ACUTE RESPIRATORY

DISTRESS SYNDROME
FANER, Ned Denebe
LACANILAO, Sunshine
PAGADUAN, Maribec
PUA, Monalisa
NUCUM, Billie Kim
 B.V., 63 Years old
Chief Complaint: Difficulty of breathing
Diagnosis: ARDS 2° to Pneumonia, Septic
Shock
 History

- Known Hypertensive for 28 years and is

maintained on Metoprolol 50mg.
- In 2004, patient has been hospitalized due
to PTB.
 2 weeks PTA:
 mild episodes of dizziness
 BP was elevated to 150/100
 2 days PTA:
 Productive cough with whitish
sputum
 Carbocisteine provided minimal relief
 Weakness after walking 2 blocks
 Few hours PTA: Symptoms persisted
 Upon Admission: conscious, coherent but
in respiratory distress.
Physical Assessment:
 (+) subcostal retractions, (+) crackles
at both lung fields
 VS: BP – 140/80 mmHg, HR – 140
bpm, RR: 42, Temp: 36.6 °C
Hooked to mechanical
ventilator, cardiac monitor
and pulse oximeter.
CXR showed confluence of
densities, R lower and
upper lung fields, L middle
and upper lungs
Furosemide drip
Metabolic Acidosis -
NaHCO3
Tachycardia at 150s –
160s – Digoxin 0.5mg/IV
Runs of Afib
Hooked to Amiodarone
drip
ABG revealed hypoxemia
Hypotensive episodes
70/40, Urine output –
inadequate
 Dopamine and
dobutamine drip started
 A clinical syndrome of severe dyspnea of rapid
onset, hypoxemia, and diffuse pulmonary
infiltrates leading to respiratory failure.
 Acute Respiratory Distress Syndrome (ARDS) is
also known as shock lung, wet lung, post
perfusion lung and a variety of other names
related to specific causes.
 According to the American Lung Association,
the incidence of ARDS ranges from 2 to 71 per
100,000 persons in the United States.
Clinical Disorders Commonly Associated with
ARDS according to HARRISON
Direct Lung Injury Indirect Lung Injury
Pneumonia Sepsis
Aspiration of gastric Severe trauma
contents
Pulmonary contusion  Multiple bone fractures
Near-drowning  Flail chest
Toxic inhalation injury  Head trauma
   Burns
  Multiple transfusions
  Drug overdose
  Pancreatitis
  Post-cardiopulmonary
bypass
• Type II pneumocyte
– proliferate
– differentiate into Type I cells
– reline alveolar walls
• Characterized by:
– local fibrosis
– resolution
ANATOMY and
PHYSIOLOGY
 The bronchiole

Alveoli alveoli

Found at the end of the terminal bronchioles,

the smallest subdivisions of the bronchial tree,
these are clusters of tiny air sacs in which most
gas exchange takes place.
The wall of each alveolus is made of a single-
cell layer of squamous (flat) epithelium.
This thin wall provides easy passage for the
gases entering and leaving the blood as the
blood circulates through the millions of tiny
capillaries covering the alveoli.
The Alveolar Epithelium

Type I alveolar cells (pneumocytes) -

extremely thin squamous cells that line
about 95% of the alveolar surface area.
responsible for the gas (oxygen and
carbon dioxide) exchange that takes place
in the alveoli. It is a very large thin cell
stretched over a very large area
 Type II alveolar cells
(pneumocytes) or septal
cells - cuboidal cells cover about
5% of the alveolar air surface

-responsible for the production and secretion of surfactant

-can replicate in the alveoli and will replicate to replace
damaged type 1 pneumocytes.
Surfactant
-Produced by Alveolar Type II cells

Functions
5.Lowers surface tension & provide
alveolar stability
6.Prevents alveolar flooding
7.Maintains patency & stabilization of
small airways
8.Plays an important role in host defense
Critical components :
2.Dipalmitoylphosphatidylcholine
3.Surfactant Proteins
a. SP-A
b. SP-B
c. SP-C
d. SP-D
Metabolic trafficking of surfactant
phospholipids
Surfactant
secreting
cell
Respiratory Membrane (Air-Blood Barrier)

