title: Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01627639.
authors.affiliation: European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Faisy
authors.affiliation: Nouvel Hôpital Civil, Medical Intensive Care Unit, Hôpitaux Universitaires de Strasbourg and EA 7293, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University, Strasbourg, France.
authors.forename: Ferhat
authors.initials: F
authors.lastname: Meziani
authors.affiliation: André Mignot Hospital, Medico-Surgical Intensive Care Unit, Le Chesnay, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Planquette
authors.affiliation: Limoges University Hospital, Medical Intensive Care Unit, Limoges, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Clavel
authors.affiliation: Rennes University Hospital, Medical Intensive Care Unit, Rennes, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gacouin
authors.affiliation: Le Raincy-Montfermeil Hospital, Medical Intensive Care Unit, Montfermeil, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bornstain
authors.affiliation: Hautepierre Hospital, Strasbourg, Medical Intensive Care Unit, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Schneider
authors.affiliation: Pitié-Salpêtrière Hospital, Department of Respiratory and Intensive Care Medicine, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Duguet
authors.affiliation: Nancy University Hospital, Medical Intensive Care Unit, Nancy, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
authors.affiliation: Angers University Hospital, Medical Intensive Care Unit, Angers, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lerolle
authors.affiliation: Louis-Mourier Hospital, Medico-Surgical Intensive Care Unit, Colombes, France.
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Ricard
authors.affiliation: European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sanchez
authors.affiliation: Tenon Hospital, Medico-Surgical Intensive Care Unit, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Djibre
authors.affiliation: Poissy-Saint Germain Hospital, Medical Intensive Care Unit, Poissy, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Ricome
authors.affiliation: Cochin Hospital, Medical Intensive Care Unit, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Rabbat
authors.affiliation: European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Heming
authors.affiliation: Cochin Hospital, Medical Intensive Care Unit, Paris, France.
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.affiliation: European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Esvan
authors.affiliation: European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Katsahian
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000368:Aged; D000472:Alkalosis, Respiratory / Q000097:blood / Q000628:therapy*; D001639:Bicarbonates / Q000097:blood; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000628:therapy*; D012121:Respiration, Artificial / Q000379:methods / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome; D015300:Ventilator Weaning / Q000706:statistics & numerical data
chemical_list: D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D000086:Acetazolamide