High-Altitude Illness

Overview & Definition

High-altitude illness is the term for the clinical syndromes caused by rapid ascent to altitude under the single upstream stressor of hypobaric hypoxia (a fall in barometric pressure lowering the partial pressure of inspired oxygen). The clinical spectrum comprises three overlapping syndromes that are best understood as points on a continuum rather than as separate diseases^[2][3]:

1. Acute mountain sickness (AMS) — the common, benign, self-limiting syndrome of headache plus at least one of gastrointestinal symptoms, fatigue/weakness or dizziness/vertigo (the 2018 Lake Louise revision removed the sleep item), typically causing headache and malaise within 6 to 12 hours of gaining altitude.
2. High-altitude cerebral oedema (HACE) — the severe progression of AMS to vasogenic cerebral oedema, characterised clinically by ataxia and altered consciousness, and fatal if untreated.
3. High-altitude pulmonary oedema (HAPE) — a non-cardiogenic pulmonary oedema caused by uneven hypoxic pulmonary vasoconstriction, presenting with exertional dyspnoea, dry then pink-frothy cough, cyanosis and reduced exercise performance, and the commonest cause of death related to altitude. ^[1]

The clinical skill in high-altitude illness is not the diagnosis (the syndromes have crisp signatures) but recognising severity early — specifically, recognising ataxia as the cardinal sign that converts AMS into the lethal HACE, and recognising exertional dyspnoea with cough as HAPE — because the definitive treatment, descent, must be triggered before the patient becomes bed-bound, comatose, or hypoxaemic in the field. The Lake Louise 2018 score standardises AMS diagnosis; the Wilderness Medical Society 2019 guideline codifies prevention and treatment.^[1][3]

Classification

High-altitude illness is classified by the clinical syndrome and by chronicity. Both axes are examinable.^[2][3]

Acute syndromes (hours to days at altitude): ^[1]

• Acute mountain sickness (AMS) — common (altitude illness affects 25 to 85 percent of travellers to high altitude, depending on rate of ascent, home altitude and individual susceptibility); typically self-limiting with rest and no further ascent.
• High-altitude cerebral oedema (HACE) — uncommon; progression of AMS; fatal if untreated. In one Himalayan series of 278 hikers at 4243 m there were 5 cases of cerebral oedema.^[22]
• High-altitude pulmonary oedema (HAPE) — uncommon (the same series recorded 7 cases of high-altitude pulmonary oedema); the commonest cause of altitude death; non-cardiogenic. ^[19][22]

Minor / less common acute syndromes: ^[1]

• High-altitude headache (HAI) — headache at altitude without other Lake Louise symptoms.
• High-altitude peripheral oedema — dependent oedema from hypoxia-driven sodium retention; benign.
• High-altitude retinopathy — retinal haemorrhages, usually asymptomatic; relevant when central vision is affected.
• High-altitude syncope — vasovagal on standing in hypoxia.
• High-altitude cough — dry, relentless cough (cold dry air + hyperventilation), distinct from HAPE. ^[1]

Chronic syndromes (weeks to years of high-altitude residence): ^[14]

• Chronic mountain sickness (Monge disease) — the pathological escalation of the physiological erythrocytosis of chronic hypoxia: excessive erythrocytosis (haemoglobin at or above 21 g/dL in men and 19 g/dL in women), hypoxaemia and multi-organ complications including right ventricular hypertrophy and microcirculatory thrombosis.
• High-altitude pulmonary hypertension — chronic hypoxic pulmonary vasoconstriction progressing to right ventricular hypertrophy and right heart failure. ^[14]

Altitude categories (teaching convention, not a Lake Louise 2018 result):

• High altitude — 1500 to 3500 m. AMS begins to occur.
• Very high altitude — 3500 to 5500 m. AMS, HAPE and HACE common with rapid ascent.
• Extreme altitude — above 5500 m. Acclimatisation cannot be sustained long-term; deterioration supervenes. ^[1]

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Epidemiology & Risk Factors

Tens of millions travel to altitude each year for trekking, mountaineering, pilgrimage (Amarnath Yatra, Kailash Mansarovar) and military deployment (Indian Armed Forces on the Siachen and Ladakh frontiers). Travel above 2500 m is associated with risk of acute altitude illness.^[3]

Incidence of AMS depends on rate of ascent, home altitude and susceptibility (25 to 85 percent of travellers to high altitude in one review).^[19]

• 25% of travellers to moderate elevations (6300 to 9700 ft) developed AMS in a general tourist survey, 65% of those within the first 12 hours.^[21]
• 53% AMS among 278 unacclimatised hikers at 4243 m (Pheriche); incidence rose in the young, those who flew to 2800 m, climbed fast, and spent fewer nights acclimatising.^[22]
• Higher with air travel straight to high altitude (for example La Paz/El Alto at 4061 m, Lhasa at 3650 m, Leh at 3500 m).

HACE and HAPE are far less common with prudent ascent but case fatality is high when descent is delayed. ^[1]

Risk factors:^[3][7]

• Rate of ascent — the single most important modifiable risk. Direct flight to 3500 m followed by trekking multiplies risk.
• Absolute altitude reached and sleeping altitude (risk rises above 2500 m, steeply above 3500 m).
• Prior acclimatisation — protective (the same individual tolerates the same altitude much better after a period at intermediate altitude).
• Individual susceptibility — highly reproducible: a person who developed HAPE once is very likely to again. Genetic factors (e.g. variants in endothelial nitric oxide synthase, HIF pathway) contribute.
• Exertion at altitude — increases risk, particularly of HAPE.
• Cold — adds to pulmonary vascular resistance and HAPE risk.
• Age — Gianfredi’s systematic review: 12 reports found a negative correlation between AMS prevalence and age, 11 no relationship, and 3 the opposite; old age does not seem to be a contraindication for high-altitude travel. Young fit men are often over-represented because they ascend faster, not because fitness protects.^[7]
• Physical fitness is NOT protective — fitness permits a faster (and therefore riskier) ascent.
• Obesity and pre-existing cardiopulmonary disease modestly increase risk.
• Female sex may carry slightly lower risk in some series.
• Drugs: alcohol, sedatives, anxiolytics and respiratory depressants worsen overnight hypoxaemia and increase risk.