Thin squamous epithelial layer lining

alveolar walls
Pulmonary capillaries cover external
surfaces of alveoli
Respiratory Membrane (Air-Blood Barrier)

Figure 13.6
4 layers:
a layer of type 1 and
2 alveolr cells and
associated alveolar
macrophage=
alveolar wall
Epithelial basement
membrane
underlying the
alveolar wall
Capillary basement
membrane
Endothelial cells of
the capillary
Respiratory membrane thickness

Increasing the thickness of the respiratory

membrane decreases the rate of diffusion.

In healthy lungs, the respiratory

membrane (alveolar membrane +
endothelial membrane + fused basement
membranes) is 0.5-1.0um thick, but the
thickness can be increased by respiratory
diseases.
Surface Area
The total surface area of the respiratory
membrane is approximately 70 m2
(approximately the area of one half of a tennis
court) in the normal adult.

When the total surface area of the respiratory

membrane is decreased to one third or one
fourth of normal, the exchange of gases is
significantly restricted even under resting
conditions.
Partial Pressure Difference
 difference between the partial pressure of the gas in the
alveoli and the partial pressure of the gas in the blood of
the alveolar capillaries.

 When the partial pressure of a gas is greater on one

side of the respiratory membrane than on the other side,
net diffusion occurs from the higher to the lower
pressure.

 Normally the partial pressure of oxygen (P02) is greater

in the alveoli than in the blood of the alveolar capillaries,
and the partial pres-sure of carbon dioxide (Pco2) is
greater in the blood than in the alveolar air.
Partial Pressure Difference

The partial pressure difference for oxygen and carbon

dioxide can be increased by increasing the alveolar
ventilation rate. The greater volume of atmospheric air
exchanged with the residual volume raises alveolar Po2,
lowers alveolar Pco2, and thus promotes gas exchange.

 Conversely, inadequate ven-tilation causes a lower-than-

normal partial pressure difference for oxygen and carbon
dioxide, resulting in inadequate gas exchange.
Events of Respiration

Pulmonary ventilation – moving air in and

out of the lungs
External respiration – gas exchange
between pulmonary blood and alveoli
Events of Respiration

Respiratory gas transport – transport of

oxygen and carbon dioxide via the
bloodstream
Internal respiration – gas exchange
between blood and tissue cells in systemic
capillaries
Mechanics of Breathing (Pulmonary
Ventilation)
Completely mechanical process
Depends on volume changes in the
thoracic cavity
Volume changes lead to pressure
changes, which lead to the flow of gases
to equalize pressure
Inspiration

Figure 13.7a
Expiration

Figure 13.7b
Pressure Differences in the Thoracic
Cavity
Normal pressure within the pleural space
is always negative (intrapleural pressure)
Differences in lung and pleural space
pressures keep lungs from collapsing
Boyle’s Law
Pressure Changes in Pulmonary Ventilation
Other Factors affecting Pulmonary
Ventilation:
Surface tension of alveolar fluid

Compliance of lungs

Airway resistance
Transport of Oxygen

2 FORMS of TRANSPORT
3.Small amount dissolves in plasma
4.Binds to hemoglobin
 O2 Concentration high
Alveolus (air sac)
Alveolus

Alveolar
Wall
Capillary
Wall
capillaries
Capillary
A CO2 Concentration high

Erythrocyte
Capillary bed
in tissue O2 Concentration high
Capillary

Capillary
Wall

Interstitial
O2 CO2 Fluid

B cells Body Cells

CO2 Concentration high
Diffusion across
ALVEOLOCAPILLARY MEMBRANE
Diffusion occurs:
• Large surface area and very thin
membrane
• partial pressure of O2 is greater in alveolar
gas than in capillary blood
↑P area → ↓ P area
Determinants of arterial oxygenation

