Canadian Journal of Anaesthesia

, Volume 49, Issue 7, pp 706–710 | Cite as

Epinephrine does not reduce the plasma concentration of lidocaine during continuous epidural infusion in children

  • Masayuki Miyabe
  • Yoshihiro Kakiuchi
  • Shinichi Inomata
  • Yoshiko Ohsaka
  • Yukinao Kohda
  • Hidenori Toyooka
Obstetrical and Pediatric Anesthesia



During continuous epidural anesthesia with lidocaine, plasma monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, increases continuously. We assessed the effect of epinephrine on the absorption of lidocaine and the accumulation of MEGX during continuous epidural anesthesia in children. Methods: Anesthesia was administered as an initial bolus of 5 mg· kg−1 of 1 % lidocaine solution followed by continuous infusion at 2.5 mg· kg−1· hr−1. Patients in the control group (n = 8) received lidocaine alone, while patients in the epinephrine group (n = 8) received lidocaine + epinephrine (5 μg· mL−1). Concentrations of lidocaine and its active metabolite, MEGX, were measured in plasma samples obtained after 15 min, 30 min, and one, two, three, four, and five hours of infusion using high-performance liquid chromatography with ultraviolet detection.


Plasma lidocaine concentrations were higher in samples from the control group for the first hour; however, after two hours the levels were the same in all samples. Plasma MEGX levels increased continuously in both groups and were significantly higher in the control group samples. The sum of lidocaine + MEGX was higher in the control group for the first two hours but there was no significant difference between groups after three hours.


Reduction of the potential for systemic toxicity by the addition of epinephrine to lidocaine is limited, because the reduction of the sum of the plasma concentrations of lidocaine and its active metabolite MEGX is small and limited to the initial phase of infusion.


Lidocaine Sevoflurane Lidocaine Concentration Continuous Epidural Infusion Lidocaine Infusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

L’épinéphrine ne réduit pas la concentration plasmatique de lidocaïne pendant une perfusion péridurale continue chez les enfants



Pendant l’anesthésie péridurale continue avec de la lidocaïne, le monoéthylglycinexylidide plasmatique (MEGX), un métabolite actif de la lidocaïne, augmente constamment. Nous avons évalué l’effet de l’épinéphrine sur l’absorption de la lidocaïne et l’accumulation de MEGX pendant l’anesthésie péridurale continue chez des enfants.


L’anesthésie a été administrée par un bolus initial de 5 mg· kg−1 d’une solution de lidocaïne à 1 % suivi d’une perfusion continue à 2,5 mg· kg−1· h−1. Les patients témoins (n = 8) ont reçu de la lidocaïne seule tandis que les autres (n = 8) ont reçu de la lidocaïne et de l’épinéphrine (5 μg· mL−1). Les concentrations de lidocaïne et de son métabolite actif, le MEGX, ont été mesurées dans des échantillons de plasma prélevés après 15 et 30 min, puis une, deux, trois, quatre et cinq heures de perfusion en utilisant la chromatographie liquide haute performance avec détection ultraviolette.


Les concentrations de lidocaïne étaient plus élevées chez les patients témoins pour la première heure; cependant, après deux heures, les niveaux étaient les mêmes dans tous les échantillons. Les niveaux de MEGX ont augmenté constamment chez les patients des deux groupes et ont été significativement plus hauts chez les témoins. La somme des concentrations de lidocaïne et de MEGX a été plus élevée dans le groupe témoin pour les deux premières heures, mais il n’y a pas eu de différence intergroupe significative après trois heures. Conclusion: La réduction des possibilités de toxicité générale, par l’ajout d’épinéphrine à la lidocaïne, est limitée, car la réduction de la somme des concentrations plasmatiques de lidocaïne et de son métabolite actif, le MEGX, est faible et n’apparaît qu’à la phase initiale de la perfusion.


