Timing, risk factors, and extra-pulmonary factors
Timing
The committee agreed that the current time frame for the diagnosis of ARDS should be retained: acute onset or worsening of hypoxemic respiratory failure is defined as occurring within one week of the onset of the predisposing risk factor or within one week of new or worsening respiratory symptoms.
Prolonging the time to onset of hypoxemic respiratory failure was considered since protracted symptoms may precede progression to frank respiratory failure, as in the case of COVID-19; however, expanding the definition to include HFNO (detailed below) should allow for earlier diagnosis, so the time frame of one week for acute onset of respiratory failure was maintained.
The committee considered existing evidence showing that almost all cases of non-COVID ARDS occur within 7 days of a known risk factor. 14,15 However, during the COVID-19 pandemic, some patients had the onset of ARDS as long as three weeks after the onset of COVID-19 symptoms, providing a rationale for extending the time window after onset of a risk factor. The consensus was that the revised definition should be flexible about the time of onset after a risk factor is identified, while continuing to emphasize acuity.
Risk factors
Although one or more risk factors is usually present at the time of diagnosis of ARDS, the diagnosis should not depend on the presence or absence of a specific risk factor.
The LUNG SAFE epidemiology study found that 8% of 3022 patients had no risk factors clearly identified.
The precipitating risk factors(s) can be used to guide clinical care and research regarding prognostic and predictive enrichment but are not necessary to include in the definition.
It is recommended that ARDS risk factors be recorded in clinical studies of ARDS and sought in clinical care to assure that the underlying cause of ARDS is adequately treated.
The acute onset or worsening of hypoxemic respiratory failure and pulmonary edema should not be exclusively or primarily attributable to cardiogenic pulmonary edema or fluid overload, atelectasis or lung collapse, pleural effusion, or pulmonary embolism.
ARDS can be diagnosed in the presence of these conditions if a predisposing risk factor for ARDS is also present, and the clinician thinks that these other conditions (e.g., fluid overload, atelectasis) are unlikely to be the primary causes of the hypoxemia.
ARDS also can be diagnosed in the presence of chronic lung disease, such as chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary hypertension, providing that acute hypoxemic respiratory failure is not primarily attributable to these underlying conditions.
The committee also emphasized that the definition should clarify that ARDS may occur in the setting of other contributors to respiratory dysfunction (as in the case of ARDS with concurrent cardiac dysfunction or chronic lung disease) but that to meet the definition of ARDS, respiratory failure cannot be exclusively or primarily attributable to other causes.
Diagnostic modalities such as cardiac ultrasound remain important for identifying alternative causes of respiratory failure.
Extra-pulmonary factors
Extra-pulmonary organ failures in ARDS increase the risk of death.
ARDS-directed interventions such as fluid management strategies may impact the development of extra-pulmonary injury.
ARDS is a syndrome of acute respiratory failure and therefore extra-pulmonary factors are not necessary for the diagnosis.
It is recommended that extra-pulmonary organ failures be recorded in clinical studies to improve phenotyping of ARDS and to study the association of organ failures with clinical outcomes.
Baseline co-morbidities and functional status (e.g., frailty score) should be collected in clinical studies because of their association with clinical outcomes.