Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest.

Abstract

Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest. Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C. HBN-1 (p < 0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p < 0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze. HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling.