Abstract

Altitude sickness, also known as acute mountain sickness (AMS), is a negative health effect of high altitude, caused by acute exposure to low amounts of oxygen at high altitude.

Although minor symptoms such as breathlessness may occur at altitudes of , AMS commonly occurs above .

It presents as a collection of nonspecific symptoms, acquired at high altitude or in low air pressure, resembling a case of "flu, carbon monoxide poisoning, or a hangover". It is hard to determine who will be affected by altitude sickness, as there are no specific factors that correlate with a susceptibility to altitude sickness. However, most people can ascend to without difficulty.

Acute mountain sickness can progress to high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE), both of which are potentially fatal, and can only be cured by immediate descent to lower altitude or oxygen administration.

Chronic mountain sickness is a different condition that only occurs after long term exposure to high altitude.

Signs and symptoms

People have different susceptibilities to altitude sickness; for some otherwise healthy people, acute altitude sickness can begin to appear at around above sea level, such as at many mountain ski resorts, equivalent to a pressure of . This is the most frequent type of altitude sickness encountered. Symptoms often manifest themselves six to ten hours after ascent and generally subside in one to two days, but they occasionally develop into the more serious conditions. Symptoms include headache, fatigue, stomach illness, dizziness, and sleep disturbance. Exertion aggravates the symptoms.

Those individuals with the lowest initial partial pressure of end-tidal pCO (the lowest concentration of carbon dioxide at the end of the respiratory cycle, a measure of a higher alveolar ventilation) and corresponding high oxygen saturation levels tend to have a lower incidence of acute mountain sickness than those with high end-tidal pCO and low oxygen saturation levels.

Signs and symptoms | Primary symptoms

Headaches are the primary symptom used to diagnose altitude sickness, although a headache is also a symptom of dehydration. A headache occurring at an altitude above a pressure of combined with any one or more of the following symptoms, may indicate altitude sickness:

Signs and symptoms | Severe symptoms

Symptoms that may indicate life-threatening altitude sickness include:

- Pulmonary edema (fluid in the lungs)

- Cerebral edema (swelling of the brain):

The most serious symptoms of altitude sickness arise from edema (fluid accumulation in the tissues of the body). At very high altitude, humans can get either high altitude pulmonary edema (HAPE), or high altitude cerebral edema (HACE). The physiological cause of altitude-induced edema is not conclusively established. It is currently believed, however, that HACE is caused by local vasodilation of cerebral blood vessels in response to hypoxia, resulting in greater blood flow and, consequently, greater capillary pressures. On the other hand, HAPE may be due to general vasoconstriction in the pulmonary circulation (normally a response to regional ventilation-perfusion mismatches) which, with constant or increased cardiac output, also leads to increases in capillary pressures. For those suffering HACE, dexamethasone may provide temporary relief from symptoms in order to keep descending under their own power.

HAPE can progress rapidly and is often fatal. Symptoms include fatigue, severe dyspnea at rest, and cough that is initially dry but may progress to produce pink, frothy sputum. Descent to lower altitudes alleviates the symptoms of HAPE.

HACE is a life-threatening condition that can lead to coma or death. Symptoms include headache, fatigue, visual impairment, bladder dysfunction, bowel dysfunction, loss of coordination, paralysis on one side of the body, and confusion. Descent to lower altitudes may save those afflicted with HACE.

Cause

Altitude sickness can first occur at 1,500 metres, with the effects becoming severe at extreme altitudes (greater than 5,500 metres). Only brief trips above 6,000 metres are possible and supplemental oxygen is needed to avert sickness.

As altitude increases, the available amount of oxygen to sustain mental and physical alertness decreases with the overall air pressure, though the relative percentage of oxygen in air, at about 21%, remains practically unchanged up to . The RMS velocities of diatomic nitrogen and oxygen are very similar and thus no change occurs in the ratio of oxygen to nitrogen until stratospheric heights.

Dehydration due to the higher rate of water vapor lost from the lungs at higher altitudes may contribute to the symptoms of altitude sickness.

The rate of ascent, altitude attained, amount of physical activity at high altitude, as well as individual susceptibility, are contributing factors to the onset and severity of high-altitude illness.

Altitude sickness usually occurs following a rapid ascent and can usually be prevented by ascending slowly. In most of these cases, the symptoms are temporary and usually abate as altitude acclimatization occurs. However, in extreme cases, altitude sickness can be fatal.

Cause | High altitude

At high altitude, , the onset of physiological effects of diminished inspiratory oxygen pressure (PiO) includes decreased exercise performance and increased ventilation (lower arterial partial pressure of carbon dioxide- PCO). While arterial oxygen transport may be only slightly impaired the arterial oxygen saturation, SaO, generally stays above 90%. Altitude sickness is common between 2,400 and 4,000m because of the large number of people who ascend rapidly to these altitudes.

