Impact of Corticosteroids on Mortality in Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis

Abstract

Objective The impact of corticosteroids on acute respiratory distress syndrome (ARDS) mortality remains controversial following the publication of numerous trials, observational studies and meta-analyses. An updated meta-analysis is warranted, as a few original studies on this topic have been published since the last meta-analysis. Methods We searched for eligible articles using four databases. In particular, we included full-length original articles providing sufficient data for evaluating the impact of corticosteroid treatment on adult ARDS mortality in the form of odds ratios. A fixed model with the confidence interval method was used. An assessment of publication bias and sensitivity analyses were also conducted. Results We included 11 of 185 articles. The pooled odds ratio for corticosteroids with respect to all-cause mortality involving 949 patients was 0.77 [95% confidence interval (CI): 0.58-1.03, p=0.079] with strong heterogeneity (I 2 =70%, p<0.001). The results of the sensitivity analysis, Begg-Kendall test (τ=0.53, p=0.024) and funnel plot consistently suggested the existence of strong publication bias. After six potentially unpublished cohorts were filled using Duval's trim and fill method, the pooled odds ratio shifted to 1.11 (95% CI 0.86-1.44, p=0.427). In addition, the sensitivity analyses suggested that corticosteroid treatment has a different impact on mortality depending on the comorbidities and trigger events. Conclusion We were unable to confirm, based on the data of published studies, the favorable impact of corticosteroid therapy on mortality in overall ARDS cases. Published articles exhibit strong publication bias, and previous meta-analyses may be affected by this publication bias. Further research focusing on pathophysiology-or trigger event-specific ARDS is anticipated.

Peptide–Gold Nanoparticle Hybrids as Promising Anti‐Inflammatory Nanotherapeutics for Acute Lung Injury: In Vivo Efficacy, Biodistribution, and Clearance

“…To date, no pharmacologic intervention has shown any benefit for ALI/ARDS patients, and only low tidal volume mechanical ventilation has been established as an effective approach that can reduce the mortality rate . The efficacy of the universal anti‐inflammatory agents, glucocorticoids, on ARDS patients is still questionable, and these agents are associated with some adverse effects . Therefore, the search for novel potent therapeutics to control excessive inflammation is urgent and may augment current clinical treatments for ALI/ARDS.…”

Efficacy of early sivelestat administration on acute lung injury and acute respiratory distress syndrome

“…Thus, the differences of the effectiveness during these studies might also be due to the differences of condition of patients . Actually, meta‐analyses have shown the difficulty to confirm the role of treatment because of heterogeneity of the studies for ALI/ARDS . In the present study, approximately 60% of the patients in the sivelestat group had received mechanical ventilation within 7 days of admission.…”

“…25 Actually, meta-analyses have shown the difficulty to confirm the role of treatment because of heterogeneity of the studies for ALI/ARDS. 19,29 In the present study, approximately 60% of the patients in the sivelestat group had received mechanical ventilation within 7 days of admission. Conversely, sivelestat was administrated at the time of starting mechanical ventilation in the previous studies.…”

“…There are several limitations associated with this study, which are similar to the previous studies using the DPC database. [12][13][14][15][16][17][18][19] First, this study was an observational and retrospective study, although the propensity score weighting method with a Cox proportional hazards model decreased this limitation. Second, we could not include several clinical data, such as the peripheral blood laboratory findings, physiological data including vital signs, and the settings of mechanical ventilation, which could also influence the mortality in patients with ALI/ARDS, because the related data were not included even in the original database.…”

Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity

“…New therapeutic strategies based on modulation of inflammation, using mesenchymal stromal cells, miRNA, or regulatory T cells, have recently been proposed [6–8]. Steroids have controversial effects when used early during the course of ARDS [9], but have been shown to reduce fibroblast proliferation and cytokine release when used in the late phase, thereby improving recovery [10]. Another effect of steroid therapy might be the induction of glucocorticoid-induced leucine zipper (GILZ).…”