Meta-analysis, systematic review of carbonic anhydrase inhibitors in respiratory failure and metabolic alkalosis

One discussion this week involved carbonic anhydrase inhibitors (CAIs) in the setting of respiratory failure and metabolic alkalosisa.

Reference: Tanios BY, et al. Carbonic anhydrase inhibitors in patients with respiratory failure and metabolic alkalosis: a systematic review and meta-analysis of randomized controlled trials. Critical Care. 2018 Oct 29;22(1):275.  doi: 10.1186/s13054-018-2207-6

Summary: Metabolic alkalosis is common in patients with respiratory failure and may delay weaning in mechanically ventilated patientsCarbonic anhydrase inhibitors (such as acetazolamide, methazolamide, and dichlorphenamide) block renal bicarbonate reabsorption, and thus reverse metabolic alkalosis. However, uncertainty remains about
their effects in the setting of respiratory failure with concurrent metabolic alkalosis on duration of hospitalization, mechanical ventilation (MV), or noninvasive positive pressure ventilation (NIPPV), and mortality.

The objective of this systematic review is to assess the benefits and harms of carbonic anhydrase inhibitor therapy in patients with respiratory failure and metabolic alkalosis.

Randomized clinical trials were included if they assessed at least one of the following outcomes: mortality, duration of hospital stay, duration of mechanical ventilation, adverse events, and blood gas parameters. Six eligible studies were identified with a total of 564 patients.

There were no definitive results for the effects of CAI therapy on clinically important outcomes such as mortality and duration of hospital stay in patients with respiratory failure and metabolic alkalosis. The results suggest that CAI therapy may decrease the duration of mechanical ventilation. There was a trend towards increased incidence of adverse events in the CAI group; however, most of these adverse events were mild.

On the other hand, the results suggest that CAI therapy has favorable effects on arterial blood gas parameters (PaCO2, PaO2, bicarbonate and pH), with decreased PaCO2, increased PaO2, and, as expected, decreased bicarbonate and pH levels.


In patients with respiratory failure and metabolic alkalosiscarbonic anhydrase inhibitor therapy may have favorable effects on blood gas parameters. The authors note that this analysis did not provide conclusive results for clinically important outcomes.

In mechanically ventilated patientscarbonic anhydrase inhibitor therapy may decrease the duration of mechanical ventilation. A major limitation was that only two trials assessed this clinically important outcome.

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