With the increasing popularity of various recreational activities, individuals tend to travel to greater altitudes raising the incidence of high altitude illness (HAI). Examples of activities that can put individuals at risk include hiking, mountain climbing, biking, skiing, snowboarding, hot air balloons, and gliding. With the ease and access to modern travel, it can be expected that the incidence of HAI will continue to rise, putting more children and adults at risk
HAI results from the decrease in barometric pressure and the individual's response to hypoxia. It can affect individuals of any age but often affects young, healthy individuals.1,2 HAI encompasses a broad spectrum of disease ranging from acute mountain sickness (AMS), the mildest form of HAI to the potentially life-threatening high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE). Symptoms of HAI may develop within hours or days after ascent. In contrast, hypoxemia occurs within minutes to hours of arrival at altitude and results in the initiation of the cascade of physiologic events that lead to AMS, HAPE, and HACE (Table 140-1).
TABLE 140-1An Overview of High-Altitude Illness ||Download (.pdf) TABLE 140-1 An Overview of High-Altitude Illness
| || |
Acute Mountain Sickness (AMS)
High-Altitude Cerebral Edema (HACE)
High-Altitude Pulmonary Edema (HAPE)
Rare below 8000 ft
Affects nearly everyone who rapidly ascends to 11,000 ft
Rare below 12,000 ft
Rare below 8000 ft
More commonly associated with altitudes >14,500 ft
Within 4–8 h of a rapid ascent but can be as long as 4 d
Peaks within 24–48 h
Usually resolves by the third or fourth day
Most often within 1–3 d after ascent to altitude
Usually within 1–4 d after ascent to altitude
Most common during the second night at altitude
Most common: headache, sleep disturbance, fatigue, shortness of breath, dizziness, anorexia, nausea, vomiting, oliguria
Other symptoms: mild peripheral edema, weakness, lassitude, malaise, irritability, decreased concentration, poor judgment, palpitations, deep inner chill, dull pain in the posterolateral chest wall
Severe headaches, nausea, vomiting, altered mental status
Cardinal sign: truncal ataxia
Will proceed to include confusion, slurred speech, diplopia, hallucinations, seizures, impaired judgment, cranial nerve palsies (third and sixth), abnormal reflexes, paresthesia, decreased level of consciousness, coma, death
Initial symptoms: dry cough, fatigue, dyspnea on exertion, few rales
Symptoms of AMS may be present
As symptoms progress: productive clear cough, orthopnea, weakness, altered mental status, tachycardia, tachypnea, fever, increased rales, cyanosis
Cardinal sign: severe dyspnea at rest
No higher ascent until symptoms have resolved
Proceed to a lower altitude if no improvement within 1–2 d or if symptoms worsen
Supplemental oxygen, if available
Symptomatic relief for headache, nausea
Immediate descent is indicated for ataxia, decreased level of consciousness, confusion, dyspnea at rest, rales, or cyanosis
Acetazolamide: adult, 125 mg bid; pediatric, 2.5 mg/kg bid
Dexamethasone 0.15 mg/kg
(maximum dose of 4 mg) every 4–6 h
Hyperbaric therapy if descent is not possible
Mild-to-moderate HAPE: bed rest, supplemental oxygen
Severe HAPE: Immediate descent, minimal exertion
Nifedipine 0.5 mg/kg (maximum 20 mg) q8h
Hyperbaric therapy if descent is not possible
Acclimatization: slow, graded ascent; first night's sleep should be at an altitude no greater than 8000 ft and the first day should be spent at rest; daily climb should then be limited to 1000 ft if the altitude is between 10,000 and 14,000 ft; beyond 14,000 climbers should take 2 d for each 1000-ft ascent.
Avoid alcohol, sedatives, smoking
Acetazolamide: start 48 h before ascent and continue for at least 48 h after arriving at the highest altitude (same as treatment dosage)
Acetazolamide or dexamethasone (same as treatment dosage)
Nifedeipine (same as treatment dosage)
There are a number of factors that influence the incidence, onset, and severity of HAI. Risk factors common to the pediatric and adult populations are rate of ascent, altitude achieved, length of stay, and physical exertion. The severity of HAI varies when any of these factors, or a combination of them exceed the individual's ability to adapt to the new environment. The highest incidence of AMS occurs between the ages of 1 and 20 years, with the severity of symptoms decreases with increasing age.
Unique anatomical and physiologic differences among infants and children may increase the risk of ventilation–perfusion mismatch resulting in hypoxia.
