Respiratory stimulant effects of acetazolamide in the intensive care unit

Abstract

Patients suffering from chronic obstructive pulmonary disease (COPD) present episodes of respiratory exacerbation, which may be severe and necessitate ventilatory support. Persistent failure to discontinue invasive mechanical ventilation is a major issue in patients suffering from COPD. Metabolic alkalosis is a common finding in the intensive care unit, associated with a worse outcome. In COPD patients, this condition is called post-hypercapnic alkalosis and represents a complication of mechanical ventilation. Reversal of metabolic alkalosis may facilitate weaning from mechanical ventilation of COPD patients. Acetazolamide, a non-specific carbonic anhydrase inhibitor, is one of the drugs used in the intensive care unit to reverse metabolic alkalosis. Acetazolamide is relatively safe. Its pharmacodynamics and compartmentalization of the different isoforms of carbonic anhydrase enzyme may in part explain the lack of evidence of acetazolamide’s efficacy as respiratory stimulant. Recent findings have suggested that acetazolamide doses routinely used in the intensive care unit may be insufficient to significantly improve respiratory parameters in mechanically ventilated COPD patients, especially in the presence of high serum chloride levels or co-administration of systemic corticosteroids or furosemide. Randomized controlled trials using adequate doses of acetazolamide are required to address this issue.