Altitude Sickness

• Occurs if sleeping at altitudes > 2500m
• Decreased oxygen
• Body responds to high altitude by
  • Hyperventilation
  • Increased sympathetic tone – HR, blood pressure, cardiac output
  • Vasoconstriction of pulmonary vasculature – extremes causes oedema
  • Cerebral vasodilation induced by hypoxia – extremes oedema
  • Late changes – increased EPO, increased Hb, diuresis increases hematocrit, decreased muscle mass, increased vascularity
• Inadequate response leads to altitude sickness

Clinical

• High altitude headache
• Cerebral oedema
• Pulmonary oedema
• Acute mountain sickness

Risk of Developing Altitude Illness

• Prevalence Variability: Due to lack of standardization in altitude, ascent rate, outcome, and populations, AMS prevalence varies across studies.
• Reported Prevalence:
  • 40% of visitors at high-altitude ski resorts and vacation destinations.
  • Up to 80% of people who rapidly reach moderate heights (e.g., those who fly to La Paz).
  • About 50% of trekkers who ascend to 5000 m develop AMS.
• Australia: No reports of AMS in mainland Australia (Mount Kosciuszko: 2228 m); however, cases reported in scientists flying to the geographic South Pole (2835 m).
• Key Risk Factors:
  • Altitude and ascent rate.
  • Previous history of altitude illness (more than 12 times likely to develop severe AMS, HACE, and HAPE).
  • Exercise at altitude.
  • Possible increased risk with oral contraceptive pill (small study).
• Non-related Factors: Physical fitness, gender, previous altitude experience, load carried, recent respiratory infections, alcohol intake, or cigarette smoking.

Prevention of Altitude Illness

• Slow Ascent:
  • Recommended ascent rate: 300 to 500 m per day at altitudes higher than 3000 m.
  • Meta-analysis: AMS incidences of 50−75% when ascending more than 500 m a day at altitudes higher than 4000 m.
  • Wilderness Medical Society guidelines: No higher than 500 m a day at altitudes above 3000 m, with a day’s rest every three to four days.
• Acclimatization:
  • Spending two or more nights at high altitudes 30 days before ascending is protective.
  • Resting during the first 48 hours after arriving at high altitudes is advisable.

Medications

Acetazolamide

• Use: Commonly prescribed off-label in Australia to prevent AMS.
• 125mg BD
• Commence day prior to ascent
• Continue until acclimatisation occurs – usually target altitude 2-3 days, or when descending without
• Mechanism:
  • Inhibits carbonic anhydrase.
  • Decreases resorption of bicarbonate in the proximal renal tubule.
  • Binds carbon dioxide in peripheral tissues, resulting in metabolic acidosis.
  • Reduces metabolic alkalosis of hypocapnia, allowing prolonged hyperventilation.
  • Acts as a mild diuretic, decreasing edema.
  • Interesting side effect: decreased effervescence of carbonated beverages due to carbonic anhydrase inhibition in saliva.
    • perioral and digital tingling
    • polydipsia
    • polyuri
    • bowel disturbance
• Effectiveness:
  • Meta-analysis of 11 randomized controlled studies: Acetazolamide 250 mg daily associated with a significant decrease in AMS (combined odds ratio of 0.41; 95% CI: 0.26, 0.64).
• Do not ascend whilst symptomatic
• Consider sulfonamide allergy

Dexamethasone

• Use: Shown to prevent AMS but primarily used for treatment.
• Mechanism: Reduces inflammation, masking AMS symptoms.
• Considerations:
  • Significant side effects.
  • Early discontinuation may lead to rebound AMS.
• Study Findings:
  • Budesonide 200 µg inhaled twice a day had an AMS incidence of 24% vs. 60% in the placebo group (P = 0.0006).
  • Fewer side effects than dexamethasone.

Nifedipine

• Use: Primary agent for prevention and treatment of HAPE.
• Mechanism: Inhibits hypoxic pulmonary vasoconstriction, preventing or relieving pulmonary edema.
• Effectiveness:
  • Prevents HAPE.
  • Does not decrease AMS.

Other Medications

• Sumatriptan and Gabapentin: Single studies support effectiveness; further research needed before recommendation as AMS prophylaxis.
• Phosphodiesterase Inhibitors (e.g., Tadalafil, Sildenafil): Debatable use as adjuncts to prevent and treat HAPE.
• Ineffective Medications: No evidence supporting codeine, aspirin, theophylline, spironolactone, and antidiuretic hormone in reducing incidence of altitude illness.

Natural Remedies

• Gingko Biloba: Inconsistent and conflicting research; not advisable for preventing AMS.
• Coca Tea: No systematic studies support its use for preventing AMS, despite anecdotal claims.

