Robert C. Roach

High-altitude illness.

Travel to a high altitude requires that the human body acclimatize to hypobaric hypoxia. Failure to acclimatize results in three common but preventable maladies known collectively as high-altitude illness: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Capillary leakage in the brain (AMS/HACE) or lungs (HAPE) accounts for these syndromes. The morbidity and mortality associated with high-altitude illness are significant and unfortunate, given they are preventable. Practitioners working in or advising those traveling to a high altitude must be familiar with the early recognition of symptoms, prompt and appropriate therapy, and proper preventative measures for high-altitude illness.

Acute Mountain Sickness in a General Tourist Population at Moderate Altitudes

Rapid ascent from low to high altitude is often followed by headache, fatigue, shortness of breath, sleeplessness, and anorexia, a symptom complex called acute mountain sickness. Although some of these symptoms may occur as a result of travel not associated with altitude, only 5% of adults traveling at sea level report similar symptoms [1]. A long-standing interest has existed in the study of acute mountain sickness because it affects a large number of mountain visitors [2-4] and can progress to the life-threatening conditions of high-altitude pulmonary edema or high-altitude cerebral edema [5]. Previous estimates of the incidence of acute mountain sickness have been obtained primarily from small groups of physically fit young men going to altitudes above 12 000 feet [2-4, 7-9]. Little information exists on the frequency and severity of the disorder in the general population at moderate altitudes, yet the population at risk is large. For example, more than 13 million persons visited the Colorado mountains in 1990 for business, conferences, or recreational activities including skiing, climbing, hiking, hunting, and fishing [10]. More needs to be learned about the incidence of acute mountain sickness at moderate altitudes in the general population and about the characteristics of those most likely to be at risk for symptom development. We therefore surveyed groups of persons visiting resorts in the Colorado mountains for conferences and seminars. Specifically, we sought to determine 1) the incidence of acute mountain sickness in visitors exposed to moderate elevations; 2) the effect of acute mountain sickness on physical activity; and 3) the visitor characteristics associated with the development of acute mountain sickness. This information would be useful for developing strategies to minimize symptoms in travelers to moderate altitudes. Methods The study cohort consisted of 4212 adults attending 45 conferences at resorts located at elevations of 6300 to 9700 feet in the Rocky Mountains of Colorado from July 1989 to May 1991. Resorts were chosen on the basis of the willingness of conference organizers to participate. Conferences whose schedules required all participants to attend a meeting within 48 hours of arrival when the study questionnaire could be distributed were included. Study personnel attended these meetings, briefly introduced the study, and distributed the questionnaires. Questions by participants concerning acute mountain sickness or the effects of altitude on health were not answered until all questionnaires were collected. Completion of the survey usually took less than 10 minutes. The participants in each meeting were counted to calculate the response rate. The questionnaire was completed by 3158 (75%) of the persons registered for these conferences, and information satisfactory for analysis was obtained from 99% of those completed. Visitors ranged in age from 16 to 87 years (mean age [SD], 657e43.8 11.8 years) (Figure 1). Of the completed surveys, 2023 (64%) were conducted at resorts located at elevations over 9000 feet and 2603 (82%) were completed in the winter season (November through April). The study was approved by the Human Research Committee of the University of Colorado Health Sciences Center. Figure 1. Distribution of visitors by age and physical condition. n n The questionnaire was designed to obtain demographic information concerning age, gender, height, weight, and permanent residence for each visitor; previous or current medications; and the duration of stops, if any, made en route. Questions asked regarding underlying health conditions included whether the participant had ever been treated for lung disease (asthma, bronchitis, or emphysema); heart conditions (angina or heart attacks); diabetes; high blood pressure; or pregnancy. Participants were asked How do you rate your physical condition? Responses were rated as great, good, average, or poor. To determine whether participants had acute mountain sickness, they were asked if they had experienced any of the following symptoms while at the resort: loss of appetite, vomiting, shortness of breath, dizziness or lightheadedness, unusual fatigue, sleep disturbance (other than related to normal travel), and headache. If the response to headache was yes, they were asked to describe it as mild or severe. Acute mountain sickness was defined as the presence of three or more of these symptoms in the setting of recent altitude exposure. This case definition was similar to that used by previous investigators [1, 2, 5, 6, 9, 12, 13] and is