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A. Characteristicsnavigator

  1. Classification of Common Syndromes
    1. Cerebral: Acute mountain sickenss, high altitude cerebral edema (HACE)
    2. Pulmonary: High altitude pulmonary edema (HAPE)
  2. Occur in unacclimatized persons shortly after ascent to high altitude
  3. Incidence
    1. Altitude 1850-2750 meters (7000-9000 feet) 22%
    2. Altitude 3000 m (10,000 ft) 42%
    3. HAPE: 0.1%-15% depending on ascent rate, previous HAPE, other cardiopulmonary disease
  4. Gradual ascent is best prevention; chemoprophylaxis also effective
  5. Other High-Altitude Conditions [2]
    1. Chronic mountain sickness
    2. Subacute mountain sickness
    3. Retinal hemorrhage
  6. Common Syndromes at HIgh Altitudes
    1. Reduced maximal oxygen consumption
    2. Impaired mental performance
    3. Disordered sleep

B. Risk Factorsnavigator

  1. Rate of ascent
  2. Altitude reached
  3. Sleeping altitude (altitude at which a person sleeps)
  4. Residence at altitude <900 m (3500 ft)
  5. Exertion
  6. Various preexisting cardiopulmonary conditions
  7. Persons <50 years are at less risk than younger persons
  8. Women are at less risk than men
  9. No effect of physical fitness
  10. No risk: hypertension, coronary artery disease, mild COPD, diabetes, pregnancy

C. Acute Mountain Sickness (AMS)navigator

  1. Nonspecific symptoms, somewhat subjective
  2. Definition
    1. Headache in unacclimatized person recently arrived at altitude >2500 m AND
    2. At least one of the following:
    3. Gastrointestinal: Anorexia, nausea, or vomiting
    4. Insomnia
    5. Dizziness
    6. Lassitude or fatigue
  3. Symptoms typically develop within 6-10 hours (as early as 1 hour) after ascent
  4. May progress to cerebral edema rapidly, particularly in those with HAPE
  5. Findings Associated with Cerebral Edema
    1. Retinal hemorrhage - common
    2. Papilledema
    3. Cranial nerve palsy (due to elevated intracranial pressure) - uncommon

D. High Altitude Pulmonary Edema (HAPE) [9] navigator

  1. Hydrostatic non-cardiogenic pulmonary edema with altered alveolar-capillary permeability
  2. Accounts for most deaths from high-altitude illness with similar risk factors as AMS
  3. Usually occurs on the 2nd night after ascent; rarely after 4 nights at a given altitude
  4. 50% with HAPE have acute mountain sickness; 14% have cerebral edema
  5. Pathophysiology [3,9]
    1. Elevated pulmonary artery systolic pressures, usually >35mm Hg
    2. Respiratory alkalosis (hypocapnia) induces vasoconstriction and pulmonary shunting [5]
    3. Elevation of pulmonary capillary pressure to >20mm Hg
    4. Leads to breakdown in alveolar capillary barrier, allows protein and fluid leakage
    5. Protein-rich and mildly hemorrhagic pulmonary edema
    6. Inflammation (cells or cytokines) is not present
    7. Poor clearance of alveolar fluid likely contributes as well
  6. Electrocardiography (ECG)
    1. Sinus tachycardia (most common)
    2. Right (R) ventricular strain: R axis deviation, R bundle branch block
    3. P-wave abnormalities
  7. Chest radiography: normal sized heart, pulmonary vascular congestion, patchy infiltrates
  8. Arterial Blood Gas
    1. Hypoxemia - PaO2 ~30-40mm
    2. Respiratory alkalosis (hypocarbia)
    3. Respiratory acidosis is not typically present
  9. Increased risk of high-altitude pulmonary edema (HAPE, including "mountain sickness") and altitude-associated arterial hypoxemia in persons with large patent foramen ovale [11]

E. Other High-Altitude Conditions [2]navigator

  1. Chronic Mountain Sickness
    1. Severe polycythemia - up to 80% hematocrit
    2. Headache
    3. Somnolence / Fatigue
    4. Depression
    5. Difficulty drawing blood samples may occur due to hematocrit
  2. Subacute Mountain Sickness
    1. Affects infants and adults
    2. Dyspnea, cought, angina with effort
    3. Right heart failure with peripheral edema
  3. Retinal Hemorrhage
    1. Common at extreme altitude, >5000 meters
    2. Rarely causes visual impairment

F. Differential Diagnosis of High-Altitude Illness (Table 1, Reference [6])navigator

  1. AMS and Cerebral Edema
    1. Acute psychosis
    2. Arteriovenous malformation (AVM)
    3. Brain tumor
    4. Carbon monoxide poisoning
    5. Central nervous system infection
    6. Dehydration
    7. Diabetic ketoacidosis
    8. Exhaustion
    9. Hangover
    10. Hypoglycemia
    11. Hyponatremia
    12. Hypothermia
    13. Ingestion of toxins, drugs, or alcohol
    14. Migraine
    15. Seizures
    16. Stroke or transient ischemic attack
    17. Viral or bacterial infection
  2. HAPE
    1. Asthma
    2. Bronchitis
    3. Heart failure
    4. Hyperventilation syndrome
    5. Mucus plugging
    6. Myocardial infarction
    7. Pneumonia
    8. Pulmonary embolus

