What is altitude sickness

Altitude sickness also called acute mountain sickness or altitude illness, can occur when you travel to a high altitude too quickly. Altitude sickness (acute mountain sickness) is caused by your body’s reaction to the reduced oxygen level in the air at altitudes above about 2,500 meters (8202 ft) and resultant tissue hypoxia ¹. However, a susceptible individual may develop acute mountain sickness at intermediate altitude such as 2,100 meters (6889 ft) ². Altitude sickness occurs when your body has not had time to adjust to less oxygen. Although the proportion of oxygen remains unchanged at 20.93%, increases in altitude result in a lower partial pressure of oxygen in the inspired air (PIO₂) ³. This reduction in the driving pressure of oxygen along the oxygen cascade from the lungs to the tissues can compromise the supply of oxygen to the tissues ³, especially the cardiovascular and pulmonary systems ⁴. The physiological responses to hypoxia and acclimatization related to high altitude sickness include hyperventilation (increased depth and rate of breathing); elevation of systemic blood pressure; and tachycardia (elevations of heart rate) ⁵. However, in many instances these physiological changes may be inadequate, so that the ascent to high altitude and the attendant hypoxia are complicated by altitude‐associated medical illness ⁶, which is also known as high altitude illness.

High altitude is arbitrarily classified as high (1500 to 3500 meters), very high (3500 to 5500 meters), and extreme (above 5500 meters) ⁷. Because of the large number of people who ascend rapidly to between 2500 m (8202 ft) and 3500 m (11,482 ft), high altitude sickness is common in this height range as a result of hypoxia ². At baseline metabolic levels, the brain is the most sensitive organ to hypoxia and oxygen stress. Therefore, the symptoms of altitude sickness (acute mountain sickness) are mediated by the central nervous system (CNS). In many travelers at altitude, respirations during sleep develop a periodic pattern that may contribute to the development of altitude sickness symptoms ⁸.

The incidence of altitude sickness increases with increasing altitude. Up to half of people who ascend to heights above 2500 meters (8202 ft) may develop acute mountain sickness, pulmonary edema (high altitude pulmonary edema [HAPE]) or cerebral edema (high altitude cerebral edema [HACE]), with the risk being greater at higher altitudes, and with faster rates of ascent ⁹. While altitude sickness (acute mountain sickness) is very uncommon under 2500 meters (8202 ft), the percentage of non-acclimated travelers affected at 3000 meter approaches 75%. It has been estimated that 84% of people who fly directly to 3860 m (12,664 ft) are affected by altitude sickness ¹⁰. The risk of high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE) is much lower than for acute mountain sickness, with estimates in the range of 0.1% to 4.0% ¹¹. The rate of ascent, altitude reached (especially the sleeping altitude), and individual susceptibility has been proposed as the most important risk factors for the development of altitude sickness conditions ¹². Other presumptive risk factors are a history of altitude sickness (acute mountain sickness) and permanent residence lower than 900 m (2952 ft), exertion in children and adults ¹¹, obesity ¹³ and coronary heart disease ¹⁴. It is advisable that those with asthma make sure that their condition is well controlled before they undertake exertion at altitude ¹⁵. Any travelers with prior episodes of altitude sickness are at greater risk than those who have tolerated similar trips in the past ¹⁶.

Altitude sickness can affect anybody – being young or physically fit does not decrease your risk of getting altitude sickness. And just because you haven’t had it before doesn’t mean you won’t develop it on another trip.

If you have a medical problem that affects your lungs, heart or circulation, you are at increased risk of getting altitude sickness. The most common conditions in this category include anemia, with a reduced oxygen-carrying capacity of the blood, and chronic obstructive pulmonary disease (COPD), due to the reduced degree of oxygenation occurring in the lungs.

Whether or not you get altitude sickness could depend on:

• your height above sea level
• the time you took to make the ascent
• whether or not you have any problems affecting you heart and lungs

If you have signs of altitude sickness affecting your lungs or your brain, this is a medical emergency. You need help to descend as soon as possible. Breathing oxygen from a tank can help. Altitude sickness can be fatal if not treated.

What is high altitude?

High altitude is arbitrarily classified as ⁷:

• High altitude (1500 to 3500 m)
  • The onset of physiologic effects of diminished inspiratory oxygen pressure (PIO₂) includes decreased exercise performance and increased ventilation (lowering of arterial partial pressure of carbon dioxide [PaCO₂]).
  • Minor impairment exists in arterial oxygen transport (arterial oxygen saturation [SaO₂] at least 90%, but arterial PO₂ (partial pressure of oxygen) which reflects the amount of oxygen gas dissolved in the blood is significantly diminished).
  • Because of the large number of people who ascend rapidly to 2500 to 3500 m, high-altitude illness is common in this range.
• Very high altitude (3500 to 5500 m)
  • Maximum arterial oxygen saturation (SaO₂) falls below 90% as the arterial PO₂ (partial pressure of oxygen) falls below 60 mm Hg.
  • Extreme hypoxemia may occur during exercise, during sleep and in the presence of high-altitude pulmonary edema (HAPE) or other acute lung conditions.
  • Severe altitude illness commonly occurs in this range.
• Extreme altitude (above 5500 m)
  • Marked hypoxemia, hypocapnia and alkalosis are characteristic of extreme altitudes.
  • Progressive impairment of physiologic function eventually outstrips acclimatization. As a result, no human habitation occurs above 5500 m ¹⁸

Where does altitude sickness happen?

Most people remain well at altitudes of up to 2,500m (8202 ft), the equivalent barometric pressure to which airplane cabins are pressurized. However, even at around 1500m above sea level you may notice more breathlessness than normal on exercise and night vision may be impaired. Above 2,500m (8202 ft), the symptoms of altitude sickness become more noticeable.

Can I take drugs to prevent altitude sickness?

