Altitude Sickness

Acute Mountain Sickness and High-Altitude Cerebral Edema

Definitions

• Acute mountain sickness (AMS): neurologic syndrome with no physical findings occurring > 6 hours after ascent to altitudes > 2,500 m (rarely, 1,500 m)
• High-altitude cerebral edema (HACE): diffuse encephalopathy without focal neurological deficits, always preceded by AMS

Epidemiology

• Because AMS becomes HACE, the epidemiological factors are the same.
• Prevalence: 40%–90% based on altitude
• Risk factors:
  • Prior history of high-altitude sickness
  • Rate of ascent
  • Exertion (lack of physical fitness is not a risk factor)
  • Neck irradiation or surgery damaging carotid bodies
  • Age > 50 years reduces risk.

Etiology

All symptomatology of AMS and HACE is related to hypoxia. The central nervous system (CNS) is the most sensitive organ to hypoxia.

Clinical presentation

• AMS:
  • Symptoms:
    • Headache (most common)
    • Nausea
    • Fatigue 
    • Dizziness 
    • Insomnia
  • Physical exam is usually unremarkable. 
• HACE:
  • Symptoms and signs: 
    • Ataxia
    • Altered level of consciousness
  • Physical exam findings:
    • Papilledema
    • ± retinal hemorrhage
    • No focal neurologic findings

Pathophysiology

• Exact mechanism is not well understood.
• AMS:
  • High altitude → decreased partial pressure of oxygen in inspired gas (hypobaric hypoxia)
  • Hypobaric hypoxia → low arterial oxygen saturation (SPA0₂ is > 90%)  
  • Low SPA0₂ → increased cerebral blood flow: 
    • Raised intracranial pressure 
    • Increased sympathetic activity
    • Hypoventilation
    • Fluid retention 
    • Further impaired gas exchange 
• HACE:
  • As above, but swelling progresses, leading to vasogenic cerebral edema
  • Swelling puts pressure on the brain, resulting in:
    • Papilledema
    • Diffuse neurological symptoms

Diagnosis

Both AMS and HACE are diagnosed clinically by noting the characteristic symptoms in a patient who ascends to high altitude. 

• Pulse oximetry, vital signs, and laboratory exams are not useful markers as they are often normal.
• Clinical trials often use the 2018 Lake Louise AMS scoring system for diagnosis: 
  • Score of ≥ 3 including headache is considered diagnostic of AMS.
  • Not routinely used for diagnosis in clinics, but scoring systems such as the Lake Louise AMS may be useful for screening purposes

Prevention

• Gradual ascent is best.
• Spending 1 night at intermediate altitude before ascending to higher ones
• Proper hydration, but not overhydration
• Acetazolamide for patients with prior history of AMS or when rapid descent necessary (e.g., rescue missions)

Management

• AMS:
  • Mild: 
    • Discontinue ascent.
    • Rest.
    • Carbonic anhydrase inhibitors (acetazolamide)
    • Ultimate treatment is descent.
  • Moderate: 
    • Immediate descent
    • Supplemental oxygen 
    • Acetazolamide and/or dexamethasone
    • Hyperbaric therapy
• HACE: 
  • Immediate descent 
  • Portable hyperbaric chamber (when descent not possible) 
  • Supplemental oxygen
  • Dexamethasone

High-Altitude Pulmonary Edema

Definition

High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema (normal capillary wedge pressure) occurring 2–4 days after arrival at high altitude.

Epidemiology

• Incidence ranges from 0.01%–15.5% based on altitude.
• Risk factors:
  • Prior history of HAPE
  • Rapid ascent
  • Respiratory tract infection
  • Cold temperatures
  • Exercise 
  • Pre-existing cardiopulmonary abnormalities leading to pulmonary hypertension

Pathophysiology

• Hypobaric hypoxia from high altitude → decreased nitric oxide and increased endothelin 1 in pulmonary vasculature causing vasoconstriction
• Patchy pulmonary vasoconstriction → overperfusion and increased capillary pressure 
• Increased pulmonary capillary pressure → interstitial fluid leak → HAPE

Clinical presentation

• Symptoms: 
  • Cough (most common, but nonspecific)
  • Hemoptysis
  • Fatigue
  • Dyspnea at rest
• Signs: 
  • Tachypnea and tachycardia, especially at rest (important markers) 
  • Crackles on lung auscultation
  • Signs of HACE

Diagnosis

• Diagnosis is primarily clinical; requires: 
  • 2 or more of the following symptoms:
    • Chest tightness or pain 
    • Cough
    • Dyspnea at rest
    • Decreased exercise tolerance 
  • 2 or more of the following exam findings: 
    • Central cyanosis 
    • Rales/wheezes
    • Tachycardia
    • Tachypnea
• Imaging and lab testing support the diagnosis:
  • Chest X-ray: patchy/localized opacities and/or streaky interstitial edema
  • Electrocardiogram (ECG): right ventricular strain and/or hypertrophy
  • Laboratory tests: hypoxia, respiratory alkalosis (unless on acetazolamide)
  • Ultrasound: findings consistent with pulmonary edema

Prevention

• Gradual ascent is best.
• Patients with prior history of HAPE or when rapid descent necessary (e.g., rescue missions):
  • Sustained-release nifedipine
  • Salmeterol
  • Tadalafil
  • Dexamethasone

Management

• Immediate descent
• Portable hyperbaric chamber (when descent not possible)
• Rest and warm temperatures
• Oxygen therapy to > 90% saturation
• Extended-release nifedipine