Contributing factors3 include:
Increased rib cage compliance.
Increased airway reactivity in response to hypoxia.
Fewer alveoli are present in early infancy.
Reduced surfactant in preterm infants.
Reduced upper and lower internal diameters of the airways.
Increased proportion of the pulmonary vascular bed with muscular arterioles in early infancy.
Tendency for a paradoxical inhibition of increased respiratory drive (up to 1–2 months of age) to hypoxia.
Presence of fetal hemoglobin until 4 to 6 months of age.
High altitude is generally considered to be ≥8000 ft (2439 m) and at this altitude arterial oxygen saturation falls below 90% (PaO2 60 mm Hg). Acclimatization is necessary to prevent illness. Although severe altitude illness is uncommon below 8000 ft, individuals with pre-existing medical conditions may become symptomatic at moderate altitude (5000–8000 ft). At extreme altitude, generally greater than 18,000 ft (∼5500 m), acclimatization is not possible and altitude illness is inevitable.
The Atmosphere and Physical Gas Laws
An understanding of the physical gas laws, along with the composition of the atmosphere explains the occurrence of HAI. The atmosphere is comprised of multiple gases. The largest percentage is nitrogen followed by oxygen. Forces exerted at any given altitude are represented as barometric pressure or atmospheric pressure. At different altitudes, while the percentage of each gas remains the same, the partial pressures of the gases will vary.
Boyle's law states that the volume of a given mass of gas will vary inversely with its pressure. As an individual ascends, barometric pressure decreases and the volume of gas within an enclosed space expands. As the individual descends, the reverse is true.
Dalton's law of partial pressure describes the pressure exerted by gases at various altitudes. It states that the total pressure of a mixture of gases is the sum of the partial pressures of all the gases in the mixture. At sea level barometric pressure is 760 mm Hg, and the percentage of oxygen in the atmosphere is equal to 20.95%. Therefore, the partial pressure of oxygen (PO2) at sea level is 159.22 mm Hg.
As altitude increases and pressure decreases, gas expansion causes the available oxygen to decrease. For example, at 10,000 ft, where the barometric pressure is 523 mm Hg, the percentage of oxygen remains 20.95%, but the partial pressure of oxygen will decrease to approximately 110 mm Hg and the alveolar PO2 will drop to 60 mm Hg.
Several different physiologic responses are seen at high altitude. The response to hypoxia is the most significant. Hypoxia causes increased cerebrospinal fluid (CSF) pressure, fluid retention, fluid shifts, and impaired gas exchange. Factors that influence an individual's threshold for hypoxia include physical activity, sleep, physical fitness, metabolic rate, diet, nutrition, emotions, and fatigue. Alcohol ingestion and smoking act as respiratory depressants and will exacerbate the effects of hypoxia. Exposure to temperature extremes will increase a person's metabolic rate, increasing oxygen requirements and reducing the hypoxic threshold.
Through acclimatization, a series of physiologic adjustments works to restore the tissue oxygen pressure to near its sea level value. Successful acclimatization varies between individuals and cannot be predicted by physical conditioning, examination, or testing.
A slow, graded ascent is the key to acclimatization, that is, staging, especially for individuals who have previously exhibited sensitivity to high-altitude changes.4 In the ideal setting, the first night's sleep occurs at <8000 ft, with the first day spent at rest. If the altitude of the desired climb is between 10,000 and 14,000 ft, then the daily ascent should be limited to 1000 ft. Beyond 14,000 ft, 2 days of rest should be taken for each 1000-ft ascent (Fig. 140-1). Climbing to higher elevations during the day and descending to a lower altitude to sleep is another option to prevent AMS and facilitate acclimatization.
Hiking across Khumbu Icefall, Mt. Everest. Altitude 20,000 ft. (Used with permission from Gary Guller.)
Pharmacologic agents may also be beneficial adjuncts to acclimatization. Acetazolamide (Diamox) has been shown to be very effective when staging is not possible or with individuals who are at an increased risk of HAI.5 Dexamethasone may also be effective in preventing AMS, but it is generally reserved for treatment.
As an individual ascends, the hypoxic ventilatory response (HVR) will attempt to compensate for the decrease in arterial PO2 through an increase in the respiratory rate. An inadequate HVR, resulting in relative hypoventilation, has been suggested as the etiology for AMS and HAPE. Individuals with low tidal volumes and children are less able to respond to the hypoxic insult and, therefore, are more prone to AMS. HVR is genetically predetermined, but can be influenced by caffeine, alcohol, and numerous medications. Further, hypoxia from chronic heart or lung problems desensitizes this effect.
