Acute lung injury

Definition

There is no single diagnostic test, and confusion has arisen in the past from differing diagnostic criteria. This has complicated comparisons of incidence, mortality, aetiology and efficacy of therapies. To address this problem, European–American consensus conferences produced the following widely accepted definitions in 1994.

ALI diagnosis required the presence of four criteria:

• 1.

  Acute onset of impaired oxygenation.

• 2.

  Severe hypoxaemia defined as a $P{\text{a}}_{{\text{o}}_2}$ to $F{\text{I}}_{{\text{o}}_2}$ ratio of 40 or less ( $P{\text{a}}_{{\text{o}}_2}$ in kPa) or 300 or less ( $P{\text{a}}_{{\text{o}}_2}$ in mmHg).

• 3.

  Bilateral diffuse infiltration on the chest radiograph consistent with pulmonary oedema.

• 4.

  Absence of left atrial hypertension.

ARDS was defined in almost identical terms, except that the impairment of gas exchange was worse, with a $P{\text{a}}_{{\text{o}}_2}$ to $F{\text{I}}_{{\text{o}}_2}$ ratio of 26.7 or less kPa or 200 or less mmHg.

These criteria were widely accepted and extremely helpful in researching ALI, though for ARDS there were concerns over the definition of ‘acute’, the effect of ventilator settings on $P{\text{a}}_{{\text{o}}_2}$ to $F{\text{I}}_{{\text{o}}_2}$ ratio and the poor reliability of chest radiograph interpretation. In 2012 these concerns were addressed with updated diagnostic criteria for ARDS, referred to as the Berlin definition, which also, for the first time, introduced three different grades of hypoxia ( Table 31.1 ). Although generally accepted as an improvement on its predecessor, the Berlin definition similarly does not relate to the typical histopathological picture seen in a patient’s lungs, with the usual features of ARDS, diffuse alveolar damage, being absent in some patients who meet the diagnostic criteria.

Predisposing conditions and risk factors for acute lung injury

Although the clinical and histopathological features of ALI are remarkably consistent, they have been described as the sequel to a large range of predisposing conditions ( Table 31.2 ). There are, however, very important differences in the progression of ALI and its response to treatment, depending on the underlying cause and associated pathology. Nevertheless, recognition of the predisposing conditions is crucially important for predicting which patients are at risk and making an early diagnosis.

The conditions listed in Table 31.2 are not equally likely to proceed to ALI. Studies have consistently identified sepsis as the condition most likely to result in development of ALI, with pneumonia, pancreatitis, trauma and transfusion-related ALI (TRALI) also being common contributors. The last of these, TRALI, is unusual in that it occurs 50 times more often in critically ill patients than other hospitalized patients, making transfusion of blood products particularly hazardous in patients who are already at risk of ALI. Overall, 25% of patients with a single risk factor develop ARDS, but this rises to 42% with two factors and 85% with three.

Age does not seem to affect the likelihood of developing ALI, but it may be more common in men than women and less common in some racial groups. ARDS also occurs in children, with an incidence of 1.8% described in a study of almost 150 000 patients under 18 admitted to an intensive care unit following a traumatic injury.

Incidence and mortality

In the past, the lack of accepted definitions of lung injury led to widely varying estimates of the incidences of ALI and ARDS. Despite more consistent diagnostic criteria in recent years, the estimated incidence of ALI remains variable at 5 to 7 cases per year per 100 000 individuals in Europe and 34 per 100 000 in the United States. The reasons for this variation in estimates of the incidence of ALI is unknown, but the incidence may be decreasing. Around 70% of cases of ALI are severe enough to be classified as ARDS. There is, however, considerable agreement that mortality from ARDS is high: 2 decades ago in excess of 50% of patients died, whatever the criteria of diagnosis. Outcome has improved in recent years, with studies indicating a decline in mortality rate from 35% in 1996 to just over 28% in 2013. In children under 18 years old a mortality of 20% is reported, although this did not improve over the decade of study data collection. Significant long-term disability is common in survivors, although this does not usually involve the respiratory system, which seems to recover well.

Clinical course

Four phases may be recognized in the development of severe ALI. In the first the patient is dyspnoeic and tachypneic, but there are no other abnormalities. The chest radiograph is normal at this stage, which lasts for about 24 hours. In the second phase there is hypoxaemia, but the arterial P co ₂ remains normal or subnormal. There are minor abnormalities of the chest radiograph. This phase may last for 24 to 48 hours. Diagnosis is easily missed in these prodromal stages and is very dependent on the history of one or more predisposing conditions. Identification of patients in this stage of ALI is becoming increasingly important as we gain a greater understanding of interventions which can worsen or improve the chances or progressing to ARDS.

It is only in phase three that the diagnostic criteria of ALI become established. There is significant arterial hypoxaemia caused by an increased alveolar/arterial P o ₂ gradient, and the arterial P co ₂ may be slightly elevated. The lungs become stiff, and the chest radiograph shows the characteristic bilateral diffuse infiltrates. Ventilatory support is usually instituted at this stage.

The fourth phase is often terminal and comprises massive bilateral consolidation with unremitting hypoxaemia even when ventilated with very high inspired oxygen concentrations. Dead space is substantially increased, and the arterial P co ₂ is only with difficulty kept in the normal range.

Not every patient passes through all these phases, and the condition may resolve at any stage. It is difficult to predict whether the condition will progress, and there is currently no useful laboratory test, although animal studies have identified biomarkers for alveolar fluid clearance which may be associated with resolution of ALI. Serial observations of the chest radiograph, the alveolar/arterial P o ₂ gradient and the function of other compromised organs are the best guides to progress.

Pathophysiology