Bupivacaine Liposomal Injection (Exparel) for Postsurgical Analgesia in Patient Undergoing Laparoscopic Bariatric Surgery

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02969187
• Collaborator: (none)
• Enrollment: 126
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.9
• Patients Per Site Per Month: 7.4

Study Details

Study Description

Brief Summary

Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain management, efforts are continuing to find effective methods to relieve pain after abdominal surgery. Although opioid is an effective analgesic it has opioid related adverse events (ORAEs). Bupivacaine should reduce postoperative pain but it has relatively shorter duration of action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively; results in lesser opioids usage and reduce the ORAEs. Transversus abdominis plane (TAP) block is a relatively new regional anesthetic technique. TAP blocks have been performed to reduce opioid use and control pain in several laparoscopic surgical procedures, including colorectal resections, cholecystectomy and bariatric surgery. The aim of this study is to study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using Exparel versus Bupivacaine as TAP block and port sites infiltration.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative	Drug: Exparel; Drug: Bupivacain; Drug: Saline	Phase 4

Detailed Description

Introduction

Despite the increasing use of patient-controlled anesthesia (PCA) for postoperative pain management, efforts are continuing to find effective methods to relieve pain after abdominal surgery. Some studies have already suggested that infusion with local anesthetics at the wound site can decrease postoperative pain levels. Further, other studies have shown equal amounts of opiate analgesic requirements (administered on patient demand) with placebo and local anesthetic administration. However, varying anesthetic administration techniques used in the different studies may explain why the controversy in the literature exists.

Although opioid is an effective analgesic it has opioid related adverse events (ORAEs). Bupivacaine should reduce postoperative pain but it has relatively shorter duration of action. Liposome bupivacaine (Exparel) has been approved as a single dose infiltration for longer postoperative period analgesic. It provides up to 72 hours analgesia postoperatively; results in lesser opioids usage and reduce the ORAEs.

Transversus abdominis plane (TAP) block is a relatively new regional anesthetic technique that targets blockage of the neural afferent of the lower intercostal, iliohypogastric and ilioinguinal nerves in the neurovascular plane between the internal oblique and the transversus abdominis muscle. TAP blocks have been performed to reduce opioid use and control pain in several laparoscopic surgical procedures, including colorectal resections, cholecystectomy and bariatric surgery.

Efficacy of wound infiltration with or without TAP block using immediate-release bupivacaine HCl for acute postsurgical pain is well established; EXPAREL has been proposed as a method for postoperative pain management. Moreover, the administration and the optimal dosage in the bariatric surgical population have not been studied.

The objective of this study is to examine postoperative pain after laparoscopic gastric bypass with TAP block and port sites infiltration using Exparel versus Bupivacaine

Background and significance

Exparel is a FDA approved long-acting, local anesthetic. This is for single-dose infiltration into the surgical site to produce postsurgical analgesia. Exparel offers longer-acting local formulation and can be administered as a single dose. Exparel has a longer duration of action with slower absorption. The mean elimination half-life of local administration of Exparel is approximately 24-34 hours 19-20 versus 2.7 hours for bupivacaine.

Liposomal bupivacaine is for single-dose infiltration and the recommended dose depends on the surgical site but the maximum dose of liposomal bupivacaine is 266 mg and it is injected into soft tissues of the surgical site with frequent aspirations to prevent intravascular injection.

A pooled analysis evaluating the effect of Exparel on pain intensity scores and opioid consumption was published by Dasta et al. This study included 5 surgical procedures (inguinal hernia repair, total knee replacement, hemorrhoidectomy, breast augmentation and bunionectomy) comparing Exparel with bupivacaine HCl, on 912 patients; it showed significantly lower pain score and opioid usage, delayed use of rescue opioid and reduced ORAEs in the Exparel group; as compared to bupivacaine HCL group.

Medication SafetLiposomal bupivacaine has been classified as a high-alert medication by the Institute of Safe Medication Practices due to its similar appearance to propofol. If liposomal bupivacaine were administered intravenously as if it were propofol, adverse cardiac effects may result.

Hypothesis

Exparel (1.3%) and 0.5% Bupivacaine usage with infiltration and TAP block decreases opiate usage, nausea and pain at 48 hours as compared to 0.5% Bupivacaine only.

Primary Objective of the study:

To study the opiate usage, pain and nausea post laparoscopic gastric bypass or sleeve gastrectomy using EXPAREL versus Bupivacaine as TAP block and port sites infiltration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bupivacaine Liposomal Injection (Exparel) for Postsurgical Analgesia in Patients Undergoing Laparoscopic Bariatric Surgery: A Randomized, Double-Blind, Controlled Trial
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Jan 31, 2018
• Actual Study Completion Date: Mar 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline	Drug: Exparel; 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites.; Drug: Bupivacain; 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.; Drug: Saline
Active Comparator: Control Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline.	Drug: Bupivacain; 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites.; Drug: Saline

Outcome Measures

Primary Outcome Measures

1. Total Amount of Opioids at 48 Hours [At 48 hours post operative]

   The total amount of opioids used will be recorded from the nurse chart.

Secondary Outcome Measures

1. Cumulative Pain Score Through 48 Hours After Surgery [Pain assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 48 hours post operatively]

   Description: We used a time weight average (TWA) pain score in frequent measurements of pain score. Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440. The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.