Cause | Very high altitude

At very high altitude, , maximum SaO falls below 90% as the arterial PO falls below 60mmHg. Extreme hypoxemia may occur during exercise, during sleep, and in the presence of high altitude pulmonary edema or other acute lung conditions. Severe altitude illness occurs most commonly in this range.

Cause | Extreme altitude

Above , marked hypoxemia, hypocapnia, and alkalosis are characteristic of extreme altitudes. Progressive deterioration of physiologic function eventually outstrips acclimatization. As a result, no permanent human habitation occurs above . A period of acclimatization is necessary when ascending to extreme altitude; abrupt ascent without supplemental oxygen for other than brief exposures invites severe altitude sickness.

Mechanism

The physiology of altitude sickness centres around the alveolar gas equation; the atmospheric pressure is low, but there is still 20.9% Oxygen, water vapour still occupies the same pressure too, this means that there is less oxygen pressure available in the lungs and blood. Compare these two equations comparing the amount of oxygen in blood at altitude:

The hypoxia leads to an increase in minute ventilation (hence both low CO, and subsequently bicarbonate), Hb increases through haemoconcentration and erythrogenesis. Alkylosis shifts the haemaglobin dissociation constant to the left, 2,3-DPG increases to counter this. Cardiac output increases through an increase in heart rate.

The body's response to high altitude includes the following:

- ↑ Erythropoietin → ↑ hematocrit and hemoglobin

- ↑ 2,3-BPG (allows ↑ release of O and a right shift on the Hb-O disassociation curve)

- ↑ kidney excretion of bicarbonate (use of acetazolamide can augment for treatment)

- Chronic hypoxic pulmonary vasoconstriction (can cause right ventricular hypertrophy)

People with high-altitude sickness generally have reduced hyperventilator response, impaired gas exchange, fluid retention or increased sympathetic drive. There is thought to be an increase in cerebral venous volume because of an increase in cerebral blood flow and hypocapnic cerebral vasoconstriction causing oedema.

Diagnosis

Diagnosis can be assisted with a number of different scoring systems.

Prevention

Ascending slowly is the best way to avoid altitude sickness. Avoiding strenuous activity such as skiing, hiking, etc. in the first 24 hours at high altitude reduces the symptoms of AMS. Alcohol and sleeping pills are respiratory depressants, and thus slow down the acclimatization process and should be avoided. Alcohol also tends to cause dehydration and exacerbates AMS. Thus, avoiding alcohol consumption in the first 24–48 hours at a higher altitude is optimal.

Prevention | Pre-acclimatization

Pre-acclimatization is when the body develops tolerance to low oxygen concentrations before ascending to an altitude. It significantly reduces risk because less time has to be spent at altitude to acclimatize in the traditional way. Additionally, because less time has to be spent on the mountain, less food and supplies have to be taken up. Several commercial systems exist that use altitude tents, so called because they mimic altitude by reducing the percentage of oxygen in the air while keeping air pressure constant to the surroundings.

Prevention | Altitude acclimatization

Altitude acclimatization is the process of adjusting to decreasing oxygen levels at higher elevations, in order to avoid altitude sickness. Once above approximately a pressure of most climbers and high-altitude trekkers take the "climb-high, sleep-low" approach. For high-altitude climbers, a typical acclimatization regimen might be to stay a few days at a base camp, climb up to a higher camp (slowly), and then return to base camp. A subsequent climb to the higher camp then includes an overnight stay. This process is then repeated a few times, each time extending the time spent at higher altitudes to let the body adjust to the oxygen level there, a process that involves the production of additional red blood cells. Once the climber has acclimatized to a given altitude, the process is repeated with camps placed at progressively higher elevations. The rule of thumb is to ascend no more than per day to sleep. That is, one can climb from () to () in one day, but one should then descend back to () to sleep. This process cannot safely be rushed, and this is why climbers need to spend days (or even weeks at times) acclimatizing before attempting to climb a high peak. Simulated altitude equipment such as altitude tents provide hypoxic (reduced oxygen) air, and are designed to allow partial pre-acclimation to high altitude, reducing the total time required on the mountain itself.

Altitude acclimatization is necessary for some people who move rapidly from lower altitudes to intermediate altitudes (e.g., by aircraft and ground transportation over a few hours), such as from sea level to as in many Colorado, USA mountain resorts. Stopping at an intermediate altitude overnight (for example, staying overnight when arriving through Denver, at , when traveling to the aforementioned Colorado resorts) can alleviate or eliminate occurrences of AMS.

