High Altitude Related Illnesses

Background

- High altitude illness (HAI) is a group of syndromes following ascent to high altitude related to hypoxia and manifesting in neurological and pulmonary dysfunction. These syndromes can affect anyone regardless of prior altitude exposure, age, and physical fitness. However, risk factors associated with HAI include the actual altitude, fast ascent, prior history of HAI, and certain comorbidities that affect respiration or circulation.

- Moderate altitude >2000m (most ski resorts); very high altitude >3500m; extremely high altitude>5500m

Pathophysiology:

At high altitudes, the PO2 is decreased which results in tissue hypoxia, even though the FiO2 is normal (21%) and the SpO2 is normal up until very high altitudes. Hypoxemia occurs with exertion, illness, and during sleep.
The body responds to hypoxia through a process termed acclimatization that occurs over 3-5 days. It does so by increasing the respiratory rate, which produces a mild respiratory alkalosis. The kidneys then excrete bicarbonate to normalize the pH to allow for the increased minute ventilation. The cardiovascular system also adapts to increased sympathetic activity by increasing BP, HR, and cardiac output (CO). 

High Altitude Pulmonary Edema (HAPE)

- The pulmonary vasculature vasoconstricts in response to hypoxia. This improves gas exchange, however it can also results in a state of pulmonary hypertension and noncardiogenic (normal ejection fraction) pulmonary edema. The pulmonary capillaries also become more leaky in response to hypoxia which exacerbates the pulmonary edema.
- HAPE occurs around 3 days after reaching high altitudes. Fatigue/weakness, shortness of breath, and dry cough are early symptoms. This syndrome can mimic pneumonia because patients often have fever, rales, tachycardia, tachypnea, and infiltrates on chest x-ray. Pulse oximetry may demonstrate a lower oxygen saturation than expected for the altitude
- HAPE is the HAI complication that most commonly causes death. It can be fatal within a few hours if untreated. If appropriately treated with oxygen and descent, rapid and complete recovery is typical without long term complications. 

Cerebral Syndromes: Acute Mountain Sickness (AMS) and High Altitude Cerebral Edema (HACE)

Cerebral blood flow quickly increases by 25% or more at high altitude>3500m and the increase is higher at higher altitudes. Cerebral vasodilation causes vasogenic edema, which is thought to precipitate these two syndromes-- AMS and HACE. 
- AMS occurs in the first 48 hours after ascent to high altitude, especially with rapid ascent. Symptoms include headache, nausea/vomiting, generalized weakness and dizziness, oliguria. If altered mental status or ataxia in addition to the above symptoms develops, then AMS has progressed to HACE
- Ataxia is an early finding and the last symptom to resolve
- HACE can progress to coma and brain herniation over several hours if left untreated
- Neurologic exam in AMS is normal except sometimes retinal hemorrhages are seen on fundoscopic exam. In HACE, patients develop ataxia and altered mental status, but the remainder of the neuro exam should be normal except in rare cases where cranial nerve palsies may develop

Prevention and Treatment:

- Slow and gradual ascent is the best way to acclimatize and prevent HAI. Spend a few days at moderate altitude before ascending further and do not progress more than 3-400m in vertical altitude per day above 3000m
- Avoid sedative-hypnotics drugs and alcohol, which can cause respiratory depression
- Avoid significant exertion, which can increase pulmonary arterial pressures, while at high altitudes
- People with pulmonary hypertension should avoid high altitude
- All HAI complications are treated with oxygen and descent. Descend to an altitude that is lower than when symptoms started is usually effective. 
- Hyperbaric oxygen for HACE and HAPE can be considered. Portable hyperbaric chambers can be used if descent isn't possible due to weather conditions or other reasons
- BiPAP can be useful for HAPE 

Medications
- Nifedipine (calcium channel blockers): dilates pulmonary vasculature, can improve oxygen saturation within minutes; does not help further if patient is already on supplemental oxygen (and oxygen is more beneficial to begin with) so really only useful when oxygen is not available
- Acetazolamide: can speed up acclimatization and is used for prophylaxis 1-2 days before ascent. It is a carbonic anhydrase inhibitor that stimulates respiration and increases renal bicarbonate excretion. There is not great evidence to support using it as treatment, but it is often given as there is minimal downside
- Dexamethasone (corticosteroid): has anti-inflammatory effects in vasogenic cerebral edema and is used to treat AMS and HACE. It can be used for HAPE prophylaxis as well though the mechanism through which it helps is unclear
- Tadalafil (Phosphodiesterase inhibitors) can relax pulmonary arteries and decrease arterial pressure; it can be used for HAPE prophylaxis
- Furosemide can cause intravascular dehydration and is not recommended