Skip to content

Liposomal Bupivacaine Block Similar to Placebo for Pain Reduction After Cesarean

Key findings

  • In this single-blind, randomized trial that compared a liposomal bupivacaine incisional block with placebo block at the time of cesarean delivery, there were no differences in pain with movement at 48 hours postoperatively
  • No differences between groups were seen in pain scores at any other time point, median opioid consumption or any other secondary outcome
  • 18% of patients required no opioids on discharge and 51% reported leftover opioids at six weeks
  • The researchers recommend additional trials of the pain-relieving and opioid-sparing effects of liposomal bupivacaine after cesarean delivery

In light of the U.S. opioid epidemic, there is an urgent need to identify postoperative pain management strategies that minimize opioid use while maintaining patient satisfaction. One potential option is the liposomal formulation of bupivacaine, which provides controlled release of local anesthetic over 48 to 72 hours.

previous retrospective study of women undergoing cesarean delivery who received intra-incisional liposomal bupivacaine had significantly less postoperative opioid consumption, compared with historical controls. However, use of non-opioid analgesics was higher in the bupivacaine group, which confounded the results.

To investigate this issue prospectively, former maternal-fetal medicine fellow Malavika Prabhu, MD, William Barth, MD, vice chair for obstetrics at Massachusetts General Hospital, and colleagues conducted a patient-blinded, randomized, controlled trial. In Obstetrics & Gynecology, they report that intra-incisional liposomal bupivacaine was similar to placebo in terms of pain reduction after cesarean delivery.

Study Design

At the time of the trial, the post-cesarean pain management regimen at Mass General was spinal or epidural morphine at the time of delivery, scheduled ketorolac for 24 hours after delivery, scheduled ibuprofen for 24 hours and scheduled acetaminophen for 48 hours. After 48 hours, acetaminophen and ibuprofen could be given as needed. Oxycodone was the initial oral opioid of choice and could be administered throughout the postoperative period, 5 to 10 mg every four hours as needed.

Eighty participants were recruited between March 3, 2017, and September 22, 2017, and stratified by cesarean delivery type (primary or repeat). They were randomly assigned to an incisional block with 80 cc liposomal bupivacaine or 80 cc normal saline.

Study participants rated their pain on an 11-point numeric scale at 24, 48 and 72 hours postoperatively. The primary outcome of the randomized trial was pain score with movement (sitting up from lying flat in bed) at 48 hours.

Short-term Efficacy Results

The researchers found that the primary outcome was not statistically different between the liposomal bupivacaine and placebo groups: the median scores were 4 and 3.5, respectively. No differences between groups were seen in pain scores at rest or with movement at any time point.

The two groups were identical in terms of median opioid consumption during the hospital stay, and they were similar in every other secondary outcome evaluated.

Short-term Safety Results

No local anesthetic toxicity or allergic reactions occurred. Opioid-related adverse events (itching, drowsiness, dizziness and nausea) were common in both groups.


Within 14 days of surgery, one patient in the placebo group was noted to have a wound seroma, and three patients (two in the placebo group and one in the liposomal bupivacaine group) were noted to have a wound infection or cellulitis. No patients were readmitted with complications. One patient in the liposomal bupivacaine group received a post-discharge opioid refill for incisional pain.

At a six-week telephone follow-up, similar proportions of patients in the two groups said they were satisfied or very satisfied with postoperative pain control (placebo, 97%; liposomal bupivacaine, 91%). No additional wound complications were reported.

Suggestion of an Opioid-sparing Effect

This study did not aim to decrease opioid prescribing on discharge or the amount of leftover opioids. However, the authors note that 18% of patients required no opioids on discharge, none required an opioid refill after 14 days postpartum and 51% reported leftover opioid tablets at six weeks.

Although the findings suggest no benefit of liposomal bupivacaine in improving pain scores after cesarean delivery, the researchers recommend additional trials of its pain-relieving and opioid-sparing effect, since there is so little previous research. Given the strong placebo effect in this trial, they suggest consideration of a third study arm with sham or no injection.

of patients required no opioids on discharge

patients required an opioid refill after 14 days postpartum

of patients reported having leftover opioid tablets at six weeks

Learn more about obstetrics at Mass General

Explore our research in obstetrics & gynecology

Related topics


Researchers in the OB/GYN Department are working to combat the opioid epidemic and mitigate its effects. Recent efforts have focused on preventing opioid use and misuse through a variety of methods including optimized prescribing practices.


A multidisciplinary, 1000-day clinical model offers a new approach to prenatal and postnatal care for mothers with opioid use disorder and their children.