1 / 58

Hypothermia in Cardiac Arrest: Should we be hot to cool?

Hypothermia in Cardiac Arrest: Should we be hot to cool?. Vanessa R. Cole, MD December 17, 2002 Resident Grand Rounds. Clinical Case. 55 yo WM w/DM, PVD, h/o CVA transferred to NCBH CCU after cardiac arrest

asha
Download Presentation

Hypothermia in Cardiac Arrest: Should we be hot to cool?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Hypothermia in Cardiac Arrest:Should we be hot to cool? Vanessa R. Cole, MD December 17, 2002 Resident Grand Rounds

  2. Clinical Case • 55 yo WM w/DM, PVD, h/o CVA transferred to NCBH CCU after cardiac arrest • Family reports USOH, states he felt “hypoglycemic”, then clenched his teeth & became unresponsive • Pulseless & apneic at OSH ED • Resuscitated with atropine, epinephrine • Delayed airway obtained 40 mins into code

  3. Clinical Case • Initial PEA, junctional rhythm after resuscitation • Briefly responsive, then became hypotensive • Coded again • To NCBH CCU on epinephrine & dopamine gtts, externally paced • Intubated, obtunded, pupils fixed at 4 mm, no corneal reflexes • ABG: 7.30/37/120/18/98% on 100% FiO2 • Lactate: 8 meq/L

  4. Questions • Would hypothermia have any benefit on neurologic prognosis in this patient? • In which patients, if any, has hypothermia after cardiopulmonary arrest been shown to improve outcome? • What are the harms associated with hypothermia?

  5. History of hypothermia in clinical use • Pathophysiology • Summary of major animal studies • Small clinical trials • 2 randomized controlled trials • Summary/Conclusions • CCU protocol • Future directions

  6. 1950’s 4 published case reports 320C to 340C for 24-72 hrs after cardiac arrest 3/4 patients recovered without neurologic deficit 5/56-11/58 Johns Hopkins Hospital Review of 27 cases 12 w/hypothermia 320C to 340C for 34-84 hrs 15 w/normothermia 8 normothermics excluded 1/7 normothermics, 6/12 hypothermics survived w/o deficit History of hypothermia

  7. Adverse effects of hypothermia • Coagulopathy - platelet dysfunction, prolonged PT/PTT •  CO,  SVR • EKG changes, arrhythmias •  susceptibility to infection •  blood viscosity •  extracellular potassium

  8. Mild = 34 + 20C Moderate = 30 + 20C Deep = 15-250C Profound < 150C Protective = cooling before the insult Preservative = cooling during the insult Resuscitative = cooling to reverse the insult, support recovery Definitions

  9. Reperfusion Injury

  10. Reperfusion injury • Barbiturates - thiopental • Ca2+ channel blockers - lidoflazine • Corticosteroids • Free radical scavengers • Neurotransmitter receptor blockers

  11. Reperfusion injury Cooling: • Retard enzymatic rxns, suppress production of free radicals • Reduction of O2 demand in low-flow regions • Inhibition of excitatory NT synthesis • Protection of membrane fluidity • Reduction of intracellular acidosis • Decrease in cerebral edema and ICP

  12. Animal Studies • 5 consecutive studies of hypothermia in dog model of cardiac arrest 1990-1996 • Hypothermia after v.fib arrest improved outcome w/bypass & CPR for resuscitation • Profound hypothermia was detrimental • Moderate hypothermia was beneficial to brain, detrimental to heart • Benefit of cooling best achieved if begun immediately • 12 hr protocol w/greatest benefit

  13. Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest* • Prospective study of active patients, retrospective review of controls, unblinded assessment of GOCS score • Australia, 11/93-3/96, 22 pts/group • Included: unconscious w/ROSC after out-of-hospital cardiac arrest • Excluded: refractory hypotension, coma for other reasons, age < 16yrs, poss. pregnancy, transfer from other hospital • Cooling: 330C w/ice packs X 12 hrs *Bernard SA et al. Annals of Emergency Medicine, 1997. 30: 146.

  14. Glascow Outcome Coma Score (GOCS)

  15. Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest* • No significant differences in study groups • Depth of coma similar • Core temp < 340C at a mean of 74 mins • More bradycardia, acidosis, K+ (assoc w/ rewarming) in hypothermia group • No complications of hypothermia *Bernard SA et al. Annals of Emergency Medicine, 1997. 30: 146.

  16. Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest* • Good outcome achieved in significantly more hypothermia patients • Mortality significantly reduced in hypothermia group *Bernard SA et al. Annals of Emergency Medicine, 1997. 30: 146.

  17. Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest* Limitations: • Retrospective controls introduce potential differences in patient groups • Unblinded assessment of outcome, ? bias • Not all v. fib arrests • Small numbers, may not have power to detect adverse effects of treatment *Bernard SA et al. Annals of Emergency Medicine, 1997. 30: 146.

  18. Preliminary Clinical Outcome Study of Mild Resuscitative Hypothermia After Out-of-Hospital Cardiopulmonary Arrest* • Prospective study of active patients, retrospective review of controls, assessment of recovery & survival to discharge • Japanese suburban hospital, 1995 • 13 pts in hypothermia group, 15 controls • Included: lack of hypotension, age < 70 yrs • Excluded: trauma, CNS disease, or terminal illness as cause of arrest • Cooling: 33-340C w/cooling blankets & EtOH on trunk/extremities X 48 hrs *Yangawa et al. Resuscitation, 1998. 39: 61.

  19. Preliminary Clinical Outcome Study of Mild Resuscitative Hypothermia After Out-of-Hospital Cardiopulmonary Arrest* • Cooling within 78+28 mins of ROSC • Target temp w/in 336+180 mins of initiation • 11/13 pts completed cooling protocol 3 10 *Yangawa et al. Resuscitation, 1998. 39: 61.

  20. Preliminary Clinical Outcome Study of Mild Resuscitative Hypothermia After Out-of-Hospital Cardiopulmonary Arrest* • No significant differences in survival to discharge • For survivors, period of no cerebral perfusion was longer in hypothermia group • Full recovery more frequent with hypothermia (3/13 vs. 1/15, p = NS) • 11/13 (85%) hypothermics developed pna vs. 5/15 (33%) normothermics (p = 0.02) *Yangawa et al. Resuscitation, 1998. 39: 61.

  21. Preliminary Clinical Outcome Study of Mild Resuscitative Hypothermia After Out-of-Hospital Cardiopulmonary Arrest* Limitations: • Retrospective controls introduce potential differences in patient groups • Fewer witnessed collapses in hypothermia group may have blunted effect • Variable etiologies of arrest *Yangawa et al. Resuscitation, 1998. 39: 61.

  22. Hypothermia After Cardiac Arrest: Feasibility & Safety of an External Cooling Protocol * • Prospective cohort study from 7/98-10/99 • UT Houston, Cleveland Clinic, Baylor • 156 screened, 15 eligible, consent obtained in 9 pts • Included: out-of-hospital arrest, ROSC, hypothermia w/in 90 mins, age 18-85 yrs, GCS < 8, informed consent from family • Excluded: cardiac instability, acute ischemia, sepsis, need for pressors, shock, coagulopathy, QTc > 470 ms, in-hospital arrest, other conditions precluding treatment *Felberg et al. Circulation, 2001. 104: 1799.

  23. Hypothermia After Cardiac Arrest: Feasibility & Safety of an External Cooling Protocol * • Cooling: 330C w/axillary & groin ice packs until cooling blankets placed, iced saline gastric lavage X 24 hrs • Outcome: 10 – feasibility of cooling 20 – discharge disposition, MMSE, Rankin score at 30 days *Felberg et al. Circulation, 2001. 104: 1799.

  24. Hypothermia After Cardiac Arrest: Feasibility & Safety of an External Cooling Protocol * • 78+20 mins from ACLS to start of cooling • 301+178 mins from initiation of cooling to goal temperature • 1 pt did not complete protocol • 4/9 survived: 3/9 Rankin score=0, MMSE=30 1/9 Rankin score=3, MMSE=20 • Pts w/good outcome had shorter anoxic periods *Felberg et al. Circulation, 2001. 104: 1799.

