Clinical review

Altitude illness

P W Barry, consultant paediatric intensivist ^a, A J Pollard, senior lecturer in paediatric infectious diseases ^b. 

^a Department of Child Health, University of Leicester, Leicester LE2 7LX, ^b Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU

Correspondence to: P W Barry pwb1{at}le.ac.uk

Altitude illness is common in people ascending to more than 2500 metres, especially if the ascent is rapid. In most cases it will manifest as a mild, self limiting illness but in a few cases it will progress to more severe, life threatening forms. This article explains the symptoms and available treatments

As more people travel to high altitudes for economic or recreational purposes, altitude medicine has become increasingly important. Doctors may be asked to give advice to people planning an excursion to high altitudes or to help with patients while they themselves are travelling. Altitude illness should be anticipated in travellers to altitudes higher than 2500 metres, although for most it will be mild, and self limiting, and will not require the intervention of a doctor. Rarely altitude illness may progress to more severe forms, which can be life threatening. The best method of preventing altitude illness is to ascend slowly, allowing time for acclimatisation. The mainstay of treatment is descent, and drugs and other treatments should be used mainly to aid this.

Summary points Altitude related illness is rare at altitudes below 2500 metres but is common in travellers to 3500 metres or more The occurrence is increased by a rapid gain in altitude and reduced by a slow ascent, allowing time for acclimatisation For most travellers, altitude related illness is an unpleasant but self limiting and benign syndrome, consisting chiefly of headache, anorexia, and nausea More severe forms of illness including cerebral or pulmonary oedema may occur and may be fatal, particularly if not recognised The treatment of altitude related illness is to stop further ascent and, if symptoms are severe or getting worse, to descend Oxygen, drugs, and other treatments for altitude illness should be viewed as adjuncts to aid descent

	Methods

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

We gathered the information in this review from several sources, including our own experience and reading of the relevant literature, supported by a search of the Cochrane database, a search of Medline by using the terms "altitude sickness" or "altitude," and by consulting a specialist database of altitude related articles.¹ We used two recently published texts (especially in regard to diagnosis), ^{2 3} and information from a recent course on high altitude medicine and physiology organised by ourselves and held at the National Mountain Centre, Plas Y Brenin, Wales. The research evidence in altitude medicine is scanty and hampered by differences between studies in ascent rates, environmental conditions, and definitions of illness. We therefore used observational studies and clinical experience to formulate recommendations.

	Altitude illness

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

Three main syndromes of altitude illness may affect travellers: acute mountain sickness, high altitude cerebral oedema, and high altitude pulmonary oedema. The risk of dying from altitude related illnesses is low, at least for tourists. For trekkers to Nepal the death rate from all causes was 0.014% and from altitude illness 0.0036%.⁴ Soldiers posted to altitude had an altitude related death rate of 0.16%.⁵ In British climbers attempting peaks over 7000 metres, altitude related illnesses contributed to death in 17%.⁶

Risk factors for developing altitude illness include the rate of ascent, the actual altitude reached, the altitude at which the traveller sleeps, and individual susceptibility.^w1 Box 1 shows definitions of altitude and associated physiological changes. Physical fitness is not protective,⁷ and exertion at altitude increases a traveller's risk of becoming unwell.^w2 Genetic make up may also influence performance at altitude.⁸ Most pre-existing illnesses, such as chronic obstructive airways disease or diabetes, are not in themselves risk factors for developing altitude illness.

Acute mountain sickness
Figure 1 shows the reported incidence of acute mountain sickness at different locations.

