The effects of exogenous epinephrine on a convulsive dose of lidocaine: relationship with cerebral circulation.
In order to understand why exogenous epinephrine decreases the convulsive dose of lidocaine, the authors investigated cerebral circulation and plasma lidocaine concentrations in Wistar rats under general anesthesia. In the first experiment, baseline evaluations of each rat's electroencephalogram (EEG), mean arterial pressure (MAP), regional cerebral blood flow (r-CBF), cerebrospinal fluid (CSF) pressure, and cerebral perfusion pressure (CPP) were made. The rats were then assigned to one of three groups: Group L (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 kg/kg/min); and Group E (n=5) received intravenous epinephrine (2.5 microg/kg/min). Cumulative doses of lidocaine at the onset of EEG spike activity in Groups L and LE were compared. Blood-brain barrier (BBB) permeability was evaluated by observing extravasation of Evans blue (EB) dye. In the second experiment, additional rats were allocated to two treatment groups: Group L' (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE' (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 microg/kg/min). Brain tissue oxygen partial pressure (PtO2) was monitored during infusion, and arterial and sagittal sinus blood samples were obtained immediately after the onset of EEG spike activity to determine plasma lidocaine concentration. The convulsive dose of lidocaine was significantly decreased when lidocaine was administered with epinephrine (Group L: 61.5+/-5.3 mg/kg (mean+/-SD); Group LE: 30.1+/-4.0 mg/kg) (p < 0.05), but there were no significant differences in plasma lidocaine concentration among these groups. R-CBF, CSF pressure, and CPP immediately before EEG spike activity were higher in Group LE than in Group L. Neither decreased PtO2 nor extravasation of EB was observed in rats treated with epinephrine and lidocaine, excluding cerebral ischemia and BBB breakdown from possible mechanisms by which epinephrine decreased the convulsive dose of lidocaine. None of the rats in Group E exhibited EEG findings suggestive of a preconvulsive state, ruling out a convulsive effect of epinephrine itself. The results suggest that an increase in lidocaine supply to the brain caused by increased CBF causes the low cumulative dose of lidocaine at the onset of convulsion in rats given lidocaine plus epinephrine.
Department of Anesthesiology, Osaka Dental University, Japan.
Y
Y
Yamauchi
J
J
Kotani
Y
Y
Ueda
D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000768:Anesthesia, General; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D015170:Cerebrospinal Fluid Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004396:Coloring Agents; D003292:Convulsants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010313:Partial Pressure; D051381:Rats; D017208:Rats, Wistar
D000322:Adrenergic Agonists; D000779:Anesthetics, Local; D004396:Coloring Agents; D003292:Convulsants; D002245:Carbon Dioxide; D005070:Evans Blue; D008012:Lidocaine; D010100:Oxygen; D004837:Epinephrine