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Chapter 2The Pre-Travel ConsultationSelf-Treatable Conditions

Altitude Illness

Peter H. Hackett, David R. Shlim

OVERVIEW

The stresses of the high-altitude environment include cold, low humidity, increased ultraviolet radiation, and decreased air pressure, all of which can cause problems for travelers. The primary concern, however, is hypoxia. At 10,000 ft (3,000 m), for example, the inspired PO2 is only 69% of sea-level value. The degree of hypoxic stress depends on altitude, rate of ascent, and duration of exposure. Sleeping at high altitude produces the most hypoxia; day trips to high altitude with return to low altitude are much less stressful on the body. Typical high-altitude destinations include Cuzco, Peru (11,150 ft; 3,400 m), La Paz, Bolivia (12,400 ft; 3,780 m), Lhasa, Tibet (12,000 ft; 3,660 m), Everest Base Camp in Nepal (17,598 ft; 5,364 m), and Kilimanjaro in Tanzania (19,341 ft; 5,895 m).

The human body adjusts very well to moderate hypoxia, but requires time to do so (Box 2-02). The process of acute acclimatization to high altitude takes 3–5 days; therefore, acclimatizing for a few days at 8,000–9,000 ft (2,500–2,750 m) before proceeding to a higher altitude is ideal. Acclimatization prevents altitude illness, improves sleep, and increases comfort and well-being, although exercise performance will always be reduced compared with low altitude. Increase in ventilation is the most important factor in acute acclimatization; therefore, respiratory depressants must be avoided. Increased red-cell production does not play a role in acute acclimatization.

RISK FOR TRAVELERS

Inadequate acclimatization may lead to altitude illness in any traveler going to 8,000 ft (2,500 m) or higher. Susceptibility and resistance to altitude illness are genetic traits, and no simple screening tests are available to predict risk. Risk is not affected by training or physical fitness. Children are equally susceptible as adults; people aged >50 years have slightly lower risk. How a traveler has responded to high altitude previously is the most reliable guide for future trips, but is not infallible. However, given certain baseline susceptibility, risk is largely influenced by rate of ascent and exertion (see Table 2-07). Determining an itinerary that will avoid any occurrence of altitude illness is difficult because of variations in individual susceptibility, as well as in starting points and terrain. The goal for the traveler may not be to avoid all symptoms of altitude illness but to ensure that any illness remains mild.

CLINICAL PRESENTATION

Altitude illness is divided into 3 syndromes: acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE).

Acute Mountain Sickness

AMS is the most common form of altitude illness, affecting, for example, 25% of all visitors sleeping above 8,000 ft (2,500 m) in Colorado. Symptoms are those of an alcohol hangover: headache is the cardinal symptom, sometimes accompanied by fatigue, loss of appetite, nausea, and occasionally vomiting. Headache onset is usually 2–12 hours after arrival at a higher altitude and often during or after the first night. Preverbal children may develop loss of appetite, irritability, and pallor. AMS generally resolves with 24–72 hours of acclimatization.

High-Altitude Cerebral Edema

HACE is a severe progression of AMS and is rare; it is most often associated with HAPE. In addition to AMS symptoms, lethargy becomes profound, with drowsiness, confusion, and ataxia on tandem gait test. A person with HACE requires immediate descent; death from HACE can ensue within 24 hours of developing ataxia if the person fails to descend.

High-Altitude Pulmonary Edema

HAPE can occur by itself or in conjunction with AMS and HACE; the incidence is 1 per 10,000 skiers in Colorado and up to 1 per 100 climbers at >14,000 ft (4,300 m). Initial symptoms are increased breathlessness with exertion, and eventually increased breathlessness at rest, associated with weakness and cough. Oxygen or descent is life-saving. HAPE can be more rapidly fatal than HACE.

Preexisting Medical Problems

Travelers with medical conditions, such as heart failure, myocardial ischemia (angina), sickle cell disease, or any form of pulmonary insufficiency, should be advised to consult a physician familiar with high-altitude medical issues before undertaking high-altitude travel. The risk for new ischemic heart disease in previously healthy travelers does not appear to be increased at high altitudes. People with diabetes can travel safely to high altitudes, but they must be accustomed to exercise and carefully monitor their blood glucose. In travelers with type 1 diabetes, diabetic ketoacidosis may be triggered by altitude illness and may be more difficult to treat in those on acetazolamide. Not all glucose meters read accurately at high altitudes.

Most people do not have visual problems at high altitudes. However, at very high altitudes some people who have had radial keratotomy may develop acute farsightedness and be unable to climb by themselves. LASIK and other newer procedures may produce only minor visual disturbances at high altitudes.

There are no studies or case reports of harm to a fetus if the mother travels briefly to high altitudes during pregnancy. However, it may be prudent to recommend that pregnant women do not stay at sleeping altitudes >12,000 ft (3,700 m), if possible. The dangers of having a pregnancy complication in remote, mountainous terrain should also be discussed.