Partial Pressure of O2
- pressure exerts by O2 dissolved in
plasma
- as PaO2 increases oxygen moves
from plasma to bind with hemoglobin
- continues to bind until hemoglobin
binding sites are saturated
Oxygen saturation
- percentage of available hemoglobin that
is bound to oxygen

Hemoglobin concentration
- amount of hemoglobin available for
binding
- as amount of hemoglobin decreases, O2
content also decreases
Oxyhemoglobin association and
dissociation
hemoglobin binds with O2 (lungs) –
OXYHEMOGLOBIN
 hemoglobin released O2 (tissues) –
HEMOGLOBIN DESATURATION
BOHR Effect – shift in the oxyhemoglobin
dissociation curve caused by changes in
CO2 and H ion concentrations in the blood.
↑CO2 → ↓O2 affinity
↓CO2→ ↑O2 affinity
4 steps transport of oxygen

 Ventilation of the lungs

 Diffusion of O2 from the alveoli into the
capillary blood
 Perfusion of systemic capillaries into the
cells
 Diffusion of CO2 form the cells into
systemic capillaries
Transport of carbon dioxide

3 forms of transport:
3.Dissolves in plasma
4.Bicarbonate
5.Carbamino compound
 carbonic
anhydrase
CO2 + H2O carbonic acid H+
(RBC)

(Hgb)

HCO3
(plasma)
↓ O2 in hgb = ↑ CO2 binds in hgb
↑O2 in hgb = ↓ CO2 binds in hgb

HALDANE EFFECTS
4 steps in transport of carbon dioxide

1. Diffusion of carbon dioxide from the cells

into the systemic capillaries
2. Perfusion of the pulmonary capillary bed
by venous blood
3. Diffusion of carbon dioxide into alveoli
4. Removal of carbon dioxide from lung by
ventilation
 LABORATORY AND
DIAGNOSTIC EXAMS

BY: FANER, NED DENEBE V. RN

Complete Blood Count
11/ 14/ 08 11/ 16/ 08 11/ 19/ 08
Hgb 143 119 ↓ 107 ↓
Hct 0.43 ↓ 0.36 ↓ 0.32 ↓
Rbc 6.12 5.20 4.65
Platelet 298 282 244
Wbc 35.20 ↑ 20.40 ↑ 24.00 ↑
Segmenters 0.83 0.93 0.93
Lymph 6.09 0.07 0.04

 ↓ Hct level and Hgb - ↓O2 in blood

 ↑RBC – compensate ↓O2 in blood
 ↑ WBC – cause by infection , inflammatory response
Chest X-ray

Patchy
Normal Chest X-ray Patient with ARDS infiltrates
Chest X-ray
11/ 14/ 08 11/ 14/ 08 11/ 16/ 08 11/ 19/ 08
Haziness on Confluent Clearing of There is
both lung densities previously progression
fields, appreaciated noted of alveolar
confluence of on both bilateral infiltrates.
densities perihilar and densities. Cardiomegaly
mostly on basal regions. Heart remains is present.
right lower Heart is enlarged.
and upper enlarged. Aorta is
lung fields, Cvp line is in atheromatous.
left middle place.
and part of
upper lung
fields
 Arterial Blood Gases
11/14 11/15 11/15 11/16 11/17 11/18 11/19 11/20 11/21

pH 7.16 ↓ 7.145 ↓ 7.27 ↓ 7.358 7.373 7.421 7.390 7.420 7.51

pCO2 38.1 39 36.7 26.4 ↓ 35.7 39.6 44.5 48.6 ↑ 42.5

pO2 74.0↓ 38.4↓ 56.8↓ 152.7 108.0 261.0 116.9 192.4 123.5

HCO3 13.7↓ 13.2↓ 16.5↓ 14.5↓ 20.4↓ 25.3 26.3 31.1↑ 33.8↑

O2 sat 90.8% 61.5%↓ 85.8%↓ 98.9% 97.9% 99.6% 98.2% 99.3% 98.8%

dFiO2 104.8 186.82 146 51 73.7 22.9 51 29.69 41.19

Arterial Blood Gas

11/14 Uncompensated Metabolic Acidosis

11/15 Uncompensated Metabolic Acidosis
11/15 Uncompensated Metabolic Acidosis
11/16 Compensated Respiratory Alkalosis
Compensated Metabolic Acidosis
11/17 Compensated Metabolic Acidosis
11/18 -
11/19 -
11/20 Compensated Respiratory Acidosis
Compensated Metabolic Alkalosis
11/21 Compensated Metabolic Alkalosis
METABOLIC ACIDOSIS RESPIRATORY ALKALOSIS

