Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis

Marie Warrer Munch^{1

2}, Anders Granholm^{1

2}, Jan Maláska^{3

4

5}, Jan Stašek⁶, Pablo O Rodriguez⁷, Tyler Pitre^{8

9}, Rebecca Wilson^{10

11}, Jelena Savović^{10

11}, Bram Rochwerg^{8

9}, Adam Svobodnik¹², Milan Kratochvíl³, Manuel Taboada¹³, Vivekanand Jha^{14

15

16}, Bharath Kumar Tirupakuzhi Vijayaraghavan^{14

17}, Sheila Nainan Myatra¹⁸, Balasubramanian Venkatesh^{19

20

21}, Anders Perner^{1

2}, Morten Hylander Møller^{1

2}

Affiliations

¹ Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.
³ Department of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁴ Department of Simulation Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁵ 2nd Department of Anaesthesiology University Hospital Brno, Brno, Czech Republic.
⁶ Department of Internal Medicine and Cardiology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁷ Pulmonary and Critical Care Medicine, Instituto Universitario CEMIC (Centro de Educación Médica e Investigación Clínica), Buenos Aires, Argentina.
⁸ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁹ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
¹⁰ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.
¹¹ NIHR Applied Research Collaboration West (ARC West), University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, England.
¹² Department of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
¹³ Department of Anaesthesiology and Intensive Care Medicine, Clinical University Hospital of Santiago, Sanitary Research Institute of Santiago (IDIS), Santiago, Spain.
¹⁴ The George Institute for Global Health, New Delhi, India.
¹⁵ School of Public Health, Imperial College, London, UK.
¹⁶ Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India.
¹⁷ Department of Critical Care Medicine, Apollo Hospitals, Chennai, India.
¹⁸ Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.
¹⁹ The George Institute for Global Health, Sydney, New South Wales, Australia.
²⁰ Department of Intensive Care Medicine, Wesley Hospital, Brisbane, Queensland, Australia.
²¹ University of Queensland, Brisbane, Queensland, Australia.

PMID: 37881881
DOI: 10.1111/aas.14346

Meta-Analysis

Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis

Marie Warrer Munch et al. Acta Anaesthesiol Scand. 2024 Feb.

. 2024 Feb;68(2):146-166.

doi: 10.1111/aas.14346. Epub 2023 Oct 26.

Authors

Affiliations

¹ Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark.
³ Department of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁴ Department of Simulation Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁵ 2nd Department of Anaesthesiology University Hospital Brno, Brno, Czech Republic.
⁶ Department of Internal Medicine and Cardiology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
⁷ Pulmonary and Critical Care Medicine, Instituto Universitario CEMIC (Centro de Educación Médica e Investigación Clínica), Buenos Aires, Argentina.
⁸ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁹ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
¹⁰ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.
¹¹ NIHR Applied Research Collaboration West (ARC West), University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, England.
¹² Department of Pharmacology/CZECRIN, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
¹³ Department of Anaesthesiology and Intensive Care Medicine, Clinical University Hospital of Santiago, Sanitary Research Institute of Santiago (IDIS), Santiago, Spain.
¹⁴ The George Institute for Global Health, New Delhi, India.
¹⁵ School of Public Health, Imperial College, London, UK.
¹⁶ Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India.
¹⁷ Department of Critical Care Medicine, Apollo Hospitals, Chennai, India.
¹⁸ Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.
¹⁹ The George Institute for Global Health, Sydney, New South Wales, Australia.
²⁰ Department of Intensive Care Medicine, Wesley Hospital, Brisbane, Queensland, Australia.
²¹ University of Queensland, Brisbane, Queensland, Australia.

PMID: 37881881
DOI: 10.1111/aas.14346

Abstract

Background: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia.

Methods: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy.

Conclusions: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

Keywords: COVID-19; corticosteroids; dexamethasone; hypoxia; meta-analysis.

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References

REFERENCES

1. WHO Rapid Evidence Appraisal for COVID-19 Therapies Working Group, Sterne JAC, Murthy S, et al. Association between Administration of Systemic Corticosteroids and Mortality among Critically ill Patients with COVID-19: a meta-analysis. JAMA. 2020;324:1330-1341.
1. Alhazzani W, Evans L, Alshamsi F, et al. Surviving sepsis campaign guidelines on the Management of Adults with Coronavirus Disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021;49:e219-e234.
1. World Health Organization. Therapeutics and COVID-19: Living Guideline, 13 January 2023 (WHO/2019-nCoV/therapeutics/2023.1). Licence: CC BY-NC-SA 3.0 IGO. World Health Organization; 2023.
1. Webb SA, Higgins AM, McArthur CJ. Glucocorticoid dose in COVID-19: lessons for clinical trials during a pandemic. JAMA. 2021;326:1801-1802.
1. Møller MH, Munch MW, Granholm A, Svobodnik A, Savovic J. Higher vs. standard doses of dexamethasone in patients with COVID-19 and hypoxia: a prospective meta-analysis. OSF. 2021. https://osf.io/em7x9

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Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis

Affiliations

Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous