Ropivacaine Wound Infiltration for Pain Management After Breast Cancer Mastectomy: A Population Pharmacokinetic Analysis

Abstract

Ropivacaine continuous wound infusions (CWIs) are extensively used as a component of multimodal analgesia. The rational application of CWI of ropivacaine requires a thorough understanding of its pharmacokinetics to investigate the risk of potential systemic toxicity. A population pharmacokinetic (popPK) study was undertaken to describe the pharmacokinetics of ropivacaine CWI during 75 hours. Women undergoing a unilateral mastectomy were scheduled to receive CWI for 40 hours for postoperative analgesia. A 10-mL ropivacaine 0.75% bolus followed by continuous infusion (400 mL of 0.2% ropivacaine at a flow rate of 10 mL/h) was administered via a multihole catheter placed on the major pectoral muscle. PopPK analysis was performed using the nonlinear mixed-effects model. A 1-compartment disposition model with an absorption compartment and a transit compartment for the infusion best describes the data (67 observations from 10 women). Population parameter estimates (between-subject variability, %) are apparent central volume (V/F) 269 L (39.1%), apparent clearance (CL/F) 18.8 h (74.9%), and absorption rate (K12) 0.406 h . The model predicted C as 1.45 ± 0.80 μg/mL, which occurred in the 42.4 hour (39-45.9 hours). This popPK model describes the pharmacokinetics of ropivacaine during continuous wound infusion and confirms the safety profile of the present technique.