Postoperative Mortality Following Extended-Release Buprenorphine, Carprofen, and Bupivacaine Administration in Male...

Extended-release buprenorphine (Bup-XR) is commonly used to manage postoperative pain in rodents while minimizing stress related to handling. An FDA-indexed Bup-XR formulation is commercially available (Ethiqa XR; Fidelis Animal Health, New Brunswick, NJ) and is indicated for the control of postprocedural pain in multiple species, including rats. Despite its widespread use in multiple rat strains, the safety and efficacy of Bup-XR in the August Copenhagen Irish (ACI) rat strain has not been reported, particularly when it is combined with nonsteroidal anti-inflammatory drugs (NSAIDs) and local anesthetics. In this study, 20 male ACI rats aged 6-13 months underwent a minor surgical procedure involving continuous-release hormone pellet implantation ('pellets'), performed either as a primary implantation or a replacement procedure. All rats were administered Bup-XR (0.65 mg/kg, SC) before the procedure. They were also administered carprofen (5 mg/kg, SC) immediately before surgery, as well as bupivacaine (1.8 mg/kg) as a line block anesthetic along the incision line after surgery. Adverse reactions were observed in all animals within 24 hours of surgery, with marked lethargy being most noticeable. Additional symptoms during the first postoperative week included pica behavior, labored breathing, gastrointestinal distress, self-injurious behavior, and dehydration. Within 9 days of the procedure, 13 of 20 males (65%) either died or were humanely euthanized due to significant welfare concerns. Statistical testing confirmed that neither age, weight, nor replacement pellet surgery was significantly associated with mortality. These findings suggest that the adverse effects observed in this strain of rat postsurgery are associated with the use of Bup-XR, possibly in combination with the other agents.