The threshold for the HVR is at approximately 4000- to 5000-ft elevation, with the maximum response occurring at 22,000 ft. At this elevation the minute volume will be nearly doubled.
The initial maximal effect of the HVR occurs approximately 6 to 8 hours after arrival to altitude. A decline in the partial pressure of inspiratory oxygen (Pio2) results in an increase in ventilation, and decreases in the Paco2 accordingly. The falling Paco2 causes a mild respiratory alkalosis and a shift of the oxyhemoglobin dissociation curve to the left. The respiratory alkalosis then provides negative feedback to the medulla, restricting the HVR. Compensation for this respiratory alkalosis is dependent on the renal excretion of bicarbonate, usually occurring within 24 to 48 hours. Ventilation will slowly increase as the pH returns to normal. With no further ascent, this response can take 4 to 6 days. As an individual continues to higher elevation, subsequent acclimatization will be directed by the declining arterial Pco2.
Hypoxia and cold stressors act as significant vasoconstrictors of the pulmonary vascular bed, resulting in an elevation of the pulmonary arterial pressure and an increase in the workload on the right side of the heart. The degree of pulmonary hypertension in response to global hypoxia is an important contributor to the development of HAPE.
Compared to the respiratory and central nervous systems, the cardiovascular system is relatively resistant to hypoxia. The cardiovascular system responds to hypoxia in two phases. In the first phase, the heart rate begins to increase at an altitude of 4000 ft. The second phase occurs when the decrease in Pao2 releases an increased catecholamine surge causing selective vasoconstriction, resulting in a slight increase in blood pressure and, thereby, increasing the cardiac output. As acclimatization occurs, the heart rate will return to normal. If the individual fails to acclimatize, the heart rate will remain elevated, and any increase in cardiac activity will require more oxygen.
The hematopoietic response to high altitude is a critical element in an individual's long-term ability to acclimatize. All changes within the hematopoietic system are geared toward increasing arterial oxygenation. Within hours of ascent, erythropoietin output is increased in response to the hypoxia. In approximately 4 to 5 days, there will be an increase in circulating red blood cells. This increase in red cell mass persists for 1 to 2 months after return to lower altitudes. At extreme altitudes, this hematopoietic response is detrimental due to the increased blood viscosity, hemoconcentration, and increased red blood cell mass impeding oxygen transport.
Increased 2,3-diphosphoglycerate (2,3-DPG) within the red blood cells is another hematopoietic response to hypoxemia. This shifts the oxyhemoglobin disassociation curve (Fig. 140-2) to the right, facilitating the release of oxygen from the blood to the tissues. With acclimatization, this shift to the right offsets the leftward shift of the oxyhemoglobin dissociation curve caused by hyperventilation and respiratory alkalosis.
Under normal conditions, cerebral blood flow is kept at a fairly constant rate. As a person's Po2 falls, the increased respiratory rate decreases the Pco2 and raises the pH of both the blood and the CSF. As the CSF pH rises, chemoreceptors in the brain cause cerebral arterioles to dilate, resulting in increased cerebral blood flow. This response increases oxygen delivered to the brain but can also increase intracranial pressure (ICP) and contribute to HACE.
Respiratory alkalosis stimulates renal excretion of bicarbonate, producing a compensatory metabolic acidosis. As the pH equalizes, ventilation may continue to increase. This ventilatory acclimatization subsides after 4 to 6 days at altitude.
During ascent, central blood volume will increase secondary to peripheral vasoconstriction. Antidiuretic hormone (ADH) and aldosterone are inhibited, resulting in a diuresis, decreased plasma volume, and hemoconcentration. Individuals without this diuretic response are at greater risk for fluid retention and HAI.
AMS is the most common and mildest form of HAI; AMS and HACE are ends on a spectrum of disease. Some individuals traveling to 8000 ft will become symptomatic although nearly everyone who ascends to elevations between 11,000 and 20,000 ft will develop some clinical signs of AMS. While obesity, exertion at altitude, and low-altitude residence increase the risk of AMS, physical fitness and youth do not offer protective properties.6
The onset of AMS symptoms usually occurs within 6 to 12 hours of a rapid ascent, but can be delayed for up to 24 hours or even longer. Symptoms develop following strenuous activity or sleeping at high altitude. In most cases, symptoms peak in 24 to 48 hours and resolve by the third or fourth day. If the individual proceeds to a higher altitude after the onset of AMS, symptoms may last longer.
