Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease: Cochrane systematic review
Assessed as up to date: 2010/10/27
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 methods
The Cochrane Airways Group Specialised Register was searched with predefined search terms. Searches were current as of October 2010.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 effects model and reported as a weighted mean difference (MD) 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 (MD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (MD 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. An update search conducted in October 2005 did not identify any further studies.Authors' 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.
Jones Paul, Greenstone Michael
Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease
Some people with advanced chronic lung disease (COPD - chronic bronchitis or emphysema) can experience breathing failure. This involves chemical changes which in turn can lower the drive to breathe. The drug acetazolamide is used for mountain sickness, and it can stimulate breathing in some circumstances. The review of trials found that a few days of using acetazolamide can improve the level of oxygen in the blood of people with COPD. It is not clear if this leads to better outcomes, so more research is needed. Not enough data were reported on the safety of the drug.
Implications for practice
Short-term clinical trial data suggest that acetazolamide has a small beneficial effect on arterial PCO2 and PO2. There is no evidence of other clinical benefits. The drug appears to be well tolerated, with few side-effects over two weeks in a dose of 250 mg twice daily, so may be considered in patients with chronic hypercapnic ventilatory failure.
Implications for research
Well-controlled randomised longer-term studies are required. Such studies should measure symptoms, sleep, health status, need for LTOT, exacerbation frequency, hospitals admissions and deaths. They would need to be multi-centred and have adequate power to detect a difference between the two treatments and sufficiently resourced to accommodate the lengthy follow-up period (between three and five years).Get full text at The Cochrane Library
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