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Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol . 23:330-337, 2022. Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions.

Hüfner, Katharina, Fabio Caramazza, Evelyn R. Pircher Nöckler, Agnieszka E. Stawinoga, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Ken Zafren, Hermann Brugger, and Barbara Sperner-Unterweger. Association of pre-existing mental health conditions with acute mountain sickness at Everest Base Camp. High Alt Med Biol. 23:338-344, 2022. Background: Mental health disorders are common, but limited data are available regarding the number of people with a past medical history of psychiatric diagnoses going to high altitude (HA). It is also unknown whether mental health conditions are associated with an increased risk of acute mountain sickness (AMS). Methods: We analyzed data from a previous study at Everest Base Camp. Participants self-reported their past medical history and history of substance use and had a brief history taken by a physician. AMS was assessed using the self-reported 2018 Lake Louise AMS Score. Results: Eighty-five participants (66 men and 19 women, age 38 ± 9 years) were included. When questioned by a physician, 28 participants reported prior diagnoses or symptoms compatible with depression (23%), anxiety disorder (6%), post-traumatic stress disorder (1%), and psychosis/psychotic experiences (9%). The prevalence of psychiatric diagnoses in the past medical history was much lower in the self-reported data (2/85) compared to data obtained via physician assessment (28/85). Increased risks of AMS were associated with a past medical history of anxiety disorder (odds ratio [OR] 22.7; confidence interval [95% CI] 2.3-220.6; p  < 0.001), depression (OR 3.6; 95% CI 1.2-11.2; p  = 0.022), and recreational drug use ever (OR 7.3; 95% CI 1.5-35.5; p  = 0.006). Conclusions: Many people who travel to HA have a past medical history of mental health conditions. These individuals have an increased risk of scoring positive for AMS on the Lake Louise Score compared with people without a history of mental health conditions.

Hüfner, Katharina, Fabio Caramazza, Agnieszka E. Stawinoga, Evelyn R. Pircher Nöckler, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Barbara Sperner-Unterweger, and Hermann Brugger. Assessment of psychotic symptoms in individuals exposed to very high or extreme altitude: A field study. High Alt Med Biol. 22:369-378, 2021. Background: Symptoms of psychosis such as hallucinations can occur at high or extreme altitude and have been linked to accidents on the mountain. No data are available on how to assess such symptoms in the field and what their prevalence or predisposing factors might be. Methods: In this field study at Everest Base Camp (5,365 m) in Nepal, 99 participants of organized expeditions underwent 279 assessments: The High Altitude Psychosis Questionnaire (HAPSY-Q), the Prodromal Questionnaire, 16-items (PQ-16), and the Mini International Neuropsychiatric Interview (M.I.N.I., psychosis section) were collected together with further clinical data. Statistical analysis was done for each phase, that is, altitude range of the climb, and overall data. Results: One of 97 climbers fulfilled the M.I.N.I. diagnostic criteria for psychosis during one acclimatization climb. At least one endorsed item on the HAPSY-Q and the PQ-16, indicating the presence of symptoms of psychosis in the absence of a psychotic disorders, were identified in 10/97 (10.3%) and 18/87 (20.7%) participants respectively. The scores of the HAPSY-Q and the PQ-16 were correlated ( r  = 0.268, p  < 0.001). Odds ratio analysis identified an increased risk for accidents in individuals with endorsed items on the HAPSY-Q. Conclusions: The diagnosis of high altitude psychosis is rare in climbers during organized expeditions. Nevertheless, subdiagnostic symptoms of psychosis occurred in a significant proportion of climbers. Future research is needed to validate these pilot findings.

Porters have accompanied trekkers and climbers to high altitude since the earliest expeditions in the Himalayas. As the existing body of knowledge on high-altitude medicine expands, the focus remains on trekkers or climbers. And published literature on medical problems in the large porter population remains sparse. It is well known that porters working at high altitude in the Nepal Himalayas are often lowland dwellers and are as prone to high-altitude illnesses such as acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema as the trekkers are. Other illnesses such as diarrhea, respiratory illnesses, and infections also occur in this population. In this review, studies reporting these findings will be discussed along with the local context of socioeconomic barriers to adequate health care for these porters.