View larger version (61K): [in this window] [in a new window]   Fig 1.   Global incidence of acute mountain sickness

Pathophysiology
The pathophysiological processes that cause acute mountain sickness are unknown. However, symptoms of acute mountain sickness may be the result of cerebral swelling, either through vasodilatation induced by hypoxia or through cerebral oedema.³ Impaired cerebral autoregulation, the release of vasogenic mediators, and alteration of the blood-brain barrier by hypoxia may also be important.¹⁰ Similar mechanisms are thought to cause cerebral oedema at high altitude, which may represent a more severe form of acute mountain sickness.^w1 Differences in individual susceptibility to acute mountain sickness are striking and inadequately explained. A reduced ventilatory drive in response to hypoxia may be important,³ as may an individual's relative volume of cerebrospinal fluid to brain tissuepeople with relatively more cerebrospinal fluid are able to displace it to compensate for cerebral oedema.¹⁰

Treatment
Resting at the same altitude often relieves the symptoms of acute mountain sickness, and most patients will improve without treatment at the same altitude in 24-48 hours. ^{2 3} Simple analgesics and antiemetics may reduce headache and nausea in mild acute mountain sickness.^{w3 w4}

Prevention
A body exposed to hypobaric hypoxia makes a series of adjustments, known as acclimatisation, that serve to increase the delivery of oxygen.¹¹ Acclimatisation is best achieved by a slow ascent, allowing the body to adjust before going higher^w5 and minimising the risks of succumbing to altitude related illness. This has led to recommendations for maximum rates of ascent (box 2). Slower ascent may be necessary for some individuals, but others may be able to ascend much faster without symptoms. A flexible itinerary is important, to allow days of rest without further ascent if needed.

High altitude cerebral oedema

Diagnosis
High altitude cerebral oedema is usually preceded by acute mountain sickness and may lead to coma and death. Prodromal symptoms of early mental impairment or a change in behaviour may be ignored by patients and their companions. Headache, nausea and vomiting, hallucination, disorientation, and confusion are often seen; seizures are less common. Clinical signs include ataxia, a common early feature that may be disabling and is often the last sign to disappear during recovery; a progressive deterioration in concious level, proceeding to coma and death; and papilloedema and retinal haemorrhages. Focal neurological signs may occur, but in the absence of other signs and symptoms of cerebral oedema these should prompt consideration of other diagnoses.

View larger version (48K): [in this window] [in a new window]   Fig 2.   High altitude pulmonary oedema and associated contributing factors. Adapted from Hornbein and Schoene.6

Treatment
Anyone with symptoms of high altitude cerebral oedema should descend immediately. Delay may be fatal. Dexamethasone (8 mg initially, then 4 mg every 6 hours orally or parenterally) will usually relieve some symptoms, making evacuation easier. Similarly oxygen, if available, should be used as an aid to evacuation. Hyperbaric chambers improve oxygenation and relieve symptoms, making unaided descent easier.^{w10 w11} Even with descent, recovery may be delayed, and good supportive care is essential.

High altitude pulmonary oedema

Diagnosis
Symptoms of high altitude pulmonary oedema occur most commonly two to three days after arrival at altitude and consist of dyspnoea with exercise, progressing to dyspnoea at rest, a dry cough, weakness, and poor exercise tolerance.^w12 As the disease worsens, severe dyspnoea and frank pulmonary oedema are obvious, with coma and death following. Early clinical signs include tachycardia and tachypnoea, mild pyrexia, basal crepitations, and dependent oedema. Patients with high altitude pulmonary oedema tend to have lower oxygen saturations than unaffected people at the same altitude, but the degree of desaturation by itself is not a reliable sign of high altitude pulmonary oedema.^w13

Pathophysiology
The pathophysiological cause of high altitude pulmonary oedema is still unknown, although several mechanisms have been proposed.³ Due to patchy pulmonary hypertension, stress failure occurs in capillaries of overperfused areas, leading to pulmonary oedema.^w14 It is not clear whether the inflammatory mediators detected in the oedema fluid^w12 reflect an underlying inflammatory cause or are a consequence of another process.

