesion
Biliary atresia can be classified by using macroscopic
molecules on their surfaces.39,40 A greater than threefold
appearance and cholangiography findings into three main
increase in HLA-B12 antigen has been found in babies
categories: atresia of the common bile duct (CBD) (type
with biliary atresia compared with controls, particularly
I), atresia of the common hepatic duct (type IIa) or atresia
in those with no associated malformations.41 Aberrant
of the CBD and the common hepatic duct (type IIb), and
expression of class II HLA-DR antigens on biliary epi-
atresia of all extrahepatic bile ducts up to the porta hepatis
thelial cells and damaged hepatocytes in patients with
(type III) (Fig. 43-1). Most patients have type III. In
biliary atresia may render these tissues more susceptible
patients with a patent CBD and cystic duct (correctable
to immune-mediated damage by cytotoxic T-cells or
type) (5% of cases), the gallbladder can be anastomosed
locally released cytokines.42 Increased expression of inter-
to the porta hepatis, (gallbladder Kasai). In more than
cellular adhesion molecule-1 (ICAM-1) has been noted
90% of cases, however, no patent extrahepatic ductal
on bile duct epithelium in patients with biliary atresia, a
structures are found at the porta hepatis (i.e., noncor-
finding that may play a role in immune-mediated
rectable type).49
damage.40 Strong expression of ICAM-1 also has been
found on proliferating bile ductules, endothelial cells,
and hepatocytes in biliary atresia. A direct relationship HISTOPATHOLOGY
exists between the degree of ductal expression of ICAM-1
and disease severity, suggesting that ICAM-1 might be Early in the course of biliary atresia, the liver becomes
important in the development of cirrhosis.43 enlarged, firm, and green. The gallbladder may be small
582 SECTION IV Abdomen
I IIa
IIb III
It is generally accepted that the pathologic changes
FIGURE 43-1 Morphologic classification of biliary atresia based
on macroscopic and cholangiographic findings. Type I, occlu-
seen in biliary atresia are panductal, affecting the intra-
sion of common bile duct; type IIa, obliteration of common hepatic biliary tree as well as the extrahepatic bile duct
hepatic duct; type IIb, obliteration of common bile duct, hepatic system. Moreover, the intrahepatic bile ducts can be
and cystic ducts, with cystic dilatation of ducts at the porta narrowed, distorted in configuration, or irregular in
hepatis, and no gallbladder involvement; type III, obliteration of shape.5052 However, some authors believe that secondary
common, hepatic, and cystic ducts without anastomosable
ducts at porta hepatis. (From Lefkowitch JH. Biliary atresia. Mayo damage occurs only to the extrahepatic biliary system as
Clin Proc 1998;73:905.) a result of obliteration of extrahepatic bile ducts during
liver formation.53 This theory is strongly supported by
the fact that outcome is better if the portoenterostomy is
performed early.
The intrahepatic biliary tree is important not only
pathologically, but also clinically. The degree of damage
that has already occurred in the intrahepatic biliary
system is actually responsible for much of the morbidity
after hepatic portoenterostomy. Intrahepatic bile duct
proliferation likely results from disturbances in formation
of the ductal plate as well as ductular metaplasia of
hepatocytes.54,55
Certain substances can act as prognostic factors in
biliary atresia. Serum levels of interleukin (IL)-6, IL-1ra,
insulin-like growth factor-1 (IGF-1), vascular cell
adhesion molecule-1 (VCAM-1), and ICAM-1 correlate
with liver dysfunction in postoperative biliary atresia
patients.43,56,57 Immunohistochemically, a reduction in the
expression of CD68 and ICAM-1 at the time of portoen-
FIGURE 43-2 Type III biliary atresia with an enlarged, firm,
green liver and hypoplastic small gallbladder was found in this terostomy is associated with a better prognosis.58 The
infant. presence of ductal plate malformation in the liver pre-
dicts poor bile flow after hepatoportoenterostomy in
infants with biliary atresia.59 Growth failure and poor
and filled with white mucus, or it may be completely mean weight z-scores three months after hepatoportoen-
atretic (Fig. 43-2). Microscopically, the biliary tracts terostomy are also associated with a poor clinical
contain inflammatory and fibrous cells surrounding outcome.60
miniscule ducts, which are probably remnants of the
original embryonic duct system. The liver parenchyma is
fibrotic and shows signs of cholestasis. Proliferation of DIAGNOSIS
biliary neoductules is seen (Fig. 43-3). This process
develops into end-stage cirrhosis if adequate biliary The cardinal signs and symptoms of biliary atresia are
drainage cannot be achieved. These early changes are jaundice, clay-colored stools, and hepatomegaly. However,
often nonspecific and may be confused with neonatal meconium staining is normal in most patients. In the
hepatitis and metabolic diseases. neonatal period, feces are yellow in more than half of
43 Biliary Atresia 583
A B C
FIGURE 43-5 Salient features of three portoenterostomy procedures are depicted. (A) Modified Kasai portoenterostomy: Interrupted
shallow sutures (thin broken lines) are placed in the liver parenchyma around the transected biliary remnant, except at the 2 and
10 oclock positions, where the right and left bile ducts should be. If sutures are necessary at the 2 and 10 oclock positions to
prevent an anastomotic leak, shallow interrupted sutures (thin dotted lines) are placed only in the connective tissue near the right
and left hepatic arteries or the hepatoduodenal ligament at the porta hepatis. (B) Kasais original portoenterostomy:23,25 A continuous
suture (looped line) is placed in the side of the transected biliary remnant, except at the 2 and 10 oclock positions, where sutures
(dotted lines) are placed in the connective tissue. (C) Extended portoenterostomy: Deep interrupted sutures (bold broken lines) are
placed in the liver parenchyma, even at the 2 and 10 oclock positions. (From Nakamura H, Koga H, Wada M, etal. Reappraising the
portoenterostomy procedure according to sound physiological/anatomic principles enhances postoperative jaundice clearance in biliary
atresia. Pediatr Surg 2012;28:205; and From Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary atresia and choledochal cyst.
Sem Pediatr Surg 2012;21:201.)
OPERATIVE MANAGEMENT
Open Surgical Technique
Prior to operative exploration, daily doses of vitamin K FIGURE 43-6 Intraoperative cholangiogram, type III biliary
should be given for several days, and broad-spectrum atresia. Note the almost atretic common bile duct (arrow).
antibiotics are administered preoperatively.
The portoenterostomy procedure for biliary atresia
has been repeatedly modified to achieve better rates of into the gallbladder through a small cholecystotomy inci-
jaundice clearance and survival, and hardly resembles sion. If bile is detected on aspiration from the gallbladder,
Kasais original portoenterostomy (Fig. 43-5B). The a small amount of contrast material is injected. However,
current favored technique involves an extended lateral in most patients with biliary atresia, the lumen of the
dissection around the porta hepatis with a very wide atrophic gall bladder is already obstructed, and it is
anastomosis (extended portoenterostomy, or EPE) impossible to insert even a 4 French catheter. Thus,
(Fig. 43-5C).80,81 cholangiography cannot be performed. Unless normal
EPE is the most widely used open approach for treat- anatomy of the intrahepatic biliary system can be con-
ing biliary atresia. The patient is placed supine on an firmed, hepatic portoenterostomy is performed.24,82
operating table with the capability for intraoperative The cystic artery is ligated and divided and the gall-
cholangiography. An extended right subcostal incision, bladder is dissected from the liver bed. The mobilized
dividing the muscle layers, is used to expose the inferior gallbladder is used as a guide for locating the fibrous
margin of the liver. After division of the falciform and remnant of the CBD. After the caudal end of the CBD
triangular ligaments, the liver is delivered from the is ligated and divided at the upper border of the duode-
abdominal cavity. This maneuver provides an excellent num, the cephalad portion of the CBD with the gallblad-
operative field for dissection of the porta hepatis. Cholan- der attached is dissected above the bifurcation of the
giography is recommended to identify the anatomy (Fig. portal vein. The portal vein and the hepatic arteries are
43-6). The fundus of the gallbladder is mobilized from exposed along their entire course. For better portal dis-
the liver bed, and a 46 French feeding tube is passed section, the right and left hepatic arteries and the right
43 Biliary Atresia 585
and left portal branches are individually encircled with fibrous cone is sharply transected at the level of the pos-
vessel loops (Fig. 43-7A). The hepatic ducts usually form terior surface of the portal vein with scissors or a scalpel,
a cone-shaped fibrous mass anterior to the bifurcation of and is removed. The fibrous cone should have an exten-
the portal vein. Several small vessels connecting the sive transected surface that allows a wide anastomosis. In
portal vein to the fibrous cone are divided after being other words, in EPE, dissection of the porta hepatis is
ligated. The posterior aspect of the fibrous cone is freed not confined just to the area around the base of the
completely. The anterior aspect of the fibrous cone and fibrous ductal plate.83,84 As much of the transected hilar
the quadrate lobe of the liver are then exposed. The surface as possible, including all potentially usable rem-
fibrous biliary plate should be dissected as far as the nants of the intrahepatic ducts in the area between and
entrance of the anterior branch of the right hepatic artery beneath the branches of the right and left portal veins, is
on the right side and as far left as the entrance of the incorporated in the anastomosis. Also, the right and left
obliterated umbilical vein into the left portal vein. The portal veins and hepatic arteries must be retracted to
C
FIGURE 43-7 The current favored technique for a portoenterostomy involves an extended lateral dissection around the porta hepatis
with a very wide anastomosis. (A) Photograph of the initial mobilization of the gallbladder and atretic bile ducts and dissection/
exposure of the porta hepatis. After the common bile duct remnants are severed from the duodenal side, the dissection proceeds
cephalad and the portal bile duct remnants are freed from the underlying structures. The portal vein and hepatic artery have been
encircled with vessel loops. Several small vessel branches between the portal vein to the fibrous remnant can be identified and
divided between ligatures. (B) The portal bile duct remnants must be dissected 5 or 6mm proximal to the anterior branch of the
right hepatic artery on the right side and as far left as the entrance of the obliterated umbilical vein into the left portal vein. The
fibrous cone is sharply transected at the level of the posterior surface with scissors or a scalpel, and is removed. The fibrous cone
should have an extensive transected surface, which allows a wide anastomosis. (C) The end of the Roux-en-Y limb is anastamosed
around the transected end of the fibrous remnant. Sutures should not be placed into the transected surface of the bile duct remnant,
because minute bile ducts may be present. As much of the transected hilar surface as possible, including all potentially usable
remnants of the intrahepatic ducts in the area between and beneath the branches of the right and left portal veins, is incorporated
in the anastomosis. It is important to retract the right and left portal veins and hepatic arteries to allow extensive reception of the
biliary remnant and a wide portoenterostomy.
586 SECTION IV Abdomen
the Roux limb is customized by measuring it to reach just cholagog (usually dehydrocholic acid) is begun on day 2
above the xiphoid process (Fig. 43-8). The Roux limb after portoenterostomy and continued until jaundice
tends to be shorter than with the open approach. The clears. Oral choleretics such as ursodeoxycholic acid or
jejuno-jejunostomy is performed extracorporeally. The aminoethylsulfonic acid are administered once oral
portoenterostomy is then performed as described using feeding is started and continued thereafter.
the M-KOPE technique.
Hepatopulmonary Syndrome
Diffuse intrapulmonary shunting can occur as a compli-
* cation of chronic liver disease in children with biliary
atresia. This shunting is likely a result of vasoactive com-
pounds from the mesenteric circulation that are not deac-
tivated in the liver. This syndrome is characterized by
cyanosis, dyspnea on exertion, hypoxia, and finger club-
bing. It appears to be more prevalent in children with
syndromic biliary atresia. The diagnosis is confirmed by
using a combination of arterial blood gas analysis with
and without inspired oxygen, radionuclide lung scans
FIGURE 43-9 CT scan of a 20-year-old woman in whom severe with macroaggregated albumin to quantify the degree of
portal hypertension developed. Note marked atrophy of the left shunting, and contrast bubble echocardiography. This
lobe of the liver, severe splenomegaly, and varices (asterisk) complication is progressive and can usually be reversed
around the stomach.
by liver transplantation. Pulmonary hypertension is an
uncommon complication, but can also develop in long-
ominous sign, and parents should be encouraged to report term survivors after portoenterostomy.
changes in stool color or signs of cholangitis immediately.
Prompt re-establishment of bile flow is imperative to Hepatic Malignancy
avoid liver damage. If bile flow ceases, a corticosteroid
pulse is given as corticosteroids both augment bile flow Rarely, malignant changes (hepatocellular carcinoma or
and reduce inflammation.106,107 If bile flow is re-established, cholangiocarcinoma) complicate long- standing biliary
then the corticosteroid dose is reduced. If bile flow is not cirrhosis after portoenterostomy. A case of hepatocellular
re-established, the corticosteroids are stopped. If bile flow carcinoma has been reported in a 19-year-old post-Kasai
was initially good, it is reasonable to consider reoperation male biliary atresia patient, indicating the need for a high
in selected cases. However, multiple attempts at reopera- index of suspicion for the development of carcinoma,
tion generally increase the technical difficulty of subse- even in young patients.115
quent transplantation.
Other Complications
Portal Hypertension Due to the presence of residual hepatic disease, metabolic
Portal hypertension is common after portoenterostomy, problems associated with malabsorption of fat, protein,
even in infants with good bile flow. The basic inflamma- vitamins, and trace minerals can occur postoperatively
tory process affecting the extrahepatic ducts also damages because of impairment of bile flow to the gut.116,117
the intrahepatic branches. Persistent hepatic fibrosis has Weight gain after portoenterostomy may be retarded if
been found in some children despite successful portoen- hepatic dysfunction persists. Essential fatty acid deficien-
terostomy.113 Clinical manifestations of portal hyperten- cies and rickets are common problems related to meta-
sion include esophageal varices, hypersplenism, and bolic derangements.118 Long-term monitoring of clinical
ascites (Fig. 43-9). Over time, the susceptibility to com-
plications from portal hypertension seems to decrease,
resulting in reduced frequency and severity of variceal
bleeding. This observation is difficult to explain and may
be related to improvement in hepatic histology or
the development of spontaneous portosystemic shunts.
This observation justifies a nonsurgical approach to the
portal hypertension as long as hepatic function is pre-
served (i.e., the patient remains anicteric with no coagu-
lopathy and normal serum albumin level). However, in
the presence of poor hepatic function, complications
from portal hypertension are an indication for liver
transplantation.
Intrahepatic Cysts
Biliary cysts, or lakes, can develop within the livers of
FIGURE 43-10 CT scan of a 17-year-old with biliary atresia.
long-term survivors, and cause recurring attacks of Multiple biliary cysts or lakes have developed within the liver
cholangitis (Fig. 43-10).114 Prolonged antibiotics and of this long-term survivor and caused recurrent attacks of
ursodeoxycholic acid may be helpful in preventing cholangitis.
43 Biliary Atresia 589
symptoms and adequate nutritional supplementation are The presence of microscopic ducts at the hilum is
needed. Ectopic intestinal variceal bleeding and pulmo- somewhat controversial.128,129 Some authors have sug-
nary arteriovenous fistulas are sometimes seen in long- gested that duct size is important, but there is not uni-
term survivors with incomplete relief of impaired liver versal agreement. Types I and II biliary atresia generally
function.119,120 have a good prognosis if treated early. In the more typical
As more postoperative biliary atresia patients are now type III disease, the presence of larger bile ductules at the
reaching adulthood, the issue of pregnancy in females is porta hepatis (>150m in diameter) is associated with a
becoming more common. In nontransplanted corrected better prognosis. The subgroup of infants with syndro-
biliary atresia patients, preterm cesarean delivery at mic biliary atresia have worse outcomes in terms of both
around the 34th week appears to be reasonable because clearance of jaundice and survival.1,28 The latter is related
this is a high risk pregnancy in a patient with poor hepatic to associated malformations (particularly congenital heart
reserve. Conversely, delivery at full term may be possible disease), a predisposition to developing hepatopulmonary
for selected mothers with good liver function.121 syndrome, and possible immune compromise from func-
tional hyposplenism. Personal experience suggests that
infants with concomitant CMV infection fare less well
RESULTS AND PROGNOSIS after a portoenterostomy.
The importance of surgeon experience was shown in
Without question, the Kasai hepatic portoenterostomy a British survey in which patients who underwent por-
has greatly improved outcomes of infants with biliary toenterostomy at centers treating one case per year had
atresia, and the results of surgical treatment have significantly worse outcomes than patients who were
improved steadily over the past 30 years. Classically, the treated at centers performing more than five cases per
major determinants of satisfactory outcome after por- year.130 Since 1999, the management of biliary atresia has
toenterostomy are (1) age at initial operation; (2) success- been centralized to three centers in England and Wales
ful achievement of postoperative bile flow; (3) presence that are able to offer both portoenterostomy and trans-
of microscopic ductal structures at the hilum; (4) the plantation. In 2011, the results of this policy change were
degree of parenchymal disease at diagnosis; and (5) tech- reported, and it was found that outcomes were better
nical factors at the anastomosis. Age at portoenterostomy than previously reported.131 These improved outcomes
is the single most widely quoted prognostic variable. A may be due to centralization of surgical and medical
favorable outcome is expected if the procedure is per- resources.
formed before 60 days of age, because cirrhosis will Recently, outcomes in infants enrolled in the prospec-
develop by 3 to 4 months of age. However, a wide dis- tive Childhood Liver Disease Research and Education
crepancy exists in reported long-term results. One study Network who underwent portoenterostomy were
from Japan found postoperative outcome to be excellent, reported. Liver anatomy, splenic malformation, presence
with a ten-year survival rate of more than 70%, if the of ascites, liver nodularity at portoenterostomy, and early
portoenterostomy was performed before 60 days of age.122 postoperative clearance of jaundice were found to be sig-
However, a nationwide survey of the Surgical Section of nificant predictors of transplant-free survival.132
the American Academy of Pediatrics found that long- Irrespective of age and other factors related to the
term survival was only 25%.26 Other reported 10-year timing of portoenterostomy, a significant decrease in
survival rates include 4050% from the UK and 68% serum bilirubin and signs of good bile excretion in the
from France.1,123 Outcomes are considerably worse if the stool may be predictive of good long-term outcome.133
infant is older than 100 days at the time of portoenteros- Due to the possibility of sudden hepatic deterioration
tomy because obliterative cholangiopathy and hepatic and the constant concern for cholangitis and portal
fibrosis have already developed.123,124 hypertension, recent reports about long-term outcomes
The impact of age at portoenterostomy on long-term in biliary atresia patients consistently emphasize lifelong
outcome, especially in patients with type III biliary follow-up.134,135
atresia, was recently evaluated.125 Age at portoenteros-
tomy was found to have a significant impact on jaundice
clearance, but not on long-term survival in type III biliary LIVER TRANSPLANTATION
atresia, suggesting that age at portoenterostomy might be
less significant as a prognostic factor over time. In another The indications for liver transplantation following
study from Hong Kong, portoenterostomies performed portoenterostomy are: (1) lack of bile drainage; (2) signs
beyond the age of 60 days was not associated with worse of developmental retardation or their sequelae; and
outcome, and a high percentage of patients could still (3) complications/side effects being socially unacceptable.
achieve good bile flow and a normal bilirubin postopera- A high hepatic artery resistance index measured on
tively.126 Of particular interest is a report by Kuroda etal, Doppler ultrasound is an indication for relatively urgent
who reviewed postoperative biliary atresia patients in transplantation.136 Deterioration in hepatic status may be
relation to pregnancy and found that age at portoenter- precipitated by adolescence or pregnancy. However, as
ostomy may not necessarily influence long-term many as 20% of patients undergoing portoenterostomy
outcome.127 However, liver function at puberty may be a will remain healthy and reach adulthood with good liver
useful indicator and may be predictive for the safety of function.
pregnancy. Also, management strategies may need to be The dramatic improvement in survival with the use of
revised accordingly after puberty. cyclosporine and tacrolimus immunosuppression after
590 SECTION IV Abdomen
liver transplantation raises the question of transplanta- 16. Fonkalsrud EW, Kitagawa S, Longmire WP. Hepatic drainage to
tion becoming a more conventional form of treatment the jejunum for congenital biliary atresia. Am J Surg 1966;112:
18894.
for biliary atresia. The donor supply is always a problem, 17. Williams LF, Dooling JA. Thoracic duct-esophagus anastomosis
alleviated to some extent by reduced-size liver transplan- for relief of congenital biliary atresia. Surg Forum 1963;14:
tation. Five-year survival after liver transplantation for 18991.
biliary atresia is currently 8090%, and techniques such 18. Swenson O, Fisher JH. Utilization of cholangiogram during
exploration for biliary atresia. N Engl J Med 1952;249:2478.
as split-liver grafting and living-related liver transplanta- 19. Thaler MM, Gellis SS. Studies in neonatal hepatitis and biliary
tion have decreased waiting times.137 Furthermore, long- atresia: II. The effect of diagnostic laparotomy on long-term
term studies of post-transplant biliary atresia patients prognosis of neonatal hepatitis. Am J Dis Child 1968;116:
have shown that survivors have an acceptable to good 26270.
quality of life.138,139 20. Kanof A, Donovan EJ, Berner H. Congenital atresia of the biliary
system: Delayed development of correctability. Am J Dis Child
A recent study summarized the largest series (n=464) 1953;86:7807.
of postportoenterostomy patients who had undergone 21. Kravetz LJ. Congenital biliary atresia. Surgery 1960;47:
living-related liver transplantation.140 The outcome of 45367.
living-related liver transplantation in adults with biliary 22. Carlson E. Salvage of the non-correctable case of congenital
extrahepatic biliary atresia. Arch Surg 1960;81:8938.
atresia was significantly worse than in infants and chil- 23. Kasai M, Suzuki S. A new operation for non-correctable biliary
dren. The overall five- and ten-year survival rates were atresia: Hepatic portoenterostomy. Shujutu 1959;13:7339.
70% and 56% in adults versus 87% and 81% in pediatric 24. Kasai M, Kimura S, Asakura Y, et al. Surgical treatment of biliary
patients, respectively. On the other hand, there is a report atresia. J Pediatr Surg 1968;3:66575.
concluding that living-related liver transplantation after 25. Kasai M. Treatment of biliary atresia with special reference to
hepatic portoenterostomy and its modification. Progr Pediatr
portoenterostomy can be performed safely in adults with Surg 1974;6:552.
a long-term survival rate equivalent to that for pediatric 26. Karrer FM, Lilly JR, Stewart BA, et al. Biliary atresia registry,
patients.141 Longer immunosuppression might ultimately 19761989. J Pediatr Surg 1990;25:107681.
lead to increased morbidity, including higher rates of 27. Kasai M. Surgery for biliary atresia, Japan Surgical Society Video
library: No.78-07.
cancer, infection, and metabolic diseases later in life. In 28. Perlmutter DH, Shepherd RW. Extrahepatic biliary atresia: A
addition, in living-related liver transplantation, the risk disease or a phenotype? Hepatology 2002;35:1297304.
to the donor is always a concern.142 The optimal timing 29. Davenport M, Savage M, Mowat AP, et al. The biliary atresia
of transplantation in postportoenterostomy patients has splenic malformation syndrome. Surgery 1993;113:6628.
yet to be established. 30. Morecki R, Glaser JH, Cho S, et al. Biliary atresia and reovirus
type 3 infection. N Engl J Med 1984;310:1610.
31. Tyler KL, Sokol RJ, Oberhaus SM, et al. Detection of reovirus
RNA in hepatobiliary tissues from patients with extrahepatic
REFERENCES biliary atresia and choledochal cysts. Hepatology 1998;27:
1. Chardot C, Carton M, Spire-Bendelac N, et al. Prognosis of 147582.
biliary atresia in the era of liver transplantation: French national 32. Mazziotti MV, Willis LK, Heuckeroth RO, et al. Anomalous
study from 1986 to 1996. Hepatology 1999;30:60611. development of the hepatobiliary system in the Inv mouse. Hepa-
2. McKiernan PJ, Baker AJ, Kelly DA. The frequency and tology 1999;30:3728.
outcome of biliary atresia in the UK and Ireland. Lancet 2000;355: 33. Jacquemin E, Cresteil D, Raynaud N, et al. CFC1 gene mutation
259. and biliary atresia with polysplenia syndrome. J Pediatr Gastro-
3. Yoon PW, Bresee JS, Olney RS, et al. Epidemiology of biliary enterol Nutr 2002;34:3267.
atresia: A population-based study. Pediatrics 1997;99:37682. 34. Arikan C, Berdeli A, Ozgenc F, et al. Positive association of
4. Fischler B, Haglund B, Hjern A. A population-based study on the macrophage migration inhibitory factor gene-173G/C polymor-
incidence and possible pre- and perinatal etiologic risk factors of phism with biliary atresia. J Pediatr Gastroenterol Nutr
biliary atresia. J Pediatr 2002;141:21722. 2006;42:7782.
5. Petersen C, Harder D, Abola Z, et al. European biliary atresia 35. Ware SM, Peng J, Zhu L, et al. Identification and functional
registries: Summary of a symposium. Eur J Pediatr Surg 2008;18: analysis of ZIC3 mutations in heterotaxy and related congenital
11116. heart defects. Am J Hum Genet 2004;74:93105.
6. Nio M, Ohi R, Miyano T, et al. Five- and 10-year survival rates 36. Kohsaka T, Yuan ZR, Guo SX, et al. The significance of human
after surgery for biliary atresia: A report from Japanese biliary jagged 1 mutations detected in severe cases of extrahepatic biliary
atresia registry. J Pediatr Surg 2003;38:9971000. atresia. Hepatology 2002;36:90412.
7. Vic P, Gestas P, Mallet EC, et al. Biliary atresia in French Poly- 37. Ku NO, Darling JM, Krams SM, et al. Keratin 8 and 18 mutations
nesia: Retrospective study of 10 years. Arch Pediatr 1994;1: are risk factors for developing liver disease of multiple etiologies.
64651. Proc Natl Acad Sci U S A 2003;13:60638.
8. Thomson J. On congenital obliteration of the bile ducts. Edin- 38. Tan CEL, Driver M, Howard ER, et al. Extrahepatic biliary
burgh Med J 1891;37:52331, 60416, 72435. atresia: A first-trimester event? Clues from light microscopy and
9. Holmes JB. Congenital obliteration of the bile ducts: Diagnosis immunohistochemistry. J Pediatr Surg 1994;29:80814.
and suggestions for treatment. Am J Dis Child 1916;11: 39. Seidman SL, Duquesnoy RJ, Zeevi A, et al. Recognition of major
40531. histocompatibility complex antigens on cultured human biliary
10. Ladd WE. Congenital atresia and stenosis of the bile ducts. JAMA epithelial cells by alloreactive lymphocytes. Hepatology 1991;13:
1928;91:10825. 23946.
11. Bill AH. Biliary atresia. World J Surg 1987;2:5579. 40. Dillon P, Belchis D, Tracy T, et al. Increased expression of inter-
12. Gross RE. The Surgery of Infancy and Children. Philadelphia: cellular adhesion molecules in biliary atresia. Am J Pathol
WB Saunders; 1953. p. 50823. 1994;145:2637.
13. Sterling JA. Experiences with Congenital Biliary Atresia. Spring- 41. Silveira TR, Salzano FM, Donaldson PT, et al. Association
field, IL: Charles C Thomas; 1960. p. 368. between HLA and extrahepatic biliary atresia. J Pediatr Gastro-
14. Potts WJ. The Surgeons and the Child. Philadelphia: WB Saun- enterol Nutr 1993;16:11417.
ders; 1959. p. 13743. 42. Kobayashi H, Puri P, OBrian DS, et al. Hepatic overexpression
15. Longmire WP, Sanford MC. Intrahepatic cholangiojejunostomy of MHC class II antigens and macrophage-associated antigen
with partial hepatectomy for biliary obstruction. Surgery 1948;24: (CD68) in patients with biliary atresia of poor prognosis. J Pediatr
26476. Surg 1997;32:5903.
43 Biliary Atresia 591
43. Kobayashi H, Horikoshi K, Li L, et al. Serum concentration of 70. Park WH, Choi SO, Lee HJ. The ultrasonographic triangular
adhesion molecules in postoperative biliary atresia patients: Rela- cord coupled with gallbladder images in the diagnostic prediction
tionship to disease activity and cirrhosis. J Pediatr Surg 2001;36: of biliary atresia from infantile intrahepatic cholestasis. J Pediatr
1297301. Surg 1999;34:170610.
44. Allison JP. CD28-B7 interactions in T-cell activation. Curr Opin 71. Kotb MA, Kotb A, Sheba MF, et al. Evaluation of the triangular
Immunol 1994;6:41419. cord sign in the diagnosis of biliary atresia. Pediatrics 2001;
45. Kobayashi H, Li Z, Yamataka A, et al. Role of immunologic 108:41620.
co-stimulatory factors in the pathogenesis of biliary atresia. 72. Tan Kendrick AP, Ooi BC, Tan CE. Biliary atresia: Making the
J Pediatr Surg 2003;38:8926. diagnosis by the gallbladder ghost triad. Pediatr Radiol
46. Bezerra JA, Tiao G, Ryckman FC, et al. Genetic induction of 2003;33:31115.
proinflammatory immunity in children with biliary atresia. Lancet 73. Farrant P, Meire HB, Mieli-Vergani G. Ultrasound features of the
2002;23:16539. gallbladder in infants presenting with conjugated hyperbilirubi-
47. Mack CL, Tucker RM, Sokol RJ, et al. Biliary atresia is associated naemia. Br J Radiol 2000;73:11548.
with CD4+ Th1 cell-mediated portal tract inflammation. Pediatr 74. Abramson SJ, Berdon WE, Altman RP, et al. Biliary atresia and
Res 2004;56:7987. noncardiac polysplenia syndrome: Ultrasound and surgical con-
48. Sokol RJ, Mack C. Etiopathogenesis of biliary atresia. Semin sideration. Radiology 1987;163:3779.
Liver Dis 2001;21:51724. 75. Han BK, Babcock DS, Gelfand MM. Choledochal cyst with bile
49. ONeill JA, Rowe MI, Grosfeld JL, et al. Pediatric Surgery. 5th duct dilatation: Sonographic and 99mTc-IDA cholescintigraphy.
ed. St. Louis: MosbyYear Book; 1998. AJR Am J Roentgenol 1981;136:10759.
50. Ito T, Horisawa M, Ando H. Intrahepatic bile ducts in biliary 76. Ochshorn Y, Rosner G, Barel D, et al. Clinical evaluation of
atresia: A possible factor determining the prognosis. J Pediatr isolated nonvisualized fetal gallbladder. Prenat Diagn 2007;
Surg 1983;18:12430. 27:699703.
51. Raweily EA, Gibson AAM, Burt AD. Abnormalities of intrahe- 77. Boughanim M, Benachi A, Dreux S, et al. Nonvisualization of the
patic bile ducts in extrahepatic biliary atresia. Histopathology fetal gallbladder by second-trimester ultrasound scan: Strategy of
1990;17:5217. clinical management based on four examples. Prenat Diagn 2008;
52. Lilly JR, Altman RP. Hepatic portoenterostomy (the Kasai opera- 28:468.
tion) for biliary atresia. Surgery 1975;78:7686. 78. Okazaki T, Miyano G, Yamataka A, et al. Diagnostic laparoscopy-
53. Ohi R, Chiba T, Endo N. Morphologic studies of the liver and assisted cholangiography in infants with prolonged jaundice.
bile ducts in biliary atresia. Acta Paediatr Jpn 1987;29:5849. Pediatr Surg Int 2006;22:1403.
54. Desmet VJ. Intrahepatic bile ducts under the lens. J Hepatol 79. Nwomeh BC, Caniano DA, Hogan M. Definitive exclusion of
1987;1:54559. biliary atresia in infants with cholestatic jaundice: The role of
55. Sherlock S. The syndrome of disappearing intrahepatic bile ducts. percutaneous cholecysto-cholangiography. Pediatr Surg Int 2007;
Lancet 1987;2:4936. 23:8459.
56. Phavichitr N, Theamboonlers A, Poovorawan Y. Insulin-like 80. Nio M, Ohi R. Biliary atresia. Semin Pediatr Surg 2000;9:
growth factor-1 (IGF-1) in children with postoperative biliary 17786.
atresia: A cross-sectional study. Asian Pac J Allergy Immunol 81. Davenport M. Surgery for biliary atresia. In: Spitz L, Coran AG,
2008;26:5761. editors. Operative pediatric surgery. New York: Hodder Arnold;
57. Kobayashi H, Yamataka A, Lane GJ, et al. Levels of circulating 2006. p. 66172.
anti-inflammatory cytokine interleukin-1 receptor antagonist and 82. Miyano T, Fujimoto T, Ohya T, et al. Current concept of the
proinflammatory cytokines at different stages of biliary atresia. treatment of biliary atresia. World J Surg 1993;17:3326.
J Pediatr Surg 2002;37:103841. 83. Kobayashi H, Yamataka A, Urao M, et al. Innovative modification
58. Davenport M, Gonde C, Redkar R, et al. Immunohistochemistry of the hepatic portoenterostomy. Our experience of treating
of the liver and biliary tree in extrahepatic biliary atresia. J Pediatr biliary atresia. J Pediatr Surg 2006;41:1922.
Surg 2001;36:101725. 84. Miyano T, Ohya T, Kimura K, et al. Current state of the treatment
59. Shimadera S, Iwai N, Deguchi E, et al. Significance of ductal plate of congenital biliary atresia (in Japanese). J Jpn Surg Soc
malformation in the postoperative clinical course of biliary atresia. 1989;90:13437.
J Pediatr Surg 2008;43:3047. 85. Kobayashi H, Horikoshi K, Yamataka A, et al. Alpha-glutathione-
60. DeRusso PA, Ye W, Shepherd R, et al. Growth failure and out- S-transferase as a new sensitive marker of hepatocellular damage
comes in infants with biliary atresia: A report from the Biliary in biliary atresia. Pediatr Surg Int 2000;16:3025.
Atresia Research Consortium. Hepatology 2007;46:16328. 86. Kobayashi H, Horikoshi K, Yamataka A, et al. Hyaluronic acid: A
61. Chiba T, Ohi R, Kamiyama T, Nio M, Ibrahim M. Japanese specific prognostic indicator of hepatic damage in biliary atresia.
biliary atresia registry: Biliary atresia. Tokyo: Icom Assoc; J Pediatr Surg 1999;34:17914.
1991. 87. Miyano T, Suruga K, Tsuchiya H, et al. A histopathological study
62. Altman RP, Levy J. Biliary atresia. Pediatr Ann 1985;14:4815. of the remnant of extrahepatic bile duct in so-called uncorrectable
63. Okazaki T, Kobayashi H, Yamataka A, et al. Long-term post surgi- biliary atresia. J Pediatr Surg 1977;12:1925.
cal outcome of biliary atresia. J Pediatr Surg 1998;34:31215. 88. Nakamura H, Koga H, Wada M, et al. Reappraising the portoen-
64. Balistreri WF. Neonatal cholestasis. J Pediatr 1985;106: terostomy procedure according to sound physiological/anatomic
17184. principles enhances postoperative jaundice clearance in biliary
65. Brough H, Houssin D. Conjugated hyperbilirubinemia in early atresia. Pediatr Surg Int 2012;28:2059.
infancy: A reassessment of liver biopsy. Hum Pathol 1974;5: 89. Kasai M. Treatment of biliary atresia with special reference to
50716. hepatic porto-enterostomy and its modifications. Prog Pediatr
66. Javitt NB, Keating JP, Grand RJ, et al. Serum bile acid patterns Surg 1974;6:552.
in neonatal hepatitis and extrahepatic biliary atresia. J Pediatr 90. Kimura K, Tsugawa C, Matsumoto T, et al. The surgical manage-
1977;90:7369. ment of the unusual forms of biliary atresia. J Pediatr Surg
67. Ukarapol N, Wongsawasdi L, Ong-Chai S, et al. Hyaluronic acid: 1979;14:65360.
Additional biochemical marker in the diagnosis of biliary atresia. 91. Nio M, Sano N, Ishii T, et al. Long-term outcome in type I biliary
Pediatr Int 2007;49:60811. atresia. J Pediatr Surg 2006;41:19735.
68. Faweya AG, Akinyinka OO, Sodeinde O. Duodenal 92. Takahashi Y, Matsuura T, Saeki I, et al. Excellent long-term
intubation and aspiration test: Utility in the differential diagnosis outcome of hepaticojejunostomy for biliary atresia with a hilar
of infantile cholestasis. J Pediatr Gastroenterol Nutr 1991;13: cyst. J Pediatr Surg 2009;44:2312315.
2902. 93. Esteves E, Clemente Neto E, Ottaiano Neto M, et al.
69. Azuma T, Nakamura T, Moriuchi T, et al. Preoperative ultrasono- Laparoscopic Kasai portoenterostomy for biliary atresia. Pediatr
graphic diagnosis of biliary atresia with reference to the presence Surg Int 2002;18:73740.
or absence of the extrahepatic bile duct. Paper presented at the 94. Wong KK, Chung PH, Chan KL, et al. Should open Kasai por-
38th Annual Congress of the Japanese Society of Pediatric Sur- toenterostomy be performed for biliary atresia in the era of lapar-
geons. Tokyo, Japan, June 2001. oscopy? Pediatr Surg Int 2008;24:9313.
592 SECTION IV Abdomen
95. Kuebler JF, Kos M, Jesch NK, et al. Carbon dioxide suppresses following surgery for biliary atresia. Trop Gastroenterol 2009;30:
macrophage superoxide anion production independent of extra- 11012.
cellular pH and mitochondrial activity. J Pediatr Surg 2007; 121. Kuroda T, Saeki M, Morikawa N, et al. Biliary atresia and preg-
42:2448. nancy: Puberty may be an important point for predicting the
96. Mogilner JG, Bitterman H, Hayari L, et al. Effect of elevated outcome. J Pediatr Surg 2005;40:18525.
intraabdominal pressure and hyperoxia on portal vein blood flow, 122. Kasai M, Mochizuki I, Ohkohchi N, et al. Surgical limitation for
hepatocyte proliferation and apoptosis in a rat model. Eur J biliary atresia: Indication for liver transplantation. J Pediatr Surg
Pediatr Surg 2008;18:3806. 1989;24:8514.
97. Von Sochaczewski OC, Petersen C, Ure BM, et al. Laparoscopic 123. Davenport M, Kerkar N, Mieli-Vergani G, et al. Biliary atresia:
versus conventional Kasai portoenterostomy does not facilitate The Kings College Hospital experience (19741995). J Pediatr
subsequent liver transplantation in infants with biliary atresia. Surg 1997;32:47985.
J Laparoendosc Adv Surg Tech 2012;22:40811. 124. Chardot C, Carton M, Spire-Bendelac N, et al. Is the Kasai opera-
98. Chan KWE, Lee KH, Mou JWC, et al. The outcome of laparo- tion still indicated in children older than 3 months diagnosed with
scopic portoenterostomy for biliary atresia in children. Pediatr biliary atresia? J Pediatr Surg 2001;138:2248.
Surg Int 2011;27:6714. 125. Nio M, Sasaki H, Wada M, et al. Impact of age at Kasai operation
99. Ure BM, Kueblaer JF, Schukfeh N, et al. Survival with the native on short- and long-term outcomes of type III biliary atresia at a
liver after laparoscopic versus conventional Kasai portoenteros- single institution. J Pediatr Surg 2010;45:23613.
tomy in infants with biliary atresia. A prospective trial. Ann Surg 126. Wong KKY, Chung PHY, Chan IHY, et al. Performing Kasai
2011;253:82630. portoenterostomy beyond 60 days of life is not necessarily associ-
100. Koga H, Miyano G, Takahashi T, et al. Laparoscopic portoenter- ated with a worse outcome. J Pediatr Gastroenterol Nutr
ostomy for uncorrectable biliary atresia using Kasais original 2010;51:6314.
technique. J Laparoendosc Adv Surg Tech A 2011;21:2914. 127. Kuroda T, Saeki M, Morikawa N, et al. Management of adult
101. Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary biliary atresia patients: Should hard work and pregnancy be dis-
atresia and choledochal cyst. Semi Pediatr Surg 2012;21:20110. couraged? J Pediatr Surg 2007;42:21069.
102. Davenport M, Yamataka A. Surgery for biliary atresia. In: Spitz 128. Chandra RS, Altman RP. Ductal remnants in extrahepatic biliary
L, Goran AG, editors. Operative Pediatric Surgery. 7th ed. atresia: A histopathologic study with clinical correlation. J Pediatr
Florida: CRC Press; 2013. p. 65566. Surg 1978;93:196200.
103. Freitas L, Gauthier F, Valayer J. Second operation for repair of 129. Tan EL, Davenport M, Driver M, et al. Does the morphology of
biliary atresia. J Pediatr Surg 1987;22:85760. the extrahepatic biliary remnants in biliary atresia influence sur-
104. Ibrahim M, Ohi R, Chiba T, et al. Indication and Results of vival? A review of 205 cases. J Pediatr Surg 1994;29:145964.
Reoperation for Biliary Atresia. Tokyo: Icom Association; 1991. 130. McClement JW, Howard ER, Mowat AP. Results of surgical treat-
105. Bondoc AJ, Taylor JA, Alonso MH, et al. The beneficial impact ment for extrahepatic biliary atresia in the United Kingdom,
of revision of Kasai portoenterostomy for biliary atresia. Ann Surg 19801982. BMJ 1985;290:3457.
2012;255:5706. 131. Davenport M, Ong E, Sharif K, et al. Biliary atresia in England
106. Muraji T, Higashimoto Y. The improved outlook for biliary and Wales: Results of centralization and new benchmark. J Pediatr
atresia with corticosteroid therapy. J Pediatr Surg 1997;32: Surg 2011;46:168994.
11037. 132. Superina RS, Magee JC, Brandt ML, et al. The anatomic pattern
107. Karrer FM, Lilly JR. Corticosteroid therapy in biliary atresia. of biliary atresia identified at time of Kasai hepatoportoenteros-
J Pediatr Surg 1985;20:6935. tomy and early postoperative clearance of jaundice are significant
108. Suruga K, Miyano T, Kimura K, et al. Reoperation in the treat- predictors of transplant-free survival. Ann Surg 2011;254:
ment of biliary atresia. J Pediatr Surg 1982;17:16. 57785.
109. Sawaguchi, S., Y. Akiyama, M. Saeki, Y. Ohta. The treatment of 133. Ohhama Y, Shinkai M, Fujita S, et al. Early prediction of long-
congenital biliary atresia with special reference to hepatic por- term survival and the timing of liver transplantation after the
toenteroanastomosis. Paper presented at the fifth annual meeting Kasai operation. J Pediatr Surg 2000;35:10314.
of the Pacific Association of Pediatric Surgeons, Tokyo, 1972. 134. Kumagi T, Drenth JPH, Guttman O, et al. Biliary atresia and
110. Nakajo T, Hashizume K, Saeki M, et al. Intussusception-type survival into adulthood without transplantation: A collaborative
antireflux valve in Roux-en-Y loop to prevent ascending cholan- multicenter clinic review. Liver Int DOI:10.1111/j.1478-3231
gitis after hepatic portojejunostomy. J Pediatr Surg 1990;25: 2011.02668.x.
31114. 135. Shinkai M, Ohhama Y, Take H, et al. Long-term outcome of
111. Tanaka K, Shirahase I, Utsunomiya H, et al. A valved hepatic children with biliary atresia who were not transplanted after the
portoduodenal intestinal conduit for biliary atresia. Ann Surg Kasai operation: > 20-year experience at a childrens hospital.
1990;213:2305. J Pediatr Gastroenterol Nut 2009;48:44350.
112. Endo M, Katsumata K, Yokoyama J, et al. Extended dissection of 136. Broide E, Farrant P, Reid F, et al. Hepatic artery resistance index
the porta hepatis and creation of an intussuscepted ileocolic can predict early death in children with biliary atresia. Liver
conduit for biliary atresia. J Pediatr Surg 1983;12:78493. Transplant Surg 1997;3:60410.
113. Altman RP, Chandra R, Lilly JR. Ongoing cirrhosis after success- 137. Tanaka K, Uemoto S, Tokunaga Y, et al. Surgical techniques and
ful portoenterostomy with biliary atresia. J Pediatr Surg innovations in living related liver transplantation. Ann Surg
1975;10:68591. 1993;217:8291.
114. Bu LN, Chen HL, Ni YH, et al. Multiple intrahepatic biliary cysts 138. Howard ER, MacClean G, Nio M, et al. Biliary atresia: Survival
in children with biliary atresia. J Pediatr Surg 2002;37:11837. patterns after portoenterostomy and comparison of a Japanese
115. Hol L, van den Bos IC, Hussain SM, et al. Hepatocellular carci- with a UK cohort of long-term survivors. J Pediatr Surg 2001;36:
noma complicating biliary atresia after Kasai portoenterostomy. 8927.
Eur J Gastroenterol Hepatol 2008;20:22731. 139. Bucuvalas JC, Britto M, Krug S, et al. Health-related quality of
116. Andrews WS, Pau CM, Chase HP, et al. Fat soluble vitamin life in pediatric liver transplant recipients: A single-center study.
deficiency in biliary atresia. J Pediatr Surg 1981;16:28490. Liver Transplant 2003;9:6271.
117. Greene HL, Helinek GL, Moran R, et al. A diagnostic approach 140. Uchida Y, Kasahara M, Egawa H, et al. Long-term outcome of
to prolonged obstructive jaundice by 24-hour collection of duo- adult-to-adult living donor liver transplantation for post-Kasai
denal fluid. J Pediatr Surg 1979;95:41214. biliary atresia. Am J Transplant 2006;6:24438.
118. Barkin RM, Lilly JR. Biliary atresia and the Kasai operation: 141. Kyoden Y, Tamura S, Sugawara Y, et al. Outcome of living donor
Continuing care. J Pediatr Surg 1980;96:101519. liver transplantation for post-Kasai biliary atresia in adults. Liver
119. Raffensperger JG. A long-term follow-up of three patients with Transpl 2008;14:18692.
biliary atresia. J Pediatr Surg 1991;26:1767. 142. Trotter JF, Adam R, Lo CM, et al. Documented deaths of hepatic
120. Agarwal GS, Saxena A, Bhatnagar V. The development of lobe donors for living donor liver transplantation. Liver Transpl
intrapulmonary arteriovenous shunts as a poor prognostic factor 2006;12:14858.
C H A P T E R 4 4
Adapted from Witcombe JB, Cremin BJ. The width of the Pancreatic duct
common bile duct in childhood. Pediatr Radiol 1978;7:1479.
Common
biliopancreatic
becomes more severe after repeated bouts of cholangitis. channel
Stones or debris may be found in the CC, along with a
dilated intrahepatic bile duct and a common biliopancre-
atic channel. Liver histology varies from normal to cir-
rhosis, depending on the patients age and degree of
cholangitis.
FIGURE 44-2 This contrast study depicts a long common bili-
opancreatic channel which allows reflux of pancreatic secre-
tions into the biliary tree. A long common biliopancreatic
channel is thought to be the etiology of an acquired choledochal
cyst.
Clinical Features
Females are affected more often than males. In our series
Type Ia Type Ib of 400 cases, the female to male ratio was 3.2 to 1.30 Clini-
cal presentations differ according to the age of onset and
the type of cyst. An abdominal mass or jaundice is a
common finding in an infant with CC, whereas abdomi-
nal pain is more often seen in older children.16,3133 The
cystic form usually presents with an abdominal mass
whereas the fusiform type is usually found in patients
presenting with abdominal pain. Choledochal cysts diag-
nosed antenatally are more likely cystic in nature.16
Type II Type III Clinical manifestations among our 400 cases included:
abdominal pain (88%), vomiting (46%), fever (28%),
icterus (25%), discolored stool (12%), abdominal tumor
(7%), and the classic triad (2%).30
Complications such as perforation and hemobilia are
rare;34,35 however pancreatitis is common.16,31 Malignant
change is a late complication, mostly seen in adults.3639
Imaging
Type IVa Type IVb
Ultrasonography (US) is the initial imaging method of
choice (Fig. 44-3A). Contour and position of the cyst, the
status of the proximal ducts, vascular anatomy, and
hepatic echotexture can all be evaluated on ultrasound.
ERCP allows excellent definition of the cyst as well as
the entire anatomy, including the pancreatobiliary junc-
tion. However, this investigation is invasive and has com-
plications such as pancreatitis, perforation of the duodenal
Type V
or biliary tracts, hemorrhage, and sepsis.40,41
FIGURE 44-1 These diagrams depict the five classifications for Magnetic resonance cholangiopancreatography
choledochal cyst according to Todani. (From Todani T, Watanabe
Y, Narusue M, etal. Congenital bile duct cyst: Classification, opera-
(MRCP) is highly accurate in the detection and classifica-
tive procedure, and review of 37 cases including cancer arising from tion of the cysts. (Fig. 44-3B) The overall detection
choledochal cyst. Am J Surg 1977;134:2639.) rate of MRCP for a CC is very high (96100%) and
44 Choledochal Cyst and Gallbladder Disease 595
A B
FIGURE 44-3 (A) Ultrasound is the initial imaging method of choice for identifying a choledochal cyst. The cyst is identified as well
as the portal vein (PV) lying posterior to it. (B) MRCP is highly accurate in the detection and classification of the cyst. On this MRCP
image, note the fusiform choledochal cyst as well as the pancreatic duct (dotted arrow) and long common channel (solid arrow).
The gallbladder is marked with an asterisk.
should be considered a first-choice imaging technique for malignant degeneration.6,4547 External drainage is indi-
evaluation.4244 cated for a perforated cyst in patients whose condition is
Intraoperative cholangiography is indicated when the too unstable to perform cystectomy and a bilio-enteric
anatomic detail of the biliary tract cannot be demon- anastomosis.34,35
strated by MRCP or ERCP (Fig. 44-4). Contrast- Cyst excision and a bilio-enteric anastomosis is the
enhanced CT may be indicated in some patients with preferred approach for most patients. The cyst should be
pancreatitis or if an associated tumor is suspected. excised at the level of the common biliopancreatic channel
orifice at its distal end and approximately 5mm from the
confluence of the right and left hepatic ducts at the proxi-
Surgical Techniques mal end. Postoperative malignancy in a residual cyst on
either hepatic duct side or from the distal part has been
General Principles
reported.48,49 A review from the English language and
Cystoduodenostomy and cystojejunostomy have been Japanese literature of 23 patients with carcinomas of the
abandoned due to cholangitis, stone formation, and bile duct developing after CC excision found that malig-
nancy developed in the intrapancreatic remnant of the
bile duct or CC in six patients, in the remnant of the CC
at the hepatic side in three patients, in the hepatic duct
at or near the anastomosis in eight patients, and in the
intrahepatic duct in six patients.48 Abdominal pain and
pancreatitis due to leaving a remnant of the cyst in the
pancreatic head has also been described.50
Operative correction can be performed safely in all age
groups.30,5153
Preoperative Preparation
Biliary infection should be treated before operation. A
prolonged prothrombin time secondary to cholestasis
should be corrected with intravenous vitamin K. Drugs
for elimination of ascaris are given in areas where ascaris
is prevalent.
Laparoscopic Approach
Endotracheal intubation general anesthesia is standard.
Epidural analgesia can provide excellent postoperative
pain relief. Broad spectrum intravenous antibiotics are
best given at induction of anesthesia and continued for
five days postoperatively. A nasogastric tube, rectal tube, FIGURE 44-6 This operative photograph depicts placement of
and urinary catheter are used to decompress the stomach, the ports for laparoscopic repair of a choledochal cyst. A 10mm
colon, and bladder. The patient is placed in a 30 lithot- cannula (1) is introduced through the umbilicus for the tele-
scope. Three additional 5mm or 3mm ports are then used for
omy position (Fig. 44-5). The surgeon stands at the lower the working instruments (2,3,4). Note the liver has been ele-
end of the operating table between the patients legs. vated anteriorly with a suture placed around the round ligament
The first laparoscopic operation for CC was reported and exteriorized in the epigastric region (arrow).
in 1995.71 This approach quickly became popular and has
become a routine procedure in many centers.30,7284 The
laparoscopic approach is preferred for most types of CC: of distal cystic duct and gallbladder fundus to elevate the
I, II, and IV. Relative contraindications are in patients liver and expose the hepatic hilum (Fig. 44-7B).
with perforation, previous biliohepatic surgery, or espe- The appearance of the cyst, liver and spleen are noted.
cially newborns with damaged hepatic functions. Intraoperative cholangiography via the gallbladder should
A 10mm cannula is inserted through the umbilicus for be performed if the anatomy has not been clearly defined
the telescope. Three additional 5 or 3mm ports are preoperatively. With a large cyst, bile is aspirated through
introduced for the working instruments: one in the right a catheter, which reduces the cyst size to facilitate the
flank, another in the left flank, and one in the left hypo- pericystic dissection.
chondrium (Fig. 44-6). Carbon dioxide pneumoperito- The duodenum is retracted downward using a dissec-
neum is maintained at a pressure of 812mmHg. The tor inserted through the left lower port. The mid-portion
liver is secured to the abdominal wall with a suture placed of the cyst is dissected circumferentially. Separation of
around the round ligament (Fig. 44-7A). The cystic the cyst from the hepatic artery and portal vein is meticu-
artery and the cystic duct are identified, clipped, and lously performed until a dissector can be passed through
divided. A second traction suture is placed at the junction the space between the posterior cyst wall and the portal
vein going from left to right. The cyst is then divided at
this site.
The inferior part of the cyst is separated from the
pancreatic tissue down to the common biliopancreatic
duct using a 3mm dissector for cautery and dissection.
Protein plugs or calculi within the cyst and common
channel are washed out and removed. The inferior part
of the cyst is opened longitudinally and inspected to iden-
tify the orifice of the common biliopancreatic channel. A
small catheter is then inserted into the common channel.
Irrigation with normal saline via this catheter is per-
formed to eliminate protein plugs until clear fluid returns
and the catheter can be passed down into the duodenum
(Fig. 44-8A). A cystoscope can be used to remove protein
plugs in the common channel if its diameter permits.85,86
The distal CC is then clipped and divided at the level of
the orifice of the common channel (Fig. 44-8B).
The cephalad portion of the cyst is further dissected
to the common hepatic duct. The cyst is initially divided
FIGURE 44-5 Older patients are placed in the lithotomy position at the level of the cystic duct. After identifying the orifice
and smaller patients are moved to the end of the bed. It is
helpful for the surgeon to stand either between the patients
of the right and left hepatic ducts, the rest of the cyst is
legs (in older patients) or at the end of the operating table (in removed, leaving a stump approximately 5mm from the
younger patients) for laparoscopic choledochal cyst repair. bifurcation of the hepatic ducts. Irrigation with normal
44 Choledochal Cyst and Gallbladder Disease 597
A B
FIGURE 44-7 (A) Suture has been placed through the round ligament and will be exteriorized in the epigastrium in order to help
elevate the liver for exposure of the choledochal cyst. (B) A second traction suture has been positioned at the junction of the distal
cystic duct and gallbladder fundus to further elevate the liver anteriorly and expose the hepatic hilum.
saline through a small catheter inserted into the right and jejunal segment containing the two sutures is grasped
then into the left hepatic duct is performed to wash out with a locking instrument. The previously-made trans
protein plugs or calculi until the effluent is clear. umbilical vertical incision is extended 1.0cm cephalad.
If the cyst is intensely inflamed with extensive peri- The jejunum is then exteriorized, and the jejunojejunos-
cystic adhesions, the cyst is opened by a transverse inci- tomy is performed extracorporeally. The jejunum is then
sion on the anterior wall. The dissection of the cyst wall returned into the abdominal cavity. The extended umbili-
from the portal vein is then carefully performed while cal incision is closed and the laparoscopic instruments are
viewing the cyst from inside and outside. After dividing reinserted.
the mid-portion of the cyst, the upper and lower parts of The Roux limb is passed through a window in the
the cyst are removed as previously described. transverse mesocolon to the porta hepatis. The jejunum
is opened longitudinally on its antimesenteric border a
few millimeters from the end of the Roux limb to avoid
Hepaticojejunostomy
the creation of a significant blind pouch as the child
The ligament of Treitz is identified. A 5-0 silk suture is grows. The hepaticojejunostomy is fashioned using two
placed 10cm distal to the ligament of Treitz in the running sutures of 5-0 PDS (interrupted sutures are used
newborn, 20cm in infants, and 30cm in children. A when the diameter of the common hepatic duct is less
second suture (5-0 PDS, Ethicon, Inc., Somerville, NJ) than 1cm). The anastomosis is performed from left to
is placed 2cm below the first suture to mark the jejunal right using 3mm instruments. If the diameter of the
limb which will be anastomosed to the hepatic duct. The common hepatic duct is too small, ductoplasty is
A B
FIGURE 44-8 (A) After opening the inferior part of the cyst to identify the orifice of the common biliopancreatic channel, a small
catheter is inserted into the common channel for irrigation and elimination of protein plugs. (B) After irrigating the common channel,
the distal choledochal cyst is being ligated with an endoscopic clip and will subsequently be divided at the level of the orifice of
the common channel.
598 SECTION IV Abdomen
performed by opening the common hepatic duct and MRCP, ERCP or perioperative cholangiography is
incising the left hepatic duct longitudinally for a variable important. Internal inspection of the distal choledochus
distance. to identify the orifice of the common biliopancreatic duct
Mesenteric defects in the transverse mesocolon and helps the surgeon decide where the distal part of the cyst
the small bowel mesentery are closed. The gallbladder is should be divided.
detached from its bed and the cyst and gallbladder are
removed through the umbilicus. The operative field is Postoperative Care
washed with warm saline and a subhepatic closed suction
drain is left. Oral feeding is initiated after the fluid from the gastric
tube becomes clear, usually by postoperative day 2 or 3.
The abdominal drain is removed on day 5 if there is no
Hepaticoduodenostomy
evidence of leak from the biliary-enteric anastomosis.
Following cyst resection, the duodenum is mobilized as Complications from the laparoscopic approach are
much as possible, and a hepaticoduodenostomy is con- similar or lower when compared to the open opera-
structed 23cm from the pylorus using two running tion.89,90 Early postoperative complications include bleed-
sutures of 5-0 PDS. As noted previously, interrupted ing, anastomotic leak, pancreatic fistula, and intestinal
sutures are used when the diameter of the common obstruction. The anastomotic leak and pancreatic fistula
hepatic duct is less than 1.0cm. The rest of the operation often resolve with drainage, intravenous antibiotics,
is performed as previously described. nasogastric decompression, and parenteral nutrition
(TPN).
Significant late complications included cholangitis,
Open Operation
anastomotic stricture, intrahepatic calculi, and bowel
The open technique is used in patients with a perforated obstruction.91 Cholangitis without anastomotic stricture
cyst, previous hepatobiliary operation, or if the surgeon or intrahepatic calculi is treated with antibiotics, whereas
does not feel comfortable with the laparoscopic approach. endoscopic maneuvers or reoperation are used for anas-
A high transverse upper quadrant incision is used. The tomotic stricture or intrahepatic calculi.
operative technique then follows that described for the
laparoscopic approach. The cyst is mobilized as previously
described, divided and removed, and either a hepaticoje-
Caroli Disease and Choledochocele
junostomy or hepaticoduodenostomy are performed. Partial hepatectomy is indicated for the localized type of
Caroli disease and liver transplantation is usually needed
Alternative Operative Techniques for diffuse disease.14,15 Endoscopic unroofing of a choledo-
chocele with sphincterotomy of the CBD, or sphincter-
An alternative biliary reconstruction technique is an end- otomy alone, are considered the preferred treatment for
to-end hepaticojejunostomy (in contrast to end-to side). choldedochocele.92,93
This should only be performed if there is no significant
size discrepancy between the hepatic duct and Roux limb.
A hepaticoduodensotomy with jejunal interposition can
Outcomes
be performed if desired. The robotic approach has also From January 2007 to June 2011, we performed laparo-
been described.87,88 This technique appears safe and effec- scopic correction in 400 patients with CC at the National
tive, but the operative time is quite long. Hospital of Pediatrics, Hanoi, Vietnam.30 A total of
238 patients underwent laparoscopic cystectomy plus
hepaticoduodenostomy, and 162 had cystectomy plus
Intraoperative Complications
hepaticojejunostomy. The mean operative time for hepa-
Injury to the Portal Vein. This complication can be ticoduodenostomy was 164.851 minutes and 21261
prevented by keeping the dissection as close to the cyst minutes for hepaticojejunostomy. Conversion to an open
wall as possible. When severe pericystic inflammation operation was required in two patients. Intraoperative
and adhesions are present, opening the cyst on its ante- complications included bleeding from the right portal
rior wall and carefully separating the left and posterior vein in one patient and injury to the right hepatic duct
walls of the cyst from the portal vein, while viewing in another. Repair was successful in both patients via
internally and externally, can help prevent injury to the laparoscopy. Early postoperative complications included
portal vein. biliary fistula in eight patients (2%), with one patient
requiring reoperation. Pancreatic fistula developed in
Transection of Both Hepatic Ducts. This situation four patients (1.1%), but none of these required
can happen when the hepatic bifurcation is low and away reoperation.
from the liver hilum. This complication can be avoided The mean postoperative hospital stay was 6.43 days
by identifying the orifice of the right and left hepatic for hepaticoduodenostomy and 6.70.5 days for hepa-
ducts by internal inspection before excising the cyst from ticojejunostomy. Follow-up from five to 57 months was
the hepatic duct. obtained in 342 patients (85.5%). Five patients had
cholangitis (1.5%) in the hepaticoduodenostomy group
Injury to the Pancreatic Duct. Understanding the and one in hepaticojejunostomy group. Gastritis due to
anatomy of the common biliopancreatic channel via bilious reflux was 3.8% in the hepaticoduodenostomy
44 Choledochal Cyst and Gallbladder Disease 599
group. Duodenal bleeding from an ulcer occurred in one Classic symptoms for cholelithiasis include right upper
patient who underwent a hepaticojejunostomy. Two abdominal pain following a fatty meal with associated
patients required reoperation, one due to an anastomotic nausea and vomiting. However, many children do not
stricture and another due to stenosis at the bifurcation of exhibit these classic symptoms and can have atypical
hepatic ducts. symptoms. In younger children especially, the abdominal
pain may be vague and poorly localized. Complications
of cholelithiasis are increasingly being reported.118120 For
GALLBLADDER DISEASE this reason, cholecystectomy is recommended once
cholelithiasis is identified. In patients with SCD, sludge
Over the past 15 years, gallbladder disease has become a has been felt to be an indication for cholecystectomy as
very common problem for older children and young ado- well, even if stones are not present.121 In a study of 35
lescents, especially in the U.S. Historically, gallbladder patients with SCD and sludge, 23 (65.7%) proceeded to
disease has been confined to children with hemolytic develop gallstones at some point.122
cholelithiasis. However, biliary dyskinesia is now the In evaluating children with gallbladder symptoms
most common reason for laparoscopic cholecystectomy from cholelithiasis, rarely is a plain abdominal film
in many centers.94,95 helpful. Ultrasound is the usual initial study and has an
accuracy approaching 95%.123 In addition, the ultrasound
can document involvement of the common and hepatic
Biliary Dyskinesia ducts, gallbladder inflammation, and other abnormalities
Biliary dyskinesia is now a commonly seen condition in in the liver and pancreas. Acute cholecystitis is usually
children.94100 In this disease, there is poor gallbladder diagnosed using a nuclear medicine study. In patients
contractility and cholesterol crystals are often seen in the with acute cholecystitis, the radioactive analogs are
bile. This disorder may have a similar pathophysiology excreted in the liver, but do not pass into the gallbladder
to other diseases with increased numbers of mast cells in due to obstruction of the cystic duct.
the gastrointestinal tract, such as eosinophilic gastroen-
teritis. A significant increase in mucosal mast cells have
been noted in the gallbladder mucosa in patients with
Special Considerations
biliary dyskinesia when compared with patients with There are four special considerations when evaluating
stone disease.101,102 the child with gallbladder disease. The first is the sickle
These patients often present with a spectrum of symp- cell child. Historically, it has been felt that these patients
toms that are found with gallbladder disease (nausea, needed preoperative transfusion.124128 Many centers still
vomiting, right upper abdominal pain), but they can also require a hemoglobin greater than 10mg/dl. However,
have atypical symptoms. In patients with this disorder, an some centers now stress the importance of adequate
ultrasound is usually normal. Therefore, a radionuclide hydration in these patients rather than transfusion.
study with cholecystokinin (CCK) injection or Lipomul The second circumstance arises in the patient with HS
is often needed to make this diagnosis.96,103 Patients often who is undergoing splenectomy. In such patients, an
complain of pain at the time the CCK is injected. Most ultrasound should be performed as it is relatively straight-
surgeons use a gallbladder ejection fraction of less than forward to remove the gallbladder at the same time if
35% as an indicator for cholecystectomy in a patient with gallstones are noted. In a study of 17 patients with sphe-
symptoms.95,98,104,105 However, not all patients with an rocytosis, but not cholelithiasis, none of these patients
ejection fraction of less than 35% will have resolution of developed cholelithiasis with a mean follow-up of 15
symptoms. Symptom resolution seems more likely the years.129 Thus, it is probably not necessary to prophylacti-
lower the gallbladder ejection fraction. In one report, cally remove the gallbladder in HS patients undergoing
unless children had an ejection fraction of less than 15%, splenectomy.
there was not predictable relief of symptoms.106 Thus, a Another area of uncertainty is whether or not one
careful discussion with the family is needed in these should routinely perform a cholangiogram in all patients
patients to inform them that their symptoms may not undergoing a laparoscopic cholecystectomy. Early in the
completely resolve following cholecystectomy. development of minimally invasive surgery, it was felt
best to perform a cholangiogram for surgeon training
Cholelithiasis purposes. Now, however, it does not appear necessary to
perform a cholangiogram unless there is a concern about
Historically, cholelithiasis has been the primary reason the anatomy or it is unclear whether or not common duct
for cholecystectomy in children. Also, in the past, most stones are present.
adolescents with cholelithiasis had hemolytic disease, A fourth situation involves the child or adolescent who
especially sickle cell disease (SCD) or hereditary sphero- presents with known or suspected choledocholithiasis. In
cytosis (HS). Other reasons for the development of adults, this situation is usually handled by ERCP with
cholelithiasis include long-term TPN, dehydration, sphincterotomy and stone extraction either before or
cystic fibrosis, short bowel syndrome, ileal resection, use after the laparoscopic cholecystectomy. ERCP with
of oral contraceptives, and obesity.107114 Nonhemolytic sphincterotomy has become a routine aspect of adult care
stones in adults are primarily cholesterol-based. In and is almost always successful in removing the stone(s).
younger children, many stones have predominantly However, in children, many pediatric gastroenterologists
calcium carbonate.115117 are not trained in this technique and many childrens
600 SECTION IV Abdomen
Jaundice, pancreatitis
patient is placed supine on the operating table and two
Suspected video monitors are positioned at the head of the table.
Ultrasound: dilated CBD,
choledocholithiasis
CBD stones An orogastric tube is inserted for decompression of the
stomach and the bladder is emptied using a Cred maneu-
ver. For the single incision approach, some surgeons
ERCP
prefer to stand between the patients legs, whereas the
surgeon stands on the patients left side for the four-port
technique. Regardless of the operative approach, the
Confirmed patient is prepped and draped widely.
choledocholithiasis
Four-Port Technique
Four small incisions are generally used for the traditional
No stones Stones Stones not laparoscopic cholecystectomy. A 10mm port is intro-
cleared cleared
duced in the umbilicus and a 10mm telescope is intro-
duced. (Although the optics are satisfactory with a 5mm
Laparoscopic Open/laparoscopic telescope, it is helpful to have a 10mm port in the umbili-
cholecystectomy CBD exploration cus to extract the gallbladder, especially if it is inflamed,
so there is no real benefit to using a 5mm umbilical port
FIGURE 44-9 This algorithm shows one approach for managing and telescope.) A 5mm cannula is inserted in the epigas-
children with suspected choledocholithiasis. With this approach,
an ERCP is performed prior to the laparoscopic cholecystectomy
trium to the patients right of the midline which becomes
in a child with suspected choledocholithiasis. If stones are iden- the main operating site for the surgeon. Two instruments
tified and the ERCP and sphinterotomy are successful, then the are then placed on the patients right side, one in the right
surgeon can proceed with the laparoscopic cholecystectomy mid-abdomen and one in the right lower abdomen (Fig.
soon thereafter. However, if the ERCP and sphinterotomy are 44-10). A stab incision technique is often possible for
not successful, the surgeon will know at the time of the laparo-
scopic cholecystectomy whether or not choledochal exploration these two right lateral instruments as they are not
is needed. exchanged during the operation. Also, 3mm instruments
can be utilized in younger patients at these two sites as
well.
hospitals require the help of an adult endoscopist. Thus, The patient is then rotated into reverse Trendelen-
the best approach in children depends on the institutional burg and to the left. The gallbladder is grasped using the
resources. right lower abdominal instrument and rotated cephalad
One approach in children with suspected CBD over the liver to expose the triangle of Calot. The surgeon
stones is to perform the ERCP and sphincterotomy before then utilizes the right upper abdominal instrument and
performing the laparoscopic cholecystectomy (Fig. the epigastric instrument to perform the procedure.
44-9).130133 If successful, then the surgeon can proceed
with the laparoscopic cholecystectomy soon thereafter.
However, if the ERCP and sphincterotomy are not suc-
cessful, the surgeon will know at the time of the laparo-
scopic cholecystectomy whether or not choledochal
exploration is needed. This can be performed laparo-
scopically for experienced surgeons and with an open
approach for those who are not as experienced.
Surgical Techniques
Laparoscopic Cholecystectomy
The revolution in minimally invasive surgery began with
the laparoscopic approach for cholecystectomy.134137
Recently, the four-port technique has been modified to a
single incision approach through the umbilicus. Cur-
rently, there is no objective evidence that the single
incision approach has advantages over the four-port tech- FIGURE 44-10 The traditional laparoscopic cholecystectomy
technique utilizes four ports. The umbilical cannula is 10mm
nique. The most obvious presumed advantage is cosme- (as seen here) or 5mm depending on the size of the telescope.
sis. However, the small incisions utilized for the four-port A 5mm cannula is inserted in the epigastrium which becomes
technique heal very nicely and the cosmetic benefit the main operating site for the surgeon. Two instruments can
appears marginal if there is a benefit at all. Only through often be placed through stab incisions on the patients right
prospective randomized trials with patient satisfaction side, one in the mid-abdomen and one in the lower abdomen.
These two lateral instruments are not exchanged during the
surveys will this cosmetic benefit be determined. operation so the stab incision technique often works well. Also,
Regardless of whether the patient is undergoing the in small patients, as depicted in this photograph, 3mm instru-
four-port technique or a single incision approach, the ments can be used on the patients right side.
44 Choledochal Cyst and Gallbladder Disease 601
Initial attention is directed towards lysing adhesions endoscopic bag. However, for inflamed gallbladders, it is
to the infundibulum. Dissection follows to identify the best to remove the specimen using a bag.
cystic duct and cystic artery. At this point, lateral retrac-
tion of the infundibulum is essential to orient the cystic Single-Site Laparoscopic Cholecystectomy
duct at 90 to the CBD to help prevent misidentification
of these two structures. It is important to visualize the For single site umbilical laparoscopic cholecystectomy
critical view of safety to correctly identify the anatomy. (SSULS), it is necessary to use an umbilical incision of
This initial view is bounded by the CBD medially, the approximately 2cm in length. In the U.S., a pre-
cystic duct inferiorly, the gallbladder laterally, and the manufactured port is often utilized. The two main devices
liver superiorly (Fig. 44-11A).138 After the cystic duct and used are the SILS Port (Covidien, Norwalk CT) or the
common duct have been correctly identified, two options TriPort (Olympus America, Center Valley PA). The SILS
exist. A cholangiogram can be performed if the anatomy Port is a foam port with three working channels. The
is unclear or if there is suspicion of common duct stones. fourth instrument can usually be placed along the left side
If the anatomy is clear and there is no suspicion of of the port (Fig. 44-12A). Although the TriPort is
choledocholithiasis, then it is appropriate to ligate the designed for three instruments, a fourth 3mm instru-
cystic duct with endoscopic clips and then divide it (Fig. ment can often be inserted through one of the insuffla-
44-11B). Similarly, the cystic artery is ligated and divided tion channels (Fig. 44-12B). It is helpful to have a long
(Fig. 44-11C). Once these two structures have been telescope so that the telescope holder is standing out of
ligated and divided, the gallbladder is then detached from the way of the operating surgeon.
the liver using retrograde dissection with cautery (Fig. Outside the U.S., many surgeons place a single port
44-11D). Either the hook cautery, spatula cautery, or in the umbilicus with instruments inserted through the
Maryland dissecting instrument connected to cautery can fascia surrounding the umbilicus. Sometimes, low profile,
be used for this purpose. Prior to complete detachment 5mm individual ports are utilized. Regardless of the
of the gallbladder from the liver, the area of dissection technique and orientation of the instruments through the
should be inspected to ensure hemostasis, and then the umbilicus, the principles of the procedure are the same
gallbladder is completely detached. If there is little to as for the traditional four-port laparoscopic cholecystec-
no inflammation, the gallbladder can usually be exterior- tomy. Lateral retraction of the infundibulum is important
ized through the umbilical incision without using an for visualization of the triangle of Calot and critical view
A B
C D
FIGURE 44-11 These four figures depict the salient points for a laparoscopic cholecystectomy. (A) The gallbladder infundibulum is
retracted laterally to orient the cystic duct (solid arrow) in relationship to the common duct (asterisk). Note the critical view of safety
is identified. In this view, the liver is seen through the opened space bounded by the cystic duct inferiorly, gallbladder laterally and
the liver superiorly. (B) The cystic duct has been ligated with endoscopic clips. Two clips are placed on the medial aspect of the
duct which will remain following duct division. (C) The cystic duct has been divided and the cystic artery (dotted arrow) is visualized.
(D) Following ligation and division of the cystic artery, the gallbladder is being dissected away from its liver bed using the hook
cautery.
602 SECTION IV Abdomen
A B
FIGURE 44-12 In the United States, a pre-manufactured port is often utilized for a single site umbilical laparoscopic cholecystectomy.
The two main devices used are the SILS Port (Covidien, Norwalk CT) seen on the left and the TriPort (Olympus America, Center
Valley PA) on the right. In (A) there are three working channels in this SILS Port. A fourth instrument (solid arrow) can be inserted
along the left side of the port. (B) The TriPort is designed for three instruments. However, a fourth 3mm instrument (dotted arrow)
can be inserted through one of the two insufflation channels.
From St. Peter SD, Keckler SJ, Nair A, etal. Laparoscopic cholecystectomy in the pediatric population. J Laparoendosc Adv Surg
Tech A 2008;18:12730.
of safety. The cystic duct and cystic artery are similarly and five had calculous cholecystitis. Six patients required
ligated and divided as with the 4-port technique. One splenectomy and were found to have gallstones. Only 29
difference between the two approaches is that it is best patients had hemolytic disease with 18 patients having
to irrigate and suction all the fluid prior to exteriorizing SCD and 11 having HS. The mean operating time was
the gallbladder as gallbladder removal entails removing 77 minutes which excluded patients undergoing a con-
the pre-manufactured port (if utilized). It can often be comitant splenectomy.
difficult to reinsert these ports so it is important to irri- ERCP was performed preoperatively in 17 patients
gate and suction prior to extracting the gallbladder. After and stones were removed endoscopically in eight of
removing the gallbladder and umbilical port, the umbili- these patients. An intraoperative cholangiogram was
cal fascia is closed with either interrupted or continuous performed in 38 patients and choledocholithiasis was
0-absorbable suture. The skin is approximated with inter- found in nine patients. CBD stones were cleared intra-
rupted 5-0 plain sutures. operatively in five patients and the other four required
postoperative endoscopy and sphincterotomy for stone
retrieval. In this series, there were no conversions, ductal
Childrens Mercy Hospital Experience
injuries, bile leaks or mortality, but one sickle cell patient
There are surprising few reports in the literature describ- required an emergency laparotomy for postoperative
ing laparoscopic cholecystectomy in more than 100 chil- hemorrhage.
dren.94,105,118,120,134 Our group at Childrens Mercy Hospital Recently, our group at CMH completed a prospective
(CMH) reported a six year experience between Septem- randomized trial comparing SSULS cholecystectomy
ber 2000 and June 2006 with 224 patients undergoing and four-port laparoscopic cholecystectomy.139 The
laparoscopic cholecystectomy (Table 44-2).98 In this primary outcome variable was operative time which
study, the mean age was 12.9 years and the mean weight was based on our own operative times for SSULS
was 58.3kg. Symptomatic gallstones were found in 166 cholecystectomy and four-port cholecystectomy. Using
children and biliary dyskinesia was diagnosed in 35 chil- an alpha of 0.05 and power of 0.80, 60 patients were
dren. Seven patients presented with gallstone pancreatitis enrolled in the study. Patients with signs of inflammation,
44 Choledochal Cyst and Gallbladder Disease 603
TABLE 44-3 Outcome Data Between Patients Randomized to Single Incision or Four-Port
Laparoscopic Cholecystecomy
Outcome Variable Single Incision (n=30) Four-Port (n=30) P-Value
Operative time (minutes) 68.622.1 56.122.1 0.03
Difficulty rating (15) 2.71.0 1.90.8 0.005
Total analgesic doses 16.417.8 10.14.3 0.06
Postoperative length of stay (hours) 22.76.2 22.26.8 0.44
Hospital charges ($) 29.7K27.3K 20.6K6.9K 0.08
From Ostlie DJ, Adibe OO, Juang D, etal. Single incision versus 4-port laparoscopic cholecystectomy: A propsective randomized
trial. J Pediatr Surg 2013;48(1):20914.
A B
FIGURE 44-13 These two patients both underwent a laparoscopic cholecystectomy. (A) The patient underwent a laparoscopic chole-
cystectomy using four ports. (B) The patient underwent a single site umbilical laparoscopic cholecystecotmy. To date, the main
advantage of the SSULS approach appears to be cosmesis, but this advantage is marginal in most patients.
complicated disease, or weight over 100kg were excluded. 5. Todani T, Watanabe Y, Narusue M, et al. Congenital bile duct
Also, surgeons participating in this study were asked to cyst: Classification, operative procedure, and review of 37 cases
including cancer arising from choledochal cyst. Am J Surg
rate the degree of technical difficult from 1 (easy) to 5 1977;134:2639.
(difficult). There were no differences in patient charac- 6. Thu NX, Cung HB, Liem NT, et al. Surgical treatment of con-
teristics preoperatively. genital cystic dilatation of the biliary tract. Acta Chir Scand
Regarding the outcome data (Table 44-3), the opera- 1986;152:66974.
7. Liem TL, Valayer J. Dilatation congenitale de la voie biliaire
tive time and degree of difficulty as determined by the principale chez lenfant. Etude dune series de 52 cas. La Presse
surgeon were statistically significantly greater for the Med 1994;23:15658.
single incision approach. There were more doses of anal- 8. Miyano T, Ando K, Yamataka A, et al. Congenital biliary dilata-
gesics and greater hospital charges in the SSULS group tion. Semin Pediatr Surg 2000;9:18795.
which trended toward significance. The postoperative 9. Lilly JR, Stellin GP, Karrer FM. Forme fruste choledochal cyst.
Pediatr Surg 1985;20:44951.
length of hospitalization was not clinically or statistically 10. Myanio T, Ando K, Yamataka A, et al. Pancreaticobiliary maljunc-
different between the two approaches. At present, cos- tion associated with nondilatation or minimal dilatation of the
mesis appears to be the sole advantage for the SSULS common bile duct in children: Diagnosis and treatment. Eur J
approach compared with the four-port technique (Fig. Pediatr Surg 1996;6:3347.
11. Shimotakahara A, Yamataka A, Kobayashi H, et al. Forme fruste
44-13). However, the cosmetic advantage appears mar- choledochal cyst: Long-term follow-up with special reference to
ginal, at best. surgical technique. J Pediatr Surg 2003;38:18336.
12. Thomas S, Sen S, Zachariah N, et al. Choledochal cyst sans cyst-
experience with six forme fruste cases. Pediatr Surg Int 2002;
REFERENCES 18:24751.
1. Hernanz-Schulman M, Ambrosino MM, Freeman PC, et al. 13. Caroli J, Soupault R, Kossakowski J, et al. La dilatation polykys-
Common bile duct in children: Sonographic dimensions. Radiol- tique congnitale des voies biliaires intrahpatiques: Essai de clas-
ogy 1995;195:1935. sification. Sem Hop Paris 1958;34:12835.
2. Witcombe JB, Cremin BJ. The width of the common bile duct in 14. Madjov R, Chervenkov P, Madjova V, et al. Carolis disease.
childhood. Pediatr Radiol 1978;7:1479. Report of 5 cases and review of literature. Hepatogastroenterol-
3. Kim HJ, Kim MH, Lee SK, et al. Normal structure, variations, ogy 2005;52:6069.
and anomalies of the pancreaticobiliary ducts of Koreans: A 15. Kassahun WT, Kahn T, Wittekind C, et al. Carolis disease: Liver
nationwide cooperative prospective study. Gastrointest Endosc resection and liver transplantation. Experience in 33 patients.
2002;55:88996. Surgery 2005;138:8889.
4. Alonso-Lej F, Rever WB, Pessagno DJ. Congenital choledochal 16. Davenport M, Stringer MD, Howard ER. Biliary amylase
cyst, with a report of two cases, and analysis of 94 cases. Surg and congenital choledochal dilatation. J Pediatr Surg 1995;30:
Gynecol Obstel 1959;108:130. 4747.
604 SECTION IV Abdomen
17. Shimotake T, Iwai N, Yanagihara J, et al. Innervation patterns in pancreaticobiliary disease in children: Our institutional experi-
congenital biliary dilatation. Eur J Pediatr Surg 1995;5:26570. ence in 231 cases. Surg Endosc 2011;25:253640.
18. Imazu M, Ono S, Kimura O, et al. Histological investigations into 42. Park DH, Kim MH, Lee SK, et al. Can MRCP replace the diag-
the difference between cystic and fusiform types of congenital nostic role of ERCP for patients with choledochal cysts? Gas-
biliary dilatation. Eur J Pediatr Surg 2003;13:1620. trointest Endosc 2005;62:3606.
19. Babbitt DP. Congenital choledochal cysts: New etiological 43. Huang CT, Lee HC, Chen WT, et al. Usefulness of magnetic
concept based on anomalous relationships of the common bile resonance cholangiopancreatography in pancreatobiliary abnor-
duct and pancreatic bulb. Ann Radiol 1969;12:23140. malities in pediatric patients. Pediatr Neonatol 2011;52:3326.
20. Jeong IH, Jung YS, Kim H, et al. Amylase level in extrahepatic 44. Irie H, Honda H, Jimi M, et al. Value of MR cholangiopancrea-
bile duct in adult patients with choledochal cyst plus anomalous tography in evaluating choledochal cysts. AJR Am J Roentgenol
pancreatico-biliary ductal union. World J Gastroenterol 2005; 1998;171:13815.
11:196570. 45. Saing H, Tam PKH, Lee JMH, et al. Surgical management of
21. Ochiai K, Kaneko K, Kitagawa M, et al. Activated pancreatic choledochal cysts: A review of 60 cases. J Pediatr Surg 1985;
enzyme and pancreatic stone protein (PSP/reg) in bile of patients 20:4438.
with pancreaticobiliary maljunction/choledochal cyst. Dig Dis Sci 46. Shi LB, Peng SY, Meng XK, et al. Diagnosis and treatment of
2004;49:19536. congenital choledochal cyst: 20 years experience in China. World
22. Jung SM, Seo JM, Lee SK. The relationship between biliary J Gastroenterol 2011;7:73247.
amylase and the clinical features of choledochal cysts in pediatric 47. Fu M, Wang YX, Zhang JZ. Evolution in the treatment of
patients. World J Surg 2012;36:2098101. choledochal cyst. J Pediatr Surg 2000;335:13447.
23. Yamashiro Y, Miyano T, Suruga K, et al. Experimental study of 48. Watanabe Y, Toki A, Todani T. Bile duct cancer developed after
the pathogenesis of choledochal cyst and pancreatitis, with special cyst excision for choledochal cyst. J Hepatobiliary Pancreat Surg
reference to the role of bile acids and pancreatic enzymes in the 1999;6:20712.
anomalous choledocho-pancreatico ductal junction. J Pediatr 49. Kobayashi S, Asano T, Yamasaki M, et al. Risk of bile duct car-
Gastroenterol Nutr 1984;3:7217. cinogenesis after excision of extrahepatic bile ducts in pancreati-
24. Komi N, Tamura T, Miyoshi Y, et al. Nationwide survey of cases cobiliary maljunction. Surgery 1999;126:93944.
of choledochal cyst. Analysis of coexistent anomalies, complica- 50. Koshinaga T, Hoshino M, Inoue M, et al. Pancreatitis compli-
tions and surgical treatment in 645 cases. Surg Gastroenterol cated with dilated choledochal remnant after congenital cyst exci-
1984;3:6973. sion. Pediatr Surg Int 2005;21:9368.
25. Spitz L. Experimental production of cystic dilatation of the 51. Lee SC, Kim HY, Jung SE, et al. Is excision of a choledochal cyst
common bile duct in neonatal lambs. J Pediatr Surg 1977;12: in the neonatal period necessary? J Pediatr Surg 2006;
3942. 41:19846.
26. Davenport M, Basu R. Under pressure: Choledochal malforma- 52. Burnweit CA, Birken GA, Heiss K. The management of choledo-
tion manometry. J Pediatr Surg 2005;40:3315. chal cysts in the newborn. Pediatr Surg Int 1996;11:1303.
27. Kimura K, Ohoto M, Ono T, et al. Congenital cystic dilatation of 53. Howell CG, Templeton JM, Weiner S, et al. Antenatal diagnosis
the common bile duct : Relationship to anomalous pancreatico- and early surgery for choledochal cysts. J Pediatr Surg 1983;
biliary ductal union. Am J Reoengenol 1977;128:5717. 18:38793.
28. Ono J, Sakoda K, Akita H. Surgical aspect of cystic dilatation of 54. Ohi R, Yaota S, Kamiyama T, et al. Surgical treatment of congeni-
the bile duct. An anomalous junction of the pancreaticobiliary tal dilatation of the bile duct with special reference to late com-
tract in adults. Ann Surg 1982;195:2038. plications after total cyst excision operation. J Pediatr Surg 1990;
29. Guelrud M, Morera C, Rodriguez M, et al. Normal and anoma- 25:61317.
lous pancreaticobiliary union in children and adolescents. Gas- 55. Miyano T, Yamataka A, Kato Y, et al. Hepaticoenterostomy after
trointest Endosc 1999;50:18993. excision of choledochal cyst in children: A 30-year experience with
30. Liem NT, Hien PD, Son TN, et al. Early and intermediate out- 180 cases. J Pediatr Surg 1996;31:141721.
comes of laparoscopic surgery for choledochal cyst with 400 56. Edil BH, Cameron JL, Reddy S, et al. Choledochal cyst disease
patients. J Laparoendosc Adv Surg Tech A 2012;22:599603. in children and adults: A 30-year single-institution experience.
31. Lai HS, Duh YC, Chen WJ, et al. Manifestations and surgical J Am Coll Surg 2008;206:10005.
treatment of choledochal cyst in different age group patients. 57. She W, Chung HY, Lan LCL, et al. Management of choledochal
J Formos Med Assoc 1997;96:2426. cyst: 30 years of experience and results in a single center. J Pediatr
32. Shukri N, Hasegawa T, Wasa M, et al. Characteristics of infantile Surg 2009;44:230711.
cases of congenital dilatation of the bile duct. J Pediatr Surg 58. Stringer MD. Wide hilar hepaticojejunostomy: The optimum
1998;33:17947. method of reconstruction after choledochal cyst excision. Pediatr
33. Okada A, Nakmura R, Higaki J, et al. Congenital dilatation of the Surg Int 2007;23:52932.
bile duct in 100 instances and its relationship with anomalous 59. Ono S, Fumino S, Shimadera S, et al. Long-term outcomes after
junction. Surg Gynecol Obstet 1991;172:2918. hepaticojejunostomy for choledochal cyst: A 1027 year follow-up.
34. Ando K, Miyano T, Kohno S, et al. Spontaneous perforation of J Pediatr Surg 2010;45:3768.
choledochal cyst: A study of 13 cases. Eur J Pediatr Surg 60. Todani T, Watanabe Y, Mizuguchi T, et al. Hepaticoduodenos-
1998;8:235. tomy at the hepatic hilum after excision of choledochal cyst. Am
35. Ahmed I, Sharma A, Gupta A, et al. Management of rupture of J Surg 1981;142:5847.
choledochal cyst. Indian J Gastroenterol 2011;30:946. 61. Oweida SW, Ricketts RR. Hepatico-jejuno-duodenostomy recon-
36. Voyles CR, Smadja C, Shands WC, et al. Carcinoma in struction following excision of choledochal cysts in children. Am
choledochal cysts. Age-related incidence. Arch Surg 1983;118: Surg 1989;55:26.
9868. 62. Cosentino CM, Luck SR, Raffensperger JG, et al. Choledochal
37. Imazu M, Iwai N, Tokiwa K, et al. Factors of biliary carcinogen- duct cyst resection with physiologic reconstruction. Surgery
esis in choledochal cysts. Eur J Pediatr Surg 2001;11:247. 1992;112:7407.
38. Kimura K, Ohto M, Saisho H, et al. Association of gallbladder 63. Santore MT, Behar BJ, Blinman TA, et al. Hepaticoduodenos-
carcinoma and anomalous pancreaticobiliary ductal union. Gas- tomy vs. hepaticojejunostomy for reconstruction after resection of
troenterology 1985;89:125865. choledochal cyst. J Pediatr Surg 2011;46:20913.
39. Todani T, Watanabe Y, Toki A, et al. Carcinoma related to 64. Mukhopadhyay B, Shukla RM, Mukhopadhyay M, et al. Choledo-
choledochal cysts with internal drainage operation. Surg Gynecol chal cyst: A review of 79 cases and the role of hepaticodochoduo-
Obstet 1987;164:614. denostomy. J Indian Assoc Pediatr Surg 2011;16:547.
40. Jang JY, Yoon CH, Kim KM. Endoscopic retrograde cholangio- 65. Bismuth H, Franco D, Corlette MB, et al. Long term results of
pancreatography in pancreatic and biliary tract disease in Korean Roux-en-Y hepaticojejunostomy. Surg Gynecol Obstet 1978;
children. World J Gastroenterol 2010;16:4905. 146:1617.
41. Otto AK, Neal MD, Slivka AN, et al. An appraisal of 66. Martino A, Noviello C, Cobellis G, et al. Delayed upper gastroin-
endoscopic retrograde cholangiopancreatography (ERCP) for testinal bleeding after laparoscopic treatment of form fruste
44 Choledochal Cyst and Gallbladder Disease 605
choledochal cyst. J Laparoendosc Adv Surg Tech A 2009;19: Intermediate-term follow-up results. Surg Endosc 2011;25:
4579. 156773.
67. Malhotra RS, Jain A, Prabhu RY, et al. Ischemic stricture of Roux- 91. Yamataka A, Ohshiro K, Okada Y, et al. Complications after cyst
en-Y intestinal loop and recurrent cholangitis. Indian J Gastroen- excision with hepaticoenterostomy for choledochal cysts and their
terol 2005;24:767. surgical management in children versus adults. J Pediatr Surg
68. Houben CH, Chan M, Cheung G, et al. A hepaticojejunostomy: 1997;32:1097102.
Technical errors with twists and turns. Pediatr Surg Int 2006;22: 92. Martin RF, Biber BP, Bosco JJ, et al. Symptomatic choledochoce-
8414. les in adults. Endoscopic retrograde cholangiopancreatography
69. Shimotakahara A, Yamataka A, Yanai T, et al. Roux-en Y hepati- recognition and management. Arch Surg 1992;127:5368.
cojejunostomy or hepaticoduodenostomy for biliary reconstruc- 93. Dohmoto M, Kamiya T, Hnerbein M, et al. Endoscopic treat-
tion during the surgical treatment of choledochal cyst: Which is ment of a choledochocele in a 2-year-old child. Surg Endosc
better? Pediatr Surg Int 2005;21:57. 1996;10:101618.
70. Takada K, Hamada Y, Watanabe K, et al. Duodenalgastric reflux 94. Hofeldt M, Richmond B, Huffman K, et al. Laparoscopic chole-
following biliary reconstruction after excision of choledochal cyst. cystectomy for treatment of biliary dyskinesia is safe and effective
Pediatr Surg Int 2005;21:14. in the pediatric population. Am Surg 2008;74:106972.
71. Farello GA, Cerofolini A, Rebonato M, et al. Congenital choledo- 95. Siddiqui S, Newbrough S, Alterman D, et al. Efficacy of laparo-
chal cyst: Video-guided laparoscopic treatment. Surg Laparosc scopic cholecystectomy in the pediatric population. J Pediatr Surg
Endosc 1995;5:3548. 2008;43:10913.
72. Tanaka M, Shimizu S, Mizumoto K, et al. Laparoscopically 96. Vegunta RK, Raso M, Pollock J, et al. Biliary dyskinesia: The most
assisted resection of choledochal cyst and Roux-en-Y reconstruc- common indication for cholecystectomy in children. Surgery
tion. Surg Endosc 2001;15:54552. 2005;138:72633.
73. Tan HL, Shankar KR, Ford WD. Laparoscopic resection of type 97. Cay A, Imamoglu M, Kosucu P, et al. Gallbladder dyskinesia: A
I choledochal cyst. Surg Endosc 2003;17:1495. cause of chronic abdominal pain in children. Eur J Pediatr Surg
74. Li L, Feng W, Jing-Bo F, et al. Laparoscopic-assisted total cyst 2003;13:3026.
excision of choledochal cyst and Roux-en Y hepatoenterostomy. 98. St. Peter SD, Keckler SJ, Nair A, et al. Laparoscopic cholecystec-
J Pediatr Surg 2004;39:16636. tomy in the pediatric population. J Laparoendosc Adv Surg Tech
75. Lee H, Hirose S, Bratton B, et al. Initial experience with complex A 2008;18:12730.
laparoscopic biliary surgery in children: Biliary atresia and 99. Halata MS, Berezin SH. Biliary dyskinesia in the pediatric patient.
choledochal cyst. J Pediatr Surg 2004;39:8047. Curr Gastroenterol Rep 2008;10:3328.
76. Jang JY, Kim SW, Han HS, et al. Totally laparoscopic manage- 100. Campbell BT, Narasimhan NP, Golladay ES, et al. Biliary dyski-
ment of choledochal cyst using a four-hole method. Surg Endosc nesia: A potentially unrecognized cause of abdominal pain in chil-
2006;20:17625. dren. Pediatr Surg Int 2004;20:57981.
77. Laje P, Questa H, Bailez M. Laparoscopic leak-free technique for 101. Rau B, Friesen CA, Daniel JF, et al. Gallbladder wall inflammatory
the treatment of choledochal cyst. J Laparoendosc Adv Surg Tech cells in pediatric patients with biliary dyskinesia and cholelithiasis:
A 2007;17:51921. A pilot study. J Pediatr Surg 2006;41:15458.
78. Aspelund G, Ling SC, Ng V, et al. A role for laparoscopic approach 102. Friesen CA, Neilan N, Daniel JF, et al. Mast cell activation and
in the treatment of biliary atresia and choledochal cysts. J Pediatr clinical outcomes in pediatric cholelithiasis and biliary dyskinesia.
Surg 2007;42:86973. BMC Research Notes 2011;4:322:18.
79. Hong L, Wu Y, Yan Z, et al. Laparoscopic surgery for choledochal 103. Hadigan C, Fishman SJ, Connolly LP, et al. Stimulation with fatty
cyst in children: A case review of 31 patients. Eur J Pediatr Surg meal (Lipomul) to assess gallbladder emptying in children with
2008;18:6771. chronic acalculous cholecystitis. J Pediatr Gastroenterol Nutr
80. Liem NT, Dung LA, Son TN. Laparoscopic complete cyst exci- 2003;37:17882.
sion and hepaticoduodenostomy for choledochal cyst: Early 104. Brugge WR, Brand DL, Atkins HL, et al. Gallbladder
results in 74 cases. J Laparoendos Adv Surg Tech 2009;19: dyskinesia in chronic acalculous cholecystitis. Dig Dis Sci 1986;31:
s8790. 4617.
81. Liem NT, Hien PD, Dung LA, et al. Laparoscopic repair for 105. Kaye AJ, Jatia M, Mattei P, et al. Use of laparoscopic cholecystec-
choledochal cyst: Lessons learned from 190 cases. J Pediatr Surg tomy for biliary dyskinesia in the child. J Pediatr Surg
2010;45:5404. 2008;43:10579.
82. Chokshi NK, Guner YS, Aranda A, et al. Laparoscopic choledo- 106. Carney DE, Kokoska ER, Grosfeld JL, et al. Predictors of suc-
chal cyst excision: Lessons learned in our experience. J Laparoen- cessful outcome after cholecystectomy for biliary dyskinesia.
dosc Adv Surg Tech A 2009;19:8791. J Pediatr Surg 2004;39:81316.
83. Lee KH, Tam YH, Yeung CK, et al. Laparoscopic excision of 107. Roy CC, Belli DC. Hepatobiliary complications associated with
choledochal cyst in children: An intermediate-term report. Pediatr TPN: An enigma. J Am Coll Nutr 1985;4:65160.