The clinical presentation of AMS includes the following symptoms, in order of prevalence: headache, sleep disturbance, fatigue, shortness of breath, dizziness, anorexia, nausea, and vomiting. AMS should be considered the etiology in any individual at altitude who develops at least three of these symptoms. Headache occurs in approximately two-thirds of individuals and is throbbing in nature and worse after exercise, at night, or on awakening. Nausea and vomiting are common in children. In young children, however, signs of AMS are often less specific and can include fussiness, poor sleep, decreased appetite, and vomiting.7
Other symptoms associated with AMS include oliguria, mild peripheral edema, weakness, lassitude, malaise, irritability, decreased concentration, poor judgment, palpitations, chills, and a dull pain in the posterolateral chest wall.
On physical examination, vital signs may be normal or slightly elevated. Fluid retention is exhibited as fine rales or peripheral edema. Also, retinal hemorrhages may be seen.
The differential diagnosis of these symptoms and examination findings includes an alcohol hangover, exhaustion, dehydration, and a viral syndrome. Respiratory and CNS infections, hypothermia, gastritis, and carbon monoxide poisoning should also be considered. However, if the symptoms occur shortly after arrival to altitude, AMS must be considered until proved otherwise. Of note, AMS does not cause a fever and alternative diagnoses should be explored if the child has a febrile illness.
Although normal acclimatization inhibits ADH and aldosterone, resulting in a high-altitude–induced diuresis, the opposite is seen with AMS. Aldosterone, ADH, and renin–angiotensin release increases, resulting in fluid retention and leakage from the vascular space to the extravascular space.
There are two theories for the development of cerebral edema in AMS. The first theory is cytotoxic edema, induced by a deficiency in the ATP-dependent sodium pump caused by hypoxic cellular injury, leading to an accumulation of intracellular fluid. The second is vasogenic edema. In this situation, hypoxia causes cerebral vasodilation, which, in turn, increases cerebral blood flow, capillary perfusion, and leakage through the blood–brain barrier.5,8
The onset of AMS may be hastened by decreased vital capacity, increased CSF pressure, proteinuria, fluid retention, recent weight gain, or relative hypoventilation. It is postulated that children are more susceptible to AMS, as they are more sensitive to cerebral hypoxemia. Physical fitness does not impact on susceptibility to AMS.
Management treatment is initially directed toward prevention. Symptoms of AMS are most often mild and self-limiting, lasting only a few days. Once symptoms do occur, activity should be minimized, with no higher ascent until signs and symptoms have resolved. Affected individuals should be symptomatically treated with analgesia for headaches and antiemetics for nausea and vomiting. Patients with AMS are to refrain from using narcotics, which depress the HVR. Descending to a lower altitude is indicated for any individual who shows no signs of improvement within 1 to 2 days or whose clinical condition worsens. Immediate descent is indicated if ataxia, decreased levels of consciousness, confusion, dyspnea at rest, rales, or cyanosis are present. A descent of 1000 to 3000 ft is recommended. In some situations, as little as a 500-ft descent may result in improvement.
If descent is not an option, the use of supplementary oxygen will relieve most of the signs and symptoms of AMS, as well as aid in diagnosis if oxygenation relieves the patient's symptoms. During sleep, 1 to 2 L/min can be of significant benefit.
A Gamow bag (Fig. 140-3), a portable fabric hyperbaric bag, has been shown to relieve the central effects of AMS. Using a foot pump, it can be pressurized in excess of 100 torr for the physiologic equivalent of a 4000- to 5000-ft descent.
Treating and preparing a patient for medical evacuation using a Gamow Bag. (Used with permission from Gary Guller.)
Acetazolamide, a carbonic anhydrase inhibitor, may be used in the treatment or prophylaxis of AMS. Acetazolamide decreases the reabsorption of bicarbonate. A renal bicarbonate diuresis occurs resulting in a mild metabolic acidosis, thus, increasing the ventilation rate and arterial Po2. For prophylactic use, it should be started 48 hours before ascent and continued for at least 48 hours after arriving at the highest altitude. When used to treat AMS, improvement is generally seen within 12 to 24 hours.9 The dosage for older children and adults is 250 mg PO q8 to 12 hours. The pediatric dosage for acetazolamide is 2.5 mg/kg twice daily with a maximum daily dose of 250 mg. Side effects include peripheral paresthesias, nausea, vomiting, polyuria, drowsiness, confusion, and is contraindicated for those with sensitivities to sulfa drugs.
