Académique Documents
Professionnel Documents
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Management Protocols in
Pediatric Emergency Medicine
Advanced Pediatrics Centre – Postgraduate Institute of Medical Education and Research
Published By
Indian Journal of Pediatrics, New Delhi, India
www.ijppediatricsindia.in
2015
CONTENTS
Initial Assessment and Triage in ER
Approach to a Child with Breathing Difficulty
Acute Community Acquired Pneumonia in Emergency Room
Acute Upper Airway Obstruction
Acute Chest Pain
Approach to a Child with Sore Throat
Acute Bronchial Asthma
Approach to a Child with Lower Airway Obstruction and Bronchiolitis
Airway Foreign Body Aspiration
Fainting Attacks in Children
Non-Traumatic Coma and Altered Mental Status
Approach to Headache in Emergency Department
Management of Acute Seizure and Status Epilepticus in Pediatric Emergency
Raised Intracranial Pressure (ICP): Management in Emergency Department
Approach to a Child with Acute Flaccid Paralysis
Tumor Lysis Syndrome
Superior Mediastinal Syndrome: Emergency Management
Febrile Neutropenia: Outline of Management
Hyperleukocytosis: Emergency Management
Management of a Child with Vomiting
Management of Acute Diarrhea in Emergency Room
Approach to a Child with Upper Gastrointestinal Bleeding
Emergency Management of Lower Gastrointestinal Bleed in Children
Approach to a Child with Bleeding in the Emergency Room
Indian J Pediatr (September 2011) 78(9):1100–1108
DOI 10.1007/s12098-011-0411-3
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 8 May 2011
# Dr. K C Chaudhuri Foundation 2011
Keywords Pediatric triage . Pediatric assessment triangle . Pediatric triage assessment is a rapid 3–5 min evaluation of a
PAT . Pediatric assessment pentagon child that gathers pertinent subjective and objective data to
determine the severity of illness. Pediatric patients who seek
emergency care require timely assessment by experienced
emergency care providers. Also it is particularly important to
triage each child according to the age, symptomatology and
M. Jayashree : S. C. Singhi (*) acuity of illness. What is assigned a high level of acuity differs
Department of Pediatrics, Advanced Pediatrics Centre,
with age and associated symptoms and signs. e.g. abdominal
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India pain or fever <39°C in older child may be non urgent but an
e-mail: sunit.singhi@gmail.com emergency for a one- month- old infant. Once the patients
M. Jayashree are triaged, they are classified into various levels of illness
e-mail: mjshree@hotmail.com acuity and prioritized accordingly.
Indian J Pediatr (September 2011) 78(9):1100–1108 1101
Goals of Triage System [6] Appearance Can be assessed while the child is in mother’s
lap. Look for posture/positioning (sniffing position, or
As the patients present to the ED, the rule of “Rights” have leaning forward on outstretched arm), muscle tone (active,
to be followed: moving or limp and listless), alertness and interaction,
Get the right patient to the right provider, in the right consolability, playful, agitated or crying, look/gaze or
moment of time, to receive the right care, to achieve speech/cry (normal weak, muffed, hoarse). A grossly
the right outcome. abnormal appearance suggests seriously ill child. It could
be due to underlying hypoxemia, poor cerebral perfusion,
1. To rapidly assess and identify patients with life
infection, poisoning, brain injury, hypoglycemia or any
threatening illness.(This initial screening and clas-
metabolic cause. Such patients should be started measure to
sification of the patient frequently determines how
improve oxygenation and perfusion before continuing with
quickly the child will receive medical and nursing
further assessment.
interventions)
2. To determine appropriate cause and initiate first aid
Work of Breathing Look for signs of increased work of
measures by experienced nurse or doctor and order
breathing (nasal flaring, lower chest wall retractions),
immediate investigations and procedures as per the
decreased or absent efforts, abnormal breath sounds
need.
(wheeze, grunt, stridor).
3. Ongoing assessments are to be performed, as
A normal appearance and increased work of breathing
pediatric patients may deteriorate rapidly
indicates a compensated state of respiratory distress, in
4. To provide safe and quality care to patients and to
which oxygenation and ventilation are reasonably well
utilize the limited resources in an efficient manner.
maintained. Abnormal appearance (agitation, restlessness,
lethargy or diminished responsiveness) with increased work
of breathing, on the other hand indicates a state of acute
Triage Assessment hypoxemia and hypercapnia (respiratory failure).
Triage evaluation can be completed in an organized and Circulation Look for abnormal skin color (pale/mottled,
systematic manner using the general assessment i.e. Pediatric cyanosed) or bleeding all over the body. When cardiac
Assessment Triangle (PAT) and primary assessment (ABCDE output is low there is constriction of blood vessels to the
approach) (details are given in triage form). This assessment is skin and blood flow to the skin is minimal. Pallor and/or
different than diagnostic evaluation. The objective here is to mottling are usually the first signs of poor perfusion
identify anatomical or functional abnormality, its severity, to (shock). Cyanosis is a sign of respiratory failure or late
plan and guide initial emergency treatment as summarized in shock. Abnormal circulation with normal appearance
Fig. 1. In the authors’ emergency room, triage assessment and suggests early or compensated shock, while abnormal
management is done by a junior (trainee) resident, well trained appearance and abnormal circulation indicate decompen-
in Pediatric Advanced Life Support (PALS), supported and sated or late shock.
supervised by the on duty senior resident (who is also trained At the end of PAT patient’s illness is categorized as
in PALS). The assessment and treatment go hand in hand. either stable or unstable (Table 1). Unstable conditions are
further classified into life threatening and non life threat-
General Assessment ening. Patients in the former category e.g. cardiac arrest,
cardio-respiratory failure, decompensated shock, deep
PAT is the immediate visual and auditory assessment while the coma, severe stridor etc. need immediate treatment/resusci-
patient is brought in, based on the triad of appearance, tation before going to primary assessment.
breathing and circulation. This initial general impression of
the patient is to be completed in initial 30–40 s. This helps in Primary Assessment
identifying the patients requiring rapid life saving decisions.
Once a child is on the way to stabilization, the primary
assessment (assessment pentagon) follows. It involves the
Appearance Breathing detailed physical examination/assessment of airway (A),
breathing (B), circulation(C), neurologic abnormalities (D)
and head to- toe examination (Exposure). Primary assess-
ment should be completed in 1–3 min. This primary
assessment also involves additional recording of parameters
Circulation like SPO2, EKG and blood glucose.
1102 Indian J Pediatr (September 2011) 78(9):1100–1108
Sick child in ER
Pediatric
Assessment
Triangle
Pediatric
assessment
pentagon
No
Position, suction, oro- Is airway maintained?
pharyngeal airway
No Yes
Yes No
No
Yes
IV access, Fluid bolus, Is Circulation appropriate? Endotracheal intubation
First dose of antibiotic
Yes
No
Adapted and improvised from APLS Pediatric Emergency Manual, 4th edition, American Academy of Pediatrics: 2008: 34
Age range, years Neonate 0–1 1–2 2–3 3–4 4–5 5–6 6–12 12–13 13–18
APLS 30–40 30–40 25–35 25–30 25–30 25–30 20–25 20–25 15–20 15–20
PALSa 30–60 30–60 24–40 24–40 24–40 22–34 22–34 18–30 18–30 12–16
EPLSb 30–40 30–40 26–34 24–30 24–30 24–30 20–24 20–24 12–20 12–20
PHTLS 30–50 20–30 20–30 20–30 20–30 20–30 20–30 (12–20) (12–20) 12–20
ATLS <60 <40 <40 <35 <35 <35 >30 >30 <30
WHOc <60 <50d <40 <40 <40 <40 – – – –
a
PALS and EPLS provide separate ranges for infants up to 3 months, and for those between 3 months and 2 years of age
b
PALS and EPLS provide multiple ranges—ranges for awake children are tabulated
c
WHO has suggested age-specific threshold for tachypnea for children up to 5 years of age to diagnose pneumonia
d
PHTLS provides separate ranges for infants up to 6 weeks, and for those between 7 weeks and 1 year of age
PALS Pediatric Advanced Life Support; EPLS European Pediatric Life Support; APLS Advanced Pediatric Life Support; PHTLS PreHospital
Traumatic Life Support; ATLS Advanced Trauma Life Support; WHO World Health Organization
1104 Indian J Pediatr (September 2011) 78(9):1100–1108
sounds include stridor, grunting, gurgling, wheezing, and one with signs of poor perfusion. Various rhythm disturbances,
crackles. or arrhythmias, can be recognized to initiate appropriate
interventions. The important dysrhythmias to recognize are
Retractions þ stridor ¼ Upper airway obstruction ventricular fibrillation, ventricular tachycardia, pulseless elec-
Retractions þ wheeze ¼ Lower airway obstruction trical activity (PEA), asystole, and supraventricular tachycardia.
Retraction þ Grunt=laboured breathing ¼ Parenchymal disease
Disability Assessment
O2 saturation ≥94% on pulse oximetry at room air suggests
adequate oxygenation. However, it should be interpreted It involves quick evaluation of neurological status: mainly
together with work of breathing. A child may be able to cerebral cortex and the brain stem. Standard evaluation
maintain oxygenation by increasing respiratory rate and work includes level of consciousness using AVPU (awake, voice,
of breathing, but gets exhausted and deteriorates rapidly. Pulse pain, unresponsive) scale, seizure, pupillary response to light
oximetry may show abnormally low SpO2 in presence of poor and posturing and motor activity (asymmetry/abnormal).
peripheral perfusion (shock) or abnormally high SpO2 in a Level of consciousness could also be assessed by applying
distressed child may be seen in methemoglobinemia and CO modified Glasgow Coma Scale (GCS). A change of at least 2
poisoning. Additional interventions are required if O2 satura- points in the GCS score from one assessment to the next
tion is <92% in a child receiving 100% O2 by non-rebreathing indicates a clinically important change in neurological status.
mask.
Exposure
Circulation
Examine whole body for evidence of trauma, unusual
The assessment of cardiovascular function includes heart markings of abuse, rashes, bleeds and core temperature, by
rate and rhythm, blood pressure, peripheral and central pulses, exposing entire body or one body area at a time.
capillary refill time, skin color and temperature. Heart rate After the primary assessment, patient’s physiological
varies according to the child’s age, and includes a wide range status is classified as; stable, respiratory distress or
(Table 3). Typically, the rate will be much slower in a sleeping respiratory failure, shock compensated or decompensated,
or athletic child. Tachycardia is a heart rate faster than expected primary brain/systemic dysfunction, cardiorespiratory fail-
for a child’s age, whereas bradycardia is slower than normal. ure or cardiorespiratory arrest and further triaged into 5
Similarly, blood pressures vary according to age (Table 4). levels (Table 5).
Hypotension is defined as a value below the fifth percentile of
expected blood pressures for age. Hypotension represents a
state of shock, either due to hemorrhage, sepsis, or cardiac Triage Classification [3]
failure. An observed fall of 10 mm Hg in systolic BP from
baseline should prompt serial evaluations for additional signs of Patients’ illness severity is triaged into 5 levels depending on
shock. the physiological abnormalities as given in the Table 5. A
If heart rate is too fast or too slow, immediately attach the simple proforma used for triage in the authors’ emergency
child to a monitor or obtain a three-lead ECG, especially the department is shown in the Appendix.
Age, years Neonate 0–1 1–2 2–3 3–5 5–6 6–10 10–12 12–13 13–18
APLS 110–160 110–160 100–150 95–140 95–140 80–120 80–120 80–120 60–100 60–100
PALSa 85–205 100–190 100–190 60–140 60–140 60–140 60–140 60–100 60–100 60–100
EPLS 85–205 100–180 100–180 60–140 60–140 60–140 60–140 60–100 60–100 60–100
PHTLSb 120–160b 80–140 80–130 80–120 80–120 80–120 (60–80) (60–80) (60–80) 60–100c
>100 >100 100 <100
ATLS <160 <160 <150 <150 <140 <140 <120 <120 <100
a
PALS and EPLS provide separate ranges for infants up to 3 months, and for those between 3 months and 2 years of age
b
PALS and EPLS provide multiple ranges—ranges for awake children are tabulated
c
PHTLS does not provide ranges for adolescents over 16 years of age
PALS Pediatric Advanced Life Support; EPLS European Pediatric Life Support; APLS Advanced Pediatric Life Support; PHTLS PreHospital
Traumatic Life Support; ATLS Advanced Trauma Life Support; WHO World Health Organization
Indian J Pediatr (September 2011) 78(9):1100–1108 1105
Table 4 Expected systolic and diastolic blood pressures according to & Triage evaluation can be completed in an organized
age
and systematic manner using Pediatric Assessment
Age Systolic BP(mmHg) Diastolic BP(mmHg) Triangle (PAT), which refers to immediate visual and
auditory assessment of appearance, breathing and
0 day 60–76 30–45 circulation.
1–4 day 67–84 35–53 & At the end of PAT, patient’s illness is categorized as
1 month 73–94 36–56 either stable or unstable.
3 month 78–103 44–65 & Unstable conditions are further classified into life-
6 month 82–105 46–68 threatening and non life threatening.
1 year 67–104 20–60 & Patients in cardiac arrest, cardio-respiratory failure,
2 year 70–106 25–65 decompensated shock, deep coma, severe stridor etc.
7 year 79–115 38–78 are assessed as having life-threatening illness. They are
15 year 93–131 45–85 in need of immediate resuscitation
& The primary assessment (assessment pentagon), which
Females have slightly lower systolic blood pressures, and higher
diastolic blood pressures than males of the same age.
takes 1–3 min, follows once stabilization measures are
in place. It involves the detailed physical assessment
Adapted from Fourth Report on the diagnosis, evaluation and treatment
of high blood pressure in children and adolescents: NHLBI; May 2004 of airway (A), breathing (B), circulation(C), neuro-
logic abnormalities (D) and head to- toe examination
(Exposure).
Key Points & After the primary assessment, patient’s illness severity
is triaged into 5 levels of acuity based on the
& Triage refers to quick assessment of a patient in the physiological abnormalities: those in need of Resusci-
Emergency Room with a view to define urgency of care tation, Emergent care, Urgent care, Less urgent and
and priorities in management. Non-urgent care.
Level 1 Resuscitation Patient with life- Immediate Cardiac arrest, severe respiratory distress/ Need continuous assessment
threatening disease or and failure, shock,seizure, unresponsive, airway and intervention to maintain
injury requiring continuous obstruction, hypothermia, coma, GCS<10, physiological stability
immediate treatment (1–5 min) major burns, severe trauma,
Level 2 Emergent Patient with significant 15 min Moderate respiratory distress, stridor, GCS< Any infant/child who requires
health problems that 13, Severe dehydration, fever: <3 months multiple interventions to
could become life age: and temp >38°C, inhalation or prevent further deterioration
threatening or ingestion of toxic substance, acute bleeding,
disabling purpuric rash, burns >10%, abdominal pain
with vomiting/diarrhea or abnormal vitals
Level3 Urgent Patient with significant 30 min Alert, oriented, with minor alteration in Level 3 patients need carefully
health problems that vitals. Febrile child >3 months old with planned reassessments while
are not immediately temperature >38.5°C, minor head injury awaiting care, since critical
life threatening or illness may present with
disabling common symptoms and may
evolve rapidly
Level4 Less urgent Patient with stable 1h Diarrhea with no dehydration, lacerations,
conditions; to be pain, sore throat
evaluated in the ED
Level 5 Non urgent Patient with stable health 2 h Afebrile, alert, well oriented, euhydrated, These patients may be referred
conditions; to be normal vitals. to other areas of hospital for
evaluated in ED/OPD management.
Appendix
Indian J Pediatr (September 2011) 78(9):1100–1108 1107
1108 Indian J Pediatr (September 2011) 78(9):1100–1108
Received: 27 January 2011 / Accepted: 8 April 2011 / Published online: 1 June 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Breathing difficulty and respiratory distress is the complications, assessment of response to therapy and rapid
most common cause of admission to the Pediatric Emergen- documentation of clinical state.
cy. Respiratory distress presents as altered breathing pattern,
forced breathing efforts or obstructed breathing, and chest Keywords Respiratory distress . Breathing difficulty .
indrawing; respiratory failure is defined as paCO2 >50 mmHg Respiratory failure . Upper airway obstruction . Lower
(inadequate ventilation) and/or a paO2 <60mmHg (inade- airway obstruction
quate oxygenation). Rapid assessment is aimed to ascertain
adequacy of airway patency, breathing, and circulation.
Immediate care is directed at (a) restoration of airway Introduction
patency- by positioning (head tilt –chin lift), cleaning the
oropharynx, and/or insertion of oropharyngeal airway; (b) Breathing difficulty accounts for a significant proportion of
supporting breathing- with high flow oxygen and assisted childhood visits to the Emergency department. It is one of four
ventilation (with bag and mask or endotracheal intubation cardinal manifestations presenting to the Emergency; the others
and ventilation), and (c) restoration of circulation- using fluid being altered consciousness, seizure, and shock [1]. In the
boluses and inotropes, if necessary. Immediate specific authors’ emergency, respiratory distress is second only to
management may require endotracheal intubation/tracheos- fever as the most common presenting symptom in the
tomy for upper airway obstruction; needle thoracotomy and Emergency [2]. Acute respiratory infection (ARI) is the most
drainage of pneumothorax; and first dose of antibiotic for common diagnosis in secondary and tertiary level health-care
febrile children. Thereafter meticulous history, focused facilities [3, 4]. Early recognition of children at risk of
physical examination, and specific laboratory/radiological respiratory failure and timely initiation of appropriate sup-
investigations are undertaken to identify the underlying portive and specific management can dramatically improve
cause. At the end of this, one should be able to categorize the outcome.
the child to one of the following: (a) upper airway
obstruction, (b) pneumonia (syndrome of cough, fever and
breathing difficulty), (c) lower airway obstruction, (d) slow Definitions
or irregular breathing without pulmonary signs, and (e)
respiratory distress with cardiac findings, to initiate specific Respiratory Distress
treatment. Further respiratory support by Continuous Posi-
tive Airways Pressure (CPAP) and mechanical ventilation Respiratory distress refers to any kind of subjective
may be required in some cases. All children with respiratory difficulty in breathing. Objectively, it manifests as one or
distress must be monitored for early detection of worsening/ more of the following: altered breathing pattern (fast, slow,
feeble or absent), forced breathing efforts or obstructed
J. L. Mathew : S. C. Singhi (*) breathing, and chest indrawing. Respiratory distress is
Department of Pediatrics, Advanced Pediatrics Centre,
defined as a clinical state characterized by increased
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India respiratory rate (tachypnea) and respiratory efforts (in-
e-mail: sunit.singhi@gmail.com creased work of breathing) [5]. In this state the child tries to
Indian J Pediatr (September 2011) 78(9):1118–1126 1119
maintain adequate gas exchange despite a respiratory Normal respiration depends on intact function and coordi-
pathology. If the child tires or respiratory function nation among (a) contraction of intercostal muscles and
deteriorates further and adequate gas exchange cannot be diaphragm and generation of negative intrapleural pressure,
maintained, the child progresses to respiratory failure. (b) expansion of lungs, (c) alveolar gas exchange through
Respiratory distress can range from mild to severe. diffusion, and (d) transport of oxygen through blood. A
When severe, it is often associated with respiratory failure. pathophysiologic approach to causes of respiratory distress is
Table 1 presents the grading of acute respiratory distress. outlined in Table 2.
Respiratory Failure
Approach to a Child with Respiratory Distress
Respiratory failure occurs when pulmonary function is
inadequate to deliver sufficient oxygen to meet demands of Rapidly assess the child, identify the presence of a functional
the body and/or there is inability to eliminate carbon dioxide. derangement, and quantify its severity. This assessment
Arterial blood gas analysis shows paCO2 >50 mmHg determines the urgency with which interventions need to be
(inadequate ventilation) and/or paO2 <60mmHg (inadequate instituted. The exact etiology of breathlessness is less
oxygenation) while breathing 40% oxygen. Clinically respi- important at this time. Specific treatment based on etiology
ratory failure may manifest with central nervous system is considered only after initial stabilization.
(CNS) changes caused by hypoxemia (somnolence or
depressed consciousness, seizures and coma), or hypoxic Initial General Assessment
cardiovascular manifestations such as marked tachycardia or
bradycardia and hypotension (Table 1). The goal is to rapidly assess for (a) airway patency, (b)
adequacy of gas exchange, (c) circulatory status.
Assessment begins with a quick visual and auditory
Pathophysiology evaluation using Pediatric Assessment Triangle [6] and includes
the following (see protocol on Initial assessment and Triage):
The unique anatomic and physiologic characteristics of the
Appearance—interaction, muscle tone, consolability,
respiratory tract in infants and children make them
look/gaze or speech/cry.
especially vulnerable to respiratory distress and failure;
Work of breathing—use of accessory muscles of
hence a systematic approach is vital to improve outcomes.
respiration (increased work of breathing) or absent
respiratory effort, abnormal breath sounds.
Circulation—abnormal skin color (pallor, cyanosis),
Table 1 Grading of acute respiratory distress bleeding.
Mild
Primary Assessment
• Tachypnea
• Dyspnea or shortness of breath
This is done using the Assessment Pentagon, which
Moderate
includes Airway, Breathing, Circulation, Disability and
• Tachypnea Exposure [6].
• Minimal chest wall retractions
• Flaring of alae nasi Airway
Severe
• Marked Tachypnea (> 70 breaths/min) Assessment is aimed at deciding whether the airway is:
• Apneic episodes/bradypnea/irregular breathing
• Lower chest wall retractions Clear—open and unobstructed.
• Head bobbing (use of sternocleidomastoid muscles)
Maintainable—maintained by simple measures like
• Cyanosis
position, suction etc.
Respiratory failure
Not maintainable—needs advanced measures like
intubation
• Respiratory distress + cyanosis or CNS* and/or cardiovascular**
signs of hypoxemia Any audible sound during breathing is suggestive of
*CNS signs of hypoxemia: restlessness, obtunded sensorium, somnolence,
airway obstruction [7].
seizures, coma Stridor is a coarse high pitched sound typically heard on
** Cardiovascular signs of hypoxemia: marked tachycardia, bradycardia, inspiration. It is a sign of (extrathoracic) upper airway
hypotension, and cardiac arrest obstruction.
1120 Indian J Pediatr (September 2011) 78(9):1118–1126
Interference with air flow (entry or exit) Upper airway obstruction Acute laryngitis, laryngotracheitis, diphtheria,
foreign body aspiration.
Lower airway obstruction Bronchiolitis, asthma
Mechanical compression Large pleural effusion, pneumothorax, tumors
and elevated dome(s) of diaphragm
Thoracic wall injuries Hemopneumothorax and flail chest.
Interference with alveolar gas exchange Failure of alveolar ventilation Pneumonia, pulmonary edema, pulmonary
hemorrhage, pulmonary fibrosis.
Failure of diffusion Pneumonia, pulmonary edema, pulmonary
fibrosis, pulmonary embolism, interstitial
lung disease
Cardiovascular problems Mechanical or inadequate function Congestive cardiac failure, arrhythmias,
myocarditis, pericarditis, Right-to-left shunts
Nervous system disturbance Depression of respiratory centre Impaired consciousness, raised intracranial
pressure, intracranial bleeding,poisoning
Stimulation of respiratory center Acidosis, salicylate intoxication.
Neuromuscular impairment of respiration Acute paralytic poliomyelitis, Guillain-Barre
syndrome, organophosphate poisoning,
snake bite, diaphragmatic paralysis.
Other Insufficient oxygen supply to tissues Sepsis, severe anemia, high altitude, carbon
and/or increased oxygen demands monoxide exposure, smoke inhalation,
meth-hemoglobinemia
Compensation for metabolic acidosis. Diabetic ketoacidosis, acute renal failure.
Wheezing is a whistling sound heard most often which is inappropriate for the clinical situation (relative
during expiration, indicating lower (intrathoracic) airway bradypnea) indicates advanced respiratory failure. In
obstruction. cardiorespiratory disorders, tachypnea is accompanied by
Grunting is typically a short, low pitched sound heard increased work of breathing. Accessory muscles of
during expiration, produced by forced expiration against a respiration are recruited, which manifests as supraclavicular,
partially closed glottis. It is an attempt to keep small suprasternal, intercostal, or subcostal retractions, nasal
airways and alveoli open to maintain oxygenation and flaring and sometimes head bobbing. See-saw respirations
ventilation. It is typically a sign of severe respiratory (abdominal breathing), is seen in neuromuscular weakness,
distress progressing to respiratory failure. At times, grunt- but can also occur in the late stages of severe respiratory
ing may accompany high fever or severe pain (often pathology.
abdominal pain), even in the absence of significant CNS disorders may result in respiratory failure
respiratory pathology. through hypoventilation. Respiration in these patients
could be too slow (bradypnea) or absent (apnea). and is
Breathing always ominous.
Normal spontaneous ventilation is quiet and effortless, and Pulse Oximetry After evaluation for triage, all children with
maintains a steady tidal volume and rate. Adequacy of tidal signs of respiratory illness should have a pulse oximetry. It
volume is assessed clinically by observation of chest wall measures percentage of hemoglobin saturated with oxygen
excursion and auscultation of the lungs. In pathological and is the best non-invasive method for early detection of
states, one of the first compensatory mechanisms is increased hypoxemia. Hypoxemia occurs frequently and is strongly
respiratory rate (tachypnea) to maintain oxygenation/CO2 associated with mortality. It is not a sine qua non of
removal. Thus, respiratory rate is also a good predictor of pneumonia (and occurs in many lower airway diseases, and
hypoxemia [8]. When the body is unable to sustain increased some upper airway problems) and may not be predictable
respiratory rate, respiratory muscle fatigue sets in, and tidal clinically [9]. Low oxygen saturation (hypoxemia) may be
volume starts falling. The respiratory rate may fall at this detected much before the appearance of cyanosis. Oximetry
stage; therefore an apparently ‘normal’ respiratory rate is unreliable in states of poor distal perfusion, abnormal
Indian J Pediatr (September 2011) 78(9):1118–1126 1121
hemoglobin, and when the heart rate displayed by the In a sick child, irrespective of the original underlying
monitor does not correlate with the clinical heart rate. illness, life is endangered because of respiratory or cardio-
vascular dysfunction. Therefore, at the end of initial assess-
ment, one should be able to categorize the child’s functional
Circulation derangement into a primarily respiratory or a primarily
circulatory problem or both; with further categorization of
Assessment of circulation includes evaluation of cardio- the severity of the derangement. Such a categorization helps to
vascular function (pulse, heart rate and blood pressure) decide the urgency with which intervention is required.
and end organ perfusion. Heart rate should be appropriate
for the child’s age, level of activity, and clinical condition. Assessment Severity
Tachycardia is a common, nonspecific response to a variety
of underlying conditions, but it could be the first sign of Respiratory problem Respiratory distress
compensated shock. Bradycardia, when associated with Respiratory failure
other signs of decreased perfusion, most commonly indi- Circulatory problem Compensated shock
cates hypoxia, and is an ominous sign demanding urgent Hypotensive shock
action.
It includes undressing the child for a focused physical Ensure Breathing/Respiration if spontaneous normal
examination, looking for evidence of trauma, petechiae/ breathing is absent/inadequate by:
purpura and warming if indicated.
(a) Assisted ventilation by bag and mask ventilation, (b)
Endotracheal intubation as soon as adequate expertise and
Categorization of Severity of the Clinical Condition equipment are available, (c) Providing oxygen. Never delay
resuscitation for lack of equipment or trained personnel.
Life Threatening Conditions Oxygen can be effectively provided to children of all
ages by nasal prongs of appropriate size. A flow rate of
If at any point during the assessment, a life threatening 0.5–1.0 l/min is used for infants and 1-2 l/min for older
condition is identified (Table 3), appropriate interventions are children. This will provide 30–35% oxygen if the source in
instituted, before proceeding with the rest of the assessment. unblended 100% oxygen.
1122 Indian J Pediatr (September 2011) 78(9):1118–1126
Oxygen can also be delivered by intranasal catheter at a antibiotic [13]. Appropriate choice of antibiotic for suspected
flow rate of 1-3 l/min; it should be inserted to half the severe pneumonia includes Ampicillin (100 mg/kg) and
distance between the tip of nose and the tip of ear. Oxygen Gentamicin (7.5 mg/kg/d single dose) for young infants;
tent, face mask, or head-box can deliver higher concentra- and Ceftriaxone (100 mg/kg/day in two divided doses) for
tion of oxygen. Humidification of inspired air/oxygen can older children/adolescents. If Staphylococcus aureus infection
be achieved using humidifier, heated water bath, or by is suspected (retropharyngeal abscess, bacterial tracheitis,
nebulization. However, there is no evidence supporting severe malnourished state, post-measles state, suspected
need for routine humidification of O2 at flows ≤4 l/min immuno-compromised state, or multiple pustules/furuncles),
Nasal prongs are the recommended way of providing Cloxacillin (100 mg/kg) should be added [14].
oxygen to most children. However, There is no significant
difference in oxygen administration by nasal prongs or Subsequent Management
nasopharyngeal catheters [11]; in fact all low-flow methods
are effective [12]. For older children, oxygen is best given If pneumothorax is suspected/detected, proceed with
by a face-mask. The ventury masks usually provide 25– needle thoracotomy in the second intercostal space under
40% oxygen. Some masks may provide upto 50% oxygen water seal (using a syringe with saline), followed by
in inspired air at a flow rate of 8–10 l/min, while >80% intercostal drainage.
oxygen concentration can be achieved in a head-box. Figure 1 outlines the management steps in a child with
Table 4 shows common oxygen delivery devices and acute respiratory distress. Once a clinical diagnosis is
delivered oxygen concentration at given flow rates. evident, specific protocols are described later for managing
each clinical condition.
Endotracheal Intubation is indicated in severe respiratory
distress, cyanosis or impending respiratory failure. Table 5
shows approximate size of endotracheal tube—length and Diagnostic Evaluation
diameter—for different ages.
Once life-saving and life-supportive therapeutic interventions
Ensure Circulation have been instituted, establish the diagnosis for further
specific therapy. The goal is to identify the cause of respiratory
If the patient is in shock, or has signs of severe sepsis, initiate distress. Evaluation consists of meticulous history-taking;
septic shock protocol [13]. Establish intravenous access and including Signs and symptoms, Allergies, Medications, Past
initiate infusion of a saline bolus (20 ml/kg). If venous access medical history, Last meal, and Events leading to the present
is not feasible, consider intraosseous infusion in young illness (mnemonic SAMPLE from PALS Guidelines). This
children [10]. The first dose of an appropriate antibiotic for should be followed by focused physical examination.
severe infections, including severe respiratory infections, Thereafter, laboratory and radiological support may be
must be administered without delay [13]. It is advisable to required. Table 6 highlights the essential components of
obtain a blood sample for culture prior to administering Diagnostic evaluation.
Table 4 Common Oxygen delivery devices and delivered oxygen Common Causes
concentration (FiO2) at given flow rates
Children who present with breathlessness are likely to be
FiO2 Device (Flow rate/min)
suffering from respiratory, cardiac or metabolic conditions.
25–50% Nasal cannula (1–6 L) Common respiratory causes include lower airway problems
35–65% Simple Face mask (6–12 L)
including pneumonia, parapneumonic effusions/empyema,
24–60% Graded Ventury mask (graded 4–12 L)
bronchial asthma; and upper airway conditions such as
60–80% Oxyhood (10–15 L)
croup, airway obstruction, and congenital airway anoma-
lies. Conditions outside the respiratory tract such as
>90% Non rebreathing masks (10–12 L)
congestive cardiac failure, neuro-muscular weakness,
Indian J Pediatr (September 2011) 78(9):1118–1126 1123
Table 5 Guidelines to approximate size of endotracheal tube (ETT)- length and diameter, laryngoscope, and suction catheter sizes required at
different ages
severe anemia, severe metabolic acidosis etc. can also (viral or acute rheumatic carditis). In either situation, other
result in clinical features of respiratory distress [15, 16]. physical findings, like disproportionate tachycardia, soft
Behavioural problems (psychological problems, drugs muffled heart sounds, cardiac murmurs, cardiomegaly,
addiction, multiple trauma) among adolescents are also hepatomegaly, raised JVP, basal crackles and occasionally,
significant causes [17]. the presence of edema may provide valuable clues.
When a breathless infant or child is found to be in shock,
Neurological Illnesses breathlessness could be due to hypoxia or metabolic acidosis,
whatever the etiology of shock. However, when the clinical
Though neurological illnesses can lead to ‘breathlessness’, features suggest cardiogenic or obstructive shock, especially
it is unlikely to be the only or chief complaint. Whether the in a young neonate, duct dependent lesions like critical
neurological illness is acute (head injury, encephalitis, coarctation or critical stenosis should be suspected (besides
meningitis), subacute or chronic (Guillian Barre syndrome, other cardiac causes) and rapidly investigated. Such patients
spinal muscular atrophy) there is usually a prominent may appear mottled, ashen and gray.
history of the initiating/primary events which suggest the When a breathless patient is cyanosed, the first step is to
possible cause. Hypo- or hyperventilation could be the end differentiate central from peripheral cyanosis. The latter is
result of progressive cardio-respiratory pathology as well. simply an indicator of poor peripheral perfusion. Central
Similarly, though see-saw respiration is classically seen in cyanosis could be either respiratory or cardiac in origin. A
neuromuscular weakness, it could be seen as a preterminal past history of cyanotic spells is useful. Deep cyanosis is
event in any severe respiratory pathology. usually cardiac or due to methemoglobinemia. Respiratory
pathologies usually present with milder cynosis. However,
Cardiac Causes mild cyanosis could also be cardiac in origin; helpful clues
to a cardiac cause are findings suggestive of cardiac failure.
Detection of cardiac failure, shock, or cyanosis may The presence and severity of respiratory distress may not
suggest a cardiac cause of breathlessness. Usually, when help in differentiating respiratory from cardiac causes.
cardiac failure presents as breathlessness, the complaint is
subacute/chronic and progressive. There could be a history Metabolic Causes
of diagnosed heart disease, or a history of feeding difficulty
(suck-rest-suck cycle). Less commonly, cardiac failure may When children manifest with tachypnea that is not
present as acute onset breathlessness as in myocarditis accompanied by increased work of breathing and clear
1124 Indian J Pediatr (September 2011) 78(9):1118–1126
Pediatric
Assessment
Triangle
Pediatric
assessment
pentagon
Secure airway
Start oxygen
Ensure breathing
Restore circulation
No
No
No
Specific Investigations
Specific Management
Fig. 1 Approach to a child with breathing difficulty. (UAO = upper airway obstruction, CNS = Central Nervous System)
chest on auscultation, a metabolic cause should be Sometimes inborn errors of metabolism could present in
suspected. The common cause of such ‘breathlessness’ are a similar fashion, but other equally prominent accompa-
metabolic acidosis accompanying poor perfusion states nying symptoms such as vomiting, convulsion etc. are
(shock); or chronic renal disease or diabetic ketoacidosis. common.
Indian J Pediatr (September 2011) 78(9):1118–1126 1125
Table 6 Diagnostic evaluation of respiratory distress 1. Upper airway obstruction-(a child with stridor)—needs
A. History urgent endotracheal intubation or tracheostomy
• Acute, recurrent or chronic and nature of progression. 2. Cough, fever and breathing difficulty/(Pneumonia)
• Associated symptoms: cough, fever, rash, chest pain
3. Lower airway obstruction-(Wheezing child)—Anti-in-
• Preceeding events:choking,foreign body inhalation, trauma/
flammatory therapy (corticosteroids) and β2 agonists.
accident, and exposure to chemical or environmental irritants. 4. Slow or irregular breathing without any pulmonary
• Family history: exposure to infections, tuberculosis, atopy. signs—Needs mechanical ventilation
B. Physical Examination 5. Respiratory distress with cardiac findings.
• Assess stability of the airways, and ventilatory status. Each of these clinical profiles is detailed separately in
⋄ Respiratory rate (counted for a full minute), rhythm, depth and later sections.
work of breathing.
⋄ Color, level of activity and playfulness.
⋄ Chest movements, indrawing of chest wall
Specific Respiratory Support
⋄ Stridor (suggests upper airway obstruction)
⋄ Wheezing (suggests lower airway obstruction) If adequate oxygenation is not achieved after establishing
⋄ Grunting (suggests alveolar disease causing loss of functional airway patency, administration of supplemental oxygen and
residual capacity)
specific bronchodilator therapy, wherever applicable, consider
• Tracheal position
using CPAP and mechanical ventilation
• Segmental percussion
• Auscultation:
Continuous Positive Airways Pressure (CPAP)
Air entry, type of breath sounds, wheeze, rhonchi, crepitations
• Clubbing, lymphadenopathy
CPAP mechanically prevents airway closure and maintains
• Assessment of CVS and CNS
alveolar patency at the end of expiration in a spontaneously
C. Diagnostic Work-up
breathing child. With CPAP a continuous flow of warmed,
• Direct laryngoscopy, if upper airway obstruction is detected/
humidified oxygen or mixed oxygen/air is provided via
suspected
nasal prongs. The continuous flow creates a positive
• X-rays: chest, lateral neck, and decubitus views
pressure when the child breathes out. This helps to prevent
• Arterial blood gas analysis for hypoxemia (paO2 <60 mm Hg),
hypercarbia (paCO2 >40 mm Hg), (acidosis pH<7.3), alkalosis alveolar collapse and reduces work of breathing. CPAP is
(pH>7.5, and SaO2 monitoring given via nasal prongs with a special CPAP circuit. CPAP
• Sepsis work-up; Blood counts and culture studies facility can be established in the emergency room after
naso-pharyngeal intubation, or endotracheal tube with T-
piece. A bubble CPAP circuit is used with an underwater
pipe coming off the oxygen supply line to the nasal prongs
Indications for Urgent X-ray
or a special nose piece is used (a flow driver). Face masks
may be ineffective in providing CPAP due to inadequate
In general, management of respiratory distress does not
require an immediate chest radiograph; most conditions are
apparent clinically and waiting for radiography to initiate
Table 7 Monitoring protocol
treatment can waste precious time [18, 19]. However, in
cases of suspected pneumothorax, pleural effusion, media- • Rate, rhythm and depth of respiration.
stinitis/pneumomediastinum [20] and traumatic chest-wall • Heart rate
injuries, radiography may guide appropriate management. • Blood pressure
Upper airway obstruction by foreign body aspiration, • Temperature
epiglottitis, retropharyngeal abscess may also require • Presence/absence of cyanosis
radiographic confirmation prior to invasive interventions • Use of accessory muscles, flaring of alae nasi and chest wall
[21]. retractions, and the degree of distress.
• Air entry in both lungs. In case an endotracheal tube has been
passed, check its position and patency and need for suction.
Differential Diagnosis • Signs of exhaustion such as somnolence, confusion, and seizures.
• Non-invasive monitoring: Oxygen saturation (pulse oximetery) and
if available End tidal CO2 (EtCO2).
Following the detailed clinical evaluation described above,
• Arterial blood gas (ABG). This must be interpreted together with the
it would be possible to categorize respiratory distress into
clinical data of the patient.
the following groups for further specific management:
1126 Indian J Pediatr (September 2011) 78(9):1118–1126
sealing and additional risk of pressure necrosis of eyes and wheezing illness) or cardiovascular system or central
face. CPAP (usually between 5–10 cm H2O) must be nervous system.
applied by an experienced person trained in using the & Chest x-ray is not mandatory in the initial stage for the
circuit. At higher CPAP (>10 cm H2O) cardiac output may most cases.
get compromised. & Specific investigations and treatment should be based
on the likely cause identified on clinical evaluation.
Mechanical Ventilation
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 4 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Community acquired pneumonia is the leading amoxicillin for 5 more days; if not, it is treated as very
killer of children under the age of 5 years. In ER, a severe pneumonia. Very severe pneumonia is treated with
diagnosis of pneumonia may be made and the severity injectable Ampicillin plus gentamicin. If improved after
graded on basis of WHO’s classification for pneumonia in 48 h, oral amoxicillin and gentamicin are continued for
children up to 5 years of age. It relies on age-specific 10 days. If not, respiratory support is enhanced, antibiotics
respiratory rate, presence of lower chest indrawing and are changed to intravenous ceftriaxone and amikacin and
signs of severe illness. A diagnosis of pneumonia is made if further work up is planned. Children with chronic diseases
a febrile child has history of cough and difficult or rapid and recurrent pneumonia require specific antibiotics
breathing and a respiratory rate above age specific depending on the underlying cause.
threshold; however, signs of airway obstruction should be
ruled out. Severe pneumonia is diagnosed if with the above Keywords Community acquired pneumonia . Children .
features lower chest wall retraction is present; nonetheless, Severe pneumonia . Very severe pneumonia . Antibiotic
all infants below 2 months and children with moderate to therapy
severe malnutrition with pneumonia are categorized as
having severe pneumonia. A chest radiograph is indicated
only if the diagnosis is in doubt; complications are Introduction
suspected and there is severe/very severe or recurrent
pneumonia. Non-severe pneumonia is treated at home with Pneumonia is the leading killer of children, causing an
oral amoxicillin for 3–5 days. If there is no improvement in estimated 1.9 million deaths worldwide under the age of
48 h it is changed to amoxicillin-clavulanate. Azithromycin 5 years. About 90% of these deaths occur in the developing
is added for atypical pneumonia. Indications for hospital- world [1]. Pneumonia is an inflammation of the parenchyma
ization include age <2 months, treatment failure on oral of the lungs. Although most cases of pneumonia are caused
antibiotics, severe/very severe or recurrent pneumonia, by micro-organisms, noninfectious causes include aspiration
shock, hypoxemia, severe malnutrition, immunocompro- of food or gastric acid, foreign bodies, hydrocarbons, and
mised state. Severe pneumonia is treated with injectable lipoid substances, hypersensitivity reactions, and drug or
ampicillin; Cloxacillin is added if clinical/radiographic radiation-induced pneumonitis.
features suggest Staphylococcal infection. On review after In developed countries, the diagnosis is usually made on
48 h, if improved, the child may be sent home on oral the basis of radiographic findings. The World Health
Organization (WHO) has defined pneumonia solely on the
basis of clinical findings obtained by visual inspection and
counting the respiratory rate, for developing countries.
P. S. Dekate : J. L. Mathew : M. Jayashree : S. C. Singhi (*) Table 1 shows the age-specific criteria used to define
Department of Pediatrics, Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
pneumonia. The clinical features of pneumonia include
Chandigarh 160012, India cough, increased respiratory rate, chest indrawing, stridor
e-mail: sunit.singhi@gmail.com and altered sensorium.
1128 Indian J Pediatr (September 2011) 78(9):1127–1135
Table 1 WHO age specific criteria for tachypnea [1] & Nonspecific complaints, such as irritability or poor
Age Approximate normal respiratory Tachypnea threshold feeding may be the presenting symptoms
rate (breaths/min) (breaths/min) & Cyanosis may be present in severe cases
& Chlamydia trachomatis pneumonia should be consid-
2–12 months 25–40 50 ered in infants aged 2–4 wks and is often associated
1–5 years 20–30 40 with conjunctivitis.
>5 years 15–25 30
Infants
The etiology of infective pneumonia in children, based on a & After the first month of life, cough is the most common
series of research studies in India [2–6] is given in Table 2. presenting symptom.
& Infants may have a history of antecedent upper
respiratory symptoms.
Approach to a Child with Pneumonia & Depending upon the degree of illness, tachypnea,
grunting, and retractions may be noted.
Presentation & Vomiting, poor feeding, and irritability are also common.
& Infants with bacterial pneumonia often are febrile, but
Any patient presenting with cough and difficult or rapid those with viral or atypical pneumonia may have low-
breathing should be considered as a case of pneumonia [1]. grade fever or could be afebrile.
Table 1 summarizes the normal respiratory rates and & Wheezing or noisy breathing. Wheeze suggests a viral
tachypnea thresholds in children of different age groups. cause.
Other symptoms may be present along with respiratory
symptoms. However, this should be differentiated from other Toddlers and Preschool Children
common respiratory illnesses such as asthma, bronchiolitis
and upper airway infections. In children, the etiologic agent, & A history of antecedent upper respiratory illness is
age of the patient, and underlying illnesses/clinical state, all common.
affect the clinical features of the illness. & Cough is the most common presenting symptom.
& The presence and degree of fever is dependent upon the
Neonates organism involved.
& Vomiting, particularly post-tussive, may be present.
& Neonates present with tachypnea, and signs of respira- & Chest pain may be observed with inflammation of or
tory distress such as grunting, flaring and retractions. near the pleura.
& Fever and cough may be absent; however hypothermia & Abdominal pain or tenderness is often seen in children
and temperature instability may be observed. with lower lobe pneumonia.
Neonates Group B streptococcus, Escherichia coli, other gram-negative bacilli cytomegalo virus.
(<1 month) Streptococcus pneumoniae, Haemophilus influenzae (type b) are uncommon
1–3 months
Febrile Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H.
pneumonia influenzae (type b)
Afebrile Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, cytomegalovirus
pneumonia
3–12 months Respiratory syncytial virus, other respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H.
influenzae (type b), C.trachomatis, Mycoplasma pneumoniae, Group A streptococcus, Staph. aureus
2–5 years Respiratory viruses (parainfluenza viruses, influenza viruses, adenoviruses), S. pneumoniae, H. influenzae (type b), Staph. aureus
M. pneumoniae, C. pneumoniae, group A streptococcus
5–18 years M. pneumoniae, S. pneumoniae, C. pneumoniae, H. influenzae (type b), influenza viruses, adenoviruses, other respiratory viruses
Indian J Pediatr (September 2011) 78(9):1127–1135 1129
Older Children and Adolescents Table 3 WHO criteria for severity assessment child age 2 months to
5 years [1]
& Atypical organisms, such as Mycoplasma are common Severity classification Clinical features
in this age group.
