Altitude Sickness

11 Interesting Facts of Altitude Sickness 

  1. Altitude sickness is a collection of symptoms, varying from mild to life-threatening, resulting from hypobaric hypoxia upon rapid ascent to high altitude (usually higher than 2500 m [8202 ft] above sea level)
  2. Acute mountain sickness is a benign form of altitude sickness, manifesting with headache and benign generalized symptoms
  3. High-altitude cerebral edema manifests as altered mental status or ataxia in person with acute mountain sickness, or as change in mental status and ataxia in person at altitude without acute mountain sickness
  4. High-altitude pulmonary edema is a noncardiogenic pulmonary edema not necessarily preceded by acute mountain sickness
  5. Chronic mountain sickness affects some people who dwell at high altitudes. It is characterized by polycythemia and pulmonary hypertension
  6. Acute mountain sickness symptoms typically begin within a few hours to a few days after arrival at high altitude (especially higher than 2500 m [8202 ft])
  7. Generally, diagnosis of acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema is made at remote locations in the field, where laboratory tests and imaging are not available
  8. Primary diagnostic tools are history and physical examination, especially as follows:
    • Neurologic examination
      • Ataxia and change in mental status are the key signs of high-altitude cerebral edema
    • Chest auscultation
      • Crackles are a sign of high-altitude pulmonary edema, which usually begins in right middle lobe
  9. Differential diagnosis includes the following:
    • Dehydration
    • Carbon monoxide poisoning
    • Hypothermia
    • Hyponatremia
    • Altitude decompression sickness
  10. Main treatment options are as follows:
    • Descent to lower altitude is gold standard treatment for all categories of altitude sickness
      • All high-altitude cerebral edema (whether confirmed or suspected) mandates immediate descent
    • Supplemental oxygen is useful for all types of altitude sickness
    • Acetazolamide is used as follows:
      • Treatment and prevention of acute mountain sickness symptoms
      • Treatment of periodic breathing during sleep, obstructive sleep apnea, and other altitude-related sleep disturbances
    • Nifedipine is mainstay drug for treatment of high-altitude pulmonary edema
    • Dexamethasone is mainstay drug treatment for high-altitude cerebral edema
  11. Best preventive strategy is acclimation, which is achieved by ascending slowly, making rest stops for several hours to a day at intermediate altitudes before continuing ascent, and descending 300 to 500 m (984 to 1640 ft) to sleep (climb high, sleep low)

Pitfalls

  • Signs and symptoms of high-altitude cerebral edema may be subtle. Apply high index of suspicion at all times, because the primary intervention (descent to lower altitude) must occur rapidly before cerebral edema progresses and mental status deteriorates
  • Because the incidence of high-altitude pulmonary edema is fairly low, and because classically it is remembered as being associated with pink, frothy sputum (which is a very late sign), the condition may not be identified until after it has reached an advanced stage. This situation can be avoided by recognizing early signs, as follows:
    • Fluid retention, indicated by oliguria despite water consumption and by puffy facial appearance
      • When noticed, these signs may also identify patients at risk of developing high-altitude cerebral edema before the appearance of neurologic signs, such as ataxia and change in mental status
      • Generally, increased diuresis during mountain climbing is a sign that a person is acclimating
    • Crackles on lung auscultation, usually beginning in right middle lobe
  • High altitude refers to terrestrial elevations more than 1500 m (4921 ft) above sea level 
    • High altitude: 1500 to 3500 m (4921 to 11,482 ft)
    • Very high altitude: 3500 to 5500 m (11,482 ft to 18,044 ft)
    • Extreme altitude: 5500 to 8850 m (18,044 to 29,035 ft)
  • Altitude sickness is a collection of symptoms, varying from mild to life-threatening, resulting from hypobaric hypoxia upon rapid ascent to high altitude (usually higher than 2500 m [8202 ft])
    • Rapid ascent refers to ascending without giving time for the body to acclimate to the new altitude
      • It may take 1 to 3 days to acclimate after climbing to a new altitude
        • New altitude means only a few hundred meters higher than previous altitude, because a small change can result in acute mountain sickness in these cases 
  • Incidence of high-altitude cerebral edema is much lower than those of acute mountain sickness and high-altitude pulmonary edema, but suspicion for cerebral edema must remain high at all times because the condition is rapidly progressive and life-threatening 

