Experimental paperIntra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest☆
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.
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Cited by (46)
Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis
2016, American Journal of Emergency MedicineCitation 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 MedicineCitation 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.
Does Initiation of Therapeutic Hypothermia in the Out-of-Hospital Environment Improve Neurologic Outcomes?
2015, Annals of Emergency MedicineTemperature Control After Cardiac Arrest: A Narrative Review
2023, Advances in Therapy
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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.