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Basics ⬇

Author: Joseph E.Allen, MD, MS, FAAFP, CAQSM

ALERT

Once symptoms are recognized, the definitive solution to HAI is descent to lower altitude.

Description

  • The atmospheric percentage of oxygen is a constant 21%. However, the partial pressure of oxygen decreases with increase in altitude. Hypobaric hypoxia forms the physiologic basis for the HAIs, AMS, HAPE, and HACE.
  • Initial AMS symptoms are typically mild and self-limited, progressing to more severe HACE if not adequately recognized and treated.
  • HAPE or HACE can present independently and progress rapidly, with or without initial warning of AMS symptoms.
  • Untreated, HAPE or HACE can be fatal.

Epidemiology

  • Incidence and severity of HAI increase with higher altitude and speed of ascent.
  • At high altitude, AMS may affect 25% of unacclimated individuals, increasing to 50–85% afflicted at very high altitude ( >4,000 m).
  • HAPE and HACE are rarely seen <4,000 m, accounting for an estimated 0.1–0.4% of all cases.

General Prevention

ALERT

  • Graded ascent is the best way to prevent HAIs.
  • Never ascend to a higher sleeping altitude with HAI symptoms.
  • If travel is planned from sea level to above 2,500 m, spend one night at an intermediate elevation.
  • Above 2,500 m, do not ascend >500 m sleeping altitude per day.
  • Spend an extra night of acclimatization for every 1,500 m altitude gained.
  • Pharmaceutical agents: Acetazolamide and dexamethasone may be used for prevention of AMS/HACE and sustained-release; nifedipine for individuals prone to HAPE

Etiology and Pathophysiology

  • Hypobaric hypoxia:
    • With ascent to high altitude comes decreased partial pressure of oxygen. Decreased atmospheric PaO2 affects absorption into the circulation at the alveolar level. Hypoxemia at the cellular level causes a myriad of physiologic stress responses.
    • Decreased partial pressure of oxygen triggers the carotid body to signal the respiratory centers in the medulla to increase ventilation. The extent of compensatory hypoxic ventilatory response (HVR) is thought to be determined at the genetic level. Increased ventilatory rate causes hypocapnia and respiratory alkalosis, which results in an increase in renal excretion of bicarbonate.
  • AMS:
    • Hypoxic stress induces the trigeminovascular system (TVS), leading to increased cerebral blood flow and resultant nausea, headache, and malaise.
    • The central respiratory center responds to HVR-induced respiratory alkalosis with periods of apnea causing disturbed sleep.
  • HACE:
    • Vasogenic cerebral edema, caused by a myriad of responses to hypobaric hypoxia, including TVS induction, endothelial activation, and sympathetic activity
  • HAPE:
    • Acute pulmonary edema induced by hypoxic pulmonary hypertension increases capillary hydrostatic pressure causing extravasation of fluid across the vascular endothelium and into the alveolar space.
    • Impaired reabsorption of alveolar fluid and amplified inflammatory mediator response then accelerate and exacerbates the process.

Risk-Factors

  • Rapid ascent
  • Sleeping at altitude >2,000 m; exceeding >500 m/day sleeping altitude above 2,500 m
  • Lack of acclimatization
  • Young age
  • Strenuous exertion at high altitude
  • Previous history and/or individual susceptibility to altitude illness
  • Obesity
  • Chronic obstructive pulmonary disease, sickle cell disease, uncompensated congestive heart failure, or pulmonary hypertension
  • Well-controlled hypertension and asthma are not considered risk factors.
  • Physical fitness does not predict or prevent altitude illness.

