No Change in Duration of Mechanical Ventilation with Acetazolamide for COPD Patients with Metabolic Alkalosis

Clinical question: Does acetazolamide decrease the duration of mechanical ventilation for patients with chronic obstructive pulmonary disease and metabolic alkalosis?

Bottom line: Although acetazolamide effectively decreased the levels of serum bicarbonate and the number of days with metabolic alkalosis in critically ill patients with chronic obstructive pulmonary disease (COPD) on mechanical ventilation, it did not produce a statistically significant difference in the duration of mechanical ventilation. However, this lack of statistical significance may have been due to an underpowered study. (LOE = 1b-)

Reference: Faisy C, Meziani F, Planquette B, et al, for the DIABOLO Investigators. Effect of acetazolamide vs placebo on duration of invasive mechanical ventilation among patients with chronic obstructive pulmonary disease. JAMA 2016;315(5):480-488.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis:
Acetazolamide is used as a respiratory stimulant for patients with COPD and metabolic alkalosis because of its ability to reduce serum bicarbonate, which may lead to a rise in minute ventilation. However, its clinical benefit has not been demonstrated previously in controlled trials.

Using concealed allocation, these investigators randomized patients with COPD who required invasive mechanical ventilation to receive either acetazolamide 500 mg intravenously twice daily (1000 mg if loop diuretics were also prescribed) or matching placebo up to 28 days. Only those patients found to have pure or mixed metabolic alkalosis received the treatment. The intention-to-treat population consisted of 380 patients and baseline characteristics were similar in both groups. The use of acetazolamide led to decreased levels of serum bicarbonate and fewer days with metabolic alkalosis but did not improve respiratory parameters such as respiratory rate, tidal volume, or minute ventilation.

For the primary outcome of duration of mechanical ventilation, the magnitude of the difference between the 2 groups was large, suggesting a clinically important effect, but the difference did not reach statistical significance (between-group difference -16 hours with acetazolamide; 95% CI -36.5 to 4.0 hours). The lack of statistical significance may be due to an underpowered study because of fewer-than-expected patients who received the treatment (more than 20% of patients in each group did not receive the assigned treatment because of lack of metabolic alkalosis or temporary contraindications) and a shorter-than-anticipated duration of mechanical ventilation in the placebo group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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