  25. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * • Randomized controlled trial, 9/96-6/99 • Multiple Australian hospitals • Included: v. fib upon arrival of EMS, ROSC, persistent coma, transfer to participating ED • Excluded: < 18 yrs ♂, < 50 yrs ♀, shock, causes of coma other than CA, ICU bed unavailable in participating center *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  26. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  27. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * • Cooling: 330C w/ice packs to head, neck, torso, limbs X 12 hrs • Normothermia: 370C, rewarmed if hypothermic on arrival • Temperature monitored via PA catheter or bladder temp probe Outcome: 10 – disposition @ hospital D/C determined by blinded rehab specialist 20 – hemodynamic, biochemical, hematologic effects of cooling *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  28. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * • 4 patients randomized to hypothermia were not cooled • Clinical characteristics similar • More males, more w/bystander CPR in normothermia group (non-significant) • Hypothermia – bradycardia,  SVR, hyperglycemia w/cooling,  K+ w/rewarming • No clinically significant adverse events *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  29. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * • Age & time from collapse to ROSC affected outcome • After adjustment for these factors, OR increased to 5.25 (95% CI 1.47-18.76, p=0.011) for good outcome *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  30. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia * Limitations: • Clinicians were not blinded to tx assignment, ? bias in care & outcome • Suboptimal randomization scheme • Lack of long-term follow-up *Bernard et al. New England Journal of Medicine, 2002. 346: 557.

  31. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • Randomized controlled trial, 3/96-1/01 • 9 centers in 5 European countries • Included: witnessed CA, v. fib or pulseless v. tach, presumed cardiac origin of arrest, age 18-75 yrs, 5-15 mins from collapse to 1st resuscitation attempts, < 60 mins from collapse to ROSC *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  32. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • Excluded: TM temp < 300C on admission, comatose prior to arrest, pregnancy, response to verbal commands after ROSC, MAP < 60 for > 30 mins after ROSC, O2 sat < 85% for > 15 mins after ROSC, preceding terminal illness, factors that made follow-up unlikely, enrollment in another study, CA after EMS arrival, known coagulopathy *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  33. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  34. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • Cooling: 320C-340C w/ external cooling device X 24 hrs • Goal to reach target bladder temp in 4 hrs; if not, ice packs applied • Temperature monitored via TM thermometer initially, then bladder probe *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  35. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  36. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * Outcome: • 10 – Favorable neurologic outcome at 6 mos, defined as Pittsburgh CPC of 1 or 2 • Neurologic outcome obtained in blinded fashion • 20 – Overall mortality at 6 mos, rate of complications during the 1st 7 days after CA • Clinicians involved in pt care during 1st 48 hrs were unblinded *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  37. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • 14 patients hypothermia discontinued early • 1 pt per group lost to neurologic follow-up • Clinical characteristics similar • Control group - larger # of pts w/DM, CAD, BLS performed by bystander (non-significant) *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  38. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • Median interval between ROSC & initiation of cooling 105 mins • Median interval between ROSC & target temperature 8 hrs • 19 pts never reached target temperature • Ice packs required in 70% of pts *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  39. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * Bladder Temperature in the Normothermia and Hypothermia Groups. *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  40. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • Adjusting for DM, CAD, BLS from bystander resulted in increased treatment effect • RR for favorable neurologic outcome 1.47 (95% CI 1.09-1.82) • RR for death 0.62 (95% CI 0.36-0.95) *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  41. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * Cumulative Survival in the Normothermia and Hypothermia Groups. *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  42. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * • 73% of hypothermic pts & 70% of normothermic pts developed complications (p=0.70) • Sepsis, pna more likely in hypothermia group (non-significant) • Total # of complications similar in the two groups (p=0.09) *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  43. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest * Limitations: • Clinicians not blinded to treatment assignment • Large # of strict inclusion/exclusion criteria • Included only witnessed CA, which represents small # of out-of-hospital arrests *The Hypothermia After Cardiac Arrest Study Group. NEJM, 2002. 346: 549.

  44. Summary • 2 RCTs demonstrate a favorable neurologic outcome in pts treated w/mild hypothermia, 320C-340C for 12-24 hrs in setting of v. fib or v. tach arrest w/ROSC • Larger RCT demonstrates a significant decrease in mortality at 6 months • Neither study had a greater number of complications in hypothermia group

  45. Conclusions • Permanent brain damage seen in 10-30% of survivors of out-of-hospital CA in U.S. • No therapy w/documented efficacy in preventing brain damage after CA • Hypothermia has a long clinical history & a body of animal studies supporting its use • Pathophysiologic basis

More Related