Colorectal Cancer, Crohn Disease, Digestive System Disease, Gastrointestinal Cancer, Gastrointestinal Disease, Inflammatory Bowel Diseases, Intestinal Disease, Pain, Pain, Neuropathic, Pain, Postoperative
Conditions
Keywords
transversus abdominis plane block, tap block, liposomal bupivacaine, exparel, dexamethasone, colorectal surgery, regional anesthesia, bupivacaine, surgery, postoperative pain, pain
Brief summary
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.
Detailed description
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.
Interventions
DRUGLiposomal bupivacaine
Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
DRUGBupivacaine/epinephrine/dexamethasone
Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male or Female 2. Undergoing major laparoscopic colorectal procedure 3. Willingness and ability to sign an informed consent document 4. No allergies to anesthetic or analgesic medications 5. ASA physical status Class I - III 6. Aged 18-90 years
Exclusion criteria
1. Refusal to participate in the study 2. Age \<18 or \> 90 years 3. Pregnancy 4. Contraindications to regional anesthetic including but not limited to: 1. Patient refusal to regional field blockade 2. Allergy 3. Infection at the site of needle insertion 4. Systemic infection 5. Bleeding diathesis or coagulopathy (as diagnosed by history or laboratory evaluation) 6. Liver or renal disease (SCr \> 1.5) 5. Chronic opioid use
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) | 48-hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-op Pain Score (Visual Analog Scale) | 72-hours post-surgery | 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. |
| Bowel Motility | 72 hours post-surgery | Time till first bowel movement |
| Postoperative Length of Stay | 30 days post-surgery | Time from operation until hospital discharge |
| Postoperative Complications | 30 days post-surgery | Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course * no pharmacological or surgical treatment, endoscopic, or radiological interventions were required. Acceptable therapeutic regiments are drugs such as anti-emetics, antipyretics, analgesics, diuretics, and electrolytes. Wound infections or small abscess requiring incision at bedside is within this category Clavien-Dindo grade II: Normal course altered * Pharacological management other than in grade 1. Blood transfusions and total parenteral nutrition are also included. Clavien-Dindo grade III: complications that require intervention of various degrees * management of these complications require an intervention under local anesthesia or general or epidural anesthesia Clavien-Dindo grade IV: complications threatening the life of a patient * manifesting in organ dysfunction, including dialysis |
Countries
United States
Participant flow
Pre-assignment details
One patient was noted to have chronic opioid use discovered after randomization. They were subsequently excluded from analysis
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| 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. | 51 |
| Total | 101 |
Baseline characteristics
| Characteristic | Bupivacaine/Epinephrine/Dexamethasone TAP Block | Liposomal Bupivacaine TAP Block | Total |
|---|---|---|---|
| Age, Continuous | 42 years | 42 years | 42 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 32 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants | 18 Participants | 32 Participants |
| Region of Enrollment United States | 50 participants | 51 participants | 101 participants |
| Sex: Female, Male Female | 29 Participants | 22 Participants | 51 Participants |
| Sex: Female, Male Male | 21 Participants | 29 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 |
| other Total, other adverse events | 0 / 50 | 0 / 51 |
| serious Total, serious adverse events | 0 / 50 | 0 / 51 |
Outcome results
Primary
Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent)
Time frame: 48-hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) | 47 Oral morphine equivalents |
| Liposomal Bupivacaine TAP Block | Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) | 69 Oral morphine equivalents |
Secondary
Bowel Motility
Time till first bowel movement
Time frame: 72 hours post-surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Bowel Motility | 1 days |
| Liposomal Bupivacaine TAP Block | Bowel Motility | 1 days |
Secondary
Postoperative Complications
Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course * no pharmacological or surgical treatment, endoscopic, or radiological interventions were required. Acceptable therapeutic regiments are drugs such as anti-emetics, antipyretics, analgesics, diuretics, and electrolytes. Wound infections or small abscess requiring incision at bedside is within this category Clavien-Dindo grade II: Normal course altered * Pharacological management other than in grade 1. Blood transfusions and total parenteral nutrition are also included. Clavien-Dindo grade III: complications that require intervention of various degrees * management of these complications require an intervention under local anesthesia or general or epidural anesthesia Clavien-Dindo grade IV: complications threatening the life of a patient * manifesting in organ dysfunction, including dialysis
Time frame: 30 days post-surgery
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Postoperative Complications | None | 29 Participants |
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Postoperative Complications | Clavien-Dindo grade I | 7 Participants |
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Postoperative Complications | Clavien-Dindo grade II | 8 Participants |
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Postoperative Complications | Clavien-Dindo grade III | 6 Participants |
| Liposomal Bupivacaine TAP Block | Postoperative Complications | Clavien-Dindo grade III | 10 Participants |
| Liposomal Bupivacaine TAP Block | Postoperative Complications | None | 32 Participants |
| Liposomal Bupivacaine TAP Block | Postoperative Complications | Clavien-Dindo grade II | 7 Participants |
| Liposomal Bupivacaine TAP Block | Postoperative Complications | Clavien-Dindo grade I | 2 Participants |
Secondary
Postoperative Length of Stay
Time from operation until hospital discharge
Time frame: 30 days post-surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Postoperative Length of Stay | 3 days |
| Liposomal Bupivacaine TAP Block | Postoperative Length of Stay | 3 days |
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.
Time frame: 72-hours post-surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bupivacaine/Epinephrine/Dexamethasone TAP Block | Post-op Pain Score (Visual Analog Scale) | 4 score on a scale |
| Liposomal Bupivacaine TAP Block | Post-op Pain Score (Visual Analog Scale) | 4 score on a scale |