in accordance with the case definition recently developed and codified for international use by the International Hypoxia Symposium [14]. If participants had any of these symptoms of acute mountain sickness, they were asked to determine how the symptoms affected their activity. Response options included no limitation, reduced activity, and required to stay in bed or room. A determination of symptom onset was assessed by asking participants How long after arrival at the resort did symptoms begin? Response options included less than 12 hours, 12 to 24 hours, 25 to 48 hours, 49 to 72 hours, or 72 hours. Alcohol use was measured as the number of beer, wine, or hard-liquor drinks consumed within the first 24 hours of arrival at the resort. Season was determined by the date of questionnaire administration, with winter defined as November through April in each of the study years. Body mass index was calculated as weight kg/in2 and was used to identify obese persons (women with a body mass index >27.3 and men with a body mass index >27.8) [11]. Persons with or without acute mountain sickness were compared using the Wilcoxon rank-sum test for ordinal variables and using the chi-square test for categoric variables. The Student t-test was used for normally distributed variables. The Fisher exact test was used for small sample sizes. Associations were considered significant at P < 0.05. A forward, stepwise, multiple logistic regression analysis was used to examine the independent effects of participant characteristics on the occurrence of acute mountain sickness. All variables associated with the occurrence of acute mountain sickness at P < 0.25 were initially included in the regression analysis. Data acquired in year 2 (June 1990 to May 1991), comprising 1241 cases after the revision of the questions concerning underlying health conditions and habitual activity level before travel, were used for the regression analysis. Variables were dichotomized for ease in presentation. The adjusted odds ratios were computed with 95% confidence intervals (CIs). All calculations were done using the Statistical Analysis Systems statistical package (Cary, North Carolina) [15]. Results Most of the visitors were middle-aged men whose permanent addresses were at sea level, who did not smoke, and who considered themselves to be in good physical condition (Table 1; Figure 1). Approximately one third (28%) stopped overnight at an intermediate altitude (5280 feet) enroute to their destination. Most (64%) had consumed one or more alcoholic beverages in the first 24 hours after arrival. Small proportions of the visitors were obese, pregnant, or had chronic illnesses (Table 1). Table 1. Characteristics and Incidence of Acute Mountain Sickness in Visitors to Areas of Moderate Altitude* Twenty-five percent (CI, 24.98% to 25.01%) of the visitors reported having three or more symptoms and thus met the case definition for acute mountain sickness, whereas 73% had at least one reported symptom. The most common symptom was headache, and the least common was vomiting (Figure 2). For most participants (65%), the onset of symptoms occurred within the first 12 hours after arrival at altitude; symptom onset occurred between 12 and 36 hours in 34% and after more than 36 hours in 1%. Most (58%) of those with symptoms took analgesics (for example, aspirin, acetaminophen, or ibuprofen). Although 44% of persons with acute mountain sickness had no reduction in activity, 51% had moderate activity reduction, and a small proportion (5%) stayed in bed. Figure 2. Distribution of symptoms of acute mountain sickness in 3072 visitors. Visitors whose permanent residence was at an elevation below 3000 feet were more likely to develop acute mountain sickness (see Table 1). The frequency with which it developed was inversely related to age and physical condition (Figure 3). Altitude visited and a previous history of acute mountain sickness were associated with an increased occurrence, whereas development was inversely related to alcohol consumption. Visitors who stopped over at lower elevations for more than 38 hours were less likely to develop acute mountain sickness than were those who did not. Obesity, female gender, and chronic lung disease were also associated with the development of acute mountain sickness. Figure 3. Percentage of acute mountain sickness in visitors to moderate altitudes according to age, physical condition, and altitude visited. n P n P n P The following nine variables were entered into the regression analysis as dichotomous variables: age (younger than 60 years), sex, altitude of permanent residence (below 3000 feet), obesity, lung disease, diabetes, overnight stops before arrival at the resort, previous symptoms during past altitude travel, and self-reported physical condition (poor or average). Although alcohol was statistically associated with acute mountain sickness, it was not included in the model because of the inability to exclude a temporal effect (that is, participants may have become sick and subsequently decided not to drink). The five independent predictors of acute mountain sickness, based on the logistic regression, were residence at an altitude less than 3000 feet; symptoms of acute mountain sickness during previous altitude travel; age younger than 60 years; physical condition self-assessed as poor or average; and the presence of lun

