High Altitude Pulmonary Edema (HAPE)

1. Definition

High Altitude Pulmonary Edema (HAPE) is a non-cardiogenic pulmonary edema occurring typically within 2–5 days of rapid ascent above 2,500–3,000 meters, caused by exaggerated hypoxic pulmonary vasoconstriction (HPV) leading to elevated pulmonary artery pressures and capillary stress failure.

It is one of the most lethal forms of high-altitude illness.

2. Altitude Classification 

HAPE usually occurs >3,000 m, but can occur at lower altitude in susceptible individuals.

3. Pathophysiology 

A. Hypoxia-Induced Pulmonary Vasoconstriction (HPV)

At altitude:

• ↓ Barometric pressure
• ↓ Inspired PO₂
• ↓ Alveolar PO₂

→ Hypoxic pulmonary vasoconstriction

Normally, HPV optimizes V/Q matching.
But in HAPE:

• HPV is uneven
• Some areas constrict more than others
• Leads to regional overperfusion
• Capillary hydrostatic pressure rises

B. Stress Failure of Capillaries

High PAP → Capillary wall damage → Leakage of:

• Plasma
• Proteins
• RBCs

→ Results in high-protein, non-inflammatory edema

C. Key Hemodynamic Abnormalities

• Markedly ↑ Pulmonary artery pressure (PAP)
• Normal PCWP
• Normal LV function

HAPE = hydrostatic, not permeability-driven (initially)

4. Risk Factors 

A. Environmental

• Rapid ascent
• Ascent >500 m/day above 3,000 m
• Cold exposure
• Strenuous exertion

B. Host Factors

• Previous HAPE
• Young males
• Respiratory infections
• Patent foramen ovale (controversial but described)
• Exaggerated HPV responders

C. Genetic Associations

• eNOS polymorphism
• RAAS variants

5. Clinical Presentation

Timeline

Usually within 2–5 days of ascent

Early Symptoms

• Decreased exercise tolerance
• Exertional dyspnea
• Dry cough
• Tachycardia

Late / Severe Symptoms

• Dyspnea at rest
• Pink frothy sputum
• Cyanosis
• Orthopnea (rare)
• Altered sensorium (hypoxia)

Examination

• Tachypnea
• Tachycardia
• Low SpO₂ (<85% at altitude concerning)
• Bibasilar crackles → may become diffuse
• Low-grade fever common (misleading → mimics pneumonia)

6. Differential Diagnosis

7. Investigations 

ABG

• Hypoxemia (severe)
• Respiratory alkalosis initially
• May progress to respiratory failure

Chest X-Ray

Findings:

• Patchy, bilateral alveolar infiltrates
• Often right middle lobe predominance
• Normal cardiac size
• No pleural effusion (usually)

Echocardiography

• Normal LV function
• Elevated pulmonary artery pressure
• RV strain possible

BNP

• Usually normal or mildly elevated
  (Helps differentiate cardiogenic edema)

8. Diagnostic Criteria (Lake Louise Criteria – HAPE)

Diagnosis requires:Recent altitude gain + ≥2 symptoms:

• Dyspnea at rest
• Cough
• Weakness
• Chest tightness

+ ≥2 signs:

• Crackles
• Central cyanosis
• Tachypnea
• Tachycardia

With no other explanation.

9. Management 

IMMEDIATE PRIORITY = OXYGEN + DESCENT

A. Descent (Definitive Treatment)

• Immediate descent by ≥1,000 m
• Even 500 m can be lifesaving

Improvement usually within hours.

B. Oxygen Therapy

• Target SpO₂ > 90%
• High-flow oxygen preferred
• NIV if needed

C. Non-Invasive Ventilation (NIV)

• CPAP reduces:
  • PAP
  • Work of breathing
  • Improves oxygenation

Very effective in ICU settings.

D. Mechanical Ventilation

Indications:

• Severe hypoxemia
• Exhaustion
• Altered sensorium

Treat like non-cardiogenic pulmonary edema

• Low tidal volume (6 ml/kg)
• PEEP titration
• Avoid fluid overload

E. Pharmacologic Therapy

1. Nifedipine (First-Line Drug)

Mechanism:

• Pulmonary vasodilation
• ↓ PAP

Used when:

• Oxygen not available
• Adjunct therapy

2. PDE-5 Inhibitors

• Sildenafil
• Tadalafil

Reduce PAP
Used in prevention & treatment.

3. Dexamethasone

Primarily for HACE
Not first-line for isolated HAPE
But may help mixed cases.

4. Acetazolamide

For prevention
Not primary treatment of HAPE.

F. Portable Hyperbaric Chamber

4

Used when:

• Descent impossible
• Remote area

Simulates descent of 1,000–2,000 m.

Temporary measure.

10. Prevention 

Gradual Ascent

• <500 m sleeping altitude gain per day above 3,000 m
• Rest day every 3–4 days

Pharmacologic Prevention

In high-risk individuals:

Acetazolamide prevents AMS but not strongly protective for HAPE.

11. Prognosis

• Rapid recovery if treated early
• Mortality high if untreated
• Recurrence common in predisposed individuals

12. HAPE vs ARDS