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.)

A 55-year-old female Nepali pilgrim presented to the Himalayan Rescue Association Temporary Health Camp near the sacred Gosainkund Lake (4380 m) north of Kathmandu, Nepal, with a complaint of severe headache, vomiting and light-headedness. She was diagnosed with severe acute mountain sickness. Intramuscular dexamethasone was administered. Paracetamol (acetaminophen in the USA and Canada) and ondansetron were given as supportive management for headache and nausea. Arrangements were made to have her carried down by a porter immediately. After the descent, all her symptoms resolved. High-altitude pilgrims are a more vulnerable group than trekkers and mountaineers. Pilgrims generally have a rapid ascent profile, have low awareness of altitude illness and are strongly motivated to gain religious merit by completing the pilgrimage. As a result, there is a high incidence of altitude illness among pilgrims travelling to high-altitude pilgrimage sites., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Baniya, Santosh, Christopher Holden, and Buddha Basnyat. Reentry high altitude pulmonary edema in the Himalayas. High Alt Med Biol. 18:425-427, 2017.-Reentry high altitude pulmonary edema (HAPE), a subset of HAPE, is a well recognized, life-threatening illness documented almost exclusively in the North and South Americans, who live at high altitude (>2500 m) and return to their homes after a brief sojourn of days to months at lower altitude. This phenomenon has not been reported in Sherpas or other people of Tibetan origin in Nepal or India. And it has rarely been reported from Tibet. In this study we document a case of reentry HAPE in Manang region (3500 m) of Nepal in a 7-year-old Nepali boy of Tibetan ancestry who fell ill when he ascended to his village (Manang, 3500 m) from Besisahar (760 m) in 1 day in a motor vehicle after spending the winter (December to March) at Besisahar with his family. With more motorable road access to high altitude settlements in the Himalayas, reentry HAPE may need to be strongly considered by healthcare professionals in local residents of high altitude; otherwise life-threatening complications may ensue as in our case report.

Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart Harris. Findings of cognitive impairment at high altitude: relationships to acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127, 2017., Objective: Acute mountain sickness (AMS) is defined by patient-reported symptoms using the Lake Louise Score (LLS), which provides limited insight into any possible underlying central nervous system (CNS) dysfunction. Some evidence suggests AMS might coexist with altered neural functioning. Cognitive impairment (CI) may go undetected unless a sensitive test is applied. Our hypothesis was that a standardized test for mild CI would provide an objective measure of CNS dysfunction, which may correlate with the symptoms of AMS and so provide a potential new tool to better characterize altitude-related CNS dysfunction. We compared a cognitive screening tool with the LLS to see if it correlated with CNS dysfunction., Methods: Adult native English-speaking subjects visiting Himalayan Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927 ft) were recruited. Subjects were administered the LLS and a slightly modified version of the environmental Quick mild cognitive impairment screen (eQmci). Medication use for altitude illness was recorded. Scores were compared using the Spearman's correlation coefficient. Data also included medication use., Results: Seventy-nine subjects were enrolled. A cut-off of three or greater was used for the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were 22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria for CI. There was a weak correlation (r 2  = 0.06, p = 0.04) between eQmci score and LLS. In matched subjects with identical LLS, recent acetazolamide use was associated with significantly more CI., Conclusion: Field assessment of CI using a rapid standardized tool demonstrated that a substantial number of subjects were found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft). The weak correlation between the LLS and eQmci suggests that AMS does not result in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS severity.

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.)

Bhandari, Sanjeeb Sudarshan, Pranawa Koirala, Sadichhya Lohani, Pratibha Phuyal, and Buddha Basnyat. Breathlessness at high altitude: first episode of bronchoconstriction in an otherwise healthy sojourner. High Alt Med Biol.. 18:179-181, 2017-High-altitude illness is a collective term for less severe acute mountain sickness and more severe high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema, which we can experience while traveling to high altitude. These get better when we get down to the lower altitudes. People with many comorbidities also have been traveling to high altitudes from the dawn of civilization. Obstructive airway diseases can be confused with HAPE at high altitude. Asthma is one of those obstructive pulmonary diseases, but it is shown to get better with travel to the altitudes higher than the residing altitude. We present a case of 55-year-old nonsmoker, athletic, female, a lowland resident who developed difficulty breathing for the first time at high altitude. She did not get better with the descent to lower altitude and timely intake of acetazolamide. Her pulmonary function test showed obstructive airway pattern, which got better with salbutamol/ipratropium nebulization and oxygen.

