You are in: eMedicine Specialties > Pediatrics: General Medicine > Pulmonology High-Altitude Cardiopulmonary DiseasesArticle Last Updated: Jul 31, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Ronald L Morton, MD, Associate Professor, Department of Pediatrics, University of Louisville School of Medicine; Consulting Staff, Pediatric Pulmonary Medicine, PSC Ronald L Morton is a member of the following medical societies: American College of Chest Physicians, American Medical Association, American Thoracic Society, and Kentucky Medical Association Coauthor(s): Mark C Duster, MD, Clinical Professor of Pediatrics, Division of Pediatric Cardiology, University of Colorado School of Medicine; Consulting Staff, The Children's Hospital and Memorial Hospital Editors: Girish D Sharma, MD, Associate Professor, Department of Pediatrics, Rush University Medical Center, Rush Children's Hospital; Director of Pediatric Pulmonary Section and Rush Cystic Fibrosis Center; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Heidi Connolly, MD, Associate Professor of Pediatrics and Psychiatry, University of Rochester;Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center; Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Associate Professor, Department of Clinical Pediatrics, State University of New York at Stony Brook; Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons Author and Editor Disclosure Synonyms and related keywords: high-altitude cardiopulmonary diseases, moderate altitude, high altitude pulmonary edema, high-altitude pulmonary edema, HAPE, air travel, hypoxia, altitude-induced hypoxia, chronic hypoxia, partial pressure of alveolar oxygen, PAO2, partial pressure of arterial oxygen, PaO2, acute mountain sickness, AMS, altitude sickness, altitude illness PHYSIOLOGIC EFFECTS OF ALTITUDESection 2 of 10
  Moderate, high, very high, and extreme high altitude are defined as follows:
In America, migration to the Western Mountain states has increased the number of children living at moderate-to-high altitudes. In isolated geographic areas of the world, adaptation to altitude has occurred over many generations. However, the population living in the United States is genetically mixed and has varied responses to the added stress of altitude-induced hypoxia. As the altitude increases, barometric pressure decreases. This decrease in barometric pressure affects the partial pressure of alveolar oxygen (PAO2). The percentage of oxygen remains stable at about 21%. At sea level, the partial pressure of oxygen available in the environment is equal to 0.21 times the barometric minus the water vapor pressure, ie, 760 - 47 mm Hg, or 149 mm Hg. PAO2 is 103 mm Hg. PAO2 is calculated by using the alveolar gas equation, as follows: PAO2 = FiO2 (PB - PH2O) - PACO2 [FiO2 + (1 - FiO2/R)], In this equation, FiO2 is the fraction of inspired oxygen, PB is the ambient barometric pressure, PH2O is the pressure exerted by water vapor at body temperature, PACO2 is the alveolar partial pressure of carbon dioxide, and R is the respiratory exchange quotient. The decrease in barometric pressure with increasing altitude reduces PAO2. PAO2 decreases from 103 mm Hg at sea level to 81 mm Hg in Denver, Colorado (5280 ft [1609 m]) and to 48 mm Hg at the top of Pikes Peak (14,110 ft [4301 m]). In mountain areas popular with vacationers, such as Leadville, Colorado (10,200 ft [3109 m]), the PAO2 is 61 mm Hg. Pneumonia, asthma, bronchiolitis, neonatal lung disease, pulmonary edema and a variety of other pulmonary diseases impair the efficiency of oxygen transfer from the alveolus to the pulmonary capillaries through ventilation-perfusion (V/Q) mismatch. Therefore, infants and children with pulmonary disease may have lower partial pressure of arterial oxygen (PaO2). Further decrements in PAO2 due to altitude result in proportionate decreases in the PaO2. Thus, infants and children with pulmonary disease may have a PaO2 on the steep slope of the oxygen dissociation curve. As a result, small changes in the PaO2 cause large changes in arterial oxygen saturation (SaO2). In infants and children with pulmonary disease who live at moderate altitudes, changes in oxygen saturation can be observed, even as the barometric pressure falls with passing storm systems. Newborns living at moderate altitudes have remarkably similar oxygen saturations during the first 24-48 hours of life. In Denver, Colorado, newborns younger than 48 hours have saturations of 85-97%, and in Leadville, Colorado, saturations during the first 24 hours are 85-93%. Afterwards, the range widens. This change probably reflects a variable adaptive response to the transition from a fetal circulation to an adult circulation. In Leadville, saturations in 1-week-old newborns are 83-93% during wakefulness and decrease to 75-86% during quiet sleep. By the age of 4 months, these values increase to 89-93% and 81-91% during waking and sleeping periods, respectively. Oxygen saturation values for healthy awake infants younger than 2 years are 89-94% in Colorado's Summit County ski area (9000 ft [2743 m]) and 90-99% in Denver. Newborns living at moderate altitudes are often sent home from the hospital with low-flow oxygen (25-50 mL/min given by nasal cannula) for 2-6 weeks to keep their oxygen saturations at an arbitrary level (>90%) for more than 90% of the time. This treatment may be unnecessary, but it is given to mimic sea-level oxygenation and to promote the transition from fetal to adult physiology. Physicians who care for infants and children with borderline oxygen saturations at their local altitude must consider these changes when they advise parents about travel to a high elevation. For excellent patient education resources, visit eMedicine's Environmental Exposures and Injuries Center. Also, see eMedicine's patient education article Mountain Sickness. EFFECTS OF CHRONIC HYPOXIASection 3 of 10
The chronic hypoxia associated with moderate altitudes can affect the fetus. Birth weights and uterine blood flow are decreased, placental morphology may be different. Moreover, the incidence of prematurity and pregnancy-induced hypertension is increased at high altitudes. Maternal smoking at high altitudes can have an additive effect. Travel by pregnant women from low to high altitude, and vice versa, can initiate premature labor because of the effects of changing barometric pressures on the amniotic sac. No difference in hematocrit levels is reported in neonates born at relatively high altitudes compared with those born at sea level. However, elevated neutrophil counts at high altitudes are reported. In some infants, the normal decrease in pulmonary vascular resistance is delayed. In addition, echocardiographic evidence of elevated right-sided pressures persists for several days, or sometimes weeks, without the clinical findings of primary pulmonary hypertension of the newborn. In addition, the frequency of delayed closure of the ductus arteriosus increases. Electrocardiographic findings of right ventricular hypertrophy often persist during the first months of life. PULMONARY VASCULAR HYPERREACTIVITYSection 4 of 10
An estimated 20% of the general population responds to a hypoxic stimulus with a marked increase in the pulmonary vascular resistance; this phenomenon is known as hypoxic pulmonary vasoconstriction. Individuals with these reactions are referred to as hyperreactors. Clinically significant increases in the right ventricular pressure can be measured in individuals who have an elevated pulmonary vascular resistance secondary to the hypoxic environment of increasing altitude. Factors that exacerbate hypoxic pulmonary vasoconstriction are acute pulmonary disease, exercise, upper airway obstruction, or congenital heart defects associated with an increase in pulmonary blood flow or restriction of pulmonary venous return. CLINICAL PRESENTATIONSection 5 of 10
Acute mountain sicknessEach winter, millions of people ski at altitudes of 8202-11,483 ft (2500-3500 m), in Colorado. Each summer, more than 250,000 people visit the summit of Pikes Peak (14,110 ft [4301 m]). On arriving at high altitude, most individuals note a sensation of breathlessness secondary to the hypoxia-induced hyperventilation and palpitations from an increased heart rate. These are normal physiologic responses. However, within 6-96 hours after their arrival, many individuals notice having a headache, insomnia, anorexia, nausea, vomiting, dizziness, dyspnea, and loss of coordination. These symptoms represent acute mountain sickness (AMS), a spectrum that, in its severest form, can manifest as high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema. Fortunately, for most individuals, the symptoms are annoying but not incapacitating. The duration of these symptoms is brief, usually only several days. The development of AMS is directly related to the speed and height of the ascent and inversely related to age, as AMS is most common in the young. Symptoms observed in preverbal children include increased fussiness, decreased appetite, poor sleep patterns, and decreased playfulness. High-altitude pulmonary edemaHealthy children and active young adults exposed to moderate altitudes are at risk for HAPE. This is an unusual form of noncardiogenic pulmonary edema that develops after an ascent to altitudes generally above 8000 ft (2438 m). The ascent is often rapid and accomplished by means of either automobile or aircraft. In this situation, exposure to high altitude typically lasts several hours, most commonly after an overnight stay. Fatigue, dyspnea, nausea, and sleeplessness progress to visible cyanosis, tachypnea, and cough productive of copious sputum. Shock and death can result if the symptoms are not recognized and treated. Chest radiographs depict patchy infiltrates consistent with pulmonary edema (see Image 1). A study done in La Paz, Bolivia (11,975 ft [3650 m]) showed echocardiographic evidence of small (<5 mm) pericardial effusions in approximately half of the subjects