A Pilot Study of Intra-arrest Therapeutic Hypothermia in Patients Suffering Non-Traumatic Out of Hospital Cardiac Arrest

Out-of-Hospital Cardiac Arrest

The objective of this study will be to assess the frequency of return of spontaneous circulation (ROSC), survival to admission, survival to discharge from the hospital, and neurologic function at time of discharge from the hospital among patients experiencing out of hospital cardiac arrest randomized to receive either intra-arrest induction of therapeutic hypothermia (IATH) or post-arrest therapeutic hypothermia (TH).

Therapeutic hypothermia improves mortality and functional neurologic outcomes in patients resuscitated from pulseless ventricular tachycardia and fibrillation (VT/VF), with several studies validating the safety of prehospital induction following successful (return of spontaneous circulation) ROSC by the rapid infusion of 2 liters of 4ºC intravenous fluids. However, the optimal timing for inducing hypothermia remains uncertain. Early studies demonstrated the efficacy of therapeutic hypothermia despite delays of 4 to 8 hours from the time of ROSC to the initiation of cooling. The post-resuscitation reperfusion injury evolves quickly and was thought to be best attenuated by hypothermia induction immediately following return of spontaneous circulation (ROSC). This was supported by animal data which demonstrated that improved neurologic outcome was associated with reduced time to goal temperature following ROSC. More recently this hypothesis has been called into question by 2 clinical trials which suggested that time to initiation of cooling was not associated with improved neurologic outcome at discharge. There may be another benefit to early therapeutic cooling. Animal data suggest that intra-arrest induction of therapeutic hypothermia (IATH) improves rates of ROSC from cardiac arrest. This is corroborated by a report describing an impressively high ROSC rate of 60.9% among patients receiving IATH. This was a higher frequency of ROSC than reported in similar patient groups. It has been demonstrated that mild hypothermia exerts a stabilizing effect on the myocardium, decreasing the rate of refibrillation following ROSC. Mild hypothermia has also been shown to prolong ventricular refractoriness and repolarization, possibly facilitating electrical defibrillation by slowing repolarization ion currents. Recently we conducted a retrospective observational study that demonstrated an association between the administration of IATH and ROSC.22 We found that the likelihood of ROSC with IATH was 2.4 (95% CI 1.41-4.24) time higher in the subset of patients who received \> 700ml of 4º C normal saline compared to those who did not receive IATH. Our study lacked sufficient power to demonstrate a difference in survival to admission or discharge; however, we noted trends towards improved survival. Current intra-arrest treatments do not obtain ROSC rates greater than those seen in our study with IATH. These associations were noted in all rhythms, including asystole and pulseless electrical activity. Obtaining ROSC quickly with the resulting decrease in time spent in a low or no flow circulation would have obvious downstream effects on both hospital mortality and neurologic function, independent of the effect of mild hypothermia in the post-arrest inflammatory state. Surprisingly these associations were seen even with fluid volumes that were too low to change core body temperature suggesting that the benefits of therapeutic hypothermia on the myocardium may be possible even at relatively low fluid volumes.

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