Altitude Sickness

Altitude sickness refers to a spectrum of symptoms caused by physiological changes in the human body at altitudes above 2,500 m. Altitude sickness includes acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Hypobaric hypoxia is a common pathophysiologic trigger. Acute mountain sickness and HACE represent 2 extremes of a neurologic disorder, from benign to life-threatening. High-altitude pulmonary edema is primarily a pulmonary problem, not necessarily preceded by AMS or HACE. The risk of altitude sickness can be reduced by gradual ascent and other precautionary measures, including medications. The symptoms of altitude sickness can be reduced with hyperbaric oxygen therapy.

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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
Reversible brain abnormalities in people without signs of mountain sickness during high-altitude exposure

Significant morphometric edge flow indicating brain volume swelling during high-altitude exposure (Test 2A) and 2 months after return to sea level (Test 3B) compared with baseline before ascent to high altitude (Test 1)

Image: “Reversible Brain Abnormalities in People Without Signs of Mountain Sickness During High-Altitude Exposure” by Cunxiu Fan et al. License: CC BY 4.0

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
Table: 2018 Lake Louise AMS self-questionnaire
Headache
  • No headache: 0
  • Mild headache: 1
  • Moderate headache: 2
  • Severe headache, incapacitating: 3
Gastrointestinal (GI) symptoms
  • No symptoms: 0
  • Poor appetite or nausea: 1
  • Moderate nausea or vomiting: 2
  • Severe nausea and vomiting, incapacitating: 3
Fatigue/weakness
  • Not tired or weak at all: 0
  • Mild fatigue or weakness: 1
  • Moderate fatigue or weakness: 2
  • Severe fatigue or weakness, incapacitating: 3
Dizziness/lightheadedness
  • No dizziness/light-headedness: 0
  • Mild dizziness/light-headedness: 1
  • Moderate dizziness/light-headedness: 2
  • Severe dizziness/light-headedness, incapacitating: 3
AMS clinical functional score: Overall, if you had AMS symptoms, how did they affect your activities?
  • Not at all: 0
  • Symptoms present, but did not force any change in activity or itinerary: 1
  • My symptoms forced me to stop the ascent or to go down on my own power: 2
  • Had to be evacuated to a lower altitude: 3
A score of 3 or higher is suggestive of AMS. This score is used more for clinical research than diagnosis by physicians.

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
Diagram of pulmonary edema

Diagram of pulmonary edema: In HAPE, the alveoli fill up with fluid, interrupting proper gas exchange.

Image by Lecturio.

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

References

  1. Hackett, P. H., & Davis, C. B. (2016). High-altitude disorders. In J. E. Tintinalli, J. S. Stapczynski, O. J. Ma, D. M. Yealy, G. D. Meckler, & D. M. Cline (Eds.), Tintinalli’s emergency medicine: A comprehensive study guide, (8e). New York, NY: McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1121514038
  2. Roach, R. C. et al. (2018). The 2018 Lake Louise acute mountain sickness score. High Altitude Medicine & Biology, 19(1), 4–6. https://doi.org/10.1089/ham.2017.0164
  3. Luks, A. M., Swenson, E. R., & Bärtsch, P. (2017). Acute high-altitude sickness. European Respiratory Review, 26(143). https://doi.org/10.1183/16000617.0096-2016

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