after an ascent to altitude. When investigators analyzed bronchoalveolar lavage (BAL) fluid obtained from patients with HAPE, they found increased levels of protein and albumin with a mild increase in RBCs, as compared with HAPE-resistant and low-altitude values. Pathophysiology of HAPE Current thinking regarding the pathophysiology of HAPE centers around the increased pulmonary edema secondary to increased alveolar-capillary permeability and elevated hydrostatic pressures. Swenson et al (2002) observed protein-rich transudative fluid in the BAL fluid of 3 patients who developed HAPE.1 In HAPE-susceptible patients, BAL samples appeared to contain normal numbers and differential values of leukocytes, arachidonic acid metabolites, and proinflammatory cytokines (interleukin-1 and tumor necrosis factor). These findings indicated that the primary event leading to the changes observed in HAPE is increased capillary hydrostatic pressures and not a proinflammatory cascade. In an intriguing study, researchers measured differences in nasal potentials among HAPE-susceptible individuals and HAPE-nonsusceptible control subjects after an ascent to high-altitude (14,957 ft [4559 m]).2 In both groups, the total nasal potential and the chloride-sensitive portion of nasal potential increased at high altitude. However, after the subjects were treated with normobaric hypoxia for 6 hours at high altitude, the investigators observed no change in total or chloride-sensitive nasal potentials in HAPE-susceptible individuals compared with control subjects. The researchers postulated that abnormal transepithelial ion transport (increased secretion of chloride ions) may help compensate for the drying or crusting of the nasal mucosa seen in individuals at high altitude. Risk factors for HAPE Altitude may adversely affect chronic illnesses such as sickle cell disease, cystic fibrosis, bronchopulmonary dysplasia, and type 1 diabetes mellitus. Effects of altitude on individuals with type I diabetes include decreased glycemic control, poor appetite or anorexia, and poor reliability with glucose meters. Recurrent episodes of HAPE in children with obstructive sleep apnea (OSA) secondary to obesity have been seen at relatively low elevations (7000 ft [2134 m]) and probably reflect worsened desaturations during sleep. In a study by Das et al (2004) in Denver, Colorado, 10 children living at high-altitude (5282-10,006 ft [1610-3050 m]) underwent cardiac catheterization after fully recovering from HAPE.3 Five patients had undetected cardiac defects before the onset of HAPE, and one had OSA secondary to obesity. PROPHYLAXIS AND TREATMENT OF HIGH-ALTITUDE ILLNESSSection 6 of 10
Staged and graded ascent To prevent AMS, one may use the techniques of staged and graded ascent. Staged ascent involves the person becoming acclimatized at a base camp over 2-3 days before ascending. Physiologic mechanisms that lead to acclimatization to high altitude include hyperventilation, increased RBC concentrations in the blood (polycythemia), increased cellular oxidative enzyme levels, and a leftward shift of the oxygen dissociation curve (which improves loading of oxygen in the pulmonary capillaries). After 5 days of exposure to high altitude (4559 m), levels of 2, 3-diphosphoglycerate levels (2,3-DPG) rise substantially (3.5 µM/g of hemoglobin). Despite this rise in 2,3-DPG levels, hemoglobin-oxygen affinity remains unchanged. Graded ascent involves ascent over limited elevation per day. Guidelines suggest that, once a person is above 8000 ft (2438 m) elevation, he or she should ascend at a rate of 1000-2000 ft/d (305-610 m/d). When a person has symptoms of AMS (headache, fatigue, dizziness, nausea, insomnia), treatment involves descent to lower altitude and oxygenation. Symptoms, oxygenation saturations, and chest radiographic findings usually improve dramatically. Pharmacologic therapies to prevent and treat high-altitude illness Tables 1 and 2 summarize the pharmacologic therapies used to prevent and treat high-altitude illness. Successful prophylaxis has been reported with acetazolamide (Diamox) and nifedipine for individuals with recurrent episodes. A recent study reported in the Archives of Internal Medicine showed no difference in the incidences of AMS between subjects treated with ginkgo biloba and those given placebo.4 However, other studies have shown a beneficial effect of ginkgo biloba in the prevention of AMS. Researchers performed a double-blind placebo-controlled trial in mountain climbers at low altitude while they were breathing hypoxic gas and while they were at an elevation of (17,716 ft [5400 m]). Sildenafil, a selective phosphodiesterase-5 inhibitor, reduced hypoxic pulmonary hypertension at rest and during exercise and increased maximum exercise capacity and cardiac output. The increase in performance was hypothesized to be secondary to increased cardiac output due to reduced right ventricular afterload, which increased oxygen transport to the exercising muscles. Some have suggested that the improvement may have been secondary to factors other than an improvement in altitude-induced right ventricular dysfunction. Examples are decreased lung interstitial edema due to the inhibition of hypoxic pulmonary venous constriction and the attenuation of hypoxia-induced depression of left ventricular diastolic function. Limited data are available for children. Table 1. Therapies to Prevent and Treat AMS