 SIGNS AND SYMPTOMS SIGN AND SYMPTOMS

 Headache Dizziness
 Lethargy Confusion
Tingling sensation
 Coma Convulsions
 Kussmaul’s breathing
 Nausea and vomiting
 Diarrhea
 Abdominal discomfort
Oxygen toxicity
Pure oxygen is being breathe in and no
nitrogen gas is present – maintainance of
alveolar expansion is loss leading to alveolar
collapse.
Oxygen has toxic effects on Type II
pneumocytes cells that produce surfactant.
Inadequate production of surfactant leads to
alveolar collapse and further fluid shifts from
capillaries to alveolar sacs, aggravating the
patient condition.
Arterial Blood Gas
↓O2 → hyperventilation → ↓CO2 =
RESPIRATORY ALKALOSIS

↓BP and ↓O2 → lactic acid production

→ bicarbonate binds to acids → ↑ loss
of bicarbonate =
METABOLIC ACIDOSIS
 ACUTE
RESPIRATORY
DISTRESS
SYNDROME
 Clinical lung injury Sepsis
antibiotics

Endothelial damage

Alveolar damage
Platelet
aggregation
Damage to type Attract / activate
II pneumocytes neutrophils

Release of
↓ surfactant
mediators Digoxin,
production
amiodarone
atelectasi Tachypne Inc Inc vascular
s Inc alveolar permeability
a permeability
DOB permeability
Impaired lung
compliance
retractio Compensator
ns y
Diffuse Fluid and protein ↓ SVR mechanisms
alveolar move into the Tachycardia
Regeneration of the infiltrates, alveoli diuretics AF
alveolar membrane with crackles, cough ↓ blood volume
thick epithelial cells Pulmonary edema

↓ BP ↓ venous Unmet
Severe
return myocardial
dyspnea,
Eventual scarring and Hypoxemia V/Q mismatch demands
loss of functional lung R-L shunting ↓ CO
tissue
unresponsive pressor
to O2
s
↓ tissue perfusion

Cellular ischemia
hypoxia

MV w/ Metabolic Severe organ dysfunction

PEEP acidosis

ACUTE RESPIRATORY FAILURE ↓ renal perfusion Myocardial ↓ cerebral tissue

depression perfusion

↓ UO
death Inc
creatinine
↓
LOC
Nursing Problems

A. Ineffective Breathing Pattern

1. Dyspnea
2. Crackles
3. Cough
Nursing Problems

B. Impaired Gas Exchange

1. Hypoxemia
2. Dizziness
Nursing Problems

c. Decreased Tissue Perfusion

1. Decreased urinary output
2. Hypotension
 Roger G. Spragg, M.D., James F. Lewis, M.D., Hans-Dieter Walmrath, M.D.,
Jay Johannigman, M.D., Geoff Bellingan, M.D., Pierre-Francois Laterre, M.D.,
Michael C. Witte, M.D., Guy A. Richards, M.D., Gerd Rippin, Ph.D.,
Frank Rathgeb, M.D., Dietrich Häfner, M.D., Friedemann J.H. Taut, M.D.,
and Werner Seeger, M.D.

N Engl J Med 2004;351:884-92.

