SummaryObjectives-Therapeutic hypothermia (TH) after cardiac arrest (CA) improves outcomes in a fraction of patients. To enhance the administration of TH, we studied brain electrophysiological monitoring in determining the benefit of early initiation of TH compared to conventional administration in a rat model.
Methods-Using an asphyxial CA model, we compared the benefit of immediate hypothermia (IH, T=33°C, immediately post-resuscitation, maintained 6 hours) to conventional hypothermia (CH, T=33°C, starting 1 hour post-resuscitation, maintained 12 hours) via surface cooling. We tracked quantitative EEG using relative entropy (qEEG) with outcome verification by serial Neurological Deficit Score (NDS) and quantitative brain histopathological damage scoring (HDS). Thirty-two rats were divided into 4 groups based on CH/IH and 7/9-minute duration of asphyxial CA. Four sham rats were included for evaluation of the effect of hypothermia on qEEG.Results-The 72-hour NDS of the IH group was significantly better than the CH group for both 7-minute (74/63; Median, IH/CH, p<0.001) and 9-minute (54/47, p=0.022) groups. qEEG showed greater recovery with IH (p<0.001) and significantly less neuronal cortical injury by HDS (IH: 18.9 ±2.5% versus CH: 33.2±4.4%, p=0.006). The 1-hour post-resuscitation qEEG correlated well with 72-hour NDS (p<0.05) and 72-hour behavioral subgroup of NDS (p<0.01). No differences in qEEG were noted in the sham group. *Corresponding author: Xiaofeng JIA MD, PhD, CRB II Building 3M-South, 1550 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA, Telephone number: +1-410-502-2820, Fax: +1-410-502-7869, E-mail address: xjia1@jhmi.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Portions of this work were previously presented in 4 th Annual Meeting of the Neurocritical Care Society in Baltimore, MD (November 2006) and at the 36 th Annual Meeting of the Society for Neuroscience at Atlanta, Georgia (October 2006) where it was selected for the lay language summary press book.
Conflict of interest statementThere are no conflicts of interest in this study. Conclusions-Immediate but shorter hypothermia compared to CH leads to better functional outcome in rats after 7-and 9-minute CA. The beneficial effect of IH was readily detected by neuroelectrophysiological monitoring and histological changes supported the value of this observation.
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