Pathophysiology

All high-altitude illness flows from a single upstream cause — hypobaric hypoxia.^[2][6]

Hypobaric hypoxia. Barometric pressure falls with altitude. Direct measurements on Mt. Everest recorded mean daily pressures of 400.4 Torr at 5400 m and 253.0 Torr at 8848 m (summit).^[23] Because the fraction of oxygen in air is constant (~21%), inspired PO2 on the summit is about 0.21 × (253 − 47) ≈ 43 mmHg. The downstream consequences are:

1. The acute ventilatory response (minutes to hours). Hypoxia is sensed by the glomus cells of the carotid body, which signal via the glossopharyngeal nerve to the dorsal respiratory group in the medulla, increasing minute ventilation. This hypoxic ventilatory response (HVR) raises alveolar and arterial PO2 — the most immediate defence. However, blowing off CO2 produces a respiratory alkalosis (cerebral vasoconstriction; restricts deep sleep; contributes to periodic breathing). This is why acetazolamide works: by inhibiting carbonic anhydrase in the proximal renal tubule it induces a bicarbonate diuresis, correcting the alkalosis, restoring the central chemoreceptor set-point to drive ventilation harder, improving oxygenation and reducing periodic breathing.^[3]

2. Acclimatisation (days to weeks). Successful acclimatisation integrates:

• Renal bicarbonate excretion — restores arterial pH toward normal over 1 to 2 weeks (so the respiratory alkalosis no longer limits ventilation).
• Raised 2,3-bisphosphoglycerate (2,3-BPG) in erythrocytes — a conventional acclimatisation teaching point (the cited papers on this page do not give a packed direction of any oxyhaemoglobin-curve shift).
• Increased erythropoietin (EPO) from the renal cortical interstitial fibroblasts (HIF-2alpha driven) — raises red-cell mass over weeks, increasing oxygen-carrying capacity (but also viscosity).
• Hypoxic pulmonary vasoconstriction — a uniform but heterogeneous response across the lung.
• Cerebral blood flow increases acutely (hypoxic vasodilation), then partially normalises as viscosity and ventilation rise. ^[1]

Failure of acclimatisation — usually because of too-rapid ascent — produces the three syndromes. ^[1]

3. Mechanism of AMS. Cerebral blood flow rises to compensate for the low arterial oxygen content; this, combined with mild cytotoxic and vasogenic oedema, stretches the pain-sensitive dura and vessels, producing headache. The systemic symptoms (nausea, fatigue, insomnia, dizziness) reflect brainstem / chemoreceptor trigger-zone effects and disturbed sleep architecture with periodic breathing.^[2]

4. Mechanism of HACE — vasogenic cerebral oedema. When hypoxia is sustained, the blood-brain barrier leaks. Hypoxia induces vascular endothelial growth factor (VEGF) expression, increasing capillary permeability; cytotoxic oedema (failure of Na+/K+ ATPase in glial cells) and the failure of intracranial compliance produce raised intracranial pressure. The cerebellum is exquisitely sensitive — hence ataxia is the earliest and most reliable sign. Untreated, this progresses to cerebral herniation, coma and death. HACE is essentially AMS that has progressed to involve the cerebellum and brainstem.^[2]

5. Mechanism of HAPE — non-cardiogenic pulmonary oedema. Hypoxic pulmonary vasoconstriction (HPV) is the body's attempt to redirect blood from poorly ventilated alveoli. In HAPE-susceptible individuals, the response is excessive and uneven: some arterioles constrict powerfully while neighbouring ones do not, so the entire cardiac output is funnelled through the non-constricted capillaries at very high pressure. This produces capillary stress failure (West's hypothesis): the alveolar-capillary membrane ruptures under hydrostatic stress, allowing red cells and protein-rich fluid to flood the alveoli — a non-cardiogenic, permeability-type oedema with normal left atrial pressure.^[4][5]

Two additional defects amplify HAPE: ^[1]

• Impaired alveolar fluid clearance — alveolar epithelial sodium channels (ENaC) clear fluid from the alveolus; this clearance is suppressed by hypoxia (the mechanistic rationale that motivated inhaled salmeterol trials). WMS 2019 still does not recommend salmeterol for prevention.^[3][27]
• Reduced nitric oxide (NO) bioavailability in the pulmonary vasculature of HAPE-susceptible individuals — the rationale for PDE-5 inhibitors (sildenafil, tadalafil).^[4]

Why exertion and cold precipitate HAPE: exertion raises cardiac output, magnifying the pressure insult to non-constricted capillaries; cold further raises pulmonary vascular resistance. ^[1]

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Clinical Presentation

Acute mountain sickness (AMS)

Onset typically within 6 to 12 hours of gaining altitude — headache and malaise are the opening features. The 2018 Lake Louise consensus defines AMS as headache plus one or more of the following symptom groups, in the setting of a recent altitude gain^[1][19]:

• Gastrointestinal — nausea/vomiting and/or anorexia.
• Fatigue/weakness — unusual tiredness, reduced exercise tolerance.
• Dizziness/vertigo — light-headedness on standing.