As with everything, many ‘quack’ treatments and untested herbal remedies are claimed to prevent mountain sickness. These treatments can make altitude sickness worse or have other dangerous side effects – many herbs are poisonous. Only one drug is currently known to prevent altitude sickness and to be safe for this purpose: acetazolamide (Diamox). It causes some minor side effects, such as tingling fingers and a funny taste in the mouth.

Who gets altitude sickness?

Anyone who travels to altitudes of over 2500m (8202 ft) is at risk of acute mountain sickness. Normally it doesn’t become noticeable until you have been at that altitude for a few hours. Part of the mystery of acute mountain sickness is that it is difficult to predict who will be affected. There are many stories of fit and healthy people being badly limited by symptoms of acute mountain sickness, while their older companions have felt fine.

There are a number of factors that are linked to a higher risk of developing altitude sickness. The higher the altitude you reach and the faster your rate of ascent, the more likely you are to get acute mountain sickness. On the Apex high altitude research expeditions, flying from sea level to the Bolivian capital, La Paz (3600m), caused over half of the expedition members to have acute mountain sickness on the day after they arrived. If you have a previous history of suffering from acute mountain sickness, then you are probably more likely to get it again. Older people tend to get less acute mountain sickness – but this could be because they have more common sense and ascend less quickly.

Figure 1. Gamow bag (Portable Hyperbaric Chamber) for treating altitude sickness

Footnote: Gamow bag simulates descent and gives symptomatic improvement within a few hours as a temporary measure while awaiting descent ¹⁵.

Altitude sickness causes

Two things are certain to make altitude sickness very likely – ascending faster than 500m (1640 ft) per day, and exercising vigorously. Physically fit individuals are not protected – even Olympic athletes get altitude sickness. Altitude sickness happens because there is less oxygen in the air that you breathe at high altitudes, but how this shortage of oxygen actually leads to altitude sickness is still not fully understood.

Some scientists believe that altitude sickness is due to swelling of the brain but the evidence for this hypothesis is not conclusive. The theory is that in susceptible individuals, brain swelling could cause a small increase in the pressure inside the skull and lead to symptoms of acute mountain sickness. The swelling may be due to increased blood flow to the brain or leakiness of blood vessels in the brain.

Altitude sickness signs and symptoms

The hallmark of altitude sickness (acute mountain sickness) is a headache, with other symptoms including nausea, vomiting, loss of appetite, fatigue/malaise (particularly at rest), sleep disturbance, and dizziness/lightheadedness ¹⁶. Altitude sickness can feel like a bad hangover. Altitude sickness (acute mountain sickness) symptoms can begin after only a few hours and typically present the first day at a given altitude, resolving after one to three days, even without treatment, as the body adjusts physiologically (acclimates) to the lower oxygen levels.

The presence of facial or extremity edema can be present with or without altitude sickness symptoms and is felt to be a marker for not yet being acclimated to the altitude. Rarely, retinal hemorrhages can occur and affect visual fields.

Altitude sickness symptoms are similar to those of a bad hangover. They include:

• headache
• nausea and vomiting
• dizziness
• tiredness
• loss of appetite
• shortness of breath

The symptoms are usually worse at night.

Altitude sickness can affect your lungs, in which case it is sometimes known as high altitude pulmonary edema or HAPE. People with HAPE (high altitude pulmonary edema) can feel short of breath and have a cough and a racing heart. In extreme cases, their lips turn blue.

Altitude sickness can also cause your brain to swell with fluid, which is sometimes known as high altitude cerebral edema or HACE. People with HACE (high altitude cerebral edema) can feel confused and irritable and behave in an erratic way.

Altitude sickness can be worse at night and can last for days, even if you stay at the same altitude.

3 forms of altitude sickness

Lake Louis Consensus definitions of high altitude sickness ¹⁹:

Acute mountain sickness (high altitude sickness)

• In the setting of a recent gain in altitude, there is presence of headache and at least one of the following:
• Gastrointestinal (anorexia, nausea or vomiting)
• Fatigue or weakness
• Dizziness or lightheadedness
• Difficulty sleeping

High-altitude pulmonary edema (HAPE)

In the presence of a recent gain in altitude, the presence of the following:

• At least two of the following symptoms:
  • Shortness of breath at rest
  • Cough
  • Weakness or decreased exercise performance
  • Chest tightness or congestion
• At least two of the following signs:
  • Crackles or wheezing in at least one lung field
  • Central cyanosis
  • Fast breathing (tachypnea)
  • Fast heart rate (tachycardia)

High-altitude cerebral edema (HACE)

Can be considered “end stage” or severe high altitude sickness. In the setting of a recent gain in altitude, there is either:

• the presence of a change in mental status and/ or impaired balance or coordination (ataxia) in a person with high altitude sickness
• or the presence of both mental status changes and impaired balance or coordination (ataxia) in a person without high altitude sickness.

Acute mountain sickness

Mild altitude sickness is called acute mountain sickness or altitude sickness and is quite similar to a hangover – it causes headache, nausea, and fatigue. This is very common: some people are only slightly affected, others feel awful. However, if you have acute mountain sickness, you should take this as a warning sign that you are at risk of the serious forms of altitude sickness: HAPE (high altitude pulmonary edema) and HACE (high altitude cerebral edema). Both HAPE (high altitude pulmonary edema) and HACE (high altitude cerebral edema) can be fatal within hours and  require immediate treatment with prompt descent to lower altitude (or artificial high pressure environment).

High altitude pulmonary edema (HAPE)

HAPE (high altitude pulmonary edema) is excess fluid on the lungs, and causes breathlessness, which typically occurs at altitudes above 3000 m (9842 ft), affecting previously healthy individuals who ascend rapidly from sea level. It is never normal to feel breathless when you are resting – even on the summit of Everest. HAPE usually occurs within the first 2 to 4 days of ascent to higher altitudes, most commonly on the second night. HAPE begins with a subtle nonproductive cough and shortness of breath, both at rest and especially with attempts to exercise modestly. It progresses to a debilitating degree of shortness of breath (dyspnea), even at rest, and cough productive of pink, frothy sputum. This should be taken as a sign that you have HAPE (high altitude pulmonary edema) and may die soon. Tachypnea (rapid breathing) and tachycardia (fast heart rate) are present; pulse oximetry reveals marked hypoxemia. Imaging of the thorax reveals patchy opacities with inconsistent predominance of location, but often infiltrates are seen initially in the region of the right middle lobe ²⁰. HAPE can also cause a fever (a high temperature). HAPE and HACE often occur together.