Classification

  • High-altitude headache
    • Simple headache experienced by most unacclimated people at altitudes higher than 2500 m (8202 ft)
      • May occur at lower altitudes 
  • Acute mountain sickness
    • Most commonly occurs in unacclimated people at altitudes higher than 2500 m (8202 ft), but may occur at lower altitudes 
    • Benign form of altitude sickness, manifesting with headache and at least 1 of the following: 
      • Fatigue or weakness
      • Dizziness or lightheadedness
      • Gastrointestinal symptoms (nausea, vomiting, or anorexia)
      • Insomnia or other sleep disturbances
    • Lake Louise score for assessing acute mountain sickness severity
      • Headache
        • No headache: 0
        • Mild headache: 1
        • Moderate headache: 2
        • Severe, incapacitating headache: 3
      • Gastrointestinal symptoms
        • No gastrointestinal symptoms: 0
        • Poor appetite or nausea: 1
        • Moderate nausea and/or vomiting: 2
        • Severe, incapacitating nausea and/or vomiting: 3
      • Fatigue and/or weakness
        • Not tired or weak: 0
        • Mild fatigue or weakness: 1
        • Moderate fatigue or weakness: 2
        • Severe, incapacitating fatigue or weakness: 3
      • Dizziness/lightheadedness
        • Not dizzy: 0
        • Mild dizziness: 1
        • Moderate dizziness: 2
        • Severe, incapacitating dizziness: 3
      • Difficulty sleeping
        • Slept as well as usual: 0
        • Did not sleep as well as usual: 1
        • Woke many times, poor sleep: 2
        • Could not sleep at all: 3
      • Overall, how did symptoms, if present, affect patient’s activity?
        • No reduction in activity: 0
        • Mild reduction in activity: 1
        • Moderate reduction in activity: 2
        • Severe reduction in activity (eg, restricted to bed rest): 4
      • Score of 3 or more: mild acute mountain sickness
      • Score of 6 or more: moderate/severe acute mountain sickness
        • Serial examinations allow comparison of severity of potentially worsening mental status
    • Acute mountain sickness and high-altitude cerebral edema exist on a spectrum of continuity 
  • High-altitude cerebral edema
    • May be considered end-stage acute mountain sickness
      • Potentially life-threatening neurologic syndrome
        • Change in mental status or ataxia in person with acute mountain sickness or
        • Change in mental status and ataxia in person at altitude without acute mountain sickness
      • Death results from brain herniation
  • High-altitude pulmonary edema
    • Noncardiogenic pulmonary edema developing at high altitude, not necessarily preceded by acute mountain sickness, and diagnosed based on both of the following criteria: 
      • 2 or more of the following symptoms:
        • Dyspnea at rest
        • Cough
        • Weakness or decreased exercise tolerance
        • Chest tightness or congestion
      • 2 or more of the following signs:
        • Crackles or wheezing in at least 1 lung field
        • Central cyanosis
        • Tachypnea
        • Tachycardia
    • Presence of 2 or more symptoms and 2 or more signs is required for the diagnosis of high-altitude pulmonary edema
  • Chronic mountain sickness
    • Chronic entity affecting some people who dwell at high altitudes 
      • Puts mountain dwellers at increased risk for pulmonary hypertension, stroke, and congestive heart failure
      • Manifests with polycythemia, which increases risk for pulmonary hypertension and stroke

Clinical Presentation

History

  • History of previous episode of altitude sickness predisposes patient to a recurrence 
    • Every ascent is different, and onset of symptoms is unpredictable
  • History of risk factors, such as the following:
    • Rapid ascent to the symptom-provocative altitude (within 1 day)
    • History of acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema
    • Naivete to high altitudes
  • History of acute mountain sickness syndrome, beginning within a few hours to a few days after arrival at high altitude (especially 2500 m [8202 ft] or higher), particularly the following: 
    • Headache
    • Insomnia or disturbed sleep
    • Gastrointestinal upset and nausea
    • Fatigue
  • History of neurologic symptoms beyond those of acute mountain sickness, such as the following:
    • Confusion
    • Difficulty speaking
    • Visual disturbances
    • Difficulty walking
  • History of symptoms suggestive of possible high-altitude pulmonary edema developing 2 to 4 days after ascent, such as the following:
    • Dyspnea and/or tachypnea at rest
    • Cough
    • Exercise intolerance
    • Chest congestion or tightness
  • Pulmonary symptoms that begin more than 5 days after arrival at a new altitude should prompt pursuit of an alternate diagnosis such as pneumonia, pulmonary embolism, or pneumothorax 
  • History of symptoms and signs related to fluid retention
    • Low urine output despite adequate water consumption since beginning ascent
    • Patient or peers report face has gotten puffier during climb and/or limbs have swelled

