Given time, humans are able to acclimatise to increasing altitude (5500 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.
Travel to altitudes of 2500 metres or greater puts people at risk of developing high-altitude illness. This could be in the form of acute mountain sickness (AMS), high-altitude pulmonary oedema (HAPE), and high-altitude cerebral oedema (HACE).
- AMS: generally a milder and common form of high-altitude illness. It is usually 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 greater risk.
- Rapid ascent.
- Climbing to higher altitudes, starting ascent at higher altitudes, and sleeping at higher altitudes.
- Continued ascent with symptoms of AMS is a risk factor for 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 HAPE.
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Acute mountain sickness
- Typically, occurs at altitudes greater than 2500 metres.
- The incidence of AMS increases with absolute height attained and with the rate of ascent. A survey in Taiwan of people ascending to above 3000 metres showed that 27% experienced AMS. 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 this is a self-limiting syndrome but it can progress to peripheral oedema, retinal haemorrhages, dyspnoea at rest, altered consciousness and ataxia, and cerebral and pulmonary oedema.
- The Lake Louise AMS score has become the standard for assessing the severity of AMS. Visitors to altitude can complete this assessment themselves - a score of 3 or greater should be considered to be AMS.
High-altitude cerebral oedema
- Incidence is around 1-2% in those who ascend rapidly to 4500 metres.
- Usually it occurs 2-4 days after ascent and presents with features of moderate to severe AMS but also:
- Hallucinations, disorientation, confusion, drowsiness, and 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 - eg, cranial nerve palsy.
- It may progress rapidly to coma and death if untreated.
High-altitude pulmonary oedema
- The incidence of HAPE at 2500 metres is around 0.01% but it rises to 1.9% at 3600 metres and 2.5-5.0% at 4300 metres.
- Risk factors for HAPE include the rate of ascent, intensity of exercise and the absolute altitude. It has been recognised that some individuals are more susceptible.
- Usually it 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, and tachypnoea.
- Other signs include mild fever, and orthopnoea.
- HAPE can occur with or without AMS or HACE and can lead to death. It is probably the leading cause of death at high altitude.
These may be limited in mountain environments but where facilities exist, the following may be helpful:
- Pulse oximetry reflects expected hypoxia at altitude, helpful in HAPE, but doesn't correlate well with severity of AMS or HACE.
- Arterial blood gases and CXR (unilateral or bilateral fluffy infiltrates) in HAPE.
- CT/MRI scan in HACE to rule out cerebrovascular accident/transient ischaemic attack (TIA).
- Other causes of respiratory distress - eg, pneumonia.
- Other causes of central neurological dysfunction - eg, brain tumour, TIA, stroke.
When feasible, descent remains the single best treatment for AMS, HACE and HAPE. Some time can be bought with the use of oxygen or hyperbaric bags but they shouldn't delay descent when it is at all possible.
- Symptom control:
- Analgesics and anti-emetics.
- 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.
- Descent with supplementary oxygen.
- Dexamethasone to relieve symptoms and aid descent, or in situations where descent is not possible.
- Hyperbaric therapy (eg, Gamow Bag®) can improve symptoms sufficiently to aid actual descent - eg, 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.
- 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 of altitude-related illness by slow ascent is the best approach, but this is not always practical.
- Gradual ascent allowing time for acclimatisation. A typical rate of ascent would be 500 metres per day with a rest day every three or four days.
- Keep warm and well hydrated.
- Avoid alcohol.
- High-carbohydrate diet.
- Modest exercise on acclimatising days.
- Visitors to altitude can monitor themselves for AMS using the Lake Louise AMS score. See separate article Preventing Acute Mountain Sickness.
- Anyone who develops symptoms should not ascend further until the symptoms have settled. If they are getting worse then immediate descent is recommended.
- Prophylactic treatment with acetazolamide has been shown to be effective in reducing the symptoms of AMS. There is evidence for total daily doses of acetazolamide ranging from 250 mg to 750 mg.
- The most common adverse effect of acetazolamide is paraesthesia. Rates as high as 91% have been reported at higher doses and lower doses of 125 mg bd are likely to be better tolerated.
- A systematic review in the BMJ showed that the lowest effective dose was 250 mg daily (usually given as 125 mg bd) and the number needed to treat to prevent AMS was six.
- Dexamethasone has evidence of benefit and the recommended adult doses are 2 mg every six hours or 4 mg every twelve hours. They should be used for a maximum of ten days to avoid adrenal suppression.
- There is no robust evidence that ginkgo biloba extract is effective in preventing AMS. 
- Nifedipine can be used prophylactically (20 mg SR bd or 30 mg LA od) for individuals with a history of 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.
High-altitude and type 1 diabetes mellitus
- Studies have not shown any difference in occurrence rates of AMS, HACE or HAPE between normal subjects and those with type 1 diabetes at altitudes ranging from 1,700 to 5,800 metres.
- 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.
- Both hyperglycaemia and sporadic hypoglycaemia have been reported in a number of individuals with type 1 diabetes at altitude. 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.
- Prolonged travel at high altitude is associated with significant anorexia and loss of body weight. 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.
Further reading & references
- Kale R et al; Altitude-Related Disorders, Medscape, Jan 2012
- Fischer R; Visiting high altitudes--healthy persons and patients with risk diseases. MMW Fortschr Med. 2004 Feb 19;146(8):33-4, 36-7.
- 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.
- Davis PR, Pattinson KT, Mason NP, et al; High altitude illness. J R Army Med Corps. 2011 Mar;157(1):12-7.
- Hall DP, Duncan K, Baillie JK; High altitude pulmonary oedema. J R Army Med Corps. 2011 Mar;157(1):68-72.
- 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.
- 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.
- 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.
- Low EV, Avery AJ, Gupta V, et al; Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: systematic review and meta-analysis. BMJ. 2012 Oct 18;345:e6779. doi: 10.1136/bmj.e6779.
- Brozen R et al; Ultraviolet Keratitis, Medscape, Aug 2011
- Brubaker PL; Adventure travel and type 1 diabetes: the complicating effects of high altitude. Diabetes Care. 2005 Oct;28(10):2563-72.
|Original Author: Dr Adrian Bonsall||Current Version: Dr Euan Lawson||Peer Reviewer: Dr Adrian Bonsall|
|Last Checked: 28/03/2013||Document ID: 1145 Version: 24||© EMIS|
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