Acute Respiratory

Distress Syndrome
Jason D. Sciarretta, M.D.
Critical Care Conference
October 13, 2010
 History ARDS
 The syndrome of acute pulmonary failure was recognized
during World War I

 “The acute onset of severe respiratory distress and cyanosis

that was refractory to oxygen therapy and associated with
diffuse CXR abnormality and decreased lung compliance”

– Ashbaugh DG. Acute Respiratory distress in Adults. Lancet

1967
 History ARDS
 In 1988, Murray:
– 4 point scoring system: Lung Injury Score (LIS)
 PEEP, compliance, CXR, PaO2/FiO2 ratio
 North American-European Consensus Committee
– devised of multiple subcommitees:
– 1994: “Adult” RDS now referred back to “acute”
– Study the pathophysiologic mechanisms, prevention &
treatment
– further defined diagnostic criteria, future studies
– 1998: severity ARDS should be assessed by the
Lung Injury Score or by APACHE

Bernard GR et al., Am J Respir Crit Care Med. 1994 Murray JF, et al. Am Rev Respir Dis. 1988;138:720
Artigas A, et al., Am J Respir Crit Care Med 1998
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 Epidemiology
 1972 - Incidence US: ~ 150,000 cases/yr
 “true” incidence defined by LIS lower—1.5 to 8 cases per
100,000 people

 ARDS Network Study (NAECC definitions), 2003

– Incidence United States: 32 cases per 100,000/y
Goss CH et al., ARDS Network, Crit Care Med 2003

 10 % ICU admission in US related ARDS

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ALI v.s. ARDS
 Chest radiographic score Lung Injury Score
0 No alveolar consolidation
1 Alveolar consolidation in one quadrant
2 Alveolar consolidation in two quadrants
3 three quadrants 4 four quadrants
Hypoxemia score 0 PaO2/FiO2 ≥300
1 PaO2/FiO2 225–299 2 PaO2/FiO2 175–224
3 PaO2/FiO2 100–174 4 PaO2/FiO2 <100
Respiratory system compliance score (mL/cm H2O)
0 ≥80 1 60–79 2 40–59 3 20–39 4 ≤19
PEEP score (cm H2O)
0 ≤5 1 6–8 2 9–11 3 12–14 4 ≥15
Final value
0 No lung injury 1–2.5 Acute lung injury (ALI)
2- >2.5 Severe lung injury (ARDS)

Murray JF, et al. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis.
1988;138:720
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 ARDS Risk
DIRECT INDIRECT
- Common: Common:
 Pneumonia  Sepsis (40%)

 Aspiration  Severe trauma

– Less common  Shock

 Pulmonary contusion
- Less Common:
 Multiple transfusions
 Fat emboli
 Cardiopulmonary bypass
 Near-drowning
 Drug overdose
 Inhalational injury
 Burns
 Reperfusion after lung
 Acute pancreatitis
transplant or pulmonary
embolectomy  Multiple transfusions

The American-European Consensus Conference on ARDS. Am J Respir Crit Care Med.

1994;149:818.
Atabai K, Matthay MA. Thorax. 2000.
Estenssoro E et al Crit Care Med 2002
Frutos-Vivar F, et al. Curr Opin Crit Care. 2004. 8
 Shock Associated Conditions
– Hemorrhagic, Cardiogenic, Septic, Anaphylactic
 Trauma
– Burns, Nonthoracic trauma (especially head trauma), Fat emboli, Lung
contusion, Near-drowning
 Infection
– Viral/bacterial/fungal pneumonia, Gram- negative sepsis, TB
 Inhalation of toxic Gas
– Oxygen, smoke, Cadmium, Phosgene NO2, NH3, Cl2
 Drug ingestion
– Cocaine, Heroin, Methadone, Barbiturates, Ethchlorvynol, Thiazides,
Fluorescein, Propoxyphene, Salicylates, Chlordiazepoxide,Colchicine,
Dextran 40
 Aspiration of Gastric contents and Metabolic
 Miscellaneous
– Pancreatitis, Postcardiopulmonary bypass, Postcardioversion, Multiple
transfusions, DIC, Leukoagglutinin reaction, Eclampsia, Air or amniotic fluid
emboli, Bowel infarction, Carcinomatosis
The American-European Consensus Conference on ARDS. 1994 9
 Pathophysiology
 Neutrophils release inflammatory mediators -->degrading
integrity of capillary endothelial cells--->capillary
permeability, interstitial edema.

 Influx of proteinaceous plasma fluid, erythrocytes, and

inflammatory cells into the interstitium
– destroyed surfactant and type 1 and 2 pneumocyte
 Increases alveolar surface tension, thus producing alveolar collapse

Asensio J, Trunkey D: Current Therapy Trauma & Surgical Critical Care

Civetta: Critical Care,4th edition Chapter 136: Acute Lung Injury & Acute Respiratory Distress Syndrome

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 Stages of ARDS
 1. Exudative (acute): 0-4 d
 2. Proliferative:4-8 d
 3. Fibrotic:>8 d
 4. Recovery

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 Histologic finding

 Exudative phase
 Histologic findings
 earlyproliferative  late proliferative stage:
stage: type 2 extensive fibroblast
pneumocytic proliferation:
proliferation, incorporation of the
widening septa & hyaline membranes
interstitial fibroblast
proliferation.
 Plasma Biologic Markers
Predictive of a Poor Outcome

