No assisted ventilation cardiopulmonary resuscitation and 24-hour neurological outcomes in a porcine model of cardiac arrest* Demetris Yannopoulos, MD; Timothy Matsuura, BS; Scott McKnite, BS; Noah Goodman, BA; Ahamed Idris, MD; Wanchun Tang, MD; Tom P. Aufderheide, MD; Keith G. Lurie, MD V entilation has been an essential element of cardiopulmonary re- suscitation (CPR) since it was first described nearly 50 yrs ago (1–3). Four yrs ago, a study demonstrated that patients in cardiac arrest are often ex- cessively ventilated; subsequent animal studies demonstrated that excessively high ventilation rates decreased venous return to the heart, decreased coronary and cere- bral perfusion pressures, and increased mortality rates in pigs in cardiac arrest (4). More recent animal data have shown that decreasing ventilation rates from 10 breaths/min to 2 breaths/min resulted in a significant decrease in carotid blood flow and oxygen content in the brain (5). Taken together, these data support the concept that there is an ideal ventilation rate dur- ing CPR, somewhere between 8 and 12 breaths/min, as recommended in the 2005 American Heart Association Guide- lines (6). These findings and recommen- dations are in conflict with another school of thought that has focused solely on compressions: animal and human data from this alternate school suggest there is no benefit from ventilation during CPR and that it is actually harmful (7, 8). This question is of fundamental importance to the future of ventilation during CPR. Building on data demonstrating that there is a tenfold decrease in brain oxy- gen content when pigs were ventilated with 2 breaths/min versus 10 breaths/ min, we tested the hypothesis that posi- tive pressure ventilation, as recom- mended in the 2005 American Heart Association Guidelines, in a porcine model of cardiac arrest would result in a significantly higher rate of 24-hr neuro- logically intact survival compared with animals treated with continuous chest compression and no assisted ventilations (NAV). METHODS The study was approved by the Institu- tional Animal Care Committee of the Minne- apolis Medical Research Foundation of Hen- nepin County Medical Center, and all animals Objectives: To evaluate the effect of no assisted ventilation cardiopulmonary resuscitation on neurologically intact survival compared with ten positive pressure ventilations/minute cardio- pulmonary resuscitation in a pig model of cardiac arrest. Design: Prospective randomized animal study. Setting: Animal laboratory. Subjects: Sixteen female intubated pigs (25.2  2.1 kg) anes- thetized with propofol. Interventions, Measurements, and Main Results: After 8 mins of untreated ventricular fibrillation, the intubated animals were randomized to 8 mins of continuous chest compressions (100/ min) and either no assisted ventilation (n  9) or 10 positive pressure ventilations/min (Smart Resuscitator Bag with 100% O 2 flow at 10 L/min) (n  7). The primary end point, neurologically intact 24-hr survival, was evaluated using a pig cerebral perfor- mance category score by a veterinarian blinded to the cardiopul- monary resuscitation method. During cardiopulmonary resuscita- tion, aortic and coronary perfusion pressure were similar between groups but cerebral perfusion pressure was significantly higher in the positive pressure ventilation group (33  15 vs. 14  14, p  0.04). After 7.5 mins of cardiopulmonary resuscitation, arterial pO 2 (mm Hg) and mixed venous O 2 saturation (%) were significantly higher in the positive pressure ventilation compared with the no assisted ventilation group (117  29 and 41  21 vs. 40  24 and 10.8  7; p  0.01 for both). PaCO 2 was significantly lower in the positive pressure ventilation group (48  10 vs. 77  26, p  0.01). After 24 hrs, four of nine no assisted ventilation pigs were alive with a mean cerebral performance category score of 3  0 vs. five of seven alive and neurologically intact positive pressure ventilation pigs with a cerebral performance category score of 1  0.3 (p < 0.001 for cerebral performance category score). Conclusions: No assisted ventilation cardiopulmonary resusci- tation results in profound hypoxemia, respiratory acidosis, and significantly worse 24-hr neurologic outcomes compared with positive pressure ventilation cardiopulmonary resuscitation in pigs. (Crit Care Med 2010; 38:000 – 000) KEY WORDS: cardiopulmonary resuscitation; ventilation; com- pressions; survival; neurological function *See also p. xxx. From the Division of Cardiology (DY), University of Minnesota, Minneapolis, MN; Minnesota Medical Re- search Foundation (TM, SM, NG), Hennepin County Medical Center, Minneapolis, MN, Department of Emergency Medicine (AI), University of Texas South- western, Dallas, TX; Department of Emergency Medi- cine (WT), Keck School of Medicine of the University of Southern California–Los Angeles, Los Angeles, CA; Department of Emergency Medicine (TPA), Medical College of Wisconsin, Milwaukee, WI; and Department of Emergency Medicine and Internal Medicine (KGL), Minnesota Medical Research Foundation, Hennepin County Medical Center, Minneapolis, MN. Dr. Lurie is the inventor of the inspiratory imped- ance threshold device and the intrathoracic pressure regulator, both CPR devices, and formed Advanced Circulatory Systems Inc (ACSI) to develop this technol- ogy. Dr. Matsuura is employed by Advanced Circula- tory Systems Inc. Dr Aufoerheide has consulted for Take Heart America. Dr. Aufoerheide has patents from the National Heart, Lung and Blood Institute, National Institute of Neurological Diseases and Stroke. The remaining authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: klurie@advancedcirculatory.com Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181b42f6c 1 Crit Care Med 2010 Vol. 38, No. 1