Hypothermia for Hemorrhagic Shock: It’s Cool to be Cool!!

1. Hypothermia for Hemorrhagic Shock:It’s Cool to be Cool!! Samuel A. Tisherman, MD Associate Professor Surgery and Critical Care Medicine Safar Center for Resuscitation Research University of Pittsburgh

3. Energy failure Oxidant injury Delayed neuronal death Excitotoxicity ICP Edema formation Cytoskeletal protein degradation BBB permeability IL-1 production Neutrophil accumulation Mechanisms of Benefit Who cares?

4. Predisposition in Trauma Patients • Exposure (field and trauma bay) • Opening of body cavities • Blood loss • Infusion of cold fluids • Limited heat production • Shock • Sedation, anesthesia, EtOH and drugs

5. Hypothermia Therapeutic/controlled  Exposure/uncontrolled

6. Temperature Levels • Mild 32-36oC • Moderate 28-32oC • Deep 10-20oC • Profound 5-10oC • Ultraprofound <5oC

7. Dying Patterns from Hemorrhage Limited FR Hypothermia Pharmacologic hibernation Uncontrolled HS Maintain pulse Transport Delayed Resuscitation Resuscitative Surgery Lose pulse Hypothermic Pharmacologic Preservation “Suspended Animation” Allow circulatory arrest Exsanguinating Hemorrhage

8. Moderate hypothermia and HS Meyer and Horton, Curr Surg, 1988.

10. 100 80 60 O2-Hth Group 4 % surviving 40 O2 Group 3 20 Control Group 1 Hth Group 2 0 0 50 100 150 200 250 300 Time (min) Kim, et al. J Trauma, 1998.

11. Survival from Pressure-controlled HS Prolonged Hypothermia Group 3 (9/10) Brief Hypothermia Group 2 (7/10) Number of rats alive Normothermia Group 1 (3/10) p = 0.02 vs. Group 3; p = 0.18 vs. Group 2 Time Prueckner, J Trauma, 2001.

12. Rewarming vs. Continued Hypothermia after HS MAP G. I: 37.5 °C to 12 h Temp. (rectal) G. III 2 h 34 C 35 °C G. II: 34 °C to 12 h 40 mmHg to 30% uptake Hemorrhagic shock Resuscitation to 4 h Observation to 72 h SCRR. 2001 Wu, et al. 2002

13. Rewarming vs. Continued Hypothermia after HS 8 Temp. under control for 12 h Rewarmed 6 Hypo-12 h Survivors 4 Hypo-2 h 2 0 0 25 50 75 Resuscitation Time (h) SCRR. 2001

14. MAP Temperature (rectal) Rewarming vs. Continued Hypothermia after HS Group I: 37.5 °C to 12 h 3ml/100g over 15 min 35 °C Group II: 34 °C to 12 h 40 mmHg 50% uptake of shed blood Hemorrhagic shock Resuscitation to 4 h Observation to 72 h SCRR. 2002

15. Rewarming vs. Continued Hypothermia after HS 8 P = 0.0029 6 Survivors 4 Cooling Group Rewarming Group 2 Temp Controlled 0 0 10 20 30 40 50 Resuscitation Time (h)

16. Very Prolonged HS (6 h)Hypothermia 14 12 Hypo-10 min (p=0.005 vs normothermia, Log Rank [Peto]) 10 8 # Survivors Hypo-1 h(p=0.01 vs normothermia, Log Rank [Peto]) 6 4 Normothermia 2 HS Temp. Controlled Observation 0 RT 72 h RT 0 RT 24 h RT 48 h 0 HS: Hemorrhagic shock; RT: Resuscitation time (hours)

17. Hypothermia is a double-edged sword.

18. Hypothermia and Trauma • High ISS • Hypothermia • Decreased shivering, thermoregulation, heat production • Coagulopathy and acidosis • "Damage control laparotomy"

19. Hypothermia - complications • Coagulopathy • Platelets -number and function, TxB2 • Elevated PT and PTT • ?Increased fibrinolysis • Dysrhythmias and hypotension • Metabolic acidosis • Infections

20. Preclinical Pig Study • Pressure-controlled HS • Hemodilution • Normothermia vs hypothermia (34oC) • Laparotomy • Excise edge of liver • Measure blood loss • Coags, platelets, TEG, ACT Wu, in preparation.

21. HYPOTHERMIA AND HEMORRHAGIC SHOCK IN PIGS BLEEDING FROM THE INJURED LIVER 2000 † Heparin 200 u/kg 1800 Normothermia Hypothermia 1600 † 1400 † † † 1200 † † Cumulative blood loss (ml) 1000 800 † 600 † † 400 † † 200 0 0 50 100 150 200 250 300 350 Resuscitation time (min) Wu, et al. SCCM 2002

22. PRECLINICAL STUDY OF HYPOTHERMIA DURING HS-PIGS Coagulation Tests in Pigs at 3 h after HS and Liver Injury Thromboelastograph (TEG) ACT(sec) PT PTT Platelets m (sec) (/ l) (sec) ° R (min) K (min) MA (mm) Alpha ( ) 127.7±21.1 Normothermia 11.2±0.3 22.9±8.0 280±53103 3.5±1.3 10.6±4.4 62.4±9.1 69±4 140.0±10.8 53.3±10.7 3.7±1.4 61±1 10.2±3.2 Hypothermia 12.1±1.1 19.6±2.0 236±77103 Wu, et al. SCCM 2002

23. Hypothermia and Trauma • Luna, et al (U of Washington) • T>36oC (n=32): ISS 28, survival 78% • T=34-36oC (n=41): ISS 29, survival 59% • T<34oC (n=21): ISS 36, survival 41% • Jurkovich, et al (U of South Alabama) • ISS 25-29 • >33oC: survival 97% • <33oC: survival 50% J Trauma, 1987.

24. Hypothermia and TRISS • UCSD • 173 with ISS >9 and known core temp • Hypothermic pt: n=37 • More hypotensive • Survival as predicted by TRISS • No difference in ICU days for survivors Steinemann, J Trauma, 1990.

25. Prospective Hypothermia Study • Harborview Medical Center, Seattle • Core temp <34.5oC and PAC needed • Standard Tx • Warm fluids, gases, air blanket, hat • Treatment • Continuous arteriovenous rewarming Gentilello, et al. Ann Surg, 1997.

26. Continuous arteriovenous rewarming technique. Gentilello, et al Ann Surg, 1997.

27. Prospective Hypothermia Study • Survival to discharge • SR = 14 (50%) • CAVR = 19 (66%) • CAVR • More late deaths - ?SR weeded out sick • No significant difference in coags Gentilello, et al. Ann Surg, 1997.

29. Political: Centers Medical: Protocols Ethical: Consent Financial: Funding Clinical Trials • Mild hypothermia for HS • Suspended animation for exsanguination arrest

30. Snowbird, Utah, SHOCK Society annual meeting, June, 2000