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High altitude cerebral edema (HACE) is a rare complication of ascent to altitudes of over 2500 m (8200 ft). We are not aware of a previously published case report of HACE in a patient under the age of 18 y. We report on 2 cases of suspected HACE in 2 patients, aged 12 and 16 y, who presented to the Manang Himalayan Rescue Association clinic at 3500 m. The 16-y-old patient presented with severe headache, vomiting, and ataxia after rapid ascent to 3800 m. The 12-y-old patient presented with severe headache, vomiting, visual disturbances, and ataxia at 4500 m, which began to resolve with descent to the clinic at 3500 m. Our cases suggest that HACE can occur in children and adolescents. Because there are no specific guidelines for treatment of acute mountain sickness or HACE in patients under the age of 18 y, we recommend treatment as for adults: oxygen, immediate descent, and dexamethasone. Simulated descent in a portable hyperbaric chamber can be used if oxygen is not available and if actual descent is not possible., (Copyright © 2019 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Introduction: North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied., Methods: We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group., Results: Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups., Conclusions: The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness., (Copyright © 2018 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

The Nepal Earthquake of 2015 killed over 8000 people and injured over 20,000 in Nepal. Moments after the earthquake, an avalanche of falling ice came down from above Everest Base Camp (EBC). The air blast created by the avalanche flattened the middle part of EBC, killing 15 people and injuring at least 70. The casualties were initially triaged and treated at EBC and then evacuated by air to Kathmandu for definitive care. There were intermediate stops at the villages of Pheriche and Lukla during which the casualties were offloaded, retriaged, treated, and loaded again for further transport. Most of the authors of this article helped to provide primary disaster relief at EBC, Pheriche, or Lukla immediately after the earthquake. We describe the process by which an ad hoc rescue chain evacuated the casualties. We discuss challenges, both medical and nonmedical, what went well, and lessons learned. We make recommendations for disaster planning in the Khumbu (Everest) region, an isolated high altitude roadless area of Nepal., (Copyright © 2018 Wilderness Medical Society. All rights reserved.)

Objective: This study investigated the impact that motor vehicle travel along a newly constructed road has on altitude illness (including acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema). The new road from Besisahar (760 m) to Manang (3540 m) in Nepal was completed in December 2014., Methods: We enrolled all patients diagnosed with altitude illness at the Himalayan Rescue Association Manang clinic in fall 2016. Phi coefficients were calculated to test for an association between Nepali ethnicity and rapid ascent by motor vehicle. A retrospective review looked at all patients with altitude illness from fall (September-November) 2010 to spring (February-May) 2016., Results: In fall 2016, more than half (54%) of patients with altitude illness traveled to Manang by motor vehicle, and one-third (33%) reached Manang from low altitude (Besisahar) in less than 48 hours. Nepali nationality had a significant association with motor vehicle travel (phi +0.69, P < .0001) as well as with rapid ascent to Manang (phi +0.72, P < .0001). Compared to previous seasons, fall 2016 saw the most patients diagnosed with altitude illness. The proportion of people with altitude illness who traveled by vehicle and reached Manang in less than 48 hours was significantly greater than the proportion prior to completion of the road (P < .0001 for both)., Conclusions: Rapid ascent by the newly constructed road from Besisahar to Manang appears to be related to a significant increase in the number of patients with all forms of altitude illness, especially among Nepalis. The authors believe that educational interventions emphasizing prevention are urgently needed., (Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain., Methods: A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score., Results: Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS., Conclusions: We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed., (Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people., (Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH)., Methods: Double-blind, randomized, placebo-controlled trial., Results: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity)., Conclusions: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS., (Copyright © 2012 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness (AMS), but to date there have been no large randomized trials investigating the efficacy of spironolactone in prevention of AMS. Hence, a prospective, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS., Methods: Participants were sampled from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach (Nepal side) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled, and 251 completed the trial from October to November 2007. Participants were randomly assigned to receive at least 3 doses of spironolactone 50 mg BID, acetazolamide 250 mg BID, or visually matched placebo. A Lake Louise AMS Score of 3 or more, together with the presence of headache and 1 other symptom, was used to evaluate the incidence and severity of AMS. Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache (HAH)., Results: Acetazolamide was more effective than spironolactone in preventing AMS (OR = 0.28, 95% CI 0.12-0.60, p < 0.01). Spironolactone was not significantly different from placebo in the prevention of AMS. AMS incidence for placebo was 20.3%, acetazolamide 10.5%, and spironolactone 29.4%. Oxygen saturation was also significantly increased in the acetazolamide group (83% ± 0.04) vs spironolactone group (80% ± 0.05, p < 0.01)., Conclusions: Spironolactone (50 mg BID) was ineffective in comparison to acetazolamide (250 mg BID) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya., (Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330 m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans. The CBF in Himalayans was slightly elevated compared with sea-level subjects, and was 24% higher compared with Andeans. After correction for hematorit and arterial oxygen saturation, CBF was ∼20% higher in Himalayans compared with Andeans. Altered brain metabolism in Andeans, and/or increased nitric oxide availability in Himalayans may have a role to explain this difference in brain blood flow.

