1. High-Altitude Medicine
Alicia Bond MD

2. High altitude Moderate altitude High altitude Extreme altitude
5,000 – 10,000 feet above sea level
Highest U.S. ski resorts
High altitude
10,000 – 18,000 feet above sea level
High peaks in the lower 48, Europe
Extreme altitude
Greater that 18,000 feet above sea level
Denali, Himalaya, Karakoram, Andes

3. Epidemiology
Most cases of high-altitude illness take place in people rapidly ascending to altitudes between 8,000 and 12,000 feet
Can affect people who live at low altitude as well as people who live at high altitude and return from travel to lower altitude (re-entry)
Millions at risk each year – roughly 20-40% affected by some type of altitude illness
30 million Western states visitors
12,000 Mt. Everest trekkers
1,200 Denali climbers
1 million visitors to extreme high ranges worldwide

4. High-altitude environments
Decreased barometric pressure = logarithmically lower partial pressure of oxygen (PO2) in inspired air
Higher latitudes have lower barometric pressure at equivalent altitudes
Weather systems can significantly lower barometric pressure transiently
Cold, dry conditions may be contribute to high-altitude illness

5. Factors affecting risk
Rate of ascent
Recent high-altitude exposure
Genetic variability
Sleeping altitude
Maximum altitude reached

6. Acclimatization
Series of physiologic adaptations to maintain tissue oxygenation
Ability to acclimatize varies genetically
Hours: Hypoxic ventilatory response (HVR), fluid shift to increase hematocrit, increase in cardiac output
Days: Increased erythropoiesis, return of cardiac function to baseline, increase in 2,3-DPG
Weeks: Increased plasma volume and red blood cell mass

7. Hypoxic ventilatory response
Most important component of acclimatization
Affected by genetics, ethanol, sleep medications, caffeine, cocoa, progesterone
PaO2 = PiO2 (PaCO2/R)
Hyperventilation decreases the partial pressure of CO2 in the alveoli, thereby increasing the partial pressure of oxygen in the alveoli to facilitate oxygenation
Resulting metabolic alkalosis slows HVR, and ventilation slowly increases over several days as kidneys excrete bicarb
Can be facilitated by acetazolamide
People with low HVR at higher risk for illness
PaO2 = partial pressure of alveolar oxygen
PiO2 = partial pressure of inspired oxygen
PaCO2 = partial pressure of carbon dioxide in alveolus
R = respiratory quotient
Acetazolamide has several mechanisms of action that allow it to aid in acclimatization, including facilitating excretion of bicarb for faster rise in ventilation. See later slide.

8. Cardiovascular
Initial increase in resting HR, which normalizes with acclimatization
Decrease in maximal heart rate
Decrease in plasma volume -> lower stroke volume, increase in hematocrit
Shift to extracellular space
Diuresis from bicarbonate excretion
Decrease in max HR and SV are cardioprotective – myocardial ischemia is rare

9. Hematopoietic response
Initial increase in hematocrit due to fluid shift and diuresis
Erythropoietin stimulated early, resulting in new RBCs within 4-5 days
Over weeks to months, red cell and total circulating volume expand to meet demand

10. Oxygen-hemoglobin curve
Above 10,000 feet (PO2 ~ 60), small changes in PO2 cause large changes in SaO2
Initial increase in 2,3-diphosphoglycerate (DPG) promotes O2 release to tissues
Opposed by respiratory alkalosis, which shifts curve left, favoring oxygen uptake in the lung and higher SaO2
Studies have shown that people with genetically left-shifted curves have less dyspnea at altitude and no change in exercise performance. Over time at altitude, a left-shifted curve is likely adaptive.

11. Sleep and periodic breathing
Disturbed sleep with less deep sleep and significant arousals common
Periodic breathing common
Hyperpnea and respiratory alkalosis cause apnea
CO2 builds during apnea, causing hyperpnea
Not usually associated with significant hypoxemia or high-altitude illness
Decreases with acclimatization
People with low HVR may have overall regular breathing pattern with periods of more significant apnea and hypoxemia, which are associated with high-altitude illness

12. Acute high-altitude illness
Spectrum of disease with intertwining pathophysiology
Acute mountain sickness (AMS)
High altitude cerebral edema (HACE)
High altitude pulmonary edema (HAPE)
All correct rapidly with descent

13. Prevention of high-altitude illness
Avoid ascent to greater than 8,000 feet in one day
Spend 2-3 nights at 8,000-9,000 feet before further ascent
Don’t ascend sleeping altitude more than 1500 feet per day
Limit exertion, alcohol, and sedative-hypnotics during first days at altitude
Day trips to higher altitude while maintaining sleeping altitude can speed acclimatization
Acetazolamide mg BID

14. Acute mountain sickness
Most common with rapid ascent from below 3,000 feet to above 8,000 feet
Develops within hours of ascent
Headache plus at least one of:
Gastrointestinal discomfort
Sleep disturbance
Generalized weakness or fatigue
Dizziness or lightheadedness
Headache is usually throbbing, bitemporal, worse at night and with Valsalva