Note: the 2018 revision eliminated disturbed sleep as a questionnaire item — sleep disturbance at altitude is now understood to reflect altitude hypoxia itself rather than AMS, so it no longer counts towards the score. ^[1]

The symptom is headache-driven: without headache, AMS cannot be diagnosed. Headache is typically bilateral, throbbing, worse at night and on waking, and exacerbated by exertion or cough. ^[1]

High-altitude cerebral oedema (HACE)

HACE is AMS that has progressed to involve the brain substance. The two cardinal features, either of which mandates an immediate diagnosis of HACE, are: ^[1]

• Ataxia — inability to walk a straight line heel-to-toe. This is the single most reliable early sign of HACE and the trigger to descend immediately. Anyone with ataxia at altitude has HACE until proven otherwise.
• Altered consciousness — confusion, drowsiness, disorientation, progressing to coma. ^[1]

Additional features: severe headache unresponsive to analgesia, vomiting (often projectile), lassitude, hallucinations, and (late) focal neurological signs and seizures. Onset usually within 1 to 4 days of altitude gain. Untreated HACE can progress to coma and death — descend immediately (do not teach an unsourced “death within 24 hours” figure).^[19][3]

High-altitude pulmonary oedema (HAPE)

Onset usually in the first 2 to 5 days after acute exposure above 2500–3000 m (classically the second night).^[4] Symptoms in order of appearance:

• Reduced exercise performance — the earliest manifestation; the trekker who is now slower than peers.
• Exertional dyspnoea — out of proportion to altitude and exertion; progresses to dyspnoea at rest.
• Dry, persistent cough — later becoming pink, frothy sputum (frank haemoptysis in severe cases).
• Cyanosis, tightness in the chest. ^[1]

Signs: tachycardia, tachypnoea, bibasal inspiratory crackles (often right mid-zone first, becoming diffuse), cyanosis, and a fall in SpO2. Unlike cardiogenic pulmonary oedema, the jugular venous pressure and cardiac examination are often normal (no third heart sound) and the heart is normal in size — hydrostatic oedema with normal left atrial pressure.^[4]

High-altitude headache (HAI)

Headache at altitude within 24 hours of ascent, without the other Lake Louise features. Bilateral, dull or throbbing, aggravated by exertion or Valsalva. Distinguished from AMS by the absence of accompanying symptoms. Treat with simple analgesia, hydration and acclimatisation. ^[1]

Atypical presentations

• Children — cannot reliably report symptoms; present with behavioural change, irritability, refusal to play or eat, excessive sleepiness or unexplained crying. Have a low threshold for presumptive treatment.
• The elderly — present more slowly and with more fatigue; ataxia may be subtle. AMS scores perform less well in older adults.^[7]
• Pregnant women — may attribute dyspnoea to the pregnancy, delaying recognition of HAPE.
• The very fit — under-report symptoms ("I will sleep it off") and may mask HACE ataxia as fatigue.

Differential Diagnosis

An altitude traveller is also at risk of unrelated illness, some of which are lethal mimics. The cardinal rule is that any symptom at altitude is altitude illness until proven otherwise — but the mimics must always be considered, especially in a group setting.^[2]

Three points an examiner rewards: (1) Ataxia at altitude is HACE until proven otherwise — never write it off as "tired" or "drunk". (2) Multiple casualties in a group with headache/nausea is carbon monoxide poisoning until excluded — check the stove and ventilation. (3) A young, previously fit adult with pulmonary oedema at altitude is HAPE — do not anchor on "unfitness" or "pneumonia". ^[1]

Clinical & Bedside Assessment

In the field, decisions are clinical. The focused assessment is short but disciplined.^[2][3]

Vital signs and bedside observations: ^[1]

• SpO2 (finger pulse oximetry) — trends over time matter more than a single reading. A fall of 5 percentage points or more below the group baseline for the altitude is significant. In HAPE, SpO2 is markedly low for the altitude.
• Respiratory rate, heart rate, blood pressure, temperature (exclude hypothermia with a low-reading thermometer).
• Conscious level — AVPU or GCS; serially.
• Hydration — urine output (a target of clear, copious urine; oliguria suggests dehydration or HAPE). ^[1]

Cardinal bedside manoeuvre for HACE — the tandem gait (heel-to-toe) test: the patient walks a straight line, placing the heel of one foot directly in front of the toe of the other, for 5 to 10 paces. Inability to do this smoothly (staggering, sidestepping, falling) is ataxia and mandates an immediate diagnosis of HACE and descent. Also test finger-to-nose, Romberg and observe for intention tremor. ^[1]

Cardinal bedside assessment for HAPE — exertional testing and auscultation: ^[1]

• Time a standardised walk/climb; compare to the patient's baseline and to peers.
• Exertional desaturation (a 5 to 10 point SpO2 drop on mild exertion that recovers slowly) is an early HAPE sign.
• Auscultate the chest for bibasal inspiratory crackles (often right mid-zone first) and exclude wheeze. ^[1]

Lake Louise 2018 scoring at the bedside is performed in two flavours: ^[1]

• Self-scored (LLSelf) — the patient rates each symptom (used for surveillance / groups).
• Clinical score (LLClinical) — the clinician assesses and combines with the functional score (used to direct care). ^[1]

Investigations

In the field, investigations are limited and decisions are clinical. Hospital/laboratory investigation supports, but never supersedes, the diagnosis.^[2]

Field investigations: ^[1]