Copyright © 2004 Massachusetts Medical Society.
Optimal Ventilator Settings in
Acute Lung Injury and Acute
Respiratory Distress
Syndrome
M. Yilmaz, O. Gajic
Mayo Clinic College of Medicine, Division of Pulmonary and
Critical Care Medicine, Rochester MN, USA
Akdeniz University, Medical Faculty, Development of
Anesthesiology and Intensive Care, Antalya, Turkey
November 16, 2007
Overdistention injury induced by
High Vt ventilation has been
identified as the single most
important determinant of VILI

Ventilation at low lung volumes in

the absence of PEEP may lead to
lung injury caused by repetitive
collapse and reopening of the
alveolar units

Better understanding of the

pathophysiology of ALI/ARDS and
the role of VILI prompted the use
of smaller Vt with lower
inspiratory pressures and a
moderate amount of PEEP to
prevent respiratory
 Strategy: Low Vt mechanical ventilation in
patients with ARDS

1990 RTC: Conventional vs Lung protective

approach

Villar, et al

Result: The incidece of barotrauma, mortality has

decreased significantly in the lung protective group

The threshold of Vt of <7.7 ml Kg PBW and Ppl < 30

mmHg to be associated with improved outocmes.
USE OF PEEP

help achieve adequate oxygenation and decrease the

requirement for high fractions of inspired oxygen.

Three mechanisms have been proposed to explain the

improvement in gas exchange with PEEP:

(1) Alveolar recruitment with increased functional residual

capacity
(2) Redistribution of extravascular lung water
(3) Improved ventilation-perfusion matching.
Computed tomography studies demonstrated PEEP induced
recruitment of previously collapsed alveoli and that lung
regions recruited with PEEP may not completely collapse at
end-expiration . This in turn leads to more even distribution
of airway pressures within the lung parenchyma.
USE OF PEEP

In conclusion, in patients with ALI/ARDS lung

protective
ventilation strategies yield better clinical
outcomes compared to traditional approaches in
which more generous tidal volumes are used.
Limiting Vt to ^6-8 mLkg ' PBW, with further
reductions of Vt if the Ppl is high (>30cmH2O)
has been shown to improve outcomes and
should be considered as a standard of care for
the majority of patients with ALI/
ARDS.
 Recent Developments in the
Management of Acute
Respiratory Distress Syndrome
in Adults

Heather R. Bream-Rouwenhorst, Elizabeth A. Beltz, Mary B. Ross, and

Kevin G. Moores
Corticosteroids
*ameliorate the cytokine- and toxic-mediator
release associated with ARDS
*benefit would be greatest in the initial exudative
phase of ARDS when neutrophils begin to invade
the pulmonary epithelium
* have not demonstrated clear benefit in patients
with ARDS. Some trials have found increased
complications and mortality related to
corticosteroid use

High-dosage, short-course
regimens.
*Two meta-analyses (1990s)=no benefit with high-dosage, short-course
administration of corticosteroids in patients who had various stages of
ARDS
*Therefore, the current standard of practice is to avoid these regimens.
oderate-dosage, tapering regimens.
Research: Methylprednisolone versus placebo at
day 7 of ARDS
*Intravenous methylprednisolone was dosed as 2
mg/kg once, 2 mg/kg/day on days1–14, 1
mg/kg/day on days 15–21, 0.5 mg/kg/day on days
22–28, 0.25 mg/kg/day on days 29 and 30, and
0.125 mg/kg/day on days 31 and 32.

Result: at day 10, 7 patients receiving

methylprednisolone were extubated,compared
with 0 patients in the placebo group. Inhospital
mortalityrates were 12% in patients treated with
methylprednisolone and 62% in those receiving
te administration of corticosteroids.
*mortality rates were higher with methylprednisolone at day 60 (35% versus
8%, p =0.02) and at day 180 (44% versus 12%, p = 0.01)
*Mortality was not significantly higher in the group receiving
methylprednisolone whose ARDS was present for 7–13 days at the time of
study enrollment.
*Hence, initiating corticosteroids more than two weeks after the onset of ARDS
may actually increase mortality

*Patients who survived 14 days of ARDS may have had less active
fibroproliferation and hence a lesser response to corticosteroids.

