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Meta-Analysis
. 2021 May;47(5):521-537.
doi: 10.1007/s00134-021-06394-2. Epub 2021 Apr 19.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

Dipayan Chaudhuri  1   2 , Kiyoka Sasaki  1 , Aram Karkar  1 , Sameer Sharif  1 , Kimberly Lewis  1   2 , Manoj J Mammen  3 , Paul Alexander  2 , Zhikang Ye  2 , Luis Enrique Colunga Lozano  2 , Marie Warrer Munch  4 , Anders Perner  4 , Bin Du  5 , Lawrence Mbuagbaw  2   6 , Waleed Alhazzani  1   2 , Stephen M Pastores  7 , John Marshall  8 , François Lamontagne  9 , Djillali Annane  10 , Gianfranco Umberto Meduri  11 , Bram Rochwerg  12   13   14
Affiliations
Meta-Analysis

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

Dipayan Chaudhuri et al. Intensive Care Med. 2021 May.

Abstract

Purpose: Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS.

Methods: The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality.

Results: We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72-0.95, ARR 8.0%, 95% CI 2.2-12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course.

Conclusion: The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.

Keywords: ARDS; COVID-19; Corticosteroids; Mechanical ventilation.

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Conflict of interest statement

AP is the sponsor and MWM the coordinating investigator of the COVID STEROID trial, which is funded by the Novo Nordisk Foundation and supported by Pfizer Inc. WA is the chair of the Surviving Sepsis COVID guideline. BR was the methodologist for the 2017 CIRCI SCCM guidelines and on the methods team for the WHO corticosteroid in COVID guideline. SP served as co-chair of the SCCM/ESICM 2017 Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients. DA has been the co-chair of the SCCM/ESICM guidelines on the diagnosis and management of CIRCI 2017 (PMID: 29095205; PMID: 29090327; PMID: 28940017; PMID: 28940011; PMID: 28938253; PMID: 28938251). He was a member of WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group which has published a prospective meta-analysis on the use of corticosteroids for COVID-19 (PMID: 32876694; PMID: 32831155); and a member of the steering committee of BMJ/GRADE rapid recommendations for corticosteroids for sepsis (PMID: 30097460; PMID: 29979221). DA is coordinating the individual patient data meta-analysis on hydrocortisone for septic shock (PMID: 33268422) and has coordinated the Cochrane trial-level meta-analysis on the use of corticosteroids for children and adults with sepsis (PMID: 31808551). DA has been the PI of the following trials on corticosteroids for sepsis (and or ARDS) PMID: 20103758; PMID: 18184957; PMID: 16374152; PMID: 12186604; PMID: 29490185. DA was the member of the steering committee of the following trials of corticosteroids for COVID-19: PMID: 32876697; PMID: 32876689. DA has received no personal rewards for any of the above mentioned academic activities. LM does paid consulting work for Bayer (oncology), AstraZeneca (biologics for asthma) and Janseen (TB drugs). GUM served as a member of the SCCM/ESICM 2017 Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients. MJM serves as a co-author on the Surviving Sepsis COVID guideline. FL contributed to systematic reviews and clinical trials of evaluating the effects of corticosteroids in ARDS and pneumonia and chaired the WHO corticosteroid in COVID guideline.

Figures

Fig. 1
Fig. 1
Effect of corticosteroids on mortality. Studies subdivided by COVID-19 status and ARDS definition. DF degrees of freedom
Fig. 2
Fig. 2
Effect of corticosteroids on mortality including studies with strict ARDS definition. DF degrees of freedom
Fig. 3
Fig. 3
Effect of corticosteroids on mortality. Studies subdivided by duration of corticosteroid therapy
See this image and copyright information in PMC

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