title: Epinephrine administration in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest: optimal timing.
abstract: OBJECTIVE
  The medical community commonly uses lipid emulsion combined with epinephrine in local anesthetic-induced cardiac arrest, but the optimal timing of epinephrine administration relative to lipid emulsion is currently unknown and needs to be determined.
  
  
  METHODS
  Thirty adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and were then randomly divided into 3 groups. The temporal administration of epinephrine varied in each group: (1) immediately after the completion of the initial bolus of lipid emulsion therapy (postILE0); (2) immediately after cardiac arrest before the initial bolus of lipid emulsion (preILE); or (3) 1 minute after the completion of the initial bolus of lipid emulsion (postILE1). External chest compression was administered until the return of spontaneous circulation or the end of a 20-minute resuscitation period.
  
  
  RESULTS
  The postILE0, preILE, and postILE1 groups displayed different survival rates (100%, 30%, and 40%; P = 0.003). After return of spontaneous circulation, the rate-pressure product of the postILE0 group was higher than that of the postILE1 group (P < 0.001). Wet-to-dry lung weight ratio of preILE and postILE1 groups was higher than that of the postILE0 group (P < 0.05). The rate of damaged alveoli of the postILE0 group was lower than those of the preILE (P = 0.001) and postILE1 (P < 0.001) groups. Concentrations of bupivacaine in the cardiac tissues of the postILE0 group were lower than that of the postILE1 group (P = 0.01).
  
  
  CONCLUSIONS
  In the rat model of bupivacaine-induced cardiac arrest, the optimal timing for the administration of epinephrine to produce best outcomes of successful cardiopulmonary resuscitation is immediately after the completion of the lipid emulsion bolus. This optimal timing/therapeutic window is of paramount importance.
authors: From the *Department of Anesthesiology, The First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China; †Department of Anesthesiology, The Ohio State University Medical Center, Columbus, OH; and ‡Department of Pathology, The First Affiliated Hospital, Wenzhou Medical University; and §Analysis and Testing Center, Wenzhou Medical University, Zhejiang, China.
authors: Zhousheng
authors: Z
authors: Jin
authors: Yun
authors: Y
authors: Xia
authors: Fangfang
authors: F
authors: Xia
authors: Cong
authors: C
authors: Wu
authors: Zhe
authors: Z
authors: Chen
authors: Fubei
authors: F
authors: Nan
authors: Bingjing
authors: B
authors: Wu
authors: Li
authors: L
authors: Wan
authors: Xianqin
authors: X
authors: Wang
authors: Thomas J
authors: TJ
authors: Papadimos
authors: Xuzhong
authors: X
authors: Xu
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004837:Epinephrine / Q000627:therapeutic use*; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D006323:Heart Arrest / Q000628:therapy*; D006324:Heart Arrest, Induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D014662:Vasoconstrictor Agents; D002045:Bupivacaine; D004837:Epinephrine