Immediate descent, of up to 500 to 1000 m (1640 to 3280ft) is required. Oxygen, if available, should be administered immediately. Oxygen increases arterial oxygenation and reduces pulmonary artery pressure, heart rate, respiratory rate and other symptoms.

Drugs are of limited necessity in HAPE. The calcium channel blocker nifedipine (30 mg slow release every 12 to 24 hours or 10 mg orally repeated as necessary) gives good results. Nifedipine reduces pulmonary artery pressure and slightly improves arterial oxygenation ²¹. Glucocorticoids have also been found to be helpful in treating HAPE. They may act by blocking the leak in the capillary layer, or by increasing the activity of the basolateral Na+K+ ATPase pump ²². In addition, nitric oxide and PDE-5 inhibitors (sildenafil and tadanafil) have been tested, but further research is needed to clarify their role.

High altitude cerebral edema (HACE)

HACE (high altitude cerebral edema) is fluid on the brain. High-altitude cerebral edema (HACE) is the most common cause of death related to high altitude. HACE also occurs in 13% to 20% of individuals with HAPE and in about 50% of individuals who die from HAPE ¹³. According to the Lake Louis consensus definitions, HACE can be diagnosed if impaired balance or coordination (ataxia) occurs in a person with acute mountain sickness, or both ataxia and mental status changes occur in the absence of high altitude sickness. Mental status changes include confusion, impaired mentation, drowsiness, stupor and coma. The first signs may be uncharacteristic behavior such as laziness, excessive emotion or violence. Drowsiness and loss of consciousness occur shortly before death. Those who survive may have memory and gait deficits that persist for months ²³. Pulse oximetry in a patient with HACE reveals exaggerated hypoxemia. Radiologic findings may reveal concomitant pulmonary edema.

HACE is a medical emergency and should be treated aggressively. Immediate descent of up to at least 600 m (1968 ft) is required. In addition, oxygen should be administered (2-4 L/min), and acetazolamide should be given in the dose of 250 mg twice daily. Dexamethasone is an excellent drug to treat HACE and is more effective in higher doses (8 to 10 mg IM, IV or orally initially, and 4 mg every 6 hour). In previously healthy individuals, the side effects of dexamethasone are inconsequential, and if the drug is started at the onset of symptoms of HACE while descent is undertaken, the drug can be life saving ¹⁹.

Altitude sickness complications

If the symptoms of altitude sickness are ignored, they can lead to life-threatening conditions affecting the brain or lungs.

High altitude cerebral edema (HACE)

High altitude cerebral edema (HACE) is a build-up of fluid in the brain caused by a lack of oxygen. HACE is life-threatening and requires urgent action. It can be fatal if it’s not treated immediately.

HACE can develop quickly over a few hours and can kill in only a few hours.

Symptoms of HACE:

• headache
• weakness
• nausea and vomiting
• loss of co-ordination
• feeling confused
• hallucinations
• coma

A person with HACE often doesn’t realize they’re ill, and may insist they’re all right and want to be left alone.

A person with HACE will find it difficult to walk heel-to-toe in a straight line – this is a useful test to perform in someone with severe symptoms of acute mountain sickness. HACE should also be suspected if a companion starts to behave irrationally or bizarrely.

Who gets HACE?

About 1% of people of ascend to above 3000m get HACE. The lowest altitude at which a case of HACE has been reported was 2100m. HACE can also occur in people with HAPE and vice versa. Factors that increase the risk of HACE are similar to those for acute mountain sickness and HAPE. The faster the rate of ascent and the higher the altitude, the more likely it is that HACE will develop. HACE is thought to occur mainly in trekkers or climbers who have ignored symptoms of acute mountain sickness and climbed higher rather than staying at the same altitude or descending.

What causes HACE?

The cause of HACE remains unknown. Several factors may play a role including increased blood flow to the brain. An increase in blood flow is a normal response to low oxygen levels as the body needs to maintain a constant supply of oxygen to the brain. However, if the blood vessels in the brain are damaged, fluid may leak out and result in HACE. Although we know that reactive chemicals are released when oxygen levels are low and that these chemicals can damage blood vessel walls, it still hasn’t been proven that the blood vessels in the brain are actually more leaky.

How to prevent HACE?

Gradual ascent

The recommended method for the prevention of high-altitude illness is to allow the body time to acclimatize via gradual ascent. The Wilderness Medical Society ²⁴ recommends one day of travel for every 1,500 ft gained above 10,000 ft and a day of rest every 3 or 4 days.

Acetazolamide (125mg orally every 12 hours) is the only medication proven to assist with acclimatization to prevent acute mountain sickness and HACE. There are two adverse effects of acetazolamide worth considering. First, acetazolamide increases urination frequency and therefore increases the risk of dehydration, which is a concern during high altitude travel ²⁵. Secondly, acetazolamide has a similar molecular structure to sulfa medications and should be used cautiously in patients with sulfa allergy. Although the risk of cross-reactivity is low, travelers with sulfa allergies are recommended to undergo a trial of acetazolamide before travel ²⁶.

How is HACE treated?

Treating HACE:

• Move down to a lower altitude immediately. Immediate descent of up to at least 600 m (1968 ft) is required.
• Take dexamethasone
• Give bottled oxygen, if available

Descent is the most effective treatment of HACE and should not be delayed if HACE is suspected. A Gamow bag, or portable altitude chamber, can be used as a temporary measure and, if available, oxygen and a drug called dexamethasone should be given. Oxygen should be administered (2-4 L/min), and acetazolamide should be given in the dose of 250 mg twice daily.

Dexamethasone is the medication of choice for the treatment of both high altitude sickness and HACE. Dexamethasone is a steroid medication that reduces swelling of the brain. Dexamethasone is more effective in higher doses (8 to 10 mg IM, IV or orally initially, and 4 mg every 6 hour). In previously healthy individuals, the side effects of dexamethasone are inconsequential, and if the drug is started at the onset of symptoms of HACE while descent is undertaken, the drug can be life saving ¹⁹.

If you can’t go down immediately, dexamethasone can help relieve symptoms until it’s safe to do so.

You should go to hospital as soon as possible for follow-up treatment.

High altitude pulmonary edema (HAPE)

High altitude pulmonary edema (HAPE) is a dangerous build-up of fluid in the lungs that prevents the air spaces from opening up and filling with fresh air with each breath. When this happens, the sufferer becomes progressively more short of oxygen, which in turn worsens the build-up of fluid in the lungs. In this way, HAPE can be fatal within hours.

HAPE usually develops after 2 or 3 days at altitudes above 2500 m. Typically the sufferer will be more breathless compared to those around them, especially on exertion. Most will have symptoms of acute mountain sickness. Often, they will have a cough and this may produce white or pink frothy sputum. The breathlessness will progress and soon they will be breathless even at rest. Heart rate may be fast, the lips may turn blue and body temperature may be elevated. It is easy to confuse symptoms of HAPE with a chest infection, but at altitude HAPE must be suspected and the affected individual must be evacuated to a lower altitude.

• If you have had HAPE, please register with the International HAPE Database to help develop new treatments for the condition (http://www.altitude.org/hape.php).

Symptoms of HAPE:

• blue tinge to the skin (cyanosis)
• breathing difficulties, even when resting
• tightness in the chest
• a persistent cough, bringing up pink or white frothy liquid (sputum)
• tiredness and weakness

The symptoms of HAPE can start to appear a few days after arrival at high altitude. It can be fatal if it’s not treated immediately.

Who gets HAPE?

Unfortunately, it is currently impossible to predict who will get HAPE. This is one of the reasons why scientists have established the HAPE database (http://www.altitude.org/hape.php). People who have had HAPE before are much more likely to get it again. Therefore, there must be some factor that puts certain individuals at high risk of the condition. However, just like acute mountain sickness, there are some known risk factors. A fast rate of ascent and the altitude attained will make HAPE more likely. Vigorous exercise is also thought to make HAPE more likely and anecdotal evidence suggests that people with chest infections or symptoms of the common cold before ascent may be at higher risk.

What causes HAPE?

Despite years of careful research the exact causes of HAPE remain poorly understood. Fluid has been shown to fill up the air pockets in the lungs preventing oxygen getting into the blood and causing the vicious circle of events that can kill people with HAPE. As with many biological processes many factors play a role in the disease and there is good evidence to support a number of theories about how this fluid gets there.

Normally, oxygen gets into your blood and is supplied to the body from your lungs. Each time you take a breath in, air rushes into the tiny air pockets at the end of all the airway branches in your lungs. At the same time, blood from your heart is brought close to these thin-walled air pockets, so that oxygen can move into your blood while waste products move out. Oxygen-rich blood then returns to the heart and is supplied to the body. If, by accident, you inhaled a small object into your lungs, it would become stuck in one of the airways branches. Little oxygen would get to the downstream air pockets. To prevent this area of lung supplying blood starved of oxygen back to the heart (and therefore the rest of body), blood vessels in the area closed down or constrict. This is normally a very good thing and is an example of the body protecting itself.

At altitude however, this same process is a cause of the disease HAPE. Because the whole lung is starved of oxygen, the whole lung reacts in the same way – blood vessels constricting all over the place and not just in small areas. The blood in these vessels is squeezed and the pressure goes up forcing fluid out of blood and into air pockets.

Very dangerous and reactive substances are formed in your blood when you are starved of oxygen and these can directly damage the special membrane between air and blood in your lungs causing further fluid leak and worsening HAPE.

How to prevent HAPE?

Gradual ascent

The Wilderness Medical Society ²⁴ recommends the same ascent profile for prevention of high altitude sickness or HACE, namely: one day of travel for every 1,500 ft gained above 10,000 ft and a day of rest every 3 or 4 days.

Preventative treatment using nifedipine (30 mg extended-release orally every 12 hours) is reserved for individuals with a history of HAPE. It helps by decreasing pulmonary hypertension. Dosing begins one day before ascent and is discontinued after four days at the highest point of ascent or beginning of the descent.

How is HAPE treated?

Treating HAPE:

• move down to a lower altitude immediately
• take nifedipine
• give bottled oxygen, if available

The most important treatment for HAPE is descent. Descent goal is at least 1,000 ft but may require further descent until symptoms resolve. Additional exercise will worsen HAPE, so care should be taken to assist the patient in limiting exertion during descent. Providing extra oxygen and/or raising the air pressure around a victim with a Gamow bag can reverse the underlying process, lack of oxygen, but these measures are really no substitute however for rapid descent down the mountain.

Nifedipine (30 mg extended-release orally every 12 hours) is a drug that helps to open up the blood vessels in the lungs. By doing so, it reduces the high pressure in those vessels that is forcing fluid out into the lungs. Nifedipine helps to reduce chest tightness and ease breathing. Sildenafil (Viagra®), by a different mechanism, also opens up the blood vessels in the lung and may be a useful treatment for HAPE.

Some drugs can be helpful, but should only be used by trained doctors. Following recent research, doctors may also give the steroid, dexamethasone. Drug treatment should only ever be used as a temporary measure when evacuation becomes delayed or unavailable; the best treatment is descent.

You should also go to hospital as soon as possible for follow-up treatment.

How to avoid and prevent altitude sickness

If you’re planning to travel to a high altitude, consider talking to your doctor about drugs that can help with acclimatization, particularly if you have had altitude sickness before.

Following the Altitude Sickness Golden Rules should mean that your body can acclimatize as you ascend and so you will be less likely to develop acute mountain sickness. It usually takes a few days for the body to get used to a change in altitude.

