Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow

Epinephrine has been combined with neuraxial and peripheral local anesthetics since Heinrich Braun first experimented with its use as a “chemical tourniquet” in the early 1900s.1 A century of use attests to the general safety of adjuvant epinephrine, yet we have only modest understanding of its intended effects, which include prolonging block duration, reducing plasma concentration of local anesthetics, reducing surgical bleeding, and intensifying anesthesia and analgesia.2-5 The long-held belief that epinephrine exerts most of these effects, including any associated complications, by causing vasoconstriction is doubtlessly too simplistic and has been recently challenged. The few controlled studies that focus on adverse side effects of adjuvant epinephrine are often difficult to interpret and compare because of interspecies differences in neural blood flow,6,7 the technical challenges of measuring epinephrine’s evanescent physiologic effects, and the confounding hemodynamic influences of local anesthetics. After briefly considering the pharmacology of epinephrine, this review examines evidence for its untoward effects when applied to the neuraxial or peripheral nervous systems as part of a regional anesthetic technique. Information is organized by how neurotoxicity is manifested—histopathologic and behavioral effects, physiologic effects, and undesirable clinical consequences.8