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

 

Abstract

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 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.

 

Plain language summary

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.

 

摘要

背景

碳酸酐酉每抑制劑(carbonic anhydrase inhibitors)在慢性阻塞性肺病高碳酸血症呼吸衰竭的治療

碳酸酐酉每抑制劑(如acetazolamide)引起輕度代謝酸中毒，可能會刺激呼吸。有些嚴重慢性阻塞性肺病患者會出現慢性高碳酸血症呼吸衰竭。理論上，這些病人應該可以從這類藥物獲益，因為這類藥物下降動脈二氧化碳分壓(PCO2)、提高氧氣分壓(PO2)。

目標

確定acetazolamide在慢性阻塞性肺病造成的高碳酸血症呼吸衰竭的療效和安全性。

搜尋策略

以預先定義好的字彙搜尋Cochrane Airways Group Specialised Register。目前搜尋到2007年10月。

選擇標準

本回顧納入的試驗是針對因慢性阻塞性肺病導致穩定慢性呼吸衰竭的患者所進行的安慰劑對照試驗。

資料收集與分析

兩位審查員(PJ和MG)擷取並分析資料，且經由共識達成協議。匯集的數據以固定效應模式(fixed effects model)進行分析，報告以加權平均差(WMD)及其95%信賴區間(CI)表示。

主要結論

本回顧納入四個研究。其中兩個為隨機平行研究，一個是交叉研究，另一個則為序列設計。共84個病患。研究品質不一，且為時很短(一般是兩週)。所有研究所顯示的作用方向和大小都差不多。在隨機平行研究中，acetazolamide引起代謝性酸中毒，PCO2下降但不明顯(加權平均差0.41kPa；95%信賴區間0.91，0.09；N = 2)，PO2則有顯著的上升(加權平均差1.54kPa；95%信賴區間0.97，2.11；N = 2)。其中一個研究報告指出：睡眠狀況改善，但沒有其他相關結果(如：健康狀況、症狀、發作率、住院或死亡等)的數據。少有副作用方面的報告。2005年10月所做的更新搜尋沒有找到任何進一步的研究。

作者結論

Acetazolamide造成動脈PO2稍微上升、PCO2下降。這些結論來自於少數幾個小規模的短期研究，而且這些研究品質參差不齊。目前不確定這樣的生理改善是否與臨床效益有關。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

對慢性阻塞性肺病導致呼吸衰竭的病患，acetazolamide可能改善血中的氧氣濃度；但還需要更多的試驗。有些末期慢性肺病(慢性阻塞性肺病、慢性支氣管炎或肺氣腫)患者會出現呼吸衰竭。這牽涉到身體的化學變化，可能因此降低呼吸驅動力。Acetazolamide藥物用於高山症，在某些情況下可以刺激呼吸。本回顧發現：使用acetazolamide短短數日即可改善慢性阻塞性肺病患者的血氧濃度。目前還不清楚這是否會導致較好的結果，還需要更多的研究證實。至於本藥的安全性，則沒有足夠的相關數據。