Facts About AMS

• Of all the organs, the brain seems to be most vulnerable to the hypoxia of high altitudes, particularly extreme altitudes.

• The dilation of the cerebral arteries caused by hypoxia is lessened by the constricting effect on the arteries caused by hypocapnea (low arterial carbon dioxide). Overall oxygen delivery to the brain is a result of the balance between vasodilation and vasoconstriction. In general, vasodilation overrides vasoconstriction.

• The combination of increased cerebral blood flow and hypoxia can lead to vasogenic cerebral edema (as described).

• Increased cerebral blood flow can also cause brain swelling from engorgement of the brain with blood.

• All brains swell on ascent to high altitudes—either as a result of cerebral edema and/or engorgement with blood, but not all climbers develop AMS.

• According to the “tight fit” hypothesis, cranial anatomy determines who might develop AMS. In climbers who remain relatively asymptomatic, the brain volume increase and corresponding rise in intracranial pressure are “buffered” by decreased intracranial blood flow (from vasoconstriction) as well as increased displacement of cerebral spinal fluid out of the skull.

• If buffering is unsuccessful, cerebral edema and intracranial pressure continue to rise, resulting in the symptoms of AMS.

• AMS can evolve into high HACE. HACE strikes only a minority of climbers, usually those at extreme altitudes.

• Cases of mild AMS are probably caused by early cerebral edema.

• There is a hazy line between moderate-to-severe AMS and HACE. Symptoms of more severe AMS include unrelieved headache, decreased urine output, vomiting, and lethargy—but not the loss of balance (ataxia) and the mental confusion or coma that define HACE.

This is the most severe form of AMS. At this stage, significant brain edema and increased intracranial pressure have developed. In general, 24–36 hours elapse between the onset of AMS and HACE, but HACE can also occur abruptly, with few antecedent sypmtoms. These symptoms include nausea and vomiting. irrational behavior, confusion, lethargy, ataxia (loss of balance), and finally, coma. The progression from initial symptoms to coma may take as little as 12 hours. Death follows if early treatment is not administered.

The second organ of the body most affected by hypoxia is the lung, but the cause of high-altitude pulmonary edema is completely different from AMS and HACE. Basically, in HAPE, a high-pressure fluid leak occurs in the lung. Here’s the mechanism: Hypoxia causes pulmonary artery vasoconstriction and an elevation of pulmonary artery pressure. The vasoconstriction, however, is unevenly distributed throughout the lung, and those regions of lung tissue less constricted become overperfused with blood, resulting in regional elevations of pulmonary capillary pressure. The increased capillary pressure disrupes the basement membrane and forces water and proteins through the capillary walls into the pulmonary air spaces, resulting in pulmonary edema (high-pressure overperfusion edema). The flooding of these patchy areas of lung tissue further reduces oxygen delivery to the blood, further increasing hypoxia.

Persons who have a low hypoxic ventilatory response (HVR) have more pulmonary hypertension and are more susceptible to HAPE. More importantly, a low HVR may permit extreme hypoxemia during sleep, explaining why HAPE often strikes in the middle of the night. In addition, persons susceptible to HAPE have other genetic differences; for example, their production of nitric oxide (a chemical that dilates arteries) in the lung is diminished.

The early symptoms of HAPE are breathlessness on exertion and reduced exercise tolerance, greater than expected for the altitude. Untreated, there is progression to breathlessness at rest, especially at night, and persistent cough. The cough can be dry or progress to produce white, watery, or frothy fluid. Severe fatigue or exercise intolerance is nearly universal and may be the most reliable hallmark of HAPE. The most reliable combination of diagnostic signs and symptoms is dry cough and fatigue plus lung crackles and oxygen desaturation (measured with a pulse oximeter and more pronounced than calculated for the altitude) or tachycardia and increased oxygen desaturation.