Surg Int 2009;25:35560. 108. El-Shafie M, Mah CL. Transient gallbladder distention in sick
84. Kirschner HJ, Szavay PO, Schaefer JF, et al. Laparoscopic Roux- premature infants: The value of ultrasonography and radionuclide
en-Y hepaticojejunostomy in children with long common pan- scintigraphy. Pediatr Radiol 1986;16:46871.
creaticobiliary channel: Surgical technique and functional 109. Manji N, Bistrian BR, Mascioli EA, et al. Gallstone disease in
outcome. J Laparoendosc Adv Surg Tech A 2010;20:L4858. patients with severe short bowel syndrome dependent on
85. Diao M, Li L, Zhang JS, et al. Laparoscopic-assisted clearance of parenteral nutrition. J Parent Enter Nutr 1989;13:4614.
protein plugs in the common channel in children with choledo- 110. Quigley EM, Marsh MN, Shaffer JL, et al. Hepatobiliary compli-
chal cysts. J Pediatr Surg 2010;45:2099102. cations of total parenteral nutrition. Gastroenterology 1993;
86. Miyano G, Koga H, Shimotakahara A, et al. Intralaparoscopic 104:286301.
endoscopy: Its value during laparoscopic repair of choledochal 111. Lindberg MC. Hepatobiliary complications of oral contracep-
cyst. Pediatr Surg Int 2011;27:4636. tives. J Gen Intern Med 1992;7:199209.
87. Woo R, Le D, Albanese CT, Kim SS. Robot-assisted laparoscopic 112. Shocket E. Abdominal abscess from gallstones spilled at laparo-
resection of a type I choledochal cyst in a child. J Laparoendosc scopic cholecystectomy. Surg Endosc 1995;9:3447.
Adv Surg Tech A 2006;16:17983. 113. Stern RC, Rothstein FC, Doershuk CF. Treatment and prognosis
88. Meehan JJ, Elliots S, Sandler A. The robotic approach to complex of symptomatic gallbladder disease in patients with cystic fibrosis.
hepatobiliary anomalies in children: Preliminary report. J Pediatr J Pediatr Gastroenterol Nutr 1986;5:3540.
Surg 2007;42:211014. 114. Kaechele V, Wabitsch M, Thiere D, et al. Prevalence of gallblad-
89. Liem NT, Pham HD, Vu HM. Is the laparoscopic operation der stone disease in obese children and adolescents: Influence of
as safe as open operation for choledochal cyst in children? the degree of obesity, sex, and pubertal development. J Pediatr
J Laparoendosc Adv Surg Tech A 2011;21:36770. Gastroenterol Nutr 2006;42:6670.
90. Diao M, Li L, Cheng W. Laparoscopic versus open Roux-en-Y 115. Stringer MD, Taylor DR, Soloway RD. Gallstone composition:
hepaticojejunostomy for children with choledochal cysts: Are children different? J Pediatr 2003;142:43540.
606 SECTION IV Abdomen
116. Stringer MD, Soloway RD, Taylor DR, et al. Calcium carbonate 128. Ware R, Filston HC, Schultz WH, et al. Elective cholecystectomy
gallstones in children. J Pediatr Surg 2007;42:167782. in children with sickle hemoglobinopathies. Ann Surg 1988;
117. Sayers C, Wyatt J, Soloway RD, et al. Gallbladder mucin produc- 208:1722.
tion and calcium carbonate gallstones in children. Pediatr Surg 129. Sandler A, Winkel G, Kimura K, et al. The role of prophylactic
Int 2007;23:21923. cholecystectomy during splenectomy in children with hereditary
118. Holcomb GW III, Morgan WM III, Neblett WW III, et al. spherocytosis. J Pediatr Surg 1999;34:10778.
Laparoscopic cholecystectomy in children: Lessons learned from 130. Mah D, Wales P, Njere I, et al. Management of suspected common
the first 100 patients. J Pediatr Surg 1999;34:123640. bile duct stones in children: Role of selective intraoperative
119. Kumar R, Nguyen K, Shun A. Gallstones and common bile duct cholangiogram and endoscopic retrograde cholangiopancreatog-
calculi in infancy and childhood. Aust N Z J Surg 2000;70: raphy. J Pediatr Surg 2004;39:80812.
18891. 131. Newman KD, Powell DM, Holcomb GW III. The management
120. Waldhausen JHT, Graham DD, Tapper D. Routine intraoperative of choledocholithiasis in children in the era of laparoscopic chole-
cholangiography during laparoscopic cholecystectomy minimizes cystectomy. J Pediatr Surg 1997;32:111619.
unnecessary endoscopic retrograde cholangiopancreatography in 132. Shah RS, Blakely ML, Lobe TE. The role of laparoscopy in the
children. J Pediatr Surg 2001;36:8814. management of common bile duct obstruction in children. Surg
121. Winter SS, Kinney TR, Ware RE. Gallbladder sludge in children Endosc 2001;15:13535.
with sickle cell disease. J Pediatr 1994;125:7479. 133. Zargar SA, Javod G, Khan BA, et al. Endoscopic sphincterotomy
122. Al-Salem AH, Qaisruddin S. The significance of biliary sludge in in the management of bile duct stones in children. Am J Gastro-
children with sickle cell disease. Pediatr Surg Int 1998;13:1416. enterol 2003;98:5869.
123. Cooperberg PL, Burhenne HJ. Real-time ultrasonography: Diag- 134. Muhe E. Die erste cholecystectomy durch das laparoscope. Lan-
nostic treatment of choice in calculous gallbladder disease. N Engl genbecks Arch Chir 1986;369:8046.
J Med 1980;302:12779. 135. Dubois F, Berthelot G, Levard H. Cholecystectomy by coelios-
124. Haberkern CM, Neumayr LD, Orringer EP, et al. Cholecystec- copy (in French). Presse Med 1989;18:9802.
tomy in sickle cell anemia patients: Perioperative outcome of 364 136. Reddick EJ, Olsen DO. Laparoscopic laser cholecystectomy. A
cases from the National Preoperative Transfusion Study. Preop- comparison with mini-lap cholecystectomy. Surg Endosc 1989;
erative Transfusion in Sickle Cell Disease Study Group. Blood 3:1313.
1997;89:153342. 137. McKernan JB. Laparoscopic cholecystectomy. Am Surg 1991;
125. Wales PW, Carver E, Crawford MW, et al. Acute chest syndrome 57:30912.
after abdominal surgery in children with sickle cell disease: Is a 138. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of
laparoscopic approach better? J Pediatr Surg 2001;36:71821. biliary injury during laparoscopic cholecystectomy. J Am Coll
126. Bhattacharyya N, Wayne AS, Kevy SV, Shamberger RC. Periop- Surg 1995;180:10125.
erative management for cholecystectomy in sickle cell disease. 139. Ostlie DJ, Adibe OO, Juang D, et al. Single incision versus 4-port
J Pediatr Surg 1993;28:725. laparoscopic cholecystectomy: A propsective randomized trial.
127. Sandoval C, Stringel G, Ozkaynak MF, et al. Perioperative man- J Pediatr Surg 2013;48(1):20914.
agement of children with sickle cell disease undergoing laparo-
scopic surgery. JSLS 2002;6:2933.
C H A P T E R 4 5
The ability to successfully perform solid organ transplan- and cirrhosis present as older children and adolescents
tation in children has led to a remarkable improvement requiring LT.
in survival and quality of life. In this chapter each of the
solid organ transplant procedures will be discussed, Biliary Atresia
including the indications, operative procedure, and post-
operative complications relevant to the practicing pedi- Children with extrahepatic biliary atresia constitute at
atric surgeon. least 50% of the pediatric LT population. Successful
biliary drainage achieving an anicteric state following the
Kasai portoenterostomy is the most important factor
LIVER TRANSPLANTATION affecting preservation of liver function and long-term
survival.1 Primary transplantation without portoenteros-
Few subspecialties have undergone the dramatic improve- tomy is not recommended in patients with biliary atresia
ments in survival that have occurred in pediatric liver unless the initial presentation is greater than 120 days of
transplantation (LT). In the early 1980s, survival rates of age and the liver biopsy shows advanced cirrhosis.2,3 We
30% limited the enthusiasm for this costly and work- believe that the Kasai portoenterostomy should be the
intensive endeavor. The introduction of more effective primary surgical intervention for all other infants with
immunosuppression along with refinements in the opera- extrahepatic biliary atresia. Patients with progressive
tive and postoperative management of infants and chil- disease following a Kasai procedure should be offered
dren has led to survival rates greater than 90%. Challenges early orthotopic liver transplantation (OLT). The sequen-
remain, including the need for donor organs suitable for tial use of these two procedures optimizes overall survival
pediatric recipients of all ages and sizes, the optimization and organ use.3
of the pretransplant patient physiology to increase peri- Patients with extrahepatic biliary atresia who are seen
transplant survival, and the improvement in long-term for transplantation form several cohorts. Infants with a
quality of life. failed Kasai have recurrent cholangitis, ascites, rapidly
progressive portal hypertension, malnutrition, and pro-
Indications for Transplantation gressive hepatic synthetic failure, and often require OLT
within the first two years of life. Children with the suc-
The most common clinical presentations prompting cessful establishment of biliary drainage have an improved
transplant evaluation in children can be classified as prognosis, but this alone does not preclude the develop-
follows: (1) primary liver disease with the expected ment of cirrhosis and portal hypertension leading to
outcome of hepatic failure; (2) stable liver disease with hypersplenism, variceal hemorrhage, ascites, and occa-
significant morbidity or known mortality; (3) hepatic- sionally hepatopulmonary syndrome. These patients may
based metabolic disease; (4) fulminant hepatic failure; and require LT later in childhood. Patients with mild hepa-
(5) hepatic malignancy, particularly hepatoblastoma, tocellular enzyme and bilirubin elevation, and mild portal
where the lesion is not resectable by conventional means. hypertension can be observed with ongoing medical
In addition, children with diffuse and extensive arteriov- therapy. Approximately 20% of all patients with biliary
enous anomalies or benign vascular tumors leading to atresia will not require OLT at some point in their life.4,5
irreversible heart failure should also be considered for
transplantation.
Alagille Syndrome
Table 45-1 reviews the leading diagnoses that lead to
LT. These disease entities define the bimodal age distri- Alagille syndrome (angiohepatic dysplasia) is an auto-
bution of pediatric transplant recipients. Infants and somal dominant genetic disorder that manifests as bile
children with biliary atresia and, occasionally, rapidly duct paucity which leads to progressive cholestasis and
progressive hepatic failure secondary to metabolic abnor- pruritus, xanthomas, malnutrition, and growth failure.
malities, such as neonatal tyrosinemia, hemochromatosis, Liver failure occurs late, if at all. Specific criteria for LT
or neonatal hepatic vascular tumors, are the patients who are difficult to quantify. Preoperative evaluation must
require transplantation early in life. Patients with hepatic include assessment for congenital cardiac disease and
tumors, metabolic disturbances, fulminant hepatic failure, renal insufficiency, both of which are associated with this
607
608 SECTION IV Abdomen
syndrome. Hepatocellular carcinoma (HCC) has also preclude transplantation, such as in patients with tyro-
been seen in occasional patients.6,7 sinemia, in whom there is a high risk of HCC.12 Although
Experience using external biliary diversion or internal results of transplantation are excellent in the metabolic
ileal bypass accompanied by ursodeoxycholic acid therapy disease subgroup, replacement of the entire liver in order
has demonstrated a significant decrease in both pruritus to correct single enzyme deficiencies is an inefficient, but
and complications of hypercholesterolemia.8 Both of presently necessary procedure. Current research centers
these procedures may ameliorate or decrease the rate of around hepatocyte transplantation and gene therapy.1317
ongoing parenchymal destruction and cirrhosis, obviat- These efforts may better serve this patient population in
ing the need for LT. Quality of life issues such as intrac- the future. Patients with primarily extrahepatic manifes-
table pruritus, hypercholesterolemia, severe growth tations of their disease, such as cystic fibrosis, are occa-
retardation, and intractable bone disease are criteria for sionally helped by LT, although their prognosis is most
consideration for LT.911 often determined by their primary illness.18
OLT, because significant increases in ICP can develop offers significantly better long-term survival compared to
postoperatively. Failure to maintain a cerebral perfusion embolization or hepatic artery occlusion which can pre-
pressure greater than 50mmHg and an ICP less than cipitate sudden and widespread hepatic necrosis. Pre-
20mmHg has been associated with very poor neurologic transplant biopsy is essential in large or complex lesions
outcomes.21 Also, survival following LT is significantly to exclude angiosarcoma.
decreased in patients who reach grade IV encephalopa-
thy. Efforts to identify and perform LT in children before
this deterioration occurs are of utmost importance. When
Contraindications
candidates are identified before they develop irreversible Contraindications to LT include (1) extrahepatic un-
neurologic abnormalities, the results of transplantation resectable malignancy; (2) malignancy metastatic to the
are dramatically improved. liver; (3) progressive terminal nonhepatic disease; (4)
uncontrolled systemic sepsis; and (5) irreversible neuro-
logic injury.
Liver Tumors
Relative contraindications to LT that need to be indi-
Transplantation for hepatoblastoma is recommended for vidually evaluated include (1) advanced or partially treated
individuals who, after the administration of several cycles systemic infection; (2) advanced hepatic encephalopathy
of chemotherapy, have a neoplasm confined to the liver (grade IV); (3) severe psychosocial difficulties; (4) portal
that is unresectable.22,23 Children who had prior isolated venous thrombosis extending throughout the mesenteric
metastasis that disappeared while undergoing preopera- venous system; and (5) serology positive for HIV.
tive chemotherapy can be considered in select instances.24
A favorable response to pretransplant chemotherapy sug-
gests a more favorable long-term outcome.25 In the Donor Considerations
current Childrens Oncology Group (COG) trial AHEP
Donor Options
0731, early referral for transplant evaluation is being
evaluated for children who present with large lesions that The single factor limiting the availability of LT is the
appear unresectable. supply of donor organs. The number of patients awaiting
Transplantation for HCC is complicated by less suc- LT has increased by eleven fold since 1991.28,29 Available
cessful chemotherapy options and frequent extrahepatic donor resources have not kept pace. As a consequence,
involvement. The reported two-year survival rates are the waiting time to transplant for all pediatric age groups
only 2030%.26 Most deaths are due to recurrent HCC has increased significantly, with young children and
within the allograft or to extrahepatic tumor involve- infants most affected (Figs 45-1 and 45-2). This severely
ment. When primary HCC is discovered incidentally limited supply of available donor organs has driven the
within the cirrhotic native liver at the time of hepatec- advancement of many innovative liver transplant surgical
tomy, the overall prognosis is unaffected by the tumor.27 procedures. The development of reduced-size LT allowed
Vascular tumors represent a group of patients with significant expansion of the donor pool for infants and
diffuse pathology who can benefit from transplantation. small children. This not only improved the availability of
Children with progressive, intractable congestive heart donor organs but also allowed access to donors with
failure, even when caused by non-neoplastic arteriov- improved stability and organ function. Evolution of these
enous malformations or diffuse hemangiomas, offer a operative techniques has resulted in the development of
unique opportunity for complete removal of the vascular both split-LT and live donor (LD) transplantation.
malformation and correction of congestive heart failure. In the hands of experienced transplant teams, these
Transplantation in these instances in our experience procedures all have similar success to whole organ
610 SECTION IV Abdomen
0
9899 0001 0203 0405 0607 0809 1011 age <1 year, and evidence of failure to thrive (Box 45-2).
The primary function of PELD is the stratification of
Year
candidates for LT by risk of 90 day waiting list mortality,
FIGURE 45-1 Graph depicting the mortality rate for adults and allowing optimal use of donor organs. When death rates
children on the liver transplant waiting list from 19992010. for all children listed were analyzed, PELD was an
Note the largest number of deaths occur in infants less than 1
year of age. The numbers represent the age of the patient (in accurate predictor of mortality risk and demonstrated
years). (Source: Scientific Registry Transplant Recipients2011 progressive risk until high scores were reached (>35)
Annual Report). (Fig. 45-3).32
Donor Selection
transplantation. Furthermore, access to these donor
options has reduced the waiting list mortality rate to less Assessment of donor organ suitability is undertaken by
than 5%. evaluating clinical information, static biochemical tests,
and dynamic tests of hepatocellular function. Static bio-
Organ Allocation chemical tests identify preexisting functional abnormali-
ties or organ trauma, but do not serve as good benchmarks
In 1998, the final rule established by the Health to differentiate among acceptable and poor donor allo-
Resources and Service Administration (HRSA) mandated grafts. Donor liver biopsy is helpful in questionable
the formation of a system for candidate stratification cases to identify preexisting liver disease or donor liver
based on a continuous severity score reflecting 90 day steatosis. The shortage of donor organs has led to
waiting list mortality, i.e., outcome.30 The system for expanded efforts to use individuals of advanced age and
pediatric patients, the Pediatric End-Stage Liver Disease marginal stability, termed extended criteria donors
(PELD) score, was created using an analysis of the pro- (ECD).33 The evolving donor risk index (DRI) is used as
spective registry of children listed for transplantation by a guide that quantifies relative risk of graft failure.34 In
the consortium Studies of Pediatric Liver Transplanta- the future, organ allocation may be based on maximal life
tion (SPLIT).31 The parameters selected included total years gained, an approach being utilized in kidney
bilirubin, international normalized ratio (INR), albumin, allocation.35
100
80
60
Percent
40
Removed from list FIGURE 45-2 This diagram describes what has
20 Died happened to children who have been listed for liver
Transplanted (LD) transplantation. Fortunately, most of the patients
Transplanted (DD) have undergone either live donor (LD) or deceased
0 Still waiting donor (DD) transplantation, although about 5%
6 12 18 24 30 36 of patients are still on the transplant list after
36 months. (Source: Scientific Registry Transplant
Months post-listing Recipients2011 Annual Report).
45 Solid Organ Transplantation in Children 611
100
95
PELD 11 to 6
85 PELD 7 to 16
FIGURE 45-3 Pediatric End-Stage Liver Disease PELD 16 to 28
score predictive of survival after transplantation. PELD >28
(Redrawn from Barshes NR, Lee TC, Udell IW, etal. 80 Status 1
The PELD model as a predictor of survival benefit and 0 1 2 3 4 5 6 7 8 9 10 11 12
of post transplant survival in pediatric liver transplant
recipients. Liver Transpl 2006;12:47580.) Months post OLTx
Anatomic replacement of the native liver in the ortho- lobar plane through the gallbladder fossa to the vena
topic position requires selection or surgical preparation cava.36,37 A crush and tie technique is preferred to achieve
of the donor liver to fill, but not exceed available space good closure of the vascular and biliary structures. The
in the recipient. When using full-sized allografts, a donor bile duct, portal vein, and hepatic artery are divided at
weight range from 50125% of the recipient weight is the right or left confluence. The vena cava is left incor-
usually appropriate, taking into consideration body porated with the allograft in both right and left lobe
habitus and factors that would increase the abdominal preparation. Vena caval reduction by posterior caval wall
size in the recipient such as ascites and hepatospleno resection and closure is occasionally necessary. Resection
megaly. The right lobe graft, using segments 5 to 8, and of the inferior protruding portion of the caudate lobe is
the right trisegmentectomy graft using segments 4 to 8 necessary during left lobe preparation to reduce the like-
can be accommodated when the weight difference is no lihood of arterial angulation, which can result in arterial
greater than 2:1 between the donor-to-recipient (D:R). thrombosis. This also facilitates shortening of the infe-
The thickness of the right lobe makes this allograft of rior vena cava to fit in a small recipient.38 When using
limited usefulness in small recipients. Right lobe grafts left lateral segment (LLS) allografts, the parenchymal
from LDs have become widely used in adults. The left dissection follows the right margin of the falciform liga-
lobe, using segments 1 to 4, is applicable with a D:R ment with preservation of the left hilar structures. Direct
disparity from 2.5:1 to 5:1, and a left lateral segment implantation of the left hepatic vein into the combined
(segments 2 and 3) can be used with up to a 10:1D:R orifice of the right and middle/left hepatic veins in the
weight difference. recipient vena cava is preferred; the donor vena cava is
Although whole organ allografts are preferred, techni- not retained with this segmental allograft. Further reduc-
cal variant grafts are commonly employed. Preoperative tion of the LLS graft to a monosegmental graft may be
preparation of variant liver allografts is based on the necessary in very small recipients. Resection of the distal
anatomy of the hepatic vasculature and bile ducts. In the LLS is technically easier than an anatomic segment II/III
past, reduced-size grafts were common, but because of division. Because this procedure adds considerably to the
the donor shortage, split-liver transplantation has become donor procurement time, and the necessary skill of
widespread using either ex situ or an in situ approach. the donor team, it is more demanding and occasionally
The result is two transplantable grafts. The ex situ split difficult to successfully orchestrate. This technique is,
procedure divides the right lobe allograft (segments 5 to however, despite these considerations, the preferred
8) from the left lateral segment allograft (segments 2 and method for split-liver donor preparation.39,40
3) after the whole donor organ has been procured. As this The benefits of split-liver transplantation are best
division is undertaken under hypothermic conditions achieved when ideal donors are selected. Strict restric-
without hepatic perfusion, the vascular integrity of tions on age, vasopressor administration, pre-donation
segment 4 is difficult to assess and is frequently discarded. hepatic function, and limited donor hospitalization have
Conventional techniques for implanting the respective been used to select optimal donor candidates. When
allografts are then used. these donors are selected, the results from both in situ
The successful experience with in situ division of the and ex-situ techniques are similar, with both techniques
living donor left lateral segment is a basis for the in situ now having patient survival for both allografts of 9093%
split procedure. Two variations of the procedure are uti- and graft survival rates of 8689%.41
lized depending on the needs of the recipients, a right The use of LDs has increased as the safety and success
left lobe split or a right trisegmentectomyleft lateral of this approach has been demonstrated (Fig. 45-4).4244
segment split. For the right trisegmentectomyleft lateral One of the critical elements of LD transplantation is the
segment split, the left lateral segment is prepared similar proper selection of a donor, usually a parent or relative.
to a living related donor graft. The viability of segment This procedure is performed on the assumption that
4 can be examined at the time of the division and is donor safety can be assured and that the donors liver
usually incorporated with the right lobe graft to increase function is normal. Careful attention to proper living
the cellular mass of the allograft. For a left-right lobe donor consent is important. Parental concerns to help
graft, the parenchymal resection follows the anatomic their ill child make true informed consent are a challenge.
612 SECTION IV Abdomen
IVC IVC
2
7 8
4 3
BD
BD
6 5
PV
HA
PV HA
Right lobe Left lobe LHV
2
IVC
BD 3
IVC
2 PV
HA
7 8 Left lateral segment
2 1
7 8 4 3
3 LHV
4
6 5 2
6 5
BD 3
In situ split liver
PV
PV
HA
Living donor
IVC Ex vivo split liver
LHV
7 8
2
BD
6 5 BD 3
HA PV 4 PV
HA
Discard
FIGURE 45-5 Anatomic donor options available through surgical reduction. The numbers correlate to the segmental hepatic
anatomy as defined by Couinaud. BD, bile duct; HA, hepatic artery; IVC, inferior vena cava; LHV, left hepatic vein; PV, portal vein.
Control of hemorrhage is essential during the recipi- to the undersurface of the diaphragm to prevent torsion
ent hepatectomy, requiring meticulous technique. Coag- and venous obstruction of this anastomosis. Similar fixa-
ulation factor assays (V, VII, VIII, fibrinogen, platelets, tion is not necessary with right or left lobe allografts or
prothrombin time, partial thromboplastin time) allow with whole organ transplants.
specific blood product supplementation to improve clot- Before completing the vena caval anastomosis, the
ting function. Use of venovenous bypass is reserved for hyperkalemic preservation solution is flushed from the
recipients >40kg who demonstrate hemodynamic insta- graft using 5001000mL of hypothermic normokalemic
bility at the time of venous interruption. intravenous (IV) solutions. When using full-sized grafts
Removal of the diseased liver is performed after vas- in older patients, we prefer to complete all venous anas-
cular isolation is achieved. Retroperitoneal hemostasis is tomoses before constructing the hepatic artery anasto-
achieved before implanting the donor liver. In standard mosis IV. In reduced-size allografts and in small recipients
LT, the suprahepatic vena cava is prepared by suture liga- where we prefer direct aortic vascular inflow reconstruc-
tion of any large phrenic orifices and creating one caval tion, the hepatic arterial anastomosis is completed before
lumen from the confluence of the inferior vena cava and the portal vein anastomosis to improve visibility of the
hepatic vein orifices. The donor liver is implanted using infrarenal aorta without placing traction on the portal
conventional vascular techniques and monofilament vein anastomosis. We prefer to complete all anastomoses
suture for the vascular anastomosis. In small recipients, using vascular isolation before organ reperfusion,
interrupted suture techniques, monofilament dissolving although some transplant teams re-perfuse after the
suture material, and a growth factor knot has been used venous reconstruction is complete.
to allow for vessel growth. When LLS grafts are used, Before re-establishing circulation to the allograft,
the left hepatic vein orifice is anastomosed directly to the anesthetic adjustments must be made to address the large
anterolateral surface of the infradiaphragmatic inferior volume of blood needed to refill the liver as well as hypo-
vena cava using the combined rightmiddle hepatic vein thermic solutions released upon reperfusion. Inotropic
orifices. The LLS allograft is later fixed when necessary support using dopamine (510g/kg/min) is also started.
614 SECTION IV Abdomen
Calcium and sodium bicarbonate are administered to the prior Roux-en-Y limb can be used, with a 3035cm
combat the effects of hyperkalemia from any remaining length being preferred. Primary bile duct reconstruction
preservation solution or from systemic acidosis due to without stenting is used in older patients with whole
aortic and vena caval occlusion. Sufficient blood volume organ allografts.
expansion, administered as packed red blood cells to raise When closing the abdomen, increased intra-abdominal
the central venous pressure (CVP) to 1520cmH2O and pressure should be avoided. In many cases, the abdominal
the hematocrit to 40%, minimizes the development of fascia is not closed and mobilized skin flaps and running
hypotension on unclamping and prevents dilutional monofilament skin closure are used. Formal musculofas-
anemia. Cooperative communication between the surgi- cial abdominal closure can be completed before patient
cal and anesthesia teams facilitates a smooth sequential discharge.
reestablishment of vena caval, portal venous, and then
arterial recirculation to the allograft.
Biliary tract reconstruction in patients with biliary
Immunosuppressive Management
atresia or in those weighing less than 25kg is achieved Most centers use an immunosuppressive protocol based
through an end-to-side choledochojejunostomy using on the administration of multiple complementary medi-
interrupted dissolving monofilament sutures. A multife- cations. All use corticosteroids and cyclosporine or
nestrated Silastic internal biliary stent is placed before tacrolimus. Additional antimetabolites (azathioprine,
completing the anastomosis (Fig. 45-6). In most cases, mycophenolate) are used when more intensive treatment
is needed. Prior protocols using polyclonal or mono-
clonal induction therapy have been abandoned in most
cases due to the extent of the immunosuppressive potency.
A sample protocol is given in Table 45-3.
Multifenestrated
internal stent Postoperative Complications
Most postoperative complications present with cholesta-
sis, increasing hepatocellular enzyme levels, and on occa-
sion fever, lethargy, and anorexia. Therapy directed at
the specific causes of the allograft dysfunction is
essential. Empiric therapy for presumed complications
is fraught with misdiagnoses, morbidity, and mortality.
Roux-en-Y Roux-en-Y A flow diagram outlining this evaluation is shown in
FIGURE 45-6 Bile duct reconstruction is shown using the Figure 45-7.
common hepatic duct in whole organ transplants (left) and seg-
mental hepatic ducts into a Roux-en-Y intestinal limb for
reduced-sized liver transplants (right). An internal multifenes- Primary Nonfunction
trated stent is used in both situations. (From Ryckman F. Liver
transplantation. In: Ziegler MM, Azizkhan RG, Weber T, editors. Primary nonfunction (PNF) of the hepatic allograft
Operative Pediatric Surgery. New York: McGraw-Hill; 2003. p. 1275.) implies the absence of metabolic and synthetic activity
D/C, discontinue.
45 Solid Organ Transplantation in Children 615
Hepatic dysfunction
Vascular
Hepatocellular Biliary
Angiogram
or Liver biopsy
Leak Obstruction
Operative
exploration
Infection Rejection Drug reaction Computed tomography
Preservation +/
Recurrent Percutaneous
Thrombectomy Steroid injury transhepatic cholangiography
Anticoagulate recycle or
Endoscopic retrograde
cholangiopancreatography
Rescue medication
OKT-3
ATG Transhepatic stent
Mycophenolate or
Operative repair
Retransplant
FIGURE 45-7 Schematic flow diagram for management of postoperative liver allograft dysfunction. ATG, antithymocyte globulin;
OKT-3, monoclonal antibody.
Factors Related to Primary donors and, when severe, is recognized grossly by the
BOX 45-3 enlarged yellow, greasy consistency of the donor liver.
Nonfunction
The risk of PNF increases as the degree of fatty infiltra-
DONOR FACTORS tion increases.54 Histologic findings are classified as mild
Preexisting disease or injury to donor, anemia, hypoxia, if less than 30% of the hepatocytes have fatty infiltration,
hypotension before organ harvest moderate if 30 to 60% are involved, and severe if more
Donor organ steatosis (>60% macrovesicular fat) than 60% of the hepatocytes have fatty infiltration. Livers
with severe fatty infiltration should be discarded, and
TRANSPLANT FACTORS donors with moderate involvement are used with some
Prolonged cold ischemic storage (>812 hours) concern, with the degree of steatosis and the condition
Prolonged warm ischemic time at implantation of the recipient determining use of the allograft.
Complex vascular anastomosis requiring surgical The use of ABO-incompatible donors has been con-
revision troversial. Allograft and patient survival rates in adult
Significant size discrepancy between donor and
recipient
recipients have not been comparable to those achieved
using ABO-identical or compatible donors.55,56 However,
RECIPIENT FACTORS pediatric recipients of ABO-incompatible allografts have
Post-reperfusion hypotension achieved survival rates equivalent to those using ABO-
Vascular thrombosis compatible and ABO-identical donors with either cadav-
Immunologic factors eric donors (CDs) or LDs.5759
ABO incompatible, positive cross-match
Vascular Thrombosis
Hepatic artery thrombosis (HAT) occurs in children
following LT. Complete nonfunction requires immediate three to four times more frequently than in adult trans-
retransplantation before irreversible coagulopathy and plant series, occurring most often within the first 30 days
cerebral edema occur. Lesser degrees of allograft dys- following transplantation.60,61 Factors influencing the
function occur more frequently, and are associated with development of HAT are listed in Box 45-4. HAT presents
several donor, recipient, and operative factors (Box 45-3). with a variable clinical picture that may include: (1) ful-
The status of the donor liver contributes significantly to minant allograft failure; (2) biliary disruption or obstruc-
the potential for PNF. Ischemic injury secondary to tion; or (3) systemic sepsis. Doppler ultrasound (US)
anemia, hypotension, hypoxia, or trauma is often difficult imaging has been accurate in identifying arterial throm-
to ascertain in the history of multiple trauma victims. bosis, and is used as the primary screening modality to
Donor liver steatosis has also been recognized as a factor assess vascular flow following transplantation or when-
contributing to severe dysfunction or nonfunction in the ever complications arise. Acute HAT with allograft failure
donor liver.53,54 Macrovesicular steatosis on donor liver most often requires immediate retransplantation. Suc-
biopsy is somewhat more common in adult than pediatric cessful thrombectomy and allograft salvage is possible if
616 SECTION IV Abdomen
Factors Affecting Vascular altered the flow within the splanchnic vascular bed or
BOX 45-4 unless severe portal vein stenosis in the recipient has
Thrombosis
impaired flow to the allograft. Preexisting PVT in the
DONOR/RECIPIENT AGE/WEIGHT ALLOGRAFT TYPE recipient can be overcome by thrombectomy, portal vein
Whole organ > reduced size replacement, or extra anatomic venous bypass. In biliary
Living donor reduced size atresia recipients, portal vein hypoplasia is best corrected
by anastomosis of the portal vein to the confluence of the
ANASTOMOTIC ANATOMY splenic and superior mesenteric veins in the recipient.
Primary hepatic artery > direct aortic When there is inadequate portal vein length on the donor
organ, iliac vein interposition grafts are used. Early
ALLOGRAFT EDEMAINCREASED VASCULAR RESISTANCE
thrombosis following LT requires immediate anasto-
Ischemic injury secondary to prolonged preservation; motic revision and thrombectomy. Discrepancies in
prolonged implantation venous size imposed by reduced-size allografts can be
Rejection
Fluid overload
modified to allow anastomotic construction.64,65 Deficien-
cies of anticoagulant proteins, such as protein C and S,
RECIPIENT HYPOTENSION AND/OR HYPERCOAGULABILITY and antithrombin III deficiency in the recipient must also
Administration of coagulation factors, fresh-frozen be excluded as a contributing cause for vascular throm-
plasma bosis.66 Failure to recognize PVT can lead to either allo-
Procoagulant factor deficiencies graft demise or, on a more chronic basis, to significant
portal hypertension with hemorrhagic sequelae or intrac-
table ascites.
Chronic Rejection
Uniform diagnosis and management of chronic rejection
is complicated by the lack of a consistent definition or
clinical course. Chronic rejection occurs in 510% of
transplanted patients. Its incidence appears to be decreas-
ing in all transplant groups, perhaps related to better
overall immunosuppressive strategies. There is some
suggestion that the use of tacrolimus based immunosup-
pression is a key element in this apparent decrease.73,74
FIGURE 45-8 Segmental bile duct stricture at the junction of the
Risk factors for its development are many, and no
left lateral and left medial segmental bile ducts in a left lobe factor predicts the outcome of treatment. The chronic
reduced-size allograft. Solid arrow, bile duct stricture; open rejection rate is significantly lower in recipients of LD
arrow, Roux-en-Y loop and bile duct anastomosis. (From grafts compared with cadaveric grafts.75 In that study,
Ryckman FC. Liver transplantation in children. In: Suchy FJ, editor. African-American recipients had a significantly higher
Liver Disease in Children. St. Louis: CV Mosby; 1994. p. 941.)
rate of chronic rejection than did Caucasian recipients.
In addition, the number of acute rejection episodes,
transplantation for autoimmune disease, occurrence of
of the biliary anastomosis and reimplantation of the bile post-transplant lymphoproliferative disease (PTLD), and
ducts into the Roux-en-Y is necessary. Percutaneous cytomegalovirus (CMV) infection were also significant
transhepatic cholangiography is essential to define the risk factors for chronic rejection. The primary clinical
intrahepatic ductal anatomy before operative revision, manifestation is a progressive increase in biliary ductal
and temporary catheter decompression of the obstructed enzymes (alkaline phosphatase, GGT) and progressive
bile ducts promotes treatment of cholangitis and allows cholestasis. Chronic rejection can be initially asympto-
elective reconstruction. Operative reconstruction is matic or may follow unsuccessful treatment for acute
accompanied by transhepatic passage of exteriorized mul- rejection. It can occur within weeks of transplantation or
tifenestrated biliary ductal stents, which remain in place later in the postoperative course.
until reconstructive success is documented. Late stenosis Chronic rejection usually follows one of two clinical
is unlikely. Dissection away from the vasobiliary sheath forms.76 In the first, the injury is primarily to the biliary
in the donor has significantly decreased the incidence of epithelium and the clinical course is slowly progressive
this complication. with preservation of synthetic function. Histologically,
Biliary complications have been seen with an increased either interlobular bile duct destruction in the absence of
frequency following LD in children. The LLS 2 and 3 ischemic injury or hepatocellular necrosis is seen. In full
bile ducts are frequently separate at the plane of paren- expression, this form is characterized as acute vanishing
chymal division. The need for individual drainage of bile duct syndrome when severe ductopenia is seen in at
these small biliary ducts makes the development of late least 20 portal tracts.77,78 The eventual spontaneous reso-
anastomotic stenosis more frequent. Individual segmen- lution in up to one-half of affected patients with tac-
tal strictures may not lead to jaundice in the recipient, rolimus therapy has led to the development of enhanced
but rather are identified by elevated gamma glutamyl immunosuppression protocols for this patient subgroup.76
transferase (GGT) or through ultrasound surveillance. Retransplantation is occasionally necessary, but it is rarely
Reoperation after ductal dilatation from the stricture needed emergently.
allows for easier reconstruction due to the increased The second subtype is characterized by the early
caliber of the segmental bile duct. development of progressive ischemic injury to both bile
ducts and hepatocytes, leading to ductopenia and ischemic
necrosis with fibrosis. The clinical picture of cholestasis
Acute Cellular Rejection
is accompanied by significant synthetic dysfunction with
Allograft rejection is characterized by the histologic triad superimposed vascular thrombosis or biliary stricture for-
of endothelialitis, portal triad lymphocyte infiltration mation. The vascular endothelial injury responsible for
with bile duct injury, and hepatic parenchymal cell the progressive ischemic changes is characterized by the
damage.70 Allograft biopsy is essential to establish the development of subintimal foam cells or fibrointimal
diagnosis before treatment. The rapidity of the rejection hypertrophy. The clinical course is relentlessly progres-
process and its response to therapy dictates the intensity sive, and nearly always requires retransplantation. Unfor-
and duration of antirejection treatment. tunately, recurrence of chronic rejection in the
Acute rejection occurs in approximately two-thirds of retransplanted allograft is common.77
patients following LT.71 The primary treatment is a short Recent studies have focused on donor specific anti-
course of high-dose steroids. Bolus doses administered body mediated abnormalities that may be the pathophysi-
over several days with a rapid taper to baseline therapy is ologic basis for chronic rejection.79 The immunologic
618 SECTION IV Abdomen
nature of this process is emphasized by the primary target suggest that earlier staged reduction of CNI prior to the
role of the biliary and vascular endothelium, the only development of severe GFR reduction will decrease, but
tissues in the liver that express class II antigen. Other not eliminate this complication. Once established,
interdependent cofactors such as CMV infection, human chronic renal failure does not appear to resolve with CNI
leukocyte antigen (HLA) mismatching, positive B-cell dose adjustment. Although CNI toxicity is now well
crossmatching, and differing racial demographics of the appreciated, the association of both hepatic and renal
donor to recipient have all failed to show consistent cor- disease in many metabolic diseases of childhood may also
relation with the development of chronic rejection.76,77 contribute to the GFR abnormalities seen after LT.
are at greatest risk, with seropositive donor-to-recipient continued until symptoms of lymphadenopathy have
combinations at the next greatest risk. Use of various resolved and viral EBV DNA PCR has returned to base-
immune-based prophylactic protocols including IV IgG line.91,96 It should however be cautioned that PTLD can
or hyper immune anti-CMV IgG, coupled with acyclovir develop and progress without increases in EBV-PCR
or ganciclovir/valganciclovir, have all achieved success in viral load.97
decreasing the incidence of symptomatic CMV infection, PTLD, a potentially fatal abnormal proliferation of
although seroconversion in seronegative recipients from B-lymphocytes, can occur in any situation in which
seropositive donor organs inevitably occurs. immunosuppression is used. The importance of PTLD
The clinical diagnosis of CMV infection is suggested in pediatric LT is a result of the intensity of the immu-
by the development of fever, leukopenia, maculopapular nosuppression required, its lifetime duration, and the
rash, hepatocellular abnormalities, respiratory insuffi- absence of prior exposure to EBV infection in 6080%
ciency, or GI hemorrhage. Hepatic biopsy or endoscopic of pediatric recipients. PTLD is the most common tumor
biopsy of colonic or gastroduodenal sites allows early in children following transplantation representing 50%
diagnosis with immunohistochemical evaluation. Rapid of all tumors compared to 15% in adults. About 80% of
blood and urine assays for CMV can also expedite the cases occur within the first two years following transplan-
diagnosis. In suspected cases, treatment should be insti- tation.94 Multiple studies analyzing immunosuppressive
tuted while awaiting culture or biopsy results owing to therapy and the development of PTLD have shown a
the potential rapidity and severity of this infection in a progressive increase in its incidence with (1) the increase
previously seronegative child. The treatment of CMV in total immunosuppressive load; (2) EBV nave recipi-
has been greatly improved by the development of ganci- ents; and (3) the intensity of active viral load.98 No single
clovir. Early treatment with IV IgG and ganciclovir is immunosuppressive agent has been directly related to
successful in most cases. PTLD, although high-dose cyclosporine, tacrolimus,
EBV infection occurring in the perioperative period polyclonal antilymphocyte sera (MALG, ALG), and
represents a significant risk to the pediatric recipient.91 It monoclonal antibodies (OKT-3) have all been impli-
has a varying presentation including a mononucleosis- cated. Prolonged treatment with antiT-cell agents and
like syndrome, hepatitis-simulating rejection, extranodal the increased duration, intensity, and total immunosup-
lymphoproliferative infiltration with bowel perforation, pressive load are the origin of the immunity that creates
peritonsillar or lymph node enlargement, and encepha- the background for neoplasia.
lopathy. In small children, its primary portal of entry is The second pathogenic feature influencing PTLD
often the tonsils, making asymptomatic tonsillar hyper- appears to be EBV infection. Primary or reactivation
trophy a common initial presentation.92 EBV infection infections usually precede the recognition of PTLD.
can occur as a primary infection or following reactivation Active EBV infection, whether primary or reactivation,
of a past infection. When serologic evidence of active involves B-cell proliferation. A simultaneous increase in
infection exists, an acute reduction in immunosuppres- cytotoxic T-cell activity is the normal hosts mechanism
sion is indicated. It has become clear that continuous for preventing EBV dissemination. Loss of this natural
surveillance is necessary as the presentation is often non- protection as a result of the administration of T-cell
specific and the prognosis is related to early diagnosis. inhibitory immunotherapy allows polyclonal B-cell pro-
Screening using quantitative PCR testing to determine liferation to progress following EBV viral replication and
the EBV blood viral load appears to be the best current release. These EBV proliferating cells express specific
predictor of risk. However, viral loads have been identi- viral antigens which represent possible targets for the
fied in asymptomatic patients and patients recovering immune system, thereby explaining the well described
from PTLD, limiting the specificity of this approach. regression of PTLD after immunosuppressive tapering.
The balance between viral load measured by quantitative With time, transformation of a small population of cells
PCR and specific cellular immune response, perhaps results in a malignant monoclonal aggressive B-cell
mediated by CD8 T-cells specific to EBV, may explain lymphoma.93,99101
this lack of specificity to viral load alone.9395 Most tumors seen in children are large cell lympho-
Many pediatric transplant centers now use serially mas, 80% being of B-cell origin. Extranodal involvement,
measured quantitative EBV DNA PCR as an indication uncommon in primary lymphomas, is seen in 70% of
for primary immunosuppression modulation. We recom- PTLD cases. Extranodal sites include central nervous
mend monthly EBV DNA PCR counts to monitor system, 27%; liver, 23%; lung, 22%; kidney, 21%; intes-
increased genomic expression. Increasing viral load levels tine, 20%; and spleen, 13%. Allograft involvement is
warrant more frequent monitoring on a weekly or every common and can mimic rejection. T-cell and B-cell
two week schedule. In the EBV seronegative pretrans- immunohistochemical markers of the infiltrating lym-
plant patients, >40 genomes/105 peripheral blood leuko- phocyte population define the B-cell infiltrate and assist
cytes (PBL), and >200 genomes/105 PBL identify patients in establishing an early diagnosis.
needing reduction in primary immunosuppression by 25 Treatment of PTLD is stratified according to the
to 100%. Institution of antiviral therapy with ganciclovir immunologic cell typing and clinical presentation.102
and CMV IgG is also used in most cases, although only Documented PTLD requires an immediate decrease or
nonrandomized observational studies support their use. discontinuation of immunosuppression and institution of
Both agents are active in vitro against linear replicating anti-EBV therapy. We prefer to use IV ganciclovir for
forms of the EBV, but have no activity against the circular initial antiviral therapy owing to the high incidence
episome in immortalized B-cells. Treatment should be of concurrent CMV infection. Acyclovir is used
620 SECTION IV Abdomen
enterocolitis, intestinal atresia, and gastroschisis in the TPN can be stopped, liver failure is a strong indication
newborn to Crohn disease and traumatic injury to the for combined liver/intestinal or multivisceral transplanta-
main intestinal blood supply in the older population. tion. Studies have shown that the presence of hyperbi-
Midgut volvulus, another frequent cause of SBS, can lirubinemia greater than 3mg/dL or bridging fibrosis
occur at any age, although the majority of cases occur in and cirrhosis found on liver biopsy in an infant dependent
infants. on TPN is associated with a 1-year survival of less than
The intestinal dysmotility syndromes include total 30%.139 The remaining criteria of limited central venous
intestinal aganglionosis (Hirschsprung disease) and the access, multiple catheter-related bloodstream infections,
constellation of disorders known as chronic idiopathic and frequent episodes of severe dehydration reflect com-
intestinal pseudo-obstruction. Absorptive disorders lead plications from chronic TPN use, and in the absence of
to intractable diarrhea due to impaired enterocyte absorp- significant concurrent liver dysfunction, are indications
tion, and include congenital epithelial mucosal diseases, for isolated intestinal transplantation.
such as microvillus inclusion disease, tufting enteropathy, Currently, with improved outcomes after intestinal
and autoimmune enteritis. Although these latter disor- transplantation, some centers advocate early intestinal
ders are rare, affected children face life-long difficulty transplantation before the onset of TPN-induced com-
with gastrointestinal absorptive function and require plications.140 These groups propose that patient and graft
TPN for long-term survival. survival after intestinal transplantation will be optimized
TPN is the standard treatment for patients who expe- if recipients undergo transplantation prior to the onset of
rience acute intestinal failure. Bowel rehabilitation should secondary organ damage, especially liver disease. Fur-
be aggressively pursued because intestinal adaptation can thermore, the quality of life in patients who have under-
result in eventual enteral autonomy. Intestinal rehabilita- gone successful intestinal transplantation may be better
tion programs that utilize a combination of TPN, gradual than that of patients who require long-term TPN admin-
re-introduction of enteral feeds, intestinal antimotility istration. This issue remains controversial and requires
agents, and treatment of small bowel bacterial over- further study because TPN is a well-established and
growth, in association with hepatoprotective lipid mini- effective means of treatment for patients with intestinal
mization strategies and ethanol lock usage to reduce the failure. In addition, with recent advances in hepatopro-
incidence of catheter-related bloodstream infections, are tective approaches to TPN administration and improved
successful in achieving enteral autonomy in many care related to central venous catheters, children with
patients.136,137 Autologous intestinal reconstruction pro- intestinal failure on TPN are now able to be maintained
cedures, such as the serial transverse enteroplasty (STEP) complication-free for longer periods of time, thereby
and longitudinal intestinal lengthening and tailoring allowing further delay in the need for intestinal trans-
(LILT), may be beneficial in selected patients. In general, plantation. Despite the lack of consensus with regard to
survival and complete return of gastrointestinal function optimal timing of intestinal transplantation, it has become
may be predicted when the post-resection length of the clear that early and timely patient referral for pretrans-
intestine exceeds 5% of normal for gestational age if the plant evaluation is critical to ensuring the best opportu-
ileocecal valve is present, or is greater than 10% of nity for long-term survival.141
normal if the ileocecal valve is absent.138
The current Medicare-approved indications for intes-
tinal transplantation are shown in Box 45-6.135 Progres-
Contraindications
sive liver dysfunction and TPN-associated cholestatic The contraindications to intestinal transplantation are
liver disease result in significant mortality. Unless the similar to those for any other solid organ transplantation.
The presence of severe cardiopulmonary dysfunction, an
active nonresectable malignancy, severe neurologic disa-
bilities, or life-threatening extraintestinal illness or infec-
Medicare-Approved Indications tion precludes intestinal transplantation.
BOX 45-6
for Intestinal Transplantation
1. Impending or overt liver failure due to TPN-induced Operative Considerations
liver injury. Liver failure defined as increased serum
bilirubin or liver enzyme levels (or both), splenomeg-
The three types of intestinal allografts include multivis-
aly, thrombocytopenia, gastroesophageal varices, ceral, liver-small bowel composite, and isolated small
coagulopathy, stomal bleeding, hepatic fibrosis, or bowel. The type of intestinal transplant utilized is dic-
cirrhosis tated by the needs of each patient. The biggest limitation
2. Thrombosis of two or more central veins (subclavian, to intestinal transplantation in the pediatric population is
jugular, or femoral) the need for size-matched grafts. Patients with intestinal
3. The development of two or more episodes of systemic failure generally have limited abdominal domain (due in
sepsis secondary to line infection that requires hospi- part to a lack of intestine volume), which necessitates
talization, or a single episode of line-related fungemia, near-identical-size donors. Advances in the use of
or septic shock and/or acute respiratory distress reduced-size liver allografts have been applied to the
syndrome
4. Frequent episodes of severe dehydration despite intra-
liver-small bowel composite allograft as a means of
venous fluid supplementation in addition to TPN increasing the flexibility of donor-to-recipient size
matching.142 However, nearly 50% of patients on the
TPN, total parenteral nutrition. intestinal transplant waiting list die before undergoing
45 Solid Organ Transplantation in Children 623
Portocaval
shunt
Residual recipient
foregut
FIGURE 45-12 Schematic diagram of reduced-size liver/intestine composite allograft. (From Reyes J, Mazariegos GV, Bond GMD, etal.
Pediatric intestinal transplantation: Historical notes, principles and controversies. Pediatr Transplant 2002;6:193207.)
that venous drainage into the native portal circulation either at sites of anastomosis or in areas of mucosal
was beneficial to the liver, but recent studies suggest injury from ischemic reperfusion injury often necessitate
minimal benefit.147 Therefore, currently, the most re-exploration. Bowel perforation can also occur follow-
common approach to venous reconstruction is an end- ing surveillance endoscopy and biopsy. Patients with a
to-side anastomosis of the donor superior mesenteric significant amount of peritoneal contamination after
vein to the native inferior vena cava. Gastrointestinal intestinal perforation may require serial operative explo-
continuity is restored by anastomosis of the recipients rations to clear foci of intra-abdominal infection. Post-
native proximal bowel to the transplanted jejunum. Once operative bleeding is frequent, especially in patients who
again, if residual colon is present, a donor ileum to native undergo transplantation with liversmall bowel compos-
colon anastomosis is created downstream from the ite allografts, because preexisting portal hypertension
ileostomy. results in varices throughout the abdominal cavity.
Chylous leaks are also frequent because lymphatic drain-
age may be disrupted during both the procurement and
Postoperative Complications the recipient operative procedure. Most chylous leaks can
Although the outcomes of intestinal transplantation be managed conservatively. A high percentage of patients
continue to improve, postoperative complications are who undergo intestinal transplantation will require
not uncommon. A breakdown of intestinal integrity re-exploration at some point in the postoperative period.
45 Solid Organ Transplantation in Children 625
Infection
Owing in large part to the high level of immunosuppres-
sion needed after intestinal transplantation, bacterial and
fungal infections are common. Patients with intestinal
failure are frequently colonized with antibiotic-resistant
bacteria due to recurrent infections while on TPN. As
mentioned previously, because intestinal perforation is
common, peritonitis is a frequent complication often
requiring repeat abdominal explorations to completely
clear foci of infection.
CMV, EBV, adenovirus, and calicivirus are the most
frequent viral pathogens found in the postoperative
period, and many can masquerade as acute rejection.
PTLD remains a significant problem because most
FIGURE 45-13 Schematic diagram of isolated small intestinal infants are EBV-negative at the time of transplantation.
transplant. SMV, superior mesenteric vein; SMA, superior Surveillance for CMV and EBV using PCR, followed by
mesenteric artery. (Adapted from Abu-Elmagd K, Fung J, Bueno J, aggressive treatment when detected, has diminished the
etal. Logistics and technique for procurement of intestinal, pancre-
atic, and hepatic grafts from the same donor. Ann Surg 2000;
impact of these dangerous pathogens on patient outcome.
232:6807.) All patients are maintained on prophylactic antiviral
agents after intestinal transplantation.
Chronic rejection is responsible for the greatest propor- past antenatal renal failure caused by obstructive malfor-
tion of allograft loss 2 years after transplantation.134 mations resulted in fetal demise or pulmonary insuffi-
Further advances in surveillance and immunosuppressive ciency incompatible with post natal survival. With the
strategies are needed to optimize long-term allograft evolution of fetal diagnosis and in-utero therapy, the pul-
function and survival. monary insufficiency can be attenuated, resulting in a
population of neonates with adequate pulmonary reserve,
but perinatal renal insufficiency.
RENAL TRANSPLANTATION Glomerulonephritis and lupus nephritis, as well as
recurrent pyelonephritis, are the common causes of
Acute renal failure in infants is most often the conse- ESRD in older children.152 As the number of patients
quence of hemodynamic instability, with poor perfusion who have undergone renal transplantation in childhood
or hypoxia resulting in acute tubular necrosis (ATN). has increased, chronic rejection following renal trans-
Most of these patients either recover sufficient renal plantation has recently become a cause of ESRD.
function for normal long-term survival or die of multi- Knowledge of the etiology of the ESRD is important
system failure. to allow assessment of the potential for recurrence
Chronic renal failure is uncommon in infants. The within a transplant allograft and consideration of LD
estimate incidence of ESRD in infants is 0.2 per million transplantation. Patients with a structural/congenital
total population of infants younger than 1 year of age.150,151 etiology, without an immunologic component, also enjoy
Renal aplasia/dysplasia, obstructive and complex urologi- better graft survival rates than those patients with
cal malformations, and focal segmental glomerulosclero- glomerulonephritis.153
sis (FSGS) are the most common causes of ESRD in
children younger than 5 years of age (Table 45-4). In the
Pretransplant Management
Pretransplant management is critical in infants and chil-
TABLE 45-4 Primary Diagnoses in Children dren with ESRD. Children with ESRD beginning in
Requiring Renal Transplantation infancy or early childhood experience significant compli-
cations from growth retardation, renal osteodystrophy,
Number of and neuropsychiatric developmental delay. Recent
Primary Diagnosis Patients Percentage advances in dialysis regimens, nutritional supplementa-
Aplasia/hypoplasia/dysplasia 1,681 14.5 tion, and recombinant human erythropoietin and growth
kidney hormone have significantly improved the pretransplant
Obstructive uropathy 1,630 14.0 management of these patients.
Focal segmental 1,246 10.7
glomerulosclerosis
Reflux nephropathy 549 4.7 Dialysis
Chronic glomerulonephritis 340 2.9
Polycystic disease 323 2.8 Dialysis is indicated when complications of ESRD occur
Medullary cystic disease 287 2.5 despite optimal medical management, specifically hyper-
Congenital nephrotic syndrome 277 2.4
Hemolytic uremic syndrome 273 2.4 kalemia, volume overload, acidosis, intractable hyperten-
Prune belly 268 2.3 sion, and uremic symptoms such as vomiting and fatigue.
Familial nephritis 241 2.1 In older children, lethargy and poor school performance
Cystinosis 221 1.9 can signal the need for more aggressive treatment. In
Membranoproliferative 186 1.6
glomerulonephritistype I
addition, dialysis may be necessary to facilitate the admin-
Pyelo/interstitial nephritis 184 1.6 istration of adequate protein as part of an extensive nutri-
Idiopathic crescentic 181 1.6 tional resuscitation plan.
glomerulonephritis When dialysis is undertaken, the use of peritoneal
SLE nephritis 159 1.4 dialysis is preferred for the following reasons: (1) it avoids
Renal infarct 140 1.2
Berger (IgA) nephritis 135 1.2 the multiple blood transfusions associated with hemodi-
HenochSchnlein nephritis 113 1.0 alysis; (2) it allows a gradual correction of electrolyte
Membranoproliferative 85 0.7 abnormalities, preventing cerebral disequilibrium syn-
glomerulonephritisType II drome in small infants; (3) it allows for easier control of
Wegeners granulomatosis 66 0.6
Wilms tumor 56 0.5
osteodystrophy; (4) it optimizes nutrition; and (5) it is
Drash syndrome 55 0.5 easy to perform.
Oxalosis 55 0.5 Hemodialysis can be used when there is an unsuitable
Membranous nephropathy 47 0.4 peritoneal cavity due to prior surgery or multiple perito-
Other systemic immunologic 34 0.3 neal infections. However, the construction and mainte-
disease
Sickle cell nephropathy 16 0.2 nance of adequate long-term vascular access sites in small
Diabetic glomerulonephritis 11 0.1 infants and children is difficult. Use of central venous
Other 1,110 9.5 catheters rather than arteriovenous fistulas is our pre-
Unknown 663 5.7 ferred mode for temporary hemodialysis access in infants
Total 11,603 100.0
and small children, although infection and vascular
Data from the North American Pediatric Renal Transplant thromboses complicate this therapy. Access via the inter-
Cooperative Study 2010 Annual Report. nal jugular veins is preferred over subclavian routes to
45 Solid Organ Transplantation in Children 627
avoid obstruction of the venous outflow from the upper assess the bladder and reflux. Any concerns about bladder
extremity, which compromises future arteriovenous function or structure requires urodynamics and
fistula sites. Although dialysis and its complications, such cystoscopy.
as infection, have a great influence on the complexity of In patients with long-standing oliguric ESRD, the
care, they do not affect the ultimate results of renal bladder may be very small. In the absence of obstructive
transplantation.154 or neuromuscular pathology, enlargement of the bladder
with normal urinary production is expected. Any opera-
tive correction of urethral obstruction or augmentation
Nutritional Support
of bladder size should be performed well in advance of
The need for vigorous nutritional support of the infant transplantation. Preoperative sterilization of the urinary
with uremia is well demonstrated by the growth retarda- tract and the development of unobstructed urinary
tion seen in infants and children with ESRD. The etiol- outflow should be the ultimate goals of evaluation and
ogy of this growth disturbance is multifactorial, including reconstruction. Although complex anomalies of the uro-
anorexia that leads to protein and calorie insufficiency, genital tract often require many operative procedures to
renal osteodystrophy, aluminum toxicity, uremic acidosis, augment, reconstruct, or create an acceptable lower
impaired somatomedin activity, and growth hormone and urinary tract, most children can undergo successful
insulin resistance.155 Because the most intense period of reconstruction with continent urinary reservoirs without
a childs growth occurs during the first 2 years of life, the need for intestinal conduits.162
careful nutritional support during that time is essential. Immunologic assessment includes tissue typing and
The mean weight at the time of renal transplantation panel reactive antibody analysis. Patients should be mon-
has improved from 2.2 SD to 1.6 SD below the appropri- itored periodically for the development of a positive
ate age-adjusted and gender-adjusted mean for normal cross-match to their potential LD or a positive cytotoxic
children in a recent North American Pediatric Renal antibody to a panel of random donors. In addition, reac-
Transplant Cooperative Study (NAPRTCS). This growth tivity to CMV, EBV, HSV, and hepatitis should also be
deficit was greater (2.8 SD) in children younger than 5 performed. Childhood immunizations should be current,
years of age. Transplantation afforded a 0.8 SD increase and immunization against hepatitis B virus is important.
in growth over the first post-transplant year. However, Any immunizations with live-virus vaccines should be
this growth then reached a stable plateau. After 2 to 3 given well in advance of transplantation because their use
years, the mean weight values were comparable to those is contraindicated in the early post-transplant period.
of normal children.152 Children 6 years of age and older Selection of the appropriate donor source for trans-
showed no improvement in their height deficit 5 years plantation is a decision for the transplant team and family
after transplantation.156,157 These limitations to catch-up to consider together. A related immediate family member
growth emphasize the need for early transplantation in has the advantage of a low incidence of postoperative
young ESRD patients. If epiphyseal closure has occurred ATN, improved histologic matching, and extended organ
(bone age >12 years), additional bone growth is often not function. In addition, any operative procedures required
achieved.151,158,159 Normalization of growth rarely occurs for preparation of the recipient, as well as the transplant
with hemodialysis or peritoneal dialysis. procedure, can be scheduled around the needs of the
The importance of efforts to normalize nutritional patient, simplifying preoperative care and potentially
parameters is emphasized by the adverse impact of uremia avoiding the complications of dialysis. Parents form the
on the infants developing nervous system. The signifi- majority of donors. The 2010 NAPRTCS report indi-
cance of this problem was emphasized in a study in which cates that 40% of children receive an LD kidney from a
progressive encephalopathy, developmental delay, micro- parent.153 Thorough evaluation of the potential donor to
cephaly, hypotonia, seizures, and dyskinesia developed in exclude intrinsic renal anomalies, vascular anomalies, and
20 of 23 children with ESRD before 1 year of age.160 All systemic illness is important.
of these patients had significant growth impairment. Deceased donor (DD) kidneys are currently used for
Monitoring of the head circumference has been sug- 49% of renal transplants.153 The unpredictability of
gested to identify the infant at risk, with the intent to donor organ availability and the need to establish a nega-
initiate dialysis, nutritional support, or transplantation if tive antibody cross-match for DD transplantation make
this parameter deviates from the normal curve.151 surgical planning impossible. The size of a potential allo-
graft, DD or related LD, is also important. Kidneys from
small adult donors can be transplanted into infants as
Preoperative Preparation small as 5kg with good success.163 DD organs from pedi-
In preparation for renal transplantation, an extensive atric donors 5 years of age or older also result in an
evaluation of the urinary tract and immunologic status of excellent survival rate. However, a progressive decrease
the patient is important. The increased frequency of in one-year graft survival has been noted when kidneys
urinary tract abnormalities as the primary cause of ESRD from donors younger than 3 to 4 years of age are used.164,165
in infants and children necessitates the investigation of This decrease in graft and patient survival is related to
the urinary tract for sites of obstruction, the presence the donor organ source. Children 2 to 5 years of age have
of ureteral reflux, and the functional state and capacity of a similar survival rate as the overall pediatric population
the urinary bladder.161 This investigation is best accom- when LDs are used. Recognition of this potential risk has
plished by obtaining an ultrasound or intravenous pyelo- led to reluctance by most centers to use donors younger
gram evaluating the upper urinary tract and a VCUG to than 2 years of age. An effect of donor age on graft
628 SECTION IV Abdomen
survival has been attributed to an increased rate of both of the allograft posterior to the right or left colon. An
graft thrombosis and acute rejection.152 extraperitoneal approach to the retroperitoneum allows
In the past, the decision to use a DD as opposed to an the possibility for peritoneal dialysis and should be used
LD was influenced by the possibility of disease recur- if possible. The arterial anastomosis is constructed end-
rence within the transplanted kidney. The incidence of to-side into the distal aorta or common iliac artery, and
disease recurrence following transplantation and the risk venous outflow of the allograft is via the inferior vena
of graft loss are listed in Table 45-5.166 With new treat- cava or common iliac vein. Ureteral implantation using
ment strategies for recurrent disease, the risk of graft loss the Lich extravesical ureteroneocystostomy avoids the
has been attenuated, and as a result, LD kidneys are now need for a cystotomy and minimizes postoperative blood
preferred. This decision to favor LD kidneys is influ- clots within the bladder, which can obstruct the urinary
enced by the recent improvements in outcomes which catheter. When larger donor kidneys are used in small
show similar one-year graft survival for DD and LD for recipients, the vessels must be shortened to avoid redun-
all age groups. dancy when the kidney is positioned in the retroperito-
neum. The internal iliac artery is not used in children so
that pelvic blood flow is preserved (Fig. 45-14). Ureteral
Pre-emptive Transplantation double-J stents are used when small ureter size may lead
The desire to perform preemptive renal transplantation to obstruction.
before undertaking dialysis is often fueled by the patients Anesthetic management of the infant and small child
or parents desire to avoid the dialysis procedures, poten- during kidney transplantation is complicated by preexist-
tial infections, or cardiovascular complications, and the ing electrolyte abnormalities and the large fluid fluxes
psychological impairment inherent with dialysis. A that occur in the operating room. In the past, perfusion
NAPRTCS review found 26% of primary transplanta- of the allograft with hypothermic lactated Ringers solu-
tions were performed without prior dialysis.167 Most cases tion before implantation to remove any remaining UW
used LDs rather than DDs. There was no difference in preservation solution was necessary to avoid massive
patient or graft survival in this group when compared potassium infusion when the allograft was perfused. This
with patients who underwent dialysis before transplanta- problem has been obviated by the use of HTK solution
tion. Pre-emptive transplantation is not possible when which has a lower potassium concentration. Volume
uncontrolled hypertension, massive proteinuria, or recur- loading to a CVP of 1012cmH2O and administration
rent infection require prior native kidney removal, or of bicarbonate, calcium, and low-dose vasopressors
when oliguric renal failure requires immediate dialysis. (dopamine 5g/kg/min) is important prior to reper-
fusion of the graft.
Transplant Procedure
Preparation for transplantation should include placing
Postoperative Management
adequate large-bore IV lines and the largest urinary cath- Post-transplant management requires careful observa-
eter possible. Central venous lines are used in all infants tion for technical complications, rejection, recurrence
and children to ensure vascular access, hemodynamic of the primary renal disease, and prevention of
monitoring, and a route for postoperative immunosup- immunosuppression-related complications. Frequent
pressive delivery. Perioperative prophylactic antibiotics fluid and electrolyte monitoring is necessary immediately
are administered. Arterial pressure monitoring lines are following transplantation because larger kidneys can
only necessary in small infants and patients with hemo- excrete the equivalent of the infants blood volume within
dynamic compromise, allowing preservation of future a single hour. Careful attention to serum concentrations
hemodialysis access sites. of calcium, phosphorus, magnesium, and electrolytes is
Renal transplantation in infants and small children also needed. Urine output is initially replaced isovolu-
can be undertaken through a generous retroperitoneal metrically, then tapered as the high-output state decreases.
approach or a transabdominal approach with placement Glucose-free replacement fluids minimize hyperglycemia
TABLE 45-5 Recurrence Rates and Graft Loss from Recurrent Disease in Children
Percentage of Those with Recurrence
Disease Recurrence Rate (%) Clinical Severity Whose Graft Failed
FSGS 2530 High 4050
MPGN type I 70 Mild 1230
MPGN type II 100 Low 1020
SLE 540 Low 5
HSP 5585 Low/mild 520
HUS (classic) 1220 Moderate 010
HUS (atypical) 25 High 4050
FSGS, focal segmental glomerulosclerosis; HSP, HenochSchnlein purpura; HUS, hemolytic uremic syndrome; MPGN,
membranoproliferative glomerulonephritis; SLE, systemic lupus erythematosus.
From Fine RN, Ettenger R. In: Morris PJ, editor. Kidney Transplantation: Principles and Practice. 4th ed. Philadelphia: WB
Saunders; 1994. p. 418.
45 Solid Organ Transplantation in Children 629
Hypertension
Renal artery
Hypertension following renal transplantation is common.
One month after transplantation, 72% of all patients
Renal vein
require treatment, although this percentage decreases to
53% at 30 months.168 Careful attention to the pretrans-
plant control of hypertension and dietary management
improves the post-transplant management. Hypertension
presents a significant risk to renal function when using
small allografts. Hypertension in the early postoperative
period is most often due to fluid overload or acute rejec-
tion, but it can also originate in the native kidneys.
Preexisting hypertension is augmented by the immu-
nosuppressive drugs cyclosporine, tacrolimus, and pred-
nisone. The development of hypertension more than
B three months after transplantation suggests possible renal
FIGURE 45-14 Schematic diagram showing the transplant artery stenosis and warrants ultrasound Doppler flow
arterial and venous anastomosis to the (A) illiac vessels or the studies for initial evaluation. Arteriography may be
(B) aorta and vena cava. Ureteral implantation using the Lich needed in unclear cases. Transluminal angioplasty has
extravesical ureteroneocystostomy is preferred. been successful in alleviating the majority of these steno-
sis. Operative correction is reserved for angioplasty fail-
and osmotic diuresis in the recipient. Selection of appro- ures and vessels with complex arterial anastomoses.
priate electrolyte concentrations is guided by urinary elec-
trolyte excretion. Central venous filling pressures should Infection
be maintained at 710cmH2O to ensure adequate intra- Much like liver and intestinal transplantation, the highest
vascular volume. In patients with high-output renal failure, risks for infectious complications arise within the first 6
urine losses from both the native and transplant kidneys months post-transplant. During this time, immunosup-
need to be replaced to avoid hypoperfusion and thrombo- pression is intense and susceptibility to life-threatening
sis. Maintenance of catheter patency is essential, and any infection is increased. In infants and children who are
episode of decreased urinary output should be rapidly seronegative, use of organs from donors who have had
investigated to exclude urinary catheter occlusion and prior exposure to CMV and EBV enhances the risk of
bladder distention. An algorithm for the evaluation of these specific infections. Expanded use of antiviral proph-
early postoperative oliguria is shown in Figure 45-15. ylaxis using ganciclovir and acyclovir has decreased the
intensity of these infections and their associated morbid-
Postoperative Complications ity or mortality.
Vascular thrombosis still accounts for graft loss in up to Immunosuppression
13% of initial transplants and 19% of repeat transplants
in children.166 Graft thrombosis is significantly more fre- Many immunosuppressive regimens are available
quent in children younger than 2 years of age and is and all share similar strategy. Most regimens
630 SECTION IV Abdomen
Oliguria
<1 mL/kg/hr
Check
CVP
Blood pressure
Orthostatic pressure
IV Fluid bolus
Repeat
Ultrasound/Doppler
Go to Resolved Nuclear renogram
postrenal oliguria
FIGURE 45-15 Algorithm for the evaluation of early postoperative oliguria after pediatric renal transplant. CVP, central venous
pressure.
include corticosteroids, cyclosporine or tacrolimus, and steroid administration alone (78%); monoclonal antiT-
azathioprine or MMF. Polyclonal or monoclonal anti cell agents such as orthoclone OKT-3 are needed in 32%.
lymphocyte antibodies are used when ATN is anticipated In patients who remain rejection free for the 1st post-
or for retransplantation in highly pre-sensitized patients. transplant year, the risk of rejection in the following year
Significant efforts to decrease or discontinue steroids is 20%.154
have been attempted to enhance growth and develop-
ment. At four years after transplantation, 31% of LD and Outcome Following Transplantation
23% of DD recipients were receiving alternate-day
prednisone.152 The overall results of renal transplantation in children
Overall, there has been a decrease in the frequency of are steadily improving. Overall one-year transplant graft
acute rejection with 12 month probabilities in LD of 32% survival rates of 88100% have been reported for LD
and DD of 36%. The risk of rejection is similar for LD allografts, with results for DD allografts being 50 to
and DD recipients in the first few post-transplant weeks. 72%.151,163166 In the a recent report, 1-, 2-, and 5-year
Factors that increase the likelihood of rejection or long- graft survival rates were as follows: DD, 78%, 72%, and
term graft loss include receiving a graft from a DD rather 59%; LD, 90%, 86%, and 85%, respectively (Fig.
than a related LD, receiving a graft from a donor younger 45-16).154
than 5 years of age, having the graft in cold storage for Chronic rejection has become the most common cause
more than 24 hours, being an African-American recipi- of graft failure, accounting for 27% of all graft losses.157
ent, and delayed graft function from ATN.152 The ability With improved immunosuppressive treatments, acute
to treat rejection has also improved with complete reversal rejection accounts for only 15% of failures. Recurrence
of acute rejection in 65% of episodes. The rate of success of the original disease caused graft failure in 6%, and
in treating rejection declines with each successive rejec- vascular thrombosis accounted for 12% of graft failures.
tion episode, increased recipient age, and late rejection Long-term graft survival following pediatric renal trans-
episodes.152 Most rejection episodes can be treated with plantation continues to deteriorate after 10 years despite
45 Solid Organ Transplantation in Children 631
94
96
98
00
02
04
06
08
10
Further expansion of this approach awaits evidence that
91
93
95
97
99
01
03
05
07
09
Year hypoglycemic correction retards the systemic complica-
FIGURE 45-16 This graph demonstrates the allograft survival tions of diabetes.
characteristics over 5 years in children as measured by half lives
in years versus year transplanted comparing living donor and
deceased donor renal transplants. One-year conditional survival REFERENCES
is the half-life after the recipient survives the first year. This 1. DeRusso PA, Ye W, Shepherd R, et al. Growth failure and out-
parameter eliminates patients with early graft failure from any comes in infants with biliary atresia: A report from the Biliary
cause. (Source: Scientific Registry Transplant Recipients2011 Atresia Research Consortium. Hepatology 2007;46:16328.
Annual Report.) 2. Kasai M, Mochizuki I, Ohkohchi N, et al. Surgical limitation for
biliary atresia: Indication for liver transplantation. J Pediatr Surg
1989;24:8514.
3. Ryckman F, Fisher R, Pedersen S, et al. Improved survival in
low patient mortality rates. Death of the recipient with a biliary atresia patients in the present era of liver transplantation.
functioning graft is an uncommon problem. In one study, J Pediatr Surg 1993;28:3825.
when this did occur, death resulted primarily from infec- 4. Zitelli BJ, Malatack JJ, Gartner JC Jr, et al. Evaluation of the
tion (40%) or cardiovascular causes (21%).169 Young pediatric patient for liver transplantation. Pediatrics 1986;78:
recipients (0 to 1 year of age) and patients with early graft 55965.
5. Nio M, Ohi R, Hayashi Y, et al. Current status of 21 patients who
failure were at the highest risk. Progressive loss of renal have survived more than 20 years since undergoing surgery for
function may be secondary to complications of hyperten- biliary atresia. J Pediatr Surg 1996;31:3814.
sion, hyperfiltration, hypercholesterolemias, chronic 6. Ryckman FC. New issues concerning the etiology of an old
indolent immunologic damage leading to chronic rejec- problem. J Am Coll Surg 1996;183:6379.
7. Reily D. Familial Intrahepatic Cholestasis Syndromes. In: Suchy
tion, and progressive primary renal disease, which all FJ, editor. Liver Disease in Children. 1st ed. St. Louis: CV Mosby;
contribute to long-term graft loss.153,166 1994. p. 44359.
In the latest NAPRTCS report, the overall half-life of 8. Ng VL, Ryckman FC, Porta G, et al. Long-term outcome after
pediatric renal transplants was about 25 years for LD and partial external biliary diversion for intractable pruritus in patients
16 years for DD grafts. Most recipients will require a with intrahepatic cholestasis. J Pediatr Gastroenterol Nutr
2000;30:1526.
second transplant in their lifetime. Overall graft survival 9. Cardona J, Houssin D, Gauthier F, et al. Liver transplantation in
for second transplants using LDs was equivalent to children with Alagille syndromea study of twelve cases. Trans-
primary DD allografts. The factor exerting negative plantation 1995;60:33942.
influence on survival in DD grafts was donor age younger 10. Hoffenberg EJ, Narkewicz MR, Sondheimer JM, et al. Outcome
of syndromic paucity of interlobular bile ducts (Alagille syndrome)
than 6 years. Better donor recipient matching improves with onset of cholestasis in infancy. J Pediatr 1995;127:2204.
graft survival. The rapidity of first allograft loss, immu- 11. Tzakis AG, Reyes J, Tepetes K, et al. Liver transplantation for
nologic protocol at retransplant, and race of recipient Alagilles syndrome. Arch Surg 1993;128:3379.
were not significant factors. 12. Ryckman FC, Alonso MH, editors. Transplantation for Hepatic
Malignancy in Children. 1st ed. Philadelphia: WB Sanders;
1996.
13. Jan D, Poggi F, Laurent J, et al. Liver transplantation: New indica-
PANCREAS TRANSPLANATION tions in metabolic disorders? Transplant Proc 1994;26:18990.
14. Mito M, Kusano M, Kawaura Y. Hepatocyte transplantation in
Children have rarely been candidates for pancreas trans- man. Transplant Proc 1992;24:30523.
15. Jan D, Laurent J, Lacaille F, et al. Liver transplantation in children
plantation. In the past, the results following pancreas with inherited metabolic disorders. Transplant Proc 1995;
transplantation have not justified the risks associated with 27:17067.
immunosuppression and operation. However, recent 16. Strom S, Fisher R. Hepatocyte transplantation: New possibilities
improvements in the operative technique and follow-up for therapy. Gastroenterology 2003;124:56871.
have improved. Overall, 1-year patient survival rate 17. Strom SC, Fisher RA, Rubinstein WS, et al. Transplantation of
human hepatocytes. Transplant Proc 1997;29:21036.
exceeds 90%, and graft survival with complete insulin 18. Fridell JA, Bond GJ, Mazariegos GV, et al. Liver transplantation
independence exceeds 70% in patients in whom com- in children with cystic fibrosis: A long-term longitudinal review
bined kidney and pancreas transplantation is undertaken. of a single centers experience. J Pediatr Surg 2003;38:11526.
632 SECTION IV Abdomen
19. Stapp J, Wilkerson S, Stewart D, et al. Fulminant neonatal liver 44. Rogiers X, Burdelski M, Broelsch CE. Liver transplantation from
failure in siblings: Probable congenital hemophagocytic lympho- living donors. Br J Surg 1994;81:12513.
histiocytosis. Pediatr Dev Pathol 2006;9:23944. 45. Klein AS, Messersmith EE, Ratner LE, et al. Organ donation and
20. Strom SC, Fisher RA, Thompson MT, et al. Hepatocyte trans- utilization in the United States, 19992008. Am J Transplant
plantation as a bridge to orthotopic liver transplantation in termi- 2010;10:97386.
nal liver failure. Transplantation 1997;63:55969. 46. Broelsch CE, Whitington PF, Emond JC, et al. Liver transplanta-
21. Lidofsky SD, Bass NM, Prager MC, et al. Intracranial pressure tion in children from living related donors. Surgical techniques
monitoring and liver transplantation for fulminant hepatic failure. and results. Ann Surg 1991;214:42837.
Hepatology 1992;16:17. 47. Otte JB. Auxiliary partial orthotopic liver transplantation for acute
22. Reyes JD, Carr B, Dvorchik I, et al. Liver transplantation and liver failure in children. Pediatr Transplant 1999;3:2526.
chemotherapy for hepatoblastoma and hepatocellular cancer in 48. Otte JB. Donor complications and outcomes in live-liver trans-
childhood and adolescence. J Pediatr 2000;136:795804. plantation. Transplantation 2003;75:16256.
23. Tiao GM, Bobey N, Allen S, et al. The current management of 49. Tissieres P, Prontera W, Chevret L, et al. The pediatric risk of
hepatoblastoma: A combination of chemotherapy, conventional mortality score in infants and children with fulminant liver failure.
resection, and liver transplantation. J Pediatr 2005;146:20411. Pediatr Transplant 2003;7:648.
24. Perilongo G, Brown J, Shafford E, et al. Hepatoblastoma present- 50. Fan ST, Lo CM, Liu CL. Technical refinement in adult-to-adult
ing with lung metastases: treatment results of the first cooperative, living donor liver transplantation using right lobe graft. Ann Surg
prospective study of the International Society of Paediatric Oncol- 2000;231:12631.
ogy on childhood liver tumors. Cancer 2000;89:184553. 51. Humar A, Beissel J, Crotteau S, et al. Whole liver versus split liver
25. Pimpalwar AP, Sharif K, Ramani P, et al. Strategy for hepatoblas- versus living donor in the adult recipient: An analysis of outcomes
toma management: Transplant versus nontransplant surgery. by graft type. Transplantation 2008;85:14204.
J Pediatr Surg 2002;37:2405. 52. Lo CM, Fan ST, Liu CL, et al. Minimum graft size for successful
26. Austin MT, Leys CM, Feurer ID, et al. Liver transplantation for living donor liver transplantation. Transplantation 1999;68:
childhood hepatic malignancy: A review of the United Network 111216.
for Organ Sharing (UNOS) database. J Pediatr Surg 2006;41: 53. Zamboni F, Franchello A, David E, et al. Effect of macrovescicular
1826. steatosis and other donor and recipient characteristics on the
27. Iwatsuki S, Gordon RD, Shaw BW Jr, et al. Role of liver trans- outcome of liver transplantation. Clin Transplant 2001;15:
plantation in cancer therapy. Ann Surg 1985;202:4017. 537.
28. Davies DB, Harper A. The OPTN waiting list, 19882003. Clin 54. Imber CJ, St Peter SD, Handa A, et al. Hepatic steatosis and its
Transpl 2004;2740. relationship to transplantation. Liver Transpl 2002;8:41523.
29. Austin MT, Feurer ID, Pinson CW. Access to pediatric liver 55. Mor E, Skerrett D, Manzarbeitia C, et al. Successful use of an
transplantation: Does regional variation play a role? J Gastrointest enhanced immunosuppressive protocol with plasmapheresis for
Surg 2006;10:38794. ABO-incompatible mismatched grafts in liver transplant recipi-
30. Organ Procurement and Transplantation NetworkHRSA. Final ents. Transplantation 1995;59:98690.
rule with comment period. Fed Regist 1998;63:16296338. 56. Farges O, Kalil AN, Samuel D, et al. The use of ABO-incompatible
31. McDiarmid SV, Anand R, Lindblad AS. Development of a pedi- grafts in liver transplantation: a life-saving procedure in highly
atric end-stage liver disease score to predict poor outcome in selected patients. Transplantation 1995;59:112433.
children awaiting liver transplantation. Transplantation 2002;74: 57. Tanaka A, Tanaka K, Kitai T, et al. Living related liver transplanta-
17381. tion across ABO blood groups. Transplantation 1994;58:54853.
32. Barshes NR, Lee TC, Udell IW, et al. The pediatric end-stage 58. Cacciarelli TV, So SK, Lim J, et al. A reassessment of ABO
liver disease (PELD) model as a predictor of survival benefit and incompatibility in pediatric liver transplantation. Transplantation
posttransplant survival in pediatric liver transplant recipients. 1995;60:75760.
Liver Transpl 2006;12:47580. 59. Yandza T, Lambert T, Alvarez F, et al. Outcome of ABO-
33. Tector AJ, Mangus RS, Chestovich P, et al. Use of extended cri- incompatible liver transplantation in children with no specific
teria livers decreases wait time for liver transplantation without alloantibodies at the time of transplantation. Transplantation
adversely impacting posttransplant survival. Ann Surg 2006; 1994;58:4650.
244:43950. 60. Warnaar N, Polak WG, de Jong KP, et al. Long-term results of
34. Schaubel DE, Sima CS, Goodrich NP, et al. The survival benefit urgent revascularization for hepatic artery thrombosis after pedi-
of deceased donor liver transplantation as a function of candidate atric liver transplantation. Liver Transpl 2010;16:84755.
disease severity and donor quality. Am J Transplant 2008;8: 61. Kim HB. Urgent revascularization for hepatic artery thrombosis:
41925. Maybe good for the few, definitely good for the many. Liver
35. Wolfe RA, McCullough KP, Leichtman AB. Predictability of sur- Transpl 2010;16:81214.
vival models for waiting list and transplant patients: Calculating 62. Langnas AN, Marujo W, Stratta RJ, et al. Hepatic allograft rescue
LYFT. Am J Transplant 2009;9:15237. following arterial thrombosis. Role of urgent revascularization.
36. Broelsch CE, Emond JC, Whitington PF, et al. Application of Transplantation 1991;51:8690.
reduced-size liver transplants as split grafts, auxiliary orthotopic 63. Stevens LH, Emond JC, Piper JB, et al. Hepatic artery thrombosis
grafts, and living related segmental transplants. Ann Surg 1990; in infants. A comparison of whole livers, reduced-size grafts, and
212:36875. grafts from living-related donors. Transplantation 1992;53:
37. Emond JC, Whitington PF, Thistlethwaite JR, et al. Reduced-size 3969.
orthotopic liver transplantation: Use in the management of chil- 64. Kirsch JP, Howard TK, Klintmalm GB, et al. Problematic vascu-
dren with chronic liver disease. Hepatology 1989;10:86772. lar reconstruction in liver transplantation. Part II. Portovenous
38. Ryckman FC, Flake AW, Fisher RA, et al. Segmental orthotopic conduits. Surgery 1990;107:5448.
hepatic transplantation as a means to improve patient survival and 65. Stieber AC, Zetti G, Todo S, et al. The spectrum of portal vein
diminish waiting-list mortality. J Pediatr Surg 1991;26:4227. thrombosis in liver transplantation. Ann Surg 1991;213:
39. Emond JC, Whitington PF, Thistlethwaite JR, et al. Transplanta- 199206.
tion of two patients with one liver. Analysis of a preliminary 66. Harper AM, Edwards EB, Ellison MD. The OPTN waiting list,
experience with split-liver grafting. Ann Surg 1990;212:1422. 1988-2000. Clin Transpl 2001;7385.
40. Reyes J. Adaptation of split liver grafts in pediatric patients. 67. Peclet MH, Ryckman FC, Pedersen SH, et al. The spectrum of
Pediatr Transplant 2001;5:14852. bile duct complications in pediatric liver transplantation. J Pediatr
41. Deshpande RR, Bowles MJ, Vilca-Melendez H, et al. Results of Surg 1994;29:21419.
split liver transplantation in children. Ann Surg 2002;236: 68. Heffron TG, Emond JC, Whitington PF, et al. Biliary complica-
24853. tions in pediatric liver transplantation. A comparison of reduced-
42. Broelsch CE, Frilling A, Testa G, et al. Living donor liver trans- size and whole grafts. Transplantation 1992;53:3915.
plantation in adults. Eur J Gastroenterol Hepatol 2003;15:36. 69. Rouch DA, Emond JC, Thistlethwaite JR Jr, et al. Choledochoc-
43. Broelsch CE, Burdelski M, Rogiers X, et al. Living donor for liver holedochostomy without a T tube or internal stent in transplanta-
transplantation. Hepatology 1994;20:49S55S. tion of the liver. Surg Gynecol Obstet 1990;170:23944.
45 Solid Organ Transplantation in Children 633
70. Snover DC, Sibley RK, Freese DK, et al. Orthotopic liver trans- 93. Smets F, Latinne D, Bazin H, et al. Ratio between Epstein-Barr
plantation: A pathological study of 63 serial liver biopsies from 17 viral load and anti-Epstein-Barr virus specific T-cell response as
patients with special reference to the diagnostic features and a predictive marker of posttransplant lymphoproliferative disease.
natural history of rejection. Hepatology 1984;4:121222. Transplantation 2002;73:160310.
71. Mor E, Solomon H, Gibbs JF, et al. Acute cellular rejection fol- 94. Smets F, Sokal EM. Epstein-Barr virus-related lymphoprolifera-
lowing liver transplantation: Clinical pathologic features and tion in children after liver transplant: Role of immunity, diagnosis,
effect on outcome. Semin Liver Dis 1992;12:2840. and management. Pediatr Transplant 2002;6:2807.
72. Adams DH, Neuberger JM. Treatment of acute rejection. Semin 95. Sokal EM, Antunes H, Beguin C, et al. Early signs and risk factors
Liver Dis 1992;12:808. for the increased incidence of Epstein-Barr virus-related post-
73. Jain A, Mazariegos G, Pokharna R, et al. The absence of chronic transplant lymphoproliferative diseases in pediatric liver trans-
rejection in pediatric primary liver transplant patients who are plant recipients treated with tacrolimus. Transplantation 1997;
maintained on tacrolimus-based immunosuppression: A long- 64:143842.
term analysis. Transplantation 2003;75:10205. 96. Holmes RD, Orban-Eller K, Karrer FR, et al. Response of ele-
74. Jain A, Mazariegos G, Kashyap R, et al. Pediatric liver transplanta- vated Epstein-Barr virus DNA levels to therapeutic changes in
tion. A single center experience spanning 20 years. Transplanta- pediatric liver transplant patients: 56-month follow up and
tion 2002;73:9417. outcome. Transplantation 2002;74:36772.
75. Gupta P, Hart J, Cronin D, et al. Risk factors for chronic rejection 97. Axelrod DA, Holmes R, Thomas SE, et al. Limitations of
after pediatric liver transplantation. Transplantation 2001;72: EBV-PCR monitoring to detect EBV associated post-transplant
1098102. lymphoproliferative disorder. Pediatr Transplant 2003;7:2237.
76. Freese DK, Snover DC, Sharp HL, et al. Chronic rejection after 98. Penn I. Post-transplant malignancy: The role of immunosuppres-
liver transplantation: A study of clinical, histopathological and sion. Drug Saf 2000;23:10113.
immunological features. Hepatology 1991;13:88291. 99. Sokal EM, Caragiozoglou T, Lamy M, et al. Epstein-Barr virus
77. Ludwig J, Wiesner RH, Batts KP, et al. The acute vanishing bile serology and Epstein-Barr virus-associated lymphoproliferative
duct syndrome (acute irreversible rejection) after orthotopic liver disorders in pediatric liver transplant recipients. Transplantation
transplantation. Hepatology 1987;7:47683. 1993;56:13948.
78. Demetris A, Adams D, Bellamy C, et al. Update of the Interna- 100. Jabs WJ, Hennig H, Kittel M, et al. Normalized quantification by
tional Banff Schema for Liver Allograft Rejection: Working rec- real-time PCR of Epstein-Barr virus load in patients at risk for
ommendations for the histopathologic staging and reporting of posttransplant lymphoproliferative disorders. J Clin Microbiol
chronic rejection. An International Panel. Hepatology 2000;31: 2001;39:5649.
7929. 101. Guthery SL, Heubi JE, Bucuvalas JC, et al. Determination of
79. OLeary JG, Kaneku H, Susskind BM, et al. High mean fluores- risk factors for Epstein-Barr virus-associated posttransplant lym-
cence intensity donor-specific anti-HLA antibodies associated phoproliferative disorder in pediatric liver transplant recipients
with chronic rejection Postliver transplant. Am J Transplant using objective case ascertainment. Transplantation 2003;75:
2011;11:186876. 98793.
80. Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease 102. Hanto DW, Frizzera G, Gajl-Peczalska KJ, et al. Epstein-Barr
(ESRD) after orthotopic liver transplantation (OLTX) using virus, immunodeficiency, and B cell lymphoproliferation. Trans-
calcineurin-based immunotherapy: Risk of development and plantation 1985;39:46172.
treatment. Transplantation 2001;72:19349. 103. Bueno J, Ramil C, Green M. Current management strategies for
81. Fisher NC, Nightingale PG, Gunson BK, et al. Chronic renal the prevention and treatment of cytomegalovirus infection in
failure following liver transplantation: A retrospective analysis. pediatric transplant recipients. Paediatr Drugs 2002;4:27990.
Transplantation 1998;66:5966. 104. Serinet MO, Jacquemin E, Habes D, et al. Anti-CD20 mono-
82. Campbell K, Yazigi N, Ryckman F, et al. Renal Function in Long- clonal antibody (Rituximab) treatment for Epstein-Barr virus-
Term Pediatric Liver Transplant Survivors. American Transplan- associated, B-cell lymphoproliferative disease in pediatric liver
tation Congress 2003. transplant recipients. J Pediatr Gastroenterol Nutr 2002;34:
83. Campbell K, Ng V, Martin S, et al. Glomerular filtration rate 38993.
following pediatric liver transplantationthe SPLIT experience. 105. Haque T, Wilkie GM, Taylor C, et al. Treatment of Epstein-Barr-
Am J Transplant 2010;10:267382. virus-positive post-transplantation lymphoproliferative disease
84. Campbell KM, Yazigi N, Ryckman FC, et al. High prevalence of with partly HLA-matched allogeneic cytotoxic T cells. Lancet
renal dysfunction in long-term survivors after pediatric liver trans- 2002;360:43642.
plantation. J Pediatr 2006;148:47580. 106. Tiao GM, Alonso M, Bezerra J, et al. Liver transplantation
85. Aw MM, Samaroo B, Baker AJ, et al. Calcineurin-inhibitor related in children younger than 1 yearthe Cincinnati experience.
nephrotoxicity- reversibility in paediatric liver transplant recipi- J Pediatr Surg 2005;40:26873.
ents. Transplantation 2001;72:7469. 107. Washburn WK, Bradley J, Cosimi AB, et al. A regional experience
86. Heffron TG, Pillen T, Smallwood GA, et al. Pediatric liver trans- with emergency liver transplantation. Transplantation 1996;61:
plantation with daclizumab induction. Transplantation 2003; 2359.
75:20403. 108. Langnas AN, Marujo WC, Inagaki M, et al. The results of
87. Wiesner RH, Hermans PE, Rakela J, et al. Selective bowel decon- reduced-size liver transplantation, including split livers, in patients
tamination to decrease gram-negative aerobic bacterial and with end-stage liver disease. Transplantation 1992;53:38791.
Candida colonization and prevent infection after orthotopic liver 109. Esquivel CO, Nakazato P, Cox K, et al. The impact of liver reduc-
transplantation. Transplantation 1988;45:5704. tions in pediatric liver transplantation. Arch Surg 1991;126:
88. Andrews W, Siegel J, Renaro T. Prevention and treatment of 127885.
selected fungal and viral infections in pediatric liver transplant 110. Studies of Pediatric Liver Transplantation (SPLIT). Year 2000
recipients. Clin Transplant 1991;5:2047. outcomes. Transplantation 2001;72:46376.
89. Patel R, Snydman DR, Rubin RH, et al. Cytomegalovirus prophy- 111. Fridell JA, Jain A, Reyes J, et al. Causes of mortality beyond one
laxis in solid organ transplant recipients. Transplantation year after primary pediatric liver transplant under tacrolimus.
1996;61:127989. Transplantation 2002;74:17214.
90. Fox AS, Tolpin MD, Baker AL, et al. Seropositivity in liver trans- 112. Mack CL, Ferrario M, Abecassis M, et al. Living donor liver
plant recipients as a predictor of cytomegalovirus disease. J Infect transplantation for children with liver failure and concurrent mul-
Dis 1988;157:3835. tiple organ system failure. Liver Transpl 2001;7:8905.
91. Holmes RD, Sokol RJ. Epstein-Barr virus and post-transplant 113. Emre S. Living-donor liver transplantation in children. Pediatr
lymphoproliferative disease. Pediatr Transplant 2002;6:456 Transplant 2002;6:436.
64. 114. Bucuvalas JC, Ryckman FC. The long- and short-term outcome
92. Broughton S, McClay JE, Murray A, et al. The effectiveness of of living-donor liver transplantation. J Pediatr 1999;134:25961.
tonsillectomy in diagnosing lymphoproliferative disease in pedi- 115. Bilik R, Greig P, Langer B, et al. Survival after reduced-size liver
atric patients after liver transplantation. Arch Otolaryngol Head transplantation is dependent on pretransplant status. J Pediatr
Neck Surg 2000;126:14447. Surg 1993;28:130711.
634 SECTION IV Abdomen
116. PRCarroll CL, Goodman DM, Superina RA, et al. Timed Pedi- 142. de Ville de Goyet J, Mitchell A, Mayer AD, et al. En block
atric Risk of Mortality Scores predict outcomes in pediatric liver combined reduced-liver and small bowel transplants: From
transplant recipients. Pediatr Transplant 2003;7:28995. large donors to small children. Transplantation 2000;69:
117. Otte JB, de Ville de Goyet J, Sokal E, et al. Size reduction of the 5559.
donor liver is a safe way to alleviate the shortage of size-matched 143. Fryer J, Pellar S, Ormond D, et al. Mortality in candidates waiting
organs in pediatric liver transplantation. Ann Surg 1990;211: for combined liver-intestine transplants exceeds that for other
14657. candidates waiting for liver transplants. Liver Transpl 2003;9:
118. Ryckman FC, Alonso MH, Bucuvalas JC, et al. Long-term sur- 74853.
vival after liver transplantation. J Pediatr Surg 1999;34:8459. 144. Furukawa H, Manez R, Kusne S, et al. Cytomegalovirus disease
119. Wallot MA, Mathot M, Janssen M, et al. Long-term survival and in intestinal transplantation. Transpl P 1995;27:13578.
late graft loss in pediatric liver transplant recipientsa 15-year 145. Eid AJ, Razonable RR. New developments in the management of
single-center experience. Liver Transpl 2002;8:61522. cytomegalovirus infection after solid organ transplantation. Drugs
120. Sudan DL, Shaw BW Jr, Langnas AN. Causes of late mortality in 2010;70:96581.
pediatric liver transplant recipients. Ann Surg 1998;227:28995. 146. Kato T, Selvaggi G, Gaynor JJ, et al. Inclusion of donor colon and
121. Sarna S, Sipila I, Jalanko H, et al. Factors affecting growth ileocecal valve in intestinal transplantation. Transplantation
after pediatric liver transplantation. Transplant Proc 1994;26: 2008;86:2937.
1614. 147. Berney T, Kato T, Nishida S, et al. Portal versus systemic drainage
122. Sarna S, Sipila I, Vihervuori E, et al. Growth delay after liver of small bowel allografts: Comparative assessment of survival,
transplantation in childhood: Studies of underlying mechanisms. function, rejection, and bacterial translocation. J Am Coll Surg
Pediatr Res 1995;38:36672. 2002;195:80413.
123. Balistreri WF, Bucuvalas JC, Ryckman FC. The effect of immu- 148. Ruiz P, Takahashi H, Delacruz V, et al. International grading
nosuppression on growth and development. Liver Transpl Surg scheme for acute cellular rejection in small-bowel transplantation:
1995;1:6473. single-center experience. Transpl P 2010;42:4753.
124. Chin SE, Shepherd RW, Cleghorn GJ, et al. Survival, growth and 149. Shin CR, Nathan J, Alonso M, et al. Incidence of acute and
quality of life in children after orthotopic liver transplantation: A chronic graft-versus-host disease and donor T-cell chimerism
5 year experience. J Paediatr Child Health 1991;27:3805. after small bowel or combined organ transplantation. J Pediatr
125. Zitelli BJ, Miller JW, Gartner JC Jr, et al. Changes in life-style Surg 2011;46:17328.
after liver transplantation. Pediatrics 1988;82:17380. 150. Potter DE, Holliday MA, Piel CF, et al. Treatment of end-stage
126. Stewart SM, Hiltebeitel C, Nici J, et al. Neuropsychological renal disease in children: A 15-year experience. Kidney Int
outcome of pediatric liver transplantation. Pediatrics 1991;87: 1980;18:1039.
36776. 151. Fine R. Renal Transplantation in Children. In: Morris P, editor.
127. Stewart SM, Uauy R, Waller DA, et al. Mental and motor devel- Kidney Transplantation: Principals and Practice. Orlando: Grune
opment, social competence, and growth one year after successful & Stratton; 1984. p. 50946.
pediatric liver transplantation. J Pediatr 1989;114:57481. 152. McEnery PT, Stablein DM, Arbus G, Tejani A. Renal transplanta-
128. Tarter RE, Hays AL, Sandford SS, et al. Cerebral morphological tion in children. A report of the North American Pediatric Renal
abnormalities associated with non-alcoholic cirrhosis. Lancet Transplant Cooperative Study. N Engl J Med 1992;326:
1986;2:8935. 172732.