Physical examination

  • Vital signs will change depending on altitude and will reflect decreased oxygen tension and atmospheric pressure
    • Tachypnea 
    • Rapid pulse 
    • Oxygen saturation 90% or greater 
  • Chest examination findings suggestive of high-altitude pulmonary edema
    • Crackles or wheezing on pulmonary auscultation
    • Tachycardia
    • Chest pain suggesting hypoxia-related cardiac ischemia
  • Neurologic signs and symptoms suggestive of high-altitude cerebral edema
    • Ataxia
      • Truncal ataxia is an alarming sign and should prompt immediate treatment 
    • Change in mental status/confusion
    • Other neurologic deficits
      • Speaking difficulty
      • Visual disturbances
      • Limb paralysis
      • Visual deficits
      • Seizures
      • Hallucinations
  • Ophthalmoscopy: signs with suspected, but not proven, association with high-altitude cerebral edema 
    • Retinal hemorrhages
      • Generally occur at altitudes of 5000 m (16,404 ft) or higher
    • Papilledema

Causes

  • Condition is provoked by atmospheric effects of altitude; lower ambient pressure produces lower PO₂
    • Generally above 2500 m (8202 ft) and especially above 3000 m (9842 ft)
      • About 25% of unacclimated travelers experience acute mountain sickness on ascending to modest altitude (2500 m [8202 ft] or higher)
      • Acute mountain sickness has been documented at elevations as low as 1500 m (4921 ft) 

Risk factors and/or associations

Age
  • People younger than 50 years are more likely to be affected by acute mountain sickness than older people 
  • High-altitude pulmonary edema occurs more often in children and younger adults 
Sex
  • Male individuals have higher risk of high-altitude pulmonary edema
Genetics
  • Accumulating genetic data are consistent with the following: 
    • Susceptibility to acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema is influenced in complex ways by interactions between multiple genes
Ethnicity/race
  • For chronic mountain sickness, elevated risk is documented in residents of the Andes (South America), but chronic mountain sickness is rare in other high-altitude populations, such as Tibetan people and Ethiopian highlanders 
Other risk factors/associations
  • Rapid ascent and ascent to high altitudes: risk can be categorized based on rate of ascent and previous acute mountain sickness, as follows:
    • Low risk
      • No history of previous altitude sickness
      • Ascending to points below 2800 m (9186 ft)
      • Taking 2 or more days to reach 2800 m (9186 ft) with subsequent increases in sleeping altitude less than 500 m (1640 ft) per day
    • Moderate risk
      • History of previous acute mountain sickness
      • Ascending to the range of 2500 to 2800 m (8202 to 9186 ft) in 1 day
      • No history of acute mountain sickness and ascending to the range of 2800 to 3500 m (9186 to 11,482 ft) in 1 day
      • Increase in sleeping altitude more than 500 m (1640 ft) per day starting between 3000 (9842 ft) and 3500 m (11,482 ft)
    • High risk
      • History of acute mountain sickness
      • Ascending more than 2800 m (9186 ft) in 1 day
      • History of previous high-altitude pulmonary edema or high-altitude cerebral edema
      • Ascending to altitude above 3500 m (11,482 ft) in 1 day
      • Increase in sleeping altitude by more than 500 m (1640 ft) per day starting above 3500 m (11,482 ft)
      • Member of a group with individual moderate or high risk
      • Very rapid ascent (eg, Mount Kilimanjaro)
    • Acute mountain sickness affects 25% to 85% of travelers to high altitudes, depending on arrival altitude, home altitude, rate of ascent, and individual susceptibility 
      • Colorado ski areas: 25%
      • Himalaya mountains: 50%
      • Direct flight to Mount Everest region: 85%
    • High-altitude pulmonary edema affects as many as 4% of unacclimated mountain climbers reaching 4600 m (15,091 ft) or higher 
  • Sleeping at altitude that is higher than the altitude that the climber reached during the day before sleep (not descending to sleep after reaching the high altitude of the day)
  • Cold environments 
  • Obesity 
  • Factors increasing risk specifically of high-altitude pulmonary edema
    • Upper respiratory tract infection 
    • Factors leading to pulmonary hypertension
      • Patent foramen ovale
      • Idiopathic pulmonary hypertension
      • Mitral stenosis
      • Unilateral absence of pulmonary artery

