Lidocaine Intraoperative Infusion Pharmacokinetics during Partial Hepatectomy for Living Liver Donation

Author:

Crouch Cara E.1ORCID,Wilkey Barbara J.2,Hendrickse Adrian3,Kaizer Alexander M.4,Schniedewind Björn5,Christians Uwe6,Henthorn Thomas K.7,Fernandez-Bustamante Ana8

Affiliation:

1. 1Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.

2. 2Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.

3. 3Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.

4. 4Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; and Center for Innovative Design and Analysis, Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, Colorado.

5. 5Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; and iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine, Aurora, Colorado.

6. 6Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; and iC42 Clinical Research and Development Clinical Mass Spectrometry Service Center, University of Colorado School of Medicine, Aurora, Colorado.

7. 7Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.

8. 8Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.

Abstract

Background Postoperative pain associated with open partial hepatectomy can be intense and persistent. The multimodal approach used to lessen this problem includes an intraoperative intravenous infusion of lidocaine hydrochloride. Decreased hepatic metabolism after resection raises concerns about safe lidocaine dosing in this patient population. The hypothesis was that the elimination clearance of lidocaine and its metabolites, monoethylglycinexylidide and glycinexylidide, is reduced after a partial hepatectomy, as reflected by observed plasma concentrations that are higher and have a longer half-life than expected based on pharmacokinetic modeling (estimated for normal liver function). Secondarily, this study postulated that plasma concentrations of lidocaine, monoethylglycinexylidide, and glycinexylidide do not reach toxic concentrations with institutional protocol up to 24 h after surgery. Methods Blood samples were collected from 15 patients undergoing a partial hepatectomy for living liver donation, at the following specific time points: before and immediately after induction of anesthesia, during hepatectomy, 30 min after hepatectomy completion, at case end, and 24 h after the end of surgery. Plasma concentrations of lidocaine and metabolites were measured by liquid chromatography–mass spectrometry. The population lidocaine pharmacokinetics were estimated, and total body weight and the fraction of remaining liver mass as potential model covariates were evaluated. The detection of any lidocaine, monoethylglycinexylidide, or glycinexylidide toxic plasma concentrations at any time point during and after hepatectomy were also evaluated. Results The typical value for lidocaine elimination clearance was 0.55 ± 0.12 l/min (± standard error of the estimate) which, on average, was reduced to about one third of the baseline clearance, 0.17 ± 0.02 l/min, once the donor graft was surgically isolated, and remained so for 24 h according to the current data and model. The fraction of remaining liver was a significant covariate for the posthepatectomy lidocaine clearance‚ such that if 50% of the liver is removed the clearance is reduced by approximately 60%. Plasma concentrations of lidocaine and its metabolites remained below their theoretical combined toxic threshold concentrations throughout the surgical and postoperative course in all patients, with one exception obtained near induction of anesthesia. Plasma lidocaine concentrations decreased at case end and postoperatively, while metabolite concentrations continued to rise at the end of surgery with reduction postoperatively. Pharmacokinetic modeling revealed that the only significant covariate in the model was the fraction of liver remaining after isolation of the donor graft. Conclusions Intravenous lidocaine infusions are an acceptable option for multimodal pain management in patients undergoing a hepatectomy for living donation if the lidocaine infusion is stopped when the liver resection is complete. Clearance of lidocaine is decreased proportionally to the remaining liver mass, which should guide lidocaine infusion administration or dosing adjustments for patients undergoing liver resection surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference23 articles.

1. United Network for Organ Sharing: UNOS Report of Living Liver Donors Performed in the U.S.Available at https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. Accessed on October 16, 2020.

2. Acute and chronic postsurgical pain after living liver donation: Incidence and predictors.;Holtzman;Liver Transpl,2014

3. Fatigue, pain, and other physical symptoms of living liver donors in the adult-to-adult living donor liver transplantation cohort study.;Butt;Liver Transpl,2018

4. Acute and chronic postsurgical pain after living liver donation: Incidence and predictors.;Soyama;Liver Transpl,2015

5. Evaluation of the enhanced recovery after surgery protocol in living liver donors.;Khalil;Clin Transplant,2018

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