129. Bernthal P, Hays A, Tarter RE, et al. Cerebral CT scan abnormali- 153. North American Pediatric Renal Transplant Cooperative Study.
ties in cholestatic and hepatocellular disease and their relationship 2010 Annual Report.
to neuropsychologic test performance. Hepatology 1987;7: 154. Warady BA, Hebert D, Sullivan EK, et al. Renal transplantation,
10714. chronic dialysis, and chronic renal insufficiency in children and
130. Tarter RE, Sandford SL, Hays AL, et al. Hepatic injury correlates adolescents. The 1995 Annual Report of the North American
with neuropsychologic impairment. Int J Neurosci 1989;44: Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol
7582. 1997;11:4964.
131. Bucuvalas JC, Britto M, Krug S, et al. Health-related quality of 155. Hanna JD, Krieg RJ Jr, Scheinman JI, Chan JC. Effects of uremia
life in pediatric liver transplant recipients: A single-center study. on growth in children. Semin Nephrol 1996;16:23041.
Liver Transpl 2003;9:6271. 156. Benfield MR. Current status of kidney transplant: Update 2003.
132. Mazariegos GV, Steffick DE, Horslen S, et al. Intestine transplan- Pediatr Clin N Am 2003;50:130134.
tation in the United States, 19992008. Am J Transplant 2010;10: 157. Benfield MR, McDonald RA, Bartosh S, et al. Changing trends
102034. in pediatric transplantation: 2001 Annual Report of the North
133. Mazariegos GV, Squires RH, Sindhi RK. Current perspectives on American Pediatric Renal Transplant Cooperative Study. Pediatr
pediatric intestinal transplantation. Curr Gastroenterol Rep Transplant 2003;7:32135.
2009;11:22633. 158. Englund M, Berg U, Tyden G. A longitudinal study of children
134. Nayyar N, Mazariegos G, Ranganathan S, et al. Pediatric small who received renal transplants 1020 years ago. Transplantation
bowel transplantation. Semin Pediatr Surg 2010;19:6877. 2003;76:31118.
135. (HCFA) HCFA. Combined Liver and Intestinal and Multi- 159. Fine RN. Growth following solid-organ transplantation. Pediatr
visceral Transplantation (#CAG-00036) Decision Memorandum. Transplant 2002;6:4752.
2000. 160. Grushkin CM, Fine RN. Growth in children following renal
136. Youssef NN, Mezoff AG, Carter BA, et al. Medical update and transplantation. Am J Dis Child 1973;125:51456.
potential advances in the treatment of pediatric intestinal failure. 161. Rotundo A, Nevins TE, Lipton M, et al. Progressive encepha-
Curr Gastroenterol Rep 2012;14:24352. lopathy in children with chronic renal insufficiency in infancy.
137. Ching YA, Gura K, Modi B, et al. Pediatric intestinal failure: Kidney Int 1982;21:48691.
nutrition, pharmacologic, and surgical approaches. Nutr Clin 162. Najarian J, Ascher NL, Mauer SM. Kidney Transplantation. In:
Pract 2007;22:65363. Welch K, Randolph J, Ravitch M, editors. Pediatric Surgery.
138. Touloukian RJ, Smith GJ. Normal intestinal length in preterm Chicago: Year Book Medical; 1986. p. 36073.
infants. J Pediatr Surg 1983;18:7203. 163. Turcotte J, Campbell DA, Dafoe D. Pediatric Renal Transplanta-
139. Bueno J, Ohwada S, Kocoshis S, et al. Factors impacting the tion. In: Cerilli G, editor. Organ Transplantation and Replace-
survival of children with intestinal failure referred for intestinal ment. Philadelphia: JB Lippincott; 1988. p. 34960.
transplantation. J Pediatr Surg 1999;34:2732. 164. Ildstad ST, Tollerud DJ, Noseworthy J, et al. The influence of
140. Fishbein TM, Matsumoto CS. Intestinal replacement therapy: donor age on graft survival in renal transplantation. J Pediatr Surg
Timing and indications for referral of patients to an intestinal 1990;25:1349.
rehabilitation and transplant program. Gastroenterol 2006;130: 165. Ildstad ST, Tollerud DJ, Noseworthy J, et al. Renal transplanta-
S14751. tion in pediatric recipients. Transpl P 1989;21:19367.
141. Avitzur Y, Grant D. Intestine transplantation in children: Update 166. Singh A, Stablein D, Tejani A. Risk factors for vascular thrombosis
2010. Pediatr Cl N Am 2010;57:41531. in pediatric renal transplantation: A special report of the North
45 Solid Organ Transplantation in Children 635
American Pediatric Renal Transplant Cooperative Study. Trans- 170. Sutherland DE. The case for pancreas transplantation. Diabetes
plantation 1997;63:12637. Metab 1996;22:1328.
167. Bereket G, Fine RN. Pediatric renal transplantation. Pediatr Clin 171. Stratta RJ, Larsen JL, Cushing K. Pancreas transplantation for
N Am 1995;42:160328. diabetes mellitus. Annu Rev Med 1995;46:28198.
168. Mahmoud A, Said MH, Dawahra M, et al. Outcome of preemp- 172. Bellin MD, Sutherland DE. Pediatric islet autotransplantation:
tive renal transplantation and pretransplantation dialysis in chil- Indication, technique, and outcome. Curr Diabetes Rep 2010;
dren. Pediatr Nephrol 1997;11:53741. 10:32631.
169. Tejani A, Sullivan EK, Alexander S, et al. Posttransplant deaths
and factors that influence the mortality rate in North American
children. Transplantation 1994;57:54753.
C H A P T E R 4 6
The pancreas originates during week 4 of gestation as and colon, but are also infrequently encountered in the
dual evaginations from the foregut endoderm. The dorsal thorax and other sites.46 These lesions are found in
pancreatic bud gives rise to the body and tail of the pan- approximately 2% of autopsy series and represent the
creas, its minor duct (Santorini) and papilla, and the con- most common anomaly of the gastric antrum. Moreover,
tinuation of the major duct (Wirsung) into the body and they may cause gastric outlet obstruction.7 Their origin
tail. The ventral pancreatic bud arises from the biliary is unknown, but may be the result of aberrant epithelial
diverticulum and swings around the dorsal aspect of the mesenchymal interactions leading to the transdifferentia-
duodenal anlage during gut rotation to give rise to the tion of embryonic epithelium into pancreatic epithelium.
head of the pancreas as well as the proximal portion of Several studies have implicated defects in hedgehog sig-
Wirsungs duct (Fig. 46-1).1 naling and Notch signaling as the cause of ectopic pan-
The two pancreatic buds fuse to form one pancreas at creatic rests.8 Ectopic rests are typically asymptomatic
approximately 7 weeks gestation, although it appears and are encountered incidentally at laparotomy or during
that complete fusion of the two ducts to form the main endoscopy. They can be identified as pancreatic tissue
pancreatic duct is delayed until the perinatal period.2 The visually, because the surface has the same granular acinar
endocrine component of the pancreas, the islets of Lang- appearance as the normal pancreas. These ectopic pan-
erhans, starts to differentiate before evagination of the creatic rests usually do not become inflamed, possibly
pancreatic buds from the wall of the foregut. The islets because they contain numerous small drainage ducts that
comprise 10% of the pancreas during early embryonic usually do not obstruct; however, they can occasionally
and fetal life, but this contribution decreases to less than cause intestinal obstruction or bleeding. When encoun-
1% in adulthood. Pancreatic acini begin to form at 12 tered at laparotomy, ectopic rests should probably be
weeks gestation and begin to accumulate organelles and excised, unless the excision would entail significant risk.
zymogen granules at this stage, but do not secrete appre- An annular pancreas is thought to result from faulty
ciable amounts of enzyme until birth.1 rotation of the ventral pancreatic bud in its course around
The pancreas is retroperitoneal and is light pink in the posterior aspect of the duodenal anlage. The duode-
children. The acini can be seen under low power loupe num is encircled and often obstructed by normal pancre-
magnification, as can the septa dividing the lobulations. atic tissue.9 Abnormal expression patterns of endodermal
The head of the pancreas lies in the C-loop of the duo- hedgehog may be responsible for the formation of annular
denum while the uncinate process, emanating from the and ectopic pancreas.8 Duodenal atresia and stenosis,
posteromedial portion of the head, projects under the intestinal malrotation, and trisomy 21 can often be found
superior mesenteric artery (SMA) and vein. The neck of in combination with an annular pancreas.10 The clinical
the pancreas is defined as that portion of the pancreas significance relates primarily to intrinsic duodenal
anterior to these vessels. The body and tail, to the left of obstruction, typically with bilious vomiting. Radiographic
these vessels, angle sharply towards the hilum of the studies may reveal the classic finding of the double-
spleen. The main pancreatic duct runs along the poste- bubble sign. Management consists of bypass of the
rior aspect of the gland and curves downward in the head obstructing lesion with a duodenoduodenostomy or gas-
to run alongside the common bile duct, which runs in a trojejunostomy, depending on the anatomy. Resection or
groove posterior to the pancreas or within the substance division of the annular pancreas should not be performed
of the posterior gland. The main pancreatic duct and due to the variable and complex ductal drainage system.
common bile duct may fuse to form a common channel Occasionally, patients with complex ductal anatomy may
before entry into the duodenum. require reoperation for pancreatobiliary anomalies not
The pancreas is convex and its midportion is reflected apparent at the time of the initial surgery.11
over the anterior surface of the upper lumbar vertebrae Cystic fibrosis (CF) is an autosomal recessive condi-
and aorta. Its lateral aspects falls posteriorly toward each tion, seen primarily in Caucasians which occurs in about
kidney (Fig. 46-2). The arterial supply of the pancreas is 1 of 2,500 births.12 It is caused by mutations in the cystic
from the celiac and SMA, which form the pancreati- fibrosis transmembrane conductance regulator (CFTR)
coduodenal arcade. The pancreas also has anastomoses gene that encodes a protein expressed on the apical mem-
from the splenic artery.3 brane of exocrine epithelial cells. CF leads to significant
pancreatic insufficiency. The pancreatic secretions
generally have a reduced amount of bicarbonate, a lower
CONGENITAL ANOMALIES pH, and a lower overall fluid volume. The inspissated
secretions lead to blockage of the ducts with dilatation.
Ectopic pancreatic rests are frequently encountered along This may lead to acinar cell degeneration, acute and
foregut derivatives such as stomach, duodenum, jejunum, chronic pancreatitis, and pancreatic fibrosis. The result
636
46 Lesions of the Pancreas 637
Accessory
pancreatic duct
(Santorinis)
a
Dorsal
pancreas
b
d
c Ventral
pancreas Pancreatic duct
A B C (Wirsungs)
FIGURE 46-1 Pancreatic embryology. (A) Stomach (a), gallbladder (b), and ventral (c) and dorsal (d) pancreatic buds develop sepa-
rately at embryologic week 4. The pancreas develops as an evagination of the developing foregut. The dorsal bud evaginates directly
off of the duodenal anlage. (B) The ventral bud evaginates from the biliary bud and then swings around to the left, with gut rotation
occurring simultaneously. (C) The main pancreatic duct of Wirsung and the minor accessory duct of Santorini are shown.
P C
L
Sp
is impaired digestion of fats and proteins from loss of resolve and then recur, it is termed acute recurrent pan-
these digestive enzymes.13 See Chapter 32 for more infor- creatitis. It is thought that complete interval resolution
mation about CF. of morphology and function occurs between episodes,
unlike in cases of chronic pancreatitis.14
The causes of acute pancreatitis include trauma, biliary
tract stone disease, choledochal cyst, ductal developmen-
PANCREATITIS tal anomalies, drugs, metabolic derangements, and infec-
Acute Pancreatitis tions. Most commonly, the cause is not apparent and
termed idiopathic. As the pancreas is fixed against the
Acute pancreatitis is an acute inflammation of the pan- lumbar spine, trauma to the upper abdomen can fracture
creas, varying in severity from mild abdominal pain to the pancreas or injure the major duct at that point
fulminant necrotizing pancreatitis and death. It has an (Fig. 46-3). Biliary stone disease, increasing in frequency
incidence between 3.6 and 13.2 cases per 100,000 chil- in children, may lead to pancreatitis from transient
dren. If episodes of acute inflammation completely pancreatic duct obstruction. Endoscopic retrograde
638 SECTION IV Abdomen
A B
FIGURE 46-5 (A) This secretin-enhanced MRCP was performed in a patient with pancreatic ductal stenosis. The white arrowhead
shows stenosis of the main pancreatic duct at the neck along with diffuse ascites (white arrow). A fluid collection communicating
with the duct is also seen (black arrowhead). (B) An ERCP in the same patient demonstrates the ductal stenosis (white arrowhead),
distal duct dilation, and the communicating fluid collection (black arrowhead). (From Akisik MF, Sandrasegaran K, Aisen AA, etal.
Dynamic secretin-enhanced MR cholangiopancreatography. Radiographics: A review publication of the Radiological Society of North America,
Inc. 2006;26:66577.)
chronic pancreatitis. A large single-institution retrospec- often resolve prior to requiring EN or TPN. More severe
tive study found a low rate of post-ERCP complications cases should be treated with EN via a nasojejunal tube,
and a high therapeutic success rate.15 ERCP was shown though studies have demonstrated tolerance of nasogas-
to be particularly useful in the diagnosis of recurrent tric feeding in severe pancreatitis as well. TPN use,
pancreatitis, though in only 60% of patients an organic especially early in the disease course during the peak
etiology was found. Sphincter of Oddi manometry was inflammatory response, has been associated with increased
particularly useful in establishing a diagnosis when no length of stay and delayed advancement of diet. When
anatomic abnormalities were present. EN is contraindicated, some advocate waiting as long as
The treatment for pancreatitis has remained unchanged 5 days prior to starting TPN. Compared to TPN, EN
for decades. The mainstays of therapy are pain control, has been shown to decrease length of stay, reduce the
intravenous fluid resuscitation, pancreatic rest, and moni- need for surgery, and reduce the risk of infection.25 When
toring for complications. Fluid resuscitation and mainte- restarting a diet, conservatively determined by resolution
nance should be guided towards a goal urine output of of symptoms, there appears to be no difference between
2mL/kg/h measured by an indwelling urinary catheter. clear liquid or solid food as the initial meal.26 Unfortu-
Because of circulating cytokines, activated digestive nately, these data come almost exclusively from the adult
enzymes, and other pro-inflammatory molecules, extra- population as pediatric trials are lacking.17,27
cellular fluid losses can be enormous. Constant monitor- Adequate analgesia is critical to minimizing the physi-
ing is necessary to avoid the development of severe ologic stress that develops from pain. While meperidine
hypovolemia. Patients with severe acute pancreatitis may (Demerol) was once advocated because morphine was
require nasogastric decompression. Most patients receive thought to cause spasm of the Sphincter of Oddi, no
histamine-2 (H2) receptor antagonists to reduce exposure clinical trials have shown superiority of meperidine over
of the duodenal secretin-producing cells to gastric acid, other narcotic analgesics. Large doses of meperidine,
a potent stimulator of pancreatic secretion. This thera- however, are associated with the risk of seizure, euphoria,
peutic regimen is logical but empirical, because no studies and drug interactions, suggesting other narcotics such as
have shown improvement in outcomes with these inter- morphine and fentanyl may be safer alternatives. The
ventions. The effectiveness of somatostatin in the treat- diagnosis of pancreatitis must be certain prior to initiat-
ment of pancreatitis is equivocal and probably serves ing treatment with high doses of narcotics as these may
more to mitigate complications of pancreatitis rather mask signs of serious nonpancreatic pathology, such as
than to treat the disease itself. Further studies are needed intestinal or gastric perforations.28
to clearly define its role in both adults and children.24 As pancreatitis progresses in severity, patients need to
Nutrition is critically important in patients with pan- be monitored closely for signs of multisystem organ
creatitis. The past decade has seen a paradigm shift in the failure. Pleural effusions, pulmonary edema, and tense
nutritional management of patients with pancreatitis. abdominal distention may lead to hypoxia requiring intu-
Early nutrition, within the first 72 hours, is still recom- bation and adult respiratory distress syndrome. Hypocal-
mended, however enteral nutrition (EN) has become the cemia, hypomagnesemia, anemia from hemorrhage,
preferred method over total parenteral nutrition (TPN). hyperglycemia, renal failure, and late sepsis can also be
Patients with mild to moderate cases of acute pancreatitis seen in these patients. Disagreement exists regarding the
640 SECTION IV Abdomen
use of prophylactic antibiotics in severe cases of pancrea- The pancreatic pseudocysts that persist, or are symp-
titis. The most recent adult data suggests a trend towards tomatic, require either a drainage procedure or excision.
decreased mortality and infection with prophylactic anti- Endoscopic treatment, well established in adults, has
biotics, but this study failed to reach statistical signifi- been reported to be safe and efficacious in children as
cance.29 Imipenem is the antibiotic therapy of choice well.34 This should only be performed at centers with
when necessary. sufficient experience with these techniques. Other options
Operative exploration is usually not necessary in acute include laparoscopic transgastric and intragastric drain-
pancreatitis. However, exploration is needed in patients age either into the stomach or jejunum (Fig. 46-7). Per-
with infected necrotic pancreatitis or a pancreatic abscess. cutaneous drainage is the preferred approach for infected
Infected pancreatic necrosis increases mortality signifi- pseudocysts because these cysts typically have thin, weak
cantly. Diagnosis is typically by CT pancreatography, walls that are not amenable to internal drainage.
with confirmation of infection by fine needle aspiration, The three major complications of pancreatic pseudo-
clinical deterioration, or positive cultures. The latest cysts are hemorrhage, rupture, and infection. Hemor-
adult data suggests that infected necrosis or peripancre- rhage is the most serious complication and usually results
atic abscesses are best treated in a stepwise manner from from pressure and erosion of the cyst into a nearby vis-
least to most invasive. When feasible, percutaneous ceral vessel. These patients require emergency angiogra-
drainage should be followed by minimally invasive necro- phy with embolization. Rupture or infection of a
sectomy if the patient fails to improve. Delayed operative pseudocyst is uncommon. In both cases, external drain-
therapy demonstrates improved mortality compared to age is indicated.
primary necrosectomy.30,31 Ascites in children usually follows trauma or pancre-
Pancreatic pseudocyst is a complication of trauma or atic surgery.35 Free fluid results from the uncontained
pancreatitis that forms after injury to the pancreatic leakage of a major pancreatic duct. Treatment initially
ductal system. The extravasated pancreatic enzymes and consists of bowel rest with hyperalimentation and the
digested tissue are contained by the formation of a cavity use of long-acting somatostatin analogs. In many cases,
composed from a fibroblastic reaction and inflammation the ascites resolves spontaneously with this treatment.
that lacks an epithelial lining. The acute pseudocyst has When suspected, CT, ERCP, or MRCP should be
an irregular wall on CT scan, is tender, and usually devel- performed to assess for duct injury. A growing body
ops shortly after an episode of acute pancreatitis or of evidence supports nonoperative management of pedi-
trauma (Fig. 46-6). Chronic pseudocysts are usually atric pancreatic trauma even in the presence of ductal
spherical with a thick wall, and are commonly seen in injury. When operative treatment is necessary, drainage
patients with chronic pancreatitis. The distinction is alone may suffice. Distal duct injuries can be treated with
important because half of acute pseudocysts resolve distal resection. Proximal injuries require Roux-en-Y
without treatment, while chronic pseudocysts rarely jejunal onlay anastomosis to preserve pancreatic tissue.
spontaneously resolve. An acute pseudocyst matures and Pseudocyst formation is common in this patient
forms a thick fibrous wall in four to six weeks, allowing population.36,37
for drainage. Those smaller than 5cm in diameter usually Pancreatic fistula can occur postoperatively. Most low-
spontaneously regress. When compared to those in output fistulas close spontaneously but may drain for
adults, pseudocysts in children tend to resolve more fre- several months. Long-acting somatostatin analogs
quently with medical therapy alone.32 There are anecdo- decrease fistula output and accelerate the rate of closure,
tal reports of pseudocyst resolution in children after but do not appear to induce closure of fistulas that would
treatment with long-acting somatostatin analogs.33 not otherwise have closed. Managing a pancreatic fistula
centers around maintaining nutrition, with hyperalimen-
tation necessary if enteral feeding increases fistula output,
and ensuring the fistula tract does not become obstructed.
Operative intervention with a Roux-en-Y jejunostomy
anastomosed to the fistula site is usually curative if the
fistula fails conservative management.38
Chronic Pancreatitis
Chronic pancreatitis is distinguished from acute pancrea-
titis by the irreversibility of the changes associated with
the inflammation.14 Chronic pancreatitis can be classified
as either calcifying or noncalcifying. The calcifying form,
most common in hereditary or idiopathic pancreatitis, is
more prevalent than the obstructive form in children, and
is associated with intraductal pancreatic stones, pseudo-
cysts, and more aggressive scar formation. The obstruc-
tive type of chronic pancreatitis, which is associated with
FIGURE 46-6 CT scan of an acute pseudocyst in a patient after
an anatomic or functional obstruction, is generally less
a severe motor vehicle accident. The wall (arrows) is irregular severe with less scarring than calcifying pancreatitis.
with nonloculated fluid inside. Single institutional experiences vary as to distributions in
46 Lesions of the Pancreas 641
A B
C D
FIGURE 46-7 This adolescent sustained blunt trauma from a motor vehicle accident which resulted in a pancreatic pseudocyst
several weeks later. After six weeks, laparoscopic cyst gastrostomy was performed. (A) The stomach has been opened. (B) A needle
is introduced into the pseudocyst through the posterior wall of the stomach. (C) The common wall between the pseudocyst and
stomach has been excised and is opened widely for adequate drainage of the pseudocyst. (D) The resulting gastrotomy has been
closed with an endoscopic stapler. The patient recovered uneventfully and has not developed any postoperative problems.
etiology, though the predominant causes are hereditary/ Oddi dysfunction, or the relatively high association with
genetic, obstructive, or idiopathic.39,40 CFTR mutations.18 Many patients with ductal dilatation
The discovery of a genetic basis for certain forms of and anatomic or functional obstruction clearly improve
chronic pancreatitis represents a major breakthrough in with endoscopic sphincterotomy and/or stents. Pancre-
our understanding of its pathogenesis. Current thinking atic dyskinesia, though not well studied in children, may
is that familial pancreatitis results from a combination of be improved by endoscopic sphincterotomy and some-
environmental triggers, genetic susceptibility, and an times temporary stent placement.42 For those in whom
inappropriate immune response leading to chronic endoscopic treatment is not feasible or fails, individual-
inflammation and fibrosis. Hereditary pancreatitis, the ized surgical treatment is reasonable based on the patients
most common genetic cause of pancreatitis, can result ductal anatomy, level of obstruction, and severity of pan-
from abnormalities in the cationic trypsinogen gene creatic fibrosis.
PRSS1.41 This autosomal dominant condition most com- Chronic pancreatitis can manifest with a characteristic
monly results from one of two mutations that either pain, diminished pancreatic function, and radiographic
prevent degradation of prematurely activated trypsin or abnormalities. Increased stool fat, diabetes, and steator-
make trypsin resistant to inactivation. Penetrance in this rhea are signs of pancreatic insufficiency. Frequently on
condition is approximately 80%. Other gene mutations a CT scan, the pancreas has microcalcifications through-
implicated in chronic pancreatitis are SPINK1 and CFTR. out the parenchyma and calcified stones in the duct (Fig.
Genetic testing is recommended for children with recur- 46-8). Additionally, pancreatic pseudocysts or inflamma-
rent, idiopathic pancreatitis, with or without a family tion may be seen on the CT scan. ERCP or MRCP can
history of pancreatitis. Notably, patients with hereditary evaluate the ductal anatomy and can identify anatomic
pancreatitis have a markedly increased risk of pancreatic causes of chronic pancreatitis. Only ERCP provides a
cancer after age 50 years. means for evaluating sphincter pressure measurements
Obstructive pancreatitis is most often due to an ana- for functional obstruction.42
tomic or functional obstruction of the pancreatic duct. Therapy for chronic pancreatitis is directed toward
The most common anatomic causes are pancreas divisum palliation of symptoms. Initial management for acute
followed by choledochal cysts. Uncertainty exists as to exacerbations is pain control and hydration. Steatorrhea
why a minority of patients with pancreas divisum develop indicates the need for pancreatic enzyme replacement. In
chronic pancreatitis while most do not. The literature general, these patients respond better with small, fre-
suggests that potential causes are the anatomic variant, quent meals. The diabetes that results from chronic pan-
structural narrowing of the minor papilla, sphincter of creatitis tends to be unusually brittle, with a propensity
642 SECTION IV Abdomen
Pancreatic duct
Roux loop
Roux loop
for severe hypoglycemic episodes after even low doses of age, the causes are different, with insulinoma being the
insulin. This hypersensitivity to insulin may be due to the most common.
loss of entire islets, which includes the glucagon-
producing alpha cells that normally oppose the glucose- Congenital Hyperinsulinism
lowering effect of insulin.
In patients with chronic pancreatitis who have severe, Nesidioblastosis, the original term for what is now called
intractable pain, ERCP or MRCP may help locate cor- congenital hyperinsulinism of infancy (CHI), comes from
rectable problems such as large stones or a stricture with the Greek nesidio, meaning island, and blast, meaning
distal duct dilatation. Surgical options in chronic pan- new formation. Nesidioblasts were originally thought to
creatitis include sphincteroplasty, excision of localized be progenitor cells in the wall of the pancreatic ducts
pancreatitis, subtotal pancreatectomy, lateral pancreati- which overproliferate in patients with this condition.45
cojejunostomy (modified Puestow procedure), and the With the advent of genetic analysis, this pathogenesis was
duodenum or pylorus-preserving Whipple. Individuali- proven to be incorrect.
zation of the operative approach and maximization of Mutations in seven genes are currently known to lead
pancreatic ductal drainage are key. Patients failing more to CHI, though roughly half of cases are caused by
conservative surgical management may require a more genetic malformations not yet understood. Initially dis-
definitive procedure to achieve symptomatic relief.43 covered was the loss of functioned mutations in the SUR1
Although the operative results in patients with hereditary and Kir6.2 components of the ATP-sensitive potassium
pancreatitis are generally disappointing, evidence exists channel (KATP) found in the cell membrane of the pan-
that complicated patients treated with a modified Puestow creatic -cell. These mutations either impair the ability
procedure may experience an improved quality of life of Mg-adenosine diphosphate (ADP) to stimulate channel
with subsequent improvement in pancreatic function and activity or affect the expression of the KATP channels at
nutritional status (Fig. 46-9).44 Unlike adults with heredi- the surface membrane, resulting in continuous depolari-
tary pancreatitis, some reversal of the steatorrhea may be zation of the -cell membrane and dysregulated insulin
seen in children. secretion.46 Heterozygous gain-of-function mutations in
GULD1, the mitochondrial gene encoding glutamate
dehydrogenase, leads to CHI caused by insensitivity of
FUNCTIONAL PANCREATIC DISORDERS the enzyme to inhibition by guanosine-5-triphosphate.
This mutation results in a milder form of CHI, which
The causes of persistent hypoglycemia in children vary may be diagnosed later in childhood, and is associated
greatly with age. In newborns and young infants, the with hyperammonemia and occasionally epilepsy. Het-
major causes are: (1) congenital hyperinsulinism of erozygous loss-of-function mutations in HNF4A, an islet
infancy, previously called nesidioblastosis; (2) a lack of transcription factor gene, are also associated with CHI
substrate for gluconeogenesis (e.g., glycogen storage through unknown mechanisms. More rare are cases of
disease); and (3) inadequate gluconeogenic hormones CHI caused by mutations in glucokinase (GCK),
(e.g., hypothyroidism or growth hormone deficiency). In hydroxyacyl-coenzyme A dehydrogenase (HADH), and
children with the onset of hypoglycemia after 1 year of the solute carrier SLC16A1.47
46 Lesions of the Pancreas 643
CHI occurs in a focal and diffuse type, the differentia- glucagon can be used as a temporizing measure until
tion of which is critical for operative management. definitive venous access is obtained.
However, the clinical presentation is identical. Patients Treatment of CHI begins with medical management.
with SUR1 mutations often have the focal type. The focal Diazoxide remains a mainstay of therapy. Diazoxide binds
type is actually a focal adenomatous hyperplasia, different the SUR1 component of the KATP channel and main-
from an adenoma. Histologically, it is seen as a conflu- tains it in a persistently open state, preventing insulin
ence of hyperplastic but otherwise normal-appearing secretion. Patients with diazoxide-sensitive CHI who can
islets. There is little insulin present within the lesion due tolerate fasting can be managed medically until they
to excess secretion, while uninvolved islets outside are outgrow their condition. Those unresponsive to diazox-
small with high insulin content. The diffuse type is mac- ide should be managed with frequent feedings, glucose
roscopically normal, but careful evaluation of the islets infusions, and somatostatin analogs. Somatostatin analogs
reveals enlarged -cells with abnormally large nuclei, a inhibit pancreatic insulin secretion and can be adminis-
large Golgi apparatus, and weak insulin staining due to tered subcutaneously either intermittently or continu-
hypersecretion.48 ously by a pump. Somatostatin analogs are associated
CHI patients typically develop hypoglycemia shortly with gallstones and biliary sludge, and have been impli-
after birth, though it may present at a later age. Infants cated in cases of necrotizing enterocolitis.50 Medical
with CHI are often macrosomic. Symptoms may be failure to control hypoglycemia necessitates surgical
subtle, such as lethargy and irritability, or severe with intervention.49
apnea, seizures, and coma. Simultaneous insulin and Distinguishing diffuse versus focal-type CHI is critical
glucose measurements show a high ratio of insulin to for operative planning. The recent development of an
18
glucose, keeping in mind that insulin levels may be F-DOPA PET-CT scanner has replaced pancreatic
normal, but inappropriate in the presence of hypoglyc- venous sampling as the optimal method for delineating
emia. These patients differ from insulinoma patients, focal versus diffuse disease with a sensitivity of 94% and
who usually have high absolute insulin levels. Another specificity of 100% (Fig. 46-10).51 Intraoperative ultra-
powerful indicator of CHI is a glucose requirement sound can provide additional anatomic detail to help
greater than 8mg/kg/min.49 Owing to the much higher avoid injury to the biliary tree.52 For the focal type, resec-
incidence of insulinoma, patients older than 1 year at the tion of the hypermetabolic focus is curative. Focal lesions
onset of hypoglycemia should be evaluated for both in the head may require duodenum-preserving pancreatic
conditions. head resection and distal pancretaticojejunostomy while
Stabilization of the CHI patient includes frequent distal lesions are excised via spleen-preserving distal pan-
intermittent or continuous feeding, with the addition of createctomy. In patients with diffuse disease, a near-total
intravenous glucose as needed. Central venous access is pancreatectomy is needed, leaving only a rim of pancre-
advised because adequate venous access is lifesaving and atic tissue along the common bile duct (Fig. 46-11). The
high concentrations of glucose infusion may be necessary. laparoscopic approach for both procedures has been
Maintaining normoglycemia is key to preventing poten- reported but data are limited.53,54 Operative complica-
tially disabling hypoglycemic brain injury. Intramuscular tions include bile duct injury, pancreatic insufficiency,
A B
FIGURE 46-10 18F-DOPA PET-CT scans of two patients with congenital hyperinsulinism of infancy. (A) A focal lesion (arrow) is
detected in the head of the pancreas. (B) The more diffuse uptake of the tracer along the entirety of the pancreas indicates the
diffuse type of this condition in this patient. (From Arnoux JB, Verkarre V, Saint-Martin C, etal. Congenital hyperinsulinism: Current trends
in diagnosis and therapy. Orphanet Journal of Rare Diseases 2011;6:63.)
644 SECTION IV Abdomen
PV
adulthood have an increased incidence of hepatic adenoma
after age 25 and have a 10% risk of malignant transforma-
tion. Liver transplantation ultimately becomes necessary
in these patients.58
95%
PANCREATIC TUMORS AND CYSTS
65%
90%
85%
Pancreatic Endocrine Tumors
The only pancreatic endocrine tumors seen in infants and
children are insulinomas, gastrinomas, and VIPomas.
IMV VIPoma is a tumor of vasoactive intestinal peptide (VIP)
SMV producing cells and only case reports exist in children.
FIGURE 46-11 Various degrees of pancreatectomy may be indi- Insulinoma is the most common of the three, though
cated for persistent hyperinsulinemic hypoglycemia of infancy. is still quite rare amongst pediatric tumors in general.59
Typically, a 95% pancreatectomy, as shown here, leaves behind
a cuff of pancreas along the C-loop of the duodenum. IMV, Only 10% of insulinomas are malignant, and these tend
inferior mesenteric vein; PV, portal vein; SA, splenic artery; to spread to the liver and peripancreatic lymph nodes.
SMV, superior mesenteric vein; SV, splenic vein. Insulinomas cause symptoms of hypoglycemia, including
dizziness, headaches, confusion, sweating, and seizures.
The classic Whipples triad was described in patients with
and the need for repeat pancreatic resection due to per- insulinoma and consists of the following: symptoms of
sistent hypoglycemia.55 hypoglycemia with fasting, glucose levels less than half of
Alternate forms of hyperinsulinemic hypoglycemia normal when fasting, and relief of symptoms with glucose
can arise secondary to maternal diabetes, birth asphyxia, administration. Patients are typically in their adolescence,
or intrauterine growth retardation (IUGR). In these though younger children have been described with insuli-
patients, the condition is transient, resolving for most noma. The lesions are usually solitary, except in multiple
patients within several days. A subgroup of patients endocrine neoplasia type I (MEN I) in which multiple
with IUGR and prenatal asphyxia will have a prolonged insulinomas may be found.60
condition that requires diazoxide for several months The gold standard test for insulinoma is the 72-hour
prior to resolution. Approximately 50% of children with fast, though studies have shown that a positive result
BeckwithWiedemann syndrome have a CHI-like condi- is achieved in 80% and 90% of patients with insulinoma
tion that tends to resolve spontaneously, but 5% will after a shorter 24-hour or 48-hour fast, respectively.
eventually require pancreatectomy.49 While fasting, periodic blood glucose levels are
The long-term outlook for these patients depends pri- obtained. When the patients blood glucose falls
marily on the age at onset which reflects severity of below 50mg/dL and symptoms are present, blood is
disease, and on an expeditious diagnosis because a late drawn for plasma glucose, C-peptide, proinsulin, insulin,
diagnosis results in a higher incidence of neurologic -hydroxybutarate, and sulfonylureas. Administration of
sequelae.56 Most patients seem to grow out of the disease exogenous insulin, followed by measurement of the
after several years, implying diminished activity of the C-peptide level, can be suggestive of an insulinoma, but
beta cells. Near-total pancreatectomy in one series was is not completely reliable. Measuring the insulin:glucose
associated with a 91% incidence of insulin-dependent ratio is no longer needed.61
diabetes by age 14, while no patient with focal resection Preoperative localization is challenging, but can be
required long-term insulin therapy, emphasizing the extremely helpful. Extrapancreatic insulinomas are rare.
need for a conservative operative approach when Most experts advocate for both transabdominal ultra-
possible.57 sound and CT for initial localization, which identifies
more than half of tumors. Centers experienced with
endoscopic ultrasound also have reported good success in
Glycogen Storage Disease detecting insulinomas,62 but expertise is not widely avail-
Glycogen storage disease type Ia (GSD-Ia) and Ib classi- able. MRI is most useful for detecting liver metastases. If
cally appear as severe hypoglycemia in infants caused by noninvasive studies fail to identify the tumor, intra-
the inability to dephosphorylate hepatic glycogen subu- arterial calcium stimulation via a catheter in several vis-
nits into glucose. GSD-Ia is caused by inactivating muta- ceral arteries with parallel venous sampling from the
tions of the glucose-6-phosphatase enzyme itself, while right hepatic vein has been reported to regionally localize
GSD-Ib results from inactivating mutations of the insulinomas in 8094% of cases.63 Intraoperative ultra-
glucose-6-phosphate transporter. Hypoglycemia becomes sound is strongly advocated for identification of adjacent
apparent when the time between feedings increases and biliary and vascular structures, and as a method of last
the liver fails to generate glucose from glycogen stores. resort if nonoperative localization fails.60,61
It is clinically diagnosed by hypoglycemia, hypoinsuline- All patients with insulinoma should undergo resection.
mia, hepatomegaly, nephromegaly, ketosis, and hyperli- Insulinomas are pink, firm, encapsulated, and are usually
pidemia. Central venous access is required for continuous amenable to enucleation. In most cases, through preop-
infusion of highly concentrated glucose. Survivors into erative and intraoperative analysis, the tumors can be
46 Lesions of the Pancreas 645
localized, but in patients in whom they cannot be local- Congenital duplications of the foregut may also
ized, blind distal pancreatic resection is no longer advised. present as pancreatic cysts. They have a gastric or intes-
The distinction between benign and malignant lesions is tinal mucosal lining and maintain pancreatic ductal com-
difficult, and is based on tumor size (<2cm tend to be munication. Gastric acid secretion from the cyst may
benign) and the presence of metastases. Insulinomas that cause episodes of pancreatitis. Surgical resection is neces-
are hard, cause puckering of surrounding tissues, appear sary, either in the form of enucleation, distal pancreate-
infiltrating, or cause distal pancreatic duct dilation should ctomy, or even pancreaticoduodenectomy.69
be assumed malignant, and resected with a margin instead Acquired non-neoplastic cysts of the pancreas are
of enucleated. Malignant tumors can be treated with called retention cysts, which appear to result from
chemotherapy, biotherapy (such as octreotide), hepatic obstruction of the smaller pancreatic ducts. The preop-
artery embolization/chemoembolization, radiation erative distinction of a retention cyst from other types of
therapy, or radiofrequency ablation.60 cysts or pseudocysts may be difficult, but is supported by
Fetal gastrin-producing cells in the pancreas are finding a small cystic lesion in communication with the
believed to give rise to pancreatic gastrinoma. In the pancreatic duct that has a proximal stricture. These can
fetus, the primary source of gastrin is the pancreas. After be excised if symptomatic, or otherwise observed.
birth, the gastric antrum becomes the principal source. However, they are often confused with neoplastic cysts
ZollingerEllison syndrome (ZES) consists of gastric and are resected for this reason.70
hypersecretion with severe peptic ulcer disease and a
gastrin-producing tumor, classically in the pancreas. ZES
may occur as part of the MEN I syndrome or sporadi-
Pancreatic Exocrine Tumors
cally. Gastrinomas are now understood to be frequently The pancreatic exocrine system includes the pancreatic
malignant, especially with spread to the liver, and their ducts, centroacinar cells, and acini. Tumors from this
removal is strongly advocated.64,65 system include pseudopapillary tumors, ductal adenocar-
The diagnosis of gastrinoma is based on hypergas- cinomas, acinar cell carcinomas, or pancreatoblastomas.
trinemia and gastric hypersecretion. Fasting gastrin levels Cystic tumors of the pancreas, including serous and
are usually elevated, but can be normal. Patients sus- mucinous cystadenomas and cystadenocarcinoma, are
pected of having ZES should undergo a secretin stimula- well described in adults, but are exceedingly rare in the
tion test, which is considered positive if the gastrin level pediatric population. Several case reports exist of serous
increases by 200pg/mL or more. Localization can be and mucinous cystadenomas, but one review suggests
challenging because the tumors are often small and may that no confirmed reports of cystadenocarcinoma in chil-
be extrapancreatic, but CT, MRI, endoscopic ultrasound, dren exist in the literature.59 Management of serous cys-
and 111Indium octreotide scintigraphy have been utilized tadenoma is debated based on its benign nature, but
to localize the tumors. Extrapancreatic tumors are often excision appears curative.
found in the duodenal wall.
Medically, patients should initially be treated with
omeprazole to control peptic ulcer disease and prevent
Adenocarcinoma/Pancreatoblastoma
bleeding. All disease should be excised if possible to Exocrine pancreatic cancers account for roughly half of
control symptoms and help prevent metastases. Patients pancreatic neoplasms in children. While ductal adeno-
cured by resection should be followed closely as recur- carcinoma is most common in adults, its embryonic
rence is common. Medical treatment for unresectable counterpart pancreatoblastoma is more common in chil-
disease includes proton pump inhibitors and octreotide. dren. Pancreatoblastoma is believed to result from the
Tumor debulking in unresectable cases is recommended persistence of embryonic pancreatic progenitor cells
to improve the patients quality of life and increase the beyond the eighth week of gestation. It tends to be diag-
life expectancy.65 Chemotherapy has been utilized in a nosed in early childhood and is more common in boys
few cases with good results reported.66 There is a report and those of Asian descent. An allelic loss on 11p is often
of a patient with a multiple gastrinomas managed medi- associated and suggests a similar pathogenesis with
cally who survived 26 years before succumbing to unre- BeckwithWiedemann syndrome and other embryonic
lated causes.67 tumors. A recent large multicenter review demonstrated
that the tumor distribution was homogenous throughout
Non-Neoplastic Cysts the pancreas, most were >5cm at presentation, and over
half had distant metastases.71 Elevation of serum alpha-
Although most cystic lesions of the pancreas are pseudo- fetoprotein was an inconsistent feature. The prognosis is
cysts and are acquired, congenital cysts may be seen at an relatively good with complete resection and with appro-
early age as a symptomatic mass with compression of priate neoadjuvant and/or adjuvant chemotherapy and
surrounding structures. Alternatively, these congenital radiation therapy. Relapse is common, so continued mon-
cysts may be noted incidentally on physical examination itoring is essential. 72
or radiographic studies. Congenital cysts contain cloudy, Acinar cell carcinoma and ductal adenocarcinoma are
straw-colored fluid. The cysts are most often found in less common pancreatic exocrine tumors. Ductal adeno-
the distal pancreas and are amenable to local resection carcinoma is infrequently reported in the pediatric litera-
with a rim of normal pancreas. Lesions in the pancreatic ture and no definitive recommendations are possible.73
head should be internally drained with a Roux-en-Y Acinar cell carcinoma is comparatively more common.
cystjejunostomy.68 Complete resection for both tumor types appears
646 SECTION IV Abdomen
A B C
FIGURE 46-12 This solid pseudopapillary tumor was found in a 14-year-old boy. (A) CT scan of the abdomen demonstrates a large,
heterogeneous mass (asterisk) in the head of the pancreas. (B) The tumor is seen at excision. Note that the tumor appears encap-
sulated and well circumscribed. (C) Cut section of the mass demonstrates solid and cystic regions as well as an area of hemorrhagic
necrosis (arrow). (From Speer AL, Barthel ER, Patel MM, etal. Solid pseudopapillary tumor of the pancreas: A single-institution 20-year
series of pediatric patients. J Pediatr Surg 2012;47:121722.)
necessary with appropriate provision of neoadjuvant or 11. Urushihara N, Fukumoto K, Fukuzawa H, et al. Recurrent pan-
creatitis caused by pancreatobiliary anomalies in children with
adjuvant chemotherapy based on pre-treatment staging. annular pancreas. J Pediatr Surg 2010;45:7416.
Long-term survival improves with an earlier stage at 12. Naruse S, Kitagawa M, Ishiguro H, et al. Cystic fibrosis and related
presentation.74,75 diseases of the pancreas. Best Pract Res Cl Ga 2002;16:51126.
Occurring slightly less frequently than pancreatoblas- 13. Taylor CJ, Aswani N. The pancreas in cystic fibrosis. Paediatr
toma is the solid pseudopapillary tumor, also known as a Respir Rev 2002;3:7781.
14. Morinville VD, Husain SZ, Bai H, et al. Definitions of pediatric
papillary-cystic tumor or Frantz tumor. It has a female pancreatitis and survey of current clinical practices: Report from
preponderance and is derived from exocrine cells, but INSPPIRE (International Study Group Of Pediatric Pancreatitis:
without acinar or ductal structures. Presenting symptoms In search for a cure). J Pediatr Gastroenterol Nutr 2012;55:
often include a palpable abdominal mass and abdominal 2615.
15. Otto AK, Neal MD, Slivka AN, et al. An appraisal of endoscopic
pain. These tumors can be very large at the time of diag- retrograde cholangiopancreatography (ERCP) for pancreaticobil-
nosis (Fig. 46-12).76 They are very slow growing, and iary disease in children: Our institutional experience in 231 cases.
there are reports of patients surviving 20 years after diag- Surg Endosc 2011;25:253640.
nosis without treatment.77 While rarely metastatic, exci- 16. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: An
sion of regional and distal metastases greatly improves update. J Clin Gastroentrol 2005;39:70916.
17. Lowe ME, Greer JB. Pancreatitis in children and adolescents. Curr
survival. Even with its indolent nature, an aggressive Gastroenterol Rep 2008;10:12835.
approach with complete resection is recommended as 18. Schneider L, Muller E, Hinz U, et al. Pancreas divisum: A differ-
one retrospective study of patients with incomplete resec- entiated surgical approach in symptomatic patients. World J Surg
tions showed poor long-term survival.78 2011;35:13606.
19. Bai HX, Lowe ME, Husain SZ. What have we learned about acute
pancreatitis in children? J Pediatr Gastroenterol Nutr
REFERENCES 2011;52:26270.
1. Gittes GK. Developmental biology of the pancreas: A comprehen- 20. Herman R, Guire KE, Burd RS, et al. Utility of amylase and lipase
sive review. Dev Biol 2009;326:435. as predictors of grade of injury or outcomes in pediatric patients
2. Dawson W, Langman J. An anatomical-radiological study on the with pancreatic trauma. J Pediatr Surg 2011;46:9236.
pancreatic duct pattern in man. Anat Record 1961;139:5968. 21. Darge K, Anupindi S. Pancreatitis and the role of ultrasound,
3. Bertelli E, Di Gregorio F, Bertelli L, et al. The arterial blood MRCP and ERCP. Pediatr Radiol 2009;39(Suppl 2):S1537.
supply of the pancreas: A review I. The superior pancreaticoduo- 22. Kim DH, Pickhardt PJ. Radiologic assessment of acute and chronic
denal and the anterior superior pancreaticoduodenal arteries. An pancreatitis. Surg Clin N Am 2007;87:134158.
anatomical and radiological study. Surg Radiol Anat 1995;17: 23. Neblett WW 3rd, ONeill JA Jr. Surgical management of recurrent
97106. pancreatitis in children with pancreas divisum. Ann Surg
4. Nakajima H, Kambayashi M, Okubo H, et al. Annular pancreas 2000;231:899908.
accompanied by an ectopic pancreas in the adult: A case report. 24. Li J, Wang R, Tang C. Somatostatin and octreotide on the treat-
Endoscopy 1995;27:713. ment of acute pancreatitisbasic and clinical studies for three
5. Heller RS, Tsugu H, Nabeshima K, et al. Intracranial ectopic decades. Curr Pharm Design 2011;17(16):1594601.
pancreatic tissue. Islets 2010;2:6571. 25. Marick PE, Zaloga GP. Meta-analysis of parenteral nutrition versus
6. Tilson MD, Touloukian RJ. Mediastinal enteric sequestration with enteral nutirion in patients with acute pancreatitis. BMJ
aberrant pancreas: A formes frustes of the intralobar sequestration. 2004;328:140712.
Ann Surg 1972;176:66971. 26. Moraes JM, Felga GE, Chebli LA, et al. A full solid diet as the
7. Ozcan C, Celik A, Guclu C, et al. A rare cause of gastric outlet initial meal in mild acute pancreatitis is safe and result in a shorter
obstruction in the newborn: Pyloric ectopic pancreas. J Pediatr length of hospitalization: Results from a prospective, randomized,
Surg 2002;37:11920. controlled, double-blind clinical trial. J Clin Gastroenterol
8. van den Brink GR. Hedgehog signaling in development and home- 2010;44:51722.
ostasis of the gastrointestinal tract. Physiol Rev 2007;87:134375. 27. McClave SA, Chang WK, Dhaliwal R, et al. Nutrition support in
9. Skandalakis JE, Gray SW. Embryology for surgeons: The embryo- acute pancreatitis: A systematic review of the literature. JPEN-
logical basis for the treatment of congenital anomalies. 2nd ed. Parenter Enter 2006;30:14356.
Baltimore: Williams & Wilkins; 1994. xx, 1101 p. 28. Thompson DR. Narcotic analgesic effects on the sphincter of
10. Sencan A, Mir E, Gunsar C, et al. Symptomatic annular pancreas Oddi: A review of the data and therapeutic implications in treating
in newborns. Med Sci Mont 2002;8:CR4347. pancreatitis. Am J Gastroenterol 2001;96:126672.
46 Lesions of the Pancreas 647
29. Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis 55. Pierro A, Nah SA. Surgical management of congenital hyperin-
against infection of pancreatic necrosis in acute pancreatitis. sulinism of infancy. Semin Pediatr Surg 2011;20:503.
Cochrane Database Syst Rev 2010:CD002941. 56. Leibowitz G, Glaser B, Higazi AA, et al. Hyperinsulinemic
30. Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute hypoglycemia of infancy (nesidioblastosis) in clinical remission:
pancreatitis. World J Surg 1997;21:1305. High incidence of diabetes mellitus and persistent beta-cell dys-
31. van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and function at long-term follow-up. J Clin Endocr Metab 1995;80:
minimally invasive approach to necrotizing pancreatitis improves 38692.
outcome. Gastroenterol 2011;141:125463. 57. Beltrand J, Caquard M, Arnoux JB, et al. Glucose metabolism in
32. Kisra M, Ettayebi F, Benhammou M. Pseudocysts of the pancreas 105 children and adolescents after pancreatectomy for congenital
in children in Morocco. J Pediatr Surg 1999;34:13279. hyperinsulinism. Diabetes Care 2012;35:198203.
33. Wensil AM, Balasubramanian SA, Bell TL. Resolution of a post- 58. Chou JY, Jun HS, Mansfield BC. Glycogen storage disease type I
traumatic pancreatic pseudocyst with octreotide acetate in a pedi- and G6Pase-beta deficiency: Etiology and therapy. Nat Rev Endo-
atric patient. Pharmacotherapy 2011;31:924. crinol 2010;6:67688.
34. Sharma SS, Maharshi S. Endoscopic management of pancreatic 59. Shorter NA, Glick RD, Klimstra DS, et al. Malignant pancreatic
pseudocyst in children-a long-term follow-up. J Pediatr Surg tumors in childhood and adolescence: The Memorial Sloan-
2008;43:16369. Kettering experience, 1967 to present. J Pediatr Surg 2002;37:
35. DCruz AJ, Kamath PS, Ramachandra C, et al. Pancreatic ascites 88792.
in children. Acta Paediatr Jpn 1995;37:6303. 60. Mathur A, Gorden P, Libutti SK. Insulinoma. Surg Clin N Am
36. de Blaauw I, Winkelhorst JT, Rieu PN, et al. Pancreatic injury in 2009;89:110521.
children: Good outcome of nonoperative treatment. J Pediatr Surg 61. Grant CS. Insulinoma. Best Pract Res Cl Ga 2005;19:78398.
2008;43:16403. 62. Patel KK, Kim MK. Neuroendocrine tumors of the pancreas:
37. Juric I, Pogorelic Z, Biocic M, et al. Management of blunt pancre- Endoscopic diagnosis. Curr Opin Gastroent 2008;24:63842.
atic trauma in children. Surg Today 2009;39:11519. 63. Guettier JM, Kam A, Chang R, et al. Localization of insulinomas
38. Butturini G, Daskalaki D, Molinari E, et al. Pancreatic fistula: to regions of the pancreas by intraarterial calcium stimulation: The
Definition and current problems. J Hepato-Biliary-Pan 2008;15: NIH experience. J Clin Endocrinol Metab 2009;94:107480.
24751. 64. Jensen RT. Gastrointestinal endocrine tumours. Gastrinoma. Bail-
39. Clifton MS, Pelayo JC, Cortes RA, et al. Surgical treatment of liere Clin Gastr 1996;10:60343.
childhood recurrent pancreatitis. J Pediatr Surg 2007;42:12037. 65. Schettini ST, Ribeiro RC, Facchin CG, et al. Gastrinoma in child-
40. Lucidi V, Alghisi F, DallOglio L, et al. The etiology of acute recur- hood: Case report and update on diagnosis and treatment. Eur J
rent pancreatitis in children: A challenge for pediatricians. Pancreas Pediatr Surg 2009;19:3840.
2011;40:51721. 66. Ohshio G, Hosotani R, Imamura M, et al. Gastrinoma with mul-
41. Kandula L, Whitcomb DC, Lowe ME. Genetic issues in pediatric tiple liver metastases: Effectiveness of dacarbazine (DTIC) therapy.
pancreatitis. Curr Gastroenterol Rep 2006;8:24853. J Hepatobiliary Pancreat Surg 1998;5:33943.
42. Halata MS, Berezin SH. Biliary dyskinesia in the pediatric patient. 67. Quatrini M, Castoldi L, Rossi G, et al. A follow-up study of patients
Curr Gastroenterol Rep 2008;10:3328. with Zollinger-Ellison syndrome in the period 19662002: Effects
43. Chromik AM, Seelig MH, Saewe B, et al. Tailored resective pan- of surgical and medical treatments on long-term survival. J Clin
creatic surgery for pediatric patients with chronic pancreatitis. Gastroenterol 2005;39:37680.
J Pediatr Surg 2008;43:63443. 68. Castellani C, Zeder SL, Spuller E, et al. Neonatal congenital pan-
44. DuBay D, Sandler A, Kimura K, et al. The modified Puestow creatic cyst: Diagnosis and management. J Pediatr Surg 2009;
procedure for complicated hereditary pancreatitis in children. 44:e14.
J Pediatr Surg 2000;35:3438. 69. Fujishiro J, Kaneko M, Urita Y, et al. Enteric duplication cyst of
45. Laidlaw GF. Nesidioblastoma, the islet tumor of the pancreas. Am the pancreas with duplicated pancreatic duct. J Pediatr Surg
J Pathol 1938;14:12534 5. 2011;46:e1316.
46. Saint-Martin C, Arnoux JB, de Lonlay P, et al. KATP channel 70. Goh BK, Tan YM, Chung YF, et al. Non-neoplastic cystic and
mutations in congenital hyperinsulinism. Semin Pediatr Surg 2011; cystic-like lesions of the pancreas: May mimic pancreatic cystic
20:1822. neoplasms. ANZ J Surg 2006;76:32531.
47. Flanagan SE, Kapoor RR, Hussain K. Genetics of congenital 71. Bien E, Godzinski J, Dalligna P, et al. Pancreatoblastoma: A report
hyperinsulinemic hypoglycemia. Semin Pediatr Surg 2011;20: from the European cooperative study group for paediatric rare
1317. tumours (EXPeRT). Eur J Cancer 2011;47:234752.
48. Rahier J, Guiot Y, Sempoux C. Morphologic analysis of focal and 72. Lee YJ, Hah JO. Long-term survival of pancreatoblastoma in chil-
diffuse forms of congenital hyperinsulinism. Semin Pediatr Surg dren. J Pediat Hematol Onc 2007;29:8457.
2011;20:312. 73. Luttges J, Stigge C, Pacena M, et al. Rare ductal adenocarcinoma
49. Kapoor RR, Flanagan SE, James C, et al. Hyperinsulinaemic of the pancreas in patients younger than age 40 years. Cancer
hypoglycaemia. Arch Dis Child 2009;94:4507. 2004;100:17382.
50. Laje P, Halaby L, Adzick NS, et al. Necrotizing enterocolitis in 74. Brecht IB, Schneider DT, Kloppel G, et al. Malignant pancreatic
neonates receiving octreotide for the management of congenital tumors in children and young adults: Evaluation of 228 patients
hyperinsulinism. Pediatr Diabetes 2010;11:1427. identified through the Surveillance, Epidemiology, and End Result
51. Mohnike W, Barthlen W, Mohnike K, et al. Positron emission (SEER) database. Klinische Padiatrie 2011;223:3415.
tomography/computed tomography diagnostics by means of 75. Ellerkamp V, Warmann SW, Vorwerk P, et al. Exocrine pancreatic
fluorine-18-L-dihydroxyphenylalanine in congenital hyperinsulin- tumors in childhood in Germany. Pediatric Blood Cancer 2012;
ism. Semin Pediatr Surg 2011;20:237. 58:36671.
52. von Rohden L, Mohnike K, Mau H, et al. Visualization of the focus 76. Speer AL, Barthel ER, Patel MM, et al. Solid pseudopapillary
in congenital hyperinsulinism by intraoperative sonography. Semin tumor of the pancreas: A single-institution 20-year series of pedi-
Pediatr Surg 2011;20:2831. atric patients. J Pediatr Surg 2012;47:121722.
53. Al-Shanafey S, Habib Z, Al Nassar S. Laparoscopic pancreatec- 77. Soloni P, Cecchetto G, Dalligna P, et al. Management of unresect-
tomy for persistent hyperinsulinemic hypoglycemia of infancy. able solid papillary cystic tumor of the pancreas. A case report and
J Pediatr Surg 2009;44:1348. literature review. J Pediatr Surg 2010;45:e16.
54. Bax KN, van der Zee DC. The laparoscopic approach toward 78. Campanile M, Nicolas A, LeBel S, et al. Frantzs tumor: Is mutilat-
hyperinsulinism in children. Sem Pediatr Surg 2007;16: ing surgery always justified in young patients? Surg Oncol
24551. 2011;20:1215.
C H A P T E R 4 7
Splenic Conditions
Frederick J. Rescorla
The essential role of the spleen in the defense against assumes a greater role. This may be a factor in the age-
bacterial organisms is well documented. King and Schu- related differences in postsplenectomy infections in
macher first described the susceptibility of splenect- young children who lack an adequate antibody response.6
omized infants to infection in 1952.1 The immunologic The spleen also serves as a reservoir for platelets and
role of the spleen led pediatric surgeons to initiate a factor VIII.
nonoperative approach to splenic injuries in children
which has evolved into the preferred method for treating
children and also adults.2 Currently, the primary role of ANATOMIC ABNORMALITIES
splenic surgery is in the management of hematologic
disorders. The most significant change in management Asplenia and Polysplenia
has been the introduction of laparoscopic splenectomy in
adults by Delaitre and Maignien3 and subsequently in Asplenia is often noted with complex congenital heart
children by Tulman and Holcomb.4 disease as well as bilateral right-sidedness such as bilat-
eral three-lobed lungs and right-sided stomach and
central liver.10 Intestinal malrotation has also been
EMBRYOLOGY, ANATOMY observed with asplenia.11 These infants are at risk for
AND PHYSIOLOGY overwhelming infection and should receive antibiotics for
prophylaxis.
The splenic primordium develops as a mesenchymal Polysplenia usually consists of a cluster of very small
bulge in the dorsal mesogastrium between the stomach splenic masses and is often found with biliary atresia.
and the pancreas, initially observed at the 810mm Other associated conditions include a preduodenal portal
embryo stage. A true epithelium is noted at the 1012mm vein, situs inversus, malrotation, and cardiac defects.10
stage as sinusoids communicate with capillaries. The These children have adequate splenic immune function.
spleen produces white and red cells by the fourth month
of fetal life, although this function ceases later in gesta-
tion. The anatomic arrangement of the spleen is consist-
Wandering Spleen
ent with the various functions of the spleen. The splenic This condition is characterized by a lack of ligamentous
artery branches into segmental vessels, which further attachments to the diaphragm, colon, and retroperito-
branch into trabecular arteries. After further bifurcations, neum, resulting in a mobile spleen. This is likely due to
small arteries enter the white pulp, which is composed of failure of development of the splenic ligaments from the
lymphocytes and macrophages arranged as a germinal dorsal mesentery.12 Children can present with an abdomi-
center around the central artery. The central artery deliv- nal mass and episodic pain, but also with torsion and
ers particulate material into the white pulp, an arrange- infarction.13,14 Pancreatitis has also been noted as a pre-
ment that may facilitate antibody formation in response senting sign.15 Splenopexy is the preferred method of
to particulate antigens.58 The red pulp consists of the treatment and can be performed with placement of the
endothelial cords of Billroth, which receive the blood spleen into a mesh basket, suture splenopexy, colonic
after it passes through the white pulp. The red pulp displacement with gastropexy, placement in an omental
destroys old and defective cells. The spleen also removes basket, or placement in an extraperitoneal pocket.1620
HowellJolly bodies (nuclear remnants), Heinz bodies The laparoscopic approach is the preferred technique,
(denatured hemoglobin), and Pappenheimer bodies (iron and the use of an absorbable or nonabsorbable mesh with
granules). These particles are noted on peripheral smear fixation in the left upper quadrant is demonstrated in
after splenectomy. The immune response occurs in the Figure 47-1.21,22 Placement of the spleen in an extraperi-
white pulp as antigens come in contact with macrophages toneal pocket is seen in Figure 47-2. Torsion with infarc-
and helper T-cells. T-cells initiate cytokine synthesis, and tion requires splenectomy. Cases of chronic torsion have
activated T-cells circulate to modulate the response. A also been reported with massive splenomegaly which may
humoral response occurs as macrophages and helper necessitate splenectomy.23
T-cells come in contact with antigens.9
Splenic function also involves removal of particulate
matter as well as production of nonspecific opsonins,
Accessory Spleens
which further activate the complement system. In addi- Accessory spleens have been noted in 1530% of chil-
tion, the spleen serves as a biologic filter. If little antibody dren, with a large series noting a 19% rate.21 Accessory
is available for opsonization of bacteria, the spleen spleens likely originate from mesenchymal remnants that
648
47 Splenic Conditions 649
fail to fuse with the main splenic mass, with most (75%) Splenic Cysts
located near the splenic hilum (Fig. 47-3). Other loca-
tions that must be evaluated during surgery include the Cysts of the spleen are most frequently primary splenic
lesser sac along the splenic vessels, omentum, and retro- cysts containing an epithelial lining and are also referred
peritoneum. Eighty-six per cent of accessory spleens are to as epithelial or epidermoid cysts (Fig. 47-4). Post-
single, 11% have two, and 3% have three or more.24,25 A traumatic pseudocysts are occasionally seen. Inclusion of
missed accessory spleen at the time of planned total surface mesothelium into the splenic parenchyma is the
splenectomy can lead to recurrence of the primary disease most likely etiology of epithelial cysts. They may present
process, which in cases of immune thrombocytopenic with symptoms related to their size with gastric compres-
purpura (ITP) is early and with hereditary spherocytosis sion or pain, an abdominal mass, rupture, or infection
(HS) is later.2628 with abscess.31,32 Simple cysts less than 5cm can be
observed, but cysts that are enlarging, symptomatic, or
larger than 5cm require treatment. Most symptomatic
Splenic Gonadal Fusion cysts are larger than 8cm.31 Percutaneous aspiration and
This condition in which the left gonad and the spleen are sclerosis utilizing alcohol or other agents have been
attached is a result of early fusion between the two struc- reported with variable success.33,34
tures prior to descent of the testes.29 The remnant can be Marsupialization is commonly performed but has been
a continuous band (see Fig 50-6) or discontinuous with associated with a high recurrence rate if an adequate
splenic tissue attached to the gonad. A splenic remnant amount of cyst wall is not removed (Fig. 47-5).35 In addi-
has also been noted in the left scrotum as an accessory tion, a high recurrence rate with laparoscopic partial exci-
splenic remnant type of abnormality.30 sion has also been observed.36,37 However, others have
had good success with this technique, and many also
recommend partial splenectomy associated with cyst
resection.38,39 Our group has reported good results with
partial splenectomy, emphasizing resection of a margin
of normal spleen so that the cut surfaces cannot oppose
which might lead to recurrence.21 Other techniques
involve lining the cyst with Surgicel (Ethicon, Inc.,
Somerville, NJ) and omentopexy.40
A B
FIGURE 47-2 (A) The upper pole of the spleen was placed in the retroperitoneal pouch, and the upper aspect of the pouch (dotted
arrow) was closed with interrupted sutures. Note the splenic vessels (solid arrow) coursing into the spleen. A generous opening
was left in the pouch for these vessels so that the vessels would not be compressed by closure of the pouch. (B) One of the inter-
rupted silk sutures is being placed to approximate the peritoneal flaps over the spleen. At this point, most of the spleen has been
placed into the extraperitoneal pouch. (From Upadhyaya P, St. Peter SD, Holcomb GW III. Laparoscopic splenopexy and cystectomy for
an enlarged wandering spleen and splenic cyst. J Pediatr Surg 2007;42:E237. Reprinted with permission.)
650 SECTION IV Abdomen
anemia, an elevated reticulocyte count, and a mild eleva- years of age to decrease the likelihood of overwhelming
tion in bilirubin concentration. The degree of hemolysis postsplenectomy infection (OPSI). Splenomegaly is
can vary, with some only having a mild anemia. Sphero- common in these patients. Gallstones are also often
cytes on peripheral smear along with a positive osmotic found, and an ultrasound evaluation of the gallbladder
fragility test confirms the diagnosis. Affected children should be performed before splenectomy. The presence
may develop an aplastic crisis associated with parvovirus of gallstones in children undergoing splenectomy has
B19 infection with suppression of bone marrow red cell been noted in 27% of those younger than age 10 years
production and ongoing splenic red cell destruction.41 compared with 56% in children 10 years of age or older.21
Splenectomy is usually performed for moderate-to-severe Partial splenectomy is an attractive alternative to total
anemia. If possible, splenectomy is delayed until 5 to 6 splenectomy in an attempt to remove enough spleen to
alleviate the anemia while preserving adequate spleen to
prevent OPSI (Fig. 47-6). This may be particularly useful
in young children requiring splenectomy, but the long-
term results are not known.
A B
FIGURE 47-4 (A) A large epithelial splenic cyst (arrow) is seen on the computed tomography scan. (B) At laparoscopy, the large
cyst (seen in A) is seen to occupy most of the spleen.
A B
FIGURE 47-5 (A) The wall of the large epithelial splenic cyst seen in Figure 47-4 is being excised. (B) The cyst was marsupialized
and the remnant lining of the cyst was ablated with the argon beam coagulator.
47 Splenic Conditions 651
the left upper quadrant and out of the abdominal cavity. right. In young children and patients with small spleens,
The short gastric vessels are divided initially, the upper midline instruments (3mm) can be inserted
followed by the hilar vessels. A careful search must without cannulas because these instruments are not
be undertaken for accessory spleens. A lateral muscle- removed during the procedure (Fig. 47-8). The first
splitting approach has been reported with a 2.7-day assistant holds the two upper midline instruments to
length of stay which is comparable to some early laparo- provide elevation of the spleen and traction on surround-
scopic series but longer than more recent series.21,52,53 ing tissues. The surgeon holds the camera (5mm, 3045
telescope) in the left hand and the energy source in the
right hand.
Laparoscopic Splenectomy Initially, the splenocolic ligament is divided with the
Laparoscopic splenectomy has evolved over the past 15 energy device, allowing the splenic flexure to fall away
to 20 years to become the preferred approach for splenec- from the spleen. The inferior portion of the gastrosplenic
tomy.3,4 Less pain, shorter hospitalization, faster return ligament is divided, and the surgeon works in a cephalad
to regular activities, and smaller scars are the main advan- direction dividing the short gastric vessels and opening
tages over open splenectomy. However, it is associated the lesser sac (Fig. 47-9). The most superior short gastric
with a longer operative time and can be difficult in vessels are often very short, and care must be taken to
patients with splenomegaly. The main technical advances avoid injury to the stomach or diaphragm. This is often
have been the result of smaller instrumentation and the most difficult part of the procedure. The lesser sac
advanced energy sources such as the Harmonic Scalpel should be inspected for the presence of accessory spleens.
(Ethicon Endosurgery Inc, Cincinnati, OH) and Ligas- The splenophrenic ligament is divided to fully mobilize
ure (Valley Lab, Tyco Healthcare Group, Boulder, CO). the upper pole. At this point, the hilum can be approached.
At our institution, we primarily utilize the Ligasure It is often easiest to divide the splenorenal ligament
because it allows division of vessels up to 7mm. because this allows the option to use the endovascular
The most significant initial concern for the laparo- stapler on the hilum. In the early era of laparoscopic
scopic approach was related to accessory spleen detection. splenectomy, clips were applied to individual hilar vessels
However, in adult studies and comparison pediatric series, with division using endoscopic scissors. Most surgeons
similar rates of accessory spleen detection at laparo- now use an endoscopic stapler which has the disadvantage
scopic and open splenectomy have been noted.26,27,5356 of requiring a 12mm port (Fig. 47-10). Proximity of the
For the laparoscopic operation, most surgeons utilize a hilum and pancreas is the main issue in terms of position-
lateral approach with slight elevation of the left flank. One ing the stapler. Pancreatitis and pancreatic fistula have
technique to improve the ease of port placement is to have been reported, although many reports have confirmed
the patients left side initially elevated approximately 45 the safety of this technique.5760 The Ligasure has limited
rather than the true lateral position. The operating table lateral thermal spread (<2mm) and is relatively easy to
is then tilted to the patients left to achieve a flat position use for dissection and ligation of the hilar vessels.61
for the port placement and then is tilted to the patients One study comparing the endoscopic stapler to the
right to achieve a lateral position for the procedure (Fig. Ligasure demonstrated safety and efficiency of both with
47-7). The surgeon and assistant stand on the patients a lower blood loss and conversion rate with the
A B C
FIGURE 47-7 (A) Initial positioning of the patient before any movement of the table. (B) The table has been tilted to the patients
left to obtain a near supine position of the patient for port placement. (C) The table is then rotated back to the patients right to
achieve a right lateral decubitus position for the operation. (From Rescorla FJ. Laparoscopic splenectomy. In: Holcomb GW III, Georgeson
KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; 2008. p. 1216. Reprinted with
permission.)
47 Splenic Conditions 653
A B
FIGURE 47-11 (A) After complete mobilization, the spleen is dropped into an endoscopic retrieval bag. (B) The neck of the bag is
then exteriorized through the umbilicus, and the surgeons finger is used to fracture the splenic capsule. A combination of ring
forceps and the surgeons finger is then used to remove the splenic fragments. (From Rescorla FJ. Laparoscopic splenectomy. In:
Holcomb GW III, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; 2008.
p. 1216. Reprinted with permission.)
series of over 200 cases noted the postoperative hospitali- anticoagulation, 13% of the entire group progressed to
zation to vary by diagnosis with HS at 1.23 days, ITP at complete thrombosis. A prospective series in children
1.20 days, and SCD at 2.37 days.21 An Italian single- noted an incidence of 5.88% with the same risk factors.105
institution series of 33 children (20002005) undergoing Of the patients with total splenic vein thrombosis, over
splenectomy (19 laparoscopic, 14 open) noted a shorter 50% were symptomatic with fever and abdominal
hospitalization (5.5 2.9 versus 8.7 4.8) in the laparo- pain, emphasizing the need to evaluate for this condition
scopic cohort but still considerably longer than contem- in patients with these symptoms. Most authors recom-
porary studies in the USA.94 The increased length of stay mend treatment with antithrombotic and antiplatelet
in patients with SCD is secondary to the higher incidence therapy.
of complications in this subgroup of patients, such as
acute chest syndrome. Other retrospective series have
confirmed the role of laparoscopy in children with SCD,
Postsplenectomy Sepsis
noting a shorter hospitalization with the laparoscopic OPSI was initially reported by King and Shumacker in a
approach without an increase in postoperative pain or group of five infants undergoing splenectomy for HS.1
acute chest syndrome compared with open splenec- The actual risk of OPSI is difficult to determine because
tomy.95,96 Splenomegaly itself, which is common in most of the data was accumulated before the routine use
HS, does not appear to affect the postoperative hospitali- of preoperative vaccinations. Data from the 1990s note
zation. An unreported benefit of the shorter hospitaliza- the rate of OPSI between 0.138.1% in children and
tion after each operation is the effect on the parents adolescents less than 15 years of age compared with 0.28
return to work. One study noted children return to full 1.9% in adults.106108 Most authors quote the current
activity faster with laparoscopy compared with open OPSI rate between 3.54.4%.75,107,108 Some have also
splenectomy.97 noted a higher mortality in children younger than 4 years
of age (8.1%) compared with a lower rate (3.3%) in older
children.106108 Most deaths occur within four years of
Complications splenectomy.109,110 The causative organism is likely Strep-
Most pediatric series have had relatively few complica- tococcus pneumoniae which has been found in 5090% of
tions with the laparoscopic technique. A meta-analysis of all infections.111,112 Pneumococcus is responsible for 60% of
adult and pediatric studies reported between 1991 and all fatal infections, followed by Haemophilus influenzae,
2002 noted a complication rate of 15.5% for laparoscopic meningococcus, and Group A Streptococcus.113 Vaccina-
and 26.6% for open splenectomy (p < 0.0001).98 The tions have been shown to decrease the risk of
laparoscopic group had fewer pulmonary, wound, and bacteremia.113,114
infectious complications but more hemorrhagic compli- A single-institution study compared two time periods.107
cations when conversions for bleeding were included. A The first one was prior to immunizations and antibiotics.
large adult comparative study noted equivalent grade I The second era (with a 70% immunization rate and 100%
and II complications (minor, potentially life threatening) antibiotic prophylaxis rate) noted a decrease in OPSI (6%
but higher grade III and IV (residual or lasting disability, to 3.8%) and mortality (3.9% to 0.9%). This study found
death) with the open approach compared with laparos- age to be important as the rate of infection was 13.8% for
copy.99 Symptomatic splenosis has been reported in ITP those children younger than 6 years of age compared with
due to rupture of an Endocatch II bag with thrombocy- 0.5% in older children. Although older studies noted
topenia occurring 13 months after the initial laparoscopic mortality rates of 50% with OPSI, more recent studies
splenectomy.100 Our review of over 200 pediatric laparo- have a rate of around 10%.107,115,116
scopic splenectomies found an overall complication rate Routine immunization against S. pneumoniae, H. influ-
of 11% with no wound infections or deaths.21 Postopera- enzae, and meningococcus as well as postoperative anti-
tive ileus, acute chest syndrome, and bleeding requiring biotics prophylaxis (usually penicillin) is recommended
transfusion were the most common complications. The by most authors. Although the optimal length of antibi-
complication rate was 22% among the children with otic prophylaxis is unclear, the highest rate of OPSI
SCD and only 8.3% among those with other conditions appears to occur within the first 2 years. An adult study
(p = 0.0083). This report documented one (0.5%) symp- of sepsis in patients splenectomized as children noted an
tomatic portal vein thrombosis. estimated frequency of late postsplenectomy infections of
Splenic vein or portal vein thrombosis is a rare com- 0.69 and deaths at 0.46 per 1,000 patient years.117 Of
plication after splenectomy but may be more common interest, one of the surviving patients had low antibody
than is clinically appreciated, and is particularly common levels against pneumococcal serotypes despite pneumo-
in patients with splenomegaly.101,102 A small adult study coccal meningitis and subsequent vaccinations, suggest-
identified a 50% incidence of portal or splenic vein ing that nonresponders may be at increased risk for OPSI.
thrombosis, with splenic weight the strongest predictor
of thrombosis.103 Another prospective study in adults REFERENCES
identified an incidence of 4.79%, and noted spleen weight 1. King H, Shumacker HB Jr. Splenic studies: I. Susceptibility to
over 650g and a platelet count over 650,000/mm3 to be infection after splenectomy performed in infancy. Ann Surg
associated with this complication.104 A retrospective eval- 1952:136:23942.
2. Douglas GJ, Simpson JS. The conservative management of splenic
uation of splenic weight and portal vein thrombosis noted trauma. J Pediatr Surg 1971:6:56570.
rates of 14%, 40%, 45%, and 71% for weights 700g1kg, 3. Delaitre B, Maignien B. Splenectomy by the coelioscopic
12kg, 23kg, and >3kg, respectively.86 Despite early approach: Report of a case. Presse Med 1991;20:2263.
47 Splenic Conditions 657
4. Tulman S, Holcomb GW III, Karamanoukian HL, et al. Pediatric 30. Emmett JM, Dreyfuss ML. Accessory spleen in the scrotum:
laparoscopic splenectomy. J Pediatr Surg 1993;26:68992. Review of literature on ectopic spleens and their associated surgi-
5. Nossal GJV, Austin CM, Pye J, et al. Antigens in immunity: XII. cal significance. Ann Surg 1943;117:754.
Antigen trapping in the spleen. Int Arch Allergy Appl Immunol 31. Tsakayannis DE, Mitchell K, Kozakewich HPW, et al. Splenic
1966;29:36883. preservation in the management of splenic epidermoid cysts in
6. Pearson HA. The spleen and disturbances of splenic function. In: children. J Pediatr Surg 1995;30:146870.
Nathan DG, Orkin SH, editors. Hematology of Infancy and 32. Rathaus V, Zissin R, Goldberg E. Spontaneous rupture of an
Childhood, vol. II. 5th ed. Philadelphia: WB Saunders; 1998. epidermoid cyst of the spleen: Preoperative ultrasonographic
p. 105168. diagnosis. J Clin Ultrasound 1991;19:2357.
7. Rowley DA. The effect of splenectomy on the formation of cir- 33. Akhan O, Baykan Z, Oguzkurta L, et al. Percutaneous treatment
culating antibody in the adult male albino rat. J Immunol of a congenital splenic cyst with alcohol: A new therapeutic
1950;64:289. approach. Eur Radiol 1997;7:106770.
8. Rowley DA. The formation of circulating antibody in the splenec- 34. Moir C, Guttman F, Jequier S, et al. Splenic cysts: Aspiration,
tomized human being following intravenous injection of heterolo- sclerosis, or resection. J Pediatr Surg 1989;24:6468.
gous erythrocytes. J Immunol 1950;65:515. 35. Morgenstern L. Nonparasitic splenic cysts: Pathogenesis, classifi-
9. Meyer AA. Spleen. In: Greenfield LJ, Mulholland MW, Oldham cation, and treatment. J Am Coll Surg 2002;194:30614.
KT, et al, editors. Surgery. 2nd ed. Philadelphia: Lippincott- 36. Fisher JC, Gurung B, Cowles RA. Recurrence after laparoscopic
Raven; 1997. p. 126281. excision of nonparasitic splenic cysts. J Pediatr Surg 2008;43:
10. Anderson C, Devine WA, Anderson RH, et al. Abnormalities of 16448.
the spleen in relation to congenital malformations of the heart: A 37. Schier F, Waag KL, Ure B. Laparoscopic unroofing of splenic
survey of necropsy findings in children. Br Heart J 1990;63: cysts results in a high rate of recurrences. J Pediatr Surg
1228. 2007;42:18603.
11. Tu ST, Wu JM, Yeh BH, et al. Intestinal obstruction in asplenia 38. Fan H, Zhang D, Zhao, X, et al. Laparoscopic partial splenectomy
syndrome: Report of three cases. Acta Paediatr Sin 1994;35: for large splenic epidermoid cyst. Chin Med J 2011;124:17513.
707. 39. Keckler SJ, Peter SD, Tsao K, et al. Laparoscopic excision of
12. Skandalakis LJ, Gray SW, Ricketts R, et al. The spleen. In: Skan- splenic cysts: A comparison to the open approach. Eur J Pediatr
dalakis JE, Gray SW, editors. Embryology for Surgeons. 2nd ed. Surg 2010;20:2879.
Baltimore: Williams & Wilkins; 1994. p. 33465. 40. McColl RJ, Hochman DJ, Sample C. Laparoscopic management
13. Greig JD, Sweet EM, Drainer IK. Splenic torsion in a wandering of splenic cysts: Marsupialization, cavity lining with surgicel and
spleen, presenting as an acute abdominal mass. J Pediatr Surg omentectomy to prevent recurrence. Surg Laparosc Endosc Per-
1994;29:5712. cutan Tech 2007;17:4558.
14. Schmidt SP, Andrews HG, White JJ. The splenic snood: An 41. Young NS, Brown KE. Parvovirus B19. N Engl J Med
improved approach for the management of the wandering spleen. 2004;350:20067.
J Pediatr Surg 1992;27:10434. 42. Davis PW, Williams DA, Shamberger RC. Immune thrombocy-
15. Lebron R, Self M, Mangram A, et al. Wandering spleen present- topenia: Surgical therapy and predictors of response. J Pediatr
ing as recurrent pancreatitis. J Soc Laparoendosc Surg 2008; Surg 1991;26:40713.
12:31013. 43. Holt D, Brown J, Terrill K, et al. Response to intravenous immu-
16. Allen KB, Andrews G. Pediatric wandering spleenthe case for noglobulin predicts splenectomy response in children with
splenopexy: Review of 35 reported cases in the literature. J Pediatr immune thrombocytopenic purpura. Pediatrics 2003;111:879.
Surg 1989;24:4325. 44. Hood JH, Partrick DA, Hays T, et al. Predicting response to
17. Lacreuse I, Moog R, Kauffmann I, et al. Laparoscopic splenopexy splenectomy in children with immune thrombocytopenic purpura.
for wandering spleen in a child. J Laparoendosc Adv Surg Tech J Pediatr Surg 2010;45:1404.
2007;17:2557. 45. Hollander LL, Leys CM, Weil BR, et al. Predictive value of
18. Caracicolo F, Bonatti PC, Castruci G, et al. Wandering spleen: response to steroid therapy on response to splenectomy in chil-
Treatment with colonic displacement. J R Coll Surg Edinb dren with immune thrombocytopenic purpura. Surgery 2011;150:
1986;31:2424. 6438.
19. Stringel G, Soucy P, Mercer S. Torsion of the wondering 46. Bromberg ME. Immune thrombocytopenic purpura-the changing
spleen: Splenectomy or splenopexy? J Pediatr Surg 1982;17: therapeutic landscape. N Engl J Med 2006;355:16435.
3735. 47. Bussel JB, Kluter DJ, Phil D, et al. AMG 531, a thrombopoiesis-
20. Upadhyaya P, St Peter SD, Holcomb GW III. Laparoscopic stimulating protein, for chronic ITP. N Engl J Med 2006;355:
splenopexy and cystectomy for an enlarged wandering spleen and 167281.
splenic cyst. J Pediatr Surg 2007;42:E237. 48. Kuter DJ, Phil D, Rummel M, et al. Romiplostim or standard care
21. Rescorla FJ, West KW, Engum SA, et al. Laparoscopic splenic in patients with immune thrombocytopenia. NEJM 2010;363:
procedures in children: Experience in 231 children. Ann Surg 1889961.
2007;246:6838. 49. Lesher AP, Kalpatthi R, Glenn JB, et al. Outcome of splenectomy
22. Palanivelu C, Rangarajan M, Senthilkumar DR, et al. Laparo- in children younger than 4 years with sickle cell disease. J Pediatr
scopic mesh splenopexy (sandwich technique) for wandering Surg 2009;44:11348.
spleen. J Soc Laparoendosc Surg 2007;11:24651. 50. Fonkalsrud EW, Philippart M, Feig S. Ninety-five percent
23. Misawa T, Yoshida K, Shiba H, et al. Wandering spleen with splenectomy for massive splenomegaly: A new surgical approach.
chronic torsion. Am J Surg 2008;195:5045. J Pediatr Surg 1990;25:2679.
24. Halpert B, Alden ZA. Accessory spleens in or at the tail of the 51. Holcomb GW III, Greene HL. Fetal intra-abdominal hemor-
pancreas. Arch Pathol 1964;77:652. rhage following partial splenectomy for Gauchers disease.
25. Halpert B, Gyorkey F. Lesions observed in accessory spleens of J Pediatr Surg 1993;18:15724.
311 patients. Am J Clin Pathol 1959;32:165. 52. Geiger JD, Dinh VV, Teitelbaum DH, et al. The lateral approach
26. Gigot JF, Jamar F, Ferrant A, et al. Inadequate detection of acces- for open splenectomy. J Pediatr Surg 1998;33:11536.
sory spleens and splenosis with laparoscopic splenectomy: A short- 53. Farah RA, Rogers ZR, Thompson RW, et al. Comparison of
coming of the laparoscopic approach in hematologic diseases. laparoscopic and open splenectomy in children with hematologic
Surg Endosc 1998;12:1016. disorders. J Pediatr 1997;131:416.
27. Targarona EM, Espert JJ, Balagu C, et al. Residual splenic func- 54. Minkes RK, Lagzdins M, Langer JC. Laparoscopic versus open
tion after laparoscopic splenectomy: A clinical concern. Arch Surg splenectomy in children. J Pediatr Surg 2000;35:699701.
1998;133:5660. 55. Reddy VS, Phan HH, ONeill JA, et al. Laparoscopic versus open
28. Crawford DL, Pickens PV, Moore JT. Hypertrophied splenic splenectomy in the pediatric population: A contemporary single-
remnants in hereditary spherocytosis. Contemp Surg center experience. Am Surg 2001;67:85963.
1998;53:1034. 56. Rescorla FJ, Breitfeld PP, West KW, et al. A case-controlled com-
29. Putschar WGJ, Manion WC. Splenic-gonadal fusion. Am J Pathol parison of open laparoscopic splenectomy in children. Surgery
1986;32:15. 1996;124:6706.
658 SECTION IV Abdomen
57. Misawa T, Yoshida K, Iida T, et al. Minimizing intraoperative 83. Szold A, Kamat M, Nadu A, et al. Laparoscopic accessory splenec-
bleeding using a vessel sealing system and splenic hilum hanging tomy for recurrent idiopathic thrombocytopenic purpura and
maneuver in laparoscopic splenectomy. J Hepatobiliary Pancreat hemolytic anemia. Surg Endosc 2000;14:7613.
Surg 2009;16:78691. 84. Choi YU, Dominguez EP, Sherman V, et al. Laparoscopic acces-
58. Gelmini R, Romano F, Quaranta N, et al. Sutureless and stapleless sory splenectomy for recurrent idiopathic thrombocytopenic
laparoscopic splenectomy using radiofrequency: LigaSure device. purpura. J Soc Laparoendosc Surg 2008;12:31417.
Surg Endosc 2006;20:9914. 85. Feldman LS, Demyttenaere SV, Polyhronopoulos GN, et al.
59. Kennedy JS, Stranahan PL, Taylor KD, et al. High burst strength, Refining the selection criteria for laparoscopic versus open
feedback controlled bipolar vessel sealing. Surg Endosc splenectomy for splenomegaly. J Laparoendosc Adv Surg Tech
1998;12:8768. 2008;16:1319.
60. Vecchio R, Marchese S, Swehli E, et al. Splenic hilum manage- 86. Pietrabissa A, Morelli L, Peri A, et al. Laparoscopic treatment of
ment during laparoscopic splenectomy. J Laparoendosc Adv Surg splenomegaly: A case for hand-assisted laparoscopic surgery. Arch
Tech 2011;21:71720. Surg 2011;146:81823.
61. Machado NO, Kindy NA, Chopra PJ. Laparoscopic splenectomy 87. Swanson TW, Meneghetti AT, Sampath S, et al. Hand-assisted
using LigaSure. JSLS 2010;14:54752. laparoscopic splenectomy versus open splenectomy for massive
62. Romano F, Gelmini R, Caprotti R, et al. Laparoscopic splenec- splenomegaly: 20-year experience at a Canadian centre. Can J
tomy: Ligasure versus EndoGIA: A comparative study. J Laparoen- Surg 2011;54:18993.
dosc Adv Surg Tech 2007;17:7637. 88. Koshenkov VP, Nemeth ZH, Carter MS. Laparoscopic splenec-
63. Lai PB, Leung KL, Ho WS, et al. The use of liposucker for spleen tomy: Outcome and efficacy for massive and supramassive spleens.
retrieval after laparoscopic splenectomy. Surg Laparosc Endosc Am J Surg 2012:203:51722.
Percutan Tech 2000;10:3940. 89. Rescorla FJ, Engum SA, West KW, et al. Laparoscopic splenec-
64. Ransom KJ, Kavic MS. Laparoscopic splenectomy following tomy has become the gold standard in children. Am Surg
embolization for blunt trauma. J Soc Laparoendosc Surg 2008; 2002;68:297302.
12:2025. 90. Terrosu G, Baccarani U, Bresadola V, et al. The impact of splenic
65. Malladi P, Hungness E, Nagle A. Single access laparoscopic weight on laparoscopic splenectomy for splenomegaly. Surg
splenectomy. JSLS 2009;13:6014. Endosc 2002;16:1037.
66. Rottman SJ, Podolsky ER, Kim E, et al. Single port access (SPA) 91. Murawski M, Patkowski D, Korlacki W, et al. Laparoscopic
splenectomy. JSLS 2010;14:4852. splenectomy in children-a multicenter experience. J Pediatr Surg
67. Hansen EN, Muensterer OJ. Single incision laparoscopic splenec- 2008;43:9514.
tomy in a 5-year-old with hereditary spherocytosis. JSLS 2010; 92. Park AE, Birgisson G, Mastrangela MJ, et al. Laparoscopic
14:2868. splenectomy: Outcomes and lessons learned from over 200 cases.
68. Colon MJ, Telem D, Chan E, et al. Laparoendoscopic single site Surgery 2000;128:6606.
(LESS) splenectomy with a conventional laparoscope and instru- 93. Casaccia M, Torelli P, Pasa A, et al. Putative predictive parameters
ments. JSLS 2011;15:3846. for the outcome of laparoscopic splenectomy. Ann Surg 2010;
69. Thalhammer GH, Eber E, Uranus S, et al. Partial splenectomy 251:28791.
in cystic fibrosis patients with hypersplenism. Arch Dis Child 94. Mattioli G, Avanzini S, Prato AP, et al. Spleen surgery in pediatric
2003;88:1436. age: Seven-year unicenter experience. J Laparoendosc Adv Surg
70. Havlik RJ, Touloukian RJ, Markowitz RI, et al. Partial splenec- Tech 2009;19:43741.
tomy for symptomatic splenic hamartoma. J Pediatr Surg 95. Goers T, Panepinto J, DeBaun M, et al. Laparoscopic versus open
1990;25:12735. abdominal surgery in children with sickle cell disease is associated
71. Rice HE, Oldham KT, Hillery CA, et al. Clinical and hematologic with a shorter hospital stay. Pediatr Blood Cancer 2008;50:6036.
benefits of partial splenectomy for congenital hemolytic anemias 96. Alwabari A, Parida L, Al-Salem AH. Laparoscopic splenectomy
in children. Ann Surg 2003;237:2818. and/or cholecystectomy for children with sickle cell disease.
72. Diesen DL, Zimmerman SA, Thornburg CD, et al. Partial Pediatr Surg Int 2009;25:41721.
splenectomy for children with congenital hemolytic anemia and 97. Waldhausen JHT, Tapper D. Is pediatric laparoscopic splenec-
massive splenomegaly. J Pediatr Surg 2008;43:46672. tomy safe and cost effective? Arch Surg 1997;132:8224.
73. Hry G, Becmeur F, Mfat L, et al. Laparoscopic partial splenec- 98. Winslow ER, Brunt LM. Perioperative outcomes of laparoscopic
tomy: Indications and results of a multicenter retrospective study. versus open splenectomy: A meta-analysis with an emphasis on
Surg Endosc 2008;22:459. complications. Surgery 2003;134:64753.
74. Bader-Meunier B, Gauthier F, Archambaud F, et al. Long-term 99. Friedman RL, Hiatt JR, Korman JL, et al. Laparoscopic or open
evaluation of the beneficial effect of subtotal splenectomy for man- splenectomy for hematologic disease: Which approach is supe-
agement of hereditary spherocytosis. Blood 2001;97:399403. rior? J Am Coll Surg 1997;185:4954.
75. de Buys Roessingh AS, de Lagausie P, Rohrlich P, et al. Follow-up 100. Lansdale N, Marven S, Welch J, et al. Intra-abdominal splenosis
of partial splenectomy in children with hereditary spherocytosis. following laparoscopic splenectomy causing recurrence in a child
J Pediatr Surg 2002;37:145963. with chronic immune thrombocytopenic purpura. J Laparoendosc
76. Buesing KL, Tracy ET, Kiernan C, et al. Partial splenectomy for Adv Surg Tech 2007;17:38791.
hereditary spherocytosis: A multi-institutional review. J Pediatr 101. Pietrabissa A, Moretto C, Antonelli G, et al. Thombosis in the
Surg 2011;46:17883. portal venous system after elective laparoscopic splenectomy. Surg
77. Stoehr GA, Stauffer UG, Eber SW. Near-total splenectomy: A Endosc 2004;18:11403.
new technique for the management of hereditary spherocytosis. 102. Winslow ER, Brunt LM, Drebin JA, et al. Portal vein thrombosis
Ann Surg 2005;241:407. after splenectomy. Am J Surg 2002;184:6316.
78. Slater BJ, Chan FP, Davis K, et al. Institutional experience with 103. Ikeda M, Sekimoto M, Takiguchi S, et al. Total splenic vein
laparoscopic partial splenectomy for hereditary spherocytosis. thrombosis after laparoscopic splenectomy: A possible candidate
J Pediatr Surg 2010;45:16826. for treatment. Am J Surg 2007;193:215.
79. Morinis J, Dutta S, Blanchette V, et al. Laparoscopic partial vs. 104. Stamou KM, Toutouzas KG, Kekis PB, et al. Prospective study of
total splenectomy in children with hereditary spherocytosis. the incidence and risk factors of postsplenectomy thrombosis of
J Pediatr Surg 2008;43:164952. the portal, mesenteric, and splenic veins. Arch Surg 2006;141:
80. Seims AD, Croop JM, Rescorla FJ. Efficacy of laparoscopic partial 6639.
splenectomy in the management of hereditary spherocytosis: An 105. Soyer T, Ciftci AO, Tanyel FC, et al. Portal vein thrombosis after
institutional review. Poster presentation at American Society of splenectomy in pediatric hematologic disease: Risk factors, clinical
Pediatric Hematology Oncology, Baltimore, MD, 2011. features, and outcome. J Pediatr Surg 2006;41:1899902.
81. Esposito C, Schaarschmidt K, Settimi A, et al. Experience with 106. Lynch AM, Kapila R. Overwhelming postsplenectomy infection.
laparoscopic splenectomy. J Pediatr Surg 2001;36:30911. Infect Dis Clin North Am 1996:4:693707.
82. Katkhouda N, Hurwitz MB, Rivera RT, et al. Laparoscopic 107. Jugenburg M, Haddock G, Freedman MH, et al. The morbidity
splenectomy: Outcome and efficacy in 103 consecutive patients. and mortality of pediatric splenectomy: Does prophylaxis make a
Ann Surg 1998;228:56878. difference? J Pediatr Surg 1999;34:10647.
47 Splenic Conditions 659
108. Meekes I, van der Staak, van Oostrom C. Results of splenectomy 114. Ejstrud P, Kristensen B, Hansen JB, et al. Risk and patterns of
performed on a group of 91 children. Eur J Pediatr Surg bacteraemia after splenectomy: A population-based study. Scand
1995;5:1922. J Infect Dis 2000;32:521.
109. Eraklis AJ, Kewy SV, Diamond LK. Hazard of overwhelming 115. Bridgen ML. Overwhelming post-splenectomy infection-still a
infection after splenectomy in childhood. N Engl J Med problem. West J Med 1992;157:4403.
1967;276:12259. 116. Bridgen ML, Pattullo AL. Prevention and management of over-
110. Horan M, Colebatch JH. Relation between splenectomy and sub- whelming postsplenectomy infection-an update. Crit Care Med
sequent infection. Arch Dis Child 1962;37:398414. 1999;27:83642.
111. Ellison EC, Fabri PJ. Complications of splenectomy. Surg Clin 117. Eber SW, Langendorfer CM, Ditzig M, et al. Frequency of very
North Am 1983;63:131330. late fatal sepsis after splenectomy for hereditary spherocytosis:
112. Styrt B. Infection associated with asplenia: Risks, mechanisms, and Impact of insufficient antibody response to pneumococcal infec-
prevention. Am J Med 1990;88:3342. tion. Ann Hematol 1999;78:5248.
113. Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis
and its mortality rate: Actual versus perceived risks. Br J Surg
1991;78:10318.
C H A P T E R 4 8
Congenital Abdominal
Wall Defects
Saleem Islam
genitourinary systems, as well as chromosomal abnor- Proponents of routine cesarean delivery (C-section)
malities in babies with gastroschisis.33 argue that the process of vaginal birth results in injury or
increased risks for infection and sepsis.34 However, the
literature suggests that both vaginal delivery and
Perinatal Care C-section are safe.35,36 A recent meta-analysis failed to
The optimal mode and timing of delivery for a fetus with demonstrate a difference in outcomes for infants deliv-
gastroschisis has been debated for many years. ered either vaginally or by C-section.37 Therefore, the
delivery method should be at the discretion of the obste-
trician and the mother, with C-section reserved for
TABLE 48-1 Differentiating Characteristics obstetric indications or fetal distress.
between Gastroschisis Preterm delivery of the fetus with gastroschisis has
and Omphalocele been advocated to limit exposure of the bowel to the
amniotic fluid.12 Interleukin-6, interleukin-8, and ferritin
Characteristic Omphalocele Gastroschisis are elevated in the amniotic fluid in fetuses with gastro-
Herniated viscera Bowel liver Bowel only schisis when compared with controls.18,38 Damage to the
Sac Present Absent pacemaker cells and nerve plexi may contribute to the
Associated Common (50%) Uncommon profound dysmotility and malabsorption seen in these
anomalies (<10%)
Location of Umbilicus Right of umbilicus infants.39 Early delivery may mitigate these effects, but
defect the literature is mixed.12 A randomized trial from the UK
Mode of delivery Vaginal/cesarean Vaginal found no benefit after induced early delivery with the
Surgical Nonurgent Urgent only trends being an improvement in length of hospitali-
management
Prognostic Associated Condition of
zation and earlier initiation of feeding.40 Another
factors anomalies bowel study demonstrated that birth weight less than 2kg was
associated with increased morbidity.41 Currently available
TABLE 48-2 Treatment Options in Patients with Gastroschisis and Intestinal Atresia
Study Number of Patients Drop in Anastomosis Stoma
Amoury etal. 197726 6 3 3
Pokorny etal. 198127 5 1 4
Gornall 198928 5 1 3 1
Shah and Woolley 199129 4 3 1
Hoehner etal. 199830 13 8 5
Fleet and de la Hunt 200031 10 6 4
Emil etal. 201232 8 7 1
A B
FIGURE 48-1 These two photographs nicely depict the differences between an omphalocele and gastroschisis. (A) In an omphalocele
both the liver and bowel can be herniated. A sac is always present and the umbilical cord (arrow) inserts onto the sac. Moreover,
this is always a midline defect. (B) With a gastroschisis, the liver is never herniated and a sac is absent. The location of the fascial
defect is to the right of the umbilicus, and the umbilical cord is attached to the umbilicus. In addition to the large and small intestine,
the stomach (asterisk) can sometimes be herniated as well.
662 SECTION IV Abdomen
evidence does not support elective preterm delivery for Primary Closure
gastroschisis.42
Historically, urgent primary closure of gastroschisis was
advocated in all cases. This approach is still commonly
Neonatal Resuscitation practiced in neonates in whom reduction of the herniated
and Management viscera appears possible.46 Attempted primary closure has
Neonates with gastroschisis have significant evaporative traditionally been performed in the operating room, but
water losses from the open abdominal cavity and exposed some authors have advocated primary closure at the
bowel. Appropriate intravenous access should be obtained bedside without general anesthesia.4749 Some surgeons
and fluid resuscitation initiated after birth. Nasogastric prefer to close the skin only and leave the fascia sepa-
(NG) decompression is important to prevent further rated. Others have described the use of the umbilicus as
gastric and intestinal distention. Routine endotracheal an allograft.50,51 Prosthetic options for fascial closure
intubation is not necessary. The bowel should be wrapped include nonabsorbable mesh or bioprosthetic materials
in warm saline-soaked gauze and placed in a central such as porcine small intestinal submucosa mesh.52 In the
position on the abdominal wall. The neonate should be past, most surgeons have excised the umbilicus during
positioned on the right side to prevent kinking of the closure. However, preservation of the umbilicus has
mesentery with resultant bowel ischemia. The bowel been shown to lead to an excellent cosmetic result
should be wrapped with plastic wrap or the infant placed (Fig. 48-4).53,54
partially in a plastic bag to reduce evaporative losses and Intra-abdominal pressure approximated from either
improve temperature homeostasis (Fig. 48-2). Although the bladder pressure or stomach pressure can be used to
gastroschisis most often is an isolated anomaly, thorough
examination of the neonate is important. In addition, the
bowel must be carefully examined for intestinal atresia,
necrosis, or perforation (Fig. 48-3). Recent evidence sug-
gests that excess fluid resuscitation is detrimental and
results in edema, an increase in time to closure, and an
increased risk of abdominal compartment syndrome.43
Surgical Management
The primary goal is to return the viscera to the abdomi-
nal cavity while minimizing the risk of damage due to
trauma or increased intra-abdominal pressure. The two
most commonly used treatment options are placement of
a silo followed by serial reductions and delayed closure,
or attempted primary closure.44 The timing and location
of surgical intervention is also controversial.45 In all cases,
inspection of the bowel for obstructing bands, perfora-
tion, or atresia must be undertaken. Bands crossing the FIGURE 48-3 This baby was born with gastroschisis and intes-
bowel loops should be lysed before silo placement or tinal atresia. Note the atretic intestinal segment is being lifted
up by the forceps. A silo was created and the baby underwent
primary abdominal closure to avoid subsequent intestinal exploration and uneventful repair of the atresia at six weeks
obstruction. of age.
guide the surgeon during reduction.55 Pressures higher opening, without the need for sutures or general anesthe-
than 1015mmHg are often associated with decreased sia.60 This has made it possible to insert the silo in the
renal and intestinal perfusion, and a silo or patch may be delivery room or at the bedside (Fig. 48-5). After place-
needed.56 Pressures higher than 20mmHg can lead to ment, the bowel is reduced daily into the abdominal cavity
renal failure and bowel ischemia.57 Similarly, an increase as the silo is shortened by sequential ligation. When the
in central venous pressure greater than 4mmHg has contents are entirely reduced, fascial and skin closure are
been correlated with the need for silo placement or patch performed. This process usually takes between one and 14
closure.58 Splanchnic perfusion pressure, the difference days with the majority being ready within a week, depend-
between mean arterial pressure and intra-abdominal ing on the condition of the bowel and the infant.
pressure, has also been used to guide the reduction. A Definitive closure in the operating room consists of
splanchnic perfusion pressure less than 44mmHg implies raising small skin flaps around the fascial defect followed
a decrease in intestinal blood flow.59 by fascial closure in a horizontal or vertical direction.
Closure of the skin in a transverse direction creates a
keyhole appearance with a horizontal scar to the right
Staged Closure
of the umbilicus. This is why some surgeons advocate a
In the mid-1990s, a prefabricated silo was developed with vertical closure to allow for a central umbilicus. Also, a
a circular spring that is positioned under the fascial purse-string skin closure around the umbilicus can be
A B
C D E
FIGURE 48-5 The use of a spring-loaded prefabricated silo is shown in these photographs. (A) The gastroschisis defect is seen.
(B) An appropriate-sized spring-loaded silo is then placed over the eviscerated intestine. (C) The ring of the silo has been positioned
under the fascial defect and attached to an overhead support to keep the bowel from torquing, which may result in intestinal
ischemia. (D) Gradual reduction of the silo is performed. (E) Finally, the bowel has been completely returned to the abdominal cavity
and the neonate is ready for transport to the operating room for closure of the fascia and skin.
664 SECTION IV Abdomen
A B
FIGURE 48-7 These two photographs show different neonates with the prenatal diagnosis of gastroschisis. In each instance, the
herniated intestine has died. At exploration, each patient was found to have short bowel syndrome due to very little small
intestine.
is the most important prognostic determinant for a poor into the scrotum in most cases.88 Most centers recom-
outcome.80,81 A number of authors have attempted to mend allowing a year for spontaneous descent and then
stratify patients with gastroschisis according to risk.82 A performing an orchiopexy if needed.89
recent population-based cohort study from the UK with If the umbilicus is sacrificed during the repair of the
301 patients noted that babies with complex gastroschisis gastroschisis defect, up to 60% of children report psy-
took a median of 21 days longer to reach full enteral chosocial stress from not having an umbilicus.91
feedings, had a longer total parenteral nutrition (TPN)
use, and had almost 2 months longer length of hospitali-
zation.70 In addition, they were twice as likely to develop
intestinal failure and six times more likely to develop liver
OMPHALOCELE
disease. Another study noted an increased incidence of Prenatal Diagnosis And Management
central venous catheter-related sepsis, a longer time to
full enteral feeding, and a longer hospital stay in infants Elevation of maternal serum AFP is also present in many
with gastroschisis complicated by atresia or necrotic pregnancies complicated by omphalocele, although not
bowel.83 Gastroschisis is the most common reason for as commonly as with gastroschisis. The diagnosis of
intestinal transplantation.84 The ability to risk-stratify omphalocele can be made by two-dimensional ultrasound
gastroschisis patients with respect to increased morbidity at the time of the normal 18-week ultrasound evaluation
and mortality has utility in counseling families, predict- for dates. Early first trimester detection is possible if
ing hospital utilization, and identifying a group of patients three-dimensional ultrasound is utilized.92 The incidence
who would benefit from further strategies to improve of omphalocele seen at 1418 weeks is as high as 1 in
outcomes. 1,100, but the incidence at birth drops to 1 in 4,000
Necrotizing enterocolitis (NEC) has been found in 6,000.93 Thus there is a considerable hidden mortality
full-term infants with gastroschisis in higher than for a fetus with an omphalocele. One review noted that
expected frequencies (up to 18.5%).85 Significant bowel requests for termination of pregnancy in omphalocele
loss from NEC can predispose to short bowel syndrome cases were as high as 83%.94
and its associated hepatic and infectious complications. Ultrasound evaluation is very useful for the detection
On the other hand, another group found that the clinical of associated anomalies in these infants. This is important
course of babies with gastroschisis who developed NEC as an isolated omphalocele has a survival rate of over
often had an uncomplicated course.86 There is a report 90%, but is reduced with other defects.93 Prenatal ultra-
suggesting that infants with gastroschisis who were fed sound and karyotyping are able to identify only 6070%
breast milk had a lower incidence of NEC than those fed of the associated defects that are found postnatally.94 One
with formula.87 study that reviewed associated defects in omphalocele
Most gastroschisis patients have some degree of intes- infants noted anomalies that involved every organ system,
tinal nonrotation. This is typically not repaired at the while another study found that only 14% of omphaloce-
time of closure and does not have the same incidence of les were truly isolated anomalies.33,93 Prenatal screening
midgut volvulus as other causes of malrotation. However, in an infant with an omphalocele requires a detailed eval-
the parents should be cautioned regarding bilious emesis uation of the cardiac (1447% incidence of anomalies)
and instructed to take urgent action if that occurs. and central nervous (333% anomalies) systems as severe
Cryptorchidism is associated with gastroschisis in defects may lead to a discussion about termination of the
1530% of cases.8890 Several retrospective analyses have pregnancy.26 Recently, there has been some attention
shown that placement of the herniated testis into the towards developing a reliable sonographic predictor of
abdominal cavity will result in normal testicular descent postnatal morbidity and survival.9597 Unfortunately, the
666 SECTION IV Abdomen
prenatal finding of a giant omphalocele has not been special situation that represents one of the most difficult
accurate in predicting outcomes. Investigators have problems in pediatric surgery. The goal is to cover the
studied ratios between the greatest omphalocele diameter exposed abdominal viscera, which can be challenging.
compared to abdominal circumference (O/AC), the There is one small series that has good outcomes in terms
femur length (O/FL), and the head circumference (O/ of survival, but there was a high incidence of intestinal
HC), and have attempted to correlate that with postnatal fistulas, sepsis, and pulmonary hypoplasia.101
morbidity and mortality.98,99 Of these variables, the most
useful may be the O/HC.98 Prospective studies are needed
to assess the usefulness of this information.
Surgical Management
There are a large variety of repairs described as a one size
fits all option does not exist. In a recent survey, authors
Perinatal Care of reports from 19672009 discussing closure of giant
The route of delivery of infants with an omphalocele omphaloceles were asked to see if they were still using the
should be dictated by obstetric considerations as C-section same approach, or whether they had modified their tech-
has not been shown to be superior.100 Pregnancies are niques.102 Interestingly, 42% of the authors no longer use
usually allowed to come to term, and spontaneous labor the approach that they favored in their original article.
and vaginal delivery is preferred. However, despite the They concluded that there is currently no completely
lack of data, many neonates with giant omphaloceles are accepted technique to treat giant omphaloceles, and two
delivered by C-section because of the fear of liver injury. methods are used the most: staged closure or delayed
closure. Also, defining a giant defect is variable as some
surgeons use size alone, others consider the presence or
Neonatal Resuscitation And absence of the liver, while others use an estimate of the
Management amount of intestinal contents, and still others have used a
After delivery, a thorough search for associated anomalies combination of the amount of liver and intestine in the
is important. All neonates should undergo an echocardio- sac. This lack of an accepted definition has resulted in an
graphic evaluation. Renal abnormalities can be detected inability to arrive at a consensus for management.44
by abdominal ultrasound. Neonatal hypoglycemia should
alert the practitioner to the possibility of Beckwith Immediate Primary Closure
Weidemann syndrome. Blood samples for genetic evalu-
ation should be obtained as well. Treatment options in infants with omphalocele depend
In preparing infants with omphalocele for transport, on the size of the defect, the babys gestational age, and
risks arising from associated anomalies should be specifi- the presence of associated anomalies. Defects that are less
cally addressed. Infants with an omphalocele do not have than 1.5cm in diameter are referred to as hernia of the
as significant fluid and temperature losses as those with cord and are repaired shortly after birth without any
gastroschisis, but these losses are higher than those with issues as long as there are no associated anomalies.103 The
an intact abdominal wall. The sac itself can be covered defects that are larger, but still easy to close without much
with saline-soaked gauze and an impervious dressing to loss of abdominal domain can also be closed soon after
minimize these losses. An NG tube should be inserted birth. Primary closure consists of excision of the sac and
and placed to suction. closure of the fascia and skin over the abdominal con-
In some cases, the omphalocele sac may have ruptured tents. It is not unusual for an omphalomesenteric duct
either prenatally, during delivery, or postnatally (Fig. remnant to be associated with a small omphalocele (Fig.
48-8). A large, prenatally ruptured omphalocele is a 48-9). When dealing with a medium-sized omphalocele,
care must be taken when excising the portion of the sac
covering the liver, because the hepatic veins are located
just under the epithelium/sac interface in the midline and
can be injured. The sac is often adherent to the liver and
significant hemorrhage can result from tears in the
Glissen capsule. Therefore, it is usually best to leave part
of the sac on the liver. The inferior portion of the sac
covering the bladder can be quite thin, and excision of
the sac in this area can lead to bladder injury as well. The
intra-abdominal pressure can be elevated during reduc-
tion, leading to abdominal compartment syndrome.
There are a number of reports of primary closure of
a giant omphalocele shortly after birth with good results.
In a report from London, 12 of 24 babies with a large
defect had an immediate repair without any mortality.
Compared to the other cases, these patients had a shorter
ventilator requirement and time to full feeding.79
FIGURE 48-8 This neonate was born with an omphalocele that
However, this trial was not prospective and there was
ruptured during delivery. Thus, immediate management was significant selection bias with using immediate repair for
needed. The sac was removed and a silo was created. the full-term and normal birth weight neonates.
48 Congenital Abdominal Wall Defects 667
A B C
FIGURE 48-9 (A, B) In patients with small omphaloceles, it is not unusual for an omphalomesenteric duct remnant to be found.
(C) The diverticulum was excised primarily and the fascia and skin closed. This neonate recovered uneventfully.
Scarification Treatment
Nonoperative techniques have in common the use of an
agent that allows an eschar to develop over the intact
amnion sac. This eschar epithelializes over time, leaving
a ventral hernia that will likely require repair later in life.
This approach is employed when the surgeon considers
the defect too large to allow for a safe primary repair, or
if the neonate has significant cardiac or respiratory issues.
This is not a new concept, having evolved from the time
of Dr Robert Gross who described using skin flaps in
1948.109 The primary concern in a baby with a large
omphalocele is that an initial repair will result in potential
life-threatening abdominal compartment syndrome or
the inability to provide skin coverage. Initial reports
FIGURE 48-10 This neonate was born with a large omphalocele.
described mercurochrome, alcohol, and silver nitrate as
As is evident, the abdominal cavity is quite small. Primary the eschar-producing agents, which were very effective,
closure is not possible in such a patient. but were associated with toxicity (Fig. 48-11).110112
668 SECTION IV Abdomen
Postoperative Course
If primary closure has been accomplished, the majority
of patients will require mechanical ventilation for a
number of days. Feeding can begin when bowel activity
resumes. Antibiotics are administered postoperatively for
48 hours unless there are signs of wound infection, in
which case they are continued. If a ventral hernia devel-
ops, repair may be possible after age one year or later.
The method used for closure (primary vs. staged with
delayed primary closure or mesh) has not been shown to
affect length of hospitalization likely because the patient
numbers are very small.117 The time to enteral feeding
may be shorter with primary closure, though this likely
reflects a more favorable defect. In a review of treatment
of omphaloceles at one institution, the authors reported
FIGURE 48-11 An infant with a large omphalocele that was a 12% incidence of complications of increased intra-
treated by scarification using mercurochrome. Note the intense
inflammation on the abdominal wall surrounding the scarred
abdominal pressure after closure, including acute hepatic
sac. Reports of death due to mercury poisoning led to abandon- congestion requiring reoperation, renal failure requiring
ment of this method. dialysis, and bowel infarction.118 In this retrospective
review, wound complications including skin and fascial
dehiscence occurred in up to 25% of patients undergoing
Subsequently there have been reports of a number of primary closure.
substances including silver sulfadiazine, povidone-iodine
solution, silver-impregnated dressings, neomycin, and
polymixin/bacitracin ointments.113 The eschar and epi-
Long-Term Outcomes
thelialization may take 4-10 weeks. There are also reports A number of long-term medical problems develop in
that combine the use of an agent listed above with com- patients with large omphaloceles.119121 These include
pression dressing, which helps in sequentially reducing gastroesophageal reflux (GERD), pulmonary insuffi-
the contents into the abdomen and facilitates subsequent ciency, recurrent lung infections or asthma, and feeding
closure. Rarely, operative closure may not be needed as difficulty with failure to thrive.122 In 23 patients with
the defect contracts and closes similar to an umbilical omphalocele, 43% were found to have GERD by esopha-
hernia. However, most patients will eventually require geal biopsy or pH monitoring. Patients younger than 2
closure of a ventral hernia between 1 and 5 years of years had an increased rate of reflux compared with those
age (Fig. 48-12).114 The ventral hernia repair is performed older than two years of age.123 Patients with large defects
using a variety of techniques: primary fascial closure, also had an increased incidence of reflux. In this study,
autologous repair with component separation, or mesh only one child required a fundoplication, suggesting that
repair.115 Although all may be successful, the number reflux improves as the child ages.
of patients in each report is small and failures are Feeding difficulties can occur in up to 60% of infants
rarely reported. In some cases, innovative techniques with a giant omphalocele.115 Many of these children
have been utilized to recreate the abdominal domain require a gastrostomy for feeding. These difficulties seem
including the use of tissue expanders (Fig. 48-13).116 to resolve by childhood, with height and weight measure-
While the initial reports of the staged Gross operation ments becoming similar to their peer group. The respira-
had significant mortality and morbidity, current results tory insufficiency associated with giant omphaloceles may
are better.114 be secondary to abnormal thoracic development with a
A B C
FIGURE 48-12 This baby presented with a large omphalocele and multiple medical problems, including significant lung disease.
(A) Initial management was with compression therapy. Subsequently, skin grafts were placed. (B) The baby is seen at 9-months-old
and again at (C) 2-years-old. The baby underwent several operations to repair the large ventral hernia.
48 Congenital Abdominal Wall Defects 669
A B
C D
FIGURE 48-13 A 4-year-old girl was born with a number of anomalies including a diaphragmatic hernia, pulmonary hypoplasia and
pulmonary hypertension, atrial septal defect, and a large omphalocele. She underwent repair of the diaphragmatic hernia shortly
after birth, but no attempt was made to repair the large omphalocele because of its massive size and the disproportion between
the extraperitoneal viscera and the peritoneal cavity. (A, B) At 4 years old, she was found to have loss of abdominal domain, a
narrow neck to the omphalocele sac, and most of the viscera in the sac. (C) She underwent placement of an intraperitoneal tissue
expander in the pelvis. As an outpatient, the tissue expander was gradually filled to 900mL of volume, through a catheter emanat-
ing from the expander (arrow). Over time, it was possible to expand the peritoneal cavity to the point that the abdominal muscles
and fascia could be approximated. However, a biosynthetic patch was needed to complete the fascial closure. (D) She has recovered
uneventfully and has a very reasonable appearing abdomen. (A and B reprinted with permission from Foglia R, Kane A, Becker D, etal.
Management of giant omphalocele with rapid creation of abdominal domain. J Pediatr Surg 2006;41:7049. Photos courtesy of Dr. Robert
Foglia.)
narrow thorax and small lung area leading to pulmonary the abdomen, with a longitudinal rather than a horizontal
hypoplasia.124 The cause of this hypoplasia is unclear as orientation.
it has been noted in omphaloceles of varying size, but
appears more common in the larger defects. Also, it may
REFERENCES
be associated with poor intrauterine diaphragmatic
motion and altered chest wall development. Prolonged 1. Feldkamp ML, Carey JC, Sadler TW. Development of gastro-
schisis: Review of hypotheses, a novel hypothesis, and implications
respiratory difficulties can occur in up to 20% of infants for research. Am J Med Genet A 2007;143:63952.
with giant omphaloceles, leading to increased time of 2. Feldkamp ML, Carmichael SL, Shaw GM, et al. Maternal nutri-
mechanical ventilation and the need for supplemental tion and gastroschisis: Findings from the National Birth Defects
oxygen during the neonatal period. Some neonates may Prevention Study. Am J Obstet Gynecol 2011;204:404.
3. Feldkamp ML, Alder SC, Carey JC. A case control population-
require a tracheostomy.125,126 Interestingly, in a study based study investigating smoking as a risk factor for gastroschisis
looking at the long-term cardiopulmonary consequences in Utah, 19972005. Birth Defects Res A Clin Mol Teratol
of large abdominal wall defects, lung volumes and oxygen 2008;82:76875.
consumption were found to be normal.127 4. Browne ML, Hoyt AT, Feldkamp ML, et al. Maternal caffeine
Many of the intra-abdominal organs in infants with intake and risk of selected birth defects in the National Birth
Defects Prevention Study. Birth Defects Res A Clin Mol Teratol
omphalocele will be abnormally positioned. The liver sits 2011;91:93101.
in a medial position with the hepatic veins in variable 5. Baird PA, MacDonald EC. An epidemiologic study of congenital
locations. The stomach is also usually in the middle of malformations of the anterior abdominal wall in more than half a
670 SECTION IV Abdomen
million consecutive live births. Am J Hum Genet 1981;33: 30. Hoehner JC, Ein SH, Kim PC. Management of gastroschisis with
4708. concomitant jejuno-ileal atresia. J Pediatr Surg 1998;33:8858.
6. Forrester MB, Merz RD. Impact of demographic factors on pre- 31. Fleet MS, de la Hunt MN. Intestinal atresia with gastroschisis: A
natal diagnosis and elective pregnancy termination because of selective approach to management. J Pediatr Surg 2000;35:
abdominal wall defects, Hawaii, 19861997. Fetal Diagn Ther 13235.
1999;14:20611. 32. Emil S, Canvasser N, Chen T, et al. Contemporary 2 year out-
7. Castilla EE, Mastroiacovo P, Orioli IM. Gastroschisis: Interna- comes of complex gastroschisis. J Pediatr Surg 2012;47:15218.
tional epidemiology and public health perspectives. Am J Med 33. Frolov P, Alali J, Klein MD. Clinical risk factors for gastroschisis
Genet C Semin Med Genet 2008;148:16279. and omphalocele in humans: A review of the literature. Pediatr
8. Lausman AY, Langer JC, Tai M, et al. Gastroschisis: What is the Surg Int 2010;26:113548.
average gestational age of spontaneous delivery? J Pediatr Surg 34. Snyder CL, St Peter SD. Trends in mode of delivery for gastro-
2007;42:181621. schisis infants. Am J Perinatol 2005;22:3916.
9. Cerekja A, Piazze J, Cozzi D. Early prenatal sonographic diagno- 35. Salihu HM, Emusu D, Aliyu ZY, et al. Mode of delivery and
sis of gastroschisis. J Clin Ultrasound 2012 ;40:5268. neonatal survival of infants with isolated gastroschisis. Obstet
10. David AL, Tan A, Curry J. Gastroschisis: Sonographic diagnosis, Gynecol 2004;104:67883.
associations, management and outcome. Prenat Diagn 2008;28: 36. Puligandla PS, Janvier A, Flageole H, et al. Routine cesarean
63344. delivery does not improve the outcome of infants with gastro-
11. Juhasz-Boss I, Goelz R, Solomayer EF, et al. Fetal and neonatal schisis. J Pediatr Surg 2004;39:7425.
outcome in patients with anterior abdominal wall defects (gastro- 37. Segel SY, Marder SJ, Parry S, et al. Fetal abdominal wall defects
schisis and omphalocele). J Perinat Med 2012;40:8590. and mode of delivery: A systematic review. Obstet Gynecol
12. Moir CR, Ramsey PS, Ogburn PL, et al. A prospective trial of 2001;98:86773.
elective preterm delivery for fetal gastroschisis. Am J Perinatol 38. Guibourdenche J, Berrebi D, Vuillard E, et al. Biochemical inves-
2004;21:28994. tigations of bowel inflammation in gastroschisis. Pediatr Res
13. Mills JA, Lin Y, Macnab YC, et al. Perinatal predictors of outcome 2006;60:5658.
in gastroschisis. J Perinatol 2010;30:80913. 39. Vargun R, Aktug T, Heper A, et al. Effects of intrauterine treat-
14. Alsulyman OM, Monteiro H, Ouzounian JG, et al. Clinical sig- ment on interstitial cells of Cajal in gastroschisis. J Pediatr Surg
nificance of prenatal ultrasonographic intestinal dilatation in 2007;42:7837.
fetuses with gastroschisis. Am J Obstet Gynecol 1996;175: 40. Logghe HL, Mason GC, Thornton JG, et al. A randomized con-
9824. trolled trial of elective preterm delivery of fetuses with gastro-
15. Piper HG, Jaksic T. The impact of prenatal bowel dilation on schisis. J Pediatr Surg 2005;40:172631.
clinical outcomes in neonates with gastroschisis. J Pediatr Surg 41. Charlesworth P, Njere I, Allotey J, et al. Postnatal outcome in
2006;41:897900. gastroschisis: Effect of birth weight and gestational age. J Pediatr
16. Langer JC, Longaker MT, Crombleholme TM, , et al. Etiology Surg 2007;42:81518.
of intestinal damage in gastroschisis. I: Effects of amniotic fluid 42. Maramreddy H, Fisher J, Slim M, et al. Delivery of gastroschisis
exposure and bowel constriction in a fetal lamb model. J Pediatr patients before 37 weeks of gestation is associated with increased
Surg 1989;24:9927. morbidities. J Pediatr Surg 2009;44:13606.
17. Olguner M, Akgur FM, Api A, et al. The effects of intraamniotic 43. Jansen LA, Safavi A, Lin Y, et al. Preclosure fluid resuscitation
human neonatal urine and meconium on the intestines of the influences outcome in gastroschisis. Am J Perinatol 2012;29:
chick embryo with gastroschisis. J Pediatr Surg 2000;35:45861. 30712.
18. Caglar M, Hakguder G, Ates O, et al. Amniotic fluid ferritin as a 44. Mortellaro VE, St Peter SD, Fike FB, et al. Review of the evi-
marker of intestinal damage in gastroschisis: A time course experi- dence on the closure of abdominal wall defects. Pediatr Surg Int
mental study. J Pediatr Surg 2007;42:171015. 2011;27:3917.
19. Hakguder G, Ates O, Olguner M, et al. Induction of fetal diuresis 45. Aldrink JH, Caniano DA, Nwomeh BC. Variability in gastro-
with intraamniotic furosemide increases the clearance of intraam- schisis management: A survey of North American pediatric
niotic substances: An alternative therapy aimed at reducing surgery training programs. J Surg Res 2012;176:15963.
intraamniotic meconium concentration. J Pediatr Surg 2002;37: 46. Alali JS, Tander B, Malleis J, et al. Factors affecting the outcome
133742. in patients with gastroschisis: How important is immediate repair?
20. Marder AL, Moise K Jr, Chuang A, et al. Amnioexchange for the Eur J Pediatr Surg 2011;21:99102.
treatment of gastroschisisan in vitro study to determine the 47. Owen A, Marven S, Jackson L, et al. Experience of bedside pre-
volume and number of exchanges needed. Fetal Diagn Ther formed silo staged reduction and closure for gastroschisis.
2008;23:959. J Pediatr Surg 2006;41:18305.
21. Luton D, Guibourdenche J, Vuillard E, et al. Prenatal manage- 48. Hassan SF, Pimpalwar A. Primary suture-less closure of gastro-
ment of gastroschisis: The place of the amnioexchange procedure. schisis using negative pressure dressing (wound vacuum). Eur J
Clin Perinatol 2003;30:55172. Pediatr Surg 2011;21:28791.
22. Hakguder G, Olguner M, Gurel D, et al. Induction of fetal diu- 49. Bianchi A, Dickson AP. Elective delayed reduction and no
resis with intraamniotic furosemide injection reduces intestinal anesthesia: minimal intervention management for gastroschisis.
damage in a rat model of gastroschisis. Eur J Pediatr Surg J Pediatr Surg 1998;33:133840.
2011;21:1837. 50. Wesson DE, Baesl TJ. Repair of gastroschisis with preservation
23. Midrio P, Stefanutti G, Mussap M, et al. Amnioexchange for of the umbilicus. J Pediatr Surg 1986;21:7645.
fetuses with gastroschisis: Is it effective? J Pediatr Surg 51. Houben CH, Patel S. Gastroschisis closure: A technique for
2007;42:77782. improved cosmetic repair. Pediatr Surg Int 2008;24:105760.
24. Arnold MA, Chang DC, Nabaweesi R, et al. Risk stratification of 52. Hernandez Siverio N, M Lpez-Tomassetti Fernndez E, Mario
4344 patients with gastroschisis into simple and complex catego- Troyano Luque J. Gastroschisis: Primary closure using umbilical
ries. J Pediatr Surg 2007;42:15205. cord strengthened by a polypropylene mesh. J Perinat Med
25. Dixon JC, Penman DM, Soothill PW. The influence of bowel 2007;35:24951.
atresia in gastroschisis on fetal growth, cardiotocograph abnor- 53. Uceda J. Umbilical preservation in gastroschisis. J Pediatr Surg
malities and amniotic fluid staining. BJOG 2000;107:4725. 1996;31:13678.
26. Amoury RA, Ashcraft KW, Holder TM. Gastroschisis compli- 54. Bonnard A, Zamakhshary M, de Silva N, et al. Non-operative
cated by intestinal atresia. Surgery 1977;82:37381. management of gastroschisis: A case-matched study. Pediatr Surg
27. Pokorny WJ, Harberg FJ, McGill CW. Gastroschisis complicated Int 2008;24:76771.
by intestinal atresia. J Pediatr Surg 1981;16:2613. 55. Olesevich M, Alexander F, Khan M, Cotman K. Gastroschisis
28. Gornall P. Management of intestinal atresia complicating gastro- revisited: Role of intraoperative measurement of abdominal pres-
schisis. J Pediatr Surg 1989;24:5224. sure. J Pediatr Surg 2005;40:78992.
29. Shah R., Woolley MM. Gastroschisis and intestinal atresia. 56. Lacey SR, Carris LA, Beyer AJ 3rd, et al. Bladder pressure moni-
J Pediatr Surg 1991;26:78890. toring significantly enhances care of infants with abdominal wall
48 Congenital Abdominal Wall Defects 671
defects: A prospective clinical study. J Pediatr Surg 1993;28: 82. Molik KA, Gingalewski CA, West KW, et al. Gastroschisis: A plea
13704. for risk categorization. J Pediatr Surg 2001;36:515.
57. Ein SH, Superina R, Bagwell C, et al. Ischemic bowel after 83. Lao OB, Larison C, Garrison MM, et al. Outcomes in neonates
primary closure for gastroschisis. J Pediatr Surg 1988;23: with gastroschisis in USA childrens hospitals. Am J Perinatol
72830. 2010;27:97101.
58. Yaster M, Scherer TL, Stone MM, et al. Prediction of successful 84. Wada M, Kato T, Hayashi Y, et al. Intestinal transplantation for
primary closure of congenital abdominal wall defects using intra- short bowel syndrome secondary to gastroschisis. J Pediatr Surg
operative measurements. J Pediatr Surg 1989;24:121720. 2006;41:18415.
59. McGuigan RM, Mullenix PS, Vegunta R, et al. Splanchnic per- 85. Oldham KT, Coran AG, Drongowski RA, et al. The development
fusion pressure: A better predictor of safe primary closure than of necrotizing enterocolitis following repair of gastroschisis: A
intraabdominal pressure in neonatal gastroschisis. J Pediatr Surg surprisingly high incidence. J Pediatr Surg 1988;23:9459.
2006;41:9014. 86. Kurbegov AC, Sondheimer JM. Pneumatosis intestinalis in non-
60. Kidd JN Jr, Jackson RJ, Smith SD, et al. Evolution of staged versus neonatal pediatric patients. Pediatrics 2001;108:4026.
primary closure of gastroschisis. Ann Surg 2003;237:75964. 87. Jayanthi S, Seymour P, Puntis JW, et al. Necrotizing enterocolitis
61. Sandler A, Lawrence J, Meehan J, et al. A plastic sutureless after gastroschisis repair: A preventable complication? J Pediatr
abdominal wall closure in gastroschisis. J Pediatr Surg 2004;39: Surg 1998;33:7057.
73841. 88. Lawson A, de La Hunt MN. Gastroschisis and undescended testis.
62. Orion KC, Krein M, Liao J, et al. Outcomes of plastic closure in J Pediatr Surg 2001;36:3667.
gastroschisis. Surgery 2011;150:1771785. 89. Hill SJ, Durham MM. Management of cryptorchidism and gas-
63. Jensen AR, Waldhausen JH, Kim SS. The use of a spring-loaded troschisis. J Pediatr Surg 2011;46:1798803.
silo for gastroschisis: Impact on practice patterns and outcomes. 90. Berger AP, Hager J. Management of neonates with large abdomi-
Arch Surg 2009;144:51619. nal wall defects and undescended testis. Urology 2006;68:1758.
64. Chiu B, Lopoo J, Hoover JD, et al. Closing arguments for gas- 91. Davies BW, Stringer MD. The survivors of gastroschisis. Arch Dis
troschisis: Management with silo reduction. J Perinat Med Child 1997;77:15860.
2006;34:2435. 92. Solerte L. Three-dimensional multiplanar ultrasound in a limb-
65. Schlatter M, Norris K, Uitvlugt N, et al. Improved outcomes in body wall complex fetus: Clinical evidence for counseling.
the treatment of gastroschisis using a preformed silo and delayed J Matern Fetal Neonatal Med 2006;19:10912.
repair approach. J Pediatr Surg 2003;38:45964. 93. Brantberg A, Blaas HG, Haugen SE, et al. Characteristics and
66. Banyard D, Ramones T, Phillips SE, et al. Method to our madness: outcome of 90 cases of fetal omphalocele. Ultrasound Obstet
An 18-year retrospective analysis on gastroschisis closure. Gynecol 2005;26:52737.
J Pediatr Surg 2010;45:57984. 94. Cohen-Overbeek TE, Tong WH, Hatzmann TR, et al. Ompha-
67. Weil BR, Leys CM, Rescorla FJ. The jury is still out: Changes in locele: Comparison of outcome following prenatal or postnatal
gastroschisis management over the last decade are associated with diagnosis. Ultrasound Obstet Gynecol 2010;36:68792.
both benefits and shortcomings. J Pediatr Surg 2012;47:11924. 95. Nicholas SS, Stamilio DM, Dicke JM, et al. Predicting adverse
68. Weinsheimer RL, Yanchar NL, Bouchard SB, et al. Gastroschisis neonatal outcomes in fetuses with abdominal wall defects using
closuredoes method really matter? J Pediatr Surg 2008;43: prenatal risk factors. Am J Obstet Gynecol 2009;201:383.
8748. 96. Kamata S, Usui N, Sawai T, et al. Prenatal detection of pulmonary
69. Pastor AC, Phillips JD, Fenton SJ, et al. Routine use of a hypoplasia in giant omphalocele. Pediatr Surg Int 2008;24:
SILASTIC spring-loaded silo for infants with gastroschisis: A 10711.
multicenter randomized controlled trial. J Pediatr Surg 97. Hidaka N, Murata M, Yumoto Y, et al. Characteristics and peri-
2008;43:180712. natal course of prenatally diagnosed fetal abdominal wall defects
70. Bradnock TJ, Marven S, Owen A, et al. Gastroschisis: One year managed in a tertiary center in Japan. J Obstet Gynaecol Res
outcomes from national cohort study. BMJ 2011;343. 2009;35:407.
71. Fleet MS, de la Hunt MN. Intestinal atresia with gastroschisis: A 98. Montero FJ, Simpson LL, Brady PC, et al. Fetal omphalocele
selective approach to management. J Pediatr Surg 2000;35: ratios predict outcomes in prenatally diagnosed omphalocele. Am
13235. J Obstet Gynecol 2011;205:284.
72. Phillips JD, Raval MV, Redden C, et al. Gastroschisis, atresia, 99. Kleinrouweler CE, Kuijper CF, van Zalen-Sprock MM, et al.
dysmotility: Surgical treatment strategies for a distinct clinical Characteristics and outcome and the omphalocele circumference/
entity. J Pediatr Surg 2008;43:220812. abdominal circumference ratio in prenatally diagnosed fetal
73. Kronfli R, Bradnock TJ, Sabharwal A. Intestinal atresia in associa- omphalocele. Fetal Diagn Ther 2011;30:609.
tion with gastroschisis: A 26-year review. Pediatr Surg Int 100. Lurie S, Sherman D, Bukovsky I. Omphalocele delivery enigma:
2010;26:8914. The best mode of delivery still remains dubious. Eur J Obstet
74. Vachharajani AJ, Dillon PA, Mathur AM. Outcomes in neonatal Gynecol Reprod Biol 1999;82:1922.
gastroschisis: An institutional experience. Am J Perinatol 101. Baird R, Gholoum S, Laberge JM, Puligandla P. Management of
2007;24:4615. a giant omphalocele with an external skin closure system. J Pediatr
75. Houben C, Davenport M, Ade-Ajayi N, et al. Closing gastro- Surg 2010;45:E1720.
schisis: Diagnosis, management, and outcomes. J Pediatr Surg 102. van Eijck FC, Aronson DA, Hoogeveen YL, et al. Past and current
2009;44:3437. surgical treatment of giant omphalocele: Outcome of a question-
76. Barsoom MJ, Prabulos A, Rodis JF, et al. Vanishing gastroschisis naire sent to authors. J Pediatr Surg 2011;46:4828.
and short-bowel syndrome. Obstet Gynecol 2000;96:81819. 103. Islam S. Clinical care outcomes in abdominal wall defects. Curr
77. Langer JC, Bramlett G. Effect of prokinetic agents on ileal con- Opin Pediatr 2008;20:30510.
tractility in a rabbit model of gastroschisis. J Pediatr Surg 104. Delorimier AA, Adzick NS, Harrison MR. Amnion inversion in
1997;32:6058. the treatment of giant omphalocele. J Pediatr Surg 1991;26:
78. Curry JI, Lander AD, Stringer MD. A multicenter, randomized, 8047.
double-blind, placebo-controlled trial of the prokinetic agent 105. Yokomori K, Ohkura M, Kitano Y, et al. Advantages and pitfalls
erythromycin in the postoperative recovery of infants with gastro- of amnion inversion repair for the treatment of large unruptured
schisis. J Pediatr Surg 2004;39:5659. omphalocele: Results of 22 cases. J Pediatr Surg 1992;27:8824.
79. Rijhwani A, Davenport M, Dawrant M, et al. Definitive surgical 106. Alaish SM, Strauch ED. The use of Alloderm in the closure of a
management of antenatally diagnosed exomphalos. J Pediatr Surg giant omphalocele. J Pediatr Surg 2006;41:e379.
2004;40:51622. 107. Kilbride KE, Cooney DR, Custer MD. Vacuum-assisted closure:
80. Arnold MA, Chang DC, Nabaweesi R, et al. Development and A new method for treating patients with giant omphalocele.
validation of a risk stratification index to predict death in gastro- J Pediatr Surg 2006;41:21215.
schisis. J Pediatr Surg 2007;42:9505. 108. Brown AL II, Roty AR Jr, Kilway JB. Increased survival with new
81. Kassa AM, Lilja HE. Predictors of postnatal outcome in neonates techniques in treatment of gastroschisis. Am Surg 1978;44:
with gastroschisis. J Pediatr Surg 2011;46:210814. 41720.
672 SECTION IV Abdomen
109. Gross RE. A new method for surgical treatment of a large ompha- of abdominal closure: The experience of a single center. Pediatr
locele. Surgery 1948;24:27792. Surg Int 2006;22:5037.
110. Mullins ME, Horowitz BZ. Iatrogenic neonatal mercury poison- 119. Dunn JCY, Fonkalsrud EW. Improved survival of infants with
ing from Mercurochrome treatment of a large omphalocele. Clin omphalocele. Am J Surg 1997;173:2847.
Pediatr 1999;38:11112. 120. Wilson RD, Biard JM, Johnson MP, et al. Giant omphalocele:
111. Festen C, Severijnen RS, vd Staak FH. Nonsurgical (conservative) Prenatal diagnosis, short, and long-term outcomes. Am J Hum
treatment of giant omphalocele. A report of 10 cases. Clin Pediatr Genet 2003;73:594.
1987;26:359. 121. Lakasing L, Cicero S, Davenport M, et al. Current outcome of
112. Whitehouse JS, Gourlay DM, Masonbrink AR, et al. Conservative antenatally diagnosed exomphalos: An 11 year review. J Pediatr
management of giant omphalocele with topical povidone-iodine Surg 2006;41:14036.
and its effect on thyroid function. J Pediatr Surg 2010;45: 122. Biard JM, Wilson RD, Johnson MP, et al. Prenatally diagnosed
11927. giant omphaloceles: Short- and long-term outcomes. Prenat
113. Almond S, Reyna R, Barganski N, et al. Nonoperative manage- Diagn 2004;24:4349.
ment of a giant omphalocele using a silver impregnated hydrofiber 123. Koivusalo A, Rintala R, Lindahl H. Gastroesophageal reflux in
dressing: A case report. J Pediatr Surg 2010;45:15469. children with a congenital abdominal wall defect. J Pediatr Surg
114. Lee SL, Beyer TD, Kim SS, et al. Initial nonoperative manage- 1999;34:11279.
ment and delayed closure for treatment of giant omphaloceles. 124. Argyle JC. Pulmonary hypoplasia in infants with giant abdominal
J Pediatr Surg 2006;41:18469. wall defects. Pediatr Pathol 1989;9:4355.
115. van Eijck FC, de Blaauw I, Bleichrodt RP, et al. Closure of giant 125. Hershenson MB, Brouillette RT, Klemka L, et al. Respiratory
omphaloceles by the abdominal wall component separation tech- insufficiency in newborns with abdominal wall defects. J Pediatr
nique in infants. J Pediatr Surg 2008;43:24650. Surg 1985;20:34853.
116. De Ugarte DA, Asch MJ, Hedrick MH, et al. The use of tissue 126. Edwards EA, Broome S, Green S, et al. Long-term respiratory
expanders in the closure of a giant omphalocele. J Pediatr Surg support in children with giant omphalocele. Anaesth Intensive
2004;39:61315. Care 2007;35:948.
117. Islam S. Advances in surgery for abdominal wall defects: Gastro- 127. Zaccara A, Iacobelli BD, Calzolari A, et al. Cardiopulmonary
schisis and omphalocele. Clin Perinatol 2012;39:37586. performances in young children and adolescents born with large
118. Maksoud-Filho JG, Tannuri U, da Silva MM, et al. The outcome abdominal wall defects. J Pediatr Surg 2003;38:47881.
of newborns with abdominal wall defects according to the method
C H A P T E R 4 9
EPIGASTRIC HERNIA A
SPIGELIAN HERNIA FIGURE 49-2 The technique for operative repair for an umbilical
hernia. (A) An infraumbilical skin crease incision is made.
(B) The hernia sac is opened, leaving a portion of the sac
Spigelian hernias are quite rare in children and can be attached to the umbilical skin for ease of subsequent umbilico-
difficult to detect and diagnose. The actual defect occurs plasty. (C) The umbilical sac has been completely divided and
at the intersection of the linea semicircularis, linea semi- excised to strong fascia. (D) The fascial defect is closed in a
lunaris, and the lateral border of the rectus abdominis transverse fashion with interrupted, simple nonabsorbable
sutures. (E) The remaining umbilical sac, which is attached to
muscle. It usually involves absence or attenuation of the the umbilical skin, is secured to the fascia with interrupted,
transversus abdominis and internal oblique muscles. absorbable sutures. (F) The skin incision is closed with a sub-
These hernias are more frequently found in girls and cuticular suture.
49 Umbilical and Other Abdominal Wall Hernias 675
A B C D
FIGURE 49-3 The steps depicted in the operative diagram in Figure 49-2 are shown. (A) An infraumbilical incision is made. (B) The
umbilical hernia sac has been encircled with a hemostat. (C) The umbilical hernia sac is excised, and transverse closure of the fascial
defect is accomplished with interrupted long-lasting absorbable sutures. (D) The umbilicus has been tacked to the fascial closure,
and the skin is approximated with a subcuticular closure.
REFERENCES
1. Crump EP. Umbilical hernia: Occurrence of the infantile type in
Negro infants and children. J Pediatr 1952;40:21433.
2. Evans AG. The comparative incidence of umbilical hernia in
colored and white infants. J Natl Med Assoc 1940;33:15860.
3. Vohr BR, Rosenfield AG, Oh W. Umbilical hernia in the low-birth
weight infant (less than 1500gm). J Pediatr 1977;90:8078.
4. Jones KL. Abdominal wall. In: Jones KL, editor. Smiths Recogniz-
able Patterns of Human Malformation. 4th ed. Philadelphia: WB
Saunders; 1988. p. P753754.
5. Tank EW, Hatch DA. Hernias complicating chronic ambulatory
peritoneal dialysis in children. J Pediatr Surg 1986;21:412.
6. Woods GE. Some observations on umbilical hernias in infants.
Arch Dis Child 1953;28:45062.
7. Heifitz CJ, Bilsel ZE, Gans WW. Observations on the disappear-
ance of umbilical hernias of infancy and childhood. Surg Gynecol
Obstet 1963;116:46773.
8. Walker SH. The natural history of umbilical hernia. Clin Pediatr
1967;6:2932.
9. Hall DE, Roberts KB, Charney E. Umbilical hernia: What happens
after age 5 years? J Pediatr 1981;98:41517.
FIGURE 49-4 At the time of epigastric hernia repair, this opera- 10. Sibley WL, Lynn HE, Harris LE. A twenty-five year study of
tive photograph shows herniation of properitoneal fat through infantile umbilical hernia. Surgery 1964;55:4628.
a small fascial defect in the linea alba. 11. Blumberg NA. Infantile umbilical hernia. Surg Gynecol Obstet
1980;150:18792.
12. Halpern LJ. Spontaneous healing of umbilical hernias. JAMA
1962;182:8512.
muscle, and internal oblique muscle. Occasionally, they 13. Mestal AL, Burns H. Incarcerated and strangulated umbilical
extend inferiorly to the iliac crest. These hernias tend to hernias in infants and children. Clin Pediatr 1963;2:36870.
develop at the site of penetration of the intercostal nerves 14. Lassaletta L, Fonkalsrud EW, Tovar JA, et al. The management of
umbilical hernia in infancy and childhood. J Pediatr Surg 1975;
and vessels, or of the ilioinguinal, iliohypogastric, and 10:4059.
lumbar nerves. The bulge is usually properitoneal fat. 15. Merci J. Umbilical hernia repair in children: Is pressure dressing
Therefore, the physical findings include a soft mass that necessary? Pediatr Surg Int 2006;22:4468.
is easily reducible. Although frequently asymptomatic, 16. Jamra F. Reconstruction of umbilicus by a double V-Y procedure.
repair is advisable because the defect never resolves spon- Plast Reconstr Surg 1979;64:10610.
17. Reyna T, Hllis H, Smith S. Surgical management of proboscoid
taneously and incarceration is possible. hernia. J Pediatr Surg 1978;22:9112.
Repair sometimes requires prosthetic reinforcement 18. Koshy C, Taams K. Umbilicoplasty. Plast Reconstr Surg 1999;
of the fascia or muscle closure because the tissue available 104:12034.
for repair is usually thin and weak. I prefer using absorb- 19. Spangen L. Spigelian hernia. Surg Clin North Am 1984;64:
35166.
able mesh in the growing child that will not cause scol- 20. Asku B, Temizoz O, Inan M, et al. Bilateral Spigelian concomitant
iosis later. Recurrence is not uncommon and several with multiple skeletal anomalies and fibular aplasia in a child. Eur
operations may be needed. Bilateral lumbar hernias can J Pediatr Surg 2008;18:2058.
C H A P T E R 5 0
and medial external oblique fibers. The floor is formed in an indirect inguinal hernia. As mentioned, the factors
by the transversalis fascia and the conjoint tendon. The driving PPV closure are incompletely understood. Intra-
anterior roof is created primarily by the aponeurosis of abdominal pressure probably plays a role because disor-
the external oblique. The inferior wall is composed by ders with increased abdominal pressure/fluid (e.g., ascites,
the inguinal ligament, lacunar ligament (medial third), VPS) are associated with an increased incidence of indi-
and iliopubic tract (lateral third). Contents include the rect inguinal hernias and an increased incidence of bilat-
ilioinguinal nerve (exiting through the external inguinal erality.17 Indirect inguinal hernias are more common on
ring) and in males, the spermatic cord. In females, it also the right. The various clinical findings related to the
contains the round ligament.21 processus vaginalis are illustrated in Figure 50-1.
The processus vaginalis is a peritoneal diverticulum The layers of the abdominal wall contribute to the
extending through the internal inguinal ring into the layers of the testis and spermatic cord as the gonad
inguinal canal. It can be seen by 3 months of fetal life.22 descends. The internal spermatic fascia is a continuation
The somatic base of this diverticulum is the transversalis of the transversalis fascia, the cremaster muscle derives
portion of the endoabdominal fascia. The gonads form from the internal oblique, and the external spermatic
on the anteromedial nephrogenic ridges in the retroperi- fascia originates from the external oblique aponeurosis.
toneum during the 5th week of gestation. The gonads are The processus vaginalis envelops the testis as the visceral
attached to the scrotum by the gubernaculum in the male and parietal layers of the tunica vaginalis.22
and to the labia via the round ligament in the female.
Gonadal descent begins by 3 months gestation, and the
testis reaches the internal inguinal ring by about 7 CLINICAL PRESENTATION
months. Descent of the testis is thought to be directed in
the abdominal phase by insulin-like 3 protein, a product Most hernias are asymptomatic except for inguinal
of the Leydig cells, and directed in the second phase by bulging with straining. They are often found by the
androgens and release of calcitonin gene-related peptide parents or pediatrician on routine physical examination.
(CGRP) from the genitofemoral nerve (via fetal andro- The diagnosis is clinical and rests squarely on the history
gen release).23,24 CGRP appears to mediate closure of the and physical examination. Maneuvers such as having the
patent processus vaginalis (PPV), although this process is child raise the head while supine or blowing up a balloon
not completely understood.24 with a thumb in the mouth may be helpful in small chil-
The testis begins to descend down the canal by the dren. Standing the child upright may also help demon-
seventh month of fetal life preceded and guided by the strate the hernia. The differential diagnosis includes a
processus vaginalis.22,24,25 The processus, which is located retractile testis, lymphadenopathy, hydrocele, and prepu-
anterior and medial to the cord structures, gradually bertal fat.
obliterates, and the scrotal portion forms the tunica vagi- A common occurrence is a normal examination in
nalis. The female anlage of the processus vaginalis is the combination with a suggestive history. Cell phone picture
canal of Nuck, a structure that leads to the labia majora. documentation by the parents has become commonplace.
This also closes by about 7 months of fetal life, and A good history is acceptable as an indication for opera-
ovarian descent is arrested in the pelvis.22 The precise tion. False-negative explorations are rare. In the previ-
incidence of PPV in newborns is unknown and depends ously mentioned series of 6,361 hernia repairs by a single
on gender and gestational age. It is estimated to be surgeon (definitive inguinal hernia on examination was
4060%, but may be lower or higher.26 However, at the indication for operation), there was only one false-
autopsy, only 5% of adults have a PPV.22 PPVs can still negative exploration (0.02%).12
close after birth, but this is felt less likely to occur with Children are often referred for inguinal pain in the
increasing age. It is failure of the PPV to close that results absence of any history of bulging or swelling, often with
Peritoneal
cavity
Process
vaginalis
a normal physical examination. Other sources such as absence of signs of hernia or tumor. Otherwise an inguinal
musculoskeletal strain, gastrointestinal, or genitourinary approach is best.36 Transumbilical diagnostic laparoscopy
abnormalities should be excluded before operative inter- for evaluation for a PPV is a good option in equivocal
vention. Diagnostic transumbilical laparoscopy is useful cases.
in a small subset with equivocal examinations or persist- An abdominoscrotal hydrocele is an hourglass-shaped
ent symptoms and no other apparent cause. collection with both an inguinoscrotal and abdominal
Ancillary findings such as a silk glove sign (feeling component. A combined inguinal and laparoscopic
the thickened peritoneum of the patent processus as the approach may be helpful.37
cord is palpated) or examination under anesthesia are of
variable reliability.27,28 Radiologic diagnostic aids are not Incarceration
generally necessary or helpful. Ultrasonography (US) can
be used to identify a PPV indirectly via widening of the The incidence of hernia incarceration is variable and
internal inguinal ring (more than 45mm is positive), but ranges from 1217%.12,38,39 Younger age and prematurity
the technique is highly operator dependent and not are risk factors for incarceration.40 The mean age of
widely used in children.29,30 It is not generally necessary patients with incarceration is significantly lower than that
to restrict an asymptomatic childs activities until repair of those who undergo elective repair.12,41
is scheduled, but prompt repair may decrease interim Symptoms of incarceration are frequently manifested
incarceration, particularly in the very young. as a fussy or inconsolable infant with intermittent abdomi-
Sometimes an incidental PPV is discovered in a child nal pain and vomiting. A tender and sometimes erythema-
undergoing operation for an unrelated problem. A tous irreducible mass is noted in the groin. Abdominal
common scenario is finding a unilateral or bilateral PPV distention is a late sign, as are bloody stools. Peritoneal
during the course of a laparoscopic appendectomy, or signs indicate strangulation. Incarceration may be the
other operation. It is probably best not to perform a PPV presenting sign of the hernia, especially in an infant. It can
repair in that setting as the patient is not symptomatic. be difficult to distinguish a hydrocele of the cord from an
The child and the family should be informed of the find- incarcerated hernia. A happy infant with no tenderness
ings and instructed to watch for symptoms. suggests the former diagnosis, but if several examiners
have vigorously attempted to reduce the hydrocele, the
distinction can be difficult and ultrasound may be helpful.
Hydrocele It has been stated that gangrenous bowel cannot be
The management of asymptomatic hydroceles in infants reduced, but exceptions make this a dangerous rule to
is somewhat controversial. There is general agreement rely on. The presence of peritonitis or septic shock is an
that a noncommunicating, asymptomatic hydrocele in an absolute contraindication to attempted reduction. Symp-
infant should simply be followed. One recent study found toms of bowel obstruction are a relative contraindication.
that 89% of 121 infants who were followed resolved by Monitored conscious sedation is used after intravenous
1 year of age.31 The duration of observation varies by access and rehydration. Firm and continuous pressure is
surgeon, with most recommending operation by one or applied around the incarceration. Successful reduction is
two years of age if the hydrocele fails to resolve or if a usually confirmed by a sudden pop of the contents back
clinical hernia is apparent.20,32 into the peritoneal cavity. Questionable or incomplete
Expectant management has been extended by some reductions should be explored. Reduction en masse, in
authors to infants with communicating hydroceles (and which the hernia contents are reduced into the peritoneal
therefore PPVs). In a 2010 report, in 110 infant boys with cavity but the bowel remains incarcerated internally in
an apparent communicating hydrocele, 63% had com- the hernia sac, is a very rare occurrence but the surgeon
plete resolution without operation by a mean age of should be aware of this possibility.
nearly one year.33 Interim incarceration did not occur in Once an incarcerated hernia is reduced, a delay of 24
this series. to 48 hours to allow resolution of edema is reasonable.
Many authors recommend operation for an infant with Reliability of the family as well as clinical (very difficult
a giant hydrocele, although the definition is subjective reduction) and geographic considerations may dictate the
and variable. Most surgeons also repair hydroceles of the need for admission and observation before definitive
cord.34 repair. Overall, 9095% of incarcerated hernias can be
Excision of the hydrocele sac is not necessary. The successfully reduced.42 In one report, only 8% required
fluid should be evacuated, and the distal sac is opened emergency operation out of 743 incarcerated hernias.12
widely. Large or thick sacs may be everted behind the Two children required bowel resection.
cord (Bottle procedure).35 Urgent operation is necessary if reduction fails. The
Hydroceles in adolescents are often a complication of hernia may reduce with induction of general anesthesia.
varicocelectomy. A de novo hydrocele in this age group If so, the hernia sac should be opened and inspected.
may represent an inguinal hernia or simply an idiopathic The presence of enteric contents or bloody fluid man-
hydrocele. A thorough history and physical examination dates either open exploration via separate incision or La
to exclude communication hernia should be performed. Roque maneuver (incision in the transversalis fascia
Also, an ultrasound (particularly if the testis is not palpa- through the same inguinal skin incision) or, more com-
ble, since a reactive hydrocele accompanies about 15% of monly, laparoscopic evaluation. It may be necessary to
testicular tumors) should be obtained. A trans-scrotal open the internal inguinal ring laterally to reduce the
hydrocelectomy is appropriate in adolescents in the bowel. Some surgeons approach an incarcerated hernia
682 SECTION V Inguinal Region and Scrotum
by transumbilical laparoscopy to both reduce the hernia neonatal intensive care unit. The incidence of bowel
and evaluate the bowel.43,44 There is some evidence that incarceration in premature infants is significantly
the laparoscopic approach is associated with fewer increased (three times in one large series).12 Many institu-
complications.45 tions use 2kg as a lower limit for repair in asymptomatic
Intestinal injury requiring treatment is rare (1% to and otherwise relatively healthy newborns. We usually
2%), even with incarceration.12 The hernia sac is often repair the hernia before discharge to avoid the need for
quite edematous and friable, and repair of the hernia can readmission for herniorrhaphy and to decrease the risk
be quite difficult. The risk of recurrence is significantly of incarceration.46,5355 However, this depends on other
increased. We do not routinely employ laparoscopy comorbidities. One recent study compared repair before
looking for a contralateral PPV in patients with discharge or as an outpatient, and found an increased
incarceration. length of hospitalization in the former group (largely
The testis on the incarcerated side is often edematous from respiratory complications) and a low incidence of
and somewhat cyanotic. Unless the gonad is frankly incarceration in the latter group.56 However, others have
necrotic, it should be preserved. The parents of any boy found that in-house repair is preferable due to a lower
with an incarcerated hernia should be counseled about incarceration rate after discharge.57,58
the possibility of testicular loss or atrophy, but the inci-
dence of this complication is only 23%.42,46 Incarcera-
tion of an ovary in a hernia sac may not always impair its
Open Repair Technique
blood supply, but most pediatric surgeons will promptly Pediatric indirect inguinal hernias are usually repaired
(but not emergently) repair the hernia in a girl even with through an inguinal crease incision by incising the exter-
an asymptomatic, nontender incarcerated ovary.47 nal oblique aponeurosis to the internal inguinal ring.
After the ilioinguinal nerve is identified, the antero-
medial hernia sac is grasped and the vas and vessels (in
the usual male hernia) are pushed away from the sac (Fig.
MANAGEMENT 50-2A). The sac is clamped and divided (Fig. 50-2B). A
Anesthesia high ligation is performed after the sac is opened and
inspected. If contralateral laparoscopic evaluation is per-
There are no good data comparing regional to general formed, a small cannula can be gently advanced through
anesthesia for pediatric inguinal hernia repair. A 2003 the opened sac (Fig. 50-2C). A 70, 2.7mm telescope
Cochrane meta-analysis of available data regarding allows examination of the contralateral side (Figs 50-3
this issue in premature infants concluded: There is no and 50-4).
reliable evidence from the trials reviewed concerning There is an uncommon but disturbing incidence of
the effect of spinal as compared to general anesthesia on late inguinal abscess formation related to the use of silk
the incidence of postoperative apnea, bradycardia, or suture material for ligation of the sac.59,60 For this reason,
oxygen desaturation in ex-preterm infants undergoing we now prefer absorbable sutures. The sac may be twisted
herniorrhaphy.48 before ligation, but too much twisting may draw the vas
Overnight hospitalization is not necessary after and cord structures into the base of the sac where they
inguinal hernia repair for healthy children or term infants. risk being inadvertently ligated. Removing the distal sac
However, the risk of postoperative apnea and bradycardia may increase the risk of injury to the cord structures and
is increased in premature infants and overnight monitor- the testis, and is not necessary. Distal hydroceles should
ing may be necessary. The postconceptual age (gesta- be opened widely and drained. It is important to ensure
tional age plus chronologic age) is commonly used to that the testis is in the scrotum at the conclusion of the
decide which infants require overnight admission. Several procedure to avoid iatrogenic cryptorchidism.
studies have addressed this issue.49,50 A review of 127 Sliding hernias are uncommon but are more frequent
premature infants admitted after inguinal hernia repair in females, with an incidence as high as 2040%. A fal-
found a incidence of apnea of about 5%, and attempted lopian tube or ovary may be involved. The bladder may
to identify factors associated with a higher risk (history constitute the medial wall of the sac in infants.61 The
of prior apnea, lower gestational age and birth weight, appendix (Amyands hernia) may form a sliding compo-
comorbidities).50 A less than 1% risk of postoperative nent on the right. More distal ligation of the sac with
apnea was found in former premature infants greater than proximal purse-string inversion is our preferred manage-
56 weeks postconceptual age in a comprehensive analysis ment technique for sliding inguinal hernias.62
of eight prospective studies.51 Sixty weeks postconceptual Mesh or prosthetic materials are almost never
age is widely used as a cut-off for admission (although required in children. One exception may be recurrent
there is substantial institutional variability). However, a hernias in children with connective tissue disorders or
more recent retrospective review at our hospital demon- mucopolysaccharidoses.
strated a low incidence of adverse events after 50 weeks
postconceptual age.52 Laparoscopic Repair Technique
An accurate description of the current state of pediatric
Timing laparoscopic inguinal hernia repair is a moving target. In
As premature infants have an increased incidence of an 2002, Schier and colleagues reported a large series of 933
inguinal hernia, this is a common diagnosis in the laparoscopic inguinal hernia repairs in children with a
50 Inguinal Hernias and Hydroceles 683
Hernia sac
Transverse
inguinal
incision
A B Vas deferens C
Vessels of the cord
FIGURE 50-2 (A) After a right inguinal incision in an infant boy, the sac has been separated from the vas and vessels by grasping
the sac and teasing the cord structures away. The hernia sac, located anteromedial to the cord, has been carefully separated from
the vas and vessels (vessel loop) and is clamped in preparation for division of the sac. (B) In preparation for diagnostic laparoscopy
to evaluate the contralateral internal ring, the sac is opened. A vessel loop is around the cord structures. (C) A cannula has been
introduced into the opened hernia sac and the sac has been tied (solid arrow) to keep the abdomen insufflated. The cord structures
(dotted arrow) are retracted with the vessel loop.
A B
FIGURE 50-3 Laparoscopic evaluation of the contralateral inguinal region is used by many pediatric surgeons. (A) A view of the left
internal ring shows the inverted V of the laterally located gonadal vessels and the medial vas. At the apex of the V, the left internal
inguinal ring is completely closed. (B) A right-patent process vaginalis is seen in a 7-year-old with a known left inguinal hernia.
A B C
FIGURE 50-4 (A) In a small percentage of cases, a veil of peritoneum will cover the contralateral internal ring and obscure the
laparoscopic findings such that the surgeon is not completely certain whether a contralateral patent processus vaginalis (CPPV) is
present. In this situation, a technique has been reported to retract the veil of tissue. (B) A silver probe is introduced in the contra
lateral lower abdomen/flank and used to retract the veil medially so that the 70-degree telescope can then look down the possible
CPPV. (C) In this patient, a significant CPPV was visualized once the veil of peritoneum was retracted medially. (Adapted from Geiger
JD. Selective laparoscopic probing for a contralateral patent processus vaginalis reduces the need for a contralateral exploration in inconclu-
sive cases. J Pediatr Surg 2000;35:11514.)
684 SECTION V Inguinal Region and Scrotum
mean age of 3.2 years and a recurrence rate of 3.4%.63 sac, or simply poor visualization.28 Contralateral hernias
Other reports followed with a similarly increased recur- after successful but negative contralateral evaluation been
rence rate compared to open repairs.64 However, in the reported in 1.62.5% of patients.81,84
last few years, there have been several large series of
laparoscopic inguinal hernia repairs in infants and chil- Incidence of Metachronous Hernia
dren with low recurrence and complication rates.6569
A recent meta-analysis of three randomized controlled Many reports have addressed the incidence of a contral-
trials and four observational studies compared 1,543 ateral clinical hernia after unilateral repair, and most have
laparoscopic repairs to 657 open repairs and found no documented a 610% incidence.74,8588 Left-sided initial
difference in recurrence, a decreased incidence of meta- hernias may be associated with an increased risk of a
chronous hernia with laparoscopy, and decreased opera- symptomatic contralateral hernia. Younger patient age
tive time for bilateral repairs done laparoscopically.65 and prematurity have also been identified as markers for
Another 2011 meta-analysis of 2,699 children found no an increased risk of metachronous hernia.
statistically significant difference in recurrence rates, but A 2007 meta-analysis of 49 papers with data on 22,846
an increased operative time with laparoscopic unilateral children found an overall incidence of 7.2%, with no
repair.66 The authors confirmed the decreased incidence gender difference.89 However, a left-sided inguinal hernia
of metachronous hernia in the laparoscopic group. had a significantly higher risk than right-sided (10.2% vs
Improvement in laparoscopic recurrence rates appears to 6.3%). A prospective study of 548 patients followed
be due to various technical modifications of the proce- for a mean of two years found that 8.8% developed a
dure. Generally, it appears that extracorporeal knot-tying contralateral hernia, with an average interval of six
yields superior results. Several recent large series have months. The incidence was higher in younger infants,
reported recurrence rates less than 0.5%.6769 premature infants, and females.90 An older meta-analysis
of 15,310 patients from several studies found a 7% inci-
dence of a metachronous hernia.72 A prospective study in
Contralateral Evaluation which 222 children with unilateral hernia underwent
Contralateral exploration for unilateral inguinal hernia in laparoscopy, and 67 clinically followed without repair of
children has a long and controversial history. Meta-, an incidental PPV noted that 6.8% developed a meta-
cost-, and decision-tree analyses have all been chronous hernia.91 MacGregor etal. followed 160 chil-
performed.7074 Routine contralateral open exploration is dren under age 10 years who underwent a unilateral
probably not justified. Surveys of pediatric surgeons have inguinal hernia repair over a 32-year period. Ninety-six
demonstrated a decrease in the practice of routine con- percent were followed for a mean of 20 years. Over this
tralateral exploration over time, while laparoscopic evalu- time, 29% developed a symptomatic contralateral
ation of the contralateral side via the ipsilateral hernia inguinal hernia. Interestingly, the authors did not recom-
opening has grown in popularity.75,76 mend routine contralateral exploration due to its risks (in
the open era).92
Incidence of PPV
Diagnostic laparoscopy in children with a unilateral
Pain Management
hernia allows identification of a contralateral PPV (see A randomized prospective trial of local instillation of
Figs 50-3 and 50-4), with the caveat that (1) some PPVs long-acting analgesics (e.g., bupivacaine) versus caudal
will not develop into clinically symptomatic hernias and block for postoperative pain control in infants and chil-
(2) it may be difficult to distinguish a peritoneal fold from dren after inguinal hernia repair demonstrated no signifi-
a true PPV. This technique was initially described in the cant difference in pain control.93 Instillation of local
early 1990s by Lobe and Holcomb.77,78 anesthetics into the wound (splash technique) is effec-
The mean additional operating time is minimal in tive as well. Ilioinguinal nerve block was also shown to
most reports (four to five minutes).79 There is some eco- provide better analgesia than transverse abdominis plane
nomic justification for this approach as well,71,80 although block in a prospective randomized trial.94
not all other reports agree.80 The reported incidence of
PPV in unilateral hernia repairs has varied, but is typi-
cally 2540%.
In a 2011 review of 684 children, contralateral laparo-
COMPLICATIONS
scopic evaluation was positive in 32% of right-sided and Recurrence
42% of left-sided hernias.81 A similar report of 1,001
children found a 24% incidence of PPV, decreasing with The risk of recurrence after an elective inguinal hernia
age and male gender.79 A contralateral PPV was found in repair is less than 1% in several large series.12,95 It is
38% of 453 children, decreasing with age.82 Younger age, higher in premature infants, in children with incarcerated
female gender, and a left-sided unilateral hernia have hernias, and those with associated diseases (e.g., connec-
been used as selection criteria, while some authors argue tive tissue disorder, VPS).17,95 Recurrence rates can be as
for routine diagnostic contralateral laparoscopy in all high as 50% in children with connective tissues disorders
children.8183 and mucopolysaccharidoses. A recurrent hernia even can
Contralateral laparoscopic evaluation is impossible in be the presenting symptom in these diseases.95 Recur-
about 5% of children, usually due to a very small hernia rence rates may also be higher in teenagers.12
50 Inguinal Hernias and Hydroceles 685
Injury to the Spermatic Cord or Testis the patients reported occasional mild groin pain, usually
related to physical activity (pain was frequent or moder-
Injury to the spermatic cord or testis is a rare occurrence ate in only 2%).101
in elective hernia repairs, with an incidence of approxi- Loss of domain due to a huge hernia is another
mately 1 in 1,000.12 The true incidence may be underes- problem more frequently seen in adults, but it can occur
timated since instrument manipulation of the cord causes in infants or children and may require staged repair or
microscopic injury and scarring in animal models.96,97 A other measures.102 Iatrogenic cryptorchidism from failure
recognized injury to the vas should be managed by imme- to replace the testis in normal anatomic position is a rare
diate repair with fine (8-0) suture under magnification, occurrence (<1%). Bladder injury in infants in whom the
and the family should be informed of the event. In insti- medial wall of the sac contains urinary bladder is also a
tutions in which hernia sacs are routinely examined by a rare complication.103
pathologist, mesonephric or adrenal rests are occasionally Mortality directly related to inguinal hernia or its
seen, but do not indicate injury to the vas. A review of repair is exceedingly rare (<1%).
7,314 male pediatric hernia specimens over a 14-year
period at a major childrens hospital found either vas
deferens or epididymis in 0.53% of specimens.98 Recent
reviews of the subject have concluded that routine histo- SPECIAL ISSUES
logic examination of male hernia sacs is not necessary.99,100
Testicular atrophy from vascular injury during routine Direct Inguinal Hernia
inguinal hernia repair is also uncommon.
Direct inguinal hernias are very unusual in children, even
older teenagers.104 However, the incidence was as high as
Other Complications 4% in one laparoscopic series.105Some recurrences after
indirect inguinal hernia repair are direct inguinal hernias.
In a recent retrospective review of 268 patients less than
Direct inguinal hernias in children are managed as stand-
2 years of age (98 of whom were premature), prematurity
ard adult inguinal hernia repairs. Our preference is
was a marker for an increased risk of complications
for a McVay repair (approximation of the transversalis
following inguinal hernia repair (28% vs 12% in term
aponeurotic arch and internal oblique aponeurosis to the
infants).58
anterior ileopubic tract and shelving edge of the inguinal
Infection occurs in 13% of cases, and postoperative
ligament). Laparoscopic repair is another option.
hematoma has a similarly low incidence. Persistent
hydrocele can occur, particularly if a very large hydrocele
was present preoperatively. It is important to educate the Femoral Hernia
family about this possibility before repair. Most postop-
erative hydroceles can be observed for six to 12 months. Femoral hernias are relatively equally distributed by
If they do not resolve, aspiration may be tried once or gender,106,107 but are much less common than indirect
twice. In our experience, aspiration is not usually perma- inguinal hernias. In two combined series of over 10,000
nently successful. Persistent non-resolving hydroceles patients, 0.2% of hernias were femoral.104,108 Most (two-
may require transumbilical diagnostic laparoscopy to thirds) are not suspected before operation (Fig. 50-5).104,107
exclude a recurrent hernia. In the absence of recurrence, A mass below the inguinal ligament should alert the clini-
a transcrotal exploration and obliteration of the hydrocele cian to this possibility. Femoral hernias are bilateral in 10
sac is usually effective. to 20%. Recurrence is increased after femoral hernia
Chronic pain after herniorrhaphy, although seen in repair compared with indirect inguinal herniorrhaphy.106
adults, is uncommon in children. However, one recent McVay repair has been the standard technique for repair,
review of 651 adults who had undergone inguinal but laparoscopic and mesh-plug repairs have been used
hernia repair before age five years found that 13.5% of as well.109,110
A B
FIGURE 50-5 This young girl presented with symptoms suggestive, but not conclusive, of a left femoral hernia. Therefore, diagnostic
laparoscopy was performed through the umbilicus to confirm the diagnosis prior to an inguinal approach and a McVay repair.
(A) The internal opening (arrow) to the femoral hernia is seen. (B) After the McVay repair, the femoral defect is closed.
686 SECTION V Inguinal Region and Scrotum
REFERENCES
1. Lau WY. History of treatment of groin hernia. World J
Surg [Internet] 2002;26(6):74859. Available from: http://
www.springerlink.com/index/10.1007/s00268-002-6297-5.
2. Lascaratos JG, Tsiamis C, Kostakis A. Surgery for inguinal hernia
in Byzantine Times (A.D. 324-1453): First Scientific Descriptions.
World J Surg 2003;27:11659.
3. Cloquets hernia (www.whonamedit.com) [Internet]. whonamedit.
com. [cited 2012 Jun. 21]. Available from: http://www.whonamedit.
com/synd.cfm/2654.html.
4. Cloquet J. Recherches Anatomiques sur les Hernies de lAbdomen.
Paris; 1817.
5. Marcy H. A new use of carbolized cat gut ligatures. Boston Med
FIGURE 50-6 Rarely, sphenogonadal fusion is found at the time Surg J 1871;85:31516.
of inguinal hernia repair. The splenic remnant (white arrow) and 6. Czerny Von V. Studien zur Radikalbehandlung der Hernien.
testis (black arrow) are fused. The splenic tissue was safely Wien Med Wochenschr 1877;27:497528554578.
excised. 7. Sachs M, Damm M, Encke A. Historical evolution of inguinal
hernia repair. World J Surg 1997;21:21823.
8. Bassini E. Nuovo Metodo Operativo per la Cura dellErnia
Inguinale. R Stabilimento Prosperini; 1889.
9. Gross RE. Inguinal Hernia. The Surgery of Infancy and Child-
Absent or Atrophic Vas hood. Philadelphia: W.B. Saunders; 1953. p. 44962.
10. Bronsther B, Abrams MW, Elboim C. Inguinal hernias in
Occasionally, a small or absent vas is found during childrena study of 1,000 cases and a review of the literature.
inguinal hernia repair. Renal ultrasound is necessary J Am Med Womens Assoc 1972;27:5225.
because of associated ipsilateral renal agenesis.111,112 This 11. Bakwin H. Indirect inguinal hernia in twins. J Pediatr Surg
should also prompt a workup for cystic fibrosis. Congeni- 1971;6:1658.
12. Ein SH, Njere I, Ein A. Six thousand three hundred sixty-one
tal absence (bilateral or unilateral) of the vas is a hetero- pediatric inguinal hernias: A 35-year review. J Pediatr Surg
geneous disorder, largely due to mutations in the cystic 2006;1:9806.
fibrosis gene. Differing genotypes are noted with con- 13. Harper RG, Garcia A, Sia C. Inguinal hernia: A common problem
genital absence of the vas as an isolated entity versus of premature infants weighing 1,000 grams or less at birth. Pedi-
congenital absence of the vas in association with renal atrics 1975;56:11215.
14. Kumar VHS, Clive J, Rosenkrantz TS, et al. Inguinal hernia in
anomalies.113 preterm infants. Pediatr Surg Int 2002;18:14752.
15. Grosfeld JL. Current concepts in inguinal hernia in infants and
children. World J Surg 1989;13:50615.
Disorders of Sexual Differentiation 16. Holsclaw DS, Shwachman H. Increased incidence of inguinal
hernia, hydrocele, and undescended testicle in males with cystic
The finding of a testis during repair of a female hernia fibrosis. Pediatrics 1971;48:4425.
should raise the suspicion of congenital androgen insen- 17. Celik A, Ergn O, Arda MS, et al. The incidence of inguinal
sitivity syndrome (CAIS) or true hermaphroditism.114 As complications after ventriculoperitoneal shunt for hydrocephalus.
many as 1% of female infants with inguinal hernias will Childs Nerv Syst 2005;21:447.
have CAIS.115 Bilateral hernias in girls are not associated 18. Clarnette TD, Lam SK, Hutson JM. Ventriculo-peritoneal shunts
in children reveal the natural history of closure of the processus
with a higher risk of CAIS than is a unilateral hernia. vaginalis. J Pediatr Surg 1998;33:41316.
Conversely, as many as 75% of CAIS patients present 19. Wu JC, Chen YC, Liu L, et al. Younger boys have a higher risk
with a hernia. of inguinal hernia after Ventriculo-Peritoneal Shunt: A 13-year
At the time of hernia repair (or later as a separate nationwide cohort study. JACS 2012;214:84551.
20. Glick PL, Boulanger SC. Inguinal Hernias and Hydroceles. In:
procedure), laparoscopy is a good way to evaluate for the Coran AG, Adzick NS, Krummel T, et al, editors. Pediatric
presence or absence of the fallopian tube, ovary, and Surgery. 7th ed. Philadelphia: Elsevier/Saunders; 2012.
uterus. The gonad should be sampled. Some advocate 21. Ilioinguinal nerve [Internet]. en.wikipedia.org. [cited 2012 Jun.
rectal examination to palpate the uterus. Vaginoscopy is 27]. Available from: http://en.wikipedia.org/wiki/Ilioinguinal_
another option. In the presence of CAIS, an absent cervix nerve.
22. Gray SW, Skandalakis JE. Embryology for surgeons. 2nd ed.
will be found, and vaginal length is shortened in this Baltimore: Williams & Wilkins; 1994. p. 54093.
syndrome.115 Karyotyping and pelvic ultrasound should 23. Lie G, Hutson JM. The role of cremaster muscle in testicular
also be performed. Eventual gonadectomy will be neces- descent in humans and animal models. Pediatr Surg Int
sary, although the optimal timing is controversial. 2011;27:125565.
24. Clarnette TD, Hutson JM. The genitofemoral nerve may link
testicular inguinoscrotal descent with congenital inguinal hernia.
Other Aust N Z J Surg 1996;66:61217.
25. Heyns CF. The gubernaculum during testicular descent in the
Incidentally discovered yellow nodules along the sper- human fetus. J Anat 1987;153:93112.
matic cord or testis are due to adrenal rests. In one study, 26. Rowe MI, Copelson LW, Clatworthy HW. The patent processus
vaginalis and the inguinal hernia. J Pediatr Surg 1969;4:1027.
the incidence was 1.7% in 1,862 pediatric hernia repairs.116 27. Luo C-C, Chao H-C. Prevention of unnecessary contralateral
These should be removed if possible. Splenogonadal exploration using the silk glove sign (SGS) in pediatric patients
fusion is a very rare entity that may be difficult to with unilateral inguinal hernia. Eur J Pediatr 2006;166:6679.
50 Inguinal Hernias and Hydroceles 687
28. Valusek PA, Spilde TL, Ostlie DJ, et al. Laparoscopic evaluation 53. Misra D. Inguinal hernias in premature babies: Wait or operate?
for contralateral patent processus vaginalis in children with Acta Paediatr 2001;90:3701.
unilateral inguinal hernia. J Laparoendosc Adv Surg Tech A 54. Lautz TB, Raval MV, Reynolds M. Does timing matter? A
2006;166:6503. national perspective on the risk of incarceration in premature
29. Chen KC, Chu CC, Chou TY, et al. Ultrasonography for inguinal neonates with inguinal hernia. J Pediatr 2011;158:5737.
hernias in boys. J Pediatr Surg 1998;33:17847. 55. Miller GG, McDonald SE, Milbrandt K, et al. Risk of incarcera-
30. Erez I, Rathause V, Vacian I, et al. Preoperative ultrasound and tion of inguinal hernia among infants and young children awaiting
intraoperative findings of inguinal hernias in children: A prospec- elective surgery. CMAJ 2008;179:10015.
tive study of 642 children. J Pediatr Surg 2002;37:8658. 56. Lee SL, Gleason JM, Sydorak RM. A critical review of premature
31. Naji H, Ingolfsson I, Isacson D, et al. Decision making in the infants with inguinal hernias: Optimal timing of repair, incarcera-
management of hydroceles in infants and children. Eur J Pediatr tion risk, and postoperative apnea. J Pediatr Surg 2011;46:
2012;171:80710. 21720.
32. Lau ST, Lee Y-H, Caty MG. Current management of hernias and 57. Vaos G, Gardikis S, Kambouri K, et al. Optimal timing for repair
hydroceles. Sem Pediatr Surg 2007;16:507. of an inguinal hernia in premature infants. Pediatr Surg Int
33. Koski M, Makari J, Adams M. Infant communicating hydroceles 2010;26:37985.
do they need immediate repair or might some clinically resolve? 58. Gholoum S, Baird R, Laberge J-M, et al. Incarceration rates in
J Pediatr Surg 2010;45:5903. pediatric inguinal hernia: Do not trust the coding. J Pediatr Surg
34. Chang Y-T, Lee J-Y, Wang J-Y, et al. Hydrocele of the spermatic 2010;45:100711.
cord in infants and children: Its particular characteristics. Urology 59. Calkins CM, St Peter SD, Balcom A, et al. Late abscess formation
2010;76:826. following indirect hernia repair utilizing silk suture. Pediatr Surg
35. Andrews EW. The Bottle Operation method for the radical cure Int 2007;23:34952.
of hydrocele. Ann Surg 1907;46:91518. 60. Nagar H. Stitch granulomas following inguinal herniotomy: A
36. Wilson J, Aaronson D, Schrader R. Hydrocele in the pediatric 10-year review. J Pediatr Surg 1993;28:15057.
patient: Inguinal or scrotal approach? J Urol 2008;180: 61. Redman JF, Jacks DW, ODonnell PD. Cystectomy: A cata-
1427727. strophic complication of herniorrhaphy. J Urol 1985;133:978.
37. Martin K, Emil S, Laberge J-M. The value of laparoscopy in the 62. Bevan A. Sliding inguinal hernia of the ascending colon and
management of abdominoscrotal hydroceles. J Laparoendosc Adv cecum, the descending colon, sigmoid, and the bladder. Ann Surg
Surg Tech A 2012;22:41921. 1930;92:7924.
38. Stephens BJ, Rice WT, Koucky CJ, et al. Optimal timing of elec- 63. Schier F, Montupet P, Esposito C. Laparoscopic inguinal hernior-
tive indirect inguinal hernia repair in healthy children: Clinical rhaphy in children: A three-center experience with 933 repairs.
considerations for improved outcome. World J Surg 1992;16: J Pediatr Surg 2002;37:3957.
9526. 64. Schier F. Laparoscopic inguinal hernia repair-A prospective per-
39. Rowe MI, Clatworthy HW. Incarcerated and strangulated hernias sonal series of 542 children. J Pediatr Surg 2006;41:10814.
in children. A statistical study of high-risk factors. Arch Surg 65. Yang C, Zhang H, Pu J, et al. Laparoscopic vs open herniorrhaphy
1970;101:1369. in the management of pediatric inguinal hernia: A systemic review
40. Palmer BV. Incarcerated inguinal hernia in children. Ann R Coll and meta-analysis. J Pediatr Surg 2011;46:182434.
Surg Engl 1978;60:1214. 66. Alzahem A. Laparoscopic versus open inguinal herniotomy in
41. Stylianos S, Jacir NN, Harris BH. Incarceration of inguinal infants and children: A meta-analysis. Pediatr Surg Int 2011;27:
hernia in infants prior to elective repair. J Pediatr Surg 1993;28: 60512.
5823. 67. Tam YH, Lee KH, Sihoe JDY, et al. Laparoscopic hernia repair
42. Puri P, Guiney EJ, ODonnell B. Inguinal hernia in infants: in children by the hook method: A single-center series of 433
The fate of the testis following incarceration. J Pediatr Surg consecutive patients. J Pediatr Surg 2009;44:15025.
1984;19:446. 68. Endo M, Watanabe T, Nakano M, et al. Laparoscopic completely
43. Shalaby R, Shams AM, Mohamed S, et al. Two-trocar needle- extraperitoneal repair of inguinal hernia in children: A single-
scopic approach to incarcerated inguinal hernia in children. institute experience with 1,257 repairs compared with cut-down
J Pediatr Surg 2007;42:125962. herniorrhaphy. Surg Endosc 2009;23:170612.
44. Takehara H, Hanaoka J, Arakawa Y. Laparoscopic strategy for 69. Chen K, Xiang G, Wang H, et al. Towards a near-zero recurrence
inguinal ovarian hernias in children: When to operate for irreduc- rate in laparoscopic inguinal hernia repair for pediatric patients.
ible ovary. J Laparoendosc Adv Surg Tech A 2009;19:S129 J Laparoendosc Adv Surg Tech A 2011;21:4458.
S131. 70. Burd RS, Heffington SH, Teague JL. The optimal approach for
45. Nah SA, Giacomello L, Eaton S, et al. Surgical repair of incarcer- management of metachronous hernias in children: A decision
ated inguinal hernia in children: Laparoscopic or open? Eur J analysis. J Pediatr Surg 2001;36:11905.
Pediatr Surg 2011;21:811. 71. Miltenburg DM, Nuchtern JG, Jaksic T, et al. Laparoscopic eval-
46. Nagraj S, Sinha S, Grant H, et al. The incidence of complications uation of the pediatric inguinal herniaA meta-analysis. J Pediatr
following primary inguinal herniotomy in babies weighing 5kg Surg 1998;33:8749.
or less. Pediatr Surg Int 2006;22:5002. 72. Miltenburg DM, Nuchtern JG, Jaksic T, et al. Meta-analysis of
47. Levitt MA, Ferraraccio D, Arbesman MC, et al. Variability of the risk of metachronous hernia in infants and children. Am J Surg
inguinal hernia surgical technique: A survey of North American 1991;174:7414.
pediatric surgeons. J Pediatr Surg 2002;37:74551. 73. Muensterer OJ, Woller T, Metzger R, et al. [The economics of
48. Craven PD, Badawi N, Henderson-Smart DJ, et al. Regional contralateral laparoscopic inguinal hernia exploration: Cost calcu-
(spinal, epidural, caudal) versus general anaesthesia in preterm lation of herniotomy in infants.]. Chirurg 2008;79:106571.
infants undergoing inguinal herniorrhaphy in early infancy. 74. Nataraja RM, Mahomed AA. Systematic review for paediatric
Cochrane Database Syst Rev 2003;(3):CD003669. metachronous contralateral inguinal hernia: A decreasing concern.
49. Cot CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in Pediatr Surg Int 2011;27:95361.
former preterm infants after inguinal herniorrhaphy. A combined 75. Antonoff MB, Kreykes NS, Saltzman DA, et al. American
analysis. Anesthesiology 1995;82:80922. Academy of Pediatrics Section on Surgery hernia survey revisited.
50. Murphy JJ, Swanson T, Ansermino M, et al. The frequency of J Pediatr Surg 2005;40:100914.
apneas in premature infants after inguinal hernia repair: Do they 76. Wiener ES, Touloukian RJ, Rodgers BM, et al. Hernia survey of
need overnight monitoring in the intensive care unit? J Pediatr the Section on Surgery of the American Academy of Pediatrics.
Surg 2008;43:8658. J Pediatr Surg 1996;31:11669.
51. Malviya S, Swartz J, Lerman J. Are all preterm infants younger 77. Lobe TE, Schropp KP. Inguinal hernias in pediatrics: Initial expe-
than 60 weeks postconceptual age at risk for postanesthetic apnea? rience with laparoscopic inguinal exploration of the asymptomatic
Anesthesiology 1993;78:107681. contralateral side. J Laparoendosc Surg 1992;2:13540.
52. Laituri CA, Garey CL, Pieters BJ, et al. Overnight observation in 78. Holcomb GW III, Brock JW, Morgan WM. Laparoscopic evalu-
former premature infants undergoing inguinal hernia repair. ation for a contralateral patent processus vaginalis. J Pediatr Surg
J Pediatr Surg 2012;47:21720. 1994;29:9703.
688 SECTION V Inguinal Region and Scrotum
79. Saad S, Mansson J, Saad A, et al. Ten-year review of groin lapar- 97. Abasiyanik A, Gvenc H, Yavuzer D, et al. The effect of iatrogenic
oscopy in 1001 pediatric patients with clinical unilateral inguinal vas deferens injury on fertility in an experimental rat model.
hernia: An improved technique with transhernia multiple-channel J Pediatr Surg 1997;32:11446.
scope. J Pediatr Surg 2011;46:101114. 98. Steigman CK, Sotelo-Avila C, Weber TR. The incidence of sper-
80. Lee SL, Sydorak RM, Lau ST. Laparoscopic contralateral groin matic cord structures in inguinal hernia sacs from male children.
exploration: Is it cost effective? J Pediatr Surg 2010;45:7935. Am J Surg Pathol 1999;23:8805.
81. Draus JM, Kamel S, Seims A, et al. The role of laparoscopic 99. Miller GG, McDonald SE, Milbrandt K, et al. Routine pathologi-
evaluation to detect a contralateral defect at initial presentation cal evaluation of tissue from inguinal hernias in children is unnec-
for inguinal hernia repair. Am Surg 2011;77:14636. essary. Can J Surg 2003;46:11719.
82. Lazar DA, Lee TC, Almulhim SI, et al. Transinguinal 100. Kim B, Leonard MP, Bass J, et al. Analysis of the clinical signifi-
laparoscopic exploration for identification of contralateral cance and cost associated with the routine pathological analysis of
inguinal hernias in pediatric patients. J Pediatr Surg 2011;46: pediatric inguinal hernia sacs. J Urol 2011;186:16204.
234952. 101. Aasvang EK, Kehlet H. Chronic pain after childhood groin hernia
83. Yerkes EB, Brock JW, Holcomb GW III, et al. Laparoscopic repair. J Pediatr Surg 2007;42:14038.
evaluation for a contralateral patent processus vaginalis: Part III. 102. Khozeimeh N, Henry MCW, Gingalewski CA, et al. Management
Urology 1998;51:4803. of congenital giant inguinal scrotal hernias in the newborn.
84. Juang D, Garey CL, Ostlie DJ, et al. Contralateral inguinal hernia Hernia 2011 (EPUB).
after negative laparoscopic evaluation: A rare but real phenome- 103. Aloi IP, Lais A, Caione P. Bladder injuries following inguinal canal
non. J Laparoendosc Adv Surg Tech A 2012;22:2002. surgery in infants. Pediatr Surg Int 2010;26:120710.
85. Chertin B, De Caluw D, Gajaharan M, et al. Is contralateral 104. Fonkalsrud EW, Delorimier A, Clatworthy HW. Femoral and
exploration necessary in girls with unilateral inguinal hernia? direct inguinal hernias in infants and children. JAMA 1965;
J Pediatr Surg 2003;38:7567. 192:5979.
86. Shabbir J, Moore A, OSullivan JB, et al. Contralateral groin 105. Gorsler CM, Schier F. Laparoscopic herniorrhaphy in children.
exploration is not justified in infants with a unilateral inguinal Surg Endosc 2003;17:5713.
hernia. Ir J Med Sci 2003;172:1819. 106. De Caluw D, Chertin B, Puri P. Childhood femoral hernia: A
87. Ballantyne A, Jawaheer G, Munro FD. Contralateral groin explo- commonly misdiagnosed condition. Pediatr Surg Int 2003;19:
ration is not justified in infants with a unilateral inguinal hernia. 6089.
Br J Surg 2001;88:7203. 107. Al-Shanafey S, Giacomantonio M. Femoral hernia in children.
88. Given JP, Rubin SZ. Occurrence of contralateral inguinal hernia J Pediatr Surg 1999;34:11046.
following unilateral repair in a pediatric hospital. J Pediatr Surg 108. Burke J. Femoral hernia in childhood. Ann Surg 1967;166:
1989;24:9635. 2879.
89. Ron O, Eaton S, Pierro A. Systematic review of the risk of devel- 109. Adibe OO, Hansen EN, Seifarth FG, et al. Laparoscopic-assisted
oping a metachronous contralateral inguinal hernia in children. repair of femoral hernias in children. J Laparoendosc Adv Surg
Br J Surg 2007;94:80411. Tech A 2009;19:6914.
90. Tackett LD, Breuer CK, Luks FI, et al. Incidence of contralateral 110. Matthyssens LEM, Philippe P. A new minimally invasive tech-
inguinal hernia: A prospective analysis. J Pediatr Surg 1999;34: nique for the repair of femoral hernia in children: About 13
6847. laparoscopic repairs in 10 patients. J Pediatr Surg 2009;44:
91. Maddox MM, Smith DP. A long-term prospective analysis of 96771.
pediatric unilateral inguinal hernias: Should laparoscopy or any- 111. Lukash F, Zwiren GT, Andrews HG. Significance of absent vas
thing else influence the management of the contralateral side? deferens at hernia repair in infants and children. J Pediatr Surg
J Pediatr Urol 2008;4:1415. 1975;10:7659.
92. McGregor DB, Halverson K, McVay CB. The unilateral pediatric 112. Schlegel PN, Shin D, Goldstein M. Urogenital anomalies in men
inguinal hernia: Should the contralateral side by explored? with congenital absence of the vas deferens. J Urol 1996;155:
J Pediatr Surg 1980;15:31317. 16448.
93. Machotta A, Risse A, Bercker S, et al. Comparison between instil- 113. Casals T, Bassas L, Egozcue S, et al. Heterogeneity for mutations
lation of bupivacaine versus caudal analgesia for postoperative in the CFTR gene and clinical correlations in patients with con-
analgesia following inguinal herniotomy in children. Paediatr genital absence of the vas deferens. Hum Reprod 2000;15:
Anaesth 2003;13:397402. 147683.
94. Fredrickson MJ, Paine C, Hamill J. Improved analgesia with the 114. Hughes IA, Davies JD, Bunch TI, et al. Androgen insensitivity
ilioinguinal block compared to the transverse abdominis plane syndrome. Lancet 2012;380:141928.
block after pediatric inguinal hernia surgery: A prospective rand- 115. Hurme T, Lahdes-Vasama T, Makela E, et al. Clinical findings in
omized trial. Pediatr Anaesth 2010;20:10227. prepubertal girls with inguinal hernia with special reference to the
95. Grosfeld JL, Minnick K, Shedd F, et al. Inguinal hernia in chil- diagnosis of androgen insensitivity syndrome. Scand J Urol
dren: Factors affecting recurrence in 62 cases. J Pediatr Surg Nephrol 2009;43:426.
1991;26:2837. 116. Ketata S, Ketata H, Sahnoun A, et al. Ectopic adrenal cortex
96. Shandling B, Janik JS. The vulnerability of the vas deferens. tissue: An incidental finding during inguinoscrotal operations in
J Pediatr Surg 1981;16:4614. pediatric patients. Urol Int 2008;81:31619.
C H A P T E R 5 1
4 Diagnosis
Given the historic variability in the definition of what
constitutes an UDT, it is not surprising that confusion
exists in the primary care setting as well. A careful history
and physical examination is thus paramount.
The patient should be examined in a warm room in
5
both supine and frog-legged sitting position. The scrotum
is observed for hypoplasia and examined for the presence
of either testis. In cases of monorchia, the solitary testis
may be compensatorily hypertrophied. The first maneu-
FIGURE 51-1 Testicular descent in males: 1, 90mm crown
ver to locate the testis is to walk the fingers from the iliac
rump length (CRL) (1224 weeks of gestational age); 2, 125mm crest along the inguinal canal towards the scrotum,
CRL (1517 weeks); 3, 230mm CRL (2426 weeks); 4, 280mm pushing subcutaneous structures toward the scrotum.