HAPE strikes 2%—4% of those who travel above 12,000 feet. (Fatal cases, however, have occurred as low as 8,000 feet.) At increased risk are those who have previously experienced HAPE; they have a 60% chance of recurrence during another ascent to high altitudes.

HAPE kills more travelers each year than any other altitude-related condition but is reversible if recognized early and treated properly.

Reduce Activity If you travel rapidly to an elevation higher than 8,000 feet (2,500 meters), you can reduce your chance of illness by not engaging in strenuous activity for the first 2 days.

Acclimatize The major cause of altitude sickness is going too high too fast. You can avoid or lessen AMS by making a slow, gradual ascent. Slow ascent means not increasing your sleeping altitude by over 2,000 to 3,000 feet (600 to 900 meters) on successive nights, especially when climbing above 10,000 feet. An alternate strategy, called staging, is to spend 2 to 3 days at an intermediate altitude (e.g., 8,000 to 10,000 feet) before resuming ascent. A stop at around 12,000 feet is especially advised, In addition, no matter how high you are climbing during the day, try to sleep at a lower altitude, if this is an option.

Unfortunately, cautious guidelines on the rate of ascent are impractical for most climbers. For example, if you were to climb Mt. Kilimanjaro on a guided tour, you would find yourself ascending on a schedule that forces you to sleep at much higher altitudes each successive night. You begin the climb at 5,000 feet. The huts where you sleep are at 9,000, 12,000, and 14,500 feet. Only a single rest day is spent (sometimes) at the highest hut before the final ascent to the 19,000-foot summit the following morning. Needless to say, AMS is a frequent occurrence among those climbing Mt. Kilimanjaro.

Take a Prophylactic Drug In situations where you are going rapidly to altitudes above 8,000 feet, or arriving by airplane at a high destination (Table 15.1), there are two drugs that can help: (1) acetazolamide, which accelerates acclimatization; and (2) dexamethasone, which reduces symptoms, but has no effect on acclimatization itself. Prophylaxis is especially important if you have previously experienced altitude sickness, but drug prophylaxis isn’t uniformly recommended by some experts for those who plan a reasonably slow ascent schedule to moderate altitudes. The problem here is: How many people actually practice slow ascent?

Table 15.1 AMS Treatment Options

Acetazolamide (Diamox)—Acetazolamide has been shown to reduce susceptibility to AMS and the incidences of HAPE and HACE. This is the drug of choice for preventing AMS and is about 75% effective. Acetazolamide works through several mechanisms: (1) It forces the kidneys to excrete bicarbonate, acidifying the blood. The resulting metabolic acidosis acts as a respiratory stimulant, increasing ventilation and improving arterial oxygenation. The drug is especially effective in preventing extreme hypoxia during sleep—a situation that can also trigger HAPE, especially in persons with a history of this disorder; (2) It reduces cerebrospinal fluid (CSF) formation and possibly CSF pressure; and (3) It causes a diuresis, counteracting the fluid retention that occurs in AMS.

Standard dosage: 125 to 250 mg every 12 hours, or 500 mg daily of the slow-release preparation (Diamox-SR). Start acetazolamide 24 hours before starting your ascent and continue it for 3 days at the higher altitude. Side effects include frequent urination (polyuria) and a tingling sensation of the face and lips (paresthesia).

Dexamethasone (Decadron)—Dexamethasone is not routinely recommended as a prophylactic agent for AMS or HAPE, but it may be the ideal prophylactic agent to reduce the risk of HAPE and AMS in HAPE-susceptible persons, or those who must ascend rapidly (for example, those going on a mountain rescue mission), as it has now been shown to reduce the incidence of both conditions in this population. *

Prophylaxis dosage: 8 mg orally twice a day, begun the day of ascent. Side effects: taking dexamethasone on an extended trekcould lead to hyperglycemia, immunosuppresion, and steroid psychosis.

