High-altitude disease: Unique pediatric considerations

INTRODUCTION — This topic will review the unique pediatric aspects of high-altitude illness (HAI).

The different types of HAI, their pathophysiology, and methods for prevention and treatment are discussed separately.

●(See "High-altitude illness: Physiology, risk factors, and general prevention".)

●(See "Acute mountain sickness and high-altitude cerebral edema".)

●(See "High-altitude pulmonary edema".)

●(See "Approach to patients with heart disease who wish to travel by air or to high altitude".)

BACKGROUND — Every year the beauty and recreational opportunities of the mountains attract millions of visitors from lowland elevations to high-altitude destinations worldwide. Resort towns in the Western United States alone attract over 30 million visitors annually, generally to sleeping elevations of 2000 to 3000 m (6560 to 9840 feet). Many more millions visit cities at these elevations, including several large cities in South America and Asia situated above 3000 m (9840 feet) (table 1) [1]. Most of these destinations can be reached within a day using modern means of transportation. Many of these mountain travelers are children.

Rapid ascents to high altitude place the unacclimatized child at risk for developing high-altitude illness (HAI). Clinicians working in mountainous areas must familiarize themselves with the presentation and management of HAI in children, while all health care workers who advise travelers need to understand the best prevention strategies and treatment options. The clinician advising families with children on wilderness and high-altitude trips should offer an organized pre-trip evaluation that evaluates individual risk factors, provides recommendations for measures to prevent HAI, and determines whether prophylactic medication is appropriate [2]. (See 'Patient risk assessment and mitigation' below and 'Prevention and pharmacologic prophylaxis' below and 'Travel advice for parents' below.)

HIGH-ALTITUDE PHYSIOLOGY — Diminished inspired partial pressure of oxygen (PIO2) at altitude is the direct result of lower barometric pressure. As PIO2 decreases, so does the partial pressure of alveolar oxygen (PAO2), arterial PO2 (PaO2), and arterial oxygen saturation (SpO2), resulting in tissue hypoxia. This form of hypoxia is termed hypobaric hypoxia, and it represents the initial cause of high-altitude illness (HAI). The physiology of HAI is discussed in more detail separately. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'High altitude physiology'.)

PATIENT RISK ASSESSMENT AND MITIGATION

Risk factors — Risk factors for high-altitude illness (HAI) that are common to children and older patients include rapid rate of ascent, the absolute altitude achieved, the degree of physical exertion, cold weather, and history of prior HAI. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Risk factors'.)

Risk factors found more commonly in children include the following:

●Acute illness with upper or lower respiratory tract infection or other infection (eg, otitis media) [3-7]

●Congenital cardiopulmonary disease [8,9] (eg, unilateral absence of pulmonary artery) [10,11]; pulmonary hypertension [3]; cardiac shunts (atrial septal defect, ventricular septal defect, patent foramen ovale)

●Down syndrome, especially with obstructive sleep apnea [3,12]

●Systemic diseases that compromise respiratory function (eg, bronchopulmonary dysplasia [13], cystic fibrosis [14], sickle cell anemia [15], severe scoliosis [16], neuromuscular disease, obstructive sleep apnea)

●Full-term infants less than six weeks of age (premature infants less than 46 weeks post-conceptual age) [13,17]

●Premature and full-term infants who have experienced respiratory distress in the immediate postnatal period; infants up to one year of age with a history of oxygen requirement or pulmonary hypertension [13,17]

●Premature infants with a history of oxygen requirement, bronchopulmonary dysplasia, or pulmonary hypertension [13,17]

●Susceptibility to re-ascent (patient lives at high altitude [above 2500 m, 8200 feet], travels to low altitude for a short time period [eg, several days to weeks], and then returns home) [18,19]

Recommendations for ascent — Healthy children should ascend to high altitudes slowly [20] and only if rapid descent is possible in the event of problems. Children have ascended safely as far as 15,580 to 18,040 feet (4570 to 5500 m). If the child has an acute upper respiratory infection, lower respiratory infection, or otitis media, extra caution should be exercised during rapid ascent above 2500 m (8200 feet) [20]. (See 'Risk factors' above.)

General measures to prevent HAI in children are derived from adult experience and include (see "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Prevention of high-altitude illness'):

●Gradual ascent – Avoid abrupt ascent to sleeping altitudes above 2800 m (9200 feet).

●Acclimatization – Take measures to permit the child to become accustomed to higher altitudes:

•When ascending above 2500 m (8200 feet), do not spend subsequent nights at elevations more than 500 m higher than the previous night.

•Include a rest day (no ascent and no vigorous activity) for every 1000-m (3280-foot) increase in sleeping altitude.

•When possible, spend five to seven days at an intermediate altitude (typically 3000 to 4000 m) before proceeding to higher elevations.