CRL (28-30 weeks); 5, at term. The convoluted structure is the The scrotum should not be palpated prior to this maneu-
epididymis. (Adapted from Hadziselimovic F. Embryology of tes- ver as it may activate the cremasteric reflex, thus retract-
ticular descent and maldescent. In: Hadziselimovic F, editor. Cryp-
torchidism: Management and Implications. New York: Springer-Verlag; ing the testis. Lubricating gel or soap may help reduce
1983. p. 23.) friction. Gentle mid-abdominal pressure may help push
the testis into the inguinal canal. A cross-legged sitting
or squatting position may also help identify the testis. It
can be particularly challenging to obtain an accurate
region, perineum, femoral canal, penopubic area, or even exam on a ticklish or obese boy. Approximately 18% of
contralateral hemiscrotum. Ascending or acquired UDT nonpalpable testes are subsequently palpated when exam-
refers to a testis that was previously descended on exami- ined under anesthesia in the operating room.30,31
nation, but at a later time can no longer be brought down On examination, both retractile testes and low UDTs
into the scrotum. While an association between retractile may be manipulated into the scrotum. Once in scrotal
testes and secondary testicular ascent has been identified, position, the retractile testis appears to remain in place,
a link between rate of height growth and ascended testes whereas the low UDT does not. The ipsilateral hemis-
suggests that the ability to reach the scrotum changes crotum is fully developed with a retractile testis, whereas
with a childs growth.22,23 Acquired UDT may also be it may be underdeveloped in a UDT.
iatrogenic, as when a previously descended testis becomes If neither testis is palpable, anorchia, androgen insen-
trapped in scar tissue cephalad to the scrotum after sitivity syndrome, or a chromosomal abnormality must
inguinal surgery. be differentiated from bilateral UDT. If the baseline
A nonpalpable testis may be simply intra-abdominal follicle-stimulating hormone (FSH) level is elevated
some of the time, or truly vanished due to intrauterine (three standard deviations above the mean) in a boy
or perinatal torsion. This condition is known as younger than 9 years, anorchia is likely and no further
monorchia, or anorchia if both testes are absent. evaluation is recommended. If baseline luteinizing
hormone (LH) and FSH levels are normal and human
Incidence chorionic gonadotropic (hCG) stimulation results in an
appropriate elevation of testosterone, functioning tes-
UDT occurs in approximately 3% of term male infants ticular tissue is likely to be present and the patient should
and in up to 3345% of premature and/or birth weight undergo exploration. However, if the testosterone level
<2.5kg male infants.24 The majority of testes descend does not increase appropriately, nonfunctional testicular
within the first 6 to 12 months such that at 1 year, the tissue may still be present and exploration should still be
incidence is down to 1%. Testicular descent after 1 year performed. The hCG stimulation test does not distin-
is unlikely.25 However, 23% of boys in the USA, and up guish between normal nonpalpable testes and function-
to 5.3% in some European series, undergo orchiopexy ing testicular remnants.32
for UDT.26,27 This discrepancy between higher orchi- Radiographic imaging is rarely helpful in locating a
opexy rates and actual incidence of the disease is thought UDT and is not recommended routinely. Multiple studies
to lie partially in misdiagnosis between retractile testes, have shown that the experienced surgeon/examiner has
but also from acquired UDT. The overall rate of second- a higher sensitivity in locating the UDT than does
ary testicular ascent has been reported between 245%.28,29 ultrasonography (US), computed tomography (CT), or
51 Undescended Testes and Testicular Tumors 691
magnetic resonance imaging (MRI), especially because arising in testes that remain in the abdomen are most
the sensitivity of imaging is poor in detection of soft frequently seminomas (74%).56,57 In contrast, malignan-
tissue masses less than 1cm.33 In unusual situations of cies arising after successful orchiopexy, regardless of
bilateral nonpalpable testes, MRI with gadolinium may original location, are most frequently nonseminomatous
be useful for detecting abdominal testes because testicu- germ cell tumors (63%).58,59
lar tissue is particularly bright on MRI.34,35 Among men with testicular cancer, up to 10% have a
While easy to perform with minimal risk, ultrasound history of UDT.60 There are two competing theories
has low accuracy with a sensitivity of 45% and specificity regarding this increased risk. First, the position theory
of 78%, and adds unnecessary cost.36,37 In one series, implicates the carcinogenic potential of the altered
ultrasound incorrectly indicated UDT for 48% of patients micro- and macro-environment of the UDT. If true, then
when the testis was retractile.38 In summary, negative the timing of correction could potentially lessen or negate
imaging is not diagnostic of testicular absence. the development of malignancy. A 2007 epidemiologic
study examining 16,983 Swedish men who underwent
correction of a UDT showed that those having orchi-
Fertility opexy before age 13 had a 2.23 relative risk of developing
A UDT and, to a lesser degree, its contralateral descended cancer.61 Those boys having surgery at 13 years or older
mate have been demonstrated to be histologically abnor- had a relative risk of 5.40 (compared with normal men).
mal by investigators who performed bilateral testes biop- An additional meta-analysis showed that orchiopexy after
sies at the time of orchiopexy.39,40 Clinically, patients with 10 years of age compared with before 10 was associated
a history of UDT exhibit subnormal semen analyses.41 with six times the risk of malignancy.62 The association
Early studies showed fertility to be related to the position of orchiopexy with a decrease in cancer risk has not been
of the UDT; men with abdominal or canalicular testes demonstrated prospectively. Nevertheless, orchiopexy
had lower fertility than those with inguinal testes (83.3% facilitates subsequent testicular examination and cancer
vs 90%).42,43 Despite these findings, the infertility rate of detection.
men with a history of unilateral UDT is equivalent to The alternate common cause or testicular dysgene-
that of the normal population (10%).43,44,45 However, men sis theory posits that the malignancy risk may be due to
with bilateral UDT have paternity rates of 5065% even an underlying genetic or hormonal etiology that predis-
if corrected early, and thus are six times more likely to be poses to both cryptorchidism and testicular cancer.63 In
infertile relative to their normal counterparts.46,47 patients with a UDT, 1520% of testicular tumors arise
Mechanisms of infertility in UDT appear to be associ- in the normally descended contralateral testis. In other
ated with effects on Sertoli and Leydig cells, as well as words, the normally descended testis still carries an
Wolffian duct abnormalities (vasal and epididymal), increased relative risk of 1.7.64 The incidence of carci-
which may further inhibit transport of already insuffi- noma in situ (CIS) is 24% in men with cryptorchidism
cient sperm.22 Elevated testicular temperature in a UDT compared with less than 1% in non-affected men. In the
results in immaturity of Sertoli cells in monkeys.22 A postpubertal male, CIS progresses to invasive germ cell
blunted normal testosterone surge at 60 to 90 days post- tumors in 50% of cases within 5 years.65 However, the
natally results in a lack of Leydig cell proliferation and natural history of CIS diagnosed in a young child at the
delay in transformation of gonocytes to adult dark sper- time of orchiopexy is less clear. It has been recommended
matogonia on histopathology.48 An experimental rat that these patients undergo repeated biopsies after
model has demonstrated preservation of germ cell puberty.66
number and spermatogenesis in rats undergoing early
orchiopexy for UDT versus germ cell apoptosis in
untreated rats.49 Furthermore, delayed orchiopexy at 3 Management and Treatment
years versus 9 months resulted in impaired testicular Indications and Timing
catch-up growth in boys.50
A clinical trial of neoadjuvant LH-releasing hormone Guidelines (AAP 1996 and EAU 2012) recommend that
(LHRH) in young boys undergoing orchiopexy appeared orchiopexy in otherwise healthy males be performed by
to improve the fertility index (spermatogonia/tubule) in 1218 months of age, as the UDT is unlikely to descend
treated versus untreated boys, though these results need after 12 months of age.67,68 Despite this recommendation,
confirmation.51 A similar prospective randomized trial on many children are referred after age 2 years. In one
neoadjuvant gonadotropin-releasing hormone therapy review of over 28,000 children with UDT in the Pediatric
prior to orchiopexy also found an improvement in the Health Information System database, only 18% under-
mean fertility index compared to the untreated group.52 went operation by 1 year of age, and 43% by 2 years of
Neoadjuvant therapy prior to 24 months achieved the age. Black and Hispanic boys less commonly underwent
best results. orchiopexy by age 2 years, regardless of payer group and
socioeconomic status.69 Repair may be undertaken even
earlier if a symptomatic hernia is present. The risk of
Risk of Malignancy general anesthesia after 6 months is acceptably low in
UDT appears to be associated with a two- to eightfold hospitals with dedicated pediatric anesthesiologists. In
increased risk of malignancy.25,53 The risk of malignancy addition to the evidence that early scrotal placement may
arising from a UDT varies with location, e.g., 1% with affect the risk of malignancy and infertility, treatment of
inguinal and 5% with abdominal testes.54,55 Cancers a UDT also reduces the risk of torsion, facilitates
692 SECTION V Inguinal Region and Scrotum
testicular examination, improves the endocrine function the testis at the time of surgery is not recommended, but
of the testis, and creates a normal-appearing scrotum. may provide prognostic information regarding fertility.77
For the unilateral palpable UDT that presents after
puberty, orchiopexy is preferred. If orchiopexy is difficult
Hormonal Treatment
and a normal contralateral testis is present, or if the UDT
The value of hormonal therapy in the treatment of UDT is abnormally soft and small, then an orchiectomy should
is controversial. Buserelin, an LHRH agonist, is fre- be performed. Likewise, orchiectomy is the treatment of
quently used to treat UDT in Europe.70 The highest choice for the postpubertal, unilateral intra-abdominal
success rates have been observed in cases where the testis UDT because of the increased cancer risk. Laparoscopic
is at or distal to the external inguinal ring.71,72 Some orchiectomy is ideal in this setting.78 In uncommon cases
authors recommend low-dose hCG therapy, regardless of such as postpubertal males with significant anesthetic
the operative plan to restore a normal endocrine milieu risks, or males older than 50, observation is an acceptable
and enhance germ cell maturation, particularly in bilat- alternative to operation.56
eral UDT.73 Trials combining buserelin and hCG have
yielded success rates in the range of 60%, but orchiopexy
Palpable Undescended Testes:
is still required in 40% of patients.74,75 Buserelin has not
Unilateral or Bilateral
been approved for this use by the USA Food and Drug
Administration, but as noted above, clinical trials of The mainstay of therapy for the palpable UDT is orchi-
LHRH used in a neoadjuvant fashion in young boys opexy with creation of a subdartos pouch.79,80 This may
undergoing orchiopexy suggest that it may improve be performed through a standard two-incision (inguinal
fertility.51 and scrotal) approach, or a single-incision high scrotal
approach.81,82 With the standard inguinal approach, the
Orchiopexy success rate is as high as 95%.83 Similar success rates have
been reported for the high scrotal approach.81,84 With
The operative approach for UDT depends on whether both techniques, scrotal fixation is achieved by scarring
the testis is palpable (Fig. 51-2). It is important to of the everted tunica vaginalis to the surrounding tissues.85
re-examine the patient under anesthesia because up to Placement of sutures in the tunica albuginea for fixation
18% of nonpalpable testes may become palpable on is generally discouraged because it causes significant tes-
examination under anesthesia.76 Unilateral and bilateral ticular inflammation, increases infertility risk, and may
palpable UDT are managed similarly. Routine biopsy of damage intratesticular vessels.86,87 Associated findings
Increased No
testosterone responsed
FIGURE 51-2 Management algorithm for undescended testis. FSH, follicle-stimulating hormone; LH, luteinizing hormone; hCG,
human chorionic gonadotropin. (a) If blind-ending vessels are unequivocally identified, then there is no need for further exploration.
(b) Baseline FSH and LH levels are elevated if values are 3 SD above the mean. (c) Increased suspicion of anorchia with elevated
baseline FSH and LH levels; however, exploration is still warranted. (d) Testicular remnant tissue may be present despite a negative
hCG stimulation test; therefore, exploration for testicular remnant tissue should still be performed.
51 Undescended Testes and Testicular Tumors 693
such as an open processus vaginalis or hernia should be 34% were located distal to the internal ring, and an
repaired. initial inguinal incision would have provided suboptimal
A standard inguinal approach to orchiopexy with a exposure for the remaining 66%.90
subdartos pouch is depicted in Figure 51-3. The opera- The surgeon may begin with diagnostic laparoscopy
tion is usually performed as an outpatient procedure through an umbilical port (Fig. 51-4).91 If the vessels
under general anesthesia. The patient is supine. Intraop- appear atretic or blind ending as they exit the abdomen,
erative administration of an ilioinguinal nerve block with some have recommended no further exploration, though
bupivacaine provides excellent postoperative analgesia. this is controversial. If the testicular vessels are seen
An incision is made along one of the Langer lines over exiting the internal ring, a laparoscopic inguinal explora-
the internal ring. The external oblique aponeurosis is tion is performed if the ring is open, or an open inguinal
incised in the direction of its fibers, avoiding injury to the exploration if the ring is closed (Fig. 51-5).89 Orchiopexy
ilioinguinal nerve. Once located, the testis and spermatic is performed if a viable testis is found. If the vessels
cord are freed from the canal and any cremasteric and end blindly in the inguinal canal, the tip of the vessels
ectopic gubernacular attachments. The tunica vaginalis is can be sent for pathologic examination. Remnants of
then dissected off the vas deferens and spermatic vessels. testicular tissue or hemosiderin and calcifications are
The proximal sac is twisted, doubly suture ligated, and indicative of probable perinatal torsion and testicular
amputated. Retroperitoneal dissection through the inter- resorption.
nal ring may provide additional cord length for the testis If diagnostic laparoscopy reveals a viable intra-
to reach the scrotum. abdominal testis, several options are available depending
A tunnel is created from the inguinal canal into the on its location. A recent review concluded that while
scrotum by using a finger or a large clamp. A subdartos there is not an optimal surgical technique for an intra-
pouch is created by placing the finger through the tunnel, abdominal testis, preservation of the spermatic vessels is
bluntly developing a space in a dependent portion of the preferable.89 If the gonadal vessels are long enough to
scrotum, making a 1.5cm incision in the skin over the allow for tension-free mobilization of the testis into the
finger, and creating a pouch using a hemostat inserted scrotum, orchiopexy may be performed open or laparo-
just under the skin to spread both superiorly and inferi- scopically depending on surgeon preference (Fig. 51-6).
orly. A clamp is carefully passed through this scrotal inci- This is often feasible when the testis lies caudal to the
sion up into the inguinal canal and the adventitial tissue iliac vessels.78
around the testis is secured, taking care not to grasp the When the gonadal vessels are too short, there are
testis or vas deferens. The testis is thereby delivered into various options. Open or laparoscopic exploration can be
the dartos pouch, and a suture is used to narrow the neck performed. The cord structures are mobilized cephalad
of the pouch to prevent testicular retraction. Testis meas- towards their origin, freed from the posterior perito-
urements and biopsy may be performed at this time. The neum, and the testicle brought into the scrotum. A neoin-
scrotal skin incision is closed with absorbable suture. The guinal ring may be created medial to the median umbilical
external oblique aponeurosis is reapproximated to restore ligament to shorten the path for scrotalization of the
the inguinal canal. The skin and subcuticular tissue are testis (Prentiss maneuver). Most series indicate a 95100%
closed with subcuticular stitches. A skin sealant is useful, success rate, defined as lack of atrophy and a normal
especially for boys in diapers. scrotal position, with single-stage laparoscopic orchi-
The patient is seen in clinic after a few weeks for a opexy.89 A staged orchiopexy can also be performed in
wound check and again several months later for testicular which the high abdominal testis with its cord structures
examination, instruction on testicular self-examination, is first mobilized as low as possible. Six to 12 months
and repeat counseling on fertility and cancer risk. Final later, it is mobilized into the scrotum. The advantage of
position and condition of the testis should be noted. this approach lies in preservation of both primary and
Although rare, complications include atrophy and retrac- collateral blood supply. However, during the second
tion. A single scrotal incision technique has also been stage, injury may occur to the vascular supply and/or vas
applied to orchiopexy, with similar success rates and deferens because of scarring to surrounding tissues.
shorter operative times, but one group demonstrated an Alternately, in the setting of a short spermatic cord, a
increased 3% risk of postoperative hernia with this first stage FowlerStephens orchiopexy can be performed,
approach.81,88 typically laparoscopically.92 The FowlerStephens orchi-
opexy involves clipping the spermatic vessels, which
makes the testis dependent on the vasal and cremasteric
Nonpalpable Undescended Testes:
vessels for viability.93,94 For this reason, the Fowler
Unilateral or Bilateral
Stephens approach is not a good option after prior
For a unilateral UDT that is not palpable under anesthe- inguinal exploration because this secondary vascular
sia, initial management may be either through diagnostic supply to the testis may have been compromised. A delay
laparoscopy or inguinal exploration. In the last decade, of six months is recommended before stage 2 to allow
laparoscopy has become the preferred approach.89 development of collateral circulation. During the second
If the surgeon decides to first perform inguinal explo- stage, the spermatic vessels are then divided between the
ration and no testis or remnant is identified, then diag- clips, and the testis located into the scrotum. The success
nostic laparoscopy or laparotomy may still be needed to rate in modern single-center case series with follow-up
ensure the testis is not in an intra-abdominal location. In longer than 3 years exceeds 90%.9597 However, a
one retrospective review of 215 nonpalpable testes, only higher failure rate was observed with a single-stage
694 SECTION V Inguinal Region and Scrotum
Sac
Skin incision
Testis
Vas
Spermatic
Internal vessels
oblique m. External ring
Internal
oblique m.
Cremaster
m.
External Deep
oblique inferior
aponeurosis epigastric
A B C vessels
Dartos
Skin
Dartos
fascia
E F
Deep inferior
epigastric vessels divided
Dartos Skin
Dartos
Skin H
G I
Skin
Dartos
Dartos
J K
FIGURE 51-3 Standard inguinal orchiopexy approach. (A) Transverse skin incision. (B) External oblique aponeurosis is opened in
the directions of its fibers, with care taken to avoid the ilioinguinal nerve. (C) The testis is delivered, and the patent processus vagi-
nalis is opened distally near the testis. (D) The processus vaginalis (or indirect hernia sac) is separated from the cord structures and
ligated at the internal ring. Adequate cord length is usually obtained by retroperitoneal dissection of the cord contents. If additional
length is required, the inferior epigastric vessels may be ligated (Prentiss maneuver), permitting medialization of the cord. (E) A
finger is passed inferiorly into the scrotum to aid in creation of the dartos pouch. (FH) Dartos pouch creation and passage of a
clamp through the scrotum into the inguinal canal. (I) Adventitial tissue of the testis is grasped with the clamp. (J) The testis is
brought into the dartos pouch. (K) Dartos fascia and skin are closed. (From Ellis DG. Undescended testes. In: Ashcraft KW, editor.
Pediatric Urology. Philadelphia: WB Saunders; 1990. p. 423.)
51 Undescended Testes and Testicular Tumors 695
FowlerStephens orchiopexy, and caution is advised with microvascular surgeon. An 8396% success rate in expe-
this approach. rienced hands has been reported.89
Other options for operative management of high If the testis is atrophic, whether found in the abdomen
intra-abdominal testes include microvascular orchiopexy or inguinal canal, a laparoscopic or open orchiectomy is
(autotransplantation). This technique is infrequently recommended, respectively. Debate exists regarding the
used as it requires special instrumentation, microsurgical role of contralateral fixation in cases of monorchism
skill, and sometimes an unexpected need for a second because of differing assumptions related to potential
torsion. This largely remains the surgeons preference.
Boys with bilateral nonpalpable UDT usually have
genetic, endocrinologic, or imaging evaluation indicating
the presence or absence of testicular tissue (i.e., hormonal
evaluation confirming testosterone production). If lapar-
oscopy reveals only one viable testicle, the child is
managed as in the situation with unilateral, nonpalpable
UDT. However, if bilateral viable testes are found, man-
agement may depend on the ease of orchiopexy. If diffi-
cult, one side may be fixed first, with the contralateral
side fixed six to 12 months later. This allows the practi-
tioner to assess the outcome of the first side prior to
operating on the contralateral testis.89
A B
FIGURE 51-5 (A) The vas deferens and testicular vessels in this patient end blindly in the retroperitoneum. The internal ring is
closed. In this very unusual situation, inguinal exploration is not necessary. (B) In the more common scenario, the testicular vessels
and vas deferens are seen to enter the inguinal canal. There is no evidence for a patent processus vaginalis. The vessels and vas
deferens appear to be of relatively normal caliber. In this situation, inguinal exploration is necessary. (From Holcomb GW III. Laparo-
scopic orchiopexy. In: Holcomb GW III, Georgeson KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadel-
phia: Elsevier; 2008. p. 1448.)
696 SECTION V Inguinal Region and Scrotum
A B
FIGURE 51-6 (A) After intra-abdominal mobilization of the testis, the gubernaculum has been grasped with forceps inserted through
a 10mm cannula that has been introduced through the scrotal incision, over the pubic tubercle and into the abdomen. The testis
is then withdrawn into the cannula. Often, it is not possible to place the testis entirely into the 10mm port. (B) The testis is delivered
over the pubic tubercle and into the right hemiscrotum. (From Holcomb GW III. Laparoscopic orchiopexy. In: Holcomb GW III, Georgeson
KE, Rothenberg SS, editors. Atlas of Pediatric Laparoscopy and Thoracoscopy. Philadelphia: Elsevier; 2008. p. 1448.)
100,000,000
10,000,000
1,000,000
100,000
10,000
1,000
100
10
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300
FIGURE 51-7 This graph displays the normal ranges of serum -fetoprotein (AFP) in early infancy. The AFP levels in nanograms
per milliliter are on the y-axis and age in days is on the x-axis. The normal range for AFP may be estimated by the middle regres-
sion line. The two flanking lines represent the 95% confidence interval. (From Ohama K, Nagase H, Ogino K, etal. Alpha-fetoprotein
(AFP) levels in normal children. Eur J Pediatr Surg 1997;7:2679.)
Grossly, YSTs are firm and yellow/white. Microscopi- the same protocols as for stage II disease, followed by
cally, they are characterized by SchillerDuval bodies and RPLND. The overall survival approaches 100%.100
stain for AFP.112,113
Contrary to the behavior of embryonal carcinoma in Teratoma
adults, YST (which is histologically similar) in children
has a more indolent course and spreads hematogenously. Teratomas account for 40% of testicular tumors in pre-
Approximately 95% of YSTs are confined to the testis, pubertal children. Histologically, teratomas are com-
and metastases to the retroperitoneum are uncommon posed of all three layers of embryonic tissue: ectoderm,
(5%).100 The lungs are the most common site of endoderm, and mesoderm. Grossly, they may contain
distant metastasis, and retroperitoneal metastases are differentiated tissue such as cartilage, muscle, bone, and
seen only 5% of the time.101 The 5-year survival for YST fat; a cystic component also may be present. Before
approaches 99%. puberty, they follow a benign course and can be cured
The standard diagnostic and therapeutic procedure for with testis-sparing surgery.116,117 Long-term mean
YST is radical inguinal orchiectomy, and this alone is follow-up of 7 years has demonstrated no tumor recur-
usually curative in children. To minimize the risk of rence in the ipsilateral or contralateral gonad with a
metastases during manipulation, the spermatic cord is testis-sparing approach.117 Also, no radiographic follow-up
clamped or ligated immediately on entry into the inguinal has been recommended for prepubertal patients who
canal. undergo partial orchiectomy.101 If one accepts the dyspla-
Staging of YST requires abdominopelvic CT and sia theory, however, whether benign or malignant, one
chest radiography (CXR), histologic examination of the might consider that a unilateral testicular tumor may
radical orchiectomy specimen, and determination of pose an increased risk for the contralateral testis. On the
serum tumor markers. Stage I tumors are limited to the other hand, when a child is seen at or after puberty,
testis, and thus are usually cured by radical inguinal radical inguinal orchiectomy is indicated because the ter-
orchiectomy.114 Tumor markers are measured monthly atoma can follow a malignant postpubertal course.101
and CXRs obtained every 2 months for the first 2 years. The enucleated tumor should always be sent for frozen
Abdominopelvic CT or MRI scans are obtained every 3 section examination. If immature elements or pubertal
months for the first year and every 6 months for the changes are seen, radical orchiectomy should be per-
second year. After 2 years without recurrence, follow-up formed. Overall disease-free survival after orchiectomy is
may be extended to every 6 months or yearly.112 excellent. 118 An elevated AFP or focus of YST may indi-
Traditionally, RPLND was recommended for boys cate potential recurrence. These patients can then be
with unknown or normal markers at diagnosis to confirm salvaged with platinum-based chemotherapy with 5-year
stage I disease. Although confirmatory RPLND may still survival rates in excess of 90%.119
be considered, it is used less often because stage 1 YST Epidermoid cysts comprise about 15% of pediatric
has a high likelihood of stage 1 presentation (85%), as testis tumors, and as monodermal teratomas, follow a
propensity for hematogenous spread to the lungs, and benign course. As such, a testis-sparing approach can be
because RPLND has a high complication rate in chil- taken.101
dren. The risk of recurrence is approximately 20% and
almost always can be salvaged with chemotherapy.101 Mixed Germ Cell Tumor
Stage II disease includes those tumors with residual
disease in the scrotum or high proximal cord, node Teratocarcinoma, or mixed germ cell tumor, accounts for
involvement on imaging, or persistent elevation of tumor 20% of pediatric germ cell tumors. Teratocarcinoma is
markers after orchiectomy. Tumors diagnosed and treated more commonly seen in an operatively corrected UDT
with trans-scrotal orchiectomy also should be considered and may contain any mixture of YST, embryonal carci-
stage II because transscrotal resection alters the normal noma, choriocarcinoma, and seminoma.120 Eighty per
lymphatic drainage of the tumor. Lymphatic drainage of cent of teratocarcinomas are confined to the testis at
the testis is to the retroperitoneal nodes, whereas the presentation. Foci of choriocarcinoma confer a poorer
scrotum drains to the inguinal nodes. Ipsilateral hemis- prognosis. RPLND is usually performed even for stage I
crotectomy can also be considered. All patients with stage disease, and higher-stage disease is treated with chemo-
II disease should receive combination chemotherapy with therapy similar to those used for adults.
cisplatin, etoposide, and bleomycin (PEB).101 Due to sig-
nificant ototoxicity and nephrotoxicity with cisplatin, the
Seminoma
UK Childrens Cancer Study Group substituted carbo-
platin for cisplatin, and were able to maintain a 100% Seminoma is rare in children, but is the most common
event-free survival at 5 years.115 Patients with a persistent tumor in an uncorrected abdominal UDT. Seminoma is
mass or elevated AFP after chemotherapy should undergo treated with radical orchiectomy and retroperitoneal
RPLND. radiation.121
Stage III disease includes retroperitoneal spread
(lymph node >4cm) seen on imaging studies. Biopsy is Nongerm Cell Tumors (Gonadal
used to confirm suspected nodal metastases, such as with
lymph nodes >2cm on CT. Metastasis beyond the retro-
Stromal Tumors)
peritoneum or to any viscera defines stage IV disease. For Leydig cell tumors are one of the most common nongerm
both stage III and stage IV disease, chemotherapy follows cell tumors (NGCTs). The peak incidence in boys occurs
51 Undescended Testes and Testicular Tumors 699
from ages 5 to 9 years.101,122 The clinical triad includes a 2. Bardin CW, Ross GT, Rifkind AB, et al. Studies of the pituitary-
unilateral testicular mass (9093%), precocious puberty, Leydig cell axis in young men with hypogonadotropic hypogonad-
ism and hyposmia: Comparison with normal men, prepubertal
and elevated 17-ketosteroid levels. As these tumors boys, and hypopituitary patients. J Clin Invest 1969;48:204656.
produce testosterone and occasionally other androgens, 3. Santen RJ, Paulsen CA. Hypogonadotropic eunuchoidism. II.
roughly 20% of patients may have signs of precocious Gonadal responsiveness to exogenous gonadotropins. J Clin
puberty and gynecomastia.123 Precocious puberty may Endocrinol Metab 1973;36:5563.
4. Husmann DA, McPhaul MJ. Time-specific androgen blockade
also be caused by pituitary lesions, Leydig cell hyperpla- with flutamide inhibits testicular descent in the rat. Endocrinol-
sia, and congenital adrenal hyperplasia so the pituitary/ ogy 1991;129:140916.
adrenal axis must be evaluated by assaying 17-ketosteroids, 5. Spencer JR, Torrado T, Sanchez RS, et al. Effects of flutamide and
FSH, LH, and performing a dexamethasone suppression finasteride on rat testicular descent. Endocrinology 1991;129:
test. Reinke crystals on histologic examination are 7418.
6. Emmen JM, McLuskey A, Adham IM, et al. Involvement of
pathognomonic for this tumor and can be found in insulin-like factor 3 (Insl3) in diethylstilbestrol-induced cryp-
3540% of all patients.124 When diagnosed preopera- torchidism. Endocrinology 2000;141:8469.
tively, testis-sparing enucleation may be considered 7. Nef S, Shipman T, Parada LF. A molecular basis for estrogen-
because these tumors tend to follow a benign course.125 induced cryptorchidism. Dev Biol 2000;15(224):35461.
8. Fentener van Vlissingen JM, van Zoelen EJ, Ursem PJ, et al. In
The granulosa cell tumor also has a benign course and vitro model of the first phase of testicular descent: identification
can be managed with testis-sparing surgery. This tumor of a low molecular weight factor from fetal testis involved in
should be suspected in neonates with scrotal swelling, proliferation of gubernaculum testis cells and distinct from speci-
normal age-adjusted AFP levels, and a complex, cystic, fied polypeptide growth factors and fetal gonadal hormones.
multiseptated, hypoechoic mass on testicular Endocrinology 1988;123:286877.
9. Heyns CF, Hutson JM. Historical review of theories on testicular
ultrasound.126 descent. J Urol 1995;153:75467.
The Sertoli cell tumor is a rare form of NGCT. A 10. Nef S, Parada LF. Cryptorchidism in mice mutant for Insl3. Nat
small percentage of patients have gynecomastia, though Genet 1999;22:2959.
these are typically not as hormonally active as Leydig cell 11. Costa WS, Sampaio FJB, Favorito LA, et al. Testicular migration:
Remodeling of connective tissue and muscle cells in human guber-
tumors.127 The clinical course is usually benign in chil- naculum testis. J Urol 2002;167:21716.
dren under 5, and tumors can be managed with testis- 12. Heyns CF. The gubernaculum during testicular descent in the
sparing surgery. Older children, however, should have a human fetus. J Anat 1987;153:93112.
metastatic evaluation with imaging.101 13. Barteczko KJ, Jacob MI. The testicular descent in human. Origin,
Gonadoblastoma is a form of NGCT usually associ- development and fate of the gubernaculum Hunteri, processus
vaginalis peritonei, and gonadal ligaments. Adv Anat Embryol
ated with intersex disorders, occurring in dysgenetic Cell Biol 2000;156:IIIX, 198.
gonads. The patients are typically 46XY phenotypic 14. Goh DW, Momose Y, Middlesworth W, et al. The relationship
females (testicular feminization) with intra-abdominal among calcitonin gene-related peptide, androgens and guber-
testes who undergo virilization at puberty. Up to one- nacular development in 3 animal models of cryptorchidism. J Urol
1993;150:5746.
third of patients have bilateral gonadal lesions. The germ 15. Park WH, Hutson JM. The gubernaculum shows rhythmic con-
cell component of these tumors carries a 10% risk of tractility and active movement during testicular descent. J Pediatr
malignant degeneration. Early gonadectomy is recom- Surg 1991;26:61517.
mended, especially if the patient is raised as a female.128,129 16. Hutson JM, Nation T, Balic A, et al. The role of the gubernacu-
Patients with mixed gonadal dysgenesis raised as males lum in the descent and undescent of the testis. Ther Adv Urol
2009;1:11521.
should have streak gonads and UDTs removed, though 17. Elder JS. Epididymal anomalies associated with hydrocele/hernia
some suggest that scrotal testes can be preserved since and cryptorchidism: Implications regarding testicular descent.
they are less prone to malignancy and can be surveyed J Urol 1992;148:6246.
more easily. 18. Gill B, Kogan S, Starr S, et al. Significance of epididymal and
ductal anomalies associated with testicular maldescent. J Urol
1989;142:5568.
Testicular Microlithiasis 19. Hadziselimovic F, Herzog B. The development and descent of the
epididymis. Eur J Pediatr 1993;152(Suppl 2):S69.
Lastly, testicular microlithiasis may be seen in conjunc- 20. Kaplan GW. Nomenclature of cryptorchidism. Eur J Pediatr
tion with testicular tumors (seen synchronously in 1993;152(Suppl 2):S1719.
21. Agarwal PK, Diaz M, Elder JS. Retractile testisis it really a
1546% of patients), but is also seen incidentally in 5% normal variant? J Urol 2006;175:14969.
of healthy young men. While the risk of testicular micro- 22. Singh R, Hamada AJ, Bukavina L, et al. Physical deformities
lithiasis in children for the development of cancer is relevant to male infertility. Nat Rev Urol 2012;9:15674.
not well studied and reported numbers are small, there 23. Stec AA, Thomas JC, DeMarco RT, et al. Incidence of testicular
ascent in boys with retractile testes. J Urol 2007;178:17225.
appear to be low-risk and high-risk individuals. Boys who 24. Sijstermans K, Hack WWM, Meijer RW, et al. The frequency of
have (1) atrophic or dystrophic testes; (2) known chro- undescended testis from birth to adulthood: A review. Int J Androl
mosomal abnormalities; (3) contralateral testis cancer, 2008;31:111.
and possibly (4) history of UDT need closer follow-up 25. Pohl H. The location and fate of the cryptorchid and impalpable
with routine serial examination and scrotal ultrasound.130 testes. Dialogues in Pediatric Urology. Pearl River, NY: William
J. Miller Associates; 1997. p. 34.
Education about testicular self-examination is important 26. Capello SA, Giorgi LJ Jr, Kogan BA. Orchiopexy practice
for these patients. patterns in New York State from 1984 to 2002. J Urol 2006;176:
11803.
27. Hack WWM, Meijer RW, Van Der Voort-Doedens LM, et al.
REFERENCES Previous testicular position in boys referred for an undescended
1. Husmann DA, Levy JB. Current concepts in the pathophysiology testis: Further explanation of the late orchidopexy enigma? BJU
of testicular undescent. Urology 1995;46:26776. Int 2003;92:2936.
700 SECTION V Inguinal Region and Scrotum
28. Barthold JS, Gonzlez R. The epidemiology of congenital 53. Herrinton LJ, Zhao W, Husson G. Management of cryptorchism
cryptorchidism, testicular ascent and orchiopexy. J Urol 2003; and risk of testicular cancer. Am J Epidemiol 2003;1(157):6025.
170:2396401. 54. Li FP, Fraumeni JF. Testicular cancers in children: Epidemiologic
29. Guven A, Kogan BA. Undescended testis in older boys: Further characteristics. J Natl Cancer Inst 1972;48:157581.
evidence that ascending testes are common. J Pediatr Surg 55. Ross JH, Rybicki L, Kay R. Clinical behavior and a contemporary
2008;43:17004. management algorithm for prepubertal testis tumors: A summary
30. Docimo SG. The results of surgical therapy for cryptorchidism: of the Prepubertal Testis Tumor Registry. J Urol 2002;168:
A literature review and analysis. J Urol 1995;154:114852. 16759.
31. Kirsch AJ, Escala J, Duckett JW, et al. Surgical management of 56. Wood HM, Elder JS. Cryptorchidism and testicular cancer: Sepa-
the nonpalpable testis: The Childrens Hospital of Philadelphia rating fact from fiction. J Urol 2009;181:45261.
experience. J Urol 1998;159:13403. 57. Raja MA, Oliver RT, Badenoch D, et al. Orchidopexy and trans-
32. Jarow JP, Berkovitz GD, Migeon CJ, et al. Elevation of serum formation of seminoma to non-seminoma. Lancet 1992;339:930.
gonadotropins establishes the diagnosis of anorchism in prepuber- 58. Halme A, Kellokumpu-Lehtinen P, Lehtonen T, et al. Morphol-
tal boys with bilateral cryptorchidism. J Urol 1986;136:2779. ogy of testicular germ cell tumours in treated and untreated cryp-
33. Esposito C, Cardona R, Centonze A, et al. Impact of laparoscopy torchidism. Br J Urol 1989;64:7883.
on the management of an unusual case of nonpalpable testis in an 59. Jones BJ, Thornhill JA, ODonnell B, et al. Influence of prior
adult patient. Surg Endosc 2003;17:1324. orchiopexy on stage and prognosis of testicular cancer. Eur Urol
34. De Filippo RE, Barthold JS, Gonzlez R. The application of 1991;19:2013.
magnetic resonance imaging for the preoperative localization of 60. Pike MC, Chilvers C, Peckham MJ. Effect of age at orchidopexy
nonpalpable testis in obese children: An alternative to laparoscopy. on risk of testicular cancer. Lancet 1986;31(1):12468.
J Urol 2000;164:1545. 61. Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery
35. Landa HM, Gylys-Morin V, Mattrey RF, et al. Magnetic reso- for undescended testis and risk of testicular cancer. N Engl J Med
nance imaging of the cryptorchid testis. Eur J Pediatr 2007;3(356):183541.
1987;146(Suppl 2):S1617. 62. Walsh TJ, DallEra MA, Croughan MS, et al. Prepubertal orchi-
36. Elder JS. Ultrasonography is unnecessary in evaluating boys with opexy for cryptorchidism may be associated with lower risk of
a nonpalpable testis. Pediatrics 2002;110:74851. testicular cancer. J Urol 2007;178:14406.
37. Tasian GE, Copp HL, Baskin LS. Diagnostic imaging in cryp- 63. Asklund C, Jrgensen N, Kold Jensen T, et al. Biology and
torchidism: Utility, indications, and effectiveness. J Pediatr Surg epidemiology of testicular dysgenesis syndrome. BJU Int 2004;
2011;46:240613. 93(Suppl 3):611.
38. Snodgrass W, Bush N, Holzer M, et al. Current referral patterns 64. Akre O, Pettersson A, Richiardi L. Risk of contralateral testicular
and means to improve accuracy in diagnosis of undescended testis. cancer among men with unilaterally undescended testis: a meta-
Pediatrics 2011;127:e3828. analysis. Int J Cancer 2009;1(124):6879.
39. Huff DS, Hadziselimovic F, Snyder HM 3rd, et al. Histologic 65. Dieckmann KP, Skakkebaek NE. Carcinoma in situ of the testis:
maldevelopment of unilaterally cryptorchid testes and their Review of biological and clinical features. Int J Cancer
descended partners. Eur J Pediatr 1993;152(Suppl 2):S1114. 1999;10(83):81522.
40. Rusnack SL, Wu H-Y, Huff DS, et al. Testis histopathology in 66. Giwercman A, Mller J, Skakkebaek NE. Cryptorchidism and
boys with cryptorchidism correlates with future fertility potential. testicular neoplasia. Horm Res 1988;30:15763.
J Urol 2003;169:65962. 67. Timing of elective surgery on the genitalia of male children with
41. Puri P, ODonnell B. Semen analysis of patients who had particular reference to the risks, benefits, and psychological effects
orchidopexy at or after seven years of age. Lancet 1988;5(2): of surgery and anesthesia. American Academy of Pediatrics. Pedi-
10512. atrics 1996;97:5904.
42. Lee PA, Coughlin MT, Bellinger MF. Paternity and hormone 68. Tekgul S. Guidelines on Paediatric Urology. European Associa-
levels after unilateral cryptorchidism: association with pretreat- tion of Urology; 2012.
ment testicular location. J Urol 2000;164:1697701. 69. Kokorowski PJ, Routh JC, Graham DA, et al. Variations in
43. Lee PA. Fertility in cryptorchidism. Does treatment make a dif- timing of surgery among boys who underwent orchidopexy for
ference? Endocrinol Metab Clin North Am 1993;22:47990. cryptorchidism. Pediatrics 2010;126:e57682.
44. Chilvers C, Dudley NE, Gough MH, et al. Undescended testis: 70. Bica DT, Hadziselimovic F. Buserelin treatment of cryptorchidism:
The effect of treatment on subsequent risk of subfertility and A randomized, double-blind, placebo-controlled study. J Urol
malignancy. J Pediatr Surg 1986;21:6916. 1992;148:61721.
45. Lee PA, Coughlin MT. The single testis: paternity after presenta- 71. Hadziselimovi; F, Huff D, Duckett J, et al. Long-term effect of
tion as unilateral cryptorchidism. J Urol 2002;168:16803. luteinizing hormone-releasing hormone analogue (buserelin) on
46. Lee PA, Coughlin MT. Fertility after bilateral cryptorchidism. cryptorchid testes. J Urol 1987;138:10435.
Evaluation by paternity, hormone, and semen data. Horm Res 72. Lala R, Matarazzo P, Chiabotto P, et al. Early hormonal and surgi-
2001;55:2832. cal treatment of cryptorchidism. J Urol 1997;157:1898901.
47. Lee PA, OLeary LA, Songer NJ, et al. Paternity after bilateral 73. Lala R, Matarazzo P, Chiabotto P, et al. Combined therapy
cryptorchidism. A controlled study. Arch Pediatr Adolesc Med with LHRH and HCG in cryptorchid infants. Eur J Pediatr
1997;151:2603. 1993;152(Suppl 2):S313.
48. Hadziselimovic F, Thommen L, Girard J, et al. The significance 74. Giannopoulos MF, Vlachakis IG, Charissis GC. 13 Years experi-
of postnatal gonadotropin surge for testicular development ence with the combined hormonal therapy of cryptorchidism.
in normal and cryptorchid testes. J Urol 1986;136(1 Pt 2): Horm Res 2001;55:337.
2746. 75. Waldschmidt J, Doede T, Vygen I. The results of 9 years of experi-
49. Mizuno K, Hayashi Y, Kojima Y, et al. Early orchiopexy improves ence with a combined treatment with LH-RH and HCG for
subsequent testicular development and spermatogenesis in the cryptorchidism. Eur J Pediatr 1993;152(Suppl 2):S346.
experimental cryptorchid rat model. J Urol 2008;179:11959. 76. Elder JS. Why do our colleagues still image for cryptorchidism?
50. Kollin C, Karpe B, Hesser U, et al. Surgical treatment of unilater- Ignoring the evidence. J Urol 2011;185:15667.
ally undescended testes: Testicular growth after randomization 77. Hadziselimovi; F, Hecker E, Herzog B. The value of testicular
to orchiopexy at age 9 months or 3 years. J Urol 2007;178: biopsy in cryptorchidism. Urol Res 1984;12:1714.
158993. 78. Esposito C, Damiano R, Gonzalez Sabin MA, et al. Laparoscopy-
51. Jaganathan K, Ahmed S, Henderson A, et al. Current manage- assisted orchidopexy: An ideal treatment for children with intra-
ment strategies for testicular microlithiasis. Nat Clin Pract Urol abdominal testes. J Endourol 2002;16:65962.
2007;4:4927. 79. Benson CD, Lotfi MW. The pouch technique in the surgical
52. Schwentner C, Oswald J, Kreczy A, et al. Neoadjuvant correction of cryptorchidism in infants and children. Surgery
gonadotropin-releasing hormone therapy before surgery may 1967;62:96773.
improve the fertility index in undescended testes: A prospective 80. Koop CE. Technique of herniorrhaphy and orchidopexy. Birth
randomized trial. J Urol 2005;173:9747. Defects Orig Artic Ser 1977;13:293303.
51 Undescended Testes and Testicular Tumors 701
81. Bassel YS, Scherz HC, Kirsch AJ. Scrotal incision orchiopexy for 107. Wallace TM, Levin HS. Mixed gonadal dysgenesis. A review of
undescended testes with or without a patent processus vaginalis. 15 patients reporting single cases of malignant intratubular germ
J Urol 2007;177:151618. cell neoplasia of the testis, endometrial adenocarcinoma, and a
82. Rajfer J. Technique of orchiopexy. Urol Clin North Am 1982; complex vascular anomaly. Arch Pathol Lab Med 1990;14:
9(3):4217. 67988.
83. Saw KC, Eardley I, Dennis MJ, et al. Surgical outcome of orchi- 108. van Casteren NJ, Looijenga LHJ, Dohle GR. Testicular micro-
opexy. I. Previously unoperated testes. Br J Urol 1992;70:904. lithiasis and carcinoma in situ overview and proposed clinical
84. Dayanc M, Kibar Y, Irkilata HC, et al. Long-term outcome of guideline. Int J Androl 2009;32:27987.
scrotal incision orchiopexy for undescended testis. Urology 109. Cortes D, Thorup JM, Visfeldt J. Cryptorchidism: aspects of
2007;70(4):7869. fertility and neoplasms. A study including data of 1,335 consecu-
85. Redman JF, Barthold JS. A technique for atraumatic scrotal pouch tive boys who underwent testicular biopsy simultaneously with
orchiopexy in the management of testicular torsion. J Urol surgery for cryptorchidism. Horm Res 2001;55:217.
1995;154:151112. 110. Heidenreich A, Moul JW. Contralateral testicular biopsy proce-
86. Coughlin MT, Bellinger MF, LaPorte RE, et al. Testicular suture: dure in patients with unilateral testis cancer: Is it indicated? Semin
A significant risk factor for infertility among formerly cryptorchid Urol Oncol 2002;20:2348.
men. J Pediatr Surg 1998;33:17903. 111. Kay R. Prepubertal Testicular Tumor Registry. J Urol 1993;150:
87. Bellinger MF, Abromowitz H, Brantley S, et al. Orchiopexy: An 6714.
experimental study of the effect of surgical technique on testicular 112. Wu HY, Snyder HM. Advances in Pediatric Urologic Oncology.
histology. J Urol 1989;142:5535. AUA Update Series XXII 2003.
88. Al-Mandil M, Khoury AE, El-Hout Y, et al. Potential complica- 113. Wold LE, Kramer SA, Farrow GM. Testicular yolk sac and
tions with the prescrotal approach for the palpable undescended embryonal carcinomas in pediatric patients: Comparative immu-
testis? A comparison of single prescrotal incision to the traditional nohistochemical and clinicopathologic study. Am J Clin Pathol
inguinal approach. J Urol 2008;180:6869. 1984;81:42735.
89. Esposito C, Caldamone AA, Settimi A, et al. Management of 114. Hayes-Lattin B, Nichols CR. Testicular cancer: A prototypic
boys with nonpalpable undescended testis. Nat Clin Pract Urol tumor of young adults. Semin Oncol 2009;36:4328.
2008;5:25260. 115. Mann JR, Raafat F, Robinson K, et al. The United Kingdom
90. Cisek LJ, Peters CA, Atala A, et al. Current findings in diagnostic Childrens Cancer Study Groups second germ cell tumor study:
laparoscopic evaluation of the nonpalpable testis. J Urol 1998; Carboplatin, etoposide, and bleomycin are effective treatment for
160:114550. children with malignant extracranial germ cell tumors, with
91. Merguerian PA, Mevorach RA, Shortliffe LD, et al. Laparoscopy acceptable toxicity. J Clin Oncol 2000;15(18):380918.
for the evaluation and management of the nonpalpable testicle. 116. Rushton HG, Belman AB, Sesterhenn I, et al. Testicular sparing
Urology 1998;51:36. surgery for prepubertal teratoma of the testis: A clinical and path-
92. Lindgren BW, Franco I, Blick S, et al. Laparoscopic Fowler- ological study. J Urol 1990;144:72630.
Stephens orchiopexy for the high abdominal testis. J Urol 117. Shukla AR, Woodard C, Carr MC, et al. Experience with testis
1999;162(3 Pt 2):9904. sparing surgery for testicular teratoma. J Urol 2004;171:1613.
93. Fowler R, Stephens FD. The role of testicular vascular anatomy 118. Marina NM, Cushing B, Giller R, et al. Complete surgical exci-
in the salvage of high undescended testes. Aust N Z J Surg sion is effective treatment for children with immature teratomas
1959;29:92106. with or without malignant elements: A Pediatric Oncology
94. Law GS, Prez LM, Joseph DB. Two-stage Fowler-Stephens Group/Childrens Cancer Group Intergroup Study. J Clin Oncol
orchiopexy with laparoscopic clipping of the spermatic vessels. 1999;17:213743.
J Urol 1997;158:12057. 119. Mann JR, Gray ES, Thornton C, et al. Mature and immature
95. Chang B, Palmer LS, Franco I. Laparoscopic orchidopexy: A extracranial teratomas in children: The UK Childrens Cancer
review of a large clinical series. BJU Int 2001;87(6):4903. Study Group Experience. J Clin Oncol 2008;20(26):35907.
96. Radmayr C, Oswald J, Schwentner C, et al. Long-term outcome 120. Batata MA, Whitmore WF Jr, Chu FC, et al. Cryptorchidism and
of laparoscopically managed nonpalpable testes. J Urol 2003; testicular cancer. J Urol 1980;124:3827.
170:240911. 121. Perry C, Servadio C. Seminoma in childhood. J Urol 1980;124:
97. Baker LA, Docimo SG, Surer I, et al. A multi-institutional analysis 9323.
of laparoscopic orchidopexy. BJU Int 2001;87(6):4849. 122. Coppes MJ, Rackley R, Kay R. Primary testicular and paratesticu-
98. Cartwright PC, Velagapudi S, Snyder HM 3rd, et al. A surgical lar tumors of childhood. Med Pediatr Oncol 1994;22:32940.
approach to reoperative orchiopexy. J Urol 1993;149:81718. 123. Cheville JC, Sebo TJ, Lager DJ, et al. Leydig cell tumor of the
99. Pohl HG, Shukla AR, Metcalf PD, et al. Prepubertal testis tumors: testis: A clinicopathologic, DNA content, and MIB-1 comparison
Actual prevalence rate of histological types. J Urol 2004;172: of nonmetastasizing and metastasizing tumors. Am J Surg Pathol
23702. 1998;22:13617.
100. Wu HY, Snyder HM 3rd. Pediatric urologic oncology: Bladder, 124. Jain M, Aiyer HM, Bajaj P, et al. Intracytoplasmic and intranuclear
prostate, testis. Urol Clin North Am 2004;31:61927, xi. Reinkes crystals in a testicular Leydig-cell tumor diagnosed by
101. Agarwal PK, Palmer JS. Testicular and paratesticular neoplasms fine-needle aspiration cytology: A case report with review of the
in prepubertal males. J Urol 2006;1176:87581. literature. Diagn Cytopathol 2001;25:1624.
102. Walsh TJ, Grady RW, Porter MP, et al. Incidence of testicular 125. Henderson CG, Ahmed AA, Sesterhenn I, et al. Enucleation for
germ cell cancers in USA children: SEER program experience prepubertal Leydig cell tumor. J Urol 2006;176:7035.
1973 to 2000. Urology 2006;68:4025. 126. Shukla AR, Huff DS, Canning DA, et al. Juvenile granulosa cell
103. Langer JE, Ramchandani P, Siegelman ES, et al. Epidermoid cysts tumor of the testis: Contemporary clinical management and path-
of the testicle: Sonographic and MR imaging features. AJR Am J ological diagnosis. J Urol 2004;171:19002.
Roentgenol 1999;173:12959. 127. Gabrilove JL, Freiberg EK, Leiter E, et al. Feminizing and non-
104. Ohama K, Nagase H, Ogino K, et al. Alpha-fetoprotein (AFP) feminizing Sertoli cell tumors. J Urol 1980;124:75767.
levels in normal children. Eur J Pediatr Surg 1997;7:2679. 128. Gourlay WA, Johnson HW, Pantzar JT, et al. Gonadal tumors in
105. Pizzocaro G, Zanoni F, Salvioni R, et al. Difficulties of a surveil- disorders of sexual differentiation. Urology 1994;43:53740.
lance study omitting retroperitoneal lymphadenectomy in clinical 129. Olsen MM, Caldamone AA, Jackson CL, et al. Gonadoblastoma
stage I nonseminomatous germ cell tumors of the testis. J Urol in infancy: Indications for early gonadectomy in 46XY gonadal
1987;138:13936. dysgenesis. J Pediatr Surg 1988;23:2701.
106. Cho J-H, Chang J-C, Park B-H, et al. Sonographic and MR 130. Dagash H, Mackinnon EA. Testicular microlithiasis: What does
imaging findings of testicular epidermoid cysts. AJR Am J Roent- it mean clinically? BJU Int 2007;99:15760.
genol 2002;178:7438.
C H A P T E R 5 2
The term acute scrotum is defined as acute scrotal pain onset of severe, unilateral pain in the testis, lower thigh,
with or without swelling and erythema. Early recognition or lower abdomen, often associated with nausea and vom-
and prompt management are imperative because of the iting. Episodes of intermittent testicular pain may precede
possibility of testicular torsion as the etiology with per- the acute presentation, suggesting prior incomplete
manent ischemic damage to the testis. Box 52-1 lists the torsion with spontaneous detorsion. Physical examina-
differential diagnoses for the acute scrotum. Although tion may reveal an enlarged testis that is retracted up
most conditions are nonemergent, prompt differentiation toward the inguinal region with a transverse orientation
between testicular torsion and other causes is critical. Age and an anteriorly located epididymis. However, it is
at presentation is important because torsion of the appen- usually difficult to obtain a good exam because of the
dix testis/epididymis is most common in prepubertal scrotal pain and tenderness. In contrast, focal tenderness
boys, whereas testicular torsion more commonly presents at the superior pole of the testis or along the epididymis
in neonates and adolescents.13 is often found with a torsed appendix testis or epididymi-
tis (Fig. 52-3). Depending on the duration of torsion, the
hemiscrotum can show varying degrees of swelling and
TESTICULAR TORSION erythema, which may obliterate landmarks and make the
examination more difficult. The cremasteric reflex is
Torsion of the testis results from twisting of the spermatic often absent with testicular torsion, but a positive reflex
cord which compromises the testicular vasculature and does not reliably exclude it.79
results in infarction. Even if the testis is not removed, the The diagnosis of testicular torsion is usually clinically
consequent ischemic damage can affect testicular mor- apparent and managed by immediate scrotal exploration.
phology and fertility. There appears to be a 4-8-hour When torsion is difficult to diagnosis, other studies may
window before significant damage occurs once torsion be beneficial. A urinalysis revealing pyuria and bacteriuria
develops.4 Table 52-1 shows that the probability of tes- is more indicative of infectious epididymitis/orchitis, but
ticular salvage declines significantly beyond six hours. can also be found with torsion. High-resolution ultra-
Emergency exploration is indicated even beyond this sonography (US) with color flow Doppler and radionu-
window because testicular viability is difficult to predict.5 clide imaging allows determination of testicular blood
Two types of torsion occur: intravaginal and extravagi- flow. Ultrasound is more commonly used because it
nal. Intravaginal torsion is more common in children and allows determination of the blood flow, is less time con-
adolescents (compared to neonates), and occurs when the suming, is more readily available, and does not expose the
spermatic cord twists within the tunica vaginalis (Fig. patient to ionizing radiation.10,11 In experienced hands,
52-1). Intravaginal torsion develops because of abnormal color flow Doppler ultrasound imaging has a sensitivity
fixation of the testis and epididymis within the tunica of 89.9%, a specificity of 98.8%, and a false-positive rate
vaginalis. Normally, the tunica will invest the epididymis of 1%.12 Also, Doppler ultrasound may detect coiling of
and posterior surface of the testis, fixing it to the scrotum the spermatic cord, indicating torsion, even with normal
with a vertical lie. Abnormal fixation occurs when the blood flow within the testis.13 Ultrasound should only be
tunica vaginalis attaches more proximally on the sper- used when the diagnosis is equivocal because imaging
matic cord, creating a long mesorchium around which studies will only delay scrotal exploration.
the testis can twist. The testis will then lie horizontally If testicular torsion is suspected but a delay to the
and the pendulous testis is predisposed to twisting with operating room is unavoidable, manual detorsion can be
leg movement or cremasteric contraction. This anatomic attempted. Detorsion is performed with a medial to
variant is classically described as the bell-clapper lateral, open book rotation because this will be the
deformity and has an incidence as high as 12% in cadav- correct direction in two-thirds of patients.14 If successful,
eric studies. Often, it is found in the contralateral scrotum the testis will drop lower in the scrotum and the patient
as well.6 will report sudden pain relief. If the initial attempt is not
Extravaginal torsion occurs perinatally when the sper- successful, an attempt in the reverse direction may be
matic cord twists proximal to the tunica vaginalis (Fig. warranted.15 Although these maneuvers may decrease the
52-2). During testicular descent into the scrotum, the degree of ischemia, prompt exploration and fixation
tunica vaginalis is not firmly fixed to the scrotum, allow- remain mandatory because the detorsion may not be
ing the tunica and testis to spin on the vascular pedicle. complete and torsion can reoccur.
Testicular torsion typically occurs before age 3 years Exploration is typically performed using a median
or after puberty. It is less common in prepubertal boys raphe scrotal incision. The symptomatic hemiscrotum is
and after age 25 years. Patients present with the sudden entered and the testis delivered, detorsed, and placed in
702
The Acute Scrotum 703
A B
FIGURE 52-2 (A) Shortly after birth, this newborn was found to have an enlarged and erythematous right hemiscrotum. It was
unclear whether or not the right hemiscrotum was enlarged at birth. The baby underwent scrotal exploration through a median
raphe incision and was found to have an extravaginal testicular torsion. (B) With this anomaly, the testis lies within the tunica vagi-
nalis and the entire complex has twisted. An alternative approach would be to explore this child through an inguinal approach due
to concerns about a possible testicular tumor.
pouch between the external spermatic fascia of the epididymo-orchitis. The testicular appendage represents
scrotum and the dartos fascia. This technique is less trau- a vestigial remnant of the Mllerian duct, and the
matic to the small, delicate neonatal gonad and provides epididymal appendage is of Wolffian duct origin. Torsion
similar fixation to using sutures.16,17 of these appendages occurs most commonly between
ages 7 and 10 years. It is hypothesized that a prepubertal
hormonal boost stimulates these structures, producing an
CONDITIONS MIMICKING increase in size and making them susceptible to
twisting.29
TESTICULAR TORSION Patients with appendage torsion present with sudden
onset of pain and nausea. Results of the urinalysis are
Torsion of Testicular Appendages usually normal. The appendage can usually be palpated
Torsion of the appendix testis or appendix epididymis is and is exquisitely and focally tender. The examiner may
the most common cause of an acute scrotum and is be able to elicit differential tenderness between the upper
frequently misdiagnosed as acute epididymitis or and lower poles of the affected testis. Classically called
the blue dot sign, the inflamed and ischemic appendage
may be seen through the scrotal skin as a subtle blue-
colored mass (see Fig. 52-3).30 As inflammation increases,
the epididymis, testis, and scrotal tissues become
edematous and erythematous, and the diagnosis becomes
more difficult. Ultrasound early in the presentation
demonstrates a discrete appendage. However, later, it
may only show increased blood flow to the adjacent
epididymis and testis or, possibly, a reactive hydrocele,
resulting in the misdiagnosis of acute epididymitis or
epididymo-orchitis.31
Torsion of these appendages is self-limited and is best
treated with nonsteroidal anti-inflammatory medications
and comfort measures such as restricted activity and
warm compresses. The pain resolves as the appendage
infarcts and necroses, and may become a calcified free
body within the tunica vaginalis.
Appendage torsion can occur at five anatomic sites:
appendix testis, appendix epididymis, paradidymis/organ
of Giraldes, and superior and inferior vas aberrans of
Haller (Fig. 52-4).3234 Exploration is indicated when the
diagnosis is unclear or when the symptoms are prolonged
and fail to resolve spontaneously. The torsed appendage
FIGURE 52-3 A torsed and gangrenous appendix testis is can be easily excised through a small scrotal incision with
shown. This is the cause of the blue dot sign. immediate symptom relief.
The Acute Scrotum 705
HenochSchnlein Purpura
Superior
Vas aberrans of Haller HenochSchnlein purpura is a vasculitic syndrome that
Inferior
can involve the skin, joints, and gastrointestinal and geni-
FIGURE 52-4 Testicular appendages. (From Rolnick D, Kawanoue tourinary systems. Up to one-third of patients develop
S, Szanto P, etal. Anatomic incidence of testicular appendages. pain, erythema, and swelling of the scrotum and sper-
J Urol 1968;100:7556.) matic cord, most commonly in boys younger than 7 years
of age. Doppler ultrasound demonstrates normal blood
flow to the testis. Patients can also experience skin
purpura, joint pain, and hematuria. Supportive measures
Epididymitis are typically adequate, although systemic corticosteroids
True bacterial epididymitis is rare in children, accounting may be helpful.37,38 Despite the rarity of coincident diag-
for 10% to 15% of patients with an acute scrotum. The noses, patients with HenochSchnlein purpura and tes-
bacterial infection extends from the bladder and urethra ticular torsion have been described.39
to the epididymis in a retrograde direction via the ejacu-
latory ducts and can be associated with a clinical urinary
tract infection or urethritis. The scrotal pain and swelling TESTICULAR TRAUMA
typically have a slow onset, worsening over days rather
than hours. Examination reveals induration, swelling, and Testicular trauma in children is rare. The diagnosis is
tenderness of the hemiscrotum. A positive urinalysis and made by taking a complete history, and paying close
culture, or urethral swab in sexually active adolescents attention to factors suggesting sexual abuse. The injured
suggests the diagnosis. Neisseria gonorrhoeae and Chlamy- testis is swollen and is markedly tender. Often there is
dia are classically found in sexually active boys, but swelling and bruising of the scrotum. The most common
common urinary pathogens, including coliforms and injury is a hematoma of the testis. Ultrasound should be
Mycoplasma species, are more likely in younger children. obtained to evaluate for rupture of the tunica albuginea,
When studies suggest a bacterial infection, appropriate which is an indication for operative repair. Repair is par-
antibiotic therapy is initiated and adjusted according to ticularly important in postpubertal boys because of the
the culture results. If acute epididymitis is found on potential for autoimmune injury to the contralateral
scrotal exploration, cultures should be obtained, but the testis. A large hematoma in the space between the tunica
contralateral side should not be opened to avoid spread- vaginalis and the tunica albuginea should be evacuated to
ing the infection. As with any urinary tract infection in a avoid pressure necrosis of the testis. Epididymal injuries
boy, a renal bladder sonogram and voiding cystourethro- can occur, including disruption of the epididymis from
gram should be obtained after the infection has resolved. the testis, with a poor outcome even after repair.
Vesicoureteric reflux is the most common finding, but an
ectopic ureter (to the vas, ejaculatory duct, or seminal OTHER CONDITIONS
vesicle), ejaculatory duct obstruction, or urethral valves
can also be found. Other causes of the acute scrotum include an incarcer-
Viral infections are believed to be a common cause ated inguinal hernia, hydrocele, voiding dysfunction, and
for acute epididymitis, but are usually diagnosed pre- neoplasia. Testicular tumors can occur in the neonatal
sumptively. Mumps orchitis is rare and occurs in approxi- period and early childhood, although they are usually not
mately one-third of infected postpubertal boys.35 associated with pain or scrotal wall changes. They are
Adenovirus, enterovirus, influenza, and parainfluenza usually firm on examination and should be further evalu-
virus infections have also been found. Management is ated with ultrasound. Management is tailored to the diag-
supportive, antibiotics are not indicated, and the pain is nosis. See Chapter 51 for more information about
generally self-limited. testicular tumors.
3. Murphy JP, Gatti JM. Current management of the acute scrotum. 21. Stone KT, Kass EJ, Cacciarelli AA, et al. Management of suspected
Semin Pediatr Surg 2007;16:5863. antenatal torsion: What is the best strategy? J Urol 1995;153:
4. Bartsch G, Frank S, Marberger H, et al. Testicular torsion: Late 7824.
results with special regard to fertility and endocrine function. 22. Olguner M, Akgur FM, Aktug T, et al. Bilateral asynchronous
J Urol 1980;124:3758. perinatal testicular torsion: A case report. J Pediatr Surg
5. Bentley DF, Ricchiuti DJ, Nasrallah PF, et al. Spermatic cord 2000;35:13489.
torsion with preserved testis perfusion: Initial anatomical consid- 23. Sorenson MD, Galansky SH, Striegl AM, et al. Prenatal bilateral
erations. J Urol 2004;172:23736. extravaginal testicular torsion: A case presentation. Pediatr Surg Int
6. Caesar RE, Kaplan GW. Incidence of the bell-clapper deformity 2004;20:8923.
in an autopsy series. Urology 2004;44:11416. 24. Ahmed SJ, Kaplan GW, DeCambre ME. Perinatal testicular
7. Cifti AO, Senocak ME, Tanyel FC, et al. Clinical predictors torsion: Preoperative radiological findings and the argument for
for differential diagnosis of acute scrotum. Eur J Pediatr Surg 2004; urgent surgical exploration. J Pediatr Surg 2008;43:15635.
14:3338. 25. Pinto KJ, Noe HN, Jerkins GR. Management of neonatal testicular
8. Nelson CP, Williams JF, Bloom DA. The cremasteric reflex: A torsion. J Urol 1997;158:11967.
useful but imperfect sign in testicular torsion. J Pediatr Surg 26. Sorenson MD, Galansky SH, Striegl AM, et al. Perinatal extrav-
2003;38:12489. aginal torsion of the testis in the first month of life is a salvageable
9. Rabinowitz R. The importance of the cremasteric reflex in acute event. Urology 2003;62:1324.
scrotal swelling in children. J Urol 1984;132:8990. 27. Lusiri A, Vogler C, Steinhardt G, et al. Neonatal cystic testicular
10. Nussbaum Blask AR, Bulas D, Shalaby-Rana E, et al. Color gonadoblastoma: Sonographic and pathologic findings. J Ultra-
Doppler sonography and scintigraphy of the testis: A prospective, sound Med 1991;10:5961.
comparative analysis in children with acute scrotal pain. Pediatr 28. Masterson JS, McCullough AR, Smith RR, et al. Neonatal gonadal
Emerg Care 2002;18:6771. stromal tumor of the testis: Limitations of tumor markers. J Urol
11. Wu HC, Sun SS, Kao A, et al. Comparison of radionuclide imaging 1985;134:5589.
and ultrasonography in the differentiation of acute testicular 29. Samnakay N, Cohen RJ, Orford J, et al. Androgen and oestrogen
torsion and inflammatory testicular disease. Clin Nucl Med receptor status of the human appendix testis. Pediatr Surg Int 2003;
2002;27:4903. 19:5204.
12. Baker LA, Sigman D, Matthews RI, et al. An analysis of clinical 30. Dresner ML. Torsed appendage. Diagnosis and management: Blue
outcomes using color Doppler testicular ultrasound for testicular dot sign. Urology 1973;1:636.
torsion. Pediatrics 2000;105:6047. 31. Karmazyn B, Steinberg R, Livne P, et al. Duplex sonographic find-
13. Karmazyn B, Steinberg R, Kornreich L, et al. Clinical and sono- ings in children with torsion of the testicular appendages: Overlap
graphic criteria of acute scrotum in children: A retrospective study with epididymitis and epididymo-orchitis. J Pediatr Surg 2006;41:
of 172 boys. Pediatr Radiol 2005;35:30210. 5004.
14. Kiesling VJ Jr, Schroeder DE, Pauljev P, et al. Spermatic cord block 32. Rolnick D, Kawanoue S, Szanto P, et al. Anatomical incidence of
and manual reduction: Primary treatment for spermatic cord testicular appendages. J Urol 1968;100:7556.
torsion. J Urol 1984;132:9213. 33. Orazi C, Fariello G, Malena S, et al. Torsion of paradidymis or
15. Sessions AE, Rabinowitz R, Hulbert WC, et al. Testicular torsion: Giraldes organ: An uncommon cause of acute scrotum in pediatric
Direction, degree, duration, and disinformation. J Urol 2003;169: age group. J Clin Ultrasound 1989;17:598601.
6635. 34. Ballesteros Sampol JJ, Munne A, Bosch A. A vas aberrans torsion.
16. Bellinger MF, Abromowitz H, Brantley S, et al. Orchiopexy: An Br J Urol 1986;58:97.
experimental study of the effect of surgical technique on testicular 35. Beard CM, Benson RC Jr, Kelalis PP, et al. The incidence and
histology. J Urol 1989;142:5535. outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974.
17. Rodriguez LE, Kaplan GW. An experimental study of methods to Mayo Clin Proc 1977;52:37.
produce intrascrotal testicular fixation. J Urol 1988;139:5657. 36. Rabinowitz R, Hulbert WC Jr. Acute scrotal swelling. Urol Clin
18. Mor Y, Pinthus JH, Nadu A, et al. Testicular fixation following North Am 1995;22:1015.
torsion of the spermatic corddoes it guarantee prevention of 37. Clark WR, Kramer SA. HenochSchnlein purpura and the acute
recurrent torsion events? J Urol 2006;175:1713. scrotum. J Pediatr Surg 1986;21:9912.
19. Stillwell TJ, Kramer SA. Intermittent testicular torsion. Pediatrics 38. Soreide K. Surgical management of nonrenal genitourinary mani-
1986;77:90811. festations in children with HenochSchnlein purpura. J Pediatr
20. Das S, Singer A. Controversies of perinatal torsion of the spermatic Surg 2005;40:12437.
cord: A review, survey and recommendations. J Urol 1990;143: 39. Loh HS, Jalan OM. Testicular torsion in Henoch-Schnlein syn-
2313. drome. BMJ 1974;2:967.
C H A P T E R 5 3
Anomalies of renal formation and position result in inter- RENAL DYSPLASIA AND HYPOPLASIA
esting radiographs, but their clinical importance lies in
their associated anomalies. For example, the multicystic Since the development of the kidney depends on proper
dysplastic kidney often involutes, yet the initial evalua- interaction between the ureteric bud and the metane-
tion aims to determine that the contralateral kidney is not phric blastema, it should not be surprising that an abnor-
a risk from vesicoureteral reflux (VUR) or ureteropelvic mality in the location of the ureteral orifice is associated
junction (UPJ) obstruction. While no therapy is needed with abnormally induced renal tissue.2 Examination of
for unilateral renal agenesis, the link between a solitary the thickness of the renal parenchyma and number of
kidney and the VACTERL (vertebral, anal, cardiac, glomeruli associated with normal and ectopic ureters in
tracheoesophageal fistula, renal, limb) and Mayer fetal specimens suggests that it is the initial interaction
Rokitansky (vaginal agenesis) syndromes is the main between bud and blastema, rather than subsequent
reason for further evaluation. Hydronephrosis is often obstruction or VUR, that determines if normal renal
seen in abnormalities of position and rotation, but does tissue will develop.2 Figure 53-2 shows how a ureter
not necessarily mean that obstruction is present. There- which arises in the proper trigonal location (A, E, F) is
fore, anomalies of renal formation and position often associated with normal renal parenchyma whereas a
pose more of a diagnostic problem than a surgical one. ureter arising from a more cranial location (B, C, D) or
caudal location (G, H) is associated with progressively
less normal renal parenchyma.
RENAL EMBRYOLOGY Renal dysplasia and hypoplasia can be considered
errors in renal induction. Figure 53-3 shows varying
The pronephros, which has no adult function, induces changes from agenesis to dysplasia and hypoplasia of the
the mesonephros to differentiate into the mesonephric kidney. Although dysplasia is technically a histologic term,
duct during the fourth to eighth week of fetal life. The it refers to kidneys which contain primitive tubules either
mesonephric duct is the basis of the Wolffian system, focally or diffusely. These ducts are lined by epithelium
which develops into the seminal vesicles, vas deferens, and surrounded by swirls of primitive collagen. No treat-
epididymis, and efferent ductules of the testis in boys, and ment is necessary for the dysplastic kidney, but there is an
the epoophoron and paraophoron (vestigial remnants increased risk of reflux in the contralateral kidney.3 Hypo-
between the fallopian tube and ovary) in girls. Between plastic kidneys are small, normal kidneys with a decreased
weeks 9 and 12, the ureteric bud branches off the mes- number of nephrons. Dysplasia can also occur in hypo-
onephric duct, contacts the metanephric blastema bud, plastic kidneys. While secondary hypoplasia can occur
and induces the entire collecting system of ureter, renal due to infection or obstruction, two types of hypoplastic
pelvis, calyx, and collecting tubules. The kidney develops kidneys are clinically important: the oligomeganephronic
via induction of the metanephric blastema by the ureteric type, and the AskUpmark kidney. In oligomeganephro-
bud into Bowmans capsule, the convoluted tubules, and nia, there is a decrease in the number of nephrons with an
the loop of Henle.1 Figure 53-1 illustrates the progres- associated hypertrophy of the ones which are present.
sion of development from pronephros, to mesonephros, Patients present with polyuria and failure to concentrate
to metanephros. their urine, but no hypertension. Imaging with ultrasound
The kidneys begin at the upper sacral level with the (US) reveals small kidneys. Medical management with
renal pelvis facing anteriorly. The kidneys ascend either protein restriction, and high fluid and salt intake is initi-
because the lumbar and sacral regions grow faster than ated. Once the glomerular filtration rate drops signifi-
the cervical and thoracic regions between 4 to 8 weeks, cantly, dialysis is required.4 The AskUpmark kidney was
or because there is active migration. As the kidneys initially felt to be a developmental problem, but is now
ascend, the renal pelvis rotates medially by 90, leading believed to represent reflux nephropathy. The key finding
to the normal configuration of the renal pelvis lying is a small kidney with segmental hypoplasia, probably
medial to the parenchyma. During this time, the blood secondary to ascending pyelonephritis. VUR and hyper-
supply shifts from inferior branches of the aorta to more tension are usually present. Most patients are over 10
cephalad branches, with the final renal artery being years of age with a 2:1 female:male ratio. If the disease is
located at about L2. Failure of normal ascent leads to the unilateral, nephrectomy may cure the hypertension.
persistence of a low-lying blood supply.1 Bilateral disease is managed medically.5
709
710 SECTION VI Urology
Appearance and regression: agenesis. Absence of a hemitrigone implies that the ure-
cranial to caudal teral bud failed to form properly. A normal trigone with
some evidence of a ureter leading to a nubbin suggests
Pronephros: involution of a multicystic dysplastic kidney.
early fourth week
(never functional) Unilateral renal agenesis occurs in 1:1,000 live births
with a 2:1 male predominance.6,7 Unilateral renal agen-
esis can result in compensatory hypertrophy of the
Nephrogenic
contralateral kidney. The left kidney is more likely to
mesoderm be affected in unilateral renal agenesis.8 Since unilateral
Mesonephros: renal agenesis is asymptomatic and eventual renal func-
Wolffian fourth to ninth week tion is normal, the diagnosis is usually made on prenatal
duct ultrasound, or it is incidentally found during imaging for
Allantoic other abdominal symptoms. Sometimes it can be sus-
Ascent of
stalk
metanephros:
pected on plain abdominal films if the colon is medially
sixth to ninth week deviated at the splenic or hepatic flexures.9 These patients
should consider obtaining a medical alert bracelet so that
in case of traumatic injury, the solitary kidney is not
inadvertently removed.
Metanephros:
In a newborn with the prenatal diagnosis of unilateral
Ureter
fifth week onward renal agenesis, physical examination at the time of birth
Cloaca
should be focused on detecting the anomalies present in
Hindgut the VACTERL association (Box 53-1).10 A voiding cys-
FIGURE 53-1 Development of the kidney. (Redrawn from Gray tourethrogram (VCUG) should also be obtained since
SW, Skandalakis JE. Embryology for Surgeons. Philadelphia: WB approximately 30% of VACTERL patients with unilat-
Saunders; 1972. p. 444.) eral renal agenesis will have VUR in the contralateral
kidney.10
Males with unilateral renal agenesis are at risk for
abnormal Wolffian structures. The vas and seminal
vesicle may be absent (or the seminal vesicle may be
present as a cyst), but the ipsilateral testis will be normal.
Since the seminal vesicle develops as a separate bud from
the Wolffian duct at 12 weeks, it can be present in cases
of unilateral renal agenesis due to regression of a multi-
D cystic dysplastic kidney. Seminal vesicle cysts which are
C
A B causing symptomatic obstruction are usually removed via
a transvesical approach. Conversely, if a vas is found to
be abnormal or absent during a hernia repair or orchi-
E opexy, the kidneys should be evaluated postoperatively
F with an ultrasound.
H Females with unilateral renal agenesis should have
G their genital anatomy evaluated since up to 30% will
F have an abnormality of the Mllerian duct due to the
E
G A
C B
D
A B C
FIGURE 53-3 Renal (A) agenesis, (B) dysplasia, and (C) hypoplasia. (Redrawn from Gray SW, Skandalakis JE. Embryology for Surgeons.
Philadelphia: WB Saunders; 1972. p. 455.)
The renal vessels are normally positioned. The renal predominance.21 The contralateral kidney often also has
pelvis and calyces will often appear abnormal on an intra- a rotational abnormality or ectopia. The development of
venous urogram due to their unusual orientation. With the ipsilateral adrenal gland is unaffected. A thoracic
oblique views the anatomy can be established, and does kidney is actually subdiaphragmatic, although it may lie
not usually require repair, even in poorly functioning in the chest through a focal eventration of the diaphragm.
units. One method to localize even poorly functioning I t
ectopic renal tissue is with a nuclear medicine study. is not associated with a true congenital diaphragmatic
There are two technical factors to be considered in inter- hernia.22 An ectopic abdominal kidney is above the iliac
preting renal scans in ectopic kidneys. First, the radionu- crest, the lumbar kidney is anterior to the iliac vessels
clide in the bladder can overlap a pelvic kidney so a at the sacral promontory, and the pelvic kidney is below
catheter may need to be inserted for the study. Second, the aortic bifurcation and opposite the sacrum. All of
the pelvic kidney is located further anterior than ortho- these ectopic kidneys are more susceptible to trauma
topic kidneys, and the function may be artificially lowered since they are not as well protected by the lower rib cage
by the distance of the kidney from the camera. Placing and are anterior in position. It may be advisable for these
the patient prone may result in a more accurate assess- patients to avoid contact sports in which there is a risk of
ment. Magnetic resonance urography (MRU) is another abdominal trauma.
emerging technique for localizing ectopic renal units. Most ectopic kidneys are asymptomatic and are
Simple ectopia results in a kidney which is detected either on prenatal ultrasound or incidentally on
located anywhere from the pelvis to the diaphragm. The other imaging studies. Ectopic kidneys are at higher risk
incidence is 1:1,000 live births with a 3:2 male for UPJ obstruction, VUR, and stone formation. The
53 Developmental and Positional Anomalies of the Kidneys 713
C D
FUSION DEFECTS
Horseshoe Kidney
A horseshoe kidney is found in 1:400 live births, and has
a 2:1 male predominance.26 The kidney is usually lower
than normal, since the lower poles fuse in the midline
and drape anteriorly over the spine. The isthmus can be
fibrotic or contain parenchyma. This anomaly is believed
to occur between 4 to 6 weeks of life, since the orienta- E F
tion of the renal pelvis is anterior. It is proposed that as
the kidneys hurdle the iliac vessels during ascent, they
come into contact at the lower pole and fuse (Fig. 53-5).
Other variations of upper pole and mid-pole contact are
possible, but much less common than the usual lower
pole fusion. The kidney is usually low due to its inability
to ascend past the inferior mesenteric artery. Each renal
moiety retains its ureter, which is draped over the isthmus.
The renal pelvis is usually anterior. The arterial supply
varies from the normal single vessel to each moiety to
vessels arising from any conceivable nearby blood supply. G H
Horseshoe kidneys are more commonly found in patients
with sacral agenesis, high cloacas, and Turner syndrome
(45,XO gonadal dysgenesis).27 They are associated with a
higher risk of renal cell carcinoma and Wilms tumor.2830
The presence of a Wilms tumor in a horseshoe kidney
was not suspected preoperatively in 13/41 patients despite
imaging studies.30
One-third of patients with horseshoe kidney have no
symptoms. The patients with symptoms often complain
of vague abdominal or back pain. 10% have ureteral
duplication, 50% have VUR, and 33% have UPJ obstruc- I J
tion.27,31,32 Repair of UPJ obstruction in a horseshoe FIGURE 53-5 Variations of horseshoe kidney. (Redrawn from
kidney requires placement of the anastomosis to avoid a Banjamin JA, Schullian DM. Observations of kidneys with horse-
secondary kinking at the UPJ. Division of the isthmus is shoe configuration: The contribution of Leonardo Botallo. J Hist Med
not required. Treatment of kidney stones in horseshoe Allied Sci 1950;5:315, after Gutierrez, 1931.)
kidneys can be accomplished by extracorporeal shock
wave lithotripsy, ureteroscopy, or percutaneous nephro- rate than ureteroscopy or shock wave lithotripsy.33,34
lithotomy. Percutaneous approaches are sometimes dif- Although there is no increase in the rate of metabolic
ficult as the kidneys do not reside next to the body wall, abnormalities in patients with horseshoe kidneys and
making access to the collecting system difficult. However, kidney stones, suggesting that stasis in an extrarenal
percutaneous approaches result in a higher stone-free pelvis contributes to the formation of kidney stones,35
714 SECTION VI Urology
patients with a horseshoe kidney and kidney stones are dilated collecting tubules. Periportal hepatic fibrosis also
more likely to have hypocitraturia than other patients occurs in varying degrees, and can lead to portal hyper-
with kidney stones.36 tension. The hepatic involvement appears to be inversely
proportional to the renal involvement. The disease has
been classified into four forms.37 The severe perinatal
Cross-fused Renal Ectopia form (>90% renal involvement) leads to death by six
This anomaly is more common than crossed, non-fused weeks from pulmonary hypoplasia. The neonatal form
renal ectopia and is more common in boys. The lower (60% renal involvement) is usually lethal by one year.
pole of one kidney crosses the midline to fuse with an The infantile form (25% renal involvement) results in
orthotopically placed contralateral kidney. Usually the hepatosplenomegaly, with survival up to 10 years. The
left kidney crosses the midline. Presumably during ascent, juvenile form (<10% renal involvement) has severe peri-
the left kidney encounters a roadblock, rotates, and fuses portal fibrosis. Some patients survive up to 15 years, but
with the lower pole of the right kidney. The ureters insert the development of portal hypertension is usually lethal.
in the normal position in the bladder. This has been Since this is an autosomal recessive disease, family screen-
described as an S- or L-shaped kidney. Diagnosis can be ing should be undertaken to determine which siblings are
made using intravenous pyelogram (IVP), CT, or MRU. carriers.
Solitary crossed ectopia (unilateral renal agenesis, con- A prenatal ultrasound showing bilaterally enlarged
tralateral kidney crossed to opposite side) is a rare finding. echogenic kidneys suggests ARPKD. The IVP or CT
Multicystic dysplasia, obstruction, and VUR can be found shows a classic striated sunburst pattern. Unfortunately,
in the ectopic kidney. the prognosis is poor for the perinatal or neonatal forms
of ARPKD. The patients who survive the neonatal period
seem to do well with some degree of renal insufficiency.
CYSTIC RENAL DISEASE Eventually, dialysis is usually required. In older patients,
the kidneys become smaller as renal failure develops. The
AND CYSTIC TUMORS overall treatment for ARPKD is supportive, with renal
Autosomal Recessive Polycystic Kidney transplantation being the ultimate therapy.
Disease (ARPKD)
Autosomal Dominant Polycystic Kidney
This disease was formerly called infantile polycystic
kidney disease, which is inaccurate since it can present in
Disease (ADPKD)
older patients. While it occurs in 1:40,000 live births, While ADPKD tends to clinically present in the third to
many patients die soon afterwards. The kidneys are bilat- fifth decade, it has been diagnosed in the ultrasound era
erally enlarged, with very small cysts radially oriented in asymptomatic children as well. The cysts in ADPKD
throughout parenchyma (Fig. 53-6). The cysts represent are different in configuration, being few and scattered in
A B
distinction to those seen in ARPKD. This condition usually feasible to monitor a patient indefinitely for a
occurs in 1:500 patients.38 Patients usually present with MCDK. We have taken an operative approach at 18 to
flank pain, hematuria, hypertension, and possibly renal 24 months of life if the MCDK is not involuting, or if
failure, if there are extensive bilateral cysts. Neonates can parenchyma remains visible on the ultrasound. Although
present with renal enlargement, although children from the indications are controversial, the kidney can be
affected families who are screened usually only have a few removed at that age via laparoscopy or a small incision as
cysts. Failure to see cysts on screening ultrasound in a an outpatient procedure (Fig. 53-7). Occasionally, the
child at risk for ARPKD does not exclude the disease MCDK can involute prenatally, leaving a ureter with a
since the cysts can develop later in life. Linkage analysis small nubbin of tissue in the renal fossa. These were
of the loci on chromosome 4 and 16 is more sensitive.39 previously called aplastic kidneys, but are now felt to
The cysts are located throughout the cortex and medulla, represent the remnants of a MCDK.
although the fetal form seems to affect the glomeruli
predominantly. Hepatic involvement is limited to biliary
cysts. Associated findings include cysts in the spleen, pan-
Cystic Nephroma
creas, and lungs, mitral valve prolapse, colon diverticuli, Formerly called a multilocular cyst, this is a well demar-
and berry aneurysms of the circle of Willis. cated tumor of cysts with an overall round configuration,
Hypertension is commonly found in these children, lined with epithelium and septae which contain tubules.49
and may be part of the presentation. Renal failure in It is considered to be the benign end of a spectrum
childhood is very rare. Periodic evaluation of blood pres- progressing from cystic Wilms tumor, cystic partially
sure and proteinuria during childhood is recom- differentiated nephroblastoma, to cystic nephroma. It
mended.40,41 Unlike ARPKD, there is no increased risk of usually is found in boys under age 4 (male:female ratio
renal cell carcinoma. Renal transplant candidates can 2:1) or women over 30 (female:male ratio 8:1). It is
obtain organs from family members who have been rarely bilateral and is cured by partial nephrectomy, shell-
screened for the disease. ing out the tumor by following the plane of the pseudo-
capsule. There is a risk of sarcomatous degeneration in
adults if it is not removed.50
Multicystic Dysplastic Kidney (MCDK)
The multicystic dysplastic kidney is believed to be caused
by severe early ureteral obstruction or a failure in ureteric
Cystic Partially Differentiated
bud-metanephric blastema induction.42,43 The main dif- Nephroblastoma
ferential diagnosis is severe hydronephrosis due to This lesion was formerly called a multilocular cystic
UPJ obstruction. Radiographically, this occurs when the nephroma. It is radiologically identical to the cystic neph-
peripheral cysts surround a dominant central cyst mim- roma, and can only be diagnosed pathologically. The
icking the renal pelvis (hydronephrotic form of MCDK).
The classic ultrasound appearance shows cysts randomly
distributed throughout the kidney without a dominant
medial cyst or evidence of communication between cysts.
The parenchyma, if present, has abnormal echogenicity
and is seen between the cysts, instead of being arranged
on their periphery. A renal scan will show no function in
a MCDK. The affected area may be the upper pole of a
duplicated collecting system, or one-half of a horseshoe
kidney.
The MCDK is the most common renal cystic mass in
the newborn. Currently, most are detected on prenatal
ultrasound. Bilateral forms are not compatible with life.
Postnatal evaluation consists of a VCUG to look for
VUR in the contralateral kidney, which is found 30% of
the time.44 If there is significant hydronephrosis (caliecta-
sis) in the contralateral kidney (this occurs 12% of the
time), then a diuretic renal scan may be necessary. Con-
tralateral UPJ obstruction or VUR is more likely with a
smaller MCDK or a lower ureteral atresia ipsilateral to
the MCDK.45,46 There are reports of malignancy arising
from a MCDK, although it is unclear whether the affected
kidneys were truly MCDK.47 Hypertension has also been
reported in association with MCDK, although resection
is not always curative, and the rate does not appear to be
any higher than the general population.48
MCDK usually involute, but they can occasionally
grow.48 The follow-up is repeat imaging with ultrasound
every six months for the first two years of life. It is not FIGURE 53-7 Resected multicystic dysplastic kidney.
716 SECTION VI Urology
majority of patients are boys less than 2 years old, or 3. Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities
women in their third to fourth decade. A classic (but not in multicystic-dysplastic kidney disease. J Pediatr 1992,121:657.
4. Royer P, Habib R, Broyer M, et al. LHypoplasie renale bilaterale
diagnostic) radiologic finding is herniation of a parenchy- congenitale avec reduction du nombre et hypertrophie des neph-
mal mass into the renal pelvis.22 The tumor is usually well rons chez lenfant. Ann Pediatr (Paris) 1962;38:13346.
circumscribed. Hemorrhage and calcification are usually 5. Arant BS Jr, Sotelo-Avila C, Bernstein J. Segmental hypoplasia
absent. Pathologically, it differs from the cystic nephroma of the kidney (Ask-Upmark). J Pediatr 1979,95:9319.
6. Doroshow LW, Abeshouse BS. Congenital unilateral solitary
in that there is blastema found in the septations. kidney: Report of 37 cases and a review of the literature. Urol Surv
Patients usually present with an asymptomatic flank 1961,11:21929.
mass, and occasionally hematuria. Operative treatment 7. Sheih CP, Hung CS, Wei CF, et al. Cystic dilatations within the
consists of partial nephrectomy as for cystic nephroma, pelvis in patients with ipsilateral renal agenesis or dysplasia. J Urol
since the tumors rarely recur and are not multifocal. 1990;144:3247.
8. Kohn G, Borns PF. The association of bilateral and unilateral renal
No chemotherapy is required for stage I (limited to aplasia in the same family. J Pediatr 1973;83:957.
capsule, fully resected) tumors. Although experience is 9. Mascatello V, Lebowitz RL. Malposition of the colon in left renal
limited, stage II (outside renal capsule but fully resected) agenesis and ectopia. Radiology 1976,120:3716.
are usually treated with vincristine, dactinomycin, 10. Kolon TF, Gray CL, Sutherland RW, et al. Upper urinary tract
manifestations of the VACTERL association. J Urol 2000;163:
and doxorubicin. Four year survival for both stages is 194951.
100%.51,52 11. Downs RA, Lane JW, Burns E. Solitary pelvic kidney. Its clinical
implications. Urology 1973;1:516.
12. Thompson DP, Lynn HB. Genital anomalies associated with soli-
Simple Cysts and Calyceal Diverticuli tary kidney. Mayo Clin Proc 1966;41:53848.
13. Tarry WF, Duckett JW, Stephens FD. The Mayer-Rokitansky
The simple renal cyst on ultrasound has the following syndrome: Pathogenesis, classification, and management. J Urol
characteristics: distinct wall, no internal echoes, and pos- 1986,136:64852.
terior enhancement. If these criteria are not met, a CT 14. Griffin JE, Edwards C, Madden JD, et al. Congenital absence of
scan is obtained to confirm that the fluid does not the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Ann
Internal Med 1976;85:22436.
enhance. The differential diagnosis is a calyceal diver- 15. Potter EL. Bilateral absence of ureters and kidneys: A report of 50
ticulum or hydrocalyx, both of which communicate with cases. Obstet Gynecol 1965;25:312.
the collecting system, and in which the fluid should 16. Ashley DJ, Mostofi FK. Renal agenesis and dysgenesis. J Urol
enhance on either IVP or CT. Ultrasound is able to 1960;83:21130.
detect milk of calcium layering within a diverticulum. 17. Carpentier PJ, Potter EL. Nuclear sex and genital malformation in
48 cases of renal agenesis, with especial reference to nonspecific
Calyceal diverticuli require treatment when they harbor female pseudoheramphroditism. Am J Obstet Gynecol 1959;78:
stones or infection. In the IVP era, 40% of calyceal diver- 23558.
ticuli were felt to be symptomatic.53 In the ultrasound era, 18. Geisinger JG. Supernumerary kidney. J Urol 1937;38:331.
with its greater number of incidental findings, it is not 19. NGuessan G, Stephens FD. Supernumerary kidney. J Urol
1983;130:64953.
clear how often calyceal diverticuli require treatment. 20. Weiss JP, Duckett JW, Snyder HM. Single unilateral vaginal
Minimally invasive approaches such as percutaneous, ectopic ureter: Is it really a rarity? J Urol 1984;132:11779.
laparoscopic, and ureteroscopic ablation appear to be 21. Malek, RS, Kelalis, PP, Burke EC. Ectopic kidney in children and
equally successful.54 frequency of association with other malformations. Mayo Clinic
Simple cysts reside in the cortex and are lined by Proc 1971;46:4617.
22. Zagoria RL, Tung GA. The kidney and retroperitoneum: Anatomy
simple columnar epithelium. They can grow, resorb, or and congenital anomalies. In: Zagoria RL, editor. Genitourinary
remain the same size. They are usually asymptomatic and Radiology: The Requisites. St. Louis: Mosby; 1997. p. 5179.
are found incidentally. Once they are found, the authors 23. Dretler SP, Pfister R, Hendren WH. Extrarenal calyces in the
usually follow with ultrasound at 3 to 6 month intervals ectopic kidney. J Urol 1970;103:40610.
24. Gleason PE, Kelalis PP, Husmann DA, et al. Hydronephrosis
to determine if the cyst is growing. The underlying in renal ectopia: Incidence, etiology, and significance. J Urol
concern is whether or not this cyst is the first sign of 1994;151:16601.
ADPKD. A family history of renal cystic disease, renal 25. Jabbour ME, Goldfischer ER, Stravodimos KG, et al. Endopyelot-
failure, or death in the neonatal period from unknown omy for horseshoe and ectopic kidneys. J Urol 1998,160:6947.
causes should be sought. Biopsy to rule out tumor, fol- 26. Dees J. Clinical importance of congenital anomalies of upper
urinary tract. J Urol 1941;46:659.
lowed by drainage, or unroofing should only be under- 27. Boatman DL, Kolln CP, Flocks RH. Congenital anomalies associ-
taken if the cyst characteristics are other than those listed ated with horseshoe kidneys. J Urol 1972;107:2057.
for a simple cyst, or if the cyst becomes symptomatic due 28. Buntley D. Malignancy associated with horseshoe kidney. Urology
to obstruction of an infundibulum or the UPJ. Minimally 1976;8:1468.
29. Hohenfellner M, Schultz-Lampel D, Lempel A, et al. Tumor in the
invasive approaches such as percutaneous puncture with horseshoe kidney: Clinical implications and review of embryogen-
instillation of sclerosing agents (absolute alcohol, esis. J Urol 1992;147:1098102.
bismuth, povidone-iodine55) or laparoscopic decortica- 30. Neville H, Ritchey ML, Shamberger RC, et al. The occurrence of
tion56 may shift the threshold for treatment of large Wilms tumor in horseshoe kidneys: A report from the National
asymptomatic simple cysts. Wilms Tumor Study Group (NWTSG). J Pediatr Surg 2002;37:
11347.
31. Segura JW, Kelalis PP, Burke EC. Horseshoe kidney in children.
REFERENCES J Urol 1972;108:3336.
1. Gray SW, Skandalakis JE. The kidney and ureter. In: Embryology 32. Whitehouse GH. Some urographic aspects of horseshoe kidney
for Surgeons. Philadelphia: WB Saunders; 1972. p. 443518. anomaly a review of 59 cases. Clin Radiol 1975;26:10714.
2. Mackie GG, Stephens FD. Duplex kidneys: A correlation of renal 33. Yohannes P, Smith AD. The endourological management of
dysplasia with position of the ureteral orifice. J Urol 1975;114: complications associated with horseshoe kidney. J Urol
27480. 2002;168:58.
53 Developmental and Positional Anomalies of the Kidneys 717
34. Miller NL, Matlaga BR, Handa SE, et al. The presence of horse- 46. Cendron J, Kiriakos S. Rein multikystique. J Urol Nephrol (Paris)
shoe kidney does not affect the outcome of percutaneous nephro- 1976,82(S2):32233.
lithotomy. J Endourol 2008;22:121925. 47. Beckwith JB. Comment, Wilms tumor and multicystic dysplastic
35. Evans WP, Resnick MI. Horseshoe kidney and urolithiasis. J Urol kidney disease. J Urol 1997;158:225960.
1981;125:6201. 48. Wacksman J, Phipps L. Report of the multicystic kidney registry:
36. Raj GV, Auge BK, Assimos D, et al. Metabolic abnormalities associ- Preliminary findings. J Urol 1993;150:18702.
ated with renal calculi in patients with horseshoe kidney. J Endou- 49. Joshi VV, Beckwith JB. Multilocular cyst of the kidney (cystic
rol 2004;12:15761. nephroma) and cystic, partially differentiated nephroblastoma.
37. Blyth H, Ockenden BG. Polycystic disease of kidney and liver Terminology and criteria for diagnosis. Cancer 1989;64:466
presenting in childhood. J Med Genet 1971;8:25784. 79.
38. Gabow PA. Autosomal dominant polycystic kidney disease. N Engl 50. Castillo OA, Boyle ET Jr, Kramer SA. Multilocular cysts of the
J Med 1993,329:33242. kidney. A study of 29 patients and review of literature. Urology
39. Gabow PA, Kimberling WJ, Strain JD, et al. Utility of ultrasonog- 1991;37:15662.
raphy in the diagnosis of autosomal dominant polycystic kidney 51. Blakely ML, Shamberger RC, Norkool P, et al. Outcome of
disease in children. J Am Soc Nephrol 1997;8:10510. children with cystic partially differentiated nephroblastoma
40. Ravine D, Walker RG, Gibson RN, et al. Treatable complications treated with and without chemotherapy. J Pediatr Surg
in undiagnosed cases of autosomal dominant polycystic kidney 2003;38:897900.
disease. Lancet 1991;337:1279. 52. Luithle T, Szavay P, Furtwangler R, et al. Treatment of cystic
41. Zerres K, Rudnik-Schoneborn S, Deget F. Routine examination of nephroma and cystic partially differentiated nephroblastoma
children at risk of autosomal dominant polycystic kidney disease. A report from SIOP/GPOH study group. J Urol 2007,177:
Lancet 1992;339:13567. 2946.
42. Beck AD. The effect of intra-uterine urinary obstruction upon the 53. Timmons JW Jr, Malek RS, Hattery RR, et al. Caliceal diverticu-
development of the fetal kidney. J Urol 1971;105:7849. lum. J Urol 1975;114:69.
43. Osathanondh V, Potter EL. Pathogenesis of polycystic kidneys: 54. Canales B, Monga M. Surgical management of the calyceal diver-
Historical survey. Arch Pathol 1964;77:45965. ticulum. Curr Opin Urol 2003;13:25560.
44. Flack CE, Bellinger, MF. The multicystic dysplastic kidney and 55. Phelan M, Zajko A, Hrebinko RL. Preliminary results of percuta-
contralateral vesicoureteral reflux: protection of the solitary kidney. neous treatment of renal cysts with povidone-iodine sclerosis.
J Urol 1993;150:18734. Urology 1999;53:81617.
45. Cendron J, Gubler JP, Valayer J, et al. Dysplasie multikystique du 56. Lifson BJ, Teichman JM, Hulbert JC. Role and long-term results
rein chez enfant. A propos de 45 observations. J Urol Nephrol of laparoscopic decortication in solitary cystic and autosomal domi-
(Paris) 1973;79:77399. nant polycystic kidney disease. J Urol 1998;159:7026.
C H A P T E R 5 4
Hydronephrosis and ureteral malformations are among Histologic evaluation reveals a decrease or complete
the most common anomalies in the urinary tract in chil- absence of smooth muscle fibers at the UPJ.11 Electron
dren. Most are now detected prenatally. Urinary tract microscopy may show an increase in collagen deposition
dilation is present in 1 in 100 fetuses, but significant between the muscle fibers that is most likely a response to
uropathy is found in only 1 in 5001,2 (Fig. 54-1). the obstruction as opposed to the cause.12 Fibrosis and
interruption of the smooth muscle continuity block trans-
mission of the peristaltic wave, while defective innerva-
URETEROPELVIC JUNCTION tion also may play a role.13 UPJ obstruction also can be
OBSTRUCTION IN CHILDREN secondary, i.e., related to other ureteral pathology. It can
be found in conjunction with high-grade vesicoureteral
With ureteropelvic junction (UPJ) obstruction, there is reflux (VUR), after cutaneous ureterostomy, and after
inadequate drainage of urine from the renal pelvis, result- decompression of the dilated urinary tract. VUR is present
ing in hydrostatic distention of the pelvis and intrarenal in 14% of patients with UPJ obstruction (Fig. 54-2).14,15
calyces. The combination of increased intrapelvic pres-
sure and urine stasis in the collecting ducts results in
progressive damage to the kidney.
Clinical Presentation
Historically, the incidence of UPJ obstruction has Most renal dilation and obstruction are detected prena-
been estimated at 1 in 5,000 live births. However, with tally. Less frequently, it is detected because of an abdomi-
the advent of antenatal ultrasonography (US), the preva- nal mass, urinary tract infection (UTI), or associated with
lence of dilation has been found to be much higher. other congenital anomalies (i.e., VACTERL syndrome).
