Background Altitude illness refers to a group of syndromes that result from hypoxia.

Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) are manifestations of the brain pathophysiology, while high-altitude pulmonary edema (HAPE) is that of the lung. Everyone traveling to altitude is at risk, regardless of age, level of physical fitness, prior medical history, or previous altitude experience.The high-altitude environment generally refers to elevations over 1500 m (4900 ft). Moderate altitude, 2000-3500 m (6600-11,500 ft) includes the elevation of many US ski resorts. Although arterial oxygen saturation is well maintained at these altitudes, low PO2 results in mild tissue hypoxia, and altitude illness is common. Very high altitude refers to elevations of 3500-5500 m (18,000 ft). Arterial oxygen saturation is not maintained in this range, and extreme hypoxemia can occur during sleep, with exercise, or illness. HACE and HAPE are most common at these altitudes. Extreme altitude is over 5500 m; above this altitude, successful long-term acclimatization is not possible and in fact deterioration ensues. Individuals must progressively acclimatize to intermediate altitudes to reach extreme altitude. Pathophysiology Acclimatization Hypoxia is the primary physiological insult on ascent to high altitude. The fraction of oxygen in the atmosphere remains constant (0.21) at all altitudes, but the partial pressure of oxygen decreases along with barometric pressure on ascent to altitude. The inspired partial pressure of oxygen (PiO2) is lower still because of water vapor pressure in the airways. At the altitude of La Paz, Bolivia (4000 m; 13,200 ft), PiO2 is 86.4 mm Hg, which is equivalent to breathing 12% oxygen at sea level. The response to hypoxia depends on both the magnitude and the rate of onset of hypoxia. The process of adjusting to hypoxia, termed acclimatization, is a series of compensatory changes in multiple organ systems over differing time courses from minutes to weeks. While the fundamental process occurs in the metabolic machinery of the cell, acute physiologic responses are essential in allowing the cells time to adjust. The most important immediate response of the body to hypoxia is an increase in minute ventilation, triggered by oxygen sensing cells in the carotid body. Increased ventilation produces a higher alveolar PO2. Concurrently, a lowered alveolar PCO2 produces a respiratory alkalosis, acting as a brake on the respiratory center of the brain and limiting the increase in ventilation. Renal compensation, through excretion of bicarbonate ion, gradually brings the blood pH back toward normal and allows further increase in ventilation. This process, termed ventilatory acclimatization, requires approximately 4 days at a given altitude and is greatly enhanced by acetazolamide. Patients with inadequate carotid body response (genetic or acquired, eg, after surgery or radiation) or pulmonary or renal disease may have an insufficient ventilatory response and thus not adapt well to high altitude. In addition to ventilatory changes, circulatory changes occur that increase the delivery of oxygen to the tissues. Ascent to high altitude initially results in increased sympathetic activity, leading to increased resting heart rate and cardiac output and mildly increased blood pressure. Within minutes of exposure, the pulmonary circulation reacts to hypoxia with vasoconstriction. This may improve ventilation/perfusion matching and gas exchange, but the resulting pulmonary hypertension can lead to a number of pathological syndromes at high altitude, including HAPE and altitude-related right heart failure (see, Altitude Illness - Pulmonary Syndromes). Cerebral blood flow increases immediately on ascent to high altitude, returning toward normal over about a week. The magnitude of the increase varies but averages 24% at 3810 m and more at higher altitude. Whether the headache of AMS is related to this flow increase is not known. Hemoglobin concentration increases after ascent to high altitude, increasing the oxygen-carrying capacity of the blood. Initially, it increases due to hemoconcentration from a reduction in plasma volume secondary to altitude diuresis and fluid shifts. Subsequently, over days to weeks, erythropoietin stimulates increased red cell production. In addition, the marked alkalosis of extreme altitude causes a leftward shift of the oxyhemoglobin dissociation curve, facilitating loading of the hemoglobin with oxygen in the pulmonary capillary. Sleep architecture is altered at high altitude, with frequent arousals and nearly universal subjective reports of disturbed sleep. This generally improves after several nights at a constant altitude, though periodic breathing (Cheyne-Stokes respiration) remains common above 2700 m. Pathophysiology of AMS/HACE The exact pathophysiology of AMS/HACE is unknown. The current hypothesis is that hypoxia elicits neurohumoral and hemodynamic responses in the brain that ultimately result in capillary leakage from microvascular beds and edema. Whether mild AMS or headache alone is actually due to brain edema remains an open question. Recent studies using ultrasonographic assessment of optic nerve sheath diameter (ONSD), which has

