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Background-Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model. Methods and Results-Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group (nϭ9), mild hypothermia (34°C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group (nϭ8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure (Pϭ0.012). Conclusions-Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible. Key Words: cardiopulmonary resuscitation Ⅲ cooling Ⅲ heart arrest Ⅲ hypothermia Ⅲ resuscitation A fter successful resuscitation from cardiac arrest (CA), hypothermia has been shown in several experimental studies to improve cerebral outcome. [1][2][3][4][5] On the basis of recent clinical studies, therapeutic mild hypothermia is recommended by the American Heart Association and the International Liaison Committee on Resuscitation for Unconscious Survivors of CA. 6,7 Despite a relatively late and slow surface cooling technique, these clinical trials in Europe and Australia documented neurological benefits with mild hypothermia in survivors of out-of-hospital CA. 8,9 Because evidence exists that a delay in cooling negates the beneficial effect of mild hypothermia, 4,10 some have suggested that hypothermia should be initiated as soon as possible after resuscitation or, preferably, during cardiopulmonary resuscitation (CPR) attempts. 5,10 In a recent study of CA in mice, application of mild hypothermia during CPR was shown to enhance outcome compared with its application after restoration of spontaneous circulation (ROSC). 11 Similarly, in a clinically relevant study of prolonged ventricular fibrillation (VF) in dogs, we documented that mild or moderate hypothermia Clinical Perspective p 2696induced during 40 minutes of CPR attempts preserves organ viability and significantly improves outcome. 12 Intact survival was achieved despite 40 mi...

Summary: We previously found mild hypothermia (34-36°C), induced before cardiac arrest, to improve neu rologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling dur ing arrest, continued with systemic cooling (34°C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37 SC was reversed with cardiopulmonary bypass and defibrillation in �5 min, and followed by controlled ven tilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normother mic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hy pertension and hemodilution. Control Group B-1 (n = 12) was maintained normothermic (6 of 12 were not hemodi luted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories This study concerns two relatively unexplored concepts: (a) hypothermia initiated during ischemia (preservation) and continued after ischemia (resus citation) in contrast to hypothermia initiated before ischemia (protection), which is known to mitigate postischemic brain damage (Bigelow et aI. , 1950;Rupp and Severinghaus, 1986); (b) mild hypother mia (temperature 34-36°C) in contrast to moderate hypothermia (28-32°C), which is known to protect the brain (Bigelow et aI. , 1950) and may be harmful. This study involves cardiac arrest (i. e. , total body