Francis Kim MD, Graham Nichol MD MPH, Charles Maynard PhD ,

1. Randomized Clinical Trial of Pre-hospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients Using a Rapid Infusion of 4oC Normal Saline Francis Kim MD, Graham Nichol MD MPH, Charles Maynard PhD, Al Hallstrom PhD, Peter Kudenchuk MD, Thomas Rea MD, Michael Copass MD, David Carlbom MD Steven Deem MD, WT Longstreth Jr MD, Michele Olsufka RN, Leonard Cobb MD University of Washington Seattle, WA

2. Background • Hospital cooling (32-34oC) improves neurologic outcome after out-of-hospital ventricular fibrillation (VF) • Pre-hospital cooling may result in better outcomes compared to hospital alone • Pre-hospital infusion of cold fluid to reduce temperature • Determine whether prehospital cooling improves outcomes from cardiac arrest with VF or non-VF

3. Trial Setting/Design • Emergency medical services (EMS) agencies in Seattle and surrounding King County • Individual subjects randomized to • Intervention-Rapid infusion of 2 liters of 4oC NS after ROSC, sedation, skeletal muscle relaxation • Control-standard care • Randomization stratified by • Receipt of hospital cooling • First recorded rhythm

4. Eligibility Inclusion Criteria Adults Return of pulse Tracheal intubation Intravenous access Unconscious Esophageal temp probe Exclusion Criteria Traumatic cardiac arrest Age < 18 Following commands Temperature < 34ºC

5. Trial Flow Field Cardiac Arrest 5696 Not Eligible (3319) Eligible 2377 Not Enrolled (1013) 1364 Enrolled N=776 Non-VF N=583 VF Intervention 292 Control 380 Intervention 396 Control 291 Outcomes: Survival at discharge/neurologic status

6. Baseline Characteristics

7. Temperature Effects

8. Outcomes-Survival VF intervention n=292 control n=291 Non-VF intervention n=396 control n=380

9. Outcomes-neurologic status at discharge

10. Secondary Outcomes- Days to achieve awakening VF

11. Safety- prehospital

12. Safety- ED and hospital

13. Summary of prehospital cooling

14. Conclusions • Cold NS reduced core temperature by hospital arrival • Use of cold NS associated with increased re-arrest during transport and increased transient pulmonary edema • Lack of benefit of prehospital cooling consistent with previous smaller trial • Prehospital cooling with cold NS did not improve survival or neurologic outcomes in patients with out-of-hospital VF or non-VF

15. Implications • Cold fluid has associated risks • Study findings do not support routine initiation of hypothermia using cold fluid in the prehospital setting

16. Acknowledgements Paramedics in Seattle and King County Hospitals: Harborview Medical Center, Swedish Medical Center, Virginia Mason Hospital, UWMC, Northwest Hospital, Overlake Hospital, Valley Medical Center, Auburn General Hospital, St. Francis Hospital, Stevens Hospital. DSMB: Chair: Kyra Becker, MD. Members: Margaret Neff, MD, Tina Chang, MD, Karl B. Kern, MD, Nancy Temkin, PhD, Ralph D’Agostino, PhD, Chief Earl Sodeman, Seattle Fire Department, Thomas Hearne, Michele Plorde, King County Public Health, Emergency Medical Services Division. Study Nurses: Dianne K. Staloch, Karen Dong, Sue Scruggs, Alana C. Clark, Jane Edelson, Debi Solberg, Sally Ragsdale, Kathleen Fair, Barbara Ricker Funding: NIH/NHLBI

17. F Kim and coauthors Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest: A Randomized Clinical Trial Published online November 17, 2013 Available at www.jama.com and also at mobile.jamanetwork.com jamanetwork.com