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination, especially as follows:
    • Chest auscultation
      • Crackles (rales) or wheezing in any lung field suggest high-altitude pulmonary edema 2 to 4 days after ascent to 2500 m (8202 ft) or higher
        • High-altitude pulmonary edema is particularly likely to develop with crackles heard over right middle lobe first (heard on right side of chest, fourth intercostal space, midclavicular line)
    • Neurologic examination
    • Funduscopic examination
    • Signs of hypoxia (other than low oxygen saturation)
      • Blue or gray fingernails and lips
    • Signs and symptoms of high-altitude cerebral edema may be subtle. Apply high index of suspicion at all times, because the primary intervention (descent to lower altitude) must occur rapidly before cerebral edema progresses and mental status deteriorates
    • Because the incidence of high-altitude pulmonary edema is fairly low and because classically it is associated with pink, frothy sputum (which is a very late sign), the condition may not be identified until after it has reached an advanced stage. This situation can be avoided by recognizing early signs, as follows:
      • Fluid retention, indicated by oliguria despite water consumption and by puffy facial appearance
        • When noticed, these signs may also identify patients at risk for developing high-altitude cerebral edema before the appearance of neurologic signs such as ataxia and mental status changes
        • Generally, increased diuresis during mountain climbing is a sign that a person is acclimating
      • Crackles on lung auscultation, usually beginning in right middle lobe
  • Pulse oximetry 
  • Laboratory tests and imaging are usually not relevant to diagnosis or treatment
    • Resources are extremely limited at high altitudes
    • Instead, laboratory tests and imaging are useful for documenting patient status after the fact or for evaluating risk before ascent to altitude

Laboratory

  • Sputum culture and Gram staining
    • For patients with high-altitude pulmonary edema suspected of developing secondary pulmonary infection or to help differentiate pneumonia from high-altitude pulmonary edema
  • Brain natriuretic peptide levels are elevated in high-altitude pulmonary edema

Imaging

  • Chest radiograph
    • Evaluate for diagnoses other than high-altitude pulmonary edema, such as pneumonia

Functional testing

  • Mini–Mental State Examination takes 5 to 7 minutes to administer and gives objective and comparable information to assess cognition 

Differential Diagnosis

Most common

  • Dehydration
    • History of not drinking enough water since beginning ascent
    • Low urine output
    • Dry mouth and skin
  • Carbon monoxide poisoning
    • No formal incidence data are available, but wilderness medicine specialists are commonly concerned based on case experience
    • Very difficult to diagnose clinically in remote high-altitude settings
      • Neurologic symptoms overlap with those of acute mountain sickness and high-altitude cerebral edema
      • Respiratory symptoms overlap with those of high-altitude pulmonary edema 
    • Factors suggestive of carbon monoxide poisoning and not acute mountain sickness 
      • History of being in a tent or snow cave with fire without adequate ventilation
      • Apparent oxygen saturation is high (95% or more) on standard pulse oximetry, despite pulmonary symptoms, such as dyspnea
        • Carbon monoxide in blood falsely elevates pulse oximetry value 
    • Tests definitive for carbon monoxide poisoning are not usually available in remote high-altitude settings
      • Blood carboxyhemoglobin level
      • Carbon monoxide oximetry
    • Ambient environmental carbon monoxide detector is a mandatory piece of equipment for ascent
  • Hypothermia
    • History of shivering that has worsened but then stopped 
    • Core body temperature will be low, which may help differentiate from acute mountain sickness
    • Symptoms should improve with rewarming
    • Symptoms will not improve with descent
  • Hyponatremia
    • Might present with cramps and muscle spasms (different from acute mountain sickness)
    • May be more likely to happen in patients who pretreat with acetazolamide, furosemide, or dexamethasone
    • Symptoms will not improve with descent
  • Pneumonia
    • Although high-altitude pulmonary edema may include a low-grade fever (less than 37.8 °C), high-grade fever is more characteristic of pneumonia 
    • Symptoms and signs may predominate in 1 lung (asymmetric)
    • Symptoms may improve with oxygen therapy but not with simple descent
  • Altitude decompression sickness
    • Upon depressurization, dissolved gases come out of solution and form bubbles in the blood, which can develop into arterial gas emboli, causing strokes, heart attacks, and other organ injuries
    • Most important factor distinguishing this from other altitude sickness comes from the history, namely diving in high-altitude lakes or diving before ascending the mountain 
    • Most important distinguishing symptom from acute mountain sickness is musculoskeletal pain, especially in knee, which is reported in 70% of altitude decompression sickness cases 

