Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis

Clin Respir J. 2013 Oct;7(4):390-6. doi: 10.1111/crj.12025. Epub 2013 Jul 4.


Introduction: Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration.

Objective: The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis.

Methods: A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital.

Results: Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group.

Conclusion: Acetazolamide may constitute a useful adjuvant treatment mainly to be considered in selected patients with respiratory failure combined with prominent metabolic alkalosis or where non-invasive ventilation is insufficient or infeasible.

Keywords: acetazolamide; chronic obstructive pulmonary disease; hypoxia; metabolic alkalosis; respiratory failure.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetazolamide / administration & dosage*
  • Aged
  • Aged, 80 and over
  • Alkalosis / drug therapy*
  • Alkalosis / metabolism
  • Carbon Dioxide / blood
  • Carbonic Anhydrase Inhibitors / administration & dosage
  • Double-Blind Method
  • Electrolytes / blood
  • Female
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Hypoxia / drug therapy
  • Hypoxia / metabolism
  • Male
  • Middle Aged
  • Oxygen / blood
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / metabolism
  • Treatment Outcome


  • Carbonic Anhydrase Inhibitors
  • Electrolytes
  • Carbon Dioxide
  • Acetazolamide
  • Oxygen