& In addition to the symptoms observed in younger Very severe pneumonia Not able to drink
children, adolescents may have other constitutional Convulsion
symptoms, such as headache, pleuritic chest pain, and Abnormally sleepy or difficult to awake
vague abdominal pain. Headache, fever and myalgia are Severe malnutrition
associated with M. pneumoniae. Central cyanosis
& Vomiting, diarrhea, pharyngitis, and otalgia/otitis are Severe pneumonia Lower chest indrawing
also common symptoms. Grunting
Cyanosis
Pneumonia (not severe) Fast breathing (>age specific threshold)
Assess for Contributing Etiology
No chest in-drawings
Cough and cold (no No fast breathing
The following history and examination should try to elicit pneumonia) No chest in-drawings
important information about the etiology:
& Contact with person(s) having respiratory infection
& Possibility of foreign body aspiration with symptoms suggestive of pneumonia has severe
& Possibility of primary aspiration pneumonia, There is no validated criteria for severity
& Stools consistent with malabsorption (may suggest assessment in children >5 years. In this age group,
cystic fibrosis) pneumonia is considered severe if the following features
& Sinusitis (of severe respiratory distress) are present. It is subjective
& Asthma and determined by same parameters as mentioned above.
& Growth and nutritional status
& Dysmorphic syndromes & Respiratory rate >30/min
& Neuromuscular weakness & Chest wall retraction
& Cardiac failure & Use of accessory muscles of respiration
& Altered sensorium
Risk Factors
Investigations
The risk factors for the development of community
acquired pneumonia [7, 8] include malnourished state, i. Chest radiography (CXR): Chest radiographs are not
young age (<6 months), post-measles state, absence of (or needed routinely in all children with suspected pneu-
inadequate) breastfeeding, and solid fuel use. The pointers monia. Specific indications include:
towards hospital acquired infection/pneumonia [9] include 1. When the diagnosis is in doubt (bronchiolitis,
hospitalization for ≥48 h, broad spectrum antibiotic therapy asthma, developmental malformation, foreign body
for ≥7 days in the preceding 30 days, immunosuppressive inhalation, aspiration pneumonia etc.)
therapy including glucocorticoid therapy, neutropenia and 2. Asymmetrical findings on chest examination
severe structural lung disease. 3. Suspected complications of pneumonia (pleural
effusion, empyema, lung abscess etc.)
Severity Assessment 4. Known case of recurrent chest infection (asthma,
cystic fibrosis, immunodeficiency etc.)
Any infant with age ≤2 months with symptoms suggestive 5. Severe and very severe pneumonia
of pneumonia should be considered as having severe Findings to be looked for in chest radiograph include:
pneumonia. Such a child needs immediate hospitalization
& Parenchymal infiltrates (evidence of consolidation)
[1, 5]. Tachypnea (respiratory rate >60/min) in this age
& Features of atypical pneumonia (bilateral streaky infiltrate)
group is often associated with hypoxemia [10] and it is
& Presence of pneumatocele
important to note severity of pneumonia in children from
& Any evidence of foreign body inhalation
2 months to 5 years. The WHO criteria for severity of
& Pleural spaces for pneumothorax, effusion
pneumonia in this age group are shown in Table 3. A child
with protein energy malnutrition or lower chest indrawing Figure 1 shows some characteristic chest radiographs.
1130 Indian J Pediatr (September 2011) 78(9):1127–1135
C D
ii. Arterial blood gas (ABG): The indications are: & First dose of antibiotic as early as possible; preferably after
obtaining a sample for blood culture. However, adminis-
1. Severe and very severe pneumonia
tration of the first dose should not be delayed for this.
2. Hypoxemia on pulse oxymetry (SpO2 <94% on
& Hydration (intravenous or nasogastric tube feed)
40% oxygen), cyanosis
3. Shock i. If child is accepting orally well—allow orally (ad
libitum)
ii. If not accepting well orally (but feeding not
Baseline Stabilization contraindicated)—Nasogastric or orogastric feed
can be started
& A-Airway assessment iii. Start 0.45 Saline in 5% dextrose as 2/3rd to 3/4th
& B-Breathing maintenance if there is respiratory distress (where
& C-Circulation feed cannot be started) or underlying dehydration
& Resuscitation if required as per the Pediatric Assess- or ongoing losses through vomiting etc.
ment Triangle and Primary Assessment & Treatment of other emergent co-morbidities
& O2 inhalation by nasal prongs, at flow rate 1–5 l/min i. Hypoglycemia
(depending on age) if child has lower chest wall ii. Electrolyte imbalance
indrawing or SpO2 ≤92%. Oxygen can be effectively
delivered by any low-flow delivery method [11];
Hospitalization
therefore the specific delivery device (nasal prongs,
face mask, nasal catheters etc.) are more a matter of
The indications for hospitalization are:
personal/institutional choice. For more details, please
see the Protocol on Acute respiratory Distress. & Age <2 months
Indian J Pediatr (September 2011) 78(9):1127–1135 1131
& Severe and very severe pneumonia (as per WHO Treatment of Non-severe Pneumonia (at home) [14–17]
definition)
& Signs of shock & Non-severe pneumonia can be treated at home with oral
& Hypoxemia (requirement for supplemental oxygen) antibiotics in most cases.
& Moderate to severe malnutrition [12] because it & Amoxicillin (50 mg/Kg/day) in 2 divided doses for 3–
increases the risk of mortality 5 days
& Recurrent chest infection (cardiopulmonary disease, & Advise to return immediately if the child develops
anatomical defects in airway, neurological disease) lower chest indrawing, is unable to drink/feed, is
& Immunocompromised state excessively sleepy or sick looking.
& Not accepting orally, dehydration, vomiting & Follow-up after 2 days
& No response or increased severity (treatment failure) on
○ Check the child for general danger signs such as
appropriate oral antibiotic therapy
inability to suck/drink, impaired sensorium, convul-
& Family unable to provide appropriate care at home.
sions, grunting, cyanosis.
○ Assess the child for cough and difficult breathing
Other Investigations in Hospitalized Patients ○ Ask: Is the child breathing slower? Is there less
fever? Is the child eating better?
& Hemogram with total and differential leukocyte count ○ If the answer to above questions is Yes, complete 3–
& Serum electrolytes and renal function test 5 days of amoxicillin
& Blood culture: These are positive in 10%–20% of ○ If the child has persistent raised respiratory rate but
children with pneumonia no indication for admission, change to Amoxicillin-
& Other diagnostic investigations: clavulanic acid (80–90 mg/kg of amoxicillin) in 2
divided doses for 5 days or add Azithromycin 5 mg/kg
In atypical pneumonia: Serology—RSV, Mycoplasma,
for 5 days if clinical and radiological features suggest
Chlamydia
atypical pneumonia. Cloramphenicol is a less desirable
CMV serology (if suspected like immune-compromised
second line agent for non severe pneumonia because of
and TORCH group of infection)
its potential for bone marrow toxicity.
& Atypical H1N1 (swine flu) testing during epidemics ○ If lower chest indrawing or a general danger sign
& CSF (if feasible) in case of appears, hospitalize urgently for treatment as severe/
i. Newborns very severe pneumonia
ii. Infants presenting with altered sensorium
iii. Seizures Treatment Failure in Non-severe Pneumonia (Table 4)
radiographic features (pneumatoceles, necrotizing pneu- & Ampicillin: 100–200 mg/kg/day IV q 6 hourly (maxi-
monia) suggest Staphylococcal infection. mum dose 12 gm/day)
& Assess and monitor for oral intake/feeding, respiratory & Amoxicillin: Standard dose 50/kg/day oral in 2 divided
rate, chest indrawing, and oxygenation (by pulse doses
oximetry) .
▪ High dose 80–90 mg/kg/day oral in 2 divided doses
& If at any time danger signs of very severe pneumonia
develop treat as very severe pneumonia & Gentamicin: 7.5 mg/kg/doe IV q 24 hourly
& After 48 h—if improved: continue: on oral amoxicillin & Ceftriaxone: 80–100 mg/kg/day IV q 12 hourly (max-
for 5 more days, if not improved in 48 h/deteriorated: imum dose 4 g/day)
treat as very severe pneumonia & Amikacin: 15 mg/kg/dose IV q 24 hourly (maximum
dose 1.5 g/day)
& Cefotaxime: 100–200 mg/kg/day IV q 8 hourly or 6
Very Severe Pneumonia
hourly (maximum dose 12 g/day)
& Cefoperazone + sulbactum: 100–150 mg/kg/day (of
Children with very severe pneumonia require immediate
cefoperazone) IV q 8 hourly (maximum dose 12 g/day)
hospitalization, oxygen, injectable ampicillin plus gentamicin,
& Cloxacillin: 100–200 mg/kg/day IV q 6 hourly (maxi-
and chest radiograph. The protocols for treatment of Very
mum dose 4 g/day)
severe pneumonia [18] and Pneumonia in infants ≤2 months
& Vancomycin: 40–60 mg/kg/day IV q 6–8 hourly (max-
are shown in Figs. 2 and 3, respectively.
imum dose 2 g/day)
& Cefoperazone + sulbactum: 100–150 mg/kg/day (of
Special Situation cefoperazone) IV q 8 hourly
& Piperacillin + tazobactum: 200–300 mg/kg/day (of
& Cystic fibrosis piperacillin) IV q 6–8 hourly
○ Start Anti-staphylococcal and anti-Pseudomonal & Meropenem: 60–120 mg/kg/day IV q 8 hourly (maxi-
antibiotics in combination mum dose 6 g/day)
& Aspiration pneumonia
○ Start Crystalline Penicillin or Metronidazole
Work up Plan in Non-responders
Improving #
#
Improvement involves (3, 4) $
Discharge criteria
* Assessment involves
1. Afebrile • Accepting orally well and normal
• RR 2. ↓ RR ≥10/min within 48h
• Retraction 3. ↓ Retraction within 72 h sensorium
• Saturation 4. Saturation >92%
• General well being • Afebrile for at least 48 h
5. Improved general well being
• Oral acceptance 6. Improved oral acceptance • No oxygen requirement for at least 48 h
• Completed IV antibiotics
& Consider hospital acquired infection ○ Fungal culture and serology (in immuno-compromised
& Consider further work up children)
○ Pleural fluid examination
○ Tuberculosis work up
Indications for PICU Transfer
▪ Mantoux test
▪ Gastric aspirate for AFB
At any stage, the following should be considered for
▪ Family screening
transfer to ICU:
▪ Sputum examination if possible
○ Cystic fibrosis work up & Very severe pneumonia
○ GER scan (if suspected GERD) & Hypoxemia/Respiratory failure
1134 Indian J Pediatr (September 2011) 78(9):1127–1135
All to be hospitalized
Resuscitation
Baseline stabilization, oxygen, iv fluids, chest radiograph
IV Cefotaxime + Amikacin
Add Cloxacillin if CXR shows pneumatocele or pus in pleural fluid
Add Azithromycin if CXR shows atypical pneumonia
#
* Assessment involves Improvement involves (3, 4) $
Discharge criteria £
Alternate antibiotic options
RR 1. Afebrile Accepting orally & normal Cloxacillin
Retraction 2. RR 10/min within sensorium Vancomycin
Saturation 48hours Afebrile for at least 48 hours + Meropenem
General well 3. Retraction within 72 hours No oxygen requirement for at Cefoperazone + sulbactum
being 4. Saturation >92% least 48 hours Piperacillin + tazobactum
Oral acceptance 5. Improved general well being Completed IV antibiotics Metronidazole
6. Improved oral acceptance
& Patients requiring intubation/ventilation & Chest radiograph is not needed routinely; specific
& Presence of shock indications include doubtful diagnosis, asymmetrical
examination findings, suspected complications, recur-
rent chest infection, and severe/very severe pneumonia.
Key Points & Indications for hospitalization are: age <2 months,
severe/very severe pneumonia, signs of shock, hypox-
& Pneumonia is diagnosed clinically in a child with cough emia, moderate to severe malnutrition, recurrent chest
and difficult or rapid breathing. infection, immunocompromised state, poor oral accep-
& Age-specific respiratory rate and presence of chest indraw- tance, treatment failure on appropriate oral antibiotic
ing can be used to categorize severity. Infants ≤2 months therapy, and inability to provide care at home.
and children with moderate to severe malnutrition should & Choice of first-line antibiotic therapy is guided by: age,
be considered as having severe pneumonia. severity, clinical features suggesting specific etiology,
& Pneumonia should be differentiated from other respiratory immune status, underlying chronic lung disease, and
illnesses such as asthma, bronchiolitis and upper airway radiographic pointers towards specific etiology and/or
infections. complication such as pneumothorax/empyema.
Indian J Pediatr (September 2011) 78(9):1127–1135 1135
& Non-severe pneumonia can be treated at home with oral 4. Patwari AK, Bisht S, Srinivasan A, Deb M, Chattopadhya D.
Aetiology of pneumonia in hospitalized children. J Trop Pediatr.
amoxicillin (50 mg/kg/day in 2 divided doses for 3–
1996;42:15–20.
5 days); with advice to return immediately if the child 5. Chaudhry R, Nazima N, Dhawan B, Kabra SK. Prevalence of
develops lower chest indrawing, is unable to drink/feed, Mycoplasma pneumoniae and Chlamydia pneumoniae in children
is excessively sleepy or sick looking. with community acquired pneumonia. Indian J Pediatr. 1998;65:717–
21.
& If the child has persistent tachpnea but no indication for
6. Jain A, Pande A, Misra PK, Mathur A, Chaturvedi UC. An Indian
admission, change therapy to Amoxicillin-clavulanic hospital study of viral causes of acute respiratory infection in
acid (80–90 mg/kg of amoxicillin in 2 divided doses for children. J Med Microbiol. 1991;35:219–23.
5 days) or add Azithromycin (5 mg/kg for 5 days) if 7. National Family Health Survey of India. Available at: http://www.
nfhsindia.org/data/india/indch6.pdf.
clinical and radiological features suggest atypical
8. Mahalanabis D, Gupta S, Paul D, Gupta A, Lahiri M, Khaled MA.
pneumonia. Follow protocol for severe/very severe Risk factors for pneumonia in infants and young children and the
pneumonia if clinical signs of these appear. role of solid fuel for cooking: a case-control study. Epidemiol
& Severe pneumonia is treated in hospital with injectable Infect. 2002;129:65–71.
9. Postgraduate Institute of Medical Education and Research.
ampicillin (50 mg/kg/dose iv 6 hourly). Add Cloxacillin
Chandigarh: practice guidelines for management of community
(100–200 mg/kg/day in 4 four divided doses) if clinical and hospital acquired pneumonias—a consensus statement. Lung
and/or radiographic features suggest Staphylococcal India. 2006;23:115–20.
infection. If danger signs of very severe pneumonia 10. Rajesh VT, Singhi S, Kataria S. Tachypnoea is a good predictor of
hypoxia in acutely ill infants under 2 months. Arch Dis Child.
develop, treat as very severe pneumonia. If improved
2000;82:46–9.
after 48 h, use oral amoxicillin for 5 more days. 11. Rojas MX, Granados Rugeles C, Charry-Anzola LP. Oxygen therapy
& Very severe pneumonia is treated with injectable ampicillin for lower respiratory tract infections in children between 3 months and
plus gentamicin. If improved after 48 h, continue oral 15 years of age. Cochrane Database Syst Rev. 2009;1:CD005975.
12. Chisti MJ, Tebruegge M, Vincente SL, Graham SM, Duke T.
Amoxicillin (100 mg/kg/d in 3 divided doses for 10 days)
Pneumonia in severely malnourished children in developing
and Gentamicin (5.0–7.5 mg/kg/d iv). If not improved, countries—mortality risk, aetiology and validity of WHO clinical
escalate respiratory support, change to IV Ceftriaxone and signs: a systematic review. Trop Med Int Health. 2009;14:1173–89.
Amikacin (or as per as per cultures), and plan further work 13. Kabra SK, Lodha R, Pandey RM. Antibiotics for community
acquired pneumonia in children. Cochrane Database Syst Rev.
up. Total duration of antibiotic therapy is 10–14 days.
2006;3:CD004874.
14. Awasthi S, Agarwal G, Singh JV, Kabra SK, Pillai RM, Singhi S, et al.
Effectiveness of 3-day Amoxicillin vs. 5-day cotrimoxazole in the
treatment of non-severe pneumonia in children aged 2–59 months of
Conflict of Interest None. age: a multi-centric open labeled trial. J Trop Pediatr. 2008;54:382–9.
15. Awasthi S, Agarwal G, Kabra SK, et al. Does 3-day course of oral
amoxycillin benefit children of non-severe pneumonia with
Role of Funding Source None. wheeze: a multicentric randomised controlled trial. PLoS ONE.
2008;3(4):e1991.
16. Grant GB, Campbell H, Dowell SF, et al. Recommendations for
treatment of childhood non-severe pneumonia. Lancet Infect Dis.
References 2009;9(3):185–96.
17. Agarwal G, Awasthi S, Kabra SK, Kaul A, Singhi S, Walter SD.
Three day versus five day treatment with amoxicillin for non-
1. Pneumonia the forgotten killer of children [database on the Internet]. severe pneumonia in young children: a multicentre randomised
UNICEF. 2006 [cited. Available from: http://www.who.int/child_ controlled trial. BMJ. 2004;328(7443):791.
adolescent_health/documents/9280640489/en/index.html. 18. Asghar R, Banajeh S, Egas J, et al. Severe Pneumonia Evaluation
2. Kabra SK, Lodha R, Broor S. Etiology of acute lower respiratory Antimicrobial Research Study Group. Chloramphenicol versus
tract infection. Indian J Pediatr. 2003;70:33–6. ampicillin plus gentamicin for community acquired very severe
3. Bansal S, Kashyap S, Pal LS, Goel A. Clinical and bacteriological pneumonia among children aged 2–59 months in low resource
profile of community acquired pneumonia in Shimla, Himachal settings: multicentre randomised controlled trial (SPEAR study).
Pradesh. Indian J Chest Dis Allied Sci. 2004;46:17–22. BMJ. 2008;336:80–4.
Indian J Pediatr (October 2011) 78(10):1256–1261
DOI 10.1007/s12098-011-0414-0
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 11 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Upper airway obstruction is defined as blockage those with endotracheal tube/ trachesotomy should be
of any portion of the airway above the thoracic inlet. transferred to PICU.
Stridor, suprasternal retractions, and change of voice are the
sentinel signs of upper airway obstruction. Most of the Keywords Children . Upper airway obstruction . Croup .
common causes among children presenting to emergency Diphtheria . Bacterial tracheitis . Retropharyngeal abscess .
department are of acute infectious etiology. Among these, Angioneurotic edema
croup is the commonest while diphteria remains the most
serious life-threatening cause. Recent reports indicate that
bacterial tracheitis has become increasingly common. In ER Introduction
evaluation the key clinical data in determining the cause
and the site of obstruction are the onset, presence of fever, Acute airway obstruction in children is one of the most
character of the stridor, retractions, the voice and the ability common life-threatening emergencies in pediatric practice.
to handle secretions. After assessment of the severity of It usually generates a great deal of anxiety since there is
respiratory distress and resuscitative or supportive therapy little time for deliberation, and it may lead to significant
including oxygen and emergent airway, specific treatment is morbidity and indeed mortality.
directed at underlying etiology. All patients with audible Upper airway obstruction is defined as blockage of any
stridor require early endotracheal intubation/tracheostomy. In portion of the airway above the thoracic inlet. Stridor,
croup the mainstay of treatment are cold humidified oxygen, suprasternal retractions, and change of voice are the
budesonide nebulization ( in mild cases), Dexamethasone sentinel signs denoting upper airway obstruction.
0.6 mg/kg iv or im (in moderate and severe cases), and Stridor is a harsh, vibratory sound of variable pitch
Adrenaline 5 ml 1:1000 (5 mg) solution as nebulization ( in caused by partial obstruction of the respiratory passages
severe cases). In diphtheria, early tracheostomy, anti- that result in turbulent airflow through the airway.
diphtheric serum and injectable penicillin are critical. Inspiratory stridor is a harsh, high pitched sound produced
Bacterial Tracheitis and Retropharyngeal abscess need when child inspires through a spasmodically closed glottis.
early administration of injectable Cloxacillin, Amikacin Expiratory stridor is a singing sound due to semi-
and Clindamycin. ENT consultation should be obtained approximated vocal cords offering resistance to exhalation
for early surgical drainage of retropharyngeal abscess. or to due to tracheobronchial obstruction.
Angioneurotic edema is treated with subcutaneous adren- Biphasic stridor is a harsh sound of vibratory quality
aline (1:1000, 0.01 ml/kg); hydrocortisone 10 mg/kg IV produced due to little change in airway size with respiration
and antihistamines. Patients with severe obstruction and caused by a fixed obstruction and, heard during both phases
of respiration. Pathophysiologic events leading to various
kinds of stridor in upper airway obstruction in children are
shown in Fig. 1.
K. Sasidaran : A. Bansal : S. Singhi (*) If a child’s stridor becomes softer but the work of
Department of Pediatrics, Advanced Pediatrics Centre, PGIMER,
breathing remains increased, the obstruction may be
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India getting worse; if the child is unable to sustain increased
e-mail: sunit.singhi@gmail.com work of breathing he is getting tired.
Indian J Pediatr (October 2011) 78(10):1256–1261 1257
Fig. 1 Pathophysiology of
Normal airway Laminar air flow pattern
upper airway obstruction
in children
Progressive airway inflammation Exposure to inciting agent
Causes of Upper Airway Obstruction & Pattern of fever, duration as well as the severity
& History of trauma to head or neck—Neurogenic stridor
Causes of upper airway obstruction can be classified & History of choking—to exclude foreign body aspiration
according to the age group, duration of symptoms (acute & Epidemiological conglomeration of similar cases—
or chronic) and whether it is of infectious origin or not as Diphtheria, Viral croup
shown in Table 1. Acute infectious cause is the commonest
among children presenting to emergency department with
upper airway obstruction. Table 1 Common causes of upper airway obstruction in children
Croup and bacterial tracheitis remain as the two common Infectious Non-infectious
causes of acute onset upper airway obstruction in children.
Recent reports indicate that bacterial tracheitis is becoming Acute
increasingly common [1]. Diphtheria remains as one of the Croup Airway burns
common causes in India. (Caustic or Thermal)
Diphtheria Upper airway foreign body
Bacterial tracheitis Angioneurotic edema of upper
Evaluation of a Child with Stridor airway
Retropharyngeal abscess Trauma
A prepared clinician can often make the diagnosis based Peritonsillar abscess Vocal cord paralysis
Acute severe tonsillitis
solely on the history and physical examination (Fig. 2);
Infectious mononucleosis
using radiographs and laboratory examinations to aid in
Epiglottitis
diagnosis when the clinical picture is unclear [2].
Chronic
Chronic tonsillitis Laryngomalacia
History (age specific—in infants)
Adenotonsillar hypertrophy Vascular ring
& Characteristics of the onset of illness, and the course of Neoplasms of upper airway
(Hemangioma, cystic hygroma
development of respiratory signs should be carefully cysts of larynx)
obtained Tracheal stenosis
& Characteristics of voice and voice change—if present
1258 Indian J Pediatr (October 2011) 78(10):1256–1261
Yes No
History of trauma or
Severe distress or drooling ?
Foreign body ?
Yes No
Yes
Diphtheria
Epiglottitis
Physical examination is important and should be performed No investigation is warranted before stabilizing the airway.
in a warm, well-lit room, preferably with the child in parent’s lap A physician who is competent in providing airway support
and the child’s chest exposed. The key physical findings in may accompany stable patients to the X-ray department.
determining the site of obstruction involve the character of the Classic features of common disorders causing upper
stridor, retractions, the voice and the ability to handle secretions airway obstruction are shown in Table 2
A diagnostic approach to child with stridor is shown in Fig. 2.
& General appearance and posture
& Cry or voice (pitch, aphonia, muffled, hoarse)
& Difficulty in a child’s ability to handle oral secretions. Specific Management Guidelines
& Nasal flaring
& Degree of dyspnea and respiratory pattern Croup Syndrome Management
& Use of accessory muscles of respiration (degree of
retractions) Assess the child for severity of respiratory distress and give
& Look for craniofacial anomalies (maxillary hypoplasia, resuscitative or supportive therapy accordingly. Westley’s
nasal septal deviation, micrognathia, retrognathia, pla- clinical croup score (Table 3) may be used to aid in the
tybasia, or macroglossia) decision as to which children should be hospitalized and to
& Throat examination: look for acute inflammation of decide upon the treatment protocol.
tonsils, faucial pillars, evident exudates and membrane. The mainstay of treatment are cold humidified oxygen,
& Neck examination: look for any extrinsic mass, evidence Budesonide nebulization (1,000 μg given 30 min apart in
of trauma and tracheal position mild cases) [4], Dexamethasone [4, 5] 0.6 mg/kg iv or im
(one dose in mild and moderate cases, otherwise 6 hourly),
Laryngoscopy or any procedure that may agitate the patient and Adrenaline 5 ml 1:1000 (5 mg) solution as nebulization
is postponed till the emergency airway is established. ( in severe cases). Avoid situations that may precipitate
Indian J Pediatr (October 2011) 78(10):1256–1261 1259
Viral croup 3 month–3 years. Gradual onset of stridor and barking cough after mild URI
Bacterial tracheitis 2–7 years. Acute onset high grade fever, toxic appearance, respiratory distress
Diphtheria Any age Gradual onset of stridor preceded by swelling over neck and URI in
an unimmunized child, membrane on throat examination
Retropharyngeal abscess Infancy—3 years. Fever, toxicity, and distress after URI or pharyngitis
Peritonsillar abscess Usually >8 years Acute onset high grade fever, toxicity, distress with unilateral throat pain,
“hot potato speech”
Foreign body aspiration Late infancy—4 years Choking episode resulting in immediate or delayed respiratory distress
distress and monitor for the response. Management guidelines Because prompt treatment is crucial, it is prudent to start
for croup based on Westley’s croup score are given in Table 4. therapy on the basis of clinical findings and microbial
culture would confirm the diagnosis later. Nevertheless,
Diphtheria Management send a throat swab for bacteriological studies (Albert’s
stain and culture) to confirm the diagnosis.
Laryngeal Diphtheria Membranous pharyngitis progress
over a period of 2 to 3 days to manifest with hoarseness & Give Oxygen. Try not to upset child and do not
of voice, dysphagia and minimal to severe inspiratory attempt to look inside the mouth as this may
stridor. The patient is usually nontoxic in appearance but precipitate airway obstruction. Send throat swab for
may have low grade fever. bacteriological studies (Albert’s stain and culture) to
confirm the diagnosis.
& Airway management: Endotracheal intubation should
be avoided, and early tracheostomy to establish emer-
Table 3 Westley’s clinical croup score [3] gency airway is advised.
& Give diphtheria antitoxin 80,000 to 120,000 units IV
Category Score
infused over 1 h.
Level of consciousness & Crystalline penicillin 40,000 U/kg/dose iv, q 6 hourly ×
Normal (including sleep) 0 14 days; Erythromycin 15 mg/kg/dose q 8 hourly (not
Disoriented 5 to exceed 2 g/day) × 14 days may be used in those
Cyanosis sensitive to penicillin.
None 0 & Patients should be isolated until three consecutive
Cyanosis with agitation 4 cultures at the completion of therapy have documented
Cyanosis at rest 5 elimination of the organism from oropharynx. Contacts
Stridor
should receive erythromycin15 mg/kg/dose q 8 hourly
None 0
for 7 days.
When agitated 1
At rest 2
Retropharyngeal Abscess Management
Air entry
Normal 0
& Start oxygen in nonthreatening manner. Try not to upset
Decreased 1
child
Markedly decreased 2
& Airway management: Endotracheal intubation should
Retractions
be done in any child with audible stridor at presentation.
None 0
Orotracheal intubation is preferred because of the risk
Mild 1
of rupture of abscess.
Moderate 2
& Start with Cloxacillin (50 mg/kg/dose q 6 hourly)
Severe 3
Amikacin (15 mg/kg/day in once a day dose) along with
Categories: Mild croup—Score 0–2; Moderate croup—Score 3–5; clindamycin (10 mg/kg/dose TID).
Severe croup—Score 6–11; Impending respiratory failure—Score 12–17. & Surgical drainage.
1260 Indian J Pediatr (October 2011) 78(10):1256–1261
0–2 Mild Budesonide nebulization therapy one dose [3] or Dexamethasone one dose of 0.6 mg/kg iv
or im [3]; If child is older than 6 months and parents are reliable, child can be discharged.
Advise cold mist therapy at home.
3–5 Moderate Dexamethasone 0.6 mg/kg im or iv stat [4]; Cold humidified oxygen; Minimize
situations that may precipitate distress in the child.
Monitor using Westley’s score at 30 min interval and re-classify. Child can be discharged
only if he improves to mild category at the end of 6 h, has age more than 6 months and
parents are reliable.
6–11 Severe Dexamethasone 0.6 mg/kg im or iv stat [4]; Cold humidified oxygen; Minimize situations
that may precipitate distress in the child; Administer Adrenaline 5 ml 1:1000 (5 mg)
solution as nebulization. Monitor using Westley’s score at 30 min interval and re-classify
according to score.
Responsive to initial therapy
Child can be observed in ER if the score improves to be classified as moderate category.
Recurrence of respiratory distress can be treated with repeat adrenaline nebulization,
Dexamethasone 0.6 mg/kg/dose q6 hourly × four doses
Poor response to initial therapy
Airway stabilization and ICU care are indicated in a child who remains in severe category
even after the above mentioned therapy
12–17 Acute life-threatening Proceed to Airway stabilization (Intubation/Tracheostomy) and ICU care
Conflict of Interest None. 2. Stroud RH, Friedman NR. An update on inflammatory disorders of
the pediatric airway: epiglottitis, croup, and tracheitis. Am J
Role of Funding Source None. Otolaryngol. 2001;22:268–75.
3. Westley CR, Cotton EK, Brooks JG. Nebulized racemic
epinephrine for the treatment of croup. Am J Dis Child.
References 1978;132:484–7.
4. Ausejo M, Saenz A, Kellner JD, et al. The effectiveness of
glucocorticoids in treating croup: meta—analysis. BMJ. 1999;3
1. Hopkins A, Lahiri T, Salerno R. Changing epidemiology of 19:595–600.
Life-threatening upper airway infections: the reemergence of 5. Russell KF, Liang Y, O’Gorman K. Glucocorticoids for croup.
bacterial tracheitis. Pediatrics. 2006;118:1418–21. Cochrane Database Syst Rev. 2011;1:CD001955.
Indian J Pediatr (October 2011) 78(10):1262–1267
DOI 10.1007/s12098-011-0413-1
Received: 27 January 2011 / Accepted: 8 March 2011 / Published online: 4 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Chest pain is a worrisome symptom that often management includes analgesics, specific treatment directed
causes parents to bring their child to emergency department at underlying etiology and appropriate referral.
(ED) for evaluation. In the majority of cases, the etiology of
the chest pain is benign, but in one-fourth of the cases Keywords Chest pain . Children . Osteochondritis .
symptoms are distressing enough to cause children to miss Psychogenic chest pain
school. The clinician’s primary goal in ED evaluation of
chest pain is to identify serious causes and rule out organic
pathology. The diagnostic evaluation includes a thorough Introduction
history and physical examination. Younger children are
more likely to have a cardiorespiratory source for their Chest pain is a worrisome symptom that often causes
chest pain, whereas an adolescent is more likely to have a parents to bring their child to emergency department(ED)
psychogenic cause. Children having an organic cause of for evaluation. No specific data from India on incidence
chest pain are more likely to have acute pain, sleep and causes of chest pain in children is available. In North
disturbance due to pain and associated fever or abnormal America, the incidence of pediatric patients presenting to
examination findings, whereas those with non-organic chest ED with a complaint of chest pain is 3–6 for every 1,000
pain are more likely to have pain for a longer duration. Chest patient visits [1, 2]. In the majority of cases, the etiology of
radiograph is required in some, especially in patients with the chest pain is benign, but symptoms are distressing
history of trauma . In children, myocardial ischemia is rare, enough to cause 27–30% of children to miss school [2, 3].
thus routine ECG is not required on every patient. However,
both pericarditis and myocarditis can present with chest pain
and fever. Musculoskeletal chest pain, such as caused by Causes
costochondritis and trauma, is generally reproducible on
palpation and is exaggerated by physical activity or breathing. The clinician’s primary goal in evaluating the chest pain is
Pneumonia with or without pleural effusion, usually presents to identify serious causes and rule out organic pathology.
with fever and tachypnea; chest pain may be presenting There are numerous causes for pediatric chest pain; these
symptom sometimes. In asthmatic children bronchospasm and are listed in Table 1.
persistent coughing can lead to excess use of chest wall In general, the most frequently reported cause is
muscles and chest pain. Patients’ who report acute pain and musculoskeletal pain, followed by respiratory causes.
subsequent respiratory distress should raise suspicion of a Despite extensive investigations, one may not find any
spontaneous pneumothorax or pneumomediastinum. ED cause in as many as 20–61% of cases [3–7] (Table 2).
Child presenting
with chest pain
Chest X-Ray
Fever and
Yes respiratory
findings
Chest X-Ray
Consider Pulmonary
Causes: Pneumonia No
Asthma
No
If concerns for
myocardial ischemia,
get troponins
Dysphagia, pain
associated with Yes Explore GI Causes,
food, or Consider Chest X-Ray
epigastric pain
for Foreign body
No
Consider
Reproducible Pain?
Yes musculoskeletal
Overuse?
causes
No
No
Idiopathic Needs
close monitoring
& Serious associated conditions (Kawasaki disease, asthma, Physical examination: Check for:
Marfan syndrome, lupus)—these children are at risk for
serious complications like ischemia, pneumothorax, pleural & Respiratory distress, abnormal vital signs
effusion & Decreased breath sounds, palpable subcutaneous air—
& Stressful life events that correlate with onset of pain— consider pneumonia, pneumothorax, subcutaneous
consider psychogenic pain (anxiety) emphysema.
Indian J Pediatr (October 2011) 78(10):1262–1267 1265
& Wheezing—consider asthma and pain related to com- examination are generally sufficient to diagnose cardiac-
plications like pneumomediastinum, pneumothorax related chest pain. If not, they should at least be sufficient
& Abnormal cardiac findings (pathologic murmur, rub, to guide the use of chest x-ray, ECG, and echocardiograms.
arrhythmia)—consider pericarditis, myocarditis, supra- Pericarditis and myocarditis both can present with chest
ventricular tachycardia, structural heart disease pain and fever. Pericarditis usually presents with sharp,
& Evidence of trauma—consider pneumothorax, chest substernal pain, which is alleviated by leaning forward. On
wall injury physical examination, the patient classically has distant
& Reproducible pain—consider musculoskeletal pain, heart sounds, a friction rub, and signs of congestive heart
costochondritis failure. Myocarditis patients often have vague symptoms
& Drooling in a young child—consider foreign body including chest pain, dyspnoea, dizziness, nausea, vomiting
aspiration/inhalation (coin) and fatigue. Physical examination usually reveals a gallop,
signs of congestive heart failure, and tachycardia unresponsive
Always look for Red flag signs (Table 3).
to fluids.
Structural abnormalities of the heart and vessels can
In these patients chest pain could be a sign of serious
cause chest pain. Hypertrophic cardiomyopathy patients
underlying illness.
usually give a history of increased chest pain with exertion.
Aortic stenosis, pulmonary stenosis, abnormal coronary
arteries, and mitral valve prolapse, depending on the
When to Consider Chest X-Ray and ECG?
severity, can lead to ischemia of the heart and papillary
muscles. History and physical examination of these patients
Chest-radiograph is needed in all the patients with history
typically reveal a heart murmur associated with the lesion.
of trauma. In others it is indicated on basis of clinical signs
Arrhythmias can cause chest pain in the pediatric patient.
given in Table 4.
Premature ventricular tachycardia can present as a fleeting,
Consider further testing: sharp pain, or palpitations. Supraventricular tachycardia
(SVT) is usually described as a rapid heartbeat. Physical
& D-dimer, chest CT scan and if available radionuclide examination should cue the physician to the possibility of
scan—if patient has increased risk for pulmonary SVT.
embolism (coagulation disorder, trauma) Myocardial infarction is rare in children, but has been
& Holter monitor—if arrhythmia suspected reported in literature in previously healthy adolescents
& Exercise stress test, pulmonary function tests—if pain is [10, 11]. These patients usually present with classic severe,
related to exercise substernal chest pain with radiation to the left arm or jaw.
& Child psychology evaluation. Patients are at greater risk for myocardial ischemia if they
have a history of congenital heart disease, acquired heart
disease (Kawasaki disease), or drug abuse (cocaine).
Differential Diagnosis
Respiratory
Cardiac
Pediatric chest pain attributed to a pulmonary etiology is usually
Pediatric chest pain is rarely due to cardiac pathology. accompanied by other symptoms and signs of organic illness.
However, it is the second most common cause for referral Pneumonia with or without pleural effusion, usually presents
to a pediatric cardiologist. Careful history and physical with fever, tachypnea, and respiratory symptoms. Physical
examination may reveal decreased breath sounds or rales.
Table 3 Chest pain in children—Red flag signs indicating serious Patients presenting with a history of asthma or reactive
underlying etiology airway disease should prompt the physician to assess the
✓ Young age possibility of chest pain secondary to an asthma exacerbation.
✓ Acute onset Bronchospasm and persistent coughing can lead to excess use
✓ Pain precipitated with exercise of chest wall muscles and is a common cause of chest pain.
✓ Pain associated with syncope Patients’ who report acute pain and subsequent respiratory
✓ Pain associated with palpitations distress should raise suspicion of a spontaneous pneumothorax
✓ Pain associated with respiratory distress
or pneumomediastinum. Patients with asthma, Marfan
✓ Pain associated with abnormal cardiorespiratory examination
syndrome or cystic fibrosis are at increased risk of developing
✓ Pain associated with trauma
pneumothorax. Physical examination may reveal decreased
breath sound on the affected side and crepitus depending on
1266 Indian J Pediatr (October 2011) 78(10):1262–1267
the extent of pathology. A hemothorax should be considered does not always exclude a musculoskeletal cause. The
if there is a history of trauma. duration of musculoskeletal chest pain can be relatively long.
Pulmonary embolism is rare in children but should be Trauma can cause fractures and contusions that may
considered in adolescents who complain of dyspnea, result in chest pain. Overuse or overexertion of the chest
pleuritic chest pain, hemoptysis and low grade fever. Risk wall muscles may cause muscle strain.
factors for pulmonary embolism are prolonged immobility, Costochondritis is a common condition which is
hypercoagulable disorders, (including nephrotic syndrome) recognised by eliciting pain while palpating the costochondral
indwelling central lines and major trauma particularly to the joints. The etiology of costochondritis is unknown but it is
lower extremities. considered to be a benign inflammatory condition. It usually
Chest wall deformities (pectus excavatum/pectus carina- involves 4th to 6th costochondral junctions and produces
tum) in children are sometimes associated with chest pain. localised tenderness. The pain is exaggerated by physical
They can lead to restricted lung function, and many are activity or breathing. A similar disease Tietze’s syndrome also
related to psychologic problems in children because of the occurs at costochondral junction but has the associated findings
associated cosmetic defects. of swelling, redness and warmth. Like costochondritis, Tietze’s
syndrome is thought to be a self limited inflammatory condition.
Gastrointestinal Slipping rib syndrome usually occurs at the false or
floating ribs. The patient describes a sharp intermittent pain
Gastrointestinal causes for pediatric chest pain make up 3–7% that lasts a few minutes and settles to a dull ache. There
of ED visits. Gastroesophageal reflux disease often causes a may be a history of trauma and aggravation with movement.
burning substernal type of pain because of resulting gastritis The pain is thought to result from the anterior end of ribs
and esophagitis. Epigastric tenderness on physical examina- slipping out of place and aggravating the adjacent intercostal
tion and association of pain with eating is suggestive of a nerves. The hooking manoeuvre can be used to help diagnose
gastrointestinal origin of the chest pain and should be further this condition. The patient is instructed to lie down on the
investigated. A trial of antacids is often diagnostic and unaffected side and the examiner reaches under the lower
therapeutic. coastal margin and pulls the rib anteriorly. A positive test results
Children that have ingested a foreign body that is lodged in in the reproduction of the patient’s pain and click sensation.
esophagus can have chest pain. Patients may have dysphagia Precordial catch syndrome or Texidor’s twinge syndrome
depending on the location of foreign body. A careful history is a benign condition that causes a brief sharp pain to the left
and chest radiograph usually reveals the diagnosis. chest without radiation. The pain may occur with exercise or
when the patient is at rest in a slouched position. The etiology
Musculoskeletal is unclear but is thought to occur from the parietal pleura,
intercostals nerves or from the stretching ligaments of the heart.
Musculoskeletal chest pain is generally considered when pain Intense chest wall pain that follows a dermatome should
is reproducible on palpation or suggested by a history of muscle raise the physician’s suspicion for a herpes zoster infection.
strain or minor trauma. Reproducibility of chest wall pain is Diagnostic studies usually do not help identify muscu-
generally a good marker for costochondritis. However, absence loskeletal chest pain. If musculoskeletal pain is identified,
Indian J Pediatr (October 2011) 78(10):1262–1267 1267
analgesics (ibuprofen or paracetamol) should be offered. & Antibiotics for suspected pneumonia
The slipping rib syndrome can be treated with education & H2 blocker or proton pump inhibitor for midsternal
and avoidance of the offending movements. An orthopedic burning pain
opinion is helpful as local nerve blocks and corticosteroid & Analgesics for musculoskeletal pain
injections are sometimes needed. A surgical alternative is to & Management of traumatic chest/chest wall injuries
have the anterior end of the rib and costal cartilage
Treat idiopathic or undiagnosed pain
removed, but this is usually done after failure of medical
management. Precordial catch syndrome is a self limiting & Analgesics for all (paracetamol or ibuprofen unless
condition that requires only education and supportive care. contraindicated)
& Consider H2 blocker or proton pump inhibitor as a
Psychogenic therapeutic trial.
Received: 6 April 2011 / Accepted: 4 May 2011 / Published online: 10 June 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Sore throat is one of the common reasons for Identification and adequate antibiotic treatment of group A
outpatient and emergency visits among children. It could be streptococcal sore throat is important for primary prevention
because of several etiologies; of these bacterial pharyngitis of acute rheumatic fever, as it carries approximately 3% risk
is the most important. Major challenge for the clinician is to of development of acute rheumatic fever.
diagnose group A beta hemolytic streptococcus (GABHS)
pharyngitis and diphtheria, which are associated with
serious complications. Throat swab smear with culture Definition
and rapid antigen tests are useful for making the diagnosis
but the later may not be available in resource poor settings. Soreness is generally described by the patient as pain in the
Many clinical scores have been devised to diagnose throat without the effort of swallowing and also a painful
GABHS with variable success but usually clinical features, swallow [2]. Sore throat is primary symptom of pharyngi-
epidemiological criteria and expert clinical judgment with tis. The terms “sore throat” and “pharyngitis or pharyngo-
or without supportive investigations indicate need for tonsillitis” are often used interchangeably. Pharyngitis
antibiotics. A child with sore throat and toxic look may refers to objective evidence of inflammation of the pharynx,
have diphtheria or parapharyngeal/retropharyngeal abscess, such as exudates, ulceration, or definite erythema. Redness
and therefore should be hospitalized. of the throat may occur as part of the general redness of all
mucous membranes in a patient with fever. A diagnosis of
Keywords Children . Group A beta-hemolytic streptococcus . pharyngitis is justified only when the pharynx is redder
Sore throat . Diphtheria . Pharyngitis . Throat swab than the rest of the oral mucosa.
Introduction Etiology
Upper Respiratory tract infections are seen with great Most sore throats are caused by viruses. Less often, sore
frequency in both children and adults and have remarkable throats are due to bacterial infections.
economic impact, related to the frequent prescription by
physicians of antibiotics, even when the causative agents of Viral Infections
infection are not bacteria. About one-fourth of children with
sore throat have bacterial pharyngitis and about half of the & Corona virus, rhinovirus, adeno virus, influenza and
families with index case have a secondary case [1]. parainfluenza are the commonest etiological agents and
usually presents as common cold.
& Other viral infections that can present with sore throat
R. Shah : A. Bansal : S. C. Singhi (*) are Ebstein Barr (EB) virus and HIV which can present
Department of Pediatrics, Advanced Pediatrics Centre,
as a sore throat in initial course of illness.
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India & Recurrent sore throat can occur due to cytomegalovirus
e-mail: sunit.singhi@gmail.com or fungal infections in immunosuppresed patients.
Indian J Pediatr (October 2011) 78(10):1268–1272 1269
& Group A beta-hemolytic streptococcus (GABHS) is the Majority of the times, history and clinical examination
most common cause of bacterial sore throat. It accounts gives clue to etiology (Table 1). The major challenge is to
for 15–36% of cases of acute pharyngitis in children in diagnose GABHS infection, because the signs and
west [1], and 13.4% of cases in India, according to one symptoms of GABHS pharyngitis overlap with other
study done at PGIMER [3]. infections and untreated GABHS can cause serious
& Streptococcus type C and G complications. No single element of the history or
& Diphtheria—is an important cause in India and many physical examination reliably confirms or excludes
developing countries. GABHS pharyngitis.