High altitude cerebral edema.

This review focuses on the epidemiology, clinical description, pathophysiology, treatment, and prevention of high altitude cerebral edema (HACE). HACE is an uncommon and sometimes fatal complication of traveling too high, too fast to high altitudes. HACE is distinguished by disturbances of consciousness that may progress to deep coma, psychiatric changes of varying degree, confusion, and ataxia of gait. It is most often a complication of acute mountain sickness or high altitude pulmonary edema. The current leading theory of its pathophysiology is that HACE is a vasogenic edema; that is, a disruption of the blood-brain barrier, and we review possible mechanisms to explain this. Treatment and prevention of HACE are similar to those for the other altitude illnesses, but with greater emphasis on descent and steroids. We conclude the review with several case histories to illustrate key clinical features of the disorder.

Acetazolamide in the Treatment of Acute Mountain Sickness: Clinical Efficacy and Effect on Gas Exchange

OBJECTIVE To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska. PARTICIPANTS Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness. INTERVENTION Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study. MAIN OUTCOME MEASURES An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours. MAIN RESULTS After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045). CONCLUSION In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment

Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subjects ability to acclimatize. Acute altitude-related problems consist of the common syndrome of acute mountain sickness, which is relatively benign and usually self-limiting, and the rarer, more serious syndromes of high-altitude cerebral edema and high-altitude pulmonary edema. A common feature of acute altitude illness is rapid ascent by otherwise fit individuals to altitudes above 3000 m without sufficient time to acclimatize. The susceptibility of an individual to high-altitude syndromes is variable but generally reproducible. Prevention of altitude-related illness by slow ascent is the best approach, but this is not always practical. The immediate management of serious illness requires oxygen (if available) and descent of more than 300 m as soon as possible. In this article, we describe the setting and clinical features of acute mountain sickness and high-altitude cerebral edema, including an overview of the known pathophysiology, and explain contemporary practices for both prevention and treatment exploring the comprehensive evidence base for the various interventions.

Frontal and motor cortex oxygenation during maximal exercise in normoxia and hypoxia.

Reductions in prefrontal oxygenation near maximal exertion may limit exercise performance by impairing executive functions that influence the decision to stop exercising; however, whether deoxygenation also occurs in motor regions that more directly affect central motor drive is unknown. Multichannel near-infrared spectroscopy was used to compare changes in prefrontal, premotor, and motor cortices during exhaustive exercise. Twenty-three subjects performed two sequential, incremental cycle tests (25 W/min ramp) during acute hypoxia [79 Torr inspired Po(2) (Pi(O(2)))] and normoxia (117 Torr Pi(O(2))) in an environmental chamber. Test order was balanced, and subjects were blinded to chamber pressure. In normoxia, bilateral prefrontal oxygenation was maintained during low- and moderate-intensity exercise but dropped 9.0 +/- 10.7% (mean +/- SD, P < 0.05) before exhaustion (maximal power = 305 +/- 52 W). The pattern and magnitude of deoxygenation were similar in prefrontal, premotor, and motor regions (R(2) > 0.94). In hypoxia, prefrontal oxygenation was reduced 11.1 +/- 14.3% at rest (P < 0.01) and fell another 26.5 +/- 19.5% (P < 0.01) at exhaustion (maximal power = 256 +/- 38 W, P < 0.01). Correlations between regions were high (R(2) > 0.61), but deoxygenation was greater in prefrontal than premotor and motor regions (P < 0.05). Prefrontal, premotor, and motor cortex deoxygenation during high-intensity exercise may contribute to an integrative decision to stop exercise. The accelerated rate of cortical deoxygenation in hypoxia may hasten this effect.

Mortality on Mount Everest, 1921-2006: descriptive study

Objective To examine patterns of mortality among climbers on Mount Everest over an 86 year period. Design Descriptive study. Setting Climbing expeditions to Mount Everest, 1921-2006. Participants 14 138 mountaineers; 8030 climbers and 6108 sherpas. Main outcome measure Circumstances of deaths. Results The mortality rate among mountaineers above base camp was 1.3%. Deaths could be classified as involving trauma (objective hazards or falls, n=113), as non-traumatic (high altitude illness, hypothermia, or sudden death, n=52), or as a disappearance (body never found, n=27). During the spring climbing seasons from 1982 to 2006, 82.3% of deaths of climbers occurred during an attempt at reaching the summit. The death rate during all descents via standard routes was higher for climbers than for sherpas (2.7% (43/1585) v 0.4% (5/1231), P<0.001; all mountaineers 1.9%). Of 94 mountaineers who died after climbing above 8000 m, 53 (56%) died during descent from the summit, 16 (17%) after turning back, 9 (10%) during the ascent, 4 (5%) before leaving the final camp, and for 12 (13%) the stage of the summit bid was unknown. The median time to reach the summit via standard routes was earlier for survivors than for non-survivors (0900-0959 v 1300-1359, P<0.001). Profound fatigue (n=34), cognitive changes (n=21), and ataxia (n=12) were the commonest symptoms reported in non-survivors, whereas respiratory distress (n=5), headache (n=0), and nausea or vomiting (n=3) were rarely described. Conclusions Debilitating symptoms consistent with high altitude cerebral oedema commonly present during descent from the summit of Mount Everest. Profound fatigue and late times in reaching the summit are early features associated with subsequent death.