Steroids are used for the prevention and treatment of high-altitude illnesses. However, these agents can cause significant side effects. We report a case of altered mental status, gastrointestinal bleeding, skin rash, and avascular necrosis in a climber taking prophylactic dexamethasone prior to an attempt to climb Mt Everest. High-altitude cerebral edema (HACE), steroid toxicity, and acute adrenal crisis can have similar clinical presentations. Differentiating between these life-threatening conditions at high altitude is essential for successful treatment., (Copyright © 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH., Methods: Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS)., Results: Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03)., Conclusions: Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness., (Copyright 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Frostbite is frequently seen in high altitude climbers. Many Sherpas, members of an ethnic community living high in the Himalayas in Nepal, help the climbers as a guide or an assistant. They often seem to undertake few precautionary measures thus suffer more from frostbite. A young Sherpa, who had reached the top of Mt Kanchenjunga in March 2009, suffered from deep frostbite in his fingers. Fortunately, he recovered well with generous treatment. Though there is no evidence whether Sherpas are more or less prone to frostbite, simple techniques for adequate prevention of hypoxia, hypothermia and dehydration will benefit any climber to the high altitudes., (Copyright (c) 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear. The objective of this study was to elucidate the genetic background underlying this characteristic among Sherpas with respect to the angiotension-converting enzyme (ACE) gene., Methods: We enrolled 105 Sherpa volunteers in Namche Bazaar (3440 meters) and 111 non-Sherpa Nepalese volunteers in Kathmandu Valley (1330 meters) in Nepal. Information about high-altitude exposure and physiological phenotypes was obtained via fieldwork investigation. The genotype of the insertion/deletion (I/D) polymorphism in the ACE gene was identified by polymerase chain reaction. Serum ACE activity was also measured., Results: The distribution of the I dominant genotype (II & ID) and the I allelic frequency were significantly more prevalent in Sherpas (II & ID: 94.3%, I allele: 73.3%) than in non-Sherpas (II & ID: 85.6%, P = .035; I allele: 64.0%, P = .036). Moreover, despite residing at high altitude, the circulating ACE levels of Sherpas were statistically similar to those of non-Sherpas at low altitudes (Sherpas: 14.5 +/- 0.4 IU/L/37 degrees C; non-Sherpas: 14.7 +/- 0.4 IU/L/37 degrees C; P = .755)., Conclusions: These findings suggest that the overrepresented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment.

Objective: During August of each year, thousands of Nepalese religious pilgrims ascend from 2050 m to 4500 m in 1 to 3 days. Our objectives were to evaluate the incidence of acute mountain sickness (AMS) among this large group of native people, to explore changes in serum electrolytes as subjects ascend to high altitude, and to attempt to determine whether decreased effective circulating volume is associated with the development of AMS., Methods: This was a prospective study with 2 parts. In the first part, demographic, physiologic, and laboratory data were collected from a cohort of 34 pilgrims at both moderate (2050 m) and high altitude (4500 m). Changes that occurred with ascent were compared in subjects who did and did not develop AMS. The second part was a cross sectional study of a different group of 57 pilgrims at the high-altitude site to further determine variables associated with AMS., Results: In the cohort of 34 subjects, Lake Louise score, heart rate, respiratory rate, blood urea nitrogen (BUN), BUN:creatinine ratio, and pH increased at high altitude, whereas oxygen saturation, bicarbonate, creatinine, and PCO2 decreased. Sixteen of these 34 subjects (42%) were diagnosed with AMS; these patients had a statistically significantly lower hematocrit, oxygen saturation, and self-reported water consumption than those without AMS. Of the 57 subjects enrolled in the cross sectional study, 31 (54%) were diagnosed with AMS. These pilgrims had higher heart rates and BUNs than did their non-AMS counterparts., Conclusions: Fifty-two percent of the subjects developed AMS. With ascent to altitude, subjects showed some evidence of decreased effective circulating volume, though there were no clinically significant changes. The data did not show whether decreased circulating volume is a significant risk factor in the development of AMS at high altitude.