High-altitude illness includes acute mountain sickness (AMS), high-altitude pulmonary (o)edema (HAPE), and high-altitude cerebral (o)edema (HACE). Given time, humans are able to acclimatise to increasing altitude (up to about 18,000 feet or 5,490 metres) by:

• Increasing ventilation (via carotid body hypoxic ventilatory response).
• Increasing red blood cell production (via erythropoietin).
• Increasing vascularity of lungs and tissues.
• Suppression of antidiuretic hormone (ADH) and aldosterone, and increasing tissue mitochondria.

However, altitude sickness commonly occurs in people ascending to more than 2,500 metres (8,202 feet).

• AMS: a milder and more common form - this is self-limiting and consists of a number of nonspecific symptoms, including headache, loss of appetite, and nausea.
• More severe forms include HACE and HAPE: these may lead to coma and death if left untreated.
• AMS and HACE are caused by hypoxia-induced changes in the blood-brain barrier leading to cerebral oedema and brain swelling.
• In HAPE, exaggerated pulmonary hypertension leads to increased vascular permeability.
• AMS usually precedes development of HACE, whereas HAPE develops during the first 2-4 days at high altitude and is not always preceded by AMS.

Patients at increased risk of high-altitude illness include those with cardiac or pulmonary disease. It is still possible for patients with coronary heart disease, hypertension or asthma to attain high altitudes, but patients with chronic obstructive pulmonary disease, interstitial pulmonary disease or pulmonary hypertension are at appreciably greater risk.¹

Risk factors

• Rapid ascent.
• Climbing to higher altitudes, starting ascent at higher altitudes, and sleeping at higher altitudes.
• Continued ascent with symptoms of acute mountain sickness (AMS) is a risk factor for high-altitude cerebral (o)edema (HACE).
• Individual susceptibility.
• Physical exertion at high altitudes.
• History of high-altitude sickness.
• Permanent residence at low altitudes (below 900 metres).
• High-altitude dwellers returning from a brief period at low altitude.
• Age less than 50 years.
• Neck irradiation or surgery.
• Upper respiratory tract infections or bronchitis.
• Exertion, low temperatures and cardiopulmonary circulation abnormalities are predisposing factors for high-altitude pulmonary (o)edema (HAPE).

Acute mountain sickness

• Typically, occurs at altitudes greater than 2,500 metres (8,202 feet).
• The incidence of acute mountain sickness (AMS) increases with absolute height attained and with the rate of ascent. A survey in Taiwan of people ascending to above 3,000 metres (9,843 feet) showed that 27% experienced acute mountain sickness.² It is not related to the level of physical fitness.
• Symptoms may take days to develop or may occur within hours, depending on the rate of ascent and the altitude attained:
  • Loss of appetite, nausea or vomiting, headache, fatigue, irritability, insomnia, dizziness.
  • Visual disturbances may be experienced at higher altitudes.
  • Peripheral oedema, pulmonary crepitations and retinal haemorrhages may sometimes occur.
• Usually a self-limiting syndrome but can progress to peripheral oedema, retinal haemorrhages, dyspnoea at rest, altered consciousness and ataxia, cerebral and pulmonary oedema.

High-altitude cerebral oedema

• Incidence is less than 1%.
• Usually occurs 2-4 days after ascent.
• Presents with features of acute mountain sickness (AMS) but also:
  • Hallucinations, disorientation, confusion, drowsiness, decreasing level of consciousness.
  • Seizures, blurred speech and double vision are less common.
  • Focal and nonfocal signs of raised intracranial pressure (severe headache, papilloedema, vomiting, IIIrd or VIth cranial nerve palsies); retinal haemorrhages and focal neurological deficits, e.g. cranial nerve palsy.
• May progress rapidly to coma and death if untreated.

High-altitude pulmonary oedema

• Incidence: 0.01-15% (slightly greater in individuals aged under 20 years).³
• Usually occurs 2-4 days after ascent:
  • Symptoms and signs are typical of pulmonary oedema, including dyspneoa at rest, cough (initially dry from interstitial oedema and then productive of frothy sputum which may be bloodstained in later stages), chest tightness, poor exercise tolerance and eventually cyanosis.
  • Pulmonary crepitations in at least one lung field, central cyanosis, tachycardia, tachypnoea.
  • Other signs include mild fever, orthopnoea.
• May occur with or without acute mountain sickness (AMS)/high-altitude cerebral (o)edema (HACE) and can lead to death.

Investigations

• Pulse oximetry reflects expected hypoxia at altitude, helpful in high-altitude pulmonary (o)edema (HAPE), but doesn't correlate well with severity of acute mountain sickness (AMS)/high-altitude cerebral (o)edema (HACE).
• Arterial blood gases and CXR (unilateral or bilateral fluffy infiltrates) in HAPE.
• CT/MRI scan in HACE to rule out cerebrovascular accident (CVA)/transient ischaemic attack (TIA).

Differential diagnosis

• Anxiety.
• Hypothermia.
• Other causes of respiratory distress, e.g. pneumonia.
• Other causes of central neurological dysfunction, e.g. brain tumour, TIA, stroke.

