High-Altitude Medicine - Clinical Tree

Acknowledgment

The author would like to acknowledge Drs. Benjamin Honigman, Michael Yaron, Ryan D. Paterson, and Christopher B. Davis for their contributions to previous editions of this chapter.

Key Concepts

All forms of altitude illness can be treated with oxygen and rapid descent.
The diagnosis of acute mountain sickness requires the presence of headache in the setting of a recent elevation change to greater than 8,000 feet. Additional nonspecific symptoms may include nausea, anorexia, and fatigue. Those with significant symptoms should not ascend further until symptoms improve.
Patients with mild high-altitude pulmonary edema may be treated in place if experienced providers and treatment options exist. Patients with moderate high-altitude pulmonary edema or high-altitude cerebral edema should descend immediately.
Dyspnea at rest is an early symptom of high-altitude pulmonary edema. More advanced findings include rest tachypnea, cough productive of frothy sputum, and altered mentation. Treatment involves oxygen and descent.
Altered consciousness and cerebellar ataxia are early signs of high-altitude cerebral edema. Failure to initiate immediate treatment with oxygen, descent, and dexamethasone can result in permanent disability or death.
Acute mountain sickness may be prevented by using acetazolamide or dexamethasone. Symptoms can be controlled with analgesia and antiemetics. High-altitude pulmonary edema may be prevented using nifedipine. In patients unable to use nifedipine, consider inhaled salmeterol, and oral phosphodiesterase type 5 inhibitors (sildenafil [50 mg every 8 hours] and tadalafil [10 mg every 12 hours]). Temazepam (7.5 mg qhs) can safely improve sleep quality.

Foundations

Background and Importance

Acute high-altitude illnesses result from exposure to low oxygen states caused by low atmospheric pressure (hypobaria). Syndromes of the brain and lung are the primary clinical manifestations of high-altitude illness. They result from ascent too rapid to allow for adequate acclimatization. Cerebral forms of altitude illness occur as a continuum, from common and benign acute mountain sickness (AMS), to rare, but potentially lethal high-altitude cerebral edema (HACE). High-altitude pulmonary edema (HAPE) is the primary lung syndrome. HAPE is the leading cause of death from altitude illness.

All forms of altitude illness have their origins in acute oxygen insufficiency due to hypobaria. All can be treated with oxygen and descent. Although the percentage of atmospheric oxygen is a constant 20.9%, as elevation increases, atmospheric pressure decreases and with it, oxygen availability. Human physiology is adaptable when given sufficient time to acclimatize by gradual ascent. Rapid ascent to elevations greater than 8,000 feet prevents adequate acclimatization and can lead to debilitating and deadly high-altitude illnesses. On the summit of Mt. Everest (8848 m), the partial pressure of inspired oxygen (Pi o ₂ ) is only 29% of the sea-level value. Although gradual ascents (over weeks) of Mt. Everest without oxygen are not uncommon, a rapid ascent to the same summit would result in loss of consciousness and death. Gradual ascent reduces symptoms and can save lives. Serious altitude illness typically follows from unheeded warning symptoms of mild altitude illness. The importance of patient and public education to reduce the morbidity and mortality of serious altitude illness cannot be overstated.

Epidemiology

It is estimated that approximately 40 million individuals worldwide live above 8,000 feet. These individuals do not suffer acute altitude illness. Instead, it is the individual who rapidly travels to high altitude (whether for skiing, climbing, or travel) who is at the greatest risk. In the United States alone, approximately 35 million visitors travel to high-altitude recreation areas every year. Internationally, millions more travel to high mountain ranges in Europe, Asia, Africa, and South America, placing these transient sojourners at risk.

The incidence and severity of altitude illness are directly related to elevation and rapidity of ascent. Other variables include prior acclimatization, individual genetic susceptibility, sleeping elevation, and duration of stay. Rapid ascent to 8000 feet is associated with an approximately 25% incidence of AMS, whereas a rapid ascent (1 or 2 days) to 14,410 feet on Mt. Rainier has rates as high as 67%. Rapidity and mode of ascent also matter; trekkers who fly into the Khumbu region to explore the Mt. Everest region are more likely to develop AMS (47%) than those who trek in from lower elevations (23%).