Recommendations for children with pre-existing illnesses — Infants and children with certain underlying diseases are at particular risk for significant complications, including exacerbation of their underlying condition or life-threatening high-altitude pulmonary edema (HAPE):

●Sickle cell disease – Patients with sickle cell disease who live at sea level should ascend cautiously if at all, as sickle cell crisis can occur at altitudes as low as 1500 m (4920 feet) [1]; symptoms are common at 2300 m (7544 feet). Patients with sickle cell trait may become symptomatic from splenic sequestration or infarct at altitudes over 2500 m (8200 feet) [21-23].

●Asthma – Asthmatic patients may find that their symptoms improve because of a relative lack of allergens at high altitudes. While theoretically bronchospasm induced by cold or exercise may worsen [24], asthmatics appear to have no higher risk of altitude illness than non-asthmatics [21,25,26].

●Other chronic lung disease – Children with chronic lung disease, such as cystic fibrosis or bronchopulmonary dysplasia, are at increased risk of significant hypoxemia and should undergo oxygen saturation monitoring during altitude travel. [27,28]. Again, ascent should be slow and cautious. One author suggests that children who are able to play and run without shortness of breath at home are unlikely to have problems lower than 3650 m (11,972 feet) [21]. Supplemental oxygen may enable these children to travel to altitudes between 2000 to 3000 m (6560 to 9840 feet) [26]. (See 'High-altitude pulmonary edema' below and "High-altitude pulmonary edema", section on 'Epidemiology and risk factors'.)

●Cardiac lesions with increased pulmonary artery blood flow – Infants and children with cardiac lesions involving an increase in pulmonary blood flow or pulmonary hypertension also are at increased risk for HAPE. Isolated absence of the right pulmonary artery has been associated with development of HAPE at relatively low altitudes [10,29]. Thus, these patients should avoid exposure to high altitude. Children with other cardiac defects that increase pulmonary flow, such as atrial and ventricular septal defects and patent ductus arteriosus, may be at increased risk for HAPE as well [25,30]. (See 'High-altitude pulmonary edema' below and "High-altitude pulmonary edema", section on 'Epidemiology and risk factors'.)

On the other hand, although an association has been reported between patent foramen ovale (PFO) and HAPE, causality is not established, and PFO is not considered a contraindication to high altitude exposure [31].

●Down syndrome – Children with trisomy 21 have increased pulmonary vascular reactivity and a higher risk of pulmonary hypertension in addition to an increased risk of congenital cardiac defects. They also are more likely to have obstructive sleep apnea and hypoventilation. These factors may be responsible for a higher risk of HAPE development, even at low altitudes [3]. Thus, travel to high altitude with infants with trisomy 21 should be approached cautiously or avoided, if possible [25].

●Young infants and older infants with a history of oxygen therapy or pulmonary hypertension – Infants younger than six weeks of age and those under one year of age with a history of oxygen requirement or pulmonary hypertension have several unique physiologic limitations that place them at risk for hypoxemia, pulmonary hypertension, and, in extreme cases, right heart failure when rapidly exposed to high altitude (3000 to 5000 m [9840 to 16,400 feet]) [13,32]. (See 'Risk factors' above and 'High-altitude cerebral edema' below.)

HIGH-ALTITUDE ILLNESS IN CHILDREN — Acute mountain sickness (AMS) is the most common of the altitude illnesses. The risk of AMS depends upon individual susceptibility, the elevation reached, and the rate of ascent. Thus, while AMS is uncommon below 2000 m (6560 feet), it is quite common (approximately 25 percent incidence in adults and children) at sleeping elevations between 2000 and 3000 m (6560 to 9840 feet), where some cities and the majority of ski resorts in the Western United States are located (table 2 and table 1) [33-36]. In most instances, pediatric high-altitude illness (HAI) can be prevented with appropriate precautions or treated before serious illness, such as high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE), occurs.

At higher altitudes, small observational studies initially suggested that AMS may occur more frequently in children and adolescents than in adults with ascent in a few hours from sea level to at elevations above 3500 m [33,37,38]. However, larger studies have found either the same incidence as adults or less:

●In one observational study that evaluated the impact of fast ascent among families with 157 children ascending 3450 m in 2.5 hours, AMS in children was lower (30 percent), compared with adolescents (37 percent) and adults (45 percent) [39]. In addition, familial clustering was consistent and explained 25 to 50 percent of variability, the first evidence of hereditary influence for AMS.

●In a separate study of 48 children who underwent the same rapid ascent profile, AMS incidence was 25 percent at 6 hours, 21 percent at 18 hours, and 8 percent at 42 hours; all AMS was mild, and none required descent [40].

●A third study took 118 children ages 6 to 16 in 2.5 hours to 3450 m in the Alps and found only a 6 percent incidence of AMS at 40 hours, confirming the rapid resolution of AMS without treatment [41].

