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(Circulation. 2006;113:2690-2696.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Critical Time Window for Intra-Arrest Cooling With Cold Saline Flush in a Dog Model of Cardiopulmonary Resuscitation

Ala Nozari, MD, PhD; Peter Safar, MD; S. William Stezoski; Xianren Wu, MD; Scott Kostelnik; Ann Radovsky, DVM, PhD; Samuel Tisherman, MD; Patrick M. Kochanek, MD

From the Safar Center for Resuscitation Research (A.N., P.S., S.W.S., X.W., S.K., S.T., P.M.K.) and Departments of Critical Care Medicine (A.N., P.S., S.W.S., X.W., S.T., P.M.K.), Anesthesiology (A.N., P.S., S.W.S., X.W.), Surgery (S.T.), and Pediatrics (P.M.K.), University of Pittsburgh, Pittsburgh, Pa; and WIL Research Laboratories (A.R.), Ashland, Ohio.

Correspondence to Ala Nozari, MD, PhD, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 02114–2696. E-mail anozari{at}partners.org

Received February 3, 2006; revision received April 10, 2006; accepted April 17, 2006.

Background— Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model.

Methods and Results— Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group (n=9), mild hypothermia (34°C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group (n=8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure (P=0.012).

Conclusions— Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible.

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