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.

2nd Department of Anaesthesiology University Hospital Brno Brno Czech Republic

Collaboration for Research in Intensive Care Copenhagen Denmark

Department of Anaesthesiology and Intensive Care Medicine Clinical University Hospital of Santiago Sanitary Research Institute of Santiago Santiago Spain

Department of Anaesthesiology Critical Care and Pain Tata Memorial Hospital Homi Bhabha National Institute Mumbai India

Department of Critical Care Medicine Apollo Hospitals Chennai India

Department of Health Research Methods Evidence and Impact McMaster University Hamilton Ontario Canada

Department of Intensive Care Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Intensive Care Medicine Wesley Hospital Brisbane Queensland Australia

Department of Internal Medicine and Cardiology University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

Department of Medicine McMaster University Hamilton Ontario Canada

Department of Paediatric Anaesthesiology and Intensive Care Medicine University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pharmacology CZECRIN Faculty of Medicine Masaryk University Brno Czech Republic

Department of Simulation Medicine Faculty of Medicine Masaryk University Brno Czech Republic

NIHR Applied Research Collaboration West University Hospitals Bristol and Weston NHS Foundation Trust Bristol England

Population Health Sciences Bristol Medical School University of Bristol Bristol England

Prasanna School of Public Health Manipal Academy of Higher Education Manipal India

Pulmonary and Critical Care Medicine Instituto Universitario CEMIC Buenos Aires Argentina

School of Public Health Imperial College London UK

The George Institute for Global Health New Delhi India

The George Institute for Global Health Sydney New South Wales Australia

University of Queensland Brisbane Queensland Australia

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