HepatectomyNCT03145805
Bupivacaine Levels in Liver Resection Patients
An observational study of Hepatectomy and Analgesia, Epidural, run by Jessica Burjorjee, MD, FRCPC at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatectomy, Analgesia, Epidural
- Type of treatment
- Injection or infusion
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 19 Jun 2017to 15 Feb 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Twenty patients over 18 years of age scheduled to undergo elective liver resection surgery and placement of an epidural catheter for continuous bupivacaine infusion to manage pain for 3-5 days postoperatively.
Who may be able to join
- 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
Who cannot join
- pregnant
- renal failure requiring dialysis
- sepsis
- ejection fraction documented as <15%
- taking fluvoxamine or itraconazole
- unable to understand or read English
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Blood Levels of Bupivacaine in Liver Resection Patients Sited With an Epidural Catheter for Postoperative Pain Control
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.
Read the detailed 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.
- Conditions
- Hepatectomy, Analgesia, Epidural
- Keywords
- blood chemical analysis, bupivacaine, local anesthetic toxicity, Drug-Related Side Effects and Adverse Reactions
- Medical subject headings
- Agnosia, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| liver resection patients | Liver resection patients sited with an epidural catheter for bupivacaine infusion for 3-5 days postoperatively to manage postoperative pain |
What is being measured
The primary outcome is the main question the study is designed to answer.
bound bupivacaine levels-1
plasma bound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit
Measured: 1-2 hours following surgery
bound bupivacaine levels-2
plasma bound bupivacaine levels on postoperative day 2.
Measured: 48 hours following surgery
bound bupivacaine levels-3
plasma bound bupivacaine levels upon discontinuation of bupivacaine infusion (3-5 days postoperatively)
Measured: 72-120 hours following surgery
unbound bupivacaine levels-4
plasma unbound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit
Measured: 1-2 hours following surgery
unbound bupivacaine levels-5
plasma unbound bupivacaine levels on postoperative day 2.
Measured: 48 hours following surgery
unbound bupivacaine levels-6
plasma unbound bupivacaine levels upon discontinuation of bupivacaine infusion
Measured: 72-120 hours following surgery
alpha-1-acid glycoprotein levels-(AGP)-1
plasma AGP levels preoperatively
Measured: 1 hour preoperatively
alpha-1-acid glycoprotein levels-(AGP)-2
plasma AGP levels postoperatively upon entry to the post anesthesia care unit
Measured: 1-2 hours postoperatively
alpha-1-acid glycoprotein levels-(AGP)-3
plasma AGP levels on postoperative day 2
Measured: 48 hours postoperatively
alpha-1-acid glycoprotein levels-(AGP)-4
plasma AGP levels upon discontinuation of the bupivacaine infusion 3-5 days postoperatively
Measured: 72-120 hours postoperatively
Secondary outcomes (8)
signs/symptoms of local anesthetic toxicity-1
tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-preoperatively
Measured: 1 hour preoperatively
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
Measured: 1-2 hours postoperatively
signs/symptoms of local anesthetic toxicity-3
tremor, tinnitus, dizziness, blurred vision, hypotension and arrhythmia (including bradycardia)-on postoperative day 2
Measured: 48 hours postoperatively
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
Measured: 72-120 hours postoperatively
surgical site pain-1
reported pain score of surgical area preoperatively on a scale of 0-10
Measured: 1 hour preoperatively
surgical site pain-2
reported pain score of surgical area preoperatively on a scale of 0-10 upon entry to PACU
Measured: 1-2 hours postoperatively
surgical site pain-3
reported pain score of surgical area preoperatively on a scale of 0-10 on postoperative day 2
Measured: 48 hours postoperatively
surgical site pain-4
reported pain score of surgical area preoperatively on a scale of 0-10 upon discontinuation of the bupivacaine infusion
Measured: 72-120 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start19 Jun 2017
- Primary completion15 Feb 2020
- Study completion15 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HepatectomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jessica Burjorjee, MD, FRCPC
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jessica Burjorjee, MD, FRCPC, Queen's University
- Investigators
- Jessica Burjorjee, MD, FRCPC, Principal investigator, Queen's University/Kingston General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03145805
- Sponsor's protocol ID
- ANAE-300-16
- Status last verified
- Mar 2025
- First submitted
- 5 May 2017
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Burjorjee J, Phelan R, Hopman WM, Ho AM, Nanji S, Jalink D, Mizubuti GB. Plasma bupivacaine levels (total and free/unbound) during epidural infusion in liver resection patients: a prospective, observational study. Reg Anesth Pain Med. 2022 Aug 24:rapm-2022-103683. doi: 10.1136/rapm-2022-103683. Online ahead of print.
