High-altitude exposure and its effects on special populations

Robert N. Suter, DO, Methodist Charlton Med- ical Center, Family Practice and Sports Medicine Center, 3500 W. Wheat- land Rd., Dallas, TX 75237.

E-mail address: robertsuter@mhd.com.

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High-altitude syndromes are a variety of conditions that affect as many as 90% of travelers to high altitudes. The severity of acute altitude illnesses range from self-limited to life-threatening and encompass a wide range of clinical and physiologic conditions. The key to treatment and prognosis of altitude illness is prompt identification of symptoms and mod- ification of activity. Family physicians should counsel patients traveling to high elevations about the risks of altitude illness and discuss safe practices and available medications for pre- vention of symptoms (Table 1).

‌Physiology: the effects of increasing altitude

The percentage of oxygen in the atmosphere remains constant (about 21%) at all elevations. As altitude increases and barometric pressure decreases, there is a proportional decrease in the partial pressure of oxygen.1 The decrease in average barometric pressure from 760 mm Hg at sea level to 523 mm Hg at 10,000 ft (3048 m) translates into a decrease in arterial oxygen saturation in non-acclimated healthy individuals from 97% to 90%. At 20,000 ft (6096 m), non-acclimated healthy individuals will average an oxygen saturation of 73%.2 This hypo- baric hypoxia is the basis for most altitude-related ill- nesses.

Immediate compensation mechanisms after ascent in- clude modest increases in cardiac output and increased pulmonary ventilation. Over time, the human body adapts to hypoxemia and individuals are able to function with less hypoxic effects. This multifactorial process involves phys- iologic changes over days, weeks, and months and is re- ferred to as acclimatization. Factors contributing to accli- matization include increased red blood cell mass, increased vascularity of tissues, and increased diffusion capacity in the lungs.2

For the non-acclimated traveler, exposure to modest al-titude may result in headache, tachypnea, and dizziness.These symptoms can develop within hours and are usuallyself-limited. Symptoms generally resolve in a few dayswithout intervention. Exposure to higher altitudes forhealthy individuals without proper acclimatization can re-sult in mental status change, cerebral edema, pulmonaryedema, coma, or death. For patients with certain cardiac andpulmonary conditions, exposure to modest altitudes mayincrease risks of complications from these diseases.

‌Acute mountain sickness

Acute mountain sickness (AMS) is a condition that af- fects individuals who rapidly ascend to altitudes above 6500 ft (2000 m). Hypobaric hypoxia leads to a cascade of physiologic changes that alter capillary permeability, leading to mild dependent edema and most likely a minimal degree of cerebral edema. Diagnosis of AMS involves the development of headache in a person who has recently arrived at the higher altitude plus one of the following symptoms: fatigue, dizziness, anorexia, nausea, vomiting, or dyspnea on exertion.4 For those ascending from sea level to 6500 ft (2000 m), the risk of symptoms is 25% for adults.4 Above 14800 ft (4500 m), risks of AMS symptoms increase to more than 50%.5

Table 1 Sample locations with elevations

Location

Los Angeles, California, USA Dallas, Texas, USA

Ayers Rock, Australia

Lake Louise, Alberta, Canada Mexico City, Mexico

Vail, Colorado, USA Machu Picchu, Peru

Mauna Kea Observatory, Hawaii, USA

South Mount Everest Base Camp, Nepal

Elevation

233 ft (71 m)

430 ft (131 m)

2831 ft (863 m)

5449 ft (1661 m)

7349 ft (2260 m)

8022 ft (2445 m)

8200 ft (2500 m)

13 800 ft (4205 m)

17 590 ft (5360 m)

In general, risk factors for AMS include rapid ascent, final altitude attained, and age younger than 60. Gender, physical fitness, and recent respiratory infections do not appear to contribute significantly to AMS.

A slow rate of ascent and time for acclimation are the best ways to prevent AMS.5 Travelers should be advised to stop ascent and rest at the onset of symptoms and to descend if symptoms do not improve or they worsen. Acetazol- amide, a carbonic anhydrase inhibitor, promotes the excre- tion of bicarbonate from the kidneys, decreases PaCO2, and increases PaO2.6 It has been shown to decrease AMS symp- toms. The usual recommended dose is 125 to 250 mg twice daily, starting at least 24 hours before ascent and continued until descent has begun.7

‌High-altitude pulmonary edema

High-altitude pulmonary edema (HAPE) is the most le- thal acute syndrome encountered at high altitudes. It occurs in about 4% of travelers above 8200 ft (2500 m), depending on individual adaptability and the ascent rate. Rapid ascent (more than 9800 ft [3000 m] in 3 days) is associated with a higher incidence of HAPE. Previous episodes of HAPE are associated with recurrence rates greater than 50%. Symptoms of HAPE usually appear between one and four days after reaching high altitude and include decreased exercise tolerance and dry cough progressing to productive cough with clear or blood tinged mucous.8 HAPE can develop with or without pre- ceding AMS symptoms.

