General medicine/critically appraised topic
Pharmacologic Prophylaxis for Acute Mountain Sickness: A Systematic Shortcut Review

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Study objective

Multiple studies have explored pharmacologic interventions to prevent acute mountain sickness. A systematic review of this subject published in 2000 found that both acetazolamide and dexamethasone were effective. Since 2000, a number of other agents have been reported to be beneficial. This EBEM review evaluates the most current evidence on this topic.

Methods

We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, SPORTDiscus, Emergency Medical Abstracts, and ClinicalTrials.gov from 2000 to July 2011. Only randomized placebo-controlled trials with an N greater than or equal to 50 and systematic reviews were reviewed. Standard criteria for assessing trial quality were independently assessed by 2 authors.

Results

Seven hundred eighty-six citations were retrieved, of which 105 were reviewed in their entirety. Eleven randomized controlled trials and 1 systematic review appeared to meet inclusion criteria; however, 4 randomized controlled trials were excluded for high risk of bias. The remaining 7 randomized controlled trials investigated antioxidants, magnesium, sumatriptan, gabapentin, acetazolamide, and Ginkgo biloba. No trials studying dexamethasone met our criteria. Acetazolamide was associated with a reduction in acute mountain sickness symptoms, with a number needed to treat ranging from 8 to 3 among 3 trials and at doses ranging from 250 to 750 mg daily. Sumatriptan showed benefit in 1 trial (number needed to treat=4), as did gabapentin (number needed to treat=6). Antioxidants, magnesium, and G biloba were not efficacious. Reported adverse events included somnolence with gabapentin and paresthesias with acetazolamide. The systematic review affirmed our results but did not capture trials studying antioxidants, magnesium, sumatriptan, or gabapentin.

Conclusion

Acetazolamide is effective for the prevention of acute mountain sickness but may be associated with paresthesias. Sumatriptan and gabapentin are beneficial but require further study.

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

References (21)

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    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

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    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.

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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.

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