Pain Management Strategies in Liver Resection Surgery
Conditions
Keywords
thoracic epidural, continuous paravertebral catheter, PCA, liver resection, pain management
Brief summary
This study aims to compare the efficacy and safety of three alternative methods of analgesia in patients undergoing complex liver resection surgery: 1) thoracic epidural analgesia (TEA), 2) continuous paravertebral block (PVB) with patient-controlled analgesia (PCA) and 3) patient-controlled analgesia (PCA) alone. Regional anesthesia techniques such as TEA and PVB may improve recovery and decrease postoperative pain scores in addition to other benefits such earlier return of bowel function and shortened length of hospital stay, although some practitioners have voiced concerns about the safety and efficacy of these techniques in patients after liver resection who may develop postoperative coagulation abnormalities. The investigators plan to enroll a total of 150 patients (adults \>/= 18 years of age who meet study criteria) scheduled for complex liver resection surgery in this study, who will then be randomized into 50 patients per arm of the study (3 total arms). Postoperative pain scores will be collected in PACU and throughout the patient's hospital stay as well as routine blood tests including complete blood count, coagulation labs (PT/INR, aPTT) and serum creatinine to measure renal function. The study team will also collect additional data prospectively on all patients enrolled in the study; these parameters will include age, sex, type of operation performed, length of operation, volume of intraoperative blood loss, volume of intraoperative fluid administration including blood products, daily postoperative intravenous fluid administration, length of time to first feeding, day of epidural catheter removal, length of hospital stay and incidence of major postoperative complications (surgical, respiratory, cardiac, renal, etc.). Once primary and secondary data points are obtained, the data will undergo rigorous statistical analysis using the appropriate statistical techniques to determine the outcomes. The investigators propose that epidural and/or paravertebral analgesia may improve recovery times and decrease hospital length of stay, which would be beneficial for the patient as well as decrease hospital costs. In addition, if better postoperative pain management scores can be achieved with epidural or paravertebral analgesia, and no significant prolonged postoperative coagulopathy is associated with patients undergoing major hepatic resection surgical procedures, these regional analgesia strategies can be considered a safe option for pain management in this patient population.
Interventions
DEVICEthoracic epidural
Thoracic Epidural catheters will be placed between T8-12 interspaces preoperatively. Epidural hydromorphone (200-600mcg) will be given preoperatively. TEA will be dosed intraoperatively with a continuous infusion of 0.25% bupivacaine at 3-6ml per hour. At the end of surgery, infusion will be changed to 0.125% bupivacaine + 10mcg/ml hydromorphone at 4-6ml/hour. In PACU, a PCEA button will given to the patient for bolus dosing of 1-2ml and a lockout of 30 minutes. Changes to the epidural infusion solution, rate, and PCEA bolus dosing will be made clinically as required by the Acute Pain Service (APS).
DEVICEcontinuous paravertebral catheter
Bilateral PVB catheters will be placed between the T8-12 interspaces preoperatively. 10ml of 0.5% ropivacaine will be injected into the paravertebral space, then catheter placed. The same procedure will be used for the placement of the PVB catheter on the opposite side. The catheter may be bolused with 5ml 0.5% ropivacaine hourly intraoperatively if needed. In PACU, PVB catheters will be infused continuously with 0.2% ropivacaine at 8-12ml/hr. Subjects will also be given a hydromorphone PCA button to deliver additional IV opioid medication to the patient as needed.
