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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.

Background and Objectives: High altitude may increase blood pressure (BP) and the kidney plays an important role in acclimatization. Little is known about how transplanted kidneys respond to the hypoxic stress at high altitude. We compared 24 hour ambulatory BP in a climber with a kidney transplant and hypertension at sea level and at high altitude (2860-4300 m). Methods: Welch-Allyn ABPM 6100 monitor was used to collect heart rate, systolic BP (SBP), and diastolic BP every 30 minutes while awake, and hourly while asleep. BP was monitored for 49 hours at sea level and for 53 hours at 2860-4300 m. Results: Overall mean SBP did not differ between altitudes. At high altitude, the participant's mean nocturnal BP increased, but this "reverse dipping" pattern was not observed at sea level. The participant had no evidence of altitude illness or infectious complications at high altitude. Conclusions: This case builds on previous reports that kidney transplant recipients may safely travel to high altitude. Further study is required to determine the generalizability to other travelers with kidney transplant and/or underlying hypertension, and the clinical significance of short-term elevated nocturnal BP at high altitude.

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.

Ujka, Kristian, Rosa Maria Bruno, Luca Bastiani, Eva Bernardi, Paolo Sdringola, Nenad Dikic, Bikash Basyal, Sanjeeb Sundarshan Bhandari, Buddha Basnyat, Annalisa Cogo, and Lorenza Pratali. Relationship between occupational physical activity and subclinical vascular damage in moderate-altitude dwellers. High Alt Med Biol. 18:249-257, 2017., Background: Occupational physical activity (OPA) has been associated with increased cardiovascular (CV) events. The aim of this study was to investigate the association between OPA and markers of subclinical vascular damage among a moderate-altitude population living in the rural village of Chaurikharka (Nepal; 2600 m sea level)., Methods: Seventy-two individuals (age 42 ± 15 years, ranges 15-85 years, 23 men) were enrolled. Physical activity (PA) was evaluated using the International Physical Activity Questionnaire (IPAQ). Carotid-femoral pulse wave velocity (PWV), carotid ultrasound assessment, and flow-mediated dilation (FMD) were performed., Results: OPA was 9860 ± 5385 Metabolic Equivalent of Task (MET)-minutes/week, representing 77% of total energy expenditure, with 97% of the population performing high-intensity PA. In the univariate analysis, OPA was significantly associated with PWV (β = 0.474, p = 0.001) and carotid stiffness (CS) (β = 0.29, p = 0.019). In the multivariate analysis, including age, sex, oxygen saturation, mean blood pressure, low-density lipoprotein (LDL), and OPA, OPA remained an independent predictor of PWV (β = 0.403, p = 0.001) but not of CS (β = 0.028, p = 0.8). OPA remained an independent predictor of PWV independently from the Framingham risk score (FRS)., Conclusion: High-intensity OPA shows a positive, independent association with aortic stiffness in Himalayan moderate-altitude dwellers. This study suggests how vigorous OPA performed in moderate altitude may be a CV risk factor.

Keyes, Linda E., Thomas Douglas Sallade, Charles Duke, Jennifer Starling, Alison Sheets, Sushil Pant, David S. Young, David Twillman, Nirajan Regmi, Benoit Phelan, Purshotam Paudel, Matthew McElwee, Luke Mather, Devlin Cole, Theodore McConnell, and Buddha Basnyat. Blood pressure and altitude: an observational cohort study of hypertensive and nonhypertensive Himalayan trekkers in Nepal. High Alt Med Biol. 18:267-277, 2017., Objectives: To determine how blood pressure (BP) changes with altitude in normotensive versus hypertensive trekkers. Secondary aims were to evaluate the prevalence of severe hypertension (BP ≥180/100 mmHg) and efficacy of different antihypertensive agents at high altitude., Methods: This was an observational cohort study of resting and 24-hour ambulatory BP in normotensive and hypertensive trekkers at 2860, 3400, and 4300 m in Nepal., Results: We enrolled 672 trekkers age 18 years and older, 60 with a prior diagnosis of hypertension. Mean systolic and diastolic BP did not change between altitudes in normotensive or hypertensive trekkers, but was higher in those with hypertension. However, there was large interindividual variability. At 3400 m, the majority (60%, n = 284) of normotensive participants had a BP within 10 mmHg of their BP at 2860 m, while 21% (n = 102) increased and 19% (n = 91) decreased. The pattern was similar between 3400 and 4300 m (64% [n = 202] no change, 21% [n = 65] increased, 15% [n = 46] decreased). BP decreased in a greater proportion of hypertensive trekkers versus normotensives (36% [n = 15] vs. 21% at 3400 m, p = 0.01 and 30% [n = 7] vs. 15% at 4300 m, p = 0.05). Severe hypertension occurred in both groups, but was asymptomatic. In a small subset of participants, 24-hour ambulatory BP monitoring showed that nocturnal BP decreased in normotensive (n = 4) and increased in hypertensive trekkers (n = 4)., Conclusions: Most travelers, including those with well-controlled hypertension, can be reassured that their BP will remain relatively stable at high altitude. Although extremely elevated BP may be observed at high altitude in normotensive and hypertensive people, it is unlikely to be symptomatic. The ideal antihypertensive regimen at high altitude remains unclear.

