High-Altitude Illness

Overview & definition

The high-altitude illness — the hypobaric hypoxia from the ascent to altitude (the low atmospheric pressure → the low PaO2). The spectrum: the AMS (the acute mountain sickness — the commonest), the HACE (the high-altitude cerebral oedema — the severe brain), the HAPE (the high-altitude pulmonary oedema — the severe lungs). The key principle: the DESCENT is the definitive treatment.[1][1]

The AMS — the acute mountain sickness

The AMS — the commonest (the 25 per cent at the 2500 m; the 50 per cent + at the 4500 m).[1][2][1]

The clinical — the headache (the hallmark) + at least one of: the nausea / the vomiting, the fatigue / the weakness, the dizziness / the lightheadedness, the sleep disturbance. The Lake Louise score.[1][2]

The management — the rest (the stop the ascent; the descend if the not the improved), the analgesia (the paracetamol / the NSAID), the antiemetic, the acetazolamide (the 125 to 250 mg the BD), the oxygen.[1]

The HACE — the high-altitude cerebral oedema

The HACE — the severe (the life-threatening). The brain oedema (the vasogenic — the hypoxia → the cerebral the vasodilation → the blood-brain-barrier the leak).[1][1]

The clinical — the AMS + the ataxia (the hallmark — the wide-based the gait) + the altered the mental state (the confusion, the lethargy, the coma).[1]

The management.[1][1]

1. The IMMEDIATE DESCENT (the definitive — the by at least 500-1000 m).[1]
2. The dexamethasone (the 8 mg the loading then the 4 mg the 6-hourly — the reduces the brain oedema).[1]
3. The oxygen (the supplemental — the target the SpO2 above 90).[1]
4. The Gamow bag (the portable the hyperbaric the chamber — the simulates the descent; the if the descent the not the possible).[1]

The HAPE — the high-altitude pulmonary oedema

The HAPE — the severe (the life-threatening). The non-cardiogenic pulmonary oedema (the uneven the pulmonary the vasoconstriction → the overperfusion of the dilated vessels → the capillary the leak → the oedema).[1][1]

The clinical — the dyspnoea (the exertional → the rest), the cough (the dry → the pink / the frothy), the cyanosis, the crackles, the tachycardia, the tachypnoea. The CXR (the patchy the infiltrates).[1][2]

The management.[1][1]

1. The IMMEDIATE DESCENT (the definitive).[1]
2. The oxygen (the supplemental — the target the SpO2 above 90).[1]
3. The nifedipine (the 30 mg the SR the 12-hourly — the pulmonary the vasodilator; the reduces the pulmonary the pressure).[1]
4. The CPAP / the PEEP (the alveolar the recruitment).[1]
5. The Gamow bag (the if the descent the not the possible).[1]

The prevention

• The gradual the ascent (the 300 to 500 m/day above the 3000 m; the rest day every the 1000 m).[1]
• The acetazolamide (the prophylactic — the 125 to 250 mg the BD; the start the day before the ascent; the continue the 2 to 4 days at the altitude). The carbonic the anhydrase the inhibitor → the metabolic the acidosis → the compensatory the hyperventilation → the acclimatisation the accelerated.[1][2]
• The avoid the alcohol, the sedatives, the high-the-altitude the sleep the medications.[1]

Prognosis

The AMS the resolves with the rest / the descent. The HACE and the HAPE the life-threatening if the not the descended. The descent the definitive. The mortality the low if the prompt; the high if the delayed.[1][2][1]

Red flags

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Altitude physiology — the barometric pressure and the alveolar gas equation

High-altitude illness is driven entirely by hypobaric hypoxia: ascent → fall in barometric pressure → fall in inspired PO2 → fall in alveolar PO2 (PAO2) → fall in arterial PO2 (PaO2). The alveolar gas equation is the foundational principle for the whole topic and the single most examined concept in the Fellowship altitude question.[1][3][4]

Barometric pressure falls exponentially with altitude (not linearly — the atmosphere is compressible, so most of the air mass sits below). Sea level 760 mmHg; 5500 m (Everest base camp) ~380 mmHg; 8848 m (Everest summit) ~253 mmHg.[3][4]

Inspired PO2 = FiO2 × (PB − PH2O). Sea level: 0.21 × (760 − 47) = 149 mmHg. At 8848 m: 0.21 × (253 − 47) = 43 mmHg. Water vapour pressure (47 mmHg) is a CONSTANT at body temperature — it does NOT fall with altitude, so it consumes a proportionally larger fraction of the low barometric pressure at altitude.[3]

