Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

BACKGROUND: Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. METHODS: We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. RESULTS: Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the incision. CONCLUSIONS: Significant suppression of postoperative pain by the slow-release bupivacaine preparation outlasts its anesthetic action on intact skin. These findings demonstrate preventive analgesia and indicate the importance of acute processes in the development of chronic postoperative pain.

Demineralized Bone Matrix in Spine Surgery: A Review of Current Applications and Future Trends.

BACKGROUND: Graft augmentation for spinal fusion is an area of continued interest, with a wide variety of available products lacking clear recommendations regarding appropriate use. While iliac crest autograft has long been considered the "gold standard", suboptimal fusion rates along with harvest-related concerns continue to drive the need for graft alternatives. There are now multiple options of products with various characteristics that are available. These include demineralized bone matrix (DBM) and demineralized bone fibers (DBF), which have been used increasingly to promote spine fusion. The purpose of this review is to provide an updated narrative on the use of DBM/DBF in spine surgery. METHODS: Literature review. RESULTS: The clinical application of DBM in spine surgery has evolved since its introduction in the mid-1900s. Early preclinical studies demonstrated its effectiveness in promoting fusion. When used in the cervical, thoracic, and lumbar spine, more recent clinical data suggest similar rates of fusion compared with autograft, although clinical studies are primarily limited to level III or IV evidence with few level I studies. However, significant variability in surgical technique and type of product used in the literature limits its interpretation and overall application. CONCLUSIONS: DBM and DBF are bone graft options in spine surgery. Most commonly used as graft extenders, they have the ability to increase the volume of traditional grafting techniques while potentially inducing new bone formation. While the literature supports good fusion rates when used in the lumbar spine and when used with adjuvant cages or additional grafting techniques in the cervical spine, care should be taken when using as a stand-alone product. As new literature emerges, DBM and DBF can be a useful method in a surgeon's armamentarium for fusion-based procedures.