The DIABOLO Study: Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease

Catherine Lister,  Mercer University College of Pharmacy

It is stated that delays in discontinuation of mechanical ventilation lead to an increased risk of complications, including pneumonia and airway trauma.  Guidelines suggest that once the condition that warranted mechanical ventilation has resolved, the ventilator should be removed as quickly as possible. [1]

Undue delay in ventilator discontinuation is stated to lead to longer hospitalization, iatrogenic lung injury, sedation, and higher mortality. [2]

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease
Design Randomized, clinical trial; N= 382
Objective To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with Chronic Obstructive Pulmonary Disease (COPD) and metabolic alkalosis
Study Groups Acetazolamide (n= 187), placebo group (n= 193)
Methods Patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of intensive care unit (ICU) admission, and continued during the ICU stay for a maximum of 28 days.  Patients satisfying spontaneous breathing-trial criteria were extubated and received supplemental oxygen to achieve arterial oxygen saturation of 90% or more.  Weaning was considered successful when reintroduction of invasive ventilation was not required within 48 hours after its termination.  Simplified acute physiology score (SAPS) indicates severity of disease, and sequential organ failure assessment (SOFA) indicates severity of organ failure.
Duration October 2011 through July 2014
Primary Outcome Measure The duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy
Baseline Characteristics Characteristic Acetazolamide (Mean) Placebo (Mean)
Age (year) 69 69
Men (%) 70 73.1
SAPS II score 49.4 50
SOFA score 7.2 7.1
Body Mass Index (kg/m2) 27.2 26.7
Blood pH 7.32 7.30
Serum Bicarbonate (mEq/L) 26.9 27.4
Results Acetazolamide Placebo Difference
Total duration of invasive mechanical ventilation 136.5 hours 163.0 hours -16.0 hours, (95% CI -36.5 to 4.0 hours)
Adverse Events Common Adverse Events: None reported
Serious Adverse Events: Events requiring intensive care procedures (0.03%)
Percentage that Discontinued due to Adverse Events: None reported
Study Author 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.

This article investigated the affect of acetazolamide on the length of invasive mechanical ventilation in patients with COPD and metabolic acidosis because acetazolamide is commonly used as a respiratory stimulant in this patient population. No statistical difference in length of invasive mechanical ventilation was found. However, the authors felt the difference of 16 hours was clinically significant, and that overestimating the duration of mechanical ventilation when powering the study may have contributed to the lack of statistical significance.  This study could provide the foundation for further studies powered to capture a 16 hour difference in length of invasive mechanical ventilation.

References

  1. MacIntyre NR. Evidence-Based Guidelines for Weaning and Discontinuing Ventilatory Support: A Collective Task Force Facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest; 2001: 120(6) 375s-395s.
  2. Macintyre NR. The ventilator discontinuation process: an expanding evidence base. Respir Care. 2013;58(6):1074-86.
  3. Faisy C, Meziani F, Planquette B, et al. Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial. JAMA. 2016;315(5):480-8.
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