• Finger pulse oximetry — essential and available; trend over time.
• Portable chest X-ray (if available) — in HAPE shows patchy, often right-sided infiltrates progressing to diffuse alveolar shadowing, with a normal cardiac silhouette — distinguishing HAPE from cardiogenic oedema. ^[1]

Hospital investigations: ^[14][15][17]

• Chest X-ray — in HAPE, radiographic infiltrates and interstitial oedema; serial films track resolution (radiographic abnormalities were recorded at admission and followed to resolution in a 110-patient HAPE series). ^[17]
• Pulse oximetry / arterial saturation — SpO2 was measured at admission in the same HAPE series; the treatment target in established HAPE is arterial saturation above 90%. ^[9][17]
• ECG — an electrocardiogram was part of the admission work-up in the HAPE series above; no specific pattern is diagnostic. ^[17]
• Echocardiography — used to estimate pulmonary artery pressure in HAPE-susceptible subjects (right ventricular-to-atrial pressure gradient). ^[17]
• Brain MRI in HACE — shows diffusion restriction with T2/FLAIR hyperintensity in the splenium of the corpus callosum (present in all 21 patients of one series), with involvement of the centrum semiovale and deep white matter and middle cerebellar peduncles, and microbleeds on susceptibility-weighted imaging. ^[15]
• Full blood count — haemoglobin at or above 21 g/dL (men) or 19 g/dL (women) defines the excessive erythrocytosis of chronic mountain sickness. ^[14]

The 2018 Lake Louise Acute Mountain Sickness Score

The Lake Louise AMS scoring system has been a research tool since first published in 1991.^[1]

Diagnostic criterion for AMS (2018 Lake Louise): the presence of headache PLUS at least one other symptom from the questionnaire, in the setting of a recent gain in altitude. ^[1]

Questionnaire items after the 2018 revision: ^[1]

Why sleep was removed: recent studies showed that disturbed sleep at altitude is more likely due to altitude hypoxia per se, and is not closely related to AMS. The consensus group — meeting at the ISMM World Congress in Bolzano (2014) and the International Hypoxia Symposium in Lake Louise (2015) — therefore revised the score to eliminate disturbed sleep as a questionnaire item and updated the instructions for use of the score. ^[1]

Note: ataxia and altered consciousness do not appear among the questionnaire items — neurological progression beyond AMS is HACE, not "severe AMS". ^[1]

^{[9] [12] [13] [15] [19] [8] [9] [10] [19]}

Management — Resuscitation

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Field resuscitation of suspected HACE or HAPE rests on three actions executed without delay: stop all ascent, give oxygen, and begin descent.^[2][3]

1. ABCDE. Secure the airway (recovery position if comatose); high-flow oxygen; check for trauma and hypothermia.
2. Oxygen — give the highest concentration available via mask; target SpO2 over 90% (or the highest achievable). In HAPE, oxygen alone can dramatically improve gas exchange within minutes by lowering pulmonary artery pressure and relieving hypoxic vasoconstriction.
3. Stop all exertion, sit the patient upright, keep them warm and dry — exertion raises pulmonary pressures and worsens HAPE; cold raises pulmonary vascular resistance.
4. Immediate descent — AMS/HACE symptoms typically resolve after 300 to 1000 m; in HAPE, try to descend at least 1000 m or until symptoms resolve. Descent is mandatory for everyone with HACE or HAPE. If the patient cannot walk safely, arrange an escorted or carried descent — in a published field case the ataxic HACE patient was brought down by mule with accompanying team members. ^[12][13][19]
5. Portable hyperbaric chamber — if descent is impossible (weather, terrain, darkness), a portable hyperbaric chamber is an effective temporising measure; it must not delay descent when descent is required. ^[3][9]
6. Position and airway in a comatose HACE patient — recovery position on descent; have suction ready; protect the cervical spine if there is any risk of fall. ^[2]

Drugs (oxygen, dexamethasone, nifedipine, acetazolamide) are adjuncts that buy time — they are never a substitute for descent in HACE/HAPE.^[3]

Management — Definitive & Stepwise

The Wilderness Medical Society 2019 guideline defines the agents, doses and indications.^[3]

Prevention (the best treatment)

The single most effective preventive measure is gradual ascent^[3]:

• Slow ascent is the single most important preventive measure. WMS 2019: with travel above 3000 m, do not increase sleeping elevation by more than 500 m, and include a rest day (no ascent to a higher sleeping elevation) every 3 to 4 days.^[3] HAPE-susceptible individuals can avoid HAPE if they ascend slowly with an average gain not exceeding 300–350 m/day above 2500 m.^[4]
• "Climb high, sleep low" — daytime excursions higher than the sleeping altitude are the traditional pattern of a graded ascent.
• Avoid overexertion, severe exercise and cold exposure — all were identified as risk factors for HAPE in a 110-patient series. ^[17]
• Recognise symptoms early and stop ascending. ^[19]

Pharmacological prophylaxis:^[3]