Thus, the overall risk of AMS appears to be the same or less in children compared with adults, and as in adults, slower ascent rates reduce illness.

The epidemiology of AMS in adults is discussed in greater detail separately. (See "Acute mountain sickness and high-altitude cerebral edema", section on 'Epidemiology'.)

Acute mountain sickness — AMS and HACE are generally considered to represent two points along a single spectrum of disease, with the same underlying pathophysiology. Although some aspects of this pathophysiology remain unclear, the concept that AMS/HACE represents a continuum, and that AMS can progress to fatal HACE, fits with clinical experience and is helpful for management. However, especially in young children and infants, recognition of AMS is hampered by the difficulty in recognizing symptoms (eg, headache) in a nonverbal child. Certain pediatric patients (eg, infants under six weeks of age, children with congenital heart disease, cystic fibrosis, or Down syndrome) also have a greater susceptibility for life-threatening disease. (See 'Recommendations for children with pre-existing illnesses' above.)

Clinical manifestations — Signs of AMS in young children are nonspecific and include decreased playfulness, pallor, fussiness, poor sleep, vomiting, and decreased appetite [27,34,35].

In older children and adolescents, signs of HAI are similar to adults; the most common symptom is headache, which may be accompanied or followed by shortness of breath, dizziness, poor sleep, anorexia, fatigue, nausea, and vomiting [36]. The presentation and diagnosis of AMS in adults is discussed in greater detail separately. (See "Acute mountain sickness and high-altitude cerebral edema", section on 'Presentation and diagnosis'.)

The onset of AMS is usually delayed for 6 to 12 hours following arrival at high altitude but can occur as rapidly as 1 to 2 hours or as late as 24 hours [42,43]. If there is no further ascent, symptoms are often most severe after the first night, generally resolve in one day with rest (eg. no skiing or hiking), and do not recur at the same altitude. AMS may reappear upon ascent to higher altitudes. On occasion, symptoms of AMS may persist for days despite no further ascent. In such cases, descent is required if there is no improvement with standard treatment. (See "Acute mountain sickness and high-altitude cerebral edema", section on 'AMS treatment'.)

Supplemental oxygen may be used to support the clinical diagnosis of AMS. Providing 2 to 4 L/minute of oxygen by nasal cannula for 15 to 20 minutes prior to other interventions should markedly improve headache and other symptoms, as does a brief excursion to a lower altitude, especially in younger children.

The onset of symptoms more than two days after arrival at a given altitude, absence of headache, dyspnea at rest, and failure to improve rapidly with supplemental oxygen should prompt the clinician to search for an alternative diagnosis. No radiographic or laboratory testing is typically required unless the diagnosis of AMS is unclear. Other etiologies to consider include carbon monoxide poisoning, migraine, dehydration, exhaustion, hyponatremia, viral syndrome, and bacterial infection (eg, pneumonia or otitis), and occult trauma such as corneal abrasion. In young children, AMS is a diagnosis of exclusion.

AMS alone does not cause an elevation in body temperature and an appropriate evaluation for fever based upon age and immunization status is warranted in febrile children at altitude. AMS is often a diagnosis of exclusion in this group. The clinician should pay close attention to the child's signs and response to oxygen, and when in doubt should err on the side of a longer observation period before attributing symptoms to a condition other than AMS. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management", section on 'Well-appearing patients'.)

Diagnosis — The diagnosis of AMS relies on typical clinical manifestations of vomiting, malaise, headache, fussiness, and/or difficulty breathing that occurs within 24 hours of arrival at high altitude without evidence of another cause (eg, otitis media, pneumonia, or viral illness). The diagnosis is supported by rapid improvement with supplemental oxygen.

Treatment — The treatment of HAI in children follows the same principles as in adults [44]. It is important that group members and the afflicted individual remain alert for any symptoms or signs of worsening disease, particularly at elevations where AMS may rapidly progress to HACE (above 4000 m [13,120 feet]). (See "Acute mountain sickness and high-altitude cerebral edema", section on 'AMS treatment' and "Acute mountain sickness and high-altitude cerebral edema", section on 'HACE treatment'.)

Treatment of HAI is based upon symptom severity:

●Mild AMS – Mild AMS can be treated conservatively with symptomatic care (eg, acetaminophen or ibuprofen for headache, ondansetron for vomiting, and fluid intake).

●Moderate AMS – Moderate AMS (ie, AMS not resolving with rest or symptomatic care) may require supplemental oxygen (if available) and specific medication (table 3).

●Persistent or worsening AMS symptoms – Pediatric patients whose symptoms persist or worsen, should descend.

•HAPE – As with adults, treatment of HAPE requires descent and/or supplemental oxygen. (See 'High-altitude pulmonary edema' below.)

