Duration of mechanical ventilation in COPD

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Among mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, administration of the respiratory stimulant acetazolamide did not significantly reduce the duration of invasive mechanical ventilation, according to a study.

Chronic obstructive pulmonary disease is a frequent cause of intensive care unit (ICU) admission. Non-invasive mechanical ventilation has altered the outcomes of patients with acute COPD exacerbation by reducing the need for intubation. Nevertheless, patients with COPD may still require invasive mechanical ventilation when non-invasive ventilation fails. Acetazolamide has been used for decades as a respiratory stimulant for patients with COPD and metabolic alkalosis (an increase in the alkalinity of body fluids due to an increase in alkali intake or a decrease in acid concentration), but no large randomised placebo-controlled trial has been available to confirm this approach.

Dr Christophe Faisy, of the European Georges Pompidou Hospital, Paris, and colleagues randomly assigned 382 patients with COPD who were expected to receive mechanical ventilation for more than 24 hours to acetazolamide (500-1000 mg, twice daily) or placebo, administered intravenously in cases of pure or mixed metabolic alkalosis. Treatment was initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days; 380 patients were included in an intention-to treat analysis. The study was conducted from October 2011 through July 2014 in 15 ICUs in France. The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy.

Among 382 randomised patients, 380 completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours), duration of weaning off mechanical ventilation (-0.9 hours), or for other respiratory parameter-values (respiratory frequency, tidal volume, and minute ventilation), although daily changes of serum bicarbonate and number of days with metabolic alkalosis decreased significantly more in the acetazolamide group.

Secondary outcomes, such as adverse events, use of non-invasive ventilation after extubation, the duration of ICU stay, and in-ICU mortality, did not differ significantly between groups.

The authors note that the primary finding of this study (duration of invasive mechanical ventilation) must be considered with prudence. “Indeed, the study may have identified a clinically important benefit of acetazolamide for the primary end point that did not demonstrate statistical significance because of a possible lack of power.2

Abstract
Importance: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach.
Objective: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis.
Design, Setting, and Participants The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis.
Interventions: Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days.
Main Outcomes and Measures: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes 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.
Results: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (−16.0 hours; 95% CI, −36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (−0.9 hours; 95% CI, −4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (−0.0 L/min; 95% CI, −0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (−0.3 mm Hg; 95% CI, −0.8 to 0.2 mm Hg; P = .25), although daily changes of 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. Other secondary outcomes also did not differ significantly between groups.
Conclusions and Relevance: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance.

JAMA material
JAMA abstract


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