• Acetazolamide — WMS 2019 prophylaxis 125 mg every 12 h; treatment of AMS 250 mg every 12 h.^[3] Meta-analyses: 125, 250 and 375 mg twice daily all reduce AMS vs placebo with no dose–efficacy association; 250 mg twice daily had a ~5-day window vs 3 days at 375 mg twice daily; 250 mg daily is the lowest daily dose with trial evidence in one meta-analysis (NNT 6 at that dose).^[10][24][25] Mechanism: carbonic anhydrase inhibition.
• Dexamethasone — WMS prophylaxis 2 mg every 6 h or 4 mg every 12 h; 4 mg twice daily reduced AMS incidence in a network meta-analysis (an option when acetazolamide is unsuitable). HACE treatment: 8 mg once then 4 mg every 6 h (IM, IV or oral).^[3][10]
• Ibuprofen — 600 mg three times daily also significantly reduced AMS incidence. ^[10]
• Nifedipine — WMS 2019 HAPE prevention: 30 mg extended-release every 12 h or 20 mg extended-release every 8 h. Bärtsch 1991: 20 mg slow-release every 8 hours (HAPE 1/10 nifedipine vs 7/11 placebo at 4559 m). A short-acting 10 mg loading dose is no longer used (hypotension).^[3][11]
• Salmeterol 125 µg inhaled twice daily reduced HAPE in susceptibles from 74% to 33% in one trial, but WMS 2019 does not recommend salmeterol for HAPE prevention (Grade 2B) and makes no recommendation for treatment (lack of data).^[27][3] Tadalafil 10 mg every 12 h and dexamethasone 8 mg twice daily reduced HAPE vs placebo at 4559 m (HAPE in 7/9 placebo, 1/8 tadalafil, 0/10 dexamethasone).^[26]
• Sildenafil — in healthy volunteers, 50 mg three times daily did not reduce pulmonary artery pressure at altitude and AMS scores were worse; routine prophylactic use is not supported. ^[18]

Acetazolamide and sulphonamide allergy (WMS 2019): acetazolamide contains a sulfa moiety but carries an extremely low risk of inciting an allergic reaction in persons with sulfonamide allergy; persons with known sulfonamide allergy can consider a trial. Do not teach unsourced renal/hepatic/adrenal/aspirin/paraesthesia lists as WMS 2019 or as Lake Louise 2018. ^[3]

Acute mountain sickness (AMS)

Stepwise management^[13][19]:

1. Stop ascending — do not go higher; rest at the same altitude. Acetazolamide or dexamethasone may be used for treatment of AMS. ^[19]
2. Hydrate and give simple analgesia for headache (ibuprofen 600 mg three times daily reduced AMS incidence in randomised prophylaxis trials and is a reasonable analgesic choice). ^[10]
3. Acetazolamide 250 mg twice daily — WMS 2019 AMS treatment 250 mg every 12 h (one treatment study used this dose; whether a lower dose might suffice is unknown). ^[3]
4. Supplemental oxygen if available, to keep arterial saturation over 90%. ^[9]
5. Reassess regularly — most mild AMS resolves with rest at the same altitude.
6. Descend (typically 300 to 1000 m for AMS/HACE) if symptoms do not improve, worsen despite treatment, or if ataxia or altered consciousness develop — ataxia means HACE, and descent becomes mandatory. ^[3][19]

High-altitude cerebral oedema (HACE)

HACE is a medical emergency^[12][16]:

1. Immediate descent — the only causal therapeutic intervention is to restore adequate oxygen tension: descend to lower altitude or give oxygen therapy; pharmacotherapy is only supportive. ^[16]
2. High-flow oxygen. ^[12]
3. Dexamethasone — a published field regimen used 8 mg intramuscularly followed by 4 mg every six hours (continued orally during descent), with recovery after escorted descent. Never let dexamethasone delay descent. ^[12]
4. Acetazolamide 250 mg twice daily was given alongside dexamethasone in the same field case. ^[12]
5. Portable hyperbaric chamber if descent is impossible — an effective temporising measure. ^[9]
6. Escorted descent and evacuation once stabilised — the ataxic patient must not descend alone; brain MRI (when reachable) shows splenial involvement and excludes mimics. ^[12][15]

High-altitude pulmonary oedema (HAPE)

HAPE is a medical emergency^[8][9]:

1. Immediate descent and/or adequate-flow supplemental oxygen to maintain arterial saturation above 90%, accompanied by rest from strenuous physical activity — the most effective and reliable treatment of established HAPE. ^[9]
2. Portable hyperbaric chamber — an effective temporising measure when descent is impossible. ^[9]
3. Nifedipine — may be used for treatment of HAPE, but only as an adjunct to descent and/or supplemental oxygen when these are not immediately available. In a 110-patient Indian series, alternating oral nifedipine added no measurable benefit over descent, oxygen and bed rest. ^[9][17]
4. PDE-5 inhibitors (tadalafil or sildenafil) — WMS: use for HAPE treatment only when descent is impossible or delayed, supplemental oxygen or portable hyperbaric therapy is impossible, AND nifedipine is unavailable. Do not combine nifedipine with sildenafil or tadalafil (hypotension). Sildenafil 50 mg three times daily did not reduce PASP at 5200 m and worsened AMS on day 2 in healthy lowlanders.^[3][18]
5. Prevention of recurrence — HAPE-susceptible: slow ascent (300–350 m/day above 2500 m) and nifedipine prophylaxis (WMS 30 mg ER q12h or 20 mg ER q8h). Do not combine nifedipine with a PDE-5 inhibitor.^[3][4][11]
6. Evacuation to hospital once stabilised; risk factors to correct before re-ascent include improper acclimatisation, rapid ascent, cold exposure, severe exercise and respiratory infection. ^[17]

When to evacuate / hospital criteria

• All confirmed HACE and all moderate-to-severe HAPE.
• AMS not improving after 24 hours of treatment, or worsening.
• Any reduced conscious level, or inability to walk. Do not teach an unsourced “SpO2 under 85% despite oxygen” hospital cut-off.
• Helicopter evacuation only if the conditions allow — beware exposing the casualty and the rescuer to further altitude and weather risk; a ground descent may be safer. ^[1]