DRUGPatient-Controlled Analgesia
Intravenous hydromorphone PCA will be initiated postoperatively with dosing prescriptions made by the primary surgical team.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age \>/= 18 years and \</= 80 years * Scheduled for elective hepatic resection surgery
Exclusion criteria
* Preexisting coagulopathy (INR \>1.5) * Spinal stenosis * Local infection in area where catheter will be inserted * Severe cardiovascular disease (NYHA Class III/IV) * Severe pulmonary disease (FEV1 \<50% of predicted value) * Allergy or sensitivity to narcotics or local anesthetics * BMI \>45 * Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Highest VAS Pain Score at Rest | postoperatively until regional catheter removed, with an expected average of 3 days and up to 7 days | Post-operative pain scores at rest, as assessed by Pain Assessment Scales (Wong-Baker Faces Scale and Visual Analog Pain Scale (VAS) will be the primary outcome measured. Pain scores will be collected per standard PACU protocol (every 60 minutes) and on the hospital ward at hours 2, 4, 6 and 12, and then daily until day 3 or when the epidural/paravertebral catheter is removed. Postoperative pain at rest will be defined as the highest VAS pain score reported by each patient at any time. Pain score is from 0 (no hurt) to 10 (hurts worst). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | time to discharge after surgery, with an expected average of approximately 7-10 days, up to 6 weeks if complications arise | Hospital length of stay will be recorded for each of the 3 groups to see if there is a statistical difference between groups. |
| Gastrointestinal Recovery | postoperatively until return of bowel function, up to 7 days | Postoperative return of bowel function and time to first feeding will be recorded for each of the 3 groups. |
| Incidence of Major Postoperative Complication | time to discharge after surgery, with an expected average of approximately 7-10 days, up to 6 weeks if complications arise | Major surgical, infectious, respiratory, cardiac, and renal complications will be recorded for subjects in each arm of the study. |
| Highest VAS Pain Scores With Coughing | postoperatively until regional catheter removed, with an expected average of 3 days and up to 7 days | Post-operative pain scores with coughing, as assessed by Pain Assessment Scales (Wong-Baker Faces Scale and Visual Analog Pain Scale (VAS) will be measured. Pain score is from 0 (no hurt) to 10 (hurts worst). |
| Cumulative Postoperative Opioid Requirement | postpoperatively until regional catheter removed or subjects transitioned to an oral pain management regimen, an expected average of 3 days and up to 7 days | Cumulative postoperative opioid use in morphine equivalents will be recorded for subjects in the 3 arms of the study. The investigators hypothesize that the TEA and/or PVB arms may show less opioid use over PCA. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events Associated With Regional Catheter Placement | postoperatively until removal of regional catheter removed, with an average of 3 days up to 7 days | Serious adverse events in the 2 arms with regional catheters (TEA and PVB) will be monitored |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thoracic Epidural thoracic epidural: Thoracic Epidural catheters will be placed between T8-12 interspaces preoperatively. Epidural hydromorphone (200-600mcg) will be given preoperatively. TEA will be dosed intraoperatively with a continuous infusion of 0.25% bupivacaine at 3-6ml per hour. At the end of surgery, infusion will be changed to 0.125% bupivacaine + 10mcg/ml hydromorphone at 4-6ml/hour. In PACU, a PCEA button will given to the patient for bolus dosing of 1-2ml and a lockout of 30 minutes. Changes to the epidural infusion solution, rate, and PCEA bolus dosing will be made clinically as required by the Acute Pain Service (APS). | 3 |
| Continuous Paravertebral Catheter continuous paravertebral catheter: Bilateral PVB catheters will be placed between the T8-12 interspaces preoperatively. 10ml of 0.5% ropivacaine will be injected into the paravertebral space, then catheter placed. The same procedure will be used for the placement of the PVB catheter on the opposite side. The catheter may be bolused with 5ml 0.5% ropivacaine hourly intraoperatively if needed. In PACU, PVB catheters will be infused continuously with 0.2% ropivacaine at 8-12ml/hr. Subjects will also be given a hydromorphone PCA button to deliver additional IV opioid medication to the patient as needed. | 4 |
| Patient-Controlled Analgesia Patient-Controlled Analgesia: Intravenous hydromorphone PCA will be initiated postoperatively with dosing prescriptions made by the primary surgical team. | 3 |
| Total | 10 |
Baseline characteristics
| Characteristic | Thoracic Epidural | Continuous Paravertebral Catheter | Patient-Controlled Analgesia | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 3 participants | 4 participants | 3 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 | 0 / 3 |
Outcome results
Primary
Highest VAS Pain Score at Rest
Post-operative pain scores at rest, as assessed by Pain Assessment Scales (Wong-Baker Faces Scale and Visual Analog Pain Scale (VAS) will be the primary outcome measured. Pain scores will be collected per standard PACU protocol (every 60 minutes) and on the hospital ward at hours 2, 4, 6 and 12, and then daily until day 3 or when the epidural/paravertebral catheter is removed. Postoperative pain at rest will be defined as the highest VAS pain score reported by each patient at any time. Pain score is from 0 (no hurt) to 10 (hurts worst).
