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Traditionally, opioids are heavily utilized in treating postoperative pain but they are associated with numerous side effects. The use of the transversus abdominis plane (TAP) blocks have become standard practice to extend the post-operative analgesic window and limit opioid use. A new liposomal-depo formulation of bupivacaine (Exparel) has gained popularity as a long-lasting TAP block medication, but has not been studied in a well-powered clinical trial specifically in colorectal patients nor compared to a bupivacaine/steroid mixture which may offer similar effects. We conduct a prospective randomized prospective randomized study of patients undergoing major laparoscopic colorectal surgery to compare the analgesic effects of a bupivacaine/steroid mixture versus liposomal bupivacaine.
Postoperative pain can pose significant challenges in the postoperative recovery of patients undergoing major colorectal surgery. Traditionally, opioids have played an important role in treating postoperative pain. It is well established that opioids are highly effective in relieving pain; however, opioids are associated with numerous side effects that include nausea, vomiting, constipation, ileus, bladder dysfunction, respiratory depression, pruritus, drowsiness, sedation, and allergic reaction. These opioid side effects, which range in severity, can significantly interfere with discharge home, particularly following colorectal surgery. Significant interest has grown for the use of guided regional anesthesia, specifically the use of the transversus abdominis plane (TAP) block to extend the post-operative analgesic window and ultimately limit opioid use. While bupivacaine formulations including a steroid has been shown to prolong the anesthetic effects of the regional field block, a new liposomal-depo formulation of bupivacaine (Exparel) has gained popularity and has additionally been shown to provide extended analgesia. Although promising data exists surrounding each modality, liposomal bupivacaine has not been studied in a well-powered clinical trial specifically in colorectal patients nor compared to a bupivacaine/steroid mixture.
We are proposing a prospective randomized study of patients undergoing major laparoscopic colorectal surgery to compare the analgesic effects of a bupivacaine/steroid mixture versus liposomal bupivacaine (Exparel). We hypothesize that the liposomal formulation of bupivacaine will provide superior perioperative pain control at 48 hours post-operation measured by total consumed oral morphine equivalents. In addition, we will measure postoperative pain scores, time until ambulation, antiemetic use, length of postoperative hospital stay, postoperative ileus, and adverse events directly related or unrelated to TAP block in the 30-day postoperative period between the three groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bupivacaine/epinephrine/dexamethasone TAP block | Active Comparator | For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. |
|
| Liposomal bupivacaine TAP block | Active Comparator | For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liposomal bupivacaine | Drug | Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) | 48-hours |
| Measure | Description | Time Frame |
|---|---|---|
| Post-op Pain Score (Visual Analog Scale) | Visual pain scale recordings will be totaled and averaged during the first 72-hours post-surgery. Visual analog scale is determined by nursing staff when assessing pain scores. Scores range from 0-10 with 10 being the most pain. These values are typically interpreted by nursing staff as mild, moderate, or severe pain and pain medication is given accordingly. |
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Inclusion Criteria:
Exclusion Criteria:
Refusal to participate in the study
Age <18 or > 90 years
Pregnancy
Contraindications to regional anesthetic including but not limited to:
Chronic opioid use
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| Name | Affiliation | Role |
|---|---|---|
| Karen Zaghiyan, MD | Cedars Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars Sinai Medical Center | Los Angeles | California | 90048 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31515761 | Background | Mujukian A, Truong A, Tran H, Shane R, Fleshner P, Zaghiyan K. A Standardized Multimodal Analgesia Protocol Reduces Perioperative Opioid Use in Minimally Invasive Colorectal Surgery. J Gastrointest Surg. 2020 Oct;24(10):2286-2294. doi: 10.1007/s11605-019-04385-9. Epub 2019 Sep 12. | |
| 31657314 | Background | Truong A, Mujukian A, Fleshner P, Zaghiyan K. No Pain, More Gain: Reduced Postoperative Opioid Consumption with a Standardized Opioid-Sparing Multimodal Analgesia Protocol in Opioid-Tolerant Patients Undergoing Colorectal Surgery. Am Surg. 2019 Oct 1;85(10):1155-1158. |