*In a study reported in 2006, the incidence of HAPE was reduced from 78% to 0% in climbers taking prophylactic dexamethasone)* Maggiorini M, et al. Both tadalafil (Cialis) and dexamethasone may reduce the incidence of high-altitude pulmonary edema. Ann Int Med. 2006;145:497-506.

Nifedipine—A climber with a history of HAPE could also use the 20-mg slow-release capsule (available in Europe and Asia under various brand names) every 8 hours, or the 30-mg slow-release (available as Adalat-CC or Procardia-XL in North America) every 12 hours. All climbers above 10,000 feet should also carry standby treatment doses of the rapid-acting 10-mg capsules. Nifedipine reduces the incidence of HAPE  from 60% to 10% in susceptinble individuals. Cialis (tadalafil), in a dose of 10 mg twice daily, has also been shown to be effective.

Aspirin—Pretreatment with aspirin before travel to high altitudes appears to decrease the incidence and severity of headaches, the main symptom of mild AMS. Take one aspirin tablet every 4 hours for three doses before arrival. After arrival, take two tablets three times daily for 3 days. (Ibuprofen also works.)

Ginkgo biloba—This herb has shown mixed results in preventing AMS.

Diagnosing Altitude Sickness

When diagnosing and treating AMS, HACE, or HAPE keep in mind other diagnoses that can mimic altitude sickness. Consider:

• Dehydration (can cause nausea, weakness, headache)

• Hypothermia (can cause loss of balance, staggering gait)

• Exhaustion (can cause lethargy, loss of balance, staggering gait)

• Respiratory infection (symptoms include coughing, shortness of breath)

• Carbon monoxide poisoning (can result from cooking in enclosed spaces such as tents, snow caves; causes rapid breathing, headache, mental changes, coma.)

• Hyperventilation (rapid breathing from anxiety; may simulate pulmonary edema)

• Psychiatric problems with psychosis can cause irrational behavior mimicking some aspects of HACE.

• The combination of high altitudes, hypoxia, and dehydration can predispose to venous thrombosis—cerebral, retinal, and pulmonary. Women on birth control pills who smoke may be at higher risk for a pulmonary embolus.

• Altitude—unrelated illness, e.g., diabetes (hypoglycekia, ketoacidosis), a seizure disorder, symptoms of an undiagnosed brain tumor, viral or bacterial infection

Although the valuable aphorism “any illness at altitude should be considered AMS until proved otherwise” is usually true, it is sometimes impossible, perhaps even unnecessary, to make an immediate diagnosis. Symptomatic treatment, such as oxygen, quickly followed by descent, should be the first priority. An exact diagnosis can often wait until after the climber has descended.

Mild AMS by itself is a benign illness but you must watch for progression to more severe AMS, HACE, or HAPE. In general, management depends on the acuity and severity of symptoms. The principles of treatment are as follows:

• Stop further ascent and rest. Administer adjunctive treatment, as indicated.

• Descend if there is no improvement or if symptoms worsen.

• Descend immediately if there are symptoms or signs of cerebral or pulmonary edema.

The first rule applies: Stop your ascent and rest. Symptoms should improve in 8 to 12 hours; if not, descend. To help the headache, take aspirin, acetaminophen, or ibuprofen. Acetazolamide (Diamox), 125 mg to 250 mg twice daily may reduce symptoms within 12 hours. Dexamethasone (4 mg orally or intramuscularly every 6 hours) works within 6 hours and is possibly more effective than acetazolamide. Combining dexamethasone and acetazolamide may be even more effective but no studies have yet proved this. No further ascent should be attempted until symptoms have cleared. Continue to take acetazolamide for several days as prophylaxis. Drinking extra fluids doesn’t help AMS but if you are dehydrated you will feel better.

Treatment of more severe AMS (which is essentially a pre-HACE condition) is directed at stopping the formation of vasogenic cerebral edema. A descent of 1,500 to 3,000 feet is the best initial treatment. Adjunctive measures include oxygen, steroids, acetazolamide, rest, and staying warm.