or lassitude) are common. HACE is estimated to occur in about 1% or less of persons traveling above 4000 m and in 1-3% of those with AMS. but without fever or myalgias. lightheadedness. fatigue). weakness. however.500 ft) or La Paz. As AMS progresses. or failure to improve with descent. Slower recovery results when treatment is delayed. nausea. 13. HACE commonly occurs in conjunction with HAPE. weakness. the incidence ranges from 10-40%. HACE may progress to stupor and coma over hours to days if untreated. in contrast to the spontaneous diuresis observed with successful acclimatization. or dexamethasone suggests another diagnosis. elevated cerebral capillary pressure. Children have similar occurrence rates of altitude cerebral syndromes to those of adults. Rapid ascent to approximately 4000 m has been associated with incidences of 60-70%. Frequency United States The incidence of AMS varies depending on the rate of ascent and the maximum altitude reached. and constitutional symptoms (weakness.been shown to correlate with intracranial pressure. Using the Lake Louise consensus criteria. impaired cerebral autoregulation. However. especially after rapid ascent (1 d or less). Sex No significant difference based on gender exists. and decreased urine output. or insomnia. rarely. Factors that might contribute to a hydrostatic brain edema are multiple and include cerebral vasodilation. 25-50% will suffer from AMS. Age Age has a small effect in adults. dizziness. and other factors. In rare cases. often after the first night's sleep. Fluid retention is characteristic of AMS. typically frontal and throbbing.200 ft) can expect an AMS incidence of 25-35%. Clinical History AMS is a syndrome of nonspecific symptoms with a broad spectrum of severity. as well as alterations in the permeability of the blood-brain barrier through cytokine activation. and persons with AMS often report reduced urination.1 Magnetic resonance imaging (MRI) studies demonstrate that the brain swells on ascent to altitude in both those with and those without AMS. Onset of symptoms more than 3 days after ascent. AMS is similar to an alcohol hangover. Once coma has developed. oxygen. constitutional (lightheadedness. Also. Tibet (3810 m. Bolivia (4000 m. younger adults are slightly more susceptible. In moderate altitude (2000-3500 m) ski resorts. with complete resolution in 1-3 days. Physical . death is due to brain herniation. nausea. vomiting). Race No race predilection exists. oliguria. or to a nonspecific viral infection. Individual susceptibility is reproducible. Ataxia and altered level of consciousness herald the onset of clinical HACE. In general. complete recovery if treatment is started promptly. however. or vomiting). and increased lassitude develop. Susceptibility to AMS demonstrates great individual variability because of genetic differences. AMS occurs in nonacclimatized persons in the first 48 h after ascent to altitudes above 2500 m. it may develop in the absence of AMS after a very rapid ascent or at extreme altitude in an apparently acclimatized person. Ataxia commonly persists for days to weeks and is often the last finding to resolve. presumably from vasodilation. as it can cause headache. and vomiting. True edema. was only detected in severe AMS and HACE. The most common history in HACE is a person ascending further despite symptoms of AMS. nausea. patients with either severe or prolonged HACE may have persistent neurologic deficits. the headache worsens. 12. with continued ascent. the illness is self-limiting and symptoms improve slowly. Mortality/Morbidity The natural history of AMS varies with altitude. ascent rate. Headache is the principal symptom. lack of headache. AMS is very likely to worsen and is more likely to progress to HACE. The incidence of AMS is not markedly affected by menstrual cycle phase and does not differ in pregnant women versus nonpregnant women. the diagnosis of AMS requires headache plus at least one of the following symptoms: gastrointestinal (anorexia. a past history of AMS is the best predictor. Symptoms usually begin a few hours after arrival at the new altitude but may arise as much as a day later. death is more likely despite aggressive treatment. Dehydration is commonly confused with AMS. International Travelers flying to a high altitude destination such as Lhasa. The usual course is rapid. Gastrointestinal symptoms (anorexia. has demonstrated increased ONSD swelling in both AMS and HAPE cases. Most conditions similar to AMS can be excluded by history and physical examination. In those who hike above 4000 m (and so ascend at a moderate pace).

