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ARDS – Definition and Pathophysiology

Created: 9/3/2007
Updated: 14/5/2007

Resource Respiratory

ARDS – Definition and Pathophysiology

Dr John Griffiths DICM MRCP FRCA MA
CriticalCareUK Editor

Focus on definition and associations of ALI and ARDS

Acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) develop in response to lung injury. A wide variety of precipitating causes are recognised (Tables 1a and 1b). Severe sepsis is the leading cause, followed by pneumonia, aspiration of gastric contents, massive blood transfusion, multiple trauma and pregnancy-related ARDS. ALI and ARDS develop very soon after the precipitating event, usually within 12-72 hours and often within 6 hours. In 1994, The American-European Consensus Conference Committee proposed definitions for ALI and ARDS (Table 2). It can be seen that ALI is a continuum of injury. When the oxygenation abnormality is more severe, the condition is termed ARDS. There are estimated to be about 3/100,000 cases of ARDS each year. Recent improvements in critical care have seen a reduction in the mortality of ARDS but it still remains at about 50% for the general population and 25% if it is pregnancy related. Fewer than 20% of deaths are due to refractory respiratory failure. This emphasises the importance of identifying and treating the precipitating cause.

Table 1a. Causes of ARDS

Septic shock

Gastric aspiration


Amniotic fluid embolus

Shock of any aetiology

Major trauma

Massive blood transfusion

Severe acute pancreatitis

Drug overdose


Raised ICP

High inspired oxygen concentration

Pulmonary contusion

Near drowning

Cardiopulmonary bypass

Inhalation toxic fumes

Massive burns

Table 1b. Causes of ARDS classified into ‘direct’ and ‘indirect’ lung injury





Aspiration of gastric contents


Severe trauma with shock and multiple blood transfusions



Pulmonary contusion

Fat emboli


Inhalational injury

Reperfusion pulmonary oedema

Drug overdose

Acute pancreatitis

Blood transfusion

Pregnancy-related ARDS

Adapted from Ware LB et al.

Table 2. American-European Consensus definitions of ALI
and ARDS


Acute onset

Bilateral infiltrates on chest radiographs

PAOP <18 mmHg if measured or absence of clinical signs of left atrial hypertension

ARDS = PaO2 / FiO2 <200 mmHg

ALI = PaO2/ FiO2 <300 mmHg

Adapted from Bernard GR, Artigas A, Brigham KL et al.

Focus on pathophysiology of ARDS

ALI and ARDS develop when inflammatory cytokines or exogenous agents injure both the epithelium and endothelium of the lung. These inflammatory insults can occur locally in the lung (“primary” ARDS) or be part of a systemic inflammatory syndrome (“secondary” ARDS). Irrespective of the precipitating cause, the pathophysiological mechanisms driving the process are identical and progress through recognised phases (Table 3). ARDS classically affects the lung in a non-homogenous manner. Supine CT scans of ARDS lung taken during the initial phases show striking asymmetry of lung involvement. Dependent posterior regions are preferentially infiltrated, consolidated or collapsed. Anterior areas are often normally or even excessively aerated during mechanical ventilation. It is this heterogeneity of lung involvement that makes effective and safe ventilation difficult to achieve.

Table 3. The clinical and pathological phases of ARDS

Initial phase

Lasts 3-5 days

Severe oxygenation defect

Reduced lung compliance

Bilateral pulmonary infiltrates

Endothelial and epithelial cell injury

Leak of protein-rich oedema fluid in interstitium and air spaces.

Abnormal surfactant/inactivation of surfactant

Neutrophil sequestration and migration in lung


Starts 5-7 days after onset of ARDS

Persistent oxygenation defect

Persistently reduced lung compliance

Increased alveolar dead space

Interstitial fibrosis with proliferation of type II alveolar cells

Widespread disruption of the pulmonary micro-circulation.


Starts about 14 days after initial insult

Persistent low lung compliance

Increase in dead space ventilation

Extensive pulmonary fibrosis

Obliteration of normal alveolar architecture

Widespread emphysema and discrete bullae.

Focus on clinical manifestations and outcome from ARDS

At the bedside, the patient is clearly in respiratory distress. Although orthopneoa may be present, the other features of congestive heart failure are seldom present. Chest X-ray reveals diffuse, bilateral infiltrates that are often patchy and asymmetric (Table 4). Arterial blood gases reveal hypoxaemia that is often refractory to oxygen therapy. An initial respiratory alkalosis invariably leads to hypercapnia as dead space ventilation increases and muscle fatigue sets in. As ARDS evolves, the cardiovascular system is commonly affected and multi-organ failure invariably ensues. Over half the patients will develop associated renal failure. Immediate prognosis is related to the number of organ systems involved. In the general population, patients with only lung involvement have 15-30% mortality. If three or more organs are involved, this becomes greater than 80%. If the multi-organ failure persists beyond 4 days, mortality is 100%.

Table 4. Typical radiological appearances of ARDS

Acute phase

Pulmonary oedema

Normal vascular pedicle

No cardiomegaly or upper lobe blood diversion

Septal lines usually absent

Subacute phase

Progressive lung destruction and transition from alveolar to interstitial opacities

Chronic phase


Focal emphysema

Key references

Ware LB, Matthay MA.
The acute respiratory distress syndrome.
N Engl J Med 2000; 342: 1334-1348.

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 Respir Crit Care Med 1994; 149: 818-824.

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