Altitude Sickness

The disease is related to the following processes:  Radiation and has an incidence of about  0 / 100.000.

Overview

Altitude sickness is a group of disorders resulting from exposure to high altitudes, usually those over 2500 meters/8200 feet [1] [2]. This group of disorders, in increasing severity, include: high-altitude headache, acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema [2]. The exact pathophysiology of altitude sickness is unclear [4], but the symptoms are caused by increased intracranial pressure and pulmonary edema resulting from high-altitude hypoxia [4].

The initial and most common symptom in all forms of the disorder is a headache that develops within several hours of reaching high altitude [1] [3] [4] [5]. The symptoms are usually self-limited and resolve with the return to normal altitudes. However, the more severe forms of cerebral and pulmonary edema may be life-threatening [2].

Rapid ascents of individuals not acclimatized to altitudes above 2500 meters increase the risk of developing altitude symptoms [2] [5] [6]. The effects of high altitude exposure can be prevented by adequate preparation, slow ascent and frequent rest periods to acclimatize properly, and possible pretreatment with prophylactic medications [2] [5].    

Etiology

All of the various forms of altitude sickness are the result of mild to severe cerebral and pulmonary edema due to high-altitude hypoxia [2] [6]. Altitude sickness symptoms are graded using the Lake Louise Scoring System [6]. The degree of illness depends on the rate of ascent, home altitude, individual susceptibility and other risk factors [5] [7]. Other factors such as low fluid intake and dehydration or overhydration, decreased diuresis, and fluid retention may also increase the risk of altitude sickness [5]. The risk of developing the more severe forms depends on a number of individual and environmental factors.

They are rated as [2] [8]:

Low risk

  • No prior history of altitude sickness
  • Two or more days ascend to 2500 meters
  • Increase sleeping elevation of less than 500 meters per day
  • Resting 1 day every 1000 meters

Moderate risk

  • History of acute mountain sickness,
  • Ascend to 2500–2800 meters in one day
  • More than 500 meters sleeping elevation per day, but with a day for rest every 1000 meters

High risk

  • History of acute mountain sickness
  • Ascending to more than 2800 meters in one day
  • History of high-altitude pulmonary edema or cerebral edema
  • Ascent to more than 3500 meters
  • More than 500 meters increase in sleeping elevation per day
  • No extra days for acclimatization and rest
  • Very rapid ascents

Individuals with preexisting medical conditions may be at higher risk of developing altitude sickness or decompensation of their underlying disease due to physiologic changes of altitude [9].
Altitude sickness and its complications can be prevented with proper preparation, appropriate climbing techniques, prophylaxis, and early identification and treatment.

Epidemiology

The susceptibility to altitude sickness varies from individual to individual. Some individuals seem to have a resistance to the effects of altitude that is thought to be related to their anti-inflammatory and/or anti-permeability responses [3].

Altitude sickness in some form affects 55% to 85% of individuals ascending to altitudes above 2500 meters [7]. The mild forms occur in over half of all climbers, the more severe forms are rare [2]. Sleep disturbances and/or high-altitude headache are experienced by 60% to 80% of individuals at high altitudes [8]. Studies have shown the prevalence of high-altitude cerebral edema at 0.28 to 1.0% and high-altitude pulmonary edema to be 0.2 to 0.49% [12]. High-altitude cerebral edema does not usually occur below 3,000 meters [8].

The incidence is not affected by gender, race, or ethnicity. Older individuals and children may be at higher risk [8]. Individuals with underlying respiratory or cardiovascular conditions are at higher risk of more severe forms of altitude sickness or exacerbation of their chronic illnesses [8] [9].

Sex distribution
Age distribution

Pathophysiology

The exact pathophysiology of altitude sickness is not fully understood, but hypobaric hypoxia plays a prime role [2] [3] [7]. Acute hypoxia, physical activity, dehydration, and cold cause activation of the sympathetic nervous system at high altitudes [2] [8]. This results in vasoconstriction and an increase in heart rate, blood pressure, and cardiac output. The increased cardiac workload and oxygen demand places increased stress upon the cardiovascular system [9].

These factors also affect the blood brain barrier and intracranial hemodynamics [2] [3] [4]. They alter the permeability of the cerebral vasculature and lead to the development of cerebral edema, increased intracranial pressure, and the symptoms of altitude sickness [3] [8] [9]. The blood brain barrier regulates the passage of fluid, proteins, and electrolytes between the blood and cerebral tissue [3]. Increased blood brain barrier permeability may also be due to the loss of autoregulation, increased capillary pressure, ischemia, and neurogenic influences [4].

Symptoms of altitude sickness are correlated with arterial oxygen tensions [10]. Barometric pressure decreases with increased altitude [8]. Although the percentage of oxygen in the atmosphere is constant (21%), at high altitude barometric pressure decreases and with it the partial pressure of oxygen [2] [8] [10]. There is a drop in alveolar oxygen pressure in the lungs, a drop in arterial oxygen pressure in the blood, and decreased arterial oxygen saturation [8]. Therefore, the amount of oxygen available to the body decreases, resulting in hypobaric hypoxia and reduced oxygen delivery to the tissues [2] [8]. This is responsible for altitude-related symptoms [2] [8].

In up to about 5800 meters of altitude the body adjusts to the decreased oxygen availability by changes which include tachycardia and hyperventilation, and increased hemoglobin concentration [2]. At medium altitudes (approximately 3500 meters) most people will acclimatize over two to four days. This allows these changes to occur gradually. This is the most important means of preventing altitude sickness [2] [8].

Prognosis

Altitude sickness, in all its forms, is generally a self-limited condition that resolves in hours or days once normal altitude is regained. Progression to the more severe forms of the disorder is dependent upon the rate of ascent, sleep elevation, scheduled periods of rest, time for acclimatization, and the individual’s personal tolerance to hypobaric hypoxia [2] [8] [9].

Untreated high-altitude cerebral edema and pulmonary edema can progress rapidly to coma and death [2]. Death in individuals with severe cerebral edema occurs from brain herniation [4].

Hyperviscosity secondary to polycythemia, dehydration, and cold exposure experienced at high altitude may increase the risk of stroke. Ischemic stroke and cerebral artery thrombosis are potential complications of high altitude cerebral edema [9].

Preexisting pulmonary diseases or history of migraines may indicate a predisposition for high-altitude sickness [8]. Elevated levels of carboxyhemoglobin due to smoking decreases the oxygen-carrying capacity of the blood and tolerance to increases in altitude [9].

Presentation

Altitude sickness is a self-limiting syndrome characterized by non-specific symptoms such as [5]:

  • Headache
  • Dizziness
  • Nausea
  • Vomiting
  • Loss of appetite
  • Fatigue
  • Insomnia

Symptoms typically appear 6 to 12 hours after arrival at high altitudes [5].

Complications associated with altitude exposure include [9]:

  • Profound hypoxemia
  • Pulmonary hypertension
  • Dysfunctional ventilator control
  • Impaired respiratory muscle function
  • Sleep-disordered breathing

High-altitude headache is the initial symptom and occurs in almost all individuals at high altitudes (above 2500 meters) [2] [9]. This is a mild to moderate dull headache that improves with simple analgesia and hydration, and resolves entirely on descent [2].
If the headache does not improve or is associated with other symptoms, the individual may be suffering from acute mountain sickness [2]. Acute mountain sickness typically causes headache and malaise within 6 to 12 hours of reaching altitude [2]. It is a syndrome of non-specific symptoms that can occur at altitudes above 2500 meters. The primary symptoms are [2] [7]:

  • Headache
  • Gastrointestinal upset
  • Anorexia
  • Fatigue
  • Sleep disturbance

Acute altitude sickness may progress to high-altitude cerebral edema or high-altitude pulmonary edema [7]. High-altitude cerebral edema is suspected with the development of changes in mental status, ataxia or other neurological abnormalities. This is a life-threatening condition [2] [7] which may, though rarely, progress to coma and death in some individuals if not treated [7].

High-altitude pulmonary edema, though uncommon, is the leading cause of death from altitude sickness. It results from changes in pulmonary vascular permeability and pulmonary arterial pressures related to altitude [2]. It can take slightly longer (two to four days) to develop [2]. The first symptoms of pulmonary edema are usually a dry cough and decreased activity tolerance. It may then progress to a productive cough, dyspnea, and frothy sputum, sometimes blood tinged [2] [7]. Symptoms may also include tachycardia, tachypnea and signs of right heart failure [2]. Untreated, pulmonary edema can progress rapidly, to hypoxemia and death [7].

Workup

There are no tests specific to the diagnosis of altitude sickness. Symptoms of the disorder are not specific to this syndrome, but are seen in many other diagnoses. Exclusion other diagnoses such as hypothermia, hypoglycemia or alcohol intoxication should be done first [2]. History of exposure to high altitudes is necessary for a diagnosis of altitude sickness.

The diagnosis and classification is made clinically using the Lake Louise scoring system [2].

Laboratory studies should include:

  • Complete blood count that may show polycythemia secondary to hypoxia
  • Plasma arterial oxygen levels are decreased

Imaging studies

  • Brain imaging studies may show evidence of cerebral edema in moderate to severe altitude sickness [3]. 
  • Magnetic resonance imaging studies in individuals with altitude sickness suggest a vasogenic mechanism in the disorder [4].
  • Chest X-ray for evidence of pulmonary edema.

Treatment

The main treatment of all altitude sicknesses is early identification and immediate descent to a lower altitude as soon as possible [2]. If symptoms fail to improve, medical management with pharmacologic agents, supplemental oxygen, rest, and possible treatment with a hypobaric chamber may be necessary. Drug therapy is only part of the treatment needed for problems related to high altitude [11].

Mild forms of altitude sickness, high-altitude headache and acute mountain sickness, often respond to stopping the ascent, rest and rehydration [7]. High-altitude headache may also benefit from the addition of mild non-steroidal anti-inflammatories (ibuprofen, naproxen, and aspirin) or acetaminophen [8].

Initial treatment for acute mountain sickness involves stopping further ascent, rest, and rehydration [2]. The individual may stay at altitude, rest, take antiemetics and/or analgesics, and maintain fluid intake until symptoms subside [8] [12]. If symptoms persist or worsen, descent is recommended.

For severe acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema treatment should include [8]:

  • Oxygen (4–6 L/min)
  • Immediate descent
  • Non-pharmacologic measures to increase oxygenation: Pursed lip breathing, application of positive airway pressure by a helmet or facemask
  • Drug therapy should be started [10]: Acetazolamide 250mg twice daily or dexamethasone 4mg every six hours 
  • Portable hyperbaric chamber should be considered [10]

Carbonic anhydrase inhibitors, like acetazolamide, can be used in the management of more severe cases [11]. Acetazolamide works by causing metabolic acidosis through increased renal bicarbonate losses. This increases respiratory drive and arterial oxygen tension [10]. Slow-release acetazolamide (500 mg daily) resulted in fewer symptoms of altitude sickness and better overall performance [10]. It is generally well tolerated [2].

Dexamethasone, a glucocorticoid, is a first line treatment for altitude sickness and cerebral edema. Dexamethasone improves cerebral hemodynamic, as well as protecting neurons and having diuretic effects [3] [8]. Suggested dosage is 2 - 4 mg of dexamethasone orally every 6 h, starting 1 hour before beginning ascent [12]. Symptoms may recur with abrupt discontinuation of the drug [8] [12]. The drug should not be used for longer than ten days to prevent suppression of endogenous glucocorticoid production [2].

Other medications that may be useful in the treatment of the more severe forms of altitude sickness include calcium channel blockers (nifedipine) and phosphodiesterase type 5 inhibitors (tadalafil) [11]. These drugs reduce pulmonary hypertension and can help prevent high-altitude pulmonary edema [8].

Both acetazolamide (125mg a night) and temazepam (10mg a night) can reduce sleep disorders [8]. They appear to act by increasing stimulation of the respiratory drive and therefore improve sleep-disordered breathing [8].

Pretreatment is recommended for anyone at moderate or higher risk of altitude sickness [2]. Pretreatment with acetazolamide or dexamethasone may reduce the symptoms by increasing serum levels of the biochemicals with anti-inflammatory and anti-permeability properties [3] [1].

Patients with stable coronary and pulmonary disease may travel to high altitudes but are at risk of exacerbation of these illnesses. Medical management and pretreatment are recommended for these patients [6].

Prevention

Slow ascent is the most important means of preventing altitude sickness [7]. The key to prevention of all forms is proper preparation for the climb, allowing time for a slow ascent, adequate acclimatization, and immediate decent if necessary [2].
Safe acclimatization at altitudes above 2,500 meters involves [2] [8]:

  • Increases of sleeping altitude of less than 300 to 500 meters per day
  • Resting for a day every 1,000 meters altitude gain
  • When early symptoms become more severe immediate descent is necessary [11]

Acetazolamide or dexamethasone may be used for prophylaxis or treatment of the early symptoms of altitude sickness [7]. Studies have shown that prophylaxis with acetazolamide decreases the severity of the symptoms and may reduce its incidence [6].