HACE is much less common than AMS, occurring in less than 1% of rapid ascents to more than 14,000 feet. Although rare, it carries a grave prognosis if not quickly recognized and treated. The incidence of HAPE varies from 0.01% to 2% but may be as high as 15.5% if flown directly to 14,500 feet without a chance to acclimatize at a lower altitude. Both HAPE and HACE are more common with a longer duration of visit (more than 2 days) and higher sleeping altitude.

Age may be a relative risk factor. Most studies of children suggest that they have the same incidence of AMS as adults. Younger individuals (younger than 20 years old) are more likely to have HAPE, although HAPE is extremely rare in children younger than 2 years old. Gender does not affect the incidence of AMS; however, women may have less risk for development of HAPE. No relationship appears to exist between AMS development and timing of the menstrual cycle.

The number of older travelers visiting mountain resorts is increasing. Many of these individuals have underlying health problems, including lung disease, heart disease, and hypertension. Despite these conditions, the risk for AMS in adults older than 50 years old may be less than in younger age groups. Nevertheless, there are indications that elders may not react well to acute high-altitude exposure. Pulmonary vital capacity decreases by one-third in elders ascending from sea level to 14,000 feet for 1 week, producing a large decrease in both oxygen saturation and maximal oxygen uptake during altitude-related exercise.

Definitions

Moderate altitude is between 5000 and 8000 feet of elevation. Rapid ascent to this altitude may result in mild, transient symptoms, but severe altitude illness is uncommon. High altitude is between 8000 and 14,000 feet. Although most people do not experience significant arterial oxygen desaturation until they reach higher altitudes, high-altitude illness is common with rapid ascent above 8000 feet, and individuals with underlying medical problems may be predisposed to develop altitude illness at lower levels. The pathophysiologic effects of high altitude begin when the oxygen saturation of the arterial blood begins to fall below the 90% level. The sigmoidal shape of the oxyhemoglobin dissociation curve prevents a significant fall of arterial oxygen saturation (Sa o ₂ ) in most individuals until an altitude of approximately 12,000 feet. At this altitude, the steep portion of the curve is encountered, and marked oxygen desaturation may occur with relatively small increases in altitude ( Fig. 132.1 ). Some predisposed individuals may desaturate to less than 90% at altitudes as low as 8000 feet. Very high altitude is between 14,000 to 18,000 feet. At this elevation, the likelihood of altitude illness is high, and the risk of serious altitude illness (HAPE and HACE) increases. Extreme altitude is above 18,000 feet. Although climbers using careful acclimatization schedules can transiently tolerate this elevation, complete acclimatization generally is not possible and long durations above this level result in progressive deterioration. Given limitations in physiologic reserves, climbers who become incapacitated at this elevation typically are dependent on others to survive.

Fig. 132.1, Oxygen-hemoglobin dissociation curve. Approximate oxygen saturations are marked for several altitudes. P o 2 , Partial pressure of oxygen.

Environmental Considerations

Barometric pressure decreases logarithmically as the altitude rises. The pernicious effects of altitude are due to hypobaric hypoxia; as atmospheric pressure decreases the partial pressure of oxygen (P o ₂ ) decreases. Due to centrifugal forces, the earth is slightly flatter at the poles and bulging at the equator. The atmospheric envelope that surrounds the earth has a similar shape; therefore, at any one elevation the barometric pressure tends to be lower at higher latitudes than at the equator. Although subtle, the physiologic reserves are so limited at extreme elevations that it has been calculated that if Mt. Everest happened to be at a more northern latitude, it would be impossible to climb without supplemental oxygen.

The atmospheric envelope also undergoes seasonal variations in local thickness. In the winter, barometric pressures tend to be lower making “relative altitudes” physiologically higher. Local weather can also significantly affect the barometric pressure. A low-pressure front can reduce the barometric pressure 12 to 40 mm Hg and so increase the “relative altitude” by 500 to 2,500 feet. At extreme elevations these changes can be physiologically relevant. High-altitude illness can occur even where mountains appear distant. Although the South Pole is on a flat, barren plain, it rests at approximately 9300 ft and severe altitude illness caused by rapid transport from sea-level research facilities is not uncommon.

