Hypothermia: The Science and Recommendations (In-hospital and Out)

Transcription

1 Hypothermia: The Science and Recommendations (In-hospital and Out) L. Kristin Newby, MD, MHS Professor of Medicine Duke University Medical Center Chair, Council on Clinical Cardiology, AHA President, Society of Cardiovascular Patient Care

2 Conflict of Interest Reporting Research grant funding GlaxoSmithKline, Bristol Myers Squibb, Merck & Company, Inc., Amylin, MURDOCK Study Consulting Jansen Pharmaceuticals, Roche Diagnostics, LG, Navigant, Novartis, Daiichi-Sankyo, DSI-Lilly, Genentech, GlaxoSmithKline, Cubist Pharmaceuticals Organizations Society of Chest Pain Centers, Journal of the American Heart Association

3 Leading Causes of Death in the United States Cancer Heart Disease ex OHCA OHCA Stroke Chronic Respiratory Condition Injury Alzheimer Diabetes Influenza and Pneumonia Renal Septicemia Annual Number of Deaths Extrapolated from and Nichol JAMA 2008

4 Survival from Cardiac Arrest Survival rates range from <5% to 10% Cumulative meta-analysis: median survival to hospital discharge for all rhythm groups 6.4% ~18% survive to d/c after in-hospital cardiac arrest 2-9% survive to d/c after out-of-hospital cardiac arrest Nadkarni, Larkin, Peberdy MA, et al. JAMA. 2006;295:50-7. Nichol, Stiell, Laupacis, et al. Ann Emerg Med. 1999;34: Peberdy MA, Kaye, Ornato JP, et al. Resuscitation. 2003;58:

5 Prevention of OHCA Not (Currently) the Answer Myerburg, et al. Circulation 1992;85:I2-I10

6 Post-Arrest Care is Critical Component of ACLS

7 Objectives of Post-Arrest Care Initial objectives of post-arrest care Optimize cardiopulmonary function and vital organ perfusion Transport to capable facility (OHCA) or ICU (IHCA) Identify and treat precipitating cause and prevent recurrent arrest Subsequent objectives of post-arrest care Control body temperature Identify and treat ACS Optimize mechanical ventilation Reduce risk of multiorgan injury and support or organ function if needed Objectively assess prognosis for recovery Assist survivors with rehabilitation services

8 Rationale for A Systems Approach to Post- Arrest Care Most deaths occur within 24 hours of arrest Best hospital care after ROSC not entirely known Associations observed between outcomes and volume of arrest cases treated at a hospital Multiple organ systems are affected by arrest

9 What Do the 2010 Resuscitation Guidelines Say? Class I, LOE B A comprehensive, structured, multidisciplinary system of care should be implemented in a consistent manner for the treatment of post-cardiac arrest patients Programs should include as part of structured interventions Therapeutic hypothermia Optimization of hemodynamics and gas exchange Coronary reperfusion with PCI when indicate Glycemic control Neurological diagnosis, management and prognostication

10 Therapeutic Hypothermia Animal Studies In early 1980s, Safar et al. and others initiated research on therapeutic hypothermia after cardiac arrest in dog models Mild hypothermia used after prolonged cardiac arrest beneficial Normal brain function and histologic findings Research in rat models revealed mild changes in brain temperature alter degree of histologic damage after incomplete forebrain ischemia Rate of complications higher with more than mild hypothermia (ie, 30 C vs. 34 C) Earliest possible induction of mild hypothermia after cardiac arrest improved functional outcome

11 Therapeutic Hypothermia Mechanisms of Action In normal brain, hypothermia reduces the cerebral oxygen consumption by 6% for every 1 C reduction in brain temp >28 C Mild hypothermia is postulated to suppress chemical reactions associated with reperfusion injury, which can lead to mitochondrial damage and apoptosis free radical production excitatory amino acid release calcium shifts Steen, Newberg, Milde, et al. Anesthesiology. 1983;58:

12 Therapeutic Hypothermia Mechanisms of Action hypothermia ischemia lower metabolic rate less oxygen consumption reperfusion glutamate release calcium shifts mitochondrial dysfunction excitotoxicity inflammatory cascades cell death blood brain barrier disruption & cerebral edema oxygen-free radicals Geocadin RG, Koenig MA, Jia X et al. Neurol Clin. 2008;22:

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14 Randomized Trial of Therapeutic Hypothermia HACA Study Group Hypothermia vs. Normothermia Methods Inclusion OHCA due to VF Ages years <60 min since collapse 5-15 min of resuscitation Exclusion cardiogenic shock Hypothermia group 32 C - 34 C Cooled for 24 hrs Rewarmed over 8 hrs 3246 ineligible 3351 assessed 30 Not included 137 hypothermia 275 enrolled 138 normothermia The HACA Study Group. N Engl J Med. 2002;346:

15 Randomized Trial of Therapeutic Hypothermia HACA Study Group Bladder Temperature The HACA Study Group. N Engl J Med. 2002;346:

16 Randomized Trial of Therapeutic Hypothermia HACA Study Group Neurologic outcome Pittsburgh cerebral performance category scale Cerebral Performance Category (CPC) Positive Outcomes Negative Outcomes CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Good cerebral performance Moderate cerebral disability Severe cerebral disability Coma or vegetative state Brain death 55% of hypothermia group and 39% of normothermia group had a favorable neurologic outcome (good recovery or moderate disability); p = Complication rates similar between groups The HACA Study Group. N Engl J Med. 2002;346:

17 Randomized Trial of Therapeutic Hypothermia HACA Study Group Hypothermia Normothermia P 0.02 The HACA Study Group. N Engl J Med. 2002;346:

18 Pseudorandomized Trial of Therapeutic Hypothermia in OHCA Bernard, et al. 77 patients with cardiac arrest due to VF, with ROSC but coma, pseudorandomized to hypothermia vs. normothermia (by day of week) Patients excluded if age of men was less than 18, and women less than 50, or cardiogenic shock Hypothermia to 33 C begun within two hours and continued for 12 hours with cold packs. Bernard et al. N Engl J Med 2002;346:

19 Pseudorandomized Trial of Therapeutic Hypothermia in OHCA Bernard, et al. Survival 21/43 hypothermia group (49%) 9/34 normothermia group (25%) p = 0.01 Good outcome (normal or with minimal or moderate disability) 49% in hypothermia group 26% in the normothermia p = Bernard et al. N Engl J Med 2002; 346:

20 Cochrane Collaboration 2013

21 Cochrane Collaboration 2013

22 Guidelines Recommendations for Therapeutic Hypothermia Scirica B. Circulation 2013

23 Implementation of Therapeutic Hypothermia Who Few true contraindications (ICH and severe bleeding, refractory hypotension, sepsis) Comatose failure to respond meaningfully after ROSC Non-shockable rhythms case by case basis Timing of initiation Meta-analysis of 5 trials of prehospital vs. hospital initiation Lower temperature at hospital arrival No improvement in survival to hospital discharge, good neurological outcome, or re-arrest Duration of cooling hours studied in trials of adult OHCA Up to 72 hours safe in newborns

24 Cooling Modalities Thermosuit Surface Traditional Energy exchange/temp reg Arctic Sun The Alsius regulation system controls temp. of saline circulating through catheter balloons via remote sensing of pts temp Alsius intravascular catheter inserted into central venous system Patient is cooled as venous blood passes over each balloon, exchanging heat w/o infusing saline into pt Internal

25 Phases of Therapeutic Hypothermia Scirica B. Circulation 2013

26 Complications of Therapeutic Hypothermia Shivering Cardiovascular bradycardia hypo- or hypertension no arrhythmias observed in RCTs or observational studies Infection (affects 2/3 of patients) Bleeding Glucose (cooling increases, rewarming decreases) and potassium (cooling decreases, rewarming increases) Alterations in drug metabolism

27 Scirica B. Circulation 2013

28 Prognostication after Therapeutic Hypothermia Paucity of data about utility of PE, EEG, SSEPs in patients treated with therapeutic hypothermia Often less reliable for predicting poor outcome Two abnormal findings have higher specificity for poorer neurological recovery Delay prognostication for at least 3 days post-rewarming (Class I, LOE C) Peberdy, et al. Circulation 2010

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30 In-hospital Cardiac Arrest Has not received same level of attention as OHCA Many gaps in science, policy and institutional application and accountability for care of these patients Variations in definition and counting make understanding incidence and outcomes challenging

31 Challenges with In-Hospital Cardiac Arrest Epidemiology Difficult to count and report incidence and outcomes Activation of ERT over-count or under-count (nonarrest activations; missed ICUs, OR, procedure units; patients vs. employees vs. visitors) Assumption that OHCA scientific advances directly apply to IHCA epidemiology and treatment may be flawed Burden of comorbidities, type of arrest Institutional practice of implementation of DNAR pre and post arrest and how DNAR patients are counted may influence arrest rate and survival estimates

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33 In-Hospital Cardiac Arrest Initial Rhythm

34 Outcomes of In-Hospital Cardiac Arrest by Initial Rhythm

35 Trends in Survival to Discharge after In-Hospital Cardiac Arrest

36 Predictors of Survival to Discharge after In-Hospital Cardiac Arrest

37 Management after In-Hospital Cardiac Arrest Similar to OHCA, but with less evidence Persistence of pre-existing conditions and precipitating pathologies after ROSC are significant challenges Multisystem organ failure more likely cause of death after IHCA than OHCA No trials of therapeutic hypothermia after IHCA (VT/VF or non-shockable rhythms) Recommended at Class IIb (LOE C)