stroke. Predicting the eventual severity from the initial clinical presentation is not possible. o Regardless of AMS symptoms. or group resources. Causes • Rapid ascent to altitudes greater than 2500 m can cause AMS. o Usually. ascents of as little as 200 m for individuals with moderate AMS have precipitated HACE. Accordingly. o Pulmonary crackles may be present in some patients. o Peripheral and facial edema may be present.• • Acute mountain sickness o Patients may appear ill but otherwise have no characteristic physical findings. a physiologic (simulated) descent of up to 2000 m may be achieved within minutes. A small percentage (<10%) of persons with AMS will go on to develop HACE. Both agents may be used to treat AMS if the victim does not descend. pressurizing the inside to 105-220 mm Hg above ambient atmospheric pressure. Daytime climbs to higher elevations. The patient is placed completely within the bag. focal neurologic signs (eg. These are all lightweight. at most. in HACE cases. (2) descend to a lower altitude if no improvement occurs with medical therapy. • Continued ascent despite symptoms of AMS is a major risk factor for developing HACE. unless a chemical scrubber system is used. which is sealed shut and inflated with a manually operated pump. o Funduscopic examination may reveal retinal hemorrhages. o Fever is absent. especially with continued ascent in the presence of AMS symptoms. and patients must be watched closely for progression of illness. but this may still require 12-24 hours. Patients are typically treated in 1-hour increments and then are reevaluated. High-altitude cerebral edema o In a patient with symptoms of AMS who develops gait ataxia (ie. Descent to an altitude below that where symptoms started is always effective treatment but may not be practical or possible given the topography. presumably because of rapidly worsening hypoxia. Depending on the elevation of use. • Special attention should be paid to the elevation at which the person sleeps. a combination of ataxia and mental status changes suggests HACE. o In rare cases. particularly in women. but these are not specific to AMS. Acetazolamide accelerates acclimatization and thus quickens resolution of the illness. CERTEC. Oxygen is extremely effective. the neurologic examination findings are otherwise normal. but availability is often limited. Dexamethasone swiftly reverses symptoms (2-4 h) but does not improve acclimatization. Immediate treatment and descent is indicated. weather. these chambers should only be used as a means of acute/temporizing care . slightly lower than acclimatized persons at the same elevation. unable to walk heel-to-toe in a straight line) or mental status changes. cranial nerve VI palsy) appear in end-stage HACE. descend immediately. Importantly. with return to a lower sleeping altitude are preferred. Continuous pumping is necessary to flush CO2 out of the system. Gamow bag. the patient's ultimate trekking or climbing goals. o Heart rate and blood pressure are variable and nondiagnostic. but oxygen saturation will be normal or. o Neurologic examination (especially mental status and gait) is normal. • The risk of HACE or AMS increases with altitude. Portable hyperbaric chambers made of coated fabric (eg. a descent of 500-1000 m is usually sufficient. It is the drug of choice for treating HACE and should be given early. transient ischemic attack [TIA]. HACE is the diagnosis until proven otherwise. cranial nerve III palsy. Acetazolamide can be taken episodically without fear of rebound symptoms when it is discontinued. At altitudes over 5000 m. it is of limited value in HACE because of its relatively slow action. • HACE frequently is seen secondary to HAPE. PAC) are now widely available among adventure travel groups on expeditions and in high-altitude clinics.7 m in diameter. and (3) at the first sign of HACE. brain neoplasm). coated fabric bags about 2 m long and 0. although they are more suggestive of other causes of focal deficits at altitude (eg. which is equivalent to continued ascent Treatment Prehospital Care Management of AMS follows 3 axioms: (1) no further ascent until symptoms resolve. migraine.

Coca leaf tea may act as a mild stimulant and improve well-being at altitude. further treatment is rarely indicated. herpes encephalitis.(eg. ibuprofen) are indicated for symptomatic treatment of headache. no studies support this claim. AMS may be treated at the discretion of the patient and physician. Additional medications not shown to have any benefit include calcium channel blockers. see Deterrence/Prevention section for further details. Alcohol and other respiratory depressants should be avoided in someone with AMS due to the risk of exaggerated hypoxemia. Carbonic anhydrase inhibitors These agents are thought to improve acclimatization by increasing renal bicarbonate excretion at high altitude. Not indicated for general prophylaxis of AMS. and antacids. and. Emergency Department Care All of the symptoms of AMS improve dramatically with descent. Helps prevent AMS in forced rapid ascent or in patients with history of repeated AMS. Garlic likewise has been advocated for prophylaxis and treatment of altitude illness. Animal studies show efficacy in preventing hypoxic pulmonary hypertension. Mild analgesics (eg. and cortical blindness have all been misdiagnosed as HACE. aspirin. Oxygen 4 L/min or to keep SaO2 above 90% should be used in patients who continue to be acutely ill with either severe AMS or HACE after descent. Consultations Ataxia due to HACE commonly persists for days to weeks after descent. Routine prophylaxis of AMS with acetazolamide can be considered in those without contraindications. on the Internet. Medication Treatment of HACE is indicated immediately upon diagnosis. to improve a patient's ability to more safely participate in their evacuation in technical terrain). Dexamethasone should be continued in symptomatic patients with HACE. Acetazolamide (Diamox) Carbonic anhydrase inhibitor for accelerating acclimatization to altitude in AMS. acetaminophen. by the time a patient reaches the emergency department. Coca leaf tea is widely recommended in South America. They act as a respiratory stimulant at high altitude. phenytoin. but persistent mental status changes or the presence of focal neurologic deficits should prompt a complete neurologic evaluation. which may be its primary effect. They should never be considered as a replacement for actual descent. Guillain-Barré syndrome. and in the popular press as a cure for altitude illness. . naproxen. but studies in humans are lacking and its use cannot be recommended at this time. however. Improves symptomatic periodic breathing and hypoxia experienced at high altitudes. Treatment of AMS may be discontinued when patient is asymptomatic. Brain tumors that suddenly become symptomatic at altitude.