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In children, the addition of epinephrine modifies the pharmacokinetics of ropivacaine injected caudally

[Chez les enfants, l’addition d’épinéphrine modifie la pharmacocinétique de la ropivacaïne administrée en injection caudale]

Luc J. Van Obbergh, MD PhD^*, Fabienne A. Roelants, MD^*, Francis Veyckemans, MD^* and Roger K. Verbeeck, PhD

^* From the Department of Anesthesiology,
and the School of Pharmacy, Université catholique de Louvain, Brussels, Belgium.

Address correspondence to: Prof L.J. Van Obbergh, Department of Anesthesiology, Cliniques St Luc, 101821 Av. Hippocrate, B1200 Brussels, Belgium. Phone: 3227641821; Fax: 3227643699; E-mail: vanobbergh{at}anes.ucl.ac.be

Purpose: To describe the modification of the ropivacaine (R) pharmacokinetics produced by the addition of epinephrine (E).

Methods: After Institutional Review Board approval, 18 ASA I boys received a caudal block (1 mL•kg^-1) with either plain 0.2% R (Group E^-) or with 0.2% R containing E (5 µg•mL^-1; Group E⁺). Venous blood samples were taken at zero, 15, 30, 60, 90, 120, 180, 240, 420, 720, 1440 min after caudal injection. Total R concentration in plasma was determined by high pressure liquid chromatography. Maximal concentration (C_max) and time to peak concentration (T_max) were obtained from the data, terminal half-life (T_1/2z), clearance (Cl) and volume of distribution (Vd) were estimated by a non-compartmental approach. Subsequently, in order to determine the absorption rate (Ka) and to reduce to number of blood samples, 25 other children, receiving plain R and another group of 25 receiving the E solution were studied using a population approach (NONMEM). A one compartment model with first order absorption was used. The effect of weight, age and E on Cl, Vd and Ka was estimated.

Results: C_max was significantly lower in Group E⁺ (0.93 mg•L^-1 ± 0.29 vs 0.61 mg•L^-1 ± 0.28, P = 0.05) and T_max occurred later (124 min ± 53 vs 47min ± 16, P = 0.003).

Weight was a significant covariate for Cl and Vd while E significantly slowed R Ka [Group I Ka 0.025 min^-1 [coefficient of variation (CV) 21%] vs 0.078 min^-1 (CV 25%) in Group II].

Conclusion: The addition of E significantly modifies the pharmacokinetics of R injected caudally.

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