Altitude Illness¶

Chapter 475 | Part 15: Disorders Associated with Environmental Exposures

KEY CLINICAL POINTS¶

Acute mountain sickness (AMS) is the most common form of altitude illness, while high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) are life-threatening complications.
AMS is characterized by headache, nausea, fatigue, and dizziness, while HACE presents with ataxia and altered consciousness, and HAPE manifests with respiratory distress and pulmonary edema.
Acetazolamide is the drug of choice for AMS prevention, while dexamethasone is effective for HACE and HAPE. Oxygen therapy and descent are critical interventions.

1. DEFINITION & OVERVIEW¶

Altitude illness encompasses a spectrum of disorders caused by hypobaric hypoxia, including acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). AMS is a benign condition, while HACE and HAPE are severe and potentially fatal.

Table 475-1 Management of Altitude Illness¶

CONDITION	MANAGEMENT
Acute mountain sickness (AMS), milda	Discontinuation of ascent, Treatment with acetazolamide (250 mg q12h), Descentb
AMS, moderatea	Immediate descent for worsening symptoms, Use of low-flow oxygen if available, Treatment with acetazolamide (250 mg q12h) and/or dexamethasone (4 mg q6h)c
High-altitude cerebral edema (HACE)	Immediate descent or evacuation, Administration of oxygen (2–4 L/min), Treatment with dexamethasone (8 mg PO/IM/IV; then 4 mg q6h)
High-altitude pulmonary edema (HAPE)	Immediate descent or evacuation, Administration of oxygen (4–6 L/min) to bring O2 saturation to >90%, Adjunctive therapy with nifedipine (30 mg, extended-release, q12h)

1.1 Pathophysiology¶

Hypobaric hypoxia leads to reduced oxygen diffusion, respiratory alkalosis, and cerebral vasodilation. Genetic factors like EPAS1 variants may contribute to adaptation in high-altitude populations. VEGF and nitric oxide pathways are implicated in cerebral and pulmonary edema.

1.2 Clinical Spectrum¶

AMS is a neurologic syndrome with nonspecific symptoms. HACE is an encephalopathy with ataxia and altered consciousness. HAPE is a noncardiogenic pulmonary edema with patchy lung opacities. These conditions represent a continuum of altitude-related pathophysiology.

2. EPIDEMIOLOGY¶

Approximately 140 million people live permanently at altitudes ≥ 2500 m, and 100 million travel to high-altitude locations annually. AMS incidence is ~50% in trekkers ascending >4000 m for ≥ 5 days, with HACE and HAPE rates of 0.1–4%. Reentry HAPE now affects Himalayan and Tibetan populations.

2.1 Risk Factors¶

Rapid ascent, prior altitude illness, exertion, and cold exposure increase risk. Genetic predisposition (e.g., EPAS1 variants) and impaired cerebral autoregulation contribute to susceptibility.

2.2 Demographics¶

AMS incidence is similar across genders. Individuals >50 years old are less likely to develop AMS. Men are more susceptible to HAPE than women.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

Hypobaric hypoxia triggers altitude illness. Pathophysiology includes hypoxic pulmonary vasoconstriction, cerebral vasodilation, and fluid shifts. Genetic factors (e.g., EPAS1, EGLN1) and inflammatory processes (e.g., VEGF, nitric oxide) play roles in disease progression.

3.1 Hypoxia-Inducible Pathways¶

Hypoxia-inducible factor (HIF) regulates VEGF, erythropoiesis, and vascular adaptation. EPAS1 variants in Tibetans confer lower hemoglobin levels but increased altitude tolerance.

3.2 Cerebral and Pulmonary Edema¶

Cerebral edema in HACE involves vasogenic mechanisms (interstitial edema, MRI findings). HAPE results from hypoxic pulmonary vasoconstriction, increased capillary pressure, and endothelial dysfunction.

4. CLINICAL FEATURES¶

AMS presents with headache, nausea, fatigue, and dizziness. HACE features ataxia and altered consciousness. HAPE manifests with respiratory distress, frothy sputum, and pulmonary edema. Retinal hemorrhages occur at ≥ 5000 m.