Treatment
Descent is the mainstay of treatment. Descent of even a few hundred metres may be beneficial. ^{2 3} Supplemental oxygen should be given if available. Nifedipine is effective in preventing and treating high altitude pulmonary oedema in susceptible individuals (10 mg orally initially, then 20 mg slow release preparation ever 12 hours^{w15 w16}). A portable hyperbaric chamber has been developed that simulates descent. This consists of an airtight bag, which is pressurised by means of a manual pump. Continuous pumping is needed. The chamber may be claustrophobic, and lying down in it may worsen orthopnoea. Despite these problems the chamber remains popular and is carried by many larger expeditions.

	Approaching an unconscious patient

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

In the field, a doctor may be called to the aid of a severely ill, comatose patient. The diagnosis of altitude illness can be supported by an appropriate history where available. The patient will almost certainly have some chest signs, and it can be difficult to know if the underlying illness is high altitude pulmonary or cerebral oedema, but this matters little, as the pragmatic management is the same: oxygen, dexamethasone 8 mg intravenously or intramuscularly, nifedipine slow release 20 mg, and hyperbaric treatment if availableand, most importantly, descent as soon as possible. Descent of even a few hundred metres may be life saving, and relays of porters, yaks, or ponies are all more likely to be available than a helicopter, which may take many hours to arrive. Box 3 lists types of treatment for altitude related illness.

	Predicting altitude illness

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

Can doctors predict who is likely to develop altitude illness? An individual's past experience is in general a good guide, although there have been well documented exceptions. Otherwise, tests undertaken at sea level are disappointingly poor at predicting altitude illness. Level of fitness, simple measures of lung function, and vascular or pulmonary responses to hypoxia are all inconsistent in predicting individual susceptibility to altitude illness, ^{2 3} and small innovative studies have not as yet been confirmed in larger trials.¹⁴

Additional educational resources Societies Medical Expeditions (www.medex.org.uk/) is a research charity dedicated to investigating the mechanisms of altitude related illness. The organisation runs courses in high altitude medicine and physiology and from 2003 will be organising a diploma in mountain medicine The International Society for Mountain Medicine (www.ismmed.org/) aims to encourage research and the dissemination of practical information about mountain medicine around the world The International Mountaineering and Climbing Federation (UIAA; www.uiaa.ch/) is the umbrella society for climbing organisations The Wilderness Medical Society (www.wms.org/) aims to improve scientific knowledge in matters related to wilderness environments and human activities in these environments Journals and journal articles High Altitude Medicine and Biology Wilderness and Environmental Medicine Bibliography of High Altitude Medicine and Physiology (http://annie.cv.nrao.edu/habibqbe.htm) lists 8600 references on high altitude medicine and physiology Pollard AJ, Murdoch DR. The high altitude medicine handbook. Abingdon: Radcliffe Medical Press, 1998 Ward MP, Milledge JS, West JB. High altitude medicine and physiology2 is the definitive UK text for altitude medicine Hornbein TF, Schoene RB. High altitudean exploration of human adaptation3 contains a collection of detailed essays on the pathophysiology of altitude related disease West JB. High lifea history of high altitude physiology and medicine. New York: Oxford University Press, 1998 Niermeyer, S. The pregnant altitude visitor. Adv Exp Med Biol 1999;474:65-77 Peacock AJ. Oxygen at high altitude. BMJ 1998;317:1063-6. (See also references 3, 11, and 16.) Information for patients Emedicine on line (www.emedicine.com/emerg/ENVIRONMENTAL.htm) is an online emergency medicine textbook with chapters on altitude illness CIWEC Clinic Travel Medicine Center (http://ciwec-clinic.com/) provides information from Kathmandu on altitude illness and traveller's diarrhoea The Himalayan Rescue Association (HRA; www.himalayanrescue.com/) is a voluntary organisation that aims to reduce casualties in the Nepal Himalayas The High Altitude Medicine Guide (www.high-altitude-medicine.com/) provides current medical information for doctors and non-doctors on the prevention, recognition, and treatment of altitude illness

	Pre-existing medical conditions and altitude illness

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

How should a practitioner advise a patient with a pre-existing chronic disease who wishes to travel to altitude? The research evidence to guide such advice is scanty, but in general is encouraging (box 4). Travellers should remember that access to medical care is difficult in many regions at high altitude. Adequate supplies of drugs should be carried, and itineraries should be selected that can offer escape routes if problems arise.