2. Cumulative Nausea Score [Nausea assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 72 hours post operatively]

   Description: We used a time weight average (TWA) method in adjusting the nausea score. Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272. The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Fulfills NIH criteria for bariatric surgery

• Planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure

Exclusion Criteria:

• BMI <35 and > 60 kg/m2

• Inability to walk (bed-bound or wheelchair dependence)

• Previous major abdominal surgery (possible adhesions and longer operation) defined as:

• open abdominal surgeries except simple appendectomy and common OB/GYN procedures in the pelvis (hysterectomy, C-section, and oophorectomy, tubal ligation)

• laparoscopic bowel or solid organ resection except laparoscopic cholecystectomy

• ventral hernia repair with mesh

• Preoperative chronic opiate use for chronic pain defined as opiate usage at least 60 mg/day of morphine equivalent for ≥ 3 months (as defined by International Association for the Study of Pain22) in the one year period prior to the bariatric surgery

• The American Society of Anesthesiologists (ASA) score > 3

• History of hypersensitivity or adverse reaction to bupivacaine or narcotics

• Inability to speak English

• Concurrent surgical procedure including:

• ventral hernia repair

• Cholecystectomy

• hiatal hernia repair with posterior cruroplasty

• extensive lysis of adhesions

• other procedures that mandate addition of "trocar(s)" or "feeding tube"

• Addition of trocar(s) or conversion of surgery to hand-assisted or open

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2016

More Information

Publications

None provided.

• Responsible Party: Philip Schauer, Staff Surgeon, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02969187
• Other Study ID Numbers: 15-1318
• First Posted: Nov 21, 2016
• Last Update Posted: Mar 3, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Pain, Postoperative; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Experimental	Control
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml
Period Title: Overall Study
STARTED	63	63
COMPLETED	51	50
NOT COMPLETED	12	13

Baseline Characteristics

Arm/Group Title	Experimental	Control	Total
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline	Total of all reporting groups
Overall Participants	51	50	101
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	41.1	41.2	41.1
Sex: Female, Male (Count of Participants)
Female	40 78.4%	38 76%	78 77.2%
Male	11 21.6%	12 24%	23 22.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
BMI (kg/m2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m2]	44	44	44

Outcome Measures

1. Primary Outcome

Title	Total Amount of Opioids at 48 Hours
Description	The total amount of opioids used will be recorded from the nurse chart.
Time Frame	At 48 hours post operative

Outcome Measure Data

Analysis Population Description

A total of 126 patients were randomized in this study. Out of that, 25 patients were excluded due either inadequate data, not prescribed post-operative ketorolac or intraoperative additional procedures performed. A total of 101 patients were included;

Arm/Group Title	Experimental	Control
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline
Measure Participants	51	50
Mean (Standard Deviation) [mg]	29.5 (17.1)	27.1 (14.3)

2. Secondary Outcome

Title	Cumulative Pain Score Through 48 Hours After Surgery
Description	Description: We used a time weight average (TWA) pain score in frequent measurements of pain score. Cumulative pain score through 48 hours after surgery is the summation of all the time weight average pain scores with a range from 0 to 440. The high score represents the worse outcomes. 0 means no pain during the whole time and 440 means severe pain during the whole time.
Time Frame	Pain assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 48 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Control
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml
Measure Participants	51	50
Mean (Standard Deviation) [score on a scale]	177.0 (62.9)	167.8 (62.3)

3. Secondary Outcome

Title	Cumulative Nausea Score
Description	Description: We used a time weight average (TWA) method in adjusting the nausea score. Cumulative nausea score through 72 hours after surgery is the summation of all the time weight average nausea scores with a range from 68-272. The high score represents the worse outcomes. 68 means no nausea during the whole time and 272 means severe nausea during the whole time.
Time Frame	Nausea assessed when the patient is admitted to the recovery room after surgery, every 8 hrs thereafter for up to 72 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Control
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Study arm receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to study arm and control arm. 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Control arm receive 60ml of 0.5% Bupivacaine + 140 ml of Saline (total: 200ml) Transverse Abdominis Plane (TAP) block: 140 ml Port site infiltration:60ml
Measure Participants	51	50
Mean (Standard Deviation) [score on a scale]	79 (12)	98 (35)

Adverse Events

Time Frame	Two patients in the study arm developed urticarial rashes over the abdominal wall at the site of injection. Their rashes were noticed on day 7 after the procedure during follow up visit in the clinic by the attending physician.
Adverse Event Reporting Description	Two patients in the study arm developed urticarial rash over the abdominal wall at the site on injection noticed at 1 week post procedure during follow up visit. The rash noticed at 1 week post procedure during follow up visit. The rash was itchy but limited only to the abdominal area at the injection site. No other adverse events noted. At subsequent follow up, the rash has resolved.
Arm/Group Title	Experimental		Control
Arm/Group Description	Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 20 ml of 1.3% Exparel + 30 ml of 0.5% Bupivacaine + 150 ml of Saline Exparel: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Exparel will be injected at port sites. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline		Patients at our Bariatric Surgery Center of Excellence fulfilling NIH criteria for bariatric surgery and planned operation of laparoscopic Roux-en Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) as primary bariatric procedure randomized to receive 60ml of 0.5% Bupivacaine + 140 ml of Saline. Bupivacain: 6 trocars are placed to perform LRYGB or LSG: two 12 mm trocars and four 5 mm trocars. Bupivacain will be injected at port sites. Saline
All Cause Mortality
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)
Serious Adverse Events
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		0/50 (0%)
Skin and subcutaneous tissue disorders
Minor adverse event	2/51 (3.9%)	2	0/50 (0%)	0

Limitations/Caveats

There is no data available to guide us on the dosage of liposome bupivacaine in bariatric surgery. We assume adequate quantity and coverage of liposome bupivacaine (266mg) in this obese population, despite that they have a bigger surface area.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.