Testing a new sustained-release local anesthetic formulation specifically designed for spine surgery in a sheep model

Instrumented spinal surgery is a frequently performed and painful intervention, with severe pain often lasting for three days. Opioids are the cornerstone of treatment of postoperative pain, but can induce severe side effects, dependence, and addiction. Novel local anesthetic applications, such as erector spinae plane blocks, and sustained release formulations have the potential to decrease opioid consumption without analgesic compromise but have limited efficacy beyond 24 h. A mismatch in duration of pain and duration of non-opioid analgesia is thus present in spine surgery. This study assessed the feasibility of a robust hydrogel for three days of sustained and stationary bupivacaine delivery, designed for co-implantation with pedicle screws, in a sheep model for spinal surgery. Fifteen sheep received six hydrogel rings loaded with bupivacaine mounted on pedicle screws (total dose 220 mg). Wound and systemic drug levels, hydrogel degradation and histological response were assessed. Moreover, in-vivo drug release was correlated to in-vitro release (IVIVC). Rings stayed in place after surgery and displayed a first-order release profile in-vivo over 72 h, with excellent IVIVC. Ring intactness after implantation did not affect release. Bupivacaine wound fluid levels exceeded plasma levels 2300-fold, and plasma bupivacaine levels were well below toxic thresholds through 168 h. Histological analysis of implant sites revealed a conventional foreign-body response that subsided during follow-up. Hydrogels degraded completely in 9 months. The present hydrogel has the potential to provide safe, localized, and sustained analgesia following instrumented spinal surgery.