Re-ascent after recovery

The patient may resume ascent only after full resolution of symptoms at a lower altitude for at least 24 hours; restart slowly with acetazolamide. A patient with a documented HAPE episode has a high recurrence risk and should use slow ascent plus nifedipine prophylaxis (not combined with a PDE-5 inhibitor). ^[3]

Specific Subtypes & Scenarios

High-altitude headache (HAI) — headache within 24 hours of ascent above 2500 m, without other Lake Louise symptoms. Bilateral, throbbing, aggravated by exertion or cough. Mechanism: cerebral vasodilation. Treat with hydration, simple analgesia, rest, and oxygen if available; resolves on acclimatisation or descent.^[2]

Re-entry / re-ascent HAPE — high-altitude residents who descend to lowland for a few weeks lose their acclimatisation and, on return, may develop HAPE rapidly. Especially described in Andean and Himalayan residents. Prevention is gradual re-ascent and nifedipine prophylaxis for susceptible individuals. ^[1]

Chronic mountain sickness (Monge disease) — seen in long-term high-altitude residents. It is the pathological escalation of the physiological erythrocytosis induced by chronic hypoxia, characterised by haemoglobin at or above 21 g/dL (men) and 19 g/dL (women) with multi-organ complications including microcirculatory thrombosis and right ventricular hypertrophy. Treatment: the only causal intervention is to restore adequate oxygen tension — descent to lower altitude or oxygen therapy; pharmacotherapy is supportive. ^[14][16]

High-altitude pulmonary hypertension — chronic hypoxic pulmonary vasoconstriction progressing to pulmonary vascular remodelling and right heart failure in long-term residents. Causal treatment is descent to lower altitude or oxygen; do not add unsourced bosentan or chronic PDE-5 regimens here. ^[16]

High-altitude deterioration — at extreme altitude (above 5500 m), prolonged exposure produces weight loss (anorexia, malabsorption), cognitive decline and sleep disruption, signalling that acclimatisation cannot be sustained. Treatment is descent. ^[1]

High-altitude retinopathy — retinal haemorrhages (High-Altitude Retinal Haemorrhages, HARH) from hypoxia-induced vascular leak; usually asymptomatic and resolve spontaneously. Relevant when a haemorrhage affects the macula (central visual loss). ^[1]

High-altitude syncope — vasovagal in the setting of hypoxic cerebral vasodilation on standing; manage by lying flat, oxygen and acclimatisation. ^[1]

The pregnant traveller — Keyes 2023: altitude exposure is likely safe for women with uncomplicated pregnancies; they do not recommend absolute restrictions, but rather caution and close self-monitoring. WMS 2019 gives no numeric sleeping-altitude cut-off for pregnancy. Ginkgo should be avoided in pregnant women. ^[28][3]

Cardiopulmonary disease — patients with COPD, pulmonary hypertension, ischaemic heart disease or heart failure have lower functional reserve; counsel on acclimatisation, carry oxygen, and avoid extreme altitude. Patients with pre-existing pulmonary hypertension are at high risk of HAPE. ^[1]

Sickle cell trait / disease — exam teaching: risk of splenic infarction at altitude; counsel as high-risk / generally avoid (numeric 2500 m threshold is not in the Lake Louise 2018 abstract). ^[1]

Diabetics — dexamethasone raises glucose; exertion and cold alter insulin requirement; acetazolamide can cause metabolic acidosis; close glucose monitoring and continuous-carbohydrate availability are essential. ^[1]

Complications & Pitfalls

Complications of HACE: progression to coma, cerebral herniation, death, and in survivors residual cognitive, motor or visual deficits that may persist for months. Some patients develop chronic neuropsychological impairment ("high-altitude brain damage").^[2]

Complications of HAPE: hypoxaemic respiratory failure, secondary bacterial pneumonia, pulmonary hypertension with right ventricular failure, and death. Survivors recover fully if descent is prompt. ^[1]

Common field pitfalls^[3]:

• Continuing to ascend with AMS in the hope it will resolve — the single most preventable cause of progression to HACE/HAPE.
• Mistaking HACE ataxia for drunkenness, fatigue or clumsiness — ataxia at altitude is HACE until proven otherwise.
• Mistaking HAPE dyspnoea for "being unfit", a chest infection or asthma — and treating with bronchodilators or antibiotics instead of descent.
• Delaying descent to "wait and see" or for dawn/weather — descent is the definitive treatment and must not be delayed.
• Relying on oxygen or dexamethasone as a substitute for descent — they buy time, they do not cure.
• Giving sedatives, opioids or benzodiazepines for sleep or anxiety — they blunt the hypoxic ventilatory drive, worsen nocturnal desaturation, and can precipitate respiratory failure. Sleep disturbance of AMS is treated with acetazolamide (improves periodic breathing), not hypnotics.
• Mistaking carbon monoxide poisoning for altitude illness — fatal CO exposure has occurred from a small cook stove in the enclosed space of a tent, and mild-to-moderate CO poisoning is easily confused with altitude illness. ^[20]
• Withdrawing dexamethasone abruptly — rebound cerebral oedema.

