This document defines acute respiratory distress syndrome (ARDS) and outlines its diagnostic criteria, etiologies, pathophysiology, stages of progression, clinical manifestations, management including mechanical ventilation strategies, complications, prognosis, and bibliography of references. ARDS is characterized by hypoxemic respiratory failure due to diffuse pulmonary edema from acute lung injury. The management focuses on supportive care including mechanical ventilation with low tidal volumes and PEEP to prevent further lung injury while the underlying condition is treated. The mortality rate for ARDS remains high but has decreased to around 40% with standardized treatment protocols.

1. Acute Respiratory Distress Syndrome (ARDS)
Glen E. Hastings, M.D.
July 2, 2002
Definition:
Acute hypoxemic respiratory failure with refractory hypoxemia due to diffuse non-cardiac
pulmonary edema resulting from acute damage to the alveoli caused by diverse etiologies.
Diagnostic Criteria1: An acute process featuring:
• Bilateral patchy infiltrates on the chest x-ray
• Hypoxemia (paO2/FiO2< 200)
• No evidence of CHF (PAWP<18 mm Hg)
• Occurring when a predisposing event or condition is present or has occurred.
Etiologies:
2
Partial list of predisposing conditions associated with ARDS
Infections (40-50%) Inhaled toxins
Gram-negative sepsis O2 (high concentrations)
Viral pneumonia Smoke
Bacterial pneumonia Corrosive chemicals (NO2,
Trauma (22-32%) Cl2, NH3, phosgene, cadmium)
Fat emboli Hematologic disorders
Lung contusion Intravascular coagulation
Non-thoracic trauma Massive blood transfusion
(including head injury) Metabolic disorders
Liquid aspiration (22-36%) Pancreatitis
Gastric juice Uremia
Fresh and salt water Paraquat® ingestion
(drowning) Miscellaneous
Hydrocarbon fluids Shock of any etiology
Drug overdose (5-8%) Increased intracranial pressure
Heroin (including seizures)
Methadone Eclampsia
Propoxyphene Post-cardioversion
Barbiturates Radiation pneumonitis
Colchicine Post-cardiopulmonary bypass
Pathophysiology3:
Pulmonary hydrostatic pressure is not elevated in ARDS, as it is in congestive heart failure.
Instead there is increased permeability of the alveolar capillary membranes, which permit fluid
and proteins to seep into the interstitium and into the alveolar spaces. The alveoli then collapse
because the alveolar closing pressures exceed the opening pressures. Cytokines are activated
which attract WBCs. WBCs secrete peroxidases that damage Type II pneumocytes decreasing
surfactant production. Surfactant loss further aggravates alveolar collapse. Arteriovenous
shunting past fluid filled alveoli causes perfusion-ventilation mismatch resulting in severe oxygen
desaturation. The compliance of “wet lungs” is reduced. Respiratory muscles fatigue more
easily, lowering tidal volume and further impairing gas exchange.
Increased vascular permeability may be caused by direct chemical injury from inhaled toxic
gasses, trauma, infections or aspirated gastric acid. Infections, trauma & aspirated gastric
contents account for 80% of ARDS cases. In septicemia or endotoxemia, polys and monocytic
phagocytes aggregate in the lung capillaries, adhere to the endothelial surfaces, release
peroxidases, leukotrienes, thromboxanes and prostaglandins which cause tissue destruction,
damage to Type II pneumocytes, and alveolar capillary membrane leakage.
Stages of Progression4
Exudative Phase: The early changes consist of alveolar-capillary leak resulting in pulmonary
edema, atelectasis, and influx of inflammatory cells and their toxic products.
Proliferative Phase: Myofibroblasts proliferate and collagen deposition begins in the interstitium.
Pneumothorax is more likely after collagen remodeling of the lung occurs12.
Fibrotic Phase: Fibrosis occurs. Pulmonary edema and inflammatory infiltration may be
minimal.

2. ARDS- Page 2
Exudative Phase: Clinical Manifestations:
Early: Tachypnea followed by dyspnea; decreased pO2 & pCO2 because of ventilation-perfusion
mismatch and impairment of diffusion. X-ray and chest exam may be normal. Oxygen
by mask elevates the arterial pO2.
Later: Cyanosis, dyspnea, tachypnea, rales, tubular breath sounds, and diffuse alveolar x-ray
infiltrates. O2 by mask may no longer be sufficient because of A/V shunting past
collapsed alveoli. Mechanical ventilation with PEEP may be required. Rising CO2 with
deteriorating pO2 and deteriorating tidal volumes indicates a poor prognosis.
Management:
A. There is no specific treatment. Mechanical ventilation buys time for the lung to heal itself.
Supportive measures include:
• Maintenance of oxygenation (usually with mechanical ventilation with PEEP)
• Avoidance of barotrauma caused by excessive volume or plateau pressures
• Identification and treatment of the underlying cause
• Monitoring and maintaining hemodynamic stability and pO2 of the tissues.
• Prevention of nosocomial infections
• Maintenance of nutritional status & skin integrity.
• Maintain blood glucose between 70 & 100 mg/dL14.
B. Maintenance of Oxygenation:
• Goal: Maintenance of the pO2 at ≥60 mm Hg and ≥90% oxygen saturation
• Before intubation (Traditional Method):
- Start with 5-10 L/minute of 100% O2 by non-rebreather mask.
- Monitor arterial pO2
- Intubate if pO2 deteriorates despite maximum (+10 L/min) of 100% O2
- Bi-PAP may be used to bridge to ventilator management.
• After intubation (Low Volume, Low Plateau Pressure Method):
- The ventilator is set in the volume-assist-control mode.
- Start with tidal volume setting of 10cc/Kg of (calculated) lean body
weight, (Larger tidal volumes may produce alveolar over-distention and
injury), and lower respiratory rate (12-15/minute).
12,13
Calculations of Lean Body Weight
Men: 50 + 0.91(centimeters of height – 152.4)
Women: 45.5 + 0.91(centimeters of height – 152.4)
- Reduce tidal volume by 1cc/Kg/hour to about 6cc/Kg, as necessary to
maintain plateau pressure ≤ 30cmH2O & peak pressures ≤40.
- Increase the ventilatory rate up to 35/minute if required to keep the
arterial pH at 7.3 – 7.45.
- Set FiO2: initially at 100% and decrease as soon as possible to “safe
levels” below 60%.
- Initial PEEP might reasonably be 5 cmH2O and increased as necessary
to 24-25 cmH2O. PEEP values up to 32mmHg are permitted12,13.
- Plateau pressures may exceed 30 cmH2O if the pH is less than 7.15 or
tidal volume<4cc/Kg,
• The goals are to maintain pO2 at 55-80 cmH2O (O2 saturation at 88-95%), pH at 7.3-
7.45 and plateau pressures not to exceed 35 cmH2O12. Plateau pressure is
measured 0.5 second after the end of inspiration. It reflects the pressure
experienced at the alveolar level. Peak pressure, by contrast may be distorted by
mucous or other obstructions in the airway. They should not exceed 40cmH2O.
- Bicarbonate infusions are allowed to prevent acidosis.
- Consider sedation if patient fights the ventilator & activates pop off valve.
- Decrease FiO2 to lowest level that will keep the PaO2 ≥55 mm Hg.

3. ARDS- Page 3
Indication for PEEP6
• If the FiO2 can't be decreased to 60% or lower, add PEEP in 3 to 5 cmH2O
increments up to a maximum of about 32 cmH2O.
Determinants of optimal PEEP6
• Maximum PEEP is 32cmH2O12,13. Above this level, alveolar distention may increase
vascular resistance, increase shunting and thereby decrease PaO2. As a general
rule, set PEEP at level where the product of Cardiac Output x PaO2 is greatest.
• PaO2 response
• Degree of decrease of cardiac output related to PEEP.
Use of the Swan-Ganz catheter:
• The only reliable way to follow hemodynamic changes is with a Swan-Ganz catheter.
• Wedge pressures and intracardiac pressures must be corrected for PEEP. Measure
vascular pressures just before inflation. Subtract half the value of PEEP; the
remainder is equal to the wedge pressure.
• Keep the wedge pressure as low as possible while maintaining the cardiac output,
BP, and urine output.
• Mixed venous blood is the best indicator of the adequacy of O2 delivery (Arterial pO2
may be falsely elevated in sepsis because of systemic shunts)
Rationale for Using the Low Volume, Low Plateau Pressure Method7,12,13:
• Traditionally recommended tidal volumes of 10-15cc/Kg are substantially above the
6-7cc/Kg tidal volumes of normal people. Such high volumes produce lung damage
in rats & may well do so in humans. Using lower volumes necessitates higher
ventilatory rates in order to prevent acidosis and hypercapnia.
Anticipated Outcomes Using Low Tidal Volumes to Maintain Low Plateau Pressures:
• A recently published multi-center trial found an overall mortality of 31% among
patients managed with lower tidal volume ventilation, and lower average plateau
pressures (e.g. up to 35cmH2O) compared to a mortality rate of 39.8% among those
managed with traditional tidal volumes12.
