title: Alterations in the pharmacokinetic properties of amide local anaesthetics following local anaesthetic induced convulsions.
abstract: The comparative pharmacokinetic properties of lidocaine, bupivacaine, etidocaine and mepivacaine were investigated in convulsing and non-convulsing dogs. The same dose of a given local anaesthetic was administered as either a 30-s intravenous (IV) bolus to produce convulsions or as a 15-min IV infusion producing no convulsions. Derived pharmacokinetic data were found to be different in convulsing and non-convulsing animals. Total body clearance was found to be significantly reduced for lidocaine (29%, P less than 0.05), bupivacaine (31%, P less than 0.05), etidocaine (60%, P less than 0.01) and mepivacaine (68%, P less than 0.01) in convulsing animals. Increases in elimination half-life only achieved statistical significance in mepivacaine-treated animals (non-convulsing 45.2 min, convulsing 105.4 min, P less than 0.01). Overall, the most profound effects of convulsions on pharmacokinetic data were seen with mepivacaine. Convulsions were associated with increases in heart rate ranging from 117% (lidocaine, P less than 0.05) to 129% (mepivacaine, P less than 0.05), increases in cardiac output ranging from 78% (mepivacaine) to 232% (bupivacaine, P less than 0.05) and increases in mean arterial pressure ranging from 45% (lidocaine, P less than 0.05) to 80% (bupivacaine, P less than 0.05). The results suggest that when local anaesthetic-induced seizures occur in man, it cannot be assumed that these drugs will be distributed and eliminated as predicted by intravenous infusion of non-toxic doses.
authors.affiliation: Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston.
authors.forename: G R
authors.initials: GR
authors.lastname: Arthur
authors.forename: H S
authors.initials: HS
authors.lastname: Feldman
authors.forename: B G
authors.initials: BG
authors.lastname: Covino
mesh_terms: D000779:Anesthetics, Local / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D002045:Bupivacaine / Q000493:pharmacokinetics / Q000633:toxicity; D004285:Dogs; D005041:Etidocaine / Q000493:pharmacokinetics / Q000633:toxicity; D008012:Lidocaine / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008619:Mepivacaine / Q000493:pharmacokinetics / Q000633:toxicity; D012640:Seizures / Q000097:blood* / Q000139:chemically induced
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine; D008619:Mepivacaine; D005041:Etidocaine; D002045:Bupivacaine