Abstract
Introduction
Intraoperative vasospasm is a challenge in large-vessel and microsurgical anastomosis alike. In response to mechanical manipulation, dissection, and temperature changes, blood vessels respond through calcium channel-mediated smooth muscle contraction, resulting in vasospasm and increased risk of thrombosis. Vasodilators have shown promising effects in reducing intraoperative vasospasm.
Papaverine is one vasodilator that has shown promising efficacy in reducing vasospasm. Papaverine is an opium alkaloid that acts as a phosphodiesterase inhibitor and calcium channel blocker to reverse vasospasm. Typically, vessels are directly irrigated with the drug via a syringe or soaked sponge; however, limited contact with the vessel may theoretically reduce the drug's efficacy in sustaining vasospasm reduction over time.
To address the vessel contact time limitation, alternative vasodilator delivery mechanisms have been tested, including electrospun polymer fibers, fibrin glue, thermosensitive hydrogels, and polymer membranes, mostly in animal models. We propose that Surgicel, as a hemostatic, biodegradable delivery reservoir, increases papaverine's contact duration and, as a result, its efficacy in reversing vasospasm.
Main Body
Surgicel is a hemostatic, resorbable, woven cellulose mesh, which, upon contact with blood, forms a gel-like matrix serving as a reservoir for liquid. Surgicel is widely available and has been utilized by the authors to prolong papaverine delivery in renal transplant anastomoses.
Papaverine is prepared as a dilute solution of 60 mg in 8 mL of intravenous normal saline (7.5 mg/mL). A piece of Surgicel is cut to approximate the vessel diameter and gently wrapped circumferentially around the vessel in the area of the intended arteriotomy or venotomy. Papaverine is applied by syringe directly to the vessel and over the Surgicel wrap before clamping. Following reperfusion and visual resolution of vasospasm, the Surgicel is removed, and the field is irrigated with saline prior to closure, thereby limiting tissue contact time.
Increasing papaverine's local application via Surgicel is not without theoretical risk. An ex vivo study applying papaverine to the outer surface of internal thoracic arteries for 15 to 45 minutes, a route and duration similar to our technique, found impaired endothelial function not explained by acidity alone, while contractile function was preserved. Despite this, topical papaverine remains standard practice at concentrations that have greatly exceeded in-vitro half-maximal inhibitory concentration (IC50) thresholds, including the concentration used here, without a significant pattern of anastomosis or graft failure.
Conclusion
Current literature largely focuses on novel extended-delivery systems and comparative in vitro efficacy and toxicity studies. Our technique is an initial step toward evaluating how a short-term drug-carrier delivery method might impact vasospasm before, during, and directly following anastomosis. Because Surgicel and papaverine are each independently approved for clinical use, further study of this technique is highly accessible compared to more novel biomaterials. Studies to prospectively quantify vessel response to this technique and retrospectively assess outcomes in patients who had Surgicel-soaked papaverine versus papaverine irrigation alone are next steps. More broadly, this approach suggests a novel biomaterials opportunity: a hemostatic matrix pre-embedded with a vasodilatory agent, applicable across all vascular anastomoses.