Introduction: Pathway-driven, post-pancreatectomy opioid reduction interventions have proven effective and sustainable and may have a "halo effect" on other major abdominal cancer operations. This study's aim was to analyze the sequential effects of expanding opioid reduction efforts from pancreatectomy on opioids prescribed after hepatectomy.

Methods: This is a retrospective cohort study utilizing data from the electronic health record and a prospective quality improvement database for consecutive hepatectomy patients (09/2016-02/2024). Cohorts were based on 5 distinct eras (E) of opioid-related protocol updates (E1/pre-intervention historical baseline: 09/2016-03/2017, E2/introduction of 5x-multiplier: 04/2017-09/2018, E3/departmental opioid education program: 10/2018-12/2019, E4/initial post-hepatectomy pathways: 01/2020-06/2022, E5/updated pancreatectomy pathways influencing hepatectomy care: 07/2022-02/2024).

Results: Of 2005 patients, 31% underwent major hepatectomy, 14% intermediate, 46% minor, and 9% combination surgery/other. Most (79%) were performed via open approach. Median hospital stay decreased from 5 to 4 days between E1-E5. Both intraoperative (E1:80mg, E5:37mg; p<0.001) and total inpatient (E1:181mg, E5:86mg; p<0.001) median oral morphine equivalents (OME) were reduced >50%. A 73% reduction in discharge OME was observed between E1 (225mg) and E5 (60mg; p<0.001), with clinically similar median pain scores at discharge (score 1-2 of 10). Concurrent universal adoption of routine 3-drug non-opioid discharge prescriptions (E1:70%, E5:98%) correlated with proportion of patients discharged opioid-free (E1:8%, E5:43%; p<0.001).

Conclusions: Directed opioid reduction efforts for pancreatectomy influenced clinically meaningful post-hepatectomy reductions in inpatient and discharge opioid volumes. A "halo effect" of intradepartmental opioid reduction efforts is attainable and corresponds to measurable increases in opioid-free or nearly opioid-free discharges after major abdominal cancer surgery.

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