Anatomy, Physiology, and Pathophysiology

Acclimatization

Exposure to acute hypobaric hypoxia results in myriad physiologic responses that act to improve oxygenation. Acclimatization is both immediate (within minutes the carotid bodies sense hypoxemia) and continuous over months (hemoglobin increases may continue over more than 6 weeks). It involves multiple systems from mitochondrial function, protein synthesis to respiratory, cardiovascular, renal, and hematologic responses. Acclimatization begins as the oxygen saturation of arterial blood falls below sea-level values. The altitude at which this occurs depends on the rate of ascent, the duration of exposure, and the individual’s physiology. Individuals with preexisting conditions that limit cellular oxygen delivery and pulmonary reserves may have a decreased altitude tolerance. Most healthy, unacclimatized visitors to high altitude will not desaturate significantly (to less than 90%) until they reach elevations higher than 8000 feet.

The risk of high-altitude illness depends, in part, on an individual’s inherent ability to acclimatize. Some people acclimatize easily without having any clinical symptoms. Others may transiently have AMS during acclimatization and a few develop severe altitude illness. This variability involves many genetic and epigenetic factors that influence acclimatization. Previous successful acclimatization may be predictive of future responses for adults in similar conditions, but this may not be the case for children.

One of the most fundamental physiologic changes that occurs during acclimatization is an increase in minute ventilation. Within minutes of exposure to high altitude, the peripheral chemoreceptors in the carotid bodies sense hypoxemia resulting from the decrease in the partial pressure of oxygen in alveoli (P ao ₂ ) and signal the respiratory control center in the medulla to increase ventilation. Increased minute ventilation causes a decrease in the partial pressure of carbon dioxide in alveolus (P aco ₂ ). As described by the alveolar gas equation, for any given inspired oxygen tension, the level of ventilation determines alveolar oxygen: as the P aco ₂ decreases, P ao ₂ correspondingly increases ( Box 132.1 ). This increased ventilation in response to hypoxic challenge is known as the hypoxic ventilatory response (HVR). The magnitude of the HVR varies among individuals and may be genetically predetermined. HVR may also be inhibited or stimulated by numerous factors, including ethanol consumption, sleep medications, caffeine, cocoa, prochlorperazine, and progesterone.

BOX 132.1

Alveolar Gas Equation

P ao ₂ = P io ₂ (P aco ₂ / R )

P ao ₂	Partial pressure of oxygen in alveolus
P io ₂	Partial pressure of oxygen in inspired air
P aco ₂	Partial pressure of carbon dioxide in alveolus
R	Respiratory quotient

As minute ventilation increases, carbon dioxide exhalation increases. Within minutes, a resulting respiratory alkalosis acts on the central respiratory center to limit further increases in ventilation. To compensate for this respiratory alkalosis, the kidneys begin to excrete bicarbonate. Acetazolamide enhances this excretion. Gradual, progressive renal excretion of bicarbonate allows ventilation to rise slowly, reaching a maximum after 6 to 8 days at a given altitude. An individual’s HVR is related to their ability to acclimatize. A low HVR and relative hypoventilation are implicated in the pathogenesis of both AMS and HAPE. For the majority of people with intermediate HVRs, however, ventilatory drive appears to have no predictive value for AMS development.

The stress of acute hypoxia leads to rapid release of catecholamines. This results in increased cardiac output and elevations in heart rate, stroke volume, blood pressure, and venous tone. Except at extreme altitudes, acclimatization over weeks results in the gradual return of the resting heart rate to near sea-level values. Continued resting tachycardia is evidence of poor acclimatization. As the altitude increases, the maximal heart rate capacity decreases. At the limits of acclimatization, maximal and resting heart rates converge. Ultimately, for most individuals it is pulmonary, not cardiac reserves that limit high-altitude performance.

The hematopoietic response to high-altitude acclimatization includes an increase in both hemoglobin and the number of red blood cells. As a result of fluid shifts into the extravascular space, hemoglobin concentration increases up to 15% after rapid ascent to high altitude. Long-term acclimatization leads to an increase in plasma volume and total blood volume. Within hours of ascent, erythropoietin is secreted in response to hypoxemia which in turn stimulates the production of red blood cells, leading to new circulatory red blood cells in 4 or 5 days. During the next 2 months, red blood cell mass increases in proportion to the degree of hypoxemia.

Hypoxemia also results in an increase in 2,3-diphosphoglycerate, causing a rightward shift of the oxyhemoglobin dissociation curve, which favors a release of oxygen from the blood to the tissues. This is counteracted by the leftward shift of the oxyhemoglobin dissociation curve caused by the respiratory alkalosis from hyperventilation. The net result is a negligible change in the oxyhemoglobin curve. Some individuals with mutant hemoglobin and high oxygen-hemoglobin affinity are found to acclimatize more efficiently than their normal counterparts at moderate altitudes.

Physiologic Response to Hypobaric Hypoxia

Although acute hypoxia elicits a broad array of physiologic responses, the clinical syndromes of high-altitude illness predominantly affect the brain and lungs. Hypobaric hypoxia’s effects on central nervous system homeostasis give rise to AMS and HACE. AMS is the common, benign form that unheeded, can develop into rare, but potentially lethal HACE. HAPE results from overly exuberant increases in pulmonary arterial pressures that lead to stress failures of the delicate pulmonary capillary beds.

Although discrete physiologic responses occur within minutes of exposure to acute hypoxia, the clinical syndromes of high altitude typically require hours to days to manifest themselves. AMS can develop within 4 to 8 hours of acute exposure to hypobaric hypoxia. HACE and HAPE typically occur 2 to 4 days after exposure to high altitude. Because hypobaric hypoxemia occurs within minutes of arrival, it cannot be the direct cause of high-altitude illness. Instead, it appears to be the initiating factor for a complex pathologic process that leads to the development of the various clinical syndromes. The proposed mechanisms for the development of AMS, HAPE, and HACE are represented schematically in Figure 132.2 .

Fig. 132.2, Flowchart of proposed mechanisms for the development of acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). CNS, Central nervous system; ICP, intracranial pressure.

HVR is the first response to insufficient oxygen, leading to increased minute ventilation. A robust HVR tends to be protective by encouraging compensatory ventilation. A limited HVR leads to relative hypoventilation and inadequate response to the hypoxemia of high altitude.

Centrally mediated periodic breathing associated with high-altitude exposure may result in periods of apnea during sleep, causing severe arterial oxygen desaturation, which further exacerbates hypoxemia. Significant hypoxemia initiates multiple systemic responses that involve the circulatory, pulmonary, endocrine, and central nervous systems.

Hypoxemia alters fluid homeostasis, resulting in generalized fluid retention followed by the shift of fluid into the intracellular spaces. This is manifested by peripheral edema, decreased urinary output, decreased central vascular volume, and increased body weight in patients with AMS. Several different mechanisms may account for these fluid shifts, including arginine vasopressin levels and centrally mediated sympathetic stimulation. Arginine vasopressin levels are elevated in some cases of AMS and HAPE and decreased in others. Aldosterone, plasma renin, and atrial natriuretic levels are higher in people with AMS.

HAPE results from hypoxia-induced acute pulmonary hypertension leading to stress failure of pulmonary capillaries with consequent alveolar and interstitial edema. Although exercise and cold stress at altitude may increase hypoxemia and exacerbate pulmonary hypertension, the hypoxic pulmonary vasoconstrictive response (HPVR) acts as the primary mediator. HPVR results in pulmonary arterial smooth muscle contraction within the typically low-pressure pulmonary arterial system, with consequent increases in pulmonary arterial pressures within minutes. The HPVR can vary widely between individuals and can even vary widely in different regions of the lungs of the same individual. This unevenness of pulmonary vasoconstriction within the lung is thought to contribute to the pathophysiology of HAPE. In patients with HAPE, exaggerated pulmonary arterial pressures (mean pressure 36 to 51 mm Hg) occur. Uneven vasoconstriction forces the pulmonary hypertension to be transmitted to delicate capillary vessels in an asymmetrical fashion, leading to the failure of capillary endothelium with resultant alveolar and interstitial edema. This uneven edema explains the patchy nature of the infiltrate seen on a chest radiograph with HAPE. Although elevated pulmonary arterial pressure is the sine qua non of HAPE, even marked acute pulmonary hypertension is not alone sufficient to cause HAPE.

