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Altitude Illness

Description:
Spectrum of cerebral and pulmonary syndromes from inadequate acclimatization on ascent to high altitude.

Altitude Categories:
- High: 1,500 to 3,500 m
- Very high: 3,500 to 5,500 m
- Extreme: 5,500 to 8,850 m (1)

  • Affects anyone including fit individuals. Mostly self-limited syndrome.

Types

  • Acute Mountain Sickness (AMS): onset 6-12 hours after ascent >2,500 m; neurologic symptoms predominate.
  • High-Altitude Pulmonary Edema (HAPE): noncardiogenic pulmonary edema; after ≥2 days at >3,000 m; rare 2,500-3,000 m.
  • High-Altitude Cerebral Edema (HACE): potentially fatal neurologic syndrome; end-stage AMS; onset >2 days at >4,000 m.

Geriatric Considerations

  • Risk does not increase with age.
  • Allow extra acclimatization time.
  • Preexisting illnesses may worsen.

Pediatric Considerations

  • Incidence similar to adults; diagnosis may be delayed.
  • Behavioral symptoms in child post-ascent should prompt altitude illness consideration.

Pregnancy Considerations

  • Risk unknown; no evidence of risk at 1,500-3,500 m in normal pregnancies.

Epidemiology

  • Incidence and severity increase with altitude and ascent rate.
  • AMS affects >25% ascending to 3,500 m; >50% above 6,000 m.
  • HACE rare in general population (<0.01% at 2,500 m), but 1-2% in trekkers near 4,000 m.
  • HAPE 0.01-0.1% general population at 2,500 m; 2-6% in trekkers at 4,000 m.

Etiology and Pathophysiology

  • Hypobaric hypoxia/hypoxemia precipitate altitude illness.
  • AMS and HACE are on a continuum.
  • AMS symptoms result from cerebral swelling via hypoxia-induced vasodilation or cerebral edema.
  • Mechanisms: impaired cerebral autoregulation, vasogenic mediator release, blood-brain barrier alteration.
  • HAPE: exaggerated pulmonary hypertension → vascular leakage via overperfusion or stress failure.
  • Genetics: poorly understood predisposition to AMS.

Risk Factors

  • Prior AMS, HACE, HAPE history
  • Improper acclimatization
  • Ascent rate >500 m/day
  • Extreme altitude trips
  • Increased time at altitude
  • Higher sleeping altitude
  • Cardiac congenital abnormalities
  • Younger age (<50 years) (1)

General Prevention

  • Richalet hypoxia sensitivity test predicts risk (79% positive predictive value) (1).
  • Preacclimatization protects against illness.
  • Staged ascent: 6-7 days at 2,200-3,000 m (3).
  • Ascend ≤500 m/day.
  • "Climb high, sleep low" principle above 3,500 m.
  • Avoid heavy exertion first 1-3 days.
  • Avoid respiratory depressants (alcohol, sedatives).
  • Preascent conditioning not preventive.

Pharmacologic Prophylaxis

  • Acetazolamide, dexamethasone, ibuprofen (see Treatment).
  • For HAPE risk: nifedipine, dexamethasone, tadalafil.

Diagnosis

History

  • AMS symptoms: headache, anorexia, irritability, fatigue, nausea, vomiting, dizziness, lightheadedness, exertional dyspnea, insomnia.
  • Symptoms usually resolve 18-36 hours without descent (1).
  • Lake Louise Questionnaire: ranks 4 symptoms 0-3; diagnostic if headache ≥1 and total ≥3.
  • Mild: 3-5 points
  • Moderate: 6-9 points
  • Severe: 10-12 points

  • Score after 6 hours at altitude recommended.

  • HAPE symptoms: reduced exercise tolerance, exertional dyspnea, cough, cyanosis, pink frothy sputum (1-3 days after ascent).

  • Diagnosis requires ≥2 symptoms (dyspnea, cough, chest tightness, etc.) and ≥2 signs (crackles, tachypnea).

  • HACE symptoms: altered mental status, irrational behavior, lethargy, coma.

  • AMS progresses to HACE in <1% cases.

Physical Exam

  • HAPE: lung crackles, wheezing, cyanosis, tachycardia, tachypnea.
  • HACE: altered mental status, truncal ataxia, papilledema, retinal hemorrhage, cranial nerve palsies, rare focal neuro deficits.

Differential Diagnosis

Syndrome Differential Diagnoses
AMS/HACE Dehydration, toxins, subarachnoid hemorrhage, CNS mass, CVA, migraine, CO exposure, CNS infection, psychosis
HAPE Pneumonia, cardiogenic pulmonary edema, pneumothorax, PE, asthma, MI, hyperventilation syndrome
  • Onset >3 days at altitude, no headache, or no rapid response to oxygen/descent → alternative diagnosis.

