T h e new england journal o f medicine clinical practice Acute High-Altitude Illnesses Peter Bärtsch, M.D., and Erik R. Swenson, M.D. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. A 45-year-old healthy man wishes to climb Mount Kilimanjaro (5895 m) in a 5-day period, starting at 1800 m. The results of a recent exercise stress test were normal; he runs 10 km 4 or 5 times per week and finished a marathon in less than 4 hours last year. He wants to know how he can prevent becoming ill at high altitude and wheth- er training or sleeping under normobaric hypoxic conditions in the weeks before the ascent would be helpful. What would you advise? The Clinical Problem From the University Clinic, Department Persons who are not acclimatized and ascend rapidly to high altitudes are at risk for of Internal Medicine, Division VII: Sports any of several debilitating and potentially lethal illnesses (Table 1) that occur with- Medicine, Heidelberg, Germany (P.B.); 1 and Pulmonary and Critical Care Medicine, in the first days after arrival at high altitudes. Traditionally, 2500 m has been used Department of Medicine, Veterans Affairs as the threshold for high-altitude illnesses; in rare cases, mild illness occurs in Puget Sound Health Care System, Univer- persons who have ascended above 2000 m but below 2500 m. sity of Washington, Seattle (E.R.S.). Ad- dress reprint requests to Dr. Bärtsch at the University Clinic, Department of Internal Acute Mountain Sickness Medicine, Division VII: Sports Medicine, Headache that occurs with an increase in altitude is the cardinal symptom of acute Im Neuenheimer Feld 410, 69120 Heidel- berg, Germany, or at peter.bartsch@med mountain sickness and is usually accompanied by anorexia, nausea, dizziness, .uni-heidelberg.de. malaise, sleep disturbance, or a combination of these symptoms.2 Acute mountain N Engl J Med 2013;368:2294-302. sickness generally occurs within 6 to 12 hours after a person ascends to 2500 m or DOI: 10.1056/NEJMcp1214870 higher. Its prevalence and severity increase with increasing altitude. Acute moun- Copyright © 2013 Massachusetts Medical Society. tain sickness occurs in approximately 10 to 25% of unacclimatized persons who ascend to 2500 m. Symptoms are usually mild at this altitude and have little effect on activity. However, acute mountain sickness occurs in 50 to 85% of unacclima- tized persons at 4500 to 5500 m and may be incapacitating.3-5 In a retrospective study, major independent risk factors for acute mountain sick- ness included a history of acute mountain sickness, fast ascent (≥625 m per day above 2000 m), and lack of previous acclimatization (<5 days above 3000 m in the preceding 2 months).6 A prospective study involving trekkers and climbers who An audio version of this article is went to altitudes between 4000 and 8848 m showed the same major risk factors 7 available at for incapacitating acute mountain sickness and other severe altitude illnesses NEJM.org (described below). Other possible risk factors include female sex, an age younger than 46 years, and a history of migraine. Exercise may exacerbate acute mountain sickness, but good physical fitness is not protective.6-8 Symptoms usually resolve within 1 to 2 days when appropriate measures are taken (see below). High-Altitude Cerebral Edema High-altitude cerebral edema is characterized by truncal ataxia, decreased con- sciousness, and usually mild fever.2,9 Without appropriate treatment, coma may evolve rapidly, followed by death from brain herniation within 24 hours. Headache 2294 n engl j med 368;24 nejm.org june 13, 2013 The New England Journal of Medicine Downloaded from nejm.org by Peter BAERTSCH on August 29, 2014. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved. clinical practice key Clinical points Acute High-Altitude Illnesses • Acute high-altitude illnesses occur in persons who are not acclimatized during the first days at an altitude of 2500 m or higher, with wide variation in the incidence according to patient characteristics and history. • Headache is the major symptom of acute mountain sickness. If acute mountain sickness is not treated adequately, it can progress to life-threatening high-altitude cerebral or pulmonary edema. • High-altitude illnesses can be prevented by ascending 300 to 500 m per day at altitudes above 3000 m and including a rest day every 3 to 4 days. • Risks of acute mountain sickness and high-altitude cerebral edema are reduced with the use of acet- azolamide or dexamethasone; the risk of high-altitude pulmonary edema is reduced with the use of nifedipine, phosphodiesterase-5 inhibitors, or dexamethasone. • Acute mountain sickness may be treated by a day of rest and nonsteroidal antiinflammatory drugs for headache, but when it is severe, descent or supplemental oxygen is indicated. Dexamethasone is indi- cated for