Diagnosis ⬆ ⬇

  • AMS:
    • Nausea
    • Light-headedness
    • Headache
    • Insomnia
    • Anorexia
    • Malaise
    • Fatigue
    • Weakness
    • Impaired memory
    • Inability to focus or concentrate
  • HAPE: Symptoms of AMS may present initially and then progress 2 to 5 days after ascent to dyspnea on exertion and/or dyspnea at rest:
    • Persistent cough, progressing to pink, foamy sputum
    • Chest tightness
    • Fatigue
    • Muscle weakness
  • HACE: Ataxia and confusion are hallmark symptoms heralding progression from AMS to HACE:
    • Headache
    • Vomiting
    • Incoordination
    • Disorientation
    • Irrational behavior
    • Auditory or visual hallucination
    • Lethargy
    • Altered level of consciousness
    • Unconsciousness or coma within 24 hr after the onset of ataxia

History

  • Rapid ascent to high altitude
  • AMS:
    • Onset of symptoms typically 12 to 24 hr and self-limited (as early as 2 hr after arrival but rarely after 36 hr)
  • HAPE:
    • Symptoms usually begin 2 to 5 days after arrival to high altitude and classically the second night sleeping at high altitude.
    • May have a sudden onset (e.g., gondola or helicopter ascent), especially in sedentary individuals at altitude
    • Decreased exercise performance and increased recovery time, cough, dyspnea on exertion, and progressive worsening of symptoms, especially at night. Pink, frothy sputum is usually a late finding.
  • HACE:
    • AMS symptomatology with progressive worsening of neurologic symptoms, including ataxia, extreme lassitude, mental status changes, and coma
    • Commonly associated with HAPE
    • AMS progression to HACE at altitude may be within 12 hr but more commonly 1 to 3 days.
    • HACE generally occurs above 3,000 m but has been described at altitude as low as 2,100 m.

Physical Exam

  • AMS:
    • Specific physical findings are uncommon in mild AMS.
    • Tachycardia or bradycardia
    • Normotensive
  • HAPE:
    • Breathlessness at rest
    • Cyanosis
    • Crackles in right middle lobe are typical but can be anywhere in the lung field.
    • Tachycardia
    • Tachypnea
    • Low-grade fever
    • Orthopnea
  • HACE:
    • Inability to perform activities such as dressing or eating
    • Truncal ataxia demonstrated by poor heel-toe walking
    • Mental status changes
    • Occasionally focal neurologic deficits
    • Funduscopic examination can demonstrate papilledema and retinal hemorrhages (not diagnostic).

Differential Diagnosis

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • HAPE:
    • Chest x-rays demonstrate normal heart size with patchy infiltrates.
  • HACE:
    • Brain magnetic resonance imaging (MRI) T2-weighted images show increased signal in the white matter, particularly the splenium of the corpus callosum, consistent with vasogenic edema and microhemorrhage.

Treatment ⬆ ⬇

ALERT

  • Descent to a lower altitude is the mainstay of treatment for any HAI.
  • Low-intensity descent of at least 500 m is recommended.
  • Avoid further ascent until symptoms resolve.
  • Supplemental oxygen 2 to 4 L/min if available
  • Preventative/treatment options

Medication

  • Oral acetaminophen 650 to 1,000 mg or ibuprofen 600 mg for pain or headache; ondansetron orally disintegrating tablet (ODT) 4 mg PO q4–6h for nausea and vomiting
  • Acetazolamide 125 to 250 mg PO BID, starting 8 to 24 hr prior to ascent (1)[A]
  • Ibuprofen 600 mg PO TID for AMS prevention and symptomatic relief of headache (2)[B]
  • Dexamethasone 2 mg PO q6h, or 4 mg PO q12h, can be used as alternative for AMS prevention if sulfa/acetazolamide allergic. Start the day of ascent, continuing for first 2 days at altitude, or for rapid increase in altitude (1,3)[A].
  • For treatment of HAPE, dexamethasone 4 mg PO/intramuscular (IM)/intravenous (IV) q6h
  • For treatment of HACE, dexamethasone 8 mg loading dose, followed by 4 mg PO/IM/IV q6h
ALERT
Rebound symptoms of AMS have been described after discontinuation of dexamethasone and continued ascent should be avoided.
  • Budesonide 200 μg inhaled BID starting 3 days prior to ascent has been shown effective in preventing AMS (4)[B].
  • Nifedipine 30 mg extended-release PO BID to treat HAPE if oxygen unavailable and rapid descent is delayed (5)[C].
  • Tadalafil 10 mg PO BID, as an alternative to nifedipine (due to potential hypotension with concomitant use), has been described for treatment of HAPE in case reports (2)[C].
  • When extreme weather or additional factors preclude rapid descent, medical treatment has been shown to be a viable option up to 4,240 m (6)[B].
  • If available, a portable hypobaric chamber, or Gamow bag, manually inflated to 2 psi, may be effectively used to simulate a descent of 1,000 to 3,000 m.
  • Upon return to low altitude, transition to inpatient hospital care as soon as possible.

