Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest*
Top Cited Papers
- 1 June 2011
- journal article
- laboratory investigations
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 39 (6), 1423-1430
- https://doi.org/10.1097/ccm.0b013e318212020a
Abstract
Objective: Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy. Design: Prospective randomized laboratory investigation. Setting: University research laboratory. Subjects: A total of 268 male Long Evans rats. Interventions: Post-cardiac-arrest therapeutic hypothermia. Measurements and Main Results: Adult male Long Evans rats that achieved return of spontaneous circulation after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37°C ± 1°C) or therapeutic hypothermia (33°C ± 1°C) initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation and maintained for 24 or 48 hrs. Therapeutic hypothermia initiated 0, 1, 4, and 8 hrs after return of spontaneous circulation resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14%, respectively, compared to 17% for normothermic controls and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0%, respectively, compared to 2% for normothermic controls (*p < .05 vs. normothermia). These outcomes were not different when therapeutic hypothermia was maintained for 24 vs. 48 hrs. In contrast, hippocampal CA1 pyramidal neuron counts were 53% ± 27%*, 53% ± 19%*, 51% ± 24%*, and 65% ± 16%* of normal, respectively, when therapeutic hypothermia was initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation compared to 9% in normothermic controls (*p < .01 vs. normothermia). Furthermore, surviving neuron counts were greater when therapeutic hypothermia was maintained for 48 hrs compared to 24 hrs (68% ± 15%* vs. 42% ± 22%, *p < .0001). Conclusions: In this study, post-cardiac-arrest therapeutic hypothermia resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4 hrs after return of spontaneous circulation. However, histologic assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when therapeutic hypothermia was maintained for 48 vs. 24 hrs.This publication has 26 references indexed in Scilit:
- Induction of Therapeutic Hypothermia by Paramedics After Resuscitation From Out-of-Hospital Ventricular Fibrillation Cardiac ArrestCirculation, 2010
- Outcome, timing and adverse events in therapeutic hypothermia after out‐of‐hospital cardiac arrestActa Anaesthesiologica Scandinavica, 2009
- Mild hypothermia during advanced life support: a preliminary study in out-of-hospital cardiac arrestCritical Care, 2008
- Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac ArrestThe New England Journal of Medicine, 2002
- Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced HypothermiaThe New England Journal of Medicine, 2002
- Hypothermia during Reperfusion after Asphyxial Cardiac Arrest Improves Functional Recovery and Selectively Alters Stress-Induced Protein ExpressionJournal of Cerebral Blood Flow & Metabolism, 2000
- Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogsCritical Care Medicine, 1993
- Protection against hippocampal CA1 cell loss by post-ischemie hypothermia is dependent on delay of initiation and durationMetabolic Brain Disease, 1992
- Mild hypothermic intervention after graded ischemic stress in rats.Stroke, 1991
- Temporal profile of neuronal damage in a model of transient forebrain ischemiaAnnals of Neurology, 1982