Peritoneal Cancer
Conditions
Keywords
Local Anesthetic Solution, Bupivacaine HCl, Liposomal Bupivacaine, Peritoneal Cancer
Brief summary
The goal of this clinical research study is to compare the effects of 4 quadrant TAP block (4Q-TAP block) with the standard-of-care thoracic epidural analgesia (TEA) in patients recovering from cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A 4Q-TAP block is also known as an abdominal wall block and TEA is also known as a thoracic epidural. Both are types of anesthetics but are given in different ways. A 4Q-TAP block is when anesthetic injections are given in 4 different parts of the abdomen. A TEA is when an anesthetic injection is given in the space surrounding the spinal cord through your back. This is an investigational study. The surgery and the levels of anesthetic participant is receiving are standard-of-care. It is investigational to compare 4Q-TAP block with TEA. Up to 140 participants will be enrolled in this study. All will take part at MD Anderson.
Detailed description
Baseline Tests: If participant agrees to take part in this study, within 60 days before participant's surgery: * Participant will have a physical exam. * Blood (about 8 teaspoons) will be drawn for routine tests. * Participant will complete a questionnaire about the quality of recovery. Participant's responses before surgery will be compared to participant's responses after surgery. It should take about 5 minutes to complete. Study Groups/Procedures: Participant will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups on the morning of participant's surgery. This is done because no one knows if one study group is better, the same, or worse than the other group. * If participant is in Group 1, participant will receive standard-of-care TEA before participant goes to sleep. * If participant is in Group 2, participant will receive the 4Q-TAP block injections after participant is asleep. If participant is in Group 1, participant will have a catheter placed in participant's back before surgery so that the TEA can be infused. If needed, participant may receive an injection of numbing medication and/or pain medication before the catheter is placed. Participant will sign a separate consent for the placement of the catheter. If participant is in Group 2, participant will receive up to four (4) injections of 4Q-TAP block directly into different parts of the abdomen. These injections will take place after participant has been given general anesthesia. An ultrasound will be used to guide these injections. Participant will not be awake for these injections. Both groups will sign a separate consent for the surgery that explains the procedures and the risks. Participant may receive standard drugs during surgery. The study staff can tell participant about the risks of these drugs and how they are given. For both groups, information about the surgery will be collected while participant is in the operating room. Post-Surgery: After surgery, participant will receive standard drugs for pain as needed. Participant will be asked to complete a questionnaire about the quality of participant's recovery on the following days after surgery: * Days 1-3 * Day 5 * Day 7 * Day 10 and * Day 30 The questionnaire should take about 5 minutes each time. Participant will complete the questionnaire in person or participant will be called on the phone to complete it if participant has already left the hospital. On Days 1, 2, and 7 after surgery, blood (about 8 teaspoons each time) will be drawn for routine tests. After participant leaves the hospital, researchers will collect information from participant's medical record about participant's standard follow-up visits. Length of Study Participation: Active participation in this study will be complete 30 days after the surgery.
Interventions
A bolus or infusion of local anesthetic solution with or without the addition opioids given before surgical incision according to anesthesia provider's clinical judgment.
DRUGBupivacaine HCl
30 mg of Bupivacaine HCl in 10 cc of preservative free normal saline (PFNS) injected before surgical incision in each of the four quadrants.
