Plasma Kinetics of Levobupivacaine After Transversus Abdominis Plane (TAP) Block in Abdominal Surgery

Official title

Plasma Kinetics of Levobupivacaine After Transversus Abdominis Plane (TAP) Block in Abdominal Surgery: A Prospective Study and Definition of a Safety Window for Intravenous Lidocaine Administration

Overview

This prospective single-center observational pharmacokinetic study will evaluate plasma levobupivacaine concentrations after ultrasound-guided transversus abdominis plane (TAP) block in adult patients undergoing elective abdominal surgery under general anesthesia at CHU Liège. Participants receiving TAP block as part of standard clinical care (levobupivacaine 0.375%, total volume 40 mL, maximum dose 150 mg) will undergo serial blood sampling at 3, 7, 15, 30, 60, 120, and 180 minutes after block completion. Plasma levobupivacaine concentrations will be measured using validated LC-MS/MS methods. The primary objectives are to estimate maximum plasma concentration (Cmax) and time to maximum concentration (Tmax). Secondary objectives include characterization of the concentration-time profile, AUC0-180, interindividual variability, and exploratory associations with clinical factors (age, sex, BMI, type of surgery). The study also aims to inform a pragmatic safety window for subsequent intravenous lidocaine infusion used in multimodal analgesia protocols. Approximately 26 participants will be enrolled. No modification of routine anesthesia or analgesic care is required apart from study-related blood sampling.

Detailed description

This prospective single-center pharmacokinetic observational study is designed to characterize systemic exposure to levobupivacaine after ultrasound-guided transversus abdominis plane (TAP) block performed as part of routine perioperative analgesia for elective abdominal surgery under general anesthesia.

TAP block is widely integrated into multimodal analgesic pathways because it may reduce postoperative pain and opioid requirements. However, administration of relatively large volumes of local anesthetic into fascial planes can result in measurable systemic absorption. Although levobupivacaine has a favorable safety profile compared with racemic bupivacaine, understanding peak plasma concentrations and their timing remains clinically relevant, particularly when additional analgesic strategies such as intravenous lidocaine may be considered during the perioperative period.

Eligible adult participants scheduled for abdominal surgery and already planned to receive TAP block according to institutional practice will be enrolled after informed consent. No changes to standard anesthetic or surgical management are mandated by the study. The TAP block will be performed by experienced anesthesiologists using the institutional standard technique with levobupivacaine 0.375% (total volume 40 mL; maximum dose 150 mg).

The reference time (T0) will be defined as completion of local anesthetic injection. Serial blood samples will be obtained during the early postoperative period at predefined time points up to 180 minutes after T0 to capture the expected absorption phase and early elimination profile. Plasma levobupivacaine concentrations will be quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.

The primary pharmacokinetic parameters of interest are maximum observed plasma concentration (Cmax) and time to maximum concentration (Tmax). Secondary analyses will include concentration-time profiles, area under the curve from 0 to 180 minutes (AUC0-180), interindividual variability, and exploratory evaluation of associations between exposure metrics and selected demographic or clinical variables such as age, body mass index, sex, and surgical category.

Results are expected to provide real-world pharmacokinetic data for levobupivacaine after TAP block and may help inform safer sequencing of multimodal analgesic approaches, including timing of intravenous lidocaine administration after fascial plane block. Safety monitoring will follow routine perioperative standards, and any suspected local anesthetic systemic toxicity will be managed immediately according to institutional protocols.

Interventions

• Procedure Ultrasound-Guided Transversus Abdominis Plane Block with Levobupivacaine
  Ultrasound-guided transversus abdominis plane (TAP) block performed as part of routine perioperative analgesia after induction of general anesthesia for elective abdominal surgery. Levobupivacaine 0.375% is injected into the transversus abdominis fascial plane under real-time ultrasound visualization, using a total volume of 40 mL (typically bilateral administration, adjusted to surgical indication), with a maximum total dose of 150 mg. The block is performed by an experienced anesthesiologist a

Primary outcome measures

• Maximum Plasma Levobupivacaine Concentration (Cmax) [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]
• Time to Maximum Plasma Levobupivacaine Concentration (Tmax) [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]

Secondary outcome measures (6)

• Area Under the Plasma Concentration-Time Curve From 0 to 180 Minutes (AUC0-180) of Levobupivacaine [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]
• Plasma Levobupivacaine Concentration at Each Sampling Time Point [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement.]
• Interindividual Variability of Maximum Plasma Levobupivacaine Concentration (Cmax) [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]
• Association Between Area Under the Plasma Concentration-Time Curve (AUC0-180) and Clinical Factors [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]
• Time to Reach Plasma Levobupivacaine Concentration Below Prespecified Safety Threshold [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]
• Interindividual Variability of Area Under the Plasma Concentration-Time Curve (AUC0-180) [Time frame: From completion of TAP block (T0) to 180 minutes post-block placement]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Scheduled elective abdominal surgery under general anesthesia
• Planned ultrasound-guided TAP block as part of standard perioperative analgesic care
• Able to understand and speak French sufficiently to understand the study information and consent form
• Able and willing to provide written informed consent

Exclusion criteria

• Refusal or inability to provide informed consent
• Known allergy or hypersensitivity to amide local anesthetics
• Severe hepatic impairment
• Renal impairment (estimated glomerular filtration rate <50 mL/min/1.73 m²)
• Contraindication to repeated blood sampling or inability to complete the sampling schedule
• Participation in another clinical study that could affect absorption, distribution, metabolism, or elimination of local anesthetics
• Pregnancy
• Emergency surgery or life-threatening urgent condition
• Immediate postoperative instability requiring intensive care transfer (e.g., hemodynamic instability)
• Inability to understand French sufficiently for study information and consent
• Persons requiring special legal protection for consent (e.g., minors, guardianship, incapacity to consent)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Jokinen MJ, Neuvonen PJ, Lindgren L, Hockerstedt K, Sjovall J, Breuer O, Askemark Y, Ahonen J, Olkkola KT. Pharmacokinetics of ropivacaine in patients with chronic end-stage liver disease. Anesthesiology. 2007 Jan;106(1):43-55. doi: 10.1097/00000542-200701000-00011. PMID 17197844
• Mann B, Burch E, Shakeshaft C. Attitudes Toward Acupuncture Among Pain Fellowship Directors. Pain Med. 2016 Mar;17(3):494-500. doi: 10.1093/pm/pnv001. Epub 2015 Dec 7. PMID 26814237
• Atwill ER, Harp JA, Jones T, Jardon PW, Checel S, Zylstra M. Evaluation of periparturient dairy cows and contact surfaces as a reservoir of Cryptosporidium parvum for calfhood infection. Am J Vet Res. 1998 Sep;59(9):1116-21. PMID 9736387
• Yun H, Park M, Lee H, Choi EK. Healthcare Interventions for Children Using Nonimmersive Virtual Reality: A Mixed Methods Systematic Review. J Pediatr Health Care. 2024 Sep-Oct;38(5):703-716. doi: 10.1016/j.pedhc.2024.01.008. Epub 2024 Mar 10. PMID 38466243

Identifiers

NCT: NCT07581275 · B7072026000035

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