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Exertional Heat Illness in Recruits with Hemoglobin S: Policies to Prevent Exercise-Related Death

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Exertional Heat Illness in Recruits with Hemoglobin S: Policies to Prevent Exercise-Related Death

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    1. Exertional Heat Illness in Recruits with Hemoglobin S: Policies to Prevent Exercise-Related Death

    4. Pathophysiology of Sickle Cell Disease Point mutation at 6th AA of beta globin glutamic acid to valine (negative to neutral charge) Deoxy Hb S polymer forms with low O2, exponential of Hb S concentration, low pH, high temperature, high 2,3-DPG Relevant to circumstances and high risk for spleen, renal medulla (papillary necrosis), & many other complications

    5. Pathophysiology of Sickle Cell Disease Micro-vascular obstruction RBCs rigid because of polymer: normal-shaped cells are the most important Youngest RBCs are the most sticky: mean age 17 days versus 55 days (turnover 6.5 x normal). Adhesion between endothelium & RBCs: sticky proteins Release of vWF by newly hypoxic RBCs: SCT Hypercoaguable state: no in vivo confirmation Oxidative & RE damage to RBC membrane

    6. Sickle Cell Trait Hb AS genotype. Hb S <50% (vs > SS, SC, Sbeta-thal etc., with Hb S >50% for disease) (median Hb S is 42%, 32%, 26% for Hb AS with 5-4, 3, or 2 alpha globin genes) Normal CBC with no anemia, hemolysis undetectable Microscopic sickling only significant in the loops of Henle of the renal medulla, rarely in the spleen and in the drainage of vitreous humor.

    7. Screening for Sickle Cell Trait and Sickle Cell Disease 1. Sickle cell screen: Place blood drop in phosphate buffer: Hb S precipitation: high specificity and sensitivity. 2. CBC - normal for Hb AS, anemia with increased RDW for 99% of sickle cell disease. 2. Quantitative Hemoglobin electrophoresis in alkali. 3. Reticulotye count elevated in 99%+ of SCD but normal in uncomplicated Hb AS.

    8. Clinical Complications Proven to Be Associated with Sickle Cell Trait Age-related loss of maximal urinary concentration, episodic hematuria, mild increase in UTI of pregnancy, altitude/exercise related splenic infarction, increased risk of traumatic hyphema, very rare renal medullary carcinoma, and unexpected exercise-related death in recruits and young athletes

    9. Ideal Features for Study of Unexpected Exercise-Related Deaths in Young Adults

    10. Hemoglobin S and Rates of Exercise-Related Death Unexplained by Preexisting Disease

    11. Sickle Cell Trait as a Risk Factor for Exercise Related Death among Recruits

    12. Exercise Related Death in Civilian* versus RecruitPopulations * (Rhode Island joggers, 1975-80, PD Thompson, JAMA 247:2535-8, 1982)

    13. Hemoglobin Phenotype and Exercise-Related Death in Recruit Basic Training, 1977-81

    14. New Standards Required for Diagnosis of Exercise-Related Deaths

    15. New Standards Required for Diagnosis of Exercise-Related Deaths

    16. Exercise-Related Deaths Unexplained by Preexisting Disease: 1977-1981

    17. Types of Exercise Related Recruit Deaths (94 military recruit deaths, 1977-90)

    18. Deaths in U. S. Military Recruit Basic Training, 1977-90 Percent of ERD explained by autopsy findings

    19. Alpha-Thalassemia Protects Against Exertional Mortality with Sickle Cell Trait 30% of African Americans have alpha-thalassemia. In those with sickle cell trait the main effect is to lower the Hb S fraction below 35% of total Hb. We collected 47 cases of exercise-related death/near death with sickle cell trait and Hb S% : we expected 14 cases with alpha-thalassemia & <35% S Two cases had Hb S = 35% , none below this: only ~ one case had alpha-thalassemia. Individuals w. sickle cell trait are protected by alpha-thalassemia, since their incidence as cases was reduced more than ten-fold.

    20. Alpha-Thalassemia Protects Against Exertional Mortality with Sickle Cell Trait Gupta et al., J Clin Invest 88:1963, 1991 established that any complication associated with Hb AS can be attributed to polymerization of Hb S if its incidence is reduced by alpha-thalassemia. Thus SCT-trait associated exercise-related death, whether due to EHI or sudden idiopathic arrest, is largely due to polymerization of Hb S Sickle-cell trait is not simply a marker for risk but contributes to pathogenesis of exercise-related death by vascular obstruction from red cells stiffened by deoxy-Hb S polymer.

    22. Wet-Bulb Globe Temperature Index The WBGT Index takes into account air temperature, humidity, radiant heat, and air movement.