PubMed 36002226
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Levels of Bupivacaine in Liver Resection Patients Sited With an Epidural Catheter for Postoperative Pain Control
- ClinicalTrials.gov ID
- NCT03145805
- Acronym / sponsor ID
- ANAE-300-16
- Conditions
- Hepatectomy, Analgesia, Epidural
- Keywords
- blood chemical analysis, bupivacaine, local anesthetic toxicity, Drug-Related Side Effects and Adverse Reactions
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Jessica Burjorjee, MD, FRCPCUniversity, hospital or other
- Study start
- 19 Jun 2017 (actual)
- Primary completion
- 15 Feb 2020 (actual)
- Study completion
- 15 Feb 2020 (actual)
- First posted
- 9 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| liver resection patients | – | –Liver resection patients sited with an epidural catheter for bupivacaine infusion for 3-5 days postoperatively to manage postoperative pain |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Twenty patients over 18 years of age scheduled to undergo elective liver resection surgery and placement of an epidural catheter for continuous bupivacaine infusion to manage pain for 3-5 days postoperatively.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- pregnant
- renal failure requiring dialysis
- sepsis
- ejection fraction documented as <15%
- taking fluvoxamine or itraconazole
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
bound bupivacaine levels-1
Time frame: 1-2 hours following surgery
plasma bound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit
bound bupivacaine levels-2
Time frame: 48 hours following surgery
plasma bound bupivacaine levels on postoperative day 2.
bound bupivacaine levels-3
Time frame: 72-120 hours following surgery
plasma bound bupivacaine levels upon discontinuation of bupivacaine infusion (3-5 days postoperatively)
unbound bupivacaine levels-4
Time frame: 1-2 hours following surgery
plasma unbound bupivacaine levels in liver resection patients upon entry to the post anesthesia care unit
unbound bupivacaine levels-5
Time frame: 48 hours following surgery
plasma unbound bupivacaine levels on postoperative day 2.
unbound bupivacaine levels-6
Time frame: 72-120 hours following surgery
plasma unbound bupivacaine levels upon discontinuation of bupivacaine infusion
alpha-1-acid glycoprotein levels-(AGP)-1
Time frame: 1 hour preoperatively
plasma AGP levels preoperatively
alpha-1-acid glycoprotein levels-(AGP)-2
Time frame: 1-2 hours postoperatively
plasma AGP levels postoperatively upon entry to the post anesthesia care unit
alpha-1-acid glycoprotein levels-(AGP)-3
Time frame: 48 hours postoperatively
plasma AGP levels on postoperative day 2
alpha-1-acid glycoprotein levels-(AGP)-4
Time frame: 72-120 hours postoperatively
plasma AGP levels upon discontinuation of the bupivacaine infusion 3-5 days postoperatively
8 secondary outcomes
signs/symptoms of local anesthetic toxicity-1
Time frame: 1 hour preoperatively
signs/symptoms of local anesthetic toxicity-2
Time frame: 1-2 hours postoperatively
signs/symptoms of local anesthetic toxicity-3
Time frame: 48 hours postoperatively
signs/symptoms of local anesthetic toxicity-4
Time frame: 72-120 hours postoperatively
surgical site pain-1
Time frame: 1 hour preoperatively
surgical site pain-2
Time frame: 1-2 hours postoperatively
surgical site pain-3
Time frame: 48 hours postoperatively
surgical site pain-4
Time frame: 72-120 hours postoperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Derived from this study: PubMed 36002226Burjorjee J, Phelan R, Hopman WM, Ho AM, Nanji S, Jalink D, Mizubuti GB. Plasma bupivacaine levels (total and free/unbound) during epidural infusion in liver resection patients: a prospective, observational study. Reg Anesth Pain Med. 2022 Aug 24:rapm-2022-103683. doi: 10.1136/rapm-2022-103683. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica Burjorjee, MD, FRCPC principal investigator
Queen's University/Kingston General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatectomy and Analgesia, Epidural, run by Jessica Burjorjee, MD, FRCPC at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
bound bupivacaine levels-1 (time frame: 1-2 hours following surgery). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03145805, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.