•HACE – In the exceedingly rare scenario of suspected pediatric HACE, immediate descent is indicated. Supplemental oxygen, dexamethasone, and hyperbaric therapy may temporize illness until evacuation is completed (table 3). (See "Acute mountain sickness and high-altitude cerebral edema", section on 'HACE treatment'.)

Prevention and pharmacologic prophylaxis — Acclimatization and slow ascent are by far the best ways to avoid AMS. Travelers who ascend to high altitudes in order to ski, hike, or climb should be encouraged to limit their activity for the first few days at altitude. Adequate hydration also is important although overhydration should be avoided so that hyponatremia does not develop.

A recommended approach to prevent AMS (and other altitude-related syndromes) is to ascend no more than 500 m (1640 feet) per day when already above 2500 m (8200 feet). This approach is particularly important in individuals in whom AMS or other altitude problems have occurred with previous ascents; such individuals are more likely to suffer from these disorders on subsequent exposure to high altitude. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Preacclimatization'.)

Acetazolamide prophylaxis — Prophylactic pharmacologic therapy with acetazolamide has not been studied in children who undergo rapid ascent. One prospective observational study of 48 older children and adolescents with rapid ascent to 3450 m found that 18 (38 percent) developed symptoms of AMS, but that no patient required specific pharmacologic treatment or evacuation to a lower altitude [40]. This study suggests that prophylactic therapy for AMS may be unnecessary in most healthy older children and adolescents who are not acclimated.

If acetazolamide is used, duration of treatment depends upon the ascent profile. Individuals ascending to a fixed sleeping altitude (eg, recreational skiers) may start acetazolamide the day before ascent and continue treatment for 48 hours. If further ascent is planned, acetazolamide can be continued until maximum elevation is attained. Acetazolamide can also be taken episodically to speed acclimatization at any point while gaining altitude or to treat mild AMS. Symptoms do not recur when the drug is discontinued. Although the danger of AMS passes after a few days of acclimatization, acetazolamide may still be useful for sleep. (See "Acute mountain sickness and high-altitude cerebral edema", section on 'Pharmacologic prevention of AMS/HACE' and "Acute mountain sickness and high-altitude cerebral edema", section on 'Acetazolamide'.)

The pediatric dose of acetazolamide for prevention of AMS is 2.5 mg/kg per dose twice a day (maximum single dose 125 mg) (table 3). The contraindication due to allergy to antibiotic sulfonamides has been challenged, and the risk of anaphylaxis from acetazolamide in such patients appears unlikely. On the other hand, a history of Stevens-Johnson reaction to an antibiotic sulfonamide is caused by a different mechanism than anaphylaxis, and some clinicians choose not to administer acetazolamide in these patients. (See "Sulfonamide allergy in HIV-uninfected patients", section on 'Between sulfonamide antimicrobials and nonantimicrobials'.)

High-altitude cerebral edema — HACE is a rare life-threatening altitude disease that theoretically may occur in children [45]. In adults, HACE generally occurs in individuals with AMS and/or HAPE at elevations over 3000 to 3500 m (9840 to 11,480 feet) and is discussed in more detail separately. (See "Acute mountain sickness and high-altitude cerebral edema" and "High-altitude pulmonary edema", section on 'Epidemiology and risk factors'.)

High-altitude pulmonary edema — HAPE is a form of noncardiogenic pulmonary edema that may be fatal. The syndrome generally occurs among individuals who rapidly ascend to sleeping altitudes above 2500 m (8200 feet) [1], although altitude alone should not be used to exclude the diagnosis [46]. The incidence of HAPE in lowland children visiting high-altitude resorts in the Rockies is unknown. The overall incidence of HAPE is approximately 1 in 10,000 visitors, and many of these are children [46].

As illustrated by the following studies, children who live at high altitudes and then temporarily descend are at risk for HAPE. Children with an acute viral upper respiratory tract infection who travel to or live at high altitude may have a slightly increased risk [4,5,18,28,47-49]:

●In a retrospective review of 39 episodes in 32 patients hospitalized for HAPE in Leadville, Colorado, the highest permanent community in the United States at an altitude of 10,152 feet (3094 m) above sea level, 25 of the 32 patients were under 15 years of age, and all but two victims were permanent residents of Leadville [18]. The majority of episodes followed a brief descent to lower altitudes; in three patients, the descent period was only 24 hours. A decrease in the incidence of HAPE was noted with increasing age, suggesting that an undefined response of the pediatric pulmonary vasculature to altitude may contribute to childhood frequency of HAPE.

●Similar childhood predominance of HAPE also was described in a study of 97 victims in the Andes; children between the ages of 2 and 12 years had more severe pulmonary edema than did older patients [49].