The mechanism for the uneven vasoconstriction in HAPE may be due to decreased nitric oxide bioavailability at the pulmonary tissue level. That HAPE has its origins in acute pulmonary hypertension and resultant over-perfusion is supported by studies revealing that pharmacologic agents that limit excessive rises in pulmonary artery pressure prevent HAPE.

Once mechanical injury and pulmonary edema occur, other factors come into play. Acute inflammatory mediators appear and likely contribute to worsening lung function. As alveolar fluid accumulates, impairment in a patient’s transepithelial sodium transport may decrease their ability to clear alveolar fluid worsening HAPE. Sodium channel–mediated alveolar fluid clearance is upregulated by inhaled beta-adrenergic agonists, which have been proven to decrease risk of HAPE.

Preexisting inflammation may also be a risk factor for HAPE. Particularly in children, preexisting respiratory infection during ascent to high altitude increases susceptibility to HAPE. Inflammation may “sensitize” the pulmonary endothelium to mechanical injury and increase susceptibility to alveolar fluid accumulation and HAPE during ascent.

The definitive etiology of the cerebral forms of altitude illness remains unclear. Evidence suggests that clinical manifestations of AMS and HACE result from the combined effects of altered cerebral hemodynamics and inflammatory mediators. Within minutes of exposure to hypoxia, cerebral vasodilation occurs with increased arterial blood velocity and volume. Hypocapnia (secondary to increased ventilation) creates a countervailing cerebral vasoconstriction, however, the overall effect is one of increased cerebral blood flow. Given the rigid confines of the skull, increases in intracranial blood volume require compensatory changes in the brain and cerebral spinal fluid or intracranial pressures will increase. CNS hypoxemia leads to impaired vascular autoregulation, causing increased pressures within the brain’s capillary beds. In addition, systemic hypertension from strenuous exercise at high altitude may overwhelm the brain vasculature, resulting in transcapillary leakage and vasogenic edema. In susceptible individuals, these hemodynamic changes are likely to contribute to clinical manifestations of AMS and HACE.

Additional circumstances, however, may be necessary for the development of vasogenic edema and clinical symptoms. Inflammatory mediators may contribute to edema formation. Vascular endothelial growth factor, the inducible form of nitric oxide synthase, reactive cytokines, mitochondrial dysfunction, and free radical formation may alter brain endothelial permeability. The roles that these play in the pathophysiologic process of altitude illness remain unclear.

The role of vasogenic edema in AMS is still under investigation. Magnetic resonance imaging (MRI) of subjects acutely exposed to hypoxia reveal similar signal changes in both subjects with and without clinical AMS. In patients with HACE, MRI studies reveal characteristic white matter changes consistent with vasogenic edema that correlate with symptoms. Although still an area of active research, AMS and HACE pathophysiology is likely due to disturbances in the blood-brain barrier through a combination of mechanical factors and biochemical mediation of permeability.

In severe AMS, MRI studies have revealed cytotoxic edema to present. Rather than being the primary mechanism of severe AMS or HACE, this cytotoxic edema is likely secondary to increased cell ischemia resulting from initial hemodynamic changes, vasogenic edema, biochemical mediators, and increased ratios of brain volume to intracranial space. Increasing data highlight the independent role of hypobaria in the development of AMS and on physiologic responses, including heart rate. In experiments where subjects are exposed to identical levels of alveolar oxygen deprivation, subjects exposed to normobaric hypoxia (by decreasing fraction of inspired oxygen [Fi o ₂ ]) alone have much lower AMS incidence than subjects exposed to a hypobaric hypoxia.

The “tight fit” hypothesis was proposed more than three decades ago to explain AMS development and its inherent individual susceptibility. This theory suggests that individuals are more susceptible to AMS and HACE as their ability to accommodate increased hypoxia-related intracranial blood volume and cerebral edema decrease. As brain volume increases from increased cerebral blood volume, the volume-buffering capacity of the central nervous system may prevent an immediate rise of intracranial pressure. As brain volume increases, the intracranial cerebrospinal fluid (CSF) is displaced through the foramen magnum into the spinal canal. Increased absorption of CSF by the arachnoid villi and decreased CSF production also occur. Individuals with less intracranial and intraspinal CSF buffering capacity have less compliance, and so experience larger increases in intracranial pressure, and become more symptomatic (i.e., manifested as AMS) from mild brain swelling. The tight fit hypothesis is supported by lumbar puncture, MRI, and computed tomography (CT) studies. More recently, optic nerve sheath ultrasonography has emerged as an early, noninvasive diagnostic tool to assess intracranial pressure. Increasing intracranial pressure correlates directly with optic nerve sheath diameter (ONSD). Studies have demonstrated that elevated intracranial pressure is associated with AMS and HACE.

Acute Mountain Sickness

Clinical Features

AMS is a clinical diagnosis. As defined by the Lake Louise Criteria, the diagnosis of AMS requires a patient to have recently ascended to an elevation to 8000 feet, with report of a headache plus at least one of the following symptoms: gastrointestinal upset (anorexia, nausea, or vomiting), general weakness or fatigue, or dizziness or lightheadedness ( Box 132.2 ). The headache may vary from mild to severe, is generally bitemporal and throbbing in nature, and is worse during the night and on awakening or when suddenly becoming upright. Anorexia and nausea, with or without vomiting, are common, and the other symptoms described can range in severity from mild to incapacitating. The disturbance of sleep caused by periodic breathing is common in all visitors to high altitudes but may be exacerbated in the setting of AMS. The symptoms of AMS develop within a few hours after arrival at high altitude and generally reach maximum severity between 24 and 48 hours, followed by a gradual resolution. Most individuals become symptom-free by the third or fourth day. Patients with continued symptoms should not ascend until symptoms abate, and descent and alternative diagnoses should also be considered.

BOX 132.2

Acute Mountain Sickness

Incidence: 12% to 67%, varies widely with elevation, rate of ascent, and individual susceptibility; rare below 8000 feet, most common with rapid ascent to altitudes above 10,000 feet.
Symptoms and signs: Headache, anorexia, nausea, fatigue, dizziness.
Treatment: Mild cases are usually self-limited and do not require treatment; discontinue ascent, rest. For moderate cases, administer acetazolamide; ibuprofen, aspirin, or acetaminophen for headache; Zofran or prochlorperazine for nausea; supplemental oxygen if available; descend if persistent or severe; add dexamethasone in severe cases.
Prevention: Gradual ascent to allow acclimatization; high-carbohydrate diet, avoidance of ethanol or smoking; acetazolamide if ascent is rapid or known history of recurrent acute mountain sickness (AMS).

Given its subjective nature, AMS is difficult to definitively diagnose in infants and pre-verbal children. AMS may be manifested by increased fussiness, decreased playfulness, decreased appetite, and sleep disturbance. Although AMS, or a change in environment, sleeping accommodation, or eating habits may result in a fussy, unhappy child, the differential diagnosis for these nonspecific findings must remain broad. If occult bacteremia or another serious illness is suspected in a young child, descent to lower altitude for an appropriate diagnostic and treatment regimen is recommended.

Differential Diagnoses

AMS is a clinical diagnosis without objective diagnostic physical findings, therefore a broad differential diagnosis when treating these nonspecific symptoms is prudent ( Box 132.3 ). Less common, but lethal etiologies of headache, nausea, and fatigue must be considered before the relatively benign diagnosis of AMS is made. Any evidence of ataxia or altered mentation suggests HACE or other malignant etiology and mandates immediate descent. Benign focal neurologic findings and transient global amnesia have been described at altitude but should be assumed to be malignant in etiology until proven otherwise. Acute carbon monoxide (CO) poisoning should also be considered in high-altitude settings and is most commonly detected in poorly ventilated shelters near campfires, stoves or gas-powered generators used for heat, cooking, and fuel. Physiologically, when coupled with hypobaric hypoxia, carbon monoxide exposure is more dangerous in cold high-altitude locations than in other environments. Although dyspnea on exertion is universal and expected at high altitudes, dyspnea at rest suggests HAPE and warrants a careful examination for pulmonary edema.

BOX 132.3

Acute Mountain Sickness Differential Diagnosis

Tension headache
Viral syndrome
Alcohol intoxication/toxidrome
Carbon monoxide (CO) poisoning
Dehydration
Caffeine withdrawal
Migraine headache
Infectious (meningitis, encephalitis/viral syndrome)
Intracranial hemorrhage or mass
Central nervous system aneurysm
Venous sinus thrombosis
Abdominal process (e.g., gastroenteritis)
Acute angle closure glaucoma/ocular process

Diagnostic Testing

Serial measurement of ONSD using ultrasound has demonstrated that subjects with symptoms and signs of worsening AMS or HACE have enlarged ONSDs on serial measurements, which may prove a useful adjunct in the diagnosis and monitoring of AMS and HACE ( Fig. 132.3 ). Given significant individual variability in ONSD, isolated ONSD ultrasonography at a single point in time has little utility in the diagnosis of AMS.

Fig. 132.3, Diagnostic image of optic nerve sheath ultrasonography. (A) Probe positioning: This study is typically performed with the subject supine and with eyes closed. The probe is placed on the closed lid, lateral of the center of the pupil, and adjusted until a longitudinal, cross-sectional image of the optic nerve (deep to the retina) is obtained. For clarity, this figure does not show the use of ultrasound gel, occlusive dressing, or a high-frequency (7- to 10-MHz) linear probe. (B) Optic nerve sheath ultrasonogram with measurements.

Management

Patients with AMS should not ascend to a higher sleeping altitude until symptoms resolve to allow acclimatization to occur. Continued ascent exacerbates the underlying pathologic processes and may lead to severe AMS or lethal HACE. If patients develop neurologic abnormalities (e.g., ataxia or altered mentation) or evidence of severe pulmonary edema, immediate descent is indicated.

Mild AMS may be treated by symptom management and cessation of ascent until acclimatization occurs. This may take 1 to 4 days. AMS that becomes worse or does not respond to maintenance of altitude, rest, and pharmacologic intervention necessitates descent. A descent of as little as 500 feet may be sufficient. Descent of 1500 to 3000 feet effectively reverses high-altitude illness in most cases. Descent should be continued until symptom improvement is seen, and efforts to minimize exertion should be instituted during the descent.

Oxygen Therapy

All forms of altitude illness, including AMS, are effectively treated with supplemental oxygen. In mild AMS, supplemental oxygen may be helpful but is not essential. For severe forms of altitude illness, oxygen can be lifesaving. In resort settings, oxygen can often be rented directly from the hotel or condominium. For AMS, low flow oxygen (1 to 2 L/min), including small amounts during sleep, is often sufficient. In the wilderness, oxygen tanks are cumbersome, heavy, and are usually unavailable in adequate quantities. To overcome this, remote clinics often use solar-powered oxygen generators. In resource-limited settings, oxygen therapy is reserved for the more serious manifestations of high-altitude illness. Hyperbaric therapy with a portable fabric chamber that simulates descent is also effective.

Analgesics and Antiemetics

Symptomatic treatment of headache and nausea can be beneficial during the course of mild AMS. Aspirin, ibuprofen, and acetaminophen are useful for the treatment of high-altitude headache. Narcotic analgesics should be avoided because of depression of the hypoventilation response (HVR) and respiratory drive during sleep. For nausea and vomiting, prochlorperazine, unlike other antiemetics, stimulates the HVR and is preferred.