4.1 Symptomatology¶

AMS: Headache (most common), nausea, fatigue, dizziness. HACE: Ataxia, confusion, papilledema. HAPE: Dyspnea, frothy pink sputum, crackles on auscultation.

4.2 Diagnostic Criteria¶

AMS: Lake Louise Scoring System ( ≥ 3 points). HACE: MRI findings of white matter hyperintensities. HAPE: Chest X-ray showing patchy opacities with improved oxygenation.

5. DIFFERENTIAL DIAGNOSIS¶

AMS must be distinguished from dehydration, hypothermia, and hyponatremia. HACE differentiates from stroke, brain tumor, and infection. HAPE must be differentiated from pneumonia, pulmonary embolism, and heart failure.

5.1 Neurologic Mimics¶

HACE vs. stroke: HACE has diffuse cerebral involvement without focal deficits. Brain tumors may present with AMS-like symptoms but lack typical imaging findings.

5.2 Pulmonary Mimics¶

HAPE vs. pneumonia: HAPE lacks fever and leukocytosis. Pulmonary embolism may present with similar chest X-ray findings but requires D-dimer and CT pulmonary angiography.

6. INVESTIGATIONS & DIAGNOSIS¶

Pulse oximetry (SpO2 <90% indicates HAPE), MRI for HACE, chest X-ray for HAPE, and arterial blood gas analysis. Lake Louise Scoring System is the primary diagnostic tool for AMS.

6.1 Diagnostic Algorithms¶

AMS: Lake Louise Scoring System ( ≥ 3 points). HACE: MRI findings of white matter hyperintensities. HAPE: Chest X-ray with oxygen saturation >90% after oxygen therapy.

6.2 Laboratory Tests¶

Arterial blood gas analysis (respiratory alkalosis in AMS), CBC with differential (leukocytosis in HAPE), and inflammatory markers (elevated ESR in HAPE).

7. MANAGEMENT & TREATMENT¶

Immediate descent is the cornerstone of treatment. Acetazolamide for AMS, dexamethasone for HACE, and oxygen therapy for HAPE. Hyperbaric chambers may be used when descent is not possible.

7.1 Pharmacologic Interventions¶

Acetazolamide (125 mg q12h) for AMS prevention. Dexamethasone (4–8 mg q6h) for HACE. Nifedipine (30 mg q12h) for HAPE. Oxygen (4–6 L/min) for HAPE.

7.2 Non-Pharmacologic Measures¶

Gradual ascent, hydration, avoidance of alcohol, and rest days. Hyperbaric therapy (portable chambers) for rapid descent simulation.

8. PROGNOSIS & COMPLICATIONS¶

AMS has a favorable prognosis with descent. HACE and HAPE have high mortality if untreated. Complications include cerebral edema, pulmonary hypertension, and secondary infections.

8.1 Mortality Rates¶

HACE mortality: ~20–40% without treatment. HAPE mortality: 10–20% without oxygen therapy. Early intervention improves outcomes.

8.2 Long-Term Effects¶

Chronic mountain sickness (CMS) may develop in highlanders. Persistent headaches or cognitive deficits may occur after severe altitude illness.

9. SPECIAL CONSIDERATIONS¶

Pregnancy: Avoid altitudes >3000 m. Obesity increases AMS risk. Sickle cell disease patients require supplemental oxygen. Asthmatics may have fewer exacerbations at high altitude.

9.1 Pregnancy¶

Low-risk pregnant women at 3000 m are not at increased risk, but ascent >3000 m may compromise fetal oxygenation.

9.2 Genetic Disorders¶

Sickle cell disease: Risk of vaso-occlusive crises. Thalassemia: No known complications at high altitude.

10. KEY POINTS & CLINICAL PEARLS¶

Immediate descent is the most effective treatment for all forms of altitude illness. 2. Acetazolamide prevents AMS but masks symptoms. 3. Dexamethasone is effective for HACE and HAPE. 4. Oxygen therapy is critical for HAPE. 5. Hyperbaric chambers may be lifesaving when descent is not possible.