Altitude-related illness

Contributed by Dr Matthew Litchfield, GP, Nottingham and Dr James Milledge, retired consultant respiratory physician, Northwick Park Hospital, Harrow.

Section 1: Epidemiology and aetiology
Millions of people holiday at high altitudes every year. Many of these will consult their GP for advice prior to departure. It is therefore important for GPs to be aware of the types of altitude illness and their treatment.

Definition
High altitude is defined as that greater than 2,500m, which equates to the top runs of many ski resorts. Altitude-related illness is defined as illness directly attributable to hypobaric hypoxia and is common in tourists, skiers, trekkers and mountaineers. The three main types of acute altitude illness are: acute mountain sickness (AMS); high-altitude pulmonary oedema (HAPE) and high-altitude cerebral oedema (HACE).

Acclimatisation
As altitude increases, barometric pressure decreases and correspondingly the partial pressure of oxygen decreases. Consequently the body becomes hypoxic. The physiological mechanism by which the body adapts is acclimatisation.

The body's initial response to hypoxia is an increase in ventilation and heart rate. The resulting hypocapnia and respiratory alkalosis limit further increased ventilation by reducing respiratory drive. Over two to three days the kidneys excrete bicarbonate to compensate for respiratory alkalosis, allowing further hyperventilation to occur.

In the first few days at altitude, plasma volume decreases and erythropoeitin is secreted in response to hypoxia. Over several days this stimulates the production of red blood cells, which further increases oxygen transport.

People acclimatise at different rates. It is likely to be a result of an interaction between genetic and environmental factors.

Epidemiology
Risk factors for altitude illness are: altitude gained, rate of ascent, sleeping altitude, obesity, level of exertion and a previous history of high altitude illness. Physical fitness does not prevent altitude illness and some studies suggest there is a lower incidence in older patients.1

Currently there is no test to accurately predict who will suffer altitude-related illness, although genetic make-up may be important.

Most pre-existing medical conditions will affect performance at high altitude; however, they are not risk factors for altitude illness. Patients with significant pre-existing conditions should seek specialist medical advice prior to departure.

Section 2: Acute mountain sickness
AMS is common in people who ascend from near sea level to high altitude. Symptoms of headache, nausea, vomiting, fatigue, anorexia, dizziness and sleep disturbance begin three to 120 hours after ascent.

There are few clinical signs, although patients may be tachycardic, pyrexial or have peripheral oedema.

The Lake Louise Score is a research tool that is commonly used in clinical practice to help diagnose AMS (see box).

Aetiology
The exact pathophysiological processes that cause AMS are still not fully understood. AMS may be caused by mild cerebral oedema, secondary to increased cerebral perfusion (due to vasodilatation induced by hypoxia) and altered permeability of the blood-brain barrier.3

The risk of developing AMS can be reduced by a sensible ascent profile allowing the body time to acclimatise and the use of drugs. Above 3,000m patients should:

  • Increase sleeping altitude by an average of no more than 300-600m per day, i.e. climb high and sleep low.
  • Take a rest day every 1,000m or three days.
  • Do not ascend further if there are symptoms of AMS.
  • Descend if symptoms deteriorate.

Prophylaxis
The carbonic anhydrase inhibitor acetazolamide 125-250mg twice daily may be used for prophylaxis against AMS. It is particularly useful in people susceptible to AMS or when fast ascent rates are unavoidable. The higher 250mg dosage is generally recommended for patients known to acclimatise badly or that weigh more than 100kg, but there may be a greater incidence of side-effects.

Acetazolamide increases renal bicarbonate excretion, causing a metabolic acidosis, allowing further hyperventilation and thus speeding up acclimatisation.

There is a small risk of allergy as it is a sulphonamide. Potential side-effects include nausea, poor appetite, diuresis, paraesthesia (especially in hands and feet) and loss of taste of carbonated drinks. Patients should be advised to take a test dosage for 48 hours at sea level prior to departure to ensure they can tolerate it. Prophylaxis should continue until the maximum altitude is reached, after which it may be discontinued.

Dexamethasone 4mg 6-8 hourly, although less effective, may also be used for short-term AMS prophylaxis. It is currently reserved for patients intolerant to acetazolamide. Its mechanism of action is unknown.

Recent studies have shown ginkgo biloba to be no better than placebo for AMS prevention.4

Planned ascent
Drug prophylaxis is no substitute for adequate planning. Flexibility needs to be built into any trip itinerary to allow extra time for people who may be struggling. A sensible ascent profile will allow more people to reach the summit or high point and to enjoy the experience.

Many commercial trips still ignore this simple advice, particularly on Kilimanjaro, where national park fees are charged per person per day. This encourages rapid ascent to reduce costs, but compromises the safety and enjoyment of the trip.

Treatment
AMS is generally a self-limiting illness that settles after two to three days, assuming no further ascent occurs. Simple analgesia and antiemetics may be used for symptom relief, but are often ineffective. Acetazolamide 250mg three times daily, dexamethasone 4mg four times daily and oxygen may be used as treatment for AMS. If symptoms worsen despite 24 hours' acclimatisation, descent to an altitude lower than where symptoms began is indicated.

Further ascent should be avoided. If symptoms are ignored and ascent continued, then more serious HAPE or HACE may develop. AMS should not recur at the same altitude, but may recur if the subject ascends further.

 

Lake Louise acute mountain sickness score2
Self Report Questionnaire
Headache
  • No headache
  • Mild headache
  • Moderate headache
  • Severe, incapacitating headache

0
1
2
3
4

SCORE
Gastrointestinal symptioms
  • Good appetit
  • Poor appetite or nausea 
  • Moderate nausea or vomiting
  • Severe nausea & vomiting
0
1
2
3
4
Fatigue/weakness
  • Not tired or weak
  • Mild fatigue/weakness
  • Moderate fatigue/weakness
  • Severe, incapacitating fatigue/weakness
0
1
2
3
4
Dizziness/light-headedness
  • No dizziness
  • Mild dizziness
  • Moderate dizziness
  • Severe, incapacitating dizziness
0
1
2
3
4
Difficulty sleeping
  • Slept as well as usual
  • Did not sleep as well as usual
  • Woke many times, poor sleep
  • Could not sleep at all
0
1
2
3
4

AMS = altitude gain + headache + at least one other symptom + total
score 3

AMS Treatment5
Mild AMS

  • Rest
  • Simple analgesia

Moderate/severe AMS

  • Descent
  • Oxygen
  • Acetazolamide 250mg three times daily
  • Dexamethasone 4mg four times daily
  • Portable hyperbaric chamber

Section 3: High-altitude pulmonary oedema
HAPE occurs two to four days after ascent to high altitude. Patients may have suffered from AMS initially and then complain of shortness of breath, dry cough, reduced exercise tolerance and, later, bloodstained sputum.

Clinical signs include tachycardia, tachypnoea, mild pyrexia, hypoxia disproportionate to unaffected patients at similar altitude, crepitations on auscultation and dependent oedema.

Aetiology
It is hypothesised that HAPE is caused by patchy hypoxic pulmonary vasoconstriction in patients who have an unusually brisk hypoxic pressor response of their pulmonary arteries. This exposes pulmonary capillaries to high pressure, causing stress failure of capillary walls and leakage of fluid, protein and erythrocytes into the alveolae.

A porter being treated for HAPE below the Mera La, Nepal

Inflammatory mediators are released contributing further to the damage caused.6 Cardiac catheter studies have demonstrated a normal pulmonary wedge pressure confirming HAPE is a non-cardiac pulmonary oedema.3

Treatment
The main treatment is descent and supplemental oxygen. Nifedipine 20mg slow-release twice daily lowers pulmonary artery pressure and is effective in prevention and treatment.

