Altitude sickness

Altitude sickness includes several related syndromes caused by decreased available O2 in the air at high altitudes. Acute mountain sickness (AMS), the mildest form, presents with headache along with one or more systemic manifestations. High-altitude cerebral edema (HACE) presents with encephalopathy in people with AMS.

High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema that causes severe dyspnea and hypoxemia. Mild forms of acute mountain sickness may occur in hikers and skiers. Diagnosis is based on clinical features. Treatment of mild acute mountain sickness includes analgesics and acetazolamide. In severe cases, the victim should be brought down as quickly as possible and, if possible, given additional O2. In addition, dexamethasone may be effective for high-altitude cerebral edema, and nifedipine for high-altitude pulmonary edema.

As altitude increases, atmospheric pressure decreases while the percentage of O2 in the air remains constant; thus, the partial pressure of O2 decreases with altitude and at 5800 m (19,000 ft) is about 1/2 the pressure at sea level.

Most people can ascend to 1,500–2,000 m (5,000–6,500 ft) during the day without problems, but approximately 20% of those who ascend to 2,500 m (8,000 ft) and 40% who reach 3,000 m (10,000 ft) develop some form of altitude sickness (AS). The likelihood of developing AS is influenced by the rate of ascent, the highest altitude reached, and sleeping at altitude.

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Risk factors for altitude sickness

High altitude affects people differently. However, in general, exercise and possibly cold increase the risk, and the risk is higher in people with a history of altitude illness and in those living at low altitude [<900 m (<3000 ft)]. Young children and young adults appear to be more susceptible. Medical conditions such as diabetes, coronary heart disease, and moderate COPD (chronic obstructive pulmonary disease) are not risk factors for altitude illness, but hypoxia may adversely affect their course. Physical fitness does not protect against altitude illness.

Pathophysiology of altitude sickness

Acute hypoxia (as occurs, for example, during rapid ascent to high altitude in an unpressurized aircraft) changes the functional state of the central nervous system within minutes. High-altitude sickness occurs as a result of the neurohumoral and hemodynamic response to hypoxia and develops over hours or days.

The central nervous system and lungs are primarily affected. In both systems, capillary pressure and capillary leakage increase, with possible development of edema.

In the lungs, hypoxia-induced increases in pulmonary artery pressure cause interstitial and alveolar edema, impairing oxygenation. Focal hypoxic vasoconstriction of small vessels causes hyperperfusion with elevated pressures, capillary wall injury, and capillary leakage in areas of lesser vasoconstriction. Various additional mechanisms have been proposed for altitude sickness; these include increased sympathetic activity, endothelial dysfunction, decreased alveolar nitric oxide concentrations (possibly due to decreased nitric oxide synthase activity), and a defect in the amiloride-sensitive sodium channel. Some of these factors may have a genetic component.

The pathophysiological mechanisms in the CNS are less clear but may involve a combination of hypoxic cerebral vasodilation, disruption of the blood–brain barrier, and cerebral edema caused by water and Na ⁺ retention. It has been suggested that patients with a low CSF-to-brain ratio have poorer tolerance of brain edema (i.e., CSF displacement) and are therefore more likely to develop HAI. The role of atrial natriuretic peptide, aldosterone, renin, and angiotensin in HAI is unclear.

Acclimatization. Acclimatization is a complex of reactions that gradually restore tissue oxygenation to normal in humans at high altitude. However, despite acclimatization, hypoxia occurs in everyone at high altitude. Most people acclimatize to an altitude of up to 3000 m (10,000 ft) in a few days. The higher the altitude, the longer the adaptation takes. However, no one can fully acclimatize to a long stay at an altitude of >5100 m (>17,000 ft).

Acclimatization is characterized by constant hyperventilation, which increases tissue oxygenation but also causes respiratory alkalosis. Alkalosis normalizes within 24 hours, since HCO3 _is excreted in the urine. As pH normalizes, ventilation volume can increase further. Cardiac output initially increases; the number and functional capacity of erythrocytes increase. Over many generations, different ethnic groups living at altitude adapt to it in slightly different ways.

Symptoms and diagnosis of altitude sickness

The various clinical forms of altitude sickness do not represent distinct manifestations of altitude sickness, but create a spectrum in which one or more forms may be present in varying degrees of severity.

Acute mountain sickness

The most common form, it occurs at lower altitudes, such as 2,000 m (6,500 ft). Probably secondary to moderate cerebral edema, AMS causes headache and at least one of the following: fatigue, gastrointestinal symptoms (anorexia, nausea, vomiting), dizziness, and sleep disturbance. Physical exertion worsens the condition. Symptoms usually begin 6–10 h after ascent and subside after 24–48 h, but occasionally they progress to high-altitude cerebral edema, pulmonary edema, or both. Diagnosis is clinical; laboratory tests are nonspecific and generally unnecessary. AMS is common at ski resorts, and some sufferers mistake it for the effects of excessive alcohol consumption (hangover) or an acute viral infection.

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High altitude cerebral edema

High-altitude cerebral edema presents with headache and diffuse encephalopathy with confusion, drowsiness, stupor, and coma. Ataxic gait is a reliable early warning sign. Seizures and neurological deficits (e.g., cranial nerve palsy, hemiplegia) are less common. Papilledema and retinal hemorrhage are possible but not necessary for diagnosis. Coma and death may occur within a few hours. High-altitude cerebral edema is usually differentiated from coma of other etiologies (e.g., infection, ketoacidosis). Fever and nuchal rigidity are absent, and blood and CSF tests are normal.

