Acute Mountain Sickness: what's the latest on evidence and medical insights?

Fast high altitude exposure can trigger acute mountain sickness; in severe cases, deadly cerebral or pulmonary oedema.

An often benign condition that hides serious dangers

High-altitude illnesses (HAIs) arise from maladaptive responses to hypobaric hypoxia in unacclimatized individuals ascending rapidly above 2.500 metres. Acute forms include acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE), whereas chronic mountain sickness (CMS) affects long-term residents. AMS is generally benign but can progress to life-threatening complications if not promptly recognized and managed.

Epidemiology and risk factors

AMS incidence is influenced by rate of ascent, maximum altitude reached, and individual susceptibility. Symptoms typically occur within 6-24 hours after arrival and peak during the first night. Prevalence rises with elevation: studies report rates of 25-40% at 3.000-3.500 m and up to 90% above 4.500 m. Rapid ascent, particularly by air, significantly increases risk, as does climbing schedules with limited acclimatization.

Evidence regarding age and sex as risk factors is conflicting; physical fitness does not appear protective. Pre-existing conditions such as COPD and pulmonary hypertension increase susceptibility, whereas asthma does not. Previous episodes of HAPE or severe AMS strongly predict recurrence.

HACE is rare, occurring in ≤1% of individuals at altitudes above 4.000 m, often as a complication of severe AMS. HAPE incidence ranges from 0,2% with slow ascent to 6% with rapid ascent to 4.500 m. Cold exposure, intense exertion, and concurrent respiratory infection can contribute to HAPE onset.

Pathophysiology

The primary driver of HAIs is hypobaric hypoxia, which triggers ventilatory, cardiovascular, and cellular adaptations to maintain oxygen delivery. AMS and HACE are considered part of a neurological continuum. In AMS, hypoxia induces mild intracellular (cytotoxic) brain oedema, possibly from Na⁺/K⁺-ATPase dysfunction, along with trigeminovascular activation causing headache. HACE involves more severe vasogenic oedema and disruption of the blood-brain barrier, with MRI evidence of microhaemorrhages, especially in the splenium of the corpus callosum.

HAPE is a non-cardiogenic pulmonary oedema driven by uneven hypoxic pulmonary vasoconstriction, leading to over-perfusion of some lung regions, increased capillary pressure, and stress failure of the alveolar-capillary barrier. Impaired alveolar fluid clearance and, in some cases, inflammatory changes further contribute.

Clinical presentation and diagnosis

AMS diagnosis is clinical, based on the onset of headache plus gastrointestinal symptoms, dizziness, or fatigue after ascent. Research tools include the Lake Louise Scoring System (LLSS) and Environmental Symptoms Questionnaire (ESQ-C), but clinical judgment remains central. Differential diagnoses include migraine, dehydration, and carbon monoxide poisoning.

HACE presents with altered mental status, truncal ataxia, and other neurological signs, usually in a patient with preceding AMS. MRI may show reversible white matter oedema, though this is rarely available in remote settings. Stroke, intracranial haemorrhage, and metabolic disturbances should be excluded.

HAPE manifests after 2–5 days at altitude with disproportionate dyspnoea, reduced exercise tolerance, dry cough progressing to pink frothy sputum, and signs of hypoxaemia (cyanosis, low SpO₂). Chest radiography, when available, shows patchy alveolar infiltrates with normal cardiac silhouette. Pneumonia and pulmonary embolism are key differentials.

Prevention

Non-pharmacological measures are fundamental:

  1. Ascend gradually, limiting sleeping altitude gain to 300-500 m/day above 2.500-3.000 m.
  2. Include rest days every 3-4 days or after significant altitude gains.
  3. Pre-acclimatization by spending several days at moderate altitude or using hypoxic training protocols can reduce incidence.

Pharmacological prophylaxis is indicated for those at high risk or unable to control ascent rate:

Management

The cornerstone of acute HAI management is reversal of hypoxaemia by supplemental oxygen, descent, or portable hyperbaric chamber use.

Mild to moderate AMS - Rest, avoid further ascent until symptom resolution, maintain hydration, and use analgesics (NSAIDs, acetaminophen) and antiemetics as needed. Acetazolamide or dexamethasone may be used if symptoms persist or worsen.

Severe AMS and HACE - Immediate descent and oxygen therapy are mandatory. Administer dexamethasone (4–8 mg initially, then 4 mg every 6 h). If descent is impossible, continue oxygen and consider portable hyperbaric treatment.

HAPE - Immediate descent and high-flow oxygen are life-saving. Administer nifedipine (30 mg extended release every 12 h) to reduce pulmonary artery pressure. In hospital settings, oxygen may suffice without descent; PDE5 inhibitors or inhaled β₂-agonists are under investigation but lack robust evidence.

Prevention of AMS is essential

Acute mountain sickness is common among unacclimatized travellers to high altitude and can evolve into life-threatening cerebral or pulmonary oedema. Prevention through controlled ascent and, when necessary, pharmacological prophylaxis remains the most effective strategy. Early recognition and prompt intervention are essential to avoid morbidity and mortality. Ongoing research aims to identify objective diagnostic markers and refine individualized risk assessment, which could improve prevention and management strategies in the growing population exposed to high-altitude environments.

Sources and Further Reading
  1. Gatterer H, Villafuerte FC, Ulrich S, Bhandari SS, Keyes LE, Burtscher M. Altitude illnesses. Nat Rev Dis Primers. 2024;10:43. doi:10.1038/s41572-024-00526-w.
  2. West JB. The physiologic basis of high-altitude diseases. Ann Intern Med. 2004;141(10):789-800. doi:10.7326/0003-4819-141-10-200411160-00010.
  3. Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001;345(2):107-114. doi:10.1056/NEJM200107123450206.
  4. Luks AM, Swenson ER, Bärtsch P. Acute high-altitude sickness. Eur Respir Rev. 2017;26(143):160096. doi:10.1183/16000617.0096-2016.
  5. Bärtsch P, Swenson ER, Maggiorini M. High altitude pulmonary edema. N Engl J Med. 2001;345(15):1072-1078. doi:10.1056/NEJMra010111.
  6. Imray C, Wright A, Subudhi A, Roach R. Acute mountain sickness: pathophysiology, prevention, and treatment. Prog Cardiovasc Dis. 2010;52(6):467-484. doi:10.1016/j.pcad.2010.02.003.
  7. Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med. 2019;30(4 Suppl):S3-S18. doi:10.1016/j.wem.2019.04.006.