Day of Ascent Dosing of Acetazolamide for Prevention of Acute Mountain Sickness

Abstract

Background: Acetazolamide is the most common medication used for prevention of acute mountain sickness (AMS), usually administered the day or night before ascent. The objective of this study was to evaluate the efficacy of day of ascent dosing of acetazolamide for AMS prevention. Methods: Double-blind, randomized, controlled noninferiority trial of acetazolamide 125 mg twice daily beginning either the night before or the morning of ascent. Healthy low altitude adults ascended from 1240 m (4100 ft) to 3810 m (12,570 ft) during summer 2018 on White Mountain, California. Primary outcome was incidence of AMS with the two different dosing patterns, assessed by the 1993 Lake Louise Questionnaire (LLQ) of ‡3 with headache and a minimum of 1 for other symptom. Results: One hundred four participants completed the study, with 54 (52%) randomized to night before acetazolamide and 50 (48%) to day of ascent dosing, without differences in baseline characteristics. There was 9% greater incidence of AMS in the day of ascent acetazolamide group (48.0% vs. 39%, 95% confidence interval [CI]-11.8 to 30, p = 0.46, number needed to treat [NNT] = 5.6 vs. 3.7), with the CI just surpassing the predetermined 26% noninferiority margin. There was a lower incidence of severe AMS (1993 LLQ >5) in the day of ascent group (n = 5, 10%, NNT = 2.3) compared with night before dosing (n = 12, 22%, NNT = 3.1) (95% CI-28 to 3.6), and lower average symptom severity in the day of ascent group (3 vs. 3.5, 95% CI-0.5 to 1.4). Conclusions: Day of ascent acetazolamide demonstrated higher rates of AMS compared with traditional dosing by a small margin. With similar rates of severe AMS and overall symptom severity, the potential for improved convenience and compliance may support day of ascent use.

Efficacy of acetazolamide for the prophylaxis of acute mountain sickness

“…According to previous arguments,[ 8 21 47 ] we expected to see different treatment effects of acetazolamide with different timing at start of acetazolamide treatment, mode of ascent, timing of AMS assessment, baseline altitude, and endpoint altitude, but these were not demonstrated by our data. Results of meta-regression analysis suggested that the above factors might not have significant influence on the treatment effect of acetazolamide for prevention of AMS.…”

Altitude, Acute Mountain Sickness, and Acetazolamide: Recommendations for Rapid Ascent

“…These authors found only a minimally higher incidence of AMS (i.e., 9%) with the day of ascent dosing versus the traditional night before approach. However, AMS severity was less (10%) for the ''day of ascent'' group compared with the ''night before ascent'' group (22%) (Lipman et al, 2019).…”

“…Common and early occurring dose-dependent adverse reactions to AZ include peripheral paresthesia (notably a tingling sensation in the hands and feet), increased urination (polyuria), loss of appetite, altered taste, particularly of carbonated beverages, and tinnitus (Simancas-Racines et al, 2018;Sridharan and Sivaramakrishnan, 2018). Less common are nausea, headache, and dizziness, which can unfortunately mimic the symptoms of AMS itself (Williamson et al, 2018) as well as GI distress with AZ (Lipman et al, 2019), and possibly occasional drowsiness and confusion (Simancas-Racines et al, 2018). Moderate, but more rare, events include ocular effects such as myopia (Szawarski and Hall-Thompson, 2009).…”

High-altitude illnesses: Old stories and new insights into the pathophysiology, treatment and prevention

“… 126 , 132 , 133 Practically, prophylaxis should be initiated 8–24 h before ascent and continued for 48 h up to the highest altitude reached, 134 but administering acetazolamide on the day of ascent was shown to be similarly effective. 135 If staging is used as the primary acclimatization strategy acetazolamide could safely be used in an on-and-off strategy, taking the before mentioned rules into account.…”