Pharmacology in Emergency Medicine| Volume 58, ISSUE 6, P953-958, June 2020

Acetazolamide Causes Worsening Acidosis in Uncompensated COPD Exacerbations: Increased Awareness Needed for Patient Safety



      Acetazolamide has been studied extensively in post-hypercapnic alkalosis as a tool to facilitate ventilator weaning in chronic obstructive pulmonary disease (COPD). It has also been utilized to facilitate respiratory drive in nonmechanically ventilated patients with COPD. Although this is generally a forgiving intervention, providers must carefully select patients for this medication, as it can cause severe acidosis and deterioration of clinical status in severe COPD cases. The present report describes two cases of patients who developed worsening acidosis and hypercapnia after receiving acetazolamide in acute respiratory failure.

      Case Report

      Case 1 was a 72-year-old obese male with COPD who was dependent on supplemental oxygen and presented to the emergency department (ED) with acute on chronic hypercapnic respiratory failure. He was given a one-time dose of acetazolamide in the ED for “respiratory failure made worse by severe metabolic alkalosis.” His arterial blood gas (ABG) worsened overnight, accompanied by decreased mental status: pH 7.32, paCO2 82 mm Hg, paO2 50 mm Hg, HCO3 41.7 mmol/L, FiO2 32% to pH 7.21, paCO2 91.7 mm Hg, paO2 59 mm Hg, HCO3 36.6 mmol/L, and FiO2 32%. Case 2 was a 62-year-old male with COPD who was dependent on supplemental oxygen and presented to the ED with acute on chronic hypercapnic respiratory failure. He was given acetazolamide in the ED with similar results: ABG on presentation pH 7.37, paCO2 79.3 mm Hg, paO2 77.6 mm Hg, HCO3 45.5 mmol/L, and FiO2 32%. The next morning, ABG was pH 7.29, paCO2 79 mm Hg, paO2 77 mm Hg, HCO3 45.5 mmol/L, and FiO2 32%.

      Why Should an Emergency Physician Be Aware of This?

      Acetazolamide given early in the uncompensated setting can worsen acidosis and potentiate clinical deterioration.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Emergency Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Acetazolamide [package insert]. Sagent Pharmaceuticals, Schaumburg, IL2013
        • Jones P.
        • Greenstone M.
        Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease.
        Cochrane Database Syst Rev. 2001; 1: CD002881
        • Bruno C.
        • Valenti M.
        Acid-base disorders in patients with chronic obstructive pulmonary disease: a pathophysiological review.
        J Biomed Biotechnol. 2012; 2012: 915150
        • Adamson R.
        • Swenson E.
        Acetazolamide use in severe chronic obstructive pulmonary disease. Pros and cons.
        Ann Am Thorac Soc. 2017; 14: 1086-1093
        • Bell A.
        • Smith C.
        • Andreae E.
        Effects of the carbonic anhydrase inhibitor 6063 (Diamox) on respiration and electrolyte metabolism of patients with respiratory acidosis.
        Am J Med. 1955; 18: 536-546
        • Schwartz W.
        • Relman A.
        • Leaf A.
        Oral administration of a potent carbonic anhydrase inhibitor (Diamox). Its use as a diuretic in patients with severe congestive heart failure due to cor pulmonale.
        Ann Intern Med. 1955; 42: 79-89
        • Wishart M.
        • Isaacs B.
        The use of acetazolamide in acute respiratory acidosis.
        Lancet. 1955; 268: 995-996
        • Miller P.
        • Berns A.
        Acute metabolic alkalosis perpetuating hypercarbia. A role for acetazolamide in chronic obstructive pulmonary disease.
        JAMA. 1977; 238: 2400-2401
        • Dickinson G.
        • Myers M.
        • Goldbach M.
        • et al.
        Acetazolamide in the treatment of ventilatory failure complicating acute metabolic alkalosis.
        Anesth Analg. 1981; 60: 8-10
        • Bear R.
        • Goldstein M.
        • Phillipson E.
        • et al.
        Effect of metabolic alkalosis on respiratory function in patients with chronic obstructive lung disease.
        Can Med Assoc J. 1977; 117: 900-903
        • Faisy C.
        • Mokline A.
        • Sanchez O.
        • et al.
        Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation.
        Intensive Care Med. 2010; 36: 859-863
        • Bahloul M.
        • Chaari A.
        • Tounsi A.
        • et al.
        Impact of acetazolamide use in severe exacerbation of chronic obstructive pulmonary disease requiring invasive mechanical ventilation.
        Int J Crit Illn Inj Sci. 2015; 5: 3-8
        • Gulsvik R.
        • Skjorten I.
        • Undhjem K.
        • et al.
        Acetazolamide improves oxygenation in patients with respiratory failure and metabolic alkalosis.
        Clin Respir J. 2013; 7: 390-396
        • Fontana V.
        • Santinelli S.
        • Internullo M.
        • et al.
        Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients.
        Eur Rev Med Pharmacol Sci. 2016; 20: 37-43
        • Faisy C.
        • Meziani F.
        • Planquette B.
        • et al.
        Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease: a randomized clinical trial.
        JAMA. 2016; 315: 480-488
        • Bahloul M.
        • Ammar R.
        • Bouattou A.
        • et al.
        Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease: still far from the truth?.
        J Thorac Dis. 2007; 9: 1393-1395
        • Sood P.
        • Paul G.
        • Puri S.
        Interpretation of arterial blood gas.
        Indian J Crit Care Med. 2010; 14: 57-64
        • Haber R.
        A practical approach to acid-base disorders.
        West J Med. 1991; 155: 146-151
        • Global Initiative for Chronic Obstructive Lung Disease (GOLD)
        Global Strategy for the Diagnosis, Management, and Prevention of chronic obstructive pulmonary disease: 2018 report.
        (Available at:)
        Date accessed: November 8, 2018