●An observational study reported cardiac catheterization results for seven children who lived in Leadville, Colorado and who had recovered from HAPE [4]. Three children had HAPE in association with a viral upper respiratory tract infection without any prior descent. These patients had a greater mean pulmonary artery pressure in response to hypoxia.

●Upper respiratory infection (colds, bronchitis, or otitis media) in the period immediately preceding ascent also appears to predispose children who live at low altitude to development of HAPE; this phenomenon may be related to the release of inflammatory mediators during infection [5]. Furthermore, children have greater pulmonary vascular reactivity than adults, and inflammation increases capillary permeability. Together, this causes proportionally more pulmonary edema in children.

Clinical manifestations — In young children, HAPE presents as increasing respiratory distress over one to two days, but may develop more precipitously. Young children and infants may manifest only pallor and depressed consciousness or other nonspecific symptoms such as increased fussiness, crying, decreased appetite, decreased playfulness, disrupted sleep, and possibly vomiting [6,25,34,35]. In infants, increased pulmonary artery pressure and fetal shunting, with or without HAPE, can cause severe hypoxemia. Thus, the pulse oximetry may be low relative to normal values at that altitude. The table provides mean values and range of normal values for arterial blood gas results and oxygen saturation at different altitudes and by exposure to assist with interpretation (table 4). (See "High-altitude pulmonary edema", section on 'Pathophysiology'.)

In older children and adolescents, HAPE may present as an insidious cough, breathlessness out of proportion to work, breathlessness at rest, and production of frothy, often rusty, sputum. Physical findings at this time include rapid breathing, cyanosis, tachycardia, and diffuse crackles on auscultation of the lungs. When available, chest radiograph reveals diffuse interstitial changes typical of noncardiogenic pulmonary edema. (See "Noncardiogenic pulmonary edema".)

HAPE may appear insidiously over the course of several hours or days, but may also present explosively. It can occur without preceding AMS. In addition, certain individuals develop HAPE upon repeated ascents above the same altitude and may, therefore, have an altitude threshold beyond which they are susceptible to HAPE. Individuals who have experienced HAPE in the past have demonstrated genetic or physiological susceptibility and are therefore at risk for recurrence with ascent to the same altitude and at the same rate. Recurrence in these individuals may be avoided with a slower rate of ascent.

Of note, elevation in body temperature over 38.3°C from HAPE alone is unusual; higher temperatures warrant evaluation for a concurrent infection or another diagnosis. Young children with a higher fever should be assessed based upon age and immunization status. However, respiratory infection and HAPE can coexist. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management", section on 'Well-appearing patients'.)

The differential diagnosis in children includes pneumonia, heart failure, and other forms of non-cardiogenic pulmonary edema. (See "Pathophysiology of left-to-right shunts" and "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis" and "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis" and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical presentation'.)

Diagnosis — The diagnosis of HAPE relies on typical clinical manifestations of cough, dyspnea, frothy sputum, diffuse crackles on auscultation of the lungs, respiratory distress, and/or hypoxemia for the specific altitude (table 4) that present one to two days after high altitude exposure without evidence of another cause (eg, pneumonia). In infants and young children, HAPE may be accompanied by other nonspecific signs of AMS such as fussiness, decreased activity, decreased appetite, and vomiting. If performed, chest radiographs show diffuse interstitial changes consistent with noncardiogenic pulmonary edema.

Treatment — The treatment of HAPE in lowland children who ascend to high altitude targets the same goal as in older patients: the prompt reduction of pulmonary artery (PA) pressure and hypoxemia via increasing the partial pressure of inspired oxygen [44,50].

Options include:

●Limiting physical exertion and cold exposure

●Providing supplemental oxygen via tank or concentrator

●Evacuation to a lower altitude

●Simulating descent using hyperbaric therapy

●Nifedipine (≥50 kg) or amlodipine (<50 kg or <17 years old) (table 3)

Of these treatments, descent (simulated or actual) and/or supplemental oxygen are often effective alone and appear to be superior to any pharmacologic therapy. In some resort areas, children with HAPE are treated as outpatients with supplemental oxygen and remain at the same altitude with their families with close follow-up. Nifedipine or amlodipine have also been suggested (table 3) [25,46,50]. Compared with nifedipine, amlodipine offers advantages for small children because of once-daily dosing and availability as liquid or appropriately sized tablets. (See "High-altitude pulmonary edema", section on 'Treatment'.)

Inappropriate use of antibiotics and diuretics in children with HAPE is not efficacious and should be discouraged [46].

A small proportion of children with HAPE may have an underlying predisposing condition. In one study, 17 percent of children with HAPE who underwent echocardiogram were diagnosed with new structural heart findings (eg, patent foramen ovale [PFO] and atrial septal defects [ASDs]) [46]. Thus, an echocardiogram is warranted to evaluate for underlying pulmonary hypertension and to rule out structural abnormalities that are known risk factors, such as an ASD, isolated pulmonary artery of ductal origin, coarctation of the aorta, ventriculoseptal defect, pulmonary vein stenosis, and PFO [30,46].

