Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets

Br J Anaesth. 2014 Apr;112(4):729-34. doi: 10.1093/bja/aet327. Epub 2013 Oct 2.

Abstract

Background: The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST).

Methods: Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid(®) alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min.

Results: ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups (P<0.05).

Conclusions: Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone.

Keywords: local anaesthesia; toxicity, local anaesthetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / toxicity*
  • Animals
  • Animals, Newborn
  • Bupivacaine / analogs & derivatives*
  • Bupivacaine / toxicity
  • Cardiopulmonary Resuscitation / methods
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Drug Therapy, Combination
  • Electrocardiography / drug effects
  • Emulsions / therapeutic use
  • Epinephrine / administration & dosage
  • Epinephrine / pharmacology
  • Epinephrine / therapeutic use*
  • Fat Emulsions, Intravenous / therapeutic use
  • Female
  • Heart Arrest / chemically induced
  • Heart Arrest / therapy*
  • Levobupivacaine
  • Male
  • Phospholipids / therapeutic use*
  • Soybean Oil / therapeutic use*
  • Sus scrofa
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / pharmacology
  • Vasoconstrictor Agents / therapeutic use

Substances

  • Anesthetics, Local
  • Emulsions
  • Fat Emulsions, Intravenous
  • Phospholipids
  • Vasoconstrictor Agents
  • soybean oil, phospholipid emulsion
  • Soybean Oil
  • Levobupivacaine
  • Bupivacaine
  • Epinephrine