A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway

doi:10.1016/j.ajog.2020.07.017

American Journal of Obstetrics and Gynecology

Volume 224, Issue 1, January 2021, Pages 70.e1-70.e11

https://doi.org/10.1016/j.ajog.2020.07.017 Get rights and content

Background

Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours).

Objective

This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway.

Study Design

A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute–designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection.

Results

In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes.

Conclusion

Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient’s self-reported pain and functional recovery compared with standard bupivacaine.

Section snippets

Materials and Methods

This was a prospective randomized single-blinded study of wound infiltration of liposomal bupivacaine mixed with 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) in patients undergoing open gynecologic surgery on an ERAS pathway. Our pathway follows published guidelines for gynecologic surgery.⁴^,⁵^,¹⁴ This protocol was approved by the institutional review board. The primary outcome measure was proportion of patients who did not receive any postoperative opioids within the first

Statistical Methods

A sample size of 100 patients per arm was estimated to yield at least 80% power to detect an absolute increase of 20% in the proportion of patients who were opioid-free up to 48 hours in the liposomal bupivacaine plus 0.25% bupivacaine arm (study arm) compared with the standard bupivacaine arm (control arm), regardless of the proportion of patients who were opioid-free in the control arm, with a 2-sided significance level of 0.05. A planned interim analysis for efficacy and futility was

Results

A total of 105 patients were accrued between August 31, 2016, and August 31, 2017, and 102 patients were eligible for analysis (Figure 1). One patient was excluded after randomization because of scheduled opioid use, and 2 patients were excluded because the surgical approach changed to minimally invasive surgery. Therefore, 54 patients in the control arm of 0.25% bupivacaine and 48 patients randomized to the study arm of liposomal bupivacaine plus 0.25% bupivacaine were included in the final

Principal findings

Within an enhanced recovery pathway, the addition of long-acting liposomal bupivacaine to 0.25% bupivacaine administered via local wound infiltration did not improve the percentage of patients who were opioid-free up to the first 48 hours after surgery. Importantly, we were also unable to detect a difference in key secondary endpoints such as time to first opioid administration, percentage of patients who were opioid-free by day, or total opioid-free days up to postoperative day 3. In addition,

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Incisional infiltration versus transversus abdominis plane block of liposomal bupivacaine after midline vertical laparotomy for suspected gynecologic malignancy: a pilot study
2023, Gynecologic Oncology Reports
To evaluate whether incisional infiltration of liposomal bupivacaine would decrease opioid requirement and pain scores after midline vertical laparotomy for suspected or known gynecologic malignancy compared with transversus abdominis plane (TAP) block with liposomal bupivacaine.
A prospective, single blind randomized controlled trial compared incisional infiltration of liposomal bupivacaine plus 0.5% bupivacaine versus TAP block with liposomal bupivacaine plus 0.5% bupivacaine. In the incisional infiltration group, patients received 266 mg free base liposomal bupivacaine with 150 mg bupivacaine hydrochloride. In the TAP block group, 266 mg free base bupivacaine with 150 mg bupivacaine hydrochloride was administered bilaterally. The primary outcome was total opioid use during the first 48-hour postoperative period. Secondary outcomes included pain scores at rest and with exertion at 2, 6, 12, 24 and 48 h after surgery.
Forty three patients were evaluated. After interim analysis, a three-fold higher sample size than originally calculated was required to detect a statistically significant difference. There was no clinical difference between the two arms in mean opioid requirement (morphine milligram equivalents) for the first 48 h after surgery (59.9 vs. 80.8, p = 0.13). There were no differences in pain scores at rest or with exertion between the two groups at pre-specified time intervals.
In this pilot study, incisional infiltration of liposomal bupivacaine and TAP block with liposomal bupivacaine demonstrated clinically similar opioid requirement after gynecologic laparotomy for suspected or known gynecologic cancer. Given the underpowered study, these findings cannot support the superiority of either modality after open gynecologic surgery.
Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update
2023, Gynecologic Oncology
Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges.
Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018–2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly.
The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.
Surgeon-administered transversus abdominis plane block in gynecologic surgery—is it time to tap out?
2023, American Journal of Obstetrics and Gynecology
Bowel preparation
2022, The ERASÂ® Society Handbook for Obstetrics & Gynecology
Preoperative bowel preparation has been part of the surgical dogma for patients undergoing planned colorectal, gynecologic, or other pelvic surgery for decades. With the introduction of enhanced recovery after surgery (ERAS), many dogmatic approaches to perioperative care were replaced by evidence-based approaches which may ultimately favorably impact the outcomes intended to be reduced by preoperative bowel preparations. There remains a greater volume of data in support of oral antibiotic preparation with mechanical bowel preparation when a preoperative bowel preparation is utilized. Mechanical bowel preparation alone carries no benefit, may be harmful in the perioperative setting, and should be avoided. Emerging research suggests that oral antibiotic preparation alone may be beneficial, and the ERAS perioperative landscape has introduced a new era that favorably impacts bowel-related outcomes even in the setting of no bowel preparation. As such, the role of preoperative bowel preparation warrants revisiting as perioperative care evolves.
Effect of continuous post-operative lidocaine infusion in an enhanced recovery program on opioid use following gynecologic oncology surgery
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The effect of liposomal bupivacaine for surgical wound infiltration: A meta-analysis of randomised controlled trials
2023, International Wound Journal

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: This study was funded by Pacira BioSciences, Inc. Pacira BioSciences, Inc. provided intellectual input to investigators who ultimately developed the final study design. However, Pacira BioSciences, Inc did not have a role in the collection, analysis, or interpretation of the data or any role in the writing or editing of the manuscript. In addition, there were no restrictions regarding submission of the report for publication. L.A.M. received a grant (K07-CA201013) from the National Institutes of Health (NIH) and National Cancer Institute (NCI). This work was supported, in part, by a core grant (P30 CA016672) from the NIH and NCI (Biostatistics Resource Group and Clinical Trials Support Resource).

: The study “Wound infiltration with liposomal bupivacaine vs standard wound infiltration with bupivacaine in patients undergoing open gynecologic surgery on an enhanced recovery pathway” was registered on ClinicalTrials.gov with identifier number NCT02740114 (https://clinicaltrials.gov/ct2/show/record/NCT02740114) on April 15, 2016. The date of initial participant enrollment was August 31, 2016.

: L.A.M. receives research funding for unrelated research from AstraZeneca. C.C.C., M.D.I., M.M., and Q.S. received partial salary support for their work on this study from Pacira BioSciences, Inc. G.M. is a consultant for Pacira BioSciences, Inc. The remaining authors reported no conflict of interest.

: Cite this article as: Meyer LA, Casadiego CC, Iniesta MD, et al. A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway. Am J Obstet Gynecol 2021;224:70.e1-11.

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Original ResearchGynecologyA prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway

Background

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Statistical Methods

Results

Principal findings

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

J Minim Invas Gynecol

New persistent opioid use after minor and major surgical procedures in US adults

JAMA Surg

Prevention and treatment of opioid misuse and addiction: a review

JAMA Psychiatry

Enhanced recovery after surgery: a review

JAMA Surg

The value of “multimodal” or “balanced analgesia” in postoperative pain treatment

Anesth Analg

Enhanced recovery in gynecologic surgery

Obstet Gynecol

Enhanced recovery implementation in major gynecologic surgeries: effect of care standardization

Obstet Gynecol

Original Research
Gynecology
A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway