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Emergency preservation and resuscitation improve survival after 15 minutes of normovolemic cardiac arrest in pigs *

Janata, Andreas MD; Bayegan, Keywan MD; Weihs, Wolfgang Mag Med Vet; Schratter, Alexandra MD; Holzer, Michael MD; Frossard, Martin MD; Sipos, Wolfgang DVM; Springler, Gregor Mag Med Vet; Schmidt, Peter DVM; Sterz, Fritz MD; Losert, Udo M. DVM, PhD; Laggner, Anton N. MD; Kochanek, Patrick M. MD; Behringer, Wilhelm MD

Laboratory Investigations
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Objective: Outcome after prolonged normovolemic cardiac arrest is poor, and new resuscitation strategies have to be found. We hypothesized that the induction of deep hypothermia for emergency preservation and resuscitation (EPR) during prolonged cardiac arrest, before the start of reperfusion, will mitigate the deleterious cascades leading to neuronal death and will thus improve outcome.

Design: Prospective experimental study.

Setting: University research laboratory.

Subjects: Thirteen pigs, Large White breed (27–37 kg).

Interventions: After 15 mins of ventricular fibrillation, pigs were subjected to 1) EPR (n = 6), 20 mins of hypothermic stasis induced with a cold saline aortic flush; or 2) 20 mins of conventional resuscitation (n = 7). Then cardiopulmonary bypass was initiated in both groups, followed by defibrillation. Controlled ventilation and mild hypothermia were continued for 20 hrs; survival was for 9 days. For neurologic evaluation, neurologic deficit score (100% = brain dead, 0–10% = normal), overall performance category (1 = normal, 5 = dead or brain dead), and brain histologic damage score were used.

Measurements and Main Results: In the EPR group, brain temperature decreased from 38.5°C ± 0.2°C to 16.7°C ± 2.5°C within 235 ± 27 secs. Five animals achieved restoration of spontaneous circulation and survived to 9 days: two pigs with overall performance category 2 and three pigs with overall performance category 3. Their neurologic deficit score was 45% (interquartile range 35, 50) and histologic damage score was 142 (interquartile range 109, 159). In the control group, four pigs achieved restoration of spontaneous circulation: one survived to 9 days with overall performance category 3, neurologic deficit score 45%, and histologic damage score 226 (restoration of spontaneous circulation,p= .6; survival,p= .03; overall performance category,p= .02).

Conclusions: EPR is feasible in an experimental pig model and improves survival after prolonged cardiac arrest in pigs. Further experimental studies are needed before this concept can be brought into clinical practice.

From the Department of Emergency Medicine (AJ, KB, WW, AS, MH, MF, FS, ANL, WB) and Core Center of Biomedical Research (UML), Medical University of Vienna, Austria; Clinical Department for Farm Animals and Herd Management (WS) and Department of Pathobiology (GS, PS), University of Veterinary Medicine, Vienna, Austria; and the Safar Center for Resuscitation Research, Department of Critical Care Medicine, Department of Pediatrics, and Department of Anesthesiology, The University of Pittsburgh School of Medicine, Pittsburgh, PA (PMK).

Supported, in part, by a Supplementary Assignment of the Austrian Councils for Development of Research and Technology (BMBWK GZ: 11.100/6-VII/1/2002 3.6.2002).

Dr. Kochanek is one of five scientists at the Safar Center (Pittsburgh, PA) holding a provisional patent for the EPR procedure. The remaining authors have no conflicts of interest to disclose.

This work is dedicated to the late Dr. Peter Safar.

For information regarding this article, E-mail: wilhelm.behringer@meduniwien.ac.at

*See also p. 2871.

Copyright © by 2007 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.