title: Epinephrine injection in lipid-based resuscitation from bupivacaine-induced cardiac arrest: transient circulatory return in rabbits.
abstract: BACKGROUND
  IV lipid emulsion has demonstrated to be effective therapy for bupivacaine-induced cardiotoxicity. However, the role of epinephrine when coadministered with lipid emulsion in toxin-induced cardiac arrest is unclear. We postulated superior resuscitation outcome in the absence of epinephrine in a rabbit model of bupivacaine-induced cardiac arrest resuscitated with IV lipid emulsion.
  
  
  METHODS
  Twenty sedated, instrumented New Zealand White rabbits received 10 mg/kg IV bupivacaine producing asystole. Mechanical ventilation and external chest compressions were commenced at 30 seconds. At 1 minute, animals received 5 mL/kg 20% lipid emulsion in addition to 1 of 4 additional IV treatments (n = 5 all groups): 0.9% saline, 2.5 microg/kg epinephrine, 10 microg/kg epinephrine, 100 microg/kg epinephrine; all at 1 mL/kg. Lipid emulsion bolus was repeated at 4 minutes. Return of spontaneous circulation and hemodynamic metrics were obtained to 15 minutes. Saline group animals additionally received high-dose epinephrine (100 microg/kg) treatment at 15 minutes, and were monitored to 20 minutes.
  
  
  RESULTS
  High-dose epinephrine administration was associated with increased rate of return of spontaneous circulation compared with saline control (0 of 5 saline-treated animals; 0 of 5 animals in the 2.5 microg/kg epinephrine group; 3 of 5 in the 10 microg/kg group [P = 0.167]; and 4 of 5 in the 100 microg/kg group [P = 0.048]). Spontaneous but decreasing circulation was maintained at 15 minutes in 4 of 5 animals in the 100 microg/kg group alone (P = 0.048); mean arterial blood pressure at 15 minutes was 12.8 (SEM 2.8) mm Hg saline, 12.0 (2.5) mm Hg 2.5 microg/kg epinephrine, 20.6 (2.7) mm Hg 10 microg/kg epinephrine, and 26.4 (3.9) mm Hg 100 microg/kg epinephrine (P = 0.008). Four of five animals in the saline-treated group exhibited return of spontaneous circulation after delayed epinephrine treatment (P = 0.048). High-dose epinephrine administration was associated with a significant increase in coronary perfusion pressure before return of spontaneous circulation.
  
  
  CONCLUSIONS
  Epinephrine seemed to be necessary for return of spontaneous circulation, but was subsequently associated with declining hemodynamic variables in this rabbit model of bupivacaine-induced cardiac arrest. Further study is required to define the role of epinephrine in lipid-based resuscitation from local anesthetic-induced cardiac arrest.
authors.affiliation: FACEM, Waikato Hospital, Emergency Department, Waikato Hospital, Pembroke St., Hamilton 3240, New Zealand. harveym@waikatodhb.govt.n
authors.forename: Martyn
authors.initials: M
authors.lastname: Harvey
authors.forename: Grant
authors.initials: G
authors.lastname: Cave
authors.forename: Gaynor
authors.initials: G
authors.lastname: Prince
authors.forename: Daniel
authors.initials: D
authors.lastname: Lahner
mesh_terms: D000779:Anesthetics, Local; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D006323:Heart Arrest / Q000139:chemically induced* / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D011817:Rabbits; D012151:Resuscitation; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D014662:Vasoconstrictor Agents; D002045:Bupivacaine; D004837:Epinephrine