High Altitude Sickness

See Also

Background
Altitudes

See FIO2 and PiO2 at Altitude
Low Altitude: <1500 meters (<4900 feet)
High Altitude: 1500 to 3500 meters (4900 to 11500 feet)
1. Most common elevations for Acute Mountain Sickness: 2500 to 3500 meters (8200 to 11482 feet)
2. Affects the greatest number of people exposed who ascend quickly (e.g. travel to alpine city)
  1. Colorado Ski Resorts: Affects 25% of travelers
  2. Himalayas: Affects 50% of travelers
Very High Altitude: 3500 to 5500 meters (11500 to 18000 feet)
1. Blood Oxygen Saturation <90% even in health persons
2. Associated with severe Acute Mountain Sickness (as well as HACE and HAPE)
3. Affects 25% who climb to this altitude
Extreme Altitude: >5500 meters (>18000 feet)
1. Significant Hypoxia and hypercarbia
2. Affects 50% who climb above 6000 meters

Pathophysiology
Mechanism

See FIO2 and PiO2 at Altitude
Oxygen Partial Pressure decreases with altitude related drop in total Ambient air pressure (atmospheric pressure)
1. Oxygen maintains its percentage (21%) of overall gas constituents in atmospheric pressure (78% Nitrogen, 1% Argon)
2. However, Oxygen Partial Pressure drops in relation to total atmospheric pressure decrease
  1. DRY Sea level Partial Pressure: 160 mmHg (21% of total atmospheric pressure, 760 mmHg)
  2. DRY Partial Pressure at 5000 feet: 132 mmHg (21% of total atmospheric pressure, 630 mmHg)
3. Partial Pressure is lowered by the humidified, heated air we inspire through our upper airways
  1. Saturated vapor pressure at Body Temperature (98.6 F or 37 C) is 47 mmHg
  2. Alveolar Partial Pressure of oxygen at sea level = 0.21 * (760 - 47 mmHg) = 0.21 * 713 = 150 mmHg
4. Decreased oxygen Partial Pressure results in fewer oxygen molecules available on inspiration of a given Lung Volume
  1. Hypoxia risk increases
Acclimitization to altitude occurs over days to weeks and decreases the risk of High Altitude Illness
1. Sleep and Exercise tolerance improve after acclimitization
2. Initial response to altitude is hypoxic Ventilatory response
  1. Increased Respiratory Rate and Minute Ventilation
  2. Effect is tempered by carbon dioxide levels that fall, resulting in Respiratory Alkalosis
    1. Respiratory Alkalosis results in decreased respiratory drive
    2. Respiratory Alkalosis is compensated over 48 hours by increased renal bicarbonate
3. Cardiovascular response (Sympathetic Nervous System)
  1. Increased Heart Rate, venous tone and Cardiac Output
4. Pulmonary Hypertension (diffuse pulmonary vessel constriction) results from Hypoxemia response
  1. Risk of High Altitude Pulmonary Edema (HAPE) in severe Pulmonary Hypertension
5. Cerebral Blood Flow results from Hypoxemia response
  1. Risk of High Altitude Cerebral Edema (HACE) in disordered autoregulation of cerebral Hypertension
6. Erythropoietin released from Kidney as a longer-term Hypoxemia response
  1. Increases Red Blood Cell production and oxygen carrying capacity
Hypobaric Hypoxemia results in paradoxical and maladaptive physiologic changes at altitude (>1500 meters)
1. Hypoxic stress due to lower barometric pressure and less available oxygen (decreased PiO2 and FIOO2)
2. Symptom onset may begin within 6-12 hours of ascent
3. Fluid retention
  1. Contrast with non-affected persons at altitude who experience diuresis
Other Changes at altitude that may exacerbate comorbid illness
1. Increased sympathetic tone
  1. Pulmonary artery Vasoconstriction
  2. Increased Systemic Vascular Resistance
2. Gas expands to take up a greater volume at altitude
  1. Ambient air pressure (atmospheric pressure) decreases with increasing altitude
  2. Allows trapped air (e.g. Pneumothorax) to expand
3. Example: helicopter transport with 5000 foot rise from sea level
  1. Results in a pressure drop (14.7 psi to 12.7 psi)
  2. Results in a Gas Volume increase of 15-20%
    1. Boyles Law states P1*V1=P2*V2

Types
High Altitude Illness

Risk Factors

Rapid ascent (as opposed to gradual acclimatization)
Very high altitude
Significant physical exertion
Prior history of altitude sickness
Traveling from low altitude
Prolonged time at altitude
Obesity
Genetic susceptibility
1. Genetic factors affect a person's ability to acclimatize to altitude
Younger age
1. Aside from comorbidity, older adults may be less affected by altitude
Substances increasing High Altitude Illness risk (decrease hypoxic Ventilatory response)
1. Alcohol use
2. Sleep Aids

Symptoms

High Altitude Illness or HAI (Acute Mountain Sickness or AMS)
1. Common Symptoms
  1. Headache
  2. Malaise
  3. Anorexia
  4. Generalized Weakness
2. Other Symptoms
  1. Fatigue
  2. Nausea or Vomiting
  3. Insomnia
  4. Irritable
  5. Decreased Urine Output
High Altitude Pulmonary Edema (HAPE)
1. Dry cough
2. Congestion
3. Epistaxis
4. Dyspnea or Dyspnea on Exertion
5. Chest tightness
6. Tachycardia
7. Edema
8. Syncope
High Altitude Cerebral Edema (HACE)
1. Altered Level of Consciousness from confusion and Hallucinations to coma
2. Headache
3. Photophobia
4. Hypertension
5. Lassitude
6. Truncal Ataxia and inability to ambulate