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.

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.

Donegani, Enrico, Peter Paal, Thomas Küpper, Urs Hefti, Buddha Basnyat, Anna Carceller, Pierre Bouzat, Rianne van der Spek, and David Hillebrandt. Drug use and misuse in the mountains: a UIAA MedCom consensus guide for medical professionals. High Alt Med Biol. 17:157-184, 2016.-Aims: The aim of this review is to inform mountaineers about drugs commonly used in mountains. For many years, drugs have been used to enhance performance in mountaineering. It is the UIAA (International Climbing and Mountaineering Federation-Union International des Associations d'Alpinisme) Medcom's duty to protect mountaineers from possible harm caused by uninformed drug use. The UIAA Medcom assessed relevant articles in scientific literature and peer-reviewed studies, trials, observational studies, and case series to provide information for physicians on drugs commonly used in the mountain environment. Recommendations were graded according to criteria set by the American College of Chest Physicians., Results: Prophylactic, therapeutic, and recreational uses of drugs relevant to mountaineering are presented with an assessment of their risks and benefits., Conclusions: If using drugs not regulated by the World Anti-Doping Agency (WADA), individuals have to determine their own personal standards for enjoyment, challenge, acceptable risk, and ethics. No system of drug testing could ever, or should ever, be policed for recreational climbers. Sponsored climbers or those who climb for status need to carefully consider both the medical and ethical implications if using drugs to aid performance. In some countries (e.g., Switzerland and Germany), administrative systems for mountaineering or medication control dictate a specific stance, but for most recreational mountaineers, any rules would be unenforceable and have to be a personal decision, but should take into account the current best evidence for risk, benefit, and sporting ethics.

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.

Competing Interests: Author Disclosure Statement No competing financial interests exist.

Competing Interests: Author Disclosure Statement No competing financial interests exist.

This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide 125 mg taken at bedtime for one night. The primary outcome was sleep quality on a 100 mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide.

Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening medical condition. We describe a case of a 47-year-old woman who presented with headache, speech defects, and visual disturbances, and was later diagnosed with cerebral venous sinus thrombosis. The article describes a possible risk of such thrombotic events with exposure to high altitude environment in patients with coagulation defects such as Factor V Leiden mutation. Besides, such neurological conditions can occur independent of altitude illness and need to be recognized as their management differs.

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.

The Sherpas' adaptation to high altitude has been hypothesized as being due to a genetic basis since the beginning of the last century, but this has yet to be demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111 non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in serum were measured. The frequencies of the Glu and eNOS4b alleles were significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas' adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary individually, thus it is not a reliable indicator for endogenous nitric oxide production.

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.

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.

A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a sudden, acute confusional state at an altitude of about 5000 m. Although described at higher altitudes, delirium presenting alone has not been documented at 5000 m or at lower high altitudes. The differential diagnosis which includes acute mountain sickness and high altitude cerebral edema is discussed. Finally, the importance of travelling with a reliable partner and using proper insurance is emphasized in treks to the Himalayas.