High Altitude: Physiology & Illness

1. Military Sports Medicine Fellowship High Altitude:Physiology & Illness “Every Warrior an Athlete” Kevin deWeber, MD, FAAFP, FACSM COL, US Army Director, Military Sports Medicine Fellowship 2012

2. Objectives • Outline strategies to optimize exercise performance at altitude • Review pathophysiology of high altitude illness (HAI) • Review the types of HAI and how they are treated • Review factors predisposing to HAI • Discuss factors in return-to-altitude decisions after HAI

3. Cuenca, Ecuador • 8,400 ft (2560 m)

4. Preview • Acclimatization and slow ascent are powerful preventives for High Altitude Illness • Acclimatize properly • Spend 2-3 nights at 2500-3000m before ascent • Slow ascent • Ascend < 500 m/day of sleeping altitude • Rest day every 3-4 days • Prophylactic meds advised if unable to comply • Acetazolamide is powerful to prevent most HAI • Dexamethasone powerfully treats serious HAI

5. Preview: RISK of HAI • Low risk: • No prior h/o HAI and ascent to <2800m (9180 ft) • Taking >= 2 days to ascend to 2500-3000m (8200-9840 ft) AND sleeping altitude increases <500m/d Luks et al. Wilderness Medicine Society consensus guidelines for prevention and Treatment of acute altitude illness. Wilderness Envir Med 2010.

6. Moderate risk of HAI: • Prior h/o AMS and ascending to 2500-2800m in 1 day (8200-9180 ft) • NO prior h/o AMS but ascending to >2800m in 1 day • ALL ascending >500m/d (sleep elev.) at >3000m

7. High risk of HAI • Prior h/o AMS and ascending to >2800m in 1 day • ALL with prior h/o HACE or HAPE • ALL ascending to >3500m (11480 ft) in 1 day • ALL ascending >500m/d (sleep elev.) at >3500m • Very rapid ascents (e.g. Mt. Kilamanjaro)

8. Preview: Prevention of HAI • Moderate and High risk persons: consider prophylactic meds • PRIMARY: Acetazolamide 125 mg bid • Start 2d prior to ascent, stop 2-3d after summit • Kids: 2.5 mg/kg/d • ALT: Dexamethasone 2mg QID or 4mg BID • Only if can’t tolerate Acetazolamide • Start day of ascent, stop 2-3d after summit • Ibuprofen 600 mg tid (two studies) Luks et al. Wilderness Medicine Society consensus guidelines for prevention and Treatment of acute altitude illness. Wilderness Envir Med 2010.

10. Environment at high altitude(>1500 m or 4920 ft) • Barometric pressure decreases • Partial pressure of oxygen decreases • “Hypobaric Hypoxia” • Lower alveolar O2 leads to lower SaO2

11. Effects of High Altitude Exposure • Decreased exercise capacity • +/- 1% decrease in VO2max per 100m above 1500m • Individual variability • MECHANISMS: • Peripheral hypoxia • Cerebral hypoxia  peripheral inhibition • High altitude illness • Individual variability

12. Acclimatization = body’s adaptation to hypobaric hypoxia

13. Acclimatization • Immediate (minutes to hours) • ↑ Sympathetic tone ↑ HR & CO • ↑ Ventilation  ↑ PaO2 and↓ PaCO2  ↑ pH • Renal bicarbonate diuresis (to balance pH) • ↑ Pulmonary artery pressure ↑ O2 absorption • Delayed (days to weeks) • Erythropoietin  ↑ RBC production, hemoconcentration • Remodeling of pulmonary arterioles

14. Altitude Illnesses (Failure to Acclimatize)

15. Cerebral Syndromes • Acute Mountain Sickness (AMS) • High Altitude Cerebral Edema (HACE) mild AMS moderate AMS HACE • Pulmonary Syndrome • High Altitude Pulmonary Edema (HAPE) • Importance • HACE and HAPE can be fatal

16. Acute Mountain Sickness (AMS) • Occurs above 1500 m (4920 ft) • More common above 2500 m • Defined as HEADACHE plus one or more symptom: • Anorexia, nausea or vomiting • Fatigue or weakness • Dizziness or lightheadedness • Difficulty sleeping • Headache alone: High-Altitude Headache • Gabapentin, Acetazolamide, or Ibuprofen preventative • J Neurol Neurosurg Psychiat 2008 • Cephalgia 2007 • Wilderness Environ Med 2010

17. Effects of AMS on performance • Mild: annoyance only • Moderate: impaired concentration, memory, speech, and physical performance; • Can be disabling • Subtle abnormalities visible on MRI • Effects can last weeks

18. High Altitude Cerebral Edema(HACE) • AMS symptoms plus ALTERED L.O.C. and ATAXIA • Other neuro findings possible • Coma develops • Death results if untreated • Pathophysiology • altered cerebral vascular permeability leads to brain swelling • MRI: cerebral edema, lesions of corpus callosum

19. High Altitude Pulmonary Edema(HAPE) • Defined by two pulmonary symptoms… • Cough, dyspnea at rest, exercise intolerance, chest tightness/congestion… • and two pulmonary signs… • Crackles, wheezing, cyanosis, tachypnea, tachycardia • Most common cause of death among HAI • 50% mortality rate if not treated quickly

20. High Altitude Pulmonary Edema(HAPE) • CXR findings • Blotchy fluffy infiltrates • Pathophysiology Hypoxia  pulmonary artery hypertension • alveolar damage  edema and hemorrhage into alveoli

