Acetazolamide for the prevention of acute mountain sickness: a systematic review and meta-analysis

Abstract

Background:
Acute mountain sickness (AMS) is a frequent complication among individuals ascending rapidly to high altitude and, if unrecognised or untreated, may progress to life-threatening high-altitude cerebral or pulmonary edema. Prophylactic pharmacotherapy is recommended for high-risk travellers, and acetazolamide is the most widely used agent. However, variability in trial designs and dosing regimens has led to ongoing uncertainty about the magnitude of benefit.
Objectives:
To evaluate the effectiveness of acetazolamide, compared with placebo, in preventing AMS in individuals ascending to high altitude.
Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing acetazolamide with placebo for AMS prevention. Electronic databases (PubMed, Ovid, Cochrane Library, Scopus and MEDLINE) were searched from inception to 2024 using the terms “acetazolamide”, “acute mountain sickness” and “prevention”. Studies enrolling participants at risk of AMS and reporting AMS incidence as a primary outcome were eligible. Duplicate publications and studies assessing only outcomes other than AMS prevention were excluded. Data were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using RevMan 5.4. Heterogeneity was quantified with the I² statistic. Risk of bias was assessed with theCochrane Risk of Bias (RoB-1) tool and visualised using robvis.
Results:
From 184 records identified, 25 RCTs, including 2,433 participants, met eligibility criteria. Compared with placebo, acetazolamide significantly increased the proportion of participants who remained free of AMS (pooled RR for being AMS-free 1.20; 95% CI 1.12–1.29; p < 0.00001). Moderate statistical heterogeneity was observed (I² = 54%; p for heterogeneity = 0.0008), indicating variability in effect estimates across trials, but the direction of effect consistently favoured acetazolamide.
Conclusions:
This meta-analysis of 25 randomized trials demonstrates that acetazolamide prophylaxis is effective in reducing the risk of AMS in individuals ascending to high altitude. In the absence of contraindications, acetazolamide should be considered as a key pharmacological strategy for AMS prevention in at-risk travellers, alongside gradual ascent and other non-pharmacological measures.