Body Temperature, Autonomic Responses, and Acute Mountain Sickness

A few studies have reported increased body temperature (T(o)) associated with acute mountain sickness (AMS), but these usually include exercise, varying environmental conditions over days, and pulmonary edema. We wished to determine whether T(o) would increase with AMS during early exposure to simulated altitude at rest. Ninety-four exposures of 51 men and women to reduced P(B) (423 mmHg = 16,000 ft = 4850 m) were carried out for 8 to 12 h. AMS was evaluated by LL and AMS-C scores near end of exposure, and T(o) was measured by oral digital thermometer before altitude and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude. Other measurements included ventilation, O(2) consumption and autonomic indicators of plasma catecholamines, HR, and HR variability. Average T(o) increased by 0.5 degrees F from A1 to A12 in all subjects (p < 0.001). Comparison between 16 subjects with lowest AMS scores (mean LL = 1.0, range = 0 to 2.5) and 16 other subjects with highest AMS scores (mean LL = 7.4, range = 5 to 11) demonstrated a transient decline in T(o) from A1 to A6 in AMS, in contrast to a rise in non-AMS (p = 0.001). Catecholamines, HR, and HR variability (increased low F/high F ratio) indicated significant elevation of sympathetic activity in AMS, where T(o) fell, but no change in metabolic rate. The apparently greater heat loss during early AMS suggests increased hypoxic vasodilation in spite of enhanced sympathetic drive. Greater hypoxic vasodilation and elevated HR in AMS in the absence of other changes suggest that augmentation of beta-adrenergic tone may be involved in early AMS pathophysiology.

Operation Everest II: ventilatory adaptation during gradual decompression to extreme altitude.

To assess the ventilatory adaptation during gradual ascent to extreme altitude, we studied seven healthy males as part of the 40 d simulated ascent of Mt. Everest in a hypobaric chamber. We measured resting ventilation (VE, l.min-1), arterial oxygen saturation (SaO2%), the ventilatory response to oxygen breathing, isocapnic hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) at sea level prior to the ascent (760 torr), 14,000 feet (428 torr), 24,000 feet (305 torr), and within 24 h of descent (765 torr). VE increased from 9.3 +/- 1.1 l.min-1 at 760 torr to 23.4 +/- 1.3 l.min-1 at 305 torr and remained elevated at 14.7 +/- 0.7 l.min-1 after descent. Oxygen breathing decreased VE by 9.6 +/- 1.3 l.min-1 at 305 torr. Isocapnic HVR (expressed as a positive slope of VE/SaO2, l.min-1.%SaO2(-1) increased from 0.18 +/- 0.07 at 760 torr to 0.34 +/- 0.11 and 0.38 +/- 0.5 at 428 torr and 305 torr (P less than 0.05) respectively. HVR was elevated further upon return to sea level (0.8 +/- 0.09, P less than 0.05). HCVR (S = VE/PETCO2, l.min-1.torr-1) increased from sea level (S = 4.4 +/- 0.09) to 305 torr (S = 18.7 +/- 3.5, P less than 0.01) and remained elevated upon return to sea level (S = 10.7 +/- 4.6, P less than 0.001). This study is the first to investigate the ventilatory response to such extreme altitude and so soon after descent and shows that hypoxic and hypercapnic responses increase during prolonged progressive hypoxic exposure and remain significantly elevated from pre-ascent levels immediately upon descent.

Does cerebral oxygen delivery limit incremental exercise performance

Previous studies have suggested that a reduction in cerebral oxygen delivery may limit motor drive, particularly in hypoxic conditions, where oxygen transport is impaired. We hypothesized that raising end-tidal Pco(2) (Pet(CO(2))) during incremental exercise would increase cerebral blood flow (CBF) and oxygen delivery, thereby improving peak power output (W(peak)). Amateur cyclists performed two ramped exercise tests (25 W/min) in a counterbalanced order to compare the normal, poikilocapnic response against a clamped condition, in which Pet(CO(2)) was held at 50 Torr throughout exercise. Tests were performed in normoxia (barometric pressure = 630 mmHg, 1,650 m) and hypoxia (barometric pressure = 425 mmHg, 4,875 m) in a hypobaric chamber. An additional trial in hypoxia investigated effects of clamping at a lower Pet(CO(2)) (40 Torr) from ∼75 to 100% W(peak) to reduce potential influences of respiratory acidosis and muscle fatigue imposed by clamping Pet(CO(2)) at 50 Torr. Metabolic gases, ventilation, middle cerebral artery CBF velocity (transcranial Doppler), forehead pulse oximetry, and cerebral (prefrontal) and muscle (vastus lateralis) hemoglobin oxygenation (near infrared spectroscopy) were monitored across trials. Clamping Pet(CO(2)) at 50 Torr in both normoxia (n = 9) and hypoxia (n = 11) elevated CBF velocity (∼40%) and improved cerebral hemoglobin oxygenation (∼15%), but decreased W(peak) (6%) and peak oxygen consumption (11%). Clamping at 40 Torr near maximal effort in hypoxia (n = 6) also improved cerebral oxygenation (∼15%), but again limited W(peak) (5%). These findings demonstrate that increasing mass cerebral oxygen delivery via CO(2)-mediated vasodilation does not improve incremental exercise performance, at least when accompanied by respiratory acidosis.