Box 2-02. Tips for acclimatization

  • Ascend gradually, if possible. Try not to go directly from low altitude to >9,000 ft (2,750 m) sleeping altitude in 1 day. Once at >9,000 ft (2,750 m), move sleeping altitude no higher than 1,600 ft (500 m) per day, and plan an extra day for acclimatization every 3,300 ft (1,000 m).
  • Consider using acetazolamide to speed acclimatization, if abrupt ascent is unavoidable.
  • Avoid alcohol for the first 48 hours.
  • Participate in only mild exercise for the first 48 hours.
  • Having a high-altitude exposure at >9,000 ft (2,750 m) for 2 nights or more, within 30 days before the trip, is useful.

Table 2-07. Risk categories for acute mountain sickness

RISK CATEGORY DESCRIPTION PROPHYLAXIS RECOMMENDATIONS
Low
  • People with no prior history of altitude illness and ascending to <9,000 ft (2,750 m)
  • People taking >2 days to arrive at 8,000–9,000 ft (2,500–3, m), with subsequent increases in sleeping elevation <1,600 ft (500 m) per day, and an extra day for acclimatization every 3,200 ft (1,000 m)
Acetazolamide prophylaxis generally not indicated.
Moderate
  • People with prior history of AMS and ascending to 8,000–9,000 ft (2,500–2,750 m) in 1 day
  • No history of AMS and ascending to >9,000 ft (2,750 m) in 1 day
  • All people ascending >1,600 ft (500 m) per day (increase in sleeping elevation) at altitudes above 9,000 ft (2,750 m), but with an extra day for acclimatization every 3,200 ft (1,000 m)
Acetazolamide prophylaxis would be beneficial and should be considered.
High
  • History of AMS and ascending to >9,000 ft (2,750 m) in 1 day
  • All people with a prior history of HACE or HAPE
  • All people ascending to >11,400 ft (3,500 m) in 1 day
  • All people ascending >1,600 ft (500 m) per day (increase in sleeping elevation) above 9,000 ft (2,750 m), without extra days for acclimatization
  • Very rapid ascents (such as <7-day ascents of Mount Kilimanjaro)
Acetazolamide prophylaxis strongly recommended.

Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema.

DIAGNOSIS AND TREATMENT

Acute Mountain Sickness/High-Altitude Cerebral Edema

The differential diagnosis of AMS/HACE includes dehydration, exhaustion, hypoglycemia, hypothermia, or hyponatremia. Focal neurologic symptoms, or seizures, are rare in HACE and should lead to suspicion of an intracranial lesion or seizure disorder. Patients with AMS can descend ≥1,000 ft (300 m), and symptoms will rapidly abate. Alternatively, supplemental oxygen at 2 L per minute will relieve headache quickly and resolve AMS over hours, but it is rarely available. People with AMS can also safely remain at their current altitude and treat symptoms with nonopiate analgesics and antiemetics, such as ondansetron. They may also take acetazolamide, which speeds acclimatization and effectively treats AMS, but is better for prophylaxis than treatment. Dexamethasone is more effective than acetazolamide at rapidly relieving the symptoms of moderate to severe AMS. If symptoms are getting worse while the traveler is resting at the same altitude, he or she must descend.

HACE is a continuation of AMS and is diagnosed when neurologic findings, particularly ataxia, confusion, or altered mental status, are present. HACE may also occur in the presence of HAPE. People developing HACE in populated areas with access to medical care can be treated at altitude with supplemental oxygen and dexamethasone. In remote areas, descent should be initiated in any person suspected of having HACE. If descent is not feasible because of logistical issues, supplemental oxygen or a portable hyperbaric chamber should be used, if available.

High-Altitude Pulmonary Edema

Although the progression of decreased exercise tolerance, increased breathlessness, and breathlessness at rest is almost always recognizable as HAPE, the differential diagnosis includes pneumonia, bronchospasm, myocardial infarction, or pulmonary embolism. Descent in this situation is urgent and mandatory, and should be accomplished with as little exertion as is feasible for the patient. If descent is not immediately possible, supplemental oxygen or a portable hyperbaric chamber should be used. Patients with mild HAPE who have access to oxygen (at a hospital or high-altitude medical clinic, for example) may not need to descend to lower elevation and can be treated with oxygen at the current elevation. In the field setting, where resources are limited and there is a lower margin for error, nifedipine can be used as an adjunct to descent, oxygen, or portable hyperbaric therapy. A phosphodiesterase inhibitor may be used if nifedipine is not available, but concurrent use of multiple pulmonary vasodilators is not recommended.

Medications

In addition to the discussion below, recommendations for the usage and dosing of medications to prevent and treat altitude illness are outlined in Table 2-08. (See also the Self-Treatable Conditions section earlier in this chapter.)

