Concentrations of lidocaine and monoethylglycine xylidide in brain, cerebrospinal fluid, and plasma during lidocaine-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 PaCO(2). In contrast, when lidocaine is introduced directly into an artery or vein, adding epinephrine to lidocaine may decrease the mean toxic dose of lidocaine. Less is known about the effects of decreased PaCO(2) on intravascular lidocaine toxicity. We infused lidocaine in 24 rabbits at 4 mg. kg(-1). min(-1) with/without epinephrine and with/without hypocapnia. We measured the time to onset of lidocaine-induced seizures, total dose of lidocaine at the time of seizures, and concentrations of lidocaine and monoethylglycine xylidide (MEGX), a metabolite of lidocaine, in plasma, brain, and cerebrospinal fluid. Epinephrine decreased onset time by 11% with hypocapnia and by 21% with normocapnia, and it increased plasma MEGX by 1 microg/mL with hypocapnia and 2 microg/mL with normocapnia. Hypocapnia increased onset time by 18% without epinephrine and by 33% with epinephrine, and it increased whole-brain MEGX by 10 microg/mL without epinephrine and by 14 microg/mL with epinephrine. We conclude that, when lidocaine is given intravascularly, hypocapnia increases onset time and lidocaine dose required for seizures. These effects occur with no change in the concentration of lidocaine in plasma or the brain.


CONCLUSIONS
Hypocapnia increases the toxic dose of lidocaine given IV without altering lidocaine concentrations in blood, brain, or cerebrospinal fluid. Whole-brain monoethylglycine xylidide concentration is greater during hypocapnia than during normocapnia, and the addition of epinephrine to lidocaine increases the concentration of monoethylglycine xylidide in plasma.
Departments of Anesthesiology, Osaka Dental University, Japan.
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Momota
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Artru
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Powers
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Mautz
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Ueda
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D015170:Cerebrospinal Fluid Pressure / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004837:Epinephrine / Q000008:administration & dosage*; D016857:Hypocapnia / Q000150:complications / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity*; D011817:Rabbits
D000779:Anesthetics, Local; D008012:Lidocaine; C001173:monoethylglycinexylidide; D004837:Epinephrine