You can reduce the chance of getting altitude sickness by:

• Avoiding a rapid ascent from sea level – don’t go above about 2,500 meters (8202 ft) for the first night’s sleep
• Take 2-3 days to get used to high altitudes before going above 3,000m (9842 ft)
• Once you get above 3,000 meters (9842 ft), ascending by no more than 300-500 meters (984-1640 ft) per day
• Have a rest day every 600-900m (1969-2953 ft) you go up, or every 3-4 days
• Spending the night below the day’s highest altitude
• Avoiding strenuous exercise before your body has had time to adjust to the lower oxygen levels
• Make sure you’re drinking enough water
• Eat a light but high calorie diet
• Avoiding alcohol at high altitude
• Avoid smoking

Go up slowly, take it easy, and give your body time to get used to the altitude. The body has an amazing ability to acclimatize to altitude, but it needs time. For instance, it takes about a week to adapt to an altitude of 5,000m (16,404 ft).

Because of the change in respiratory pattern during sleep, the altitude at which the traveler sleeps is more important for altitude sickness risk than the maximal altitude reached during the day. The optimal rate of ascent (sleep altitude) should be no more than 500 m per day at levels greater than 2500 m. Also, allowing at least one day to acclimate around 2500 m before further ascent, and then again for every additional 1000 m ascent, will reduce risk.

However, if you need to go up more quickly, you could consider taking a drug called acetazolamide (also known as Diamox). There is now good evidence ²⁷ that acetazolamide reduces symptoms of acute mountain sickness in trekkers, although it does have some unusual side-effects: it makes your hands and feet tingle, and it makes fizzy drinks taste funny.

You should begin taking acetazolamide (125 mg orally every 12 hours) 1-2 days before you start to go up in altitude and continue to take it while going up.

If using acetazolamide, you should still go up gradually and follow the general prevention advice.

If you get symptoms of altitude sickness while taking acetazolamide, you should rest or go down until you feel better before going up again.

For those unable to take acetazolamide, dexamethasone may be used as a preventive agent. Dexamethasone also may be considered for individuals involved in an unusually high-risk situation (i.e., search and rescue personnel airlifted to above 11,000 ft). Dosages for dexamethasone is the same for oral, IM, and IV routes of administration (4 mg oral, IM, or IV every 12 hours). If used for longer than ten days, it must be tapered slowly to prevent withdrawal symptoms.

Preventing high altitude sickness using drugs

In 2014, the Wilderness Medical Society published an update of their 2010 guidelines ²⁸, detailing prevention and treatment directives for high altitude illness (acute mountain sickness, HACE, HAPE). This guideline was developed by an expert panel that compiled and classified all available evidence on high altitude illness prevention and treatment. Recommendations based on evidence, using American College of Chest Physicians strategies, were agreed upon. For acute mountain sickness and HACE, the experts proposed a risk classification where low‐risk people are discarded for prevention interventions. For HAPE, pharmacological prophylaxis is recommended for those with a previous diagnosis of high altitude illness ²⁸. However, the document does not include all of the most frequent and broadly‐described pharmacological interventions for prevention and treatment of high altitude illness. The most commonly suggested interventions are summarized below.

• Carbonic anhydrase inhibitors: acetazolamide and methazolamide ²⁹. Carbonic anhydrase inhibitors (acetazolamide and methazolamide) generate inhibition of carbonic anhydrase in the kidneys, resulting in increased bicarbonate excretion in the urine and metabolic acidosis. The result is an offsetting of hyperventilation‐induced respiratory alkalosis, allowing chemoreceptors to respond more fully to hypoxic stimuli at altitude ³⁰. Acetazolamide can also cause pulmonary vasodilation unrelated to carbonic anhydrase inhibition ³¹. Acetazolamide (125 mg orally every 12 hours) is the only medication proven to speed acclimatization. There are two adverse effects of acetazolamide worth considering. First, acetazolamide increases urination frequency and therefore increases the risk of dehydration, which is a concern during high altitude travel ²⁵. Secondly, acetazolamide has a similar molecular structure to sulfa medications and should be used cautiously in patients with sulfa allergy. Although the risk of cross-reactivity is low, travelers with sulfa allergies are recommended to undergo a trial of acetazolamide before travel ²⁶.
• Steroids: budenoside, prednisolone and dexamethasone ³². Steroids (dexamethasone, budesonide and prednisolone): Hypoxia‐induced vasogenic oedema has been suggested as one of the major mechanisms responsible for development of acute mountain sickness (mild altitude sickness) ³³. Glucocorticoid (corticosteroid) blocks hypoxia‐induced endothelial dysfunction ³⁴.
• Bronchodilator drugs: Include salmeterol, theophylline or aminophylline and montelukast ³⁵. The human beta‐2 adrenergic receptor has been found to play a very important role in the pathogenesis of HAPE and salmeterol was found to have a high binding affinity with human beta‐2 adrenergic receptor ³⁶. Furthermore, salmeterol enhances alveolar clearance by stimulating amiloride‐sensitive sodium channels ³⁷. Non‐selective phosphodiesterase inhibitor (theophylline or aminophylline): anti‐hypoxia and antioxidation effects of aminophylline ³⁸ could be responsible for reducing periodic breathing, cerebral and pulmonary microvascular permeability, and pulmonary artery pressure ³⁵. Montelukast is a leukotriene receptor antagonist that reduces the bronchoconstriction ³⁹.
• Selective inhibitor of phosphodiesterase type 5 (PDE5): taladafil ⁴⁰ and sildenafil ⁴¹. Selective inhibitors of phosphodiesterase type 5 (taladafil and sildenafil) induce overproduction of nitric oxide, which attenuates pulmonary vasoconstriction during acute hypoxia ⁴². It causes a reduction in pulmonary hypertension.
• Calcium modulators: Include nifedipine and flunarizine ⁴³. Calcium channel blockers or calcium channel antagonists or calcium antagonists (nifedipine, flunarizine) are a group of medications that disrupt the movement of calcium (Ca2+) through calcium channels and reduce pulmonary vascular resistance ⁴⁴, leading to a reduction of the pulmonary hypertension. Nifedipine (20 mg slow release every 8 hours) prevented HAPE in those with a previous history of episode ²¹.
• Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other analgesic: aspirin, carbasalate and ibuprofen ⁴⁵. Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other analgesics (aspirin, ibuprofen, carbasalate): it is postulated that prostaglandin‐mediated increases in cerebral microvascular permeability may contribute to the pathophysiology of acute mountain sickness (mild altitude sickness) and treatment with prostaglandin synthesis inhibitors could reduce this response ¹⁵.