Patient Information

What is Altitude Sickness?

Altitude sickness refers to a group of disorders that occur due to the exposure to of individuals to altitudes above 2500 meters (8200 feet). This group includes illnesses of varying severity from simple high-altitude headache and acute mountain sickness to the more severe, potentially life-threatening high-altitude pulmonary edema and high-altitude cerebral edema. The cause of all of these conditions is the body’s response to the decreased oxygen availability at low barometric pressure and the subsequent hypobaric hypoxia (low blood oxygen level).

What are the symptoms?

The most common symptom is a high-altitude headache which occurs in almost 80% of individuals. Other symptoms are non-specific to this disorder and include:

  • Increased respiratory rate
  • Increased heart rate
  • Decreased exercise tolerance
  • Malaise
  • Decreased appetite
  • Sleep disturbances
  • Dizziness

More severe forms of the disorder have more serious symptoms. These conditions and their symptoms include: 

High-altitude pulmonary edema

  • Dry cough initially
  • Shortness of breath with or without exertion
  • Frothy, often blood tinged sputum

High-altitude cerebral edema

  • Severe headache
  • Disequilibrium
  • Mental confusion
  • Eventual coma and death

What causes altitude sickness?

Altitude sickness is caused by the body’s response to decreased circulating oxygen available to the tissues. This hypoxia, especially in the brain, causes leakage of fluid into the tissue causing swelling, edema. Edema in the brain causes headache and the other symptoms of altitude sickness. Edema of the respiratory system causes the pneumonia like symptoms and increases the work effort of the heart.

Who gets altitude sickness?

Anyone traveling to or moving to altitudes above 2500 meters may experience altitude sickness. Some individuals are more susceptible than others. Those who have had altitude sickness before, are subject to migraines, or have underlying respiratory diseases are at higher risk of developing altitude sickness.

How is it diagnosed?

There are no specific tests for altitude sickness. It is diagnosed by its symptoms and ascent to high altitudes. Lab tests may show a decreased in blood oxygen and an increase in red blood cells.
Magnetic resonance imaging (MRI) may show indications of cerebral edema.

How is altitude sickness treated?

High-altitude headache, if not accompanied by any other symptoms may be treated with non-steroidal anti-inflammatories (ibuprofen, naproxen, aspirin) or mild analgesics (acetaminophen).
For more severe forms immediate descent to lower elevations is the first and most important treatment. Medications (acetazolamide or dexamethasone) to reduce swelling and the effects of hypoxia are also needed. Supplemental oxygen, decreased activity, rest, and adequate fluids are also of use.

What are the complications?

The complications of altitude sickness include cerebral edema and pulmonary edema. Bothe of these can be life-threatening.
Worsening of any underlying respiratory or cardiovascular condition may also occur with altitude sickness.

How can it be prevented?

Altitude sickness can be prevented by adequate preparation for the ascent to high altitudes, slow ascents, time to acclimatize to increases in elevation, at least 1 day of rest for every 1,000 meters of ascent. Prophylaxis with acetazolamide or dexamethasone, beginning prior to ascent and continuing until after descent, may prevent the incidence of altitude sickness. Those at higher risk should consider this precaution.

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References

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  2. Dick AG. Altitude-related illness and men’s health. Trends In Urology & Men’s Health. July/August, 2012: 27-30.
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  8. Netzer N, Strohl K, Faulhaber M, Gatterer H, Burtscher M. Hypoxia-Related Altitude Illnesses. Journal of Travel Medicine. 2013; 20 (4): 247–255.
  9. Mieske K, Flaherty G, O’Brien T. Journeys to High Altitude—Risks and Recommendations for Travelers with Preexisting Medical Conditions. Journal of Travel Medicine. 2010;17 (1): 48–62.
  10. Birmingham Medical Research Expeditionary Society Mountain Sickness Study Group. Acetazolamide in control of acute mountain sickness. Lancet. 1981;1(8213):180-3.
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  12. Wright A, Brearey S, Imray C. High hopes at high altitudes: pharmacotherapy for acute mountain sickness and high-altitude cerebral and pulmonary oedema. Expert Opin Pharmacother. 2008;9(1):119-27.

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