What is the recommended preventive treatment for a patient with a history of altitude sickness traveling to high altitude, considering potential sulfa allergy and other medical conditions such as pulmonary or cardiac disease?

Acetazolamide for High-Altitude Prophylaxis

For patients with a history of altitude sickness traveling to high altitude, acetazolamide 125 mg twice daily (or 250 mg once daily) is the first-line prophylactic medication, started 12-24 hours before ascent and continued for 3-4 days at altitude. 1, 2

Primary Prevention Strategy

Gradual ascent remains the most effective prevention method and should always be the foundation of your approach. 1

• Ascend at a rate of 300-600 m/day above 2500 m 1
• Include a rest day for every 600-1200 m of elevation gained 1
• Avoid vigorous exertion before proper acclimatization 1
• Delay further ascent if initial symptoms appear 1

Pharmacological Prophylaxis

First-Line: Acetazolamide

Acetazolamide is recommended by the American Heart Association as the first-line prophylactic medication for altitude sickness. 1

• Dosing: 125 mg twice daily or 250 mg once daily 1, 2
• Timing: Start 12-24 hours before ascent 3, 2
• Duration: Continue for 3-4 days after arrival at terminal altitude 1
• Mechanism: Carbonic anhydrase inhibitor causing mild diuresis and metabolic acidosis, which stimulates ventilation and improves oxygenation 1
• Efficacy: Reduces AMS incidence from 45% to 14% in high-risk rapid ascent scenarios (number needed to treat = 3) 4

Critical Contraindication: Sulfa Allergy

If the patient has a sulfa allergy, acetazolamide is absolutely contraindicated as it is a sulfonamide derivative. 5

• Severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, and blood dyscrasias have been reported 5
• Fatalities have occurred, although rarely 5
• Alternative: Dexamethasone is the recommended alternative when acetazolamide is contraindicated 1, 3

Alternative: Dexamethasone

Dexamethasone is effective for AMS prophylaxis when acetazolamide cannot be used. 1, 3

• Particularly useful for patients with sulfa intolerance 3
• Side effects limit its use for routine prophylaxis 3
• Effective for treatment of AMS including early cerebral edema 3

Special Populations Requiring Modified Approach

Patients with History of HAPE

For patients with a documented history of high-altitude pulmonary edema (HAPE), nifedipine is the drug of choice, not acetazolamide. 6, 1

• Dosing: Extended-release nifedipine (typically 20 mg three times daily) 7, 8
• Timing: Start with ascent 6, 1
• Duration: Continue for 3-4 days after arrival at terminal altitude 6, 1
• Efficacy: Reduces HAPE incidence from 64% (7 of 11) to 10% (1 of 10) in susceptible individuals 6
• Alternatives: PDE5 inhibitors (sildenafil, tadalafil) may be used, but tadalafil has been associated with severe acute mountain sickness in some subjects 6, 1

Patients with Pulmonary Disease

Patients with pulmonary obstruction or emphysema require special caution with acetazolamide as it may precipitate or aggravate acidosis. 5

• COPD, interstitial pulmonary disease, and pulmonary hypertension patients are at appreciably greater risk at altitude 8
• These patients should receive supplemental oxygen when visiting high-altitude destinations 6
• Pre-travel medical evaluation is essential 6

Patients with Cardiac Disease

Patients with cardiovascular disease should continue their pre-existing medications at high altitude. 1

• Acetazolamide may reduce the risk of subendocardial ischemia at high altitude in healthy subjects 1
• For heart failure patients, carefully evaluate acetazolamide use with other diuretics due to risk of dehydration and electrolyte imbalances 1
• Hypertensive patients may benefit from acetazolamide, which can lower blood pressure at high altitude while improving oxygen saturation 1

Critical Warnings and Drug Interactions

Avoid concomitant high-dose aspirin with acetazolamide, as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported. 5

Common Pitfalls to Avoid

• Do not underestimate the importance of gradual ascent - pharmacological prophylaxis is adjunctive, not a replacement for proper acclimatization 1
• Do not use acetazolamide in patients with sulfa allergy - the risk of severe reactions outweighs any benefit 5
• Do not forget adequate hydration - dehydration worsens altitude sickness symptoms 1
• Do not use acetazolamide alone for HAPE-susceptible patients - nifedipine is specifically indicated for this population 6, 1
• Do not ignore baseline monitoring - obtain CBC and platelet count before starting acetazolamide and monitor serum electrolytes periodically 5

Emergency Management

Immediate descent to lower altitude and supplemental oxygen are the primary therapies for established altitude illness, regardless of prophylaxis used. 6, 1