• Start oxygen, if available, at a flow rate of 2 to 4 liters/minute
• Administer dexamethasone, 8 mg immediately, then 4 mg every 6 hours, plus acetazolamide, 250 mg every 12 hours.
• Plan for descent as soon as possible.

The hallmarks of HACE are confusion and ataxia (staggering gait). To test for ataxia, have the climber attempt to walk a straight line, one foot in front of the other, heel to toe. A climber who struggles to stay on the line, falls off to one side, or falls down should be considered to have HACE. At the first sign of ataxia, if not before, descent should be started. Adjunctive treatments are listed in the preceding paragraph. A portable hyperbaric chamber, such as the Gamow bag (see below), will improve oxygenation, give temporary relief, and will facilitate descent; but use of the Gamow bag should not unduly delay descent. NOTE: HACE and high-altitude pulmonary edema (HAPE) often occur simultaneously, but HACE can also occur as a single entity without pulmonary symptoms.

Treatment depends on the severity of the illness and the environment. If oxygen and medical expertise are not available, immediate descent is indicated. If diagnosed early, a descent of 1,500 to 3,000 feet usually gives rapid improvement. Two or 3 days of rest at the lower elevation usually adequate for complete recovery. Once the symptoms have resolved, cautious re-ascent may be attempted. NOTE: Some authorities state, however, that once a diagnosis of HAPE is made, the individual should be evacuated to a medical facility for proper follow-up treatment. This is probably indicated only in more severe cases. Re-ascent can be attempted cautiously, but only if prophylactic acetazolamide and nifedipine or a PDE-5 inhibitor is available.

Treatment Options for HAPE 

• Oxygen, at an initial flow rate of 2 to 4 liters/minute, can be lifesaving. Reduce flow to 1 to 2 liters to keep SaO₂ >90%.

• Administer nifedipine, Viagra, or Cialis (see below). Although oxygen and descent are the best treatments for HAPE, nifedipine and PDE-5 inhibitors are effective adjuncts, especially when oxygen is not available.

• If conscious, have the patient swallow the first dose. If lethargic or comatose, pierce the capsule (if using nifedipine) and squirt it under the tongue. Continue treatment with the slow-release form, 20 to 30 mg every 12 hours.

• Nifedipine rapidly reduces pulmonary vasoconstriction, thus reducing pulmonary hypertension and over-perfusion edema. The reduction in vasoconstriction also makes pulmonary blood flow more homogeneous, which improves oxygenation. Sublingual administration of nifedipine results in a 10% rise in arterial oxygen saturation within 10 to 15 minutes. Nifedipine and PDE-5 inhibitors  can sometimes be used alone with strict bed rest in a person with only very mild HAPE, otherwise they is used only in combination with the other treatments: descent, oxygen, and hyperbaric therapy.

• Administering hyperbaric treatment in the Gamow bag (see next) for a total of 2 to 4 hours usually results in dramatic improvement, facilitating descent.

• Keep the patient warm. Not only will the patient be more comfortable, cold stress increases pulmonary artery pressure.

This device is an airtight, 7-foot cylindrical bag made of coated nylon weighing about 18 lbs. with a pump and/or rebreathing unit. It is used for the treatment of more severe AMS or HACE, especially when a person is too ill to descend immediately. The stricken climber is placed inside the bag, which is then pressurized with a foot or hand pump. This pressurization simulates a decrease of 1,500 to 2,500 meters in altitude and, depending on the starting altitude, is usually sufficient to raise arterial oxygen saturation to more than 90%. A 1-hour treatment provides rapid relief from most symptoms of AMS, but the effect is temporary, lasting only 10 to 11 hours. This may buy enough time to walk the stricken climber to a lower altitude. By contrast, climbers receiving dexamethasone will improve more slowly but with sustained, longer-lasting effects. Although the administration of dexamethasone is simple, the same can’t be said for the mobile hyperbaric chamber. Maintaining therapeutic pressure and air flow in often extreme weather can be a daunting task. In addition, access to the victim is restricted.