According to a 2017 Cochrane systematic review ⁴⁶, the most commonly‐used pharmacological interventions suggests that acetazolamide (also known as Diamox) is an effective pharmacological agent to prevent acute high altitude sickness in dosages of 250 to 750 mg/day. Acetazolamide is associated with an increased risk of paraesthesia (abnormal sensation tingling or pricking or ‘pins and needles’ sensation), although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for the other pharmacological agents, to evaluate their effectiveness and safety.

Altitude sickness diagnosis

Altitude sickness (acute mountains sickness) is a clinical diagnosis based on the presence of a headache, with or without the other typical symptoms which include anorexia, nausea, vomiting, insomnia, dizziness or fatigue, in the setting of recent altitude gain at elevations above 2500 meters (8202 ft) ⁴⁷. Headache is the cardinal symptom; it is bitemporal, throbbing, worse during the night and on awakening ⁷. These initial symptoms are strikingly similar to an alcohol hangover. There is no specific lab or other testing recommended. Since the symptoms of altitude sickness (acute mountains sickness) are nonspecific, the presence of atypical symptoms, such as diarrhea, should trigger an evaluation for other causes. Also, the patient may have increased their alcohol intake while traveling, and this should be considered when evaluating.

Specific physical signs are lacking. Heart rate is variable, blood pressure is normal and pulse oximetry is of limited diagnostic value. Absence of the normal high-altitude diuresis, evidenced by lack of increased urine output and retention of fluid, is an early finding in altitude sickness (acute mountains sickness), though not always present.

Given the nonspecific nature of the symptoms, altitude sickness (acute mountains sickness) is commonly confused with other conditions like viral flu–like illness, hangover, exhaustion, medication or drug effect. However, a trial of oxygen breathing or descent can help to discriminate these other conditions from altitude sickness (acute mountains sickness).

Finally, the presence of additional or more severe neurologic symptoms is indicative of possible High Altitude Cerebral Edema (HACE) and should be treated as a medical emergency ⁴⁸.

Altitude sickness treatment

It is better to prevent acute mountain sickness than to try to treat it.

If you have altitude sickness, the best treatment is descent until the symptoms disappear. Descent to an altitude lower than where symptoms began effectively reverses altitude sickness (acute mountains sickness). Descending 500 to 1000 m is usually sufficient. Exertion should be minimized. Oxygen, if available, is particularly effective. Hyperbaric chambers, which simulate descent, have been used to treat altitude sickness (acute mountains sickness) and aid acclimatization. They are effective and require no supplemental oxygen ⁴⁹. Do not continue to climb higher.

Rest, fluids and pain killers are likely to improve your symptoms.

• Don’t go any higher for at least 24-48 hours
• If you have a headache, take ibuprofen (or other NSAIDs) or acetaminophen (paracetamol)
• If you feel sick, take an anti-sickness medication, like promethazine. Promethazine (25-50 mg) is useful for the treatment of nausea and vomiting.
• Make sure you’re drinking enough water
• Avoid alcohol
• Don’t smoke
• Avoid exercise
• Tell your travel companions how you feel, even if your symptoms are mild – there’s a danger your judgement can become clouded.

Painkillers may ease the headache, but they don’t treat the condition. Acetazolamide, a carbonic anhydrase inhibitor, may be helpful, especially if you need to stay at the same altitude, and resting for a day or two might give your body time to recover. Acetazolamide should be given in the dose of 250 mg twice a day for 3-5 days. Acetazolamide decreases the pH level of your blood, which then causes an increased breathing rate. It is well tolerated in general, but patients should be advised that use can cause tingling of the digits and even lips (paraesthesia).

Steroids, particularly dexamethasone, are effective in relieving symptoms. Dexamethasone was used by Hackett and colleagues ⁵⁰ in the dose of 4 mg orally or intramuscularly. Its mechanism of action is not known. Because symptoms recur after stopping dexamethasone, it is thought not to aid acclimatization. Hence it should be given in conjunction with acetazolamide.

It is best not to drink alcohol or take sedatives or sleeping pills because they interfere with the body’s adaptation to high altitude.

You can continue going up with care once you feel fully recovered.

If you don’t feel any better after 24 hours, you should go down by at least 500m (about 1,640 feet).

Don’t attempt to climb again until your symptoms have completely disappeared.

After 2-3 days, your body should have adjusted to the altitude and your symptoms should disappear.

See a doctor if your symptoms don’t improve or get worse.

It is essential that you should NEVER go up higher if you have acute mountain sickness.

If a traveling companion has symptoms of acute mountain sickness and becomes confused or unsteady, or develops an extremely severe headache or vomiting, they may have a life-threatening condition called high altitude cerebral edema (HACE).

Treatment of HAPE (high altitude pulmonary edema) and HACE (high altitude cerebral edema)

If you have signs of altitude sickness affecting your lungs or your brain, this is a medical emergency. You need help to descend as soon as possible. Breathing oxygen from a tank can help.

