Research in context
Evidence before this study
There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). A meta-analysis of nine small randomised clinical trials investigating prolonged corticosteroid (methylprednisolone or hydrocortisone) treatment in early and late ARDS reported, with consistency, a significant reduction in markers of inflammation, improvement in gas exchange, reduction of duration of mechanical ventilation, and reduction in length of stay in the intensive care unit. However, the aggregate data of these randomised trials provided insufficient evidence for a mortality benefit. A large confirmatory trial was needed. We searched the PubMed and Web of Science databases for all randomised trials describing the effects of dexamethasone as adjunctive therapy for mechanically ventilated patients with the ARDS. We used the search terms “acute respiratory distress syndrome”, OR “adult respiratory distress syndrome”, OR “acute lung injury”, OR “ARDS” AND “dexamethasone” OR “randomized” OR “randomized controlled trial” OR “clinical trials” OR “trials”. We also added “humans” and “NOT infant” for a second search field. No language restrictions were applied. The last search was done in April 23, 2019. No published trials with dexamethasone in ARDS were identified.
Added value of this study
To our knowledge, this is the first randomised clinical trial testing the efficacy of dexamethasone in patients with established ARDS. Our study shows that starting treatment with intravenous dexamethasone at 24 h of ARDS onset for a maximum of 10 days, or until mechanical ventilation and extubation (if occurring before day 10 after randomisation) is not needed, is associated with a substantial reduction in duration of mechanical ventilation and all-cause 60-day mortality in patients with established moderate-to-severe ARDS ventilated with lung-protective mechanical ventilation.
Implications of all the available evidence
Despite the substantial heterogeneity of clinical conditions associated with ARDS in our study, our findings support the notion that early therapy with dexamethasone could change the systemic immune responses and thereby could reduce the duration of mechanical ventilation and the overall mortality in patients with established moderate-to-severe ARDS.