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.

BACKGROUND: Acute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study. METHODS: Before their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of > 3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at ClinicalTrials.gov: NCT03154645 RESULTS: Ninety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI],-11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P =.8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67-0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P =.001). CONCLUSION: Ibuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease. (C) 2018 Elsevier Inc. All rights reserved.

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.

BACKGROUND: Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide. METHODS: This double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire = 3 and another symptom). RESULTS: A total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups (P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4. CONCLUSION: Budesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent. (c) 2018 Elsevier Inc. All rights reserved.

Luks, Andrew M., Colin Grissom, Luanne Freer, and Peter Hackett. Medication use among mount Everest climbers: practice and attitudes. High Alt Med Biol. 17:315-322, 2016.-The lay public, media, and medical experts have expressed concern about the ethics of climbers using medications to improve performance and increase the odds of summit success while climbing at high altitude, but the true incidence of this practice remains unclear. We conducted an anonymous survey of climbers who have attempted to climb Mt. Everest to gather information about medication use and attitudes toward medication and supplemental oxygen use while climbing the mountain. One hundred eighty-seven individuals completed the survey, providing information about medication and oxygen use for 262 expeditions to Mt. Everest between 1963 and 2015, the majority of which occurred after the year 2000. The majority of respondents were male (82%) and from English-speaking countries (75%). Medications were used on 43% of climbs, with acetazolamide being the most commonly used medication. Reported use of dexamethasone, nifedipine, sildenafil, or tadalafil was uncommon as was use of multiple medications at the same time. The majority of respondents indicated that it was acceptable for climbers to use medications and supplemental oxygen to prevent altitude illness while climbing Mt. Everest. Opinions were more mixed regarding whether summiting without the use of medications or oxygen carried the same value as reaching the summit using those interventions. Our data suggest that less than one-half of Mt. Everest climbers use medications during their expedition, with the primary medication used being acetazolamide, for prevention of altitude illness. Given the limitations of the study design and preliminary nature of these data, further research is warranted to further clarify these issues.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the original guidelines published in Wilderness & Environmental Medicine 2011;22(2):156-166.