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

Abstract

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 (Cmax) and time to peak concentration (Tmax) were obtained from the data, terminal half-life (T1/2z), 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: Cmax 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 Tmax 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.