What's on this Page

Treatment Goals

  • Completely reverse all symptoms

Admission criteria

Upon return to lower altitude, admit all patients with high-altitude cerebral edema or high-altitude pulmonary edema for observation until all symptoms and signs resolve 

Criteria for ICU admission
  • Admit all patients with high-altitude cerebral edema to ICU for treatment and observation until all symptoms and signs resolve
  • For patients with high-altitude pulmonary edema, admit to ICU if they require endotracheal intubation, mechanical ventilation, or 100% oxygen to maintain pulse oximetry values at 95% or greater

Treatment Options

Descent to lower altitude is the gold standard treatment for all categories of altitude sickness 

Descent of 500 to 1000 m (1640 to 3280 ft) is generally adequate to arrest and reverse signs and symptoms of acute mountain sickness

  • High-altitude headache will respond to acetaminophen or NSAIDs
  • When altitude sickness is limited to high-altitude headache or acute mountain sickness, descent is not mandatory, but further ascent should be avoided until patient has acclimated
    • Climbers planning to remain at high altitude overnight should descend slightly (at least 300 to 500 m [984 to 1640 ft]) to sleep, before reascending the next day and progressing to higher altitude 

Provision of oxygen is an absolute requirement for all forms of acute mountain sickness

  • CPAP has been shown to be beneficial for high-altitude pulmonary edema

Stepwise treatment of high-altitude cerebral edema

  • Immediate descent is mandatory in all suspected cases
    • Condition is life-threatening and mandates abortion of ascent
  • Dexamethasone is very effective and works quickly. It should be the first drug given

Stepwise drug treatment of high-altitude pulmonary edema

  • Nifedipine will help prevent worsening and should be the first drug given
    • Avoid nifedipine if blood pressure is low (mean arterial pressure of 66 mm Hg or lower)
  • There is little downside and some possible benefit to dexamethasone in acute high-altitude pulmonary edema
    • Use of acetazolamide is unproven but there is little reason not to use it, so it is included as a third line therapy
    • Inhaled β₂-agonists are easy to administer, have excellent safety profile, and are useful to relieve pulmonary bronchospasm
    • Phosphodiesterase inhibitors are another possible option in patients not responding to other therapies
  • Diuretics such as furosemide have different and unpredictable effects at altitude and are not routinely recommended for all cases of high-altitude pulmonary edema

