title: Relative Contribution of Adjuvants to Local Anesthetic for Prolonging the Duration of Peripheral Nerve Blocks in Rats.
abstract: OBJECTIVE
  A chemically compatible, safe 4-drug multimodal formulation of bupivacaine combined with 3 adjuvants (clonidine, buprenorphine, and dexamethasone) has been proposed for long-lasting single-injection peripheral nerve blocks in patients. However, the relative importance of each of the adjuvants of the 4-drug formulation in producing long-lasting nerve blocks has not been determined. The aim of this study in rats was to determine which adjuvants (clonidine, buprenorphine, or dexamethasone) are essential for producing a long-lasting nerve block.
  
  
  METHODS
  After baseline sensory and motor responses were recorded, 0.1 mL of drug solution was injected into the sciatic notch of rats. Animals were reevaluated at 10-minute intervals after injection for the absence or presence of sensory and motor response in the sciatic nerve. The 4-drug formulation of 0.25% bupivacaine plus all 3 adjuvants (clonidine, buprenorphine, and dexamethasone), 0.25% bupivacaine with 1 or 2 of the adjuvants added separately, and 0.25% bupivacaine alone were compared for duration of nerve block.
  
  
  RESULTS
  The 4-drug multimodal solution produced a longer duration of sensory and motor nerve block than 0.25% bupivacaine alone (P < 0.0001). Bupivacaine plus clonidine also produced a longer duration of nerve block than 0.25% bupivacaine alone (P = 0.0157), but bupivacaine plus buprenorphine or bupivacaine plus dexamethasone did not prolong nerve block compared to bupivacaine alone. There was no difference (P = 0.1414) in the duration of nerve block between the 4-drug multimodal solution versus bupivacaine plus clonidine.
  
  
  CONCLUSIONS
  This animal study confirmed that the 4-drug multimodal formulation proposed for clinical nerve block produces superior duration of action compared to local anesthetic alone. This rat sciatic nerve model also indicated that one of the 3 adjuvants, clonidine, could by itself account for the extended duration of nerve block of bupivacaine.
authors.affiliation: From the Department of Anesthesiology, Rush University Medical Center, Chicago, IL.
authors.forename: Asokumar
authors.initials: A
authors.lastname: Buvanendran
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kroin
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Li
authors.forename: Mario
authors.initials: M
authors.lastname: Moric
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Tuman
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D002047:Buprenorphine / Q000008:administration & dosage*; D003000:Clonidine / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004338:Drug Combinations; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D009407:Nerve Block / Q000379:methods*; D017288:Pain Threshold / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000033:anatomy & histology / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D002047:Buprenorphine; D003907:Dexamethasone; D003000:Clonidine; D002045:Bupivacaine