Definition and causes
This syndrome was originally described in 1967 as acute respiratory distress in adults characterized by severe dyspnoea, tachypnoea, cyanosis refractory to oxygen therapy, a reduction in lung compliance and diffuse alveolar infiltrates seen on the chest X-ray. ARDS can therefore be defined as diffuse pulmonary infiltrates, refractory hypoxaernia, stiff lungs and respiratory distress. A PAWP less than 16 mmHg is often included in the definition in an attempt to exclude cardiogenic pulmonary oedema. ARDS can occur as a non-specific reaction of the lungs to a wide variety of insults, including shock (especially septic shock), sepsis, fat embolism, trauma, burns, pancreatitis, cardiopulmonary bypass, lung contusion, inhalation of smoke or toxic gases, Goodpasture’s syndrome, amniotic fluid embolism and aspiration pneumonia. By far the commonest predisposing factor is sepsis and 20- 40% of patients with severe sepsis will develop ARDS. Pneumonia is a common complication of ARDS.
ARDS can be considered as the earliest manifestation of a generalized inflammatory reaction and is therefore usually associated with the development of MOF.
Non-cardiogenic pulmonary oedema
This is the cardinal feature of ARDS and is the first and clinically most evident sign of a generalized increase in vascular permeability caused by the microcirculatory changes and release of inflammatory mediators described previously. The pulmonary epithelium is also damaged in the early stages of ARDS, reducing surfactant production and lowering the threshold for alveolar flooding.
This is a common feature of ARDS. Initially, mechanical obstruction of the pulmonary circulation may occur as a result of vascular compression by interstitial oedema and subsequently oedema of the vessel wall itself. Later, constriction of the pulmonary vasculature may develop in response to increased autonomic nervous activity and circulating substances such as catecholarnines, 5-hydroxytryptamine, thrornboxane, FDPs, complement and activated leucocytes. Those vessels supplying alveoli with low oxygen tensions constrict (the ‘hypoxic vasoconstrictor response’), diverting pulmonary blood flow to better oxygenated areas of lung, thus limiting the degree of shunt.
Haemorrhagic intra-alveolar exudate
This is rich in platelets, fibrin, fibrinogen and clotting factors; fibrin and fibronectin are deposited along the alveolar ducts with the incorporation of cellular debris. This exudate may inactivate surfactant and stimulate inflammation, as well as promoting hyaline membrane formation.
Within 7 days of the onset of ARDS, formation of a new epithelial lining is underway and activated fibroblasts accumulate in the interstitial spaces. Subsequently, interstitial fibrosis progresses, with loss of elastic tissue and obliteration of the lung vasculature, together with lung destruction and emphysema.
Shunt and dead space increase, compliance falls and there is evidence of airflow limitation. Although the lungs in ARDS are diffusely injured, the pulmonary lesions, when identified as densities on a CT scan, are predominantly located in dependent regions. This is probably explained by the effects of gravity on the distribution of extravascular lung water and areas of lung collapse.
The first sign of the development of ARDS is often an unexplained tachypnoea, followed by increasing hypoxaemia, dyspnoea and laboured breathing. Fine crackles are heard throughout both lung fields. Later, the chest X-ray shows bilateral, diffuse shadowing with an alveolar pattern and air bronchograms that may then progress to the picture of complete ‘white-out’.
This is based on treatment of the underlying condition (e.g. eradication of sepsis) and supportive measures (such as mechanical ventilation). Pulmonary oedema formation should be limited by minimizing left ventricular filling pressure with fluid restriction, the use of diuretics and, if these measures fail to prevent fluid overload, by haemofiltration. The aim should be to achieve a consistently negative fluid balance. If possible plasma oncotic pressure should be maintained by administering colloidal solutions with a long half-life. In patients with ARDS, however, colloids are unlikely to be retained within the vascular compartment; once they enter the interstitial space, the transvascular oncotic gradient is lost and the main determinants of interstitial oedema formation become the microvascular hydrostatic pressure and lymphatic drainage. There is therefore some controversy concerning the relative merits of colloids or crystalloids for volume replacement in patients likely to develop ARDS, or in whom the condition is established. Cardiovascular support and the reduction of oxygen requirements are also important. The administration of high-dose steroids to patients with established ARDS does not appear to improve outcome and current evidence suggests that prophylactic administration to those at risk of developing ARDS is of no value. Moreover, there is a suggestion that steroids may have an adverse effect on the prognosis of ARDS and their use is no longer recommended.
Inhaled nitric oxide
This vasodilator, when inhaled, can improve V/Q matching and oxygenation by increasing perfusion of ventilated lung units, as well as reducing pulmonary hypertension. Its role in the management of ARDS has yet to be established.
Although this agent reduces pulmonary and systemic vascular resistance, and consequently improves cardiac output, its use may be complicated by hypotension and a deterioration in gas exchange. Outcome does not seem to be improved.
Despite the treatment outlined, the mortality from established severe ARDS remains high at more than 50% overall. Prognosis is, however, very dependent on aetiology;
when ARDS occurs in association with septic shock mortality rates may be as high as 90%, whereas in ARDS associated with fat embolism around 90% may survive. Approximately 40% of uncomplicated cases die, but the mortality rises with increasing age and failure of other organs such as kidneys and liver. Many of those dying with ARDS now do so as a result of MOF and haemodynamic instability rather than impaired gas exchange.