Dexamethasone is also used in the treatment and prevention of AMS.10 This medication should be used for those with sulfa allergies or intolerance to acetazolamide. Dexamethasone minimizes the symptoms of AMS, but does not impact acclimatization. A loading dose of 4 mg PO or IM is given, and improvement is generally seen within 2 to 6 hours. If there is no improvement, immediate descent should occur with a dose of 0.15 mg/kg (maximum dose of 4 mg) every 4 to 6 hours for 24 hours until the patient is fully descended or the symptoms fully resolved (maximum of 7 days). Rebound AMS may occur if the dexamethasone is discontinued at altitude.
Prevention of AMS through acclimatization is not always possible for vacationing climbers, skiers and other sports enthusiasts. Beyond acetazolamide, prevention includes a slow, graded ascent, a diet high in carbohydrates, low in salt, and adequate fluid intake. Alcohol and tobacco are to be avoided.
High-Altitude Cerebral Edema
HACE is the most severe, life-threatening point in the disease spectrum of AMS to HACE. HACE is uncommon, affecting <1% to 2% of individuals who ascend without acclimatization. While this entity is rare below altitudes of 12,000 ft, deaths from HACE have occurred at elevations as low as 8200 ft. A common problem for the clinician is difficulty in differentiating between AMS and early HACE.
HACE presents with the symptoms of AMS and progresses to diffuse neurologic dysfunction. Onset of severe symptoms is 1 to 3 days after ascent to altitude, but early signs of AMS may rapidly deteriorate to severe HACE in as few as 12 hours. Evidence of HAPE may also be present.
Severe headaches, nausea, vomiting, and altered mental status are common symptoms associated with HACE. Truncal ataxia is the cardinal sign and this alone warrants immediate descent. If not recognized, HACE will proceed to include confusion, slurred speech, diplopia, hallucinations, seizures, impaired judgment, cranial nerve palsies (third and sixth), abnormal reflexes, paresthesias, decreased level of consciousness, coma, and finally death. Once coma is present HACE has a 60% mortality. A diagnosis of HACE can be made in a patient with recent ascent and signs of encephalopathy.
The differential diagnosis includes head injury, subarachnoid hemorrhage, meningitis, encephalitis, carbon monoxide poisoning, transient ischemic attack, and cerebrovascular accident. Patients who become symptomatic at high altitude warrant a complete evaluation to rule out other etiologies.
HACE is thought to be associated with cytotoxic edema, vasogenic edema, or a combination of these two processes causing cerebral edema. (Fig. 140-4) The time of onset for HACE supports the cytotoxic edema theory, whereas the response of HACE to corticosteroids supports the vasogenic edema theory.
Diffuse cerebral edema consistent with HACE. (Used with permission from Christopher Straus, MD.)
While AMS is pinned around symptomatic care, HACE requires early recognition and rapid definitive treatment. The most important treatment for HACE is evacuation and descent as quickly as possible. High-flow oxygen should be initiated as soon as symptoms are recognized to keep the SpO2 above 90%.6 Dexamethasone can produce dramatic improvement. A dose of 0.15 mg/kg (maximum dose of 4 mg) every 4 to 6 hours for 24 hours until the patient is fully descended or the symptoms fully resolved (maximum of 7 days).11 Acetazolamide has not been shown to be effective in the treatment of HACE. Hyperbaric therapy with the Gamow bag has been reported to be useful in mild HACE and may be life-saving if descent is not possible—this treatment should be done in conjunction with dexamethasone and supplemental oxygen.12
For severe cases requiring intubation, the management of HACE presents a precarious situation. The same hyperventilation used to acutely decrease ICP can also cause cerebral ischemia. Use of oxygen can also decrease cerebral blood flow and ICP; hyperventilation should be reserved for only dire circumstances. Furosemide and mannitol can also be used as second-line treatments to lower ICP; upon descent the ICP should normalize.
Acute episodes of HACE may result in long-term neurologic deficits. Coma may persist for days. Ataxia, impaired judgment, and behavioral changes have been reported to last as long as 1 year. Despite all interventions, HACE can be irreversible and lead to death. For this reason, it is essential that any evidence of HACE be rapidly recognized and treated early.
The key to prevention of HACE is acclimatization. However, cases of HACE have been reported in individuals who have limited their ascent to 1000 ft a day. Acetazolamide is recommended for patients who have a history of HAI—this is the drug of choice when a graded ascent cannot be preformed. As with AMS, for patients with sulfa allergies, dexamethasone can be used to prevent HACE.
