Inhibition of Cerebral Metabolism by Lidocaine

Abstract

The effects of lidocaine in high doses, i.e. higher than seizure doses, on cerebral function and metabolism are reviewed. Evidence is presented that lidocaine (160 mg/kg) reduces membrane Na⁺-K⁺ permeability, restricts leak fluxes of these ions, and decreases the load on the associated ion transport. In the ischemic brain (circulatory arrest in dogs on cardiopulmonary bypass circulation), lidocaine delays K⁺ efflux, indicating reduced membrane permeability. In the nonischemic brain lidocaine has two effects. One is to abolish electrocortical activity and reduce oxygen and glucose consumption accordingly (‘barbiturate-like’ effect). The other is a specific membrane sealing effect by which Na⁺-K⁺ leak fluxes are restricted and associated demand for active transport accordingly reduced. By this effect lidocaine is able to reduce cerebral metabolism by an additional 15–20% below the barbiturate minimum at flat EEC These effects of lidocaine resemble those of hypothermia and may enhance the hypothermic protection of the ischemic brain.

Time Course of Acute Neuroprotective Effects of Lidocaine Evaluated by Brain Impedanciometry in the Global Ischemia Model

“…The first fast voltage decay phase induced by ischemia and lasting about 8 min is probably an expression of ATP rollout and the consequent reduced Na/K-ATPase activity leading to an increase in the intracellular concentration of Na + and Ca 2+ [14,15] . The strong anti-edema effect of lidocaine reported here, more intense for the first 8 min of ischemia, can be a product of several processes beginning on the blocking action on voltage-activated sodium and potassium channels [4][5][6] , which produces a selective inhibition of Na + cellular influx and a subsequent reduction of Ca 2+ influx due to decreased membrane depolarization [24] together with reduced mitochondrial Na/Ca-ATPase activity, glucose and oxygen consumption [8,[24][25][26][27] . These reported ionic and membrane events could be the explanation to the strong increase in the time constant for voltage decay induced by lidocaine.…”

“…Lidocaine, a well-known drug used as a local anesthetic [1] , heart antiarrhythmic [2] and antiepileptic drug [3] , produces a presynaptic block by reducing Na + inflow to the cell and K + outflow by means of the blockade of Na/K channels [4][5][6] .…”

Evaluation of continuous intravenous lidocaine on brain relaxation, intraoperative opioid consumption, and surgeon’s satisfaction in adult patients undergoing craniotomy tumor surgery: A randomized controlled trial

“…The effect of reducing ion leak fluxes is also seen in hypothermia but not in thiopental, indicating lidocaine, not thiopental, has a membrane-sealing effect. [13] This membrane sealing effect (membrane stabilization) is related to energy to maintain cellular integrity that accounts for 40% of brain metabolism. 19 In this experiment, Astrup et al also measured the effect of lidocaine on CMRO 2 and cerebral metabolic rate for glucose (CMRgluc) by the sagittal sinus outflow method that allows continuous measurement of oxygen and glucose consumption.…”

“…In mammal experiments done by Astrup et al, lidocaine infusion resulting in flat electroencephalogram concluded that spontaneous electrocortical activity is abolished by lidocaine, similar to barbiturate action. [13,14] The abolition of electrocortical activity reduces 60% of energy consumption or brain metabolism. [19] In addition, lidocaine also affects Na-K leak fluxes.…”

“…[13] Based on these experimental results, lidocaine can reduce cerebral metabolism by inhibiting synaptic transmission and membrane sealing effect that reduces ion transport demand. 13 Sakabe et al also studied lidocaine effect on cerebral metabolism in mammal experimental using a lower dose of lidocaine and have the similar result that lidocaine can decrease CMRO 2 significantly. [15] Furthermore, lidocaine can reduce CBF due to decreased cerebral metabolism and cerebrovascular vasoconstrictor properties.…”