Modeling the anesthetic effect of ropivacaine after a femoral nerve block in orthopedic patients: a population pharmacokinetic-pharmacodynamic analysis.

Abstract

Even though ropivacaine is frequently used during orthopedic surgery, the relationship between plasma concentrations and degree of sensory anesthesia after a peripheral nerve block is currently unknown. The aim of this study was to characterize this relation using population pharmacokinetic-pharmacodynamic modeling. Femoral nerve block was performed by the anterior approach using a single injection (20 ml) of 0.5% ropivacaine hydrochloride in 20 patients scheduled for total knee arthroplasty under spinal anesthesia. Sensory thresholds in response to a gradual increase in transcutaneous electrical stimulation (primary endpoints), loss and recovery of ice-cold sensation, as well as total ropivacaine plasma concentrations were determined up to 4 days after administration of the local anesthetic. Using NONMEM (ICON, USA), sensory block was modeled by assuming an equilibration delay (ke0) between amount in the depot and effect-site compartments. Mean effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 mg. At 2 × AE90, the sigmoid Emax model predicted a mean onset time of 23.4 min and mean duration of 22.9 h. Interindividual variability (IIV) for AE50 was 49%. Typical ke0 half-life was 34.7 min (IIV = 52%) and steepness parameter 8.7 (IIV = 48%). None of the pharmacodynamic model parameters showed sex, age, or body weight dependency. A population pharmacokinetic/pharmacodynamic model was developed that quantitatively describes the sensory component of a femoral nerve block in orthopedic patients. Further clinical studies will be needed to validate the clinical relevance of this finding.