High-Altitude Pulmonary Edema (HAPE)
HAPE is a life-threatening manifestation of HAI and represents a unique form of noncardiogenic pulmonary edema. HAPE affects an estimated 0.5% to 15% of those who ascend rapidly to high altitudes. Other than trauma, this disease is the most common cause of death at altitude. While HAPE has occurred below 8,000 ft,13 it is more commonly associated with altitudes greater than 14,500 ft. Risk factors for HAPE are rapid ascent, cold stressors, a history of HAPE, excessive exertion, and an inability to acclimatize. History of a recent upper respiratory tract infection has also been thought to be contributory.
Children and young adults are more susceptible to HAPE and individuals with a history of HAPE are at a greater risk for recurrence. Children are also more susceptible to a special form of this HAI identified as reentry HAPE. This commonly occurs in individuals who are living at higher altitudes and then return to the original elevation after spending as little as 24 hours at lower altitude.
The onset of HAPE usually occurs within 1 to 2 days after ascent to altitude. It most commonly occurs during the second night at altitude; however, initial symptoms may develop within hours following ascent.
Early in the course the patient develops a dry cough, fatigue, and dyspnea on exertion. Infants display nonspecific symptoms, such as decreased activity and pallor. Symptoms of AMS often accompany these initial signs. Localized rales may be audible in the right middle lobe auscultated over the right axilla. Rales increase with exercise. As HAPE progresses, a productive clear cough, orthopnea, weakness, and altered mental status develop. This quickly intensifies to severe dyspnea at rest, a cardinal sign of HAPE. Rales become bilateral and the patient can exhibit pink, frothy sputum. The patient may become tachycardic, tachypneic, exhibit a low-grade fever up to 38ºC and an abnormally low SpO2. Peripheral cyanosis can occur and advances to central cyanosis if treatment is not initiated quickly. Dyspnea at rest, while at altitude, is HAPE until proven otherwise.
A chest radiograph reveals bilateral, fluffy, asymmetric infiltrates and dilated pulmonary arteries (Fig. 140-5). Cardiomegaly, a butterfly pattern of infiltrates, and Kerley-B lines, commonly seen in cardiogenic pulmonary edema, are not seen in HAPE. An electrocardiogram (ECG) may show sinus tachycardia, right ventricular strain, right axis deviation, P-wave abnormalities, prominent R waves in the right chest leads, and S waves in the left chest leads. Without treatment, florid pulmonary edema and respiratory failure will develop. Dysfunction of the CNS will ensue, leading to coma and death.
Noncardiogenic pulmonary edema consistent with HAPE. (Used with permission from Christopher Straus, MD.)
The differential diagnosis includes pneumonia, congestive heart failure, undetected intracardiac shunt, opening of fetal shunts in infants, high-altitude bronchitis, pharyngitis, asthma, neurogenic pulmonary edema, pulmonary embolism, and adult respiratory distress syndrome. HAPE does not cause a fever above 38ºC, and alternative diagnoses should be explored.
HAPE can affect individuals without prior history of cardiac or pulmonary disease and is primarily a dysfunctional response to hypoxia. Hypoxia causes uneven pulmonary vasoconstriction which then elevates pulmonary artery pressures. Peripheral vasoconstriction, and fluid retention lead to an increase in the blood volume, which then exacerbates pulmonary hypertension. Pulmonary microvascular pressures are elevated causing a breakdown in the alveolar–capillary barrier. Also contributing to this complex pathophysiology is decreased production of endothelial nitric oxide and overproduction of endothelin. The end result is noncardiogenic pulmonary edema.14
Individuals with an elevated pulmonary artery pressure or with a blunted HVR have been shown to be at increased risk for HAPE. Children and infants with pulmonary arterial hypertrophy are more prone to the development of HAPE. Congenital absence of a pulmonary artery may also predispose an individual to HAPE. Children who develop HAPE should have testing for underlying cardiopulmonary abnormalities including pulmonary hypertension.15 Also, infants under 6 weeks old are at an increased risk for pulmonary hypertension and right heart disease.16 However, not all individuals with pulmonary hypertension will develop HAPE.
Hyperviscosity from dehydration and increased red blood cell mass results in a hypercoagulable state, which may play a role in the development of HAPE.
The treatment of HAPE centers on the alleviation of the increased pulmonary arterial pressure responsible for edema formation. As with any form of HAI, immediate descent may be life-saving and is not to be delayed. Descent alleviates alveolar hypoxia and, thus, the increase in pulmonary arterial pressure. There is a delicate balance between rapid descent and the amount of energy the patient expends to descend quickly. Individuals may deteriorate from overexertion as they proceed to a lower altitude. Therefore, care must be taken to minimize the effort while maximizing the effect. A descent of 1000 to 2000 ft is usually adequate for symptomatic relief. In addition to rapid descent, bed rest, supplemental oxygen, and keeping the patient warm are necessary.14
Physical activity and exposure to cold increase the catecholamine response, which increases pulmonary pressure. Supplemental oxygen effectively lowers pulmonary arterial pressure, which raises arterial oxygen saturation. As a result, heart rate and respiratory rate will decrease. High-flow oxygen at 6 to 8 L/min by mask is administered to anyone with significant symptoms. Oxygen alone (without descent) over a period of 2 to 3 days can reverse the effects of HAPE. An end-expiratory airway pressure (EPAP) mask that can deliver 5 to 10 cm H2O of end-expiratory pressure can be used to improve oxygen delivery. When oxygen is not available and descent is not possible, the portable Gamow bag may be used for hyperbaric treatment and has been shown to be effective in patients with HAPE.12
Pharmacologic agents play a limited role in the prevention and treatment of HAPE. However, the literature does not mention the use of preventative or therapeutic agents with children. Adult literature suggests that nifedipine can be used as an adjunctive therapy to reduce pulmonary arterial pressure for the prevention and treatment of HAPE17 but may also cause hypotension. Nifedipine is the first-line medical therapy and typically is administered as 0.5 mg/kg (maximum 20 mg) every 8 hours. Phosphodiesterase inhibitors, including sildenafil and tadalafil, have been shown to be effective agents in the treatment of HAPE. As opposed to nifedipine, tadalafil and dexamethasone were found to be beneficial without causing a drop in blood pressure.18 Caution must be exercised in the use of a potentially hypovolemic dehydrated patient. Newer agents, such as the β-adrenergic agonist salmeterol, have shown promising results in preventing pulmonary edema at high altitudes. Salmeterol when administered at 125 μg every 12 hours was associated with a significant decrease in the incidence of HAPE.19 Traditionally, furosemide was considered an adjunctive treatment in HAPE, but now there is no role for furosemide as diuretics may exacerbate pre-existing hypovolemia and dehydration.
Rapid improvement and resolution of symptoms usually occur after descent to a lower altitude. If oxygen saturation is <90%, then hospitalization is indicated. Expiratory positive airway pressure can improve gas exchange in HAPE patients.20 In severe cases of HAPE, intubation and ventilation with positive end-expiratory pressure may be needed.
The overall mortality of HAPE is 11%. Without treatment (descent or supplemental oxygen), the mortality increases to 44%.
An episode of HAPE is not a contraindication to further attempts to reach altitude; however, there is a higher incidence for recurrence of symptoms with subsequent ascents.
Pre-existing Cardiovascular Disease
Patients with pre-existing cardiovascular disease are at risk for exacerbations of their chronic disease, as well as HAI. The risk of HAPE is increased in patients with congenital heart disease that increase pulmonary vascular perfusion. Eisenmenger syndrome, unilateral absence of a pulmonary artery, patent ductus arteriosus, atrial or ventral septal defects will all increase the risk of HAPE. Also, children with patent foramen ovales are predisposed to HAPE.21 During travel to altitude with these patients, special care must be paid to the child's oxygen saturation and respiratory status. Further, a plan for expeditious descent must be available in this patient population.
Pre-existing Pulmonary Disease
Any pulmonary disease that affects breathing at sea level has the potential to cause further complications at higher altitudes. Supplemental oxygen may be necessary for any child with known hypoxemia, sleep disorder, or pulmonary hypertension. Reactive airway disease is not aggravated by high-altitude exposure, but exposure to cold, dry air could worsen this disease.
Patients with chronic lung disease, e.g., cystic fibrosis and bronchopulmonary dysplasia, are at an increased risk of hypoxia and the sequelae of hypoxia. Ascent should occur at a slower pace than usual, and oxygen saturations should be monitored throughout the journey.
High-Altitude Retinal Hemorrhage
An estimated 50% of individuals who ascend to 16,000 ft and 100% of those who ascend to 21,000 ft will develop high-altitude retinal hemorrhage (HARH) within 2 to 3 days after arrival to altitude. HARH presents with tortuous dilation of the retinal arteries and veins, retinal hemorrhages, and papilledema. The hemorrhages are most often throughout the fundus and spare the macula. This disease is painless and usually asymptomatic, with no visual disturbances noted. If the macula is involved, the patient may complain of cloudy or blurred vision. In these situations, descent to a lower altitude is indicated.
In most cases, HARH is self-limiting and usually resolves spontaneously within 2 to 3 weeks after descent. If the macula was involved, visual changes may be permanent. HARH may occur alone or in the presence of AMS, HAPE, or HACE. The incidence of HARH increases with strenuous activity and with a history of previous HARH.
High-Altitude Sleep Apnea
Under normal sea level conditions, there is a mild decrease in oxygen saturation during sleep—a phenomenon that is more pronounced at altitude. When sleeping, the increased respiratory rate that accompanies high-altitude exposure causes a mild respiratory alkalosis that inhibits the respiratory drive, resulting in hypoventilation and periods of apnea. Brief episodes of hyperventilation occur next, increasing oxygen saturation while exacerbating the hypocapnia and further inhibiting ventilation. These episodes of periodic breathing with apnea last up to 90 seconds (Cheyne–Stokes respirations), continue throughout the night, and increase the hypoxia associated with being at altitude.
Chronic Mountain Sickness
Chronic mountain sickness (CMS), also referred to as Monge disease, is a rare complication of HAI. Certain individuals fail to acclimatize despite prolonged exposure or living at high altitude. Symptoms are similar to those of AMS and include headache, dyspnea, sleep disturbance, and fatigue.
CMS is associated with an inadequate HVR, resulting in persistent hypoxia and excessive erythropoietin production. These physiologic changes lead to polycythemia, with hematocrits greater than 60, and can cause or lead to congestive heart failure.
Treatment for CMS includes descent to a lower altitude, oxygen, phlebotomy, and the use of respiratory stimulants such as acetazolamide.22
Snow blindness is caused by increased ultraviolet (UV) light exposure. At higher altitudes, the UV light exposure is increased secondary to the loss of the protective atmosphere and fewer pollutants. For every 1000 ft of ascent, UV exposure will increase by 5%. Patients develop a foreign-body sensation or severe pain approximately 12 hours after exposure. They may also have periorbital edema, excessive tearing, photophobia, and conjunctival erythema.
Treatment is with oral analgesics to alleviate the severe discomfort. Symptoms resolve within 24 hours. Sunglasses with polarized lenses and side blinders are preventative of this disease.
High-Altitude Pharyngitis and Bronchitis
High-altitude bronchitis and pharyngitis are common at altitudes >8000 ft, secondary to the excessive inhalation of dry, cold air that causes drying and cracking of the upper airway mucous membranes.
Symptoms include a dry, hacking, and, often, painful cough. Symptoms are prevented or minimized by ensuring adequate hydration and salivation. Throat lozenges and hard candy help to maintain oral secretions. Inhaled steam, gargling, and oral fluids will also keep the mucous membranes moist. A cloth worn over the mouth and nose helps to warm the inspired air and trap moisture. Antibiotics are not helpful whereas analgesics may be beneficial.
Patients with sickle cell disease are at increased risk for vaso-occlusive crisis and hypoxemia over 5000 to 6500 ft. Patients with sickle cell trait are without risk for vaso-occlusive crisis but are at an increased risk for splenic infarction at increased altitudes. Patients with sickle cell disease are advised to use supplemental oxygen at elevations >5000 ft. Nonnarcotic analgesics and hydration are also indicated.
Pregnancy is not a contraindication for women to participate in activities at reasonable altitude levels. There is no increase in complications, maternal or neonatal, associated with short-term exposure to high altitude. However, women who live at high altitude have been shown to have a higher incidence of low-birth-weight babies, maternal hypertension, and neonatal hyperbilirubinemia.
Peripheral edema is a common complication at higher altitudes. Swelling of the face and distal extremities is most common, especially in females. Although such edema resolves spontaneously within 1 to 2 days, these findings should raise the suspicion of an AMS diagnosis.
Other syndromes associated with ascent to high altitude include altitude syncope and migraine headaches. Arterial or venous thrombosis (both peripheral and central) develop secondary to increased viscosity, causing transient ischemic attacks. CNS tumors may be unmasked as a result of increased brain volume from the increased ICPs. Seizures may be secondary to the hypoxia.