Course

Onset: 6-12 hours following high altitude ascent

Diagnosis

Headache and
One or more of the following
1. Fatigue or weakness
2. Dizziness or Light Headedness
3. Gastrointestinal distress (Nausea, Vomiting, Anorexia)
4. Sleep disturbance

Differential Diagnosis

Viral illness
Alcohol Hangover
Heat Exhaustion
Dehydration
Hypothermia
Hypoglycemia
Hyponatremia
Sedative Hypnotic Medications
Carbon Monoxide Poisoning (e.g. cooking in tent)
Migraine Headache

Complications (0.1 to 4 percent Incidence)

See Pathophysiology above
Altitudes above 11,400 feet (3500 meters) are associated with a more complicated course
High Altitude Pulmonary Edema (HAPE)
High Altitude Cerebral Edema (HACE)

Management

Very mild symptoms may resolve spontaneously with acclimitization
Immediate descent (at least 300 meters or 1000 feet) is most critical for moderate to severe symptoms
1. Descent of 500-1000 meters (1640 to 3280) is optimal (typically sufficient in all but the most severe cases)
Other measures for moderate to severe symptoms where descent is not immediately possible
1. Supplemental Oxygen to keep Oxygen Saturation >90%
2. Acetazolamide 250 mg orally every 12 hours
3. Dexamethasone 8 mg PO/IV/IM loading dose, then 4 mg every 6 hours
Other measures to consider if descent is delayed and/or Supplemental Oxygen is unavailable
1. Nifedipine ER 30 mg every 6 hours
2. Phosphodiesterase Inhibitors (Tadalafil)
3. Gamow Bag (Portable Hyperbaric Chamber)
Symptomatic measures
1. Antiemetics (e.g. Zofran) for Nausea, Vomiting
2. Acetaminophen or Ibuprofen for Headache

Prevention

Medication Prophylaxis
1. Indications
  1. Travel to 11,000 feet in one day (or over 9,000 feet if history of prior altitude sickness)
2. Acetazolamide (Diamox)
  1. See Acetazolamide for mechanism
  2. Adults: 125 mg every 12 hours (FDA approved)
    1. Up to 250 mg twice daily may be used (but 125 mg is typically sufficient)
  3. Children: 2.5 mg/kg up to 125 mg every 12 hours (off-label)
  4. Start 1 day or more before ascent
  5. Continue until acclimitization to the highest sleeping altitude (approximately 2 days)
3. Dexamethasone
  1. Dose: 4 mg orally every 12 hours, or 2 mg every 6 hours (not FDA approved)
  2. Alternative, in those who cannot take Acetazolamide
  3. Decreases inflammation, intracerebral pressure (ICP) and Hypoxia-related endothelial dysfunction
  4. Some Wilderness Medicine experts recommend limiting Dexamethasone for treatment (not prophylaxis)
  5. Risk of rebound mountain sickness when discontinued
  6. May require taper with prolonged use (risk of adrenal suppression)
  7. Does not speed acclimitization, but does reduce symptoms
4. Additional mild symptom management (severe symptoms require immediate descent)
  1. Acetaminophen
  2. Ibuprofen 600 mg every 8 hours
    1. May have a prophylactic role (limited evidence)
5. Other agents that show promise in studies (but are experimental)
  1. Nifedipine ER 30 mg every 12 hours starting 24 hours before ascent
  2. Tadalafil
General Pointers
1. Gradual ascent to allow for acclimitization is the most important single preventive factor
2. Recognize the symptoms of Acute Mountain Sickness
3. Never ascend to sleep higher if you have symptoms
4. Descend if symptoms do not resolve or worsen
5. Never leave a person with altitude sickness alone
6. Maintain hydration
7. Avoid overexertion
8. Avoid Alcohol and Sedatives
9. For altitudes above 9800 feet (3000 meters)
  1. Recommended ascent rate <1000 feet/day (300 meter/day)
  2. Spend an additional rest day if ascent over 2000 feet (600 meters)
  3. Do not sleep >2000 feet (600 meters) higher than the night before
Comorbid Conditions
1. See Air Travel Restriction
2. Patients with asymptomatic cardiopulmonary disease may ascend safely to at least 8200 feet (2500 meters)
3. Conditions which absolutely contraindicate high altitude travel
  1. Severe Chronic Obstructive Pulmonary Disease (COPD)
  2. Uncontrolled Congestive Heart Failure (CHF)
4. Conditions for which caution should be Exercised due to risk of exascerbation (emphasize acclimitization)
  1. Arrhythmias
  2. Coronary Artery Disease
  3. Hypertension
  4. Sickle Cell Anemia (splenic infarct risk increases above 4900 feet (1500 meters)
    1. Keep Supplemental Oxygen available

References

(2018) Presc Lett 25(2)
Candy and Contant in Herbert (2020) EM:Rap 20(3): 3-4
Comp and Rogich (2021) Crit Dec Emerg Med 35(4): 3-8
Comp and Rogich (2026) Crit Dec Emerg Med 40(9): 29-35
Basnyat (2003) Lancet 361(9373): 1967-74 [PubMed]
Fiore (2010) Am Fam Physician 82(9): 1103-10 [PubMed]
Hackett (2001) N Engl J Med 345(2): 107-14 [PubMed]