Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest* Tao Yu, MD; Denise Barbut, MD; Giuseppe Ristagno, MD; Jun Hwi Cho, MD; Shijie Sun, MD, FCCM; Yongqin Li, PhD; Max Harry Weil, MD, PhD, FCCM; Wanchun Tang, MD, FCCM S udden cardiac arrest is a lead- ing cause of death, with 300,000 victims in North America and approximately 700,000 in Europe every year (1, 2). More than 50% of patients die before leaving the hospital, and the majority of deaths are attributed to postresuscitation myo- cardial dysfunction. Furthermore, ap- proximately 30% of survivors exhibit per- manent brain damage (3). Experimental and clinical studies have demonstrated that hypothermia improves survival and long-term neurologic out- comes in cardiac arrest patients (4 –7). Based on data from two of the largest randomized clinical trials (6, 7), the most recent American Heart Association Guidelines for Cardiopulmonary Resusci- tation (CPR) recommend mild therapeu- tic hypothermia for all unconscious pa- tients after cardiac arrest, specifically in the setting of ventricular fibrillation (VF) arrest (8). It is now well-recognized that, to achieve the greatest benefit from hypo- thermia, cooling should be initiated as soon as possible after cardiac arrest (9). In an attempt to “move from defense to offense” (10), therapeutic hypothermia initiated during CPR and before restora- tion of spontaneous circulation (ROSC) has also been shown in several recent studies to enhance outcome compared to initiation of hypothermia after ROSC (11, 12). This represents the so-called transi- tion from therapeutic hypothermia to preservative hypothermia (9). Current methods for inducing hypo- thermia have limitations when applied in out-of-hospital settings such that “pre- servative hypothermia” is difficult to achieve. Internal cooling is invasive and technically inadequate for field use (13, 14). Surface cooling with ice packs or cooling blankets is slow to reach target temperature. Peripheral vein cold saline infusion (CSI) started immediately after ROSC was shown to be an effective, safe, and feasible method for inducing hypo- thermia in resuscitated out-of-hospital cardiac arrest patients (5, 15). Some stud- ies demonstrated that this method could be started during CPR (16), but the safety of large volumes of CSI for patients and *See also p. 1006. From the Weil Institute of Critical Care Medicine (TY, GR, JHC, SS, YL, MHW, WT), Rancho Mirage, CA; the Department of Emergency Medicine (TY, WT), the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guang Dong, China; the Keck School of Medicine of the University of Southern California (SS, MHW, WT), Los Angeles, CA; BeneChill Inc. (DB), San Diego, CA. Supported in part by BeneChill Inc., San Diego, CA. This study was performed at the Weil Institute of Critical Care Medicine, Rancho Mirage, CA. Dr. Denise Barbut is an employee of BeneChill Inc. The authors resident at the Weil Institute have not received, nor will they receive, any individual benefits other than academic recognition. The other authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: drsheart@aol.com Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181cd1291 Objective: We have previously demonstrated that nasopharyn- geal cooling initiated during cardiopulmonary resuscitation im- proves the success of resuscitation. In this study, we compared the effects of nasopharyngeal cooling with cold saline infusion initiated during cardiopulmonary resuscitation on resuscitation outcome in a porcine model of prolonged cardiac arrest. We hypothesized that nasopharyngeal cooling initiated during cardio- pulmonary resuscitation would yield better resuscitation outcome when compared with cold saline infusion. Design: Randomized, prospective animal study. Setting: University-affiliated research laboratory. Subjects: Yorkshire-X domestic pigs (Sus scrofa). Interventions: Ventricular fibrillation was induced in 14 pigs weighing 38  2 kg. After 15 mins of untreated ventricular fibrillation, cardiopulmonary resuscitation was performed for 5 mins before defibrillation. Coincident with the start of cardiopul- monary resuscitation, animals were randomly assigned to receive nasopharyngeal cooling with the aid of the RhinoChill Device (BeneChill, San Diego, CA) or cold saline infusion with 30 mL/kg 4°C saline. One hour after restoration of spontaneous circulation, surface cooling was begun with the aid of a water blanket in both groups and maintained for 4 hrs. Measurements and Main Results: Jugular vein temperature significantly decreased in animals subjected to nasopharyngeal cooling in comparison with those receiving cold saline infusion (p < .01). Core temperature, however, decreased only in animals receiving cold saline infusion (p < .01). Coronary perfusion pres- sure was significantly higher in the animals treated with naso- pharyngeal cooling (p  .02). All seven animals treated with nasopharyngeal cooling were successfully resuscitated in con- trast to only two animals resuscitated in the cold saline infusion group (p  .02). Conclusion: In this model, nasopharyngeal cooling initiated during cardiopulmonary resuscitation improved the success of resuscitation compared to cooling with cold saline infusion. (Crit Care Med 2010; 38:916 –921) KEY WORDS: cardiac arrest; cardiopulmonary resuscitation; hy- pothermia; ventricular fibrillation 916 Crit Care Med 2010 Vol. 38, No. 3