Acetazolamide

Acetazolamide prevents AMS when taken before ascent and can speed recovery if taken after symptoms have developed. The drug works by acidifying the blood, which causes an increase in respiration and thus aids acclimatization. An effective adult dose that minimizes the common side effects of increased urination and paresthesias of the fingers and toes is 125 mg every 12 hours, beginning the day before ascent and continuing the first 2 days at altitude, or longer if ascent continues. Allergic reactions to acetazolamide are uncommon. As a nonantimicrobial sulfonamide, it does not cross-react with antimicrobial sulfonamides. However, it is best avoided by people with history of anaphylaxis to any sulfa. People with history of severe penicillin allergy have occasionally had allergic reactions to acetazolamide. The pediatric dose is 5 mg/kg/day in divided doses, up to 125 mg twice a day.

Dexamethasone

Dexamethasone is effective for preventing and treating AMS and HACE, and perhaps HAPE as well. Unlike acetazolamide, if the drug is discontinued at altitude before acclimatization, rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, with dexamethasone reserved for treatment, as an adjunct to descent. The adult dose is 4 mg every 6 hours. An increasing trend is to use dexamethasone for “summit day” on high peaks such as Kilimanjaro and Aconcagua, to prevent abrupt altitude illness.

Nifedipine

Nifedipine prevents HAPE and ameliorates it as well. For prevention, it is generally reserved for people who are particularly susceptible to the condition. The adult dose for prevention or treatment is 30 mg of extended release every 12 hours, or 20 mg every 8 hours.

Other Medications

Phosphodiesterase-5 inhibitors can also selectively lower pulmonary artery pressure, with less effect on systemic blood pressure. Tadalafil, 10 mg twice a day, during ascent can prevent HAPE and is being studied for treatment. When taken before ascent, gingko biloba, 100–120 mg twice a day, was shown to reduce AMS in adults in some trials, but it was not effective in others, probably due to variation in ingredients. Ibuprofen 600 mg every 8 hours was recently found to help prevent AMS, although it was not as effective as acetazolamide. However, it is nonprescription, inexpensive, and well tolerated.

PREVENTION OF SEVERE ALTITUDE ILLNESS OR DEATH

The main point of instructing travelers about altitude illness is not to eliminate the possibility, but to prevent death or evacuation due to altitude illness. Since the onset of symptoms and the clinical course are sufficiently slow and predictable, there is no reason for someone to die from altitude illness, unless trapped by weather or geography in a situation in which descent is impossible. Three rules can prevent death or serious consequences from altitude illness:

  • Know the early symptoms of altitude illness, and be willing to acknowledge when they are present.
  • Never ascend to sleep at a higher altitude when experiencing symptoms of altitude illness, no matter how minor they seem.
  • Descend if the symptoms become worse while resting at the same altitude.

For trekking groups and expeditions going into remote high-altitude areas, where descent to a lower altitude could be problematic, a pressurization bag (such as the Gamow bag) can be beneficial. A foot pump produces an increased pressure of 2 lb/in2, mimicking a descent of 5,000–6,000 ft (1,500–1,800 m), depending on the starting altitude. The total packed weight of bag and pump is about 14 lb (6.5 kg).

Table 2-08. Recommended medication doses to prevent and treat altitude illness

MEDICATION INDICATION ROUTE DOSE
Acetazolamide AMS, HACE prevention Oral 125 mg twice a day;
250 mg twice a day if >100 kg.
Pediatric: 2.5 mg/kg every 12 h
AMS treatment1 Oral 250 mg twice a day
Pediatric: 2.5 mg/kg every 12 h
Dexamethasone AMS, HACE prevention Oral 2 mg every 6 h or 4 mg every 12 h
Pediatric: should not be used for prophylaxis
AMS, HACE treatment Oral, IV, IM AMS: 4 mg every 6 h
HACE: 8 mg once, then 4 mg every 6 h
Pediatric: 0.15 mg/kg/dose every 6 h up to 4 mg
Nifedipine HAPE prevention Oral 30 mg SR version every 12 h, or
20 mg SR version every 8 h
HAPE treatment Oral 30 mg SR version every 12 h, or
20 mg SR version every 8 h
Tadalafil HAPE prevention Oral 10 mg bid
Sildenafil HAPE prevention Oral 50 mg every 8 h
Salmeterol HAPE prevention Inhaled 125 μg bid2

Abbreviations: AMS, acute mountain sickness; HACE, high-altitude cerebral edema; IV, intravenous; IM, intramuscular; HAPE, high-altitude pulmonary edema; SR, sustained release.
1Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone remains the primary treatment for that disorder.
2Should not be used as monotherapy and should only be used in conjunction with oral medications.

 

BIBLIOGRAPHY

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  8. Maggiorini M, Brunner-La Rocca HP, Peth S, Fischler M, Bohm T, Bernheim A, et al. 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.
  9. Pollard A, Murdoch D. The High Altitude Medicine Handbook. 3rd ed. Abingdon, UK: Radcliffe Medical Press; 2003.
  10. Pollard AJ, Niermeyer S, Barry P, Bartsch P, Berghold F, Bishop RA, et al. Children at high altitude: an international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001. High Alt Med Biol. 2001 Fall;2(3):389–403.
  11. Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003 Oct 23;349(17):1628–35.
  12. 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.
 
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