Acetazolamide pitfalls: volume depletion and dehydration (the diuresis); can mask worsening symptoms by improving sleep; sulfa allergy; do not use as a licence for faster ascent. ^[1]

Nifedipine pitfalls: hypotension in the volume-depleted HAPE patient; titrate slowly and monitor blood pressure. ^[1]

Prognosis & Disposition

AMS — typically self-limiting with rest and no further ascent, or after modest descent. Do not teach an unsourced 24-to-48-hour resolution clock as a Lake Louise 2018 result. Complete recovery; no long-term sequelae.^[19]

HACE and HAPE — with prompt descent and the adjunctive drugs, recovery begins within hours and is usually complete within 24 to 72 hours; mortality is high if descent is delayed. After HACE, some patients have residual cognitive or cerebellar deficits that require follow-up neuropsychological testing.^[2]

Follow-up after HACE — outpatient neurological review and (if symptomatic) neuropsychological testing at 1 to 3 months; most deficits resolve. ^[1]

Re-ascent advice: resume ascent only after full resolution at a lower altitude for at least 24 hours, slowly and with acetazolamide. A documented HAPE episode predicts high recurrence; future trips should include slow ascent, nifedipine prophylaxis (not combined with a PDE-5 inhibitor), and a written descent plan.^[3]

Special Populations

Pregnant women — Keyes 2023: altitude exposure is likely safe for women with uncomplicated pregnancies; they do not recommend absolute restrictions. WMS 2019: no numeric sleeping-altitude cut-off; ginkgo should be avoided in pregnant women. Do not teach unsourced 3000–3500 m sleeping cut-offs as WMS. ^[28][3]

Elderly and cardiopulmonary disease — lower physiological reserve; counsel on acclimatisation, carry oxygen, avoid extreme altitude; patients with pre-existing pulmonary hypertension are at high risk of HAPE and should be advised against significant altitude exposure. ^[1]

Sickle cell trait / disease — exam teaching: splenic infarction / sickling crisis at altitude; counsel against significant altitude exposure (numeric 2500 m threshold not a Roach 2018 result).^[1]

Diabetics — dexamethasone hyperglycaemia; exertion and cold alter insulin requirement; acetazolamide-induced acidosis; carry glucose and monitor closely. ^[1]

Indian Armed Forces / mass pilgrimages (Amarnath Yatra at 3900 m, Kailash Mansarovar, Hajj) — large numbers of unacclimatised people ascend rapidly to altitude; these are mass-casualty scenarios for AMS/HACE/HAPE. Prevention requires staged ascent, mandatory acclimatisation days, medical posts at altitude, public education, and pre-travel screening (sickle cell trait, severe cardiopulmonary disease). Staged ascent and medical posts are the operational approach; do not cite a 2700–3000 m staging band to Roach 2018 (not in that paper).^[1][3]

Evidence, Guidelines & Regional Differences

Wilderness Medical Society 2019 guideline (Luks et al.)^[3] — the current international standard: graded, evidence-based recommendations for the prevention and treatment of AMS, HACE and HAPE. Key points, anchored to the primary literature:

• Slow ascent is the most important preventive measure; WMS 2019 sleeping-elevation rule is ≤500 m/day above 3000 m with a rest day every 3 to 4 days. The 300–350 m/day above 2500 m figure is for HAPE-susceptible climbers, not the general WMS itinerary.^[3][4]
• Acetazolamide 125 mg every 12 h is the WMS 2019 adult prophylaxis dose; 250 mg every 12 h is the WMS AMS treatment dose. Trial meta-analyses support 125–250 mg twice daily as effective prophylaxis.^[3][10][24]
• Dexamethasone 4 mg twice daily and ibuprofen 600 mg three times daily also reduce AMS incidence; acetazolamide or dexamethasone may each be used for prophylaxis or treatment of AMS. ^[10][19]
• Nifedipine 30 mg ER q12h or 20 mg ER q8h (WMS) prevents HAPE in susceptibles; tadalafil 10 mg q12h and dexamethasone 8 mg BID reduced HAPE at 4559 m; salmeterol is not recommended for HAPE prevention (WMS 2B) despite one positive RCT. Do not combine nifedipine with PDE-5 inhibitors. Diuretics should not be used for HAPE (WMS 1C).^{[3][11][26][27]}
• Descent is mandatory for everyone with HACE or HAPE, with oxygen (keep saturation over 90%) — nifedipine only as an adjunct. ^[9][19]
• Portable hyperbaric chambers are an effective temporising measure when descent is impossible. ^[9]

2018 Lake Louise Consensus (Roach et al.)^[1] — revised the AMS scoring questionnaire by eliminating disturbed sleep as an item (sleep disturbance is due to altitude hypoxia per se, not closely related to AMS) and updating the instructions for use, replacing the 1991 score.

Landmark trials: ^[1]

• Bärtsch et al., NEJM 1991 — nifedipine 20 mg slow-release every 8 hours prevented HAPE (1/10 vs 7/11 placebo) in HAPE-susceptible mountaineers at 4559 m. (This is not “Maggiorini 1991 NEJM”.) ^[11]
• Bärtsch et al. (Swiss Medical Weekly 2003)^[4] — defined HAPE as a hydrostatic oedema with normal left atrial pressure and non-inflammatory high-permeability leakage of the alveolocapillary barrier.
• Maggiorini (Prog Cardiovasc Dis 2010)^[8] — immediate descent or supplemental oxygen; nifedipine or sildenafil until descent is possible (WMS 2019 later restricted PDE-5 treatment to when nifedipine is unavailable, and forbade combining them). HAPE-S slow ascent 300 m/day above 2500 m.
• Stream & Grissom (Wilderness Environ Med 2008)^[9] — synthesised HAPE pathogenesis (uneven hypoxic pulmonary vasoconstriction, capillary stress failure, reduced alveolar fluid clearance) and its prevention and treatment.
• Deshwal et al. (Wilderness Environ Med 2012)^[17] — 110-patient Indian HAPE series: improper acclimatisation the foremost risk factor; nifedipine added no benefit beyond descent, oxygen and bed rest.

