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Medicine and Work Performance at High Altitude Stephen R. Muza, Ph.D.

Medicine and Work Performance at High Altitude Stephen R. Muza, Ph.D. U.S. Army Research Institute of Environmental Medicine Natick, MA, USA 01760. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed

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Medicine and Work Performance at High Altitude Stephen R. Muza, Ph.D.

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  1. Medicine and Work Performance at High Altitude Stephen R. Muza, Ph.D. U.S. Army Research Institute of Environmental Medicine Natick, MA, USA 01760 The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or as reflecting the views of the Army or the Department of Defense.

  2. Overview 1. Biophysics of the Altitude Environment 2. Altitude Acclimatization: Key Physiological Adaptations Time-Course 3. High Altitude Stress: Medical Problems - Altitude Illness Performance – Physical & Neuropsychological

  3. Easy Access to High Altitude Creates a Health and Performance Problem

  4. Biophysics of High Altitude Human Performance Physiology and Environmental Medicine at Terrestrial Extremes, 1988 Medical Aspects of Harsh Environments, 2002

  5. Biophysics of High Altitude SL: CaO2 = 19.6 ml O2% 1850 m: CaO2 = 19.2 ml O2% 4300 m: CaO2 = 16.5 ml O2%

  6. High Altitude Stress: Impact on Low Altitude Residents • Decreased Physical Performance (>1,200 m) • Risk of Altitude Sickness (>2,400 m) • Decreased Neuropsychological Performances (>2,400 m) Medical Aspects of Harsh Environments , 2002

  7. High Altitude Stress: Acute Physiological Responses • Increased alveolar ventilation • Increased heart rate, and cardiac output • Peripheral vasodilation • Pulmonary arterial vasoconstriction • Increased 2,3-diphosphoglycerate • Increased epinephrine release from adrenal medulla • Increased HIF-1a up regulates >100 genes: EPO, VEGF, HSP(s) • ??? PIO2 PAO2 PaO2 Disruption in Homeostasis

  8. High Altitude Stress: Acute Physiological Responses: HIF Target Genes Bernhardt, W.M. et al 2007

  9. High Altitude Stress: <1% of All Genes Changed Over Acclimatization

  10. High Altitude Stress: Acute Physiological Responses PIO2 PAO2 PaO2 Disruption in Homeostasis e.g.: Increased Alveolar Ventilation Causes Respiratory Alkalosis

  11. High Altitude Stress: Summary of Acute Physiological State • Systemic hypoxia • Respiratory alkalosis (disrupted acid-base balance) • Orthostatic intolerant (light-headed, syncope) • Pulmonary arterial hypertension (impaired gas exchange) • Altered body fluid regulation: vascular space is leaking, some tissues develop edema • ??? PIO2 PAO2 PaO2 Disruption in Homeostasis

  12. Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Altitude Acclimatization A series of physiological adjustments that compensate for the reduction in ambient oxygen, and restores homeostasis Benefits of Acclimatization: • Restored Mental Performance: 1-2 Days • Decreased Susceptibility to Altitude Illness: 2-5 Days • Improved Sleep Quality: 5-7 Days • Improved Physical Work Performance: 5-14 Days • Overall, improved Resilience

  13. Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Altitude Acclimatization Summary of major physiological adaptations characteristic of altitude acclimatization

  14. Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Time Course of Altitude Acclimatization

  15. Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatization Altitude Acclimatization Summary of major physiological adaptations characteristic of altitude acclimatization

  16. Altitude Acclimatization Ventilatory Acclimatization: Increased Hypoxic Ventilatory Response (HVR) Decreased PaCO2 set point Near normalization of pHa Compensated Respiratory Alkalosis Elevated PaO2, SaO2, and CaO2

  17. Altitude Acclimatization Hematological Acclimatization: Early Response: Decreased Plasma Volume Increases [HB] Long-term Response (up to 18 months): Stimulation of Erythropoietin Increases RBC mass Near normalization of CaO2

