Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection

Abstract

AIMSThe aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. METHODSThis work is based on a single-centre, double-blinded, randomized, placebocontrolled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. RESULTSThe free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. CONCLUSIONSAlthough large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery. WHAT THIS STUDY ADDS• The free ropivacaine fraction is low after liver resection surgery (<2%).• The size of the liver resection affects the free ropivacaine clearance.• The pharmacokinetics of free and total ropivacaine could be analysed effectively even without α 1 -acid glycoprotein measurements. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Ropivacaine is highly bound to plasma proteins (α 1 -acid glycoprotein).• Ropivacaine is mainly metabolized by the liver.• Liver resection affects the protein binding and metabolism of ropivacaine.

Pharmacokinetics of 400 mg Locally Infiltrated Ropivacaine After Total Knee Arthroplasty Without Perioperative Tourniquet Use

“…In different pharmacokinetic studies, the unbound fraction of ropivacaine varies widely, the 2 main reasons being differences in analytical methods and differences in α1-acid glycoprotein. 21 Because we used the same analytical method and ultrafiltration technique in both studies and differences in α1-acid glycoprotein between the 2 study populations seem unlikely, we have no explanation for this difference in the unbound fraction of ropivacaine.…”

The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision

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<p>The Safety and Efficacy of Ultrasound-Guided Bilateral Dual Transversus Abdominis Plane (BD-TAP) Block in ERAS Program of Laparoscopic Hepatectomy: A Prospective, Randomized, Controlled, Blinded, Clinical Study</p>

“…One of the most important pharmacological characteristics of ropivacaine is that high systemic exposure to it often results in central nervous system disorders and cardiovascular disorders. 9 In a study including individuals receiving titrated intravenous infusions of ropivacaine, it was indicated that the onset of neurological symptoms occurred at a mean total plasma ropivacaine concentration of 2.20 μg/mL and free ropivacaine concentration of 0.15 (0.08) μg/mL. 10 In previous studies, potentially toxic plasma concentrations of ropivacaine have been assessed after ultrasoundguided CL-TAP blocks for cesarean sections and open major gynecological surgery.…”