• Immediate descent is absolutely essential
• Dexamethasone and acetazolamide should both be given, if available
• Pressure bags and oxygen gas can buy time

Altitude sickness medicine

Consider traveling with these medicines for altitude sickness:

• Acetazolamide to prevent and treat high altitude sickness
• Ibuprofen and paracetamol for headaches
• Anti-sickness medication, like promethazine, for nausea

1. Prince TS, Thurman J, Huebner K. Acute Mountain Sickness. [Updated 2021 Jul 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430716
2. Davis C, Hackett P. Advances in the Prevention and Treatment of High Altitude Illness. Emerg Med Clin North Am. 2017 May;35(2):241-260. doi: 10.1016/j.emc.2017.01.002
3. Wilson MH, Newman S, Imray CH. The cerebral effects of ascent to high altitudes. Lancet Neurol. 2009 Feb;8(2):175-91. doi: 10.1016/S1474-4422(09)70014-6
4. Leissner KB, Mahmood FU. Physiology and pathophysiology at high altitude: considerations for the anesthesiologist. J Anesth. 2009;23(4):543-53. doi: 10.1007/s00540-009-0787-7
5. Naeije R. Physiological adaptation of the cardiovascular system to high altitude. Prog Cardiovasc Dis. 2010 May-Jun;52(6):456-66. doi: 10.1016/j.pcad.2010.03.004
6. Luks AM, Swenson ER, Bärtsch P. Acute high-altitude sickness. Eur Respir Rev. 2017 Jan 31;26(143):160096. doi: 10.1183/16000617.0096-2016
7. Paralikar, S. J., & Paralikar, J. H. (2010). High-altitude medicine. Indian journal of occupational and environmental medicine, 14(1), 6–12. https://doi.org/10.4103/0019-5278.64608
8. Schneider M, Bärtsch P. Characteristics of Headache and Relationship to Acute Mountain Sickness at 4559 Meters. High Alt Med Biol. 2018 Dec;19(4):321-328. doi: 10.1089/ham.2018.0025
9. Murdoch D. Altitude sickness. BMJ Clinical Evidence. 2010;2010:1209. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907615/
10. Murdoch DR. Altitude Illness Among Tourists Flying to 3740 Meters Elevation in the Nepal Himalayas. J Travel Med. 1995 Dec 1;2(4):255-256. doi: 10.1111/j.1708-8305.1995.tb00671.x
11. Basnyat B, Murdoch DR. High-altitude illness. Lancet. 2003 Jun 7;361(9373):1967-74. doi: 10.1016/S0140-6736(03)13591-X
12. Schneider M, Bernasch D, Weymann J, Holle R, Bartsch P. Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate. Med Sci Sports Exerc. 2002 Dec;34(12):1886-91. doi: 10.1097/00005768-200212000-00005
13. Ri-Li G, Chase PJ, Witkowski S, Wyrick BL, Stone JA, Levine BD, Babb TG. Obesity: associations with acute mountain sickness. Ann Intern Med. 2003 Aug 19;139(4):253-7. doi: 10.7326/0003-4819-139-4-200308190-00007
14. Dehnert C, Bärtsch P. Can patients with coronary heart disease go to high altitude? High Alt Med Biol. 2010 Fall;11(3):183-8. doi: 10.1089/ham.2010.1024
15. Committee to Advise on Tropical Medicine and Travel (CATMAT). Statement on high-altitude illnesses. An Advisory Committee Statement (ACS). Can Commun Dis Rep. 2007 Apr 1;33(ACS-5):1-20. English, French.
16. Prince TS, Gossman WG. Mountain Sickness, Acute. [Updated 2017 Oct 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430716
17. Altitude Sickness. http://www.altitude.org/altitude_sickness.php
18. Hackett PH, Roach RC. High altitude medicine. In: Auerbach PS, editor. Wilderness medicine. 5th ed. Philadelphia: Mosby Elsevier; 2007.
19. Berg JT, Ramanathan S, Swenson ER. Inhibitors of hypoxic pulmonary vasoconstriction prevent high-altitude pulmonary edema in rats. Wilderness Environ Med. 2004 Spring;15(1):32-7. doi: 10.1580/1080-6032(2004)015[0032:iohpvp]2.0.co;2
20. Schoene RB. Illnesses at high altitude. Chest. 2008 Aug;134(2):402-416. doi: 10.1378/chest.07-0561
21. Bärtsch P, Maggiorini M, Ritter M, Noti C, Vock P, Oelz O. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med. 1991 Oct 31;325(18):1284-9. doi: 10.1056/NEJM199110313251805
22. Noda M, Suzuki S, Tsubochi H, Sugita M, Maeda S, Kobayashi S, Kubo H, Kondo T. Single dexamethasone injection increases alveolar fluid clearance in adult rats. Crit Care Med. 2003 Apr;31(4):1183-9. doi: 10.1097/01.CCM.0000059640.77535.29
23. Meier D, Collet TH, Locatelli I, Cornuz J, Kayser B, Simel DL, Sartori C. Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review. JAMA. 2017 Nov 14;318(18):1810-1819. doi: 10.1001/jama.2017.16192. Erratum in: JAMA. 2018 Jun 19;319(23):2443.
24. Luks AM, Auerbach PS, Freer L, Grissom CK, Keyes LE, McIntosh SE, Rodway GW, Schoene RB, Zafren K, Hackett PH. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update. Wilderness Environ Med. 2019 Dec;30(4S):S3-S18. doi: 10.1016/j.wem.2019.04.006
25. Castellani JW, Muza SR, Cheuvront SN, Sils IV, Fulco CS, Kenefick RW, Beidleman BA, Sawka MN. Effect of hypohydration and altitude exposure on aerobic exercise performance and acute mountain sickness. J Appl Physiol (1985). 2010 Dec;109(6):1792-800. doi: 10.1152/japplphysiol.00517.2010
26. Shah, T. J., Moshirfar, M., & Hoopes, P. C., Sr (2018). “Doctor, I have a Sulfa Allergy”: Clarifying the Myths of Cross-Reactivity. Ophthalmology and therapy, 7(2), 211–215. https://doi.org/10.1007/s40123-018-0136-8