severe acute mountain sickness or high-altitude cerebral edema, and nifedipine or phospho- diesterase-5 inhibitors are indicated for high-altitude pulmonary edema; treatment with these agents should be followed by descent as soon as possible. that is poorly responsive to nonsteroidal anti- increases to 6% and 15%, respectively, when inflammatory drugs (NSAIDs) and vomiting in- these altitudes are reached within 1 to 2 days. dicate probable progression of acute mountain The risk is further increased among persons with sickness to high-altitude cerebral edema, but the a history of high-altitude pulmonary edema (e.g., absence of headache and other symptoms of the risk of recurrence is 60% among persons acute mountain sickness does not rule it out. who ascend to 4500 m in 2 days).14 The estimated High-altitude cerebral edema usually develops mortality among persons with untreated high- after at least 2 days at altitudes above 4000 m. altitude pulmonary edema is 50%. This disorder The prevalence is estimated to be 0.5 to 1.0% is a noncardiogenic pulmonary edema caused by among persons at 4000 to 5000 m.10 Magnetic exaggerated hypoxic pulmonary vasoconstriction resonance imaging in patients with high-altitude and abnormally high pulmonary-artery pressure cerebral edema shows vasogenic edema11 and and capillary pressure.15 These high pressures microhemorrhages that are located predominant- lead to a noninflammatory and hemorrhagic al- ly in the corpus callosum.12 veolar capillary leak that secondarily may evoke an inflammatory response.16 High-Altitude Pulmonary Edema High-altitude pulmonary edema is characterized Strategies and Evidence by loss of stamina, dyspnea, and dry cough with exertion, followed by dyspnea at rest, rales, cya- Risk Assessment nosis, cough, and pink, frothy sputum.13 Deteri- Risk assessment (Table 2) should start with a oration in gas exchange also increases the risk of clinical evaluation directed toward any cardio- high-altitude cerebral edema. This condition de- pulmonary diseases that might worsen during a velops 2 or more days after exposure to altitudes sojourn involving high altitude. Although a dis- above 3000 m and is rare in persons at altitudes cussion of the effect of altitude in persons with below 2500 to 3000 m. The risk increases with preexisting disease is not within the scope of this increased altitude and faster ascent. For example, article, reviews of this topic are available.17,18 the incidence among persons with an unknown Given that previous altitude illness is a strong history of high-altitude pulmonary edema is predictor of recurrence, detailed information 0.2% if they ascend to 4500 m in 4 days and 2% about the person’s history with respect to visits if they ascend to 5500 m in 7 days; the incidence to high-altitude areas, acclimatization before pre- n engl j med 368;24 nejm.org june 13, 2013 2295 The New England Journal of Medicine Downloaded from nejm.org by Peter BAERTSCH on August 29, 2014. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved. T h e new england journal o f medicine Table 1. Symptoms, Signs, and Differential Diagnosis of High-Altitude Illnesses. Variable Acute Mountain Sickness High-Altitude Cerebral Edema High-Altitude Pulmonary Edema Symptoms Headache plus one or more of the follow- Moderate-to-severe symptoms Initial illness: inappropriate dyspnea during ing symptoms: nausea, vomiting, diz- of acute mountain sickness exercise, reduced exercise performance, ziness, fatigue, and insomnia. Mild-to- mild fever; advanced illness: orthopnea, moderate illness: a few symptoms of pink frothy sputum, drowsiness mild-to-moderate intensity within 6 to 12 hr after exposure to altitudes of ≥2500 m; severe illness: many or all symptoms of severe intensity, usually evolving from mild-to-moderate illness Signs None Lassitude, truncal ataxia, altered Tachypnea, arterial oxygen saturation consid- mental status such as drows- erably below average value for other per- iness or loss of conscious- sons in climbing group, mild fever, signs ness, often mild fever of high-altitude cerebral edema with ad- vanced stages Differential Exhaustion, dehydration, hangover, Transient ischemic attack or Hyperventilation syndrome, pulmonary em- diagnosis migraine stroke, acute psychosis, in- bolism, mucus plugging toxication (from carbon monoxide, alcohol, or drugs) vious ascents, maximum altitudes for climbing physical activity, rate of previous ascent, and sta- and sleeping, rates of ascent, and any altitude tus with respect to previous severe high-altitude illness should be obtained. The estimation of risk illness and migraines). is most reliable for persons with previous rates of Persons who are considered to be susceptible ascent and final altitudes that were similar to to high-altitude pulmonary edema because of two those planned.