Key Recommendations

• Acetazolamide: Effective for preventing AMS.
• Dexamethasone: Useful for treatment; prevention for those intolerant to acetazolamide.
• Nifedipine: Effective for preventing and treating HAPE.
• Slow Ascent and Acclimatization: Best preventive measures, with medication as adjunct support.

Fitness to Travel to High Altitude

General Considerations

• Stable Conditions Safe Up to 3000 m:
  • Stable heart conditions
  • Epilepsy
  • Diabetes

Contraindications

• Absolute Contraindications:
  • Severe chronic obstructive airways disease (COAD)
  • Unstable asthma
  • Severe ischemic heart disease
  • Severe or uncontrolled heart failure
  • Pulmonary hypertension
  • Complicated pregnancy
• Relative Contraindications:
  • Moderate COAD
  • Stable angina
  • Previous cerebrovascular disease
  • Poorly controlled diabetes
  • Recurrent arrhythmias

Special Considerations

• Deep Vein Thrombosis (DVT): Higher risk at high altitude; follow similar recommendations as for flying.
• Post-Diving: Delay of at least 24 hours after an uncomplicated dive, and at least a week after recompression therapy, similar to air travel recommendations.

Pregnancy

• Uncomplicated Pregnancies:
  • Safe travel up to 2500 m
  • Should travel before 36 weeks’ gestation

Older Adults

• Older People Without Comorbidities:
  • No increased risk of altitude illness

Children

• Incidence and Diagnosis:
  • Higher incidence suggested by one study, but generally considered similar to adults
  • Diagnosing altitude illness in children is more challenging
  • Best advice: travel with children who can adequately communicate symptoms

Key Points

• Individual variation and comorbidities make it difficult to provide standardized advice.
• Stable pre-existing conditions generally pose no significant risk up to 3000 m.
• Severe respiratory and cardiovascular conditions, along with complicated pregnancies, are significant contraindications.
• Relative contraindications require careful consideration and assessment by healthcare providers.
• Special precautions for DVT, post-diving, pregnancy, older adults, and children should be followed.

Condition	Clinical features	Course and management
High-altitude headache (HAH)	Most common symptom at high altitude: – 25% of travelers at 1920–2956 m: Headache – Up to 90% of unacclimatized people who travel to 5000 m: Headache Mechanism: – Thought to be due to activation of pain fibers in the trigeminal nerve in response to vasodilation – Brain’s vulnerability to hypoxia – Contribution by vascular mediators such as arachidonic acid	HAH settles with oxygen after 10–15 minutes, and resolves with decrease in altitude and a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen 600 mg three times a day35
Acute mountain sickness (AMS)	Headache after a rise in altitude in the past four days Accompanied by at least one of the following symptoms: – Gastrointestinal upset (e.g., anorexia, nausea, vomiting) – Fatigue or weakness – Dizziness or light-headedness – Difficulty sleeping	Presents within six to 36 hours of high-altitude exposure, is usually benign and commonly resolves in two to four days with simple rest and ceasing further rise in altitude Severe AMS is best treated with oxygen and medical care, including dexamethasone, otherwise progression to HACE is possible
High-altitude cerebral oedema (HACE)	Rapidly progressing, life-threatening marked elevation of intracranial pressure and cerebral edemaConsidered a progression from severe Acute Mountain Sickness (AMS) Usually preceded by a further decrease in oxygenation in a person with severe AMS Patients with AMS are advised not to continue to ascend until symptoms have settled	Usually develops later than AMS, 24–36 hours after arrival at a place of high altitude.Rare in travellers at altitudes <3500 m,Affects 0.5–1% of travellers at altitudes >3500 m8,17 Characterised by symptoms of severe AMS and cerebral symptoms, signs of impaired mental state, and the cardinal symptom and signs of ataxia Rapidly leads to coma and death if untreated- medical emergency requiring immediate reduction in altitude (300 m or more), oxygen and intravenous dexamethasone
High-altitude pulmonary oedema (HAPE)	Non-cardiogenic form of pulmonary oedema Occurs 0.5–4% of predisposed previously healthy individuals who ascend higher than 3000 m37 People with HAPE report dyspnoea, cough, decreased exercise tolerance, or chest tightness, and exhibit signs of pulmonary oedema: – pulmonary crepitations – tachypnoea – tachycardia – cyanosis	Usually commences two to four days after arrival at a place of high altitude, Can develop independently of AMSAccounts for most of the deaths related to altitude illness38 Urgent treatment by trained medical staff requires rapid descent of about 1000 m, oxygen, and nifedipine with adjunctive drugs