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Therapeutic Hypothermia after Cardiac Arrest

5th New York Symposium on Neurological Emergencies and Neurocritical Care New York June 4-6, 2008. Therapeutic Hypothermia after Cardiac Arrest. Mauro Oddo, MD Clinical Research Division Department of Neurosurgery University of Pennsylvania Medical Center Philadelphia .

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Therapeutic Hypothermia after Cardiac Arrest

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  1. 5th New York Symposium on Neurological Emergencies and Neurocritical Care New York June 4-6, 2008 Therapeutic Hypothermia after Cardiac Arrest Mauro Oddo, MD Clinical Research Division Department of Neurosurgery University of Pennsylvania Medical Center Philadelphia

  2. 1. Anoxo-ischemic brain injury after cardiac arrest

  3. Global Ischemia andReperfusion

  4. Global ischemia-reperfusion injurypost-resuscitation disease Ischemia VF = ventricular fibrillation ROSC= return of spontaneous circulation

  5. Electrical Circulatory Metabolic Electrical & Circulatory  reduction of the duration of global ischemia (primary brain injury) Metabolic  attenuation of post-resuscitation disease due to reperfusion injury (secondary brain injury) 3-phase time sensitive model 4 min 4-10 min > 10 min time to ROSC Weisfeldt ML, Becker LB JAMA 2002

  6. Hypothermic neuroprotection Lo EH, Nature Reviews. Neuroscience 2003

  7. hypothermia Post-resuscitation disease

  8. Effect of mild hypothermia during the early phase after initial brain injury

  9. Hypothermic neuroprotection

  10. Intra-ischemic vs. Post-ischemic Hypothermia

  11. Crit Care Med 2004

  12. 2. Therapeutic Hypothermia to Improve Outcome in Comatose Survivors of Cardiac Arrest

  13. Inclusion criteria • Persistent coma • absence of arousal & of verbal and eye response • GCS 3 – 5 • Cardiac arrest due ventricular fibrillation • Absence of circulatory shock • MAP <60 /SBP <90 mmHg after 60 min, despite volume loading, requiring vasopressors

  14. Patient population

  15. Therapeutic hypothermia improves outcome after cardiac arrest HACA trial - Austria * *External cooling device (time 0: hospital admission)

  16. Therapeutic hypothermia improves outcome after cardiac arrest Bernard’s trial - Australia * * Ice packs (time 0: ambulance)

  17. International recommendations • July 2003: ILCOR Advisory statement • Therapeutic hypothermia is recommended after • witnessed cardiac arrest • due to ventricular fibrillation • in the absence of post-resuscitation circulatory shock

  18. Circulation 2005

  19. Circulation 2005

  20. 3. From evidence to clinical practice: application of therapeutic hypothermia

  21. Crit Care Med, 2006;34(7):1865 • 109 comatose patients with OHCA • Swiss tertiary university hospital • 54 treated with standard resuscitation + normothermia • 55 treated with standard resuscitation + therapeutic hypothermia • End-points • Feasibility • Safety • Outcome

  22. Therapeutic hypothermia : 3 phases T°C 38 37 NORMOTHERMIA (n=54) 36 maintenance 35 rewarming 34 HYPOTHERMIA (n=55) induction 33 Time (hrs) 32 0 3 6 12 18 24 36 48

  23. Time to target Median time to T° target: 5 hrs

  24. Hemodynamic support

  25. Side-effects of therapeutic hypothermia

  26. * * * * * * Therapeutic hypothermia after cardiac arresta successful translation from bench to bedside • > 500 patients studied % good outcome

  27. Hypothermia (HT) vs. Normothermia (NT)21st century • VF, no shock • HACA trial 2002 (275 pts) • Good outcome TH 55% vs. NT 39% P<0.05 • Bernard 2002 (77 pts) • Good outcome TH 49% vs. NT 26% P<0.05 • Oddo 2006 (109 pts) • Good outcome TH 56% vs. NT 26% P<0.05 • Busch 2006 (61 pts) • Good outcome TH 59% vs. NT 32% P<0.05 • Belliard 2007 (68 pts) • Good outcome TH 56% vs. NT 36% P<0.05

  28. Hypothermia after cardiac arresta treatment that works ! • number needed to treat : 6 Crit Care Med 2005;33(2):414

  29. Therapeutic hypothermia should be a standard of care in comatose survivors of cardiac arrest due to ventricular fibrillation • Can we expand the use of therapeutic hypothermia to all comatose survivors of cardiac arrest ? • VF and circulatory shock • Non-VF

  30. Therapeutic hypothermia in patients with shock • Oddo M 2006 • Good outcome in 5/17 pts treated with TH vs. 0/14 NT • Hovdenes J 2007 • 23/50 with cardiogenic shock treated with TH and IABP • 61% good outcome (74% in pts without shock) • Skulec R 2008 • 28/56 pts had cardiogenic shock • 37% good outcome (71% in pts without shock)

  31. Therapeutic hypothermia in patients with non-VF and long duration of cardiac arrest Oddo M, Crit Care Med 2006

  32. Therapeutic hypothermia in comatose survivors of CA due to VF and non-VF Oddo M Crit Care Med 2008, in press

  33. Early predictors of outcome Oddo M Crit Care Med 2008, in press

  34. Early predictors of outcome

  35. Early predictors of outcome Oddo M Crit Care Med 2008, in press

  36. Summary of the findings • Excellent outcome (> 60% survivors at hospital discharge) in patients with CA due to VF • Circulatory shock not a significant predictor of outcome • Time to ROSC is the strongest predictor of outcome after CA treated with TH • 6/36 survivors of non-VF CA • time to ROSC < 25 min • 2/16 survivors of unwitnessed CA • Time to ROSC < 25 min

  37. Conclusions • All comatose patients with cardiac arrestdue to ventricular fibrillation, independently from initial hemodynamic status • Aggressive treatment with hypothermia needed !! • Good recovery in 50-60% of patients • Post-cardiac arrest circulatory shock is not a contra-indication • careful hemodynamic monitoring • Vasodilatory shock • Cardiogenic shock

  38. Conclusions • Future studies are required to better establish the benefit of therapeutic hypothermia in patients with non-VF cardiac arrest • Time to ROSC can be used in the clinical setting to estimate the severity of global ischemia-reperfusion injury

  39. Acknowledgements • Mauro Oddo has received research grants from • SICPA Foundation, Lausanne Switzerland • Lausanne University Hospital, Switzerland

  40. Therapeutic Temperature Management Congress • Barcelona, Spain, October 1- 4 2008

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