Hypothermic for Cardiac Arrest The Evidence Base Stephan A. Mayer, MD Director, Neuro-ICU Columbia University New York, NY
Disclosures Columbia University Clinical Trials Pilot Award Radiant Medical, Inc. Scientific Advisory Board Stock Options Medivance, Inc. Research Grant Stock Options Seacoast Technologies Scientific Advisory Board
PETER SAFAR 1924-2003 Father of CPR Pioneered Intensive Care Units Conceptualized Hypothermia for Suspended Animation
HYPOTHERMIA: Mechanisms of Ischemic Neuroprotection ti Profound reduction of active and basal cellular energy requirements Reduced excitotoxic neurotransmitter release Reduced oxygen free radical production Improved BBB stability Decreased ischemic depolarizations in the penumbra Protection against cytoskeletal proteolysis Decreased neutrophil infiltration Decreased cytokine and leukotriene production
The Challenge Intensivists manipulate physiology We now have improved tools to precisely control body (and brain) temperature As intensivists, we are obliged to identify and maintain an optimal temperature in patients with acute brain injury
Out-of-hospital cardiac arrest is common 350,000+ per year in US One out of 5 out-of hospital deaths occurs as a sudden cardiac arrest Overall survival in US / Western Europe is 5-8% By some estimates, t good neurologic recovery occurs in only 3% of out-of-hospital arrests Best EMS systems: Seattle 1998-2001 Overall survival to hospital discharge 17.5% VF/VT: 34% survived (vs. 6% with other rhythms) NEJM 2004; 351 (7): 632
Out-of-hospital cardiac arrest Factors (likely) influencing outcome: Duration of non-perfusing rhythm Bystander CPR AEDs / early defibrillation Quality of CPR (adequate cardiac output) t) Age Therapeutic hypothermia NEJM 2004; 351 (7): 632
Out-of-hospital cardiac arrest Factors (likely) influencing outcome: Duration of non-perfusing rhythm Bystander CPR AEDs / early defibrillation Quality of CPR (adequate cardiac output) t) Age Therapeutic hypothermia NEJM 2004; 351 (7): 632
Effect of early time to defibrillation NEJM 2004; 351 (7): 632
Improving OOHCA Outcomes FDNY Medics 2002 2003 2004 2005 2006 2007 # of arrests 1537 1636 1555 1688 1801 % VF 12.88% 13.99% 13.69% 12.26% 12.66% ROSC - overall 15.81% 17.60% 15.31% 15.40% 16.49% ROSC nonvf 14.04% 16.13% 13.71% 14.04% 15.44% ROSC VF/VT 27.78% 26.64% 25.35% 25.12% 23.25% Sustained ROSC 11.13% 12.78% 10.03% 11.32% 11.94%
Improving OOHCA Outcomes FDNY Medics 2002 2003 2004 2005 2006 2007 # of arrests 1537 1636 1555 1688 1801 1735 % VF 12.88% 13.99% 13.69% 12.26% 12.66% 14.72%** ROSC - overall 15.81% 17.60% 15.31% 15.40% 16.49% 23.69%** ROSC nonvf 14.04% 16.13% 13.71% 14.04% 15.44% 18.32%** ROSC VF/VT 27.78% 26.64% 25.35% 25.12% 23.25% 54.88%** Sustained ROSC 11.13% 12.78% 10.03% 11.32% 11.94% n/a
NYC Project Hypothermia Phase #1: Beginning July 1, 2008, all OOHCA patients achieving ROSC in New York City will only be transported to facilities actively employing therapeutic hypothermia.