Religious pilgrims have been going to high altitude pilgrimages long before trekkers and climbers sojourned in high altitude regions, but the medical literature about high altitude pilgrimage is sparse. Gosainkunda Lake (4300 m) near Kathmandu, Nepal, and Shri Amarnath Yatra (3800 m) in Sri Nagar, Kashmir, India, are the two sites in the Himalayas from where the majority of published reports of high altitude pilgrimage have originated. Almost all travels to high altitude pilgrimages are characterized by very rapid ascents by large congregations, leading to high rates of acute mountain sickness (AMS). In addition, epidemiological studies of pilgrims from Gosainkunda Lake show that some of the important risk factors for AMS in pilgrims are female sex and older age group. Studies based on the Shri Amarnath Yatra pilgrims show that coronary artery disease, complications of diabetes, and peptic ulcer disease are some of the common, important reasons for admission to hospital during the trip. In this review, the studies that have reported these and other relevant findings will be discussed and appropriate suggestions made to improve pilgrims' safety at high altitude., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Acute mountain sickness (AMS) is very common at altitudes above 2500 m. There are few treatment options in the field where electricity availability is limited, and medical assistance or oxygen is unavailable or difficult to access. Positive airway pressure has been used to treat AMS at 3800 m. We hypothesized that continuous positive airway pressure (CPAP) could be used under field conditions powered by small rechargeable batteries. Methods Part 1. 5 subjects trekked to 3500 m from 2800 m in one day and slept there for one night, ascending in the late afternoon to 3840 m, where they slept using CPAP 6-7 cm via mask. The next morning they descended to 3500 m, spent the day there, ascended in late afternoon to 3840 m, and slept the night without CPAP. Continuous overnight oximetry was recorded and the Lake Louise questionnaire for AMS administered both mornings. Methods Part 2. 14 trekkers with symptoms of AMS were recruited at 4240 m. All took acetazolamide. The Lake Louise questionnaire was administered, oximetry recorded, and CPAP 6-7 cm was applied for 10-15 min. CPAP was used overnight and oximetry recorded continuously. In the morning the Lake Louise questionnaire was administered, and oximetry recorded for 10-15 min. The equipment used in both parts was heated, humidified Respironics RemStar® machines powered by Novuscell™ rechargeable lithium ion batteries. Oximetry was recorded using Embletta™ PDS. Results Part 1. CPAP improved overnight Sao2 and eliminated AMS symptoms in the one subject who developed AMS. CPAP was used for 7-9 h and the machines operated for >8 h using the battery. Results Part 2. CPAP use improved Sao2 when used for 10-15 min at the time of recruitment and overnight CPAP use resulted in significantly reduced AMS symptoms. Conclusion. CPAP with rechargeable battery may be a useful treatment option for trekkers and climbers who develop AMS., Competing Interests: Author Disclosure Statement No competing financial interests exist.

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.)

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.)

In this randomized, double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema (HAPE) in trekkers traveling between 4250 m (Pheriche)\4350 m (Dingboche) and 5000 m (Lobuje) in Nepal; to determine if acetazolamide decreases pulmonary artery systolic pressures (PASP) at high altitude; and to determine if there is an association with PASP and signs and symptoms of HAPE. Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje. The Lake Louise Consensus Criteria were used for the diagnosis of HAPE, and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP. Complete measurements were performed on 339 of the 364 subjects (164 in the placebo group, 175 in the acetazolamide group). No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups. Mean PASP values did not differ significantly between the acetazolamide and placebo groups (31.3 and 32.6 mmHg, respectively). An increasing number of signs and symptoms of HAPE was associated with elevated PASP (p < 0.01). The efficacy of acetazolamide against acute mountain sickness, however, was significant with a 21.9% incidence in the placebo group compared to 10.2 % in the acetazolamide group (p < 0.01). Given the lack of cases of HAPE in either group, we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE, but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 m.

