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

3. 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

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

6. Ft. Carson, CO, ~6500 ft Pikes Peak, 14,110 ft (4300 m) US Air Force Academy, ~7,000 ft

7. 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

8. Acclimatization = body’s adaptation to hypobaric hypoxia

9. 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

10. Implications for Athletes • Endurance performance of lowlanders is impaired at altitude • Mexico City Olympics 1968, elev 2240m • Sprint & projectile performance might be enhanced • Thinner air • Altitude training enhances altitude performance • Altitude training MAY affect sea-level performance Bob Beaman shatters world high jump record by 22”

11. Training Strategies to Optimize Altitude Performance • Live High – Train High (LHTH) • “classic” method • Live High - Train Low (LHTL) • Natural (descend for training) • Artificial live-high • Long-continuous low-O2 • Brief-continuous low-O2 • Brief-Intermittent low O2 • Live Low – Train High in low-O2 Application of Altitude/Hypoxic Training by Elite Athletes, Med Sci Sports Exer 2007

14. Sea-level exercise performance following adaptation to hypoxia: a meta-analysis Bonetti DL, Hopkins WG Sports Med 2009

15. Classic Live High – Train High (LHTH) • Sub-elite athletes: • LIKELY GOOD FOR VO2MAX (?placebo) • Elite: BAD • Collegiate runners returned to SL 3-8% detrained in 1- and 2-mile times

16. Live High - Train Low (LHTL) • LH: Deer Valley, UT 2500m, 22 h/d • TL: SLC, UT 1250m, 2 h/d • Logistically difficult • Elite athletes: POSSIBLE benefit (4% +/- 3.7%) • Sub-elite: LIKELY benefit (4.2% +/- 2.9%)

17. Artificial LH – TLLong-continuous hypoxia, 8-18 hrs • Live at sea level but in hypoxic environment • Nitrogen dilution (Scandinavia) • Oxygen filtration (OTC Chula Vista, CA) • Train at normoxic sea level • Unproven but assumed altitude advantage • Results equivocal at sea level performance • Sub-elite: POSSIBLE 1.4% +/- 2.0% • Elite: UNCLEAR

18. Artificial LH - TLBrief-continuous hypoxia, 1.5-5 hrs • Sub-elite: UNCLEAR • Elite: UNCLEAR

19. Artificial LH – TLBrief-Intermittent, < 1.5 hrs ea • Sub-elite: VERY LIKELY (2.6% +/- 1.2%) • Elite: UNCLEAR

20. Live Low – Train High • UNCLEAR

21. Live Low - Train High Methods - IHE: intermittent hypoxic exposure - IHT: intermittent hypoxic training • Dosing variation (hrs/day, # weeks) • Ventilatory benefits >> hematologic • Effective for pre-acclimatization, not performance • ? Tissue effect (increased skeletal muscle mitochondrial density, capillary to fiber ratio, fiber area)

22. How long do benefits of altitude training last after cessation? • 3-6 weeks upon return to sea level

23. Altitude Illnesses (Failure to Acclimatize)

24. 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

25. 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

26. 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

27. 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

28. 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

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

30. 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

31. 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

32. 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)

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

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

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

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

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

38. 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

39. 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

40. Portable Hyperbaric Chambers

41. Treatment of HACE (cont.) • Management of coma • Bladder catheterization • Airway control • Diagnostic studies • CXR to rule out concurrent HAPE • MRI to rule out other conditions

42. Recovery from HACE:highly variable • 1-3 days for symptoms to resolve • Days to 12 weeks for neuropsychological function to normalize • 3-4 weeks for papilledema to resolve • Days to 5 weeks for MRI to normalize

43. 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

44. Treatment of HAPE (cont.) • Admit if: • >4L/min O2 requirement • Elderly, very young • Concomitant HACE or co-morbid cardio-pulmonary disease • Dexamethasone if concomitant HACE • Low-flow outpatient O2for others; check daily

45. Recovery from HAPE • Variable; little evidence in literature • May take 2 weeks to recover strength • Resume some activity when SaO2 > 90% without supplemental O2 • Remaining at some altitude fosters acclimatization via pulmonary arteriolar remodeling

46. PREVENTION OFHAI

47. 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

48. “Effect of ascent protocol on AMS and success at Muztagh Ata, 7546 m”Bloch KE at al, High Alt Med Biol2009 • Randomized, controlled trial, 48 climbers • 15 day vs 19 day ascent • 15 day: 3d at 3000, 500m/d x 2d, then rest day • 19 day: 4d at 3000, 500m/d x 3d, then rest day • Slow (19d): • OddsRatio 9.5 for reaching high camp w/o AMS • Fewer days of AMS (p<.04) • Lower AMS scores (p<.008)

49. 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

50. “Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate” Schneider M et al. Med Sci Sports Exerc 2002