G. Pathophysiology [2] navigator

  1. Hypoxia is major initiator in both brian and lungs
  2. Immediate effect is increased sympathetic activity
  3. Lungs [9]
    1. Hypoxic vasoconstriction --> elevated pulmonary artery pressures
    2. Uneven vasoconstriction contributes to focal or region overperfusion
    3. Pulmonary venous constriction --> elevated capillary pressures
    4. This leads to capillary leakage
    5. Reduced clearance of sodium and water from alveolar space also occurs
    6. Reduced clearance of sodium is believed to be important predisposing factor
    7. Reduced activity of amiloride-sensitve sodium channel leads to reduced fluid clearance
    8. Capillary leakage and reduced clearance lead to HAPE
    9. ß-adrenergic agonists stimulate sodium transport and can reduce fluid accumulation
    10. Dexamethasone, also effective in HAPE, alters sodium transport
  4. Brain
    1. Hypoxia induces vasodilation
    2. Cerebral blood volume and blood flow increase
    3. Cerebral blood autoregulation is impaired at high altitudes
    4. Increased cerebral blood flow leads to overperfusion
    5. Capillary pressures increase (due to sympathetic outflow and high aldosterone)
    6. Vasogenic edema ensues
    7. Inadequate volume buffering by cerebropsinal fluid occurs
    8. Vasogenic edema and inadequate volume buffering lead to cerebral edema
  5. Renal Effects [8]
    1. Hypoxia induces compensatory increases in red blood cell (RBC) mass
    2. This leads to increased hemoglobin (Hb) concentrations
    3. Raised Hb helps maintain oxygenation to tissues
    4. Increased RBC mass is mediated by erythropoietin (EPO) production from kidney
    5. Persons at high altitude have elevated EPO levels
    6. ~15% of persons at high altitude have hematocrits (HCT) >55%
    7. HCT >55% is called high altitude polycythemia (HAP)
    8. HAP associated with proteinuria and/or chronic renal dysfunction in 40% of persons

H. Treatmentnavigator

  1. Descent by 500-1000 meters is most helpful
  2. Salmeterol (Serevent®) [4]
    1. Long-acting, ß-adrenergic agonist
    2. Dose 125µg po bid
    3. Reduces risk of HAPE by >50%
    4. Likely improves sodium transport across epithelium
  3. Oxygen
  4. Hyperbaric chamber if available
  5. Acetazolamide - treatment and prevention of AMS
  6. Dexamethasone
    1. Treatment and prevention of AMS
    2. Treatment of cerebral edema
    3. Prevention of HAPE [10]
  7. Furosemide - treatment of AMS or cerebral edema
  8. Nifedipine - treatment and prevention of HAPE
  9. Nonsteroidal antiinflammatory drugs (NSAIDS) - treatment and prevention of headache
  10. Antiemetics
    1. Treatment of nausea and vomiting
    2. Prochlorperazine or promethazine recommended
    3. May also consider serotonin receptor antagonists (ondansetron and others)
  11. Zolpidem (Ambien®) - treatment of insomnia
  12. ACE Inhibitors for HAP [8]
    1. Patients randomized to 5mg/d enalapril or control
    2. Enalapril reduces HCT, RBC mass, proteinuria in patients with HAPE
    3. Enalapril or other ACE inhibitor strongly recommended in HAPE
  13. HACE
    1. Immediate descent
    2. Oxygen
    3. Dexamethasone (Decadron®)
  14. Phosphodiesterase-5 Inhibitors [7,10]
    1. Sildenafil (Viagra®, Revatio®), tadalafil (Cialis®) [7]
    2. Induces vasodilation in certain vascular beds including lungs, penis
    3. Reduces pulmonary resistance in hypoxia induced pulmonary hypertension
    4. Effective in various forms of precapilary pulmonary hypertension
    5. Tadalafil prevents HAPE [10]

References navigator

  1. Basnyat B and Murdoch DR. 2003. Lancet. 361(9373):1967 abstract
  2. West JB. 2004. Ann Intern Med. 141(10):789 abstract
  3. Swenson ER, Maggiorini M, Mongovin S, et al. 2002. JAMA. 287(17):2228 abstract
  4. Sartori C, Allemann Y, Duplain H, et al. 2002. NEJM. 346(21):1631 abstract
  5. Laffey JG and Kavanagh BP. 2002. NEJM. 347(1):43 abstract
  6. Hackett PH and Roach RC. 2001. NEJM. 345(2):107 abstract
  7. Ghofrani HA, Reichenberger F, Kohstall MG, et al. 2004. Ann Intern Med. 141(3):169 abstract
  8. Plata R, Cornejo A, Arratia C, et al. 2002. Lancet. 359(9307):663 abstract
  9. Swenson ER. 2006. Ann Intern Med. 145(7):550 abstract
  10. Maggiorini M, Brunner-La Rocca HP, Peth S, et al. 2006. Ann Intern Med. 145(7):497 abstract
  11. Allemann Y, Hutter D, Lipp E, et al. 2006. JAMA. 296(24):2954 abstract