Skip to main content
  • Letter to the Editor
  • Open access
  • Published:

A reassessment about included studies and certainty of evidence on a systematic review and meta-analysis of steroid for patients with acute respiratory distress syndrome

A Letter to the Editor to this article was published on 16 March 2021

The Original Article was published on 07 December 2020


We comment on the study by Hirano et al. about the effect of steroids in patients with acute respiratory distress syndrome. It might be necessary to include only the existing randomized control trials and to reassess the certainty of evidence about the primary outcomes.

Main text

Hirano et al. reported that prolonged administration of steroids to patients with early onset of acute respiratory distress syndrome (ARDS) was associated with improved mortality [1]. This study is a valuable report that suggests the need to extend the duration of steroid administration for patients with ARDS. However, it is possible that this study is not a systematic review based on the best available evidence. Therefore, we would like to focus on two concerns related to the primary outcomes of this systematic review and meta-analysis.

Only randomized control trials (RCTs) published on 1 August 2020 should be included in the systematic review. Annanne et al. performed a post hoc analysis of RCTs and did not stratify patient allocation by patients with ARDS in their original study [2]. The authors’ search method did not describe about statements to exclude articles that were published in languages other than English, although the RCT of Liu et al. was not included [3]. In addition, the RCT of Rezk et al. may need to be assessed for eligibility [4]. It might be necessary to re-synthesize studies to include only the existing RCTs.

We believe that the certainty of evidence about the primary outcomes may be much lower. The imprecision and risk of bias of 60- and 28- or 30-day mortality rates were evaluated as “not serious.” The 60-day mortality did not meet the optimal information size (OIS) because the total number of events was 179. In 28- or 30-day mortality, when the study by Annane et al. was excluded and Liu's study was included (4 RCTs, N = 591), the relative risk reduction was 35%, which did not appear to meet the OIS criteria. Downgrades might be needed. A pre-protocol was not published in the study of Meduri et al; therefore, the selective reporting bias was unclear. Although, the Egger’s test was used to analyze publication bias, it was not appropriate when the number of studies was less than 10 because of insufficient power [5]. An appropriate response would be to check the number of studies that have not been published on the Clinical and the International Clinical Trials Registry Platform.

We suggest reassessing the certainty of evidence regarding the primary outcome.

Availability of data and materials

Not applicable.



Acute respiratory distress syndrome


Randomized control trial


  1. Hirano Y, Madokoro S, Kondo Y, Okamoto K, Tanaka H. Corticosteroid treatment for early acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials. Journal of Intensive Care. 2020;8:91.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Annane D, Sébille V, Charpentier C, Bollaert P-E, François B, Korach J-M, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862–71.

    Article  CAS  PubMed  Google Scholar 

  3. Liu L, Li J, Huang YZ, Liu SQ, Yang CS, Guo FM, et al. The effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome combined with critical illness-related corticosteroid insufficiency. Zhonghua Nei Ke Za Zhi. 2012;51:599–603.

    PubMed  Google Scholar 

  4. Abdelsalam Rezk N, Mohamed IA. Effects of methyl prednisolone in early ARDS. Egyptian Journal of Chest Diseases and Tuberculosis. 2013;62:167–72.

    Article  Google Scholar 

  5. Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane. 2020. Accessed 13 Dec 2020.

Download references


Not applicable.


Not applicable.

Author information

Authors and Affiliations



All authors contributed to writing, revising, and approval of the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shodai Yoshihiro.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshihiro, S., Taito, S. A reassessment about included studies and certainty of evidence on a systematic review and meta-analysis of steroid for patients with acute respiratory distress syndrome. j intensive care 9, 25 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: