37-14: High-Altitude Illness

General Considerations

As altitude increases, there is a decrease in both barometric pressure and oxygen partial pressure resulting in hypobaric hypoxia. High-altitude illnesses are due to hypobaric hypoxia at high altitudes (usually greater than 2000 meters or 6562 feet). High-altitude illness includes a spectrum of disorders categorized by end-organ effects (mostly cerebral and pulmonary) and exposure duration (acute and long-term). Acute high-altitude illnesses are acute hypoxia, acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE). Long-term exposure to high altitude over months or years with inadequate acclimatization can result in subacute mountain sickness and chronic mountain sickness (Monge disease).

Acclimatization occurs as a physiologic response to the increasing altitude and increasing hypobaric hypoxia. Physiologic changes include increases in alveolar ventilation and oxygen extraction by the tissues and increased hemoglobin level and oxygen binding. High-altitude illness results when the hypoxic stress is greater than the individual’s ability to acclimatize. This is a result of fluid shifts from intravascular to extravascular spaces, especially in the brain and lungs. Risk factors for high-altitude illness include increased physical activity with insufficient acclimatization, inadequate education and preparation, individual susceptibility (preexisting medical conditions and medication use), and previous high-altitude illness. The key determinants of high-altitude illness risk and severity include both individual susceptibility factors and altitudinal factors, such as rate and height of ascent and total change in altitude over time. Presentations may be acute, subacute, or chronic disturbances that result from hypobaric hypoxia. Acclimatization to altitudes above 5500 meters (18,045 feet) is incomplete or physiologically impossible, although individual differences in tolerance to hypoxia exist.

Individual susceptibility factors include underlying conditions such as cardiac and pulmonary disease, patent foramen ovale, blood disorders (eg, anemia, sickle cell disease), pregnancy, neurologic conditions, smoking, recent surgery, diabetes, and many other chronic medical conditions. Those with symptomatic neurologic, cardiac, or pulmonary disease must avoid high altitudes.

Patient assessment for high-altitude illness must also include evaluation for other conditions (eg, severe dehydration, hyponatremia, hypoglycemia, infection, or trauma), which may coexist or may present in a similar manner.

There is a spectrum of neurologic conditions caused by high altitude, ranging from acute mountain sickness (AMS) to the more serious form, high-altitude cerebral edema (HACE) Clinicians may utilize various diagnostic tools to assess the level of cerebral impairment due to high altitude (visual analog scale [VAS] score, Acute Mountain Sickness-Cerebral [AMS-C] score, clinical functional score [CFS], Lake Louise Questionnaire Score [LLQS]).

AMS includes symptoms such as headache (most severe and persistent symptom), lassitude, drowsiness, dizziness, chilliness, nausea and vomiting, and difficulty sleeping. Later symptoms include irritability, difficulty concentrating, anorexia, insomnia, and increased headaches.

HACE includes the severe symptoms of AMS and results from cerebral vasogenic edema and cerebral cellular hypoxia. It usually occurs at elevations above 2500 meters (8202 feet) but may occur at lower elevations. It is more common in unacclimatized individuals. Hallmarks are altered mental status, ataxia, severe lassitude, and encephalopathy. The patient appears “mildly drunk.” Examination findings may include confusion, ataxia, urinary retention or incontinence, focal neurologic deficits, papilledema, and seizures. Symptoms may progress to obtundation, coma, and death. High-altitude retinopathy is a separate but related effect of altitude. It can include dilated vessels, retinal hemorrhage, vitreous hemorrhage, and papilledema.

Treatment

Definitive treatment is immediate descent of at least 610 meters (2001 feet), and descent must continue until symptoms improve. Descent is essential if the symptoms are persistent, severe, or worsening, or if HACE or HAPE is present. If immediate descent is not possible, portable hyperbaric chambers can provide symptomatic relief, but this must not delay descent.

Initial treatment involves oxygen administration to keep the pulse oximetry S_pO₂ to greater than 90%.

Acetazolamide (250 mg orally twice daily) is an effective medication for both prophylaxis and treatment of mild symptoms of AMS. This is a sulfonamide drug and must be used with caution or avoided in persons with past reactions to this class of drug. Adverse reactions include peripheral paresthesias, altered taste of carbonated beverages, polyuria, nausea, drowsiness, erectile dysfunction, and myopia.

