Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest

Dongfang Che, Luchuan Li, Catherine M. Kopil, Ziyue Liu, Wensheng Guo, Robert W. Neumar

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1423-1430
Number of pages8
JournalCritical Care Medicine
Volume39
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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Induced Hypothermia
Heart Arrest
Nervous System
Long Evans Rats
Pyramidal Cells
Coma
Neurons

Keywords

  • brain
  • heart arrest
  • hypothermia
  • prognosis
  • resuscitation
  • survival
  • targeted temperature management

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest. / Che, Dongfang; Li, Luchuan; Kopil, Catherine M.; Liu, Ziyue; Guo, Wensheng; Neumar, Robert W.

In: Critical Care Medicine, Vol. 39, No. 6, 06.2011, p. 1423-1430.

Research output: Contribution to journalArticle

Che, Dongfang ; Li, Luchuan ; Kopil, Catherine M. ; Liu, Ziyue ; Guo, Wensheng ; Neumar, Robert W. / Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest. In: Critical Care Medicine. 2011 ; Vol. 39, No. 6. pp. 1423-1430.
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AU - Liu, Ziyue

AU - Guo, Wensheng

AU - Neumar, Robert W.

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N2 - 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.

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