Prevention — As with AMS, slow ascent is the best method to prevent HAPE. Individuals with previous HAPE should be encouraged to ascend slowly and be prepared to descend quickly if symptoms of HAPE appear. (See "High-altitude pulmonary edema", section on 'Prevention'.)

For healthy children residing at low altitude and without a history of HAPE, we recommend adequate acclimatization and do not use pharmacologic HAPE prophylaxis. Some experts have suggested using nifedipine or amlodipine for prevention of HAPE in susceptible children based on adult data and class effect [50]. However, calcium channel blockers have not been studied specifically in children for HAPE prophylaxis. Nifedipine is the preferred drug for the prevention of HAPE in susceptible adults, but the commonly available nifedipine formulations contain inappropriately large doses for children [26]. In the rare circumstance that a child has had past episodes of HAPE and slow ascent is not possible, prophylaxis with amlodipine would be a reasonable option. The dose is 2.5 to 5 mg orally once daily (child 6 to 17 years old and ≥25 kg) or 0.1 to 0.6 mg/kg/dose orally once daily (maximum 5 mg/day; child 1 to 5 years old or <25 kg). Ideally, prophylaxis is started 24 hours prior to ascent and continued for five days at the destination altitude (table 3). In higher-risk scenarios, treatment may be continued for a longer period. (See "High-altitude pulmonary edema", section on 'Prophylactic medications'.)

Experience among clinicians in Colorado suggests that acetazolamide prophylaxis for children with recurrent re-entry HAPE may be effective (table 3). Although this has not been formally studied, acetazolamide is known to reduce pulmonary artery pressure on ascent to altitude as well as speed acclimatization. Some experts recommend a lower prophylactic dose (1.25 mg/kg instead of 2.5 mg/kg, both twice daily). However, this lower dose is based on adult studies, and we do not suggest its use until further pediatric-specific data are available.

Other altitude-related illness — High-altitude retinal hemorrhage and high-altitude periodic breathing of sleep are other types of altitude illness that may occur in children. In addition, children are more prone to hypothermia because of the larger surface area to mass ratio and the decreased glycogen stores available for increased energy needs in cold weather. Young children are also prone to frostbite if proper attention to appropriate clothing and limitation of cold exposure is not provided by caregivers. (See "Hypothermia in children: Clinical manifestations and diagnosis", section on 'Pediatric considerations' and "Frostbite: Emergency care and prevention", section on 'Risk factors'.)

High-altitude pulmonary hypertension — Serious high-altitude pulmonary hypertension (HAPH) is rare in healthy infants and children. However, infants less than six weeks of age are at particular risk for pulmonary hypertension and progression to right heart failure [51]. This entity has been described in up to 1 percent of infants of lowland parents who are born or arrive at high altitude (3000 to 5000 m [9840 to 16,400 feet]) and remain there for more than a month; it occurs almost exclusively in this group [25]. Because of the risk of this disorder, exposure to prolonged high altitude should be avoided in infants younger than six weeks of age who normally live at low altitude or whose gestation primarily occurred at low altitude [32].

Infants between six weeks and one year of age may have a higher incidence of pulmonary hypertension with hypoxia, patent ductus arteriosus (PDA), and PFO with prolonged exposure to high altitudes [13,52]. Those infants who will be remaining indefinitely at altitude warrant physical examination and an initial measurement of pulse oximetry followed by regular monitoring at well child visits. Patients with physical findings suggesting pulmonary hypertension (eg, systolic ejection murmur with a single or narrowly split second heart sound) or other structural heart disease should have an electrocardiogram. An echocardiogram is also necessary if clinical findings suggest structural heart disease or pulmonary hypertension. (See "Pulmonary hypertension in children: Classification, evaluation, and diagnosis", section on 'Evaluation'.)

High-altitude retinal hemorrhage — High-altitude retinal hemorrhage (HARH) is a relatively common finding at altitudes above 4270 m (14,005 feet), but it usually is asymptomatic and thus, unrecognized unless the macula is involved. The usual complaint is blurring of vision and funduscopy shows flame-like retinal hemorrhages. As with all other forms of altitude disease, slow ascent is preventative, and descent is the best treatment. No medications have been found to prevent or treat HARH. Any individual with hemorrhage affecting vision should descend. The retinal hemorrhages resolve slowly over the course of several weeks to months. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Other altitude-related illnesses'.)

