Altitude sickness

Altitude sickness, the mildest form being acute mountain sickness (AMS), is a harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptoms may include headaches, vomiting, tiredness, confusion, trouble sleeping, and dizziness. Acute mountain sickness can progress to high-altitude pulmonary edema (HAPE) with associated shortness of breath or high-altitude cerebral edema (HACE) with associated confusion. Chronic mountain sickness may occur after long-term exposure to high altitude.

Altitude sickness typically occurs only above 2500 m, though some are affected at lower altitudes. Risk factors include a prior episode of altitude sickness, a high degree of activity, and a rapid increase in elevation. Diagnosis is based on symptoms and is supported for those who have more than a minor reduction in activities. It is recommended that at high altitude any symptoms of headache, nausea, shortness of breath, or vomiting be assumed to be altitude sickness.

Sickness is prevented by gradually increasing elevation by no more than 300 m per day. Being physically fit does not decrease the risk. Generally, descent and sufficient fluid intake can treat symptoms. Mild cases may be helped by ibuprofen, acetazolamide, or dexamethasone. Severe cases may benefit from oxygen therapy and a portable hyperbaric bag may be used if descent is not possible. Treatment efforts, however, have not been well studied.

AMS occurs in about 20% of people after rapidly going to 2500 m and in 40% of people after going to 3000 m. While AMS and HACE occurs equally frequently in males and females, HAPE occurs more often in males. The earliest description of altitude sickness is attributed to a Chinese text from around 30 BCE that describes "Big Headache Mountains", possibly referring to the Karakoram Mountains around Kilik Pass.

Signs and symptoms
People have different susceptibilities to altitude sickness; for some otherwise healthy people, acute altitude sickness can begin to appear at around 2000 m above sea level, such as at many mountain ski resorts, equivalent to a pressure of 80 kPa. This is the most frequent type of altitude sickness encountered. Symptoms often manifest within ten hours of ascent and generally subside within two days, though they occasionally develop into the more serious conditions. Symptoms include headache, confusion, fatigue, stomach illness, dizziness, and sleep disturbance. Exertion may aggravate the symptoms.

Those individuals with the lowest initial partial pressure of end-tidal pCO2 (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 pCO2 and low oxygen saturation levels.

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 2400 m – a pressure of 76 kPa – combined with any one or more of the following symptoms, may indicate altitude sickness:

Severe symptoms
Symptoms that may indicate life-threatening altitude sickness include:
 * Pulmonary edema (fluid in the lungs)
 * Symptoms similar to bronchitis
 * Persistent dry cough
 * Fever
 * Shortness of breath even when resting


 * Cerebral edema (swelling of the brain)
 * Headache that does not respond to analgesics
 * Unsteady gait
 * Gradual loss of consciousness
 * Increased nausea and vomiting
 * Retinal hemorrhage

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 with 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 affected by HACE.

Cause
Altitude sickness can first occur at 1500 m, with the effects becoming severe at extreme altitudes (greater than 5500 m). Only brief trips above 6000 m 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 21000 m. 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.

High altitude illness can be classified according to the altitude: high (1500 –), very high (3500 –) and extreme (above 5500 m).

High altitude
At high altitude, 1500 to 3500 m, the onset of physiological effects of diminished inspiratory oxygen pressure (PiO2) includes decreased exercise performance and increased ventilation (lower arterial partial pressure of carbon dioxide: PCO2). While arterial oxygen transport may be only slightly impaired the arterial oxygen saturation (SaO2) generally stays above 90%. Altitude sickness is common between 2400 and 4000 m because of the large number of people who ascend rapidly to these altitudes.

Very high altitude
At very high altitude, 3500 to 5500 m, maximum SaO2 falls below 90% as the arterial PO2 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.

Extreme altitude
Above 5500 m, 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 6000 m. 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 CO2, and subsequently bicarbonate), Hb increases through haemoconcentration and erythrogenesis. Alkalosis shifts the haemoglobin dissociation constant to the left, 2,3-BPG increases to counter this. Cardiac output increases through an increase in heart rate.

The body's response to high altitude includes the following: 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.
 * ↑ Erythropoietin → ↑ hematocrit and haemoglobin
 * ↑ 2,3-BPG (allows ↑ release of O2 and a right shift on the Hb-O2 disassociation curve)
 * ↑ kidney excretion of bicarbonate (use of acetazolamide can augment for treatment)
 * Chronic hypoxic pulmonary vasoconstriction (can cause right ventricular hypertrophy)

Diagnosis
Altitude sickness is typically self-diagnosed since symptoms are consistent: nausea, vomiting, headache, and can generally be deduced from a rapid change in altitude or oxygen levels. However, some symptoms may be confused with dehydration. Some severe cases may require professional diagnosis which can be assisted with multiple different methods such as using an MRI or CT scan to check for abnormal buildup of fluids in the lung or brain.

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 may reduce 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.

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. Examples of pre-acclimation measures include remote ischaemic preconditioning, using hypobaric air breathing in order to simulate altitude, and positive end-expiratory pressure.

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 3000 m – a pressure of 70 kPa – 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 300 m per day to sleep. That is, one can climb from 3000 m (70 kPa) to 4500 m (58 kPa) in one day, but one should then descend back to 3300 m (67.5 kPa) 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 higher altitudes.

Medications
The drug acetazolamide (trade name Diamox) may help some people making a rapid ascent to sleeping altitude above 2700 m, 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.

There is insufficient evidence to determine the safety of sumatriptan and if it 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.

Over-the-counter herbal supplements and traditional medicines
Herbal supplements and traditional medicines are sometimes suggested to prevent high altitude sickness including ginkgo biloba, R crenulata, minerals such as iron, antacids, and hormonal-based supplements such as medroxyprogesterone and erythropoietin. Medical evidence to support the effectiveness and safety of these approaches is often contradictory or lacking. Indigenous peoples of the Americas, such as the Aymaras of the Altiplano, have for centuries chewed coca leaves to try to alleviate the symptoms of mild altitude sickness. This therapy has not yet been proven effective in a clinical study. In Chinese and Tibetan traditional medicine, an extract of the root tissue of Radix rhodiola is often taken in order to prevent the symptoms of high altitude sickness, however, no clear medical studies have confirmed the effectiveness or safety of this extract.

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 3400 m (67 kPa), raising the oxygen concentration level by 5% via an oxygen concentrator and an existing ventilation system provides an effective altitude of 3000 m (70 kPa), 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 use 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 4000 m. The application of high-purity oxygen from one of these methods increases the partial pressure of oxygen by raising the FiO2 (fraction of inspired oxygen).

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 3700 m 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 1500 m. 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.
 * Paracetamol (acetaminophen) has also shown to be as good as ibuprofen for altitude sickness when tested on climbers ascending Everest.