Elsevier

Resuscitation

Volume 81, Issue 5, May 2010, Pages 617-621
Resuscitation

Experimental paper
Intra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest

https://doi.org/10.1016/j.resuscitation.2010.01.027Get rights and content

Abstract

Aims of study

We have previously demonstrated that early intra-nasal cooling improved post-resuscitation neurological outcomes. The present study utilizing a porcine model of prolonged cardiac arrest investigated the effects of intra-nasal cooling initiated at the start of cardiopulmonary resuscitation (CPR) on resuscitation success. Our hypothesis was that rapid nasal cooling initiated during “low-flow” improves return of spontaneous resuscitation (ROSC).

Methods

In 16 domestic male pigs weighing 40 ± 3 kg, VF was electrically induced and untreated for 15 min. Animals were randomized to either head cooling or control. CPR was initiated and continued for 5 min before defibrillation was attempted. Coincident with starting CPR, the hypothermic group was cooled with a RhinoChill™ device which produces evaporative cooling in the nasal cavity of pigs. No cooling was administrated to control animals. If ROSC was not achieved after defibrillation, CPR was resumed for 1 min prior to the next defibrillation attempt until either successful resuscitation or for a total of 15 min.

Main results

Seven of eight animals in the hypothermic group (87.5%) and two of eight animals in control group (25%) (p = 0.04) were successfully resuscitated. At ROSC, brain temperature was increased from baseline by 0.3 °C in the control group, and decreased by 0.1 °C in the hypothermic animals. Pulmonary artery temperature was above baseline in both groups.

Conclusion

Intra-nasal cooling initiated at the start of CPR significantly improves the success of resuscitation in a porcine model of prolonged cardiac arrest. This may have occurred by preventing brain hyperthermia.

Introduction

Sudden cardiac arrest (SCA) is a leading cause of death in the United States, Canada and Europe.1, 2, 3, 4 The annual incidence of SCA in North America is almost 0.55 per 1000 population3, 5 and about 700,000 patients in Europe.4 Despite huge efforts to improve outcomes from sudden cardiac death, including reassessment and publication of new Cardiopulmonary Resuscitation Guidelines every 5–8 years for the past 3 decades, survival rate remains dismal.6

Systemic hypothermia initiated after resuscitation has been shown to improve survival and long-term neurologic outcome after cardiac arrest.7, 8, 9, 10, 11 Based on data from two recent randomized clinical studies,8, 9 the most recent American Heart Association Guidelines of Cardiopulmonary Resuscitation (CPR) now stipulate that unconscious, adult patients successfully resuscitated from an out-of-hospital ventricular fibrillation (VF) cardiac arrest should be cooled to 32–34 °C for 12–24 h.12

In addition to neuroprotection, hypothermia has also been documented to improve CPR outcome. In a porcine cardiac arrest model, systemic hypothermia (30–35 °C) established before cardiac arrest improved the defibrillation success and resuscitation outcome suggesting hypothermia may be beneficial to the resuscitation efforts.13 Intra-arrest systemic hypothermia has also been shown to reduce mortality rates in mice.14 Furthermore, we have previously demonstrated in a porcine model that intra-nasal cooling initiated during CPR required fewer defibrillation shocks to achieve return of spontaneous circulation (ROSC) in the absence of systemic hypothermia15 after 10 min of untreated VF. The mechanism remains unclear whether systemic or intra-nasal cooling benefits the resuscitative effort.

In the present study, we investigated the effect of intra-nasal cooling at the initiation of CPR on the success of resuscitation and its potential mechanisms. Our hypothesis was that rapid intra-nasal brain cooling during “low-flow” CPR following 15 min of untreated cardiac arrest would improve ROSC in a porcine model.

Section snippets

Methods

Experiments were performed on an established swine model of cardiac arrest and CPR.15 All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86-32, 146 revised 1985). The protocol was approved by the Institutional Animal

Results

There were no significant differences in baseline measurements between the two groups, including brain and core temperatures (Table 1).

At 15 min of VF, immediately prior to the initiation of cooling, brain temperature was increased from baseline value by 0.2 °C in the hypothermic group (38.0 °C) and by 0.2 °C in the control group (37.9 °C). Similarly, core temperature was increased by 0.3 °C in the hypothermic group (38.3 °C) and by 0.2 °C in the control group (38.2 °C).

ROSC was achieved within min of

Discussion

In the current study in the pig, we have shown that intra-nasal cooling, started at the initiation of CPR, dramatically improved the ROSC rate following 15 min of untreated VF. It also facilitated the resuscitation effort by reducing CPR duration. Improvement in ROSC rates following early induction of hypothermia has previously been reported.13 However, in that study, systemic cooling was established before the induction of VF. In the current study, cooling was purposefully started at the same

Conclusion

We have shown that intra-nasal cooling initiated at the start of CPR facilitates resuscitation and improves ROSC rates in animal models of VF arrest. Whether the beneficial effect also applies to non-VF arrest in animal models and whether these findings can be reproduced in humans needs to be determined in our further studies.

Conflicts of interest

Denise Barbut, MD is an employee of Benechill, Inc., San Diego, CA. The authors resident at the Weil Institute of Critical Care Medicine, Rancho Mirage, CA, USA, have not, nor will receive any individual benefits other than academic recognition.

Acknowledgement

This study was supported in part by BeneChill, Inc., San Diego, CA, USA.

References (30)

  • Z.J. Zheng et al.

    Sudden cardiac death in the United States, 1989 to 1998

    Circulation

    (2001)
  • C. Vaillancourt et al.

    Cardiac arrest care and emergency medical services in Canada

    Can J Cardiol

    (2004)
  • S. Sans et al.

    The burden of cardiovascular diseases mortality in Europe. Task Force of the European Society of Cardiology on Cardiovascular Mortality and Morbidity Statistics in Europe

    Eur Heart J

    (1997)
  • A.B. Sanders et al.

    Cardiopulmonary resuscitation in Real World: when will the guidelines get the message?

    JAMA

    (2005)
  • F. Kim et al.

    Pilot study of rapid infusion of 2 L of 4 degrees C normal saline for induction of mild hypothermia in hospitalized, comatose survivors of out-of-hospital cardiac arrest

    Circulation

    (2005)
  • Cited by (46)

    • Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis

      2016, American Journal of Emergency Medicine
      Citation Excerpt :

      There was no increase in serious adverse events except epistaxis in 3 patients and underlying coagulopathy secondary to hepatic failure in 1 patient [35]. In animal studies, intranasal cooling significantly increased the rate of ROSC and neurologically intact survival [36,37]. However, there are no human data to demonstrate that intranasal cooling can improve survival and favorable neurological outcomes.

    • Prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation model

      2015, American Journal of Emergency Medicine
      Citation Excerpt :

      However, many unanswered questions remain, including the optimal timing for hypothermia [7]. Animal studies that induced intra-arrest or prearrest hypothermia with cooling at approximately the same time as defibrillation and CPR reported improved defibrillation or ROSC [8–14]. However, only a few studies have reported the effects of preexisting hypothermia on resuscitation and myocardial function.

    View all citing articles on Scopus

    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2010.01.027.

    View full text