Acetazolamide

Periodic breathing causes insomnia, which is best treated with the respiratory stimulant acetazolamide. Doses of acetazolamide as low as 62.5 mg to 125 mg bid may prevent intermittent breathing and eradicate insomnia. Most benzodiazepines and other sedative-hypnotics should be avoided because of their tendency to decrease ventilation during sleep. Even individuals who have previously used diazepam at lower altitudes without difficulty describe unusual reactions, including agitation, hallucinations, and disorientation when this agent is used at high altitude. Studies suggest that low doses of benzodiazepines in combination with acetazolamide are safe at high altitude and can improve sleep quality and reduce episodes of nocturia without increasing oxygen desaturation. Nonbenzodiazepine sleep agents (such as zolpidem and zaleplon) do not depress ventilation and may prove useful in AMS-related insomnia.

Acetazolamide accelerates acclimatization and, if given early in the development of AMS, may rapidly resolve symptoms. Although the optimal dose has not yet been definitively established, a dose of 250 mg of acetazolamide at the onset of symptoms and repeated twice daily is effective therapy for AMS. The treatment of AMS in children is not formally studied, but anecdotal experience supports the use of acetazolamide in children. The dose for children is 2.5 mg/kg/dose every 6 to 8 hours or 125 mg given twice daily to a maximum of 250 mg.

Acetazolamide has myriad beneficial effects. By acting as a carbonic anhydrase inhibitor, it enhances renal bicarbonate diuresis and so improves renal correction of the ventilation-related respiratory alkalosis by causing continued increased ventilation and arterial oxygenation. It improves sleep by decreasing nocturnal period breathing. Acetazolamide also acts as a diuretic and so attenuates fluid retention common in patients with AMS. It lowers CSF volume and pressure, which may play an additional role in its therapeutic effect. In addition, it has positive effects beyond its role as a carbonic anhydrase inhibitor, with beneficial chemoreceptor effects on ventilatory drive, alterations of cerebral blood flow, relaxation of smooth muscles, and upregulation of fluid resorption in the lungs.

The most common adverse reactions to acetazolamide are paresthesias and polyuria. Less common reactions include nausea, diarrhea, drowsiness, tinnitus, and transient myopia. Carbonic anhydrase inhibition at the tongue causes dysgeusia, altering the flavor of carbonated beverages, including carbonated beers (of note, nitrogenated beers are unaffected). Acetazolamide is a sulfa compound and carries a low risk of cross-reactivity for individuals with an allergy to sulfa antibiotics. Patients with known sulfonamide allergy may consider administration of a trial dose of acetazolamide in a controlled environment before ascent. Acetazolamide is contraindicated in patients with a history of anaphylaxis or severe skin reactions to any sulfa-containing medication, and it should be avoided in breast-feeding mothers and pregnant women.

Dexamethasone

Dexamethasone is an effective alternative treatment of moderate to severe AMS. An initial dose of 8 mg followed by 4 mg every 6 hours is recommended. As a treatment option, concurrent use with acetazolamide is advocated by some to promote acclimatization. Dexamethasone is known to have antiinflammatory properties. Additionally, it may reduce cerebral blood flow and block the action of vascular endothelial growth factor. Reduction of AMS symptoms with the use of dexamethasone may be the result of these or its euphoric effects. Prophylactic use of dexamethasone should generally be reserved for use in individuals forced to rapidly ascend (e.g., professional mountain search and rescue operations). Although dexamethasone effectively relieves the symptoms of AMS, unlike acetazolamide, it does not enhance acclimatization. If used as a prophylactic agent to allow ascent beyond physiologic acclimatization, acute cessation can result in rapid onset of severe altitude illness. For treatment, use should be limited to patients with acetazolamide intolerance or more advanced cases of AMS, especially to help facilitate descent. Common side effects of dexamethasone include gastrointestinal irritation, gastritis, esophagitis, altered mood, and gastroesophageal reflux disease (GERD). Dexamethasone should not be used for more than 3 days for this indication because more serious side effects such as GI bleed and altered mental status with aberrant behavior have been described.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here