COMPLEMENTARY & ALTERNATIVE MEDICINE

Limited research on Ginkgo biloba for AMS prophylaxis has produced conflicting results but may be a viable alternative for those seeking natural sources. Coca preparations have shown potential for increasing blood oxygenation and decreasing AMS symptoms in some studies (7)[B].

Ongoing Care ⬆ ⬇

  • General measures:
    • Minimize heavy exertion for 2 to 3 days upon arrival to high altitude.
    • Maintain adequate hydration.
    • Eat frequent, small, high-carbohydrate meals.
    • Avoid alcohol or other sedative/hypnotic medications which could suppress respiratory drive.
    • Smoking worsens hypoxia and should be avoided.
  • In critically ill patients:
    • Monitor vital signs periodically because hypotension may lead to cerebral hypoperfusion.
    • Intravenous fluid (IVF) is not contraindicated in HAPE. Administer if available to treat dehydration and maintain cardiac perfusion.
    • Gradually decompress portable hypobaric chambers to minimize potential barotrauma to the middle ear.
    • HACE progressing to coma warrants advanced airway management and bladder decompression if possible. Hyperventilation may lead to further cerebral ischemia and should be avoided.

Additional Reading ⬆ ⬇

  • Centers for Disease Control and Prevention. https://wwwnc.cdc.gov/travel/yellowbook/2018.

  • Flaherty G, O’Connor R, Johnston N. Altitude training for elite endurance athletes: a review for the travel medicine practitioner. Travel Med Infect Dis. 2016;14(3):200–211.
  • Shackleton M, Tondora CM, Whiting S. The effect of homeopathic coca on high altitude mountain sickness: Mt. Everest base camp. J Evid Based Integr Med. 2000;6:44–55.
  • SuttonJR, CoatesG, HoustonCS, eds. The Lake Louise consensus on the definition and quantification of altitude illness. In: Hypoxia and Mountain Medicine. Burlington, VT: Queen City Press; 1992:272–274.

  • Wilderness Medical Society. http://m.wms.org/

References ⬆ ⬇

  1. Kitsteiner J, Whitworth JD, Nashelsky J. FPIN’s clinical inquiries. Preventing acute mountain sickness. Am Fam Physician. 2011;84(4):398–400.
  2. Lipman GS, Kanaan NC, Holck PS, et al. Ibuprofen prevents altitude illness: a randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med. 2012;59(6):484–490.
  3. Eide RP III, Asplund CA. Altitude illness: update on prevention and treatment. Curr Sports Med Rep. 2012;11(3):124–130.
  4. Chen GZ, Zheng CR, Qin J, et al. Inhaled budesonide prevents acute mountain sickness in young Chinese men. J Emerg Med. 2015;48(2):197–206.
  5. Davis C, Hackett P. Advances in the prevention and treatment of high altitude illness. Emerg Med Clin North Am. 2017;35(2):241–260.
  6. Fagenholz PJ, Gutman JA, Murray AF, et al. Treatment of high altitude pulmonary edema at 4240 m in Nepal. High Alt Med Biol. 2007;8(2):139–146.
  7. Biondich AS, Joslin JD. Coca: high altitude remedy of the ancient Incas. Wilderness Environ Med. 2015;26(4):567–571.

Clinical Pearls ⬆

  • Proper acclimatization (i.e., graded ascent) is the best method for preventing HAI.
  • Never ascend to a higher sleeping altitude if symptoms of HAI are present.
  • Acetazolamide 125 to 250 mg PO BID remains a safe and effective means to prevent and treat AMS.
  • Dexamethasone is effective for treating significant AMS as well as HACE.
  • Early recognition and treatment of HAPE/HACE are critical.
  • Once the symptoms of HAI are recognized, supplemental oxygen (if available), and/or controlled descent to a lower altitude are the mainstay of treatment.