Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, California, USA
Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, California, USA.
BMJ Open Respir Res. 2020 Apr;7(1). doi: 10.1136/bmjresp-2020-000557.
Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our objective was to estimate the risk of commonly reported side effects based on meta-analyses. We hypothesised that these risks are dose-dependent.
We queried MEDLINE/EMBASE (Medical Literature Analysis and Retrieval System Online/Excerpta Medica dataBASE) up until 04/10/2019, including any randomised placebo-controlled trial in which adults received oral AZM versus placebo reporting side effects. Eligibility assessment was performed by two independent reviewers. Data were abstracted by one reviewer who verified key entries at a second time point. For side effects reported by 3 studies a pooled effect estimate was calculated, and heterogeneity assessed via I; for outcomes reported by 5 studies effect modification by total daily dose (EMbyTDD; <400 mg/d, 400-600 mg/d, >600 mg/d) was assessed via meta-regression. For pre-specified, primary outcomes (paraesthesias, taste disturbances, polyuria and fatigue) additional subgroup analyses were performed using demographics, intervention details, laboratory changes and risk of bias.
We included 42 studies in the meta-analyses (N=1274/1211 in AZM/placebo groups). AZM increased the risk of all primary outcomes (p<0.01, I ≤16% and low-to-moderate quality of evidence for all)-the numbers needed to harm (95% CI; n) for each were: paraesthesias 2.3 (95% CI 2 to 2.7; n=39), dysgeusia 18 (95% CI 10 to 38, n=22), polyuria 17 (95% CI 9 to 49; n=22), fatigue 11 (95% CI 6 to 24; n=14). The risk for paraesthesias (beta=1.8 (95% CI 1.1 to 2.9); P=0.01) and dysgeusia (beta=3.1 (95% CI 1.2 to 8.2); P=0.02) increased with higher AZM doses; the risk of fatigue also increased with higher dose but non-significantly (beta=2.6 (95% CI 0.7 to 9.4); P=0.14).
This comprehensive meta-analysis of low-to-moderate quality evidence defines risk of common AZM side effects and corroborates dose dependence of some side effects. These results may inform clinical decision making and support efforts to establish the lowest effective dose of AZM for various conditions.
乙酰唑胺（AZM）用于各种病症（例如高原病、睡眠呼吸暂停、青光眼），但其治疗常因副作用而受限。我们的目的是基于荟萃分析评估常见不良反应的风险。我们假设这些风险与剂量有关。
我们检索了 MEDLINE/EMBASE（在线医学文献分析与检索系统/Excerpta Medica dataBASE），截至 2019 年 10 月 4 日，包括了所有接受口服 AZM 与安慰剂治疗并报告不良反应的成人随机安慰剂对照试验。两名独立评审员进行了资格评估。由一名评审员摘录数据，然后在第二个时间点进行关键条目核对。对于 3 项研究报告的不良反应，我们计算了汇总效应估计值，并通过 I 评估了异质性；对于 5 项研究报告的结局，我们通过亚组分析评估了总日剂量（<400mg/d、400-600mg/d、>600mg/d）的效应修饰。对于预先指定的主要结局（感觉异常、味觉障碍、多尿和疲劳），我们使用人口统计学、干预措施细节、实验室变化和偏倚风险进行了额外的亚组分析。
我们纳入了 42 项荟萃分析研究（AZM/安慰剂组各 1274/1211 例）。AZM 增加了所有主要结局的风险（p<0.01，I≤16%，所有结局的证据质量为低到中度）-危害人数比（95%置信区间；n）分别为：感觉异常 2.3（95%置信区间 2 至 2.7；n=39）、味觉障碍 18（95%置信区间 10 至 38，n=22）、多尿 17（95%置信区间 9 至 49；n=22）、疲劳 11（95%置信区间 6 至 24；n=14）。感觉异常（β=1.8（95%置信区间 1.1 至 2.9）；P=0.01）和味觉障碍（β=3.1（95%置信区间 1.2 至 8.2）；P=0.02）的风险随 AZM 剂量增加而增加；疲劳的风险也随剂量增加而增加，但无统计学意义（β=2.6（95%置信区间 0.7 至 9.4）；P=0.14）。
本低到中度质量证据的综合荟萃分析定义了 AZM 常见不良反应的风险，并证实了一些不良反应与剂量有关。这些结果可能有助于临床决策，并支持为各种病症确定 AZM 的最低有效剂量。