High altitude pulmonary edema

High-altitude pulmonary edema usually develops within 24–96 h after rapid ascent to >2500 m (>8000 ft) and is more likely to cause death than other forms of altitude illness. Respiratory infections, even minor ones, increase the risk of high-altitude pulmonary edema. High-altitude pulmonary edema is more common in men (in contrast to other forms of altitude illness). Residents of high altitudes may develop high-altitude pulmonary edema after a brief stay at low altitude upon returning home.

Patients initially present with dyspnea, decreased exercise tolerance, and a dry cough. Pink or bloody sputum and respiratory distress syndrome develop later. Physical examination reveals cyanosis, tachycardia, tachypnea, and a moderate increase in body temperature (<38.5 °C). Focal or diffuse wheezing (sometimes audible without a stethoscope) is also common. Hypoxemia is often severe, with saturations of 40 to 70% by pulse oximetry. Chest radiography, if available, shows normal cardiac borders and focal pulmonary edema (often middle or lower lobes), which is not usually present in heart failure. High-altitude pulmonary edema may progress rapidly; coma and death may occur within hours.

Other violations

At high altitudes, peripheral edema and facial edema are common. Headache without other symptoms of acute mountain sickness is quite common.

Retinal hemorrhages can occur as low as 2,700 m (9,000 ft), but are most common at altitudes >5,000 m (>16,000 ft). Retinal hemorrhages are usually asymptomatic unless they occur in the sclera; they resolve quickly and without complications.

People who have previously undergone radial keratotomy may experience significant visual impairment at altitudes >5000 m (>16,000 ft) and even lower [3000 m (10,000 ft)]. These alarming symptoms disappear quickly, immediately after descent.

Chronic mountain sickness (Monge's disease) is rare and affects those who have lived at altitude for a long time. It is characterized by fatigue, dyspnea, pain, severe polycythemia, and sometimes thromboembolism. The disease is often accompanied by alveolar hypoventilation. Patients should be lowered; recovery is slow, and returning to altitude may cause relapse. Repeated phlebotomies may reduce the severity of polycythemia, but relapse is possible.

Treatment of altitude sickness

Acute mountain sickness. Climb should be stopped and exercise reduced until symptoms resolve. Other treatments include fluids, analgesics for headaches, and a light diet. If symptoms are severe, rapid descent to 500–1,000 m (1,650–3,200 ft) is usually effective. Acetazolamide 250 mg orally twice daily may reduce symptoms and improve sleep.

High-altitude cerebral edema and high-altitude pulmonary edema. The patient must be evacuated from the altitude immediately. If descent is delayed, complete rest and O2 inhalations are necessary. If descent is impossible, O2 inhalations, drugs, and sealing in a portable hyperbaric bag can buy time, but cannot replace the therapeutic effect of descent.

In high-altitude cerebral edema, nifedipine 20 mg sublingually, then long-acting tablets 30 mg reduce pulmonary artery pressure. Diuretics (eg, furosemide) are contraindicated. The heart is not affected by high-altitude cerebral edema, and the use of digitalis is inappropriate. With rapid descent, high-altitude cerebral edema usually resolves within 24-48 hours. If there is a history of high-altitude cerebral edema, a relapse is likely, and this should be known.

In high-altitude pulmonary edema (and severe acute mountain sickness), dexamethasone helps, initially 4-8 mg, then 4 mg every 6 hours. It can be administered orally, subcutaneously, intramuscularly, or intravenously. Acetazolamide can be added at 250 mg 2 times a day.

Prevention of altitude sickness

It is important to drink plenty of fluids, as breathing large volumes of dry air at altitude greatly increases water loss, and dehydration with mild hypovolemia worsens symptoms. It is best to avoid adding salt. Alcohol worsens AMS, worsens breathing during sleep, and worsens respiratory distress. Frequent small meals containing a lot of easily digestible carbohydrates (e.g., fruits, jams, starches) are recommended for the first few days. Although physical fitness increases tolerance to stress at altitude, it does not protect against the development of any form of altitude sickness.

Ascent. Gradual ascent is essential when at altitudes >2,500 m (>8,000 ft). The first night should be at <2,500-3,000 m (8,000-10,000 ft), with 2-3 more nights at the first bivouac if further bivouacs are planned at higher altitudes. Each day after that, the bivouac altitude can be increased to approximately 300 m (1,000 ft), although higher ascents during the day are acceptable, but descents for sleep are mandatory. The ability to ascend without developing symptoms of altitude sickness varies among individuals, with the group usually focusing on the slowest member.

Acclimatization ends quickly. After staying at a lower altitude for several days, acclimatized climbers must ascend gradually again.

Medications. Acetazolamide 125 mg every 8 hours reduces the incidence of acute mountain sickness. It is available as a sustained-release capsule (500 mg once daily). Acetazolamide can be started on the day of ascent; it inhibits carbonic anhydrase and thus increases pulmonary ventilation. Acetazolamide 125 mg orally before bedtime reduces the respiratory rate (an almost universal aid for sleeping at high altitude), thus preventing acute drops in blood O2 partial pressure. The drug is contraindicated in patients with allergy to sulfa drugs. Acetazolamide analogues have no advantages. Acetazolamide may cause numbness and paresthesia of the fingers; these symptoms are benign but may be bothersome to the patient. Carbonated drinks may be tasteless to patients taking acetazolamide.

Low flow O2 delivery during sleep at altitude is effective but inconvenient due to the bulkiness of the equipment.

Patients with a history of high-altitude cerebral edema should be given prophylactic prolonged-release nifedipine 20-30 mg orally twice daily. Inhaled beta-adrenergic agonists may be effective.

Analgesics may prevent altitude headache. Prophylactic use of dexamethasone is not recommended.