Dexamethasone is given for moderate to severe AMS (4 mg orally every 6 hours). Dexamethasone is the primary treatment for HACE (8 mg once then 4 mg orally every 6 hours). Acetazolamide can be added as an adjunct in severe HACE cases. In most individuals, symptoms clear within 24–48 hours. Dexamethasone does not facilitate acclimatization, so the patient needs to complete dexamethasone therapy and be asymptomatic before they can ascend any further. HACE treatment must continue until 24 hours after resolution of symptoms or until descent is completed. Dexamethasone should not be given for longer than 7 days.

It is imperative that the clinician also assess for other conditions that may mimic or coexist with AMS and HACE (eg, dehydration, exhaustion, hypoglycemia, hypothermia, hyponatremia, trauma, infection).

If HAPE symptoms and signs are present along with HACE, nifedipine or a selective phosphodiesterase inhibitor may be added for pulmonary vasodilation. The clinician must be cautious when using combinations of vasodilators. These medications lower the mean arterial pressure, and in combination, these may result in lowering the cerebral perfusion pressure and thereby increasing the risk of cerebral ischemia.

HAPE is the leading cause of death from high-altitude illness. Although it is often seen in conjunction with AMS and HACE, the important difference is its underlying pathology of hypoxia-induced pulmonary hypertension, which requires different management and treatment approaches than AMS and HACE. The hallmark is markedly elevated pulmonary artery pressure followed by pulmonary edema. It usually occurs at altitudes above 3000 meters (9840 feet), although it may occur at lower levels. High altitude increases pulmonary arterial pressure and decreases the oxygen uptake and saturation and alters oxygen kinetics. Early symptoms may appear within 6–36 hours after arrival at a high-altitude area. These include incessant dry cough, shortness of breath disproportionate to exertion, headache, decreased exercise performance, fatigue, dyspnea at rest, and chest tightness. Recognition of the early symptoms may enable the patient to descend before incapacitating pulmonary edema develops. Strenuous exertion must be avoided. As pulmonary edema worsens, wheezing, orthopnea, and hemoptysis may develop.

Physical findings may include tachycardia, mild fever, tachypnea, cyanosis, prolonged respiration, rales, wheezing, and rhonchi. The clinician must assess for other potential medical conditions because the clinical picture may resemble other entities (pneumonia, viral upper respiratory tract infection, mucous plugging, bronchospasm, or acute coronary syndrome). Diagnosis is usually clinical; ancillary tests are nonspecific or unavailable on site. Prompt recognition and medical attention of early symptoms of HAPE may prevent progression.

The white blood cell count is often slightly elevated, but the erythrocyte sedimentation rate is usually normal. Chest radiographic findings vary from irregular patchy infiltration in one lung to nodular densities bilaterally or with transient prominence of the central pulmonary arteries. Transient nonspecific ECG changes, occasionally showing right ventricular strain, may occur. Pulmonary arterial blood pressure is elevated, whereas wedge pressure is normal. Research has shown benefits from chest ultrasonography for diagnosis and monitoring of high-altitude pulmonary edema.

Treatment

Immediate descent (at least 610 meters [2000 feet]) is essential, although this may not be immediately possible and may not alone improve symptoms.

Treatment must often be initiated under field conditions. The patient must be placed at rest, reclined with head elevated. Supplemental oxygen must be administered to maintain pulse oximetry reading S_pO₂ greater than 90%. Recompression in a portable hyperbaric bag will temporarily reduce symptoms if rapid or immediate descent is not possible, but must not delay descent.

Nifedipine (60 mg slow extended-release tablets daily, given in divided doses of 30 mg twice daily, or 20 mg three times daily) can be used as an adjunct if the other therapies (descent, oxygen, or portable hyperbaric chambers) are not successful or available. Selective phosphodiesterase inhibitors (tadalafil, 10 mg orally every 12 hours; sildenafil, 50 mg orally every 8 hours) may be used for HAPE prevention and may also provide effective symptom relief as an alternative or if nifedipine is not available. Tadalafil and sildenafil have also been shown to improve exercise capacity in adults with high-altitude pulmonary vasoconstriction. Administering nifedipine plus a phosphodiesterase inhibitor as pulmonary vasodilators is not recommended because this combination may also lower the mean arterial pressure and decrease cerebral perfusion. Treatment for ARDS (see Chapter 9) is required for some patients. If neurologic symptoms are present concurrently with HAPE and do not resolve with improved oxygenation, dexamethasone may be added according to HACE treatment guidelines.

There is an international effort to advance the understanding of high-altitude pulmonary edema through the research and database registry (https://www.altitude.org). Susceptible individuals should register with this International HAPE Database.