High-altitude periodic breathing of sleep — Periodic breathing of sleep at high altitude is a form of Cheyne-Stokes respiration that occurs almost exclusively during non-REM sleep and can awaken subjects if the hyperventilation phase is strong enough. Children may be less disposed to this problem than adults. As an example, an observational study of 20 children between 9 and 12 years of age and their fathers which compared respiratory inductive plethysmography, pulse oximetry, and end-tidal CO2 measurements during sleep at 3450 m (11,316 feet) versus 490 m (1607 feet), children were noted to have markedly less periodic breathing but similar hyperventilation and decrease in nocturnal oxygen saturation compared with adults [33]. Furthermore, 50 percent of children met criteria for AMS versus 30 percent of adults during the course of the study. This finding suggests that the more stable breathing pattern displayed by these children is related to a lower apnea threshold for CO2 and does not render them more tolerant of high altitude. (See "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Other altitude-related illnesses'.)

TRAVEL ADVICE FOR PARENTS

Healthy infants and children — Healthy infants over six weeks of age and young children, including those with well-controlled asthma, typically tolerate travel to altitude well and rarely experience any serious high-altitude illness (HAI).

Clinicians should discourage high altitude travel for infants under six weeks of age who were born at or whose gestations was primarily at low elevation (<1500 m [4920 feet]) because they are at risk for abrupt severe hypoxemia, pulmonary hypertension, and right-sided heart failure. (See 'Risk factors' above and 'High-altitude cerebral edema' above.)

The following measures reduce the risk or enable easy management of HAI in young children [17]:

●Gradual ascent – As a general guideline, individuals who normally reside below 1500 m (4920 feet) elevation should avoid an abrupt ascent to sleeping altitudes above 2800 m (9184 feet). This is best accomplished by spending one night at an intermediate altitude such as 1600 to 2200 m (particularly when traveling to an elevation that caused symptoms previously). Two nights is even better. (See 'Prevention and pharmacologic prophylaxis' above and "High-altitude illness: Physiology, risk factors, and general prevention", section on 'Gradual or staged ascent'.)

●Avoid overexertion the first two days – Strenuous hiking, skiing, etc, should only follow one to two days of acclimatization. If exertion is unavoidable, such as backpacking that requires carrying a heavy pack, ascent needs to be even slower.

●Acetazolamide prophylaxis – Most experts do not routinely prescribe acetazolamide prophylaxis in otherwise healthy children or adults who are gradually ascending to high altitudes [1]. Prophylaxis may be indicated in situations where gradual ascent is not possible (eg, rapid ascent by airplane to a destination above 2800 m [9184 feet]) and in children who have had repeated episodes of acute mountain sickness (AMS) when previously exposed to a similar altitude and rate of ascent. However, in contrast to adults, a past history of AMS in children is an unreliable predictor of repeat illness [53]. (See 'Acetazolamide prophylaxis' above.)

●Symptomatic treatment – Parents should travel with ibuprofen. The appropriate dose of ibuprofen can quickly improve fussiness in young children or alleviate headache in older children.

Ondansetron may also be prescribed, especially if the patient is sleeping over 9000 feet or is participating in a long trek.

●Availability of descent – Descent from altitude should be readily available if serious HAI occurs. Destinations for which rapid descent is difficult or requires initial ascent should be avoided.

●Medical resources – Resort communities generally have health care providers with expertise in HAI and who are excellent resources for parents. If HAI is diagnosed in these settings, it can usually be managed so that the family trip does not have to be disrupted.

Clinicians should counsel caregivers to assess emergency rescue or medical care capabilities in remote settings relative to the risk of HAI in their children.

With proper education, most parents can recognize risk factors and symptoms and signs of HAI, even in preverbal children [35]. This knowledge can help parents decide when AMS is likely the problem, and how to respond as described above [17]. (See 'Acute mountain sickness' above.)

Parents should also know to seek immediate medical attention for altered mental status such as marked drowsiness, respiratory distress, or ataxia. (See 'High-altitude cerebral edema' above and 'High-altitude pulmonary edema' above.)

Children who develop mild AMS that resolves with descent or medication do not require specific evaluation [17].

Children who normally reside at altitude and manifest severe hypoxemia or high-altitude pulmonary edema (HAPE) warrant an evaluation for pulmonary hypertension or structural cardiac abnormality [4,9].

Susceptible infants and children — Parents of children with the following conditions should be advised to avoid travel to high altitude (>2000 m [6560 feet]) [13,17] (see 'Risk factors' above):

●Full-term infants less than six weeks of age (premature infants less than 46 weeks postconceptual age) or full-term infants up to one year of age with a history of oxygen requirement or pulmonary hypertension

●Premature infants beyond 46 weeks post conceptual age with a history of oxygen requirement, bronchopulmonary dysplasia, or pulmonary hypertension

●Congenital heart disease with pulmonary hypertension, cyanosis, or intracardiac shunts

●Sickle cell disease

●Down syndrome with cardiac shunts or pulmonary hypertension

●Active respiratory disease such as pneumonia, bronchiolitis, or cystic fibrosis with exacerbation

Children with stable cystic fibrosis may be able to travel to high altitude if pulse oximetry monitoring is performed during travel and supplemental oxygen can be provided. Assessment of FEV₁ and hypoxia inhalation testing can be performed in children over six years of age and can help identify those children who warrant supplemental oxygen during the trip [26]. Almost all resort areas have home oxygen companies that honor prescriptions for oxygen written by licensed providers. Parents should ensure strict adherence to established chest physiotherapy, mucolytic, and antibiotic regimens during the trip.