DRUGLiposomal Bupivacaine
65 mg of Liposomal Bupivacaine in 10 cc of PFNS injected before surgical incision in each of the four quadrants.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written Informed consent 2. 18 years old or older 3. American Society of Anesthesiologists physical status (ASA) 1-3 4. Scheduled surgery: open elective CRS-HIPEC 5. Able to complete the QoR 15 questionnaire 6. Patients scheduled to receive intraoperative chemotherapy
Exclusion criteria
1. Thrombocytopenia (platelet count: \<100,000 cell/dL), coagulopathy (International Normalized Ratio \> 1.5, PT\>16.5 seconds or aPTT \> 35.9 seconds) 2. Bupivacaine or liposomal bupivacaine sensitive or known allergy; 3. Pregnancy or breastfeeding patients 4. Patients with recent (within 60 days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. \>1.5) 5. Patients with recent (within 15 days preoperatively) history deteriorate kidney function (creatinine serum concentrations \> 2.5 mg/dL or eGFR \< 30 mL/kg/min) 6. Chronic opioid use defined as daily opioid use for more than one month prior the scheduled date of surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2 | 48 hours after CRS-HIPEC surgery | To compare the efficacy of 4 quadrants TAP blocks (4Q-TAP) versus Thoracic Epidural Analgesia (routine care) on the quality of recovery 48 hours after CRS-HIPEC surgery, measure by QoR-15 changes from Pre-Op to POD2. The QoR scale is a validated scoring system that allows for the quantification of a patient's early postoperative health status. The minimum score 0 and maximum score 150. The higher score mean a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA | During the 48 hours after CRS-HIPEC surgery | Opioid Consumption reported as morphine equivalents required during the 48 hours after the end of surgery. |
| Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA | Length of stay calculated from day of surgery to date of hospital discharge, up to 46 days | Length of stay calculated from day of surgery to date of hospital discharge. |
| 4Q-TAP Versus TEA on Postoperative Pain | 48 hours after CRS-HIPEC surgery | Pain intensity at rest and cough measure using a Validity and Reliability of the Verbal Numerical Rating Scale (VNRS) (0 = no pain - 10 = worst pain ever). Higher numerical scores on the scale indicate more pain, thus a worse outcome. Data reported as time-weighted pain scores from discharge from the PACU until 48 hours after the end of surgery. |
| Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48 | Within the first 48 hours after the end of CRS-HIPEC surgery | Opioid-related adverse (i.e. respiratory depression, pruritus, sedation, delirium) within the first 48 hours after the end of surgery. |
| Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | 48 hours after CRS-HIPEC surgery | Postoperative complications recorded using Clavien-Dindo scale and POMS. |
| Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA | 48 hours after CRS-HIPEC surgery | An adverse event is any symptom, sign, illness, or experience which develops or worsens during the course of the study, whether or not the event is considered related to study drug. Adverse events (AEs) related to the study interventions recorded within the first 48 hours after the end of surgery. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from November 2017 to February 2020.
Pre-assignment details
A total of 75 participants consented, 5 participants were inevaluable.
Participants by arm
| Arm | Count |
|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered. | 33 |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance. | 35 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Total | Standard-of-Care Thoracic Epidural Analgesia (TEA) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 15 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 53 Participants | 24 Participants |
| Age, Continuous | 57 years | 58 years | 58 years |
| Dexmedetomidine use No | 4 Participants | 8 Participants | 4 Participants |
| Dexmedetomidine use Yes | 31 Participants | 60 Participants | 29 Participants |
| Frozen plasma transfusions intraoperatively No | 34 Participants | 67 Participants | 33 Participants |
| Frozen plasma transfusions intraoperatively Yes | 1 Participants | 1 Participants | 0 Participants |
| History of Depression No | 27 Participants | 54 Participants | 27 Participants |
| History of Depression Yes | 8 Participants | 14 Participants | 6 Participants |
| Median Anesthesia Duration | 634 Minutes | 641 Minutes | 649 Minutes |
| Median BMI | 25.4 kg/m^2 | 26.6 kg/m^2 | 26.6 kg/m^2 |
| Median Crystalloids use | 3050 mililiters | 3050 mililiters | 3000 mililiters |
| Median propofol consumption | 200 milligrams | 235 milligrams | 672.7 milligrams |
| Perfusion completed No | 4 Participants | 8 Participants | 4 Participants |
| Perfusion completed Yes | 31 Participants | 60 Participants | 29 Participants |
| Preoperative antidepressants No | 28 Participants | 55 Participants | 27 Participants |
| Preoperative antidepressants Yes | 7 Participants | 13 Participants | 6 Participants |
| Preoperative Opioids No | 34 Participants | 66 Participants | 32 Participants |
| Preoperative Opioids Yes | 1 Participants | 2 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Red blood cell transfusion intraoperatively No | 33 Participants | 65 Participants | 32 Participants |
| Red blood cell transfusion intraoperatively Yes | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 35 participants | 68 participants | 33 participants |
| Sex: Female, Male Female | 21 Participants | 39 Participants | 18 Participants |
| Sex: Female, Male Male | 14 Participants | 29 Participants | 15 Participants |
| Urinary output | 900 mililiters | 783 mililiters | 665 mililiters |
| Volatile anesthesia No | 5 Participants | 8 Participants | 3 Participants |
| Volatile anesthesia Yes | 30 Participants | 60 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 |
| other Total, other adverse events | 17 / 33 | 16 / 35 |
| serious Total, serious adverse events | 0 / 33 | 1 / 35 |
Outcome results
Primary
Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2
To compare the efficacy of 4 quadrants TAP blocks (4Q-TAP) versus Thoracic Epidural Analgesia (routine care) on the quality of recovery 48 hours after CRS-HIPEC surgery, measure by QoR-15 changes from Pre-Op to POD2. The QoR scale is a validated scoring system that allows for the quantification of a patient's early postoperative health status. The minimum score 0 and maximum score 150. The higher score mean a better outcome.
Time frame: 48 hours after CRS-HIPEC surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2 | -45 score on a scale |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2 | -50 score on a scale |
Secondary
4Q-TAP Versus TEA on Postoperative Pain
Pain intensity at rest and cough measure using a Validity and Reliability of the Verbal Numerical Rating Scale (VNRS) (0 = no pain - 10 = worst pain ever). Higher numerical scores on the scale indicate more pain, thus a worse outcome. Data reported as time-weighted pain scores from discharge from the PACU until 48 hours after the end of surgery.
Time frame: 48 hours after CRS-HIPEC surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | 4Q-TAP Versus TEA on Postoperative Pain | Pain at Rest | 3 score on a scale |
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | 4Q-TAP Versus TEA on Postoperative Pain | Pain with Cough | 5 score on a scale |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | 4Q-TAP Versus TEA on Postoperative Pain | Pain at Rest | 4 score on a scale |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | 4Q-TAP Versus TEA on Postoperative Pain | Pain with Cough | 5 score on a scale |
Secondary
Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA
Length of stay calculated from day of surgery to date of hospital discharge.
Time frame: Length of stay calculated from day of surgery to date of hospital discharge, up to 46 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA | 11 days |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA | 11 days |
Secondary
Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA
Opioid Consumption reported as morphine equivalents required during the 48 hours after the end of surgery.
Time frame: During the 48 hours after CRS-HIPEC surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA | 4.5 morphine milligram equivalents (MME) |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA | 21 morphine milligram equivalents (MME) |
Secondary
Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA
An adverse event is any symptom, sign, illness, or experience which develops or worsens during the course of the study, whether or not the event is considered related to study drug. Adverse events (AEs) related to the study interventions recorded within the first 48 hours after the end of surgery.
Time frame: 48 hours after CRS-HIPEC surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA | 3 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA | 1 Participants |
Secondary
Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48
Opioid-related adverse (i.e. respiratory depression, pruritus, sedation, delirium) within the first 48 hours after the end of surgery.
Time frame: Within the first 48 hours after the end of CRS-HIPEC surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48 | 7 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48 | 7 Participants |
Secondary
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA
Postoperative complications recorded using Clavien-Dindo scale and POMS.
Time frame: 48 hours after CRS-HIPEC surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Renal Complications | 5 Participants |
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Cardiac Complications | 7 Participants |
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Gastrointestinal Complications | 1 Participants |
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Hematological Complications | 2 Participants |
| Standard-of-Care Thoracic Epidural Analgesia (TEA) | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Pulmonary Complications | 5 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Hematological Complications | 6 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Pulmonary Complications | 8 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Renal Complications | 5 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Gastrointestinal Complications | 0 Participants |
| Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block | Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA | Cardiac Complications | 4 Participants |