The alveolar gas equation: PAO2 = PiO2 − (PaCO2 / R). R = respiratory quotient (~0.8 mixed diet). Sea level: PAO2 = 149 − (40/0.8) = 149 − 50 = ~99 mmHg. The key insight: at altitude PAO2 depends HEAVILY on PaCO2 — the LOWER the PaCO2 (the more hyperventilation), the HIGHER the PAO2. This is precisely why acclimatisation (hyperventilation) saves the climber.[3][4]

[1]

The crucial insight. At the summit of Everest the only reason a human survives is extreme hyperventilation (PaCO2 7–8 mmHg — the lowest ever recorded in a living person), which pushes PAO2 back up to ~35 mmHg, just enough to sustain consciousness. Without hyperventilation the alveolar PO2 would fall to ~30 mmHg → loss of consciousness. Acclimatisation saves the climber by lowering PaCO2.[3][4]

Acclimatisation — the cascade of physiological adaptations

Acclimatisation is the series of adaptations over days to weeks at altitude that restore tissue oxygen delivery. TIME is the essence — gradual ascent allows acclimatisation; rapid ascent (flight, car, ski-lift) bypasses it and causes illness. The ventilatory component takes 4–7 days; the haematological takes weeks; tissue adaptation takes months.[1][2][4]

[1]

Sleep and periodic breathing (Cheyne-Stokes). At altitude hypoxia drives hyperventilation → ↓PaCO2 → central apnoea → ↑PaCO2 + ↓PaO2 → hyperventilation resumes. The cycle is 12–20 seconds, near-universal above 3000 m, causing poor sleep and daytime fatigue. Acetazolamide abolishes periodic breathing (smoothes the CO2 response) and improves sleep. Do NOT use sedatives — they depress ventilation.[1][4]

The AMS — the Lake Louise score

The Lake Louise score (2018 revision — self-reported + clinical). The diagnosis requires headache + total score ≥ 3 with at least one symptom.[1][6]

[1]

The functional score (clinician-assessed): 0 = no symptoms; 1 = symptoms but activity unchanged; 2 = activity reduced; 3 = bedbound / severe. Mild AMS = headache + 1–3 points; moderate = 4–5; severe = 6+. HACE = AMS + ataxia OR altered mental state (a separate diagnosis, NOT a high score).[1][6]

AMS vs HACE vs HAPE — the comprehensive comparison

[1]

HACE — the pathophysiology deep dive

HACE is severe brain oedema. Two synergistic mechanisms:[1][3]

1. Vasogenic oedema (EARLY). Hypoxia → cerebral vasodilation (hypoxia is a potent vasodilator) → ↑cerebral blood flow → ↑capillary hydrostatic pressure → blood-brain-barrier leak → fluid into the extracellular space (white matter). Dexamethasone reverses this (↓BBB permeability).[1][3]

2. Cytotoxic oedema (LATE). Severe hypoxia → failure of the Na/K ATPase → intracellular Na+ and water → cellular swelling (grey matter). Late and irreversible. Dexamethasone is less effective for cytotoxic oedema.[3]

3. Raised intracranial pressure (consequence). Oedema → ↑ICP → headache, vomiting, altered mental state, late herniation (Cushing triad — bradycardia + hypertension + irregular respiration).[3]

Ataxia is the earliest and most reliable sign. The cerebellum is exquisitely sensitive to hypoxia (high metabolic demand) → ataxia PRECEDES confusion. ANY ataxia at altitude = HACE → IMMEDIATE descent. A simple tandem-gait test (heel-to-toe walking) is the best screening tool. Do NOT wait for coma.[1][3]

HAPE — the pathophysiology deep dive

HAPE is non-cardiogenic pulmonary oedema. Pulmonary artery pressure is the driver.[1][1][4]

1. Hypoxic pulmonary vasoconstriction (HPV) — unique to the pulmonary circulation (systemic vasodilates; pulmonary constricts). Uniform HPV is benign. UNEVEN (patchy/heterogeneous) HPV → some vessels constrict tightly (low flow) while others dilate (high flow) → overperfusion of the dilated vessels.[1][4]

2. Capillary stress failure (West 1991 — rabbit model). High pressure → capillary wall stress → mechanical disruption of the alveolar-capillary membrane → leak of red cells, protein and fluid into the alveoli. HAPE fluid is BLOODY (red cells) and high-protein (an exudate) — NOT a transudate.[4]