Prevention | Medications

The drug acetazolamide (trade name Diamox) may help some people making a rapid ascent to sleeping altitude above , and it may also be effective if started early in the course of AMS. Acetazolamide can be taken before symptoms appear as a preventive measure at a dose of 125 mg twice daily. The Everest Base Camp Medical Centre cautions against its routine use as a substitute for a reasonable ascent schedule, except where rapid ascent is forced by flying into high altitude locations or due to terrain considerations. The Centre suggests a dosage of 125 mg twice daily for prophylaxis, starting from 24 hours before ascending until a few days at the highest altitude or on descending; with 250 mg twice daily recommended for treatment of AMS. The Centers for Disease Control and Prevention (CDC) suggest the same dose for prevention of 125 mg acetazolamide every 12 hours. Acetazolamide, a mild diuretic, works by stimulating the kidneys to secrete more bicarbonate in the urine, thereby acidifying the blood. This change in pH stimulates the respiratory center to increase the depth and frequency of respiration, thus speeding the natural acclimatization process. An undesirable side-effect of acetazolamide is a reduction in aerobic endurance performance. Other minor side effects include a tingle-sensation in hands and feet. Although a sulfonamide; acetazolamide is a non-antibiotic and has not been shown to cause life-threatening allergic cross-reactivity in those with a self-reported sulfonamide allergy. Dosage of 1000 mg/day will produce a 25% decrease in performance, on top of the reduction due to high-altitude exposure. The CDC advises that Dexamethasone be reserved for treatment of severe AMS and HACE during descents, and notes that Nifedipine may prevent HAPE.

A single randomized controlled trial found that sumatriptan may help prevent altitude sickness. Despite their popularity, antioxidant treatments have not been found to be effective medications for prevention of AMS. Interest in phosphodiesterase inhibitors such as sildenafil has been limited by the possibility that these drugs might worsen the headache of mountain sickness. A promising possible preventive for altitude sickness is myo-inositol trispyrophosphate (ITPP), which increases the amount of oxygen released by hemoglobin.

Prior to the onset of altitude sickness, ibuprofen is a suggested non-steroidal anti-inflammatory and painkiller that can help alleviate both the headache and nausea associated with AMS. It has not been studied for the prevention of cerebral edema (swelling of the brain) associated with extreme symptoms of AMS.

For centuries, indigenous peoples of the Americas such as the Aymaras of the Altiplano, have chewed coca leaves to try to alleviate the symptoms of mild altitude sickness. In Chinese and Tibetan traditional medicine, an extract of the root tissue of "Radix rhodiola" is often taken in order to prevent the same symptoms, though neither of these therapies has been proven effective in clinical study.

Prevention | Oxygen enrichment

In high-altitude conditions, oxygen enrichment can counteract the hypoxia related effects of altitude sickness. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At (), raising the oxygen concentration level by 5% via an oxygen concentrator and an existing ventilation system provides an effective altitude of (), which is more tolerable for those unaccustomed to high altitudes.

Oxygen from gas bottles or liquid containers can be applied directly via a nasal cannula or mask. Oxygen concentrators based upon pressure swing adsorption (PSA), VSA, or vacuum-pressure swing adsorption (VPSA) can be used to generate the oxygen if electricity is available. Stationary oxygen concentrators typically use PSA technology, which has performance degradations at the lower barometric pressures at high altitudes. One way to compensate for the performance degradation is to utilize a concentrator with more flow capacity. There are also portable oxygen concentrators that can be used on vehicular DC power or on internal batteries, and at least one system commercially available measures and compensates for the altitude effect on its performance up to . The application of high-purity oxygen from one of these methods increases the partial pressure of oxygen by raising the FiO (fraction of inspired oxygen).

Prevention | Other methods

Increased water intake may also help in acclimatization to replace the fluids lost through heavier breathing in the thin, dry air found at altitude, although consuming excessive quantities ("over-hydration") has no benefits and may cause dangerous hyponatremia.

Treatment

The only reliable treatment, and in many cases the only option available, is to descend. Attempts to treat or stabilize the patient "in situ" (at altitude) are dangerous unless highly controlled and with good medical facilities. However, the following treatments have been used when the patient's location and circumstances permit:

- Oxygen may be used for mild to moderate AMS below and is commonly provided by physicians at mountain resorts. Symptoms abate in 12 to 36 hours without the need to descend.

- For more serious cases of AMS, or where rapid descent is impractical, a Gamow bag, a portable plastic hyperbaric chamber inflated with a foot pump, can be used to reduce the effective altitude by as much as . A Gamow bag is generally used only as an aid to evacuate severe AMS patients, not to treat them at altitude.

- Acetazolamide 250 mg twice daily dosing assists in AMS treatment by quickening altitude acclimatization. A study by the Denali Medical Research Project concluded: "In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange."

- The folk remedy for altitude sickness in Ecuador, Peru and Bolivia is a tea made from the coca plant. See mate de coca.

- Steroids can be used to treat the symptoms of pulmonary or cerebral edema, but do not treat the underlying AMS.

- Two studies in 2012 showed that Ibuprofen 600 milligrams three times daily was effective at decreasing the severity and incidence of AMS; it was not clear if HAPE or HACE was affected.