Retrospective reviews show that although the incidence In older children, vague, poorly localized, cyclic or acute
of detected dilation has increased, the actual number of abdominal pain associated with nausea is common (Fig.
operations for UPJ obstruction has been relatively con- 54-3). Some of these children are initially seen by gastro-
stant at 1:1,250 births.3,4 UPJ obstruction is more enterologists. The cause for the intermittent obstruction
common in boys (2:1), and two-thirds occur on the left is unclear, but renal function is almost always preserved.
side. Bilateral dilation occurs in 510% of patients, and Hematuria after minor trauma or vigorous exercise may
is much more frequently seen in younger children. Bilat- be a presenting feature, most likely secondary to rupture
eral obstruction is much less common.5 of mucosal vessels in the dilated collecting system.5
Etiology Diagnosis
During development of the upper ureter, the lumen of When the antenatal diagnosis of UPJ obstruction is
the ureteral bud solidifies with ureteral lengthening and made, the initial postpartum evaluation should be per-
later recanalization.6 Failure to recanalize adequately is formed at 10 to 14 days of life to avoid false-negative
thought to be the cause of most intrinsic UPJ obstruc- studies resulting from the transitional nephrology of the
tions. Other causes of intrinsic UPJ obstruction include newborn. Bilateral dilation is rarely associated with sig-
ureteral valves, polyps, and leiomyomas.7 nificant enough obstruction to cause oligohydramnios
The most common observation is ureteral narrowing and warrant antenatal intervention. Ultrasound confirms
of a variable length that joins the renal pelvis above the the presence of pelvic and calyceal dilation, with variable
expected dependent position.8 At low volume, peristaltic thinning of the renal parenchyma. The Society for Fetal
waves of urine cross the UPJ. However, as the flow Urology (SFU) classification is typically used to describe
increases beyond a threshold, the renal pelvis dilates.9 the degree of dilation (Fig. 54-4).16 The presence of
The dilated pelvis may functionally kink the ureter corticomedullary junctions is indicative of preserved
further, increasing the pelvic pressure. In 2030% of function.15 Ultrasound is used to evaluate the contralat-
patients, the ureter is draped over a lower-pole vessel, eral kidney, the bladder, and the distal ipsilateral
producing an extrinsic UPJ obstruction. In most situa- ureter to avoid confusion with a ureterovesical junction
tions, there is also a coexisting luminal narrowing of the (UVJ) obstruction, but it does not provide functional
ureter.10 information.
718
54 Ureteral Obstruction and Malformations 719
A B C
FIGURE 54-3 This CT scan was obtained for evaluation of severe abdominal pain. (A) Axial view shows marked dilation of the left
renal pelvis (asterisk) with preserved renal parenchyma. (B, C) A lower pole crossing vessel is seen (arrow).
A B C
D E
FIGURE 54-4 These neonatal ultrasound images come from infants with a history of prenatally detected renal dilation. (A) This
ultrasound is normal for comparison purposes. There are dark renal pyramids (arrow) and no renal pelvic dilation. (B) This image
shows isolated renal pelvic dilation (arrow) (SFU grade I). (C) This image shows dilation of the renal pelvis (solid arrow) and upper
and lower-pole calyces (dotted arrows) (SFU grade II). (D) Calyceal dilation and cortical thinning are seen (SFU grade IV).
(E) Hydronephrosis with peripheral cysts (arrow) indicating dysplasia is seen. This kidney had no function on renal scan.
720 SECTION VI Urology
In the past, routine antibiotic prophylaxis was utilized drainage (Fig. 54-5). In this study, the transit of an injected
in all infants with prenatal dilation but the risk of UTI is radioisotope through the urinary tract is monitored by a
very small in the absence of reflux.17 A voiding cystoure- gamma camera. The early uptake (first 1 to 2 minutes) of
throgram (VCUG) was previously recommended in all the tracer indicates the split renal function, while the
patients being evaluated for UPJ obstruction. VUR washout, augmented by the administration of a diuretic, is
increases the chance that infection will occur, even in a evaluated and plotted by a computer to demonstrate
partially obstructed system. Between 530% of infants drainage.1820 The study is obtained with either 99mTc-
with prenatally detected dilation will have reflux, and the mercaptoacetyltriglycine (99mTc-MAG3), whose clearance
majority will spontaneously resolve without an infec- is predominantly via proximal tubular secretion, or with
tion.15 Children with isolated pyelectasis and no ureteral technetium-99m-labeled diethylenetriamine pentaacetic
dilation have a very low incidence of reflux and do not acid (99mTc-DTPA), whose renal clearance is by glomerular
need a screening VCUG. filtration. 99mTc-MAG3 is more efficiently excreted than
99m
The diuretic isotopic renogram is very useful for evalu- Tc-DTPA and gives better images, particularly in
ating hydronephrosis, differential renal function, and renal patients with impaired renal function.19,20
Renal Flow
02-03-12
21257
Right
Left
100% 100%
60 60
Right Left 60
The technique for diuretic renography is standard- obstruction. This is rarely required because a well-
ized.20 Patients should be hydrated intravenously performed ultrasound evaluation and radionuclide study
(15mL/kg) 15 minutes before injection of the radionu- will exclude distal obstruction.23 As there are risks with
clide. An indwelling catheter maintains an empty bladder using instruments in the infant male urethra and the
and monitors urine output. The diuretic (1mg/kg ureteral orifice, these retrograde studies are not usually
furosemide, up to 40mg) is not administered until the performed.
activity peaks in the hydronephrotic kidney and renal
pelvis. The tracer activity is then monitored for an addi-
tional 30 minutes, and a quantitative analysis is per- Management
formed. Historically, persistence of more than 50% of the Indications for Intervention
tracer in the renal pelvis 20 minutes after diuretic admin-
istration (t 12 >20) is diagnostic of obstruction, although Intermittent obstruction and pain are probably the most
the applicability of this threshold in pediatric patients is reliable indication for operation. Diminished function,
debatable. False-positive results may occur when the delayed drainage, progression of pelvic and calyceal dila-
immature neonatal kidney fails to respond to diuretic, tion on ultrasound, and loss of renal function are all
when the diuretic is administered prior to maximal renal potential indicators of obstruction. Randomization to
pelvic distension, when the patient is dehydrated, when operative and observational arms is complicated by a dif-
the bladder is distended, or when the pelvis is signifi- ficult decision that a parent has to make for the asymp-
cantly dilated. tomatic child.24 The morphologic appearance of a dilated
Magnetic resonance urography (MRU) can be used at renal pelvis on excretory urography or ultrasound is not
any age. T2-weighted images are independent of renal a good indication for operation because many of these
function, and hydronephrosis is readily detected. The findings will resolve without the need for operation (see
anatomic images are excellent (Fig. 54-6). Enhanced MR Fig. 54-5).25 Neonatal hydronephrosis can often be
images with gadolinium can give information regarding explained by physiologic polyuria and natural kinks and
differential function if one kidney is anatomically and folds in the ureter.
functionally normal.21 The ongoing debate in the management of neonatal
Rarely, when imaging is equivocal, invasive pressure UPJ obstruction centers on the definition of significant
flow studies may be indicated.22 These tests assume that obstruction. Diuretic renography has limitations in the
obstruction produces a constant restriction to outflow neonate, although using the well-tempered approach
that necessitates elevated pressure to transport urine at increases its value.20 The standard half-time of 20 minutes
high flow rates. However, not all obstructions are con- for obstruction in the neonate is misleading in many
stant. If the obstruction is intrinsic, a linear relationship cases.
exists between pressure and flow. However, in some cases, Differential renal function or individual kidney
the results reflect only the response of the renal pelvis to uptake is the most useful information obtained during
distention and may be positive in the absence of obstruc- renography.2426 An indication for operation is diminished
tion. These studies require general anesthesia in children renal function in the presence of an obstructive pattern
and have limited applicability. on renography. The threshold is arbitrary, but most sur-
Retrograde urography at the time of operative correc- geons believe that less than 3540% function in the
tion is helpful if uncertainty exists regarding the site of hydronephrotic kidney warrants correction. However,
one series of patients with dilated kidneys and no more
than 25% total renal function were found to improve to
more than 40% of total function in all cases without
operative correction.25 Long-term studies of kidneys with
greater than 40% function have shown that fewer than
1520% will require operation for diminishing function,
UTIs, or unexplained abdominal pain.26,27 Some of these
kidneys will regain some of the lost function.
The concern with an observational approach is that
delaying correction until there is measurable deteriora-
tion of renal function is not optimal. In the past, urinary
stasis (infection, calculi, hypertension, and pain) was the
indication for correction. Whether more emphasis should
be placed on stasis and less emphasis on differential renal
function is an unanswered question. Pyeloplasty can be
safely performed in the infant. Early intervention elimi-
nates the indefinite period of surveillance. The decision
to follow neonates nonoperatively requires vigilance and
parental cooperation to avoid complications.
FIGURE 54-6 In this 6-month-old infant, an ultrasound showed If the child is initially seen with acute pain or infection,
a dilated ureter below the kidney, but not at the level of the
bladder. This coronal image shows marked dilation of the proxi-
it is advisable to wait one to two weeks to allow the
mal ureter (arrow) and pelvis (asterisk) due to a proximal ure- inflammation to resolve. Percutaneous drainage or stent
teral valve. placement for sepsis is rarely required preoperatively. It
722 SECTION VI Urology
should be avoided in the absence of infection because of left near the anastomosis and can usually be removed
the inflammation that develops from a tube in the renal within 48 hours. If drainage is prolonged, the child can
pelvis. Exploration of a poorly functioning kidney requires be discharged with the drain in place. Renal drainage is
assessment of the renal parenchyma. If the parenchyma indicated in solitary kidneys or when simultaneous bilat-
is grossly dysplastic or frozen-section analysis shows only eral pyeloplasties are performed. In reoperation, it is
dysplasia, then nephrectomy should be performed. No technically more difficult to achieve a watertight anasto-
test accurately predicts recovery of function. Thus, mosis and internal drainage (stent, nephrostomy or neph-
nephrectomy is rarely performed in the infant with UPJ rostent) is indicated.
obstruction. Extrinsic UPJ obstruction associated with an aberrant
lower-pole vessel requires division of the ureter at the
UPJ and performance of a standard dismembered pyelo-
Operative Techniques
plasty after transposing the ureter to a nonobstructed
A dismembered pyeloplasty is the preferred technique to position. This is preferable to laparoscopic transposition
correct UPJ obstruction (Fig. 54-7). A successful outcome of the crossing vessel. In the case of an intrarenal pelvis
is achieved with construction of a funnel-shaped, depend- or when significant scarring is found at reoperation, a
ent UPJ complex. The renal pelvis and upper ureter are ureterocalicostomy is a useful technique.31 A portion of
mobilized and the ureter is divided just below the the lower pole should be resected to prevent a postopera-
obstructed segment. It is spatulated on its lateral border tive stricture. The ureter is spatulated and then anasto-
through the aperistaltic segment. Usually, it is necessary mosed to the exposed calyx in the lower pole.
to resect some of the renal pelvis to avoid postoperative The open approach still has a role in infants and young
obstruction. If this segment is particularly long, a flap of children. Laparoscopic pyeloplasty has been performed
renal pelvis can be created. Foley YV-plasty and the Culp in all ages and the age of the patient is inversely related
spiral flap were designed to maintain the continuity of to benefits of decreased pain and convalescence.32 Open
the ureter and the pelvis.28,29 These techniques are used pyeloplasty can be performed through a flank, anterior
in unusual cases of malrotation, fusion anomalies, or extraperitoneal approach, or posterior lumbotomy
long, stenotic segments. approach. The anterior approach involves a transverse
The anastomosis is performed with 6-0 polydioxanone incision from the edge of the rectus to the tip of the 12th
or 6-0 polyglycolic acid. The anastomosis begins at the rib.33 The retroperitoneum is entered and the UPJ is
most dependent portion of the pyeloplasty with place- exposed, with the kidney left in situ. In infants, this is a
ment of interrupted everting sutures that do not bunch muscle-splitting incision with low morbidity. The poste-
the tissues and cause obstruction. After the anastomosis rior lumbotomy also can be easily performed in infancy
to the dependent portion of the pelvis is completed, the and provides direct access to the UPJ.34 The kidney does
remainder of the ureter and pelvis can be approximated not require mobilization, and the ureter and renal pelvis
with continuous suture, taking care to irrigate any clots can usually be delivered into the incision. In bilateral
from the pelvis before the closure is completed. It is not cases, the child does not need to be repositioned. The
necessary to pass a catheter distally into the bladder lumbotomy approach should not be used with a malro-
because preoperative studies should have excluded a tated kidney or a kidney that has an intrarenal pelvis. An
distal obstruction. anterior or flank approach is always preferred for reop-
Pyeloplasties are frequently performed without diver- eration although laparoscopy and endopyelotomy have
sion so it is important to be as gentle as possible.30 Exces- largely replaced open re-operative pyeloplasty.35
sive handling of the pelvis and ureter increases edema. A Endoscopic approaches (endopyelotomy) for UPJ
stent is typically left in place after a laparoscopic repair. obstruction were popularized in the 1980s and 1990s,
Even if leakage from the anastomosis occurs, a satisfac- but have been replaced by laparoscopic approaches.36,37
tory outcome can usually be expected. A Penrose drain is Endopyelotomy successfully relieves primary UPJ
obstruction in 70% of children.38 As the success pales in
comparison to pyeloplasty, it is not routinely utilized for
primary repair. Endopyelotomy clearly has a role in
recurrent UPJ obstruction, in which the success rate is
>95%.38 Depending on the age of the patient and the size
of the ureter, this can be performed in either an antegrade
or retrograde fashion (Fig. 54-8).
The first laparoscopic pyeloplasty in a child was
reported in 1995 by Peters.39 The first series was pub-
lished by Tan in 1999.40 Laparoscopic pyeloplasty has
been reported in children as young as 2 months.41 The
introduction of robotic surgery with articulating instru-
ments and three-dimensional visualization has made
intracorporeal suturing easier and more precise. The
success rate with minimally invasive techniques is equiva-
lent to open pyeloplasty.42,43 The benefits of laparoscopic
FIGURE 54-7 Dismembered pyeloplasty showing reduction of and robotic surgery over an open approach may include
the renal pelvis and spatulation of the ureter (see the text). a decreased length of hospitalization, decreased analgesic
54 Ureteral Obstruction and Malformations 723
A B C
FIGURE 54-8 Retrograde endopyelotomy. Sixteen-month-old infant with persistent hydronephrosis and preserved function, but no
washout on renal scan 6 months after undergoing a dismembered pyeloplasty. (A) The retrograde pyelogram shows a UPJ configu-
ration with dilute contrast in a dilated renal pelvis (arrow). (B) A balloon catheter is passed retrograde and inflated. The black arrow
shows the narrowing (waist) and the white arrow demonstrates the cutting wire that is positioned laterally. (C) An indwelling stent
is positioned after the endopyelotomy is performed. The white arrow points out the extravasation that is indicative of an appropriate
depth of incision.
A B C
D E F
FIGURE 54-9 Laparoscopic pyeloplasty. (A) Transperitoneal view of crossing vessel (solid white arrow) that is causing intermittent
obstruction of the ureter (dotted black arrow). IVC, inferior vena cava. (B) The ureteropelvic junction has been transected and the
ureter spatulated (arrow), and a double J stent has been positioned in the bladder and out the proximal ureter. This can be accom-
plished via a retrograde or antegrade approach. (C) The posterior anastomosis between the renal pelvis and ureter is being per-
formed. (D) The proximal end of the stent is inserted into the renal pelvis (solid white arrow). The ureter is marked with the dotted
black arrow. (E) The anterior anastomosis is being performed. (F) The completed anastomosis is seen with the crossing vessel (white
arrow, CV) now located posterior to the pyleloplasty. Again, the ureter is marked with the dotted black arrow. (Images courtesy of
R. Sherburne Figenshau, MD.)
requirements, improved cosmesis, and quicker return to transabdominal and retroperitoneal approaches, the child
normal activity.42 is placed in a flank or modified flank position.
Laparoscopic pyeloplasties are mostly performed
using the AndersonHynes dismembered technique (Fig.
54-9). This can be performed through either a transperi-
UPJ Obstruction in a Duplex Kidney
toneal or retroperitoneal approach using a similar tech- In a duplex kidney, the lower pole is most commonly
nique once access and exposure are obtained. With both affected because the upper pole lacks a true pelvis.44
724 SECTION VI Urology
Ultrasound may not be reliable for diagnosis because the URETERAL ABNORMALITIES
duplex nature of the kidney may not be identified. A
pyelogram or renogram will show a small nonobstructed Ureteral development begins during the fourth week of
upper segment. gestation when the ureteral bud arises from the mesone-
The anatomy of the duplication dictates the operation. phric duct.45 The bud elongates cephalad, and forms the
If the ureter is incompletely duplicated and a long ureter, renal pelvis, calyces, and collecting tubules. The
lower-pole ureteral segment is found, a standard distal end of the mesonephric duct from the ureteral bud
dismembered pyeloplasty can be performed. If a high to the vesicourethral tract is called the common excretory
bifurcation with a short distal segment is present, duct and expands in trumpet fashion into the bladder and
then the end of the renal pelvis can be anastomosed to urethra to form half of the trigone. The attachment of
the side of the upper-pole ureter. The appropriate tech- the ureter to the mesonephric duct switches from a pos-
nique can be determined after the kidney and pelvis are terior to an anterolateral location. With expansion and
exposed. absorption of the common excretory duct into the urinary
tract, the orifices of the ureteral bud and mesonephric
duct become independent and move away and settle in
Surgical Results and Complications the bladder and urethra, respectively.
The results of operative correction have been uniformly Alterations in bud number, position, and time of
successful when performed at childrens hospitals.27,30,35 development result in anomalies. VUR results from
The rate of recurrent UPJ obstruction is less than 1%, caudal displacement of the ureteral bud, whereas ureteral
and the nephrectomy rate is less than 2%. The most ectopia and obstruction result from cranial displacement.
common early complications are prolonged urinary Renal development and dysplasia are related to the ure-
extravasation and delayed drainage through the anasto- teral orifice location.46
mosis. If a significant leak develops, either a stent or a
percutaneous nephrostomy tube can be inserted. Once Ureteral Duplication
diversion is instituted, the leak will usually cease within
48 hours. Late scarring at the anastomotic site is common, Duplication is the most common ureteral anomaly. Both
but rarely occurs due to a leak. sides are equally affected, and girls are affected twice as
Delayed opening of the anastomosis is seen most com- often as boys. The autopsy incidence is approximately 1%,
monly when a nephrostomy tube is used. When this but the incidence was 24% in clinical series in which
occurs, patience is important because 80% of these will pyelograms were obtained for urinary symptoms.45,46
open within three months. Secondary obstruction or Many of the duplicated units show congenital dysplasia
failure of the primary procedure occurs due to scarring (scarring) and hydronephrosis. There is an increased inci-
or fibrosis, a nondependent anastomosis, ureteral angula- dence of infection because both VUR and obstruction are
tion secondary to renal malrotation, or ureteral narrow- much more common in duplicated systems.45
ing distal to the anastomosis. A partial or complete duplication of the ureter occurs
A functional assessment of the anastomosis should be when a single bud branches prematurely or when two
obtained two to three months after the operation. Further ureteral buds arise from the mesonephric duct. A bifid
evaluation is recommended 12 to 24 months after surgery. renal pelvis is the highest level of bifurcation and occurs
Problems are uncommon after this time in the absence in 10% of the population. Other incomplete duplications
of symptoms. occur throughout the ureter (Fig. 54-10). An inverted-Y
A B C D
FIGURE 54-10 Types of duplication. (A) Bifid pelvis. (B) Y ureter. (C) V ureter. (D) Complete duplication with various ectopic
orifices.
54 Ureteral Obstruction and Malformations 725
ureter is the rarest of all branching anomalies.47 This is vena cava. The supracardinal vein (vena cava) lies dorsal
presumably the result of separate ureteral buds that fuse to the developing ureter, whereas subcardinal veins lie
before entering the metanephros. ventral to the ureter. If the subcardinal vein persists as
In complete duplications, reflux into the lower renal the vena cava, the ureter passes behind the vena cava and
moiety is the most common cause of renal disease. The anterior to the iliac vein. If both veins persist, the ureter
more caudal ureteral bud ends up laterally and cranially passes between the duplicated vena cava.57
deviated in the bladder and has a shorter intramural Symptoms are related to chronic ureteral obstruction
tunnel. The upper-pole ureter enters the bladder adja- and infection, and rarely occur in children.58 The radio-
cent or distal to the lower ureter, as defined by the graphic appearance depends on the level of obstruction.
WeigertMeyer law.48 Reflux is identified in up to two- The more common distal obstruction appears as a
thirds of children with duplicated systems that develop reversed J on intravenous pyelogram. Less commonly,
infection.49 Reflux may occur into the upper-pole ureter the ureter crosses at the level of the UPJ. Both of these
if the ureteral orifices are immediately adjacent or if the can be confused with UPJ obstruction and should be
upper ureter is distally located at the level of the bladder suspected when pyelectasis and dilation of the upper third
neck without any submucosal support (Fig. 54-11). of the ureter are seen.
The treatment of VUR in duplicated ureters follows Treatment is required only when significant obstruc-
the same principles as that in a single system. Initial treat- tion or symptoms are present. Reconstruction is essen-
ment includes preventive antibiotics and radiographic tially a dismembered ureteroplasty with division of the
monitoring. Low grades of VUR are associated with the ureter and anastomosis anterior to the vena cava. The
same rate of spontaneous resolution as a single system. other option is division and reconstruction of the vena
The distal ureters share a common vascular supply so cava, which is more problematic.
reimplantation involves mobilization and reimplantation
of the common sheath.50 If an associated lower-pole UPJ
obstruction is noted, ipsilateral end-to-side pyeloureter-
Megaureter
ostomy is an effective management for both obstruction Megaureter is not a diagnosis, but a descriptive term for
and reflux.51 Even if significant scarring is present in the a dilated ureter. Normal ureteral diameter in children is
lower pole, reimplantation is usually effective unless rarely greater than 5mm. Ureters greater than 7mm are
major ureteral dilation is present. In the latter case,
lower-pole nephroureterectomy may be needed.
Ureteral Triplication
This is one of the rarest anomalies of the upper urinary
tract and results from either several ureteral buds or early
branching. In most cases, all three ureters drain into a
single orifice.52 Triplication presents with incontinence,
infection, and symptoms of obstruction, and is associated
with both ectopia and ureteroceles.53,54 Ureteral quadru-
plication has also been described.55
Retrocaval Ureter
FIGURE 54-12 Retrocaval ureter. A retrograde pyelogram shows
The retrocaval or circumcaval ureter is a right ureter that reverse J-hooking of the ureter (arrow) as it passes behind the
passes behind the vena cava (Fig. 54-12).56 This is the inferior vena cava. Note that the ureteral caliber is the same
result of a developmental error in the formation of the proximally and distally which indicates no obstruction.
726 SECTION VI Urology
PEL TRANS
BL
*
* URETER
A B C
FIGURE 54-13 This patient has congenital megaureter. (A) Renal ultrasound image shows diffuse caliectasis and cortical thinning
with a markedly dilated left ureter (asterisk). (B) Ultrasound image of the bladder confirms the markedly dilated ureter adjacent to
the bladder (BL). A MAG-3 scan was performed and showed preserved renal function on the left side. (C) The voiding cystourethro-
gram shows reflux into the markedly dilated left ureter (asterisk). Note that the contrast agent in the ureter is diluted (compared
with the bladder), which is indicative of partial obstruction on that side.
54 Ureteral Obstruction and Malformations 727
A B
FIGURE 54-15 This 3-year-old girl had continuous urinary incontinence despite a normal voiding pattern. The renal ultrasound image
was essentially normal on both sides with no evidence of hydronephrosis or an echogenic upper pole. (A) A ureteral catheter has
been inserted into an ectopic left ureter. (B) The retrograde ureterogram shows a very small upper left ureter and a small cystic
calyx (arrow) in the left upper pole medial to the lower-pole collecting system that was opacified through an orifice on the trigone.
The patient was continent after a laparoscopic left upper pole partial nephroureterectomy.
Ectopic Ureter in Boys The distal ureteral stump rarely causes a problem in
genital ectopia. However, if urethral or bladder neck
The most common sites of ectopic ureteral insertion in insertion of the ectopic ureter and reflux into the ureter
boys are the posterior urethra (4050%) and the seminal is identified preoperatively, excision of the distal stump is
vesicle (2060%), depending on the age at presentation.81 important, but can be tedious.83 If the plane of dissection
Symptoms in boys may not occur until after the onset of is kept immediately adjacent to the ureter behind the
sexual activity and include prostatitis, seminal vesiculitis, bladder, the bladder neck and sphincter should not be
or an infected seminal vesical cyst causing painful bowel damaged. A transvesical approach can also be useful and
movements. The genital insertion accounts for the aids in exposure of the urethral insertion. In a postpuber-
common presentation with epididymitis. He may have tal girl, access to the urethra can be performed transvagi-
postvoid dribbling secondary to pooling of urine in the nally as well.
prostatic urethra, but incontinence is never as pronounced
as in a female.
Ectopic ureters in the boy are more commonly Bilateral Single Ectopic Ureters
obstructed and hydronephrotic so ultrasound is often
more useful. If the ectopic insertion site is outside the This is a rare finding in which the altered ureteral embry-
urethra, it is rarely identified on endoscopy. ologic development is associated with failure of normal
bladder neck development.87 Genital and anal anomalies
are commonly present. In girls, the ureter inserts into the
Management of Ectopic Ureters distal urethra. They are usually initially seen with infec-
Operative treatment is dependent on the associated renal tion or are noted to have continuous urinary leakage. The
parenchyma.82,83 Single-system ectopic ureters that enter bladder is usually poorly developed because it has never
the genital system usually have poor function, and neph- stored urine. Boys have somewhat larger bladders because
roureterectomy is appropriate. When the ectopic ureter some urine will have entered it. However, because the
is associated with duplication, the function in the upper bladder neck is not formed normally, they also have some
pole is usually poor, and an open or laparoscopic partial degree of urinary incontinence.
nephroureterectomy has historically been the most The child who is incontinent with bilateral single
common approach. The distal ureter can be left open. A ectopic ureters presents a major reconstructive challenge
ureteroureterostomy can be performed proximally or dis- that may require ureteral reimplantation, bladder neck
tally as well. The dilated upper pole is diverted into the reconstruction, and bladder augmentation if the bladder
normal caliber lower pole system. There are potential capacity is insufficient.
concerns regarding the size discrepancy of the ureters
and injury to the recipient ureter, but large series show
excellent success with a very low complication rate.84 This URETEROCELES
approach avoids potential injury to the lower pole of the
kidney and can be performed through a small inguinal Ureteroceles are cystic dilatations of the terminal, intra-
incision85 or laparascopically.86 The obstruction, dilation, vesical ureter that usually have a stenotic orifice.46 In
and incontinence usually resolve following ureteroureter- children, ureteroceles are most commonly associated
ostomy. Even if the upper pole is poorly functioning, it with the upper pole of a duplex system (80%) and an
should not cause significant long-term problems. A ectopic orifice (60%) in the urethra. In adults, they are
common sheath ureteral reimplantation can be per- usually part of a completely intravesical single system.
formed with tailoring of the ureter in the upper pole, but Ureteroceles occur four to seven times more frequently
the increased morbidity and complication rate associated in girls and are more common in whites. Bilateral urete-
with ureteral tapering limit the utility of this approach. roceles are found 10% of the time.
54 Ureteral Obstruction and Malformations 729
TRANS PEL
A B
FIGURE 54-17 (A) Ultrasound image of the bladder demonstrates a ureterocele (asterisk). (B) The ureterocele appears as a nonopaci-
fied filling defect (arrow) at the base of the bladder on the cystogram.
730 SECTION VI Urology
A B
FIGURE 54-18 (A) This intravesical ureterocele was found at cystoscopy. (B) The ureterocele was punctured (black arrow) and
decompressed using a 3 French electrode (white arrow).
The usual treatment of duplex ectopic ureteroceles has However, subsequent reconstructive surgery may be
been upper-pole heminephrectomy through a separate needed in 5090% of patients with ectopic ureteroceles.
flank incision, ureterocele excision, and ipsilateral lower- Reflux into the ureterocele moiety is the most common
pole ureteral reimplant via a lower incision. The bladder- indication for reconstruction in these infants. Previous
level operation may require repair of a sizable defect in decompression of the system makes this reconstruction
the bladder base and tapering or plication of the lower easier.93 For an infected system, unroofing of the urete-
ureter. The distal extent of the ureterocele can often be rocele is advocated only as an initial drainage procedure
dissected through the bladder neck. Incomplete excision prior to the definitive operation because it invariably
may result in an obstructing urethral flap. Also, resection results in reflux.103,104
of the entire ureterocele risks damaging the continence Ureterocele incision should probably be the initial
mechanisms of the bladder neck. Experienced surgeons procedure in most neonates because reflux into the lower-
report excellent results with low rates of reoperation pole moiety is usually present (>50%). Even when ultra-
(<10%) and low complication rates (<10%).9698 These sound shows little renal parenchyma in the upper pole of
approaches assume that ureterocele excision is an essen- a duplex system, incision can be performed. The decom-
tial component of management. However, because the pressed system may not require further treatment if iatro-
distal ureter and bladder defect may not cause symptoms genic upper-pole reflux does not develop. In older
after decompression, an absolute indication to proceed children, incision is the preferred option when function-
with a simultaneous bladder operation is rarely present. ing renal parenchyma is found, the ureterocele is intra-
In older children, when absence of function is noted on vesical, or the kidney is drained by a single system.
the affected side (upper and lower pole), nephroureter- Single-system ureteroceles are more commonly seen
ectomy is the preferred option. in older children and adults, and are associated with
Another option is upper-pole partial nephroureterec- better function and less hydronephrosis than is found in
tomy that avoids bladder-level reconstruction and its duplex kidneys. Most often, they are incidental findings
potential risks.91,99 Nearly all of the ureter can be removed that do not require treatment. Antenatally detected
either through a flank incision or laparoscopically. The single-system ureteroceles may not show significant
need for subsequent bladder-level excision and recon- obstruction on a furosemide washout renal scan. Clini-
struction varies between 1062%, and is largely depend- cally, these behave like nonobstructed megaureters and
ent on the presence of reflux.91,93,99 can be safely followed with preventive antibiotics. If
Most partial nephrectomy specimens show dysplasia, treatment is required, endoscopic incision is effective
but some show only inflammatory and obstructive most of the time.
changes.99,100 In patients with preserved function, a pye-
loureterostomy or ureteroureterostomy (high or low) REFERENCES
may be performed, along with distal ureterectomy and 1. Dicke JM, Blanco VM, Yan Y, et al. The type and frequency of
ureterocele decompression.82 fetal renal disorders and management of renal pelvis dilation.
J Ultrasound Med 2006;25:9737.
Ureterocele incision is the least invasive technique for 2. Lee RS, Cendron M, Kinnamon DD, et al. Antenatal hydrone-
upper pole preservation (Fig. 54-18). Using a 3 French phrosis as a predictor of postnatal outcome: A meta-analysis. Pedi-
Bugbee electrode to incise the ureterocele just above the atrics 2006;118:58693.
bladder neck is the recommended approach because 3. Hubert KC, Palmer JS. Current diagnosis and management of
reflux does not always develop (see Fig. 54-18).92 Endo- fetal genitourinary abnormalities. Urol Clin North Am
2007;34:89101.
scopic incision successfully decompresses the ureterocele 4. Capello SA, Kogan BA, Giorgi LJ, et al. Prenatal ultrasound has
most of the time.92,100103 It is the definitive procedure in led to earlier detection and repair of ureteropelvic junction
more than 90% of infants with intravesical ureteroceles. obstruction. J Urol 2005;174:14258.
54 Ureteral Obstruction and Malformations 731
5. Carr MC, El-Ghoneimi A. Anomalies and surgery of the uretero- 30. Austin PF, Cain MP, Rink RC. Nephrostomy tube drainage with
pelvic junction in children. In: Wein AJ, Kavoussi LR, Novick AC, pyeloplasty: Is it necessarily a bad choice? J Urol 2001;57:
editors. Campbell-Walsh Urology. 9th ed. Philadelphia: WB 33841.
Saunders; 2007. p. 335982. 31. Casale P, Mucksavage P, Resnick M, et al. Robotic ureterocalicos-
6. Ruano-Gil D, Coca-Payeras A, Tejedo-Mateu A. Obstruction and tomy in the pediatric population. J Urol 2008;180-2643-8.
normal recanalization of the ureter in the human embryo: Its 32. Tanaka ST, Grantham JA, Thomas JC, et al. A comparison of open
relation to congenital ureteric obstruction. Eur Urol 1975;1: vs. laparoscopic pediatric pyeloplasty using the pediatric health
28793. information system database-do benefits of laparoscopic approach
7. Arams HJ, Buchbinder ME, Sutton AP. Benign ureteral lesions: recede at younger ages. Journal of Urology 2008;180:147985.
Rare causes of hydronephrosis in children. Urology 1977;9: 33. Duckett JW, Gibbons MD, Cromie WJ. An anterior extraperito-
51720. neal muscle-splitting approach for pediatric renal surgery. J Urol
8. Stephens FD. Ureterovascular hydronephrosis and the aberrant 1980;123:7980.
renal vessels. J Urol 1982;128:9847. 34. Orland SM, Snyder HM, Duckett JW. The dorsal lumbotomy
9. Koff SA, Hayden LJ, Cirulli C, et al. Pathophysiology of UPJ incision in pediatric urological surgery. J Urol 1987;138:9636.
obstruction: Experimental and clinical observations. J Urol 1986; 35. Lindgren BW, Hagerty J, Meyer T, et al. Robot-Assisted laparo-
136:3368. scopic reoperative repair for failed pyeloplasty in children: Safe
10. Starr NT, Maizels M, Chou P, et al. Microanatomy and mor- and highly effective treatment option. J Urology 2012;188:
phometry of the hydronephrotic obstructed renal pelvis in 9328.
asymptomatic infants. J Urol 1992;148:51924. 36. Nakada SY, Johnson M. Ureteropelvic junction obstruction:
11. Hanna MK, Jeffs RD, Sturgess JM, et al. Ureteral structure and Retrograde endopyelotomy. Urol Clin North Am 2000;27:
ultrastructure: II. Congenital UPJ obstruction and primary 67784.
obstructive megaureter. J Urol 1976;116:72530. 37. Streem SB. Percutaneous endopyelotomy. Urol Clin North Am
12. Kjurhuus JC, Nerstrom B, Gyrd-Hansen N, et al. Experimental 2000;27:68593.
hydronephrosis: An electrophysiologic investigation before and 38. Kim EH, Tanagho YS, Traxel EJ, et al. Endopyelotomy for pedi-
after release of obstruction. Acta Chir Scand Suppl 1976;472:1728. atric ureteropelvic junction obstruction. A review of our 25-year
13. Wang Y, Puri P, Hassan J, et al. Abnormal innervation and altered experience. J Urol 2012;188: in press October 2012.
nerve growth factor messenger ribonucleic acid expression in ure- 39. Peters CA, Schlussel RN, Retik AB. Pediatric laparoscopic dis-
teropelvic junction obstruction. J Urol 1995;154:67983. membered pyeloplasty. J Urol 1995;153:19625.
14. Hollowell JG, Altman HG, Snyder HM III, et al. Coexisting UPJ 40. Tan HL. Laparoscopic Anderson-Hynes dismembered pyelo-
obstruction and vesicoureteral reflux: Diagnostic and therapeutic plasty in children. J Urol 1999;162:10458.
implications. J Urol 1989;142:4903. 41. Cascio S, Tien A, Chee W. Laparoscopic dismembered pyelo-
15. Coplen DE, Austin PF, Yan Y, et al. Correlation of prenatal and plasty in children younger than 2 years. J Urol 2007;177:3358.
postnatal ultrasound findings with the incidence of vesicoureteral 42. Minnillo BJ, Cruz JA, Sayao RH, et al. Long-term experience and
reflux in children with fetal renal pelvic dilatation. J Urol outcomes of robotic assisted laparoscopic pyeloplasty in children
2008;180:16314. and young adults. J Urology 2011;185:145560.
16. Nguyen HT, Herndon CD, Cooper C, et al. The Society for Fetal 43. Lam PN, Wong C, Mulholland TL, et al. Pediatric laparoscopic
Urology consensus statement on the evaluation and management pyeloplasty: 4-year experience. J Endourol 2007;21:146771.
of antenatal hydronephrosis. Journal of Pediatric Urology 44. Ossandon F, Androulakakis P, Ransley PG. Surgical problems in
2010;6:21231. pelviureteral junction obstruction of the lower pole moiety in
17. Islek A, Gven AG, Koyun M, et al. Probability of urinary tract incomplete duplex systems. J Urol 1981;125:8712.
infection in infants with ureteropelvic junction obstruction: Is 45. Mackie GG, Awang H, Stephens FD. The ureteric orifice: The
antibiotic prophylaxis really needed? Pediatric Nephrology embryologic key to radiologic status of the kidneys. J Pediatr Surg
2011;(26):183741. 1975;10:47381.
18. Heyman S, Duckett JW. Extraction factor: An estimate of single 46. Schlussel RN, Retik AB. Ectopic ureter, ureterocele and other
kidney function in children during routine radionucleotide renog- anomalies of the ureter. In: Wein AJ, Kavoussi LR, Novick AC,
raphy with 99m technetium diethylenetriamine pentaacetic acid. et al, editors. Campbell-Walsh Urology. 9th ed. Philadelphia: WB
J Urol 1988;140:7803. Saunders; 2007. p. 33837.
19. Chung S, Majd M, Rushton HG, et al. Diuretic renography in 47. Klauber GT, Reid EC. Inverted Y reduplication of the ureter.
the evaluation of neonatal hydronephrosis: Is it reliable? J Urol J Urol 1972;107:3624.
1993;150:7658. 48. Meyer R. Normal and abnormal development of the ureter in the
20. Conway JJ. Well-tempered diuresis renography: Its historical human embryo: A mechanistic consideration. Anat Rec 1946;
development, physiological and technical pitfalls and standardized 96:355.
technique protocol. Semin Nucl Med 1992;22:7484. 49. Fehrenbaker LG, Kelalis PP, Stickler GB. Vesicoureteral reflux
21. Grattan-Smith JD, Little SB, Jones RA. MR urography evaluation and ureteral duplication in children. J Urol 1972;107:8624.
of obstructive uropathy. Pediatric Radiology 2008;38(Suppl 1): 50. Barrett DM, Malek RS, Kelalis PP. Problems and solutions in
S4969. surgical treatment of 100 consecutive ureteral duplications in chil-
22. Veenboer PW, de Jong TP. Antegrade pressure measurement as a dren. J Urol 1975;114:12630.
tool in modern pediatric urology. World J Urol 2011;29:73741. 51. Shelfo SW, Keller MS, Weiss RM. Ipsilateral pyeloureterostomy
23. Rushton HG. Pediatric pyeloplasty: Is routine retrograde pyelog- for managing lower-pole reflux with associated ureteropelvic junc-
raphy necessary? J Urol 1994;152:6046. tion obstruction in duplex systems. J Urol 1997;157:14202.
24. Palmer LS, Maizels M, Cartwright PC, et al. Surgery versus 52. Kohri K, Nagai N, Kaneko S, et al. Bilateral trifid ureters associ-
observation for managing obstructive grade 3 to 4 unilateral ated with fused kidney, ureterovesical stenosis, left cryptorchidism
hydronephrosis: A report from the Society for Fetal Urology. and angioma of the bladder. J Urol 1978;120:24950.
J Urol 1988;159:2228. 53. Zaontz MR, Maizels M. Type I ureteral triplication: An extension
25. Ulman I, Jayanthi VR, Koff SA. The long-term follow-up of of the Weigert-Meyer law. J Urol 1985;134:94950.
newborns with severe unilateral hydronephrosis initially treated 54. Finkel LI, Watts FB, Cobrett DP. Ureteral triplication with a
nonoperatively. J Urol 2000;164:11015. ureterocele. Pediatr Radiol 1983;13:3468.
26. Yiee J, Wilcox D. Management of fetal hydronephrosis. Pediatr 55. Soderdahl DW, Shiraki IW, Schamber DT. Bilateral ureteral
Nephrol 2008;23:34753. quadruplication. J Urol 1976;116:2556.
27. Cartwright PC, Duckett JW, Keating MA, et al. managing appar- 56. Considine J. Retrocaval ureter. Br J Urol 1966;38:41223.
ent ureteropelvic junction obstruction in the newborn. J Urol 57. Hollinshead WH. Anatomy for Surgeons, vol 2. 3rd ed. Philadel-
1992;148:1224. phia: Harper & Row; 1982.
28. Foley FE. A new plastic operation for stricture at the UPJ: Report 58. Zhang XD, Hou SK, Zhu JH, et al. Diagnosis and treatment of
of 20 cases. J Urol 1937;38:643. retrocaval ureter. Eur Urol 1990;18:20710.
29. Culp OS, DeWeerd JH. Pelvic flap operation for certain types of 59. Hellstrom M, Hjalmas K, Jacobsson B, et al. Normal ureteral
ureteropelvic obstruction. Mayo Clin Proc 1951;26:4838. diameter in infancy and childhood. Acta Radiol 1985;26:4339.
732 SECTION VI Urology
60. Khoury AE, Bagli DJ. Reflux and megaureter. In: Kavoussi LR, 83. Plaire JC, Pope JC, Kropp BP, et al. Management of ectopic
Novick AC, Partin AW, et al, editors. Campbell-Walsh Urology. ureters: Experience with upper tract approach. J Urol 1997;158:
9th ed. Philadelphia: WB Saunders; 2007. p. 342381. 12457.
61. Leibowitz S, Bodian M. A study of the vesical ganglia in children 84. Lashley DB, McAleer IM, Kaplan GW. Ipsilateral ureteroureter-
and their relationship to the megaureter megacystis syndrome and ostomy for the treatment of vesicoureteral reflux or obstruction
Hirschsprungs disease. J Clin Pathol 1963;16:34250. associated with complete ureteral duplication. J Urol 2001;165:
62. Tanagho EA. Embryologic basis for lower ureteral anomalies: A 5524.
hypothesis. Urology 1976;7:45164. 85. Prieto J, Ziada A, Baker L, Snodgrass W. Ureteroureterostomy
63. Boyd SD, Raz S, Ehrlich RM. Diabetes insipidus and nonobstruc- via inguinal incision for ectopic ureters and ureteroceles without
tive dilation of urinary tract. Urology 1980;16:2669. ipsilateral lower pole reflux. J Urol 2009;181:18448.
64. Kass EJ, Silver TM, Konnak JW, et al. The urographic findings 86. Storm DW, Modi A, Jayanthi VR. Laparoscopic ipsilateral ure-
in acute pyelonephritis: Non-obstructive hydronephrosis. J Urol teroureterostomy in the management of ureteral ectopia in infants
1976;116:5446. and children. J Pediatr Urol 2011;7:52933.
65. Mollard P, Foray P, De Godoy JL, et al. Management of primary 87. Noseworthy J, Persky L. Spectrum of bilateral ureteral ectopia.
obstructive megaureter without reflux in neonates. Eur Urol Urology 1982;19:48994.
1993;24:50510. 88. Chwalla R. The process of formation of cystic dilations of the
66. Cozzi F, Madonna L, Maggi E, et al. Management of primary vesical end of the ureter and of diverticula at the ureteral ostium.
megaureter in infancy. J Pediatr Surg 1993;28:10313. Urol Cutan Rev 1927;31:499.
67. Keating MA, Escala J, Snyder HM, et al. Changing concepts in 89. Coplen DE, Austin PF. Outcome of prenatally detected urete-
management of primary obstructive megaureter. J Urol roceles associated with multicystic dysplasia. J Urol 2004;172:
1989;142:63640. 16625.
68. Baskin LS, Zderic SA, Snyder HM, et al. Primary dilated megau- 90. Glassberg KI, Braren V, Duckett JW, et al. Suggested terminology
reter: Long-term follow-up. J Urol 1994;152:61821. for duplex systems, ectopic ureters and ureteroceles. J Urol
69. Hendren WH. Operative repair of megaureter in children. J Urol 1984;132:11534.
1969;101:491507. 91. Caldamone AA, Snyder HM, Duckett JW. Ureteroceles in chil-
70. Hendren WH. Commentary: Surgery of megaureter. In: White- dren: Follow-up of management with upper tract approach. J Urol
head D, Leiter E, editors. Current Operative Urology. Philadel- 1984;131:11302.
phia: Harper & Row; 1984. p. 47382. 92. Cooper CS, Passerini-Glazel G, Hutcheson JC, et al. Long-term
71. Fretz PC, Austin JC, Cooper CS. Long-term outcome analysis of follow-up of endoscopic incision of ureteroceles: Intravesical
Starr plication for primary obstructive megaureters. J Urol versus extravesical. J Urol 2000;164:1097100.
2004;172:7035. 93. Husmann DA, Ewalt DH, Glenski WJ, et al. Ureterocele associ-
72. Perdzynski W, Kalicinski ZH. Long-term results after megaureter ated with ureteral duplication and nonfunctioning upper pole
folding in children. J Pediatr Surg 1996;31:121117. segment: Management by partial nephroureterectomy alone.
73. McLorie GA, Jayanthi VR, Kinahan TJ, et al. A modified extra- J Urol 1995;154:7236.
vesical technique for megaureter repair. Br J Urol 1994;74: 94. Sen S, Beasley SW, Ahmed S, et al. Renal function and vesicouret-
71519. eric reflux in children with ureteroceles. Pediatr Surg Int 1992;
74. Peters CA, Mandell J, Lebowitz RL, et al. Congenital obstructed 7:1924.
megaureters in early infancy: Diagnosis and treatment. J Urol 95. Sumfest JM, Burns MW, Mitchell ME. Pseudoureterocele: Poten-
1989;142:6415. tial for misdiagnosis of an ectopic ureter as a ureterocele. Br J Urol
75. Christman MS, Kasturi S, Lambert SM, et al. Endoscopic man- 1995;75:4015.
agement and the role of double stenting for primary obstructive 96. Coplen DE, Barthold JS. Controversies in the management of
megaureters. J Urol 2012;187:101822. ectopic ureteroceles. Urology 2000;56:6658.
76. Garcia-Aparicio L, Rodo J, Krauel L, et al. High pressure balloon 97. Scherz HC, Kaplan GW, Packer MG, et al. Ectopic ureteroceles:
dilation of the ureterovesical junctionfirst line approach to treat Surgical management with preservation of continence: Review of
primary obstructive megaureter? J Urol 2012;187:18348. 60 cases. J Urol 1989;142:53841.
77. Schulman CC. Les implantations ectopiques de luretre. Acta 98. Shekarriz B, Upadhyay J, Fleming P, et al. Long-term outcome
Urol Belg 1972;40:201478. based on the initial surgical approach to ureterocele. J Urol
78. Johnston JH, Davenport TJ. The single ectopic ureter. Br J Urol 1999;162:10726.
1969;41:42833. 99. Rickwood AM, Reiner I, Jones M, et al. Current management of
79. Kreissl MC, Lorenz R, Ohnheiser G, et al. Dystopic dysplastic duplex-system ureteroceles: Experience with 41 patients. Br J
kidney with ectopic ureter: Improved localization by fusion of MR Urol 1992;70:196200.
urography and (99m)Tc-DMSA SPECT datasets. Pediatr Radiol 100. Tank ES. Experience with endoscopic incision and open unroof-
2008;38:2414. ing of ureteroceles. J Urol 1986;136:2412.
80. Wyly JB, Lebowitz RL. Refluxing urethral ectopic ureters: Diag- 101. Hagg MJ, Mourachov PV, Snyder HM, et al. The modern endo-
nosis by the cyclic voiding cystourethrogram. AJR Am J Roent- scopic approach to ureterocele. J Urol 2000;163:9403.
genol 1984;142:12637. 102. Husmann D, Strand B, Ewalt D, et al. Management of ectopic
81. Berrocal T, Lopez-Pereira P, Arjonilla A, et al. Anomalies of ureterocele associated with renal duplication: A comparison of
the distal ureter, bladder, and urethra in children: Embryologic, partial nephrectomy and endoscopic decompression. J Urol
radiologic, and pathologic features. Radiographics 2002;22: 1999;162:14069.
113964. 103. Monfort G, Guys JM, Coquet M, et al. Surgical management of
82. Lashley DB, McAleer IM, Kaplan GW. Ipsilateral ureteroureter- duplex ureteroceles. J Pediatr Surg 1992;27:6348.
ostomy for the treatment of vesicoureteral reflux or obstruction 104. Snyder HM, Johnston JH. Orthotopic ureteroceles in children.
associated with complete duplication. J Urol 2001;165:5524. J Urol 1978;119:5436.
C H A P T E R 5 5
URINARY TRACT INFECTIONS suprapubic aspiration) clearly offers the lowest risk of
false-positive results.11 The results of a bag specimen or
Urinary tract infections (UTIs) are a common and sig- clean-catch specimen in a non-toilet-trained child are
nificant source of morbidity in children. By 7 years of helpful only if negative.12 Bag specimens can be useful in
age, approximately 8% of girls and 2% of boys will have an infant with a history of UTIs or structural abnormali-
had at least one UTI.1,2 Children who have had at least ties in whom a fever is present, but the suspicion for a
one UTI are at risk for having a recurrence.3 The long- UTI is otherwise low. Positive findings should be con-
term sequelae include renal scarring, hypertension, firmed using a catheter or aspiration specimen unless the
chronic renal insufficiency, and pregnancy-related com- clinical presentation and laboratory findings are unequiv-
plications. Predisposing risk factors for UTIs include ocal. The accuracy of positive findings from a bag speci-
renal and bladder structural abnormalities as well as func- men in an infant has been estimated at 7.5%,13 whereas
tional bladder and bowel dysfunction.4 Pediatric UTIs those of the midstream clean catch specimen varies with
constitute a significant health burden and has been esti- age: 42% under 18 months of age and 71% from 3 to 12
mated to result in at least 13,000 hospital admissions with years of age.14 Specimens should be either analyzed and
inpatient costs exceeding $180 million per year.5 plated immediately, or placed on ice to minimize bacterial
multiplication prior to testing.
The accepted gold standard for diagnosis remains the
Diagnosis quantitative urine culture. The historically accepted cri-
Localized clinical signs and symptoms are important clues terion for diagnosis is greater than 105 colony-forming
in the diagnosis, but they are age dependent. Combina- units per milliliter of a single bacterial species. The accu-
tions of findings can be more useful than individual ones racy of such a positive finding on culture is estimated at
in identifying affected children.6 For example, neonates 80% (single specimen) and 96% (confirmed by second
rarely present with symptoms specific to the urinary tract. culture).15 Table 55-2 outlines the probability of infection
Nonspecific symptoms of lethargy, irritability, tempera- as a function of colony count and methods of collection
ture instability, anorexia, emesis, or jaundice predominate. that are used in children.16 One must avoid applying these
Bacteremia is common with neonatal UTI, and a urine criteria too strictly. The colony count varies as a function
culture is an important aspect in the evaluation of neonatal of hydration (dilution) and urinary frequency (bacterial
sepsis.7 Confirmation of a UTI by microscopic examina- multiplication time). One study of six untreated children
tion and quantitative culture of a properly collected speci- with proven bacteriuria found colony counts to vary from
men is important. Older infants may present with 103 to 108 over a 24-hour period.17
nonspecific abdominal discomfort, emesis, diarrhea, poor Although clearly the most accurate laboratory test,
weight gain including failure to thrive, and fever. Malo- urine culture results cannot provide an immediate diag-
dorous or cloudy urine may be reported by the parents. nosis. As a result, initial treatment is generally guided by
Older children frequently present with dysuria and the urinalysis. Microscopic evaluation of a urine speci-
urinary frequency, urgency, and enuresis. Table 55-1 out- men should be done immediately on collection. This
lines the incidence of UTI symptoms as a function of practice minimizes misleading ex vivo bacterial multipli-
age.8,9 As the symptoms can sometimes be obscure, it is cation and deterioration of cellular elements. The iden-
important that care providers have a high index of suspi- tification of bacteria in an unspun urine specimen is very
cion in ill-appearing children. An unexplained high fever suggestive of significant bacteriuria.17 Pyuria (more than
in an infant or toddler should prompt the clinician to 10 leukocytes/mm3) is suggestive,18 but may also be seen
obtain a urine sample. in vaginitis, dehydration, calculi, trauma, chemical irrita-
Analysis of a properly collected urine sample is tion, gastroenteritis, and viral immunization. Urinary
the cornerstone in the diagnosis of UTI.10 Errors in Gram stain has been found to be reliable in detecting
diagnosis most commonly result from failure to confirm UTIs in young infants.19
a clinically suspected UTI by culture, or by reliance A popular and indirect measurement of bacteriuria
on a specimen that has been inadequately collected or employs nitrite and leukocyte esterase analysis. Nitrate,
mishandled. Specimens may be obtained by bag collec- normally present in urine, is converted to nitrite in the
tion, clean catch, urethral catheterization, and suprapubic presence of bacteria. A positive nitrite reaction is indica-
aspiration. Although invasive, urethral catheterization (or tive of bacteria with specificity and a positive predictive
733
734 SECTION VI Urology
TABLE 55-1 Presenting Symptoms in 200 Children with Urinary Tract Infection as a Function of Age
Symptom Age
01 MONTHS 124 MONTHS 25 YEARS 512 YEARS
Failure to thrive, poor feeding 53% 36% 7% 0
Jaundice 44% 0 0 0
Screaming, irritability 0 13% 7% 0
Foul-smelling, cloudy urine 0 9% 13% 0
Diarrhea 18% 16% 0 0
Vomiting 24% 29% 16% 3%
Fever 11% 38% 57% 50%
Convulsions 2% 7% 9% 5%
Hematuria 0 7% 16% 6%
Frequency, dysuria 0 4% 34% 41%
Enuresis 0 0 27% 29%
Abdominal pain 0 0 23% 44%
Loin pain 0 0 0 12%
Male-to-female ratio 1:2 1:13 1:10 1:10
From Smellie JM, Hodson CJ, Edwards D, etal. Clinical and radiological features of urinary tract infection in childhood. BMJ
1964;2:1222; Bickerton MW, Duckett JW. Urinary tract infections in pediatric patients. AUA Update Service, Lesson 26, 1985;4:4.
Obstructive uropathy
tain sterile urine. The most critical is the act of regular urine flow
(any level)
Defective urothelial
defense
10.0
Operative antimicrobial Imbalanced voiding, e.g.,
urothelial activity 1. Neurogenic bladder-
8.0 infrequent, incomplete
Regular, complete
Married, nonpregnant voiding
% incidence
bladder emptying
2. Constipation, inflammation
6.0
Normal perineal Diverticula
resistance Periurethral colonization
4.0 Unmarried 1. Soilage (diaper, encopresis)
2. Inflammation
2.0 Females a. diaper rash
b. tub baths with chemical
Nuns Males irritant:
0 -bubble bath
0 10 20 30 40 50 60 70 80 -harsh soaps
(shampoo)
Age in years 3. Phimosis
FIGURE 55-2 The age and gender distribution of urinary tract FIGURE 55-3 Host factors that protect the urinary tract from
infection incidence. (From Devine CJ, Stecker JF. Urology in Prac- infection and abnormalities that potentiate the establishment of
tice. Boston: Little, Brown; 1978. p. 444.) invasive bacterial infection.
736 SECTION VI Urology
Abnormalities at the ureterovesical junction (UVJ) and bladder entry. Uroepithelial adherence promotes bacte-
altered ureteral peristalsis may allow vesicoureteral reflux rial proliferation and tissue invasion. This series of events
(VUR), which potentiates but is not always necessary for is facilitated by the presence of one or more host factors
upper tract invasion. Distortion of the pyramids allows (see Fig. 55-3).
renal parenchymal invasion, which results in irreversible
renal injury. The anatomy of the renal papillae usually
prevents intrarenal reflux (Fig. 55-4).9 Structural abnor- Investigation
malities that potentiate infection include phimosis, Rationale for Radiographic Imaging
obstructive uropathy at any level (e.g., ureteropelvic and
UVJ obstructions, posterior urethral valves [PUV]), Although many patients with UTI do not develop serious
VUR, bladder diverticula, urinary calculi or foreign illness, the pediatric caregiver must be cognizant of
bodies, and the renal papillary anatomy. several important risks. Urinary abnormalities are found
in approximately 50% of children up to the age of 12
years who present with UTI.34 VUR is found in up to
Bacterial Factors
Several bacterial factors may potentiate a UTI and are
outlined in Box 55-1.9,33 O antigens are lipopolysaccha- Bacterial Factors Potentiating
rides that are part of the cell wall. They are thought to BOX 55-1
Infection
be responsible for many of the systemic symptoms associ-
ated with infection. Of the more than 150 strains of O antigens (lipopolysaccharides)
Escherichia coli identified by O antigens, nine are respon- Primarily O1, O2, O4, O6, O7, O11, O18, O35, O75
sible for the majority of UTIs. Responsible for systemic reactions (e.g., fever, shock)
K antigens
K antigens are also polysaccharides, and their presence
Primarily K1, K5
on Gram negative bacterial capsules is considered to be Adhesive properties
an important virulence factor. They are thought to Low immunogenicity
protect against phagocytosis, to inhibit the induction of H antigens (flagella)
a specific immune response, and to facilitate bacterial Bacterial locomotion
adhesion. Bacterial strains causing UTI exhibit consider- Chemotaxis
ably more K antigen than those isolated from the feces. Hemolysins (bacterial enzymes)
Urease, a virulence factor especially prominent with Tissue damage
Proteus species, allows the breakdown of urea to ammo- Facilitates bacterial growth
nium. This process alkalinizes the urine and facilitates Urease
Alkalinizes urine
stone formation. Such bacteria are generally incor-
Facilitates stone formation
porated into the stone structure, making eradication P fimbriaeadherence
extremely difficult. Mannose-resistant pili are important Mannose sensitive (MS)
adherence factors. They promote adherence to uroepi- Mannose resistant (MR)
thelial cells as well as renal epithelial cells. This factor
appears to counter the normal cleansing action of urine
flow and allows tissue invasion and bacterial proliferation.
That these factors truly are associated with virulence is 80
O-Ag
shown in Figure 55-5. K-Ag
Increasingly invasive urinary infections are associated MR pili
with bacteria with a high number of virulence factors. 60
Percent factor positive
20
0
Feces ABU Cystitis Pyelo-
nephritis
FIGURE 55-5 Presence of bacterial virulence factors as a func-
tion of the clinical setting. More invasive infections are associ-
FIGURE 55-4 The normal oblique insertion of the collecting ated with a high incidence of virulence factors, implicating these
ducts onto the surface of simple papillae prevent intrarenal factors in pathogenesis. MR, mannose resistant; Ag, antigen;
reflux (left). Collecting duct insertion onto the surface of com- ABU, asymptomatic bacteriuria. (From Mannhardt W, Schofer O,
pound papillae may allow intrarenal reflux (right). (From Ransley Schulte-Wisserman H. Pathogenic factors in recurrent urinary tract
PG. Intrarenal reflux: Anatomic, dynamic and radiological studies. infection and renal scar formation in children. Eur J Pediatr
Urol Res 1977;5:61.) 1986;145:330.)
55 Urinary Tract Infections and Vesicoureteral Reflux 737
1 or 2 IRR
Ascent
Upper tract colonization
Facilitates reflux
Alters peristalsis
Cystitis
Colonization Bladder colonization ABU
Cleared
FIGURE 55-6 The pathogenesis of destructive Adherence
infection is shown. The process is facilitated
by, but does not require, defects in the
host protective factors outlined in Fig. 55-3. Fecal colonization
IRR, intrarenal reflux; ABU, asymptomatic with virulent organisms
bacteriuria.
35% and obstructive lesions in 8%. Nonobstructive, recommends deferring a voiding cystourethrography
nonrefluxing lesions are found in 7%. (VCUG) until after the second documented UTI in chil-
While renal scars develop in about 13% of girls and dren ages 2 to 24 months if the ultrasound (US) is normal
5% of boys with unspecified infection,35 they develop in and the child has a complete clinical response to treat-
up to 43% of kidneys involved in acute pyelonephritis.36 ment.45 The urologic community has significant concerns
A recent meta-analysis assessing the prevalence of renal about the paradigm shift made in these guidelines and the
scarring in children after an initial episode of UTI found methodology employed in the meta-analysis upon which
that 57% had acute renal cortical changes consistent with these recommendations were based.46
pyelonephritis in the acute phase and 15% had evidence
of renal scarring on the follow-up Tc-99m dimercapto- Imaging Studies
succinic acid (DMSA) scan.37 Pyelonephritic scarring is The initial radiographic evaluation ideally includes
responsible for 11% of childhood hypertension cases38 a fluoroscopic VCUG to precisely grade vesicoureteral
and a majority of cases of severe hypertension.39 Although reflux and assess for bladder and urethral abnormalities.
hypertension is most common with bilateral scarring, it Follow-up studies in females can be adequately per-
is also seen with unilateral scarring. 40 Pyelonephritic formed with a radionuclear cystogram (RNC) that allows
scarring is also an important cause of end-stage renal a somewhat lower radiation exposure to the ovaries. The
failure in childhood and may require specific pretrans- exception is the girl with neurogenic bladder, ectopic
plantation treatment, especially if associated with reflux.41 ureter, bladder diverticulum, or ureterocele documented
Additionally, approximately 50% of patients will suffer by ultrasound or previous cystograms. Radionuclide
from recurrent UTI.33 scanning using DMSA is readily available and can be used
to diagnose acute pyelonephritis,47 detect renal scarring,
Current Controversies and assess differential renal function.48
The standard of care for many years has been to perform
imaging studies in children to assess for structural abnor- Treatment
malities that might lead to recurrent UTIs and renal scar-
Acute Phase
ring. It was felt that not only infants 42 but older children,
particularly males, should be investigated after the initial The treatment of an acute UTI is dependent on the clini-
infection.43 Several evidence-based guidelines have been cal presentation. Ill-appearing children with pyelone-
published over the years.44 Controversy persists, however, phritis should be treated immediately and aggressively
with many researchers proposing even less aggressive with broad-spectrum antimicrobial therapy and intrave-
approaches to the child with a UTI. Recent published nous hydration. Initial empiric therapy should be initi-
guidelines from the American Academy of Pediatrics ated with broad-spectrum parenteral antibiotics until
738 SECTION VI Urology
cultures return. Prompt, effective treatment is the most long-term suppressive antibiotics. It is unclear whether
important factor in preventing permanent renal injury.49 the benefit outweighs the risks, particularly in low-grade
Further therapy is dictated by culture and sensitivity VUR without nephropathy.45,54 The urothelial injury
findings. Indications for inpatient parenteral antibiotic from an infection takes several months to fully recover.
therapy include very young age (<3 months), unusual or As a result, irritative voiding symptoms, such as dysuria,
multi-resistant pathogens, persistent vomiting, concern incontinence, and frequency, may persist despite the
for compliance with treatment, and/or significant urinary finding of sterile urine. A propensity for re-infection also
tract anomalies. exists.
Once clinically stabilized and afebrile for 2448 hours, Patients without obvious urinary tract structural
patients with pyelonephritis and sensitive organisms may abnormalities should be evaluated for functional bowel
complete the course of parenteral culture-specific antibi- and bladder dysfunction. Regular and complete elimina-
otics on an outpatient basis, via a peripherally inserted tion is mandatory to diminish the risk of recurrence.
central catheter (PICC) and a home-based nursing Along with aggressive treatment of constipation and
service. Some studies have shown that initial parenteral voiding dysfunction, three months of antibiotic suppres-
therapy followed by oral antibiotics can be as effective as sion therapy may help to break the cycle. Table 55-4
a prolonged course of intravenous therapy in preventing outlines the characteristics of the drugs that are most
renal scarring.50,51 Patients with obstruction or renal commonly used for suppression.
abscess who do not become afebrile or have persistent
severe symptoms require repeat upper tract imaging. An
abscess or obstructed kidney may require percutaneous, VESICOURETERAL REFLUX
or very rarely, open drainage.
Initial empiric therapy in less toxic appearing children VUR refers to the retrograde passage of urine from the
without vomiting can be performed with oral broad- bladder into the ureter. Although VUR was first discov-
spectrum antibiotics (e.g., cephalosporins) after obtaining ered in the late 1800s, its clinical importance has only
a reliable urine culture. Short treatment courses appear been recognized in the last five decades. Hutchs studies,
to be insufficient for treatment of childhood UTI.52 reported in the 1950s, demonstrated the pathophysio-
Therefore, we prefer a 710-day course dictated by logic changes with VUR in children.55 These reports and
culture and sensitivity results.53 Retention by the toilet- Hodsons observations in 1959 regarding the association
trained patient due to fear of voiding or dysuria may be between VUR, UTI, and pyelonephritic scarring set the
managed with phenazopyridine (Pyridium) and hydra- stage for the modern era of reflux management.56
tion, and allowing the child to void while sitting in a tub Although most commonly diagnosed during the evalu-
of warm clear bath water. ation for UTI, VUR may also be discovered during eval-
uations for hypertension, proteinuria, voiding dysfunction,
Prophylactic Antibiotics or chronic renal insufficiency. In addition, VUR has been
identified in asymptomatic patients with prenatally-
Patients who have recurrent UTIs or those who are detected hydronephrosis as well as through sibling
managed nonoperatively for VUR are often treated with screening.57
Ureter
B High bladder pressure:
BOO
Classification
NVD Many attempts at classification of VUR have been
D Weak floor:
NVD
advanced. Reflux has been described as low pressure
Urethral (occurring during the filling phase of the VCUG) or high
orifice Diverticulum
pressure (occurring only during voiding). Reflux due to
Detrusor a congenitally deficient UVJ is referred to as primary
FIGURE 55-7 Components of the competent ureterovesical
reflux, whereas that due to a BOO or neurogenic bladder
junction. Those abnormalities most often implicated in the etiol- is referred to as secondary reflux. Further classification
ogy of vesicoureteral reflux are outlined. BOO, bladder outlet includes simple reflux and complex reflux. Complex
obstruction; NVD, neurovesical dysfunction. reflux includes the refluxing megaureter, the refluxing
duplicated ureter, the refluxing ureter associated with a
diverticulum or ureterocele, and the occasional refluxing
ureter associated with ipsilateral ureteropelvic or ureter-
Pathophysiology ovesical obstruction.
Figure 55-7 depicts the various anatomic components of The most clinically pertinent classification systems,
the competent UVJ as well as the abnormalities most however, have attempted to quantitate the degree of
often implicated in the genesis of VUR. The normal UVJ reflux. At the present time, VUR is graded from I to V
is characterized by an oblique entry of the ureter into the according to the international classification system dia-
bladder and a length of submucosal ureter providing a grammed in Figure 55-8.65 This classification system is
high ratio of tunnel length to ureteral diameter. This based not only on the proximal extent of retrograde urine
anatomic configuration provides a predominantly passive flow and ureteral and pelvic dilatation, but also on the
valve mechanism.58,59 As the bladder fills and the intra- resultant anatomy of the calyceal fornices. This system is
vesical pressure rises, the resulting bladder wall tension currently universally accepted and used extensively in the
is applied to the roof of the ureteral tunnel. This results literature.
in a compression of the ureter which prevents retrograde Grade I VUR refers to the visualization of a nondi-
passage of urine. Intermittent increases in bladder pres- lated ureter only, whereas grade II VUR refers to visuali-
sure, such as the act of voiding, upright posture, activity, zation of a nondilated renal pelvis and calyceal system in
and coughing, are met with an equal and immediate addition to the ureter. Grade III reflux involves mild to
increase in resistance to retrograde urine flow. This effect moderate dilatation or ureteral tortuosity with mild
is supplemented by the active effects of ureterotrigonal to moderate dilatation of the renal pelvis and calyces.
muscle contraction and ureteral peristalsis. 59,60 The fornices, however, remain sharp or only minimally
Ureters with marginal tunnels can be made to reflux blunted. Once the forniceal angle is completely blunted,
during infection due to UVJ distortion, loss of compli- grade IV reflux has developed. Papillary impressions in
ance of the valve roof, and intravesical hypertension. the majority of calyces can still be appreciated. Loss of
Excessively high intravesical pressure in neurovesical dys- the papillary impressions along with increased dilatation
function (NVD) or bladder outlet obstruction (BOO) and tortuosity is referred to as grade V reflux.
may also potentiate reflux as may a structurally weak
detrusor floor (e.g., diverticulum or ureterocele). As the Epidemiology
submucosal ureter tends to lengthen with age, the ratio
of tunnel length to ureteral diameter increases, and the The incidence of VUR in otherwise normal children is
propensity for reflux may disappear.58,59 thought to be quite low.66 A much higher incidence of
Of critical importance is the concept of intrarenal VUR, between 3040%, is reported in patients undergo-
reflux (IRR), which has been demonstrated clinically61 as ing evaluation for UTI.6770 It is important to note that
well as experimentally.62 The usually oblique entry of the the incidence rises as age decreases.71 Thus, the infant
papillary ducts onto the surface of simple papillae inhibits who is most vulnerable to the combination of UTI and
IRR. In contrast, the papillary duct entrance onto com- VUR is precisely the pediatric patient in whom this com-
pound papillae facilitates IRR (see Fig. 55-4). The critical bination is most likely to occur.
pressure for IRR is considered to be about 35mmHg in Although females account for the majority of reflux
compound papillae.62,63 Experimentally, this same pres- patients, a few important characteristics of males with
sure may cause scar formation in the absence of infec- VUR require comment. Although males account for
tion.62,64 When occurring intravesically, this pressure has approximately 14% of patients with VUR,72 an increased
been associated with an increased risk of renal deteriora- incidence of VUR (30%) is found in those males present-
tion. Higher pressure is thought to be necessary to induce ing with UTI.69 Boys with VUR tend to present at a
740 SECTION VI Urology
GRADE OF REFLUX (3) control over bladder smooth muscle. Delay in this
maturation leads to UDCs. Many children with reflux
and recurrent UTI have UDCs. Such involuntary or
uninhibited bladder contractions are not caused by neu-
rologic disease. Intense voluntary constriction of the stri-
ated sphincter occurs in an attempt to ensure continence
and results in excessively high intravesical pressures.
Pressures often exceeding 150cmH2O have been
observed resulting in intravesical distortions, such as
diverticula, saccules, trabeculations, and abnormal ure-
teral orifices.85 Reflux occurred in almost half of the chil-
I II III IV V dren studied with UDC and UTI.
FIGURE 55-8 The international grading system for vesi-
Thus, all patients with VUR should be screened for
coureteral reflux. See text for description. (From The International frequency, urgency, and incontinence, which suggest
Reflux Committee. Medical versus surgical treatment of primary UDCs and voiding dysfunction. Vincents curtsy, a squat-
vesicoureteral reflux. Pediatrics 1987;67:396.) ting maneuver spontaneously employed to prevent incon-
tinence, is particularly suggestive.84 That these UDCs
relatively young age (25% under 3 months) and younger may cause reflux is suggested by an enhanced resolution
children tend to have the more severe degrees of reflux.72 of reflux with anticholinergic drug therapy. Equally
Multiple studies have documented a significant risk of important is the potential for UDCs to cause a false-
VUR in family members of patients with reflux. The negative cystogram.
reported risk of sibling reflux ranges from 2734%,7375
while as much as 66% of offspring of women with reflux Diagnostic Evaluation
also have VUR.76 As a result of these studies, it has been
suggested that siblings, especially those under 2 years of VUR is diagnosed with a cyclic voiding cystourethro-
age, should have a screening investigation.56,73,76 Another gram (VCUG), with either radiopaque contrast medium
option is to perform a renal and bladder ultrasound in or radioisotope.86,87 Body temperature contrast material,
younger siblings and defer the VCUG if the ultrasound which is not excessively concentrated, is instilled into the
is normal, unless they have a documented UTI. bladder through a small catheter by gravity with modest
A particularly important subset of patients with reflux pressure in a non-anesthetized child.
includes those who have secondary reflux. Most have NVD Imaging of the upper urinary tract (kidneys and
or BOO as the primary disease. Many patients, however, ureters) is extremely important and may be accomplished
have reflux not because of increased bladder pressure alone, by ultrasound and/or isotope renography. Both may
but rather because UVJ deficiency is associated with other detect scarring, but isotope renography is particularly
congenital anomalies, such as imperforate anus,77 urete- sensitive and also defines the split differential function in
rocele,78 and bladder exstrophy. Although many patients the case of a small kidney. Ultrasound is helpful in quan-
with PUV have reflux due to or exacerbated by high intra- titating renal growth and dilatation of the renal pelvis
vesical pressure, as demonstrated by VUR resolution after and/or ureters. Bladder views are important to obtain to
valve ablation or vesicostomy, the incidence of VUR in check for bladder wall thickening, diverticula, distal ure-
PUV patients is only approximately 50%. Many have con- teral dilatation, ureteroceles, and bladder emptying.
genitally abnormal ureteral insertions.79 Patients with frequency, urgency, incontinence, and
Although a significant incidence of NVD exists in Vincents curtsy should also be considered for non-
patients with imperforate anus, this is not a prerequisite invasive urodynamic studies including a uroflow and peri-
for VUR.80 The diagnosis of VUR in imperforate anus neal electromyogram with a postvoid residual. A filling
thus assumes a critical importance to the pediatric cystometrogram is indicated to follow neurovesical dys-
surgeon. Not only may the association of NVD potenti- function or in those who have failed therapy. The pres-
ate increased severity of reflux and the development of ence of UDCs or detrusor-sphincter dyssynergia should
infection, the presence of a rectourethral or rectovesical be resolved before consideration is given to an antireflux
fistula provides the opportunity for severe urinary con- operation. Although not formally described in the litera-
tamination. Consequently, we believe that the patient ture, our impression is that intervention in an unstable
with a rectovesical or rectourethral fistula should be bladder is likely to result in a failed repair.
managed with a completely diverting colostomy rather
than a loop. Natural History
In addition to these structural associations, important
functional associations are found as well, including florid The natural history of VUR is extremely variable, and
NVD, as seen in myelodysplasia,81 and a variety of more ranges from spontaneous resolution without nephropa-
subtle voiding disturbances.8284 A particularly important thy to clinically silent scar formation to recurrent
subset of VUR patients are those who have uninhibited pyelonephritis with hypertension and end-stage renal
detrusor contractions (UDCs). Three important compo- disease (ESRD). Numerous factors may contribute to the
nents of maturation are found with successful toilet train- potential for resolution, including the patients age,
ing: (1) growth in bladder volume; (2) development of the grade of reflux, the appearance of the ureteral orifice,
volitional control over the striated muscle sphincter; and the length of the ureteral submucosal tunnel, and the
55 Urinary Tract Infections and Vesicoureteral Reflux 741
33
relatively independent of grade in secondary reflux, 40
implicating management of primary bladder dysfunction
as the primary prognostic variable (Fig. 55-10).89
Renal injury due to VUR may take the form of focal
scarring, generalized scarring with atrophy, and failure of 20
renal growth.90 As a result, kidneys drained by refluxing
ureters should be observed not only for scarring but also
for renal growth with serial upper tract imaging by ultra-
sound.91 Reflux-induced renal injury is usually a result of 0
the association of VUR with UTI.92 It has been generally I II III IV
considered that such injury is most likely in children Reflux grade
under the age of 2 years.71 It is now clear, however, that
FIGURE 55-10 The rate of spontaneous resolution of secondary
the risk of renal injury from VUR extends well beyond vesicoureteral reflux as a function of reflux grade. (From Cohen
this age.70,9294 Reflux can also cause renal injury in the RA, Roston MG, Belman AB, etal. Renal scarring and vesicoureteral
absence of UTI because of the pressure effects from reflux in children with myelodysplasia. J Urol 1990;144:541.)
742 SECTION VI Urology
are monitored. The role of urodynamics has been previ- exceeds 4:1. These goals can be attained by a variety of
ously outlined. Cystoscopy is rarely necessary except at procedures, most commonly via an open Pfannensteil
the time of antireflux surgery when it is performed to approach but also laparoscopically and robotic-assisted
exclude urothelial inflammation and to confirm the posi- (Fig. 55-11).
tion and number of ureteral orifices. Important differences exist between these operative
While the decision to perform antireflux surgery must procedures. Variables include (1) presence or absence of a
be carefully individualized, absolute indications for ureteral anastomosis; (2) need for detrusor closure;
surgical correction of VUR include (1) progressive (3) transgression of urothelium; and (4) whether the neo-
renal injury; (2) documented failure of renal growth; hiatus is fashioned by an appropriately sized detrusor
(3) breakthrough pyelonephritis; and (4) intolerance or incision or by the closure of the detrusor around the
noncompliance with antibiotic suppression. Other rela- ureter. Performance of a ureteral anastomosis increases
tive indications for correction of VUR are high grade the risk of postoperative obstruction, whereas the need for
(IVV) reflux in young children after a year of conserva- detrusor closure increases the risk of diverticula. Table
tive follow-up, pubertal age with nephropathy at diagno- 55-6 outlines the specific advantages and disadvantages of
sis, parental preference, and failure to spontaneously some representative procedures. Three of the most com-
resolve with watchful waiting. monly employed operations for the treatment of primary
The American Urological Association (AUA) Pediat- VUR are diagramed in Figures 55-12 to 55-14.
ric Vesicoureteral Reflux Guidelines Panel published In general, excellent results are nearly uniformly
their recommendations for management of VUR in chil- attainable with an open approach and early reports of
dren in 1997 and updated their guidelines in 2010. For robotic-assisted laparoscopic outcomes are encourag-
VUR in an infant diagnosed after a febrile UTI or found ing.107 A meta-analsysis in 1997 of 86 reports, including
to be high grade (IIIV), then continuous antibiotic 6472 patients (8563 ureters), found overall success for an
prophylaxis is still recommended. It is also recommended open ureteral reimplantation to be 96%.88 Success was
for an older child (>1 year of age) with recurrent febrile achieved in 99% with grade I, 99.1% with grade II,
UTI, bowel/bladder dysfunction, and/or renal cortical 98.3% with grade III, 98.5% with grade IV and 80.7%
anomalies. For asymptomatic older children with normal in grade V.
kidneys, suppression is an option. Breakthrough UTI At our institution, we prefer the extravesical detrusor-
management guidelines are summarized in Table 55-5.4,88 rhaphy approach (see Fig. 55-12).108110 Because the lumen
There is little solid evidence or consensus about the man- of the bladder is not entered, there is no postoperative
agement of VUR in older school-age patients or about hematuria, with minimal bladder spasms and a short hos-
the length of time that the clinician should observe non- pitalization. The absence of a uretero-vesical anastomosis
operatively before recommending surgery. The actual decreases the risk of postoperative obstruction. No ure-
decision must be carefully individualized after a thorough teral stents, suprapubic catheters, or perivesical drains are
discussion of all the treatment options with the parents. needed. The urethral catheter is removed on the first day
The established principles of successful ureteral reim- after unilateral surgery and the second day following
plantation include: (1) adequate ureteral exposure and bilateral reimplantation. Once the patient voids, he/she is
mobilization; 2) meticulous preservation of the blood discharged on oral antibiotics for 1 week, then is placed
supply; and (3) creation of a valvular mechanism whose back on suppression for 3 months.
submucosal tunnel length to ureteral diameter ratio Postoperative analgesia can be maintained with either
an indwelling or single-shot epidural placed at the time
of surgery, or infiltration of local anesthesia in the inci-
TABLE 55-5 Breakthrough UTI Management sion supplemented by intravenous narcotics as needed.
According to the 2010 American The majority of children are discharged home simply
Urological Association Guidelines on oral acetaminophen alone. Postoperative imaging
Recommendation (R)/
includes a renal and bladder ultrasound at 2 weeks, 3
Clinical Scenario Option (O) months, 12 months, and 24 months after the procedure.
A VCUG is not typically obtained in an asymptomatic
Symptomatic BT-UTI R: Change of therapy
guided by scenario
patient due to the high success rate of the procedure.
Patient on CAP with febrile R: Consider open or The four major principles of a successful extravesical
BT-UTI endoscopic surgical detrusorrhaphy are: (1) complete mobilization of the
intervention ureter from the peritoneal reflection to the UVJ, leaving
Patient on CAP with single O: Change to alternative a wide sheath of its peri-adventitial blood supply; (2) distal
febrile BT-UTI without antibiotics is an option
evidence of existing or new before surgical fixation of the ureter with long-acting absorbable sutures;
renal cortical abnormalities intervention (3) wide mobilization of the detrusor muscle flaps to
Patient not on CAP with febrile R: Initiation of CAP enable firm approximation of the detrusor over the ureter;
UTI and (4) development of a sufficient tunnel length. The use
Patient not on CAP with R: Initiation of CAP
afebrile UTI
of the extravesical detrusorrhaphy has been successfully
All patients with BT-UTI O: Open or endoscopic expanded to include a tapered excisional megaureter
surgical intervention repair,109 reimplantation of the ureters associated with
paraureteral Hutch diverticula,111 as well as correction of
BT, breakthrough; CAP, continuous antibiotic prophylaxis.
Adapted from Peters CA, Skoog SJ, Arant BS Jr, etal.
VUR associated with duplicated collecting systems.112
Summary of the AUA guideline on management of primary Complications of ureteral reimplantation are rare.88,113
vesicoureteral reflux in children. J Urol 2010;184:1134. The most common complication is de novo contralateral
744 SECTION VI Urology
SUBTRIGONAL
A INJECTION Urothelial closure
Ureteral
anastomosis
Detrusor Detrusor
B closure closure
C
Fixation suture
ADVANCEMENT
EXTRAVESICAL
DETRUSORRHAPHY
Urothelial closure
Urothelial closure
Ureteral
anastomosis
Detrusor
Detrusor Urothelial closure closure
closure E
D
HUTCH LEADBETTER
POLITANO
Ureteral
anastomosis
F
PAQUIN
FIGURE 55-11 Conceptual comparison of techniques to correct reflux. A common theme is the achievement of a long length of
intravesical ureter based on a strong detrusor floor and covered with compressible urothelium.
TABLE 55-6 Specific Advantages and Disadvantages of Commonly Performed Antireflux Procedures
Procedure Advantages Disadvantages
Subtrigonal injection Endoscopic procedure Material injected:
Teflonmigration, granuloma
formation
Collagenuncertain durability
Extravesical detrusorrhaphy Bladder never opened
No hematuria
No ureteral anastomosis
Minimal bladder spasms
Endoscopically accessible ureteral orifices
Advancement Avoids complications of neohiatus formation in
LeadbetterPolitano reimplantation
Cohen (transtrigonal) Transtrigonal: difficult to access
ureter endoscopically
GlennAnderson GlennAnderson: limited length of
tunnel achievable
Hutch No ureteral anastomosis
Good alternative with large associated congenital
diverticulum
LeadbetterPolitano Excellent ureteral tunnel dimensions with endoscopically Risk of ureteral obstruction
accessible ureteral orifices Risk of sigmoid colon injury with
left reimplantation
Paquin Versatility, extremely useful during complex
reconstructive procedures
55 Urinary Tract Infections and Vesicoureteral Reflux 745
Anchoring
FIGURE 55-12 The extravesical detrusorrhaphy sutures
antireflux technique conceptually viewed from
behind the bladder. (A) The detrusor is incised. (B)
The dissection is continued until the plane between
urothelium and muscle has been developed. (C) The
ureter is advanced and fixed into position with A B C
anchoring sutures. The detrusor is closed.
A B C D
FIGURE 55-13 The Cohen cross-trigonal ureteral reimplantation. (A) The ureter is intubated and the mucosa is incised circumferen-
tially around the ureteral orifice. (B) The ureters are dissected from the muscular attachments and mobilized until free within the
retroperitoneum. (C) Cross-trigonal tunnels are created by scissor dissection. (D) The ureteral anastomoses are completed.
A B C D
FIGURE 55-14 The LeadbetterPolitano ureteral reimplantation. (A) The ureter is intubated. (B) The ureter is mobilized. The hiatus
is dilated, and the retroperitoneal ureter is mobilized. Under direct vision the peritoneum is reflected from the outer surface of the
bladder. (C) The neohiatus is created, and the ureter is internalized into the bladder. The tunnel is created by scissor dissection, and
the original hiatus is closed. (D) The ureteral anastomosis is completed.
reflux,114 while the most common technical complications reimplantation remains a safe and highly successful oper-
are ureteral obstruction, persistent reflux, and diverticula ation. The extravesical approach for bilateral ureteral
formation. Persistent reflux may be caused by an insuf- reimplantation has been questioned because of a report-
ficient tunnel length to ureteral diameter ratio. However, edly high incidence of postoperative urinary retention.115
the greatest risk for postoperative reflux is related to the In our experience with a large group of patients, we have
high-pressure voiding dynamics due to uninhibited found acceptable rates of temporary incomplete bladder
bladder contraction, detrusor sphincter dyssnergia, and/ emptying (4%) which is transient and has minimal mor-
or urinary retention. Ureteral obstruction may be due to bidity.116 Risk factors appear to be infants under age one
ureteral kinking (at the neohiatus or obliterated umbilical and girls with large, thin-walled bladders and preexisting
artery), an excessively high placed neohiatus, construc- retentive voiding dysfunction.
tion of a tight neohiatus, twisting, anastomotic stricture, In 1984, a minimally invasive endoscopic procedure
devascularization, and tight tunnel. for the correction of VUR was reported (Fig. 55-15).
With attention directed toward the avoidance of tech- This subureteral transurethral injection (STING) uti-
nical complications and the selection of a procedure lized polytetrafluoroethylene (Teflon) and has been
associated with the lowest complication rate, ureteral used successfully outside the USA for many years.117
746 SECTION VI Urology
A B C
FIGURE 55-15 Technique of subureteric transurethral injection of dextranomer/hyaluronic acid copolymer (STING procedure). (Figure
used with permission from the Salix Corporation, Raleigh, NC, USA.)
Many different injectable materials have subsequently 5. Freedman AL. Urologic diseases in North America Project:
been investigated and reported.118120 This ambulatory Trends in resource utilization for urinary tract infections in chil-
dren. J Urol 2005;173:94954.
procedure performed under a brief general anesthetic has 6. Shaikh N, Morone NE, Lopez J, et al. Does this child have a
low morbidity and children may return to full activity as urinary tract infection? JAMA 2007;298:2895904.
soon as the next day. The initial success rates were prom- 7. Hoberman A, Chao HP, Keller DM, et al. Prevalence of urinary
ising; however, they did not quite match those of ureteral tract infection in febrile infants. J Pediatr 1993;123:1723.
8. Smellie J, Hodson C, Edwards D, et al. Clinical and radiological
reimplantation.121 features of urinary infection in childhood. Br Med J 1964;
In 2001, the Food and Drug Administration approved 14(5419):12226.
dextranomer/hyaluronic acid copolymer (Deflux) as the 9. Bickerton MW, Duckett JW. Urinary tract infections in pediatric
first injectable substance indicated in the USA for grades patients. AUA update series 1985;4.
I-IV vesicoureteral reflux.122 This substance is biodegrad- 10. Liao JC, Churchill BM. Pediatric urine testing. Pediatr Clin
North Am 2001;48:142540.
able, has no immunogenic properties, and does not seem 11. Pollack CV Jr, Pollack ES, Andrew ME. Suprapubic bladder aspira-
to have potential for malignant transformation. Results tion versus urethral catheterization in ill infants: Success, efficiency
vary, but most studies show success rates of around and complication rates. Ann Emerg Med 1994;23:22530.
7080% for abolishing reflux.122125 Higher success rates 12. Li PS, Ma LC, Wong SN. Is bag urine culture useful in monitor-
ing urinary tract infection in infants? J Paediatr Child Health
with larger injected volumes and multiple injection sites 2002;38:37781.
have been reported.126 Long-term reflux resolution rates 13. Edelmann CM, Ogw JE, Fine BP, et al. The prevalence of bacte-
appear to be stable, but recurrence has been found a year riuria in full-term and premature newborn infants. J Pediat
after the procedure.127 1973;82:12532.
Other complications such as ureteral obstruction 14. Aronson AS, Gustafson B, Svenningsen NW. Combined suprapu-
bic aspiration and clean voided urine examination in infants and
appear to be very low. Dysuria, gross hematuria, and children. Acta Paediatr Scand 1973;62:396400.
urinary frequency occasionally occur, but are self-limiting. 15. Iravani A. Treatment of urinary tract infections in young women.
Flank pain and fever are rare. In our institution, a VCUG AUA update series 1993;12.
and renal ultrasound are obtained 3 months after the 16. Hellerstein S. Recurrent urinary tract infections in children.
Pediatr Infect Dis 1982;1:27181.
procedure, but the cystogram is not subsequently repeated 17. Pryles CV, Lustik B. Laboratory diagnosis of urinary tract infec-
if the patient remains asymptomatic off antibiotic proph- tion. Pediatr Clin North Am 1971;18:233.
ylaxis. Patients having a febrile UTI after an apparently 18. Hoberman A, Wald ER, Reynolds EA, et al. Pyuria and bacteriu-
successful procedure should be re-investigated with a ria in urine specimens obtained by catheter from young children
VCUG to assess for recurrent reflux.128 with fever. J Pediatr 1994;124:51319.
19. Gorelick MH, Shaw KN. Screening tests for urinary tract infec-
tion in children: A meta-analysis. Pediatrics 1999;104:e54.
20. Lohr JA, Portilla MG, Geuder TG, et al. Making a presumptive
REFERENCES diagnosis of urinary tract infection by using a urinalysis performed
1. Hellstrom A, Hanson E, Hansson S, et al. Association between in on-site laboratory. J Pediatr 1993;122:225.
urinary symptoms at 7 years old and previous urinary tract infec- 21. Durbin WA, Peters G. Management of urinary tract infections in
tion. Arch Dis Child 1991;66:2324. infants and children. Pediatr Infect Dis 1984;3:56474.
2. Montini G, Tullus K, Hewitt I. Febrile urinary tract infections in 22. Liptak GS, Campbell J, Stewart R, et al. Screening for urinary
children. N Engl J Med 2011;365:23950. tract infection in children with neurogenic bladders. Am J Physical
3. Panaretto K, Craig J, Knight J, et al. Risk factors for recurrent Med & Rehab 1993;72:1226.
urinary tract infection in preschool children. J Paediatr Child 23. Sheldon CA, Gonzalez R. Differentiation of upper and lower
Health 1999;35:4549. urinary tract infections: How and when? Med Clin North Am
4. Peters CA, Skoog SJ, Arant BS Jr, et al. Summary of the AUA 1984;68:32133.
Guideline on Management of Primary Vesicoureteral Reflux in 24. Pecile P, Romanello C. Procalcitonin and pyelonephritis in chil-
Children. J Urol 2010;184:113444. dren. Curr Opin Infect Dis 2007;20:837.
55 Urinary Tract Infections and Vesicoureteral Reflux 747
25. Fowler J, Stamey T. Studies of introital colonization in women 50. Hoberman A, Wald ER, Hickey RW, et al. Oral versus initial
with recurrent urinary infections. VII. The role of bacterial adher- intravenous therapy for urinary tract infections in young febrile
ence. J Urol 1977;117:4726. children. Pediatrics 1999;104:7986.
26. Stamey TA, Mihara G. Studies of introital colonization in women 51. Montini G, Toffolo A, Zucchetta P, et al. Antibiotic treatment for
with recurrent urinary tract infection. VI. Analysis of segmented pyelonephritis in children: Multicentre randomised controlled
leukocytes in vaginal vestibule in relation to enterobacterial colo- non-inferiority trial. BMJ 2007;335:386.
nization. J Urol 1976;116:723. 52. Johnson CE, Maslow JN, Fattlar DC, et al. The role of bacterial
27. Roberts JA. Pathogenesis of nonobstructive urinary tract infec- adhesions in the outcome of childhood urinary tract infections.
tions in children. J Urol 1990;144:47580. Amer J Dis Children 1993;147:10903.
28. Rushton HG, Majd M. Pyelonephritis in male infants: How 53. Keren R, Chan E. A meta-analysis of randomized, controlled trials
important is the foreskin? J Urol 1992;148:7338. comparing short- and long-course antibiotic therapy for urinary
29. Parsons CL, Greenspan C, Mullholland SG. The primary anti- tract infections in children. Pediatrics 2002;109:E700.
bacterial defense mechanism of the bladder. Invest Urol 54. Mattoo TK. Evidence for and against urinary prophylaxis in vesi-
1975;13:728. coureteral reflux. Pediatr Nephrol 2010;25:237982.
30. Koff SA, Murtagh DS. The uninhibited bladder in children: 55. Hutch JA, Bunge RG, Flocks RH. Vesicoureteral reflux in chil-
Effect of treatment on recurrence of urinary infection and on dren. J Urol 1955;74:60720.
vesicoureteral reflux resolution. J Urol 1983;130:113841. 56. Hodson CJ, Edwards D. Chronic pyelonephritis and vesico-
31. Koff SA, Wagner TT, Jayanthi VR. The relationship among dys- ureteric reflux. Clin Radiol 1960;11:21931.
functional elimination syndromes, primary vesicoureteral reflux 57. Noe HN. The current status of screening for vesicoureteral reflux.
and urinary tract infections in children. J Urol 1998;160: Pediatr Nephrol 1995;9:63841.
101922. 58. King LR, Kazmi SO, Belman AB. Natural history of vesicoureteral
32. Asscher AW, Sussman M, Waters WE, et al. Urine as a medium reflux: Outcome of a trial of nonoperative therapy. Urol Clin
for bacterial growth. Lancet 1966;2:103741. North Am 1974;1:44155.
33. Mannhardt W, Schofer O, Schulte-Wiserman H. Pathogenic 59. Stephens FD, Lenaghan D. Anatomical basis and dynamics of
factors in recurrent urinary tract infection and renal scar forma- vesicoureteral reflux. J Urol 1962;87:66980.
tion in children. Eur J Pediatr 1986;145:3306. 60. Eckman H, Jacobsson B, Kock NG, et al. High diuresis: A factor
34. Smellie J, Normand I. Urinary tract infection: Clinical aspects. In: in preventing vesicoureteral reflux. J Urol 1966;95:51115.
Johnston JH, Williams DI, editors. Paediatric Urology. London: 61. Rolleston GL, Maling TM, Hodson CJ. Intrarenal reflux and the
Butterworths; 1982. p. 95. scarred kidney. Arch Dis Child 1974;49:5319.
35. Hanson L. Prognostic indicators in childhood urinary infection. 62. Hodson CJ, Maling TM, McManamon PH, et al. The pathogen-
Kidney Int 1982;21:65967. esis of reflux nephropathy. Br J Radiol (suppl) 1975;(Suppl.
36. Rushton HG, Majd M, Jantausch B, et al. Renal scarring following 13):126.
reflux and nonreflux pyelonephritis in children: Evaluation with 63. Thomsen H, Talner LB, Higgins CB. Intrarenal backflow during
99 mtechnetium-dimercaptosuccinic acid scintigraphy. J Urol retrograde pyelography with graded intrapelvic pressure. A radio-
1992;147:132732. logic study. Invest Radiol 1982;17:593603.
37. Shaikh N, Ewing AL, Bhatnagar S, et al. Risk of renal scarring in 64. Hodson CJ, Twohill SA. The time factor in the development of
children with a first urinary tract infection: A systematic review. sterile reflux scarring following high pressure vesicoureteral
Pediatrics 2010;126:108491. reflux. Contr Nephrol 1984;39:35869.
38. Wallace D, Rothwell D, Williams D. The long term follow up of 65. Medical versus surgical treatment of primary vesicoureteral reflux:
surgically treated vesicoureteral reflux. Br J Urol 1978;50: Report of the International Reflux Study Committee. Pediatrics
47984. 1981;67:392400.
39. Still J, Cottom D. Severe hypertension in childhood. Arch Dis 66. Arant BS Jr. Vesicoureteric reflux and renal injury. Am J Kid Dis
Child 1967;42:349. 1991;17:49511.
40. Scott J. Hypertension, reflux and renal scarring. In: Johnston JH, 67. Mattoo TK. Vesicoureteral reflux and reflux nephropathy. Adv
editor. Management of Vesicoureteral Reflux. Baltimore: Wiliams Chronic Kidney Dis 2011;18:34854.
and Wilkins; 1984. p. 60. 68. Bourchier D, Abbott GD, Maling TM. Radiological abnormali-
41. Sheldon CA, Geary DF, Shely EA, et al. Surgical consideration in ties in infants with urinary tract infections. Arch Dis Child
childhood end-stage renal disease. Pediatr Clin North Am 1984;59:6204.
1987;34:1187207. 69. Sargent MA, Stringer DA. Voiding cystourethrography in chil-
42. Cascio S, Chertin B, Yoneda A, et al. Acute renal damage in infants dren with urinary tract infection: The frequency of vesicoureteric
after first urinary tract infection. Pediatr Nephrol 2002;17: reflux is independent of the specialty of the physician requesting
5035. the study. AJR 164 1995;164:123741.
43. Chon CH, Lai FC, Shortliffe LM. Pediatric urinary tract infec- 70. Benador D, Benador N, Slosman D, et al. Are younger children
tions. Pediatr Clin North Am 2001;48:144159. at highest risk of renal sequelae after pyelonephritis? Lancet
44. UTI Guideline Team C. Evidence-based care guideline for 1997;349:1719.
medical management of first urinary tract infection in children 12 71. Ditchfield M, deCampo, JF, Nolan TM, et al. Risk factors in the
years of age or less. (Cincinnati Childrens Hospital Medical developement of early renal cortical defects in children with
Center) Guidelines 2006;7:123. urinary tract infection. AJR 1994;162:13937.
45. Roberts KB. Urinary tract infection: clinical practice guideline 72. Deckter RM, Roth DR, Gonzales ET. Vesicoureteral reflux in
for the diagnosis and management of the initial UTI in febrile boys. J Urol 1988;40:108991.
infants and children 2 to 24 months. Pediatrics 2011;128: 73. Noe HN. The long-term results of prospective sibling reflux
595610. screening. J Urol 1992;148:173942.
46. Wan J, Skoog SJ, Hulbert WC, et al. Section on Urology response 74. Wan J, Greenfield SP, Ng M, et al. Sibling reflux: A dual center
to new guidelines for the diagnosis and management of UTI. retrospective study. J Urol 1996;156:6779.