    23. Common Characteristics of the Sudden Exercise-related Deaths

    28. Effect of Sickle Cell Trait on Rates of Non-Fatal Exertional Heat Illness Collected all cases of EHI at Parris Island among African American recruits for 3 yrs. The incidence of EHI was 0.55% of 1,500 recruits with hemoglobin AS. The incidence of EHI was 0.54% of 36,325 recruits without hemoglobin S. Sickle cell trait did not appear to alter the risk of non-fatal exertional heat illness

    29. Exertional heat illness (EHI) is a risk factor for exercise-related sudden death POPULATION: 269,000 Marine Corps recruits at Parris Island, SC, 1979-1990. (Too small a study for an effect of Hb AS) COLLECT: All EHI and all threatened or actual sudden deaths during training. (Too small for mortality alone as the end-point) COMPARE: Rates of fatal or serious cardio- vascular events in those with or without EHI. HYPOTHESIS

    30. Spectrum of Clinical Presentations We sought cases of exertional heat stroke, rhabdomyolysis, or isolated acute renal failure as risk factors, but only found serious cases with exertional heat stroke. We sought cases of distributive shock, life-threatening arrhythmias, and ischemia/infarction as outcomes. Serious cases presented as shock. Two cases had poorly documented arrhythmias prior to shock.

    31. Exertional Heat Illness as a Risk Factor for Threatened or Actual Sudden Death Exertional Without Heat Heat Stroke Illness . Cardiovascular events 7 (2d) 4 (4d) Population at risk 137 267,000 Case Rate 5.1% 0.0015% Relative Risk 3,400 1 (ref)

    32. Heat stress exposure contributes to exercise-related sudden death POPULATION: 5.8 million military recruits during basic training, 1977-1991. COLLECT: All exercise-related deaths during training and hourly WBGTs. COMPARE: Percent of deaths with high WBGT exposure versus control deaths, by cause of death. HYPOTHESIS

    33. Percent of Exercise Related Recruit Deaths Exposed to Substantial Heat Stress (Same or Prior Day WBGT > 75°F)

    34. Review of 120 recruit cases & 50 additional cases of fatal EHI w SCT More than 15 patients had hyperthermia or typical chemical changes of rhabdomyolysis and a substantial preexisting cardiac lesion. Cardiac stress from EHI can provoke fatal complications due to preexisting heart disease. Such deaths might be preventable. Cases of Sudden Cardiac Death with Features of EHI

    35. Effective intervention to prevent EHI will reduce exercise-related deaths, especially in recruits w SCT POPULATION: All military recruits entering in 1977-81 before (2.1 million ) and in 1982-1991 during intervention (2.7 million participants and 1.1 million non-participants). DATA: Information on all exercise-related deaths during training and determine cause of death. COMPARE: Exercise-related death rates and estimates of lives saved in the intervention and non-intervention recruit populations. HYPOTHESIS

    36. Intervention for Prevention of EHI During Armed Forces Basic Training In the Hot Season, Drill instructors would: record WBGT at least hourly at the exercise site decrease exercise intensity and increase rest cycles as WBGT rises, to minimal effort at 90°F increase water intake & observe water consumption exercise using light track clothing in hot weather immediate cooling and rehydration with early symptoms Participating Centers Army, Air Force, Parris Island Marine Corps Non-Participating Centers Navy, San Diego Marine Corps

    37. Data Collection for Military Recruit Deaths

    38. Estimate of Lives Saved by Intervention, U. S. Military Basic Training, 1982-1991 [Number of deaths predicted from 1977-81 rates]

    39. EHI Measures Among Non-Participants

    40. CONCLUSIONS 1. There is a significant association between high-risk hot weather for 24 hrs before collapse and exercise-related sudden death, greatest for people with sickle cell trait. 2. Heat stroke increases the rate of exercise-related threatened or actual sudden cardiac death by 3,400-fold, probably because life-threatening cardiovascular collapse is common. 3. Intervention to prevent exertional heat illness appears to eliminate the excess risk of death for recruits with sickle cell trait. 4. Exertional heat illness is a major preventable factor contributing to exercise-related death of young adults.

    41. Advice to Military Members with SCT There is a greater risk of fatal EHI for those with sickle cell trait. Risk is high if one is poorly conditioned for an event, dehydrated, obese, sleep deprived, at altitude, conditions limit ability to loose body heat, and heroic effort is made with disregard for effort-related symptoms. This risk can be largely eliminated by intervention to improve hydration, improve ability to sweat, and limit exercise when occlusive clothing or high ambient temperature increase the threat of excessive body temperature. Rapid treatment to correct early mild signs or symptoms of EHI, e.g. unusual muscle pain or weakness, is important. Each person should recognize and act upon such symptoms by reducing effort & seeking medical advice.

    42. Advice to Military Members with SCT After entry training , risk of unexpected exercise-related death is much less, but still significant. The same precautions should be taken to avoid heroic effort, to remain conditioned for any task, and to follow sensible procedures to minimize risk of EHI at all times.

    43. The Utility of Screening for SCT The diagnosis and management of EHI is identical for those with or without SCT. While knowledge that one has SCT can motivate a person to better protect themselves from EHI, a beneficial effect on behavior or medical outcome has not been demonstrated. SCT Mortality has varied widely irrespective of screening policy. In our prospective study 35,000 Army recruits with SCT completed basic training without deaths in the absence of expensive screening for SCT.

    44. The Utility of Screening for SCT The main advantage of screening for SCT would be the detection of recruits with unrecognized sickle cell disease, because of mild or undisclosed cases. Since recruits with SCD are at high risk of developing serious or fatal sickle crisis episodes from mild EHI, it would be important to complete screening prior to any PT. The cost of not screening for SCD involves not only the loss of personnel but the expense of investigations of hospitalizations and training deaths. These may have major legal implications and potential impact upon the military careers of all training personnel.

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