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.
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.
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.
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.
- Postoperative pain associated with living donor open partial hepatectomy can be intense and persistent
- Intraoperative IV lidocaine infusions in patients undergoing open abdominal procedures reduce both postoperative pain scores and morphine requirements in the first 72 postoperative hours
- Lidocaine undergoes hepatic metabolism to the active metabolites monoethylglycinexylidide and glycinexylidide, which also undergo hepatic metabolism
- Pharmacokinetic changes experienced by patients undergoing living donor hepatectomy are likely due to the anesthesia, laparotomy, and isolation of hepatic blood vessels for liver resection
- The hypothesis that the elimination clearances of lidocaine, monoethylglycinexylidide, and glycinexylidide are reduced after a partial hepatectomy for living liver donation was tested in 15 patients who received intraoperative lidocaine infusions until graft isolation
- The typical value (± standard error of the estimate) for baseline lidocaine elimination clearance, 0.55 (± 0.12) l/min, decreased to 0.17 (± 0.02) l/min once the donor graft was surgically isolated, and monoethylglycinexylidide and glycinexylidide clearances were proportionately reduced after hepatectomy
- The fraction of the liver remaining was a significant model covariate