Enhanced Recovery Program May Be Effective at Reducing Opioid Use After Pancreatic Cancer Surgery

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Improving hospital care pathways may help reduce inpatient opioid use by 50% and cut the median opioid prescription volumes at discharge to zero in patients undergoing pancreatic cancer surgery, according to a recent study published by Boyev et al in JAMA Surgery. The new findings could help reduce the risk of long-term opioid dependence.


Because pancreatic cancer surgery affects multiple organs simultaneously, the procedure is considered one of the most complex abdominal operations and can result in a high level of pain during the early recovery period.

Opioids are often prescribed after major surgical procedures to manage postoperative pain.

The use of opioids can be reduced or avoided by performing nerve block procedures, prescribing nonopioid drugs such as muscle relaxers and anti-inflammatories, and practicing early patient mobilization. These low-risk, low-cost maneuvers are not commonly employed because opioids are easy to prescribe. However, opioid misuse and addiction have become serious public health issues, and medical professionals are increasingly mindful of their prescribing habits.

“Patients not regularly taking opioids are at risk of developing a new dependence after surgery, and excess pills also create a risk of misuse by family members or others in their community,” explained senior study author Ching-Wei Tzeng, MD, FACS, Associate Professor of Surgical Oncology at The University of Texas MD Anderson Cancer Center. “Pancreatic cancer surgery can be a painful operation with a difficult recovery. This study shows that, even in this setting, easy-to-implement strategies can achieve effective pain control for our patients without putting them at risk for opioid dependence,” he highlighted.

Study Methods and Results

In the new study, researchers enrolled 832 patients with a median age of 65 years who had pancreatic cancer and were undergoing surgical resection—including 541 pancreatoduodenectomies, 285 distal pancreatectomies, and 6 other pancreatectomies. The researchers then investigated how making incremental modifications to postsurgery procedures could affect the amounts of opioids used by inpatients and at the point of discharge.

The study included three consecutive cohorts, each with iterative revisions to postsurgical clinical pathways, from 2018 to 2022. After establishing a baseline and reducing the length of stay, the researchers updated patient-provider education handouts, limited intravenous opioids, suggested a three-drug nonopioid bundle, and implemented a “5x-multiplier” (equal to oral morphine equivalents over the last 24 hours multiplied by 5) to calculate an appropriate amount of opioids to prescribe the patients at discharge.

After a follow-up of less than 4 years, the researchers found that the total inpatient oral morphine equivalents decreased from a median of 290 mg to 129 mg, whereas oral morphine equivalents at discharge decreased from a median of 150 mg to 0 mg. Over 75% of the patients were discharged with ≤ 50 mg of oral morphine equivalents—which is fewer than 10 pills.

Additionally, the median pain scores remained at ≤ 3 out of 10 in all of the cohorts involved in the study, with no differences in postdischarge refill requests. The researchers noted that most of the patients did not require opioid refills after discharge, with no statistically significant differences between the cohorts. A subgroup analysis separating open and minimally invasive cases showed similar results in both groups.


“Our enhanced recovery program—which includes generalizable protocols to reduce reliance on opioid medications—is the first to demonstrate continuous decreases in opioid use and distribution after pancreatic [cancer] surgery,” Dr. Tzeng emphasized. “By making purposeful, successive improvements to existing processes, we showed that we can reduce the amount of opioids patients need after a major surgery while ensuring they recover well without any extra costs,” he concluded. 

Disclosure: The research in this study was supported by The University Cancer Foundation, Duncan Family Institute for Cancer Prevention and Risk Assessment via a Cancer Survivorship Research Seed Money Grant at The University of Texas MD Anderson Cancer Center, and an Andrew Sabin Family Foundation Fellowship. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.