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 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.