Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries Hasan B. Alam, MD, a,b Zheng Chen, MD, PhD, a Yongqing Li, MD, PhD, b George Velmahos, MD, b Marc DeMoya, MD, b Christopher E. Keller, DVM, MPH, c Kevin Toruno, BS, a Tina Mehrani, BS, a Peter Rhee, MD, MPH, a,d and Konstantinos Spaniolas, MD b Bethesda, Md, Boston, Mass, and Los Angeles, Calif Background. Rapid induction of profound hypothermia can improve survival from uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this setting remains unknown. This experiment was designed to compare the impact of deep (15°C), profound (10°C), and ultraprofound (5°C) hypothermia on survival and organ functions. Methods. Uncontrolled lethal hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Hypothermia was induced rapidly (2°C/min) by infusing cold organ preservation solution into the aorta through a thoracotomy. The experimental groups were (n = 8 per group): a normothermic control, and 3 hypothermic groups in which the core temperature was reduced to 15°C, 10°C, and 5°C. Vascular injuries were repaired during 60 minutes of hypothermia. Animals were then rewarmed (0.5°C/min) and resuscitated on cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits, cognitive function, and organ dysfunction. Results. All normothermic animals died, whereas 6-week survival rates for the 15°C, 10°C, and 5°C groups were 62.5%, 87.5%, and 25%, respectively (P .05: normothermic vs 15°C and 10°C; 10°C vs 5°C). The surviving animals from the 15°C and 10°C groups were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. The survivors from the 5°C group displayed slower recovery and impaired cognitive functions. Conclusions. In a model of lethal injuries, rapid induction of profound hypothermia can prevent death. The depth of hypothermia influences survival, with a better outcome associated with a core temperature of 10°C compared with 5°C. (Surgery 2006;140:307-14.) From the Trauma Research and Readiness Institute for Surgery a and Center for Laboratory Animal Medicine, c Uniformed Services University of the Health Sciences, Bethesda; the Department of Surgery, b Massachusetts General Hospital/Harvard Medical School, b and the Los Angles County-University of Southern California Medical Center d Uncontrolled hemorrhage is the leading cause of preventable death following trauma. 1 Often the underlying injuries are potentially reparable, but the patients die before definitive care can be ren- dered. 2 One of the major limiting factors is the period of normothermic ischemia that can be tol- erated by the brain (5 minutes) 3,4 and the heart (about 20 minutes). 5 Induction of hypothermia is a time-honored method for maintaining cellular via- bility during periods of ischemia, and is commonly utilized during complex cardiac, transplant, and neurosurgical procedures. Numerous preclinical experiments have convincingly demonstrated the feasibility of using profound hypothermia as a pro- tective strategy after hemorrhagic shock. 6 However, Presented at the 67 th Annual Meeting of the Society of Univer- sity Surgeons, First Annual Academic Surgical Congress, Febru- ary 7-11, 2006, San Diego, California. Supported by a research grant (RO1 HL71698 to HBA) from the National Institutes of Health. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense at large. Reprint requests: Hasan B. Alam, MD, FACS, Massachusetts General Hospital, Director of Research. Division of Trauma, Emergency Surgery, and Surgical Critical Care. 165 Cambridge St, Ste 810. Boston, MA 02114. E-mail: hbalam@partners.org. 0039-6060/$ - see front matter © 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.surg.2006.03.015 SURGERY 307