& H influenza, Staphylococcus aureus, Mycoplasma, Several scoring systems have been developed to
Chlamydia pneumoniae, Moraxella catarrhalis and predict which patients will have GABHS. Use of these
Yersinia are some uncommon bacterial causes. does improve quality of care but none of these systems,
& Fusobacterium necrophorum infection. This uncommon however, is totally reliable in identifying children who
infection which starts as fever and sore throat, can need treatment [4]. A clinical scoring system has been
complicate into Lemierre’s syndrome. (Positive blood designed in India but it has to be validated for local use.
culture, clinical or radiographic evidence of internal This scoring system uses variables such as age, season,
jugular vein thrombosis, and at least one metastatic focus.) fever, erythema of pharynx, size of tonsil, pharyngeal
exudates; lymphadenopathy and pain in throat, and scores
are assigned according to throat culture positivity in
Other Causes
association with the same. Cut off value of 15 predicts
GAS infection with 91% sensitivity and 98% specificity
& Peritonsillar, Retropharyngeal and Lateral Pharyngeal
[3].
abscesses—usually due to spread of infection from
The evaluation of patient should include the following:
local site like bacterial tonsillitis. Along with fever and
sore throat, other features like painful swallowing,
History
drooling, trismus, visible swelling below mandible and
deviation of uvula to opposite side may be present. & Onset and duration
& Allergies—especially when complicated by postnasal & Fever—degree (doesn’t help much to differentiate)
drip. & Associated cough, coryza, conjunctivitis (more with
& Irritants—Dust, tobacco smoke (in teenagers) or chem- viral); headache, myalgia (more with GABHS)
icals (occupational hazard for children/adolescents & Any breathing difficulty especially new onset snoring at
working in factories). Sore throat in such patients is night or stridor (a likely sign of developing abscess)
usually chronic. & History of rash, diarrhea, allergy
& Muscle strain—talking in loud noise without rest for & History of regurgitation, epigastric or retrosternal pain
long period. usually indicates GERD
& GastroEsophageal Reflux Disease (GERD) & History of sore throat in family in past 2 wks.
& Psychogenic & Similar complaints in past, with vaccination history
Note: antibiotics are indicated in any child who is looking sick and/or suspected to have complications.
○ X ray soft tissue neck (lateral view) for retrophar- & Antibiotics: Aqueous crystalline penicillin G 40,000 U/
yngeal abscess. kg/dose 6 hourly IV or erythromycin 15 mg/kg 8 hourly
○ CT scan of neck including base of skull for abscess. (not to exceed 2 g/day) oral/IV for 14 days.
For prophylaxis to contacts same dose of erythromycin for
Throat Swab Sampling Technique 7 days or a single injection of benzathine penicillin G
(600,000 U IM for <30 kg, 1,200,000 U IM for ≥30 kg.) is
Samples should be obtained by vigorous swabbing of both recommended.
tonsillar surfaces or fossae and the posterior pharynx [6, 7].
Correctly sampled and plated, throat swab culture has 90– Indication for Hospitalization
95% sensitivity. Swabbing the soft palate and uvula should
be avoided, because it dilutes the inoculums. & Toxic looking child
& Not accepting orally well
& Suspected to having associated complications or diphtheria.
Management
Conflict of Interest None.
GABHS pharyngitis is self-limiting illness. Antibiotic treat-
ment provides acute symptom relief, prevent suppurative Role of Funding Source None.
(otitis media, sinusitis, quinsy) and non suppurative compli-
cations, and reduce communicability. Antibiotics reduce References
incidence of rheumatic fever by more than two third [8].
Clinical decision guideline for sore throat is given in Fig. 1. 1. Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational
Clinical features, epidemiological criteria and expert clinical examination. Does this patient have strep throat? JAMA.
clinician judgment with or without supportive investigation 2000;284:2912–8.
2. Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic
usually indicate need for antibiotics. Currently used score for treatment of children with sore throat. JAMA. 2005;294:2315–
decision making in pharyngitis has been adapted by adding 22.
age to four components of original Centor score (absence of 3. Nandi S, Kumar R, Ray P, Vohra H, Ganguly NK. Clinical score
cough, swollen and tender anterior cervical nodes, temper- card for diagnosis of Group A Streptococcal sore throat. Indian J
Pediatr. 2002;69:471–5.
ature >38°C and tonsillar exudates or swelling) [9]. Each 4. Wigton RS, Connor JL, Centor RM. Transportability of a decision
component is given 1 point; age of 3–14 years carries 1 point rule for the diagnosis of streptococcal pharyngitis. Arch Intern
while that of 14–44 years, zero. Patients with a score of zero Med. 1986;146:81–3.
or 1 do not require testing or antibiotic therapy. Patients with 5. Schwartz B, Marcy SM, Phillips WR, Gerber MA, Dowell SF.
Pharyngitis-principles of judicious use of antimicrobial agents.
score of 2 or 3 should be tested and prescribed antibiotics if Pediatrics. 1998;101:171–4.
found positive while patients with score of 4 or higher, are at 6. Van der Veen EL, Sanders EAM, Videler WJM, van Staaij BK,
high risk of streptococcal pharyngitis and should be given van Benthem PPG, Schilder AGM. Optimal site for throat culture:
empiric treatment [10]. tonsillar surface versus posterior pharyngeal wall. Eur Arch
Otorhinolaryngol. 2006;263:750–3.
7. American Academy of Pediatrics, Committee on Infectious
Antibiotics Diseases. Red Book, 26th edn. Elk Grove Village, Ill.: American
Academy of Pediatrics; 2003. pp. 578–80.
8. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat.
Based on cost, narrow spectrum of activity, safety, and
Cochrane Database Syst Rev. 2006;4:CD000023.
effectiveness, penicillin is the drug of choice [10, 11]. Shorter 9. McIsaac WJ, Goel V, To T, Low DE. The validity of a sore throat
duration of treatment increases risk of bacteriological score in family practice. CMAJ. 2000;163:811–5.
recurrence [12] Inappropriate use of macrolides for treatment 10. McIsaac WJ, White D, Tannenbaum D, Low DE. A clinical score
to reduce unnecessary antibiotic use in patients with sore throat.
of GABHS pharyngitis has been the main cause of resistant CMAJ. 1998;158:75–83.
strains in western countries [13]. The various alternatives to 11. Rimoin AW, Hamza HS, Vince A, et al. Evaluation of the WHO
penicillin and the dosage of antibiotics are given in Table 3. clinical decision rule for streptococcal pharyngitis. Arch Dis
Child. 2005;90:1066–70.
12. Zwart S, Sachs APE, Ruis GJHM, Gubbels JW, Hoes AW, de
Diphtheria Management Melker RA. Penicillin for acute sore throat: randomised double
blind trial of 7 days versus 3 days treatment or placebo in adults.
& Stabilize child (ABC…) (For details refer to section on BMJ. 2000;320:150–4.
13. Hasenbein ME, Warner JE, Lambert KG, Cole SE, Onderdonk
upper airway obstruction).
AB, McAdam AJ. Detection of multiple macrolide- and
& Diphtheria antitoxin: 50,000–120,000 U IV depending lincosamide-resistant strains of Streptococcus pyogenes from
on extent of involvement. patients in the Boston area. J Clin Microbiol. 2004;42:1559–63.
Indian J Pediatr (November 2011) 78(11):1388–1395
DOI 10.1007/s12098-011-0524-8
Received: 20 April 2011 / Accepted: 30 May 2011 / Published online: 16 July 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Acute asthma is the third commonest cause of exacerbation of asthma is the 3rd commonest diagnosis
pediatric emergency visits at PGIMER. Typically, it presents after acute diarrhea and seizures among the patients
with acute onset respiratory distress and wheeze in a patient attending pediatric emergency service [2]. Despite advanc-
with past or family history of similar episodes. The severity of ing knowledge of the pathophysiology and treatment,
the acute episode of asthma is judged clinically and catego- asthma related morbidity and mortality is on the rise.
rized as mild, moderate and severe. The initial therapy consists
of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline),
inhaled budesonide (three doses over 1 h, at 20 min interval) Definition
in all and ipratropium bromide and systemic steroids
(hydrocortisone or methylprednisolone) in acute severe Acute exacerbation of asthma can be defined as episodes of
asthma. Other causes of acute onset wheeze and breathing coughing (particularly at night/early morning), wheezing,
difficulty such as pneumonia, foreign body, cardiac failure etc. breathlessness or chest tightness associated with widespread,
should be ruled out with help of chest radiography and but variable, airflow obstruction within the lung that is often
appropriate laboratory investigations in first time wheezers reversible either spontaneously or with treatment [3, 4].
and those not responding to 1 h of inhaled therapy. In case of The term ‘status asthmaticus’ relates severity to the
inadequate response or worsening, intravenous infusion of outcome and has been used to define a severe asthmatic
magnesium sulphate, terbutaline or aminophylline may be exacerbation that does not respond to repetitive or continuous
used. Magnesium sulphate is the safest and most effective administration of inhaled short-acting β2-adrenergic receptor
alternative among these. Severe cases may need ICU care and agonists (SABAs) in the emergency setting [5].
rarely, ventilatory support.
increasing pulmonary vascular resistance and right ventric- Table 1 Differential diagnosis of wheezing in childhood
ular afterload. Due to large negative intrathoracic pressure 1. Infection
during inspiration, left ventricular afterload is increased, A. Viral
and systolic blood pressure decreases. Exaggerated varia- • Respiratory syncytial virus/bronchiolitis
tion in systolic blood pressure during inspiration is termed • Parainfluenza, Influenza, Adenovirus, Rhinovirus, Human
as pulsus paradoxus. metapneumovirus
B. Bacterial pneumonia
C. Chlamydia
Principles of Management 2. Asthmaa
3. Aspiration syndromesa
Emergency room management of acute asthma includes the • Gastro-esophageal reflux disease (GERD)
following: 4. Heart diseasea
& Rapid diagnosis and assessment of the severity based 5. Anatomic abnormalitiesa
on clinical evaluation A. Extrinsic airway anomalies
& Appropriate interventions to relieve breathing difficulty • Vascular ring/sling
and airway obstruction B. Intrinsic airway anomalies
& Assessment of response to the therapy (using clinical • Airway hemangioma
asthma severity scores) [6] and • Cystic adenomatoid malformation
& Stepping up the therapy to overcome unresponsiveness • Bronchial lung cyst
• Congenital lobar emphysema
• Sequestration of lung
• Mediastinal lymph node/tumor/TB lymphadenitis
Clinical Evaluation and Assessment of Severity
C. Malacia of larynx, trachea, or bronchi
6. Foreign body
A child with acute exacerbation of asthma presents with
7. Anaphylaxis
cough and wheezing, and exhibits signs of dyspnea,
increased work of breathing, and anxiety. The sick 8. Inhalational injuries (burns)
asthmatic child may also present in respiratory failure or 9. Mucociliary clearance disordersa
even frank cardiopulmonary arrest. Ominous signs include • Cystic fibrosis
distant or absent breath sounds (“silent chest”) in the face of • Primary ciliary dyskinesia
increased respiratory effort. While there is no diagnostic • Bronchiectasis
test for asthma, a family history of reactive airway disease, Entities marked a
are causes of recurrent wheeze
a history of recurrent symptoms, and a good response to
therapy support the diagnosis.
Peak flow measures obstruction in larger airways, spirometry
The diagnosis can be difficult in the “first time wheezer”
assesses the more peripheral airways.
or in a child with atypical symptoms (Table 1). In such
Based on history and clinical examination, the severity of
patients, pneumonia, bronchiolitis, airway foreign body and
acute asthma may be regarded as mild, moderate and severe
congestive heart failure must be rapidly differentiated from
(Tables 2 and 3). The same parameters can be used to assess
asthma.
the initial severity and also to monitor the response to therapy.
Clinical history should include history of cough, fever,
Presence of disturbed level of consciousness (drowsy,
respiratory distress, noisy breathing, whistling sounds,
confused), inability to speak, markedly diminished or
cyanosis and lethargy, past history of asthma, details of
absent breath sounds, central cyanosis, diaphoresis, pulsus
treatment, whether on regular treatment, previous hospital-
paradoxus >20 mm Hg, PEFR <25% of predicted or
ization and if yes, details of treatment, and pointers to rule
patient’s best, abdominal paradox, SpO2 <90% often
out foreign body inhalation and pneumonia.
indicate respiratory failure and imminent respiratory arrest.
In clinical examination, note the respiratory rate, temper-
One should always remember:
ature, heart rate, peripheral pulses, blood pressure, pulsus
paradoxus, air entry, nasal flaring, retractions, accessory – A calm patient usually denotes, at the most, mild
muscle usage, wheeze (phase and length of wheeze), oxygen distress
saturation (off and on oxygen) by pulse oximetry and any – An anxious asthmatic child indicates severe obstruction
abnormality in other systems’ examination. and probably hypoxia
Peak flow and spirometry are useful in older than 5 years and – “Silent chest” indicates inadequate air exchange and
co-operative children (especially if baseline values are known). severe airway obstruction
1390 Indian J Pediatr (November 2011) 78(11):1388–1395
– Unilateral diminished breath sounds (in a case of asthma) indicated if clinical examination suggests the possibility of
indicates severe obstructive atelectasis or a pneumotho- pneumothorax or pneumonia, or when there is doubt about
rax, and needs urgent attention. other cause of wheeze such as airway foreign body,
anatomic abnormality etc.
Arterial blood gas measurement yields quantitative infor-
Chest Radiography and Other Laboratory Studies
mation on pulmonary gas exchange and is used in severely
distressed or ventilated patients. Typical findings during the
Laboratory studies are generally not indicated in a routine
early phase of severe asthma are hypoxemia and hypocarbia.
acute exacerbation. However if the child is unusually ill or
With increasing airflow obstruction, hypercarbia develops.
there is doubt of an infection, blood samples should be
PaO2 <60 mm Hg and PaCO2 >45 mm Hg often indicate
taken for the following:
respiratory failure and imminent respiratory arrest.
1. White blood cell count
2. Serum electrolytes
Treatment of Acute Asthma
3. Blood culture
Chest radiographs are not routinely indicated in the Goals
unintubated asthmatic child, as unexpected radiographic
abnormalities are very rare [7]. A chest radiograph is – Correction of hypoxemia with oxygen
– Rapid reversal of airflow obstruction using inhaled For children who need more frequent doses of β-
bronchodilators and corticosteroids agonist, continuous nebulization appears to be superior to
– Close monitoring of the clinical response and titration intermittent doses. Use of continuous nebulization with
and escalation of therapies (including parenteral salbutamol may lead to more rapid improvement,
bronchodilators) to achieve rapid reversal of airflow improved sleep, and may also be more cost-effective in
obstruction. patients with severe exacerbation of asthma [10]. Orally
– To establish a future plan of management administered β-agonists are ineffective in severe asthma.
Subcutaneous epinephrine is indicated only in extreme
The flowchart illustrates the treatment plan to circumstances where inhaled β2-agonists are unavailable
achieve above goals (Fig. 1). All children with acute or undeliverable (no aeration, intubated patient without
exacerbation of asthma should be cared in a comfortable proper delivery device), when there are other systemic
and supportive environment, ideally with a parent or in signs of anaphylaxis, and when intravenous access has
the presence of a family member. Although hypoxemia not been established in a patient with impending
and anxiety may lead to agitation and restlessness, respiratory failure.
sedatives are contraindicated in the nonintubated asth- Major adverse effects of β-agonists include tachycardia,
matic patient. Cardiorespiratory monitoring should be prolonged QTc interval, hypokalemia and tremors. Cardio-
established. vascular adverse effects and tremors show tachyphylaxis,
whereas bronchodilator response usually does not.
Oxygen
Corticosteroids (Inhaled and Systemic)
High-flow humidified oxygen should be delivered to all
the patients with acute asthma exacerbation to maintain a Early use of anti-inflammatory therapy with systemic
SpO2 >92%; they are at risk of hypoxemia caused by steroids is effective in the emergency room treatment of
ventilation/perfusion mismatch. Oxygen is best delivered acute, moderate and severe exacerbations of asthma.
via a partial or nonrebreathing mask. There is no evidence Inhaled glucocorticosteroids have a potential benefit in the
that oxygen will suppress the respiratory drive in the acute setting because they are delivered directly into the
absence of preexisting chronic pulmonary disease. airways, have few systemic side effects and induce a
reduction in the airway hyperreactivity [11].
Beta-2 Receptor Agonists Studies from the authors’ centre have shown a signifi-
cant reduction in the number of patients requiring hospital-
β2-receptor agonists remain the mainstay of therapy in ization, total duration of oxygen treatment, and the number
acute exacerbation of asthma. These agents mediate of patients requiring intravenous infusion and steroids
bronchodilatation via stimulation of β2-receptors on among patients receiving inhaled budesonide therapy early
airway smooth muscle, which in turn mediates smooth- in the emergency room treatment of acute moderately
muscle relaxation. All patients with acute asthma should severe exacerbations of asthma [12, 13]. A 2003 Cochrane
receive nebulized salbutamol in a dose of 0.15 mg/kg Database review also supports improved outcomes for
every 20 min, three doses over 1 h. Tidal volume, children who receive corticosteroids early in their emer-
breathing pattern, and nebulizer gas flow vary the amount gency department course [14].
of drug delivery, hence some experts recommend higher Systemic steroids should be started at the outset in the
doses of nebulized β-agonists. Presently, there is no following situations:
recommendation regarding the use of the much more
1. A child with a very severe attack of asthma.
expensive (R)-albuterol in children with acute exacerba-
2. Previous history of life-threatening attack or severe
tion of asthma [8].
attacks not responding to bronchodilators.
The nebulization device should be driven by oxygen.
3. Child on regular oral steroids or high dose inhaled
Care must be taken to utilize the correct flow rate. Each
steroids.
nebulizer device has a different flow-particle size
relationship, but most devices require 6–12 L/min in Studies suggest that a substantially increased dose of
order to deliver particles in the 1- to 3 μm range. inhaled steroid may be as effective as systemic steroids for
Although a Cochrane meta-analysis showed no overall all but the most severe exacerbations.
difference between the effects of albuterol delivered by Dose of inhaled steroids for the management of acute
metered dose inhaler (MDI) spacer or nebulizer, MDI- severe asthma is 800 μg/dose. An oral dose of 1–2 mg/kg
spacer administration can be difficult in patients in severe of prednisolone may be as effective as an equivalent dose
distress [9]. of hydrocortisone (10 mg/kg) given intravenously, be-
1392 Indian J Pediatr (November 2011) 78(11):1388–1395
Indian J Pediatr (November 2011) 78(11):1388–1395 1393
cause the time for onset of action is same. Cortico- Intravenous infusion of β-agonists can be considered in
steroids may be continued as 0.25–0.5 mg/kg/dose of patients unresponsive to treatment with continuous nebu-
prednisolone or 2.5–5 mg/kg/dose of hydrocortisone lisation. Accepted indications for β2-agonist infusion
every 6 hourly. Duration of steroid therapy depends on includes progressive retention of CO2 (hypoventilation)
severity of the attack and on chronicity of underlying and signs of imminent respiratory fatigue. Intravenous
inflammation. The total duration of therapy may be 3– salbutamol affected a rapid drop in PaCO2 levels and
7 days depending upon the response. averted the need for ventilation in over two-thirds of
patients [19]. In authors’ experience, children with asthma
Anticholinergics: Ipratropium Bromide who failed to respond to nebulized bronchodilators and
intravenous steroids, terbutaline was similar to aminophyl-
Ipratropium bromide is preferred in the emergency setting line, but had lesser side effects [18].
because of its selective muscarinic action on airway smooth The doses of intravenous salbutamol and terbutaline are
muscle receptors (through which bronchodilation is mediated) as follows:
and absence of systemic anticholinergic adverse effects.
Salbutamol—10 μg/kg loading dose. Maintenance dose
Three doses of nebulized ipratropium bromide (250–500 μg),
5–10 μg/kg/min for 1 h followed by 1–2 μg/kg/min.
combined with salbutamol, at 20 min intervals are recom-
Terbutaline—10 μg/kg loading dose, followed by
mended in acute severe asthma. It produces additional
0.1–10 μg/kg/min.
bronchodilation, resulting in fewer hospital admissions,
in patients who have acute severe or life-threatening asthma Terbutaline is the intravenous beta agonist being used in
or those with a poor initial response to β-agonist therapy. authors’ set up. It is generally started at a minimal dose, and
Subsequently, the recommended dose is 250–500 μg at a can be subsequently titrated up every 15–20 min to desired
dosing interval of 6 h [15]. clinical response. Serious side effects include hypokalemia,
arrhythmia, hypotension and myocardial ischemia.
Magnesium Sulphate
Methylxanthines: Aminophylline
A study at the authors’ centre in 1997 had clearly
shown that administration of intravenous Magnesium sulfate Aminophylline acts as phosphodiesterase inhibitor, stim-
(i.v. MgSO4) in children with acute severe asthma not ulates endogenous catecholamine release, augments dia-
responding to conventional therapy (oxygen, nebulized phragmatic contractility, increases binding of cAMP, acts as
salbutamol, and corticosteroids) resulted in earlier improve- prostaglandin antagonist, and has other unspecified anti-
ment in clinical signs and symptoms of asthma and PEFR inflammatory effects.
[16]. A Cochrane meta-analysis of seven studies supports The role of the Aminophylline in the treatment of children
these early observations and concluded that IV magne- with severe asthma has been debated. Several recent studies,
sium sulphate improves pulmonary function and reduces however, suggest that aminophylline may offer some benefit.
hospital admissions, particularly for the patients with the In a recently completed study from authors’ centre, intravenous
most severe exacerbations of asthma [16, 17]. It acts by aminophylline was found to be equally efficacious intravenous
bronchodilating effects on smooth muscle cells, reduction terbutaline but had more side effects [17]. To avoid the side
of the neutrophilic burst associated with inflammation, and effects, the dosage needs to be adapted to age groups and
by decreasing uptake of calcium by bronchial smooth individual patient’s serum levels (goal 10–20 μg/mL). A
muscles. reasonable starting point is a 5 mg/kg loading dose, followed
Recommended dose is 50 mg/kg (range 25–75 mg/kg) by a 0.9 mg/kg/h infusion. The narrow therapeutic range of
administered IV over 20–30 min; the maximum dose theophylline overlaps with its toxicity range. Toxicity
allowed is 2 g. The onset of action is within 2–5 min. Its includes nausea and vomiting, tachycardia, and agitation.
main adverse effects are skin reddening and nausea, usually Severe and life-threatening toxicity has been reported in the
during infusion. form of cardiac arrhythmias, hypotension, seizures, and death
In a recently completed randomized trial at the present with high theophylline serum concentrations [20, 21].
centre, magnesium sulphate infusion was found to be
superior to terbutaline and aminophylline infusion in Ketamine
children who had failed to respond to 1 h treatment with
salbutamol, ipratropium and inhaled and systemic cortico- Ketamine acts as a sympathomimetic by inhibiting neuronal
steroids [18]. norepinephrine reuptake, and blocking airway N-methyl-D-
1394 Indian J Pediatr (November 2011) 78(11):1388–1395
aspartate receptors linked to the mediation of increased airway Before intubation, the child must be preoxygenated with
tone. Because of its anesthetic and bronchodilatory properties, 100% oxygen. Rapid sequence intubation should proceed
ketamine can be very useful as an induction agent for with atropine (if indicated), a sedative or anesthetic,
intubation in children with severe asthma going on mechan- followed by a rapid-acting muscle relaxant. Ketamine, is
ical ventilation. The usual dose is IV bolus of 2 mg/kg the preferred induction agent in patients with severe
followed by a continuous infusion of 0.5–2 mg/kg/h, but asthma. A cuffed or sufficiently large endotracheal tube is
higher doses have been used for asthmatic children. Unwant- recommended to minimize air leak with the anticipated
ed effects of ketamine include increase of bronchial secretions high inspiratory pressures.
(atropine or glycopyrrolate should be co-administered), and
postanesthesia emergence reaction in older children.
Indications for Transfer to an Intensive Care Unit
Antibiotics
1. Any child with signs of life-threatening attack
Asthma attacks triggered by infection mostly involve viral 2. If the child has been receiving therapy in emergency
pathogens; therefore, antibiotics are not indicated as a department for a few hours and has shown poor
routine measure. Antibiotics are indicated when more than response.
one of following is present: 3. Development of clinical signs of respiratory failure
such as persisting hypoxemia, exhaustion or change in
1. High grade fever the level of consciousness.
2. Purulent sputum with presence of polymorphs and not
eosinophils and
3. Chest radiograph showing a consolidation Treatments that are not Recommended in the
Emergency Care [3]
Supportive Treatment
– Antibiotics (except as needed for co-morbid conditions)
Overall care of the child should also be given due – Aggressive hydration
consideration, with maintenance of good hydration status, – Chest physical therapy
control of temperature and strict fluid and electrolyte – Mucolytics
balance. Poor fluid intake, increased loss of insensible – Sedation
fluids and vomiting may cause dehydration in the asthmatic
child. Euvolemia should be maintained. In a normally
hydrated child, fluid should be restricted to 65% of Discharge Advice
maintenance volume as the syndrome of inappropriate
antidiuretic hormone has been described in severe asthma. – MDI with spacer (ensure proper technique)
Overhydration may lead to pulmonary edema. Fluid – A course of oral steroids (1–2 mg/kg) if steroids
balance should be monitored carefully. have been used during the treatment of acute episode
Potassium level should be monitored frequently; hypoka- (total duration 5 days).
lemia could occur because of beta-agonist therapy (causing – Health education/councelling.
potassium to move into the intracellular compartment), and
due to increased losses caused by the use of steroids and
theophylline induced diuresis. Key Messages
every 20 min in three doses, and systemic steroids are 7. Brooks LJ, Cloutier MM, Afshani E. Significance of roentgeno-
graphic abnormalities in children hospitalized for asthma. Chest.
the mainstay of therapy.
1982;82:315–8.
& Magnesium sulphate infusion (50 mg/kg) should be 8. Qureshi F, Zaritsky A, Welch C, Meadows T. Clinical efficacy of
used in patients failing to respond to beta-agonists, racemic albuterol versus levalbuterol for the treatment of acute
inhaled and systemic steroids and inhaled ipratropium. pediatric asthma. Ann Emerg Med. 2005;46:29–36.
9. Camargo Jr CA, Rowe BH, Spooner CH. Continuous versus
& IV and subcutaneous administration of β2-agonists is
intermittent beta agonists in the treatment of acute asthma.
most beneficial for patients with severe status asthma- Cochrane Database Syst Rev. 2003;4:CD001115. Review.
ticus and limited airflow, in whom distribution of 10. Papo MC, Frank J, Thompson AE. A prospective, randomized study
inhaled medications may be significantly reduced. of continuous versus intermittent nebulized albuterol for severe
status asthmaticus in children. Crit Care Med. 1993;21:1479–
& Endotracheal intubation is indicated for patients with 86.
cardiorespiratory arrest, refractory hypoxemia, or those 11. Edmonds ML, Camargo Jr CA, Pollack Jr CV. Early use of inhaled
who have significant respiratory acidosis unresponsive corticosteroids in the emergency department treatment of acute
to pharmacotherapy. asthma. Cochrane Database Syst Rev. 2003;3:CD002308.
12. Devidayal SS, Kumar L, Jayshree M. Efficacy of nebulized
& When maximal medical therapy is failing, mechanical
budesonide compared to oral prednisolone in acute bronchial
ventilation should be considered. asthma. Acta Pediatr. 1999;88:835–40.
13. Singhi S, Banerjee S, Nanjundaswamy H. Inhaled budesonide in
acute asthma. J Paediatr Child Health. 1999;35:483–7.
Conflict of Interest None. 14. Smith M, Iqbal SMSI, Rowe BH, N’Diaye T. Corticosteroids for
hospitalised children with acute asthma. Cochrane Database Syst
Rev. 2003;2:CD002886.
Role of Funding Source None. 15. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the
treatment of children and adults with acute asthma: a systematic
review with meta-analysis. Thorax. 2005;60:740–6.
16. Devi PR, Kumar L, Singhi SC, Prasad R, Singh M. Intravenous
References magnesium sulphate in acute severe asthma not responding to
conventional therapy. Indian Pediatr. 1997;34:389–97.
17. Rowe BH, Bretzlaff JA, Bourdon C, et al. Magnesium sulphate
1. Robinson PD, Asperen PV. Asthma in childhood. Pediatr Clin N for treating exacerbations of acute asthma in the emergency
Am. 2009;56:191–226. department. Cochrane Database Syst Rev. 2000;2:CD001490.
2. Singhi S, Jain V, Gupta G. Pediatric emergencies at a tertiary care 18. Singhi SC, Bansal A, Chopra K, Grover S. Randomized
hospital in India. J Trop Pediatr. 2003;49:207–11. comparison of intravenous magnesium sulfate, terbutaline and
3. National Heart, Lung, and Blood Institute. Expert panel report 3: aminophylline infusions in acute severe asthma in children.
guidelines for the diagnosis and management of asthma—full Pediatr Crit Care Med. 2011;12:A1.
report 2007. August 28, 2007. Available at: www.nhlbi.nih.gov/ 19. Kambalapalli M, Nischani S, Upadhyayula S. Safety of intrave-
guidelines/asthma. Accessed August 29, 2007. nous terbutaline in acute severe asthma: a retrospective study.
4. Global Initiative for Asthma (GINA). Global strategy for asthma Acta Pediatr. 2005;94:1214–7.
management and prevention. (Updated 2008). Available at: www. 20. Mitra A, Bassler D, Ducharme FM. Intravenous aminophylline for
ginaasthma.org. acute severe asthma in children over 2 years using inhaled
5. Werner HA. Status asthmaticus in children. Chest. 2001;119:1913– bronchodilators. Cochrane Database Syst Rev. 2001;4:CD001276.
29. 21. Wheeler DS, Jacobs BR, Kenreigh C, Bean J. Theophylline versus
6. Becker AB, Nelson NA, Simons FE. The pulmonary index: terbutaline in treating critically ill children with status asthmati-
assessment of a clinical score for asthma. Am J Dis Child. cus: a prospective, randomized, controlled trial. Pediatr Crit Care
1984;138:574–6. Med. 2005;6:142–7.
Indian J Pediatr (November 2011) 78(11):1396–1400
DOI 10.1007/s12098-011-0492-z
Received: 25 April 2011 / Accepted: 16 May 2011 / Published online: 28 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Lower airway obstruction can occur at the level of specific clinical pointers are prolonged expiration and
trachea, bronchi or bronchioles. It is characterized clinically hyperinflated chest. Wheeze is most often expiratory, but it
by wheeze and hyperinflated chest, apart from other signs of may also be inspiratory or biphasic. Expiration becomes an
respiratory distress. Common causes include bronchiolitis, active rather than a passive process in such cases. There are
asthma, pneumonia, laryngotracheo-bronchitis, congenital many causes of wheezing in infancy and childhood. These are
malformations and foreign body inhalation. Bronchiolitis summarized in Table 1. The most common among these,
usually occurs in children aged 2 months to 2 years. It is presenting with an acute illness in authors’ emergency
most commonly caused by respiratory syncytial virus infec- department are bronchiolitis, acute asthma, pneumonia,
tion. The diagnosis is mainly clinical, and investigations have congestive cardiac failure, laryngotracheo-bronchitis, airway
a very limited role. Humidified oxygen and supportive therapy foreign bodies and congenital malformations. In a study
are the mainstays of treatment. A trial of inhaled epinephrine published in 2002 from a teaching hospital in north
or parenteral steroids may be considered for non-responders. It India, the common causes of wheezing in children aged
is usually associated with good outcome. 2 months to 1 year were bronchopneumonia(50%),
bronchiolitis(34%), bronchial asthma(16%) after exclud-
Keywords Children . Lower airway obstruction . Wheeze . ing foreign body inhalation, congestive cardiac failure,
Bronchiolitis and anatomical malformations [1]. In Singapore, 22.7%
children had at least one episode of wheeze by the second
year of life [2], while in the West one-third children had at
Lower Airway Obstruction least one lower respiratory tract infection with wheeze in
the first 3 years of life [3].
Obstruction in the lower airways (i.e. airways within the Older patients with lower airway obstruction tend to
thorax) may occur in the trachea, bronchi or bronchioles. breathe at a slower rate; however infants breathe faster. This
The general symptoms/signs of respiratory tract disease is because of a highly compliant chest wall; wherein slower
include cough, tachypnea, and increased respiratory effort. breathing would lead to subatmospheric intrapleural pres-
The most characteristic symptom and sign of lower airway sure and collapse of the chest wall.
obstruction is wheezing. Wheeze is a high pitched whistling
sound usually heard during expiration (sometimes heard
with stethoscope only). It is caused by vibrations of airways Approach to a Wheezing Child
during passage of air through narrow lumen. Other relatively
In pediatric emergency, important points in history and
examination are as follows:
S. Grover : J. Mathew : A. Bansal : S. C. Singhi (*)
Department of Pediatrics, Advanced Pediatrics Centre, History
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India & Age of onset: Onset in neonatal period/early infancy sug-
e-mail: sunit.singhi@gmail.com gests CCF, anatomic malformation, or immunodeficiency.
Indian J Pediatr (November 2011) 78(11):1396–1400 1397
Table 1 Differential diagnosis of acute wheezing in infants & Signs of allergy or atopy like rhinitis, conjunctivitis,
1. Infection eczema suggest asthma/allergic bronchitis.
• Viral: Respiratory syncytial virus bronchiolitis, Parainfluenza, & Look for the signs of CCF like hepatomegaly, neck
Influenza, Adenovirus, Rhinovirus, Human metapneumovirus veins, dependent edema, and growth pattern.
• Bacterial pneumonia Remember
• Chlamydia pneumonia
2. Asthmaa & In a child with acute onset wheezing, with history of
3. Aspiration syndromesa preceding fever and abdominal pain, and presence of
4. Heart diseasea temperature >38°C at presentation, pneumonia is the
• Congestive cardiac failure
likely diagnosis [4].
• Myocarditis
& All infants/children with bilateral wheezing do not have
• Cardiomyopathy
bronchial asthma [4]
& Foreign body aspiration can present with non-
5. Anatomic abnormalitiesa
lateralization of findings; it should be suspected in non-
• Extrinsic airway compression
responders to inhaled bronchodilators and corticosteroids
- Vascular ring/sling
[4].
- Mediastinal lymph node/mass
& Asthma and congenital heart disease can coexist [4].
• Intrinsic airway anomalies
& In a young infant (2 to 6 months) with mild to moderate
- Airway hemangioma
grade fever and wheeze along with respiratory distress,
- Cystic adenomatoid malformation
bronchiolitis is the most likely diagnosis.
- Bronchial lung cyst
- Congenital lobar emphysema
- Sequestration of lung
Bronchiolitis
- Mediastinal lymph node/tumor/TB lymphadenitis
• Central airway obstruction: laryngotracheo-malacia
“Bronchiolitis” refers to inflammation of peripheral air-
6. Foreign body
ways. It is the most common cause of wheezing in young
7. Anaphylaxis
infants.
8. Inhalational injuries (burns)
9. Mucociliary clearance disordersa
Etiology
• Cystic fibrosis
• Primary ciliary dyskinesia
Respiratory syncytial virus (RSV) is responsible for more
• Bronchiectasis than 50% cases. Other etiologic agents include Para-
10. Gastro-esophageal reflux influenza, Adenovirus, Mycoplasma, and Human Meta-
11. Immunodeficiencies – HIV, IgA deficiency, B-cell deficiency pneumovirus. Human Metapneumovirus is an important
a
These conditions can be associated with recurrent wheezing
primary cause or it can occur as a co-infection. There is no
evidence for a bacterial cause of bronchiolitis.
& Frequency: Recurrent or persistent symptoms point to-
wards asthma, cardiac cause, or anatomical malformation. Clinical Features
& A positive family history or a personal history of atopy
indicates asthma. & Age—Bronchiolitis generally occurs in young infants
& Other specific symptoms like fever, cardiac symptoms, 2 to 6 months of age. It may occur up to 2 years of
GERD may suggest the definitive cause of wheeze. age.
& Previous treatment and response to the treatment is also & History—Fever (mild to moderate grade), refusal to
important in making a diagnosis. feed, breathing difficulty, wheeze, lethargy
& On examination: wheeze, hyperinflation, hyper- reso-
Examination
nant percussion note, obliteration of liver and cardiac
& Clubbing is an indicator of chronic disease (e.g. dullness.
bronchiectasis)
& Chest shape: Barrel shaped chest is seen in asthma/ Differential Diagnoses
chronic lung disease; precordial pulsation/bulge is seen
in congenital heart disease. The differential diagnoses of wheezing in infants/children
& Lateralization of findings suggests foreign body, ana- are presented in Table 1. First episode of asthma,
tomical malformations, mediastinal lymph nodes/mass. pneumonia, and congestive cardiac failure are the most
1398 Indian J Pediatr (November 2011) 78(11):1396–1400
Nebulized Salbutamol
Assess response
Stop epinephrine.
PICU transfer
Give Dexamethasone (0.6 mg/kg) 1 dose
Inadequate response
Steroids are no different from placebo with respect to hard A recent randomized controlled trial (n=31) compared the
outcomes and several surrogate outcomes (clinical scores, use of nasal CPAP with standard treatment. CPAP im-
oxygenation parameters, respiratory rate, readmission rate). proved ventilation and hypercapnea [23].
One trial (n=174) showed that a single dose of intravenous
dexamethasone (0.6 mg/kg) results in (statistically but not Treatment Modalities That Should Be Avoided
clinically significant) shorter duration of hospitalization and
time for resolution of respiratory distress [15, 16]. & Chest physiotherapy should not be used routinely in the
Inhaled dexamethasone does not show any difference in management of bronchiolitis.
clinical score and oxygenation compared to saline [17]. & No antibiotics should be given routinely [19].
A recent randomized controlled trial studied 800 patients
divided in 4 intervention groups: 1) Epinephrine–dexa-
Indications for Hospitalization
methasone group, 2) Epinephrine group 3) Dexamethasone
group 4) Placebo group. The doses used were:- Epineph-
Indications for hospitalization are mentioned in Table 2.
rine: 3 ml of generic epinephrine in a 1:1000 solution;
Dexamethasone: 1.0 mg/kg body weight (maximum dose,
Criteria for Discharge
10 mg) or placebo given after the first nebulized treatment
in the emergency department, followed by five once-daily
The following criteria are recommended for sending home
doses of dexamethasone (0.6 mg/kg; maximum daily dose,
an infant with bronchiolitis [24]:
10 mg). The study concluded that combined therapy with
dexamethasone and epinephrine may significantly reduce & Normal respiratory rate
hospital admissions [18]. & Oxygen concentration of at least 94%
& Adequate oral intake
Ribavirin (Aerosol) & Absence of respiratory distress
Ribavirin should not be used routinely in children with Table 2 Indications for hospitalization/markers for severe disease
bronchiolitis [19]. Indications for using ribavirin include • Age less than 3 months
selected patients with life threatening RSV infection [20]: • Gestational age at birth < 34 wks
such as prematurity, infants with congenital heart disease, • Cardiopulmonary disease/immunodeficiencies
chronic lung disease and immunocompromised host. • Anatomical defects of airways
One systematic review and two subsequent RCTs • Neurological disease associated with hypotonia and pharyngeal
found that, in children and infants admitted to hospital in-coordination
with RSV bronchiolitis, ribavirin did not significantly • Respiratory rate > 70/min
reduce mortality, respiratory deterioration, or duration of • Lethargic appearance
hospital stay compared with placebo [21], but it signif- • Wheezing and respiratory distress associated with SpO2 <92%
icantly reduced the duration of ventilation compared with • Atelectasis or consolidation on chest radiography
placebo [22].
1400 Indian J Pediatr (November 2011) 78(11):1396–1400
Conflict of Interest None. 12. Gadomski AM, Bhasale AL. Bronchodilators for bronchiolitis.
Cochrane Database Syst Rev. 2006;3:CD001266.
13. Flores G, Horwitz RI. Efficacy of b2 agonists in bronchiolitis: a
Role of Funding Source None. reppraisal and meta-analysis. Pediatrics. 1997;100:233–9.
14. Mathew JL. Hypertonic saline nebulization for bronchiolitis.
Indian Pediatr. 2008;45:987–9.
15. Teeratakulpisarn J, Limwattananon C, Tanupattarachai S, et al.
References Efficacy of dexamethasone injection for acute bronchiolitis in
hospitalized children: a randomized, double-blind, placebo-
1. Kumar N, Singh N, Locham KK, Garg R, Sarwal D. Clinical controlled trial. Pediatr Pulmonol. 2007;42:433–9.
evaluation of acute respiratory distress and chest wheezing in 16. Garrison MM, Christakis DA, Harvey E, et al. Systemic cortico-
infants. Indian Pediatr. 2002;39:478–83. steroids in infant bronchiolitis: a meta-analysis. Pediatrics.
2. Tan TN, Lim DLC, Chong YS, Lee BW, Van Bever HP. 2000;105:E44.
Prevalence of eczema symptoms in the second year of life. J 17. Bentur L, Shoseyov D, Feigenbaum D, et al. Dexamethasone
Allergy Clin Immunol. 1078;2004:113. inhalations in RSV bronchiolitis: a double-blind, placebo-
3. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, controlled study. Acta Paediatr. 2005;94:866–71.
Morgan WJ. Asthma and wheezing in the first six years of life. 18. Plint AC, Johnson DW, Patel H, et al. Epinephrine and
NEJM. 1995;332:133–8. dexamethasone in children with bronchiolitis. N Engl J Med.
4. Singhi SC, Mathew JL, Jindal A. Clinical Pearls in Respiratory 2009;360:2079–89.
Diseases. Indian J Pediatr. 2010 Dec 14.[Epub ahead of print] 19. American Academy of Pediatrics. Subcommittee on diagnosis and
doi:10.1007/s12098-010-0270-3. management of bronchiolitis. Diagnosis and management of
5. Poddar U, Singhi S, Ganguli NK, Sialy R. Water electrolyte bronchiolitis. Pediatrics. 2006;118:1774–93.
homeotasis in acute bronchiolitis. Indian Pediatr. 1995;32:59–65. 20. American Academy of Pediatrics. Chapter on respiratory
6. Bush A, Thomson S. Acute bronchiolitis. BMJ. 2007;335:1037–41. syncytial virus. In: Pickering LK, editor. Red Book: 2009
7. Mathew JL. What works in bronchiolitis? Indian Pediatr. Report of the Committee on Infectious Diseases. 28th ed.
2009;46:154–8. Elk Grove Village: American Academy of Pediatrics; 2009.
8. Hartling L, Wiebe N, Russell K, Patel H, Klassen TP. Arch Pediatr p. 560–4.
Adolesc Med. 2003;157:957–64. 21. Hartling L, Russell KF, Patel H, et al. Epinephrine for bronchio-
9. Ray MS, Singh V. Comparison of nebulised adrenaline versus litis. Cochrane Database Syst Rev. 2004;1:CD003123.
salbutamol in wheeze associated respiratory infections in infants. 22. Ventre K, Randolph AG. Ribavirin for respiratory syncytial virus
Indian Pediatr. 2002;39:12–22. infection of the lower respiratory tract in infants and young
10. Bertrand P, Aranibar H, Castro E, Sanchez I. Efficacy of nebulised children. Cochrane Database Syst Rev. 2007;1:CD000181.
epinephrine versus salbutamol in hospitalized infants with 23. Thia LP, McKenzie SA, Blyth PB, et al. Randomised controlled
bronchiolitis. Pediatr Pulmonol. 2001;31:284–8. trial of nasal continuous positive airways pressure (CPAP) in
11. Menon K, Sutcliffe T, Klassen TP. A randomized trial comparing bronchiolitis. Arch Dis Child. 2008;93:45–7.
the efficacy of adrenaline with salbutamol in the treatment of 24. Basco WT. Predicting which pediatric bronchiolitis patients can be
acute bronchiolitis. J Pediatr. 1995;126:1004–7. safely discharged from the ED. Pediatrics. 2008;121:680–8.
Indian J Pediatr (November 2011) 78(11):1401–1403
DOI 10.1007/s12098-011-0488-8
Received: 23 April 2011 / Accepted: 11 May 2011 / Published online: 26 May 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Foreign body aspiration into the airway is one of The following factors make the children more prone to
the dramatic pediatric emergencies. It is more common in foreign body aspiration:
children aged 6 months to 5 years. Pea nuts and food items
1) Absence of molars—inadequate chewing
account for most cases. Right main stem bronchus is the
2) In-coordinated swallowing mechanism
most common site involved. The initial cough and choking
3) Curiosity / carelessness
like episodes may be followed by a symptomless interval
before leading to further complications. Chest radiograph
findings may vary from normal to hyperinflation, obstruc-
tive emphysema or pneumothorax. Removal by rigid Pathophysiology
bronchoscopy is the definitive treatment.
The pathophysiology (and clinical picture) depends upon
Keywords Foreign body . Choking . Bronchoscopy the type of foreign body and location in the airway. The
object itself may cause obstruction. Foreign body causing
total obstruction at trachea/larynx may cause respiratory
Introduction failure/arrest and death within minutes. Acute obstruction
of the level of carina or main bronchus may cause lung
Foreign body aspiration is one of the common emergency collapse and hypoxemia. Overtime, pooled secretion
problems encountered in pediatric age group. At PGIMER, caused by partial obstruction may get infected and
it is responsible for approximately 0.6% of admissions in present with pneumonia. A sharp foreign body (FB)
pediatric emergency [1]. A male preponderance has been may lead to erosion, as is the case with battery cells.
noted. Delay in identification can lead to complications Vegetable matter may swell over hours or days leading to
including death. Most common age group affected is obstruction. Organic foreign bodies (nuts) may produce
6 months to 5 years. Most common objects inhaled are inflammation and edema.
pea nuts and food items. Organic objects may cause local
inflammation and swelling and convert partial obstruction
to complete obstruction. According to various studies, the Clinical Features
right main stem bronchus is the most common site of
obstruction [2, 3]. The larynx is the least common site. There may be definite history of foreign body aspiration
in 40–70% cases [4, 5]. The initial symptoms may include
cough, gagging, choking, wheezing, dyspnea, cyanosis,
hoarseness, and drooling. Partial obstruction at larynx may
S. Grover : A. Bansal : S. C. Singhi (*) present with inspiratory stridor, drooling and voice
Department of Pediatrics, Advanced Pediatrics Centre, change.
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India Partial obstruction at trachea often presents with chok-
e-mail: sunit.singhi@gmail.com ing, cough, whereas partial obstruction at bronchus presents
1402 Indian J Pediatr (November 2011) 78(11):1401–1403
X-ray chest
Definitive history
Doubtful history
Strong suspicion of foreign body
*Note: Even after removing the foreign body, inflammatory changes and edema may persist for
some time leading to persistence of the symptoms.
Treatment
Received: 12 May 2011 / Accepted: 1 June 2011 / Published online: 22 June 2011
# Dr. K C Chaudhuri Foundation 2011
Evaluation
Introduction
The aim of emergency evaluation is not to miss the rare
Fainting or syncope is a common clinical problem in occurrence of serious underlying disorder in a child with
children and adolescents, with as many as 15% of children syncope and to differentiate syncope from seizures
experiencing at least one episode of syncope before the end (Table 2). A thorough clinical evaluation, including
of adolescence. The overall incidence in children is 0.1– history and physical examination is the first step in
0.5% and constitutes 1–3% of emergency visits [1]. The identifying the three major categories of syncope (Tables 3
vast majority of episodes of syncope are benign and only a and 4).
minority are caused by something potentially more serious
or even life threatening.
Laboratory Investigations
K. M. Naranje : A. Bansal : S. C. Singhi (*) Laboratory investigations for syncope in childhood will
Department of Pediatrics, Advanced Pediatrics Centre,
almost always be normal; the key to the diagnosis is a
Postgraduate Institute of Medical Education and Research,
Chandigarh, India detailed and careful history. A 12-lead ECG is required
e-mail: sunit.singhi@gmail.com in all children with syncope with special emphasis on the
Indian J Pediatr (March 2012) 79(3):362–366 363
Table 1 Common causes of pediatric syncope and their relative mediated syncope. Further diagnostic work up is required
incidence in children [2, 3]
if the following are present [2]:
Categories of syncope Causes
& Exercise-induced syncope that occurs during exertion
(Incidence %)
& Chest pain that precedes an episode of fainting
Neurally-mediated Vasovagal syncope & Seizure activity
syncope (73) Reflex syncope & Recurrent syncope (three or more episodes)
Orthostatic hypotension & An abnormal cardiac examination
Postural orthostatic tachycardia & Unexplained syncope
syndrome
For Cardiovascular Syncope
Cardiovascular
syncope (2.9) & Chest radiograph
Arrhythmias & Echocardiography
Tachyarrhythmia Long QT syndrome & Holter ECG
WPW syndrome & Electrophysiological studies
Bradyarrhythmia Heart block
For Non-cardiovascular Syncope
Sick sinus syndrome
Structural Congenital heart diseases & Neurology referral for EEG, CT or MRI head
Aortic stenosis & Psychiatric referral
Cardiomyopathies & Metabolic-blood glucose, complete blood count,
Non-cardiovascular electrolytes, toxicological screen
syncope (24)
For Unexplained Syncope
Neurological (2.1) Seizures
Migraine & Head up tilt test
Psychogenic Conversion reaction
(pseudosyncope) (2.3) Depressive disorder Head Up Tilt Test (HUT)
Generalised anxiety disorder
Hyperventilation The child is asked to rest supine for 15 min and is then
Metabolic (0.8) Hypoglycemia tilted to 60° head-up for a maximum of 45 min. During
Severe anemia this time the blood pressure and ECG are continuously
Drugs recorded. HUT is considered positive when syncope is
Carbon monoxide reproduced in association with hypotension (decrease in
Electrolyte abnormalities systolic blood pressure >60% of the maximal value
Unexplained syncope (18.9) observed in the upright position), bradycardia (decrease
>30% of the maximal value observed in the upright
position), or both. Three patterns of positive response
according to the changes in blood pressure and heart rate
QT interval and T wave morphology for evidence of long are: (1) the cardioinhibitory pattern, which is character-
QT syndrome. In most cases, no further diagnostic tests ized by a rapid decrease in heart rate, presenting as
are needed when the history, physical examination and bradycardia; (2) the vasodepressor pattern, with a rapid
ECG suggest neurally mediated syncope. A standing test decrease in blood pressure; and (3) the mixed pattern,
should be performed at this stage to identify neurally which is most common, in which both blood pressure
and heart rate decrease during the tilting and is usually during the test. Figure 1 summarises approach to a child
seen with vasovagal syncope [5]. with syncope in emergency department.
Standing Test
Management
Standing test is performed in a quiet and warm environ-
ment. Blood pressure and pulse are recorded after child had Syncope usually does not require hospital admission. The
rested in a supine position for at least 5 min. He is then indications for hospital admission include
asked to stand for 10 min, and pulse and blood pressure are
measured immediately and after 1, 2, 3, 5 and 10 min [3]. & Syncope occurring several times a day
Orthostatic hypotension is identified as persistent decrease & Infants who have recurrent and severe episodes of
of more than 20 mmHg systolic blood pressure or decrease syncope
of more than 10 mmHg diastolic blood pressure within & Abnormal cardiac rhythm disturbances requiring acute
3 min after the start of HUT or standing test [6]. stabilisation
These tests should be done cautiously. Resuscitation & Abnormal neurological/metabolic state requiring acute
equipment should be available at hand on the bedside stabilisation
• Standing test
Specific Behavioural
management therapy
Fig. 1 Approach to a child with syncope, Abbreviations: CBC Complete Blood Count, HUT Head Up Tilt Test, NMS Neurally Mediated Syncope
Neurally Mediated Syncope & Temporary pacemaker therapy for a sick sinus or heart block
& Disposition—Cardiology referral for definitive management
& Reassurance—especially that the episodes are not
caused by epilepsy or a cardiac problem
& Prevent triggering events Non-cardiovascular Syncope
& Plenty of fluids; older children and adolescents should & Neurological
be advised to drink around 2 L water or fluids per day
& Small amount of salty food – Antiepileptics for seizures
& Manoeuvres such as crossing the legs and folding the – Neurology consultation
arm, sitting or lying down at the onset of prodromal
symptoms & Metabolic
& Drugs are reserved for syncope not responding to above – Dextrose for hypoglycaemia
measures and frequent and recurrent episodes [7]. – Correction of electrolyte imbalance
– Fludrocortisone 100 μg/d – Iron supplements for anemia
– Specific management for drug overdose, carbon
– Beta-blockers
monoxide poisoning
& Disposition—Pediatric outpatient department follow up
& Psychogenic
Cardiovascular Syncope
– Psychiatric consultation
& Management of arrhythmias, wherever applicable – Anxiolytics, antidepressants and/or behavioral thera-
& Beta-blocker therapy in cases of long QT syndrome py after specialist consultation
366 Indian J Pediatr (March 2012) 79(3):362–366
Received: 9 July 2011 / Accepted: 2 August 2011 / Published online: 26 August 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Non traumatic coma in childhood is an etiology, initial management of the comatose child in
important emergency. It can result from wide range of emergency room involves immediate attention to sustain
etiologies. CNS infections are the most common cause of life and prevent irreversible damage.
non traumatic coma in children. However, multiple
interrelated factors may be present in one patient.
Management of a comatose child goes hand in hand Definitions
with clinical evaluation. It is an emergency that requires
simultaneous institution of immediate life support, Consciousness is a state of awareness of self and
identification of the cause and institution of definite surroundings which involves complex interaction of cere-
therapy. The primary goal is to establish airway, bral cortex and reticular activating system. This state is
breathing and circulation and to identify and treat raised determined by two separate functions:
intracranial pressure and seizures.
& Awareness (content of consciousness), depends on an
intact cerebral cortex.
Keywords Coma . Encephalopathy . Impaired
& Arousal (level of consciousness), depends on an intact
consciousness . Intracranial pressure
ascending reticular activating system (ARAS) and its
connections with diencephalic structures.
Introduction Coma is a state of altered consciousness with loss of
both wakefulness (arousal) and awareness of self and
Non traumatic coma in childhood is a common pediatric surroundings characterized by a state of sustained, patho-
emergency. The incidence of non traumatic coma is 30/ logic, unarousable unresponsiveness and absence of sleep-
100,000 children per year [1]. The diagnosis and manage- wake cycles, which must last for at least 1 h [3].
ment of a comatose child in the emergency room is a Vegetative state describes a condition of complete
challenging task. Central nervous system (CNS) infections unawareness of the self and the environment accompanied
are the most common cause of non traumatic coma in by sleep wake cycles with variable preservation of
children in the authors’ setting [2]. Regardless of the brainstem functions [4].
Minimally conscious state is defined as a condition of
severely altered consciousness in which the patient dem-
onstrates minimal but definite behavioral evidence of self-
A. Jindal : S. C. Singhi (*) : P. Singhi or environmental awareness [5].
Department of Pediatrics, and Advanced Pediatrics Centre, Brain death is defined as the permanent absence of all
Postgraduate Institute of Medical Education and Research
brain functions including those of the brainstem [6].
(PGIMER),
Chandigarh 160012, India Descriptive terms such as somnolence, stupor, obtunda-
e-mail: sunit.singhi@gmail.com tion, and lethargy used to denote different levels of
368 Indian J Pediatr (March 2012) 79(3):367–375
wakefulness are best avoided, given the lack of uniformity imal elements of ARAS. However, comparatively small
in the way these states are defined in the literature [7]. brainstem and diencephalic lesions that disrupt or impair
the ARAS and its projections can cause coma.
Toxic and metabolic etiologies of coma have been linked
Etiopathogenesis to an interruption in the delivery or utilization of oxygen or
substrate (hypoxia, hypoglycemia); alterations in neuronal
Common causes of non-traumatic coma seen in children in the excitability and signalling (seizures, drug toxicity, acidosis)
authors’ emergency department are central nervous system or changes in brain volume (hyper/hyponatremia).
infections, which includes tubercular meningitis (19%), The degree of neurologic impairment is related to the
encephalitis (18%), and bacterial meningitis (16%),toxic- time course of the underlying cerebral pathology. An acute
metabolic encephalopathies (19%), status epilepticus (10%), lesion is usually associated with depressed consciousness
intracranial bleed (7%), and other (4%) [2]. Coma can be due whereas a slowly developing lesion at identical location and
to a primary/direct insult to the cerebral cortex, diencephalic volume may be asymptomatic.
structures, midbrain or rostral pons, or a secondary manifes-
tation of systemic derangements caused by toxins, metabolic
or endocrine disorders (Table 1). However, multiple interre- Evaluation of a Comatose Child
lated factors may be present in one patient.
Coma can be precipitated by a critical hemispheric lesion Management of a comatose child goes hand in hand with
if there is bilateral diffuse involvement, or a large unilateral clinical evaluation. It is an emergency that requires
lesion causing midline shift leading to central or tentorial simultaneous institution of immediate life support, identifi-
herniation with midbrain compression, compromising prox- cation of the cause and definitive therapy.
Table 1 Causes of
non-traumatic coma in Infections Metabolic
children Tubercular meningitis Hypoglycemia
Viral meningoencephalitis Diabetic ketoacidosis
Bacterial meningitis Uremia
Cerebral malaria Hyperammonemia (hepatic encephalopathy, Reye
syndrome, disorders of fatty acid metabolism)
Rickettsial meningoencephalitis Mitochondrial encephalopathies
Rabies Dyselectrolytemia (hyponatremia, hypernatremia,
hypercalcemia, hypermagnesemia, hypophosphatemia)
Brain abscess Acute Porphyria
Subdural/epidural empyema Acidosis/alkalosis
Toxic encephalopathy ( enteric fever, shigella Toxic
encephalopathy)
Severe systemic infections with shock Opioids
Post infectious Barbiturates
Acute demyelinating encephalomyelitis Organophosphates and carbamates
Acute necrotising encephalopathy Sedatives
Hemorrhagic shock encephalopathy syndrome Tricyclic antidepressants
Post immunisation Lead encephalopathy
Whole cell DPT Snake bite
Semple rabies vaccine Structural
Hypoxia-ischemia Tumor
Shock Hydrocephalus
Cardiac/pulmonary failure Miscellaneous
Near drowning Post ictal state
Vascular Status epilepticus (convulsive, non convulsive)
Arterial ischemic stroke Hypertensive encephalopathy
Sinus venous thrombosis Acute complicated migraine
Intracranial bleed
Indian J Pediatr (March 2012) 79(3):367–375 369
Primary Assessment and Emergency Management (Table 4). If signs of raised ICP or impending herniation
are present, start manual hyperventilation with a bag
& The primary goal is to establish airway, breathing and (PaCO2 30–35 mmHg) and give 20% mannitol (0.5 g/kg)
circulation and to identify and treat raised intracranial or hypertonic saline (preferred if patient in shock).
pressure (ICP). & Perform Dextrostix testing and send for simultaneous
& Establish airway by jaw thrust/ oropharyngeal airway venous blood sugar. Give dextrose 2 ml/kg of 25% dextrose
and give high flow oxygen by mask. or 5 ml/kg of 10% dextrose if blood sugar is<60 mg/dl and
& Perform endotracheal intubation by rapid sequence increase glucose infusion rate to 6–8 mg/kg/min.
induction and start bag ventilation if the patient has & Take samples for serum electrolytes, arterial blood
modified Glasgow coma score≤8, impaired airway gases, lactate, complete blood count, platelet count,
reflexes, shock or evidence of herniation. Invasive blood cultures, liver and kidney function tests, MP
interventions can aggravate ICP; avoid trauma as far as smears, toxicology screen, urine sugar and ketones.
possible and try to keep oxygen saturation above 92%. & Maintain normothermia—treat fever and hypothermia.
& If signs of compensated/ hypotensive shock are present, & In a febrile child give empiric first dose of ceftriaxone
establish a vascular access and resuscitate with isotonic (100 mg/kg i.v. in 2 divided doses) and acyclovir/
saline and inotropes. If there is high BP at contact, it could artesunate as indicated, obtain CT scan and decide about
be both cause and effect of coma; reduce it slowly. further management.
& Assess level of consciousness using the modified
– In a child with focal neurologic deficit, focal seizures,
Glasgow coma scale (GCS) (Table 2). If in doubt on
behavioral changes, aphasia, neuroimaging suggestive
scoring, record a lower score initially.
of fronto-temporal involvement or hemorrhagic CSF,
& Examine the fundi for papilledema (rarely seen in acute
give first dose of Acyclovir (30 mg/kg i.v. in 3 divided
encephalopathy; absence does not exclude intracranial
doses) and obtain MRI.
hypertension), retinal hemorrhage, and macular star
– If child is resident of P.falciparum endemic area, and
suggestive of hypertension.
has hypoglycemia, anemia or absent meningeal signs
& Look for tonic deviation of the eyes or nystagmus. If
then give empiric IV Artesunate/Quinine.
there is tonic deviation of the eyes or nystagmus,
assume subtle status epilepticus and give benzodiaze-
pine (inj. Lorazepam 0.1 mg/kg or inj. diazepam Focussed History
0.3 mg/kg) and load with inj. Phenytoin 20 mg/kg.
& Assess brain stem function (Table 3) and decide whether A detailed history may not be available during initial
the patient has evidence of herniation or raised ICP resuscitation phase of the comatose child but it should be
Hepato-splenomegaly (malaria, enteric fever, viral hepatitis, Herniation syndromes The details are given in Table 4.
sepsis), murmurs (congenital heart disease, rheumatic fever, Also look for focal deficits which may suggest presence
infective endocarditis), signs of infective endocarditis, and of intracranial space occupying lesion (abscess, tuber-
evidence of pneumonia may be helpful clues to the cause. culoma, infarcts).
372 Indian J Pediatr (March 2012) 79(3):367–375
Pontine Pinpoint
Opiate/ Organophosphate poisonings Pinpoint
Hypothalamic Small reactive
Metabolic Small reactive
Midbrain Mid position, fixed
Oculomotor nerve, uncal herniation Ipsilateral pupil fixed and dilated
Hypoxic ischemic encephalopathy Bilateral fixed dilated
Tectal Large, nonreactive, hippus
Anticholinergic, sympathomimetic, antidepressant poisoning Dilated and fixed
Second Line Investigations Once the child is stabilised with emergency management as
described above, next comes:
Electroencephalography (EEG) Serial EEG’s are more
useful than single isolated EEG. EEG helps in detection 1. Specific management according to etiology
of non convulsive status epilepticus as a cause of coma. It is 2. Prevention and treatment of secondary complications
relatively specific in herpes simplex encephalitis (periodic (Fig. 1).
Indian J Pediatr (March 2012) 79(3):367–375 373
*
Focussed history and neurological examination
* Assess the level of consciousness (table 2) *Focussed neurological examination (table 3,4,5)
No Yes
Sepsis – broad spectrum antibiotics Refer to protocol for Febrile
DKA – Insulin, fluid and other supportive encephalopathy
therapy.
Hepatic encephalopathy – refer to
protocol for acute liver failure.
Uremia – refer to protocol for acute renal
failure.
Heat stroke- specific treatment
Focal signs with or without raised Raised ICP without Normal ICP and
ICP focal signs No Focal Signs
Dyselectrolytemia
Urgent CT Scan Toxins – naloxone, flumazenil
Metabolic
Abnormal
Snake Bite - ASV
Normal Hypoxic
Stroke – refer to protocol for stroke. Diabetic ketoacidosis DKA
Todd’s paresis ICSOL Acute hydrocephalus Postictal
Stroke Intracranial bleed Reye’s syndrome
Brain abscess
Urgent neurosurgery
evaluation and MRI
if possible
All comatose children should be transferred to PICU. Till Prognosis largely depends on the underlying etiology and
then following measures should continue: severity of brain injury. A patient with delayed initiation of
treatment also will have poor prognosis. In a study of 100
1. Maintain ABC, correction of hypoglycemia.
consecutive patients in the authors’ Unit , survival rate was
2. Treatment of seizures.
65%. Among those who died, deep coma (GCS<6),
3. Maintain normothermia and euglycemia.
abnormal respiration patterns, abnormalities of vitals like
4. Correct electrolyte and acid base abnormalities.
hypothermia, hypotensive shock, abnormal tone (flaccidity)
5. Ensure adequate intravascular volume by use of N/2 or
were suggestive of poor prognosis. Among acute CNS
normal saline with added glucose in full maintenance
infections, rabies, herpes encephalitis, severe stages of
doses. Restriction of fluids does not improve the
TBM had poor prognosis. Among metabolic encephalopa-
outcome.
thies, children with hepatic coma had high mortality [2].
6. Measures to control raised ICP: Keep head in midline
with 30° elevation to promote cerebral venous drainage
(but may be kept flat if the child is in shock or if the
Key Messages
mean arterial blood pressure falls with change in
position).
& Urgent management is required in any child with coma.
7. Gentle suctioning and avoid vigorous physiotherapy,
& Stabilization of ABC in emergency room is most
catheterise the bladder to prevent urinary bladder
important to sustain life and prevent secondary brain
distension and surge in ICP, ensure deloading of colon
injury.
with use of laxatives, and early institution of nasogas-
& Secure airway, oxygenate, bag ventilate to keep CO2
tric feeds.
within low normal range.
8. General care: Minimal handling, care of eyes to prevent
& Identify the signs of impending brain herniation and
exposure keratitis, frequent change of position to
treat immediately.
prevent pressure sores, adequate analgesia (morphine)
& Identify and treat seizures.
and sedation (benzodiazepines).
& Identify and treat reversible and acute causes (e.g.,
9. Look for and treat nosocomial infections.
hypoglycemia) immediately.
& Diagnosis and specific treatment depends on the
etiology of coma.
Monitoring & Prognosis largely depends on the etiology and extent of
brain damage.
Monitor continuously for vital signs (at least hourly),
changing level of consciousness (GCS hourly), neurologi-
cal status, brainstem signs, ICP, Cerebral perfusion pressure,
SpO2 and EtCO2 or ABG, assess adequate sedation and Conflict of Interest None.
analgesia, input and output daily, weigh daily if possible
and if not contraindicated (raised ICP, ventilated), urine
Role of Funding Source None.
output, bowel sounds, blood counts, serum electrolytes,
blood sugar, serum and urine osmolality, EEG.
References
Follow Up
1. Wong CP, Forsyth RJ, Kelly TP, et al. Incidence, Aetiology, and
Outcome Of Non-Traumatic Coma: A Population Based Study.
These children should be followed up to ensure early Arch Dis Child. 2001;84:193–9.
detection and development for long duration. They should 2. Bansal A, Singhi S, Singhi P. Non Traumatic Coma. Indian J
be looked for early development of - Pediatr. 2005;72:467–73.
3. Medical Aspects of the Persistent Vegetative State (1): The Multi-
& Neurologic sequelae like motor, visual and hearing Society Task Force on PVS. N Engl J Med. 1994; 330:1499–1508.
deficits. 4. Giacino J, Whyte J. The Vegetative and Minimally Conscious
States: Current Knowledge and Remaining Questions. J Head
& Developmental and intellectual disabilities. Trauma Rehabil. 2005;20:30–50.
& Learning and behaviour problems. 5. Giacino JT, Ashwal S, Childs N, et al. The Minimally Conscious State:
& Seizures Definition and Diagnostic Criteria. Neurology. 2002;58:349–53.
Indian J Pediatr (March 2012) 79(3):367–375 375
6. Task Force for the Determination of Brain Death in Children. 8. Tatman A, Warren A, Williams A, et al. Development of a Modified
Guidelines for the Determination of Brain Death in Children. Paediatric Coma Scale in Intensive Care Practice. Arch Dis Child.
Pediatrics. 1987;80:298. 1997;77:519–21.
7. Laureys S, Owen AM, Schiff ND. Brain Function in Coma, 9. Baringer JR. Herpes Simplex Virus Encephalitis. In: Davis N,
Vegetative State, and Related Disorders. Lancet Neurol. Kennedy PGE, editors. Infectious Diseases of the Nervous System.
2004;3:537–46. Oxford: Butterworth-Heinemann; 2000. p. 139–64.
Indian J Pediatr (March 2012) 79(3):376–380
DOI 10.1007/s12098-011-0570-2
Received: 21 July 2011 / Accepted: 27 September 2011 / Published online: 20 October 2011
# Dr. K C Chaudhuri Foundation 2011
Keywords Children . Headache . Migraine . Brain tumor . Headaches can be caused by primary entities as in migraine
Neuroimaging . Analgesics or tension-type headaches or the pain may result from
secondary causes. Secondary headaches usually have
identifiable etiologies. Although the vast majority of
K. Nallasamy : S. C. Singhi (*) : P. Singhi secondary headaches in children have benign underlying
Department of Pediatrics, Advanced Pediatrics Centre, cause (such as viral infections), the goal of the emergent
Postgraduate Institute of Medical Education and
evaluation of children with headaches is to identify as a first
Research, (PGIMER),
Chandigarh 160012, India priority those with serious or life-threatening etiology
e-mail: sunit.singhi@gmail.com (brain tumors, CNS infections).
Indian J Pediatr (March 2012) 79(3):376–380 377
MRI / CT scan
+ -
(Unless contraindicated) LP
Spontaneous IC bleed
Fever
Yes No
Migraine
Conversion
Meningitis
Table 1 Indications for neuroimaging in a child with headache in Table 2 Diagnostic criteria for migraine in children [3]
emergency department [1]
A. Five or more headache attacks that:
• Headache associated with abnormal neurological findings B. Last 1 to 48 h
(papilledema, cranial nerve and motor abnormalities)
C. Have at least two of the following features:
• Early morning headache or the headache that awakens a
Bilateral or unilateral (frontal/temporal) location
child from sleep
Pulsating quality
• Acute headache associated with episodes of confusion,
disorientation or signs of raised ICP Moderate to severe intensity
• Presence of ventriculo-peritoneal shunt Aggravated by routine physical activities
• History of recent trauma D. Are accompanied by at least one of the following:
• Age less than 3 y Nausea and/or vomiting
• Severe parental anxiety Photophobia and/or phonophobia
MRI is considered superior especially in detecting small Antiemetics:Promethazine—0.25 to 0.5 mg/kg/dose P.O,
lesions, posterior fossa lesions and vascular malformations. Prochlorperazine—0.25 to 0.5 mg/kg/dose P.O
Migraine
Intracranial Space Occupying Lesion
Migraine is one of the most common causes of acute and
recurrent headache in children. By 15 y of age, at least 5% to A wide variety of Childhood tumors and CNS infections
10% of children have had a migraine headache. Migraine’s present with headache. The commonest among them include:
incidence begins to peak in early adolescence and may be a
& Tumors (medulloblastoma, astrocytoma)
concern in children as young as 5 or 6 y of age.
& Brain abscess
& Tuberculoma
Features
& Neurocysticercosis
Classically the onset of pain is preceded by an aura (visual, They often present with associated abnormal neurolog-
GI) and then an increasing severity of pulsatile pain often ical features (projectile vomiting, Cranial nerve palsy,
felt unilaterally (frontal, temporal). However, children may seizures, focal neurodeficits and papilledema) which alert
present with bilateral headache of shorter duration and the physician towards the diagnosis of these conditions.
without the combination of photo and phonophobia. Neuroimaging (CECT/MRI) is mandatory.
Diagnostic criteria for migraine in children are given in
Table 2 [3]. Treatment
16 mg/d) or oral prednisolone 2 mg/kg/d in 3 divided and intracranial hemorrhage need i.v. dexamethasone
doses. 1 mg/kg loading, then 1–1.5 mg/kg/d in four divided
doses and further definitive neurosurgical management.
Disposition
Received: 4 August 2011 / Accepted: 20 October 2011 / Published online: 26 November 2011
# Dr. K C Chaudhuri Foundation 2011
Abstract Acute seizure and status epilepticus constitute one within the cerebral cortex. These discharges occur in
of the major medical emergencies in children. Among various locations and may spread in different directions
children, the incidence ranges from 4-38/100,000 children and at different speeds, resulting in several types of
per year respectively. The incidence in developing countries is seizures, each with its own clinical manifestation.
somewhat higher because of infections. Although, the
definition of status epilepticus is based on duration of seizures,
the operational definition is to treat any child who is brought Incidence
seizing to the emergency room, as status epilepticus. An
urgent time bound approach is of paramount importance when Incidence of seizures ranges from 40–70 per 100,000
managing a child in status epilepticus. Benzodiazepines population [1] in developed countries, and somewhat
remain the first line antiepileptic drugs in the emergency higher, approximately, 60–124 in developing countries [2,
room; a long acting drug (Lorazepam) is preferred when 3]. Studies have shown that 4–6% of children will have
available. This is followed by Phenytoin (20 mg/kg) loading. atleast one seizure in the first 16 y of life [4]. Among
In patients refractory to above drugs, valproate (30 mg/kg) children, the incidence of status epilepticus ranges from 4–
loading is commonly used and if effective, followed by an 38 episodes per 100,000 children per year [5].
infusion (5 mg/kg/h) for seizure free period of 6 h. In non-
responders, a trial of Levetiracetam (40 mg/kg infused at
5 mg/kg/min) can be used before starting benzodiazepine or Definitions [6, 7]
thiopental coma (3–4 mg/kg loading dose, followed by
2 mg/kg/min infusion). When pharmacological coma is Epileptic Seizure: It is a transient occurrence of signs and/
initiated, the child needs to be shifted to pediatric intensive or symptoms due to abnormal or excessive synchronous
care unit for proper monitoring and titration of medications. neuronal activity in the brain
Keywords Acute seizure . Children . Status epilepticus . Epilepsy: It is a disorder of brain characterized by an
Febrile seizures . Refractory status epilepticus enduring predisposition to generate epileptic seizures
and by the neurobiologic, cognitive, psychological and
social consequence of the condition. The definition of
Introduction epilepsy requires occurrence of atleast one epileptic
seizure; generally it includes two or more unprovoked
A seizure results from abnormal, excessive, paroxysmal seizures
electrical discharge of neurons within the brain, primarily
Convulsion: Attack of involuntary muscle contractions,
K. Sasidaran : S. Singhi (*) : P. Singhi which may be sustained (tonic) or interrupted (clonic).
Department of Pediatrics, Advanced Pediatric Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160 012, India Status epilepticus: Operational definition: It is a condition
e-mail: sunit.singhi@gmail.com of prolonged seizure activity (more than 5 min) or
Indian J Pediatr (April 2012) 79(4):510–517 511
persistent, repetitive seizure activity without recovery of Table 1 Causes of refractory SE in children admitted to Pediatric
Intensive Care Unit, PGIMER, Chandigarh in 1995 and 2005
consciousness in between episodes. Any child who is
brought seizing to the emergency room should be treated Causes Number of Patients
as status epilepticus.
In 1995 (n=62) In 2005 (n=40)
Postictal period: It usually follows the seizure. During
Bacterial/ purulent meningitis 26 5
this time, the patient may be confused, lethargic,
Encephalitis 11 20
fatigued, or irritable; also, headache, vomiting, and
Idiopathic epilepsy 10 4
muscle soreness may occur. In general, the length of
Post-hypoxic encephalopathy 4 –
the postictal period is proportional to the length of the
Reye’s encephalopathy 2 –
seizure.
Shigella encephalopathy 2 –
Intracranial bleed – 2
Neuro metabolic disorders – 2
Pathophysiology
Others 5 7
Afebrile +
Simple febrile seizure Fever triggered seizure in a CNS infections
Normal on clinical examination
child with epilepsy
Complex febrile seizures
Fig. 1 Steps for Confirming the diagnosis and type of Seizures. risk than generalized tonic clonic events), Positive family history of
* First episode seizure requiring antiepileptic therapy. epilepsy, Seizures associated with head injury/ Seizures in a predisposed
Symptomatic seizures due to underlying etiology (inflammatory child (developmental delay), Myoclonic seizures, Absence seizures,
granuloma, infarct, migration defect), Partial seizures (greater relapse seizure during sleep
& Documentation of fever (>38°C) outlines the team approach to a seizing child presenting to
& One convulsion within 24 h period the pediatric emergency.
& Absence of pre-existing neurological abnormality
Initial Stabilization (Supporting Vital Functions)
Assessment Pentagon
Appearance
Breathing
Circulation
Disability
Exposure
Stabilize Airway
Breathing
Circulation
& Reassess the need for bag and mask ventilation (BMV). & If vascular access cannot be quickly achieved, give
Bag and mask ventilation should be started if there are rectal diazepam or midazolam IM and continue to
signs of inadequate ventilation and oxygenation such as establish vascular access.
inadequate chest movements, poor air entry on auscul- & If the patient has no response to first dose of lorazepam/
tation, tachypnea, poor respiratory efforts, central diazepam, repeat the dose and
cyanosis, or oxygen saturation <90%. If bag mask & Administer loading dose of phenytoin 20 mg/kg over
ventilation is unsatisfactory, endotracheal intubation 20 min (Phenobarbitone is preferred in neonates and in
should be done. SE associated with fever - loading dose of 20 mg/kg IV
& Indications for endotracheal intubation (Rapid sequence at a rate of 1.5 mg/kg/h).
intubation):
– Severe hypoxia (bradycardia, hypotension, poor Drug Therapy to Terminate Seizure Activity
perfusion) [10, 11, 16–18]
– Failure or prolonged requirement of bag and mask
ventilation Intravenous Benzodiazepines
– Children with features of raised intracranial pressure
– Refractory status epilepticus (seizure persists even Intravenous administration of benzodiazepines stops
after adequate treatment with benzodiazepines and seizures most rapidly regardless of the etiology. Hence,
Phenytoin) these are accepted as first-line treatment of convulsive
or non-convulsive SE. Midazolam 0.1–0.2 mg/kg (max-
& Obtaining a vascular access is the next important step.
imum 5 mg), or diazepam 0.3 mg/kg (maximum 10 mg)
This is needed for administration of fluids to stabilize
at a rate no greater than 2 mg/min, or lorazepam 0.05–
circulating volume and anticonvulsants therapy to abort
0.1 mg/kg (maximum 4 mg) given over 2 min, can be
seizure. In a convulsing child, at times it may be
used as a first line treatment. The onset of action of
difficult to establish an intravenous access. In such a
these drugs is within 1–3 min of administration.
situation one may use intraosseous (IO) route. In
However, the need to keep lorazepam refrigerated and
children less than 6 y, all emergency anticonvulsants
dilute it prior to administration makes diazepam use
and medications and fluids that are given by IV route
easier in acute situations.
may be administered by IO infusions.
Rectal Diazepam
Termination of Seizure
Rectal diazepam is as effective as intravenous diazepam
& Administer lorazepam 0.1 mg/kg IV or diazepam 0.2– in aborting seizures if given within 15 min of seizure
0.3 mg/Kg IV. onset. Diazepam parentral solution can be administered
514 Indian J Pediatr (April 2012) 79(4):510–517
per rectum at the dose of 0.5 mg/kg up to a maximum is followed by infusion at a rate of 5 mg/kg/h, which can be
of 10 mg. The anal opening should be strapped after continued until a seizure free period of 6 h and then tapered
administration for about half an hour to prevent off over 6 h.
spillage.
Diazepam or Midazolam Infusion
Intramuscular (IM) Midazolam
Diazepam or midazolam infusion could be considered if
Midazolam being water soluble can be administered by IM there was an initial response to benzodiazepines. Both of
route The IM use of 0.2 mg/kg is as effective as intravenous these drugs, when used in rapidly incremental doses
diazepam for the initial therapy of SE. controlled RSE on an average within 15 min [10, 11].
Diazepam is diluted in normal saline, Ringer’s lactate or
Phenytoin dextrose water to give strength of 0.04 mg/ml. The starting
dose is 0.01 mg/kg/min. Most children require 0.02–
Phenytoin is given intravenously, in a loading dose of 0.03 mg/kg/min. Midazolam infusion starting with 2μg/
20 mg/kg, at a rate not exceeding 1 mg/kg/min (to avoid kg/min up to 12 μg/kg/min may be used. In the authors’
hypotension and cardiac arrhythmias). An additional load- experience midazolam was associated with about four times
ing dose up to 10 mg/kg may be used in young infants if SE higher risk of breakthrough seizures as compared to
persists after 10 min. Phenytoin should be diluted only with diazepam [11].
normal saline, and never with glucose containing solutions.
Fosphenytoin, a phenytoin prodrug, can be administered Barbiturate Coma
IM with rapid and complete absorption. The dose of
Fosphenytoin is 15–20 mg/kg of phenytoin equivalents/ Barbiturate coma using thiopental is highly effective for
kg, infused at a rate of not more than 3 mg/kg/min. The cost treatment of refractory SE. Recommendations for the
is however a limiting factor. choice of barbiturate have been solely based on theoretical
basis and there is no study directly comparing the efficacy
Phenobarbitone and safety of this drug. Thiopental is given in an initial dose
of 3–4 mg/kg IV over 2 min, followed by a continuous
Phenobarbitone is preferred over phenytoin in neonates and infusion of 2.0 mg/kg/min. The rate is increased every 3–
in SE associated with fever. However, there is no evidence 5 min by 0.1 mg/kg/min until SE is controlled or a burst
to favor this preference. It is given in a loading dose of suppression EEG recording is obtained. The major limita-
20 mg/kg IV at a rate of 1.5 mg/kg/h. In neonates an tion of the barbiturates is a need for mechanical ventilation,
additional dose of 5–10 mg/kg may be given if seizure hypotension requiring vasopressors support, delayed recov-
persists (total of 30 mg/kg). ery and pneumonia.
If seizures persist even after the adequate treatment with Propofol The initial dose is 1–3 mg/kg I.V. followed by a
benzodiazepine, and phenytoin and/or phenobarbitone, it is continuous infusion of 2–10 mg/kg/h as guided by EEG.
referred as RSE. About 10–15% of SE is refractory to
conventional therapies. The causes of RSE in the authors’ Lidocaine The initial loading dose is 1–2 mg/kg I.V. given
unit are given in Table 1. over 2 min. If seizures stop, continuous infusion of 2–4 mg/
Traditionally RSE is treated with barbiturate coma, kg/h is given under EEG monitoring. It may cause
continuous benzodiazepine infusion or anesthetic agents. hypotension, heart block and arrhythmia, and may exacer-
At this point of time one has to consider intensive care unit bate seizures at higher doses.
transfer, put patient on a ventilator and initiate continuous
EEG monitoring regardless of the drug used. In absence of Ketamine Infusion Ketamine is an anesthetic agent shown
ready availability of ventilator, Sodium valproate can be to be effective in control of refractory status epilepticus.
tried. Borris et al. [18] found it to be more effective than
phenobarbital in prolonged status epilepticus. SE is a life-
Sodium Valproate [17] threatening emergency that requires prompt and vigorous
treatment. Uncontrolled seizure activity results in progres-
Sodium valproate is given as an initial loading bolus of sive neuronal damage. Hence, all treating units should
30 mg/kg diluted 1:1 in normal saline, over 2–5 min. This establish a time framed protocol. Table 2 outlines the
Indian J Pediatr (April 2012) 79(4):510–517 515
Table 2 Stepwise antiepileptic drug escalation protocol aiming at terminating the seizure activity
0–3 min Initial stabilization and supporting vital functions as mentioned above
3–5 min Benzodiazepine first line therapy Start second IV line for simultaneous
Lorazepama 0.1 mg/kg over 2 min (max 4 mg) OR administration of second medication
Diazepam 0.3 mg/kg over 2 min (max 10 mg) and IV fluids
7–8 min Phenytoinb 20 mg/kg dilute in saline and infuse at a rate of not more than Thiamine 100 mg iv push; Pyridoxine
1 mg/kg/min 100 mg iv push in children <3 y of age
10 min Repeat Diazepam 0.3 mg/kg OR
Lorazepam 0.1 mg/kg
15 min Repeat Diazepam (same dose) OR
Lorazepam 0.1 mg/kg
25 min Phenytoin 10 mg/kg dilute in saline and infuse at a rate not more than
1 mg/kg/min
35 min IV Valproate 30 mg/kg diluted 1:1 in normal saline over 2–5 min. If the Transfer to PICU, prepare for intubation,
status is not controlled within 10 min of bolus, repeat 10 mg/kg bolus ventilation, get EEG
dose, followed by continuous infusion at the rate of 5 mg/kg/h [18]c OR
Midazolam OR Diazepam infusion [19]d Cardiorespiratory monitoring
Diazepam: 0.01 mg/kg/min, max 0.1 mg/kg/min
Midazolam: 2 mcg/kg/min upto 12 mcg/kg/min in increments of
2 mcg/kg/min every 5 min
Levetiracetam 40 mg/kg at 5 mg/kg/min can be infused after valproate before
initiating thiopental coma
45–50 min Thiopentale3–4 mg/kg iv over 2 min followed by an infusion at 2 mg/kg/h. Mechanical ventilation
a
Lorazepam must be refrigerated and diluted before administration
b
If the patient is already on Phenytoin, then administer 8 mg/kg of Phenytoin as the initial anticonvulsant
c
If the patient is already on Valproate, then 10 mg/kg is the loading dose. The infusion is continued until seizure free period of 6 h, then tapered
off @ of 1 mg/kg/h every 2 hourly
d
Midazolam or Diazepam infusion is preferred over Valproate in children less than 2 y. Benzodiazepine infusion is discontinued once thiopental
infusion is started
e
Infused in a separate IV line to avoid mixing with acidic drugs. Increase the infusion @ 1 mg/kg/h every 30 min to 6 mg/kg/h till seizure control
and burst suppression on EEG, The infusion is continued until seizure free period of 6 h, then tapered off
& Serum electrolytes (Sodium, Calcium) in all infants and & EEG evidence of persistent epileptiform discharges in a
young children with first episode seizures. clinically nonconvulsing child, would be helpful to
& Studies such as liver function tests, renal function tests, identify Non Convulsive Status Epilepticus (NCSE)
lead level, urine amino acids, and organic acids should
Guideline for diagnostic work-up in a child with statue
be individualized.
epilepticus is provided in Table 3
& If there is a history of drug exposure, toxicology screen
needs to be considered.
& For febrile patients, etiology of fever needs to be
Complications of Status Epilepticus
investigated, if not determined on physical examination.
& A lumbar puncture should be performed in any child
Complications occur because of prolonged seizure activity
suspected of having a central nervous system infection.
and sometimes due to the drug therapy. These should be
However, if there are focal findings on physical
looked for and attended to. Table 4 outlines the common
examination or suspicion of a mass lesion or increased
complications of status epilepticus.
intracranial pressure, the lumbar puncture is delayed till
a CT scan of head is obtained [15].
& In infants younger than 6 mo with a first afebrile seizure,
Disposition
with no etiology, and persistent decreased level of con-
sciousness, a lumbar puncture should be performed [15].
Any child who has received Lorazepam or a long acting
anticonvulsant medication should be admitted to the hospital.
Radiologic Evaluation Intensive care admission is required in any child with
Refractory Status Epilepticus, requiring mechanical venti-
Indications for Emergent Neuroimaging (Usually CT Scan) lation, or in whom the evaluation has revealed an etiology
requiring close monitoring.
& Child with focal onset seizures Rescue medication: In children who are likely to get
& Child with features of raised ICP recurrent seizures after status epilepticus, rescue medication
& Suspected trauma – CT scan is preferred as an acute for prehospital use such as buccal or intranasal midazolam
hemorrhage can be detected, but MRI is preferred for is advised
brain damage, old hemorrhage detection and postictal In case of febrile children, the etiology of the fever should
focal deficit that doesn’t resolve in 12 h. be investigated and managed in the standard fashion.
In case of simple febrile seizures, parents or caregivers
need to be counseled emphasizing the following facts:
Electroencephalogram
& Patients with a simple febrile seizure have a 32%
& EEG is indicated in all children who remain in altered incidence of recurrence before their sixth birthday;
sensorium even after complete control of clinical subsequent use of antipyretics at fever onset does not
convulsions lower the recurrence rate [20].
& A simple febrile seizure lasting less than 15 min is not Conflict of Interest None.
associated with any long-term effects on brain function
or intelligence [21].
Role of Funding Source None.
& Whenever seizure recurs “Ensure that child is removed
from an area with sharp or dangerous surfaces; position
him to the side, and look at the clock at the onset to
note the exact duration of seizure”. References
& “Swallowing of the tongue” is not a real concern, and
aggressive airway interventions such as bite-blocks 1. Commission on Epidemiology and Prognosis, International
should be discouraged. League Against Epilepsy. Guidelines for epidemiologic studies
& If there are more than 3 episodes of simple febrile on epilepsy. Epilepsia. 1993;34:592–6.
2. Bharucha NE. Epilepsy in India. In: Singhal BS, Nag ND, editors.
seizure recurrence, it is advisable to review the child Indian epilepsy association Mumbai. 2000: 08-14.
with a pediatric neurologist. 3. Chowdry GVS, Murthy JMK, Vijay S, et al. Prevalence of seizure
& Advice to use rectal diazepam (Diazepam IV solution disorders associated with neurocysticercosis: a community based
per rectum 0.5 mg/kg up to a maximum of 10 mg) when study – Comprehensive Rural Epilepsy Study South India
(CRESSI) Presented at Asian and Oceanic congress of Neurology,
parental anxiety about febrile seizures is severe, this Singapore, 2005.
may be effective in preventing recurrence [22]. 4. Hauser WA, Hersdorffer DC. Epilepsy, frequency, causes,
& Intermittent prophylaxis may be advised in some consequences. New York: Demos Publications; 1990.
children with recurrent febrile seizures. 5. Chin RF, Neville BG, Scott RC. A systematic review of the
epidemiology of status epilepticus. Eur J Neurol. 2004;11:800–10.
6. Nordli DR, Bazil CW, Scheuer ML, Pedley TA. Recognition and
classification of seizures in infants. Epilepsia. 1997;38:553–60.
7. Engel J. Report of the ILAE classification core group. Epilepsia.
Key Points 2006;47:1558–68.
8. Holmes GL. Seizure-induced neuronal injury: animal data.
& Acute seizure and status epilepticus constitute one of Neurology. 2002;59:S3–6.
the major medical emergencies in children. 9. Dunn DW. Status epilepticus in children: etiology, clinical
features and outcome. J Child Neurol. 1988;3:167.
& Any child who is brought seizing to the emergency 10. Singhi S, Singhi PD, Banerjee S. Refractory status epilepticus-role of
room to be treated as status epilepticus. continuous diazepam infusion. J Child Neurol. 1998;13:23–261.
& Management is focused at stabilization of airway, 11. Singhi S, Murthi A, Singhi P, Jayashree M. Continuous
breathing, circulation and aborting the seizure activity. midazolam versus diazepam infusion for refractory convulsive
status epilepticus. J Child Neurol. 2002;17:106–10.
Longer the status, it becomes more difficult to control 12. Major P, Thiele EA. Seizures in children. Determining the
and results in poor outcome. variation. Pediatr Rev. 2007;28:363–71.
& Be watchful for hypoglycemia and hypocalcemia while 13. Wilfong A. Differential diagnosis of seizures in children. In: Rose
managing acute seizure. BD, editors. UpToDate. Waltham, MA, 2007.
14. Tamer SK. Pediatric non-epileptic seizure. Indian J Pediatr.
& Search for precipitants (Missed antiepileptic drug dose, 1997;64:671–6.
Acute diarrhea, Toxins, Dyselectrolytemia (Mg/Na/Ca), 15. Chapman K. Controversies in the treatment of epilepsy. Epilepsy
hypoglycemia) and treat if present. – making the diagnosis. San Francisco: American Academy of
& Benzodiazepines remain the first line antiepileptic drugs Pediatrics, National Conference and Exhibition; 2007.
16. Louis CH, Louis AS. Evaluation and management of pediatric
in the emergency room; Lorazepam is preferred over febrile seizures in emergency department. Emerg Med Clin North
diazepam when available. This is followed by Phenytoin Am. 2011;29:83–93.
(20 mg/kg) loading. 17. Mehta V, Singhi P, Singhi S. Intravenous sodium valproate versus
& Swift escalation of anti-epileptic without any delay is diazepam infusion for the control of refractory status epilepticus in
children: a randomized controlled trial. J Child Neurol.
the cornerstone of status epilepticus management. 2007;22:1191–7.
& In SE refractory to above drugs, use Valproate (30 mg/kg 18. Borris DJ, Bertam EH, Kapur J. Ketamine controls prolonged
loading followed by an infusion 5 mg/kg/h for seizure free status epilepticus. Epilepsy Res. 2000;42:117–22.
period of 6 h) and if needed, a trial of Levetiracetam 19. Singhi S, Singhi P, Dass R. Status epilepticus: emergency
management. Indian J Pediatr. 2003;70:S17–22.
(40 mg/kg infused @ 5 mg/kg/min) before starting 20. Offringa M, Bossuyt PM, Lubsen J, et al. Risk factors for seizure
benzodiazepine or thiopental coma (3–4 mg/kg loading recurrence in children with febrile seizures: a pooled analysis of
dose, followed by 0.2 mg/kg/min infusion). individual patient data from five studies. J Pediatr. 1994;124:574–84.
& Refractory status epilepticus can be best managed in 21. Norgaard M, Ehrenstein V, Mahon BE, et al. Febrile seizures and
cognitive function in young adult life: a prevalence study in
PICU settings. Danish conscripts. J Pediatr. 2009;155:404–9.
& Uncontrolled seizure activity results in progressive 22. Knudsen FU. Recurrence risk after first febrile seizure and effect of
neuronal damage. short term diazepam prophylaxis. Arch Dis Child. 1985;60:1045–9.
Indian J Pediatr (April 2012) 79(4):518–524
DOI 10.1007/s12098-011-0648-x
Received: 29 August 2011 / Accepted: 30 November 2011 / Published online: 6 January 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Raised intracranial pressure is a life threatening reduced Cerebral perfusion pressure (CPP), and progress
condition; unless recognized and treated early, it may prog- into herniation syndrome and death.
ress into herniation syndrome and death. Symptoms and Aim of management in a child with raised intracranial
signs are neither sufficiently sensitive nor specific, hence a pressure (ICP) is to break the vicious cycle of cerebral
high index of suspicion and vigilance are needed for early edema and compromised cerebral blood flow (CBF) at the
recognition. Immediate goal of management is to prevent / earliest and to maintain adequate cerebral perfusion pressure
reverse herniation and to maintain good cerebral perfusion (CPP). The creation of standardized management protocol
pressure. The therapeutic measures include stabilization of has reduced variations in ICP, decreased duration of raised
airway, breathing and circulation, along with neutral neck ICP and improved outcome.
position, head end elevation by 30°, adequate sedation and
analgesia, minimal stimulation, and hyperosmolar therapy
(mannitol or 3% saline). Short-term hyperventilation (to Pathophysiology
achieve PCO2 ≈30 mm Hg) using bag ventilation can be
resorted to if signs of impending herniation are present. Monroe-Kellie Doctrine states that in a non-compliant skull
vault, ICP is the sum total of pressure exerted by the brain
Keywords Raised ICP . Cerebral perfusion pressure . Auto- (≈80%), blood (≈10%) and CSF (≈10%). The volume of
regulation . Herniation . Hyperventilation . Modified brain tissue increases without a significant change in ICP
Glasgow coma score . Mortality because of adaptive reductions in CSF and CBV, but when
these adaptations have been exhausted, an inflection point is
reached beyond which ICP increases exponentially [2].
Raised ICP is a life threatening condition that is commonly The normal range for ICP varies with age. The normal
seen in emergency with both traumatic and non-traumatic values for ICP in children are not well established. The
neurological illnesses. Almost 93% of children with acute usual normal range is considered as 5 to 15 mmHg [2]. In
meningitis have signs of raised ICP at admission or develop new born term infants it is 1.5–6 mmHg, in young children
these within 48 h of admission [1–3]. Unless recognized and 3–7 mmHg and in older children 10–15 mmHg.
treated early it may cause secondary brain injury due to
ICP Threshold for Treatment
Ramesh
R. : S. C. Singhi
K. R. Kumar R. : S. C.
(*) : P. Singhi
Singhi (*) : P. Singhi
Department of Pediatrics, Advanced Pediatrics Centre, Current pediatric data support a definition of ICP more than
Postgraduate Institute of Medical Education
and Research (PGIMER),
20 mmHg as intracranial hypertension requiring treatment
Chandigarh 160012, India [3]. For all practical purposes, if symptoms and signs of
e-mail: sunit.singhi@gmail.com raised ICP are present, one should consider that ICP is more
Indian J Pediatr (April 2012) 79(4):518–524 519
than 20 mmHg and treat accordingly. Sustained ICP values GCS≤8 are likely candidates for raised ICP and in particular
>40 mmHg indicate severe life threatening raised ICP. the patients with following diagnosis:
1. Acute CNS infection with change in mentation/focal
Cerebral Perfusion Pressure (CPP) signs.
2. Traumatic brain injury: Severe TBI (m-GCS≤8), mild
CPP is the pressure at which brain is perfused. It provides an to moderate TBI with abnormal admission head CT scan
indirect measure of adequacy of cerebral blood flow (CBF). or hypotension, motor posturing
It is calculated as the difference between mean arterial 3. Acute hepatic encephalopathy Grade III or IV
pressure (MAP) and ICP (CPP0MAP—ICP). Normal CPP 4. Diabetic ketoacidosis with encephalopathy
values for children are not clearly established, but the values 5. Toxic encephalopathy, hypertensive encephalopathy
that are generally accepted as the minimal CPP necessary to 6. Hypoxemic encephalopathy- Gross ischemia—more
prevent ischemia are as follows: infants/toddlers: > 40– than 50% MCA territory infarction
50 mmHg; children: > 50–60 mmHg.
CPP<40 mmHg is a significant predictor of mortality in Urgent neuro-imaging may be needed, after stabilization
children with traumatic brain injury (TBI). Autoregulation of ABC and reversing potential or clinically manifest herni-
that maintains a steady cerebral blood flow (CBF) within a ation, to rule out surgically correctable causes of raised ICP.
CPP range of 50–150 mmHg, despite fluctuations in sys-
temic blood pressure, is lost at CPP values <50 mmHg.
Once auto regulation is lost, CBF and cerebral blood vol- Clinical Signs
ume (CBV) become dependent on changes in systemic
blood pressure. Clinical symptoms and signs of raised ICP are highly vari-
able and depend on the nature of the primary brain insult,
the extent of compartmentalization, the presence and loca-
Etiology tion of a mass lesion, and the rate of increase in ICP.
In awake patients: irritability, headache, vomiting, con-
Common causes of raised ICP with respect to pathophysi- fusion and decreased alertness, and neck retraction may be
ology are shown in Table 1. the presenting features. These are neither sufficiently sensi-
tive nor specific for timely recognition of raised ICP. Tense
fontanel on palpation and papilledema, are reliable signs of
raised ICP, but the later is usually absent in acute conditions,
Approach in an Emergency Department
even in patients with documented elevated ICP.
In unconscious/comatose patients, raised ICP should be
Approach to a child presenting with raised ICP in an Emer-
suspected in all patients with head injury, meningitis, en-
gency department is shown in Fig. 1. All patients with an m-
cephalitis, liver disease and diabetes mellitus. The clinical
Table 1 Common causes of raised ICP features strongly favoring raised ICP are generally seen late,
when brain herniation is imminent or has already set in.
A. Increase in Brain Volume These are abnormal posturing (decerebration or decortica-
• Cerebral edema: Primary CNS illness: encephalitis, meningitis, tion), abnormal pupillary dilatation, hypertension, bradycar-
Head injury, Reye’s syndrome.
dia, irregular breathing, sixth nerve palsy and papilledema.
• Cerebral edema: Secondary to systemic illness: Hypoxic ischemic
Cushing reflex (hypertension, bradycardia, irregular
injury (hypoventilation, shock), ischemic stroke/ infarct, metabolic
encephalopathy– hyperpyrexia, hepatic failure, lead intoxication. breathing) becomes evident only later in the course of ill-
• Space-occupying lesions: Hematomas, tumors, abscesses ness, and may not occur in young children. Abnormal pu-
B. Increase in Blood Volume pillary dilatation and posturing can occur in the absence of
• Venous obstruction- Cerebral venous sinus thrombosis raised ICP.
• Hemorrhage CT scan signs of brain swelling are predictive of in-
• Vasodilatation: Due to hypoxia, drugs or hypercapnia creased ICP, but the CT scan may be normal even in the
• Status epilepticus presence of documented raised ICP.
C. Increases in CSF Volume
• Obstructive hydrocephalus, Communicating hydrocephalus
• Impaired reabsorption: Subarachnoid hemorrhage.
Signs of Brain Herniation
• Increased production: Tumors
D. Idiopathic or Benign Intracranial Hypertension
Pressure gradient between various intracranial compartments
may lead to herniation of brain from one compartment to
520 Indian J Pediatr (April 2012) 79(4):518–524
Fig. 1 Approach to
Neurological Examination
Neurological examination
management of raised ICP
Si gns and
Signs andssymptoms
ym ptomsS/O
S/O raised
raised ICP
ICPorormm- GCS
- GCS≤ 8
Hyperventilation
If signs of impending herniation -Double of the normal breathing rate
present (unequal pupils, posturing ) for the given child for 10 min only
-Look for reversal of unequal pupils and
posturing
Elevate head end Minimum stimulation Normocarbia(PaCo2≈35mmHg Maintain MABP >50th centile
to 30° Sedation analgesia Normoxia(PaO2>60mmHg,Sp2O by fluid and vasoactive agent
Midline (Midazolam/Morphine) >92%) Prevent or treat Fever and
Normovolemia seizures
No response
another . Early signs of herniation are mainly due to compres- Herniation of cerebellar tonsils through the foramen
sion and ischemia rather than displacement of brain tissue. magnum can occur in patients with posterior fossa space
Prompt recognition of the clinical signs of herniation is critical occupying lesions. It causes compression of the cerebellum,
to salvage life. and respiratory centers in the lower brain stem, resulting in
Central (or transtenorial) herniation syndrome occurs irregular breathing and respiratory arrest.
when diffuse edema or a supratentorial mass causes down-
ward displacement of the brain through the tentorial notch.
It is characterized by progressive diencephalic dysfunction, Goals and Principles of Therapy
in a rostro -caudal direction. The earliest signs are nonspe-
cific: confusion and stupor, and small and sometimes poorly The immediate goal is to prevent progression to herniation
reactive pupils. This is followed progressively by appear- or to reverse the herniation if present, and then to maintain a
ance of decorticate (flexor) posturing, decerebrate (extensor) CPP >60 mmHg and ICP <20 mmHg.
posturing, obtundation and coma, and midposition, fixed The principles of management include maintaining nor-
mid-size pupils. Cushing’s triad (hypertension, bradycardia, moxia and normocarbia; avoiding factors that aggravate or
and irregular respirations) is a late finding associated with precipitate raised ICP namely fever, hypoxia, hypoglyce-
coma and impending death [4]. mia, hypotension and any noxious stimulation; treatment
Lateral (or uncal) herniation syndrome occurs when a of underlying cause—whether intracranial or extracranial
lateral mass lesion causes displacement of the midbrain and including surgical intervention; maintain adequate MAP
temporal lobe. The earliest signs are changes in mental (more than 50th centile for given age and gender) with help
status and unilateral dilated pupil, most often on the same of fluid and, if needed vasoactive therapy; and bringing
side as the mass. This is followed progressively by an down ICP.
ipsilateral hemiplegia (due to compression of the contra- Therapeutic measures to bring down ICP, after surgi-
lateral corticospinal tract) and progressive diencephalic cal management of mass lesions, are divided into first-
dysfunction. tier and second-tier therapies (Table 2). First-tier
Indian J Pediatr (April 2012) 79(4):518–524 521
Table 2 Therapeutic modalities to reduce raised intracranial pressure 3. Patients unable to protect airway
General measures and First tier therapy 4. Signs of inadequate ventilation and oxygenation, such
• Head in neutral position, 30° elevation. as irregular respiratory effors, inadequate chest move-
• Ensure oxygenation- Normoxia (PaO2 >60 mmHg, SpO2 >92%)
ments, poor air entry, central cyanosis
• Ensure adequate circulating volume- Normovolemia Rapid sequence induction (RSI) accompanied by cricoid
• Maintain normal BP pressure (Sellick maneuver) is preferred for emergency in-
• Ventilation to achieve PaCO2 035 mmHg tubation to prevent aspiration and sudden surge in intracra-
• Osmotic diuretic- Mannitol 0.25–0.50 /kg i.v. over 20 min, nial pressure (ICP). The medications that facilitate
repeat S.O.S or intubation without increasing the ICP, should be used. [5].
Hypertonic (3%) saline infusion: 10 ml/kg bolus, followed by Monitor heart rate, blood pressure, SpO2; provide 100%
0.1 ml−1.0 ml/kg h infusion
oxygen and bag ventilation as tolerated by patient and if
• Dexamethasone - 1–2 mg/kg i.v.q 6 h—cytotoxic cerebral
no airway contraindications, administer sedation and neuro-
edema (brain abscess, granuloma, tumor)
muscular blocking agents [5]: Midazolam (0.2–0.3 mg/kg
• CSF drainage - Obstructive hydrocephalus
IV), Morphine (0.1 mg/kg IV) / Fentanyl (5–10 μg/kg IV),
• Prevent all events that increase ICP
and lidocaine (1–1.5 mg/kg IV) and short acting non-
Fever / hypothermia, pain- adequate sedation–analgesia,
seizures- anticonvulsant, loud noise, invasive stimuli depolarizing neuromuscular blocking agents (vecuronium
Second tier therapy 0.1 mg/kg IV/atracurium 0.5 mg/kg IV/ rocuronnium 0.6–
• Hyperventilation (PaCO2 30–35 mmHg) 1.2 mg/kg IV). Ketamine and succinyl choline should be
• Barbiturates coma- Thiopental or pentobarbital avoided.
• Moderate hypothermia(32–34°C)
Third tier therapy Breathing
• Decompressive craniectomy or temporal lobectomy
• Profound hyperventilation to PaCO2 <30 mmHg (use transiently) Maintain normoxia and normocarbia. 100% oxygen should
be started with non re-breathing mask and if needed, bag
valve mask ventilation to ensure adequate oxygenation.
Mild short-term hyperventilation should be undertaken if
therapies include elevation and positioning of head, danger of impending herniation is present ((unequal pupils,
sedation and analgesia, hyperosmolar therapy, and mild posturing; see above). To achieve this with manual ventila-
hyperventilation and placement of an ICP monitor. Sec- tion, administer double the normal breathing rate for given
ond and third tier therapies include lumbar drainage of age for 10 min duration. Monitor reversal of unequal pupils,
CSF, high-dose barbiturates, decompressive craniectomy, posturing and improvement in mentation. Target a PaCO2 ≈
and hypothermia; these treatments are reserved for increased 30–32 mmHg. There is no role for prophylactic hyperven-
ICP that does not respond to first-tier therapies. Much of these tilation Fig. 1.
treatment principles and guidelines are extrapolated from
studies on adult patients and patients with traumatic brain
injury. Few studies have directly evaluated treatment of raised Circulation
intracranial pressure in children.
Maintain euvolemia. If there are signs of poor perfusion,
give a bolus of normal saline 20 ml/kg. Maintain MAP to
Airway, Breathing and Circulation achieve desired CPP, if needed by using fluid and vasoactive
agents (dopamine, nor-epinephrine). Colloids are not rec-
Airway ommended in acute brain injury (except in acute ischemic
stroke) due to their adverse effect on survival [7].
In unconscious patients airway patency should be ensured
by proper positioning of the head or by positioning the
patient on the side and suctioning of the oral secretion. General Measures and First Tier Therapy
Oro- or naso- pharyngeal airways can be used.
Indications for endotracheal intubation [5]: 1. Head position
1. Modified Glasgow coma score (m-GCS)≤8 Elevate head end of bed by 30° and keep head in neutral
2. Patients with signs of respiratory distress position to promote venous drainage via the external jugular
- Declining O2 saturation veins. Ensure adequate intravascular volume to prevent
- Increasing O2 requirement orthostatic hypotension.
522 Indian J Pediatr (April 2012) 79(4):518–524
2. Sedation and Analgesia benefit. A recent systematic review found that HS appears
to achieve a greater reduction in ICP than other osmotic
Use midazolam 1–3 μg/kg/min, Morphine 0.1 mg/kg/
agents in TBI and in one series of non traumatic encepha-
dose Q6h. Sedative doses have to be individualized, and
lopathies, there was less mortality with use of HS as com-
titrated to achieve Ramsay sedation scale score of 3–4. At
pared to mannitol [8].
score 3 the patient responds to commands only and at score
of 4 the patient is asleep, but has brisk response to glabellar 4. Temperature
tap or loud auditory stimulus.
Fever increases metabolic rate by 10% to 13% per degree
3. Osmotherapy—Mannitol, 3% hypertonic saline (HS) Celsius and is a potent cerebral vasodilator. Keep the tempera-
ture below 38°C (36–37°C axillary). If child is febrile, use
paracetamol 15 mg/kg/dose oral or IV Q4h and surface cooling.
Mannitol (20%)
5. Glucose control
Early effect includes reduction of blood viscosity, with Keep random blood sugar (RBS) around 150 mg/dl.
improvement in microvascular CBF, cerebral oxygenation, Hypogycemia (<60 mg/dl) and hyperglycemia (>180 mg/
and CPP with reduction in cerebral blood volume (CBV), dl) should be avoided.
and ultimately lowering of ICP. Late effect, that occurs
within 15–30 min and lasts upto 6 h, results from direct 6. Seizure prophylaxis
osmotic effect on neural cells with reduction in total brain Consider seizure prophylaxis in patients at high risk of
water. Additional effects include reduced CSF production. seizures such as those with severe head injury, focal symp-
For optimal effect, serum osmolality should be maintained toms and signs and CNS infections (meningitis and enceph-
below 320 mOsm [6]. alitis). Use phenytoin—20 mg/kg IV loading, followed by
Standard dosage: 0.5 g/kg i.v bolus, if further dose is 5 mg/kg/d for the first 7 d only.
required use 0.25 g/kg/dose. Do not repeat mannitol in less Comatose children should also be considered for EEG
than 4 h. Monitor the urine output and take care of hypo- monitoring and seizure prophylaxis as non-convulsive seiz-
volemia. Mannitol is contraindicated in decompensated ures are not uncommon in them. These can cause sudden
shock, oliguria, anuria and heart failure. surge in ICP.
7. Use Lidocaine 1 mg/kg/dose 5 min before endotracheal
Hypertonic Saline (3%HS) suctioning and procedure (IV and ET). Do not repeat
within 2 h.
Hypertonic saline creates an osmotic force to draw water
from the interstitial space of the brain parenchyma into the 8. GI bleed prophylaxis
intravascular space. It promotes rapid CSF absorption,
Use Antacid 1 ml/kg/dose Q 8 h or pantoprazole 1 mg/
increases cardiac output, and expands intravascular volume
kg/dose Q 12 h, (if G.I bleed is present use pantoprazole).
thereby augmenting the CPP with a positive inotropic effect
[7, 8]. 9. Anemia
Standard dosage: For continuous infusion, 3% HS is
Maintain Hb concentration around 10 g/dl, to help cerebral
preferred via central line. Usual dose is 10 ml/kg as a
oxygen delivery. In cases with severe anemia, a marked in-
loading followed by 0.1–1 ml/kg/h. In cerebral edema, the
crease in CBF occurs to maintain cerebral oxygen delivery.
initial serum sodium goal is commonly set at 145–155 mEq/
L and is intensified upto 160 mEq/L if clinically indicated.
In general it is well tolerated and complications are rare. 10. Hypertension
Monitor serum sodium and creatinine every 6 h. It is contra- Increase in blood pressure is common in response to
indicated if serum sodium is >150 mEq/l, and /or osmolality raised ICP. Characteristically rise in systolic-BP increase is
>320mOsmol/L. greater than diastolic-BP. When autoregulation is impaired,
Therapy must be tapered after 24 h of continued infusion hypertension may increase CBF and ICP, and may exacer-
to prevent rebound rise of ICP. bate cerebral edema and postoperative IC bleeds. Generally
it is left untouched in acute raised ICP unless underlying
Mannitol vs. Hypertonic Saline cause is hypertensive encephalopathy. Treatment is also
reasonable in patients with impending congestive cardiac
It is unclear which of these two therapies is superior for failure, those with evidence of rapidly worsening brain
reduction of ICP. Hypertonic saline is effective in reducing edema on CT scan, and those with a persistent extreme surge
raised ICP, but does not have clear survival or outcome in blood pressure. If it is decided to treat hypertension,
Indian J Pediatr (April 2012) 79(4):518–524 523
Received: 26 January 2012 / Accepted: 8 June 2012 / Published online: 12 July 2012
# Dr. K C Chaudhuri Foundation 2012
This protocol focuses on the clinical evaluation of a & Evaluate for cardiovascular instability: Conditions
child presenting with AFP and provides a practical leading to AFP (Spine trauma, myelitis, Guillain
clinical approach to diagnosis in the Emergency depart- Barre syndrome) can also result in cardiac rhythm
ment. For a detailed discussion on AFP the reader is abnormalities and cardiovascular insufficiency. These
referred to other reviews on the subject [1]. The objec- issues will require a priority management. Hence,
tives of this article are: to provide a practical approach attaching a quadriparetic child to an ECG/cardiac
to diagnosis in an individual patient; to provide an monitor is an early step in the management.
approach to rational use of diagnostic tests and discuss & Rule out dyselectrolytemia or toxemia: Hypokalemia
the common causes of AFP in children. and snake envenomation are important causes of flaccid
paralysis. These causes should be excluded in all chil-
dren with AFP by history and examination, early in
management course. A rapid assessment of electrolytes
Diagnostic Approach
and ECG should be sought in all such children.
& To rule out a spinal compression (traumatic, intraspinal
Initial Assessment and Stabilization
collections). : At the outset, patients with possible
spinal injury due to trauma or other lesions requiring
Every child with AFP is a medical emergency requiring
urgent neurosurgical intervention should be identified
systematic evaluation and management. Initial assess-
on history and examination. Immediate spinal stabili-
ment of any such acutely ill child should concentrate
zation and administration of corticosteroids in those
on rapid cardiopulmonary assessment and resuscitation.
with trauma would be a priority, while neurosurgical
Following are the key areas on initial assessment;
relief of spinal compression may be warranted to
& Detect and manage respiratory muscle weakness: Any prevent long term disability.
child with acute weakness should be evaluated for res-
piratory muscle weakness. Younger children with respi-
ratory muscle weakness may present with non-specific History
irritability, sweating, poor feeding and shallow or para-
doxical respiratory efforts. Older children may complain The first step is to determine if an unwell child actually has
of respiratory difficulty, may have excessive sweating, muscle weakness. Many children with weakness present
agitation, air hunger, reduced single breath count/chest with nonspecific symptoms of irritability, lethargy and
expansion or shallow/paradoxical respiratory efforts. clumsy walk or refusal to walk. Children with abnormal
Careful serial examinations may be critical in such chil- gait, limp or refusing to walk may present initially to ortho-
dren to pick up the weakness early. Early elective intu- pedic or trauma clinics. Pseudoparalysis due to limb pain
bation and respiratory support are critical to save these may result from trauma, arthritis/arthralgia, myostis, joint or
affected children. periosteal bleeds or joint or periarticular infections or
& Detect and manage bulbar weakness: Symptoms of inflammations.
voice change, poor cry, pooling of secretions, gur- It is useful to remember the possible causes of AFP
gling sounds in throat, poor ability to swallow and in children using a neuro-anatomical approach (Table 1).
choking on feeds may be markers of bulbar dysfunc- Information is derived from the history and focused
tion. Care should be taken to avoid oral feeding, neurological examination looking at pattern of tone,
providing regular suction and ensuring entral nutri- tendon reflexes, sensory examination, signs and symp-
tion via nasogastric feeding. toms of bladder and/or bowel involvement. (Table 2).
Indian J Pediatr (October 2012) 79(10):1351–1357 1353
Yes No
Compressive Noncompressive
Ocular/bulbar Symmetric?
myelopathy myelopathy
+ involvement?
+
polyneuropathy or rarely may be seen in transverse infection triggered immune mediated attack on the nerve axons
myelitis. The CSF can be normal early in the course of or myelin. Antecedant respiratory or gastrointestinal illnesses
these illnesses. are commonly found in the history [3]. The most common
3. Nerve Conduction studies and Electro Myography underlying subtype of the syndrome is the acute inflammatory
(EMG): These studies confirm the involvement of demyelinating polyradiculoneuropathy (AIDP) but the other
nerves and help in diagnosis of anterior horn cell dis- common subtype of acute motor axonal neuropathy (AMAN)
eases. These are particularly helpful to confirm Guillain may be equally common in Indian children [4]. In the typical
Barre syndrome. The repetitive nerve stimulation test cases, the first symptoms are usually pain, paraesthesia, or
helps to diagnose myasthenia gravis and botulism. weakness in the limbs which spreads proximally. Weakness
Rarely, these may aid the diagnosis of an inflammatory may progress rapidly, and approximately 50 % of the children
myopathy. will reach nadir by 2 wk, 80 % by 3 wk, and the rest by 4 wk.
4. Creatine Kinase: Raised levels of muscle enzyme crea- Risk factors for children requiring ventilation are cranial nerve
tine kinase reflects acute muscle fiber injury and may involvement, increased CSF protein during first week of illness
point towards a muscle disease. In the setting of AFP and short period between antecedent illness and the onset of
this may be seen in children with viral myositis or symptoms [5]. Investigations required for confirming the diag-
inflammatory myopathy. nosis are; nerve conduction studies and lumbar puncture (to
document CSF albumin-cytological dissociation). A raised
CSF protein concentration is present in about 80 % of patients,
but CSF protein content is more likely to be normal during the
Differential Diagnosis of AFP (Table 3) first days of the illness [3]. When a child presents in the acute
phase, the differentiation from polio or enetroviral myelitis can
Some of the commonly encountered causes of AFP are be done based on CSF. Viral myeltis would show CSF pleocy-
discussed below; tosis, which would be conspicuously absent in GBS. CSF
should be analyzed before treatment with intravenous immu-
Guillain Barre Syndrome (GBS) noglobulin (IVIG) as IVIG can cause aseptic meningitis. Man-
agement of a child with GBS would involve a meticulous
With the control of polio, GBS is the most common cause of observation for respiratory, bulbar muscle weakness. Early
AFP in children. Worldwide its incidence is 0.6–4 cases per elective intubation and ventilatory support are important in
100,000 per year [2]. It most commonly occurs after an the acute phase. During hospitalization, monitoring for
Indian J Pediatr (October 2012) 79(10):1351–1357 1355
Development From hours to four days 24 to 48 h from onset From hours to 4 wk From hours to four days
of paralysis to full paralysis
Fever at onset May be present High, always present at Uncommon Present, if underlying
of weakness onset of flaccid paralysis infection being treated
with IM injections
Paralysis Symmetric Asymmetric, Symmetric, mostly ascending Affects only one limb
Progression Descending• Ascending
of paralysis
Muscle tone Reduced during Reduced Reduced Reduced
acute phase
Deep-tendon Absent in lower Decreased or absent Absent Decreased or absent
reflexes limbs(early);
hyperreflexia(late)
Sensation Anesthesia of lower Severe myalgia, backache, Cramps, tingling, hypoanesthesia Pain in gluteus
limbs with sensory no sensory changes of palms and soles
level
Cranial nerve Absent Only when bulbar Often present, affecting nerves VII, Absent
involvement involvement is present IX, X, XI, XII
Respiratory Sometimes Only when bulbar Occurs in severe cases Absent
insufficiency involvement is present
Autonomic signs Present Rare Frequent in severe cases (blood pressure Hypothermia in
and symptoms alterations, sweating, blushing, and affected limb
body temperature fluctuations)
Cerebrospinal Normal or Mild elevation of Albumin-cytologic dissociation (usually Normal
fluid Pleocytosis lymphocytes 10 <10 cells/ml, never >50cells/ml)
to 200/mL
Bladder dysfunction Present- early Rare Occasionally (Transient, at the Never
and persistent peak of weakness, 1–3 d (30 %))
Nerve conduction Normal Abnormal: anterior Abnormal: slowed conduction, Abnormal: s/o
velocity: third wk horn cell disease decreased motor-sensory
(normal during motor amplitudes axonal damage
first 2 wk)
Diagnostic test MRI–spine Stool viral detection Nerve conduction studies Nerve conduction studies,
Electromyography
Adapted and modified from Global Program for Vaccines and Immunization: Field Guide for Supplementary Activities Aimed at Achieving Polio
Eradication. Geneva, World Health Organization, 1996
autonomic instability and prevention of nosocomial complica- poliomyelitis. The initial symptoms of polio are non-specific
tions are essential to optimize outcomes. IVIG is the and include fever, headache, vomiting, constipation, neck
treatment of choice in the authors’ setting for GBS, stiffness and pain in limbs. The paralysis follows or accom-
given the availability, ease of administration and the panies these symptoms. The maximal weakness evolves
safety compared with plasmapheresis. It is given in the quickly over 1–2 d. A history of intramuscular injections
dose of 2 g/kg spread over 2–5 d. precedes paralytic poliomyelitis in about 50–60 % of patients,
patients may present initially with fever and paralysis (prov-
Anterior Horn Cell Viral Myelitis ocation paralysis). Clinical characteristics of poliomyelitis
include; 1. Fever at onset 2. Rapid progression of paralysis
Poliomyelitis within 24–48 h 3. Asymmetric, proximal more than distal
limb paralysis 4. Preservation of sensory function often with
Both the wild polio virus and the vaccine associated polio severe myalgias 5. Residual paralysis at 60 d [6]. Most of the
virus cause anterior horn cell affliction to result in flaccid children with paralytic polio die from complications of bulbar
paralysis. Children under 5 y are the most frequently affected. paralysis and respiratory failure. Management is mainly fo-
However, older individuals and adults can also develop cused on meticulous supportive care.
1356 Indian J Pediatr (October 2012) 79(10):1351–1357
Non Polio Enteroviral Myelitis Table 4 Summary of approach to diagnosis in a child with acute
flaccid paralysis
myelitis consists of immunosuppression and supportive care. (snake bite). Evaluation of spine by imaging may be
Attention is needed to maintain airway, breathing and circu- needed urgently in patients with suggestive clinical fea-
lation, bladder catheterization and exclusion of compressive tures. Once these causes are excluded, most distal pa-
myelopathy by imaging. High dose pulse corticosteroids are thologies are generally immune mediated and respond to
the recommended form therapy [11]. Methylprednisolone is immunomodulation. Irrespective of the cause, general-
given in a dose of 10–30 mg/kg/d (max:1 g/d) for 5 d followed ized weakness frequently affects respiratory and bulbar
by oral prednisolone 1–2 mg/kg/d for 2 wk and then tapered function. Such children need to be carefully monitored
over subsequent 2–4 wk. and treated.
Received: 10 March 2012 / Accepted: 4 June 2012 / Published online: 1 July 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Tumor lysis syndrome (TLS) refers to the constel- susceptible patients, in an attempt to prevent precipitous lysis
lation of deranged metabolic state, characterized by hyper- of tumor cells. Presentation and management of TLS in
kalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, relevance to the pediatric emergency room is outlined.
and/or azotemia, secondary to rapid breakdown of tumor
cells. It is a life threatening emergency that typically follows Keywords Alkalinization . Allopurinol . Furosemide .
administration of chemotherapy or may be spontaneous. Tetany . Urate oxidase
Malignancies which have a large tumor burden, rapid turn-
over, as well as speedy breakdown following chemotherapy
are susceptible. Acute lymphoblastic leukemia and non- Introduction
Hodgkins lymphoma (particularly Burkitt’s lymphoma) are
typically predisposed. TLS is best managed by early antici- Tumor lysis syndrome (TLS) refers to the constellation of
pation and preventive measures than the complicated task of deranged metabolic state, characterized by hyperkalemia,
treating an established TLS. Vigorous intravenous hydration hyperphosphatemia, hyperuricemia, hypocalcemia, and/or
is the cornerstone of prevention as well as treatment. Ras- azotemia, secondary to rapid breakdown of tumor cells. It is
buricase has revolutionized the management. It is available in a life threatening oncological emergency which can be
India for past 1 1/2 y, although the cost is a limiting factor. encountered by physicians in emergency medicine, pediatri-
Children with acute leukemia in developing countries may cians, oncologists or by a nephrologist, depending on the
reach health facility late, with severe anemia and hyperleu- presentation of the patient. Early identification of high risk
kocytosis. Exchange transfusion may have to be restored to patients and initiation of preventive measures are more reward-
in such patients to simultaneously correct anemia and hyper- ing than the painstaking management of established TLS.
leukocytosis and enable safe administration of fluids. Dialy-
sis may be required when the metabolic ‘trash’ overwhelms
the renal excretion, resulting in renal failure. Chemothera- Pathophysiology
peutic drugs are often administered in a phased manner in
Rapid cell breakdown results in release of intracellular ions
A. Rajendran : D. Bansal : R. K. Marwaha (K+, PO4, uric acid), overwhelming the renal excretion
Hematology/Oncology Unit, Department of Pediatrics, (Fig. 1). Delayed recognition of metabolic disturbances can
Advanced Pediatrics Centre, lead to acute renal failure, cardiac arrhythmia or seizures. Cell
Postgraduate Institute of Medical Education and Research,
lysis can be spontaneous, or typically follows chemotherapy.
Chandigarh, India
S. C. Singhi (*)
Department of Pediatrics, Pediatric Emergency and Intensive Care, Etiology
Advanced Pediatrics Centre,
Postgraduate Institute of Medical Education and Research,
Chandigarh 160012, India Lymphoproliferative disorders with rapidly multiplying
e-mail: sunit.singhi@gmail.com malignant cells, including acute lymphoblastic leukemia
Indian J Pediatr (January 2013) 80(1):50–54 51
DNA Purine Table 2 Definitions of laboratory and clinical tumor lysis syndrome [3]
Laboratory TLS
Hypoxanthine Two or more following metabolic abnormalities should be present
within 3 d before, or up to 7 d following initiation of therapy
Xanthine oxidase
Uric acid: >8 mg/dl in adults or above the upper limit of normal
Allopurinol
Xanthine range for age in children
Xanthine oxidase Phosphate: >4.5 mg/dl in adults and >6.5 mg/dl in children
Potassium: >6.0 mEq/L
Uric acid
(Insoluble) Calcium: Corrected calcium <7.0 mg/dl or ionized calcium <1.12
Urate oxidase not present in humans
(Rasburicase) Clinical TLS
Presence of Laboratory TLS + abnormalities in any one of the
Allantoin following end organs:
(Highly soluble)
Kidney: Acute Kidney Injury
• Increase in serum creatinine of 0.3 mg/dl
Fig. 1 Pathway of cell lysis in tumor lysis syndrome
• A single value >1.5 times the upper limit of normal for age, in the
absence of baseline value
(ALL) and Burkitt’s lymphoma are prone for TLS (Table 1). It • Oliguria (< 0.5 ml/kg/h), lasting for 6 h
is uncommon in solid tumors (e.g., wilms tumor, retinoblas- Cardiac: Arrhythmia, death
toma, and neuroblastoma) but not unknown, particularly Neurological: Seizures
with the usage of highly effective therapies [2]. Patients
with compromised baseline renal function are more prone
than those with normal kidney function. The mortality rate manifestations occur 12–72 h following the initiation of
in TLS is up to 20 %. chemotherapy. Rarely, the onset is spontaneous. Significant
hyperkalemia (>7 mEq/L) can lead to electrocardiogram
changes, including peaked T waves and QRS complex
Definition widening, which, when untreated, may result in ventric-
ular dysrhythmia and death. Hyperphosphatemia can
Classification of TLS, as laboratory and clinical TLS is manifest as cardiac arrhythmia as well. Tetany or seizures
enumerated in Table 2. can be features of hypocalcemia. The metabolic ‘trash’
can overwhelm the renal excretion, resulting in renal
failure. At this stage, patient may become oliguric or
Clinical Features anuric, an ominous sign. Rarely, renomegaly, hypertension
and acute renal failure are frontline presentation of acute
In the majority, TLS is asymptomatic to begin. This is leukemia. Unattended TLS rapidly progresses and can result
the opportunity to identify the high risk patient and in death.
initiate preventive measures to circumvent metabolic
compromise or end organ damage. Typical clinical
Management
Table 1 Risk stratification of tumors on the basis of potential for The components include:
tumor lysis syndrome [1]
1. Early identification of high risk patient
High risk 2. Hyper-hydration
○ Burkitt’s lymphoma/leukemia 3. Management of specific electrolyte imbalances
○ Lymphoblastic lymphoma 4. Role of alkalinization
○ Acute lymphoblastic leukemia, with TLC >1,00,000/μL 5. Renal replacement therapy
○ Acute myeloid leukemia, with TLC >50,000/μL
Intermediate risk
○ Acute lymphoblastic leukemia, with TLC 50,000–1,00,000/μL Early Identification of High Risk Patient
○ Acute myeloid leukemia, with TLC 20,000–50,000/μL
○ Diffuse large B cell lymphoma
TLS is best managed by early anticipation and preventive
Low risk
measures than the herculean task of treating an estab-
○ Hepatoblastoma, Neuroblastoma, Wilm’s tumor, Germ cell tumor
lished TLS. In patients with underlying predisposing
factors (Table 3), monitoring urine output, electrolytes
52 Indian J Pediatr (January 2013) 80(1):50–54
Table 3 Predisposing factors for tumor lysis syndrome [4] Management of Specific Electrolyte Imbalances
Tumor characteristics
• Malignancies prone for rapid lysis: High chemo sensitivity and rapid Hyperkalemia
growth rate
○ Acute Leukemia (ALL) and non-Hodgkin’s lymphoma Defined as serum potassium level >6 meq/L. Management is
(esp. Burkitt’s) similar to that of any other cause. Monitor ECG continuously.
• Large tumor volume Perform electrolytes every 4–6 h.
○ Massive intra-abdominal tumor
1. Cardiac membrane stabilization is achieved by infusing
○ Bone marrow involvement ± hyperleucocytosis
2 ml/kg of 10 % calcium gluconate over 20 min
○ Extramedullary disease (huge lymphadenopathy, massive
hepatosplenomegaly)
2. Intracellular shifting of K+ ions is achieved with 0.1 ml/
kg of Insulin and 2 ml/kg 25 % dextrose infused over
Host characteristics
30 min, salbutamol nebulization and/or sodium bicar-
• Small child with a large tumor
bonate infusion at 1–2 meq/kg I.V push (can aggravate
• Volume depleted state: Poor oral intake, GI loses (vomiting,
diarrhea) hypocalcemia!)
Aggravating factors 3. Furosemide along with hydration increases urinary
• Co-administration of nephro-toxic drugs (vancomycin, amikacin, potassium excretion
amphotericin, contrast agents) 4. Exchange resins (Kayexalate: 1 g/kg/dose q 6 h)
• Tumor infiltrating the kidneys (Leukemia, Lymphoma) or eliminates potassium through the bowel and gradually
obstructing the ureters decreases serum level
• Highly effective targeted therapies (e.g., Rituximab in non-Hodgkin 5. Emergence of hyperkalemia is itself an indication to
lymphoma) initiate dialysis, particularly if the above listed measures
fail to lower the level
(sodium, potassium, calcium, phosphorus, uric acid, and
creatinine) every 6–8 h during the initial 48–72 h of
Hyperphosphatemia and Hypocalcemia
chemotherapy, vigorous hydration and administration of
prophylactic allopurinol, play the key role in prevention.
Defined as serum phosphate concentration >6.5 mEq/L and
Continuous ECG monitoring is useful, as electrolyte
serum calcium <7 mEq/L (ionized calcium <1.12 mmol/L),
imbalance can be rapid. In a high risk patient, the nephrologist
respectively. Hyperphosphatemia can result in cardiac
should be involved early in the course of management, with a
arrhythmia and nephrocalcinosis. Reduction in serum phos-
low threshold for dialysis.
phate is achieved with:
Hyper-hydration 1. Hydration, the most effective measure
2. Insulin with hypertonic dextrose, as above
Vigorous intravenous hydration is the cornerstone of 3. Oral phosphate binders, such as aluminum hydroxide
prevention as well as treatment of TLS. The guidelines (50–150 mg/kg/d, divided every 4–6 h) and sevelamer [7]
are: 4. Dialysis, if the above measures fail
& Saline dextrose fluids at a rate 2–4 times the mainte- Increase in serum phosphate is accompanied by concom-
nance [5]. Aim is to achieve a urine output that exceeds itant hypocalcemia due to calcium consumption. Hypocalce-
2–3 ml/kg/h. Fluids should to be started 48 h prior, and mia manifests as muscle cramps, tetany, seizures, prolonged
continued at least 48–72 h following the initiation of QT interval, or fatal dysrhythmias. Any measure to increase
chemotherapy. Fluids should be potassium and calcium the serum calcium will increase the calcium/phosphate prod-
free. uct to more than 60, leading to metastatic calcification. Cal-
& If the urine output is below 2 ml/kg/h, with a volume cium supplementation is reserved only for the symptomatic
replete state, furosemide can be added at 0.5 mg/kg/dose, patient (tetany, cardiac arrhythmia, seizures) at the lowest
every 8–12 h [6] possible dose (50–100 mg/kg slow i.v infusion under cardiac
& In the authors’ unit, prior to hyper hydration, the authors monitoring), to relieve the symptoms [6].
ensure a ‘reasonable’ hemoglobin (Hb≥7 g/dl), to avoid
precipitating fluid overload. If Hb is low (<7 g/dl), with Hyperuricemia
no hyperleukocytosis, packed red cells are transfused
prior to hyper-hydration. If Hb is very low (<5 g/dl), It is defined as uric acid >8 mg/dl in adults, or above the upper
along with hyperleucocytosis, an exchange transfusion limit of normal range for age in children. Xanthine oxidase
is performed. inhibitors (Allopurinol) and hydration should be initiated 48 h
Indian J Pediatr (January 2013) 80(1):50–54 53
NO YES
• Hyperhydration ± Furosemide
• Nephrology consultation
• Allopurinol
• Rasburicase for hyperuricemia
• Maintain Urine output ≥ 2ml/kg/h
• Electrolytes + renal function monitoring
• Specific measures for Hyperkalemia, if present
Renal replacement
Reassess at 6 h
therapy + supportive
treatment
No
Improving electrolytes and urine
output maintained
YES
prior, and continued for at least 72 h, post initiation of chemo- for prevention and treatment of hyperuricemia. The dose is
therapy. Allopurinol (available as 100 and 300 mg tablets) is 0.05–0.2 mg/kg/d I.V infusion, over 30 min. It acts by
administered in a dose of 10 mg/kg/d in three divided doses; converting uric acid to inactive, soluble allantoin. Rapid
maximum dose: 800 mg/d. The dose is reduced to 50 % or reduction in uric acid levels without accumulation of pre-
more in renal failure. Allopurinol prevents formation of addi- cursor products is possible. The availability of Rasburicase
tional uric acid; it however does not lower the level of preexist- has significantly reduced the need for dialysis. It is contra-
ing raised uric acid. indicated in patients with G-6PD deficiency. The drug is
expensive; a single dose often suffices in clinical practice. It
Established or High Propensity to Develop Clinical TLS can be repeated after 24 h, if required (Inj Rasburicase
Rasburicase, a recombinant urate oxidase can be used both 1.2 mg; ≈Rs 12,000)
54 Indian J Pediatr (January 2013) 80(1):50–54
Uric acid is soluble at physiological pH. In the past, systemic In patients who are at risk of TLS, chemotherapeutic
alkalinization was performed with addition of 25–50 mEq drugs are often administered in a phased manner (e.g.,
sodium bicarbonate to 500 ml maintenance fluids, to achieve prednisolone monotherapy in ALL), so as to prevent
a urine pH in a narrow range, between 6.5 and 7.5 [8]. Urinary massive tumor lysis.
alkalinization increases uric acid solubility. However, the
potential problems are:
& Aggravation of symptomatic hypocalcemia
Conflict of Interest None.
& Obstructive uropathy due to intratubular calcium phos-
phate precipitation in alkalinized urine
& Crystallization of uric acid precursors, hypoxanthine and Role of Funding Source None.
xanthine at alkaline pH
Therefore, alkalinization has pros and cons and is a sub-
ject of controversy [6]. In the authors’ unit, alkalinization is References
not performed routinely. It may be considered in a patient
with hyperuricemia when Rasburicase cannot be adminis- 1. Abu-Alfa Ali K, Younes A. Tumor lysis syndrome and acute kidney
tered for financial constraints. injury: evaluation, prevention, and management. Am J Kidney Dis.
2010;55:S 1–S 13.
Renal Replacement Therapy 2. Gemici C. Tumor lysis syndrome in solid tumors. J Clin Oncol.
2009;27:2738–9.
3. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J
Despite above measures for prevention and treatment of Med. 2011;364:1844–54.
TLS, few children do develop renal failure (6 %) or refrac- 4. Mughal TI, Ejaz AA, Foringer JR, Coiffier B. An integrated
tory metabolic abnormalities [4]. Dialysis effectively and clinical approach for the identification, prevention, and treat-
ment of tumor lysis syndrome. Cancer Treat Rev. 2010;36:164–
rapidly reduces the load of metabolic products and maintains
76.
euvolemia in anuric children. Continuous renal replacement 5. Fisher MJ, Rheingold SR. Oncologic emergencies. In: Pizzo
therapy is the preferred modality in patients with hypoten- PA, Poplack DG, eds. Principles and practice of pediatric
sion, large metabolic burden and volume overloaded state oncology. 6th ed. Philadelphia: Williams & Wilkins; 2011.
pp. 1143–5.
[1]. In a resource constraint setting, a peritoneal dialysis may
6. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guide-
be better than no dialysis. Prognosis for complete recovery is lines for the management of pediatric and adult tumor lysis
excellent if renal replacement therapy is initiated early and is syndrome: an evidence-based review. J Clin Oncol. 2008;26:2767–
of prime importance than in choosing a specific dialysis 78.
7. Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients
modality [4]. However, it must be emphasized that dialysis
with kidney failure. N Engl J Med. 2010;362:1312–24.
is a suboptimal option as compared to prevention of acute 8. Cairo MS, Bishop M. Tumor lysis syndrome: new therapeutic
kidney injury. The management of TLS is outlined in Fig. 2. strategies and classification. Br J Haematol. 2004;127:3–11.
Indian J Pediatr (January 2013) 80(1):55–59
DOI 10.1007/s12098-012-0884-8
Received: 10 March 2012 / Accepted: 23 August 2012 / Published online: 10 October 2012
# Dr. K C Chaudhuri Foundation 2012
return and resultant cerebral edema; the patient may obstruction may be present beyond the trachea, resulting in
have lethargy, confusion, headache, irritability, blurred compression of the main bronchi; in such cases, intubation
vision or syncope. and mechanical ventilation may not be effective. These
Clinically, the important parameters of severity of children often have orthopnea; it may be treacherous to
SMS include the degree, as well as rapidity of obstruc- perform investigations, including CT scan, bone marrow
tion [2]. In patients with NHL involving the mediastinal examination, lumbar puncture, etc. The children with a
nodes, there may be rapid enlargement in size of the low PEFR (<50 % expected) and a decreased cross-
nodes. A very rapidly progressive obstruction does not sectional tracheal area (<50 % expected) form the highest
provide adequate duration for development of collateral anesthetic risk group [5].
channels for venous drainage. These patients tend to be The investigations which would help in reaching an early
more symptomatic than those with a similar degree of diagnosis include:
obstruction that has developed gradually, with sufficient-
Imaging
period for formation of collaterals.
1. Chest radiograph (PA and lateral view) is required
Etiology to confirm the presence of the mediastinal mass.
Location is an important indicator of underlying
The common causes of SMS in children are listed in Table 1. etiology (Table 2). Other findings that may coexist
The primary cause of SMS in children is compression by include pleural effusion, cardiomegaly suggesting
malignant mediastinal mass [3, 4]. pericardial effusion, and compression of the tra-
cheobronchial tree.
2. CT chest (contrast enhanced): CT is a very useful
(though not mandatory) investigation in patients with
Investigations
SMS. Ensure normal renal function and do not ad-
minister sedatives while performing the imaging. It
The point of utmost importance to remember while investi-
provides information regarding the exact location and
gating patients with SMS is that they are at a very high risk
size of mass, infiltration into surrounding structures
for adverse cardio-respiratory events in case they are admin-
and vascularity. It aids in planning tissue diagnosis.
istered any kind of anesthetic, anxiolytics or sedatives. The
3. Ultrasonography (USG) chest: This may be useful
need to avoid these medications cannot be stressed more as
when a CT scan cannot be performed due to logistic
they result in reduced respiratory drive, poor respiratory
issues, concerns of transporting a sick patient, in
muscle tone, relaxation of bronchial muscles and diminution
younger children who are not cooperative for a CT
of lung volume. Their use may precipitate the requirement
scan in absence of sedation, or if the patient cannot lie
for resuscitation and cardiorespiratory support. Once intu-
supine. A reasonable knowledge on the site, size and
bated, it is difficult to wean off mechanical ventilation and
nature (cystic versus solid) of mass can be determined.
extubate, till the resolution of SMS [1].At times, the
4. Echocardiography may be required if there is a
suspicion of pericardial effusion or infiltration by
the mass into the pericardial cavity, e.g., in NHL.
Table 1 Common causes of superior mediastinal syndrome [2–4]
Blood Investigations
Malignant
• Non-Hodgkin lymphoma 1. Complete blood count with differential count (re-
• Acute lymphoblastic leukemia quest the pathologist to look for any immature/blast
• Hodgkin disease cells). Presence of blasts in the peripheral blood film
• Neuroblastoma would confirm the diagnosis of acute leukemia with-
• Germ cell tumor out any invasive investigations. In addition, presence
• Sarcomas:including Ewings sarcoma of any cytopenia or leukoerythroblastic picture would
• Thymic tumors indicate plausible bone marrow involvement and pro-
• Acute myeloid leukemia (rarely) vide an opportunity to confirm the diagnosis by bone
marrow examination. NHL may be suspected clini-
Non malignant cally and the peripheral blood examination may be
• Infections: Tuberculosis, fungal infections, histoplasmosis, unremarkable. In such a situation,if a tissue diagnosis
thymic infections, infected cysts in mediastinum. from the mediastinal mass is considered challenging
• Venous thrombosis caused by cardiac surgery or presence due to constraints of resources or expertise, a bone
of a central line
marrow examination may be an option,as it may
Indian J Pediatr (January 2013) 80(1):55–59 57
Anterior mediastinum Lymphoma/Leukemia, germ cell tumors, thymoma Thymic infections, thyroid tumors, parathyroid adenoma,
infectious lymphadenopathy
Middle mediastinum Lymphoma/Leukemia Thyroid tumors, bronchogenic cyst, cystic hygroma,
infectious lymphadenopathy
Posterior mediastinum Neuroblastoma, ganglioneuroblastoma Neuroenteric cysts
2. In presence of pleural or pericardial effusion, a tap combination includes cyclophosphamide (200 mg/m2) with
may be performed which may be diagnostic, as well as dexamethasone and vincristine (1–1.5 mg/m2). Both drugs
therapeutic. The fluid should be submitted for malig- should be used as a single dose, and steroids should be given
nant cytology, besides the routine investigations, in- round the clock. The likelihood of precipitating tumor lysis
cluding work up for tuberculosis, if clinically relevant. syndrome with steroids/chemotherapy has to be borne in mind
Flowcytometry and immunocytochemistry can be per- and managed.
formed and may yield a definitive diagnosis. The role of radiation is largely obsolete as leukemias and
3. An image (CT/USG) guided FNAC/biopsy may be lymphomas are highly chemosensitive. In addition, in children,
cautiously attempted from the mass. radiation may lead to a post-radiation respiratory deterioration
due to airway edema, necessitating emergency steroids. It
If the above studies are not diagnostic, and the patient is a
frequently renders the subsequent tissue sample difficult to
high risk candidate for anesthesia, it is preferable to post-
interpret [8].
pone diagnostic studies, and treat the patient for SMS.
In case of symptomatic SVCS secondary to central venous
line associated thrombosis, line removal in conjunction with
thrombolysis should be considered, especially if symptoms
Therapy have been present for less than 5 d. The patient should be
placed on anticoagulation with low molecular weight heparin
Supportive Care at a dose of 1 mg/kg BD, for a minimum period of 3 mo.
An outline for management of SMS is illustrated in Fig. 1.
The patient should have head end elevated, to assist the venous
drainage and decrease the edema [4]. Intravenous fluids, free of
potassium and calcium (N/2 or N/4 with 5 % dextrose) should Monitoring
be administered at a rate of 1500 mL/m2/d. A higher fluid
intake (up to 3000 ml/m2) may be required in case a diagnosis Clinical Monitoring The child should be continuously
of ALL or NHL is suspected, to prevent tumor lysis syndrome. monitored for vitals including respiratory rate, saturation,
Allopurinol and recombinant urate oxidase (rasburicase) may heart rate, blood pressure (look for pulsus paradoxus),
be indicated for prevention of tumor lysis syndrome in children sensorium, JVP, and signs of airway obstruction (stridor,
with hyperuricemia. All intravenous lines should be placed in air entry), frequently. Urine output should be monitored as
the lower limbs. This will prevent raised hydrostatic pressure well.
in the superior vena cava and resultant increased edema.
Laboratory Monitoring should include complete blood
Definitive Therapy counts and evaluation for tumor lysis syndrome in patients
with a large tumor burden, every 6–12 hourly. It should
Steroids As the most frequent cause of SMS in children is include electrolytes (Sodium, potassium, calcium, phospho-
lymphoma/leukemia, the administration of systemic steroids rous) and renal function tests (urea, creatinine) and uric acid.
is the frontline therapy [1, 2, 7]. Steroids work by decreasing
the tumor burden and reducing the airway edema. In the
authors’ unit, either dexamethasone (4–6 mg/m2/d) or hy-
drocortisone (5 mg/kg/dose, q6H) is administered intrave-
nously. At times, a single dose of steroid may stabilize the Conflict of Interest None.
patient, and diagnostic procedures can be performed subse-
quently. There is a possibility that prolonged use of steroids Role of Funding Source None.
(beyond 24–48 h) in emergency, without a prior tissue
diagnosis may render subsequent tissue diagnosis is difficult
to interpret in upto 20–25 % cases. However, it is better to treat References
the patient for a life threatening emergency, than to undertake
a risky diagnostic procedure and delay therapy, even in the
1. Fischer MJ, Rheingold SR. Oncologic emergencies. In: Pizzo PA, Poplack
face of potential failure of accurate tissue diagnosis. DG, eds. Principles and Practices of Pediatric Oncology. 6th ed. Philadel-
phia: Lippencott Williams and Wilkins; 2011. pp. 1125–51.
Chemotherapy A combination of chemotherapy including ste- 2. Wilson LD, Detterbeck FC, Yahalom J. Superior vena cava syn-
drome with malignant causes. N Engl J Med. 2007;356:1862–9.
roids, vincristine, an alkylating agent and/or anthracycline may
3. Ingram L, Rivera GK, Shapiro DN. Superior vena cava syndrome
be used in a life threatening situation, when steroids alone may associated with childhood malignancy: analysis of 24 cases. Med
not provide a rapid enough relief [1]. The most commonly used Pediatr Oncol. 1990;18:476–81.
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4. Cheng S. Superior Vena Cava Syndrome: A contemporary review of 7. Borenstein SH, Grestle T, Malkin D, Thorner P, Filler RM. The
a historic disease. Cardiol Rev. 2009;17:16–23. effects of prebiopsy corticosteroid treatment on the diagnosis of
5. Ricketts RR. Clinical management of anterior mediastinal tumors in mediastinal lymphoma. J Pediatr Surg. 2000;35:973–6.
children. Semin Pediatr Surg. 2001;10:161–8. 8. Loeffler JS, Leopold KA, Recht A, Weinstein HJ, Tarbell NJ.
6. Chapman S, Nakielny R. Respiratory tract. In: Chapman S, Emergency prebiopsy radiation for mediastinal masses. Impact on
Nakielny R, eds. Aids to Radiological Differential Diagnosis. 4th subsequent pathological diagnosis and outcome. J Clin Oncol.
ed. London: Saunders; 2003. pp. 180–7. 1986;4:716–21.
Indian J Pediatr (February 2013) 80(2):138–143
DOI 10.1007/s12098-012-0901-y
Received: 9 March 2012 / Accepted: 18 September 2012 / Published online: 22 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Febrile neutropenia is a common emergency en- a significant cause of morbidity and mortality. It commonly
countered in children receiving chemotherapy for a malignan- occurs in children diagnosed to have acute leukemia, lym-
cy. Left untreated, it can lead to serious morbidity and phoma, solid tumor or aplastic anemia [1]. It may result
mortality. Febrile neutropenia is suspected in any patient on from the underlying malignancy per se or typically due
chemotherapy who presents with fever. Prompt evaluation and to the effect of chemotherapy. Fever may be the sole
management by the primary contact pediatrician is essential manifestation of a serious infection in neutropenic chil-
for a successful outcome. A detailed history and physical dren as other signs of systemic inflammation might be
examination is warranted to identify source of infection, al- attenuated. Therefore, all children with febrile neutrope-
though two thirds of them may not have localizing symptoms nia should undergo a systematic evaluation, including a
or signs. Risk stratification is valuable in categorizing the history and physical examination, appropriate diagnostic
severity and guiding therapy. Initial stabilization, prompt ini- tests, and prompt initiation of empirical antimicrobial
tiation of appropriate antibiotics and adequate supportive care therapy.
are the cornerstone of treatment. Knowledge of the locally
prevailing bacteriological profile and antimicrobial suscepti-
bility data is crucial for each hospital/unit to frame and peri- Definitions
odically modify guidelines for the choice of antimicrobials.
Delay in initiating antimicrobials significantly worsens the Febrile neutropenia A single oral temperature of ≥38.3 °C
outcome. Education of the family as well as the members of (101 °F) or a temperature of ≥38.0 °C (100.4 °F) for ≥1 h,
the treating unit is important in this regard. Pro-active steps with an absolute neutrophil count [Absolute neutrophil count
must be taken to reduce incidence of hospital acquired sepsis. (ANC) 0 mature granulocytes + neutrophil band or stab cells]
Diagnosis and management in relevance to the emergency of <500/mm3, or an ANC that is expected to decrease to <500
room is reviewed and institutional practice is shared. cells/mm3 during the next 48 h [2].
Keywords Absolute neutrophil count . Acute lymphoblastic Profound neutropenia ANC<100 cells/mm3
leukemia . ALL . Cancer . Culture . Growth-factors
Prolonged neutropenia Neutropenia lasting >7 d
Introduction
Evaluation
Febrile neutropenia is the most common emergency encoun-
tered in children on treatment for a malignancy and remains
History
& Phase of chemotherapy (intensive vs. non intensive) 1. Complete blood count, including differential leukocyte
& Duration since the last chemotherapy count and ANC
& Recent hospitalization and antibiotics received, if any 2. Serum electrolytes, urea and creatinine
3. Blood culture: Obtain as early as possible and always
before the administration of antibiotics. Two sets of blood
Examination cultures from separate venipuncture sites should ideally
be drawn. In the presence of a central venous catheter, a
Vitals (temperature, heart rate, respiratory rate, capillary refill blood culture should be obtained from each lumen of the
time, blood pressure, saturation) should be checked in every catheter and another from a peripheral vein.
patient of suspected febrile neutropenia who walks in to the 4. Chest radiograph: In patients with respiratory symptoms
emergency room. The patient may appear well despite being and signs
in a state of hemodynamic compromise. A detailed physical 5. Cultures from any other site, as clinically relevant. This
examination focusing on possible sites of infection must be includes stool, urine, cerebrospinal fluid, skin, respira-
undertaken. Sites that deserve attention and are commonly tory secretions or pus.
overlooked include oral cavity, ear, sinuses, skin, nails, peria- Second line investigations. These are dictated by the
nal area, intravascular catheter insertion site and the site of clinical course:
bone marrow aspiration. The potential causes of infection in
1. Serum Galactomannan test, CT scan of chest/paranasal
patients with febrile neutropenia are listed in Table 1.
sinuses may be indicated in patients with suspected
Indicators in history and examination can provide valuable
fungal infection.
clues to the etiology of fever. For e.g., a child with respiratory
2. Bronchoalveolar lavage: If pneumonia is non-resolving/
distress and hypoxemia with bilateral diffuse infiltrates on
non-responding.
chest radiograph may have infection with Pneumocystis jir-
3. Skin biopsy, from skin nodules, if any.
oveci or respiratory syncytial virus. Fungal infection should be
suspected in the presence of skin lesions (necrotic eschars,
nodules or target lesions), sinusitis, orbital cellulitis or pleu- Risk Stratification
ritic pain. Fever, headache, seizures, encephalopathy or focal
deficits may occur due to encephalitis, encephalomyelitis, Assessment of risk is crucial in determining the appropriate
bacterial meningitis or brain abscess. Cytomegalovirus, Vari- choice of antimicrobials, the route of administration (intra-
cella zoster virus, Epstein-Barr virus, mumps and Human venous vs. oral), setting (inpatient vs. outpatient) and dura-
herpesvirus-6 are the common viruses responsible for enceph- tion. The patients can be classified as low or high risk [2, 3].
alitis. Brain abscess typically results from invasive infections
due to aerobic and anaerobic bacteria or fungi.
Low Risk Patients
& Non-intensive phase of chemotherapy, e.g., maintenance in patients with prolonged febrile neutropenia who are
phase of chemotherapy receiving broad spectrum antibiotics [1, 2].
& Malignancy in remission
& Lack of any focus of infection e.g., pneumonia, abscess, Antibiotics
sinusitis or diarrhea etc.
& Lack of medical co-morbidities It is important that patients are administered the first dose of
& ANC≥100/mm3 and likely to rise within the next 7 d. antibiotics without any delay. The patients in the authors
& Absolute monocyte count >100/mm3 unit who are receiving intensive blocks of chemotherapy are
& Not fulfilling any criteria for the high risk category instructed to reside in the vicinity of the hospital, so that
If a close follow-up can be ensured, such episodes can antibiotics can be started promptly at the onset of fever.
often be managed with oral antibiotics [5]. The choice Delay in initiating antimicrobials significantly increases
includes cefixime, amoxicillin-clavulanate or levofloxacin the morbidity and mortality. Education of the family as well
[2]. If there is a doubt regarding the clinical condition or as the members of the treating unit is important in this
reliability of follow-up, the patient should be admitted and regard. Care-takers are advised not to administer paraceta-
administered intravenous antibiotics, as in the high risk mol at home as it may mask fever and can lead to delay in
group. seeking medical care.
& Anti-pseudomonal β-lactam agents: Monotherapy with
High-Risk Patients anti-pseudomonal β-lactam agents such as anti-
pseudomonas penicillin (piperacillin-tazobactum), anti-
Any of the following indicators categorize a patient as pseudomonal cephalosporin (cefoperazone-sulbactum) or
‘high-risk’ [2, 4]: carbepenems (meropenem or imipenem-cilastatin) or
cefepime is recommended as first line by Infectious Dis-
& Recent intensive chemotherapy
ease Society of America [2]. However, no significant
& Profound neutropenia (ANC<100 cells/mm3), anticipat-
differences in treatment failure, including antibiotic mod-
ed to extend for >7 d. It is typically observed during or
ification, infection-related mortality, or adverse events
following the intensive phases of therapy, e.g., induc-
were observed while comparing anti-pseudomonas peni-
tion, consolidation or intensification blocks of chemo-
cillin±aminoglycoside regimen with carbapenem mono-
therapy in patients with acute lymphoblastic leukemia
therapy in a recent metaanalysis [9]. Hence, carbapenems
& Any focus of infection, e.g., cellulitis, abscess, pneumo-
can be reserved as second line antibiotics to prevent the
nia, diarrhea, etc.
emergence of drug resistant organisms. Cefoperazone-
& Evidence of hypotension, respiratory distress or
sulbactum along with Amikacin are the current first line
hypoxemia
choice in authors unit. Therapy is switched to second line
& Mucositis interfering with oral intake or resulting in
drugs: Vancomycin and Carbepenems (meropenem or
diarrhea
imipenem-cilastatin) after 48–72 h, if fever is unrelenting
and there is no improvement in the clinical condition.
Colistin is reserved as a third line drug.
Management
& In a hemodynamically unstable patient, an adequate
coverage for drug-resistant gram-negative and gram-
‘High-risk’ patients are to be hospitalized and adminis-
positive organisms, as well as for anaerobes should be
tered broad-spectrum intravenous antibiotics (Fig. 1).
given. Hence, second line antibiotics should be admin-
Knowledge of the locally prevailing bacteriological pro-
istered upfront. A combination of an anti-pseudomonal
file and antimicrobial susceptibility data is crucial for
carbapenem, such as imipenem or meropenem, as well
the choice of antimicrobials. Each hospital/unit must
as addition of an aminoglycoside, together with vanco-
review the prevalance of common pathogens and their
mycin (three antibiotics) provides this cover [2].
antimicrobial susceptibility data periodically to frame
& Specific gram positive cover is not a standard part of
and modify the choice of antimicrobials in their setting.
initial empiric antibiotic therapy [2]. It should be added
Majority of infections in febrile neutropenia are caused
in initial therapy, if patient has evidence of any of the
by gram negative organisms e.g., Pseudomonas aerugi-
following:
nosa, E. coli, Klebsiella pneumonia and Acinetobacter
species [5, 6]. Staphylococcus aureus, coagulase nega- – Hemodynamic instability
tive Staphylococcus and Enterococcus are the common – Severe sepsis
gram positive organisms [6–8]. Fungal infections with – Radiographically confirmed pneumonia
Candida, Aspergillus or Mucor are usually encountered – Clinically suspected catheter related infection
Indian J Pediatr (February 2013) 80(2):138–143 141
– Skin or soft tissue infection – Frequent hand washing is often not practical in busy
– Known colonization with methicillin-resistant Staphy- units. However, the use of alcohol based hand rub in
lococcus aureus (MRSA), Vancomycin-resistant En- between patients must be ensured by each medical
terococcus (VRE), or Penicillin-resistant Streptococcus and nursing personnel.
– Severe mucositis, if fluoroquinolone prophylaxis – Use of IV fluids, central lines, foley’s catheter etc. must
has been given and ceftazidime is employed as be restricted, if possible. Administration of IV fluids
empirical therapy for minor reasons should be avoided. Nasogastric
feeding should be encouraged in patients with anorexia
& Empirical or presumptive anti-malarial therapy is not
or mucositis.
recommended [10].
– Rectal enemas, suppositories, and rectal examinations
are contraindicated in neutropenic patients [2, 11]
General Considerations and Supportive Care & Patients with severe sepsis and septic shock should
be managed as per the survival sepsis guidelines
& Pro-active steps must be taken to reduce incidence of [12]. Non-invasive intermittent positive pressure
hospital acquired sepsis, an increasingly common and ventilation should be attempted in case of acute
challenging complication in hospitalized patients. respiratory failure, before restoring to mechanical
142 Indian J Pediatr (February 2013) 80(2):138–143
ventilation, except in those with severe hemodynam- fever after 4–7 d of antibiotics and whose overall
ic compromise [13, 14]. duration of neutropenia is expected to exceed 7 d.
& Hemoglobin<8 g/dl is generally an indication for blood
transfusion in a stable patient.
& Indication for platelet transfusion: These vary with the
Conflict of Interest None.
clinical condition of the patient. In a stable patient with-
out any co-morbidities and bleeds, prophylactic trans-
fusions are recommended at a count below 10×109/ Role of Funding Source None.
mm3. Few studies have suggested that this threshold
can be further lowered to 5×109/mm3 [1, 15, 16]. Trans-
fusion threshold of 20×109/mm3and 100×109/mm3 is References
recommended in patients with minor (mucosal, epistax-
is) and major bleeds (hemoptysis, GI or CNS bleed), 1. Walsh TJ. Infectious complications in pediatric cancer patients.
respectively [1]. The practice may often be varied in In: Pizzo PA, Poplack DG, eds. Principles and practice of
pediatric oncology. 5th ed; Philadelphia: Williams and Wilkins;
different units, depending on physician preferences and
2006. pp. 1269–329.
extent of availability of blood products. 2. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Infectious Diseases
& Growth factors: Administration of G-CSF has no role in Society of America. Clinical practice guideline for the use of
the management of children with uncomplicated febrile antimicrobial agents in neutropenic patients with cancer: 2010
Update by the Infectious Diseases Society of America. Clin Infect
neutropenia [12]. However, they might be useful in Dis. 2011;52:427–31.
reducing the duration of neutropenia and length of hos- 3. Badiei Z, Khalesi M, Alami MH, et al. Risk factors associated with
pital stay in children with complicated febrile neutrope- life-threatening infections in children with febrile neutropenia: a
nia (pneumonia, hypotension, invasive fungal infection data mining approach. J Pediatr Hematol Oncol. 2011;33:e9–e12.
4. Härtel C, Deuster M, Lehrnbecher T, Schultz C. Current
or multi organ dysfunction) [17, 18].
approaches for risk stratification of infectious complications in
pediatric oncology. Pediatr Blood Cancer. 2007;49:767–73.
5. Vidal L, Paul M, Ben-Dor I, Pokroy E, Soares-Weiser K, Leibovici
L. Oral versus intravenous antibiotic treatment for febrile neutro-
penia in cancer patients. Cochrane Database Syst Rev. 2004;4:
Subsequent Management CD003992.
6. Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood acute
It depends upon response to initial antibiotics, clinical status lymphoblastic leukemia: an analysis of 222 febrile neutropenic
of the patient, culture results and ANC. The patient should episodes. Pediatr Hematol Oncol. 2008;25:385–92.
7. Kanafani ZA, Dakdouki GK, El-Chammas KI, Eid S, Araj GF,
be transferred under the care of a Pediatric Oncologist at this Kanj SS. Bloodstream infections in febrile neutropenic patients at a
point. tertiary care center in Lebanon: a view of the past decade. Int J
Infect Dis. 2007;11:450–3.
& Patient who is without a focus of infection, afebrile 8. Mathur P, Chaudhry R, Kumar L, Kapil A, Dhawan B. A study of
within 2–3 d after first line antibiotics, along with a bacteremia in febrile neutropenic patients at a tertiary-care hospital
rising ANC, with negative cultures, may be discharged with special reference to anaerobes. Med Oncol. 2002;19:267–72.
9. Manji A, Lehrnbecher T, Dupuis LL, Beyene J, Sung L. A sys-
after 24–48 h or may be shifted to oral antibiotics, till
tematic review and meta-analysis of anti-pseudomonal penicillins
ANC exceeds 500/cumm. and carbapenems in pediatric febrile neutropenia. Support Care
& In case of documented infections, including soft tissue Cancer. 2012;20:2295–304.
infection, pneumonia, or bacteremia, appropriate anti- 10. Bansal D, Gautam P, Dubey ML, Marwaha RK. Presumptive
treatment for malaria is not justified in children receiving cancer
biotics should be given for 10–14 d.
chemotherapy. Pediatr Blood Cancer. 2010;55:1108–10.
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investigations for invasive fungal infections should pediatric patients: eight years of experience in a pediatric oncology
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Indian J Pediatr (February 2013) 80(2):144–148
DOI 10.1007/s12098-012-0917-3
Received: 9 March 2012 / Accepted: 26 October 2012 / Published online: 24 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Hyperleukocytosis is defined as peripheral blood Keywords Acute lymphoblastic leukemia . ALL . CML .
leukocyte count exceeding 100,000/mm3. Acute leukemia is Hydration . India . Leukostasis . Priapism
the most common etiology in pediatric practice. Hyperleu-
kocytosis is a medical emergency. The increased blood
viscosity, secondary to high white cell count and leukocyte Introduction
aggregates, results in stasis in the smaller blood vessels.
This predisposes to neurological, pulmonary or gastrointes- Hyperleukocytosis is defined as peripheral blood leukocyte
tinal complications. In addition, patients are at risk for tumor count exceeding 100,000/mm3 [1]. It typically occurs in
lysis syndrome due to the increased tumor burden. Initial hematological malignancies, including acute lymphoblastic
management includes aggressive hydration, prevention of leukemia(ALL), particularly T-cell ALL, infant ALL or
tumor lysis syndrome, and correction of metabolic abnor- hypodiploid ALL, and acute myeloid leukemia (AML).
malities. A red cell transfusion is not indicated in a hemo- Chronic myeloid leukemia, especially in blast crisis may
dynamically stable child, as it adversely affects the blood present with hyperleukocytosis [2]. Hyperleukocytosis com-
viscosity. Leukapheresis is the treatment of choice for a very plicates the course of leukemia in 5–22 % children [3, 4].
high count, or in patients with symptomatic hyperleukocy-
tosis. The technical expertise required, a relative difficult
venous access in younger children, risk of anticoagulation Differential Diagnosis
and possible non-availability of the procedure in emergency
hours are limitations of leukapheresis. However, it is a Hyperleukocytosis should be differentiated from leukemoid
rewarding procedure and performed with relative ease in reaction, when a high total leukocyte count (TLC) (typically
centers that perform the procedure frequently. An exchange >50,000/mm3) occurs in the presence of non-malignant dis-
transfusion is often a practical option when hyperleukocy- orders. It is observed in certain infections, including pertus-
tosis is complicated with severe anemia. The partial ex- sis, staphylococcus aureus, Pneumococcus, tuberculosis and
change aids in correcting both, without the risk of volume varied inflammatory conditions [5, 6]. Generally, the counts
overload or hyperviscosity, which are the limitations of do not exceed 100,000/mm3. The predominant cells are
hydration and blood transfusion, respectively. Etiology and mature lymphocytes and granulocytes. Differentiation can
management of hyperleukocytosis in relevance to the pedi- be done through history, examination and peripheral smear
atric emergency room is outlined. examination. A high number of nucleated RBCs (nRBC) in
blood can also raise the TLC erroneously, especially when a
counter is used. This is commonly observed in patients with
thalassemia major and in neonates. The counter generates a
R. Jain : D. Bansal (*) : R. K. Marwaha raised value of TLC, as the nRBC’s are spuriously counted
Hematology/Oncology Unit, Department of Pediatrics, as leucocytes. The TLC generally is less than 100,000/mm3.
Advanced Pediatrics Center,
Here again, the examination of peripheral smear will con-
Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India firm the presence of nRBC’s, and a corrected TLC can be
e-mail: deepakritu@yahoo.com calculated.
Indian J Pediatr (February 2013) 80(2):144–148 145
Hyperleukocytosis
• Send tumor lysis work up, coagulogram, chest X-ray, blood gas
• Obtain EDTA sample for cross match
• Establish IV access; start potassium and calcium free fluids
• Start Allopurinol (250-500 mg/m2/d)
Hb >6-7g% Hb >6-7 g%
Severe anemia with impending
congestive cardiac failure (Hb <5-6g%)
• IVF: Two times maintenance • IVF: 70-100% maintenance • IVF: 3-4 times maintenance
• No red cell transfusion • Urgent leukapheresis or exchange transfusion • No red cell transfusion
• Treat coagulopathy (Platelets, FFP as needed)
maintenance. Typically, the fluids may be initiated at a rate that blood cell transfusion is not indicated in a hemodynamically
is twice the maintenance, and can be increased in a symptom- stable child, as it increases the blood viscosity. In case of
atic patient who persists to have a high TLC. The fluid rate severe anemia, with impending congestive cardiac failure,
depends on the tumor burden as well as the hemoglobin (Hb). leukapheresis or exchange transfusion are better options. Coa-
If the Hb is ‘reasonable’ (≈7–8 g/dL or more), higher fluid gulopathy may be observed in children with AML (particu-
volumes can be administered, while monitoring for fluid over- larly promyelocytic variant). If present, it should be corrected
load and urine output. If the Hb is very low (less than ≈6 g/dL), by transfusion of 10–15 mL/kg of fresh frozen plasma.
less fluids should be given, as higher volumes may precipitate
congestive heart failure. There is no role of routine use of Prevention of Tumor Lysis
diuretics in hyperleukocytosis, as the goal is hemodilution
and reduction of viscosity. Diuretics are however indicated if Aggressive hydration therapy administered for hyperleuko-
there is co-existing TLS and fluid overload. cytosis, aids in the prevention of TLS as well. The reader
may wish to read a recent review on TLS [13]. Briefly,
Transfusion of Blood Products Allopurinol is started in all children, at a dose of 250–
500 mg/m2/d (maximum 800 mg/d) in three divided doses.
Platelets should be transfused at counts below 20,000/mm3 Tablet Zyloric is available in 100 and 300 mg strengths. In
to prevent CNS bleed, or in the presence of any active case of established TLS with raised uric acid, the preferred
mucosal or visceral bleeds [1]. A platelet transfusion does therapy is with recombinant urate oxidase, administered intra-
not increase the blood viscosity significantly. Packed red venously, at a dose of 0.05–0.2 mg/kg, to be repeated if
Indian J Pediatr (February 2013) 80(2):144–148 147
needed. It is more effective than allopurinol in preventing and children with ALL, who have a high risk of TLS, and may
treating TLS, and decreasing the need for dialysis. A small case develop renal shut down necessitating dialysis, with full dose
series has shown its efficacy in preventing TLS in spite of a chemotherapy given upfront. In patients with AML, on the
very high TLC [3, 14]. (Inj Rasburicase1.5 mg; ≈ Rs 12,000). other hand, regular chemotherapy can often be administered
Reduction of TLC is necessary to prevent morbidity and even with a high TLC, as the metabolic complications are less
mortality in symptomatic leukostasis and preventing tumor common. Lower doses of steroids alone may be given to
lysis prior to initiating chemotherapy. It can be done by children with ALL, while continuing hyper-hydration and
leukapheresis or exchange transfusion. other measures for control of hyperleukocytosis. In a study
Leukapheresis is the treatment of choice for a very high of 15 children with ALL and hyperleukocytosis, intravenous
TLC (>2–3 lakh), or in patients with symptomatic hyper- prednisone started at a low dose and gradually escalated over
leukocytosis [15]. It is the removal of circulating leukocytes 5 d to full dose, led to significant reduction in TLC by day 3,
from the blood and re-infusion of the leukodepleted blood. without developing severe metabolic complications [20]. In
A single leukapheresis decreases the TLC by 20–50 %. authors experience, 2–3 d of steroids in patients with ALL as a
Most patients require a single procedure; rarely more than single agent chemotherapy along with aggressive fluid thera-
two procedures are necessary [8, 16]. The difficult venous py, as against initiation of multi-agent chemotherapy, is often
access in younger children, technical difficulty of the pro- successful in preventing TLS.
cedure in small children, particularly those less than 15 kg, Monitoring forms an integral part of management of a
risk of anticoagulation, inadequate experience and non- child with hyperleukocytosis. Clinical as well as lab parame-
availability of the procedure in emergency hours are the ters should be recorded. Vitals should be monitored frequently
limitations. (q 3–4 hourly). Monitoring includes observation for respira-
Exchange transfusion can be done with fresh whole blood or tory distress and any hemodynamic instability which may
with a mix of packed red blood cells and plasma (in a ratio of 2– indicate a bleed or congestive cardiac failure. Sensorium
3:1), with platelet supplementation. Recommended volume should be evaluated periodically as the earliest manifestations
varies from 70 to 150 mL/kg, with an aim to reduce the blasts of a CNS event are generally headache or persistent vomiting.
by at least 50 % [17, 18]. It is a safe procedure even in neonates Adequate fluid intake and urine output (2–4 ml/kg/h) should
or infants with hyperleukocytosis, and in neonates can be be ensured. Urinary catheterization is not recommended in a
performed through the umbilical catheterization [19]. It is par- conscious and hemodynamically stable child. It leads to un-
ticularly beneficial when hyperleukocytosis is accompanied necessary discomfort and increases the risk of infection. Lab
with severe anemia. The partial exchange aids in correcting monitoring includes daily or more frequent complete blood
both, without the risk for volume overload or hyperviscosity, counts, and evaluation for TLS (serum electrolytes including
which are the limitations of hydration and blood transfusion, K, Ca, iP, uric acid, urea and creatinine) every 8–12 hourly.
respectively. In the authors experience, a partial exchange with Coagulogram should be repeated if initially deranged.
~2 bags of whole or reconstituted blood in a child weighing 15–
25 kg, corrects the anemia safely, following which aggressive
hydration can be instituted. There has been no head to head Indian Experience
comparison between exchange transfusion and leukapheresis
on efficacy and safety. However, there is data to suggest that In a study from Delhi, Arya et al reported 38 % of patients
both the procedures may be equally efficacious in reducing the with T-cell ALL to have hyperleukocytosis; the survival of T-
TLC, with a mean reduction in TLC of 50–60 % with either. cell ALL was equivalent to B-lineage ALL [21]. The inci-
The choice between the two would depend on the clinical dence of hyperleukocytosis was 11 % in children with ALL in
scenario, with age, weight, ease of procedure and availability a study from Tata Memorial Hospital, Mumbai; leucocyte
of equipment being some of the deciding factors [18]. In the count at diagnosis did not affect the incidence of off therapy
authors’ institute, leukapheresis is increasingly preferred, in relapses [22]. Another study from the same center however
parallel with the increasing expertise and experience of the reported a high TLC (>60,000/mm3) to be a poor prognostic
transfusion medicine services. marker in children with ALL [23]. From the authors center,
Chemotherapy It is important to remember that leukaphe- hyperleukocytosis was documented in 111 (14.6 %) of 762
resis or exchange transfusion is not the definitive therapy. patients [24]. Significant lymphadenopathy (45 %), mediasti-
They are temporary measures, which aid in stabilizing the nal adenopathy (26 %) and superior vena cava-obstruction
patient, while establishing diagnosis and initiating chemother- (9 %) were accompanying clinical features. TLS was observed
apy. Chemotherapy must be initiated as early as possible. in 33 % and CNS complications (altered sensorium, raised
However, starting regular dose, multi-agent chemotherapy in intracranial pressure, stroke or intracranial hemorrhage) in
patients with hyperleukocytosis may result in life-threatening 19 %. The estimated mean survival for the entire cohort was
metabolic derangements and TLS. This is particularly true for significantly inferior to that of other ALL patients [24]. With
148 Indian J Pediatr (February 2013) 80(2):144–148
improved supportive care and risk-stratified chemotherapy the 11. Inaba H, Fan Y, Pounds S, et al. Clinical and biologic features and
treatment outcome of children with newly diagnosed acute mye-
outcome is very likely to improve in the future.
loid leukemia and hyperleukocytosis. Cancer. 2008;113:522–9.
12. van Furth R, van Zwet TL. Cytochemical, functional, and prolif-
Conflicts of Interest None. erative characteristics of promonocytes and monocytes from
patients with monocytic leukemia. Blood. 1983;62:298–304.
13. Rajendran A, Bansal D, Marwaha RK, Singhi SC. Tumor lysis
Role of Funding Source None. syndrome. Indian J Pediatr. 2012 Jul 1. [Epub ahead of print].
14. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines
for the management of pediatric and adult tumor lysis syndrome:
an evidence-based review. J Clin Oncol. 2008;26:2767–78.
15. Haase R, Merkel N, Diwan O, Elsner K, Kramm CM. Leukapheresis
References and exchange transfusion in children with acute leukemia and hyper-
leukocytosis. A single center experience. Klin Padiatr. 2009;221:374–
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Poplack DG, editors. Principles and practices of pediatric oncolo- irradiation in patients with hyperleukocytic acute myeloid leuke-
gy. 6th ed. Philadelphia: Lippencott Williams and Wilkins; 2011. mia: no impact on early mortality and intracranial hemorrhage. Am
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2. Majhail NS, Lichtin AE. Acute leukemia with a very high leuko- 17. ALL-BFM 2000 Protocol, Version 12/2008, S99.
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3. Macfarlane RJ, McCully BJ, Fernandez CV. Rasburicase prevents in children. Med Pediatr Oncol. 1987;15:232–5.
tumor lysis syndrome despite extreme hyperleukocytosis. Pediatr 19. Warrier RP, Ravindranath Y, Emami A, Lusher J. Exchange trans-
Nephrol. 2004;19:924–7. fusion for hyperleukocytosis, anemia, and metabolic abnormalities
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nous leukemia. Associations with hyperleukocytosis and acute Management of hyperleukocytosis and prevention of tumor lysis
monocytic leukemia. Cancer. 1987;60:3071–9. syndrome with low-dose prednisone continuous infusion in chil-
5. Macdougall LG, Strickwold B. Myeloid leukaemoid reactions in dren with acute lymphoblastic leukemia. Acta Haematol.
South African Blacks. S Afr Med J. 1978;53:14–6. 2009;121:56–62.
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sis, diagnosis, management, and the role of protective immunity. lineage acute lymphoblastic leukemia: management and out-
Eur J Clin Microbiol Infect Dis. 2000;19:77–88. come at a tertiary care center in North India. Indian Pediatr.
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Early complications in children with acute lymphoblastic leukemia 22. Vaidya SJ, Advani SH, Pai SK, et al. Survival of childhood
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2005;45:10–5. Memorial Hospital, Bombay, India. Leuk Lymphoma.
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Indian J Pediatr (April 2013) 80(4):318–325
DOI 10.1007/s12098-012-0959-6
Received: 10 August 2012 / Accepted: 28 December 2012 / Published online: 23 January 2013
# Dr. K C Chaudhuri Foundation 2013
Abstract Vomiting is a protective reflex that results in force- 0.15 mg/kg; maximum 4 mg) is indicated in children unable
ful ejection of stomach contents up to and out of the mouth. It to take orally due to persistent vomiting, post-operative vom-
is a common complaint and may be the presenting symptom iting, chemotherapy induced vomiting, cyclic vomiting syn-
of several life-threatening conditions. It can be caused by a drome and acute mountain sickness.
variety of organic and nonorganic disorders; gastrointestinal
(GI) or outside of GI. Acute gastritis and gastroenteritis (AGE) Keywords Children . Vomiting . Antiemetic
are the leading cause of acute vomiting in children. Important
life threatening causes in infancy include congenital intestinal
obstruction, atresia, malrotation with volvulus, necrotizing Introduction
enterocolitis, pyloric stenosis, intussusception, shaken baby
syndrome, hydrocephalus, inborn errors of metabolism, con- Vomiting is a very common complaint in infants and chil-
genital adrenal hypoplasia, obstructive uropathy, sepsis, men- dren who present to the emergency department (ED). A
ingitis and encephalitis, and severe gastroenteritis, and in large percentage of infants and children with vomiting have
older children appendicitis, intracranial mass lesion, diabetic a non-serious etiology for their symptoms and have a self-
ketoacidosis, Reye’s syndrome, toxic ingestions, uremia, and limiting illness. However, vomiting may be the presenting
meningitis. Initial evaluation is directed at assessment of symptom in several life-threatening conditions. The ED
airway, breathing and circulation, assessment of hydration management is primarily tailored to identify and manage
status and red flag signs (bilious or bloody vomiting, altered those with a serious underlying cause, and provide symp-
sensorium, toxic/septic/apprehensive look, inconsolable cry tomatic relief to others.
or excessive irritability, severe dehydration, concern for symp-
tomatic hypoglycemia, severe wasting, Bent-over posture).
The history and physical examination guides the approach in Terminology
an individual patient. The diverse nature of causes of vomiting
makes a “routine” laboratory or radiologic screen impossible. Vomiting is a complex behavior. It is usually composed of
Investigations (Serum electrolytes and blood gases,renal and three linked activities: nausea, retching and expulsion of
liver functions and radiological studies) are required in any stomach contents.
child with dehydration or red flag signs, to diagnose surgical Nausea is a sensation of impending emesis and is fre-
causes. Management priorities include treatment of dehydra- quently accompanied by autonomic changes, such as in-
tion, stoppage of oral fluids/feeds and decompression of the creased heart rate and salivation. Vomiting can occur
stomach with nasogastric tube in patients with bilious vomit- without preceding nausea, for e.g., projectile vomiting in
ing. Antiemetic ondansetron(0.2 mg/kg oral; parenteral individuals with increased intracranial pressure.
Retching is defined as strong, involuntary efforts to vomit
but without expelling material from the mouth, which may
S. C. Singhi (*) : R. Shah : A. Bansal : M. Jayashree
be seen as preparatory manoeuvres to vomiting.
Department of Pediatrics, Advanced Pediatrics Centre, PGIMER,
Chandigarh 160012, India Vomiting is a protective reflex and is defined as forceful
e-mail: sunit.singhi@gmail.com ejection of stomach contents up to and out of the mouth [1].
Indian J Pediatr (April 2013) 80(4):318–325 319
It is caused by violent co-ordinated contraction of the dia- identify and often are viewed as diagnoses of exclusion.
phragm and abdominal muscles accompanied by pyloric con- Examples of non-organic causes are psychogenic vomiting,
striction and gastroesophageal relaxation in response to cyclic vomiting syndrome, abdominal migraine, and bulim-
stimulation of the medullary vomiting centre. This stimulation ia. Mnemonic ‘VOMITINGs’ can help to remember wide
may occur from a variety of impulses -from pelvic and ab- ranging causes of vomiting:
dominal viscera, the heart, the peritoneum, the inner ear, and
the chemoreceptor trigger zone (caused by circulating drugs, & Vestibular: Otitis media
toxins, and metabolic derangements). Vomiting is complete & Obstruction: Pyloric stenosis, malrotation, volvulus, in-
emptying of the stomach as compared to regurgitation, which tussusception, incarcerated hernia
is nearly effortless return of short amount of food during or & Metabolic: Diabetic ketoacidosis, inborn errors of metab-
shortly after eating. When regurgitation occurs in a baby at or olism, congenital adrenal hyperplasia, Reye’s syndrome
after milk feed, it is known as posseting. & Infections:
IEM Inborn error of metabolism; DKA Diabetic Ketoacidosis ; GE Gastro esophagial; UTI Urinary tract infection; ICP Intracranial pressure; GERD
Gastroesophageal reflux diseases
320 Indian J Pediatr (April 2013) 80(4):318–325
Evidence of Lethargy/Altered
sepsis/meningitis? mental status?