Pediatrics 2012;129:e10513. 75. Chertin B, Puri P. Familial vesicoureteral reflux. J Urol
47. Craig JC, Wheeler DM, Irwig L, et al. How accurate is dimer- 2003;169:18048.
captosuccinic acid scintigraphy for the diagnosis of acute pyelone- 76. Noe HN, Wyatt RJ, Peeden JN Jr, et al. The transmission of
phritis? A meta-analysis of experimental studies. J Nucl Med vesicoureteral reflux from parent to child. J Urol 1992;148:
2000;41:98693. 186971.
48. Kogan BA, Kay R, Wasnick RJ, et al. 99mTc-DMSA scanning to 77. McLorie GA, Sheldon CA, Fleisher M, et al. The genitourinary
diagnose pyelonephritic scarring in children. Urology 1983;21: system in patients with imperforate anus. J Pediatr Surg 1987;22:
6414. 11004.
49. Hiraoka M, Hashimoto G, Tsuchida S, et al. Early treatment of 78. DeFoor W, Minevich E, Tackett L, et al. Ectopic ureterocele:
urinary infection prevents renal damage on cortical scintigraphy. clinical application of classification based on renal unit jeopardy.
Pediatr Nephrol 2003;18:11518. J Urol 2003;169:10924.
748 SECTION VI Urology
79. Henneberry MD, Stephens FD. Renal hypoplasia and dysplasia 104. Hinchliffe SA, Kreczy A, Ciftci AO, et al. Focal and segmental
in infants with posterior urethral valves. J Urol 1980;123: glomerulosclerosis in children with reflux nephropathy. Ped
91215. Pathology 1994;14:32738.
80. Sheldon CA, Cormier M, Crone K, et al. Occult neurovesical 105. Williams GJ, Wei L, Lee A, et al. Long-term antibiotics for pre-
dysfunction in children with imperforate anus. J Pediatr Surg venting recurrent urinary tract infection in children. Cochrane
1991;26:4954. Database Syst Rev 2006;3:CD001534.
81. Agarwal SK, Khoury AE, Abramson RP, et al. Outcome analysis 106. Mathews R, Carpenter M, Chesney R, et al. Controversies in the
of vesicoureteral reflux in children with myelodysplasia. J Urol management of vesicoureteral reflux: The rationale for the
1997;157:9802. RIVUR study. J Pediatr Urol 2009;5:33641.
82. Koff SA. Relationship between dysfunctional voiding and reflux. 107. Casale P, Kojima Y. Robotic-assisted laparoscopic surgery
J Urol 1992;148:17035. in pediatric urology: an update. Scand J Surg 2009;98:
83. Chandra M, Maddix H, McVicar M. Transient urodynamic dys- 11019.
function of infancy: Relationship to urinary tract infections and 108. Zaontz MR, Maizels M, Sugar EC, et al. Detrusorrhaphy: Extra-
vesicoureteral reflux. J Urol 1996;155:6737. vesical ureteral advancement to correct vesicoureteral reflux in
84. van Gool JD, Hjalmas K, Tamminen-Mobius T, et al. Historical children. J Urol 1987;138:9479.
clues to the complex of dysfunctional voiding, urinary tract infec- 109. Wacksman J, Gilbert A, Sheldon CA. Results of the renewed
tion and vesicoureteral reflux. The International Study in Chil- extravesical reimplant for surgical correction of vesicoureteral
dren. J Urol 1992;148:1699702. reflux. J Urol 1992;148:35961.
85. Koff SA, Lapides J, Piazza DH. Association of urinary tract infec- 110. Minevich E, Sheldon CA. Extravesical detrusorrhaphy (uretero-
tions and reflux with uninhibited bladder contractions and volun- neocystostomy). AUA Updates XX, 2001.
tary sphincteric obstruction. J Urol 1979;122:3736. 111. Jayanthi VR, McLorie GA, Khoury AE, et al. Extravesical detru-
86. Paltiel HJ, Rupich RC, Kiruluta HG. Enhanced detection of vesi- sorrhaphy for refluxing ureters associated with paraureteral diver-
coureteral reflux in infants and children with use of cyclic voiding ticula. Urology 1995;45:6646.
cystourethrography. Radiology 1992;184:7535. 112. Minevich E, Tackett L, Wacksman J, et al. Extravesical common
87. Lebowitz RL. The detection and characterization of vesicoureteral sheath detrusorrhaphy (ureteroneocystotomy) and reflux in dupli-
reflux in child. J Urol 1992;148:16402. cated collecting systems. J Urol 2002;167:28890.
88. Elder JS, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral 113. Gibbons MD, Gonzales ET. Complications of antireflux surgery.
Reflux Guidelines Panel summary report on the management Urol Clin North Am 1983;10:489501.
of primary vesicoureteral reflux in children. J Urol 1997;157: 114. Minevich E, Wacksman J, Lewis AG, et al. Incidence of contral-
184651. ateral vesicoureteral reflux following unilateral extravesical
89. Cohen RA, Rushton HG, Belman AB, et al. Renal scarring and detrusorrhaphy (ureteroneocystostomy). J Urol 1998;159:
vesicoureteral reflux in children with myelodysplasia. J Urol 21268.
1990;144:5414; discussion 545. 115. Fung LC, McLorie GA, Jain U, et al. Voiding efficiency after
90. Smellie JM, Normand ICS. Reflux nephropathy in childhood. In: ureteral reimplantation: A comparison of extravesical and intra-
Hodson J, Kincaid-Smith P, editors. Reflux Nephropathy. New vesical techniques. J Urol 1995;153:19725.
York: Masson; 1979. p. 14. 116. Minevich E, Aronoff D, Wacksman J, et al. Voiding dysfunction
91. Claesson I, Jacobsson B, Olsson T, et al. Assessment of renal after bilateral extravesical detrusorrhaphy. J Urol 1998;160:
parenchymal thickness in normal children. Acta Radiol Diagn 10046.
1981;22:30514. 117. ODonnell B, Puri P. Treatment of vesicoureteric reflux by endo-
92. Smellie JM, Ransley PG, Normand ICS, et al. Development of scopic injection of Teflon. Br Med J (Clin Res Ed) 1984;
new renal scars: A collaborative study. Br Med J 1985;290: 289:79.
195760. 118. Leonard MP, Canning DA, Peters CA, et al. Endoscopic injection
93. McLorie GA, McKenna PH, Jumper BM, et al. High grade vesi- of glutaraldehyde cross-linked bovine dermal collagen for correc-
coureteral reflux: Analysis of observational therapy. J Urol tion of vesicoureteral reflux. J Urol 1991;145:11519.
1990;144:53740. 119. Smith DP, Kaplan WE, Oyasu R. Evaluation of polydimethylsi-
94. Shimada K, Matsui T, Ogino T, et al. Renal growth and progres- loxane as an alternative in the endoscopic treatment of vesi-
sion of reflux nephropathy in children with vesicoureteral reflux. coureteral reflux. J Urol 1994;152:12214.
J Urol 1988;140:1097100. 120. Diamond DA, Caldamone AA. Endoscopic correction of vesi-
95. Ransley PG, Risdon RA. Reflux and renal scarring. Br J Radiol coureteral reflux in children using autologous chondrocytes: Pre-
Suppl 1978;14:1. liminary results. J Urol 1999;162:11858.
96. Yeung CK, Godley ML, Dhillon HK, et al. The characteristics of 121. Chertin B, Kocherov S. Long-term results of endoscopic treat-
primary vesico-ureteric reflux in male and female infants with ment of vesicoureteric reflux with different tissue-augmenting
pre-natal hydronephrosis. Br J Urol 1997;80:31927. substances. J Pediatr Urol 2010;6:2516.
97. Marra G, Barbieri G, DellAgnola CA, et al. Congenital renal 122. Elder JS, Diaz M, Caldamone AA, et al. Endoscopic therapy for
damage associated with primary vesicoureteral reflux detected vesicoureteral reflux: A meta-analysis. I. Reflux resolution and
prenatally in male infants. J Pediatrics 1994;124:72630. urinary tract infection. J Urol 2006;175:71622.
98. Makie GG, Stephens FD. Duplex kidneys: A correlation of renal 123. Higham-Kessler J, Reinert SE, Snodgrass WT, et al. A review of
dysplasia with position of the ureteral orifice. J Urol 1975;114: failures of endoscopic treatment of vesicoureteral reflux with dex-
27480. tranomer microspheres. J Urol 2007;177:71014.
99. Najmaldin A, Burge DM, Atwell JD. Reflux nephropathy second- 124. Yucel S, Gupta A, Snodgrass W. Multivariate analysis of factors
ary to intrauterine reflux. J Pediatr Surg 1990;25:38790. predicting success with dextranomer/hyaluronic acid injection for
100. Cortez J, Sheldon CA. Focal and diffuse renal parenchymal lesions vesicoureteral reflux. J Urol 2007;177:15059.
associated with hypertension: the urologic surgeons approach to 125. Kirsch AJ, Perez-Brayfield M, Smith EA, et al. The modified sting
evaluation and managemen. In: Loggie J, editor. Pediatric and procedure to correct vesicoureteral reflux: Improved results with
Adolescent Hypertension. Cambridge: Blackwell Scientific; 1991. submucosal implantation within the intramural ureter. J Urol
p. 217. 2004;171:241316.
101. Salvatierra O, Kountz SL, Belzer FO. Primary vesicoureteral 126. Kalisvaart JF, Scherz HC, Cuda S, et al. Intermediate to long-term
reflux and end-stage renal disease. JAMA 1973;226:14546. follow-up indicates low risk of recurrence after Double HIT
102. McEnery PT, Alexander SR, Sullivan K, et al. Renal transplanta- endoscopic treatment for primary vesico-ureteral reflux. J Pediatr
tion in children and adolescents: The 1992 annual report of the Urol 2012;8:35965.
North American pediatric Renal Transplant Cooperative Study. 127. Lee, EK, Murphy JP, Gatti JM, et al. Long term follow-up of
Ped Nephr 1993;7:71120. Dextranomer/Hyaluronic acid for reflux: Late failure warrants
103. Avner ED, Chavers B, Sullivan K, et al. Renal transplantation and continued follow-up. J. Urol 2009;181:186975.
chronic dialysis in children and adolescents: The 1993 annual 128. Traxel E, DeFoor W, Reddy P, et al. Risk factors for urinary tract
report of the North American Pediatric Renal Transplant Coop- infection after dextranomer/hyaluronic acid endoscopic injection.
erative Study. Pediatr Nephrol 1995;9:6173. J Urol 2009;182:170812.
C H A P T E R 5 6
The bladder and urethra normally function as a coordi- sphincter, the bladder empties by sustained and complete
nated unit to store and discharge urine from the body. contraction of the detrusor, leaving a residual urine
Both structural and functional disorders of the bladder or volume of less than 5mL.
urethra may be responsible for bleeding, incontinence, Spinal pathways connect the sacral micturition center
infection, discomfort, pain, and obstruction that can cause with three areas in the brain stem, collectively referred
upper tract deterioration to the point of compromising to as the pontine micturition center.4 This center func-
renal function. This chapter focuses on the major diseases tions to inhibit urination during storage and to produce
and dysfunctional conditions of the bladder and urethra external sphincter relaxation during the voiding phase.
as a unit and the management of such problems. Above this level are areas of cerebral cortex which oversee
The bladder and upper urethra are composed of and modulate the autonomic process. It is the mature,
bundles of smooth muscle fibers arranged in a reticular integrated function of all these components that pro-
lattice, the outermost bundles being more circular and duces urinary continence.
the inner bundles more longitudinal in orientation at the Toilet training is, in large part, a learned phenomenon.
bladder neck.1 The smooth muscle bundles blend into the It requires adequate recognition by the brain that mictu-
striated muscle of the external urethral sphincter, which rition would be socially unacceptable in a given situation.
is derived from the pelvic diaphragm. The bladder is With maturation, the bladder gains capacity, allowing for
lined by transitional epithelium, which is sensitive to irri- longer intervals between voiding. The approximate
tants such as bacterial toxins and various urinary crystals. bladder volume in ounces may be estimated in a child as
The urethra and trigone are especially sensitive, and the age in years plus 2. It may also be calculated by a more
presence of any irritant in these areas can create signifi- precise formula if needed.5 Infants void 20 times per day,
cant discomfort. which decreases to about ten times per day by age 3
Proper function of the lower urinary tract depends on years.6 The child also learns to resist the urge to void by
intact autonomic and somatic nervous innervation. The voluntary contraction of the external sphincter until the
detrusor muscle of the bladder is innervated by both detrusor contraction passes and the bladder once again
sympathetic and parasympathetic fibers. Storage func- relaxes. Thus, toilet training depends on the develop-
tions are mediated by the sympathetic component, which ment of voluntary detrusor sphincter dyssynergia (DSD),
arises from spinal levels T10L1. The chemical mediator which at times is dysfunctional.7 Finally, full bladder
of this process is norepinephrine, which acts on control relies on the child developing volitional control
-adrenergic receptors in the fundus of the bladder over the spinal micturition reflex to be able to initiate or
and causes muscle relaxation for low-pressure storage inhibit detrusor contractions. Most children attain day
of urine. The same sympathetic stimulus acts on the and night continence by 4 years of age.
-adrenergic receptors of the trigone, bladder neck, and Urinary incontinence may be in part due to immatu-
proximal urethra to increase internal sphincter activity rity of the bladder and its nervous system connections.
and promote continence during urine storage by main- The usual sequence of bladder development is linked to
taining outlet resistance. The external urinary sphincter, bowel development and is as follows: (1) control of bowel
innervated by the pudendal nerve, progressively increases at night; (2) control of bowel during the day; (3) control
its tone as the bladder fills, providing additional resist- of bladder during the day; and (4) control of bladder at
ance. As the child develops, the external sphincter may night.
be consciously contracted at times of urgency or stress to
prevent the unwanted passage of urine. Properly coordi-
nated function of the external urinary sphincter relies on CHILDHOOD INCONTINENCE
an intact sacral reflex arc which should be well developed
in normal infants, but is variably functional in infants Incontinence is the term used for the unintentional loss
with spinal cord abnormalities or pelvic lesions.2,3 of urine after toilet training is achieved. The following
The sensation of bladder fullness initiates a response definitions are clinically useful:8
in toilet-trained children that causes them to discharge Enuresis or nocturnal enuresis: intermittent inconti-
their urine. When ready, the parasympathetic nervous nence while sleeping
system, via acetylcholine, causes cholinergic fibers of the Primary nocturnal enuresis: never been continent at
detrusor to contract, resulting in a widened and short- night
ened proximal urethra, eliminating its resistance to Secondary nocturnal enuresis: nighttime incontinence
outflow. With relaxation of the volitional external following a dry period of at least 6 months.
749
750 SECTION VI Urology
Daytime incontinence: daytime wetting after toilet deeply and are difficult to arouse. However, this is prob-
training ably not true. Enuretic patients sleep no more deeply
Stress incontinence: urine leakage due to physically than age-matched controls, wet in all stages of sleep, and
stressful activities such as coughing. show no different awakening patterns. Wetting episodes
Urge incontinence: unintentional loss of urine when occur as the bladder fills throughout the night.18
bladder urgency occurs.
The discussion of incontinence is divided into sections Antidiuretic Hormone. Antidiuretic hormone (ADH)
on nocturnal enuresis and daytime incontinence, realiz- is released from the pituitary in a circadian rhythm so
ing that some children have both. The current recom- that levels are higher at night and thus diminish urine
mendation for children with nocturnal enuresis and output. Some children may undersecrete ADH at night
daytime incontinence is to focus on daytime treatment resulting in bed wetting.1922 Although some patients
first followed by nocturnal enuresis therapy. follow this pattern, others do not; the altered circadian
patterns appear to normalize with maturation.23
Nocturnal Enuresis
Evaluation
About 1520% of children at 5 years of age continue to
have bed wetting.913 As so many children still wet at The screening evaluation should include a history, physi-
night before this age, it is considered within the range of cal examination, and urinalysis. If these are normal, then
normal and not termed nocturnal enuresis. After age 5, no other testing is needed because organic disease rarely
night wetting resolves at the rate of about 15% each year. causes monosymptomatic nocturnal enuresis. Any associ-
By age 15 years, it has resolved in 99% of children.13 ated anomaly or problem such as urinary tract infection
(UTI), sacral anomalies, or complex enuresis patterns
warrant medical imaging.
Etiology
Children with monosymptomatic nocturnal enuresis are, Treatment
in general, physically and emotionally similar to their
peers. The difference lies in their inability to awaken The treating physician should recognize enuresis as a
during sleep when their bladder is full or contracts. The symptom and not a disease. Realizing that there may be
etiology of this disorder is likely complex and several more than one cause permits the physician to consider
factors should be considered. more than one treatment option. Specific treatment is
generally discouraged before the age of 7 years. Certain
Genetic. Family history is significant. If both the parents measures are sensible in all nocturnal enuretic patients:
had enuresis, 77% of their offspring will as well. If one void just before getting into bed, avoid huge fluid
parent was affected, 44% of the offspring are affected. If loads during the evening hours, and avoid caffeine after
neither parent has a history, only 15% of their children 3:00 pm.
have this problem.12,14
Enuretic Alarms. Wetting alarms are devices that fit in
Psychological. Psychological stress can induce noctur- the underwear of the patients. When moistened, an alarm
nal enuresis in certain children. Secondary nocturnal is sounded. This type of conditioning therapy requires a
enuresis often raises this concern. Common factors motivated patient and parents. A variety of products are
include divorce, changing homes, birth of a new sibling, available with either an audio alarm, a vibrating alarm, or
trouble at school, or just starting school.
both. In our experience, the best alarm is simply one that
Developmental. As children grow, bladder capacity is easy to set up and is able to wake the child. The parent
increases significantly each year at a proportion greater may need to help arouse the child, take him or her to the
than urine volume produced.11,15,16 Volitional control over bathroom, and reset the alarm. This may occur multiple
bladder and sphincter also may mature at variable rates times each night, particularly at the onset of therapy. In
and may be related to subtle delays in perceptual abilities two studies, wetting alarms were shown to give the best
or fine motor skills.17 long-term results when compared with other treat-
ments.24,25 The length of treatment to achieve dryness
Urodynamic. Studies show that enuretic episodes occur varied between 18 nights and 2.5 months. Relapse may
when the bladder is full, and they simulate normal awake occur in 2030% of treated children, but re-treatment
voiding.16 Although nocturnal enuretic patients have can be successful.25
more nighttime unstable bladder contractions, these are
at low pressure and do not cause leakage. Medications. Imipramine, a tricyclic antidepressant, has
Night wetting appears to occur in three ways: wetting been used for many years. The exact mechanism of action
associated with significant restlessness and visceral and is unknown. Initial success has been reported in the 50%
somatic activity (deep respirations), wetting with a quick range. However, a recent review showed only a 20%
contraction and minimal movement, and wetting with no success with a relapse rate of 96%.26 Clinical practice
central nervous system response (parasomnia). reveals that the longer the initial treatment, the more
benefit before the effect wanes. It is suggested that
Sleep Disorders. Parents of children with nocturnal the medication be weaned slowly rather than stopped
enuresis are generally convinced that these children sleep abruptly.
56 Bladder and Urethra 751
Side effects include anxiety, insomnia, dry mouth, over the perineum (Vincent curtsy). In our experience,
nausea, and personality changes. An overdose can cause children with hyperactivity disorders or a willful disposi-
fatal cardiac arrhythmias.27 Therefore, medication safety tion appear prone to this pattern.
in the home is important. Imipramine may improve Urodynamic studies demonstrate significant unstable
response rates to the enuretic alarm. (unwanted) contractions during bladder filling that cause
Desmopressin is an analog of ADH that mimics its leakage before sphincter contraction (or posturing) can
urine-concentrating activity without the vasopressor control it. Because these unstable contractions or spasms
effect.28 The effect is dose dependent, usually requiring occur frequently during the day, there develops a reten-
20 40g/day for success. tive pattern of using the external sphincter to hold on.
Complete dryness rates may be highest in patients When these children do get to the bathroom and try to
with a strong family history of success. Efficacy and safety void, the sphincter relaxes poorly or only intermittently,
have been demonstrated in a number of studies, but long- resulting in stop-and-go voiding, difficulty initiating a
term success remains lower than with alarm systems.2830 urinary stream, straining, and poor emptying which is
Desmopressin may occasionally have side effects, includ- described by the term voiding dysfunction (VD). The ele-
ing electrolyte changes, nasal irritation, and headaches. vated pressure during voiding and the poor emptying
Desmopressin is available as a nasal spray. However, this may result in secondary vesicoureteral reflux (VUR) and
route is not approved for treating nocturnal enuresis due UTI. Finally, the overactivity of the urinary sphincter
to a higher incidence of hyponatremia. Parents should be may carry over to the anal sphincter, making stool reten-
warned to avoid over-hydration to prevent this side effect. tion and encopresis commonly associated findings.
Oxybutynin is the most common drug used for enu-
resis. It is effective when day and nighttime wetting occur Treatment. Effective treatment rests on managing all
in the same patient, but has no benefit over placebo when aspects of this condition simultaneously. Constipation is
nighttime wetting is the only symptom.31 treated with fiber or laxatives, and mineral oil after initial
bowel clean-out. Recurring UTIs are managed with pro-
General Approach. Although many parents consider phylactic antibiotics. Bladder instability is treated with
bed wetting a problem, they often do not consider it timed voiding at frequent intervals (an alarm watch for
significant enough to treat, especially when medications the child is helpful) and anticholinergics such as oxybu-
are being considered. If therapy is desired, it is often most tynin or tolterodine.3537
reasonable to begin with an enuretic alarm. This has the Biofeedback has gained in popularity for treatment of
highest response rate, no side effects, and the lowest the VD. Electrodes placed on the perineum near the
relapse rate. Combination therapy with imipramine may genitourinary diaphragm can be attached to monitors, an
be considered when the alarm is not successful. If desmo- audio signal, or a computer display so the children can
pressin has proved effective in a specific patient, the learn to relax their external sphincter voluntarily, result-
patient and family may choose to keep it available and ing in better voiding coordination.3840 The process typi-
use it only on specific nights when dryness is especially cally requires four to eight weekly visits, with follow-up
desired (e.g., sleepovers, campouts). Some patients do not as needed.
respond to therapy, and time, reassurance, and a caring Neuromodulation has been used mainly in adults who
approach are all that can be offered. have a refractory overactive bladder; however, there has
been recent use in children. Transcutaneous electrical
nerve stimulation (TENS) has been popular because of
Daytime Incontinence its non-invasive nature, though it requires numerous ses-
The patient history is of paramount importance in sorting sions. The TENS unit is thought to inhibit bladder activ-
out the various categories of daytime incontinence.32,33 ity via the pudendalpelvic nerve reflex. Initial studies
The physical examination and evaluation should always show promise with improvements ranging from 73100%
assess for an abdominal mass or tenderness, distended in small series.41,42
bladder, normal genitalia, signs of spina bifida occulta, Initial success with any treatment is often followed by
perineal sensation, sacral reflexes, gait, lower extremity later relapse. If initial treatment is unsuccessful, it may
reflexes, and urinalysis. Radiographic evaluation, usually be successful if re-tried later. Patients older than 8 years
voiding cystourethrogram (VCUG) and renal ultra- who fail treatment should be considered for urodynamic
sonography (US), are important in patients with UTI or testing. Secondary VUR usually resolves (80%) as bladder
complex incontinence patterns. function improves.43 The unstable bladder of childhood
is usually age limited.
Bladder Instability
Isolated Frequency Syndrome
Bladder instability is by far the most common diagnosis
in children with persistent daytime wetting.34 These chil- A separate, and much less common, group of children
dren are usually toilet trained, but later develop increas- present with acute onset of urinary frequency. They
ing accidents associated with urgency. They describe appear healthy, are normal on examination, and have
not knowing that the bladder contraction was coming. normal urinalysis and culture. They do not have true
They dash to the bathroom or try to hold it in. Boys urgency or any wetting, but feel that they must urinate
grab and compress the penis, and girls often cross their frequently, sometimes every 5 to 10 minutes. They void
legs and dance around or squat with the heel compressed a very small amount each time. Most sleep through the
752 SECTION VI Urology
*
A B
FIGURE 56-1 (A) This cystogram shows the typical findings in a patient with Hinman syndrome: trabeculated bladder and severe
reflux. (B) This voiding study in the same patient demonstrates dilation of the posterior urethra (asterisk) as a result of chronic
contraction of the external sphincter during voiding.
night and void a large amount on awakening. The pattern to be a deeply ingrained learned disorder of severe vol-
may come and go over weeks or months. untary DSD. In these patients, the urinary tract has the
The cause is unclear but is related to emotional stress appearance of a patient with a neurogenic bladder. There
in many cases. Careful assessment is crucial, and reassur- is hydronephrosis, a trabeculated bladder, reflux, and
ance to parent and child is paramount. Sometimes, setting sometimes progressive loss of renal function (Fig. 561).
an alarm to progressively lengthen voiding intervals with Aggressive therapy with prophylactic antibiotics, anti-
a reward for success is helpful. This condition is benign cholinergics, alpha blockers, urodynamic biofeedback
and self-limited, although it may persist intermittently training, timed voiding, or clean intermittent catheteriza-
for months. Anticholinergics have no benefit, and further tion (CIC) may be required.47,48 Some recalcitrant cases
evaluation is not needed. may require bladder diversion or augmentation to avoid
renal failure. As with many functional disorders, the
severity of Hinman syndrome tends to wane with matura-
Infrequent Voider/Underactive Bladder
tion, but progressive deterioration may not permit the
On the other end of the voiding spectrum are those chil- surgeon to wait.
dren who void only once or twice daily and may not
urinate until afternoon after waking in the morning.44
These children have developed urinary retentive behav- NEUROGENIC BLADDER
ior without any bladder instability and have dilated, high-
capacity, low-pressure bladders.45 Some show an aversion True neurogenic dysfunction of the bladder in childhood
to bathrooms or exhibit excessive neatness, whereas many results from acquired or congenital lesions that affect
others appear reasonably adjusted. They may be some- bladder innervation. Acquired lesions may occur from
what prone to UTI and stress incontinence. trauma to the brain, spinal cord, or pelvic nerves, or as a
It is important to exclude a neurologic cause and a result of tumor, infection, or vascular lesions affecting
structural obstruction to emptying. Ultrasound can dem- these same structures. Congenital lesions include spina
onstrate good emptying if performed before and after bifida and other neural tube defects (most common),
voiding. A timed voiding regimen is usually required to degenerative neuromuscular disorders, cerebral palsy,
get these children to urinate regularly if problems are tethered cord, sacral agenesis, and other causes.49
occurring. This pattern tends to improve with age. The most practical way to classify neurogenic bladder
abnormalities is by a simple functional system: failure to
store, failure to empty, or a combination of both.50 Failure
Continuous Incontinence to store urine may be caused by the detrusor muscle itself
Patients who present with total incontinence and con- or by the bladder outlet. Detrusor hyperactivity or poor
stant dribbling have a higher probability of urinary tract compliance causes elevated bladder pressures and incon-
anomaly pathology, and require radiographic and possi- tinence on this basis. An incompetent bladder neck or
bly urodynamic evaluation. urethral sphincter mechanism can be the outlet cause of
failure to store urine even if storage pressures are reason-
able. Failure to empty can be secondary to the hypotonic,
Hinman Syndrome
neurogenic bladder which may not generate enough pres-
A small number of children demonstrate persistent sure to empty, or increased outlet resistance secondary to
incontinence, repeated febrile UTI, VUR, high bladder striated or smooth muscle sphincter dyssynergia. This
storage pressures, and very poor emptying.46 This appears classification helps to base treatment on urodynamic data.
56 Bladder and Urethra 753
applied to children with neurogenic bladder in an effort what CIC interval would keep bladder pressures in a safe
to decrease bladder pressures and increase compliance; range. Medications can then be adjusted to extend CIC
however, data remains limited to small case series in chil- intervals, achieve dryness, and avoid the development or
dren.70,71 The effects of the injection are short term and progression of hydronephrosis.
repeated injections are required. In children with high bladder storage pressures and
Urodynamic assessment may be elaborate in certain deterioration of the upper tracts that cannot be managed
situations, but is usually a simple measurement of the by CIC and pharmacologic therapy, temporary diversion
pressurevolume relationship of the bladder during with cutaneous vesicostomy may be necessary.72,73 Protec-
filling. It is performed using a double-lumen catheter in tion of the upper urinary tracts from high bladder pres-
the bladder and involves simultaneous assessment of sures is thus accomplished until such time that other
external sphincter function with a perineal electrode. It treatments can be effective. We reserve this treatment for
also can be performed with contrast material and moni- infants who have serious deterioration of the upper tract
tored fluoroscopically to add information. Evaluation of and those who, for social, medical, or anatomic reasons,
bladder compliance, hyperreflexic contractions, leak- cannot be managed with the other aforementioned forms
point pressure, stress leak-point pressure, and sphincter of medical treatment. As an alternative, some advocate
dyssynergia can be extremely helpful in choosing among urethral dilation in girls to diminish the leak-point pres-
treatment options. Figure 56-2 demonstrates the effect sure. Surprisingly, relatively long-term benefit has been
of anticholinergics in shifting the pressurevolume curve found.74
to the right and thus permitting the bladder to store more
urine at any given pressure. Figure 56-3 shows the effect
of -adrenergic agonists on raising the leak-point pres-
Surgical Treatment
sure and thus improving continence. Although most patients with neurogenic bladder can be
It is crucial to understand that when bladder pressures managed adequately without operation, those with VUR,
remain greater than 3540cmH2O, ureteral peristalsis a poorly compliant bladder that is not responsive to
does not effectively empty the upper tracts, and hydrone- medical therapy, or refractory incontinence may benefit.
phrosis and renal insufficiency eventually result. Thus, Treatment of VUR in the neurogenic bladder is much
coupling UD data with a particular patients estimated (or the same as that for the normal bladder.75 It is imperative
measured) hourly output permits the clinician to decide that the bladder is adequately treated for poor compli-
ance and hyperreflexia (CIC and anticholinergics) before
and after operation to diminish the risk of recurrence.76
A B In some cases, bladder augmentation may be required.
Bladder augmentation is designed to create a reservoir
with good compliance and adequate capacity to store
urine until it can be emptied by CIC at socially appropri-
P (cmH2O)
Leak
Bladder autoaugmentation or detrusorectomy is an
alternative augmenting technique that may prove useful
in selected patients (Figs 56-5 and 56-6).80 This approach
Normal
involves removal of the detrusor muscle over the superior
portion of the bladder, leaving the underlying bladder
mucosa intact. This creates a large compliant surface,
V (mL)
essentially a large diverticulum, which decreases bladder
FIGURE 56-3 Bladder filling pressure-volume curve demon- pressures and increases bladder capacity at the time
strating a higher leak-point pressure (from A to B), sometimes
achieved with -adrenergic agents such as pseudoephedrine
of filling. The advantage of this technique is that the
and imipramine. The effect is to decrease incontinence at lower bladder epithelium is preserved and not replaced with
pressures. gastrointestinal epithelium as in bowel augmentation,
56 Bladder and Urethra 755
25 cm
Antimesenteric
incision
A B
A B
FIGURE 56-5 (A) Radiographic and (B) ultrasonographic images of a patient with spina bifida showing a small, poorly compliant
bladder and worsening hydronephrosis.
756 SECTION VI Urology
A B
FIGURE 56-6 (A) Radiographic and (B) ultrasonographic images in the patient shown in Fig. 56-5 after bladder autoaugmentation,
demonstrating improved bladder capacity and better compliance, which resulted in continence and diminished hydronephrosis.
thus eliminating the problems associated with the secre- posterior incised strip up the middle of the trigone.88
tory and absorptive functions of bowel mucosa. Long- Owing to the lack of a pop-off mechanism in both these
term follow-up data on large numbers of children are procedures, if the bladder becomes overfilled, there is an
lacking, but this technique appears to be a viable alterna- increased potential for bladder rupture or for upper tract
tive for use in bladders with reasonable capacity and deterioration if high bladder pressure develops.
mainly poor compliance.81 The concept has been extended One of the more popular forms of increasing urethral
to create composite bladders by placing demucosalized resistance in a neurogenic bladder is by a bladder neck
bowel or stomach patches over the urothelial bulge fascial sling.8993 This procedure has many advocates and
created in autoaugmentation.82,83 This concept of urothe- involves securing a rectus fascial strip (or other material)
lial preservation during augmentation is carried forward around the bladder neck and suspending it from the ante-
by current innovative approaches to replace bladder wall rior rectus fascia or pubis. This elevates and compresses
with biodegradable scaffolds, typically seeded with the urethra to increase outlet resistance.
urothelial and detrusor smooth muscle cells.84 The artificial urinary sphincter is a fluid-filled pres-
Persistent incontinence, despite adequate treatment of surized cuff around the urethra or bladder neck, which
the bladder to lower pressures and increase compliance, can be deflated by a pump-reservoir device that permits
may require bladder outlet repair to increase resistance. the urethra to open and the bladder to drain (Fig. 56-7).
The YoungDees technique, which lengthens the urethra The artificial urinary sphincter can also be used in higher-
by infolding and tubularizing the trigone of the bladder, pressure bladders in conjunction with bladder augmenta-
still has some advocates.85 Kropps procedure uses a tubu- tion.94 The main disadvantage is that it is a mechanical
larized anterior bladder strip reimplanted in the submu- device that can erode into the urethra and malfunction
cosa of the trigone to gain continence by a flap valve over time. If the device is in situ long enough, it will
mechanism.86 Continence is commonly achieved, but eventually need revision. For this reason, we prefer to use
catheterization is sometimes difficult.87 Pippi Salles pro- autologous tissue techniques in children, when possible.
cedure creates a similar (but easier to catheterize) flap The periurethral injection of dextranomer/
valve by onlaying an anterior bladder wall flap onto a hyaluronic acid copolymer (Deflux), Teflon, or
56 Bladder and Urethra 757
Reservoir
Bladder
Prostate
Pump
Meatal Stenosis
Meatal stenosis is the narrowing of the male urinary
meatus following circumcision. It is thought to result
from exposure and irritation of the meatus in the
diaper.104,105 For reasons that are uncertain, the stenosis
is always on the ventral aspect of the meatus, causing
dorsal deflection of the urinary stream that is forceful. It
is important for the physician to not only examine the FIGURE 56-10 A scaphoid megalourethra is seen in a boy with
meatus but also watch the child void. If the stream is not prune-belly syndrome.
narrow in caliber or is not dorsally deflected, then the
meatal stenosis is not significant enough to require treat-
ment. Occasionally, voiding causes the web to tear, result-
ing in dysuria or a drop of blood after urination. Some
Urethral Duplication
boys will have ongoing inflammation around the meatus Urethral duplications occur in varied forms and can be
which will respond to topical steroid application (betam- broadly classified as dorsal or ventral to the normal
ethasone 0.05 %). meatus.110113 The duplication may be complete, but
Meatotomy may be necessary and can be performed incomplete forms predominate. Occasionally, side-by-
under general anesthesia or as an office procedure. side duplications occur, usually associated with a dupli-
Lidocaine/prilocaine (EMLA) cream can be applied topi- cated phallus and bladder. Most commonly, the two
cally, covered with a bio-occlusive dressing, and left for channels form in the sagittal plane. The urethral channel
one hour before meatotomy with oral midazolam for closest to the rectum is generally the more functional
sedation in selected patients. This can lead to a painless conduit, having more normal spongiosal tissue and
office procedure.104 Once the glans is anesthetized, the sphincter mechanism.113 The more dorsal urethra is often
ventral web is clamped with a hemostat and left for one small and poorly developed, and will commonly be in an
minute for hemostasis. The ventral web is then incised epispadiac position and associated with dorsal chordee.
one-half the distance to the coronal margin. Parents Partial duplications that course along the penile urethra
spread the meatus and apply ointment several times daily have been called Y-type duplications.114 When the dupli-
for 23 weeks. Meatal stenosis rarely recurs. Imaging cated opening is in the perineum, it has been termed an
studies and cystoscopy are not needed. H-type duplication.115
Treatment of urethral duplications must be individual-
Megalourethra ized. When only a minor septum is present, cystoscopic
division of the septum may be successful. Traditionally,
Megalourethra is a rare genital anomaly, causing a with more significant duplications, efforts have been
deformed and elongated penis, that occurs in either a fusi- made to lengthen the ventrally-placed urethra to the tip
form or scaphoid form (Fig. 56-10). These two forms of the penis using various hypospadias reconstruction
differ in embryology and appearance. Megalourethra is techniques. Progressive dilation of the dorsal urethral
seen more commonly in patients with prune-belly syn- channel to make it functional has also been
drome and has been reported in association with the advocated.116
VATER (vertebral defects, anorectal atresia, tra-
cheoesophageal fistula, and renal dysplasia) syndrome.105
The less severe and most common form is the scaphoid
Congenital Urethral Fistula
variety, in which spongiosal tissue fails to invest the A urethral fistula can develop in the anterior urethra with
urethra.106 The more severe fusiform variety is caused by incomplete development of the spongiosum, permitting
failure of the penile mesoderm to form spongiosal tissue a small diverticulum to form that ruptures antenatally.117
or corpora cavernosa within the penis.107 It has been These are uncommon and difficult to repair due to the
found in patients with prune-belly syndrome, stillborn lack of spongiosal tissue around the fistula.
fetuses, and patients with cloacal anomalies.108,109 Associ-
ated urologic anomalies have been described, including
megacystis, reflux, bladder diverticula, and renal dyspla-
Urethral Strictures and Stenosis
sia.108 Upper tract assessment is indicated in all cases. Most urethral strictures are acquired. Trauma, inflamma-
Repair of the megalourethra relies on hypospadias tech- tory conditions, and instrumentation by medical person-
niques that tailor the urethra to a more normal size. nel are common causes. Congenital urethral stenosis is
56 Bladder and Urethra 759
REFERENCES
1. Yeung CK, Sihoe JD. Non-neuropathic dysfunction of the lower
FIGURE 56-11 This voiding cystogram shows an anterior ure- urinary tract in children. In: Wein AJ, Kavoussi LR, Novick AC,
thral diverticulum (asterisk) that functions as a valve, causing et al, editors. Campbells Urology. Philadelphia: Elsevier Saun-
outflow obstruction. Note the bladder trabeculation. ders; 2012. p. 3411230.
2. McGuire E, Woodside JR, Borden TA, et al. Prognostic value of
urodynamic testing in myelodysplastic patients. J Urol 1981;
126:2059.
rare and generally focal. These stenoses are usually in the 3. Wan J, Park JM. Neurologic control of storage and voiding. In:
bulbar urethra, within the area of embryologic joining of Docimo SG, Canning DA, Khoury AE, editors. Clinical Pediatric
Urology. UK: Informa Healthcare; 2007. p. 76580.
the bulbous urethra which arises from genital folds and 4. Zderic S, Chacko S, DiSanto ME, et al. Voiding function: Rele-
the posterior membranous urethra which arises from the vant anatomy, physiology, pharmacology, and molecular aspects.
urogenital sinus. If this junction is misaligned or incom- In: Gillenwater JY, Grayhack J, Howards SS, et al, editors. Adult
pletely canalized, a focal stricture may develop.117 and Pediatric Urology. Philadelphia: Lippincott Williams &
Wilkins; 2002. p. 1061216.
Both of these entities can be treated with an internal 5. Kaefer M, ZurakowskiD, Bauer SB, et al. Estimating normal
urethrotomy, resection and end-to-end anastomosis, or bladder capacity in children. J Urol 1997;158:22614.
pedicle flap/free graft urethroplasty. One report suggests 6. Goellner M, Ziegler EE, Fomon SJ. Urination during the first
a single internal urethrotomy for short strictures fol- three years of life. Nephon 1981;28:1748.
lowed by an open repair for failures may be the best 7. Allen T, Kaplan WE, Kroovand RL. Sphincter dysynergia. Dialog
Pediatr Urol 1979;2:18.
approach.118 8. Neveus T, von Gontard A, Hoebeke P, et al. Standardization
of terminology of lower urinary tract function in children
and adolescents: Report from the standardization committee
Urethral Atresia of the International Childrens Continence Society. J Urol 2006;
176:31424.
In order to be compatible with life, a patent urachus must 9. Miller F. Children who wet the bed. In: Kolvin I, McKeith R,
be present when urethral atresia develops. Reconstruc- Meadow SR, editors. Bladder Control and Enuresis. London: W
tion can be difficult, and a vesicostomy followed by Heinemann Medical Books Ltd.; 1973. p. 4752.
creation of a catheterizable stoma may be the best 10. Tietjen D, Husmann DA. Nocturnal enuresis. A guide to evalua-
alternative.98 tion and treatment. Mayo Clin Proc 1996;71:85762.
11. Yeung CK. Nocturnal enuresis (bedwetting). Curr Opin Urol
2003;13:33743.
Urethral Diverticulum or Anterior 12. von Gontard A, Heron J, Joinson C. Family history of nocturnal
enuresis and urinary incontinence: Results from a large epidemio-
Urethral Valve logical study. J Urol 2011;185:23036.
13. Forsythe W, Redmond A. Enuresis in spontaneous cure
A urethral diverticulum can occur ventrally when the rate: Study of 1,129 enuretics. Arch Dis Child 1974;49:259
spongiosum is absent or is thinned. The distal lip of the 63.
diverticulum functionally serves as an anterior urethral 14. Bakwin H. The genetics of enuresis. In: Kolvin I, MacKeith R,
Meadow S, editors. Bladder Control and Enuresis. London: WP
valve, blocking the urinary stream as it flows antegrade Heinemann Medical Books Ltd.; 1973. p. 737.
(Fig. 56-11). The diverticulum progressively fills during 15. Norgaard J. Urodynamics in enuresis 1: Reservoir function
urination and further compresses the urethra. This valve pressure-flow study. Neurourol Urodyn 1989;8:199211.
effect can cause marked proximal dilation.119121 In some 16. Norgaard J. Pathophysiology of nocturnal enuresis. Scand J Urol
cases, there is a diverticulum with a narrow neck that does Nephrol Suppl 1991;140:135.
17. Jarvelin M. Developmental history and neurological findings in
not function as a valve. Such a diverticulum may allow enuretic children. Dev Med Child Neurol 1989;31:72836.
urinary stasis and can be a site of urethral infection. 18. Norgaard J, Hansen J, Nielsen J, et al. Simultaneous registration
The diagnosis is made either by urethrogram or cys- of sleep stages and bladder activity in enuresis. Urology 1985;
toscopy. Treatment is accomplished by endoscopic inci- 26:31619.
19. Norgaard J, Pedersen E, Djurhuus J. Diurinal antidiuretic
sion in the distal lip of the neck of the diverticulum or, if Hormone levels in enuretics. J Urol 1985;134:102931.
more pronounced, by open excision and closure of the 20. Puri VN. Urinary levels of antidiuretic hormone in nocturnal
urethral defect.122 enuresis. Indian Pediatrics 1980;17:6756.
760 SECTION VI Urology
21. Rushton H, Belman AB, Zaontz MR, et al. The influence of small 46. Hinman F. Non-neurogenic neurogenic bladder (the Hinman
functional bladder capacity and other predictors on the response syndrome) fifteen years later. J Urol 1986;136:76975.
to desmopressin the management of monosymptomactic noctur- 47. Austin P, Homsy YL, Masel JL, et al. Alpha-adrenegic blockage
nal enuresis. J Urol 1996;156:6515. in children with neuropathic and non-neuropathic voiding
22. Eller D, Austin PF, Tanguay S, et al. Daytime functional bladder dysfunction. J Urol 1999;162:10647.
capacity as a predictor of response to desmopressin in monosymp- 48. Austin P. The role of alpha blockers in children with dysfunctional
tomatic nocturnal enureseis. Eur Urol 1998;33:259. voiding. Scientific World Journal 2009;9:8803.
23. Hansen M, Rettig S, Siggaared C, et al. Intra-individual variability 49. Bauer S. Neurogenic voiding dysfunction and non-surgical man-
in nighttime urine production and functional bladder capacity agement. In: Docimo SG, Canning DA, Houry AE, editors. Clini-
estimated by home recordings in patient with nocturnal enuresis. cal Pediatric Urology. UK: Informa Healthcare; 2007.
J Urol 2001;166:24525. p. 781818.
24. Monda J, Husmann D. Primary nocturnal enuresis: A comparison 50. Steers W, Barrett DM, Wein AJ. Voiding dysfunction: diagnosis,
among observation, Imipramine, Desmopressin Acetate and bed- classification and management. In: Gillenwater JY, Grayhack JT,
wetting alarm systems. J Urol 1995;154:7458. Howards SS, et al, editors. Adult and Pediatric Urology. Philadel-
25. Glazener CM, Evans JHC, Peto RE. Alarm interventions phia: Lippincott Williams & Wilkins; 2002. p. 1115216.
for nocturnal enuresis in children. Cochrane Data Syst Rev 51. Mandell J, Bauer SB, Hallett M, et al. Occult spinal Dysraphism:
2005;(2):Art. No.: CD002911. A rare but detectable cause of voiding dysfunction. Urol Clin
26. Glazener CM, Evans JHC, Peto R. Tricyclic and related drugs for North Am 1980;7:34956.
nocturnal enuresis in children. Cochrane Data Syst Rev 2003;(Issue 52. Kaplan W. Management of myelomeningocele. Urol Clin North
3):Art. No.: CD002117. Am 1985;12:93101.
27. Blackwell B, Currah J. The psychoparmacology of nocturnal enu- 53. MacLellan DL, Bauer SB. Infection of the lower urinary tract. In
resis. In: Kolvin I, MacKeith R, Meadow S, editors. Bladder Wein AJ, Kavoussi LR, Novick AC, et al, editors. Campbells
Control and Enuresis. London: W Heinemann Medical Books Urology. Philadelphia: Elsevier Saunders; 2012. p. 2193216.
Ltd; 1973. p. 23157. 54. Bauer S, Joseph DB. Management of the obstructed urinary tract
28. Klauber G. Clinical efficacy and safety of desmopressin in the associated with neurogenic bladder dysfunction. Urol Clin North
treatment of nocturnal enuresis. J Pediatr 1989;114:71922. Am 1990;17:395406.
29. Rittig SM, Knudsen U, Sorensen S, et al. Desmopressin and 55. Weler M, Shapiro S, Mitchell AA. Periconceptual folic acid expo-
nocturnal enuresis: Proceedings of an internal symposium. In: sure and risk of occult neural tube defects. JAMA 1993;
Meadow S, editors. London: Horus Medical Publications, 269:125763.
England; 1989. p. 4354. 56. Bauer S, Hallett M, Khoshbin S, et al. Predictive value of urody-
30. Zong H, Yang C, Peng X, et al. Efficacy and safety of desmo- namic evaluation in newborns with myelodysplasia. JAMA
pressin for treatment of nocturia: A systematic review and meta- 1984;252:6502.
analysis of double-blinded trials. Int Urol Nephrol 2011;44: 57. Wang S, McGuire EJ, Bloom DA. A bladder pressure manage-
37784. ment system for myelodysplasia: Clinical outcome. J Urol
31. Robson W. Diurnal enuresis. Pediatr Review 1997;18:40712. 1988;140:1499502.
32. MacKeith R, Meadow S, Turner R. How children become dry. 58. Galloway N, Mekras JA, Helms M, et al. An objective score to
In: Kolvin I, MacKeith R, Meadow S, editors. Bladder predict upper tract deterioration in myelodysplasia. J Urol
Control and Enuresis. Philadelphia: LB Lippincott Co.; 1973. 1991;145:5357.
p. 321. 59. Adzick NS, Thom EA, Spong CY, et al. A randomized trial of
33. Bernard-Bonnin A. Diurnal enuresis in childhood. Canad Fam prenatal versus postnatal repair of myelomeningocele. N Engl J
Physician 2000;46:110915. Med 2011;364:9931004
34. Fernandes E, Veraier R, Gonzalez R. The unstable bladder in 60. Carr MC. Fetal myelomeningocele repair: Urologic aspects. Curr
children. J Pediatr 1991;118:8317. Opin Urol 2007;17:25761.
35. ReinbergY, Crocker J, Wolpert J, et al. Therapeutic efficacy of 61. Tarcan R, Bauer S, Olmedo E, et al. Long-term follow up of
extended release oxybutynin chloride and immediate release and newborns with myelodysplasia and normal urodynamic findings:
long-acting tolterodine tartrate in children with diurnal urinary Is it necessary? J Urol 2001;165:5647.
incontinence. J Urol 2003;169:31719. 62. Lapides J, Diokno AC, Silber SJ, et al. Clean intermittent self-
36. Munding M, Wessells H, Thornberry B, et al. Use of tolterodine catheterization in the treatment of urinary tract disease. J Urol
in children with dysfunctional voiding: an initial report. J Urol 1971;107:45862.
2001;165:9268. 63. Klose A, Sackett CK, Mesrobian H. Management of children with
37. Goessl C, Sauter T, Michael T, et al. Efficacy and tolerability of myelodysplasia: Urologic alternatives. J Urol 1990;144:14469.
tolterodine in children with detrusor hyperreflexia. Urology 64. Joseph D, Bauser SB, Colodny AH, et al. Clean intermittent
2000;55:41418. catheterization of infants with neurogenic bladder. Pediatrics
38. Herndon CD, Decambre M, McKenna PH. Interactive computer 1989;84:7882.
games for treatment of pelvic floor dysfunction. J Urol 65. Cass A. Urinary tract complications in myelomeningocele
2001;166:18938. patients. J Urol 1976;115:1024.
39. McKenna PH, Herndon CD, Connery S, et al. Pelvic floor muscle 66. Plunkett J, Braren V. Clean intermittent catheterization in chil-
retraining for pediatric voiding dysfunction using interactive com- dren. J Urol 1979;121:46971.
puter games. J Urol 1999;162:105662. 67. Klauber G, Sant GR. Complications of intermittent catheteriza-
40. Koenig JF, McKenna PH. Biofeedback therapy for dysfunctional tion. Urol Clin North Am 1983;10:55762.
voiding in children. Curr Urol Rep 2011;12:14452. 68. Abrams P. Tolterodine, a new antimuscarinic agent: As effective
41. Lordelo P, Teles A, Veiga ML, et al. Transcutaneous electrical but better tolerated than oxybutynin in patients with an overactive
nerve stimulation in children with overactive bladder: A rand- bladder. Br J Urol 1998;81:80110.
omized clinical trial. J Urol 2010;184:6839. 69. Dmochowski R, Davila G, Zinner N, et al. Efficacy and safety of
42. DeGennaro M, Capitanucci ML, Mosiello G, et al. Current state transdermal oxybutynin in patients with urge and mixed urinary
of nerve stimulation technique for lower tract dysfunction in chil- incontinence. J Urol 2002;168:5806.
dren. J Urol 2011;185:1571577. 70. Schulte-Baukloh H, Knispel HH, Stolze T, et al. Repeated
43. Koff S, Murtagh DS. The uninhibited bladder in children: Effect botulinum-A toxin injections in treatment of children with neu-
of treatment on recurrence of urinary infection and vesico-ureteral rogenic detrusor overactivity. Urology 2006;66:86570.
reflux. J Urol 1983;130:115860. 71. Patel AK, Patterson JM, Chapple CR. Botulinum toxin injections
44. DeLuca F, Swenson O, Fisher JH, et al. The dysfunctional for neurogenic and idiopathic detrusor overactivity: A critical
lazybladder syndrome in children. Arch Dis Child analysis of results. Eur Urol 2006;50:684709.
1962;37:197223. 72. Duckett JJ. Cutaneous vesicostomy in childhood. Urol Clin
45. Bloom D, Seeley WW, Ritchey ML, et al. Toliet habits and con- North Am 1974;1:48595.
tinence in children: An opportunity sampling in search of normal 73. Mandell J, Bauer SB, Colodny AH, et al. Cutaneous vesicostomy
parameters. J Urol 1993;149:108790. in infancy. J Urol 1981;126:923.
56 Bladder and Urethra 761
74. Bloom D, Knechtel JM, McGuire EJ. Urethral dilation improve 99. Keating M, Rink RC, Adams MC. Appendicovesicostomy: A
bladder complicance in children with myelomeningocele and high useful adjunct to continent reconstruction of the bladder. J Urol
leak point pressures. J Urol 1990;144:4303. 1993;149:10914.
75. Jeffs R, Jonas P, Schillinger JF. Surgical correction of vesicoureteral 100. Monti P, Lava R, Dutra M, et al. Newer techniques for construc-
reflux in children with neurogenic bladder. J Urol 1976;114: tion of efferent conduits based on mitrofanoff principle. Urology
44951. 1997;49:11215
76. Agarwal S, McLorie GA, Grewal D, et al. Urodynamic correlates 101. Cass A, Luxenberg M, Gleich P, et al. A 22 year follow up of ileal
of resolution of reflux in myelomeningocele patients. J Urol conduits in children with a neurogenic bladder. J Urol 1984;132:
1997;158:5802. 52931.
77. Adams M, Mitchell ME, Rink RC. Gastrocystoplasty: An alterna- 102. Husmann D, McLorie GA, Churchill BM. Nonrefluxing colonic
tive solution to the problem of urological reconstruction in the conduits: A long-term life table analysis. J Urol 1989;142:
severely compromised patient. J Urol 1988;140:11526. 12015.
78. Adams M, Bihrle R, Rink RC. The use of stomach in urologic 103. Brown M, Cartwright P, Snow B. Common office problems in
reconstruction. AUA Update Series 1995;14:21823. pediatric urology and gynecology. In: Pediatri Clin North Am.
79. Nguyen D, Bain MA, Salmonson KL, et al. The syndrome of Philadelphia: WB Saunders; 1997. p. 109111115.
dysuria and hematuria in pediatric urinary reconstruction with 104. Cartwright P, Snow B, McNees D. Office meatotomy utilizing
stomach. J Urol 1993;150:7079. EMLA cream as the anesthetic. J Urol 1996;156:8579.
80. Cartwright P, Snow BW. Bladder augmentation: Early clinical 105. Fernbach S. Urethral abnormalities in male neonates with VATER
experience. J Urol 1989;142:5958. association. AJR Am J Roentgenol 1991;156:13740.
81. Snow B, Cartwright PC. Bladder augmentation. Urol Clin North 106. Stephens F, Smith ED, Huston JM. Congenital intrinsic lesions
Am 1996;23:32331. of the anterior urethra. In: Congenital Anomalies of the Urinary
82. Gonzalez R, Buson H, Reid C, et al. Seromuscular colocystoplasty and Genital Tracts. Oxford, England: Isis Media; 1996.
lined with ureothelium: Experience with 16 patients. Urology p. 11924.
1994;45:1249. 107. Dorairajan T. Defects of spongy tissue and congenital
83. Dewan P, Byard R. Autoaugmentation gastrocystoplasty in a sheep diverticuli of the penile urethra. Aus NZJ Surg 1963;32:209
model. Br J Urol 1993;72:569. 14.
84. Atala A, Bauer SB, Soker S, et al. Tissue-engineered autologous 108. Hudson RG, Skoog SJ. Prune-Belly Syndrome. In: Docimo SG,
bladders for patients needing cystoplasty. Lancet 2006;367: Canning DA, Khoury AE, editors. Clinical Pediatric Urology.
12416. UK: Informa Healthcare; 2007. p. 1081114.
85. Reda E. The use of the Young-Dee Leadbetter procedure. Dialog 109. Shrom S, Cromie W, Duckett J, et al. Megalourethra. Urology
Pediatr Urol 1991;14:78. 1981;17:1526.
86. Kropp K, Angwafo FF. Urethral lengthening and reimplantation 110. Gross R, Moore T. Duplication of the urethra. Arch Surg
for neurogenic incontinence in children. J Urol 1986;135:5336. 1950;60:749.
87. Kropp K. Management of urethral incompetence in the patient 111. Das S, Brosman S. Duplication of the male urethra. J Urol
with neurogenic bladder. Dialo Pediatr Urol 1991;14:67. 1977;117:4524.
88. Salle J, McLorie GA, Bagli DJ, et al. Urethral lengthening with 112. Woodhouse C, Williams D. Duplications of the lower urinary
anterior bladder wall flap (Pippi Salle procedure): Modification tract in children. Br J Urol 1979;51:46187.
and extended indications of the technique. J Urol 1997;158: 113. Salle J, Sibai H, Rosenstein D, et al. Urethral duplication in the
58590. male: Review of 16 cases. J Urol 2000;163:19368.
89. McGuire J, Lytton B. Pubovaginal sling procedure for stress 114. Williams D, Bloomberg S. Bifid urethra with three anal accessory
incontinence. J Urol 1978;119:824. tract (Y Duplication). Br J Urol 1976;197;47:87782.
90. Bauer S, Peters CA, Colodny AH, et al. The use of rectus fascia 115. Stephens F, Donnellan W. H-Type urethral anal fistula. J Pediatr
to manage urinary incontinence. J Urol 1989;142:51619. Surg 1977;12:95102.
91. McGuire E, Wang C, Usitalo H, et al. Modified pubovaginal sling 116. Passerini-Glazal G, Araguna F, Chiozza L. P.A.D.U.A. (Posterior
in girls with myelodysplasia. J Urol 1986;135:946. augmentation by dilating the urethra anterior). Procedure of
92. Elder J. Periurethral and puboprostatic sling repair for inconti- choice for treatment of severe urethral hypoplasia. J Urol
nence in patients with myelodysplasia. J Urol 1990;144:4347. 1988;140:12479.
93. Norbeck J, McGuire EJ. The use of pubovaginal and pubopros- 117. Duckett J, Snow B. Disorders of the urethra and penis. In: Walsh
tatic slings. Dialogs Pediatr Urol 1991;14:34. P, Gittes R, Perlmutter A, Stamey T, editors. Campbells Urology.
94. Gonzalez R, Nguyen DH, Koleilat N, et al. Compatibility of Philadelphia: WB Saunders Co.; 1986. p. 201415.
enterocystoplasty and the artificial urinary sphincter. J Urol 118. Hsaio K, Baez-Trinidad L, Lendvay T, et al. Direct vision internal
1989;152:5024. urethrotomy for the treatment of pediatric urethral strictures:
95. Dyer L, Franco I, Firlit CT, et al. Endoscopic injection of bulking Analysis of 50 patients. J Urol 2003;170:052.955.
agents in children with incontinence: Dextranomer/hyaluronic 119. Firlit C, King L. Anterior urethral valves in children. J Urol
acid copolymer versus polytetrafluroethylene. J Urol 2007;178: 1972;108:9725.
162831. 120. Rudhe U, Ericsson N. Congenital urethral diverticuli. Ann Radiol
96. Lottmann HB, Margaryan M, Lortat-Jacob S, et al. Long-term 1970;13:289.
effects of dextranomer endoscopic injections for the treatment of 121. Williams D, Retik A. Congenital valves and diverticuli of the
urinary incontinence: An update of a prospective study of 61 anterior urethra. Br J Urol 1969;41:22834.
patients. J Urol 2006;176:17626. 122. Firlit R, Firlit C, King L. Obstruction anterior urethral valves in
97. Mitrofanoff P. Cystostomie continente trans-appendiculaire dans children. J Urol 1978;119:81921.
le traitement des vessies neurolgigues. Chir Pediatr 1980;21: 123. Colodny A, Lebowitz R. Lesions of Cowpers ducts and gland in
297301. infants and children. Urology 1978;11:3215.
98. Cain M, Casale A, King S, et al. Appendicovesicostomy and newer 124. Maizel S, Stephens F, King L, et al. Cowpers syringocele: A clas-
alternatives for Mitrofanoff procedure: Results in the last 100 sification of dilatations of Cowpers gland duct based upon clinical
patients at Rileys Childrens Hospital. J Urol 1999;162:174952. characteristics of eight boys. J Urol 1983;129:11114.
C H A P T E R 5 7
Posterior urethral valves (PUV) are the most common (US) include bilateral hydroureteronephrosis, a distended
cause of bladder outlet obstruction in boys, with an inci- bladder, and a dilated prostatic urethra, called a keyhole
dence of 1 in 5,000 to 8,000 male births.1 Although the sign.5 Discrete focal cysts in the renal parenchyma are
majority of boys with PUV are diagnosed antenatally, diagnostic of renal dysplasia. Amniotic fluid volume is
approximately one-third will be diagnosed during child- variable. Those with normal or slightly reduced amniotic
hood or adolescence. PUV is the most common obstruc- fluid have a better prognosis. In contrast, oligohydram-
tive cause of end-stage renal disease (ESRD) in children, nios suggests significant obstructive uropathy, and pul-
and is the etiology for approximately 35% of children monary hypoplasia secondary to renal dysplasia is
who require renal transplantation.2 common. Oligohydramnios prevents normal lung devel-
opment in utero. Pathologically, this process results in
reduced branching of the bronchial tree and reduced
EMBRYOLOGY AND ANATOMY numbers and size of alveoli.
The gestational age at which hydronephrosis is recog-
At 5 to 6 weeks gestation, the orifice of the mesonephric nized influences prognosis. In one study, fetuses with
duct migrates from an anterolateral position in the cloaca normal appearing renal anatomy before 24 weeks were
to Mllers tubercle on the posterior wall of the urogeni- more likely to have normal renal function than were
tal sinus, occurring simultaneously with division of the those with hydronephrosis before 24 weeks.6 One meta-
cloaca. Remnants of the mesonephric duct normally analysis showed the best predictive value for postnatal
remain as small distinct, paired lateral folds termed the renal function was the appearance of the fetal renal
inferior urethral crest and plicae colliculi. When the cortex.7 A more recent study showed that ultrasound
insertion of the mesonephric ducts into the cloaca is too parameters alone are not able to predict postnatal renal
anterior, normal migration of the ducts is impeded, and function.8 Prune-belly syndrome, urethral atresia, and
the ducts fuse anteriorly, resulting in abnormal ridges, bilateral high-grade vesicoureteral reflux (VUR) can have
which become the PUV. A smaller aperture between the a similar prenatal sonographic appearance to PUV. Col-
leaflets causes more obstruction than those with a larger lectively, bladder outlet obstruction found prenatally can
aperture and a less prominent anterior component.3 result in a significant (57%) incidence of renal failure by
Three distinct types of PUV have been described. 2 years of age.9
Type I is an obstructing membrane that radiates distally In the fetus with suspected PUV and normal amniotic
and anteriorly from the verumontanum toward the mem- fluid volume, serial fetal sonograms are necessary to
branous urethra, fusing in the midline. Approximately monitor the status of the hydronephrosis and amniotic
95% of PUV are type I, in which the valves are thought fluid volume. If oligohydramnios develops, bladder drain-
to be a single membranous structure with the opening age may help restore the amniotic fluid and allow normal
positioned posteriorly near the verumontanum. Type III pulmonary development. Before any intervention, a kary-
appears as a membranous diaphragm with a central otype should be obtained to confirm the male gender and
opening at the verumontanum. The obstructing tissue to detect chromosomal abnormalities, which occur in
also has been termed a congenital obstructing posterior about 12%.10 Fetal renal function is assessed with serial
urethral membrane.4 It is thought that instrumentation urinary electrolytes and 2-microglobulin levels. Nor-
with a urethral catheter might disrupt the posterior aspect mally, fetal urine is hypotonic (favorable prognosis),
of the membrane, resulting in the appearance of a type I with sodium less than 100mEq/L, chloride less than
valve. Type II valves are prominent longitudinal folds of 90mEq/L, osmolality less than 210mEq/L, and 2-
hypertrophied smooth muscle that radiate cranially from microglobulin levels less than 6mg/L.5 Elevated fetal
the verumontanum to the posterolateral bladder neck, urine electrolytes and 2-microglobulin levels are an indi-
but these are nonobstructive and clinically insignificant. cation of irreversible renal dysfunction. Sequential
bladder aspiration every 48 to 72 hours should be per-
formed because the initial urine sample may be stagnant
ANTENATAL DIAGNOSIS, and fresh urine more accurately reflects the function of
MANAGEMENT, AND OUTCOMES the fetal kidneys.11,12
If fetal urine is hypotonic, and oligohydramnios is
About 10% of antenatally diagnosed obstructive uropa- present, then fetal intervention to restore the amniotic
thy is due to PUV, and approximately two thirds of PUV fluid volume should be considered, with the goal of
are diagnosed antenatally. Typical findings on ultrasound preventing life-threatening pulmonary hypoplasia. This
762
57 Posterior Urethral Valves 763
procedure has been performed in the first trimester,13 have evaluated the role of fetal cystoscopy to improve the
although the majority of fetuses are diagnosed and treated accuracy of the prenatal ultrasound findings regarding a
in the second trimester. If the gestational age of the fetus definite etiology.24,25 In addition, if PUV is identified at
is 32 weeks, early delivery is advisable. If the fetus is <32 cystoscopy, then ablation can be considered.
weeks gestation, however, the urine may be diverted into
the amniotic fluid with a percutaneously placed vesi-
coamniotic shunt (VAS). In a recent meta-analysis, ante- CLINICAL PRESENTATION
natal bladder drainage appears to improve perinatal
survival and relieve bladder outlet obstruction, especially Neonates with PUV not diagnosed prenatally can present
in those fetuses with poor prognostic criteria.14 To date, with symptoms of delayed voiding or a reduced urinary
there is no evidence that drainage of the obstructed fetal stream.15 Also, respiratory distress secondary to pulmo-
bladder will improve renal or bladder function. nary hypoplasia may be the primary manifestation of
In theory, VAS does not allow the bladder to cycle. PUV. Other postnatal signs and symptoms include an
Consequently, when counseling expectant parents, they abdominal mass, failure to thrive, lethargy, poor feeding,
need to understand that their newborn may have limited urinary tract infection (UTI), and urinary ascites. Physi-
renal function or ESRD, even if the drainage procedure cal examination in the newborn typically discloses a pal-
is successful. VAS can have complications in up to 45%.5,15 pable walnut-sized bladder, secondary to the hypertrophic
The shunts become obstructed or displaced in 25% of detrusor muscle. Urinary ascites can result in significant
cases, necessitating additional procedures that increase abdominal distention. Older boys can have persistent
morbidity to the mother and fetus, and there is a 5% diurnal incontinence or abdominal distention.
procedure-related chance of fetal loss. In addition,
omental or bowel herniation through the fetal abdominal
wall can occur. RADIOGRAPHIC EVALUATION
Despite adequate bladder drainage, renal function may
be so limited that the amniotic fluid volume remains low. Significant bilateral hydroureteronephrosis and a thick-
In one study of high-risk fetuses identified in the first walled, distended bladder are seen on ultrasound. Corti-
trimester with severe bilateral hydroureteronephrosis, comedullary differentiation is a favorable prognostic sign
bladder distention, and oligohydramnios managed with a regarding renal function (Fig. 57-1). Conversely, echo-
VAS, a 60% overall survival rate and a 33% incidence of genic kidneys or subcortical cysts and the loss of corti-
renal failure were found.16 In a review of 14 fetuses with comedullary differentiation are unfavorable signs.
proven PUV and favorable fetal urinary electrolytes Suprapubic or perineal ultrasound may demonstrate a
undergoing VAS at a mean gestational age of 22.5 weeks, dilated prostatic urethra, which is pathognomonic for
six deaths occurred before term delivery. Of the surviving PUV.
eight neonates, three had ESRD, and the other five had The voiding cystourethrogram (VCUG) is the only
an elevated serum creatinine.17 In a more optimistic study radiographic study that definitively establishes the diag-
of 20 boys with lower urinary tract obstruction managed nosis of PUV (Fig. 57-2). The valves appear as a defined
by VAS, the overall 1-year survival was 91%. In this lucency in the distal prostatic urethra. The posterior
study, the mean birth weight was 2574g, 40% had urethra is dilated and elongated. The bladder is
acceptable renal function, 20% had mild renal insuffi-
ciency, and 30% required dialysis.18 Of this group, seven
had PUV and seven had prune-belly syndrome, a nonob-
structive condition. This lack of evidence regarding fetal
drainage is the impetus for the study on Percutaneous
Shunting in Lower Urinary Tract Obstruction (PLUTO)
trial, which is an international randomized controlled
trial comparing the effect of VAS versus no intervention.
This study is evaluating prenatal and perinatal mortality,
renal function, and other variables.19
Fetal ultrasound is useful in the diagnosis of lower
urinary tract obstruction (LUTO). Sonographic features
of LUTO include bilateral hydronephrosis, a thick wall
dilated bladder, and dilated upper urethra. Unfortunately,
there are a number of etiologies for this sonographic
appearance, including urethral atresia, prune-belly syn-
drome, as well as PUV. The first two causes would not
necessarily be an indication for either VAS or in utero
endoscopic ablation. Percutaneous endoscopic ablation is
now being performed in a few centers in the USA.2022
One meta-analysis showed a perinatal survival advantage
using endoscopic ablation compared to observation, but FIGURE 57-1 This renal sonogram demonstrates a hydroneph-
there was no significant improvement in survival with rotic kidney with intact corticomedullary junction (arrow) in an
ablation when compared to VAS.23 Two small studies infant with posterior urethral valves.
764 SECTION VI Urology
A B *
FIGURE 57-2 These two voiding cystourethrograms show varying degrees of obstruction from posterior urethral valves. In both
studies the location of the valves is marked with an arrow and the posterior urethra is identified with an asterisk. (A) There is no
evidence of vesicoureteral reflux. (B) There is massive, bilateral grade V reflux.
trabeculated due to muscular hypertrophy with a clear bladder decompression. Metabolic acidosis and hyperka-
delineation of the bladder neck. Unilateral VUR is lemia are common complications if renal function is
present in 25% and bilateral VUR in 25% of infants impaired. Consultation with a pediatric nephrologist is
with PUV. invaluable because renal tubular acidosis (RTA), renal
Renal nuclear scintigraphy with a technetium-99m insufficiency, ESRD, and somatic growth abnormalities
labeled dimercaptosuccinic acid (99mTc-DMSA) is per- are common and need long-term monitoring. Neonates
formed if imaging studies show thin or abnormal with respiratory distress may require immediate pulmo-
parenchyma in either kidney on ultrasound and/or high- nary resuscitation with endotracheal intubation and
grade VUR. The study should be delayed until 6 to 8 positive-pressure ventilation. If urinary ascites is present,
weeks of age to allow maturation of renal function. This paracentesis may be necessary to correct the fluid and
study is effective in establishing baseline differential renal electrolyte imbalance.
function. However, if renal function is poor, visualization
of the kidneys will be suboptimal. An alternative to renal
scintigraphy is dynamic contrast-enhanced magnetic
Primary Valve Ablation
resonance urography (MRU). This study provides high- Endoscopic valve ablation is performed after the neonate
resolution renal images and assessment of differential is stabilized. Well-lubricated infant urethral sounds
renal function, but requires an anesthetic.26 should be passed to gently dilate the meatus and glandu-
lar urethra. The neonatal male urethra usually accepts a
9.5 French endoscope. Overly aggressive dilation of the
INITIAL MANAGEMENT urethra in order to pass a larger endoscope may lead to
urethral trauma with subsequent stricture formation, and
The initial treatment of neonates suspected of having should be avoided. Vigorous dilation may also result in
PUV is to decompress the bladder with a 5 French or 8 iatrogenic hypospadias due to splitting of the glans to the
French feeding tube. The catheter can be difficult to pass subcoronal level.27
because of the valvular obstruction as well as the signifi- An 8 French or 9.5 French cystoscope typically is used
cant dilation of the prostatic urethra and hypertrophy of with a Bugbee electrode on low cutting current inserted
the bladder neck. The catheter tends to coil in the pros- through the operating channel. The valve leaflets should
tatic urethra. A Coud tip catheter may help overcome be incised using a low cutting current at the 5 and 7
this problem. Ultrasound can confirm placement of the oclock positions (Fig. 57-3). Incision at the 12 oclock
catheter within the bladder. Insertion of a Foley catheter position, where the valve leaflets fuse, also may be helpful.
is discouraged because the inflated balloon can obstruct An alternative technique employs the Nd:YAG laser.28 In
the ureteral orifices when the thick-walled bladder is a premature or small neonate, a cystoscope as small as 6.9
decompressed, and can cause bladder spasm that obstruct French can be used, although visualization of the PUV
the intramural ureters. may be suboptimal. If urethral bleeding develops, coagu-
Amoxicillin or cephalexin prophylaxis should be initi- lation should be performed carefully because injury to the
ated. Electrolytes, BUN (blood urea nitrogen), creati- urethra can occur with overzealous cautery. Following
nine, and fluid status should be monitored carefully. The valve ablation, a pediatric feeding tube is left for one to
serum creatinine concentration at birth reflects maternal two days.
renal function. With satisfactory newborn renal function, A VCUG and renal ultrasound should be obtained two
the creatinine value should gradually decrease to to four weeks after ablation to confirm satisfactory valve
0.30.4mg/dL. However, with limited renal function, disruption and assess the upper urinary tracts. In addi-
the creatinine will remain the same or increase, even with tion, renal function should be monitored carefully. Valve
57 Posterior Urethral Valves 765
small or premature neonate when the pediatric cysto-
ablation is successful in more than 90% of patients. The
scope is too large for the urethra or if severe hydroureter-
most common complication is incomplete valve ablation
onephrosis, urinary ascites, or high-grade VUR and poor
in which case repeat cystoscopy and valve incision is nec-
renal function are present. In these cases, optimal upper
essary. Urethral stricture is uncommon if small endo-
urinary tract drainage is necessary to maintain existing
scopes are used.
renal function. The most popular technique was described
by Blocksom and popularized by Duckett.29 A small
Temporary Urinary Diversion transverse incision is performed midway between the
umbilicus and pubic symphysis, and the dome of the
An alternative to primary valve ablation is cutaneous vesi-
bladder is brought to the skin. The vesicostomy should
costomy (Fig. 57-4). This approach is appropriate in a
calibrate to 2426 French to avoid stenosis. Daily dilation
of the stoma with a plastic medicine dropper helps prevent
stomal contraction. The vesicostomy allows urine to
drain directly into the diaper, obviating the need for a
collection device. Complications include stomal stenosis,
if the stomal size is less than 2426 French, and prolapse,
if the anterior wall of the bladder is exteriorized rather
than the bladder dome.
Valve ablation should not be performed at the time of
vesicostomy because the urethra will remain dry and
stricture is likely. A vesicostomy allows the bladder to
cycle and grow at low pressures, and does not reduce
bladder capacity. These neonates should be maintained
on antibiotic prophylaxis.
In the past, after insertion of a urinary catheter into
the bladder, proximal diversion with cutaneous pyelos-
tomy or cutaneous ureterostomy was advocated for
FIGURE 57-3 This cystoscopic view shows valve ablation with
neonates and infants with severe hydronephrosis and a
an electrode placed through the operating channel of the persistently elevated creatinine.30 Theoretically, proximal
cystoscope. diversion provides better renal drainage than a
A B C
D
E G
FIGURE 57-4 Technique of cutaneous vesicostomy. (AC) Transverse incision is made midway between the umbilicus and pubic
symphysis. (D,E) Traction sutures are placed through the bladder, and it is mobilized superiorly to the dome of the bladder. (F) The
detrusor should be fixed to the rectus fascia. The bladder is opened, and the mucosa is sutured to the skin. (G) Completed vesicos-
tomy should be calibrated to 24 French.
766 SECTION VI Urology
vesicostomy, particularly with ureterovesical obstruction, Evaluation for extravasation begins with ultrasound,
and optimizes the potential for renal function and somatic VCUG, and renal scintigraphy. The early uptake phase of
growth. However, proximal drainage has not been shown a 99mTc-MAG3 renal scan often demonstrates which
to prevent ESRD because at least 85% of these patients kidney is involved. Inserting a 5 French or 8 French
have renal dysplasia.31 In addition, by diverting the urine feeding tube into the bladder may decompress the bladder
away from the bladder, regular cyclical bladder filling and and upper urinary tract sufficiently that the forniceal
contraction does not occur which results in a smaller, less extravasation stops. Percutaneous drainage is needed if
compliant bladder.32 the extravasation and the serum creatinine continue to
Currently, proximal diversion is reserved for the rare increase, or respiratory compromise, infection, hyperten-
case in which valve ablation or vesicostomy fails to sion, or significant parenchymal compression develop. If
improve upper tract drainage. When needed, the pre- extravasation persists, insertion of a percutaneous neph-
ferred method of proximal diversion is the Sober-en-T rostomy often solves the problem. Unfortunately, with
ureterostomy in which the proximal ureter is divided and forniceal extravasation, typically the renal pelvis is decom-
exteriorized on the abdominal wall (Fig. 57-5). The prox- pressed, making it difficult to insert the nephrostomy
imal end of the distal ureteral segment is then anastomo- tube. In these cases, a drain can be inserted into the
sed to the renal pelvis. The advantage of this form of urinoma. Occasionally, exploration through a small flank
diversion is that it allows urine to drain into the bladder, incision may be necessary. In most cases, the kidney is
thereby maintaining bladder cycling, while providing intact. A cutaneous pyelostomy or ureterostomy is rarely
good upper tract drainage.33 In one retrospective study necessary. However, in most cases, mobilizing the kidney,
of 36 boys who underwent bilateral Sober ureterosto- separating it from the adjacent peritoneum, and leaving a
mies, the mean duration of diversion was 55 months.34 drain in the retroperitoneum will allow the leak to resolve,
Bladder compliance was normal in 69%, and bladder provided lower tract decompression has been achieved.
capacity was normal in 80%.
Rupture of the renal fornix with urinary extravasation
and transudation into the peritoneum occurs in 5% to
Follow-up After Initial Therapy
15% of neonates with PUV.35,36 Some infants develop a Antibiotic prophylaxis should be continued until the
perirenal urinoma, whereas others have urinary ascites upper tract dilation improves, which may take several
(Fig. 57-6). The differential renal function of kidneys years if VUR persists. Most infants benefit from com-
with urinoma vs. those without is similar. However, with bined urologic and nephrologic care starting at birth.
urinary ascites, significant electrolyte abnormalities can Common clinical problems include significant polyuria
result from urinary reabsorption, and respiratory com- secondary to an inability of the kidneys to concentrate
promise may also occur from the abdominal distention. urine, metabolic acidosis (which may complicate somatic
growth), renal insufficiency with hypocalcemia and hyper-
phosphatemia, and hypertension. If the patient remains
clinically well with good somatic growth, periodic
follow-up with ultrasound, electrolyte measurements,
BUN and creatinine, urinalysis, and blood pressure evalu-
ations will ensure satisfactory growth and development.
Early treatment with anticholinergic therapy (oxybu-
tynin) may also be beneficial. In a nonrandomized study
of infants with PUV, treatment with oxybutynin for two
years resulted in significant reduction in high voiding
pressures and significant improvement in bladder
capacity.37
A B C
FIGURE 57-6 Posterior urethral valves and ascites. (A) Prenatal ultrasound image demonstrating a perirenal urinoma around the
right kidney, which is not hydronephrotic. (B) Prenatal ultrasound image showing ascites and stretched umbilical vessels (arrow).
(C) Plain radiograph of the abdomen in a neonate with a distended abdomen from urinary ascites.
*
*
A B C
FIGURE 57-7 The VURD syndrome. A 7-year-old boy was found to have posterior urethral valves and a bladder diverticulum.
(A) The voiding cystourethrogram demonstrates a large, dilated posterior urethra (asterisk) secondary to the valves. (B) The lateral
view of this study shows a trabeculated bladder with a large bladder diverticulum (asterisk). (C) The excretory urogram shows
normal upper urinary tracts and deviation (arrow) of the distal left ureter due to the large bladder diverticulum. This boy underwent
endoscopic valve ablation, excision of the bladder diverticulum, and left ureteroneocystostomy.
feature is the presence of a pressure pop-off mechanism echogenicity,46 and loss of corticomedully differentia-
such as massive VUR into a nonfunctioning kidney tion.46 In addition, failure to achieve diurnal continence
(termed the VURD syndrome: valves, unilateral reflux, is an indication of bladder instability and detrusor sphinc-
dysplasia), urinary ascites, or a large bladder diverticulum ter dyssynergia (DSD), which can result in elevated upper
(Fig. 57-7).42 The concept is that the high intravesical urinary tract pressures and a gradual deterioration in
pressure is dissipated, allowing more normal renal devel- renal function.
opment. Although short-term studies have suggested that Review of studies of long-term renal function is dif-
these mechanisms allow more normal renal development, ficult because of variable follow-up among study patients.
at age 8 to 10 years only 30% of boys with the VURD In one report of 27 boys diagnosed between 1956 and
syndrome have a normal serum creatinine.43 One impor- 1970 with a 31- to 44-year follow-up, 18% died at an
tant favorable prognostic sign is the normal appearance early age and 11% were lost to follow-up.47 Of the
of the contralateral kidney at diagnosis. Such patients had remaining surviving men, 32% were uremic, 21% had
no UTIs or incontinence with long-term follow-up.44 moderate renal insufficiency, and 40% had signs of
Finally, absence of reflux on the initial VCUG is also a bladder dysfunction. This historical study does not reflect
favorable sign. the impact of early diagnosis with prenatal ultrasound
Adverse prognostic factors include bilateral VUR, per- and lower tract pharmacotherapy. For example, in a more
sistence of the serum creatinine higher than 1.0mg/dL recent study of 79 cases of PUV prenatally diagnosed
after initial therapy,45 identification of small subcapsular between 1987 and 2004, 65 were live births managed
renal cysts (indicative of renal dysplasia), increased renal with primary valve ablation. In follow-up, only 17% had
768 SECTION VI Urology
renal failure and 76% of toilet-trained men were com- UTIs are noted with the vesicostomy, closure may be
pletely continent.48 Early gestational age at diagnosis and helpful because it will reduce the risk of bacterial con-
the presence of oligohydramnios were negative prognos- tamination of the urinary tract. In other patients, closure
tic factors. may be necessary as a prerequisite to renal transplanta-
A contemporary retrospective study of 260 boys with tion. In most cases, vesicostomy closure is performed
PUV from 19922008 showed risk factors for progres- after the upper urinary tracts have stabilized and the child
sion to ESRD include nadir serum creatinine greater is large enough to undergo simultaneous valve ablation,
than 1.0mg/dL, bilateral grade III or higher reflux at generally between ages 1 and 3 years. Preoperatively, a
diagnosis, recurrent febrile UTIs, and severe bladder cystogram using a Foley catheter, introduced via the vesi-
dysfunction. About 12% of these boys progressed to costomy with the balloon inflated to avoid leakage of
ESRD at a mean age of 11 years (range 516 years). contrast, is performed to assess whether significant VUR
Nadir serum creatinine and bladder dysfunction were is present and to evaluate the appearance of the bladder.
found to be independent risk factors predictive of ulti- If significant VUR is seen and the child is quite young,
mate progression to ESRD.49 Another recent study con- it is usually safe to close the vesicostomy at the time of
firmed the high prognostic value of an elevated creatinine valve ablation and delay reflux correction until the child
after primary valve ablation.50 is older and the bladder is larger. Anticholinergic medica-
tion is useful as long as the bladder is emptying. Follow-
ing closure of the vesicostomy, the upper tracts should be
LATE DIAGNOSIS monitored for worsening hydronephrosis, incomplete
bladder emptying, and a significant change in serum
Although late presentation of PUV has been thought to
creatinine.
be a more benign entity, studies over the past 15 years
have shown that this may not be true. In a study of 47
patients, age 535 years, found to have PUV postnatally,
common presenting symptoms were daytime inconti-
VESICOURETERAL REFLUX
nence (60%), UTI (40%), and voiding pain (13%).51
At the initial presentation of PUV, VUR is present in
Hydronephrosis was found in 40% and VUR in 33%.
approximately 50% of boys. Half of these boys will have
Serum creatinine was elevated in 35% and 10% had
bilateral VUR and half unilateral. After valve ablation,
ESRD. If a VCUG had been performed only in those
nearly all patients will show improvement in reflux grade
with hydronephrosis, an abnormal ultrasound, or a UTI,
at 1 year.32,54 Another 25% will develop spontaneous
30% of PUVs would not have been diagnosed.
VUR. However, in these patients VUR may not resolve
A recent study evaluated the impact of the timing of
for as long as 3 years after initial treatment, and resolu-
diagnosis on long-term outcome in 52 patients with PUV
tion of high-grade VUR is unlikely.55 Antibiotic prophy-
who were diagnosed between 1994 and 2008.52 Thirty-
laxis is continued, and periodic upper tract imaging and
nine boys were diagnosed by 1 year of age and 13 were
cystography should be performed. Renal deterioration
diagnosed after 1 year. There was no statistical difference
without infection may be a sign of bladder dysfunction.
between groups in the rate of ESRD at a mean of 7.2
Lower tract evaluation with videourodynamics is
years following valve ablation. In the early diagnosis
important.
group, 10% required renal transplant, while no patient
VUR should be corrected if breakthrough infections
in the late diagnosis group developed ESRD, suggesting
occur or if it remains high grade. The efficacy of endo-
a lower risk of long-term renal insufficiency. Chronic
scopic subureteric injection therapy has not been proved,
renal failure (CRF) occurred in 52% with early diagnosis
but its use remains an option. Most pediatric urologists
who had abnormal renal parenchyma while CRF devel-
are adept at performing ureteral reimplantation, but
oped in 33% in the late diagnosis group who had normal
reimplanting thick, dilated ureters into the abnormal
appearing kidneys.
bladder can be challenging. A 1530% complication rate
A retrospective review was performed on 141 boys
has been reported, most often persistent reflux or ureteral
with PUV that presented after birth.53 Most (90%)
obstruction.56,57 If bilateral high-grade VUR is found, a
patients were born after 1990 with a mean age of 46
transureteroureterostomy can be performed in conjunc-
months. The most common symptoms were UTI (28%)
tion with a single, long, tapered reimplant and a psoas
and voiding complaints (50%). In long-term follow-up,
hitch. However, if the single reimplanted ureter becomes
12 patients (9%) had chronic renal disease. Five of the 12
obstructed, the upper tracts may deteriorate rapidly. If
had chronic disease at initial presentation without
unilateral high-grade reflux into a kidney with reasonable
improvement following treatment, and seven of 12 devel-
function occurs, transureteroureterostomy into the non-
oped chronic kidney disease 5 to 23 years after diagnosis.
refluxing ureter is an option.
Disease progression was associated with bilateral
In boys with unilateral VUR into a dysplastic kidney,
hydronephrosis, increased severity of hydronephrosis,
a nephrectomy should be performed at some point. The
and bilateral VUR.
ureter should be removed unless the bladder is small and/
or poorly compliant. In this case, an ureterocystoplasty
VESICOSTOMY CLOSURE can be considered (Fig. 57-8). Postoperatively, the
remaining kidney should be monitored carefully for the
In those boys requiring early vesicostomy, the decision to development of hydronephrosis because the pressure
close the vesicostomy should be made carefully. If febrile pop-off mechanism has been removed.
57 Posterior Urethral Valves 769
A B C
FIGURE 57-8 Technique of ureterocystoplasty. (A) Left nonfunctional kidney and ureter are exposed. (B) After the left kidney is
removed, the ureter is spatulated medially. (C) Left ureter is folded into a U and sutured to opened bladder.
BLADDER DYSFUNCTION AFTER 3. DSD in which the sphincter muscle fails to relax
during bladder contraction
INITIAL THERAPY 4. Polyuria secondary to a concentrating defect as a
result of long-standing obstructive uropathy that
The prognosis for boys with PUV depends on the status
causes renal tubular damage
of the kidneys and the bladder at the time of diagnosis,
5. Valve bladder, which is a bladder with poor compli-
and the method of bladder management as the child
ance resulting from fibrosis secondary to long-
grows. In as many as 40% with PUV, ESRD or chronic
standing obstruction.6466 This clinical situation can
renal insufficiency develops, and the vast majority of
cause secondary ureteral obstruction with worsen-
these boys have voiding dysfunction.41 Many boys with
ing hydronephrosis if the bladder pressure is greater
PUV have a spectrum of urodynamic abnormalities that
than 35cmH2O pressure (Table 57-1).
change over time as they age. For example, in a study of
Consequently, long-term therapy for the boy with
16 prepubertal boys with PUV who were seen before age
PUV includes management of the bladder as well as
1 year and observed from ages 4 to 14 years, initial
attention to renal function.6773 See Chapter 56 for more
bladder overactivity was observed.58 Over time, however,
information about management of bladder dysfunction.
the overactivity improved and the bladder capacity
increased. Adolescent boys had a high-capacity bladder
with low contractility and incomplete emptying. Other
groups have reported similar findings.59,60 LONG-TERM RISK OF END-STAGE
The bladder abnormalities seen in boys with PUV are RENAL DISEASE
manifested as incontinence and/or persistent hydroneph-
rosis. Boys with significant urodynamic abnormalities A recent study from Finland reported outcomes in
most likely will develop severe renal functional impair- 193/200 males with PUV from 1953 to 2003 with only
ment.61 The cause of the bladder dysfunction is not com- seven patients lost to follow-up.74 With a median age of
pletely understood, but experimental evidence suggests 31 years (range 669 years), 22.8% had progressed to
that fetal urethral obstruction causes irreversible changes ESRD. The lifetime risk of ESRD in this cohort was
in the smooth muscle cells of the bladder62 and results in 28.5%. The time to progression to ESRD correlated with
deposition of type III collagen in the bladder wall. In a the lowest serum creatinine value during the first post-
study of fetuses with PUV, a greater than twofold increase operative year. An increased risk of ESRD was associated
in bladder wall thickness was demonstrated when com- with early presentation, pneumothorax, bilateral VUR,
pared to normal controls.63 and recurrent UTI following valve ablation. No patient
As many as 50% of boys with PUV have ongoing progressed to ESRD after their mid 30s. In another
daytime incontinence into late childhood.41 Significant series, one-third developed ESRD.41 In a smaller series,
urodynamic abnormalities may persist following relief of 54% developed ESRD.75 With improved neonatal care
the bladder outlet obstruction. Several potential causes and management of ESRD in newborns, it is likely that
for urinary incontinence are known in boys with PUV,18,56 the risk of ESRD will decrease.
including the following:
1. Detrusor abnormalities such as (a) an overactive
bladder secondary to uninhibited detrusor contrac- RENAL TRANSPLANTATION
tions, (b) overflow incontinence, (c) poor compli-
ance, and (d) myogenic failure In many cases, impaired renal function can be stabilized
2. High-pressure voiding secondary to incomplete during childhood. However, during adolescence, there
valve ablation may be insufficient renal reserve, and dialysis or renal
770 SECTION VI Urology
From Close CE. The valve bladder. In: Gillenwater JY, Grayhack JT, Howards SS, etal, editors. Adult and Pediatric Urology. 4th
ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 231118.
transplantation becomes necessary. Retrospective studies Danish Prostatic Symptom Score.82 Mild hesitancy, weak
of boys with PUV undergoing renal transplantation have stream, incomplete bladder emptying, and straining were
suggested that the valve bladder may have a detrimental twice as common in patients with PUV than controls.
effect on graft survival. For example, in an older study, a The prevalence of lower urinary tract symptoms (LUTS)
significantly worse 5-year graft survival was noted for was increased about twofold in PUV men when com-
patients undergoing transplantation for ESRD due to pared to controls. Most of the study group reported little
PUV than was found in patients with nonobstructive to no symptoms. Infrequently, pyospermia and reduced
abnormalities.76 More recent studies, however, have dem- sperm counts were noted in men with a history of PUV
onstrated no difference in graft survival or serum creati- and severe LUTS. Azoospermia was uncommon, but
nine levels between boys with PUV and children with when observed, it was usually related to CRF. Another
nonobstructive causes of renal failure.7780 These results study of 16 men treated for PUV in infancy reported that
may reflect more effective treatment of the valve bladder sexual function and voiding symptoms were normal, and
in the recent past. their semen analysis was adequate for fertility.83
REFERENCES
ADULT SEXUAL FUNCTION 1. Malin G, Tonks A, Morris R, et al. Congenital lower urinary tract
AND FERTILITY obstruction: A population-based epidemiological study. BJOG
2012, Epub ahead of print.
2. Penna FJ, Elder JS. CKD and bladder problems in children. Adv
Few long-term studies have evaluated the reproductive Chronic Kidney Dis 2011;18:3629.
status of men who were born with PUV. Theoretically, 3. Krishnan A, de Souza A, Konijeti R, et al. The anatomy and
prostate function might be affected because of elevated embryology of posterior urethral valves. J Urol 2006;175:
121420.
urethral pressure during embryonic development and 4. Dewan PA, Zappala PG, Ransley PG, et al. Endoscopic reappraisal
ongoing voiding dysfunction. In addition, some boys of the morphology of congenital obstruction of the posterior
with PUV have reflux into the seminal vesicles and ejacu- urethra. Br J Urol 1992;70:43944.
latory ducts as well as a history of cryptorchidism, which 5. Elder JS. Management of antenatal hydronephrosis. In: Puri P,
editor. Newborn Surgery. 3rd ed. London: Hodder-Arnold; 2011.
might contribute to impaired fertility. In a recent report, p. 85671.
sexual function was assessed using the International Index 6. Hutton KA, Thomas DF, Arthur RJ, et al. Prenatally detected
of Erectile Function.81 There were 67 men with PUV and posterior urethral valves: Is gestational age at detection a predictor
102 age-matched controls with a mean age of 38 years in of outcome? J Urol 1994;152:698701.
both groups. Increasing age was the only risk factor for 7. Morris RK, Malin GL, Khan KS, et al. Antenatal ultrasound to
predict postnatal renal function in congenital lower urinary tract
developing erectile dysfunction. Only one of 61 (2%) obstruction: Systematic review of test accuracy. BJOG 2009;
sexually active men could not ejaculate. In this series, 116:12909.
there was no increase in ejaculatory problems in those 8. Bernardes LS, Salomon R, Aksnes G, et al. Ultrasound evaluation
men who had undergone both PUV ablation and bladder of prognosis in fetuses with posterior urethral valves. J Ped Surg
2011;46:141218.
neck incision, which was commonly performed several 9. Anumba DO, Scott JE, Plant ND, et al. Diagnosis and outcome of
decades ago. Almost half of the men had children and fetal lower urinary tract obstruction in the northern region of
four of seven with a renal transplant had children. Pater- England. Prenat Diagn 2005;25:713.
nity rates were similar to the general Finnish population. 10. Elder JS, Duckett JW, Snyder HM. Intervention for fetal obstruc-
Eight (12%) men had attempted to father children tive uropathy: Has it been effective? Lancet 1987;2:100710.
11. Johnson MP, Bukowski TP, Reitleman C, et al. In-utero surgical
without success. treatment of fetal obstructive uropathy: A new comprehensive
In another Finnish study, 68 men with PUV and 272 approach to identify appropriate candidates for vesicoamniotic
controls with a median age of 38.5 years responded to the shunt therapy. Am J Obstet Gynecol 1994;170:17709.
57 Posterior Urethral Valves 771
12. Johnson MP, Corsi P, Bradfield W, et al. Sequential urinalysis newborns with posterior urethral valves. J Urol 2012, Epub ahead
improves evaluation of fetal renal function in obstructive uropathy. of print.
Am J Obstet Gynecol 1995;173:5965. 38. Smith GH, Canning DA, Schulman SL, et al. The long-term
13. Kim SK, Won HS, Shim JY, et al. Successful vesicoamniotic shunt- outcome of posterior urethral valves treated with primary valve
ing of posterior urethral valves in the first trimester of pregnancy. ablation and observation. J Urol 1996;155:17304.
Ultrasound Obstet Gynecol 2005;26:6668. 39. Denes ED, Barthold JS, Gonzalez R. Early prognostic value of
14. Morris RK, Malin GL, Khan KS, et al. Systematic review of the serum creatinine levels in children with posterior urethral valves.
effectiveness of antenatal intervention for the treatment of con- J Urol 1997;157:14413.
genital lower urinary tract obstruction. BJOG 2010;17:38290. 40. Hulbert WC, Rosenberg HK, Cartwright PC, et al. The predictive
15. Cendron M, Elder JS. Perinatal urology. In: Gillenwater JY, Gray- value of ultrasonography in evaluation of infants with posterior
hack JT, Howards SS, Mitchell M, editors. Adult and Pediatric urethral valves. J Urol 1992;148:1224.
Urology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 41. Parkhouse HF, Barratt TM, Dillon MJ, et al. Long-term outcome
2002. p. 2041127. of boys with posterior urethral valves. Br J Urol 1988;16:5962.
16. Freedman AL, Bukowski TP, Smith CA, et al. Fetal therapy for 42. Kaefer M, Keating MA, Adams MC, et al. Posterior urethral valves,
obstructive uropathy: Specific outcomes diagnosis. J Urol 1996;156: pressure pop offs and bladder function. J Urol 1995;154:70811.
7204. 43. Cuckow PM, Dinneen MD, Risdon RA, et al. Long-term renal
17. Holmes N, Harrison MR, Baskin LS. Fetal surgery for posterior function in the posterior urethral valves, unilateral reflux and renal
urethral valves: Long-term postnatal outcomes. Pediatrics 2001; dysplasia syndrome. J Urol 1997;158:10047.
108:e17. 44. Narasimhan KL, Mahajan JK, Kaur B, et al. The vesicoureteral
18. Biard JM, Johnson MP, Carr MC, et al. Long-term outcomes in reflux dysplasia syndrome in patients with posterior urethral valves.
children treated by prenatal vesicoamniotic shunting for lower J Urol 2005;174:14335.
urinary tract obstruction. Obstet Gynecol 2005;106:5038. 45. DeFoor W, Clark C, Jackson E, et al. Risk factors for end stage
19. Morris RK, Kilby MD. An overview of the literature on congenital renal disease in children with posterior urethral valves. J Urol
lower urinary tract obstruction and introduction to the PLUTO 2008;180:17058.
trial: Percutaneous shunting in lower urinary tract obstruction. 46. Duel BP, Mogbo K, Barthold JS, et al. Prognostic value of initial
Aust NZJ Obstet Gynecol 2009;49:610. renal ultrasound in patients with posterior urethral valves. J Urol
20. Quintero RA, Romero R, Johnson MP, et al. In-utero percutaneous 1998;160:1198200.
cystoscopy in the management of fetal lower obstructive uropathy. 47. Holmdahl G, Sillen U. Boys with posterior urethral valves:
Lancet 1995;346:53740. Outcome concerning renal function, bladder function and pater-
21. Quintero RA, Shukla AR, Homsy YL, et al. Successful in-utero nity at ages 31 to 44 years. J Urol 2005;174:10314.
endoscopic ablation of posterior urethral valves: A new dimension 48. Sarhan O, Zaccaria I, Macher MA, et al. Long-term outcome of
in fetal urology. Urology 2000;55:774. prenatally detected posterior urethral valves: Single center study of
22. Clifton MS, Harrison MR, Ball R, et al. Fetoscopic transuterine 65 cases managed by primary valve ablation. J Urol 2008;179:
release of posterior urethral valves: A new technique. Fetal Diagn 30712.