Hypobaric hypoxia can cause heterogeneous areas of pulmonary vasoconstriction and vasodilatation.8 Concur- rently, worsening hypoxia leads to increased pulmonary artery pressure. Under these conditions, areas of pulmonary vasodilatation can develop capillary leakage and alveolar hemorrhage. The resulting pulmonary edema appears as patchy infiltrates on chest radiographs.9

Arrangements for descent should be made immedi- ately once HAPE is suspected, and pressurized suits and supplemental oxygen can be used if descent is delayed. Medications that can be considered for prophylaxis and treatment of HAPE include calcium channel blockers like nifedipine (Procardia, Pfizer, New York, NY) to prevent or blunt the hypoxia-induced rise in pulmonary artery pressure, and phosphodiesterase-5 inhibitors like tadalafil (Adcirca, United Therapeutics, Silver Spring, MD) to induce pulmonary arterial vasodilatation.9 There is some evidence that acetazol- amide may prevent calcium ion influx into pulmonary artery smooth muscle cells, leading to reduced hypoxic vasoconstric- tion. There is conflicting evidence whether glucocorticoids should be a first-line treatment for HAPE.6

Table 2 Physical and environmental effects of altitude change

Altitude (ft) Atmospheric PO2 (mm Hg) PaO2 (mm Hg)

PaO2 = partial pressure of oxygen in arterial blood.

Adapted from Gong H: Exposure to moderate altitude and cardio- respiratory diseases. Cardiologica 40:477, 1995.

‌and allows a greater surface area for oxygen to bind. Once the athlete returns to sea level, he is able to perform with greater intensity. A 1997 study using 39 competitive runners validated this theory by showing increased velocity and oxygen con- sumption in those who underwent four weeks of training at 4100 ft (1250 m) while residing at 8200 ft (2500 m).

‌Chronic mountain polycythemia

Monge disease, also known aschronic mountain polycythe-mia, is characterized by the development of excessive redblood cell mass for a given altitude. Typically, patientsbecome symptomatic with hemoglobin levels
20 mg/dL.7Characteristic complaints include headache, impairedconcentration, drowsiness, and chest congestion. Males areaffected more than females and most patients have otherchronic conditions that can cause hypoxemia such aschronic obstructive pulmonary disease (COPD) or sleepapnea. Therapies include phlebotomy, descent from alti-tude, and use of respiratory stimulants like acetazolamide.

‌Altitude and exercise

Exercise capacity is diminished with increased altitude largely because of decreased oxygen consumption at high elevations. Exercise capacity is linearly correlated to atmo- spheric oxygen (Table 2) up to an altitude of 13,000 ft (4000 m). At greater altitudes, the decrease in exercise ability is ex- ponential. Acclimatization improves exercise competence, but it does not return to baseline.

A 2009 study found dexamethasone (Decadron, Merck & Co., Inc., Whitehouse Station, NJ) treatment on the day before exercise and on the days of activity improves oxygen uptake in high altitudes.10 Investigators used echocardiog- raphy during low-intensity exercise to compare pulmonary artery pressures between participants who received dexa- methasone and those who did not. The dexamethasone group was found to have significantly decreased pulmonary artery pressures. This is thought to be related to corticoste- roid stimulation of nitric oxide (a vasodilator) in the pul- monary vasculature.

Along with prophylactic medications, lifestyle changes may also improve exercise capacity. Some studies support the idea of “Living high–training low”.11 This theory is based on increased erythropoietin levels in hypoxic condi- tions. Elevated erythropoietin expands red blood cell mass

‌Altitude and ultraviolet radiation

Ultraviolet radiation (UVR) increases by 6% to 8% for every 1000-meter increase in altitude. Acute reactions caused by UVR exposure include skin erythema and ocular keratitis.12 Reactions with long latency consist of various forms of skin cancers, skin aging, and cataract formation.12 Snow and ice cause UVR reflection and increase eye dam- age by a factor of 16. Patients hiking in snow-covered terrain should be instructed to avert their eyes from the ground and

wear sunglasses with UVR protection at all times.12

Fair-skinned people are at highest risk for altitude-re- lated skin cancer. Preventive measures for skin cancer in- clude wearing long sleeved shirts, avoiding the sun between 10 AM and 4 PM, and using sunscreen with SPF 30, which blocks both UVA and UVB radiation.

