Critical Time Window for Intra-Arrest Cooling With Cold Saline Flush in a Dog Model of Cardiopulmonary Resuscitation

Abstract

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...

Therapeutic mild hypothermia improves outcome after out-of-hospital cardiac arrest

“…The suggested time window is short, lasts a few hours and is directly adjacent to the OHCA. 1,20 Therefore, the early and rapid application of TMH with only a difference of, for instance, two hours can have significant effects on the prognosis post-OHCA. Although showing an effect of TMH overall, we could not confirm these results from animal studies in our retrospective study.…”

“…[1][2][3][4] The poor prognosis is related to the associated hypoxic cerebral damage during circulation arrest. 5,6 Therapeutic mild hypothermia (TMH) is recommended by the current guidelines on the post-resuscitation care of comatose subjects post-OHCA from the International Liaison Committee on Resuscitation (ILCOR) and European Resuscitation Council (ERC) 7,8 TMH post-OHCA is usually performed in an intensive care unit (ICU) and improves neurological outcome and decreases mortality.…”

Pre‐hospital cardiac arrest and induction of mild hypothermia: studies on epidemiology and feasibility

“…Animal studies have shown that there exists a critical time window after cardiac arrest during which cooling should be initiated to achieve the beneficial effects of induced hypothermia Nozari et al 2006). Although the mean delay to target temperature in the study by the Hypothermia After Cardiac Arrest Study group was up to eight hours and improved outcome was still observed (HACA 2002), current recommendation is that hypothermia should be induced as soon as possible (Castrén et al 2009;ERC 2005).…”

“…Preferably, the treatment should be initiated as soon as possible (ERC 2005;Safar and Kochanek 2002b) such as in the prehospital setting. Furthermore, reports from experimental studies 6 have suggested that delay to cooling diminishes the beneficial effects of induced hypothermia and that ideally cooling should occur already during resuscitation Nozari et al 2006).…”

Scandinavian Clinical practice guidelines for therapeutic hypothermia and post‐resuscitation care after cardiac arrest

“…Animal studies have demonstrated that hypothermia initiated during or immediately after ROSC is associated with better organ preservation and increased survival. 56,57 Recently, in 49 patients treated with MTH, early achievement of the target temperature was an independent factor for good outcome 58 (GOE V). However, larger trials are warranted to assess the advantage of early vs. late cooling in humans.…”