JAMA Clinical Guidelines Synopsis
October 24, 2024
Prevention, Diagnosis, and Treatment of Acute Altitude Illness
Mia Derstine, Elan Small, Andrew M. Davis
JAMA. Published online October 24, 2024. doi:10.1001/jama.2024.19562
Guideline title Prevention, Diagnosis, and Treatment of Acute Altitude Illness
Release date January 2024
Developer and funding source Wilderness Medical Society (WMS)
Target population Unacclimatized adults and children traveling or ascending to high altitude
Selected recommendations
- Primary prevention of acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) for travel above 2500 m (8202 ft) includes gradual ascent, limiting sleeping elevation increase to no more than 500 m/d (1640 ft/d), and including a rest day without elevation gain every 3 to 4 days (strong recommendation [SR]; low to moderate quality of evidence [QOE]).
- Acetazolamide is the first-line medication for AMS/HACE chemoprophylaxis in moderate- to high-risk travelers (those with a history of altitude illness, sleeping at an elevation of ≥2800 m [≥9186 ft] on day 1, and/or with an ascent rate of ≥500 m/d above 3000 m [9842 ft]). Dexamethasone is an alternative in adults (SR; high QOE) but is not recommended for children due to lack of data.
- Mild to moderate AMS can be treated by halting ascent. Severe AMS and HACE should be treated by descent, acetazolamide (SR; low QOE), dexamethasone (SR; low QOE), and oxygen supplementation (SR; high QOE).
- HAPE is primarily treated by descent. Supplemental oxygen (SR; high QOE), portable hyperbaric chambers (SR; low QOE), and nifedipine (SR; moderate to high QOE) can be used as temporizing/adjunct measures.
Summary of the Clinical Problem
People traveling to high altitude are at risk of developing acute altitude illnesses, including AMS, HACE, and HAPE. Incidence and risk are assessed by history of acute altitude illness, sleeping elevation above sea level on day 1 of travel, and rate of ascent. AMS incidence can range from approximately 3% in persons traveling to 2000 m (6561 ft) to 25% to 40% at altitudes above 4300 m (14 107 ft),1,2 with symptoms varying from mild to marked.3 While rare, HACE and HAPE are potentially life-threatening if untreated.
Characteristics of the Guideline Source
The WMS created a panel of experts in altitude medicine to update guidelines on high-altitude illness.4 The authors graded recommendations based on the American College of Chest Physicians format (eTable in the Supplement).
Evidence Base
AMS and HACE, which can occur concomitantly or independent of HAPE, are clinical diagnoses in unacclimatized individuals who become ill after arrival to altitude. AMS is primarily associated with headache, as well as nausea/anorexia (6%-12%), lightheadedness/dizziness (8%-27%), and fatigue, with more frequent symptoms and greater impairment of daily activities occurring at higher altitudes.2,4 HACE is characterized by signs of encephalopathy such as ataxia. HAPE presents with symptoms ranging from nonproductive cough and dyspnea on exertion beyond expected for altitude achieved to pink frothy sputum, cyanosis, and dyspnea at rest.
Observational studies suggest that gradual ascent (<500 m/d [1640 ft/d] once above 3000 m [9842 ft]) and halting ascent for a rest day (every 3-4 days for every 1000 m [3280 ft] gained) are useful methods to lower risk of acute altitude illness (SR; moderate QOE). Observational studies also support spending 6 to 7 days at 2200 to 3000 m (7218-9842 ft) prior to arrival at altitudes above 3000 m when possible (SR; low QOE).
