Bupivacaine Levels in Liver Resection Patients

Hepatectomy Clinical Trial

Official title:

Blood Levels of Bupivacaine in Liver Resection Patients Sited With an Epidural Catheter for Postoperative Pain Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03145805
• Other study ID #: ANAE-300-16
• Status: Completed
• Start date: June 19, 2017
• Est. completion date: February 15, 2020

Study information

• Verified date: July 2021
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 15, 2020
• Est. primary completion date: February 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• scheduled to undergo elective liver resection surgery

• indicated to be sited with an epidural catheter for bupivacaine infusion for the management of postoperative pain

• competent to provide informed consent

• American anesthesiologists physical classification of I-IV

Exclusion Criteria:

• pregnant

• renal failure requiring dialysis

• sepsis

• ejection fraction documented as <15%

• taking fluvoxamine or itraconazole

• unable to understand or read English

Related Conditions & MeSH terms

• Analgesia, Epidural
• Hepatectomy

Locations

Country	Name	City	State
Canada	Kingston General Hospital	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Queen's University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bound bupivacaine levels-1	plasma bound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit	1-2 hours following surgery
Primary	bound bupivacaine levels-2	plasma bound bupivacaine levels on postoperative day 2.	48 hours following surgery
Primary	bound bupivacaine levels-3	plasma bound bupivacaine levels upon discontinuation of bupivacaine infusion (3-5 days postoperatively)	72-120 hours following surgery
Primary	unbound bupivacaine levels-4	plasma unbound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit	1-2 hours following surgery
Primary	unbound bupivacaine levels-5	plasma unbound bupivacaine levels on postoperative day 2.	48 hours following surgery
Primary	unbound bupivacaine levels-6	plasma unbound bupivacaine levels upon discontinuation of bupivacaine infusion	72-120 hours following surgery
Primary	alpha-1-acid glycoprotein levels-(AGP)-1	plasma AGP levels preoperatively	1 hour preoperatively
Primary	alpha-1-acid glycoprotein levels-(AGP)-2	plasma AGP levels postoperatively upon entry to the post anesthesia care unit	1-2 hours postoperatively
Primary	alpha-1-acid glycoprotein levels-(AGP)-3	plasma AGP levels on postoperative day 2	48 hours postoperatively
Primary	alpha-1-acid glycoprotein levels-(AGP)-4	plasma AGP levels upon discontinuation of the bupivacaine infusion 3-5 days postoperatively	72-120 hours postoperatively
Secondary	signs/symptoms of local anesthetic toxicity-1	tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-preoperatively	1 hour preoperatively
Secondary	signs/symptoms of local anesthetic toxicity-2	tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-upon entry to the post anesthesia care unit	1-2 hours postoperatively
Secondary	signs/symptoms of local anesthetic toxicity-3	tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-on postoperative day 2	48 hours postoperatively
Secondary	signs/symptoms of local anesthetic toxicity-4	tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-upon discontinuation of bupivacaine infusion-3-5 days postoperatively	72-120 hours postoperatively
Secondary	surgical site pain-1	reported pain score of surgical area preoperatively on a scale of 0-10	1 hour preoperatively
Secondary	surgical site pain-2	reported pain score of surgical area preoperatively on a scale of 0-10 upon entry to PACU	1-2 hours postoperatively
Secondary	surgical site pain-3	reported pain score of surgical area preoperatively on a scale of 0-10 on postoperative day 2	48 hours postoperatively
Secondary	surgical site pain-4	reported pain score of surgical area preoperatively on a scale of 0-10 upon discontinuation of the bupivacaine infusion	72-120 hours postoperatively