EFFICACY AND SAFETY OF ACETAZOLAMIDE FOR HYPERCAPNIC RESPIRATORY FAILURE ASSOCIATED WITH METABOLIC ALKALOSIS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
CCCF ePoster library. Barbon C. Oct 2, 2017; 198104
Carla Emille D. Barbon
Carla Emille D. Barbon
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EFFICACY AND SAFETY OF ACETAZOLAMIDE FOR HYPERCAPNIC RESPIRATORY FAILURE ASSOCIATED WITH METABOLIC ALKALOSIS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Barbon, Carla Emille D., M.D.1, Ortal, Abigail Z., M.D.1, Duya, Jose Eduardo DL, M.D.1,2, Maghuyop, Norman, M.D.1,2,3

1Department of Medicine, Philippine General Hospital, Manila, Philippines; 2Philippine College of Physicians, Manila, Philippines; 3Philippine College of Chest Physicians, Manila, Philippines

 


Background:  Patients with COPD can develop respiratory acidosis and metabolic alkalosis, with the latter causing impaired ventilation. Acetazolamide, a carbonic anhydrase inhibitor, can be used to stimulate breathing by producing mild metabolic acidosis, thereby theoretically reducing the duration of mechanical ventilation.
 
Research question: Among COPD patients with hypercapnic respiratory failure, how effective is acetazolamide compared to placebo in reducing the duration of mechanical ventilation, the length of ICU stay, and ICU mortality?
 
Research objective: To determine the effectiveness and safety of acetazolamide use among COPD patients with hypercapnic respiratory failure
 
Selection criteria: Studies included are randomized clinical trials in patients with COPD and hypercapnic respiratory failure which compared the use of acetazolamide versus placebo measuring the following outcomes: duration of mechanical ventilation, length of intensive care unit (ICU) stay, ICU mortality, and arterial blood gas (ABG) parameters including change in pH, PaCO2, PaO2, and bicarbonate (HCO3).

Search methods: Various research databases were searched using the following terms (MeSH): “acetazolamide”, “pulmonary disease, chronic obstructive”, “mechanical ventilation”, “hypercapnia”, “respiratory failure’, “respiratory insufficiency, “ventilator weaning”. Any unpublished data were obtained by correspondence with the authors.
 
Data extraction and analysis: The authors independently extracted trial characteristics, patient characteristics, intervention characteristics, and outcome data. The risk of bias of the included studies was assessed using the Cochrane risk of bias tool. Data were analysed using Review Manager 5.3 with continuous outcomes reported as mean differences ± standard deviation and dichotomous outcomes as relative risks using 95% confidence intervals.
 
Results:  Three randomized placebo-controlled trials were included in the analysis, with a total of 499 patients (246 received acetazolamide and 251 received placebo). All trials were assessed to have low overall risk of bias. A trend towards benefit with acetazolamide use was seen in the clinical outcomes of duration of mechanical ventilation, length of ICU stay, and all-cause mortality, but was not statistical significant. Acetazolamide did not induce significant changes in pH and PaCO2, but produced a mild improvement in hypoxemia by increasing PaO2 (MD 0.48 kPa; 95% CI 0.15, 0.82; P = 0.004).  There was no statistically significant difference in serious adverse effects experienced with acetazolamide compared to placebo. The most common adverse effects were nausea or diarrhea (N = 5) and fatigue (N = 4).
 
Conclusions: A decrease in number of hours in mechanical ventilation, number of days in the ICU, and number of deaths from any cause is seen with acetazolamide use in COPD patients with ventilatory failure, but the small sample sizes of identified trials does not show these to be statistically significant. Acetazolamide is not shown to improve blood gas parameters apart from a small improvement in oxygenation. Its use in such patients cannot be recommended yet based on currently available data. More large-scale randomized controlled trials on acetazolamide use are needed.

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