The guideline proposes a novel, pragmatic risk stratification tool to define low, moderate, or high risk of HAPE and HACE, with moderate- and high-risk individuals identified by a history of altitude illness, a sleeping elevation on day 1 of 2800 m (9186 ft) or higher, and/or an ascent rate of 500 m/d or more above 3000 m. However, this tool has not yet been clinically validated.4
Acetazolamide, the most well-studied AMS chemoprophylactic, should be started the day prior to ascent and can be stopped after 2 to 4 days at peak altitude. A meta-analysis (12 trials; 1512 participants) noted a pooled absolute risk reduction of 15.4% in AMS with acetazolamide, 250 mg/d (19.1% vs 34.5%; odds ratio, 0.41; 95% CI, 0.26-0.64).5 For people with moderate to high risk of AMS or HACE, acetazolamide is recommended as first-line treatment for adults (125 mg every 12 hours orally) and children (1.25 mg/kg every 12 hours) and dexamethasone as second-line treatment for adults only (4 mg every 12 hours orally) (Table). The WMS recommends against prophylaxis with inhaled budesonide (SR; high QOE), ginkgo biloba (SR; low QOE), or hypoxic tents (SR; moderate QOE) for acclimatization. Due to lack of evidence, the WMS did not make recommendations on coca leaves, brief oxygen bar therapy, or over-the-counter oxygen canister therapy.
The primary prevention of HAPE is gradual ascent. Chemoprophylaxis is recommended only for those with a history of HAPE and should be initiated the day prior to ascent and continued for 4 to 7 days (limited evidence) or until descent. Preventive medications target excessive hypoxic pulmonary vasoconstriction. The first-line HAPE chemoprophylaxis medication is extended-release nifedipine (30 mg every 12 hours orally or 20 mg every 8 hours) (SR; moderate QOE based on a single small study6 and extensive clinical experience) (Table). Second-line preventive medication is tadalafil (10 mg every 12 hours orally) (SR; low QOE), and dexamethasone is considered third-line treatment (SR; low QOE). Salmeterol (weak recommendation [WR]; moderate QOE) and acetazolamide (SR; moderate QOE) should not be used for HAPE prevention. There are limited data on HAPE chemoprophylaxis in children.7
The definitive treatment for severe AMS, HACE, and HAPE is immediate descent until symptoms resolve (SR; high QOE), which typically occurs after descending 300 to 1000 m (984-3280 ft) but may vary by individual.
The approach to AMS treatment relies on severity of disease. For mild to moderate AMS, individuals can remain at their current altitude but limit further ascent. For severe AMS or HACE, the WMS recommends descent and supplemental oxygen to achieve Spo2 >90% (SR; high QOE) or portable hyperbaric chambers when supplemental oxygen and descent are not available (SR; moderate QOE). Both acetazolamide, 250 mg every 12 hours orally (2.5 mg/kg every 12 hours in children), and dexamethasone, 4 mg every 6 hours orally, intravenously, or intramuscularly (0.15 mg/kg every 6 hours orally, intravenously, or intramuscularly in children), can be considered for treatment of AMS (Table).4,5 For individuals with HACE, dexamethasone is recommended, with adult dosing of 8 mg once followed by 4 mg every 6 hours orally, intravenously, or intramuscularly (0.15 mg/kg every 6 hours orally in children).
Suspected HAPE calls for immediate descent of at least 1000 m or until symptoms resolve (SR; high QOE), with all other treatments considered as adjuncts or temporizing.1,4 Adjunctive treatments for adults include supplemental oxygen to target Spo2 >90% (SR; high QOE), portable hyperbaric chambers (SR; low QOE), extended-release nifedipine (30 mg every 12 hours orally) (SR; low QOE), tadalafil or sildenafil (WR; low QOE), or continuous positive airway pressure (WR; low QOE). Diuretics (SR; low QOE), β-agonists, dexamethasone, and acetazolamide (SR; low QOE) are not recommended for HAPE.
No specific pediatric HAPE treatment was outlined in the WMS guideline, but an international consensus statement on children at altitude extrapolated adult data to suggest a similar strategy of immediate descent, supplemental oxygen, and extended-release nifedipine (0.5 mg/kg every 8 hours orally) when response to the prior steps is unsatisfactory, with use of hyperbaric chambers only when supplemental oxygen and descent are not available.7
Discussion
The 2024 WMS guideline update provides a concise risk stratification tool, assessment after COVID-19 infection, clarification on diagnosis, and updated findings on staged ascent and hypoxic tents.7,8 More general advice on medical conditions and high-altitude travel has been recently published.1 Future research needs to include prospective studies to refine optimal ascent rates and randomized trials to better support pediatric recommendations.7,8