Future advances
A small study has suggested that salmeterol is helpful in preventing HAPE. It is postulated that beta-agonists promote clearance of alveolar fluid, relieving pulmonary oedema and therefore may be helpful too.7

Sildenafil and similar compounds may help prevent HAPE by lowering pulmonary artery pressure, with less chance of hypotension than nifedipine.8

HAPE treatment

  • Descent
  • Oxygen
  • Nifedipine modified release 20mg twice daily
  • Portable hyperbaric chamber

Section 4: High-altitude cerebral oedema
AMS and HACE are probably two ends of a spectrum of symptoms caused by the same pathophysiology.

HACE is a clinical diagnosis characterised by preceding AMS, then the development of ataxia, behaviour change, hallucination, disorientation and confusion. The patient may deteriorate quickly over a few hours or days to a decreased level of consciousness, coma and death.

Neurological examination should include heel-toe walking to assess for ataxia, fundoscopy for papilloedema and an assessment for neurological deficit.

Like AMS, HACE is thought to be caused by cerebral oedema secondary to increased cerebral perfusion and altered permeability of the blood-brain barrier.3

The treatment of HACE is immediate descent, oxygen, dexamethasone 8mg immediately and then 4mg, six-hourly. Acetazolamide is also commonly used.

A portable hyperbaric chamber such as a Gamow bag may be used to improve oxygenation, relieving symptoms and facilitating unaided descent.

Summary
Altitude illness is common in people ascending to high altitude. A sensible ascent profile will allow time to acclimatise and will increase enjoyment. Correspondingly this will reduce the risk of altitude-related illness.

AMS is a common self-limiting illness that can occur on ascent to high altitude. HACE and HAPE are more serious, potentially fatal, conditions that require immediate descent.

GPs can help travellers by directing them to further information, encouraging safe ascent profiles and discussing medication that they might require on their trips.

HACE treatment

  • Immediate descent
  • Oxygen
  • Dexamethasone 8mg immediately, then 4mg four times daily
  • Acetazolamide 250mg three times daily
  • Portable hyperbaric chamber

References

1. Hackett P, Rennie D, Levine H. The incidence, importance and prophylaxis of acute mountain sickness. Lancet 1976; 2: 1,149-55.

2. Roach R, Bartsch P, Oelz O, Hackett P. The Lake Louise acute mountain sickness scoring system. In: Hypoxia and Molecular Medicine, edited by Sutton JR, Houston CS, Coates G. Burlington, V T: Queen City Press, 1993.

3. West J. The physiologic basis of high-altitude diseases. Ann Intern Med 2004; 141: 789-800.

4. Gertsch J, Basnyat B, Johnson E, Onopa J, Holck P. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT). BMJ 2004; 328: 797.

5. Pollard A, Murdock D. The High Altitude Medicine Handbook, 3rd edition. Oxford: Radcliffe Medical Press, 2003.

6. West J, Mathieu-Costello O. High altitude pulmonary edema is caused by stress failure of pulmonary capillaries. Int J Sports Med 1992; 13 (Suppl 1): S54-8.

7. Sartori C, Allemann Y, Duplain H et al. Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med 2002; 346: 1,631-6.

8. Ghofrani H, Reichenberger F, Kohstall M et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp. Ann Int Med 2004; 141: 169-77.

Further resources

- The UIAA/University of Leicester Diploma in Mountain Medicine is an exciting way for doctors to learn more about mountain medicine. The course comprises four, week-long residential courses in North Wales, Scotland and the Alps. www.medex.org.uk/dimm_(mountain_medicine_diploma).htm

- Alternate winters there is the Mountain Medicine and High Altitude Physiology Course at Plas-Y-Brenin (5-7 December 2008) Email: cc44@le.ac.uk for details.

- Travel at High Altitude is a booklet that is designed to help the non-medic understand altitude-related illness. It can be downloaded free at www.medex.org.uk/medex_book.htm

- Medex is a club that organizes adventurous expeditions worldwide and supports the work of Medical Expeditions. Medex has run successful expeditions to Everest in 1994, Kangchenjunga in 1998 and Hongu in 2003. www.medex.org.uk.

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