3. The HAPE-susceptible (HAPE-S) phenotype. ~5–10% of climbers have exaggerated (uneven) HPV → ↑pulmonary artery pressure at moderate altitudes where others tolerate. Single-nucleotide polymorphisms in NO synthase and amiloride-sensitive channels contribute. A PRIOR HAPE is the strongest risk factor.[4]

Clinical progression. Reduced exercise tolerance (earliest) → dyspnoea at rest → dry cough → pink-frothy sputum → cyanosis → coma (hypoxia) → death (~50% untreated). The 2nd-night rule: HAPE is typically worst on the 2nd night (sleep exacerbates it — nocturnal hypoxia).[1][4]

Pharmacology — the altitude drugs compared

[1]

The descent adjuncts — Gamow bag, oxygen, CPAP

[1] [1]

The management — the field protocol

ICU management of severe HACE and HAPE

For the patient who reaches the ICU comatose (HACE) or in refractory hypoxaemic respiratory failure (HAPE), the principles are oxygenation, lung-protective ventilation, control of intracranial pressure, and reversal of the pulmonary hypertension — combined with the ongoing imperative that the patient must remain at low altitude.[1]

HACE in ICU. (1) Airway protection — intubate for GCS ≤8 or loss of airway reflexes. (2) Normocapnia / mild hyperventilation only if signs of impending herniation (avoid prolonged hyperventilation — cerebral ischaemia). (3) Continue dexamethasone 4 mg 6-hourly. (4) Head of bed 30°, normoglycaemia, normothermia, avoid hypotension (CPP >60). (5) Hyperosmolar therapy (mannitol / hypertonic saline) for cerebral oedema with herniation signs. (6) Seizure control (benzodiazepines; levetiracetam). (7) CT brain to exclude alternative causes (infarct, haemorrhage) once stable — MRI shows characteristic corpus callosum splenium signal change.[1][3]

HAPE in ICU. (1) Oxygen — target SpO2 >90% (PAO2 >60). (2) Non-invasive ventilation (CPAP/BiPAP) if distress/hypoxaemia persists on high-flow oxygen — splints alveoli and drives oedema back. (3) Intubate + lung-protective ventilation if NIV fails or the patient tires — VT 6 mL/kg PBW, plateau <30 cmH2O, PEEP titrated to SpO2 (typically 10–14 cmH2O). (4) Continue nifedipine SR 30 mg 12-hourly. (5) Position upright to aid venous return. (6) AVOID diuretics, nitrates, and preload-reducers — the HAPE patient is intravascularly volume-depleted; these worsen output and perfusion. (7) Treat secondary infection if present; otherwise no role for routine antibiotics. Resolution over 24–48 h with oxygen + descent is the rule.[1][4]

[1]

Special populations at altitude

[1]

Clinical pearls

Additional red flags

Landmark trials and guidelines

[1] [1] [1] [1] [1] [1]

Prognosis — summary

The AMS resolves with rest or descent within 12–24 h. The HACE and HAPE are life-threatening if descent is delayed — untreated HACE mortality approaches 60% and untreated HAPE approaches 50%. With prompt descent, oxygen and matched drug therapy, HACE/HAPE mortality falls below 5%. Resolution of HAPE over 24–48 h with oxygen and descent is the rule; residual neurological deficit after HACE is uncommon with early treatment but can follow delayed or severe cases. The single most important determinant of outcome is the SPEED of descent.[1][2][1][3]

SaqBlocks — fellowship exam practice

[1] [1]

References

1. [1]Luks AM, et al. Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update Wilderness Environ Med, 2024.PMID 37833187
2. [2]Luks AM, et al. Medical Conditions and High-Altitude Travel N Engl J Med, 2022.PMID 35081281
3. [3]Hackett PH, Roach RC High-altitude illness N Engl J Med, 2001.PMID 11450659
4. [4]Bärtsch P, Swenson ER Longitudinal fluorescent observation of retinal degeneration and regeneration in zebrafish using fundus lens imaging Mol Vis, 2013.PMID 23734077
5. [5]Low EV, Avery AJ, Gupta V, Schedlbauer A, Grocott MP Gene therapy in animal models of autosomal dominant retinitis pigmentosa Mol Vis, 2012.PMID 23077406
6. [6]Imray C, Booth A, Wright A, Bradwell A Normal mammalian cells negatively regulate telomere length by telomere trimming Hum Mol Genet, 2011.PMID 21903669