No Yes No Yes
Table 2 Red flag signs in a child presenting with vomiting fructose intolerance. History of binge eating should be asked
• Altered sensorium (cause or effect) when behavioral cause is suspected.
• Toxic/ septic /apprehensive look
• Bilious or bloody vomiting
Associated Symptoms
• Presence of inconsolable cry or excessive irritability
(meningitis, intussusception) GI Symptoms
• Signs of severe dehydration or concern for & Diarrhea: Gastroenteritis (diagnosis is made if vomiting
symptomatic hypoglycemia
and diarrhea both are present), bacterial colitis, inborn
• Visible severe wasting
error of metabolism and partial intestinal obstruction.
• Bent-over posture (drawing of legs up to the chest), and pained
avoidance of unnecessary movement typical of peritoneal
& Abdominal pain and its location
irritation (peritonitis, intussusception)
– Generalized : [peritonitis, abdominal migraine
(recurrent)]
– Substernal : Esophagitis
counted as a single episode. Recurrent vomiting is defined – Epigastric: Gastritis, pancreatitis
as at least 3 episodes occurring over 3 mo period. Recurrent – Right upper quadrant : Cholelithiasis, pneumonia
vomiting is further subdivided into chronic vomiting, which – Right lower quadrant : Appendicitis (vomiting after
is low grade frequent (>2/wk) vomiting episodes, and epi- pain)
sodic or cyclic vomiting, which is discrete episodes of high – Lower abdominal or suprapubic- UTI
intensity vomiting that occur sporadically in between
asymptomatic intervals. Cyclic vomiting syndrome is dis-
tinct clinical entity.It is important to elicit temporal pattern Extra Intestinal Symptoms
of vomiting because any single attack of episode or cyclic & Sore throat, ear pain: Sinusitis, otitis media
vomiting may resemble an acute vomiting attack. & Urinary retention, dysuria: Urinary tract infection,
Time of day vomiting occurs can give some clue to pyelonephritis
diagnosis. Vomiting consistently in early morning is com- & Jaundice: Hepatitis, biliary disorders
mon with increased intracranial pressure from various & Headache: Allergy, chronic sinusitis, migraine
causes and cyclic vomiting syndrome.
– Nocturnal or early morning worsened by coughing or
Contents of Vomiting valsalva manoeuvre
& Vertigo: Migraine, Meniere disease
Contents of vomiting gives important clue to diagnosis and
& Rash or urticaria: Food allergy, Henoch Schonlein purpura
sometimes helps in identifying serious illness. These are
& Back pain- Pyelonephritis
given in Table 4.
History of Toxic Ingestions: Food, iron, alcohol,
Relationship with Diet organophosphates
History of Drug Intake: digoxin (vomiting is first sign
Vomiting is aggravated by food in patients with gastritis, of toxicity), theophylline, salicylates, chemotherapeutic
cholecystitis, pancreatitis, protein allergy, and hereditary drugs, acetaminophen
Epidemiology Most common 2/3 of those with recurrent vomiting 1/3 of those with recurrent vomiting
Etiology See Table 1 Gastrointestinal (GI) more common Extra-intestinal causes outnumber
than extra-intestinal ones (7:1) GI ones (5:1)
Acid peptic disease, H. pylori Cyclic vomiting syndrome (88 %), DKA,
Addison disease, metabolic disorders,
malrotation, hydronephrosis
Vomiting severity Moderate to severe ± dehydration Mild (1–2 emeses/h at peak). Moderate to severe (6 emeses/h at peak),
Rarely dehydrated >50 % require IV hydration
Migraine family history Up to 14 % positive Up to 82 % positive
322 Indian J Pediatr (April 2013) 80(4):318–325
History of recent head trauma, similar symptoms in family life (2–4 wk commonly) in an otherwise healthy infant [5].
or neighbourhood (gastroenteritis, food poisoning, Affected children may appear irritable during or after the
hepatitis) feedings and stereotypic opisthotonic movements with exten-
sion and stiffening of arms and legs and extension of the head
Physical Examination (Sandifer syndrome) occasionally may be observed. Infants
who have the classic history of recurrent emesis but who are
The physical examination is directed towards evaluation of thriving and have normal physical examination findings do
degree of toxicity and dehydration and then focused according not need specific treatment; up to 95 % of them have resolu-
to possible clinical etiology. tion of symptoms by 12 mo (majority by 6 mo). Thickening
the formula or human milk by adding cereal may help reduce
Abdominal Examination vomiting in such infants, but elevating the head in the supine
position has no proven beneficial effect [6].
& Look for signs of obstruction such as distension, tender-
Infants with severe GER can have recurrent microaspira-
ness, high-pitched bowel sounds (or absent sounds in
tion into their lungs resulting in chronic wheezing, respira-
ileus), or visible peristalsis
tory symptoms, and even failure to thrive. This is known as
& Look for organomegaly
GER Disease. Basic reflux precautions such as smaller,
& Genitalia and hernia sites for ovarian/testicular torsion,
more frequent feeds and allowing the infant to remain up-
strangulated hernia
right for 30 min after feeds can be helpful. Reassuring the
& Per rectal examination: especially when intussusception
family that most children spontaneously outgrow GER by
is suspected.
the age of 1 usually helps alleviate parental anxiety.
Clinical features of some common surgical causes of
vomiting are given in Table 5. Minor Head Injury Minor head injury can present as vomit-
ing in children, especially toddlers [7]. There is evidence to
Extra Abdominal Examination suggest that vomiting after a minor head injury may be
related to intrinsic patient factors rather than the severity
& Look for icterus (hepatitis, biliary disease), pallor (intra-
of the injury [8]. Vomiting that is persistent or latent in onset
cranial bleed), rash or petechiae (CNS infection or bleed)
may more likely to signify head injury.
& Ear examination- Bulging red tympanic membrane (otitis
media)
Rumination Syndrome Rumination syndrome, an under-
& Abnormal muscle tone : Cerebral palsy (GER), metabolic
recognised condition, is characterised by effortless, often
disorder, mitochondriopathy
repetitive, regurgitation of recently ingested food into the
& Abnormal fundoscopic exam or bulging fontanelle: In-
mouth. It was originally described in children and in the
creased intracranial pressure, pseudotumorcerebri
developmentally disabled but it is now well -recognised that
& Neck stiffness, Kernig’s and Brudzinski’s sign: Meningitis
the condition occurs in patients of all ages and cognitive
[Sensitivity and specificity of vomiting is 71 % and 62 %
abilities [9]. The pathophysiology is incompletely under-
respectively for diagnosis of meningitis in a child with
stood, but involves a rise in intra-gastric pressure, generated
clinically suspected meningitis [4]].
by a voluntary, but often unintentional, contraction of the
Infant Regurgitation is defined as vomiting occurring two abdominal wall musculature, at a time of low pressure in the
or more times per day for 3 or more wk in the first 1–12 mo of lower oesophageal sphincter, causing retrograde movement
of gastric contents into the oesophagus [9]. A typical history (acidosis with elevated anion gap), renal tubular acidosis
can be highly suggestive but oesophageal manometry may (metabolic acidosis with a normal anion gap) and renal
help to distinguish rumination syndrome from other belching/ or prerenal failure (elevated creatinine).
regurgitation disorders [9].
Hepatic or pancreatic enzymes may be elevated in the
setting of liver or pancreatic disease.
Laboratory Investigations
Radiographic Tests
The diverse nature of causes of vomiting makes a “routine”
laboratory or radiologic screen impossible. The history and
Radiographic tests are needed to differentiate surgical
physical examination must guide the approach in individual
causes from nonsurgical etiologies.
patients. Investigations are not required in following conditions
and a therapeutic trial of medications should be given if required. & Plain Radiograph Abdomen: Abdominal X ray (erect
& Well appearing infant with typical regurgitant reflex (no preferably) should be done in any child with suspected
diarrhea, fever, nausea and forceful abdominal contractions) intestinal obstruction. Upright or cross-table lateral view
& Well child with suspected gastritis or gastroesophagial reflux. can reveal distended bowel loops and/or air-fluid levels
& Brief episode of vomiting with no dehydration and clear consistent with intestinal obstruction(in a child with
etiology like gastroenteritis bilious vomiting, abdominal pain and distension); dilat-
& Chronic vomiting where acid peptic disease is suspected ed stomach in pyloric stenosis; free air under diaphragm
in case of a hollow viscus perforation; abnormal calcifi-
Selected tests can give useful clues to diagnosis.
cations like renal or biliary stones or fecoliths; and
basilar infiltrates caused by lower lobe pneumonias.
Urinalysis
& Ultrasound: Uitrasonography of abdomen should be
obtained according to the clinical possibility. Abdominal
Presence of glucose and ketones suggest diabetic ketoaci-
ultrasound can be helpful in diagnosis of appendicitis,
dosis; red blood cells suggest a renal cause (nephritis, UTI,
pyloric stenosis, and intussusceptions. Pelvic ultrasound
renal calculi or trauma); and leukocytes or nitrites suggest a
is the test of choice for renal, ovarian or uterine pathol-
urinary tract infection.
ogy in children.
& An Upper GI Series best demonstrates malrotation and
Blood Investigations
upper gastrointestinal tract obstructions and may some-
times be needed for diagnosis of pyloric stenosis.
In any child with dehydration or red flag signs (Table 2),
& CT Scan: A limited CT with rectal contrast can be
total blood counts, blood sugar, serum electrolytes, blood
helpful in diagnosis of appendicitis. An abdominal CT
gases, Liver enzymes, and renal function tests should be
is most useful in imaging the liver and pancreas, and for
obtained according to the clinical possibility.
evaluating mass lesions in the abdomen.
& Serum Electrolytes and Blood Gases: Typical abnormal-
ities occur in an infant with projectile vomiting from Upper GI Endoscopy
pyloric stenosis (hypochloremic, hypokalemic metabolic
alkalosis), congenital adrenal hypoplasia (hyperkalemia Upper GI endoscopy is useful for defining upper GI muco-
and hyponatremia), increased lactate production caused sal pathology such as acute gastritis, gastric erosions, esoph-
by alcohols, salicylates, uremia, and metabolic defects agitis, acute duodenitis, duodenal ulcers, stricture, varices,
324 Indian J Pediatr (April 2013) 80(4):318–325
mass (polyp, lymphoma), and foreign body impaction. The 5. Acute motion sickness
diagnostic yield of upper gastrointestinal endoscopy in chil-
dren up to 18 y of age with vomiting in one study from Dose of Ondansetron Oral: 0.2 mg/kg and Parenteral
Saudi Arabia was 67 %. [10] 0.15 mg/kg (maximum 4 mg); range 0.13–0.26 mg/kg. Higher
doses are not beneficial nor do they have more side effects [14].
Metabolic Work Up While there are existing older studies evaluating domper-
idone, dexamethasone and promethazine, these studies have
In a child with episodic vomiting or suspected metabolic small sample sizes, low methodological quality and reveal
disorders, blood and urine screening are positive only dur- inconsistent results and their use is not recommended, par-
ing actual vomiting episode. Therefore, attempt should be ticularly in the light of increased concerns regarding the
made to obtain samples (blood pH, ammonia, lactate, safety of these medications for children.
ketones, urine ketones and electrolytes, porphyrins and re-
& Drugs for acid peptic disease: can be given empirically
ducing substances) during acute episode only.
for 2 wk to 4 wk. H2 receptor antagonist or proton pump
In chronic vomiting if therapeutic drug trial fails to im-
inhibitor can be used.
prove symptoms, screening laboratory tests (complete blood
& Cyclic vomiting syndrome is an idiopathic disorder that
count, ESR, celiac screening, liver enzymes) and abdominal
usually begins in early childhood and is characterised by
ultrasound can be obtained along with pediatric gastroenter-
repeated, discrete attacks of vomiting to the point of
ology consultation.
dehydration, (on average 12 episodes/d, typically lasting
for 2–3 d) and intervening periods of normal health.
Relatively little is known about its’ pathogenesis or
Emergency Management
cause [15]. Episodes usually occur in morning hours,
and may have associated prodrome of nausea, pallor and
& Treat dehydration (refer to protocol for diarrhea)
headache. Treatment is supportive, focused on fluid
& If bilious vomiting, stop oral fluids/feeds (nil per oss –
management in cases where dehydration and electrolyte
NPO) and decompress the stomach with nasogastric
imbalance occur. Amitriptyline and propranolol have
tube. Start intravenous fluids. Seek surgical consult.
been described as effective for prophylactic therapy
& Antiemetics: Antimetics are not routinely indicated due to
(antiemetics may be of benefit during an acute episode).
concerns about side effects of earlier generation of antie-
& The mainstay of treatment for rumination syndrome is
metics (promethazine, prochlorperazine, and metoclopra-
explanation and behavioral treatment which consists of
mide) which cause somnolence, nervousness, irritability,
habit reversal techniques that compete with the urge to
dystonic reactions and other extrapyramidal symptoms.
regurgitate [9].
Newer antiemetics such as ondansetron have far fewer
side effects [11]. Evidence based on a limited number of
Conflict of Interest None.
studies evaluating the role of ondansetron in the treatment
of acute gastroenteritis complicated by vomiting, favour
the use of ondansetron and metoclopramide to reduce the Role of Funding Source Used available resources of Department of
number of episodes of vomiting. However, diarrhea Pediatrics
increases with both ondansetron and metoclopramide,
which is thought to be as a result of retention of fluids
and toxins that would otherwise have been eliminated References
through the process of vomiting [12]. A recent RCT
concluded that administration of oral ondansetron in chil-
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dren with acute gastroenteritis with vomiting who are 2. Taylor AT. Nausea and vomiting. In: DiPiro JT, Talbert RL, Yee G,
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hospitalization as well as IV fluid requirement [13]. Stanford: Appleton & Lange; 1999. pp. 586–96.
3. Li BU, Sunku BK. Vomiting and Nausea in Pediatric Gastrointenstinal
Use of antiemetics prior to evaluation for surgical abdomen and Liver Disease. In: Wyllie R, Hyams JS, eds. Pathophysiology/
should be avoided. Following are acceptable indications for Diagnosis/Management. 3rd ed. Philadelphia: Saunders; 2006. pp.
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4. Amarilyo G, Alper A, Ben-Tov A, Grisaru-Soen G. Diagnostic
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2. Post-operative vomiting gitis. Pediatr Emerg Care. 2011;27:196–9.
5. Hyman PE, Milla PJ, Bnenninga MA, Davidson GP, Fleisher DF,
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Database Syst Rev. 2004;4:CD003502. reducing vomiting related to acute gastroenteritis in children
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Indian J Pediatr (March 2013) 80(3):235–246
DOI 10.1007/s12098-012-0909-3
Received: 3 July 2012 / Accepted: 8 October 2012 / Published online: 30 November 2012
# Dr. K C Chaudhuri Foundation 2012
Abstract Acute diarrhea is the second leading cause of Keywords Children . Acute diarrhea . Oral rehydration
under-five mortality in India. It is defined as the passage therapy . Severe dehydration
of frequent watery stools (>3/24 h). Recent change in con-
sistency of stools is more important than frequency. Acute
diarrhea is caused by variety of viral, bacterial and parasitic Introduction
agents. The common ones are: Rotavirus, E. coli, Shigella,
Cholera, and Salmonella. Campylobacter jejuni, Giardia Diarrhea remains second commonest cause of death in chil-
and E. histolytica are also not uncommon. The most impor- dren under 5 y in developing countries despite improving
tant concern in management of acute diarrhea in Emergency trends in diarrhea mortality; it accounts for 15 % of all
room (ER) is fluid and electrolyte imbalances and treatment deaths of children less than 5 y in developing countries
of underlying infection, wherever applicable. It includes, [1, 2]. On average, children < 5 y in developing countries,
initial stabilization (identification and treatment of shock), suffer a median of 3.2 episodes of diarrhea/child/year and up
assessment of hydration and rehydration therapy, recogni- to 4.9 children/1000/year die because of diarrhea. Most of the
tion and treatment of electrolyte imbalance, and use of deaths are because of fluid and electrolytes imbalance. The
appropriate antimicrobials wherever indicated. For assess- most common concern in Emergency management is acute
ment of hydration clinical signs are generally reliable; how- fluid and electrolytes imbalances and treatment of underlying
ever, in severely malnourished children sunken eyes and infection wherever indicated.
skin turgor are unreliable. Oral Rehydration Therapy is the
cornerstone of management of dehydration. Intravenous
fluids are not routinely recommended except in cases of Definition
persistent vomiting and/or shock. Majority of cases can be
managed in ER and at home. Hospitalization is indicated in Diarrhea Diarrhea is defined as passage of unusually loose or
infants <3 mo, children with severe dehydration, severe watery stools with an increase in the frequency, usually at least
malnutrition, toxic look, persistent vomiting and suspected three times in 24 h period. However, it is the consistency of the
surgical abdomen. Supplementations with zinc and probiot- stools rather than the number that is most important. Breast
ics have been shown to reduce severity and duration of fed babies may normally pass 5–7 stools a day. Diarrhea
diarrhea; however evidence does not support the use of lasting longer than 14 d is labeled as ‘persistent diarrhea’.
antisecretary, antimotility and binding agents. Education of
parents about hand hygiene, safe weaning and safe drinking Dysentery Presence of gross blood in the stool is the hall-
water etc., can help in reducing incidence of this important mark of dysentery and may be accompanied by abdominal
health problem in the country. cramps and fever.
& Passage of stool during or immediately after feeding due apathy may be present in both the types of malnutrition. In
to gastrocolic reflex. such children thirst, dry tongue and mouth (inner side of
& Passage of frequent loose greenish yellow stools on the cheek), and signs of hemodynamic compromise (fast thread
3rd and 4th day of life called as transitional stools. pulse, delayed capillary refill time and orthostatic
changes in BP, and hypotension) are most reliable indicators
of dehydration [4].
On abdominal examination children with uncomplicated
Etiology
diarrhea generally tend to have diffuse abdominal tenderness
and loud bowel sounds. Presence of localized tenderness,
Common organisms causing diarrhea, their incidence and
rebound tenderness to absent bowel sounds indicates a possi-
pathogenesis are given in Table 1.
ble surgical cause. Palpation of a loop of bowel or a mass
Viral diarrhea infects small intestinal epithelium. The
suggests intussusception, enterocolitis or inflammatory bowel
onset is generally abrupt, patient is likely to be afebrile
disease.
and may have associated vomiting or respiratory symptoms.
Toxigenic bacteria also involves small bowels and causes
Laboratory Investigations
secretary diarrhea (Table 2)
Invasive bacterial and protozoal diarrhea involves colon.
Laboratory investigations are not required routinely in major-
Diarrhea is bloody or mucoid and may have associated col-
ity of cases of acute diarrhea. Indications for selective use of
icky abdominal pain, fever and tenesmus. Food poisoning is
laboratory investigations are as summarized in Table 7.
caused by preformed bacterial toxins. Onset is abrupt with
vomiting followed by diarrhea (Table 3).
Differential Diagnosis of Acute Diarrhea [3, 9]
Clinical Evaluation [2–4, 8–10]
Systemic Disease with Acute Diarrhea
The objectives of initial clinical evaluation of the patient in
Infants and young children with systemic disease can some-
emergency department are:
times present with acute diarrhea. They generally have sys-
1. Assessment of the severity of the illness, grade of de- temic signs of sepsis and sick look, but not necessarily. In such
hydration and rehydration needs. children following clinical diagnosis should be kept in mind.
2. Identification of likely causes on the basis of the history
& Otitis media, bacterial pharyngitis
and clinical findings.
& Urinary tract infection
A rapid assessment of airway, breathing and circulation & Pneumonia
should be done in all children at presentation. Tachycardia, & Meningitis
prolonged capillary refill time, decreased urine output, al- & Bacterial sepsis
tered mental status and hypotension indicates presence of
shock and calls for oxygen, and fluid resuscitation with
20 ml/kg normal saline bolus. Diarrhea with Surgical Acute Abdomen
Viruses Rotavirus Causes 15–20 % of diarrhea Cytopathic to small intestinal epithelial cells
Responsible for upto 50 % of diarrhea associated with clinical
dehydration in children aged 6–24 mo.
Enterovirus Virus replication and cytopathic effect on small intestinal cells
Adenovirus 2–5 % Cytolysis, cytokine production, and induction of host inflammatory response
Bacteria Enterotoxigenic E. coli (ETEC) Causes up to 25 % diarrhea in all age groups Produces heat labile (LT) and/or heat stable (ST)
enterotoxins causing secretory diarrhea of small intestine
Shigella Causes upto 5–10 % of acute diarrhea in all age groups Dysentery syndrome by invasion of large bowel and enterotoxin
mediated small bowel diarrhea
Vibrio cholera Frequent cause of diarrhea in endemic areas in children 2–10 y Toxin mediated secretory diarrhea
of age. Accounts for 5–10 % hospitalization in non endemic areas.
Non typhoidal salmonella Causes 2–10 % of diarrhea in developing countries Intracellular invasion of ileal epithelium
Campylobacter jejuni Causes 5–15 % of all diarrhea. It is a zoonosis Invasive and toxigenic diarrhea
Protozoal Giardia duodenalis[5] Most common protozoal infection causing diarrhea Damage to the endothelial brush border, enterotoxins,
immunologic reactions, and altered gut motility and
fluid hypersecretion
Entamoeba histolytica [6] Annually 0.09 episodes/child of E. histolytica-associated diarrhea Excystation in the small bowel and invasion of the colon
and 0.03 episodes/child of E. histolytica-associated dysentery by the trophozoites
Cryptosporidium [7] Causes a self-limited diarrheal illness in healthy individuals Infects distal small intestine and proximal colon, no
and persistent diarrhea in immunocopromised children cytopathic effect. Causes villous atrophy, lymphocytic infiltration etc.
237
238 Indian J Pediatr (March 2013) 80(3):235–246
Table 2 Etiologic agents and and pattern of small vs. large bowel Table 4 History and clinical evaluation of diarrhea patient [2, 4, 8, 9]
diarrhea [3, 4]
History Assessment of dehydration
Site Organisms Characteristics
Onset, frequency, quantity General appearance, alertness
Small bowel Rotavirus, Salmonella, Frequent, large Character: bile, blood and mucus Temperature
diarrhea V. cholera, Giardia, quantity, watery,
Vomiting (color and frequency) Pulse rate, volume
Cryptosporidium greenish to white
stools Fever Respiratory rate (acidotic breathing)
Large bowel Shigella, Enteroviruses, Semi-loose, small Oral acceptance Blood pressure
diarrhea E. coli, C. jejuni, quantity, with or Abdominal distension Capillary refill time
E. histolytica without blood in Level of consciousness, Mucus membrane
the stool abnormal movements (tongue, inner cheek)
Urine output (passage Sunken fontanels, sunken eyes
of urine in last 6 h) Skin turgor
having severe dehydration and a selective group of very Perianal excoriation or redness Glasgow coma score (GCS)
young, malnourished, toxic-sick looking patients need hospi- Underlying medical condition Signs of malnutrition
talization as shown below. Past medical history Change in body weight
Epidemiological history (if previous body weight known)
Table 5 Assessment
of dehydration [2–4, 8, 9] Characteristics Mild Moderate dehydration Severe dehydration (>2signs)
dehydration (≥2 signs)
ORT consists of & If the child is not exclusively breastfed, give one or
more of the following home made food-based fluids
& Rehydration
(such as soup, rice water, and yoghurt drinks), or
& Maintenance therapy
clean water.
& Prevention of ongoing losses
& If the child wants more ORS than shown, give more.
ORT may be contraindicated in children who are in hemo- & For infants less than 6 mo who are not breastfed, also
dynamic shock or with ileus. For children who are unable to give 100–200 ml clean water during this period.
tolerate ORS via oral route (with persistent vomiting), & Show the mother how much fluid to give in addition
naso-gastric feeding can be used to administer ORS. to the usual:
Treatment of Mild and Moderate Dehydration Up to 2 y: 50 to 100 ml after each loose stool and in
between them.
1. Oral Rehydration Therapy (ORT) [2, 4, 10] 2 y or more: 100 to 200 ml after each loose stool
& Determine amount of ORS to be given during first and in between them.
4 h (Table 9) 3. Continue Feeding [2, 10]
& Show the mother how to mix and give ORS solution.
Give frequent small sips from a cup. If the child vomits, Begin feeding the child in emergency itself with
wait for 10 min. Then continue, but more slowly. Con- whatever is appropriate for the age of the child. Avoid
tinue breastfeeding whenever the child wants. high fiber and bulky food, very dilute soups and food
& Give recommended amount of ORS over 4–h period as with lot of sugar.
mentioned in Table 9 according to the degree of
dehydration.
& Reassess for the degree of dehydration after 2–4 h and Points to be Kept in Mind During Rehydration [4]
select the appropriate plan for further rehydration.
& Rehydration must be assessed by clinical examination
2. Give Extra Fluids [2, 4, 11] and not by fluid volume given.
& If breast fed, breastfeed frequently and for longer at & The volumes can be increased to achieve rehydration.
each feed. & Puffiness around the eyes suggests over hydration.
Infants (EWL) 0–5 % of body wt. loss 5–10 % of body wt. loss >10 % of body wt. loss
Children and adolescents(EWL) <3 % of body wt. loss 3–9 % of body wt. loss >9 % of body wt. loss
Table 7 Indications for various investigations in a patient with acute diarrhea and their importance [4, 10]
Stool routine 1. Mucoid and bloody diarrhea Presence of leukocytes, protozoa, RBC’s and bacteria.
2. Suspected cholera (hanging drop preparation) Presence of polymorphs suggest infection by invasive bacteria
Stool culture 1. Toxic looking infants <1 y having Available after 2–3d
polymorphs in stool Start/change antibiotic as per sensitivity pattern
2. Suspected cholera
3. Immunocompromised children
4. Children with hemoglobinopathies
Blood counts, blood 1. Newborns with diarrhea Distinguishes Salmonella and Shigella infection -
culture, CRP 2. Toxic infants and children’s Shigella having a marked shift to left.
3. Infants <3 mo, with fever >38.5°C Start/change antibiotic as per sensitivity pattern
4. Older children with sepsis, fever, seizures Monitoring of systemic inflammation
and altered sensorium
Blood biochemistry (Na, K, 1. All those requiring hospitalization These parameters will guide the treatment plan and
urea, creatinine, glucose) 2. Seriously ill toxic patients guide the response to treatment. Some abnormalities
3. Severe dehydration/shock need urgent treatments (hypo kalemia, hypoglycemia,
hyponatremic seizures etc. )
4. Malnourished patients with dehydration
5. Newborns and infants <3 mo
6. Children with altered sensorium
Blood gas analysis 1. All seriously ill patients Will tell about metabolic acidosis, bicarbonate
2. Patients with acidotic breathing losses from the body, body compensation and
improvement with treatment
3. Patients with severe dehydration or shock
4. Malnourished patients with dehydration
ECG 1. Malnourished patients Will tell about the K+ status
2. Severely dehydrated patients
3. Patients with high output diarrhea
4. Patients having acidosis
Maintenance therapy should be started as soon as the signs of & Has sunken eyes
dehydration have gone, but not before it. A simplified algorithm & Has fever
for rehydration therapy of acute diarrhea is shown in Fig. 1. & Does not eat or drink normally
& Not passing urine for 6 h
When to Return & Having altered mentation
& Not getting better after 2 d
Mother/caretaker should be advised to return to health
care facility immediately if any of the following symp-
toms are noticed. Treatment of Severely Dehydrated Children
& Passes many stools (>10 times/d) (Replacement Therapy) [2, 4, 10]
& Is very thirsty
Start IV fluid immediately. If the child can drink, give
Table 8 Composition of WHO ORS [2] ORS by mouth while the drip is set up. Give 100 ml/kg
Components g/L Constituents Concentration Ringer’s Lactate Solution (or, if not available, normal
(ionic form) (mmol/L) saline) divided as follows: 20 ml/kg body weight intra-
venously till perfusion and mental status improve; then
Sodium chloride 2.6 Sodium 75 administer 100 ml/kg ORS over 4 h or 5 % dextrose ½
Anhydrous glucose 13.5 Chloride 65 saline IV at twice maintenance fluid rate (Table 9).
Potassium chloride 1.5 Glucose 75
Trisodium citrate, dihydrate 2.9 Potassium 20
& Reassess the child every 1–2 h. If hydration status is not
- - Citrate 10
improving; give IV drip more rapidly. Also give ORS
(about 5 ml/kg/h) as soon as the child can drink; usually
Total osmolality 245
after 3–4 h (infants) or 1–2 h (children).
Indian J Pediatr (March 2013) 80(3):235–246 241
& Reassess an infant after 6 h and a child after 3 h. Therapeutic End Points in Intravenous Rehydration Therapy
Classify dehydration. Then choose the plan to con-
tinue treatment 1. Adequate urine output
& If ORT is not possible or feasible, same amount of fluid 2. Urine specific gravity (1.010–1.015)
can be given intravenously. Type of fluid used is Ringer 3. Normal serum electrolytes
lactate or N/2 in 5 % dextrose (Fig. 1). 4. BUN decreased by one half every 15–20 h till normalized
5. Normal acid base status are signs of systemic infections, recognizable bloody
6. Urinary K+> 40 mEq/L diarrhea and in immunocompromised hosts as follows:
Antimicrobial Therapy [2, 3, 8, 10] 1. Diarrhea with clinical signs of sepsis: (toxic look,
leukocytosis, fever > 38.5° C, septic shock): Ceftriaxone
The decision to treat with antimicrobial therapy should 50 –100 mg/kg/d IV/IM divided 12 hourly for 7–10 d.
be made on a patient-by-patient basis, and may differ 2. Diarrhea in a child with severe malnutrition: Ampicillin
according to the age group. Antimicrobials are not 200 mg/kg/d IV/IM divided 6 hourly along with genta-
needed for small bowel diarrhea and food poisoning micin 5 mg/kg/d IV/IM 8 hourly for 7–10 d.
except cholera. Large bowel diarrhea is invasive. Sal- 3. Neonates and very young infants (< 3 mo) with fever
monella can cause bacteremia in about 10–45 % of (> 38.5°C): Cefotaxime 150 mg/kg/d IV/IM divided
infected infants and neonates, while shigella and inva- 8 hourly along with amikacin 15 mg/kg/d IV/IM OD for
sive E. coli can cause high fever and toxemia. In 7–10 d
shigellosis,therapy is required in severely ill children 4. Dysentry (bloody stools) and diarrhea during outbreak
or children with persistent symptoms. Yersinia needs of shigellosis: Ceftriaxone IV/IM 50–100 mg/kg/d for
treatment when there is severe disease, bacteremia or 7 d or Ciprofloxacin orally 20–30 mg/kg/d divided
underlying illness. Timely antibiotic therapy in selected 12 hourly for 7–10 d.
cases of diarrhea may reduce the duration and severity 5. Suspected Cholera (‘Rice water stools’ with high
of diarrhea and prevent complications. While these purge rate i.e., > 10 large volume stools/d): Doxy-
agents are important to use in specific cases, their cycline 300 mg OD for 3 d or Azithromycin 20 mg/
widespread and indiscriminate use leads to development kg single dose. Treatment of cholera decreases du-
of anitmicrobial resistance. Use of antimicrobials is rec- ration of disease and mortality, and controls the
ommended in the treatment of acute diarrhea when there transmission.
30–40 mEq/L
<10 mEq/L
24–36 h a
12–15 %
> 15 %
Antimicrobials to be given in acute diarrhea when the
10 %
pathogen is known are given in detail in Table 10.
The maximum accepted change in serum osmolality is 1–1.5 mOsmol/L per hour, thus it restricts change of serum Na+ to 0.5 –1 mEq/L per hour
Other Ways of Management
Isotonic dehydration
nous rehydration further management of fluid and electro-
½ normal saline
50–80 mEq/L
lyte therapy with respect to serum sodium concentration is
Decreased
given in Table 11.
Variable
<5%
6–8 h
10 %
15 %
15 h
Enteral Feeding and Diet Selection [2]
80–100 mEq/L
Isotonic saline
10–20 h
throughout the day (six meals/day); avoid high fibre,
<5%
4–6 h
bulky diet. Gradually increase energy intake as tolerated to 10 %
5%
of antimicrobials.
Rate of replacement
Deficit estimation
Total body water
Urine sodium
duration and reducing stool frequency in acute infectious Antiemetic Agents [2, 4, 10]
diarrhea [11, 12]. There are varieties of microorganisms
(Lactobacillus, Bifidobacterium) that have good safety re- Phenothiazines are of little value and are associated
cord; therapy has not been standardized and most effective with potentially serious side effects. Ondensetron is an
and safe organisms and regimens for specific groups have effective and less toxic antiemetic agent (Dose: 2 mg in
not been identified. The authors give their patients probi- children 8–15 kg, 4 mg in children >15–30 kg, 8 mg in
otics for 5 d. children >30 kg). A comprehensive approach to man-
agement of acute diarrhea is shown in Fig. 2.
Antimotility Agents [2, 4, 10]
Specific Aspects of Management of Acute Diarrhea
Gut stasis following use of antimotility agents may lead to in Children with Severe Malnutrition
invasion of the bowel wall by infecting organisms leading to
worsening of the condition. These agents are contra-indicated Diarrhea is a serious and often fatal event in children
in children with dysentery and probably should not be given to with severe malnutrition [13, 14]. Management of acute
infants and young children. diarrhea in these children presents unique challenges as
Fig. 2 Algorithm for
management of a patient
with diarrhea
Indian J Pediatr (March 2013) 80(3):235–246 245
malnutrition predisposes to severe and prolonged diar- edema and appearance of periorbital puffiness indicates
rhea due to underlying micronutrient deficiency (partic- overhydration.
ularly zinc) that causes suppressed immune function.
Care of these children, in addition to correction of dehydra-
Prevention [2, 3, 7, 8]
tion, must focus on management of malnutrition, con-
tinuation of feeding which lessens weight loss and early
Use this opportunity to educate parents about following
detection and treatment of underlying infections and probable
measures to prevent further episodes of diarrhea: Safe water
sepsis [14].
and sanitation, hand hygiene, exclusive breast feeding for
initial 6 mo, appropriate and safe weaning, safe food han-
Assessment of Dehydration dling habits, Vitamin A supplementation and vaccination-
against Rotavirus, Typhoid fever, and Measles.
As mentioned earlier, typical signs of dehydration such
as skin turgor, sunken eyes, mental status and peripheral
temperature are unreliable for assessment of hydration Conflict of Interest None.
status in a malnourished child. In such children thirst,
dry tongue and inner side of cheek, and signs of hemo-
Role of Funding Source None.
dynamic compromise (fast weak or absent pulses,
delayed capillary refill time and orthostatic changes in
BP, and hypotension) and reduced or absent urine flow
indicates severe dehydration [4]. References
11. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr.
for treating acute infectious diarrhoea. Cochrane Database 2001;33:S17–25.
Syst Rev. 2010;11:CD003048. doi:10.1002/14651858. 13. Sachdev HP, Kumar S, Singh KK, Satyanarayana L, Puri RK. Risk
CD003048.pub3. factors for fatal diarrhea in hospitalized children in India. J Pediatr
12. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and Gastroenterol Nutr. 1991;12:76–81.
prevention of acute infectious diarrhea in infants and chil- 14. Uysal G, Sökmen A, Vidinlisan S. Clinical risk factors for fatal
dren: a systematic review of published randomized, double- diarrhea in hospitalized children. Indian J Pediatr. 2000;67:329–33.
Indian J Pediatr (April 2013) 80(4):326–333
DOI 10.1007/s12098-013-0987-x
'
SYMPOSIUM ON PGIMER MANAGEMENT PROTOCOLS IN GASTROINTESTINAL EMERGENCIES
Received: 12 August 2012 / Accepted: 4 February 2013 / Published online: 17 March 2013
# Dr. K C Chaudhuri Foundation 2013
Table 1 Causes of UGIB among Indian children presenting to a the setting of trauma, liver biopsy, and acute/chronic pancrea-
hospital (adapted from reference 2 & 3)
titis. Henoch-Schönlein purpura and vasculitis such as poly-
Cause Yachha et al. 1996 Mittal et al. 1994 arteritis nodosa are rarer causes of UGIB in this age group.
Varices 95 % 39.4 %
Esophagitis - 23.7 % Key Issues
Gastritis 1.3 % 7.2 %
Gastric ulcer - 1.2 % Initial Assessment and Stabilization
Duodenal ulcer - 0.42 %
Esophageal ulcer - 0.42 % As for any other emergency the first priority should be to
Henoch Schönlein purpura 1.3 % - assess the airway, breathing and circulation of a patient
ITP 1.3 % - presenting with UGIB. The most important aspect of the
Gastroduodenal artery 1.3 % - evaluation is to determine the degree and rapidity of blood
aneurysm loss. Orthostatic changes in blood pressure (more than
Unknown - 27.5 %
10 mm of Hg) suggest a moderate bleed (15–20 % of blood
loss) and warrant a more aggressive approach to manage-
Infants and Toddlers ment. Presence of signs of shock (tachycardia, prolonged
capillary refill time, cold-clammy skin, supine hypotension)
Stress ulcers and gastritis in a sick infant or toddler, peptic ulcers, indicates severe bleed of more than 25–30 % of blood loss
variceal bleeding in children with portal hypertension and vas- and a need for immediate volume expansion and stabiliza-
cular malformations can cause major bleeds in this age group. tion before proceeding to a diagnostic algorithm (Fig. 1).
Reflux esophagitis, esophageal or gastrointestinal foreign body, Once the patient is stable the following issues should be
communicating duplication cysts, NSAIDS and corrosive injury addressed before more elaborate diagnostic workup:
can cause non life threatening bleeds. History of a choking
episode, even if it was transient or occurred days or even weeks 1. Whether actual blood or ingested substances
before the bleeding episode, is an important clue for a foreign The first consideration in evaluating children who have
body. new-onset “bleeding” is to determine whether the material
passed is actual blood. A number of substances may
Older Children and Adolescents simulate bright red blood (food coloring, colored gelatin
or children’s drinks, red candy, beets, tomato skins, rifam-
Causes of UGIB in older children and adolescents are similar pin, phenytoin, antibiotic syrups) or malena (bismuth or
to those seen in adults. Varices, peptic ulcers, Dieulafoy’s iron preparations, charcoal, spinach, blueberries, grapes,
lesions and vascular malformations can cause major bleeds. licorice). For detecting blood in vomitus or nasogastric
Reflux esophagitis, Drug induced gastritis, Mallory Weiss aspirate, the Gastroccult® test is more accurate [4]. The
tears, communicating duplication cysts, stromal tumors, lym- test uses Gastroccult slides, sealed in special wrapper, and
phomas (rarely), Crohn’s disease and portal hypertensive gas- stored at room temperature (15–30 °C). One drop of
tropathy can cause minor bleeds. Haemobilia or bleeding from gastric sample is placed to the occult blood test area of
the pancreas (splenic artery aneurysm) should be considered in the slide and two drops of Gastroccult Developer is applied
Endoscopic Management
Endoscopic
Not controlled Injection therapy
sclerotherapy (EST) or
(adrenaline+saline)/
variceal ligation (EVL)
Mechanical hemostasis-
Endoclip/Themocoagulation
Balloon tamponade
Continue PPIs- Test and treat
H. pylori
TIPSS (Cirrhotics) or
Devascularisation / Shunt Surgical/ Intervention
Surgery Radiologist consult
Fig. 1 Algorithmic approach to management of a patient with significant acute upper GI bleed
directly over the sample. The test is read within 60 s. functional, blue color will appear in the positive area, and
The development of any trace of blue color in the occult the negative area will remain colorless.
blood test area is regarded as a positive for occult blood. 2. In a neonate- whether it is patient’s own blood or
Simultaneously, functionality of test should be tested. For swallowed blood
this, one drop of Gastroccult Developer is added between This is often applicable for neonates. The Apt-
the positive and negative Performance Monitor areas and Downey Test is used to differentiate between swallowed
results interpreted within 10 s. If the slide and developer are maternal blood and patient’s blood.
Indian J Pediatr (April 2013) 80(4):326–333 329
3. Is there a pulmonary, oral or ENT source of bleed? and palpation of abdomen for localized tenderness and
Bleeding from these sources may mimic GI bleed organomegaly.
especially when the blood is swallowed. It may be seen
in conjunction with epistaxis, sore throat or may follow & The presence of hepatosplenomegaly and prominent
dental procedures or tonsillectomy. Hence these areas abdominal vessels and a protruding abdomen may indi-
must be explored to rule out in cases of doubt. cate portal hypertension and bleeding from esophageal
4. Level of bleeding varices,
Vomiting of bright red or coffee ground vomitus is & Epigastric tenderness might suggest acute gastritis or
the classic presentation of upper GI bleeding. Bloody peptic ulcer disease.
diarrhea and bright red blood mixed or coating normal & Vascular malformations like hemangiomas and telangi-
stool are the classic presentations of lower GI bleeding. ectases should also be noted.
However, hematochezia, malena, or occult GI blood & Clinical evidences of bleeding diathesis like petechiae,
loss could represent upper or lower GI bleeding. In case echymoses, purpura etc. should also be noted.
of acute-onset hematochezia or malena, the level of & Stigmata of chronic liver disease
bleeding can be confirmed by passage of a nasogastric
tube. Presence of blood in the stomach and clearing of Investigations
nasogastric aspirate with lavage are diagnostic of UGIB.
In an emergency setting only a few laboratory tests are
essential in the beginning to evaluate UGIB. These include
Diagnostic Evaluation complete blood count, prothrombin time (PT) and partial
thromboplastin time (PTT), liver function tests and blood
Focused History grouping and cross matching if there is significant bleed.
Testing for H. pylori (urea breath test, stool antigen and
History is directed at finding the likely source and cause of serological tests) is indicated in a patient with a probability
bleed. It should include the following: of peptic ulcer. Additional laboratory evaluation depends on
the result of the initial evaluation, the patient’s response to
& Recent or recurrent epistaxis: it raises the possibility of a treatment, and clinical suspicion of a particular diagnosis.
nasopharyngeal source of bleeding.
& Recent onset of jaundice and/or change in stool color: Radiographic Studies
may suggest underlying liver disease.
& History of easy bruising or bleeding: may suggests Abdominal ultrasound is useful in patients where extra
a disorder of coagulation, platelet dysfunction, or hepatic portal hypertension, portal hypertension due to liver
thrombocytopenia. disease, hemobilia, splenic artery aneurysm or large vascu-
& History of any co-morbid illnesses: Personal or family lar anomalies are suspected. Doppler blood flow can identi-
history of liver, kidney or heart disease, or coagulation fy evidence of cirrhosis and portal blood flow dynamics.
disorders.
& Epigastric pain, food pain relationship, may be an indi- Endoscopy
cator of gastritis, esophagitis or ulcer disease.
& Details of recent medications ingested as well as an Upper gastrointestinal endoscopy is the gold standard for
‘over the counter’ or ‘alternative’ drug history is impor- diagnosis and treatment of UGIB. It is the procedure of
tant to assess potential contributions from medications choice for all patients with UGIB. In the hands of skilled
that may induce ulceration (such as NSAIDs and corti- endoscopist, this procedure now can diagnose the etiology
costeroids). Even short-term use of ibuprofen can cause in 85– 90 % of cases. It is indicated to identify the site of the
gastric ulcers and hematemesis. bleeding, to diagnose the specific cause of the bleeding, and
& History of previous bleeding episodes can point to to initiate therapeutic interventions when indicated. In case
EHPVO, vascular malformations and duplication cysts. the endoscopic appearance suggests esophagitis, gastritis or
duodenitis a biopsy should be obtained; in suspected peptic
Physical Examination ulcer disease antral biopsies for H. pylori work up (histo-
logical examination, rapid urease test, and culture) should be
Focused physical examination, besides assessing the sever- taken. Though there is no definite time frame given, in all
ity of bleed, should include a good inspection of skin (for cases of major upper GI bleed, an early endoscopy (within
petechiae and echymoses, and vascular malformations) and first 24 h) is recommended by most of the reviews [5].
mucous membranes of the nose and throat (for bleeding), Endoscopy is contraindicated in hemodynamically unstable
330 Indian J Pediatr (April 2013) 80(4):326–333
Some observers believe that solutions at 32 °C may interfere which has been found to be as effective as Octreotide in
with local coagulation mechanisms [7]. adults. Experience with Terlipressin in children is limited
though it is expected to be equally effective. An advantage
Correction of Coagulopathies is intermittent 4–6 hourly dosing.
