Liposomal Bupivacaine Incisional Infiltration for Postoperative Analgesia After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Randomized Placebo-Controlled Trial.

Abstract

Introduction: Moderate-to-severe postoperative pain is common after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence that liposomal bupivacaine provides clinically important advantages over conventional local anesthetics is inconsistent, and evidence in CRS + HIPEC remains limited. This trial evaluated the incremental efficacy and safety of liposomal bupivacaine incisional infiltration added to patient-controlled intravenous analgesia (PCIA) compared with saline infiltration plus PCIA.

Methods: In this single-center, randomized, participant- and assessor-blinded, placebo-controlled trial, adults aged 18-65 years scheduled for elective CRS + HIPEC were assigned 1:1 to standardized PCIA plus liposomal bupivacaine incisional infiltration (PCIA-LB) or PCIA plus normal saline infiltration (PCIA-NS). The primary endpoint was the incidence of moderate-to-severe movement-evoked incisional pain (numeric rating scale >  = 4) within 72 h. The prespecified primary efficacy analysis used the per-protocol set (PPS), with a conservative intention-to-treat (ITT) sensitivity analysis. PCIA followed an institutional standard operating procedure. Monitoring was continuous in the intensive care unit (ICU); after transfer to the ward, pulse oximetry was continued through postoperative day 3, with intermittent electrocardiography and noninvasive blood pressure monitoring.

Results: The PPS included 94 patients (PCIA-NS, n = 48; PCIA-LB, n = 46). Moderate-to-severe movement-evoked pain within 72 h was less frequent with PCIA-LB than with PCIA-NS (19.6% versus 70.8%, P < 0.001). The conservative ITT sensitivity analysis supported the same conclusion (26.0% versus 68.0%, P < 0.001). PCIA-LB also produced a modest reduction in cumulative 72-h study-recorded oral morphine milligram equivalents (556.8 [473.4, 600.0] versus 600.0 [557.4, 630.0] mg, P = 0.002) and reduced rescue analgesia (30.4% versus 54.2%, P = 0.020). QoR-15 scores did not differ significantly. Overall analgesia-related adverse events occurred in 23.9% and 10.4% of the PCIA-LB and PCIA-NS groups, respectively (P = 0.143). No participant required naloxone, emergency airway intervention, or ventilatory support for a clinically recognized opioid-related respiratory event, and no local anesthetic systemic toxicity, incisional infection, or fat liquefaction was observed.

Conclusions: Compared with saline infiltration, liposomal bupivacaine incisional infiltration reduced early movement-evoked incisional pain and rescue analgesia and produced a statistically significant but quantitatively modest reduction in 72-h opioid consumption captured by the study records after CRS + HIPEC. It did not improve QoR-15. These findings do not establish superiority over plain bupivacaine, ropivacaine, or catheter-based regional techniques, and the study was not powered to establish safety.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2500100826. Registered at 00:00 on 15 April 2025, before enrollment of the first participant later the same day.