Acetazolamide's Effect on Mechanical Ventilation Duration in COPD Patients

The carbonic anhydrase inhibitor acetazolamide (Diamox) has been used to stimulate ventilation in patients with chronic obstructive pulmonary disease (COPD) in the past, but until recently, no randomized trial with a placebo or sample size large enough had been conducted to confirm the drug’s effectiveness.

The recent DIABOLO study, conducted in France between 2011 and 2014, failed to support the hypothesis that higher doses of acetazolamide would lead to a shorter duration of time that mechanical ventilation would be necessary in critically ill COPD patients—but results, published in JAMA, suggested that acetazolamide could still be beneficial.

The randomized, double-blind trial sorted 382 COPD patients who were expected to receive mechanical ventilation for more than 24 hours into either a placebo group or experimental group to receive acetazolamide. All patients remained on invasive mechanical ventilation until they demonstrated tolerance to breathing-trial criteria. Weaning off of mechanical ventilation was considered successful when patients did not require re-ventilation within 48 hours of its termination.

Trial results found no statistically significant difference in duration of mechanical ventilation between those taking acetazolamide and those taking placebo. Out of the 380 patients who continued the IV intervention until the end of their intensive care unit stay, median duration for the acetazolamide group was 136.5 hours compared with 163 hours for the placebo group. The duration of weaning off mechanical ventilation was also similar in the 2 groups, as were daily changes of minute-ventilation and partial carbon-dioxide pressure in arterial blood. In the acetazolamide group, there were significantly greater decreases in daily serum bicarbonate change and number of days with metabolic alkalosis.

However, according to main study author Christophe Faisy, MD, PhD and the other researchers, the magnitude of the difference (16 hours) was still clinically significant:

“This overall conclusion must be considered with prudence,” the authors wrote. “Indeed, the study may have identified a clinically important benefit of acetazolamide for the primary endpoint that did not demonstrate statistically statistical significance because of a possible lack of power.”

Another limitation could have been in part due to acetazolamide’s mechanism of action (carbonic anhydrase enzyme inhibitor) being dependent on level of metabolic alkalosis.

“The lack of acetazolamide respiratory effect may be because so many of the patients had a degree of metabolic alkalosis too mild for the intervention,” authors wrote.

Though this study did not prove its hypothesis, it is still important in providing a foundation for powering future studies. In critically ill patients, any delay in the removal of mechanical ventilation provides more of a risk for complications such as development of pneumonia, airway trauma, and higher mortality. Therefore, it is vital for healthcare professionals to optimize ventilator use in patients—and this trial was an important first step towards one day discovering that optimization.