Acute inflammation IL-6, IL-8

Endothelial injury vWF antigen
Epithelial type II cellSurfactant protein-D
Adhesion molecule Intercellular adhesion molecule
(ICAM-1)
Neutrophil-endothelial Soluble TNF receptors I & II
interation (sTNFRI/II)

Procoagulant activity Protein C

Fibrinolytic activity Plasminogen activator inhibitor-1
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Ware LB, Crit Care Med. 2005
 Clinical Progression
 Phase 1: Acute Injury
• Normal physical examination and chest radiograph
• Tachycardia, tachypnea, and respiratory alkalosis develop
 Phase 2: Latent Period
• Lasts ~ 6–48 h after injury: remains clinical stable
• Hyperventilation & hypocapnia persist; mild increase work breathing
• Minor abnormalities on physical examination and chest radiograph
 Phase 3: Acute Respiratory Failure
• Decreased lung compliance: marked tachypnea & dyspnea
• Diffuse infiltrates on chest radiograph
• High-pitched crackles heard throughout all lung fields
 Phase 4: Severe Abnormalities
• Severe hypoxemia unresponsive to therapy
• Metabolic and respiratory acidosis
• lethargy, obtunded

Gomez AC: Pulmonary insufficiency in non-thoracic trauma [discussion]. J Trauma. 1968;8:666

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Radiography
 Radiography
 CT scan findings: 74 patient review
– Bilateral abnormalities in almost all the patients,
predominantly dependent abnormalities (86%)
– Patchy abnormalities (42%)
– Homogeneous abnormalities (23%)
– Ground-glass attenuation (8%)
– Mixed ground-glass appearance and
consolidation (27%)
– Basilar predominant abnormalities (68%)
– Areas of consolidation with air bronchograms
(89%)

– Tagliabue M, Casella TC, Zincone GE, Fumagalli R, Salvini E. CT and chest radiography in the evaluation
of adult respiratory distress syndrome. Acta Radiol. May 1994;35(3):230-4
 Clinical Risk Factors Predictive of Poor Outcomes
 Independent predictors repeatedly: higher mortality rates
– Severity of the illness
– Non-pulmonary organ dysfunction
– Comorbid diseases, Sepsis, Liver dysfunction/cirrhosis
– Advanced age
 Other independent risk factors:
– Organ transplantation
– HIV infection and Immunosuppression
– Active malignancy
– Mechanisms of lung injury
– Barotrauma
– Fio2 (High)

– Atabai K, Matthay MA. Thorax. 2000. Ware LB. Crit Care Med. 2005. Ferguson ND, et al. Crit Care Med. 2005.

18
 Management
 In 1990, Hickling et al.: improved mortality w/ lower than
“traditional” Vt
 ARMA (Acute Respiratory Distress Syndrome Network Low
Tidal Volume) trial:
– limited Vt & plateau pressures compared to higher values
 result: reduction in mortality from 40% to 31%
 Considered Standard: Vt = 6–8 mL/kg ideal body wt & plateau pressure <30 cm H2O
– Strategy associated with:
 PaO2/FiO2 lower
 High RR prevented hypercapnia
 less organ failures
 reduction in IL-6 and IL-8 levels
 ~ 10% mortality reduction
Hickling KG, et al., Intensive Care Med. 1990;16(6):372–377.
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ARDS Network. N Engl J Med. 2000. Hough CL, et al., Critical Care Med 2005.
 Non-Ventilatory Base Strategies
 Inhaled Nitric Oxide
– selectively vasodilates pulmonary capillaries
– anti-inflammatory properties
 Prone Positioning
 Steroids: ? controversial
 Further Investigations:
– Liquid Ventilation
– Surfactant

Davis JW. et al, J Trauma. 2007 May;62(5):1201-6.

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 Mortality
 ARDS mortality rates - 31% to 74% --> 30-58% 1990s
– Variability: difference populations studied & definitions used.
– age & etiology of lung injury
 Main causes of death: nonrespiratory (i.e., die w/, rather than
of ARDS).
 Respiratory failure cause of death: 9% to 16% of patients with
ARDS.
 Early deaths (within 72 hours): underlying illness or injury;
late deaths sepsis or multi-organ dysfunction.

Frutos-Vivar F, et al. Curr Opin Crit Care. 2004.

Vincent JL, et al. Crit Care Med. 2003. Ware LB. Crit Care Med. 2005.
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 One-year Outcomes in Survivors of ARDS

Persistent functional limitation

• Extrapulmonary diseases (primarily):
Muscle wasting and weakness
(corticosteroid-induced & critical-illness-associated myopathy),

• Intrinsic pulmonary morbidity (5%):

Bronchiolitis obliterans organizing pneumonia

Herridge MS, et al. N Engl J Med. 2003.

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 Long term outcomes
 Outcomes variable
 Lung mechanics may return to normal 1 year
– gas exchange abnormalities may persist
 Spirometry normal at 6 months
 Mild to moderate: Quality of Life
 78% patients return to work

McHugh LG, et al. Recovery of function in survivors of the acute respiratory distress syndrome. Am J Respir Crit Care Med.
1994;150:90.
Herridge MS, Cheung AM, Tansey CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J
Med. 2003;348:683
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