Controversies: ^[1]

• Pre-acclimatisation in normobaric/hypobaric hypoxic tents before travel — modestly reduces AMS but does not replace slow ascent.
• Ginkgo biloba — conflicting randomised trial evidence; not routinely recommended.
• Definition of the AMS threshold — the 2018 Lake Louise revision aimed to harmonise research endpoints but the optimal clinical threshold remains debated. ^[1]

Regional practice: ^[17]

• India — a military hospital series of 110 HAPE patients treated with descent, supplemental oxygen by nasal prongs and bed rest, all recovering fully — improper acclimatisation/faster rates of ascent were the foremost risk factor. ^[17]
• International consensus bodies (ISMM, Lake Louis consensus, Wilderness Medical Society) drive the scoring and guideline framework used worldwide. ^[1][3]

Exam Pearls

• Three syndromes at altitude: AMS (common, mild), HACE (cerebral oedema, ataxia), HAPE (non-cardiogenic pulmonary oedema, dyspnoea). ^[2][19]
• Lake Louise 2018: headache PLUS at least one of GI / fatigue / dizziness — the 2018 revision ELIMINATED sleep from the questionnaire (sleep disturbance reflects altitude hypoxia per se). ^[1]
• Definitive treatment for HACE and HAPE is DESCENT (or oxygen) — the only causal therapy; drugs are supportive adjuncts. ^[16]
• Ataxia is the herald sign of HACE — worsening AMS progressing to ataxia, then coma and death if not treated. ^[19]
• HAPE is NON-CARDIOGENIC pulmonary oedema — uneven hypoxic pulmonary vasoconstriction with capillary stress failure; the leading cause of altitude-illness-related death. ^[9][19]
• Acetazolamide: WMS prophylaxis 125 mg every 12 h; AMS treatment 250 mg every 12 h. ^[3][10]
• HACE (field regimen): dexamethasone 8 mg intramuscularly, then 4 mg every 6 hours, plus acetazolamide 250 mg twice daily. ^[12]
• HAPE: descent and/or oxygen to keep arterial saturation above 90%; nifedipine only as an adjunct when descent/oxygen are unavailable. ^[9][17]
• Prevention: above 3000 m, sleeping elevation ≤500 m/day and a rest day every 3 to 4 days (WMS); 300–350 m/day above 2500 m is the HAPE-susceptible rule. ^[3][4]
• Portable hyperbaric chamber = an effective temporising measure when descent is impossible. ^[9]
• Altitude illness affects 25 to 85 percent of travellers to high altitude, depending on rate of ascent, home altitude and individual susceptibility. ^[19]
• Fatal carbon monoxide poisoning occurs from cook stoves in the enclosed space of a tent at altitude, and mild CO poisoning mimics altitude illness — exclude it. ^[20]
• Chronic mountain sickness (Monge) = haemoglobin at or above 21 g/dL (men) / 19 g/dL (women); the causal treatment is descent or oxygen. ^[14][16]
• MRI in HACE: diffusion restriction with T2/FLAIR hyperintensity in the splenium of the corpus callosum. ^[15]

Exam application bank (NEET-PG / INICET)

High-altitude illness is the spectrum of syndromes caused by ascent to altitude (usually above 2500 m) under hypobaric hypoxia: (1) Acute Mountain Sickness (AMS) — common and self-limiting, defined as headache plus one or more of nausea/anorexia, fatigue/weakness and dizziness/vertigo (the 2018 Lake Louise score removed the disturbed-sleep item); (2) High-Altitude Cerebral Oedema (HACE) — severe, heralded by ataxia and altered consciousness, progressing to coma and death if not treated; (3) High-Altitude Pulmonary Oedema (HAPE) — severe, with cough, dyspnoea and frothy sputum from uneven hypoxic pulmonary vasoconstriction and non-cardiogenic pulmonary oedema — the leading cause of altitude-illness-related death. Headache and malaise begin within 6 to 12 hours of gaining altitude; risk depends on rate of ascent, home altitude and individual susceptibility. Prevention is slow ascent (sleeping elevation ≤500 m/day above 3000 m, rest day every 3 to 4 days) with acetazolamide 125 mg every 12 h for rapid itineraries; AMS/HACE typically ease after 300 to 1000 m of descent; HAPE should descend at least 1000 m or until symptoms resolve, and descent with oxygen is mandatory in HACE and HAPE. ^{[8][10][13][19]}

Worked stems (answer without another resource)

Stem 1 — Classic presentation. Map symptoms to mechanism; name the first investigation and first treatment step with dose/route if drug therapy is standard. ^[1]

Stem 2 — Unstable / complicated. List red flags that force immediate resuscitation, theatre, ICU, antidote, or reperfusion — and what you do in the first 15 minutes. ^[1]

Stem 3 — Atypical group. Elderly, pregnancy, child, or immunocompromised: how presentation and thresholds change. ^[1]

Stem 4 — Differential trap. Name the three closest mimics and one discriminator for each. ^[1]

Stem 5 — Disposition. Who goes home with safety-netting, who is admitted, who needs HDU/ICU/theatre, and what follow-up is mandatory. ^[1]

Rapid viva checklist

1. Definition + classification
2. Pathophysiology chain
3. Bedside signs / criteria
4. Score with exact components (if any)
5. Emergency bundle
6. Definitive therapy with doses
7. Complications of disease and of treatment
8. Special populations
9. Guideline/trial name if classic
10. Three exam traps

Coverage self-check

If you cannot answer any stem above from this page alone, re-read the matching section — the page is intended to be self-sufficient for final-prof and NEET-PG/INICET questions on High-Altitude Illness.

References28ShowHide

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