Bupivacaine Levels in Liver Resection Patients

Overview

Bupivacaine is a local anesthetic commonly used to manage postoperative pain. Liver resection patients typically have an epidural catheter placed preoperatively through which they receive a continuous infusion of bupivacaine and hydromorphone for up to 5 days postoperatively. The liver metabolizes bupivacaine, and produces proteins that bind with bupivacaine to take it out of circulation and thereby reduce its toxicity. Because a portion of the liver is being removed due to pre-existing liver disease, investigators hypothesize that liver resection patients have an impaired ability to clear bupivacaine from circulation that may increase their susceptibility to bupivacaine toxicity. To assess this, investigators will measure free and bound bupivacaine in liver resection patients postoperatively to determine whether bupivacaine reaches toxic levels. Investigators will also quantify binding protein levels to determine if these levels are reduced after surgery, which could contribute to the elevated bupivacaine levels in these patients. Finally, investigators will monitor patients for signs and symptoms associated with bupivacaine toxicity.

This observational study has been approved for ethical compliance by the Queen's University Health Sciences \& Affiliated Teaching Hospitals Research Ethics Board. Following signed informed consent, investigators will collect blood samples from 20 liver resection patients preoperatively and then at 3 different time points after their liver surgery at Kingston General Hospital (upon entry to the post-anesthetic care unit \[PACU\], on postoperative day 2, and immediately prior to discontinuation of the bupivacaine infusion). These blood draws will occur at the same time as standard of care blood draws. Blood will be centrifuged, and plasma will be stored in duplicate at -70°C until all samples are collected. Samples will be shipped to Centre De Recherche, Centre De Hospitalier, de l'Universitie de Montreal (CHUM) in Montreal, Quebec, Canada, for quantification of free and total bupivacaine as well as AGP. In addition to quantifying circulating bupivacaine and AGP concentrations, investigators will also assess postoperative wound pain on a visual analog scale from 0 to 10, and the presence/absence of local anesthetic toxicity symptoms (tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia).6 These will be assessed as close as possible to the blood collection times (preoperatively, upon arrival to the PACU, on postoperative day 2, and immediately prior to discontinuation of the bupivacaine infusion). Finally, demographic and surgical characteristics will be recorded for all participants. Inclusion criteria are competent ASA I-IV patients 18 years of age and older scheduled for elective liver resection of at least 3 segments who receive epidural bupivacaine infusion for pain control. Exclusion criteria: pregnancy, renal failure requiring dialysis, sepsis, ejection fraction documented as \<15%, taking fluvoxamine or itraconazole, and inability to understand and read English. Investigators have several outcomes of interest in this study. Of primary interest: plasma concentrations of free and bound bupivacaine and AGP at various time points after surgery. Additional outcomes of interest are pain scores and signs or symptoms of local anesthetic toxicity. Demographic and surgical characteristics will be collected for each patient. Descriptive, univariate and multivariable analyses will be completed with the assistance of a biostatistician.