D. Unconventional Therapies3:
• Positioning of the Patient as a Therapeutic Maneuver:
- Atelectasis produced by the weight of gravity is an important cause of vascular
shunting in ARDS so the strategy of positioning the patient so the less involved
lung is on the bottom in order to diminish arteriovenous shunting has been
reported. The technique is to alternate patients from supine to prone position.
The strategy works best when used early with severely hypoxemic patients.6
• Inverse-ratio ventilation and high frequency ventilation using breathing frequencies
up to 300/minute have shown no benefit over conventional therapies.
• Extra corporeal membrane oxygenation in which a catheter is inserted in the vena
cava and back into the aorta after oxygenation has shown no survival advantage.
• Exogenous surfactant improves survival in the neonatal respiratory distress
syndrome, but not in ARDS.
• Inhaled nitric oxide (NO) improves initial gas exchange but doesn’t affect mortality8.
• Monoclonal antibodies directed against the lipid A component of bacterial endotoxin,
TNF-α, and IL-1 have not been shown to improve survival in ARDS.
• Cyclooxygenase inhibitors and leukotriene inhibitors have improved survival in
animal models and in being investigated.
• Steroids do not improve survival or oxygenation7 in ARDS unless 2o to fat
embolism.4,7.
Complications:
• Left ventricular failure
• Pneumonia
• Disseminated Intravascular Coagulation (DIC Syndrome)
• Bronchial obstruction

4. ARDS- Page 4
• Pneumothorax or tension pneumothorax
• Pneumomediastinum
Prognosis:
Depends on etiology, ARDS caused by drug overdose has low mortality. Overall 18% of ARDS
patients die of respiratory failure. The first 3 days’ mortality is usually secondary to the underlying
condition. Seventy-three percent of deaths over the first 3 days occur because of sepsis or
multiorgan failure.9 Mortality approaches 100% with multiorgan failure. Overall mortality was
+50% for many years and has decreased to around 40% in most recent series. Of those who
survive, about 50% recover completely, 25% have mild lung impairment, 20% are moderately
impaired, and 5% are severely impaired.4
Bibliography:
1. Bernard, GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS.
Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Resp Crit Care Med
1994;149:818-824.
2. Flick MR: Pulmonary edema and acute lung injury, Chapter 56 in Murry JF &
Nadel JA (eds) Textbook of Respiratory Medicine, ed 2. Philadelphia, W B Saunders Co, 1994, p 1740.
3. Fulkerson WJ, MacIntyre N, Stamler J, Crapo JD: Pathogenesis and treatment of the
adult respiratory distress syndrome Arch Int Med 1996;156:29-38
4. Weidemann HP, Tai YT: Adult respiratory distress syndrome (ARDS): Current
management, future directions. Cleve Clin J Med 1997;64(7):365-372.
5. Schuster DP, Kollef MH: Acute Respiratory Distress Syndrome. Disease-a-Month 1996;42(5):265-328.
6. Blanch L, Mancebo J. Perez,M, Martinez M, et al: Short term effects of prone position in
critically ill patients with acute respiratory distress syndrome. Intensive Care Med 1997;23(10)1033-
1039.
7. Kollef MH, Schuster DP: The acute respiratory distress syndrome N Eng J Med 1995;
332(1):27-37.
8. Troncy E, Collet J-P, Shapiro S, Guimond J-G, Blair L, Charbonneau M, Blaise G:
Should we treat acute respiratory distress syndrome with inhaled nitric oxide? Lancet
1997;350:111-112.
9. Montgomery AB, Stager MA, Carrico CJ, Hudson LD: Causes of mortality in patients with acute respiratory
distress syndrome. Am Rev Resp Dis 1985;132:485-9.
10. Stewart TE, Meade MO, Cook DJ, Granton JT, et al: Evaluation of a ventilation strategy to prevent barotrauma
in patients at high risk for acute respiratory distress syndrome. N Engl J Med 1998;338:355-61
11. Amato MBP, Barbas CSV, Medeiros DM Magaldi RB, et al.: Effect of a protective-ventilation strategy on
mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:347-54.
12. The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with
traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med.
2000;342:1301-8.
13. Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334-49.
14. van den Berghe G, Wouters P, Weekers F, Verwaest C, et al. Intensive insulin therapy in the critically ill
patients. N Engl J Med. 2001;345(19):1359-67.