Diagnostic Tests & Interpretation

  • AMS: labs nonspecific, rarely needed.
  • HAPE: oximetry or blood gases show severe hypoxemia.
  • Chest X-ray: patchy infiltrates typical; clear lungs suggest alternate diagnosis.
  • ECG: sinus tachycardia or right heart strain (2).

Treatment

General Measures

  • Adhere to acclimatization guidelines if no prior altitude exposure.
  • Stop ascent, acclimatize at same altitude, or descend if symptoms persist >24 hours.
  • Descent is definitive treatment; modest altitude reduction causes dramatic improvement.
  • Oxygen therapy: continuous via cannula/mask; titrate to SaO2 >90% (2).

AMS and HACE

  • Acetazolamide reduces mild/moderate AMS (see Medication).
  • Dexamethasone effective for moderate AMS (see Medication).
  • HACE: acetazolamide prophylaxis, dexamethasone treatment, immediate descent, oxygen therapy (3)[A].
  • Portable hyperbaric therapy if descent impossible (3)[B].

HAPE

  • Oxygen therapy to maintain SaO2 >90% (3)[A].
  • Minimize exertion; keep warm.
  • Immediate descent/evacuation (3)[A].
  • Portable hyperbaric therapy (Gamow bag) effective if descent impossible (3)[C].
  • Nifedipine for pulmonary hypertension (see Medication).

Medication

  • Oxygen: 2-15 L/min to maintain SaO2 >90%.
  • Acetazolamide:
  • Primary prevention adult: 125 mg PO BID starting 24 hours pre-ascent, continued 2-4 days at altitude (3)[A].
  • Pediatric: 2.5 mg/kg q12h max 125 mg (3)[C].
  • AMS treatment adult: 250 mg PO BID until symptoms resolve (3)[C].
  • Pediatric same dosing.
  • Dexamethasone:
  • Prevent AMS: 2 mg PO q6h or 4 mg PO q12h starting 1 day pre-ascent (not pediatric) (3)[A].
  • Treat AMS: 4 mg PO/IV/IM q6h (peds 0.15 mg/kg) (3)[B].
  • Treat HACE: 8 mg initially, then 4 mg q6h (peds 0.15 mg/kg) (3)[B].
  • Nifedipine:
  • Prevent HAPE: 30 mg ER PO BID starting 1 day pre-ascent, continued 2 days (3)[B].
  • Treat HAPE: 30 mg ER PO q12h (3)[C].
  • Tadalafil:
  • Prevent HAPE: 10 mg PO BID 1 day pre-ascent in susceptible individuals (3)[C].
  • Treat HAPE when descent/oxygen unavailable (3)[C].

Adjuncts

  • Salmeterol inhaled BID (limited evidence) (3)[B].
  • NSAIDs: aspirin 325 mg q4h ×3 doses; ibuprofen 600 mg q8h ×1-2 days prophylaxis or headache treatment (3)[B].
  • Antiemetics: prochlorperazine 10 mg q6-8h; promethazine 25-50 mg q6h.
  • Ginkgo biloba, inhaled budesonide, acetaminophen for AMS prevention (3)[C].
  • Remote ischemic preconditioning, antioxidants, dietary nitrites, leukotriene blockers, PDE inhibitors, etc. lack quality evidence.
  • Coca-containing products used traditionally but not well studied.
  • Furosemide not recommended for HAPE prophylaxis or treatment (3)[C].

Admission & Nursing Considerations

  • Mild cases treated outpatient.

Ongoing Care

  • Mild cases: no follow-up required.
  • Severe cases: monitor until symptom resolution.

Patient Education

  • Counsel on high-altitude risks and symptom recognition.

Prognosis

  • Mild/moderate AMS self-limiting; HAPE and HACE respond well to early descent and treatment.

Complications

  • High-altitude retinal hemorrhage: usually asymptomatic, may cause visual changes.

References

  1. Savioli G, Ceresa IF, Gori G, et al. Pathophysiology and therapy of high-altitude sickness. J Clin Med. 2022;11(14):3937.
  2. Burtscher M, Hefti U, Hefti JP. High-altitude illnesses: new insights. Sports Med Health Sci. 2021;3(2):59-69.
  3. Luks AM, Auerbach PS, Freer L, et al. Wilderness Medical Society guidelines: altitude illness. Wilderness Environ Med. 2019;30(4S):S3-S18.

Additional Reading

  • Ucrós S, Aparicio C, Castro-Rodriguez JA, et al. High altitude pulmonary edema in children: systematic review. Pediatr Pulmonol. 2023;58(4):1059-67.

ICD10 Codes

  • T70.20XA Unspecified effects of high altitude, initial encounter
  • T70.20XD Unspecified effects of high altitude, subsequent encounter
  • T70.20XS Unspecified effects of high altitude, sequela

Clinical Pearls

  • Slow ascent and timely descent key to prevention and treatment.
  • Lack of symptom resolution with descent suggests alternate diagnosis.
  • High-flow oxygen titrated to SaO2 >90% first-line treatment for >mild altitude illness.