Management

When feasible, descent remains the single best treatment for acute mountain sickness (AMS) and high-altitude cerebral (o)edema (HACE).⁴

• Symptom control:
  • Analgesics and antiemetics.
  • Ibuprofen, which is more effective than aspirin for relieving high-altitude headache.
• Mild AMS:
  • Rest and avoiding further ascent until symptoms improve.
• Moderate-to-severe cases of AMS:
  • Descent with supplementary oxygen therapy.
  • Acetazolamide (125-250 mg bd) and/or dexamethasone (8 mg stat then 4 mg qds), especially if descent is not possible.
• HACE:
  • Descent with supplementary oxygen.
  • Dexamethasone to relieve symptoms and aid descent, or in situations where descent is not possible.
  • Hyperbaric therapy (e.g. Gamow® Bag) can improve symptoms sufficiently to aid actual descent, e.g. bring an individual out of a coma or improve ataxia; it can be life-saving when descent is not possible and oxygen is unavailable.
  • If symptoms persist after descent, treatment with oxygen and dexamethasone should be continued.
• HAPE:
  • Descent with supplementary oxygen if available; descent of even a few hundred metres may be enough.
  • Nifedipine can relieve symptoms and aid descent; or can be used in situations where descent is not possible.
  • Hyperbaric therapy can be useful to aid descent or in situations where descent is impossible or oxygen is unavailable.
  • If there are persistent symptoms after descent, then the patient may require continued treatment with oxygen and nifedipine.

Prevention

Prevention of altitude-related illness by slow ascent is the best approach, but this is not always practical.⁵

• Gradual ascent allowing time for acclimatisation.
• Keep warm and well hydrated.
• Avoid alcohol.
• High-carbohydrate diet.
• Modest exercise on acclimatising days.
• Prophylactic treatment with acetazolamide (125 mg bd)⁶ or dexamethasone (4 mg qds) can be effective in those with a history of altitude sickness, or in situations where rapid ascent is unavoidable. Start treatment 1 day before ascent and discontinue 2 days after reaching high altitude.
• Ginkgo biloba extract has recently been shown to be effective in preventing acute mountain sickness (AMS) but the evidence is not as strong as for acetazolamide.⁶
• Nifedipine can be used prophylactically (20 mg SR bd or 30 mg LA od) for individuals with a history of high-altitude pulmonary (o)edema (HAPE).

Other high-altitude conditions

• Peripheral oedema.
• High-altitude retinopathy.
• High-altitude pharyngitis and bronchitis.
• Chronic mountain polycythaemia (CMP).
• Ultraviolet keratitis (snow blindness); foreign-body sensation, irritation, pain, photophobia, tearing, blepharospasm, and decreased visual acuity 6-12 hours after the exposure; prognosis is usually excellent with full recovery in 24-76 hours.⁷

High-altitude and type 1 diabetes mellitus

• Studies have not shown any difference in occurrence rates of acute mountain sickness (AMS), high-altitude cerebral (o)edema (HACE) or high-altitude pulmonary (o)edema (HAPE) between normal subjects and those with type 1 diabetes at altitudes ranging from 1,700 to 5,800 metres.⁸
• Those with pre-existing diabetic retinopathy may be at higher risk for high-altitude retinal haemorrhage (HARH) and/or disease progression, and it is recommended that such individuals have a dilated pupil ophthalmological examination and/or fluorescein angiogram before considering any trip involving exposure to high altitude.⁸
• Both hyperglycaemia and sporadic hypoglycaemia have been reported in a number of individuals with type 1 diabetes at altitude.⁸
  Therefore, it is essential to have close glucose monitoring and rapid access to a glucagon kit (and to ensure that at least one of their travelling companions can locate and knows how to use the kit in the case of an emergency).
• Both overestimation and underestimation of glycaemia and of standard glucose control solutions have been demonstrated at altitude.⁸
• Prolonged travel at high altitude is associated with significant anorexia and loss of bodyweight. Insulin injections should be carefully timed and titrated to ensure that they match actual nutrient ingestion.
• Average temperatures decrease by 2°C for every 300 metres of elevation so temperatures at freezing point can be expected at >3,000 metres. Insulin should not be exposed to temperatures that are <2°C because of potential loss of bioactivity. Therefore, adequate protection of insulin from extremes of temperature, including carrying supplies next to the skin, are essential.⁸

Document references

1. Fischer R; Visiting high altitudes--healthy persons and patients with risk diseases. MMW Fortschr Med. 2004 Feb 19;146(8):33-4, 36-7. [abstract]
2. Kao WF, Kuo CC, Hsu TF, et al; Acute mountain sickness in Jade Mountain climbers of Taiwan. Aviat Space Environ Med. 2002 Apr;73(4):359-62. [abstract]
3. Hultgren HN; High-altitude pulmonary edema: current concepts. Annu Rev Med. 1996;47:267-84. [abstract]
4. Luks AM et al; Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness. Wilderness Environ Med. 2010 Jun;21(2):146-55.
5. Imray C, Wright A, Subudhi A, et al; Acute mountain sickness: pathophysiology, prevention, and treatment. Prog Cardiovasc Dis. 2010 May-Jun;52(6):467-84. [abstract]
6. Chow T, Browne V, Heileson HL, et al; Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial. Arch Intern Med. 2005 Feb 14;165(3):296-301. [abstract]
7. Brozen R et al; Ultraviolet Keratitis, eMedicine, Dec 2009
8. Brubaker PL; Adventure travel and type 1 diabetes: the complicating effects of high altitude. Diabetes Care. 2005 Oct;28(10):2563-72.

Internet and further reading

• Kale R et al; Altitude-Related Disorders, eMedicine, Apr 2009

Acknowledgements