Hypothermia: Techniques
LIFE RECOVERY SYSTEMS
Intravascular heat exchange catheter designed for insertion in the jugular vein and combined central venous capabilities (multiple infusion ports) Heat exchange 3 infusion lumens Inflow Outflow
INNERCOOL
MEDIVANCE ARCTIC SUN
Polderman et al. Induction of hypothermia in patients with various types of neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med 2005;33:2744 134 brain- injured patients In addition to surface cooling 30 ml/kg (mean 2.3 liters) of cold normal saline over 50 minutes MAP increased 15 mm Hg No CHF 37 Temp ( 36 35 34 33 32 31 30 Baseline 1 Hour 2 Hours
METHODS: Mild/Moderate Hypothermia Protocol (33 C) Endotracheal intubation Sedation: Meperidine 25-100 mg IVP q 2-4 H Dexmedetomidine 0.3 0.7 µg/kg/hr /h Paralysis: Vecuronium 0.1 mg/kg PRN Thermistors: bladder, rectal, esophageal Radial artery and internal jugular lines Intraparenchymal ICP & temperature monitor Insulin drip for BS >180 mg/dl Hypokalemia <3.4 meq/l replaced 1
Hemodynamic Support after Cardiac Arrest % pts 100 90 80 70 60 50 40 30 20 10 0 Norepinephrine Dobutamine 100 90 80 70 60 50 40 30 20 10 0 0-6 hrs 6-24 hrs 24-48 hrs 0-6 hrs 6-24 hrs 24-48 hrs 100 90 80 70 60 50 40 30 20 10 0 Volume Expansion 0-6 hrs 6-24 hrs 24-48 hrs Hypothermia Normothermia Oddo M, Crit Care Med, 2006;34(7):1865
METHODS: Mild/Moderate Hypothermia Protocol ABGs at room temp (alpha-stat) Vasopressors to keep CPP >70 mm Hg ICP >20 mm Hg treated per protocol Feedings held x 48 hours Cultures/antibiotics for work of device heat transfer (indicating thermogenesis) Passive controlled rewarming (0.25 to 0.3 C C /hr) Active cooling is maintained at 36.5 C thereafter for 24 hrs to avoid overshoot 2
Volume 346:549-556 February 21, 2002 Number 8 Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest The Hypothermia after Cardiac Arrest Study Group Volume 346:557-563 February 21, 2002 Number 8 Treatment of Comatose Survivors of Cardiac Arrest Treatment of Comatose Survivors of Cardiac Arrest with Induced Hypothermia Stephen A. Bernard, MB, BS,.and others
European HACA Trial SUBJECTS: 273 patients with out-of-hospital VT/VF arrest Ages 18-75 Initiation of CPR within 15 minutes Interval from collapse to ROSC <60 mins INTERVENTION: 32-34 C 34 C for 24 hours Mean 8 hours from initiation of cooling to temperature <34 C HACA Study Group, NEJM, 2002
Kinetic Concepts Air Cooling Device Cool air blanket initiated ~2 hours after ROSC Target temp attained ~8 hours later
HACA: Rate of Cooling
HACA: Rate of Cooling
European HACA Trial OUTCOME MEASURE: Survival with minimal or moderate disability at 6 months 55% hypothermic 39% normothermic Risk ratio for good outcome 1.40 (1.08-1.81) 81) Number needed to treat = 6 HACA Study Group, NEJM, 2002
Absolute mortality difference of 14% Relative mortality reduction of 26%
AUSTRALIAN Hypothermia Trial SUBJECTS: 77 patients with out-of-hospital VT/VF arrest No upper age limit Comatose Refractory shock (MAP <90) excluded Randomization according to date (odd-even) INTERVENTION: 32-34 C for 12 hours Cooling started in the field using ice bags within 2 hours of collapse Cooling period 12 hours Rewarming over 6 hours Bernard et al, NEJM, 2002
35% 21%
International Task Force 2003 ILCOR meeting on hypothermia recommends: Unconscious patients with spontaneous circulation after out of hospital arrest should be cooled to 32-34 C for 12-24 hours when the initial rhythm is ventricular fibrillation. AND Such cooling may also be beneficial for other rhythms or in-hospital arrest. Nolan, JP, Resuscitation, 2003
Post Resuscitation Care
The Second Translation FROM SCIENCE TO DAILY PRACTICE
Therapeutic hypothermia utilization among physicians after cardiac arrest Raina M. Merchant, et al, Crit Care Med 2006;34;1935. Web-based survey of 2,248 physicians USA: 74% have never cooled EU: 64% have never cooled Have you ever? If not why not?
Out-of-hospital cooling by Emergency Physician (Markus Födisch, Bonn)
Can evidence-based Swiss retrospective study: 14 medicine be bed MICU in university hospital medical center implemented outside of June 1999 May 2002: the multicenter RCT 54 patients with OHCA environment? June 2002-December 2004: Does TH work in smaller 55 patients with OHCA medical centers? treated with TH CCM 2006:34:1865
Improved Outcomes
Time from collapse to ROSC Probability of good outcome Duration of cardiac arrest predicts outcome (OR of good outcome for each additional 5 min: 0.53, 95% CI: 0.37-0.72, p<0.001) Oddo et al, CCM 2007
Results VUMC
Preliminary evidence in patients with asystole/pea Polderman KH et al. Induced hypothermia improves neurological outcome in asystolic patients with out-of hospital cardiac arrest. Circulation 2003; 108: IV-581 [abstract 2646]
Northern Hypothermia Network www.scctg.org www.hypothermianetwork.com Six scandanavian countries >500 patients 64% VT/VF 28% PEA 8% Asystole Hypothermic
Polderman KH. Lancet 2008; 371:1955-1969
City Pushes Cooling Therapy for Cardiac Arrest December 4, 2008
Chain of Survival VF / pulseless VT (AHA level 2A) Pulseless electrical activity / asystole (HA level 2B) Comatose Absence of refractory post-resuscitation shock Duration of cardiac arrest t5-30 minutes Age 75 years
Getting Serious about Hypothermia for CA: Keys to Implementation Education and Knowledge Champion Team Building Administration and Nursing Protocols
The New Paradigm CPR CCR Cardio-Pulmonary Resuscitation Cardio-Cerebral Resuscitation