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Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review
  1. Timothy John Bemand1,2,3,
  2. Richard Chatoor1,2,4,
  3. Patrizia Natale3,5,6,
  4. Giovanni Strippoli3,5,
  5. Anthony Delaney4,7,8,9
  1. 1 Wagga Wagga Base Hospital, Wagga Wagga, New South Wales, Australia
  2. 2 Rural Clinical School Wagga Wagga Campus, University of New South Wales, Wagga Wagga, New South Wales, Australia
  3. 3 Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
  4. 4 Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  5. 5 Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
  6. 6 Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
  7. 7 Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  8. 8 Division of Critical Care, The George Institute for Global Health, Newtown, New South Wales, Australia
  9. 9 Department of Epidemiology and Preventative Medicine, Monash University, ANZIC-RC, Melbourne, Victoria, Australia
  1. Correspondence to Dr Timothy John Bemand, Wagga Wagga Base Hospital, Wagga Wagga, NSW, Australia; timothy.bemand{at}


Background Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression.

Methods We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2 value and χ2 test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.

Results Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference −0.8 days (95% CI −7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty).

Conclusion Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required.

PROSPERO registration number CRD42021278757.

  • Critical Care
  • COPD Exacerbations
  • Assisted Ventilation

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  • Contributors AD, TJB, PN and GS contributed to the concept and design of the review. TJB and RC performed data collection and interpretation. TJB performed data analysis, had full access to all of the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. TJB wrote the first draft. All authors contributed to critical revision of the publication and final approval to submit. TJB is the guarantor of this study and accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.