Drug therapy

  • Prophylaxis
    • Acute mountain sickness and high-altitude cerebral edema prophylaxis
      • Acetazolamide
        • Acetazolamide Oral tablet; Infants†, Children†, and Adolescents†: 2.5 mg/kg/dose (Max: 125 mg/dose) PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated.
        • Acetazolamide Oral tablet; Adults weighing 100 kg or less: 125 mg PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated.
        • Acetazolamide Oral tablet; Adults weighing more than 100 kg: 250 mg PO every 12 hours starting the day before ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated.
      • Dexamethasone
        • Prophylaxis
          • Dexamethasone Oral tablet; Adults: 2 mg PO every 6 hours or 4 mg PO every 12 hours starting the day of ascent and continuing for 2 to 3 days after reaching the target altitude or until descent is initiated for a maximum of 10 days. May consider 4 mg PO every 6 hours for very high risk situations.
    • High-altitude pulmonary edema prophylaxis
      • Nifedipine
        • Nifedipine Oral tablet, extended-release; Adults: 30 mg PO every 12 hours or 20 mg PO every 8 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated.
      • Phosphodiesterase 5 inhibitors
        • Sildenafil
          • Sildenafil Citrate Oral tablet; Adults: 50 mg PO every 8 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated.
        • Tadalafil
          • Tadalafil Oral tablet; Adults: 10 mg PO twice daily starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated.
      • β-agonists
        • Patients with any subtle or transient symptoms consistent with high-altitude pulmonary edema at altitude should undergo prophylaxis with β-agonists before ascending to higher altitude
        • Salmeterol
          • NOTE: The following dose recommendations are based on data using a formulation of salmeterol inhalation aerosol that is no longer available. The salmeterol dosage suggested in clinical practice guidelines is much higher than approved by the FDA and may be associated with adverse effects.
          • Salmeterol Xinafoate Inhalation powder; Adults: 125 mcg by oral inhalation every 12 hours starting the day before ascent and continuing for 5 days after reaching the target altitude or until descent is initiated.
  • Treatment
    • Acute mountain sickness and high-altitude cerebral edema treatment 
      • Acetazolamide
        • Acetazolamide Oral tablet; Infants†, Children†, and Adolescents†: 2.5 mg/kg/dose (Max: 250 mg/dose) PO every 8 to 12 hours until symptoms resolve.
        • Acetazolamide Oral tablet; Adults: 250 mg PO every 12 hours until symptoms resolve.
      • Dexamethasone 
        • Acute mountain sickness without high altitude cerebral edema treatment
          • Oral
            • Dexamethasone Oral solution; Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) PO every 6 hours until symptoms resolve.
            • Dexamethasone Oral tablet; Adults: 4 mg PO every 6 hours until symptoms resolve.
          • Parenteral
            • Dexamethasone Sodium Phosphate Solution for injection; Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) IV or IM every 6 hours until symptoms resolve.
            • Dexamethasone Sodium Phosphate Solution for injection; Adults: 4 mg IV/IM every 6 hours until symptoms resolve.
        • Acute mountain sickness and high altitude cerebral edema treatment
          • Oral
            • Dexamethasone Oral solution; Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) PO every 6 hours until symptoms resolve.
            • Dexamethasone Oral tablet; Adults: 8 mg PO once, then 4 mg PO every 6 hours until symptoms resolve.
          • Parenteral
            • Dexamethasone Sodium Phosphate Solution for injection; Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) IV/IM every 6 hours until symptoms resolve.
            • Dexamethasone Sodium Phosphate Solution for injection; Adults: 8 mg IV/IM once, then 4 mg IV/IM every 6 hours until symptoms resolve.
      • Furosemide
        • Field-experienced altitude/wilderness physicians suggest that it can be used as adjunct treatment in patients with acute mountain sickness who have peripheral edema
        • Prescribed only on a case-by-case basis in very small doses, especially in healthy climbers who are furosemide naive 
          • Furosemide Solution for injection; Adults: 20 mg IV as a single dose; or in severe cases, 80 mg IV every 12 hours for 2 days, or longer if needed, has been reported.
    • High-altitude pulmonary edema treatment
      • Nifedipine
        • Nifedipine Oral tablet, extended-release; Children and Adolescents: 0.5 mg/kg/dose (Max: 40 mg/dose) PO every 8 hours until symptoms resolve.
        • Nifedipine Oral tablet, extended-release; Adults: 30 mg PO every 12 hours or 20 mg PO every 8 hours until symptoms resolve.
      • Furosemide
        • Furosemide Solution for injection; Adults: 20 mg IV as a single dose; or in severe cases, 80 mg IV every 12 hours for 2 days, or longer if needed, has been reported.
      • Acetazolamide, β-agonists, and phosphodiesterase 5 inhibitors are all unproven for treatment, but they may be beneficial and thus should be used as second tier therapies
  • Summary by drug
    • Acetazolamide
      • Promotes acclimation by stimulating bicarbonate diuresis and respiration
      • Indications
        • Prophylaxis of symptoms of acute mountain sickness (first line drug for this indication)
        • Prophylaxis of symptoms of high-altitude pulmonary edema unless there is a prior history of high-altitude pulmonary edema
        • Treatment of periodic breathing during sleep, obstructive sleep apnea, and other altitude-related sleep disturbances
          • Anyone who reports sleeping difficulty at altitude should be given a trial of acetazolamide
            • Typically takes 12 to 24 hours for onset of action
      • May be combined with dexamethasone for treatment of high-altitude cerebral edema and high-altitude pulmonary edema
    • Dexamethasone
      • Mainstay drug for treatment and prophylaxis of high-altitude cerebral edema
      • May work by reducing brain blood volume or blocking brain capillary leakage
    • Nifedipine
      • Mainstay drug for treatment and prevention of high-altitude pulmonary edema 
      • Reduces pulmonary artery pressure by relaxing smooth muscle
      • No value in acute mountain sickness or high-altitude cerebral edema
    • Phosphodiesterase 5 inhibitors, such as sildenafil
      • Useful for high-altitude pulmonary edema prophylaxis 
        • Anyone with any symptoms consistent with high-altitude pulmonary edema should receive phosphodiesterase 5 inhibitors as fifth or sixth option of multidrug therapy
    • Long-acting β₂-agonists, such as salmeterol
      • Upregulate active transport of sodium across transepithelial alveolar membrane to increase clearance of alveolar fluid
      • Useful for prevention of high-altitude pulmonary edema
      • May be useful for treatment of high-altitude pulmonary edema
    • Furosemide
      • Loop diuretic that promotes diuresis by reducing reabsorption of sodium chloride
      • Old treatment, not a mainstay drug in altitude sickness, but can be used carefully in treatment for the following:
        • High-altitude pulmonary edema
        • Acute mountain sickness in patients with signs/symptoms of fluid retention
          • Use extremely low dose of furosemide in this setting, given that climbers tend to be furosemide naive