SUMMARY
Corticosteroids should be started early in the course of ARDS (before
day14), at moderate dosages (i.v. methylprednisolone <2 mg/kg/day), and
tapered over three to four weeks. Initiation of corticosteroid therapy on day
14 or later in patients with ARDS should be discouraged due to the
increased mortality rates found
Pharmacological Therapy
for Acute Respiratory
Distress Syndrome

Raksha Jain, MD and Anthony DalNogare, MD

Mayo Clinic Proc
February 2006
Vasodilators
2.Inhaled Nitric Oxide
relaxes pulmonary vascular smooth muscle and thus has important
regulatory effects on regional lung ventilation and perfusion ratios

Although endogenous nitric oxide, produced from nitric oxide synthase,

impairs gas exchange during ARDS, exogenous inhaled nitric oxide relaxes
vascular smooth muscle that supplies ventilated alveoli and thus may improve
ventilation-to-perfusion relationships.

In 1993, Rossaint et al: inhaled nitric oxide reduced pulmonary artery pressures
and increased arterial oxygenation without producing systemic vasodilation.

Other studies showed: adverse effects of methohemoglobinemia, production of

toxic compounds such as nitrogen dioxide and peroxynitrate ion, increased
pulmonary edema, and rebound pulmonary hypertension. Other studies showed
increased mortality with infants treated with NO. Other studies showed no oerall
survival benefit
Fig. 1. A. Schematic of vasoconstriction of pulmonary bed with normal and
atelectatic alveoli. B. Nitroprusside (NTP) causes non-selective vasodilation of all
pulmonary arteries, which may worsen ventilation-perfusion (V/Q) matching. C.
Inhaled nitric oxide (NO) dilates only ventilated alveoli, an outcome that improves
V/Q matching. (From Lunn R: Subspecialty clinics: Anesthesiology; Inhaled nitric
oxide therapy. (Mayo Clin Proc 1995; 70:247-255; with permission.)
Decreased Alveolar Surface
Tension
2.Surfactant
Lowers surface tension and
prevents alveolar collase

1 study showed: a decrease in Fio2

requirement

RTC on 448 adult ARDS patients who

received recombinant protein C-
based surfactant showed improved
gas exchange and oxygenation, but
no difference occurred in the number
of ventilator-free days or 28-day
mortality
References:
Books
•McCance. Pathohysiology: The Biologic Basis for Disease in Adults
& Children, 5th ed., 2006. Mosby
•Fauci et. Al.. Harrison’s Principles of Internal Medicine, 17th ed.,
2008. McGraw Hill.
•Bullock. Pathophysiology: Adaptations & Alterations in Function, 4th
ed., 1996. Lippincott.
•Apostalakos & Papadalos. The Intensive Care Manual, 2001.
McGraw Hill
•Rumrakhd & Moore. Oxford Handbook of Acute Medicine, 2nd ed.
2004. Oxford University Press.
6. Murray & Nadel's Textbook of Respiratory Medicine, 4th ed., 2005
Saunders, An Imprint of Elsevier
7. Mayo Clinic Internal Medicine: Concise Textbook, edited by
Thomas M. Habermann, Amit K. Ghosh., 2008©
For Bibliography:
1. “Recent developments in the management of acute respiratory distress
syndrome in adults”, by Heather R. Bream-Rouwenhorst et. al, American
Journal of Health System Pharmacy Vol. 65 Jan 1, 2008

2. “Optimal ventilator setting in acute lung injury and acute respiratory

distress syndrome”, by M. Ylmaz and O. Gajic, European Journal of
Anesthesiology 2008: 25: 89-96, 2007 ©

3. “Prone position in Acute Respiratory Distress Syndrome”, P. Pelosi, L.

Brazzi and L. Gattinoni, European Respiratory Journal, 2002: 20: 1017 –
1028, 2002 ©

4. “Effect of Recombinant surfactant protein c-Based Surfactant on the Acute

Respiratory Distress Syndrome”, Roger G. Spragg et. al The New England
Journal of Medicine, 2004: 351:884- 92, 2004 ©

5. “Surfactant alteration and replacement in acute respiratory distress

syndrome”, Andreas Gunther et. al., Respiratory Research Vol.2 No.6, Oct
2001