Concentrations of lidocaine and monoethylglycine xylidide in brain, cerebrospinal fluid, and plasma during liodcaine-induced epileptiform electroencephalogram activity in rabbits: The effects of epinephrine and hypocapnia

When injecting lidocaine into tissues, the mean toxic dose of lidocaine may be increased by adding epinephrine to lidocaine and by decreasing the Pace ,. In contrast, when lidocaine is introduced directly into an artery or vei n, adding epinephrine to lidocaine may decrease the mean toxic dose of lido caine. Less is known about the effects of de creased Paco(2) on intravascul ar lidocaine toxicity. We infused lidocaine in 24 rabbits at 4 mg . kg(-1) . min(-1) with/ without epinephrine and with/without hypocapnia. We measure d the time to onset of lidocaine-induced seizures, total dose of lidocaine at the time of seizures, and concentrations of lidocaine and monoethylglyci ne xylidide (MEGX), a metabolite of lidocaine, in plasma, brain, and cerebr ospinal fluid. Epinephrine decreased onset time by 11% with hypocapnia and by 21% with normocapnia, and it increased plasma MEGX by 1 mu g/mL with hyp ocapnia and 2 mu g/mL with normocapnia. Hypocapnia increased onset time by 18% without epinephrine and by 33% with epinephrine, and it increased whole -brain MEGX by 10 mu g/mL without epinephrine and by 14 mu g/mL with epinep hrine. We conclude that, when lidocaine is given intravascularly, hypocapni a increases onset time and lidocaine dose required for seizures. These effe cts occur with no change in the concentration of lidocaine in plasma or the brain.