Nondrug and supportive care

In settings of high-altitude pulmonary edema and high-altitude cerebral edema, when immediate descent is not possible because of weather or darkness, administer oxygen (mandatory)

  • Patient should remain on oxygen as needed to keep oxygen saturation at 99% or greater
  • Often, portable oxygen is limited in mountain climbing settings, but it is generally more available in high-altitude tourist destinations, such as Machu Picchu, Peru

Additional treatments

  • CPAP with oxygen: useful for high-altitude pulmonary edema and sleep breathing disturbances 
Procedures
Hyperbaric oxygen

General explanation

  • Patient is enclosed in portable hyperbaric chamber (known commonly as a Gamow bag), which is filled with air at pressure greater than 1 atmosphere absolute (usually 2 to 2.8 atmospheres absolute)

Indication

  • High-altitude cerebral edema 

Contraindications

  • Most commonly encountered contraindications are as follows:
    • Untreated pneumothorax
    • History of bleomycin use

Comorbidities

  • Coronary artery disease
    • Cardiac symptoms generally worsen with rapid ascent, but risk of cardiac death does not increase measurably 
    • With acclimation, coronary artery disease symptoms may improve; thus people with coronary artery disease who reside at high altitude do better than visitors with coronary artery disease 
    • High-risk ischemic patients should not ascend to high altitude
  • Cardiac arrhythmias
    • Lower threshold for increased incidence of arrhythmias at high altitude 
    • Supplemental oxygen and limitation of activity are indicated in these patients 
    • Patients prone to serious arrhythmias should not be exposed to altitudes above 3000 to 3500 m (9842 to 11,482 ft), particularly in cases of ventricular arrhythmias 
  • Chronic obstructive pulmonary disease
    • Generally gets worse with increasing altitude
    • Acclimation does not improve symptoms; patients with the disease who undergo chronic altitude exposure can develop cor pulmonale
  • Asthma
    • Generally improves with altitude 
    • People with severe asthma should be advised against ascending to high altitude, because attacks will be harder to treat in remote location
    • Anyone with asthma (mild, moderate, or severe) who does ascend should do so with all medications at hand
  • Diabetes mellitus (type 1 and type 2)
    • Acclimation to altitude is normal, but glycemic control can be disrupted, particularly if acute mountain sickness develops (and especially if it includes anorexia). This puts patient at risk for dysglycemia 
    • People with diabetes who are otherwise healthy and fit can ascend to high altitude safely, provided they are capable of frequent blood glucose monitoring and self-management 
  • Hypertension
    • Blood pressure may rise slightly with acute exposure to altitude, but there is no clear evidence of an increased risk of complications due to this blood pressure increase 
    • Hypertensive patients should monitor blood pressure upon ascent to high altitude and bring a plan for altering medications in the event of marked or symptomatic blood pressure change 
    • Patients with uncontrolled or severe hypertension should avoid high-altitude exposure to prevent risk of organ damage 
  • Congestive heart failure
    • Risk depends on disease severity, activity level, and elevation
    • Supplemental oxygen must be increased in some patients with congestive heart failure
    • Patients with uncompensated congestive heart failure should not travel to high altitudes