  18. Altitude Acclimatization Long-term Adaptation: Tibetans: High HVR, Low PHPR Larger TLC Ward, Milledge & West, 2000

  19. Altitude Acclimatization Procedures • Ascend High Enough to Induce Acclimatization, but Not Too High • Reside at High Altitude for a Sufficient Length of Time • Methods For Inducing Acclimatization: • Staged or Gradual Ascent Profiles • Intermittent Altitude Exposure Protocols ABOVE 8,000 ft (2,400 m): Slow ascent (no greater than 1,000 ft/day) Staged ascent (4 - 10 days at 6,000 - 8,500 ft) Intermittent Altitude Exposures (4+ hr exposure to high altitude each day for 1 or more weeks)

  20. Staged Ascent Acclimatization Strategies Ascend high enough to induce acclimatization, but to avoid developing AMS, do not ascend too high or too fast. After staging, single day ascent up to 2,000 m above staging altitude has low risk of AMS.

  21. Graded Ascent Acclimatization Strategies Ascend high enough to induce acclimatization, but to avoid developing AMS, do not ascend too high or too fast. Recommendations: above 2,400 m no more than 300 m/d. Add a rest day every 900-1,200 m.

  22. High Altitude Stress: Acute Physiological State • Medical Issues: Altitude Sickness and Deterioration • Performance Issues: Physical and Neuropsychological PIO2 PAO2 PaO2 Disruption in Homeostasis

  23. Altitude Sickness Acute Mountain Sickness High Altitude Cerebral Edema High Altitude Pulmonary Edema High Altitude Retinal Hemorrhage High Altitude Peripheral Edema High Altitude Bronchitis Chronic Mountain Sickness

  24. Altitude Sickness Susceptibiity: Currently not predictable, but maybe? Individual susceptibility is reproducible Men greater susceptibility than women Risk Factors: Unacclimatized state Rapid ascent >2400 m Exercise or heavy physical work Hypohydration Very, very low HVR Cold Exposure Obesity Compromised cardiopulmonary function Age < 50 yrs

  25. Altitude Sickness Acute Mountain Sickness (AMS) – “most common” Incidence: 20 – 90% Symptom Complex: Headache, Nausea, Vomiting, Lassitude, Dizziness, Insomnia High Altitude Cerebral Edema (HACE) – “rare below the death zone” Incidence: ~1% Symptom Complex: Severe Headache, Impaired Mental Status, Truncal Ataxia, Coma High Altitude Pulmonary Edema (HAPE) – “leading cause of death” Incidence: 5-15% Symptom Complex: Dyspnea, Severe Fatigue, Non-productive Cough, becoming productive, Pink & Frothy, Coma Roach , R.C. et al., Medical Aspects of Harsh Environments , 2002

  26. Acute Mountain Sickness (AMS) • Prediction of AMS: • Time and altitude are key factors • AMS increases 145% every 1000 m • AMS severity peaks 18-24 h • Physical activity increases AMS • Physical activity delays recovery from AMS • Women have lower AMS severity Beidleman, B.A.. et al., Med. Sci. Sports Exerc.:45, 2013

  27. Acute Mountain Sickness (AMS) Time Course

  28. Acute Mountain Sickness (AMS) Pathophysiology Prevailing theory: hypoxia-induced mild edema of both cytotoxic (intracellular) and vasogenic (extracellular) origin Evidence: DW-MRI, volumetric MRI, CSF volume, IR-NIR scattering Problem: everyone affected, no correlation with AMS symptoms, no evidence of BBB failure Recent controversial theory: hypoxia-induced cerebral oxidative-nitrative stress releases noxious biomolecules that activate trigeminovascular nocioceptors to cause headache and AMS (Bailey, D.M. et al, 2009)

  29. High Altitude Cerebral Edema (HACE) Pathophysiology Prevailing theory: continuum of AMS progressing to vasogenic edema MRI of acute and recovered phases of HACE. 7 of 9 patients with HACE showed intense T2 signal in white matter areas, especially the splenium of the corpus callosum. (Hackett, P. et al., JAMA 1998) 33 yr male, SL to 5200 m in 6 days, MRI day 2 and 11 months later

