The Detrimental Effect of Lidocaine on Cerebral Metabolism Measured in Dogs Anesthetized with Isoflurane

Abstract

Previous studies in dogs have demonstrated that massive doses of intravenous loidocaine (160 mg .cntdot. kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg .cntdot. kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 .+-. 19 ml .cntdot. min-1 .cntdot. 100 g-1 during 3% isoflurane anesthesia, and was 102 .+-. 11 ml .cntdot. min-1 .cntdot. 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 .+-. 0.23 ml .cntdot. min-1 .cntdot. 100 g-1 during isoflurane anesthesia, and was 2.18 .+-. 0.09 ml .cntdot. min-1 .cntdot. 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 .+-. 0.04 .mu.mol .cntdot. g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 .+-. 0.01 .mu.mol .cntdot. g-1). Cerebral ATP concentration was significantly reduced to 1.77 .+-. 0.05 .mu.mol .cntdot. kg-1 by lidocaine. The cerebral energy charge (EC) under 3% isoflurane was 0.904 .+-. 0.011. The administration of lidocaine significantly decreased the EC to 0.844 .+-. 0.002. From this study, it is concluded that, although a large but clinically tolerated dose of lidocaine did not produce additional metabolic suppression in the presence of maximal metabolic suppression produced by isoflurane, it may have a direct toxic effect on oxidative phosphorylation. Therefore, any measured decrease in cerebral metabolism produced by large doses of lidocaine may be due to a combination of factors, both "protective" and toxic, including suppression of electrical cortical activity, stabilization of membranes, and uncoupling of oxidative phosphorylation.