Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies. Methods: We performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results. Results: Eight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64-0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42-0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66-5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68-1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01-1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs. Conclusion: Among patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors.

Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis

“…However, the impact of corticosteroid therapy on clinically relevant outcomes in ARDS patients remains controversial. Clinical trials evaluating corticosteroids in the management of ARDS reported conflicting results [6][7][8], and previous meta-analyses were underpowered to draw determinate conclusions [9,10]. Thus, we conducted an updated meta-analysis with trial sequential analysis to assess the effect of corticosteroids in the treatment of patients with ARDS and determine whether the current evidence is reliable.…”

The Role of Glucocorticoids in the Management of COVID-19

“…The recent Dexa-ARDS trial found that patients receiving high-dose dexamethasone had a lower all-cause mortality than patients receiving standard care (21% vs. 36% respectively) 64 . A meta-analysis, which included the Dexa-ARDS trial, as well as others, also favored the use of glucocorticoids in ARDS, although some reservations remained regarding the reliability of the findings 65 . Additionally, a recent meta-analysis attempted to dissect the issues of timing and dosing of glucocorticoid use in ARDS and came to the conclusion that early initiation of glucocorticoid therapy and use of a low to medium dose were associated with lower mortality 66 .…”

Current and evolving standards of care for patients with ARDS

“…However, these meta-analyses predated a recently published multicenter RCT in 277 patients by Villar et al that found that early administration of dexamethasone (20 mg/day from days 1-5, and 10 mg/day from days 6-10) reduced duration of mechanical ventilation and mortality. A subsequent sequential meta-analysis published this year does show a significant reduction in mortality with the use of corticosteroids, but the low number of total patients randomized raised concerns about false positive results in the sequential analysis [96]. Thus, the role for corticosteroids in early ARDS remains controversial.…”