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One patient was noted to have chronic opioid use discovered after randomization. They were subsequently excluded from analysis
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| ID | Title | Description |
|---|---|---|
| FG000 | Bupivacaine/Epinephrine/Dexamethasone TAP Block | For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 23, 2018 |
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| Bupivacaine/epinephrine/dexamethasone | Drug | Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively. |
|
|
| 72-hours post-surgery |
| Bowel Motility | Time till first bowel movement | 72 hours post-surgery |
| Postoperative Length of Stay | Time from operation until hospital discharge | 30 days post-surgery |
| Postoperative Complications | Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course
Clavien-Dindo grade II: Normal course altered
Clavien-Dindo grade III: complications that require intervention of various degrees
Clavien-Dindo grade IV: complications threatening the life of a patient
| 30 days post-surgery |
| 27505115 | Background | Knudson RA, Dunlavy PW, Franko J, Raman SR, Kraemer SR. Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital. Dis Colon Rectum. 2016 Sep;59(9):862-9. doi: 10.1097/DCR.0000000000000648. |
| 34086002 | Derived | Truong A, Fleshner PR, Mirocha JM, Tran HP, Shane R, Zaghiyan KN. A Prospective Randomized Trial of Surgeon-Administered Intraoperative Transversus Abdominis Plane Block With Bupivacaine Against Liposomal Bupivacaine: The TINGLE Trial. Dis Colon Rectum. 2021 Jul 1;64(7):888-898. doi: 10.1097/DCR.0000000000002008. |
| FG001 | Liposomal Bupivacaine TAP Block | For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Bupivacaine/Epinephrine/Dexamethasone TAP Block | For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively. |
| BG001 | Liposomal Bupivacaine TAP Block | For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) | Posted | Median | Inter-Quartile Range | Oral morphine equivalents | 48-hours |
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| Secondary | Post-op Pain Score (Visual Analog Scale) | Visual pain scale recordings will be totaled and averaged during the first 72-hours post-surgery. Visual analog scale is determined by nursing staff when assessing pain scores. Scores range from 0-10 with 10 being the most pain. These values are typically interpreted by nursing staff as mild, moderate, or severe pain and pain medication is given accordingly. | Posted | Median | Inter-Quartile Range | score on a scale | 72-hours post-surgery |
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| Secondary | Bowel Motility | Time till first bowel movement | Posted | Median | Inter-Quartile Range | days | 72 hours post-surgery |
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| Secondary | Postoperative Length of Stay | Time from operation until hospital discharge | Posted | Median | Inter-Quartile Range | days | 30 days post-surgery |
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| Secondary | Postoperative Complications | Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course
Clavien-Dindo grade II: Normal course altered
Clavien-Dindo grade III: complications that require intervention of various degrees
Clavien-Dindo grade IV: complications threatening the life of a patient
| Posted | Count of Participants | Participants | 30 days post-surgery |
|
Data was collected for each patient for a maximum period of 3 months postoperatively.
Adverse events are defined by complications or unexpected sequelae as a result of TAP block administration
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bupivacaine/Epinephrine/Dexamethasone TAP Block | For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively. | 0 | 50 | 0 | 50 | 0 | 50 |
| EG001 | Liposomal Bupivacaine TAP Block | For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively. | 0 | 51 | 0 | 51 | 0 | 51 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Karen Zaghiyan | Cedars-Sinai | (310) 289-9224 | kzaghiyan@yahoo.com |
| Nov 8, 2020 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D003424 | Crohn Disease |
| D015212 | Inflammatory Bowel Diseases |
| D015179 | Colorectal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D010146 | Pain |
| D009437 | Neuralgia |
| D007410 | Intestinal Diseases |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D005759 | Gastroenteritis |
| D007414 | Intestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D003108 | Colonic Diseases |
| D012002 | Rectal Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D002045 | Bupivacaine |
| D002123 | Calcium Dobesilate |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Participants |
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For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered.
Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
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