title: Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect.
abstract: BACKGROUND
  Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose.
  
  
  METHODS
  Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml x kg x min, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min.
  
  
  RESULTS
  Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min.
  
  
  CONCLUSIONS
  Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.
authors.affiliation: Department of Anesthesiology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Hiller
authors.forename: Guido Di
authors.initials: GD
authors.lastname: Gregorio
authors.forename: Richard
authors.initials: R
authors.lastname: Ripper
authors.forename: Kemba
authors.initials: K
authors.lastname: Kelly
authors.forename: Malek
authors.initials: M
authors.lastname: Massad
authors.forename: Lucas
authors.initials: L
authors.lastname: Edelman
authors.forename: Guy
authors.initials: G
authors.lastname: Edelman
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Feinstein
authors.forename: Guy L
authors.initials: GL
authors.lastname: Weinberg
mesh_terms: D000779:Anesthetics, Local / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D062787:Drug Overdose; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D002045:Bupivacaine; D004837:Epinephrine