Pharmacokinetics and efficacy of ropivacaine for continuous epidural infusion in neonates and infants

Introduction: The primary objective of this noncomparative study was to evaluate the pharmacokinetics of ropivacaine during a 48-72-h continuous epidural infusion of ropivacaine in children under 1 year. The secondary objectives were to assess efficacy and safety. Methods: Neonates and infants (ASA I-III, gestational age >= 37 weeks, >= 2.5 kg, scheduled for major abdominal or thoracic surgery) were included and separated into age groups: 0-30 (neonate), 31-90, 91-180, and 181-365 days. Ethics committee approval and informed parental consent were obtained before inclusion. An epidural catheter was introduced under general anesthesia at the appropriate dermatomal level. An initial bolus dose (0.9-2.0 mg.kg(-1) of ropivacaine 0.2%) was followed by an epidural infusion (0.2 mg.kg(-1).h(-1) for infants < 180 days or 0.4 mg.kg(-1).h(-1) for infants > 180 days). Plasma samples were collected every 12 h from 24 h, and on termination of the epidural infusion. Postoperative pain was evaluated using both the Objective Pain Scale and a four-graded descriptive scale. Results: Forty-five infants, median age 116 (0-362) days, were included. Forty-three and 19 patients received an infusion for at least 48 and 72 h, respectively. Satisfactory analgesia was provided in the majority, only 20 patients were given supplementary medication during the infusion. In all age groups, plasma concentrations of unbound ropivacaine leveled at 24 h, without any further increase at 48 and 72 h. Because of lower clearance of unbound ropivacaine in neonates (mean 33 ml.min(-1).kg(-1)) than in infants above the age of 30 days (80, 124, and 163 ml.min(-1).kg(-1), respectively, in the age groups 31-90, 91-180, and 180-365 days), unbound ropivacaine concentrations at the end of infusion were higher in neonates [median 0.10 mg.l(-1) (0.04-0.21 mg.l(-1))] than in infants > 30 days [median 0.03 mg.l(-1) (0.003-0.10 mg.l(-1))]. Conclusion: Epidural infusions (0.2-0.4 mg.kg(-1).h(-1) ropivacaine) provided satisfactory pain relief in neonates and infants under 1 year. As plasma concentrations of unbound ropivacaine were not influenced by the duration of the infusion, ropivacaine can be safely used for postoperative epidural infusion for 48-72 h. Levels of unbound ropivacaine were higher in the neonates than in the infants, but were below threshold concentrations for CNS toxicity in adults (>= 0.35 mg.l(-1)). This should not preclude the use of ropivacaine infusions in neonates but suggests a need for caution during the first weeks of life.