This occurs most frequently in unacclimated individuals and at high altitudes (above 4500 meters) for a prolonged period of time. The hypobaric hypoxia results in pulmonary hypertension. Symptoms of dyspnea and cough are probably due to hypoxic pulmonary hypertension and secondary heart failure. Dehydration, skin dryness, and pruritus can also occur. The hematocrit may be elevated, and there may be ECG and chest radiographic evidence of right ventricular hypertrophy. Treatment consists of rest, oxygen administration, diuretics, and return to lower altitudes.

This uncommon condition is seen in residents of high-altitude communities who have lost their acclimatization to such a hypobaric hypoxic environment. It is difficult to differentiate from chronic pulmonary disease. The disorder is characterized by somnolence, mental depression, cyanosis, clubbing of fingers, chronic hypoxia, hemoglobin greater than 22 g/dL, polycythemia (hematocrit often greater than 75%), signs of right ventricular failure, ECG evidence of right axis deviation and right atrial and ventricular hypertrophy, and radiographic evidence of right heart enlargement and central pulmonary vessel prominence, and pulmonary hypertension in some cases. There is no radiographic evidence of structural pulmonary disease. Pulmonary function tests usually disclose alveolar hypoventilation and elevated PaCO₂ but fail to reveal defective oxygen transport. There is a diminished respiratory response to CO₂.

Almost complete disappearance of all abnormalities eventually occurs when the patient returns to sea level. Recommended treatments include phlebotomy, oxygen supplementation, respiratory training, medroxyprogesterone (20–60 mg/day orally for 10 weeks), acetazolamide (250 mg/day orally for 3 weeks), and enalapril (5 mg orally daily).

Prevention of High-Altitude Disorders

Pre-trip preventive measures include participant education, medical preparticipation evaluation, pre-trip planning, optimal physical conditioning before travel, and adequate rest and sleep the day before travel and during the trip. Preventive efforts during ascent include reduced food intake and avoidance of alcohol, tobacco, and limiting any unnecessary physical activity during travel. Due to the widely variable difference in each individual's physiologic responses to high altitude and rates of acclimatization, these prevention measures may not be successful in all high-altitude travelers.

Gradual ascent is the most effective way to allow acclimatization. Low-risk ascension rate is 2 or more days to arrive at 2500–3000 meters. For elevations above 3000 meters, the sleeping elevation should increase less than 500 meters every day with an extra day of rest for acclimatization every 1000 meters and with no ascent to higher sleeping elevation every 3–4 days. The altitude reached during waking hours is not as important as the altitude at which the hiker sleeps. If the terrain does not allow a sleeping elevation increase below 500 meters, an extra rest day must be added before or after the increased sleep elevation more than 500 meters. Mountaineering parties at altitudes of 3000 meters or higher must carry a supply of oxygen and medical equipment sufficient for several days.

Drug prophylaxis may be prescribed for AMS and HACE if no contraindications exist. Prophylactic low-dose acetazolamide (125 mg twice daily orally) has been shown to reduce the incidence and severity of AMS and HACE when started 3 days prior to ascent and continued for 48–72 hours at high altitude. Dexamethasone is an alternative prophylactic medication for AMS and HACE (2 mg every 6 hours or 4 mg every 12 hours orally beginning on the day of ascent, continuing for 3 days at the higher altitude, and then tapering over 5 days). Higher doses of dexamethasone (4 mg every 6 hours) may be considered in high-risk situations requiring immediate physical exertion (those airlifted to high altitudes for search and rescue or military).

Individuals with a past history of HAPE should use drug prophylaxis to reduce the risk of recurrence. Nifedipine, 30-mg extended-release orally every 12 hours, started the day before ascent and continued through the fourth day at target elevation, or through the seventh day if the ascent rate was faster, is recommended. Salmeterol can be added at doses of 125 mcg by inhaler every 12 hours beginning 24 hours prior to ascent. Salmeterol is used as an adjunct to nifedipine but not as monotherapy.

Phosphodiesterase inhibitors (eg, tadalafil 10 mg orally twice a day or sildenafil 50 mg orally every 8 hours) may be beneficial in the treatment of HAPE based on their physiologic effects of decreased pulmonary arterial pressures and pulmonary vasodilation. This drug class may be used if nifedipine is not available, but phosphodiesterase inhibitors must not be administered along with nifedipine since the additive vasodilation effects may increase the patient’s risk of hypotension and cerebral hypoperfusion.

When to Admit

• All patients with HACE or HAPE must be hospitalized for further observation.

• Hospitalization must also be considered for any patient who remains symptomatic after treatment and descent.

• Pulmonary symptoms and hypoxia may be worsened by complications such as pulmonary embolism, secondary respiratory infection, bronchospasm, mucous plugging, or acute coronary syndrome.