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.

750 mg per day of acetazolamide in the prevention of acute mountain sickness (AMS), as recommended in the meta-analysis published in 2000 in the British Medical Journal, may be excessive and is controversial. To determine if the efficacy of low-dose acetazolamide 125 mg bd (250 mg), as currently used in the Himalayas, is significantly different from 375 mg bd (750 mg) of acetazolamide in the prevention of AMS, we designed a prospective, double-blind, randomized, placebo-controlled trial. The participants were sampled from a diverse population of (non-Nepali) trekkers at Namche Bazaar (3440 m) in Nepal on the Everest trekking route as they ascended to study midpoints (4280 m/4358 m) and the endpoint, Lobuje (4928 m), where data were collected. Participants were randomly assigned to receive 375 mg bd of acetazolamide (82 participants), 125 mg bd of acetazolamide (74 participants), or a placebo (66 participants), beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd (24% vs. 21%, 95% confidence interval, -12.6%, 19.8%), in contrast to significantly greater AMS (51%) observed in the placebo group (95% confidence interval for differences: 8%, 46%; 12%, 49% for low and high comparisons, respectively). Both doses of acetazolamide improved oxygenation equally (82.9% for 250 mg daily and 82.8% for 750 mg daily), while placebo endpoint oxygen saturation was significantly less at 80.7% (95% confidence interval for differences: 0.5%, 3.9% and 0.4%, 3.7% for low and high comparisons, respectively). There was also more paresthesia in the 375-mg bd group (p < 0.02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m.

Altitude sickness in its commonly recognized forms consists of acute mountain sickness and the two life-threatening forms, high altitude cerebral and pulmonary edema. Less well known are other conditions, chiefly neurological, that may arise completely outside the usual definition of altitude sickness. These, often focal, neurological conditions are important to recognize so that they do not become categorized as altitude sickness because, besides oxygen and descent, treatment may be vastly different. Transient ischemic attacks, cerebral venous thrombosis, seizures, syncope, double vision, and scotomas are some of the well-documented neurological disturbances at high altitude discussed here in order to enhance their recognition and treatment.

Objective: To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness., Design: Prospective, double blind, randomised, placebo controlled trial., Setting: Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002., Participants: 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent., Main Outcome Measures: Incidence measured by Lake Louise acute mountain sickness score > or = 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores > or = 5), incidence of headache, and severity of headache., Results: Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70)., Conclusions: When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.

The objective of this study was to determine the efficacy of low-dose acetazolamide (125 mg twice daily) for the prevention of acute mountain sickness (AMS). The design was a prospective, double-blind, randomized, placebo-controlled trial in the Mt. Everest region of Nepal between Pheriche (4243 m), the study enrollment site, and Lobuje (4937 m), the study endpoint. The participants were 197 healthy male and female trekkers of diverse background, and they were evaluated with the Lake Louise Acute Mountain Sickness Scoring System and pulse oximetry. The main outcome measures were incidence and severity of AMS as judged by the Lake Louise Questionnaire score at Lobuje. Of the 197 participants enrolled, 155 returned their data sheets at Lobuje. In the treatment group there was a statistically significant reduction in incidence of AMS (placebo group, 24.7%, 20 out of 81 subjects; acetazolamide group, 12.2%, 9 out of 74 subjects). Prophylaxis with acetazolamide conferred a 50.6% relative risk reduction, and the number needed to treat in order to prevent one instance of AMS was 8. Of those with AMS, 30% in the placebo group (6 of 20) versus 0% in the acetazolamide group (0 of 9) experienced a more severe degree of AMS as defined by a Lake Louise Questionnaire score of 5 or greater (p = 0.14). Secondary outcome measures associated with statistically significant findings favoring the treatment group included decrease in headache and a greater increase in final oxygen saturation at Lobuje. We concluded that acetazolamide 125 mg twice daily was effective in decreasing the incidence of AMS in this Himalayan trekking population.