Special considerations arise in respect of children, pregnant women, or elderly people (box 5). Recommendations come largely from consensus documents or expert opinion. ^{2 3 15 16}

	Acknowledgments

We thank Jim Milledge and David Murdoch for their helpful comments on the paper and Brownie Schoene and David Murdoch for permission to reproduce figures.

	Footnotes

Competing interests: PWB has received reimbursement from Medical Expeditions, a UK charity that supports altitude research, for organising educational activities in the field of altitude medicine and physiology. He is also a member of MEDEX, a limited company that supports the activities of Medical Expeditions.

Extra references and definitions appear on bmj.com

	References

Top Methods Altitude illness Approaching an unconscious... Predicting altitude illness Pre-existing medical conditions... References

1.	Roach R, Houston C, Hackett P, Richalet JP. Bibliography of high-altitude medicine and physiology. April 2002. http://annie.cv.nrao.edu/habibqbe.htm (accessed 25 Mar 2003).
2.	Ward MP, Milledge JS, West JB. High altitude medicine and physiology. 3rd ed. London: Arnold, 2000.
3.	Hornbein TF, Schoene RB. High altitudean exploration of human adaptation. New York: Marcel Dekker, 2001. (Lung biology in health and disease. Vol 161.)
4.	Shlim DR, Gallie J. The causes of death among trekkers in Nepal. Int J Sports Med 1992; 13(suppl 1): S74-S76.
5.	Singh I, Khanna PK, Srivastava MC, Lal M, Roy SB, Subramanyam CS. Acute mountain sickness. N Engl J Med 1969; 280: 175-184[ISI][Medline].
6.	Pollard AJ, Clarke C. Deaths during mountaineering at extreme altitude. Lancet 1988; i: 1277.
7.	Milledge JS, Beeley JM, Broome J, Luff N, Pelling M, Smith D. Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response. Eur Respir J 1991; 4: 1000-1003[Abstract].
8.	Woods DR, Montgomery HE. Angiotensin converting enzyme and genetics at high altitude. High Alt Med Biol 2001; 2: 201-210[CrossRef][Medline].
9.	Roach RC, Bärtsch P, Hackett PH, Oelz O. The Lake Louise acute mountain sickness scoring system. In: Sutton JR, Coates G, Houston CS, eds. Hypoxia and molecular medicine. Burlington, VT: Queen City Printers, 1993:272-274.
10.	Hackett PH. High altitude cerebral oedema and acute mountain sickness: a pathophysiology update. Adv Exper Med Biol 1999; 474: 23-45[ISI][Medline].
11.	Mason NP. The physiology of high altitude: an introduction to the cardio-respiratory changes occurring on ascent to altitude. Curr Anaesthesia Crit Care 2000; 11: 34-41.
12.	Dumont L, Mardirosoff C, Tramer MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systemic review. BMJ 2000; 321: 267-272[Abstract/Free Full Text].
13.	Sartori C, Allerman Y, Duplain H, Lepori M, Egli M, Lipp E, et al. Salmeterol for the prevention of high altitude pulmonary oedema. N Engl J Med 2002; 346: 1631-1636[Abstract/Free Full Text].
14.	Austin D, Sleigh J. Prediction of acute mountain sickness. BMJ 1995; 311: 989-990[Free Full Text].
15.	Pollard AJ, Niermeyer S, Barry P, Bärtsch P, Berghold F, Bishop RA, et al. Children at altitude. High Alt Med Biol 2001; 2: 389-403[CrossRef][Medline].
16.	Pollard AJ, Murdoch DR, Bärtsch P. Children in the mountains. BMJ 1998; 316: 874-875[Free Full Text].

(Accepted 10 March 2003)