Special populations

  • Patients with uncomplicated pregnancy
    • Not at special risk for altitude sickness, but should be aware of lack of medical facilities at remote high-altitude sites, especially in developing countries 
      • Ascent to higher than 3000 m (9842 ft) is not advisable in pregnancy 
  • People with sickle cell disease and sickle cell trait
    • Ascent to high altitude is contraindicated in these patients, owing to potential for splenic infarct or sickle cell crisis
    • Ascent to high altitude is one of only a few conditions that puts people with sickle cell trait at risk of sickle cell crisis 
      • Sickle cell crisis develops owing to hypobaric hypoxia, but not via the same mechanism that leads to acute mountain sickness
    • People with sickle cell trait should avoid high altitude, but if they do ascend, they should do so with supplemental oxygen 
  • People who are obese
    • Elevated risk of developing acute mountain sickness 
    • Increased risk for sleep apnea and other sleep disturbances can exacerbate altitude-related sleep disturbances 
  • People with elevated susceptibility or sensitivity to hypoxic pulmonary vasoconstriction 
    • This means patients with the following:
      • Patent foramen ovale
      • Ventricular septal defects
      • Idiopathic pulmonary hypertension
    • These patients should avoid high altitude, but if they do ascend, the following treatments can be helpful: 
      • Supplemental oxygen
      • Calcium channel blockers
      • Isoproterenol

Complications

  • Complications of high-altitude cerebral edema
    • If untreated, can lead to coma and death 
    • Can lead to injury or death indirectly via deteriorated mental status
  • Complications of high-altitude pulmonary edema
    • Death from hypoxia and suffocation is possible if condition is left untreated for a few hours

Prognosis

  • Acute mountain sickness is not life-threatening, and its complications resolve completely with acclimation or with return to low altitude
  • When high-altitude pulmonary edema and high-altitude cerebral edema are recognized and treated early (via immediate descent or other treatments followed by descent), recovery is almost certain 
  • A rate of 7.7 deaths related to untreated high-altitude pulmonary edema and high-altitude cerebral edema has been reported per 100,000 trekkers in the mountains of Nepal 

Screening

At-risk populations

  • Anyone traveling to high altitude
  • Anyone predisposed to pulmonary hypertension, such as patients with the following:
    • Patent foramen ovale 
    • Mitral stenosis 
    • Primary pulmonary hypertension 
    • Unilateral absence of pulmonary artery 

Screening tests

  • Doppler echocardiography
    • Assess for susceptibility to high-altitude pulmonary edema 
    • Prudent for anyone considering high-altitude mountain climbing, because about 25% of the general population has patent foramen ovale or pro–patent foramen ovale (foramen ovale closed but can open if pulmonary pressure increases) 

Prevention

  • Acclimation
    • Achieve by ascending slowly and making rest stops for several hours to a day at intermediate altitudes before continuing ascent
    • Climb high, sleep low: after ascending to an altitude that is high compared with beginning altitude of current day, climbers should descend slightly (300 to 500 m [984 to 1640 ft]) to sleep for the night before continuing the ascent
  • Recent altitude exposure (within the past 2 months)
    • 3000 m (9842 ft) or higher for 5 or more days (not necessarily consecutive) is protective in those with history of acute mountain sickness
  • Acetazolamide
    • Works well for both prophylaxis and treatment of acute mountain sickness
  • Nifedipine
  • Dexamethasone
  • β₂-agonists
  • Phosphodiesterase 5 inhibitors
  • Furosemide
  • Treatment of periodic breathing and other altitude sleep disorders: via acetazolamide or CPAP 
  • Remote ischemic preconditioning has been shown to decrease the chance of developing acute mountain sickness (exposure to normobaric hypoxia at 12%, via altitude simulation tent)

References

Gallagher SA et al: High-altitude illness. Emerg Med Clin North Am. 22(2):329-55, viii, 2004 Reference

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