Acetazolamide Does Not Facilitate Weaning in Patients with COPD

Abstract & Commentary

By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.

Synopsis: This case-control study of 26 mechanically ventilated patients with severe COPD and metabolic alkalosis demonstrated that daily doses of acetazolamide caused a modest decrease in serum bicarbonate levels but had no effect on the duration of weaning or any other examined outcome.

Source: Faisy C, et al. Effectiveness of acetazolamide for reversal of metabolic alkalosis in weaning COPD patients from mechanical ventilation. Intensive Care Med 2010 Mar 9; Epub ahead of print.

This clinical study was carried out to test the hypothesis that acetazolamide (Diamox®) would correct metabolic alkalosis and facilitate weaning in intubated patients with severe chronic obstructive pulmonary disease (COPD) who had elevated serum bicarbonate and were alkalemic. The authors enrolled 26 patients with COPD and acute respiratory failure (causes not stated) who had been hypercapnic (PCO2, 77 ± 22 mmHg) and acidemic (pH, 7.25 ± 0.10) at the time of intubation. They were considered to be ready to wean from ventilatory support when there had been resolution of the acute process for which the patient was intubated, were receiving no sedation and had a Glasgow Coma Scale Score > 12, had an adequate cough and absence of excessive secretions, were afebrile and hemodynamically stable, and had no significant abnormalities in plasma electrolytes and serum glucose levels. For weaning, the patients were also required to have a respiratory rate ≤ 35 breaths/min, to be on ≤ 50% oxygen and ≤ 8 cm H2O of positive end-expiratory pressure with PaO2/F1O2 ≥ 150 mmHg, and to have "no significant respiratory acidosis" (not further defined).

Once these criteria were met the patients received a single daily intravenous infusion of acetazolamide, 500 mg. Weaning was carried out via progressive reduction of pressure support and/or daily T-piece trials. Weaning success as well as bicarbonate levels and arterial blood gas values were recorded and compared with those of a 1:1 historical control group managed in the same ICU using the same protocols who were matched for demographics, pulmonary function, and other factors but did not receive acetazolamide.

There were no statistically significant differences between the acetazolamide patients and the controls with respect to age, gender, BMI, FEV1 (35% and 37% of predicted, respectively), baseline COPD management, ventilator management, arterial blood gases (pH 7.45 and 7.44; PCO2 48 and 50 mmHg), or serum bicarbonate (34.5 and 32.5 mmol/L) at the time of readiness to wean. Acetazolamide was administered for a mean of 4 days (range, 1-11 days) in the experimental group, whose serum bicarbonate values decreased significantly (mean, 3.8 mmol/L; P = 0.01) by the time of extubation. However, serum bicarbonate, PCO2, and pH were no different between the experimental and control patients at the time of extubation. There were no significant differences in any other evaluated outcome variable — duration of weaning, total number of days ventilated, extubation success, use of non-invasive ventilation as rescue, or re-intubation rate — between the acetazolamide and historical control groups.

Commentary

This case-control study showed that the administration of acetazolamide to patients with severe COPD who were recovering from acute respiratory failure and who were alkalemic but otherwise considered ready for weaning had no effect on outcome except for a somewhat lower serum bicarbonate level. Acetazolamide (Diamox) is a carbonic anyhdrase inhibitor that essentially causes metabolic acidosis. It has been used for many years to stimulate respiratory drive and to counter elevated bicarbonate levels, and it continues to be administered to patients with COPD in an attempt to facilitate ventilator weaning by reducing alkalemia. However, even theoretically the rationale is shaky. Patients with severe COPD and underlying chronic hypercapnia need their compensatory metabolic alkalosis in order to ameliorate the acidemia that would exist without the elevated serum bicarbonate. If such patients were to maintain a normal pH in the face of a "normal" bicarbonate, they would also have to normalize alveolar ventilation and PCO2, something that may not be feasible physiologically, at least during recovery from acute respiratory failure.

A fundamental aspect of managing patients with severe COPD who require intubation and mechanical ventilation is to avoid over-ventilation and alkalemia. When the latter occurs, the depressant effect of alkalosis on ventilatory drive is often cited as a rationale for using acetazolamide to decrease serum bicarbonate. However, patients with COPD who fail weaning nearly always manifest rapid shallow breathing and respiratory distress, signs of inadequate mechanical capabilities rather than diminished drive to breathe. In any event, although its case-control design is problematic, this study failed to demonstrate any clinically relevant effect of acetazolamide on weaning. This agent does not appear to be helpful in weaning patients with COPD from mechanical ventilation.