title: Neurotoxicity of common peripheral nerve block adjuvants.
abstract: OBJECTIVE
  This review outlines the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluates current knowledge regarding whether adjuvants modulate the neurocytologic properties of local anesthetics.
  
  
  RESULTS
  Perineural adjuvant medications such as dexmedetomidine, clonidine, buprenorphine, dexamethasone, and midazolam play unique analgesic roles. The dosing of these medications to prevent neurotoxicity is characterized in various cellular and in-vivo models. Much of this mitigation may be via reducing the dose of local anesthetic used while achieving equal or superior analgesia. Dose-concentration animal models have shown no evidence of deleterious effects. Clinical observations regarding blocks with combined bupivacaine-clonidine-buprenorphine-dexamethasone have shown beneficial effects on block duration and rebound pain without long-term evidence of neurotoxicity. In-vitro and in-vivo studies of perineural clonidine and dexmedetomidine show attenuation of perineural inflammatory responses generated by local anesthetics.
  
  
  CONCLUSIONS
  Dexmedetomidine added as a peripheral nerve blockade adjuvant improves block duration without neurotoxic properties. The combined adjuvants clonidine, buprenorphine, and dexamethasone do not appear to alter local anesthetic neurotoxicity. Midazolam significantly increases local anesthetic neurotoxicity in vitro, but when combined with clonidine-buprenorphine-dexamethasone (sans local anesthetic) produces no in-vitro or in-vivo neurotoxicity. Further larger-species animal testing and human trials will be required to reinforce the clinical applicability of these findings.
authors.affiliation: aDepartment of Anesthesiology, University of Pittsburgh Medical Center bVA Pittsburgh Health System, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Knight
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schott
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kentor
authors.forename: Brian A
authors.initials: BA
authors.lastname: Williams
mesh_terms: D000759:Adjuvants, Anesthesia / Q000009:adverse effects*; D000777:Anesthetics / Q000009:adverse effects*; D006801:Humans; D009407:Nerve Block / Q000009:adverse effects*
chemical_list: D000759:Adjuvants, Anesthesia; D000777:Anesthetics