The main advantages of the Gamow-type bag are its rapid action and independence from consumable oxygen. The device is best suited for alpine expeditions and search and rescue teams that don’t carry bottled oxygen. Gamow bags can be purchased or rented form Chinook Medical Gear, Inc., 120 Rock Point Drive, Unit C, Durango, CO 81301; 970-375-1241; 800-766-1365.

This is usually supplied by “E” type cylinders that weigh about 18 lbs. One full tank will last about 4 hours at a flow rate of 2 liters/minute. Supplemental oxygen is slightly more effective than the Gamow bag in raising arterial oxygen saturation and its use does not restrict access to the victim.

It is usually recommended that high-altitude travelers not take sleeping pills because they might depress respiration, increase oxygen desaturation and hypoxia, and increase the incidence or severity of AMS. However, a recent study (conducted at an elevation of 5,300 meters) among members of the British Mount Everest Expedition found that small doses (10 mg) of the short-acting benzodiazepine, temazepam (Restoril), improved the subjective quality of sleep without adversely affecting respiration. Better sleep, defined as longer periods without arousal, resulted in less daytime drowsiness and improved endurance. In 1996, French researchers found that a 10-mg dose of zolpidem (Ambien) taken at a simulated altitude of 4,000 meters was associated with fewer sleep arousals and no increase in period breathing. From these studies, it appears that the short-acting hypnotics may actually be safe adjuncts for improving comfort and rest as well as high-altitude performance.

The incidence of AMS in children is about the same as in adults, but diagnosing the condition can be problematic because the symptoms—cough, headache, irritability, and loss of appetite—are often mistaken for a viral illness. If a child does become sick at altitude, the parents should assume that AMS is a possibility, descend, and seek prompt medical consultation. Drug prophylaxis/treatment for AMS could be considered as for adults, but with appropriate pediatric doses. These medications have not been specifically studied for treating children with AMS.

• If you are younger than age 50, without symptoms of heart disease, and in good physical condition, and you have no cardiac risk factors, especially no family history of early heart disease, you don’t need a cardiac evaluation before your trip. Standard pre-travel counseling (Chapter 2) is sufficient. Follow the guidelines in this chapter for preventing altitude illness.

• If you have one or more risk factors (including male older than age 50), but have no cardiac symptoms, consult your physician. Depending on the nature of your planned excursion, the number of risk factors, your overall medical and physical condition, plus whatever anxiety you might have about your heart—pre-ascent treadmill exercise testing may be recommended. However, there can be drawbacks to testing asymptomatic people. The exercise test can be normal even when there is significant underlying coronary artery disease. And if the test is equivocal, or mildly abnormal, it could open a diagnostic Pandora’s box. Next you’ll need a nuclear perfusion scan; you may even get an angiogram. Angiograms are invasive, and not without risk. A newer technology, the multidetector CT scanner, can show your coronary arteries in enough detail to diagnose coronary artery disease and the extent of any plaque formation. The test is noninvasive and takes only 15 minutes.

• If you have a history of heart attack, coronary artery bypass grafting (CABG) surgery or angioplasty, climbing or travel to high altitudes is certainly possible, but the indications for ascent should be examined carefully. If you have a normal exercise stress test you are probably at low risk. If you are in a higher risk category, as shown by your stress test and/or symptoms, precautionary measures should be more rigorous.

• If you have symptoms or established CAD, and your exercise test is abnormal, your activity level should be related to the test results. If the test is mildly abnormal and you are able to perform the test at a high exercise level, almost no limits should be imposed on your physical activities, except those that evoke symptoms. If you have symptoms or an abnormality at a low exercise level, it is best to exercise below that level.