  1. 1.
    Berde CB. Convulsions associated with pediatric regional anesthesia. Anesth Analg 1992; 75: 164–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Miyabe M, Kakiuchi Y, Kihara S, et al. The plasma concentration of lidocaine’s principal metabolite increases during continuous epidural anesthesia in infants and children. Anesth Analg 1998; 87: 1056–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Braid DP, Scott DB. The systemic absorption of local analgesic drugs. Br J Anaesth 1965; 37: 394–404.PubMedCrossRefGoogle Scholar
  4. 4.
    Tucker GT, Mather LE. Pharmacokinetics of local anaesthetic agents. Br J Anaesth 1975; 47: 213–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Mather LE, Tucker GT, Murphy TM, Stanton-Hicks MD, Bonica JJ. The effects of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia II: pharmakokinetics. Br J Anaesth 1976; 48: 989–94.PubMedCrossRefGoogle Scholar
  6. 6.
    Takasaki M, Kajitani H. Plasma lidocaine concentrations during continuous epidural infusion of lidocaine with and without epinephrine. Can J Anaesth 1990; 37: 166–9.PubMedGoogle Scholar
  7. 7.
    Kihara S, Miyabe M, Kakiuchi Y, et al. Plasma concentrations of lidocaine and its principal metabolites during continuous epidural infusion of lidocaine with or without epinephrine. Reg Anesth Pain Med 1999; 24: 529–33.PubMedCrossRefGoogle Scholar
  8. 8.
    Kohda Y, Kakiuchi Y, Miyabe M, Sato S, Toyooka H, Sagara E. Simultaneous determination of lidocaine and its deethyl-metabolites in plasma and its application to drug level monitoring in infants. J Appl Ther Res 1998; 2: 33–8.Google Scholar
  9. 9.
    Kakiuchi Y, Kohda Y, Miyabe M, Momose Y. Effect of plasma α1-acid glycoprotein concentration on the accumulation of lidocaine metabolites during continuous epidural anesthesia in infants and children. Int J Clin Pharmacol Ther 1999; 37: 493–8.PubMedGoogle Scholar
  10. 10.
    Tucker GT, Mather LE. Clinical pharmacokinetics of local anaesthetics. Clin Pharmacokinet 1979; 4: 241–78.PubMedGoogle Scholar
  11. 11.
    Scott DB, Jebson PJR, Braid DP, Örtengren B, Frisch P. Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 1972; 44: 1040–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Sharrock NE, Go G, Mineo R. Effect of i.v. low-dose adrenaline and phenylephrine infusions on plasma concentrations of bupivacaine after lumbar extradural anaesthesia in elderly patients. Br J Anaesth 1991; 67: 694–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Ward RJ, Bonica JJ, Freund FG, Akamatsu T, Danziger F, Englesson S. Epidural and subarachnoid anesthesia. Cardiovascular and respiratory effects. JAMA 1965; 191: 275–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Burm AGL, van Kleef JW, Gladines MPRR, Olthof G, Spierdijk J. Epidural anesthesia with lidocaine and bupivacaine: effects of epinephrine on the plasma concentration profiles. Anesth Analg 1986; 65: 1281–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Kozody R, Palahniuk RJ, Wade JG, Cumming MO, Pucci WR. The effect of subarachnoid epineprine and phenylephrine on spinal cord blood flow. Can Anaesth Soc J 1984: 31; 503–8.PubMedGoogle Scholar
  16. 16.
    Blumer J, Strong JM, Atkinson AJ Jr. The convulsant potency of lidocaine and its N-dealkylated metabolites. J Pharmacol Exp Ther 1973; 186: 31–6.PubMedGoogle Scholar
  17. 17.
    Drayer DE, Lorenzo B, Werns S, Reidenberg MM. Plasma levels, protein binding, and elimination data of lidocaine and active metabolites in cardiac patients of various ages. Clin Pharmacol Ther 1983; 34: 14–22.PubMedGoogle Scholar
  18. 18.
    Strong JM, Atkinson AJ Jr. Simultaneous measurement of plasma concentrations of lidocaine and its desethylated metabolite by mass fragmentography. Anal Chem 1972; 44: 2287–90.CrossRefGoogle Scholar
  19. 19.
    Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 1977; 4: 439–48.PubMedGoogle Scholar
  20. 20.
    Savarese JJ, Covino BG. Basic and clinical pharmacology of local anesthetic drugs.In: Miller RD (Ed.). Anesthesia, 2nd ed. New York: Churchill Livingstone Inc., 1986: 985–1013.Google Scholar

Copyright information

© Canadian Anesthesiologists 2002

Authors and Affiliations

  • Masayuki Miyabe
    • 1
  • Yoshihiro Kakiuchi
    • 2
  • Shinichi Inomata
    • 1
  • Yoshiko Ohsaka
    • 1
  • Yukinao Kohda
    • 2
  • Hidenori Toyooka
    • 1
  1. 1.Department of Anesthesiology, Institute of Clinical MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Department of Pharmacy, Institute of Clinical MedicineUniversity of TsukubaTsukubaJapan

Personalised recommendations