  30. High Altitude Pulmonary Edema (HAPE) Pathophysiology SNS Pulmonary Venoconstriction (HVR, A-a O2, exercise, sleep) Altitude Hypoxia PaO2 Uneven HPVR Pulmonary Htn Pulmonary Pcap Capillary Stress Failure Pulmonary Capillary Leak High Altitude Pulmonary Edema Vascular Permeability Agents? (exercise, cold) (Endothelin-1, NO) ( Alveolar Fluid Absorption) Swenson, E. et.al. JAMA 2002

  31. Altitude Sickness Prevention Altitude acclimatization above 1,200 m For AMS consider Diamox (Acetazolamide) - carbonic anhydrase Inhibitor facilitates HCO-3 diuresis For HACE consider Dexamethasone (corticosteroid) For HAPE consider Nifedipine (calcium channel blocker), Sildenafil, Tadalafil (5-PDE Inhibitor), Salmeterol (b2-adrenergic agonist)

  32. Altitude Sickness Treatment Stop ascent Descend (most efficacious treatment) Rest Medications listed for prevention Oxygen Hyperbaric treatment bag (>2 psi)

  33. HIGH ALTITUDE DETERIORATION Key Features: >5000 m long-duration exposures Excessive weight loss Poor appetite Slow recovery from fatigue Poor wound healing Lethargy Irritability Lack of willpower Possible permanent brain damage

  34. High Altitude Stress: Acute Physiological State • Medical Issues: Altitude Sickness and Deterioration • Performance Issues: Physical and Neuropsychological PIO2 PAO2 PaO2 Disruption in Homeostasis

  35. Altitude Impact on Physical Work Performance Maximal Aerobic Exercise Performance 146 mean data points from 67 studies Fulco CS, et al., Aviat Space Environ Med 69: 793-801, 1998

  36. Altitude Impact on Physical Work Performance Decreased Maximal Arterial Oxygen Delivery . . VO2max = Qmax x (CaO2 – CvO2) (ml/min) (L/min) (ml/L) At Sea Level (SaO2=97%): 4200 ml/min = 25 L/min x (196-28 ml/L) At 4300 m (SaO2=80%): 3425 ml/min = 25 L/min x (165-28 ml/L) SL: CaO2 = 19.6 ml O2% 1850 m: CaO2 = 19.2 ml O2% 4300 m: CaO2 = 16.5 ml O2%

  37. Altitude Impact on Physical Work Performance Endurance Exercise Performance . ~31% decrease VO2max 150 W steady-state exercise . 50 %VO2max 73

  38. Altitude Impact on Physical Work Performance Endurance Exercise Performance . ~31% decrease VO2max 150 W decreased to 105 W steady-state exercise . 50 %VO2max 50

  39. Altitude Impact on Physical Work Performance Endurance Exercise Performance

  40. Altitude Impact on Physical Work Performance Acclimatization Improves Submax Exercise Performance Performance Metric: Endurance Time at a Fixed Work Intensity

  41. Altitude Impact on Physical Work Performance Performance Improvement is Strongly Correlated to Ventilatory Acclimatization

  42. Optimizing Exercise Performance At High Altitude: What’s the fuss? Sanctioned Competitions: 2010 FIFA World Cup (~5,000 ft) 2002 Winter Olympics (4,675 – 5,742 ft) Pikes Peak Marathon (7,000 – 14,110 ft) Leadville 100 (9,200 – 12,600 ft) 2014 Winter Olympics (5,000 ft) Recreational Activities: Trekking & Mountaineering Snow Sports Hunting & Fishing Occupational Activities: Military & Law Enforcement Forestry & Mining Civil Engineering

  43. Altitude Impact on Neuropsychological Performance Kryskow et al., ASEM, 2013

  44. Altitude Impact on Neuropsychological Performance Take home message: immediate impairment, but rapid recovery

  45. Summary 1. Biophysics of the Altitude Environment 2. Altitude Acclimatization: Key Physiological Adaptations Time-Course 3. High Altitude Stress: Medical Problems - Altitude Illness Performance – Physical & Neuropsychological

  46. Questions? Pikes Peak Sunset Mt. Kilimanjaro Crater

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