Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials

Abstract

BACKGROUND: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it.METHODS: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a PaO 2 to FIO 2 ratio (PaO 2 :FIO 2 ) > 300 on the first study day following enrollment. RESULTS:The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P < .0001) than ARDS > 1 day. PaO 2 :FIO 2 at screening, change in PaO 2 :FIO 2 from screening to enrollment, use of vasopressor agents, FIO 2 at enrollment, and serum bilirubin levels were useful predictive variables.CONCLUSIONS: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials.

Embracing the Heterogeneity of ARDS

“…It has been postulated for some time that rapid improvement, including improved oxygenation on standardized ventilator settings 24 h after presentation, is not "real ARDS" given that this cohort has lower mortality and shorter time on mechanical ventilation, 6 similar to patients with riARDS described by Schenck and colleagues. 5 We believe this view incorrectly conflates the clinical syndrome of ARDS with diffuse alveolar damage and the perception that DAD is always radiographically diffuse, clinically severe, and necessarily prolonged. Both the American-European Consensus Conference and Berlin definitions recognized and codified the milder end of the ARDS spectrum (American-European Consensus Conference used the term acute lung injury) and noted that qualifying radiographic opacities could be focal and mild so long as they were bilateral.…”

Supervised Machine Learning for the Early Prediction of Acute Respiratory Distress Syndrome (ARDS)

“…These metrics outperform those reported in other studies. 69 While the quality of diagnostic metrics decay as they are made increasingly early prior to ARDS onset, the 12-hour prediction of ARDS offers operating points with high sensitivity and specificity. Table 3 illustrates a clinically relevant operating point with sensitivity of 0.806 and specificity of 0.823.…”

ARDS Subphenotypes: Understanding a Heterogeneous Syndrome

“…Not surprisingly, rapidly improving ARDS (ARDS that resolves within 1 day) has a better prognosis than persistent ARDS. More interesting, however, is the finding that most (63%) patients with rapidly improving ARDS present with moderate or severe hypoxemia [17], highlighting the limitations of using the PaO 2 :FiO 2 ratio alone to identify patients for enrollment in clinical trials. Recognizing this issue, the PROSEVA trial of prone positioning only enrolled patients if they continued to meet inclusion criteria (PaO 2 :FiO 2 ratio < 150 mmHg) after 12-24 h of stabilization [7].…”