Time frame: postoperatively until regional catheter removed, with an expected average of 3 days and up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thoracic Epidural | Highest VAS Pain Score at Rest | 5.67 units on a scale | Standard Deviation 2.08 |
| Continuous Paravertebral Catheter | Highest VAS Pain Score at Rest | 7.0 units on a scale | Standard Deviation 2.94 |
| Patient-Controlled Analgesia | Highest VAS Pain Score at Rest | 7.67 units on a scale | Standard Deviation 2.51 |
Secondary
Cumulative Postoperative Opioid Requirement
Cumulative postoperative opioid use in morphine equivalents will be recorded for subjects in the 3 arms of the study. The investigators hypothesize that the TEA and/or PVB arms may show less opioid use over PCA.
Time frame: postpoperatively until regional catheter removed or subjects transitioned to an oral pain management regimen, an expected average of 3 days and up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thoracic Epidural | Cumulative Postoperative Opioid Requirement | 388.33 mg | Standard Deviation 430.71 |
| Continuous Paravertebral Catheter | Cumulative Postoperative Opioid Requirement | 224.6 mg | Standard Deviation 236.5 |
| Patient-Controlled Analgesia | Cumulative Postoperative Opioid Requirement | 176.20 mg | Standard Deviation 40.14 |
Secondary
Gastrointestinal Recovery
Postoperative return of bowel function and time to first feeding will be recorded for each of the 3 groups.
Time frame: postoperatively until return of bowel function, up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thoracic Epidural | Gastrointestinal Recovery | 4.33 days | Standard Deviation 0.58 |
| Continuous Paravertebral Catheter | Gastrointestinal Recovery | 4.25 days | Standard Deviation 2.63 |
| Patient-Controlled Analgesia | Gastrointestinal Recovery | 5.33 days | Standard Deviation 1.53 |
Secondary
Highest VAS Pain Scores With Coughing
Post-operative pain scores with coughing, as assessed by Pain Assessment Scales (Wong-Baker Faces Scale and Visual Analog Pain Scale (VAS) will be measured. Pain score is from 0 (no hurt) to 10 (hurts worst).
Time frame: postoperatively until regional catheter removed, with an expected average of 3 days and up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thoracic Epidural | Highest VAS Pain Scores With Coughing | 7.33 units on a scale | Standard Deviation 2.52 |
| Continuous Paravertebral Catheter | Highest VAS Pain Scores With Coughing | 8.0 units on a scale | Standard Deviation 2.45 |
| Patient-Controlled Analgesia | Highest VAS Pain Scores With Coughing | 8.33 units on a scale | Standard Deviation 1.53 |
Secondary
Hospital Length of Stay
Hospital length of stay will be recorded for each of the 3 groups to see if there is a statistical difference between groups.
Time frame: time to discharge after surgery, with an expected average of approximately 7-10 days, up to 6 weeks if complications arise
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thoracic Epidural | Hospital Length of Stay | 10.33 days | Standard Deviation 4.93 |
| Continuous Paravertebral Catheter | Hospital Length of Stay | 6.25 days | Standard Deviation 2.5 |
| Patient-Controlled Analgesia | Hospital Length of Stay | 7.0 days | Standard Deviation 1 |
Secondary
Incidence of Major Postoperative Complication
Major surgical, infectious, respiratory, cardiac, and renal complications will be recorded for subjects in each arm of the study.
Time frame: time to discharge after surgery, with an expected average of approximately 7-10 days, up to 6 weeks if complications arise
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thoracic Epidural | Incidence of Major Postoperative Complication | 2 complications |
| Continuous Paravertebral Catheter | Incidence of Major Postoperative Complication | 2 complications |
| Patient-Controlled Analgesia | Incidence of Major Postoperative Complication | 0 complications |
Other Pre-specified
Serious Adverse Events Associated With Regional Catheter Placement
Serious adverse events in the 2 arms with regional catheters (TEA and PVB) will be monitored
Time frame: postoperatively until removal of regional catheter removed, with an average of 3 days up to 7 days
Population: only patients who had a catheter
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thoracic Epidural | Serious Adverse Events Associated With Regional Catheter Placement | 0 serious adverse events |
| Continuous Paravertebral Catheter | Serious Adverse Events Associated With Regional Catheter Placement | 0 serious adverse events |