Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease.

BACKGROUND

Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary disease (COPD) develop chronic hypercapnic ventilatory failure. In theory, they may benefit from use of these drugs with a fall in arterial carbon dioxide level (PCO2) and a rise in arterial oxygen (PO2).

OBJECTIVES

To determine the effectiveness and safety of acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD SEARCH STRATEGY: The Cochrane Register of Controlled Clinical Trials was searched along with Medline, Embase, Central and CINAHL for relevant randomised control trials.

SELECTION CRITERIA

Trials were included in the review provided they were placebo controlled, carried out in patients with stable chronic ventilatory failure due to COPD.

DATA COLLECTION AND ANALYSIS

Data were extracted and analysed by two reviewers (PJ and MG) and agreement was reached by consensus. Where data could be aggregated they were analysed using a fixed efefcts model and reported as a weighted mean difference (WMD) and its associated 95% confidence interval (95% CI).

MAIN RESULTS

Four trials were included in the review. Of these, two were randomised parallel studies, one was a crossover study and the other had a sequential design. A total of 84 patients were involved. Study quality was mixed and the studies were short (typically two weeks). All studies showed a similar direction and size of effect. In the randomised parallel studies, acetazolamide caused a metabolic acidosis and produced a non-significant fall in PCO2 (WMD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (WMD 1.54 kPa; 95% CI 0.97, 2.11; N=2). One study reported an improvement in sleep but there were no data concerning outcomes such as health status, symptoms, exacerbation rate, hospital admissions or deaths. Side effects were reported infrequently.

REVIEWER'S CONCLUSIONS: Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.