Acetazolamide with Ventilation: Inconclusive but Promising

The use of acetazolamide does not appear to decrease the time patients require invasive mechanical ventilation, however, further studies are warranted. An article published in the Journal of the American Medical Association on February 2, 2016, details the findings of Chrisophe Faisy, MD, PhD, of the European Georges Pompidou Hospital at the Public Assistance Hospital in Paris, France, and colleagues.

The researchers used the DIABLO study to investigate whether acetazolamide reduces the time patients who are critically ill and have chronic obstructive pulmonary disease require mechanical ventilation. The DIABLO study was “a randomized, double-blind, multicenter trial” according to the authors, and was conducted from October 2011 through July 2014.

There were 380 study participants, with 187 in the acetazolamide group and 193 in the placebo group. The researchers said that “the total durations of invasive ventilation was a median of 136.5 hours in the acetazolamide group vs 163.0 hours in the placebo group, for a between-group difference of -16.0 hours, which did not differ significantly.” They added that the secondary outcomes including how long it took to wean off of mechanical ventilation, use of tracheotomy, unplanned extubations, and several other factors, did not differ significantly.

Despite the results of the study, the researchers say, “this overall conclusion must be considered with prudence.” They suggest that the study may have lacked the power to demonstrate a statistically significant difference of acetazolamide, and say that “the between-group difference in median durations of invasive mechanical ventilation was clinically substantial (16 hours) although it did not reach statistical significance.”

The authors suggest that the design of the study complicated the interpretation of the results, and say, “Our trial was prospectively powered to detect a 15% difference in the invasive ventilation duration, considered clinically relevant in light of the usual duration of intubation in these patients.” The possible underpowering of the study, along with some limiting factors, such as “the presence of mixed metabolic alkalosis in most patients” according to the researchers.