15. AMS: Pathophysiology Pathophysiology incompletely understood
Vasodilatory response to hypoxemia, fluid shift, inflammatory mediators, and alterations in cerebrospinal fluid buffering capacity are all implicated
No evidence of cerebral edema in AMS, but some studies suggest transient ICP elevations with exertion and Valsalva
At risk may be people with low HVR and people with smaller CSF capacity (“tight fit”)
Hyperbaria contributes, but role unclear (AMS does not develop with hypoxia alone)

16. AMS: Management
Usually resolves within 1-3 days if no additional ascent
Mild: Stop ascent, symptomatic treatment, may consider acetazolamide
Moderate to severe: Low-flow oxygen, acetazolamide +/- dexamethasone 4 mg q 6 hours, hyperbarics, or descend
Immediate descent if s/sx HAPE or HACE

17. Acetazolamide Carbonic anhydrase inhibitor
Promotes bicarbonate diuresis and metabolic acidosis, speeding acclimatization
Decreases CSF production
Maintains oxygenation during sleep
Side effects: polyuria and paresthesias
mg BID for treatment and prevention of AMS

18. High-altitude cerebral edema
Least common but most severe form of high-altitude illness
Incidence 1-2% of ascents
Usually develops above 12,000 feet
Usually preceded by AMS and associated with HAPE
Most commonly develops days 1-3 after ascent, but can develop later

19. HACE: Presentation
Ataxia and altered mentation are hallmarks – ataxia usually first symptom
Focal neuro deficits may be present
Seizures uncommon but reported
Usually preceded by AMS symptoms
Any ataxia or change in consciousness in a person at altitude should elicit immediate action!

20. HACE: Pathophysiology
Vasogenic cerebral edema caused by same group of mechanisms as AMS (vasodilation, leakage of fluid from vessels) – reversible
Increased ICP causes decreased cerebral blood flow, resulting in cell death
At advanced stages, cytotoxic edema and necrosis are present - not reversible

21. HACE: Management Immediate descent is key
High-flow oxygen and dexamethasone 8 mg (IV, IM, PO) followed by 4 mg q 6 hours if available
Hyperbarics may result in temporary improvement but may delay descent
Intubation, hyperventilation if severely altered
Can try mannitol or furosemide but caution due to dehydration common at altitude

22. HACE: Prognosis
If descent initiated early, may be completely reversible over days to weeks without sequelae
Reports of ataxia and other neuro deficits persisting months to years
Mortality rate greater than 60% if progresses to coma

23. High-altitude pulmonary edema
Most common cause of altitude-related death
Incidence up to 15% of ascents
Usually greater than 10,000 feet, or greater than 8,000 feet with heavy exertion
Develops within 2-4 days of ascent, classically on the second night

24. HAPE: Presentation
Early signs are severe dyspnea on exertion, fatigue with minimal activity, and dry cough
Dyspnea at rest and clear, watery sputum develop as illness progresses
Dyspnea at rest is red flag for HAPE and should prompt immediate action!
Patchy infiltrates on CXR, worst right middle lobe

25. HAPE: Pathophysiology
Hypoxic vasoconstriction causes pulmonary hypertension
Uneven vasoconstriction (areas of extreme hypoxia or anatomic difference) causes hyperperfusion of some areas, leading to vascular leak and patchy edema
Both hypoxia and pulmonary hypertension are exacerbated by exertion
The hypoxic vasoconstrictor response is physiologic when there is a small area of the lung that is poorly ventilated – this allows blood to flow to well-perfused areas. However, when hypoxia is global, the result is pulmonary hypertension.

26. HAPE: Management
Symptoms resolve quickly upon descent of feet
Mild cases may be treated with bedrest and O2 to maintain SaO2 > 90
Descent for severe symptoms, minimizing exertion
High-flow oxygen
Continuous positive airway pressure if available
Air drops of O2 may be lifesaving if descent not possible
Hyperbarics may help conserve O2 supply

27. Hyperbarics
Portable, lightweight, manually-pressurized hyperbaric bags
Raise atmospheric pressure 2 psi (103 mmHg)
Simulates descent of 4,000-5,000 feet at moderate altitudes, more at higher altitudes
Can be lifesaving in HAPE and HACE, relieving symptoms so that patients can descend without evacuation
Photo: Rosen’s Emergency Medicine, Courtesy of Thomas Dietz, MD

28. Take-home
Slow ascent and acetazolamide are effective in preventing illness
Ataxia, altered mentation, and dyspnea at rest are red flags for serious illness
Early recognition of HAPE and HACE with descent prevents morbidity and mortality
Have fun up there!

29. Key References
Marx, JA, ed. Rosen’s Emergency Medicine, 7th Ed. Philadelphia: Mosby Elsevier, 2010
Auerbach, PS, ed. Wilderness Medicine, 6th Ed. Philadelphia: Mosby Elsevier, 2012