Children with neuromuscular disorders or conditions causing restrictive lung disease (eg, severe kyphoscoliosis) should undergo assessment by a pediatric pulmonologist prior to travel to determine the need for supportive measures while at high altitude, such as supplemental oxygen (continuous or nocturnal) or nighttime bilevel positive airway pressure [26].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Altitude sickness (including mountain sickness) (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Altitude and risk for high-altitude illness (HAI) – The risk of HAI depends upon individual susceptibility, the rate of ascent, and the elevation reached. Ascent above 2500 m (8200 feet) may be associated with HAI in children. However, most healthy children do well without any serious effects at altitudes less than 3500 m (11,480 feet). (See 'High-altitude illness in children' above.)

●Risk factors for HAI – Children at particular risk for serious HAI include the following (see 'Risk factors' above and 'High-altitude cerebral edema' above and 'High-altitude pulmonary hypertension' above):

•Infants under six weeks of age

•Infants up to one year of age with a history of oxygen requirement or pulmonary hypertension, including premature infants

•Children who live at very high altitude and undergo a temporary descent

•Children with Down syndrome, congenital heart disease, cystic fibrosis or neuromuscular problems compromising ventilation

●Acute mountain sickness (AMS)

•Clinical manifestations – Clinical manifestations of AMS are nonspecific in young children and infants and include decreased playfulness, pallor, fussiness, poor sleep, vomiting, and decreased appetite (table 5). A high index of suspicion is required for detection. (See 'Clinical manifestations' above.)

Symptoms of AMS in older children and adolescents are similar to what is seen in adults. The most common symptom is headache, which may be accompanied or followed by shortness of breath, dizziness, poor sleep, anorexia, fatigue, nausea, and vomiting. (See "Acute mountain sickness and high-altitude cerebral edema", section on 'Presentation and diagnosis'.)

•Diagnosis – The diagnosis of AMS relies on typical clinical manifestations that occur within 24 hours of arrival at high altitude without evidence of another cause (eg, otitis media, pneumonia, or viral illness). AMS is a diagnosis of exclusion in preverbal children. Improvement of symptoms after administration of supplemental oxygen (eg, 2 to 4 L/minute by nasal cannula for 15 to 20 minutes) or a brief descent supports the diagnosis of AMS if no other cause is found. (See 'Diagnosis' above.)

•Treatment – Children with AMS are treated based upon symptom severity following the same principles as in adults (table 3). (See 'Treatment' above.)

●High-altitude pulmonary edema (HAPE)

•Clinical manifestations – Although rare in young children, HAPE presents as increasing respiratory distress over one to two days, but may develop more precipitously. In some young children and infants, primary signs may not include tachypnea, but oxygen saturation will always be low relative to normal values at that altitude (table 4). Symptoms of HAPE in older children and adolescents are similar to those in adults: dyspnea, tachypnea, rales, and cough productive of frothy, rusty sputum. (See 'Clinical manifestations' above.)

•Diagnosis – The diagnosis of HAPE relies on typical clinical manifestations that present one to two days after high-altitude exposure without evidence of another cause (eg, pneumonia). If performed, chest radiographs show diffuse interstitial changes consistent with noncardiogenic pulmonary edema. (See 'Diagnosis' above.)

•Treatment – Children with HAPE warrant immediate supplemental oxygen, descent or both. In emergency settings without the option of oxygen or descent, pharmacotherapy with nifedipine (≥50 kg) or amlodipine (<50 kg or <17 years old) may be effective (table 3). (See 'Treatment' above.)

●Prevention of AMS and HAPE – Acclimatization and slow ascent are the most effective ways to avoid AMS and HAPE in otherwise healthy children. (See 'Prevention and pharmacologic prophylaxis' above and 'Prevention' above.)

Healthy children should ascend to very high altitudes (over 3500 m [11,480 feet]) slowly and only if rapid descent is possible in the event of problems. (See 'Recommendations for ascent' above.)

●Travel advice for parents – Healthy children generally tolerate travel to altitude well and rarely experience any serious HAI. The clinician should advise parents that resort communities generally have health care providers with expertise in altitude-related problems who are excellent sources for parents and children if they feel their child might be experiencing HAI. (See 'Travel advice for parents' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Erin Endom, MD, who contributed to an earlier version of this topic review.