Ther 2008;23:8994. 49. Ansari MS, Surdas R, Farai S, et al. Renal function reserve in
23. Morris RK, Kilby MD. Long-term renal and neurodevelopmental children with posterior urethral valve- a novel test to predict long-
outcome in infants with LUTO, with and without fetal interven- term outcome. J Urol 2011;185:232933.
tion. Early Hum Dev 2011;87:60710. 50. Sarhan OM, El-Ghoneimi AA, Helmy TE, et al. Posterior urethral
24. Welsh A, Agarwal S, Kumar S, et al. Fetal cystoscopy in the man- valves: Multivariate analysis of factors affecting the final renal
agement of fetal obstructive uropathy: Experience in a single Euro- outcome. J Urol 2011;185:24915.
pean centre. Prenat Diagn 2003;30:103341. 51. Bomalaski MD, Anema JG, Coplen DE, et al. Delayed presentation
25. Ruano R. Fetal surgery for severe lower urinary tract obstruction. of posterior urethral valves: A not so benign condition. J Urol 1999;
Prenat Diagn 2011;31:66174. 162:21302.
26. McMann LP, Kirsch AJ, Scherz HC, et al. Magnetic resonance 52. Kibar Y, Ashley RA, Roth CC, et al. Timing of posterior urethral
urography in the evaluation of prenatally diagnosed hydronephro- valve diagnosis and its impact on clinical outcome. J Ped Urol
sis and renal dysgenesis. J Urol 2006;176:178692. 2011;7:53842.
27. Shapiro E, Elder JS. Complications of surgery for posterior ure- 53. Engel DL, Pope JC IV, Adams MC, et al. Risk factors associated
thral valves. In Taneja SS, Smith RB, Ehrlich RM, editors. Com- with chronic kidney disease in patient with posterior urethral valves
plications of Urologic Surgery. 4th ed. Philadelphia: WB Saunders; without prenatal hydronephrosis. J Urol 2011;185:25028.
2010. p. 66983. 54. Priti K, Rao KL, Menon P, et al. Posterior urethral valves: Inci-
28. Bhatnagar V, Agarwala S, Lal R, et al. Fulguration of posterior dence and progress of vesicoureteric reflux after primary fulgura-
urethral valves using the Nd:YAG laser. Pediatr Surg Int 2000; tion. Pediatr Surg Int 2004;20:1369.
16:6971. 55. Hassan JM, Pope JC IV, Brock JW III, et al. Vesicoureteral reflux
29. Duckett JW Jr. Cutaneous vesicostomy in childhood: The Block- in patients with posterior urethral valves. J Urol 2003;170:
som technique. Urol Clin North Am 1974;1:48595. 167780.
30. Krueger RP, Hardy BE, Churchill BM. Growth in boys with pos- 56. Warshaw BL, Hymes LC, Trulock TS, et al. Prognostic features
terior urethral valves: Primary valve resection vs. upper tract diver- in infants with obstructive uropathy due to posterior urethral
sion. Urol Clin North Am 1980;7:26572. valves. J Urol 1985;133:2403.
31. Tietjen DN, Gloor JM, Husmann DA. Proximal urinary diversion 57. El-Sherbiny MT, Hafez AT, Ghoneim MA, et al. Ureteroneocys-
in the management of posterior urethral valves: Is it necessary? tostomy in children with posterior urethral valves: Indications and
J Urol 1997;158:100810. outcome. J Urol 2002;168:183640.
32. Close CE, Carr MC, Burns MW, et al. Lower urinary tract changes 58. Holmdahl G, Silln U, Hanson E, et al. Bladder dysfunction in
after early valve ablation in neonates and infants: Is early diversion boys with posterior urethral valves before and after puberty. J Urol
warranted? J Urol 1997;157:9848. 1996;155:6948.
33. Liard A, Seguier-Liqszyc E, Mitrofanoff P. Temporary high diver- 59. De Gennaro M, Capitanucci ML, Mosiello G, et al. The changing
sion for posterior urethral valves. J Urol 2000;164:1458. urodynamic pattern from infancy to adolescence in boys with pos-
34. Ghanem MA, Nijman RJ. Long-term followup of bilateral terior urethral valves. Br J Urol 2000;85:11048.
high (sober) urinary diversion in patients with posterior urethral 60. Emir H, Eroglu E, Tekant G, et al. Urodynamic findings of pos-
valves and its effect on bladder function. J Urol 2005;173:17214. terior urethral valve patients. Eur J Pediatr Surg 2002;12:3841.
35. Patil KK, Wilcox DT, Samuel M, et al. Management of urinary 61. Ghanem MA, Wolffenbuttel KP, de Vylder A, et al. Long term
extravasation in 18 boys with posterior urethral valves. J Urol bladder dysfunction and renal function in boys with posterior ure-
2003;169:150811. thral valves based on urodynamic findings. J Urol 2004;171:
36. Hekkila J, Taskinen S, Rintala R. Urinomas associated with poste- 240912.
rior urethral valves. J Urol 2008;180:14768. 62. Karim OM, Cendron M, Mostwin JL, et al. Developmental altera-
37. Casey JT, Hagerty JA, Maizels M, et al. Early administration of tions in the fetal lamb bladder subjected to partial urethral obstruc-
oxybutynin improves bladder function and clinical outsomes in tion in-utero. J Urol 1993;150:10603.
772 SECTION VI Urology
63. Freedman AL, Qureshi F, Shapiro E, et al. Smooth muscle develop- 74. Hekkila J, Holmberg C, Kyllonen L, et al. Long-term risk of end
ment in the obstructed fetal bladder. Urology 1997;49:1047. stage renal disease in patients with posterior urethral valves. J Urol
64. Mitchell ME. Persistent ureteral dilatation following valve resec- 2011;186:23926.
tion. Dial Pediatr Urol 1982;5:810. 75. Caione P, Nappo SG. Posterior urethral valves: Long-term
65. Close CE. The valve bladder. In: Gillenwater JY, Grayhack JT, outcome. Pediatr Surg Int 2011;27:102735.
Howards SS, editors. Adult and Pediatric Urology. 4th ed. Phila- 76. Reinberg Y, Gonzalez R, Fryd D. The outcome of renal transplan-
delphia: Lippincott Williams & Wilkins; 2002. p. 231118. tation on children with posterior urethral valves. J Urol
66. Donohoe JM, Weinstein RP, Combs AJ, et al. When can persistent 1988;140:14913.
hydroureteronephrosis in posterior urethral valve disease be con- 77. Indudhara R, Joseph DB, Perez LM, et al. Renal transplantation in
sidered residual stretching? J Urol 2004;172:70611. children with posterior urethral valves revisited: A 10-year
67. Glassberg KL. The valve bladder syndrome: 20 years later. J Urol follow-up. J Urol 1998;160:12013.
2001;166:140614. 78. DeFoor W, Tackett L, Minevich E, et al. Successful renal trans-
68. Capitanucci M, Marciano A, Zaccara A, et al. Long-term bladder plantation in children with posterior urethral valves. J Urol 2003;
function followup in boys with posterior urethral valves: Compari- 170:24024.
son of noninvasive vs invasive urodynamic studies. J Urol 2012; 79. Fine MS, Smith KM, Shrivastava D, et al. Posterior urethral valve
188:9537. treatments and outcomes in children receiving kidney transplants.
69. Cain MP, Wu SD, Austin PF, et al. Alpha blocker therapy for J Urol 2011;185:250711.
children with dysfunctional voiding and urinary retention. J Urol 80. Kamal MM, El-Hefnawy AS, Soliman S, et al. Impact of posterior
2003;1770:151415. urethral valves on pediatric renal transplantation: A single-center
70. Koff SA, Mutabagani KH, Jayanthi VR. The valve bladder syn- comparative study of 297 cases. Pediatr Transplantation 2011;15:
drome: Pathophysiology and treatment with nocturnal bladder 48297.
emptying. J Urol 2002;167:2917. 81. Taskinen S, Heikkil J, Santtila P, et al. Posterior urethral valves
71. Montane B, Abitbol C, Seeherunvong W, et al. Beneficial effects and adult sexual function. BJU Int 2012;110:E3926.
of continuous overnight catheter drainage in children with polyuric 82. Tikkinen KA, Heikkila J, Rintala RJ, et al. Lower urinary tract
renal failure. BJU Int 2003;92:44751. symptoms in adults treated for posterior urethral valves in child-
72. Johal NS, Hamid R, Aslam Z, et al. Ureterocystoplasty: Long-term hood: Matched cohort study. J Urol 2011;186:6606.
functional results. J Urol 2008;179:23735. 83. Lopez Pereira R, Miguel M, Martinez Urrutia MJ, et al. Long-term
73. Austin PF, Lockhart JL, Bissada NK, et al. Multi-institutional expe- bladder function, fertility and sexual function in patients with pos-
rience with the gastrointestinal composite reservoir. J Urol 2001; terior urethral valves treated in infancy. J Ped Urol 2011; Epub
165:201821. ahead of print.
C H A P T E R 5 8
The exstrophic anomalies, often referred to as the however, is rarely associated with other organ system
exstrophyepispadias complex,1 are considered a spec- malformation.
trum of embryological abnormalities including:
Epispadiasthe least severe anomaly, in which the
urethra is a partial or complete open plate on the
Diagnosis
dorsal surface of the phallus BE can be diagnosed antenatally, although many affected
Classic bladder exstrophy (BE)the most common fetuses are not identified before birth.9 Ultrasound (US)
of these anomalies, in which the bladder is an open can reliably detect BE before the twentieth week of gesta-
plate on the lower abdomen and always includes tion.10,11 Absence of the bladder is the hallmark. Other
epispadias ultrasound findings include:
Cloacal exstrophy (CE)the bladder and the ile- A semisolid mass protruding from the abdominal
ocecal junction of the bowel are an open plate on wall12
the lower abdomen. This condition, commonly A lower abdominal protrusion
associated with other defects, is also known as An anteriorly displaced scrotum with a small phallus
the omphalocele/exstrophy/imperforate anus/spinal in male fetuses
defect (OEIS) complex Normal kidneys in association with a low-set umbil-
Exstrophy variantspartial manifestations are seen ical cord13
of the above anomalies, and commonly lack sym- An abnormal iliac crest widening.10
metry in the sagittal plane. Subtle findings such as low umbilical cord insertion and
the location of the genitalia will only be seen if the fetus
is examined in a sagittal alignment with the spine.14 As
BLADDER EXSTROPHY exstrophy affects the external genitalia, the diagnosis is
easier to make in males than females. Iliac crest widening
Classic BE occurs in one per 10,00050,000 live births,2,3 can also be seen during the routine prenatal evaluation
with a male to female ratio of 36:1.4,5 CE is even more of the lumbosacral spine to evaluate for myelomenin-
rare with an incidence of 1 in 200,000400,000,6 but is gocele. The iliac angle will be about 110 rather than the
more common when stillborns are included in the data usual 90.14 Since urine production is normal in these
(1 in 10,000 to 1 in 50,000).7 The natural history of BE fetuses, amniotic fluid levels are normal.
is well known; the anomaly is nonlethal although it is Prenatal diagnosis allows for prenatal counseling,
associated with significant morbidity. Since the 19th optimal perinatal management, and the chance to be
century, various efforts to manage BE have been described. delivered near a pediatric center trained to treat these
As the condition is rare, these approaches were empiric babies. This counseling should include the expertise of
and usually unsuccessful. Until the 20th century, there an experienced pediatric urologist or surgeon. The overall
was no effective surgical technique. prognosis for these children can be good if treated at
BE results from an anterior herniation of the develop- medical centers with experience with this disorder.15
ing bladder and urethra with subsequent herniation of In many areas of the developing world, early treatment
posterior developing structures, preventing the normal remains problematic due to the lack of healthcare infra-
development of the lower abdominal wall and anterior structure and resources to care for these patients. Man-
fusion of the pelvis. The result is a flattened pelvis with agement of these patients often includes significantly
wide diastasis of the symphysis pubis. This anomaly has delayed time to closure and adds another level of chal-
been described as if one blade of a pair of scissors were lenge to achieve optimum outcomes in this patient group.
passed through the urethra of a normal person; the other A recent overview from South Africa highlighted this
blade were used to cut through the skin, abdominal wall, problem: 58% of the patients presented in a delayed
anterior wall of the bladder and urethra, and the symphy- fashion and mortality rates approached 42% due to
sis pubis; and the cut edges were then folded laterally as concomitant medical conditions and poor primary
if the pages of a book were being opened (Fig. 58-1).8 health care.16
Children with BE typically have an anteriorly located
anus. Also, the female genital anatomy is altered with
a more vertically oriented vaginal opening following
Pathogenesis
repair and a wider and shorter vagina than normal. The In the prescientific era, the cause of BE was attributed to
anterior component of the penis is also foreshortened in trauma to the unborn child causing ulceration of the
males compared to the general population. Classic BE, abdominal wall and subsequent bladder herniation.
773
774 SECTION VI Urology
in favor of an anatomically based approach. However, II pouch) approach 92% with continence rates up to
continent urinary diversion techniques can produce a 97%.37 The HeitzBoyerHovelaque procedure involves
more consistent degree of urinary continence with less isolation of a rectal segment for ureteral implantation
intervention than that achieved with anatomic recon- followed by posterior sagittal pull-through of the sigmoid
struction.37 Some urodynamic studies demonstrate low colon through the anal sphincter. A small series using
urine flow rates and poor contractility and continence in this approach reported continence rates of 95% with an
patients following primary bladder repair.38,39 acceptable complication rate.47 Complications of this
Internal or incontinent urinary diversion avoids the form of diversion include fecal-urinary incontinence in
potential complications associated with functional recon- patients with impaired anorectal sphincter control. Meta-
struction such as urinary retention and subsequent kidney bolic electrolyte imbalances can be treated with frequent
damage, and potential later dependence on clean inter- emptying of the rectal reservoir that reduces the contact
mittent catheterization (CIC) to empty the bladder. time between urine and the absorptive rectal mucosa
Advocates of early urinary diversion also cite a decreased along with oral bicarbonate replacement. The significant
risk of epididymitis and obstruction of the vas deferens risk of malignancy also remains a concern. Various modi-
by the creation of a receptacle with a suprapubic window fications of the rectal reservoir to prevent admixture of
at the level of the prostatic urethra.40 Diversion can also feces and urine may decrease the incidence of adenocar-
be combined with cosmetic and functional reconstructive cinoma if the risk is due to conversion of urinary nitrates
procedures for the external genitalia. Because of the dif- into carcinogenic nitrites by fecal bacteria.48 Long-term
ficulties encountered with functional bladder reconstruc- results are not yet available. Techniques for constructing
tion, advocates of early urinary diversion argue that their urinary diversions are listed in Table 58-3.
approach achieves the primary goals with fewer opera- As a result of these complications with urinary diver-
tions and higher success rates than are achieved with sion, and even though anatomic reconstruction may
bladder closure and urethral reconstruction. produce less consistent results, anatomic resconstruction
Urinary diversion is also useful to achieve urinary con- has become the standard approach when possible.
tinence in patients who have failed multiple attempts at
anatomic reconstruction. Also, urinary diversion may be Anatomic Reconstruction
best for patients with bladder plates deemed too small to
close. However, because we cannot accurately predict The first efforts at anatomic reconstruction for BE were
which bladder plates will increase significantly in size unsuccessful, but set the stage for the current anatomic
after primary closure, we do not use this as criteria for approach. In 1881, Trendelenberg described an exstro-
primary diversion and do not divert the urine primarily phy closure emphasizing the importance of pubic
in young BE patients. re-approximation in front of the reconstructed bladder in
Given the successes of urinary diversion, why abandon order to achieve continence and prevent dehiscence.49
it? Long-term complications associated with ureterosig- However, because of discouraging results, anatomic
moidostomy (USO) are significant and include hyper- reconstruction was largely replaced by urinary diversion
chloremic metabolic acidosis, chronic pyelonephritis, in the early part of the 20th century. During this time
bladder calculi, and a 250- to 300-fold increased risk of there were scattered published reports of successful
adenocarcinoma developing at the anastomosis.4143 As a outcomes.5053 However, several large series of patients
result of these complications, USO was subsequently who underwent single-stage anatomic reconstruction in
replaced by incontinent urinary diversions such as colonic the 1960s and 1970s reported continence rates of only
and ileal conduits. A significant disadvantage to these 1030%.5459 Renal damage was as high as 90% in these
conduits is the incontinent abdominal stoma that is asso- series, generally because of bladder outlet obstruction.54
ciated with them. As a result of these complications and the low rate of
The Mainz II pouch and the Sigma pouch represent urinary continence with single-stage approaches, recon-
significant improvements to the USO.4446 These rectal structive efforts were subsequently modified toward
reservoirs permit urinary continence without reliance on staged bladder reconstruction, an approach pioneered in
CIC. In one study, renal preservation rates in children the 1970s, and further refined to what is now known as
treated primarily with a urinary rectal reservoir (Mainz the modern staged repair of exstrophy (MSRE).6062
Recent advances in single-stage reconstruction for BE Assessment of the adequacy of the bladder template is
have been advocated and complete primary repair for subjective. Even a small bladder template, if distensible
exstrophy (CPRE) has gained favor.63 and contractile, can enlarge to a useful size once closed.
The primary goal of these approaches is to reconstruct However, if the bladder template appears too small and
and achieve anatomic and functional normalcy with stiff on initial assessment, some surgeons choose to defer
minimal operative morbidity. In the subsequent section, early operation and re-evaluate the bladder at 46 months
two currently popular surgical techniques, the CPRE and of age under anesthesia.70 If the bladder continues to
the MSRE, are detailed. Closure of the female with BE appear inadequate for closure, a nonrefluxing colon
is similar in the CPRE and MSRE methods with the end conduit can be created in combination with an abdominal
result being closure of the bladder, urethra, and abdomi- wall closure and epispadias repair. At a later age this can
nal wall. The main difference is a more aggressive mobi- be converted to a continent diversion or anastomosed to
lization of the vagina and urethral plate into the pelvic the rectosigmoid.
diaphragm in the CPRE technique. In contrast, closure During general anesthesia, nitrous oxide should be
of the male with BE is quite different in the CPRE and avoided during primary closure as it can cause bowel
MSRE techniques. The CPRE closes and repositions the distension, which decreases exposure during the opera-
bladder and entire urethra at one stage. In contrast, the tion and may increase the risk of wound dehiscence.
MSRE closes and repositions the bladder and posterior Some advocate postoperative nasogastric tube drainage
urethra at the first stage with the remainder of the urethra to decrease abdominal distension although we do not
closed at a later stage. routinely use it.71 We prefer an epidural catheter to
reduce the inhaled anesthetic requirement during the
Preoperative Care operation. Tunneling the epidural may reduce the risk of
infection if it is left in for prolonged periods after repair.72
After delivery, to reduce trauma to the bladder plate, the For patients older than 3 days, or newborns with a
umbilical cord should be ligated with silk suture rather wide pubic diastasis, we perform anterior iliac osteoto-
than a plastic or metal clamp. A hydrated gel dressing or mies. Osteotomies are recommended in most patients
plastic wrap can be used to protect the exposed bladder unless the pelvis is very pliable. Osteotomies assist closure
from superficial trauma. Dressings should be changed and enhance anterior pelvic floor support, which may
daily, and the bladder should be irrigated with normal improve future urinary continence.60,73
saline with each diaper change. A humidified air incuba- Factors that appear to be important in the periopera-
tor may also minimize bladder injury.64 tive period include:
Intravenous antibiotic therapy in the pre- and postop- Use of osteotomies in many cases to decrease the
erative period is used to decrease the risk for infection tension on the repair, especially if the repair is per-
following reconstruction. Preoperative ultrasound is formed >72 hours after birth
helpful to evaluate the kidneys and to establish a baseline Ureteral stenting and bladder drainage catheters
examination for later ultrasound studies. Preoperative placed intraoperatively to divert the urine in the
spinal ultrasound examination should be considered if postoperative period
sacral dimpling or other signs of spina bifida occulta are Avoidance of abdominal distension
noted on physical examination. Use of intraoperative antibiotics.74,75
In the CPRE (or Mitchell) technique,63 the bladder, chromic suture. Bladder polyps should be removed prior
bladder neck, and urethra are relocated posteriorly within to beginning the dissection as these can act as space-
the pelvis. This shift positions the proximal urethra occupying lesions after the bladder is reconstructed.
within the pelvic diaphragm in an anatomically more Initial dissection begins superiorly and proceeds inferi-
normal position to maximize the effect of the pelvic orly to separate the bladder from the adjacent skin and
muscles and support structures needed for urinary conti- fascia since it is usually easiest to identify tissue planes in
nence. Posterior location of the bladder neck and urethra these areas. The umbilical vessels are ligated as the
also facilitates reapproximation of the pubic symphysis umbilicus will be moved superiorly to a more anatomi-
which, in turn, helps prevent anterior migration of the cally normal location, and will be later used as the loca-
urethra and bladder neck, and provides a more anatomi- tion to exteriorize the suprapubic (SP) catheter.
cally normal pelvic diaphragm. Penile/Urethral Dissection. Traction sutures are
Total penile disassembly reduces anterior tension on placed into each hemiglans of the penis to aid in dissec-
the urethra because the urethra is separated from its tion. These sutures will rotate to a parallel vertical ori-
attachments to the underlying corporal bodies. These entation because the corporal bodies will naturally rotate
attachments otherwise pull the urethral plate anteriorly medially after they are separated from the urethral wedge
and prevent posterior placement of the proximal urethra (urethral plate plus underlying corpora spongiosa). We
and bladder neck in the pelvis. Reducing this tension begin the penile dissection along the ventral aspect of the
theoretically decreases the risk of bladder dehiscence and penis with a circumscribing incision (Fig. 58-3A). This
also temporarily reduces the dorsal tension on the cor- step precedes dissection of the urethral wedge from the
poral bodies that may contribute to dorsal chordee in corporal bodies because it is easier to identify the plane
males. Combining the epispadias repair with primary of dissection ventrally above Bucks fascia. Bucks fascia is
closure allows for the most important advantage of deficient or absent around the corpora spongiosum. As
primary closure which is division of the intersymphyseal the dissection progresses medially to separate the urethra
ligament or band located posterior to the urethra in these from the corpora cavernosa, it is important to realize that
patients. the plane shifts subtly from above Bucks fascia to just
Closure in the newborn period optimizes the chance above the tunica albuginea. Failure to adjust the plane of
for early bladder cycling and may aid in bladder develop- dissection will carry the dissection into the corpora spon-
ment. It may obviate the need for a multi-staged repair giosa which will result in excessive, difficult-to-control
of the exstrophied bladder including further bladder neck bleeding during the deep ventral dissection of the ure-
reconstruction (BNR), bladder augmentation, and penile thral wedge from the corporal bodies.
reconstructive surgery. The principles of this operation Shallow incisions are made laterally along the dorsal
are also useful in some reoperations or delayed repairs aspect of the urethra to begin the urethral dissection.
for exstrophy. Sharp dissection is used to develop the plane between the
urethral wedge and the corporal bodies. Careful dissec-
CPRE Technique: Boys. After sterile preparation and tion will preserve urethral width and length. This is par-
draping, the lines of dissection are marked (Fig. 58-2). ticularly important since the urethra is often too short to
When marking these lines, it is important to exclude reach the glans penis once the bladder has been relocated
dysplastic tissue at the edges of the exstrophic bladder into the pelvis.
and bladder neck. This is particularly important at the Careful lateral dissection of the penile shaft skin and
bladder neck where remaining dysplastic tissue may dartos fascia from the corporal bodies will avoid damag-
impair later bladder neck function. Catheters (35 ing the laterally located neurovascular bundles on the
French) are placed into both ureters and sutured with 5-0 corpora of the epispadic penis. The lateral dissection on
A B
FIGURE 58-2 In a male undergoing complete primary repair for bladder exstrophy, the outlines of the planes of dissection are seen
in these drawings. (A) Ventral view. (B) Dorsal view. The ureteral stents are marked with arrows.
58 Bladder and Cloacal Exstrophy 779
A B
FIGURE 58-3 These two diagrams show early portions of the ventral subcoronal and corporeal dissection. (A) Initiation of the sub-
coronal dissection is seen. This is typically the easiest plane to initiate dissection. (B) Corporeal dissection proximally and dorsally
is shown. Initiation of corporeal separation is easiest to establish proximally. Note the ureteral catheters (arrows), which have been
introduced into the ureteral orifices.
A B
FIGURE 58-4 (A) Separation of corporeal bodies and urethra. (B) Deep pelvic dissection. Note the division of the intersymphyseal
band (inset) is critical to allowing placement of the bladder in the pelvis. Also note the tubularization of the neourethra over the
urethral catheter (solid arrow) and the suprapubic tube in the still-open bladder (dotted arrow).
the penis should be superficial to Bucks fascia because of urethra is based on this corporal tissue (which should
the lateral location of the neurovascular bundles in the appear wedge-shaped after its dissection from the adja-
epispadic penis. cent corpora cavernosa). The urethral/corpora spongiosa
Complete Penile Disassembly and Deep Dissection. component will later be tubularized and placed ventral to
Once a plane is established between the penis and the the corporal bodies. Para-exstrophy skin flaps should not
urethral wedge, the penis may be disassembled into three be made with this technique because creating these flaps
components: the right and left corporal bodies with their may injure the blood supply to the distal urethra. As the
respective hemiglans, and the urethral wedge.77 This is bladder and urethra are located posteriorly in the pelvis
performed in order to provide exposure to the intersym- as a unit (with a common blood supply), division of the
physeal band and to allow adequate proximal dissection. urethral wedge is counter-intuitive to the intent of the
We have found the easiest plane of dissection to com- repair.
pletely isolate the corporal bodies is proximal and ventral. In some cases, a male infant with a wide symphaseal
The plane of dissection should be carried out at the level diastasis and short urethral plate will be left with a hypo-
of the tunica albuginea on the corpora (Fig. 58-3B). After spadias that will require later repair. Likewise, in patients
a plane is established between the urethral wedge and the with less symphysis separation and a longer segment of
corporal bodies, this dissection is carried distally to sepa- distal corporal midline connection, the urethra and cor-
rate the three components from each other (Fig. 58-4A). poral bodies do not always have to be completely sepa-
Complete separation of the corporal bodies increases rated distally. In such cases, the urethra is long enough
exposure to the pelvic diaphragm for deeper dissection. and the bladder mobile enough to preserve the connec-
The corporal bodies can be completely separated from tion between them while still effectively carrying out the
each other since they are nourished via a separate blood deep pelvic dissection that is integral to this repair.
supply. It is important to keep the underlying corpora After separating the components distally, the urethral
spongiosa with the urethra as the vasculature to the dissection is carried proximally to the bladder neck.
780 SECTION VI Urology
Exposure to the pelvic diaphragm is optimized by com- until the pelvic floor musculature becomes visible and the
plete proximal separation of the urethra and corporal future bladder neck and proximal urethra lie deep in the
bodies (Fig. 58-4B). This creates the exposure to perform pelvis with little anterior tension. Failure to adequately
the deep incision of the intersymphyseal band (the con- dissect the bladder and urethral wedge from these sur-
densation of anterior pelvic fascia and ligaments) which rounding structures will prevent posterior movement of
is necessary to move the bladder and urethra posteriorly the bladder in the pelvis and will create anterior tension
(Fig. 58-5). When dissecting the urethral wedge from the along the urethral plate, all of which can lead to failure
corporal bodies medially, the dissection plane is along the of the closure (Fig. 58-5).
tunica albuginea of the corpora cavernosa. This medial Primary Closure. Once the above steps are com-
dissection should be carried down through the intersym- pleted, the bladder closure and urethral tubularization
physeal band. can be initiated. This portion of the repair is straightfor-
With a deep incision of the intersymphyseal band pos- ward and anatomic (Fig. 58-6A). To provide urinary
terior and lateral to each side of the urethral wedge, the drainage, an SP tube is used. The bladder is closed in
bladder and bladder neck can be moved to a posterior three layers with monofilament absorbable suture. The
position in the pelvis. This dissection should be carried urethra is tubularized using a two-layer running closure
Cross section
Plane of cross section
Incision through
perineal membrane
Bladder
Symphysis
Prostate
Urethra
Corpus spongiosum
Perineal membrane
Superior transverse
perineal muscle
Anus
A B
FIGURE 58-6 Once the intersymphyseal band is adequately incised and the bladder and urethral wedge are dissected from the
surrounding tissues, bladder repair and urethral tubularization can be performed. (A) The bladder is being closed in three layers
using monofilament absorbable suture (solid arrow). The urethra has been tubularized using a two-layer running closure with
monofilament and braided absorbable suture (dotted arrow). (B) This schematic depicts closure of the pubic symphysis with two
number 1 polydioxanone interrupted sutures placed in a figure-of-eight fashion. The knots are placed anteriorly to prevent suture
erosion into the neck of the bladder. The urethra (dotted arrow) has been placed ventral to the corpora.
58 Bladder and Cloacal Exstrophy 781
then be closed in the midline. We mature the neourethra satisfactory aesthetic result to the introital area and can
with 5-0 polyglycolate sutures and reapproximate the be performed at the time of the primary repair.78
bifid clitoris with 7-0 PDS by denuding each half medi-
ally. The labia majora should be advanced to the peri- Other Primary Reconstructive Techniques. Other
neum at this time as well (Fig. 58-11B). A Z-plasty approaches for primary BE repair include the radical soft
technique aids in skin closure. A monsplasty provides a tissue mobilization technique (Kelly technique) which has
58 Bladder and Cloacal Exstrophy 783
been used at some institutions for decades. This approach Male MSRE Bladder and Posterior Urethral Closure
avoids the need for osteotomies as the periosteum is Technique. In MSRE stage 1 in the male child, ureteral
mobilized to allow the soft tissues of the bladder, bladder catheters are inserted and secured. A traction suture is
neck and urethra to be reconstructed in the midline. In a placed in the glans penis. The posterior urethra is devel-
recent study, long-term continence rates were reported at oped by incising a 2cm wide strip of mucosa from the
70% for complete or partial urinary control.79 Over half distal trigone to below the distal verumontanum. Initial
did not require bladder augmentation or CIC. Prolapse dissection begins at the umbilicus and is continued
rates may be lower in adult females closed in this fashion. circumferentially, incising around the bladder plate.
The abdominal wall was perceived as abnormal in adults The two umbilical arteries are ligated and divided. The
repaired with this technique. Others have also reported underlying detrusor muscle is mobilized from the rectus
successful short-term outcomes with the use of this sheath to expose the peritoneum. The peritoneum is
approach. Complications such as bladder neck-cutaneous dissected off the dome of the bladder to allow deep
fistulas and penile loss have been described.80 pelvic placement of the bladder. Extraperitoneal dissec-
tion lateral to the bladder exposes the retroperitoneal
Delayed Primary Closure. Several recent studies have space, and allows the dissection in the correct plane at
advocated for delayed primary closure, especially in regard the level of the bladder neck. At this level, the rectus
to the CPRE approach. Proponents of delayed repair fascia meets the pubis and the urogenital diaphragm
argue that it is safer for the child, allows a more coordi- fibers meet the posterior urethra/bladder neck. The
nated surgical effort, and allows an elective operation so urogenital diaphragm fibers and the intersymphyseal
that the most expert team of clinicians and personnel are band must be completely taken down from the pubic
available.81 Others have shown it is possible to wait months subperiosteum to the pelvic floor on each side, or the
after birth.82 Another group used the delay to stimulate the posterior urethra and bladder cannot be recessed deep
penis with testosterone with the goal of reducing the into the pelvis.
chance for glans injury, and reported good short-term At this point, the posterior urethra is assessed. If the
outcomes with this approach in six patients.83 The success- child has severe dorsal chordee and a short urethra that
ful use of a delayed closure approach is predicated on inhibits attempts at penile lengthening, an incision in the
adequate protection of the exposed tissue. One series urethral plate may be necessary, but only after extensive
showed that the CPRE technique can be used in delayed mobilization of the bladder and prostatic plate from the
or previous failed exstrophy closures.84 Another study rectus fascia, the pubic bones, and the inferior ramus of
found an increased cost of as much as 50% with delayed the pubis. After complete division of the urogenital dia-
closure.85 Long-term outcomes will take years to mature. phragm from the posterior urethra/bladder neck area, the
prostatic urethra can be displaced into the pelvis. Lack of
an adequate urethral plate length can be managed by
Modern Staged Repair of Exstrophy
dividing the prostatic plate distal to the verumontanum
A staged approach for exstrophy repair developed in in a V-shaped fashion. After corporal mobilization and
response to high rates of renal damage seen in single- midline reapproximation, the penile urethral plate is
stage approaches in the 1970s. The sequence for staged fashioned from a lateral rotational flap which is generated
reconstruction initially consisted of bladder and posterior after a single lateral incision into the paraexstrophy skin.
urethral closure at birth, BNR at 23 years of life, and Paraexstrophy skin flaps should be used with great caution
epispadias repair later.86 This sequence later shifted when because of a high complication rate.55,91,92
bladder capacity was noted to increase with added resist- The corporal bodies are not approximated at this time
ance from early epispadias repair.87 Currently, as described since this will be performed after the urethra has been
by the Johns Hopkins group, MSRE consists of bladder transposed beneath the corpora at the time of epispadias
and posterior urethral closure at birth or soon thereafter closure. An adequate dissection can be assessed by com-
(stage 1), epispadias repair at 612 months of life (stage pressing a sound on the posterior urethra while manually
2), and BNR when the bladder capacity is adequate and approximating the pelvis.
the child is showing interest in toilet training (usually at After an SP tube has been placed, the umbilicus is
45 years of life) (stage 3).88 Occasionally, epispadias excised and the bladder is closed in the midline in mul-
repair and BNRureteral reimplantation can be tiple layers with a running 2-0 polyglycolate suture. The
combined.89,90 posterior urethra is also closed onto the base of the penis,
sizing it to accept a 12- to 14 French sound. It is impor-
MSRE Stage 1: Initial Early Bladder Exstrophy tant to perform a horizontal mattress closure of the pubic
Closure. In the first stage of this repair, the objectives bones with heavy suture, and place the knot on the ante-
include: (1) closure and repositioning of the bladder and rior surface of the pubis. Once the suture is placed but
urethra (posterior urethra in males and entire urethra in not tied, three sterile personnel are used to approximate
females) inside the pelvic ring; and (2) approximation of the pubic symphysis. One individual applies pressure over
the pelvic ring with closure of the abdominal wall. In each greater trochanter to push the pubic rami to the
male patients, at the end of stage 1, this repair ideally midline. A second individual depresses the posterior
produces a result that mimics complete epispadias with urethra and bladder neck. The third individual ties the
incontinence and balanced posterior outlet resistance suture. If the rectus fascia is strong, a second suture is
stimulating bladder growth while preserving renal placed just above the symphysis. The abdominal wall,
function. subcutaneous tissues, and skin are then closed in multiple
784 SECTION VI Urology
layers with construction of a neoumbilicus at or above at the distal urethral plate allows advancement of the
the level of the iliac crests. urethral meatus onto the glans. Skin incisions are then
Female MSRE Bladder and Posterior Urethral made on the lateral edges of the urethral plate and around
Closure Technique. In stage 1 of the MSRE in the female the epispadic meatus. This plate is dissected from the
child, the technique of bladder, pelvic ring, and abdomi- corporal bodies to the level of the glans distally and to
nal wall closure are identical to that described for the the prostatic urethra proximally. Glans wings should be
male. However, the female closure differs from the male developed distally as well. The corporal bodies are then
closure in that the female urethra is completely recon- separated from each other to allow medial rotation. The
structed at stage 1.1,93 The incision in the urethral plate urethra is then tubularized over a 6 or 8 French urethral
mucosa is 2cm wide, traversing from the distal trigone catheter using running 6-0 absorbable suture. The cor-
to the vaginal orifice, in the female. Paraexstrophy skin poral bodies are rotated over the urethra and reapproxi-
flaps are not necessary in females.94 The medial aspect of mated using interrupted 5-0 absorbable suture.
each hemiclitoris is deepithelialized to permit approxima- Cavernocavernosotomies may be performed prior to
tion of the two glans clitori and reconstruction of the reapproximating the corporal bodies to help correct per-
mons. The bladder and female urethra are closed in two sistent chordee. These are performed at the point of
layers with polyglycolate suture and the pubic bones, maximal angulation. The neurovascular bundles may
abdominal wall, subcutaneous tissue, and skin are closed require mobilization to avoid injuring them if caverno-
as outlined in the male. The monsplasty and genitoplasty sotomies are performed. The glans wings are then closed
are then performed. over the urethra using interrupted 5-0 absorbable suture.
Postoperative Care of Stage 1 MSRE. An adequate The penile shaft skin can be trimmed and tailored to
urethral caliber and minimal post-void residuals are cover the penis using interrupted 5-0 or 6-0 absorbable
assessed prior to removal of the SP tube at four weeks. sutures. Z-plasties at the level of the pubis may decrease
The status of the upper tracts is assessed prior to dis- the chance of a dorsal retractile scar at the base of the
charge and is followed by ultrasound in 3 months and penis. Postoperative care includes bladder antispasmod-
then every 6 months to 1 year. Antibiotic vesicoureteral ics, broad-spectrum antibiotics, and removal of the ure-
reflux (VUR) prophylaxis is also given. Increasing thral catheter at two weeks. In the event of a significantly
hydronephrosis, worsening VUR, retained urine in the delayed primary closure or failure of an initial bladder
bladder, and recurrent urinary infections should prompt closure, a simultaneous closure of the exstrophy bladder
further evaluation for suture erosion or outlet obstruc- and the epispadias can be performed.
tion. Between the ages of 1 to 3 years, yearly cystograms Bladder Neck Reconstruction. In incontinent chil-
under anesthesia are performed to assess the degree of dren after CPRE or MSRE, a continence procedure is
reflux, and more importantly, to assess the bladder capac- appropriate when (1) the urethra is stricture-free and
ity (ideally 6085mL at this age). capable of catheterization if necessary; (2) under anesthe-
sia, the bladder capacity has achieved a minimum volume
MSRE Stage 2: Epispadias Repair. Epispadias repair of 6085mL; and (3) the child is mature enough to par-
is now typically performed at 12 to 18 months of age via ticipate in the postoperative voiding program.97 This is
the modified CantwellRansley technique. The goals of typically around 45 years of age at the earliest. Cystos-
epispadias repair include a straight penis and urethra, copy and gravity cystography are helpful for providing
easy urethral catheterization, normal erectile function, information regarding bladder capacity and the status of
and a cosmetically satisfactory phallus. These goals allow any previous repairs. Advocates of the staged reconstruc-
the patient to stand while voiding and to have intromis- tion approach emphasize the importance of achieving
sion during intercourse. adequate bladder capacity prior to performing BNR. A
Preoperative Considerations. Prior to performing the bladder capacity less than 60mL under anesthesia or
epispadias repair, several surgeons have described topical during urodynamic evaluation reduces the likelihood of
or intramuscular testosterone to increase the size of the continence after BNR. BNR requires an adequate bladder
phallus and the phallic skin.71,95 Intramuscular testoster- capacity because some volume is lost during construction
one enanthate in oil (2mg/kg) can be administered at five of the bladder neck. Factors that increase the potential
and two weeks prior to epispadias closure. Penile length- for the bladder to achieve an adequate capacity prior to
ening can usually be achieved at this time by division of BNR include:
all remnants of the suspensory ligament and scar tissue Avoidance of urinary tract infections
as well as further release of the crura from the inferior Complete bladder emptying with institution of CIC
pubic rami. In some cases, further urethral lengthening if bladder emptying is incomplete
may require free skin grafts, buccal mucosal grafts, ure- Epispadias repair
teral grafts, or pedicle skin flaps. These same maneuvers Avoidance of bladder prolapse.
can be used to repair the scarred or stenosed posterior Preoperative urodynamic evaluation should be consid-
urethra as well. ered because it allows detection of detrusor hyperactivity
The Modified CantwellRansley Technique. Cantwell or atony as well as assessment of functional bladder capac-
first described mobilization of the urethra and moving it ity and leak point pressures. However, the urethra in these
ventrally for epispadias repair in the late nineteenth patients may be difficult to catheterize. In these situations,
century. The technique has subsequently been modi- a urodynamic catheter can be placed suprapubically at the
fied.92,96 To begin this procedure, a stay suture is placed time of the cystourethroscopic examination and can be
into the glans. A reverse MAGPI or IPGAM procedure used later that day for the urodynamic evaluation.
58 Bladder and Cloacal Exstrophy 785
Ureteroneocystostomy may be required at the time of and bladder neck. After cross trigonal ureteral reimplan-
BNR to correct VUR and to relocate the ureters away tation, the urethral strip is tubularized in two layers using
from the lower bladder where the bladder neck will be absorbable or monocryl suture (4-0 or 5-0) over an 8 to
constructed. Although the Cohen technique is often 10 French urethral catheter, depending on the size of the
employed, others have described a cephalotrigonal tech- patient. The bladder may be closed in continuity with the
nique which is particularly applicable to exstrophy urethral closure. This procedure effectively narrows and
patients because of the angle of ureteral entry into the lengthens the proximal urethra. It also moves the anterior
bladder.98 The MarshallMarchettiKranz (MMK) fibrotic tissue at the level of the original bladder neck to
bladder neck suspension, or a bladder neck wrap using a more cephalad position, away from the new bladder
rectus or gracilis muscle or fascia, may be combined with neck. This anterior redundant tissue can be used as a
BNR as well. Osteotomies may also be necessary to sta- fibromuscular flap to encircle and support the new
bilize the intersymphyseal bar and improve continence at bladder neck. If a fibromuscular bladder wrap is not pos-
the time of BNR. sible, then a fascial sling or wrap may be performed fol-
The following section describes the most commonly lowing the bladder and urethral closure.
employed BNR techniques, including the modified Postoperatively, urine drains through a combination
YoungDeesLeadbetter (YDL) and the Mitchell repairs. of ureteral stents through the urethra and an SP tube.
The ureteral catheters are removed 710 days later. The
MSRE Stage 3: Modified YDL-BNR. The modified SP tube remains for at least 3 weeks. Voiding trials are
YDL-BNR and the transtrigonal/cephalotrigonal bilat- performed with measurement of post-void residual urine
eral ureteral reimplantation are the techniques employed volumes to assess for urinary retention before removing
in the MSRE Stage 3.98,99 The combined thoughts of the SP tube. As with any BNR procedure (without aug-
several surgeons spanning an 80-year period has led to mentation), several months of adjustment will be required
the modern YDL-BNR.97 To perform a modified YDL before the patient develops adequate bladder awareness,
procedure, the bladder neck is extensively dissected and capacity, and control to achieve urinary continence.
a vertical cystotomy is made. Occasionally, a portion of Occasionally, trigonal tubularization must be com-
the intersymphyseal band needs to be divided completely bined with bladder augmentation because of a small
for visualization. After transtrigonal/cephalotrigonal bladder capacity. Most BNRs decrease bladder capacity
bilateral ureteral reimplantation, a strip of bladder since the bladder is used to create the continence mecha-
mucosa, approximately 1.51.8cm wide and 34cm, nism.101 The stomach offers the best potential to preserve
long is generated, and the lateral bladder triangles are spontaneous volitional voiding in this group, but places
demucosalized. Use of an epinephrine-soaked sponge these children at risk of hematuriadysuria syndrome
during this dissection aids in hemostasis. The bladder which can be especially troubling in patients with persist-
neck may be funneled further with small vertical incisions ent urinary incontinence and normal sensory innerva-
along the cut edge of the lateral bladder walls. The tion.102 Other intestinal segments may also be used
neourethra is tubularized over an 8 French catheter using depending on surgeon preference. If augmentation is
interrupted or running polyglycolate suture (4-0 or 5-0). needed and if the urethra is difficult to catheterize,
The two triangular regions of demucosalized detrusor appendicovesicostomy or another form of the Mitro-
muscle are then closed over the mucosal tube in a two- fanoff operation is also performed because of the likeli-
layer vest over pants double-breasted technique using hood that they will require CIC to empty the bladder
3-0 polyglycolic acid suture. This reinforces the neoblad- after BNR and augmentation.
der neck, decreases the risk of fistula, and augments the
outlet resistance.100 The sutures in the third layer are not
cut since they are used in the subsequent MMK bladder Outcomes
neck suspension.97 Exstrophy
Some surgeons recommend avoidance of a urethral
catheter in the postoperative period because of concerns Complications can occur with any initial BE repair. The
that it may later adversely affect urinary continence. most commonly reported complication is an urethrocu-
Therefore, urinary drainage is achieved by using bilateral taneous fistula (at the penopubic angle dorsally) in males.
ureteral catheters and SP tube drainage. Ureteral stents These fistulas may close spontaneously. They may ini-
are removed around two to three weeks, and voiding tially be managed conservatively with urinary diversion
trials begin in the third week. The urethra is calibrated via catheter drainage. If the fistula does not close, the
with a soft 8 French catheter, and voiding trials are begun bladder and urethra should be examined cystoscopically
with the SP tube in place after the urine has been steri- for the possibility of obstruction at the bladder neck or
lized. If no urine is passed, cystoscopy and urethral stent- urethra. Complete breakdown of the bladder and abdom-
ing may be required for a short period of time. A bladder inal wall closure is uncommon today, and usually reflects
readjustment period may span several months before day significant postoperative infection or a technical error in
and subsequently night continence is achieved. closure.
BNR: The Mitchell Repair. This repair employs a If a child develops chronic bladder and kidney infec-
modification of the YDL technique described previ- tions following BE closure, he or she should be evaluated
ously.99 In this modification, a full-thickness incision is for possible outlet obstruction. Early intervention with
made in the anterior urethra and parallel incisions are CIC for several months will often protect the patient
extended cephalad to define the proximal urethral plate during this period. We routinely maintain our patients
786 SECTION VI Urology
on suppressive antibiotic therapy because of the high female exstrophy patients developed inguinal hernias
incidence of VUR. over a 10-year period.64 The authors recommended these
In the long term, patients are also concerned with hernias be repaired at the time of primary bladder closure
issues of fertility. For men, fertility may be compromised to prevent incarceration.
as a consequence of dissection needed in the region of the Due to the high incidence of VUR, we prescribe low-
bladder neck and posterior urethra. The vas deferens and dose suppressive antibiotics for all newborns after bladder
ejaculatory ducts are normal at birth. Most men can expe- closure. This is continued until the VUR is corrected or
rience orgasm, but some cannot effectively ejaculate. resolves spontaneously. Some surgeons perform neourete-
Intracystoplasmic sperm injection can be useful in this rocystotomies at the time of initial closure. The success
setting. Women with BE can become pregnant, but are of this approach has not been reported.
prone to develop uterine prolapse, especially after deliv-
ery. The prolapse is thought to be due to further stress and Osteotomies
damage to the already abnormal pelvic musculature.
Approximation of the open pelvic ring eases abdominal
wall closure, diminishes the rate of bladder and abdomi-
Epispadias
nal wall dehiscence,74,115 allows the construction of an
The urethrocutaneous fistula rate varies widely from intrapelvic urethra, and reapproximates the pelvic floor
540%. In one study, complications were more common musculature likely contributing to long-term conti-
in those patients who underwent epispadius repair at the nence.60,115 Therefore, pelvic ring reapproximation is
same time as BE closure versus an isolated epispadias useful at the initial bladder closure or at later stages of
repair.103 Other complications include atrophy of the reconstruction. If the pelvis is not sufficiently malleable,
corpora cavernosa and urethra. These complications can osteotomies are performed.
occur if the vascular supply to the corporal bodies or Osteotomies offer several advantages to the anatomic
urethral wedge is damaged during dissection or during approach to BE closure including: (1) optimizing pubic
closure.104 Similar complications have been found follow- symphysis apposition, diminishing tension on the fascial
ing the initial stage of a staged reconstruction as well as repair; (2) optimizing anatomic placement of the bladder,
after the use of the complete penile disassembly tech- bladder neck, and urethra in the pelvis; (3) improving the
nique.105 In experienced hands, these complications are reapproximation of the corporal and clitoral bodies; and
unusual and underscore the importance of involving sur- (4) possibly decreasing the chance for later uterine
geons experienced in the management of these patients. prolapse.
The need for osteotomies is typically assessed under
general anesthesia. Indications include patients more
Bladder Neck Reconstruction
than 72 hours old, newborns with a wide pubic diastasis,
After BNR, a good outcome is defined as a dry interval newborns with CE, and patients who have had a previ-
>23 hours accompanied by spontaneous voiding without ously failed closure. Osteotomies are usually performed
catheterization. YDL-BNR and its variants have yielded at the same setting as bladder closure to help secure the
urinary continence rates of 30% to 80% for patients with closure. Although classic exstrophy represents a spectrum
BE.99,106108 Many factors influence these outcomes. An of pelvic abnormalities, it has been our impression that
initial failed bladder closure or prior failed BNR reduces osteotomies improve the potential for successful repair
the chance for achieving subsequent urinary conti- and the potential for voiding with continence. Therefore,
nence.109 A preoperative bladder capacity of >85mL por- osteotomies are routinely performed in our primary
tends a greater continence rate after YDL-BNR.110 Use exstrophy closures.
of osteotomies and patient immobilization in the postop- Several operative approaches are available. Posterior
erative period increases the success of bladder closure and iliac osteotomies are performed with the patient in a
subsequent continence. Delayed bladder closure increases prone position, after which the patient is then reposi-
the likelihood of the eventual need for bladder augmenta- tioned for the bladder closure. Increased blood loss and
tion due to inadequate bladder capacity that, in turn, occasional malunion of the ileum have led to the pursuit
reduces the chance for volitional voiding. One long-term of other approaches. Anterior iliac osteotomies offer the
study found that eight of 13 patients with an initially advantage of not having to turn the patient. Compared
successful bladder closure and BNR required further to posterior iliac osteotomies, an anterior approach also
surgery in their second decade of life because of poorly has been shown to result in less blood loss and better
compliant, low-capacity bladders that caused urinary apposition and mobility of the pubic rami. Anterior
incontinence.111 approaches include an anterior diagonal technique or a
combination of bilateral combined anterior innominate
Adjunctive Aspects of the Repair and vertical iliac osteotomies which have had excellent
initial and long-term results compared to anterior iliac
Indirect inguinal hernias are commonly associated with osteotomies alone in some series.73,116 Both osteotomies
BE in both male and female patients.112,113 They arise as can be performed through the same anterior skin incision
a consequence of enlarged internal and external inguinal on each side and with minimal blood loss and 4% com-
rings combined with compromised fascial support and plication rate.117,118 A diagonal mid-iliac osteotomy per-
lack of obliquity of the inguinal canal.114 In one study formed through the same incision as the exstrophy
56% of classic male exstrophy patients and 15% of classic closure has also been described.119 Division of the
58 Bladder and Cloacal Exstrophy 787
superior pubic ramus is not as effective as the other Adolescent males with exstrophy are psychosexually
methods described, but can be used in the newborn delayed for 2 to 4 years compared to their peers, and
period.120,121 teenage girls with exstrophy struggle with sexual self-
After the primary reconstructive procedure for exstro- esteem issues such as body image and genital perception/
phy, the patient must be immobilized to decrease lateral appearance.123 We recommend regular assessment of
stresses on the closure. Choice of immobilization remains social development in this patient group including psy-
controversial with a variety of techniques available. chiatric evaluation and parental education.124 Assessment
Current options include: (1) Bryants traction; (2) use of can begin as early as 12 to 18 months of age and then as
an external fixator; (3) spica casting; and (4) mummy or needed. Evaluation and intervention is also useful prior
mermaid wrapping. The most important variable with to reconstructive procedures. In these patients, anxiety
these techniques is familiarity of the user as they all have and even suicidal ideation is greater than the general
learning curves. We prefer a spica cast for 3 weeks to population.125 Fortunately, adolescents with exstrophy
prevent external hip rotation and optimize pubic apposi- are resilient and often develop creative strategies for
tion. It can facilitate early discharge and home care (Fig. coping with the chronic aspects of their condition.126
58-12). Modified Bucks traction has also been used by Most adolescents with exstrophy express a strong desire
many groups with success. A posterior lightweight splint to be normal and resent arrangements that emphasize
can be used in newborns when the child is out of traction their differences.127
to maintain hip adduction. We have stopped using Bucks
traction because spica casts are easier for the families at Sexual Function
home. External fixation devices have also been used with
success.116 Fixator pins for these devices should be cleaned Although sexual function is of little relevance to the
several times a day to reduce infection. Internal fixation newborn or prepubertal child born with exstrophy, it is
may be necessary in older patients. Femoral nerve palsy an issue of considerable importance to the parents of the
is a possible complication with fixation which must be child who will worry and wonder what future sexual func-
monitored and can be reduced by gradually tightening tion their children will experience, and also for the ado-
the fixator. lescents with exstrophy for whom sexual function or the
To avoid osteotomies, a technique has been developed potential for sexual function is an area of focus. Erectile
that secures the pubic symphyseal closure with deeply function and sensation is usually intact for most male
placed polyglycolate sutures through the bone followed BE patients.128,129 However, persistent or recurrent
by placement of a miniature metal plate which may be chordee and small penile size can create difficulty in
removed later. Initial results are promising.122 Osteoto- achieving intercourse for some males.129 Libido is usually
mies are not usually needed with the Kelly technique.79 present with or without operative correction. Studies of
adult men with exstrophy have found that approximately
one-third choose not to or cannot engage in inter-
Long-Term Considerations course.130 In one series, 33 of 43 BE patients were married
or living with a partner. Sexual counseling in these
Psychosocial Concerns
patients is important because of the difficulties they may
Children with exstrophy can experience marked difficulty encounter.
in the development of their psychosocial identity. Exceedingly small penile size can severely limit the
potential of some men to have sexual intercourse. In this
setting, reconstruction with a radial forearm flap to con-
struct a penis analogue has shown an improved quality
of life.131
Ejaculation is often possible despite the extensive
reconstructive procedures that are performed. However,
seminal emission may be slow and continue several
hours after orgasm. Sperm quality and quantity is often
diminished which may be due to partial obstruction
after surgery, epididymitis, or recurrent urinary infec-
tions. In one series, 63% had antegrade ejaculation.132
Long-term studies in adults with BE found that a minor-
ity were able to conceive without assisted reproductive
techniques.130,133,134
For women with exstrophy, sexual intercourse is pos-
sible and sexual function is often intact.128 In one series,
14 of 23 patients were able to have typical intercourse.135
FIGURE 58-12 In order to immobilize the patient to decrease Narrowing at the vaginal introitus can be problematic.
lateral stresses on the closure after the primary reconstructive This can be addressed with serial calibration and dilation
procedure, a number of immobilization techniques are possible. as a first option, or with vaginal advancement skin flaps
This photograph shows a spica cast that was applied to prevent
external hip rotation and optimize pubic apposition in the early
as another option. Fertility is unimpaired in female
postoperative period. Note the suprapubic bladder catheter patients with BE. However, prolapse occurs more com-
(arrow). monly because of the lack of pelvic floor support
788 SECTION VI Urology
structures and bed-rest may be necessary in the later pelvic kidney or crossed fused renal ectopia. Horseshoe
stages of pregnancy. Pregnancy in these patients is con- kidneys, renal agenesis, and ureteropelvic junction
sidered a high risk event.28,136 Pregnancy complications obstruction are also found.
such as hydronephrosis and bacteriuira are common, In CE, the penis is often separated into two hemi-
and may necessitate antimicrobial prophylaxis.137 phalluses due to the wide pubic diastasis. This can make
Cesarean section is the recommended mode of delivery reconstructive efforts technically more challenging if a
as vaginal delivery can be problematic.138 Vaginal and male phenotype is preserved. Cryptorchidism is the rule
uterine prolapse is more common in women with BE and with CE. For girls, in addition to the genital pathology
treatment occurs at a younger age than in the general described previously with BE, uterus didelphys and other
population.139 fusion anomalies of the Mllerian duct structures are
seen in up to two-thirds of CE females. Vaginal agenesis
occurs in one-third of CE females.
CLOACAL EXSTROPHY In addition to the typical exstrophy of the hindgut,
ileal intussusception and the exposed appendices,
Although CE has been recognized for several hundred other associated intestinal abnormalities include imper-
years, Spencer was the first surgeon to report successful forate anus, foreshortening of the midgut, bowel duplica-
repair and survival in 1965.140 Mortality rates of CE tion, malrotation, intestinal atresia, and Meckels
infants remained high for years following this initial diverticulum.
success. Affected infants routinely died of malnutrition In addition to the features seen with BE, up to one-
and sepsis. With continuing improvement in total half of patients with CE can have other skeletal abnor-
parenteral nutrition and neonatal management, mortality malities. These anomalies include congenital hip
rates currently are less than 10%.141 Quality of life issues dislocation, talipes equinovarus, and a variety of limb
are now paramount in this patient group. deficiencies.143
The bladder plate associated with CE is divided in half The fascial anomalies associated with CE include
by the hindgut plate, which represents the development those previously described for BE. In addition, ompha-
anomaly of the colon that occurs with CE. Ileum enters loceles are often found as well.144,145 The omphalocele can
and intussuscepts into the middle of the hindgut creating be repaired during the initial bladder closure if it is small.
the trunk of an elephants face appearance with appen- If the omphalocele is large, it may require closure with
diceal appendages located laterally to give the impression the reapproximated bladder halves acting as a silo to
of tusks on the face of the elephant (Fig. 58-13).142 reduce the intra-abdominal pressure. Alternatively, the
With CE, the bladder neck and external urethral omphalocele can be treated with antiseptic paint to
sphincter are not fully developed due to the failed devel- promote epithelialization. The intra-abdominal pressure
opment of the bladder and urethral remnant located on following omphalocele closure determines whether we
the anterior and dorsal surfaces of the body wall and penis can proceed with primary bladder closure at the same
respectively. However, because innervation to these time or whether bladder closure is performed later. Too
structures may be intact, anatomic closure theoretically aggressive an attempt at one-stage CE repair can lead to
offers the possibility of achieving urinary continence. organ ischemia from the increased intra-abdominal pres-
The urethral plate is characteristically short as well. sure. On the other hand, rupture of an omphalocele
clearly requires immediate attention and takes priority
over other considerations.
Associated Anomalies Neurologic involvement of the lower spinal cord is
Renal anomalies are much more common in CE than reported to occur in 50100% of patients.144,146,147 Most
with BE. They include anomalies in locations such as a patients have lumbar or sacral cord involvement, but
O O
IL
BP
BP BP
C
C BP
IL UO UO
CB HG CB CB
CB HG
A
B
FIGURE 58-13 Photograph and schematic drawing of a neonate with cloacal exstrophy. BP, bladder plate; C, cecal plate; CB, corpo-
real body; HG, hindgut; IL, ileum; O, omphalocele; UO, ureteral orifice.
58 Bladder and Cloacal Exstrophy 789
Perioperative Management IL
CE patients are best managed by an experienced team of
pediatric urologists, surgeons, orthopedists, gastroenter- C
ologists, endocrinologists and neurosurgeons. Advances
in neonatal care, intravenous nutrition, and the operative
CO
approach have markedly reduced the mortality and mor-
bidity of this condition. Nonetheless, the management HG
remains challenging.
In the neonatal period, the bladder and hindgut plate
should be covered (plastic wrap or Vigilon) to protect A
the exposed structures. Similar to BE, the umbilical cord
is ligated with a suture to prevent an umbilical clamp
from abrading the bladder or hindgut plate. Antibiotic
prophylaxis should be administered because of the high O
incidence of renal abnormalities. CO
Preoperative studies include ultrasound, abdominal
films and karyotyping. Sonographic examination allows BP BP
the evaluation of the upper urinary tracts, internal genital
structures, and spinal cord. Because of the associated
genital anomalies, accurately identifying the gender may CO
be difficult, and karyotyping is helpful to define the chro-
mosomal sex in unclear situations. CB
B
Cloacal Exstrophy Closure Techniques
Each CE patient is unique, requiring an individualized FIGURE 58-14 (A) Depiction of removal and tubularization of the
operative plan. In general, this plan would include: (1) cecal plate. (B) Reapproximation of the bladder plates. BP,
bladder plate; C, cecum; CB, corporeal body; CO, colostomy site;
closure of the omphalocele with reapproximation of the HG, hindgut; IL, ileum; O, omphalocele; UO, ureteral orifice.
posterior bladder halves, tubularization of the cecum and
incorporation of the hindgut into the gastrointestinal
tract (functionally this creates the anatomy of classic BE); blind-ending hindgut all in continuity. The hindgut
and (2) repair of the exstrophic bladder and genitalia. If segment can then be exteriorized as a colostomy.
the baby is medically stable, the initial reconstructive In some cases, there are hindgut duplications. No
procedures can be performed within the first 72 hours of segment of bowel should be discarded unless absolutely
life, thus taking advantage of the pliable bony pelvis if unusable, since it might be useful at some time for the
closure of the entire defect is possible. However, in up to bowel, bladder or vaginal reconstruction. Similarly,
75% of these children, spina bifida is present and may appendiceal segments should be preserved for possible
need urgent closure, delaying the ventral abdominal wall use in reconstruction of the urinary tract. Because of
closure. Also, the omphalocele, seen in almost 90% of altered innervation to the pelvis, not all patients with CE
the patients,148 may require immediate care to prevent are candidates for an anal pull-through procedure. The
rupture. The size of the omphalocele, the size of the best candidates are children with an anocutaneous fistula
hindgut plate and bladder plates, the extent of the pubic and preserved innervation.
diastasis, and the extent of comorbidities largely dictate At initial repair, ureteral catheters are positioned in
the timing and staging of the initial closure. If the large the ureteral orifices and secured with 5-0 chromic suture.
omphalocele cannot be closed because of increased For the omphalocele repair, the dissection begins supe-
abdominal pressure, a silo can be placed or a biosynthetic riorly. Next, the umbilical vessels are ligated and the
patch used to bridge the abdominal wall fascial defect. bladder plates separated from the adjacent skin as
In the past, an ileostomy was routinely performed, but described in the CPRE and MSRE techniques. The
the metabolic consequences can be significant. Currently, medial cecal hindgut plate is separated from the paired,
management decisions focus around the use of the separated bladder plates, and tubularized. The bladder
exstrophic cecal plate and the terminal blind-ending halves are then reapproximated in the midline (Fig.
hindgut. The cecal plate can be retained in the bladder 58-14B). Inguinal hernias should be repaired if found.
closure as a bladder augmentation or can be separated Bladder repair can be performed if the intra-abdominal
from the bladder plates and used in the gastrointestinal pressure remains low after omphalocele closure. This is
tract (Fig. 58-14A). However, to improve bowel length determined clinically by assessing a change in ventilatory
and water resorption, most feel the cecal plate should be parameters. A one-stage CE closure, including closure of
tubularized, making the terminal ileum, cecum, and the the omphalocele, cecal plate tubularization and hindgut
790 SECTION VI Urology
terminal colostomy, bladder and urethral closure, recon- diminutive, the small one is removed, and the reconstruc-
struction of the external genitalia and osteotomies, should tion is performed using only the larger half.
be performed only under optimal anatomical conditions. Female genital reconstruction is complex as well. In
The decision to proceed with one-stage closure versus genetic females, complete Mllerian and vaginal duplica-
staged reconstruction spanning a period of months must tion often leads to attempted midline reapproximation.
be weighed carefully. Following tight closure, increased However, if one system appears more substantial, exci-
abdominal pressure can cause organ ischemia, excessive sion of the lesser unit may be prudent. In genetic males
tension on the midline closure, or compromised lower raised as female, neovaginal reconstruction is typically
extremity blood flow. If necessary, CE repair can be delayed and may require use of a hindgut segment or
staged at this point by converting the CE into a classic perineal skin.
BE. A colostomy is then created.
If staging is indicated, once the baby has recovered Gastrointestinal Reconstruction
sufficiently to tolerate another operation, reconstruction
of the bladder, bladder neck and genitalia is performed Short-gut syndrome is usually present at birth in babies
using either the CPRE or MSRE approach.149 with CE, even those with a normal length of bowel. The
Osteotomies are almost always necessary to assist in effects of malabsorption and fluid loss appear to be most
closure and posterior positioning of the urinary tract, clinically significant early in life.158 Many such children
given the pubic diastasis is usually more severe than in require parenteral nutritional support in early infancy.159,160
BE. Prior to the initial incision, the need for osteotomies As a result of this problem, we feel the hindgut should
is assessed by watching for ischemia of the lower extremi- be constructed and placed in continuity with the intestine
ties and external genitalia with reapproximation of the during the initial operation. This may improve intestinal
pubic symphysis. The Hopkins group recommends bilat- absorption and nutrition, and will also preserve intestinal
eral anterior innominate and vertical iliac osteotomies tissue that can be used in later reconstruction of the
with gradual approximation of the bones over one to two urinary tract or vagina if needed.
weeks via external fixture and interfragmentary pins.150,151
The Seattle group prefers iliac osteotomies. Other REFERENCES
authors prefer to avoid osteotomies because they believe 1. Gearhart JP. The exstrophy-epispadias complex in the new
millenniumscience, practice and policy. J Urol 1999;162:
that osteotomies make the abdominal closure more dif- 14213.
ficult,152 but this has not been our experience. Fewer 2. Lattimer JK, Smith MK. Exstrophy closure: A followup on 70
wound dehiscences and abdominal wall hernias have been cases. J Urol 1966;95:3569.
reported with osteotomies.151 3. Engel RM. Exstrophy of the bladder and associated anomalies.
Secondary procedures may be required on the urinary Birth Defects Orig Artic Ser 1974;10:1469.
4. Epidemiology of bladder exstrophy and epispadias: A communica-
tract to achieve continence, including BNR, bladder neck tion from the International Clearinghouse for Birth Defects
closure, bladder augmentation with stomach, ileum or Monitoring Systems. Teratology 1987;36:2217.
hindgut, and creation of a continent catheterizable 5. Ives E, Coffey R, Carter CO. A family study of bladder exstrophy.
stoma.144,153156 As most of these children will need CIC J Med Genet 1980;17:13941.
6. Ziegler M, Duckett JW, Howell JG. Cloacal exstrophy. In: Welch
to achieve dryness, urinary reconstruction must be indi- J, editor. Pediatric Surgery. Chicago: Year Book Publishers; 1986.
vidualized to meet their needs. 7. Keppler-Noreuil KM. OEIS complex (omphalocele-exstrophy-
imperforate anus-spinal defects): A review of 14 cases. Am J Med
Genet 2001;99:2719.
Gender of Rearing 8. Brock J III, ONeill J Jr. Bladder exstrophy. In: ONeill J Jr,
editor. Pediatric Surgery. Philadelphia: Lippincott; 1998.
Gender assignment for patients with CE is currently p. 170932.
debated both by the medical profession and by the lay 9. Skari H, Bjornland K, Bjornstad-Ostensen A, et al. Consequences
public. Traditionally, male patients underwent gender of prenatal ultrasound diagnosis: A preliminary report on neonates
conversion in infancy because of concerns that the small, with congenital malformations. Acta Obstet Gynecol Scand
1998;77:63542.
paired male hemi-phalluses were inadequate in size. This 10. Gearhart JP, Ben-Chaim J, Jeffs RD, et al. Criteria for the prenatal
approach was supported by anecdotal data of unsatisfied diagnosis of classic bladder exstrophy. Obstet Gynecol
patients following genital reconstruction.144 However, 1995;85:9614.
these observations, in conjunction with the prevailing 11. Mirk P, Calisti A, Fileni A. Prenatal sonographic diagnosis of
notion that humans are gender neutral at birth and can bladder extrophy. J Ultrasound Med 1986;5:2913.
12. Barth RA, Filly RA, Sondheimer FK. Prenatal sonographic find-
undergo gender conversion safely in infancy, have recently ings in bladder exstrophy. J Ultrasound Med 1990;9:35961.
come into question.157 Gender identity now appears to be 13. Jaffe R, Schoenfeld A, Ovadia J. Sonographic findings in the
a much more complex issue than previously imagined. prenatal diagnosis of bladder exstrophy. Am J Obstet Gynecol
Currently we reconstruct males with CE as males 1990;162:6758.
14. Lee EH, Shim JY. New sonographic finding for the prenatal
whenever technically possible. Many gender assigned diagnosis of bladder exstrophy: A case report. Ultrasound Obstet
individuals will later identify themselves in a male Gynecol 2003;21:498500.
gender role in adolescence and adulthood.157 Technically, 15. Cacciari A, Pilu GL, Modenti M, et al. Prenatal diagnosis of
however, reconstruction of external male genitalia in bladder exstrophy: What counseling? J Urol 1999;161:25962.
these patients can be quite challenging. The wide pubic 16. Wiersma R. Overview of bladder exstrophy: A third world per-
spective. J Pediatr Surg 2008;43:15203.
diastasis and small phallic size add to the technical diffi- 17. Muecke EC. The Role of the Cloacal Membrane in Exstrophy:
culty because it is more difficult to join the two phallic The First Successful Experimental Study. J Urol 1964;92:
halves in the midline. In some cases, if one phallic half is 65967.
58 Bladder and Cloacal Exstrophy 791
18. Klimberg I. The Development of Voiding Control. AUA Update 47. Tacciuoli M, Laurenti C, Racheli T. Sixteen years experience with
Series 1988;7:1627. the Heitz Boyer-Hovelacque procedure for exstrophy of the
19. Marshall FF. Embryology of the lower genitourinary tract. Urol bladder. Br J Urol 1977;49:38590.
Clin North Am 1978;5:315. 48. Crissey MM, Steele GD, Gittes RF. Rat model for carcinogenesis
20. Thomalla JV, Rudolph RA, Rink RC, et al. Induction of cloacal in ureterosigmoidostomy. Science 1980;207:107980.
exstrophy in the chick embryo using the CO2 laser. J Urol 49. Trendelenberg F. The treatment of ectopia vesicae. Ann Surg
1985;134:9915. 1906;44:9819.
21. Patten BM, Barry A. The genesis of exstrophy of the bladder and 50. Ansell JS. Surgical treatment of exstrophy of the bladder with
epispadias. Am J Anat 1952;90:3557. emphasis on neonatal primary closure: Personal experience with
22. Manner J, Kluth D. A chicken model to study the embryology of 28 consecutive cases treated at the University of Washington
cloacal exstrophy. J Pediatr Surg 2003;38:67881. hospitals from 1962 to 1977: Techniques and results. J Urol 1979;
23. Beaudoin S, Barbet P, Bargy F. Pelvic development in the rabbit 121:6503.
embryo: implications in the organogenesis of bladder exstrophy. 51. Young H. Exstrophy of the bladder: The first case in which a
Anat Embryol (Berl) 2004;208:42530. normal bladder and urinary control have been obtained by plastic
24. Slaughenhoupt BL, Mathews RI, Peppas DS, et al. A large animal operations. Surg Gynecol Obstet 1942;74:72937.
model of bladder exstrophy: Observations of bladder smooth 52. Montagnani CA. One stage functional reconstruction of exstro-
muscle and collagen content. J Urol 1999;162:211922. phied bladder: Report of two cases with six-year follow-up. Z
25. Slaughenhoupt BL, Chen CJ, Gearhart JP. Creation of a model Kinderchir 1982;37:237.
of bladder exstrophy in the fetal lamb. J Urol 1996;156:81618. 53. Fuchs J, Gluer S, Mildenberger H. One-stage reconstruction of
26. Verpoest W, Platteau P, Van Steirteghem A, et al. Pregnancy in a bladder exstrophy. Eur J Pediatr Surg 1996;6:21215.
couple with a male partner born with severe bladder exstrophy. 54. King L, Wendel E. Primary cystectomy and permanent urinary
Reprod Biomed Online 2004;8:2402. diversion in the treatment of exstrophy of the urinary bladder. In:
27. Gross SD. A Practical Treatise on the Diseases, Injuries, and Scott JR, Gordon H, Carlton C, Beach PD, editor. Current Con-
Malformations of the Urinary Bladder, the Prostate Gland, and troversies in Urologic management. Philadelphia: WB Saunders
the Urethra. 3rd ed. Philadelphia: Henry C. Lea; 1876. Co; 1972. p. 24250.
28. Burbige KA, Henslel TW, Chambers WJ, et al. Pregnancy and 55. Johnston JH, Kogan SJ. The exstrophic anomalies and their surgi-
sexual function in women with bladder exstrophy. Urology cal reconstruction. Curr Probl Surg 1974;139.
1986;28:1214. 56. Williams DI, Keeton JE. Further progress with reconstruction of
29. Mathews R, Gan M, Gearhart JP. Urogynaecological and obstetric the exstrophied bladder. Br J Surg 1973;60:2037.
issues in women with the exstrophy-epispadias complex. BJU Int 57. Megall, M, Lattimer JK. Review of the management of 140 cases
2003;91:8459. of exstrophy of the bladder. J Urol 1973;109:2468.
30. Froster UG, Heinritz W, Bennek J, et al. Another case of auto- 58. Engel RM. Bladder exstrophy: Vesicoplasty or urinary diversion?
somal dominant exstrophy of the bladder. Prenat Diagn 2004;24: Urology 1973;2:204.
3757. 59. Ezell WW, Carlson HE. A realistic look at exstrophy of the
31. Messelink EJ, Aronson DC, Knuist M, et al. Four cases of bladder bladder. Br J Urol 1970;42:197202.
exstrophy in two families. J Med Genet 1994;31:4902. 60. Aadalen RJ, OPhelan EH, Chisholm TC, et al. Exstrophy of the
32. Shapiro E, Lepor H, Jeffs RD. The inheritance of the exstrophy- bladder: Long-term results of bilateral posterior iliac osteotomies
epispadias complex. J Urol 1984;132:30810. and two-stage anatomic repair. Clin Orthop Relat Res 1980;151:
33. Paidas MJ, Crombleholme TM, Robertson FM. Prenatal diagno- 193200.
sis and management of the fetus with an abdominal wall defect. 61. Jeffs RD. Functional closure of bladder exstrophy. Birth Defects
Semin Perinatol 1994;18:196214. Orig Artic Ser 1977;13:1713.
34. Tang Y, Ma CX, Cui W, et al. The risk of birth defects in multiple 62. Saltzman B, Mininberg DT, Muecke EC. Exstrophy of bladder:
births: A population-based study. Matern Child Health J Evolution of management. Urology 1985;26:3838.
2006;10:7581. 63. Grady RW, Mitchell ME. Complete primary repair of exstrophy.
35. Gambhir L, Hller T, Mller M, et al. Epidemiological survey of J Urol 1999;162:141520.
214 families with bladder exstrophy-epispadias complex. J Urol 64. Churchill B, Merguerian PA, Khoury AE, et al. Bladder exstrophy
2008;179:153943. and epispadias. In: ODonnel B, Koff S, editor. Pediatric Urology.
36. OKane HO, Megaw JM. Carcinoma in the exstrophic bladder. Oxford, England: Reed Elsevier; 1997. p. 495508.
Br J Surg 1968;55:6315. 65. Gearhart JP, Jeffs RD. Bladder exstrophy: Increase in capacity
37. Hohenfellner R, Stein R. Primary urinary diversion in patients following epispadias repair. J Urol 1989;142:5256.
with bladder exstrophy. Urology 1996;48:28830. 66. Mathews R, Gosling JA, Gearhart JP. Ultrastructure of the bladder
38. Hollowell JG, Hill PD, Duffy PG, et al. Lower urinary tract in classic exstrophy: Correlation with development of continence.
function after exstrophy closure. Pediatr Nephrol 1992;6: J Urol 2004;172:14469.
42832. 67. Mathews R, Willis M, Perlman E, et al. Neural innervation of the
39. Nisonson I, Lattimer JK. How well can the exstrophied bladder newborn exstrophic bladder: An immunohistochemical study.
work? J Urol 1972;107:6646. J Urol 1999;162:5068.
40. Stein R, Fisch M, Stckle M, et al. Colonic conduit in children: 68. Lee BR, Perlman EJ, Partin AW, et al. Evaluation of smooth
Protection of the upper urinary tract 16 years later? J Urol muscle and collagen subtypes in normal newborns and those with
1996;156:114650. bladder exstrophy. J Urol 1996;156:20346.
41. Husmann DA, Rathbun SR. Long-term follow up of enteric 69. McMahon DR, Cain MP, Husmann DA, et al. Vesical neck recon-
bladder augmentations: The risk for malignancy. J Pediatr Urol struction in patients with the exstrophy-epispadias complex.
2008;4:3816. J Urol 1996;155:141113.
42. Vemulakonda VM, Lendvay TS, Shnorhavorian M, et al. Meta- 70. Dodson JL, Surer I, Baker LA, et al. The newborn exstrophy
static adenocarcinoma after augmentation gastrocystoplasty. bladder inadequate for primary closure: evaluation, management
J Urol 2008;179:10947. and outcome. J Urol 2001;165:16569.
43. Husmann DA, Spence HM. Current status of tumor of the bowel 71. Gearhart JP. Bladder exstrophy: Staged reconstruction. Curr Opin
following ureterosigmoidostomy: A review. J Urol 1990;144: Urol 1999;9:499506.
60710. 72. Kost-Byerly S, Jackson EV, Yaster M, et al. Perioperative anes-
44. Fisch M, Wammack R, Hohenfellner R. The sigma rectum pouch thetic and analgesic management of newborn bladder exstrophy
(Mainz pouch II). World J Urol 1996;14:6872. repair. J Pediatr Urol 2008;4:2805.
45. Hohenfellner R. Continent urinary diversion in childhood: Euro- 73. Gearhart JP, Forschner DC, Jeffs RD, et al. A combined vertical
pean experience. Scand J Urol Nephrol Suppl 1992;142:825. and horizontal pelvic osteotomy approach for primary and sec-
46. Ghoneim MA. The modified rectal bladder: A bladder substitute ondary repair of bladder exstrophy. J Urol 1996;155:68993.
controlled by the anal sphincter. Scand J Urol Nephrol Suppl 74. Husmann DA, McLorie GA, Churchill BM. Closure of the
1992;142:8991. exstrophic bladder: An evaluation of the factors leading to its
792 SECTION VI Urology
success and its importance on urinary continence. J Urol 99. Jones JA, Mitchell ME, Rink RC. Improved results using a modi-
1989;142:5224. fication of the Young-Dees-Leadbetter bladder neck repair. Br J
75. Gearhart JP, Peppas DS, Jeffs DS. The failed exstrophy closure: Urol 1993;71:55561.
Strategy for management. Br J Urol 1993;71:21720. 100. Ben-Chaim J, Gearhart JP. Current management of bladder
76. Close CE, Carr MC, Burns MW, et al. Lower urinary tract exstrophy. Tech Urol 1996;2:233.
changes after early valve ablation in neonates and infants: Is early 101. Mansi M, Ahmed S. Young-Dees-Leadbetter bladder neck recon-
diversion warranted? J Urol 1997;157:9848. struction for sphincteric urinary incontinence: The value of aug-
77. Mitchell ME, Bagli DJ. Complete penile disassembly for mentation cystoplasty. Scand J Urol Nephrol 1993;27:50917.
epispadias repair: The Mitchell technique. J Urol 1996;155: 102. Ganesan GS, Nguyen DH, Adams MC, et al. Lower urinary tract
3004. reconstruction using stomach and the artificial sphincter. J Urol
78. Cook AJ, Farhat WA, Cartwright LM, et al. Simplified mons 1993;149:11079.
plasty: A new technique to improve cosmesis in females with the 103. Lottmann HB, Yaqouti M, Melin Y. Male epispadias repair: Surgi-
exstrophy-epispadias complex. J Urol 2005;173:211720. cal and functional results with the Cantwell-Ransley procedure in
79. Jarzebowski AC, McMullin ND, Grover SR, et al. The Kelly 40 patients. J Urol 1999;162:117680.
technique of bladder exstrophy repair: Continence, cosmesis and 104. Gearhart JP. Complete repair of bladder exstrophy in the newborn:
pelvic organ prolapse outcomes. J Urol 2009;182:18026. Complications and management. J Urol 2001;165:24313.
80. Berrettini A, Castagnetti M, Rigamonti W. Radical soft tissue 105. Gearhart JP, Mathews R. Penile reconstruction combined with
mobilization and reconstruction (Kelly procedure) for bladder bladder closure in the management of classic bladder exstrophy:
extrophy [correction of exstrophy] repair in males: Initial experi- Illustration of technique. Urology 2000;55:76470.
ence with nine cases. Pediatr Surg Int 2009;25:42731. 106. Mollard P. [Bladder and urethral reconstruction for bladder
81. Canning D. Vesical Exstrophy Complete primary closure com- exstrophy]. Bull Soc Sci Med Grand Duche Luxemb 1987;124(Spec
mentary. In: Hinman JaLBF, editor. Hinmans Atlas of Pediatric No):22530.
Urologic Surgery. Philadelphia, PA: Saunders Elsevier; 2009. p. 107. Surer I, Baker LA, Jeffs RD, et al. Modified Young-Dees-Lead-
388. better bladder neck reconstruction in patients with successful
82. Baradaran N, Stec AA, Schaeffer AJ, et al. Delayed primary primary bladder closure elsewhere: A single institution experi-
closure of bladder exstrophy: Immediate postoperative manage- ence. J Urol 2001;165:243840.
ment leading to successful outcomes. Urology 2012;79:41519. 108. Shaw MB, Rink RC, Kaefer M, et al. Continence and classic
83. Zaccara A, Stec AA, Schaeffer AJ, et al. Delayed complete repair bladder exstrophy treated with staged repair. J Urol
of exstrophy with testosterone treatment: An alternative to avoid 2004;172:14503.
glans complications? Pediatr Surg Int 2011;27:41721. 109. Gearhart JP, Canning DA, Peppas DS, et al. Techniques to create
84. Hafez AT, De Gennaro M, Di Lazzaro A, et al. Complete primary continence in the failed bladder exstrophy closure patient. J Urol
repair of bladder exstrophy in children presenting late and those 1993;150:4413.
with failed initial closure: single center experience. J Urol 110. Chan DY, Jeffs RD, Gearhart JP. Determinants of continence in
2005;174:154952. the bladder exstrophy population: predictors of success? Urology
85. Nelson CP, North AC, Ward MK, et al. Economic impact of 2001;57:7747.
failed or delayed primary repair of bladder exstrophy: Differences 111. Woodhouse CR, Redgrave NG. Late failure of the reconstructed
in cost of hospitalization. J Urol 2008;179:6803. exstrophy bladder. Br J Urol 1996;77:5902.
86. Jeffs RD. Exstrophy and cloacal exstrophy. Urol Clin North Am 112. Stringer MD, Duffy PG, Ransley, PG. Inguinal hernias associated
1978;5:12740. with bladder exstrophy. Br J Urol 1994;73:3089.
87. Gearhart JP, Jeffs RD. State-of-the-art reconstructive surgery for 113. Connolly JA, Peppas DS, Jeffs RD, et al. Prevalence and repair of
bladder exstrophy at the Johns Hopkins Hospital. Am J Dis Child inguinal hernias in children with bladder exstrophy. J Urol
1989;143:14758. 1995;154:19001.
88. Baker LA, Gearhart JP. The staged approach to bladder exstrophy 114. Husmann DA, McLorie GA, CHurchill BM, et al. Inguinal
closure and the role of osteotomies. World J Urol pathology and its association with classical bladder exstrophy.
1998;16:20511. J Pediatr Surg 1990;25:3324.
89. Baka-Jakubiak M. Combined bladder neck, urethral and penile 115. Oesterling JE, Jeffs RD. The importance of a successful initial
reconstruction in boys with the exstrophy-epispadias complex. bladder closure in the surgical management of classical bladder
BJU Int 2000;86:51318. exstrophy: Analysis of 144 patients treated at the Johns Hopkins
90. Baird AD, Mathews RI, Gearhart JP. The use of combined bladder Hospital between 1975 and 1985. J Urol 1987;137:25862.
and epispadias repair in boys with classic bladder exstrophy: Out- 116. Sponseller PD, Jani MM, Jeffs RD, et al. Anterior innominate
comes, complications and consequences. J Urol 2005;174: osteotomy in repair of bladder exstrophy. J Bone Joint Surg Am
14214. 2001;83:18493.
91. Duckett JW. Use of paraexstrophy skin pedicle grafts for correc- 117. Okubadejo GO, Sponseller PD, Gearhart JP. Complications in
tion of exstrophy and epispadias repair. Birth Defects Orig Artic orthopedic management of exstrophy. J Pediatr Orthop
Ser 1977;13:1759. 2003;23:5228.
92. Gearhart JP, Sciortino C, Ben-Chaim J, et al. The Cantwell- 118. Sponseller PD, Gearhart JP, Jeffs RD. Anterior innominate oste-
Ransley epispadias repair in exstrophy and epispadias: Lessons otomies for failure or late closure of bladder exstrophy. J Urol
learned. Urology 1995;46:925. 1991;146:13740.
93. Gearhart JP, Ben-Chaim J, Sciortino C, et al. The multiple reop- 119. McKenna PH, Khoury AE, McLorie GA, et al. Iliac osteotomy:
erative bladder exstrophy closure: What affects the potential of A model to compare the options in bladder and cloacal exstrophy
the bladder? Urology 1996;47:2403. reconstruction. J Urol 1994;151:1827.
94. Ben-Chaim J, Jeffs RD, Gearhart JP. Loss of urethrovaginal 120. Schmidt AH, Keenen TL, Tank ES, et al. Pelvic osteotomy for
septum as a complication of exstrophy closure in girls. Eur Urol bladder exstrophy. J Pediatr Orthop 1993;13:21419.
1998;33:2068. 121. Frey P. Bilateral anterior pubic osteotomy in bladder exstrophy
95. Perovi; S, Scepanovi; D, Sremcevi; D, et al. Epispadias surgery closure. J Urol 1996;156:81215.
Belgrade experience. Br J Urol 1992;70:6747. 122. Kajbafzadeh AM, Tajik P. A novel technique for approximation of
96. Borzi PA, Thomas DF. Cantwell-Ransley epispadias repair in the symphysis pubis in bladder exstrophy without pelvic osteot-
male epispadias and bladder exstrophy. J Urol 1994;151: omy. J Urol 2006;175:6928.
4579. 123. Lee C, Reutter HM, Grsser MF, et al. Gender-associated differ-
97. Ferrer FA, Tadros YE, Gearhart J. Modified Young-Dees-Lead- ences in the psychosocial and developmental outcome in patients
better bladder neck reconstruction: New concepts about old ideas. affected with the bladder exstrophy-epispadias complex. BJU Int
Urology 2001;58:7916. 2006;97:49353.
98. Canning DA, Gearhart JP, Peppas DS, et al. The cephalotrigonal 124. Reiner WG, Gearhart JP, Jeffs R. Psychosexual dysfunction in
reimplant in bladder neck reconstruction for patients with exstro- males with genital anomalies: Late adolescence, Tanner stages IV
phy or epispadias. J Urol 1993;150:1568. to VI. J Am Acad Child Adolesc Psychiatry 1999;38:86572.
58 Bladder and Cloacal Exstrophy 793
125. Reiner WG, Gearhart JP, Kropp B. Suicide and suicidal ideation 143. Sponseller PD, Bisson LJ, Gearhart JP, et al. The anatomy of the
in classic exstrophy. J Urol 2008;180:16614. pelvis in the exstrophy complex. J Bone Joint Surg Am 1995;77:
126. Wilson CJ, Pistrang N, Woodhouse CR, et al. The psychosocial 17789.
impact of bladder exstrophy in adolescence. J Adolesc Health 144. Lund DP, Hendren WH. Cloacal exstrophy: Experience with 20
2007;41:5048. cases. J Pediatr Surg 1993;28:13609.
127. Wilson C, Christie D, Woodhouse CR. The ambitions of adoles- 145. Hesser JW, Murata Y, Swalwell CI. Exstrophy of cloaca with
cents born with exstrophy: a structured survey. BJU Int 2004; omphalocele: Two cases. Am J Obstet Gynecol 1984;150:
94:60712. 10046.
128. Woodhouse CR, Ransley PG, Williams DI. The patient with 146. Howell C, Caldamone A, Snyder H, et al. Optimal management
exstrophy in adult life. Br J Urol 1983;55:6325. of cloacal exstrophy. J Pediatr Surg 1983;18:3659.
129. Woodhouse CR. The management of erectile deformity in adults 147. Hurwitz RS, Manzoni GA, Ransley PG, et al. Cloacal exstrophy:
with exstrophy and epispadias. J Urol 1986;135:9325. A report of 34 cases. J Urol 1987;138:10604.
130. Gobet R, Weber D, Horst M, et al. Long-term followup (37 to 148. Diamond DA, Jeffs RD. Cloacal exstrophy: A 22-year experience.
69 years) in patients with bladder exstrophy treated with ureter- J Urol 1985;133:77982.
osigmoidostomy: Psychosocial and psychosexual outcomes. J Urol 149. Lee RS, Grady R, Joyner B, et al. Can a complete primary repair
2009;182:181923. approach be applied to cloacal exstrophy? J Urol 2006;176:
131. Ricketts S, Hunter-Smith DJ, Coombs CJ. Quality of life after 26438.
penile reconstruction using the radial forearm flap in adult bladder 150. Silver RI, Sponseller PD, Gearhart JP. Staged closure of the pelvis
exstrophy patients - technique and outcomes. ANZ J Surg in cloacal exstrophy: first description of a new approach. J Urol
2011;81:525. 1999;161:2636.
132. Ben-Chaim J, Jeffs RD, Reiner WG, et al. The outcome of 151. Ben-Chaim J, Peppas DS, Spnseller PD, et al. Applications of
patients with classic bladder exstrophy in adult life. J Urol 1996; osteotomy in the cloacal exstrophy patient. J Urol 1995;154:
155:12512. 8657.
133. Gambhir L, Reutter H, Ludwig M. Successful assisted reproduc- 152. Husmann DA, Vandersteen DR, McLorie GA, et al. Urinary
tion in adult males with bladder extrophy-epispadias complex. Eur continence after staged bladder reconstruction for cloacal exstro-
J Obstet Gynecol Reprod Biol 2008;139:25960. phy: The effect of coexisting neurological abnormalities on
134. DHauwers KW, Feitz WF, Kremer JA. Bladder exstrophy and urinary continence. J Urol 1999;161:1598602.
male fertility: pregnancies after ICSI with ejaculated or epididy- 153. Gearhart JP, Mathews R, Taylor S, et al. Combined bladder
mal sperm. Fertil Steril 2008;89:3879. closure and epispadias repair in the reconstruction of bladder
135. Woodhouse CR, Hinsch R. The anatomy and reconstruction of exstrophy. J Urol 1998;160:118290.
the adult female genitalia in classical exstrophy. Br J Urol 1997;79: 154. Mathews R, Jeffs RD, Reiner WG, et al. Cloacal exstrophy
61822. improving the quality of life: The Johns Hopkins experience.
136. Woodhouse CR. The gynaecology of exstrophy. BJU Int 1999; J Urol 1998;160:24526.
83:348. 155. Gearhart JP, Jeffs RD. Techniques to create urinary continence in
137. Ebert AK, Falkert A, Hofstdter A, et al. Pregnancy management the cloacal exstrophy patient. J Urol 1991;146:61618.
in women within the bladder-exstrophy-epispadias complex 156. Mitchell ME, Brito CG, Rink RC. Cloacal exstrophy reconstruc-
(BEEC) after continent urinary diversion. Arch Gynecol Obstet tion for urinary continence. J Urol 1990;144:5548.
2011;284:10436. 157. Reiner WG, Gearhart JP. Discordant sexual identity in some
138. Nikolov A, Markov P, Chanachev S. [Pregnancy and delivery in genetic males with cloacal exstrophy assigned to female sex at
patients with surgically corrected congenital extrophy of the birth. N Engl J Med 2004;350:33341.
bladder, through the operations of the continent urinary deriva- 158. Husmann DA, McLorie GA, Churchill BM, et al. Management
tion]. Akush Ginekol (Sofiia) 2011;50:603. of the hindgut in cloacal exstrophy: Terminal ileostomy versus
139. Rose CH, Rowe TF, Cox SM, et al. Uterine prolapse associated colostomy. J Pediatr Surg 1988;23:110713.
with bladder exstrophy: surgical management and subsequent 159. Georgeson KE, Breaux CW Jr. Outcome and intestinal adaptation
pregnancy. J Matern Fetal Med 2000;9:1502. in neonatal short-bowel syndrome. J Pediatr Surg 1992;27:
140. Spencer R. Exstrophia Splanchnica (Exstrophy of the Cloaca). 34450.
Surgery 1965;57:75166. 160. Figueroa-Colon R, Harris PR, Birdsong E, et al. Impact of intes-
141. Davidoff AM, Hebra A, Balmer D, et al. Management of the tinal lengthening on the nutritional outcome for children with
gastrointestinal tract and nutrition in patients with cloacal exstro- short bowel syndrome. J Pediatr Surg 1996;31:91216.
phy. J Pediatr Surg 1996;31:7713.
142. Warren B. Exstrophy of the Cloaca. In: Ashcraft K, Holder T,
editor. Pediatric Surgery. Philadelphia: W.B. Saunders Co.; 1993.
p. 40212.
C H A P T E R 5 9
Hypospadias
J. Patrick Murphy
Hypospadias is a developmental anomaly characterized The corpus spongiosum is the supportive erectile
by a urethral meatus that opens onto the ventral surface tissue that normally surrounds the urethra and commu-
of the penis, proximal to the end of the glans. The meatus nicates with the erectile tissue of the glans. Bucks fascia
may be located anywhere along the shaft of the penis is the deep layer of fascia that surrounds the corporeal
from the glans to the perineum. bodies and invests the spongiosum. The dorsal neuro
Chordee, which is ventral curvature of the penis, has vascular bundles are deep to this layer. Superficial to this
an inconsistent association with hypospadias. The degree layer is the dartos fascia, which is the loose subcutaneous
of chordee is ultimately more significant in the surgical layer that contains the superficial veins and lymphatics.
treatment of hypospadias than is the initial location These structures form subsequent to completion of the
of the meatus. A subcoronal hypospadias with little or urethra by medial fusion of the outer genital folds, pro-
no chordee is much less complicated to repair than is ceeding from the proximal to the distal aspect of the
one with significant chordee and insufficient ventral penis. This development accounts for how a fully formed
skin. For this reason, when discussing the degrees of urethra can have a poorly formed spongiosum with thin
hypospadias, it is more appropriate to use the clinically overlying skin and ventral tethering, despite the meatus
relevant and common classification system that refers to being located at the tip of the glans. Finally, the prepuce
the meatal location after the chordee has been released is formed, originating at the coronal sulcus. It gradually
(Box 59-1).1 encloses the glans circumferentially.
Arrested development of the urethra may leave the
meatus located anywhere along the ventral surface of the
EMBRYOLOGY penis. Typically, this leads to foreshortening of the ventral
aspect of the penis distal to the meatus and failure of the
Normal phallic development occurs in weeks 7 to 14 of prepuce to form circumferentially. However, in the mega
gestation. By 6 weeks of gestation, the genital tubercle is meatus form of hypospadias, the prepuce may form
formed anterior to the urogenital sinus. In the next week, normally.
two genital folds form caudad to the tubercle and a ure-
thral plate develops between them. Under the influence
of testosterone from the fetal testes, which begins to be HISTORICAL PERSPECTIVE
produced at about 8 weeks of gestation, the inner genital
folds fuse medially to create a tube that communicates The first description of hypospadias and its operative
with the urogenital sinus and runs distally to end at the correction was reported in the 1st and 2nd centuries
base of the glans. The formation of the penile urethra by the Alexandrian surgeons Heliodorus and Antyllus.
is thus generally completed by the end of the first They described the defect of hypospadias and its
trimester.2 relation to problems with urination and ineffective
Classically, the glanular urethra is thought to form as coitus. They further described a surgical treatment con-
an ectodermal ingrowth on the glans. This ingrowth sisting of amputation of the glans distal to the hypospa-
deepens to meet the distal urethra that has formed from diac meatus.5,6
the closure of the endodermal genital folds. The capa- Little progress was made in the surgical treatment of
cious junction of these two structures is the fossa navicu- hypospadias until the 19th century, when two Americans,
laris.3 Recently, this theory has been challenged by the Mettauer and Bush, described using a trocar to establish
endodermal ingrowth theory. It suggests that the entire a channel from the meatus to the glans. Dieffenbach also
urethra forms from the urogenital sinus, which is endo- described a similar technique in the 1830s. None of these
derm. This endoderm differentiates into stratified squa- methods was very successful.5
mous epithelium.4 The formation of the glanular urethra In 1874, Theophile Anger reported the successful
is the last step in the formation of the completed urethra. repair of a penoscrotal hypospadias using the technique
This sequence probably accounts for the predominance described in 1869 by Thiersch for the repair of epispadias
of glanular and coronal hypospadias. in which lateral skin flaps were tubularized to form the
Dorsal to the developing urethra, the paired corporeal neourethra. Angers report initiated the modern era of
bodies develop from mesenchymal tissue. These are the hypospadias surgery characterized by the use of local skin
major erectile tissue components and are invested by the flaps.7,8 Duplay soon described his two-stage technique.6
tunica albuginea. Mesenchyme also forms Bucks fascia, In the first stage, the chordee was released; in the second
the dartos fascia, and corpus spongiosum. stage, a ventral midline strip of skin was covered by
794
59 Hypospadias 795
A B
Objectives of Repair
The objectives of hypospadias correction are divided into
the following categories:
1. Complete straightening of the penis
2. Locating the meatus at the tip of the glans
3. Forming a symmetric, conically shaped glans
4. Constructing a neourethra uniform in caliber
5. Completing a satisfactory cosmetic skin coverage.
FIGURE 59-7 Perineal/scrotal hypospadias (arrow) with severe If these objectives can all be attained, the ultimate goal
chordee and a bifid scrotum. of forming a normal penis for the child with hypospadias
can be accomplished.