Stable plasma concentrations of unbound ropivacaine during postoperative epidural infusion for 24-72 hours in children

Background and objectives: The aim of this open, non-controlled, multi-centre study was to evaluate the pharmacokinetics and safety of a 24-72 h continuous epidural ropivacaine infusion in children aged 1-9 yr. Methods: After induction of general anaesthesia, 29 ASA I-II children, scheduled for major surgery in dermatomes below T10 had lumbar epidural catheters placed. A bolus of ropivacaine, 2 mg kg^-1, was given over 4 min, followed immediately by an infusion of 2 mg mL^-1 ropivacaine 0.4 mg kg^-1 h ^-1 for the next 24-72 h. Results: Plasma concentrations of total ropivacaine (mean 0.83 and 1.06 mg L^-1 at 16-31 and 59-72 h, respectively) and α1-acid-glucoprotein (mean 13 and 25 μmol L ^-1 at baseline and 59-72 h) increased over the course of the infusion. Plasma concentrations of unbound ropivacaine were stable throughout the epidural infusion (mean 0.021 range 0.011-0.068 and mean 0.016 range 0.009-0.023 mg L^-1 at 16-31 and 59-72 h, respectively) and were well below threshold levels associated with central nervous system toxicity in adults (0.35 mg L^-1). Apparent unbound clearance (mean 346, range 86-555 mL min^-1 kg^-1) showed no age-dependency. No signs of systemic toxicity or cardiovascular effects were observed. All patients received additional analgesics with morphine. Conclusion: Following a 24-72 h epidural infusion of ropivacaine 0.4 mg kg^-1 h^-1 in 1-9-yr-old children, the plasma concentrations of unbound ropivacaine were stable over time with no age-dependency.