Somatostatin is also used for control of active bleed, in a
Parenteral vitamin K should be administered empirically dose of 250 mcg/kg IV bolus followed by 250 mcg/kg/h
even when results of coagulogram are pending (infants, continuous infusion. In case of response, the infusion can be
1–2 mg/dose; children, 5–10 mg/ dose). Coagulopathy maintained for 2 to 5 d, while frequently monitoring for
with an international normalized ratio (INR) higher than hyperglycemia [1]. Side effects include abdominal discom-
1.5 or abnormal partial thromboplastin time (PTT) should fort, flushing, nausea, bradycardia, steatorrhoea and
be corrected with fresh frozen plasma (10 ml/kg initially); dyspepsia.
cryoprecipitates may be tried in the face of severe coa-
gulopathy especially if volume of fluid has to be restrict- Prokinetic Agents Erythromycin has been used as a prokinetic
ed; Factor VIIa has little additional advantage, even in agent to clear the stomach of blood prior to emergent endos-
chronic liver disease, and is not routinely recommended; copy. Metoclopramide has also been used to act as a prokinetic
Platelets transfusion is also not recommended unless there for similar reasons besides acting as a ‘pharmacologic tampo-
is active bleeding with low platelet counts. All these nade’ – it increases the lower esophageal sphincter tone.
products should be included in the calculated resuscitation
fluids. Mucosal Bleeds
twice a day for 10–14 d. These combinations are sinusoidal portal hypertension), selective or non-selective
expected to cure 70 % to 85 % of infections [10]. surgically created portosystemic shunts, and nonshunt
procedures aimed at interrupting and ligating varices
Endoscopic Techniques directly (devascularization) [13]. Non variceal bleed can
be tackled by transcatheter embolization by an interven-
Variceal Bleed tion radiologist. If this is not technically feasible or
expertise is unavailable, surgical ligation / resection can
Upper gastrointestinal endoscopy should be performed as be resorted to.
soon as possible after initial stabilization. Endoscopic ther-
apy should be done if variceal source of hemorrhage is
confirmed. A meta-analysis has shown that endoscopic var- Key Points
iceal ligation (EVL) is superior to sclerotherapy in the initial
control of bleeding. However EVL cannot be performed in
& Upper GI bleeding is often a medical emergency.
infants and toddlers due to the large size of available devi-
& Specific etiologies at different ages should be kept in
ces; EST is the mainstay of therapy in this group. Combi-
mind while assessing pediatric patients.
nation of pharmacological and endoscopic therapy is the
& Variceal bleed is the most common cause of significant
most rational approach in the treatment of acute variceal
upper GI bleeding in children.
hemorrhage [11]. Endoscopic injection of ‘tissue glue’ is
& Immediate stabilization should be given priority before
effective for controlling bleeding gastric varices. Argon
proceeding to diagnostic algorithm.
Plasma Coagulation can be used for bleeding portal hyper-
& Upper GI endoscopy is the gold standard for diagnosis
tensive gastropathy lesions, e.g., GAVE- Gastric Antral
and treatment of UGIB.
Vascular Ectasias.
& Therapy in patients with mucosal bleeds is directed at
neutralization and/or prevention of the gastric acid re-
Non Variceal Ulcer Bleeds
lease. Proton Pump Inhibitors (PPIs) are more effica-
cious than H2 receptor antagonists.
In case of peptic ulcers with stigmata indicating high risk
& Octreotide and terlipressin are useful in control of sig-
of rebleed (spurting or oozing vessel in ulcer base/
nificant UGIB especially due to variceal hemorrhage.
adherent clot), any of the following endoscopic therapy
& Refractory variceal hemorrhage or non-variceal hemor-
may be given: Injection therapy with adrenaline and
rhage requires multidisciplinary approach.
saline, mechanical hemostasis (Endoclip Devices) with
or without adrenaline, or thermocoagulation with or with-
out adrenaline.
Conflict of Interest None.
Balloon Tamponade
In patients with variceal bleed who continue to bleed despite Role of Funding Source None.
pharmacologic and endoscopic methods, a Sengstaken-
Blakemore tube can be placed to stop hemorrhage by me-
chanically compressing esophageal and gastric varices.
References
However, its use is associated with potentially lethal com-
plications such as aspiration, migration, and necrosis/perfo-
ration of the esophagus with mortality rates as high as 20 % 1. Boyle JT. Gastrointestinal bleeding in infants and children. Pediatr
Rev. 2008;29:39–52.
[12]. The tube should never be kept inflated for durations 2. Yachha SK, Khanduri A, Sharma BC, Kumar M. Gastrointestinal
exceeding 12 h in children. bleeding in children. J Gastroenterol Hepatol. 1996;11:903–7.
3. Mittal SK, Kalra KK, Aggarwal N. Diagnostic upper gastrointes-
Surgical Treatment tinal endoscopy for hematemesis in children: experience from a
pediatric gastroenterology centre in north India. Indian J Pediatr.
1994;61:651–4.
Consultation with a pediatric surgeon and interventional 4. Rodgers BM. Consultation with the specialist: Upper gastrointes-
radiologist is necessary for children with massive bleed- tinal hemorrhage. Pediatr Rev. 1999;20:171–4.
ing, ongoing significant blood loss, and failed endoscopic 5. Exon DJ, Sydney Chung SC. Endoscopic therapy for upper gas-
trointestinal bleeding. Best Pract Res Clin Gastroenterol.
procedure. Approaches to manage refractory variceal 2004;18:77–98.
hemorrhage include insertion of transjugular intrahepatic 6. Afshani E, Bergee P. Gastrointestinal tract angiography in infants
porto-systemic shunt stents (in sinusoidal and post and children. J Pediatr Gastroenterol Nutr. 1986;5:173–86.
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7. Ponsky JL, Hoftman M, Swayngim OS. Saline irrigation in gastric 11. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Practice Guide-
hemorrhage: The effect of temperature. J Surg Res. 1980;28:204–5. lines Committee of the American Association for the Study of
8. D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclero- Liver Diseases; Practice Parameters Committee of the American
therapy versus vasoactive drugs for variceal bleeding in cirrhosis: A College of Gastroenterology. Prevention and management of gas-
Cochrane meta-analysis. Gastroenterology. 2003;124:1277–91. troesophageal varices and variceal hemorrhage in cirrhosis. Hep-
9. Eroglu Y, Emerick KM, Whitingon PF, Alonso EM. Octreotide atology. 2007;46:922–38.
therapy for control of acute gastrointestinal bleeding in children. J 12. Avgerinos A, Armonis A. Balloon tamponade technique and effi-
Pediatr Gastroenterol Nutr. 2004;38:41–7. cacy in variceal haemorrhage. Scand J Gastroenterol Suppl.
10. Chey WD, Wong BC. Practice Parameters Committee of the 1994;207:11–6.
American College of Gastroenterology. American College of Gas- 13. Superina RA, Alonso EM. Medical and surgical management of
troenterology guideline on the management of Helicobacter pylori portal hypertension in children. Curr Treat Options Gastroenterol.
infection. Am J Gastroenterol. 2007;102:1808–25. 2006;9:432–43.
Indian J Pediatr (March 2013) 80(3):219–225
DOI 10.1007/s12098-012-0955-x
Received: 2 July 2012 / Accepted: 21 December 2012 / Published online: 25 January 2013
# Dr. K C Chaudhuri Foundation 2013
Abstract Lower gastro intestinal bleed (LGIB) is de- Proctosigmoidoscopy remains the first investigation to
fined as any bleeding that occurs distal to the ligament be done and reveals majority of etiology. Multidetector
of Treitz (situated at the duodeno jejunal junction). It CT scan, Tc 99 m RBC scan, angiography and Push
constitutes the chief complaint of about 0.3 % of chil- enteroscopy are the further investigation choices accord-
dren presenting to the pediatric emergency department ing to the clinical condition of the child. Intra operative
(ED). Among Indian children the most common causes enteroscopy is reserved for refractory cases with an ob-
are colitis and polyps. In most of the cases of LGIB scure etiology.
the bleeding is small and self limiting, but conditions
like Meckel’s diverticulum often presents with life Keywords Children . Lower gastrointestinal bleed .
threatening bleeds. The approach in ED should include Proctosigmoidoscopy . Infectious colitis
in order of priority—assessment and maintenance of
hemodynamic stability, confirmation of LGIB and then
to attempt for specific diagnoses and their management. Introduction
This is achieved with help of rapid cardiopulmonary
assessment, focused history and examination. The man- Lower gastro intestinal bleed in children is a common clin-
agement of all serious hemodynamically significant ical problem, but most of the cases are benign and self
bleeds includes, rapid IV access, volume replacement limiting. It constitutes the chief complaint of about 0.3 %
with normal saline 20 ml/kg, blood sampling (for cross of children presenting to the pediatric emergency depart-
matching, hematocrit, platelet, coagulogram and liver ment [1]. The sight of blood in a child’s stool is always
function tests), Inj. Vit K 5–10 mg IV, acid suppression anxiety provoking and mandates an aggressive attempt at
with H2 antagonists/PPI and nasogastric lavage to rule determining a diagnosis.
out upper gastrointestinal bleed. Continuous ongoing
monitoring of vital signs is important after stabilization.
In ill looking infant, infectious colitis, Necrotizing Definitions
enterocolitis (NEC), Hirschsprung enterocolitis and vol-
vulus and in older infants and children, intussuscep- Any bleeding that occurs distal to the ligament of Treitz
tions, typhoid fever, volvulus should be looked for. (situated at the duodeno jejunal junction) is classified as
lower gastrointestinal bleed (LGIB). Hematochezia
refers to the passage of bright red blood per rectum. It
usually suggests LGIB (typically from colon), but rarely
can occur in massive upper gastrointestinal bleeds
B. Balachandran : S. Singhi (*) (UGIB). Melena refers to the passage of black, sticky
Department of Pediatrics, Advanced Pediatrics Centre,
(tarry) stools and is generally a symptom of UGIB, and
Post Graduate Institute of Medical Education and Research
(PGIMER), Chandigarh 160012, India usually indicates a blood loss of at least 2 % of blood
e-mail: sunit.singhi@gmail.com volume.
220 Indian J Pediatr (March 2013) 80(3):219–225
Colitis 42 23.5 18
Polyps 41 54.1 75
Solitary rectal ulcer syndrome 4.5 4.7 3.5
Typhoid fever with complication 4.5
Portal colopathy 3 1.2
Henoch schonlein Purpura 2.4
Lympho nodular hyperplasia 3
A-V malformation 1.5
Hemorrhoids 1.5
Pseudo membranous colitis 1.2
Foreign body 0.5
Idiopathic 1.5 12.9
Indian J Pediatr (March 2013) 80(3):219–225 221
Table 2 Differential diagnosis of LGIB depending on the clinical 6. A history of abnormal bleeding from other sites (bleed-
presentation
ing and clotting disorders)
Hematochezia, Melena 7. Past episodes of gastrointestinal hemorrhage
• Intestinal ischemia 8. Recent use of nonsteroidal anti-inflammatory agents
○ Complicating intussusception, mid-gut volvulus, incarcerated or any other medications (intestinal ulcers)
hernia, or mesenteric thrombosis
Insertion of a naso gastric tube and aspiration is an easy
• Meckel diverticulum
and a rapid way of excluding upper gastro intestinal bleed as
• Upper GI source of bleeding
a cause of melena/hematochezia.
• Bleeding and clotting disorders
Look for the signs suggestive of specific etiologies, such as:
• Typhoid fever with complication
• Vasculitis & Oro buccal pigmentation suggestive of Peutz-Jegher’s
○ Henoch-Schonlein purpura syndrome
• Sloughed polyp & Sausage shaped mass in abdomen in case - intussusceptions
• Intestinal or colonic ulcer & Cutaneous bruising -abnormal hemostasis, jaundice -
○ NSAID gastropathy, Crohn disease liver failure
• Ulcerative colitis & Eczema -milk allergy
• Vascular malformations (including angiodysplasia) & Clubbing- Cirrhosis, inflammatory bowel disease and
Rectal Bleeding with Signs of Colitis (Bloody Diarrhea, Abdominal cystic fibrosis
Cramps, Tenesmus, Nighttime Stooling) & Cutaneous hemangiomas may indicate vascular abnor-
• Infectious colitis malities in intestine
○ Salmonella, Shigella, Campylobacter jejuni, Escherichia coli & Fissures and anal tags in perianal area may indicate an
O157:H7, Clostridium difficile, Entamoeba histolytica, Trichuris underlying Inflammatory Bowel Disease
trichiura etc. & On per rectal examination look for stool impaction and
• Hemolytic-uremic syndrome rectal polyps
• Necrotizing enterocolitis
• Eosinophilic proctocolitis The common causes and the respective signs and symp-
• Inflammatory bowel disease toms [5, 6] are summarized in the Table 4
○ Ulcerative colitis, Crohn disease
Rectal Bleeding with Normal Stool Pattern
• Juvenile polyp Investigations
• Nodular lymphoid hyperplasia
• Eosinophilic colitis & Hemogram (Hemoglobin, hematocrit, total and differen-
• Inflammatory bowel disease tial leukocyte counts) should be obtained in all patients
• Vascular malformation with significant or ongoing bleeds/hemodynamical in-
Bright Red Blood Coating Normal or Hard Stool stability. A platelet count and a coagulogram should be
• Anal fissure done to rule out bleeding and clotting disorders in all
• Rectal prolapse such cases.
• Solitary rectal ulcer & Stool examination is indicated in all children with colitis
• Internal hemorrhoids symptoms and those presenting with blood mixed stools.
• Beta-hemolytic streptococcal cryptitis One should look for the presence of pus cells, ova cysts
• Ulcerative proctitis and parasites. A stool culture is indicated when pus cells
and/or colitis symptoms are present.
& Plain X ray abdomen (erect and cross table prone lateral)
have limited role in emergency evaluation of LGIB. It is
1. Duration and amount of bleeding indicated if there is associated abdominal distension and/
2. Color of the blood or clinical suspicion of necrotizing enterocolitis, and
3. Consistency of accompanying stool obstruction.
4. Is the blood mixed in the stool or coating the outside? & USG abdomen is diagnostic in intussusceptions and is
Does blood drip in the toilet after bowel movement indicated in all suspected cases and also in cases with
(anorectal bleed)? necrotizing enterocolitis, and obstruction.
5. Associated symptoms (such as abdominal pain, fever, & Proctosigmoidoscopy is diagnostic as well as therapeu-
diarrhea, weight loss and fatigue) tic if the bleed is rectosigmoidal in origin. It can detect
222 Indian J Pediatr (March 2013) 80(3):219–225
evidence of colitis, rectal varices, polyps and hemor- useful in cases of bleeding Meckel’s diverticulum. Tc
rhoids [2]. Colonoscopy after bowel preparation (with 99 RBC scan detects ongoing bleeds if it is at least
poly ethylene glycol) is the investigation of choice in 0.1 ml/min [7] and so is more sensitive than angiogra-
proximal colonic bleeds. It also allows examination of phy but less specific than endoscopic or angiographic
the terminal ileum and is therapeutic in many cases. study [8]. The reported sensitivity and specificity of
& Nuclear scans: The nuclear scan can be done using RBC scans range from 78.6–97 % and 70.4–100 %
either technetium sulphur colloid or [99Tcm] respectively [9]. Many clinicians prefer to do it
pertechnetate-labeled red blood cells. Tc 99 m pertech- before the conventional angiography, as it is non
nate scan is commonly employed . It is particularly invasive and helps in selecting the artery (e.g.,
Infectious colitis Abdominal cramps, stool mixed with blood and mucus, fever
Necrotizing enterocolitis Preterm infant with abdominal distension, feed intolerance
Hirschsprung enterocolitis Delayed passage of meconium, chronic constipation, abdominal distension
Intussusception Episodic pain, vomiting. Red currant jelly stool
Henoch schonlein purpura Purpura, joint pain, abdominal pain
Inflammatory bowel disease Most commonly among 5–16 y-old. Occult bleed or bloody diarrhea; also have
aphthous ulcers, joint pain, anorexia, fever, growth failure and skin lesions
Allergic colitis Well appearing, normal weight top fed infant with loose stool mixed with blood
and anemia onset after introduction of milk.
Anal fissure Most commonly among 6–24 mo. History of constipation with painful passage
of large hard stools streaked with bright red blood
Meckel’s diverticulum, vascular anomalies Painless massive bleeding in a previously well child usually < 5 y
Polyps Most commonly in 2–8 y-olds. Painless passage of small amount of bright red blood
on the surface of stool
Indian J Pediatr (March 2013) 80(3):219–225 223
Hemodynamic instability
Stable/ well Blood for cross matching, hematocrit, platelet, coagulogram and
looking child liver function tests
11
Intra operative enteroscopy
superior mesenteric artery, celiac trunk etc.) for con- reported to be more sensitive than conventional
ventional angiography. The sulphur colloid scan has screen-film angiography [13]
a relatively higher sensitivity but due to its shorter & Contrast enema and barium studies do not have much
half life, intermittent bleeds are more often missed role in LGIB. These are indicated only if there is a
[10]. Radionuclide scan is usually well tolerated by clinical suspicion of Hirschsprung disease.
the patient but the accuracy rating for localizing & Multidetector computed tomography (MDCT) is an
bleeding is highly variable (24–91 %) [11] emerging modality for the diagnosis of LGIB. It can
& Selective mesenteric angiography(superior and inferior detect bleeding as low as 0.3 ml/mt. The sensitivity of
mesenteric artery) requires an ongoing bleed of at least CT in localizing the LGIB is more in patients with active
0.5 ml/mt. It is very helpful in diagnosis of vascular bleed (91–92 %) than in patients with obscure hemor-
causes of LGIB and allows therapeutic interventions, rhage (45–47 %) [14, 15]. In pediatric patients, the
e.g., Sclerosant injection or embolisation of the vessel reported sensitivity, specificity and diagnosis accuracy
in such cases. Angiography requires no special bowel of MDCT in LGIB are 82 %, 50 %, and 74 % respec-
preparation and it may be the first investigation i.e., tively [16]. It is a time efficient investigation and needs
before colonoscopy in a hemodynamically unstable pa- no bowel preparation and is noninvasive. The additional
tient with massive bleed, where endoscopy can be anatomic information provided by CT is helpful for
difficult to perform. Angiography has a specificity of further therapeutic angiographic procedures. However
100 % but a sensitivity of only 30–47 % [11, 12]. this may miss an intermittent bleeding and causes sig-
Digital subtraction angiography (DSA) has been nificant radiation exposure.
224 Indian J Pediatr (March 2013) 80(3):219–225
& Other investigations: Capsule endoscopy does not have the ongoing loss of coagulation factors. Platelet transfusion is
much role in acute management of LGIB. It is more useful indicated if the platelet count is <50,000.
in diagnosis of obscure bleeds. Explorative Laparotomy is An algorithm for evaluation and treatment [18–20] of
reserved as a last step of investigation and maybe needed LGIB is given in Fig. 1. The sequence of investigations like
if the bleeding is torrential and an exact localization is not colonoscopy, angiography, and nuclear scans depends large-
possible even after other investigative modalities. ly on the facilities available and the expertise of available
gastroenterologist. No pediatric studies evaluating such
treatment protocols are currently available. Specific man-
agement of selected conditions are given in Table 5.
Treatment
All children with ongoing/significant bleed and those with Conflict of Interest None.
hemodynamic instability should be admitted in the hospital.
Those children with colitis symptoms, with stool for pus cell
Role of Funding Source Used available resources of department of
positive can be treated on OPD basis provided they have no
pediatrics.
signs of dehydration and the oral intake is good.
The most important step in managing a child with LGIB is
the continuous monitoring of vital signs and arrangement with References
blood bank for likely need for blood. In majority of the cases
(up to 80 %) the bleeding responds to supportive management 1. Teach SJ, Fleisher GR. Rectal bleeding in the pediatric emergency
alone, but episodes of rebleeding can occur [17]. department. Ann Emerg Med. 1994;23:1252–8.
If clinical deterioration occurs without obvious blood loss, 2. Ya c h h a S K , K h a n d u r i A , S h a r m a B C , K u m a r M .
this should be considered as hidden bleed in the bowel lumen. Gastrointestinal bleeding in children. J Gastroenterol Hepatol.
1996;11:903–7.
Blood transfusion is required in cases with hemodynamic 3. Khurana AK, Saraya A, Jain N, Chandra M, Kulshreshta R. Profile
instability. Transfusion of fresh frozen plasma is required once of lower gastrointestinal bleeding in children from a tropical coun-
every 2–3 units of packed red blood cells (PRBC), to correct try. Trop Gastroenterol. 1998;19:70–1.
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4. Mandhan P. Sigmoidoscopy in children with chronic lower gastro- experimental comparison of conventional screen-film angiography
intestinal bleeding. J Pediatr Child Health. 2004;40:365–8. and digital subtraction angiography. Investig Radiol. 1996;31:451–7.
5. Boyle JT. Gastrointestinal bleeding in infants and children. Pediatr 14. Geffroy Y, Rodallec MH, Boulay-Coletta I, Julles MC, Ridereau-
Rev. 2008;29:39–52. Zins C, Zins M. Multidetector CT angiography in acute gastroin-
6. Silber G. Lower gastrointestinal bleeding. Pediatr Rev. testinal bleeding: why, when, and how. Radiographics. 2011;31:
1990;12:85–93. E35–46.
7. Squires Jr RH. Gastrointestinal bleeding. Pediatr Rev. 1999;20:95–101. 15. Laing CJ, Tobias T, Rosenblum DI, Banker WL, Tseng L,
8. Dusold R, Burke K, Carpentier W, Dyck WP. The accuracy of Tamarkin SW. Acute gastrointestinal bleeding: emerging role of
technetium-99 m-labeled red cell scintigraphy in localizing gastro- multidetector CT angiography and review of current imaging
intestinal bleeding. Am J Gastroenterol. 1994;89:345–8. techniques. Radiographics. 2007;2:1055–70.
9. Currie GM, Kiat H, Wheat JM. Scintigraphic evaluation of acute 16. Shih SL, Liu YP, Tsai YS, Yang FS, Lee HC, Chen YF. Evaluation
lower gastrointestinal hemorrhage: current status and future direc- of arterial phase MDCT for the characterization of lower gastroin-
tions. J Clin Gastroenterol. 2010;45:92–9. testinal bleeding in infants and children: preliminary results. AJR
10. Voeller GR, Bunch G, Britt LG. Use of technetium-labeled red Am J Roentgenol. 2010;194(2):496–9.
blood cell scintigraphy in the detection and management of gas- 17. Longstreth GF. Epidemiology and outcome of patients hospitalized
trointestinal hemorrhage. Surgery. 1991;110:799–804. with acute lower gastrointestinal hemorrhage: a population-based
11. Farrell JJ, Friedman LS. Review article: the management of lower study. Am J Gastroenterol. 1997;92:419–24.
gastrointestinal bleeding. Aliment Pharmacol Ther. 2005;21:1281–98. 18. Al Qahtani AR, Satin R, Stern J, Gordon PH. Investigative mo-
12. Fiorito JJ, Brandt LJ, Kozicky O, Grosman IM, Sprayragen S. The dalities for massive lower gastrointestinal bleeding. World J Surg.
diagnostic yield of superior mesenteric angiography: correlation 2002;26:620–5.
with the pattern of gastrointestinal bleeding. Am J Gastroenterol. 19. Leung AK, Wong AL. Lower gastrointestinal bleeding in children.
1989;84:878–81. Pediatr Emerg Care. 2002;18:319–23.
13. Kruger K, Heindel W, Dolken W, Landwehr P, Lackner K. 20. Singhi S, Surpure JS. Synopsis of pediatric emergency care. 2nd
Angiographic detection of gastrointestinal bleeding. An ed. Delhi: Peepee; 2010.
Indian J Pediatr (May 2013) 80(5):411–420
DOI 10.1007/s12098-012-0918-2
Received: 1 June 2012 / Accepted: 26 October 2012 / Published online: 27 December 2012
# Dr. K C Chaudhuri Foundation 2012
Systemic Bleeding Disorder vs. Local Etiology in infancy. It is commonly observed in infants who have
not received vitamin K prophylaxis at birth, typically in
At the outset, it should be identified whether bleeding is due the setting of a home delivery. In older children, it may
to a local cause or result of a systemic bleeding disorder. occur due to underlying liver disease, malabsorption or
Typically, recurrent bleeding from a single site is likely to chronic diarrhea.
have a local etiology (e.g., trauma, tumor, surgery) and & Acute ITP typically occurs in children 2–6 y of age.
concurrent bleeding from multiple sites is usually due to a Acute onset, widespread mucocutaneous bleeds (pete-
systemic bleeding disorder. Self-limiting isolated recurrent chiae, purpura or epistaxis) in an otherwise well-child,
epistaxis, particularly in young boys is often due to frequent following a viral infection is the typical presentation.
nose picking and detailed investigations are unwarranted. & Children with severe VWD or platelet function defect
Similarly, it is uncommon for a bleeding disorder to present usually present with mucocutaneous bleeding in early
as recurrent isolated hematuria. Frequent bruises limited to childhood. Less severe disease may manifest in adoles-
the shin are often physiological, due to susceptibility of the cence with recurrent epistaxis or menorrhagia.
vessels in the region devoid of subcutaneous fat.
Family History
Type of Bleeding
X-linked recessive inheritance is observed in factor VIII and
The step following the clinical suspicion of a bleeding disorder
IX deficiency. All other coagulation factor deficiencies, e.g.,
is to identify whether the bleeding is due to a primary hemostatic
factor V, VII, X, XI or XIII have autosomal recessive inheri-
defect or a clotting factor deficiency (Table 1) [1, 3]. Bleeding
tance. VWD has an autosomal inheritance. It is classified into
from umbilical stump is typical of factor XIII deficiency, but
three types: Type 1, 2 and 3. Type 1, 2A, 2B and 2 M have
may occur in deficiencies of fibrinogen or factor X, as well. The
autosomal dominant pattern of inheritance, while type 2 N and
common disorders of bleeding are listed in Table 2 [2].
3 are inherited recessively. It is important to remember that a
negative family history does not rule out the possibility of an
Age and Gender inherited disorder. Spontaneous mutation has been observed
in up to one third of patients with hemophilia [1].
These provide valuable clues towards the diagnosis.
& Inherited coagulation disorders typically manifest when
a child begins to bear weight in infancy. Medical History
& Infants with Wiskott-Aldrich syndrome, an X-linked
recessive immunodeficiency disorder, may present with A past history of prolonged or difficult to control bleeding
thrombocytopenic purpura and/or eczema beginning in during common surgical procedures, viz., dental extraction,
early infancy. circumcision, appendectomy, tonsillectomy or following vac-
& Clinical presentation of Vitamin K deficiency bleeding cination should be elicited. A major inherited bleeding disor-
(VKDB), earlier known as hemorrhagic disease of new- der is unlikely if patient has had an uneventful surgery in the
born may range from ecchymosis to an intracranial bleed past. Recent ingestion of drugs that effect platelet function/
Table 1 Clinical manifestations of primary hemostatic defect vs. clotting factor deficiency
Table 2 Common platelet and coagulation disorders causing bleeding count is normal. Purpura localized to palms and soles may
in children
indicate rickettsial infection. Purpuric or ecchymotic lesions
Platelet disorders that are at unusual site or of unusual shape, particularly in a
Thrombocytopenia female child should arouse a suspicion of child abuse.
Decreased platelet survival Children with purpura fulminans (thrombotic DIC) may
● Immune mediated have well-demarcated purple papules with erythematous
○ Immune thrombocytopenia borders, along with petechiae and ecchymosis. Pallor, jaun-
○ Collagen vascular diseases dice, lymphadenopathy, hepatomegaly or splenomegaly
○ Drug induced point towards an underlying systemic disorder, including
● Disseminated intravascular coagulation infections, leukemia, infiltrative disorders or liver disease.
● Hemolytic uremic syndrome Presence of splenomegaly typically goes against the diag-
● Thrombotic thrombocytopenic purpura nosis of ITP or aplastic anemia.
● Wiskott-Aldrich syndrome
Decreased platelet production
● Malignancies (leukemia, neuroblastoma)
Investigations
● Sepsis: viral and bacterial
● Aplastic anemia
The initial laboratory evaluation for bleeding disorder
includes a complete blood count with review of the periph-
Platelet sequestration
eral smear, prothrombin time (PT) and activated partial
● Congestive splenomegaly
thromboplastin time (aPTT).
● Large hemangiomas (Kasabach-Merritt syndrome)
Disorders of platelet function
Complete Blood Count
Congenital
● Glanzmann’s thrombasthenia
A complete blood count obtained from a well calibrated
● Bernard-Soulier syndrome
electronic coulter will promptly identify or refute thrombocy-
Acquired
topenia as the cause of bleeding. Uncommonly, spurious
● Drug induced: aspirin
thrombocytopenia may result from EDTA induced clumping
Coagulation disorders
of platelets; examination of peripheral smear will confirm the
presence of platelet clumps. A low hemoglobin may be sec-
Congenital
ondary to the underlying bleed. However, anemia dispropor-
● Hemophilia A (Factor VIII), Hemophilia B
(Factor IX) and other factor deficiencies tionate to bleeding is ominous and may suggest underlying red
● Von Willebrand disease cell destruction, bone marrow failure or leukemia. WBC count
Acquired provides information suggestive of sepsis or leukemia.
● Disseminated intravascular coagulation
● Vitamin K deficiency Peripheral Blood Smear
● Liver disease
● Warfarin therapy
Commonly overlooked, a smear provides valuable informa-
● Renal disease
tion about platelet size, morphology and presence of clump-
● Cyanotic congenital heart disease
ing. Giant sized platelets are commonly observed in ITP or
inherited disorders including Bernard-Soulier syndrome.
Wiskott-Aldrich syndrome is characterized by micro-
number, including aspirin, valproate, chloramphenicol, or thrombocytopenia. Schistocytes may suggest microangio-
non-steroidal anti-inflammatory drugs, should be explored. pathic hemolytic anemia, observed in hemolytic uremic
syndrome, thrombotic thrombocytopenic purpura or sepsis.
A search for bleeds from head to toe should be performed to Bleeding time is measure of interaction of platelets with the
look for petechiae, purpura, gingival bleeding, ecchymosis, blood vessel wall (primary hemostatic pathway). Clotting
hematomas, and hemarthrosis. Purpura localized to the low- time gives a rough estimate of the integrity of intrinsic
er body (buttocks, legs, ankles), with or without joint swell- clotting pathway. Sensitivity and specificity of both is not
ing suggests a possibility of Henoch-Schönlein purpura acceptable, particularly in children. These tests are largely
(HSP). The rash in HSP results from vasculitis; platelet obsolete except in rare situations.
414 Indian J Pediatr (May 2013) 80(5):411–420
PT (Prothrombin time) and aPTT (Activated Partial Elevated levels are observed in DIC, recent trauma or sur-
Thromboplastin Time) gery and venous thromboembolism [4, 6].
Petechiae/Purpura/Abnormal bleeding
Screening tests
• Complete blood count
• Peripheral smear: Platelet size/morphology
• PT and aPTT
Thrombocytopenia?
Yes No
Abnormal Normal
Yes No
• DIC • ITP
• Sepsis • HUS • Child abuse
• TTP • HSP
• Acute leukemia • Factor XIII deficiency
• Aplastic anemia • Von Willebrand disease#
• Platelet function disorder*
• Vascular disorders e.g., Hereditary
hemorrhagic telengiectasia,
Ehler- Danlos syndrome
Abnormal PT and normal aPTT Normal PT and abnormal aPTT Abnormal PT and aPTT
Fig. 1 Step wise approach to a child with bleeding. CBC Complete thrombocytopenic purpura; HSP Henoch-Schönlein purpura. #Thrombo-
blood count; PT: Prothrombin time; aPTT Activated partial thrombo- cytopenia is observed in type 2B VWD. *Mild thrombocytopenia can be
plastin time; DIC Disseminated intravascular coagulation; ITP Immune present in Bernard-Soulier syndrome
thrombocytopenia; HUS Hemolytic uremic syndrome; TTP Thrombotic
often administered as the only feasible, though, inferior Composition, dose and indications of FFP and cryoprecipi-
alternative. FFP can be administered to patients with hemo- tate are illustrated in Table 3. The formula for calculating the
philia A as well as B, whereas cryoprecipitate can only be replacement dose of factor VIII and IX in patients with
used in hemophilia A, as it does not contain factor IX. haemophilia is outlined below.
416 Indian J Pediatr (May 2013) 80(5):411–420
Table 3 Composition,
dose and indications of Component Contents Indications and Dose
plasma derived products
in a bleeding child Fresh frozen plasma All coagulation factors: ● Correction of bleeding due to excess warfarin,
[9–11] (1 unit: 150–300 ml) 1 unit of factor/ml of vitamin K deficiency, or deficiency of multiple
FFP & plasma proteins coagulation factors (e.g., DIC, liver disease,
massive blood transfusion with coagulopathy)
● For infusion or plasma exchange in TTP-HUS
● Congenital or acquired coagulation factor
deficiency; only when virus-inactivated
concentrates are unavailable
● Dose: 10–15 ml/kg
Factor VIII required dose of recombinant VIII is 200 units (40 units/dL X
10 kg X 0.5). If cost is a limitation, the dose of factor can be
One unit of recombinant or plasma derived factor VIII raises reduced to half. One ml of FFP will provide 0.8-1 unit, and 1
the measured factor level by 2 %. unit of cryoprecipitate contains 80–110 units of factor VIII. To
raise the factor level by 20 %, the dose of FFP and cryopreci-
Dose of factor VIII ðunitsÞ ¼ Desired rise ðU=dlÞð%Þ pitate will therefore be 200 ml and 2 units (40 ml), respectively.
weight of the patient ðkgÞ Cryoprecipitate is preferred over FFP due to lower chances of
volume overload. The corresponding dose of recombinant fac-
0:5 tor IX in a child with hemophilia B, who presents with similar
scenario will be 480 units (40 X 10 X 1.2), to raise the factor IX
Half-life: 10–12 h, Technique: slow IV push at a rate not to
level by 40 U/dl. It is a common practice to round the dose to
exceed 100 units/min Frequency: q 12 hourly, factor is
the nearest vial size, to prevent wastage of the expensive
stable at room temperature for 12 h
factors.
Factor IX
RICE Therapy
One unit of plasma derived factor IX raises the measured
factor level by 1 %. Along with the factor replacement, analgesics, Rest, Immobi-
lization, Cold compression and Elevation (RICE) should be
Dose of factor IX ðunitsÞ ¼ Desired rise ðU=dlÞð%Þ advised as well. Rest is done in the position of function (a sling
for an upper limb bleed and bed rest or splint for lower limb
weight of the patient ðkgÞ
bleed) for one day, followed by avoidance of weight bearing for
(*If recombinant factor IX is used, the dose is increased by next 3–4 d. Application of ice aids by decreasing pain and
1.2-1.5 units, because of the poor recovery of factor IX in swelling. It can be performed with crushed ice cubes wrapped
some patients) in a wet towel or with cold packs, intermittently for a period of
Half-life: 18–24 h. Technique: slow IV push at a rate not to 5–15 min over 24–48 h. Ice should not be applied directly to the
exceed 100 units/min. Frequency: q 24 hourly, factor is skin, as prolonged application can lead to skin damage. It is not
stable at room temperature for 12 h useful, if applied beyond 48 h [8]. Wrapping the joint gently
with bandage or elastic stocking may help in limiting the
Example A 10 kg child with hemophilia A presents with bleeding and supporting the joint. The application of these
acute hemarthrosis of right knee to the emergency room. adjunctive interventions is not evidence based; however, they
What is the dose of Factor VIII or FFP or cryoprecipitate are commonly recommended, as they help in reducing pain,
that should be administered? swelling and promoting early mobilization [7, 12–14].
In a landmark order, in 2007, the Delhi High Court had
Answer The choice of product is determined by finances and directed the Delhi state Government to make factors available
availability. To achieve a factor level of 40 U/dl on day 1, the to patients with hemophilia [15]. Under the scheme, below-
Indian J Pediatr (May 2013) 80(5):411–420 417
poverty-line families are to be supplied factors free of cost. This 3. It is recommended that every patient with VWD should
was followed by a similar ruling in Lucknow, Uttar Pradesh, in have therapeutic trial of desmopressin to assess the
response to a public interest litigation [15]. Based on these response at diagnosis or when the patient is not bleeding.
developments, hospital authorities should be convinced to make In responsive patients, 0.3 μg/kg (maximum 20 μg) of
factors available in the hospital at least for emergency use. desmopressin diluted in 50 mL saline is administered i.v
over 20–30 min. Although i.v route is the most effective,
subcutaneous injection or nasal spray (150 μg/puff) can
Intracranial Bleed and Other Hemorrhages be used as well [23, 24]. The desired concentration of
the drug as a nasal spray is not available in India. The
In patients with head trauma, a quick neurological examina- commercially available nasal spray (Minirin: 10 μg/puff),
tion, followed by CT head should be performed. Factor re- indicated for nocturnal enuresis and diabetes insipidus, is
placement should not be delayed pending the imaging. Raised too dilute to be used for VWD. Facial flushing, headache,
intracranial pressure, if any, should be managed with medical hyponatremia, hypo/hypertension and tachyphylaxis are com-
measures. Level of the appropriate factor should be immedi- mon adverse effects. VWF concentrate is preferred for major
ately raised to 100 % and a level of 50-60 % should ideally be bleeds. High purity VWF concentrate is not available in the
maintained for at least 2 wk. If resources are limited, a dose of market. Hence, intermediate purity factor VIII concentrates
30–50 U/kg of factor VIII or 60–100 U/kg of factor IX may be containing VWF are used (Immunate: 1 vial0500 units of
used for 3–5 d, followed by maintenance with lower doses, factor VIII and 290 units of VWF; cost~Rs 3400). Initial dose
depending on the response [7, 14]. In children with known of 40–60 units/kg followed by 20–40 units/kg q 12–24 h is
inhibitors to factor VIII or IX, administration of activated recommended. Antifibrinolytic agents should be used con-
prothrombin complex (FEIBA, 1 vial of 500 units costs~Rs comitantly in patients with mucosal bleeds [23, 24].
25,000) or activated factor VIIa may be considered, in con-
sultation with a hematologist [1]. Treatment of commonly
observed hemorrhages in hemophilia is outlined in Table 4. Disseminated Intravascular Coagulation
Table 4 Outline of treatment of bleeds in hemophilia in the emergency room [1, 7, 14, 16]
Desired plasma level Duration (d) Desired plasma level Duration (d)
Acute hemarthrosis 40-60 % 40-60 % 1-2, may be longer if 10-20 % 10-20 % 1–2, may be longer
or muscle hematomas response is inadequate if response is inadequate
(except iliopsoas)
Iliopsoas
• Initial 80-100 % 60-80 % 1-2 20-40 % 15-30 % 1-2
• Maintenance 30-60 % 30-60 % 3–5, sometimes longer 10-20 % 10-20 % 3–5, sometimes
as secondary prophylaxis longer as
during physiotherapy secondary prophylaxis
during physiotherapy
CNS
• Initial 80-100 %a 60-80 %b 1-7 50-80 % 50-80 % 1–3
• Maintenance 50 % 30 % 8-21 30-50 % 30-50 % 4–7
20-40 % 20-40 % 8–14 (up to 21)
Hematuriac 50 % 40 % 3-5 20-40 % 15-30 % 3-5
Gastrointestinal
• Initial 80-100 % 60-80 % 1-6 30-50 % 30-50 % 1–3
• Maintenance 50 % 30 % 7-14 10-20 % 10-20 % 4–7
Epistaxisd 20-30 % 20-30 % 1 d or longer 10-20 % 10-20 % 1 d or longer if
if response is inadequate response is inadequate
a
To achieve a plasma level of 100 %, administer 50–75 U/kg factor VIII concentrate as bolus, followed by a continuous infusion of 4–5 U/kg/h, to
maintain factor VIII >100 U/dL for 24 h. Subsequently administer 2-3/kg/h for 5–7 d to maintain factor level >50 U/dL.
b
To achieve a plasma level of 100 %, administer 80–100 U/kg factor IX concentrate at outset, followed by 20–40 U/kg q 12–24 h to maintain factor
IX >30 U/dL for 5–7 d
c
Treat painless hematuria with bed rest and vigorous hydration (3 L/m2 /d) for 48 h. Raise the patient’s factor level if there is pain or persistent gross
hematuria. Avoid antifibrinolytics. Rule out other causes if hematuria is persistent. Prednisone (1 mg/kg x 3–5 d) can be used, though the benefit is
unclear
d
If bleeding is not controlled by firmly pinching the nose for 15–20 min. and with antifibrinolytic agents
due to DIC. Thus, instead of conventional doses, weight may be administered without the intention of prolonging the
adjusted doses (e.g., 10 U/kg/h) of unfractionated heparin aPTT to 1.5-2.5 times the control.
Table 6 Indications for platelet transfusion in children [17, 18, 21] symptomatic hyperviscosity helps to restore hemostasis as
Indications of prophylactic platelet transfusions well. However, in severe hemorrhage, FFP and platelet trans-
■ Platelet count <10×106/μLa fusions should be given to control bleeding [32, 33].
■ Platelet count 20–40×109/μl and one or more of the following
● DIC in association with induction therapy for leukemia
e.g., acute promyelocytic leukemia Antifibrinolytic Therapy
● Extreme hyperleukocytosis
● Prior to invasive procedures Control of bleeding from mucosal surfaces, particularly
Indications of therapeutic platelet transfusions epistaxis, gum bleeding and menorrhagia in platelet or
■ ITP with major and/or dangerous bleeding (e.g., severe coagulation disorders, can be aided with antifibrinolytic
intestinal, intracranial or intraocular haemorrhage) agents. Two agents, aminocaproic (Hamostat; 1 vial of
■ Acute disseminated intravascular coagulation with major 5000 mg costs~Rs 75, one tablet of 500 mg costs~Rs 6)
bleeding and platelet count <50×106/μL and tranexamic acid (Trenaxa; 1 injection of 500 mg costs~
■ Platelet function defects (congenital or acquired) with active Rs 45, one tablet of 500 mg costs~Rs 13) are available.
bleeding Tranexamic acid is preferred due to its longer half-life,
■ Surgical patient with active bleeding and platelet count higher potency and lower toxicity. Aminocaproic acid is
<50-100×106/μL
administered as a stat dose of 100–200 mg/kg (maximum:
■ During massive transfusions with platelet count <75×106/μL
10 g), followed by 50–100 mg/kg/dose q 6 hourly
a
In a stable patient threshold can be decreased to 5×106 /μL (maximum dose: 5 g). The dose of tranexamic acid is
25–50 mg/kg q 6–8 h [1]. Tranexamic acid is absorbed from
Vitamin K Deficiency Bleeding the buccal mucosa and subsequently secreted in the saliva.
Hence, in oral bleeding, hemostasis is better achieved with a
Infants with vitamin K deficiency bleeding should receive mouth-wash rather than by swallowing. Patient should be
250–300 μg/kg (maximum 10 mg) of i.v vitamin K without advised to crush the tablets in 10–15 ml of water and retain
any delay. As a rough guide, 1–2 mg of vitamin K is more the solution in the mouth for nearly 5 min before swallow-
than sufficient to correct the deficiency in majority of infants ing (‘swish and swallow’). For younger children, tablets can
[29, 30]. It may be administered by subcutaneous route, but be crushed and made into paste with water; this can be
not by intramuscular route, if venous access is difficult. applied at the site of bleeding in the mouth. Antifibrinolytic
Correction of coagulation parameters within 2–6 h of ad- agents are contraindicated in hematuria; formation of clots
ministration of vitamin K is diagnostic of VKDB. FFP (10– can result in colic and obstruction of outflow from the renal
15 ml/kg) is indicated if urgent control of bleeding is desired pelvis [1, 14].
in case of life threatening hemorrhage [1, 30].
Recombinant Factor VIIa
q 2–3 h, till the cessation of bleeding. The high cost 16. Rizza CR, Kernoff PBA, Matthews JM, et al. A comparison of
(Novo-seven: 1 vial01 mg, cost~Rs 42,000) precludes coagulation factor replacement with and without prednisolone in
the treatment of haematuria in haemophilia and Christmas disease.
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17. Gibson BE, Todd A, Roberts I, et al. Transfusion guidelines for
neonates and older children. Br J Hematol. 2004;124:433–53.
18. Liumbruno G, Bennardello F, Lattanzio A, et al. Recommenda-
Conflict of Interest None. tions for the transfusion of plasma and platelets. Blood Transfus.
2009;7:132–50.
19. Ness PM, Campbell-Lee SA. Single donor versus pooled random
Role of Funding Source None. donor platelet concentrates. Curr Opin Hematol. 2001;8:392–96.
20. Slichter SJ. Relationship between platelet count and bleeding risk
in thrombocytopenic patients. Tranfus Med Rev. 2004;18:153–67.
21. Wandt H, Schaefer-Eckart K, Frank M, et al. A therapeutic platelet
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PGIMER
Management Protocols in
Pediatric Emergency Medicine
Advanced Pediatrics Centre – Postgraduate Institute of Medical Education and Research
Published By
Indian Journal of Pediatrics, New Delhi, India
www.ijppediatricsindia.in
2015
CONTENTS
Initial Assessment and Triage in ER
Approach to a Child with Breathing Difficulty
Acute Community Acquired Pneumonia in Emergency Room
Acute Upper Airway Obstruction
Acute Chest Pain
Approach to a Child with Sore Throat
Acute Bronchial Asthma
Approach to a Child with Lower Airway Obstruction and Bronchiolitis
Airway Foreign Body Aspiration
Fainting Attacks in Children
Non-Traumatic Coma and Altered Mental Status
Approach to Headache in Emergency Department
Management of Acute Seizure and Status Epilepticus in Pediatric Emergency
Raised Intracranial Pressure (ICP): Management in Emergency Department
Approach to a Child with Acute Flaccid Paralysis
Tumor Lysis Syndrome
Superior Mediastinal Syndrome: Emergency Management
Febrile Neutropenia: Outline of Management
Hyperleukocytosis: Emergency Management
Management of a Child with Vomiting
Management of Acute Diarrhea in Emergency Room
Approach to a Child with Upper Gastrointestinal Bleeding
Emergency Management of Lower Gastrointestinal Bleed in Children
Approach to a Child with Bleeding in the Emergency Room