27. BMJ. 2004;328:797
28. Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, Zafren K, Hackett PH; Wilderness Medical Society. Wilderness Medical Society practice guidelines for the prevention and treatment of acute altitude illness: 2014 update. Wilderness Environ Med. 2014 Dec;25(4 Suppl):S4-14. doi: 10.1016/j.wem.2014.06.017
29. van Patot MC, Leadbetter G 3rd, Keyes LE, Maakestad KM, Olson S, Hackett PH. Prophylactic low-dose acetazolamide reduces the incidence and severity of acute mountain sickness. High Alt Med Biol. 2008 Winter;9(4):289-93. doi: 10.1089/ham.2008.1029
30. Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol (1985). 2007 Apr;102(4):1313-22. doi: 10.1152/japplphysiol.01572.2005
31. Höhne C, Pickerodt PA, Francis RC, Boemke W, Swenson ER. Pulmonary vasodilation by acetazolamide during hypoxia is unrelated to carbonic anhydrase inhibition. Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L178-84. doi: 10.1152/ajplung.00205.2006
32. Basu M, Sawhney RC, Kumar S, Pal K, Prasad R, Selvamurthy W. Hypothalamic-pituitary-adrenal axis following glucocorticoid prophylaxis against acute mountain sickness. Horm Metab Res. 2002 Jun;34(6):318-24. doi: 10.1055/s-2002-33260
33. Hackett PH. High altitude cerebral edema and acute mountain sickness. A pathophysiology update. Adv Exp Med Biol. 1999;474:23-45. doi: 10.1007/978-1-4615-4711-2_2
34. Murata T, Suzuki N, Yamawaki H, Sato K, Hori M, Karaki H, Ozaki H. Dexamethasone prevents impairment of endothelium-dependent relaxation in arteries cultured with fetal bovine serum. Eur J Pharmacol. 2005 May 16;515(1-3):134-41. doi: 10.1016/j.ejphar.2005.04.005
35. 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 Jan;9(1):119-27. doi: 10.1517/14656566.9.1.119
36. Chandramoorthi GD, Piramanayagam S, Marimuthu P. An insilico approach to high altitude pulmonary edema – Molecular modeling of human beta2 adrenergic receptor and its interaction with Salmeterol & Nifedipine. J Mol Model. 2008 Sep;14(9):849-56. doi: 10.1007/s00894-008-0322-z
37. Maggiorini M. Prevention and treatment of high-altitude pulmonary edema. Prog Cardiovasc Dis. 2010 May-Jun;52(6):500-6. doi: 10.1016/j.pcad.2010.03.001
38. Yang B, Wang GY, Chen B, Qin RB, Xi SL, Chen L. Anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure. Chin Med Sci J. 2007 Mar;22(1):62-5.
39. Tintinger, G. R., Feldman, C., Theron, A. J., & Anderson, R. (2010). Montelukast: more than a cysteinyl leukotriene receptor antagonist?. TheScientificWorldJournal, 10, 2403–2413. https://doi.org/10.1100/tsw.2010.229
40. Maggiorini M, Brunner-La Rocca HP, Peth S, Fischler M, Böhm T, Bernheim A, Kiencke S, Bloch KE, Dehnert C, Naeije R, Lehmann T, Bärtsch P, Mairbäurl H. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med. 2006 Oct 3;145(7):497-506. doi: 10.7326/0003-4819-145-7-200610030-00007
41. Bates MG, Thompson AA, Baillie JK. Phosphodiesterase type 5 inhibitors in the treatment and prevention of high altitude pulmonary edema. Curr Opin Investig Drugs. 2007 Mar;8(3):226-31.
42. Ozaki M, Kawashima S, Yamashita T, Ohashi Y, Rikitake Y, Inoue N, Hirata KI, Hayashi Y, Itoh H, Yokoyama M. Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium. Hypertension. 2001 Feb;37(2):322-7. doi: 10.1161/01.hyp.37.2.322
43. Hohenhaus E, Niroomand F, Goerre S, Vock P, Oelz O, Bärtsch P. Nifedipine does not prevent acute mountain sickness. Am J Respir Crit Care Med. 1994 Sep;150(3):857-60. doi: 10.1164/ajrccm.150.3.8087361
44. Hackett PH, Roach RC, Hartig GS, Greene ER, Levine BD. The effect of vasodilators on pulmonary hemodynamics in high altitude pulmonary edema: a comparison. Int J Sports Med. 1992 Oct;13 Suppl 1:S68-71. doi: 10.1055/s-2007-1024599
45. Burtscher M, Likar R, Nachbauer W, Philadelphy M, Pühringer R, Lämmle T. Effects of aspirin during exercise on the incidence of high-altitude headache: a randomized, double-blind, placebo-controlled trial. Headache. 2001 Jun;41(6):542-5. doi: 10.1046/j.1526-4610.2001.041006542.x
46. Nieto Estrada, V. H., Molano Franco, D., Medina, R. D., Gonzalez Garay, A. G., Martí-Carvajal, A. J., & Arevalo-Rodriguez, I. (2017). Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs. The Cochrane database of systematic reviews, 6(6), CD009761. https://doi.org/10.1002/14651858.CD009761.pub2
47. Litch JA. High altitude illnesses. In: Rakel RE, Bope ET, editors. Conn’s Current Therapy 2008. Philadelphia: Elsevier Saunders; 2007.
48. Brodmann Maeder, M., Brugger, H., Pun, M., Strapazzon, G., Dal Cappello, T., Maggiorini, M., Hackett, P., Bärtsch, P., Swenson, E. R., & Zafren, K. (2018). The STAR Data Reporting Guidelines for Clinical High Altitude Research. High altitude medicine & biology, 19(1), 7–14. https://doi.org/10.1089/ham.2017.0160
49. Hackett PH, Roach RC. High altitude medicine. In: Auerbach PS, editor. Wilderness medicine. 5th ed. Philadelphia: Mosby Elsevier; 2007
50. Hackett PH, Roach RC, Wood RA, Foutch RG, Meehan RT, Rennie D, Mills WJ Jr. Dexamethasone for prevention and treatment of acute mountain sickness. Aviat Space Environ Med. 1988 Oct;59(10):950-4.