• G R Arthur, H S Feldman, and B G Covino.
• Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston.
• Acta Anaesthesiol Scand. 1988 Oct 1; 32 (7): 522-9.

AbstractThe 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.

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