Acetazolamide to decrease invasive mechanical ventilation in critically ill patients with Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease (COPD) can lead to intensive care unit (ICU) admission with some patients requiring the need for invasive mechanical ventilation. Acetazolamide has been used as a respiratory stimulant in patients with COPD and metabolic alkalosis. Faisy and colleagues conducted the DIABLO study to determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. The DIABLO study was a randomized, double-blind, multicenter, parallel-group trial conducted from October 2011 to July 2014 in 15 ICU’s in France. Patients were randomized to receive either 500 mg or 1000 mg (if loop diuretics were co-prescribed) of acetazolamide twice daily or placebo (10mL of saline). The primary end point of the study was duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy with secondary end points including alterations in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. Of the 380 patients that completed the study, 187 were randomzed to the acetazolamide treatment group and 193 to the placebo treatment group. The study resulted in a total duration of invasive ventilation median of 136.5 hours in the acetazolamide group versus 163.0 hours in the placebo group, for a between group difference of -16.0 hours, which did not differ significantly (statistically). Secondary end point analysis between the groups showed no respiratory stimulant effect on respiratory rate, tidal volume, or median minute ventilation change. However, daily changes in serum bicarbonate (between group difference, −0.8 mEq/L; 95% CI, −1.2 to −0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, −1; 95% CI, −2 to −1 days; P < .001) decreased significantly more in the acetazolamide group. The study concluded that patients with COPD receiving invasive mechanical ventilation that were treated with acetazolamide, compared with placebo, showed no statistically significant reduction in duration of invasive mechanical ventilation.

It was noted in the study that although the data suggested that no statistically significant change was observed, there was a reduction in the drug treatment group by 16 hours indicating a clinically significant result. The sooner that critically ill patients can be weaned off artificial respiration, the sooner they are to be discharged.
JAMA. 2016;315(5):480-88.