Source.—Adapted from Hackett and Roach, 2001.5 Table 2. Therapies to Prevent and Treat HAPE
Source.—Adapted from Hackett and Roach, 2001.5 CONGENITAL HEART DISEASESection 7 of 10
The murmur from a ventricular septal defect is caused by flow disturbance as blood moves from the high-pressure left ventricle through the defect into the low-pressure right ventricle. At high altitudes, delayed reduction in fetal pulmonary vascular resistance and a genetic predisposition to hyperreactivity may maintain an elevated pulmonary vascular resistance and result in right-sided pressure near systemic levels. Therefore, even with a large ventricular septal defect, atrial septal defect, or patent ductus arteriosus, little or no left-to-right shunting may occur, and no typical cardiac murmur may be detected. A child with such findings may not have the typical symptoms associated with increased pulmonary blood flow, such as sweating, tachypnea, and delayed growth. Therefore, large defects can be missed in this group of patients. One must maintain a high index of suspicion and exclude an increased right ventricular impulse when a single loud second heart sound is detected during clinical examination. The incidence of patent ductus arteriosus and atrial septal defect is reported to be highest in populations living at moderate altitudes. Patients with cardiac defects who depend on a low pulmonary vascular resistance, such as those who have received a caval-pulmonary or Glenn shunt or undergone a Fontan operation, may be adversely affected by altitude-induced hypoxia and its effect on pulmonary vascular resistance. As a general rule, patients who have difficulty with postoperative hemodynamics at sea level have even more difficulty at rising altitudes. Patients with primary pulmonary hypertension and Eisenmenger syndrome probably have greater difficulty at moderate altitudes than at sea level, and their disease may progress more rapidly at altitude than at sea level. Patients with a large ventricular septal defect who have substantially increased pulmonary vascular resistance secondary to the hypoxic environment at moderate altitudes may be at risk for increased symptoms when they travel to relatively low altitudes. Improved oxygenation may decrease pulmonary vascular resistance and increase pulmonary blood flow and related symptoms. These changes can be controlled by increasing diuretic therapy while such patients are at low altitudes. AIR TRAVELSection 8 of 10
Traveling by means of a commercial aircraft is equivalent to visiting Colorado Springs, Colorado (6200 ft [1890 m]); Santa Fe, New Mexico (7000 ft [2134 m]); or any location with an altitude of 6000-8500 ft (1828-2438 m) for the duration of the flight. Studies in adults have confirmed the expected 6-8% decrease in baseline saturations. Furthermore, the duration is brief, and the journey is not associated with prolonged sleep-induced hypopnea. As expected, patients with cyanosis who tolerate living at moderate altitudes also tolerate commercial air travel, whereas patients who require oxygen supplementation at moderate altitudes should continue to receive oxygen during travel to relatively low altitudes. In addition, increasing oxygen-flow prescriptions during air travel is reasonable for patients receiving long-term oxygen therapy at sea level. Patients at risk because of air travel are those who were previously intolerant to brief decreases in oxygenation. In the authors' experience, patients at greatest risk are those with an elevated pulmonary vascular resistance who do not meet the criteria for surgery (eg, a Fontan procedure) at a moderate altitude and who are referred to an institution at sea level for surgery. The authors' postoperative recommendations include transfer of these patients back to a moderate altitude with supplemental oxygenation and close observation during the first 72 hours of their return. Regulations of most airlines do not allow patients to use their own oxygen sources. Therefore, air travelers must make arrangements with the airline and obtain clearance from the airline's medical director before they fly. The Aerospace Medical Association lists the following cardiovascular contraindications to commercial air travel:
Additional information can be found from Aviation Health Guide for General Practitioners and Medical Advice for Commercial Air Travelers. MULTIMEDIASection 9 of 10
REFERENCESSection 10 of 10
High-Altitude Cardiopulmonary Diseases excerpt Article Last Updated: Jul 31, 2007 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