‌Altitude exposure in patients with chronic diseases

Patients with chronic diseases that can cause hypoxemia are at highest risk for experiencing exacerbations traveling or relocating to high altitudes.3 Patients with COPD and/or pulmonary hypertension may have increased dyspnea and 

should consider additional or increased supplemental oxy- gen. Patients with sleep apnea can experience hypoxemia during sleep. Appropriate use of continuous positive airway pressure equipment should be encouraged.3

The physiologic response to high-altitude exposure can result in a modest rise in blood pressure, mainly because of increased sympathetic tone. Hypertensive patients should be counseled about continuing their medications during travel to high altitudes.3

Patients with sickle cell trait should avoid extreme exer- tion without acclimatization to high altitudes. Sickle cell disease poses special risks, and travel to even modest alti- tudes can result in vaso-occlusive crises.3

Table 4 Children’s Lake Louise Acute Mountain Sickness Scoring System: Pediatric Symptom Score

Eating 0: Normal

1: Slightly less than normal 2: Much less than normal 3: Vomiting or not eating

Playfulness 0: Normal

1: Playing slightly less

2: Playing much less than normal 3: Not playing

Sleeping 0: Normal

1: Slightly less or more than normal 2: Much less or more than normal 3: Not able to sleep

Children were scored by combining the mean fussiness score (0 – 6) with the pediatric symptom score (0 –9). Total score >7 (including a fussiness score >4 and pediatric symptom score >3) is considered to be diagnostic of acute mountain sickness.

Adapted from Yaron M, Waldman N, Niermeyer S, et al: The diag- nosis of acute mountain sickness in preverbal children. Arch Pediatr Adoles Med 152:683, 1998

‌Altitude illness in children

In addition to adult patients with chronic diseases, infants and children are also highly susceptible to altitude sick-

ness. Factors that predispose children to altitude illness include reduced surfactant (preterm infants), reduced air- way diameters, and increased airway reactivity in re- sponse to hypoxia.13

According to a 2008 study, children are 20% more likely to develop AMS when compared with adults.14 They are also more likely to have increased tachycardia and de- creased oxygen saturation after rapid ascent.

AMS in young children presents differently than in adults. Signs and symptoms are less specific and include fussiness, poor sleep, vomiting, and decreased appetite.14 The Children’s Lake Louise AMS Score was developed in 1998 to assess AMS in preverbal children.13 It uses fussi- ness and a pediatric symptom score (symptoms include appetite, playfulness, and sleep) as diagnostic measures of AMS (Tables 3 and 4). A score greater than seven indicates altitude disease.

Pharmacological treatment for altitude illness has not been studied in children. In life-threatening situations, a pediatric dose of acetazolamide should be used.15 When cerebral edema or severe AMS is suspected, oxygen and dexamethasone should be given in combination with imme- diate descent15 (Table 5).

‌Altitude and pregnancy

Pregnant patients residing in high altitudes are at in- creased risk for diminished fetal growth and low-birth- weight infants. Chronic hypoxemia causes systemic va- sodilatation, which leads to decreased preload and, inevitably, lower maternal cardiac output.16 In altitudes above 4900 ft (1500 m), this may cause intrauterine growth restriction. There is an associated 65-g decrease in birth weight for every 1600 ft (500 meter) increase in altitude over 6600 feet (2000 m).17

Altitude related fetal growth is also affected by impaired maternal development during pregnancy. Studies in guinea pigs link chronic hypoxia to decreased vascular DNA synthe- sis.18 This causes incomplete remodeling of uteroplacental vessels and leads to decreased uterine blood flow at term.19

‌Table 5 SORT: Key Recommendations For Practice

Clinical recommendation Evidence rating References

A slow rate of ascent and appropriate time for acclimation are recommended to prevent AMS. B 5

Acetazolamide 125–250 mg twice daily, starting at least 24 hours before ascent and continued until descent begins has shown to decrease AMS symptoms.

In life-threatening situations of altitude illness in children, a pediatric dose of acetazolamide is recommended.

When cerebral edema or severe AMS is suspected in children, oxygen and dexamethasone should be given in combination with immediate descent.

B 7

C 15

C 15

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series.

For information about the SORT evidence rating system, go to: http://www.aafp.org/afpsort.xml.

Elevated blood pressure is another problem associated with high-altitude pregnancy. Pregnancy-induced hyperten- sion and preeclampsia are four times more common in women living in elevations above 8200 ft (2500 m). Inciting factors may include increased vascular reactivity, oxidative stress, and decreased prostaglandin production. Although much data has been collected, most reports are inconclusive in determining the etiology of hypertension in high-altitude pregnancy.19

‌Acknowledgments

The authors wish to thank Sarah Holder, DO, and Brett Johnson, MD, for their help in preparation of this manuscript.

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