Plasma levels of clonidine following epidural bolus injection in children

Background: The use of clonidine as an adjunct to epidural administration of local anesthetics in children has been reported to substantially improve the duration and quality of postoperative analgesia. The aims of the present study were to determine the pharmacokinetic profile and to investigate the interaction between postoperative sedation and analgesia after epidurally administered clonidine in children. Methods: Plasma levels of clonidine (0–10 h postop) and assessment of postoperative analgesia and sedation (0–24 h postop) were performed at predetermined intervals following lumbar epidural administration of bupivacaine 2.0 mg/kg and clonidine 2 mg/kg in 8 children undergoing ureteral re‐implantation surgery using general anesthesia (age range: 1–9 yr, weight range: 9–11 kg). Plasma levels of clonidine were analyzed by radioimmunoassay, and sedation and analgesia were assessed by previously described scoring systems. Results: The venous plasma pharmacokinetics of clonidine following epidural administration showed a considerable interindividual variation. Cmax and Tmax values of clonidine were found to be within the 0.45–0.77 ng/mL and 48–193 min range, respectively. The time to absorb 95% of the clonidine dose from the epidural space into plasma varied between 36 min and 7.6 h. In 6 of the 8 patients postoperative analgesia substantially outlasted the duration of sedation (≥2 h). Sedation could not be detected in any patients at plasma concentrations below 0.3 ng/mL. Conclusions: The pharmacokinetic profile associated with epidural clonidine administration in children (1–9 y) was similar to that previously reported in adults. The postoperative analgesia seen after administration of epidural bupivacaine‐clonidine during general anesthesia in children cannot only be explained by residual postoperative sedation.