Abstract
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p < 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.
Highlights
The clinical and biological heterogeneity of acute respiratory distress syndrome (ARDS) involves complex pathophysiologic mechanisms encompassing a multitude of risk factors, all of which can contribute to distinct clinical outcomes and the varied responses to therapeutics observed in failed clinical trials [1,2,3,4,5,6,7]
After excluding 37 patients, a total of 152 patients with severe ARDS rescued by extracorporeal membrane oxygenation (ECMO) were enrolled in the current analysis, and the overall hospital mortality rate was 53.3%
The causal relationship between fluid overload and organ dysfunction was difficult to determine due to the retrospective nature of our study, our findings showed that indirect ARDS patients had a significantly higher cumulative fluid balance and higher organ failure during early phase of ECMO than direct ARDS patients, which may contribute to higher mortality
Summary
The clinical and biological heterogeneity of acute respiratory distress syndrome (ARDS) involves complex pathophysiologic mechanisms encompassing a multitude of risk factors, all of which can contribute to distinct clinical outcomes and the varied responses to therapeutics observed in failed clinical trials [1,2,3,4,5,6,7].The main priority in caring for patients with ARDS is identifying and treating the underlying etiologies, which can be divided into those directly or indirectly related to lung injury [1]. Direct (primary or pulmonary) ARDS results from an insult that directly affects lung parenchyma (e.g., pneumonia, aspiration of gastric contents), and indirect (secondary or extrapulmonary) ARDS results from an insult outside of the lungs with an acute systemic inflammatory response (e.g., nonpulmonary sepsis, trauma, pancreatitis) [3]. Alveolar epithelial injury with a local alveolar inflammatory response is a direct insult resulting from pulmonary ARDS (i.e., direct or primary ARDS) with predominant consolidation, whereas systemic vascular endothelial damage caused by inflammatory mediators in the bloodstream is the indirect insult of extrapulmonary ARDS (i.e., indirect or secondary ARDS) with prevalent interstitial edema, ground-glass opacification, and alveolar collapse [2,3,5,6,7]. Irrespective of the initial insult, the final result is a disruption to the pulmonary alveolar-capillary barrier with consequent hypoxemia, inflammation, noncardiogenic pulmonary edema, and eventual organ failure [9]
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