21. Risk factors for HAI • Rapid gain in altitude • Prior history of HAI • genetic factors involved • Alcohol, sedatives • Strenuous exercise • HAPE: cold ambient temperature, resp. infxn

22. HAI Protective Factors • Residence at elevation >900 m (2950 ft) • Slow gain in elevation • <500 m (1640 ft) per day in sleeping elevation • Genetic factors • Physical fitness NOT protective

23. Treating HAI:General Principles • Rest, halt ascent • Descend • Moderate AMS: >500 m (1640 ft) • HACE/HAPE: > 1000 m (3280 ft) • Oxygen if available (keep Pox >90%) • Keep warm (esp. for HAPE)

24. Treating HAI:Medications • Acetazolamide • Speeds acclimatization • Treats moderate AMS & HACE • Dose: 125-250 mg BID • Anti-emetics • Non-narcotic analgesics

25. Meds (cont.) • Dexamethasone • Decreases cerebral edema • Treats moderate AMS and HACE • Prevents AMS, HACE, HAPE • Dose • 8-16 mg/d in div doses

26. Meds (cont.) • Nifedipine • Decreases pulmonary artery pressure • Prevents HAPE • Dose: 30 mg SR BID (one study) • NOT EFFECTIVE FOR TREATMENT (one study)

27. Meds (cont.) • Salmeterol • Decreases alveolar fluid transport • May prevent HAPE • Dose: 125 mcg inhaled BID

28. Meds (cont.) • Tadalafil • Dilates pulmonary vessels, prevents pulmonary hypertension • May prevent HAPE • Dose: 10 mg po BID

29. Treatment of AMS • Descend > 500 m (1640 ft) OR • Rest 1-2 days at same altitude • Oxygen 12-24 hours, if available • Symptomatic treatment with analgesics, anti-emetics • Consider acetazolamide 125-250 mg po BID

30. Treatment of HACE • Immediate descent > 1000 m and hospitalize • Oxygen to maintain SaO2 >90% • Dexamethasone—8 mg PO/IM/IV initially followed by 4 mg QID • Consider adding acetazolamide • Portable hyperbaric therapy if descent impossible

31. Portable Hyperbaric Chambers

32. Treatment of HAPE • Immediate descent >1000 m • Oxygen to keep SaO2 >90%. • If descent/O2 not immediately available… • Portable hyperbaric therapy • Nifedipine 30 mg extended release BID (avoid if concomitant HACE) and • Salmeterol 125 mcg inhaled

33. PREVENTION OFHAI

34. Prevention of HAI:General Principles • Proper acclimatization protocols are paramount • Avoid abrupt ascent to >3000 m (9843 ft) • Spend 2-3 nights at 2500-3000 m before ascending further • Ascend no more than 500 m (1640 ft) per day in sleeping altitude when >2500 m (8200 ft) • Rest day every 3-4 days

35. Prevention of HAI:Other protective factors • Living at altitude >2200 m days to weeks • >5days above 3000m last 2 months --> less AMS (Schneider et al, MSSE 2002) • Intermittent Hypoxic Exposure (IHE) 4hr/d x15d  less AMS @4300 m • Beidleman et al, Clin Sci 2004

36. Prevention of HAI:FIRST DETERMINE RISK • Low risk: • No prior h/o HAI and ascent to <2800m (9180 ft) • Taking >= 2 days to ascend to 2500-3000m (8200-9840 ft) AND sleeping altitude increases <500m/d Luks et al. Wilderness Medicine Society consensus guidelines for prevention and Treatment of acute altitude illness. Wilderness Envir Med 2010.

37. Cuenca, Ecuador • 8,400 ft (2560 m)

38. Moderate risk of HAI: • Prior h/o AMS and ascending to 2500-2800m in 1 day (8200-9180 ft) • NO prior h/o AMS but ascending to >2800m in 1 day • ALL ascending >500m/d (sleep elev.) at >3000m

39. High risk of HAI • Prior h/o AMS and ascending to >2800m in 1 day • ALL with prior h/o HACE or HAPE • ALL ascending to >3500m (11480 ft) in 1 day • ALL ascending >500m/d (sleep elev.) at >3500m • Very rapid ascents (e.g. Mt. Kilamanjaro)

40. Prevention of AMS/HACE • Moderate and High risk persons: consider prophylactic meds • PRIMARY: Acetazolamide 125 mg bid • Start 2d prior to ascent, stop 2-3d after summit • Kids: 2.5 mg/kg/d • ALT: Dexamethasone 2mg QID or 4mg BID • Only if can’t tolerate Acetazolamide • Start day of ascent, stop 2-3d after summit • Ibuprofen 600 mg tid (two studies) Luks et al. Wilderness Medicine Society consensus guidelines for prevention and Treatment of acute altitude illness. Wilderness Envir Med 2010.

41. Prevention of AMS/HACE SPECIAL SCENARIOS • Military Ops requiring exertion and >3500m: • Dexamethasone (also increases VO2max)

42. Prevention of HAPE • ALL: ascent/rest precautions • Moderate/High risk: consider meds: • PRIMARY: Acetazolamide 125 mg BID • PRIOR HAPE: Nifedipine 60 mg SR daily + Salmeterol 125 mcg BID • ALTERNATE: Tadalafil 10 mg BID or Dexamethasone 16 mg/d divided doses Luks et al. Wilderness Medicine Society consensus guidelines for prevention and Treatment of acute altitude illness. Wilderness Envir Med 2010.

43. Considerations for high-altitude activities in those with prior HAI • Risk level • Severity and type of prior HAI • Ascent requirements • Feasibility of descent/extra rest days if needed • Availability of medical treatments

44. Questions?