Ropivacaine (total and unbound) and AGP concentrations after transversus abdominis plane block for analgesia after abdominal surgery

Abstract

BACKGROUND: The goal of this study was to assess the safety of single bolus dose of ropivacaine (ROP) followed by continuous infusion through transversus abdominis plane block catheter. The aim was to determine ROP absorbed from the infusion site, changes in protein binding after surgery, and clinical determinants of adverse effects. METHODS: Twelve patients undergoing laparotomy, received bilateral transversus abdominis plane block under ultrasound guidance using a 20-mL bolus of 0.5% ROP followed by 10 mL/h of 0.2% ROP infusion for 48 hours. Serial blood samples were drawn presurgery and to 48 hours postbolus. Plasma concentrations of total and unbound ROP were measured by high performance liquid chromatography with ultraviolet detection. Alpha-1 acid glycoprotein concentrations were measured by enzyme-linked immunosorbent assay. Patients were monitored for any signs or symptoms of central nervous system and chorionic villus sampling toxicity. RESULTS: After the bolus dose, the mean (±SD) peak plasma total (bound plus unbound) ROP concentration (Cmax) was 2.1 (±0.8) mg/L and unbound ROP concentration was 0.04 (±0.02) mg/L. During the infusion phase, total ROP concentration continued to rise to a mean (±) Cmax of 3.3 (±1.6) mg/L, and the peak unbound concentration was 0.06 (±0.0) mg/L. No patients showed symptoms of ROP toxicity or unacceptable QTc intervals. CONCLUSIONS: Although the total ROP concentrations approached or exceeded reported neurotoxicity thresholds, no patients had unbound ROP concentrations approaching the unbound toxicity threshold, nor showed any signs or symptoms of toxicity. This result was consistent with changes in protein binding to alpha-1 acid glycoprotein after surgery.