On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve block

Anesthesiology. 2003 Jan;98(1):181-8. doi: 10.1097/00000542-200301000-00028.


Background: Adding epinephrine to lidocaine solutions for peripheral nerve block potentiates and prolongs the action, but by incompletely understood mechanisms. In an effort to discriminate the pharmacokinetic from the pharmacodynamic effects of epinephrine, the authors measured the lidocaine content of peripheral nerve over the course of block produced by 0.5% lidocaine, with and without epinephrine, and correlated it with the degree of analgesia.

Methods: Percutaneous sciatic nerve blocks were performed in 18 groups of rats (10 in each) with 0.1 ml of either 0.5% lidocaine or 0.5% lidocaine with epinephrine (1:100,000). Over the full course of nerve block, the authors regularly measured analgesia to toe pinch and then rapidly removed nerves to assay intraneural lidocaine content at 2-120 min after injection.

Results: The kinetics of lidocaine's clearance from nerve was composed of a fast-decaying transient superimposed on a very slowly decaying component. The effect of epinephrine on the intraneural lidocaine content was to increase the amount of lidocaine in the slow-decaying component by threefold to fourfold, although the total neural content was not altered by epinephrine for the first 10 min after injection. Epinephrine prolonged blockade by almost fourfold and enhanced the intensity of peak analgesia, as well as the fraction of rats with complete block, almost throughout the 2-120-min period of behavioral observation.

Conclusions: Adding epinephrine to lidocaine solutions increases the intensity and duration of sciatic nerve block in the rat. The early increase in intensity is not matched with an increase in intraneural lidocaine content at these early times, although the prolonged duration of block by epinephrine appears to correspond to an enlarged lidocaine content in nerve at later times, as if a very slowly emptying "effector compartment" received a larger share of the dose. The increase in early analgesia without increased lidocaine content may be explained by a pharmacodynamic action of epinephrine that transiently enhances lidocaine's potency, but also by a pharmacokinetic effect that alters the distribution of the same net content of lidocaine within the nerve.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Local / pharmacokinetics
  • Anesthetics, Local / pharmacology*
  • Animals
  • Drug Synergism
  • Epinephrine / pharmacology*
  • In Vitro Techniques
  • Lidocaine / pharmacokinetics
  • Lidocaine / pharmacology*
  • Male
  • Methyl Ethers / pharmacology
  • Nerve Block*
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Sevoflurane
  • Vasoconstrictor Agents / pharmacology*


  • Anesthetics, Inhalation
  • Anesthetics, Local
  • Methyl Ethers
  • Vasoconstrictor Agents
  • Sevoflurane
  • Lidocaine
  • Epinephrine