General medicine/critically appraised topicPharmacologic Prophylaxis for Acute Mountain Sickness: A Systematic Shortcut Review
Section snippets
Clinical Scenario
You are excited to spend winter break leading a group of medical students on a trip from Indianapolis, IN (elevation 823 ft, or 251 m), to Breckenridge, CO (base elevation 9,600 ft, or 2,926 m), for a week of skiing and snowboarding. You plan to fly into Denver and drive to Breckenridge on day 1. Because the trip is short, you do not want to spend the first few days dealing with complaints of headache, nausea, fatigue, and dizziness that are common among travelers to altitude. Several of the
Formulating the Question
The clinical question is, In adult patients who travel to high elevations, is there a pharmacologic intervention that safely prevents the symptoms of acute mountain sickness?
Slow ascent, allowing ample time for acclimatization, is accepted by consensus and has been shown in practice to effectively prevent acute mountain sickness.2 However, this simple nonpharmacologic intervention is not feasible for those who travel rapidly to high altitude.
Acute mountain sickness most frequently occurs at
Searching for and Selecting the Best Evidence
Because the mountain sickness literature is relatively limited, we searched broadly for studies dealing with either prevention or treatment that were comparative by design or included a control group. Studies focusing on prevention were then manually selected from these results.
The following databases (interfaces) were searched without language restrictions: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, SPORTDiscus, Emergency Medical Abstracts,5 and ClinicalTrials.gov.
Description of the trials
A description of the key elements for the 7 included randomized controlled trials is summarized in Table 1. The studies were conducted in the mountains of Nepal, Bolivia, Italy, and Iran. The subjects in each trial were all adult travelers vacationing or trekking in a given location, offering the benefit of controlling for altitude within each trial. The exclusion criteria for trial subjects were clearly described in 6 of the 7 studies.9, 10, 14, 15, 16, 17 The trial by Baillie et al,18 which
Applying the Evidence
In the initial clinical scenario, the clinician seeks pharmacologic interventions that will safely and effectively prevent acute mountain sickness. The last large systematic review, by Dumont et al1 in 2000, found 2 interventions to be efficacious in the prevention of acute mountain sickness, dexamethasone and acetazolamide. However, the dose of acetazolamide recommended by this review was quite high, 750 mg daily, which may have resulted in an increased risk for uncomfortable adverse effects.
Patient Communication
Traveling to altitude carries the inconvenient and often unsuspected risk of developing acute mountain sickness. Physicians should be prepared for a discussion with patients, colleagues, and friends about potential interventions that can prevent the symptoms and negative consequences of acute mountain sickness. Along with discussing methods of prevention, including slow ascent, physicians need to provide patients with information on available pharmacologic interventions. Reviewing the patient's
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Cited by (30)
A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention
2020, American Journal of MedicineCitation Excerpt :The carbonic anhydrase inhibitor acetazolamide is the most common medication used globally for prevention of acute mountain sickness,1-3 a debilitating illness common in the tens of millions who annually ascend to high altitude. Acetazolamide has been examined in more than 200 high-altitude studies in the past 50 years,4 with the lowest effective dose for acute mountain sickness prevention found to be 125 mg twice daily, beginning the day or evening prior to ascent.5-9 A recent trial found acetazolamide 62.5 mg twice daily non-inferior to 125 mg for prevention of acute mountain sickness,10 but the low incidence of disease caused the study to be underpowered, leading to an inadequate effect size and limiting any definitive conclusions.11,12
Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial)
2019, Wilderness and Environmental MedicineCitation Excerpt :In Europe, anonymously collected urine from male climbers on Mont Blanc tested positive for acetazolamide in 21% of samples,21 indicating that acetazolamide use is prevalent in European high-altitude areas as well. Six meta-analyses to date have reviewed the literature on acetazolamide.22–27 The most recently published meta-analysis27 established that doses of 750 mg, 500 mg, and 250 mg per day are all effective with numbers needed to treat of 3, 7, and 6, respectively.
Diuretics
2014, Side Effects of Drugs AnnualCitation Excerpt :In a randomised crossover high-altitude study, one of the patients complained of dyspepsia while on oral acetazolamide (500 mg per day) at 1860 m who recovered after antacid therapy [2]. Urinary System Increased urinary frequency was commonly identified with higher daily dose of oral acetazolamide 500 or 750 mg [1,3,4]. Eyes As a sulphonamide-derived drug, acetazolamide was shown to cause secondary angle-closure glaucoma (ACG) with choroidal effusion and anterior lens-iris displacement in three patients.
Physiology and Pathophysiology of Diuretic Action
2013, Seldin and Geibisch's The KidneyNrf2 activation: A potential strategy for the prevention of acute mountain sickness
2013, Free Radical Biology and MedicineCitation Excerpt :This is an important issue that will need to be addressed in a clinical study. Acetazolamide, a CAI, is considered standard of care therapy for AMS [2,3,26,27]. However, our data showed that it was not a Nrf2 activator.
Physiology and Pathophysiology of Diuretic Action
2012, Seldin and Giebisch's The Kidney: Physiology and Pathophysiology
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist.