title: Local Anesthetic-Induced Neurotoxicity.
abstract: This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor.
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. m.h.verlinde@amc.uva.nl.
authors.forename: Mark
authors.initials: M
authors.lastname: Verlinde
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. m.w.hollmann@amc.uva.nl.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. m.f.stevens@amc.uva.nl.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Stevens
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. h.hermanns@amc.uva.nl.
authors.forename: Henning
authors.initials: H
authors.lastname: Hermanns
authors.affiliation: Department of Anesthesiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. robert.werdehausen@med.uni-duesseldorf.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Werdehausen
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. p.lirk@amc.uva.nl.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lirk
mesh_terms: D000765:Anesthesia, Conduction / Q000009:adverse effects / Q000295:instrumentation; D000779:Anesthetics, Local / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D059035:Perioperative Period; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D020169:Caspases
keywords: adverse event; anesthetics; local; toxicity