Prolonging peripheral ropivacaine nerve block with an in situ-formed hydrogel carrier: randomized controlled trial in an ovine model

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Background Local anesthetics are effective for regional anesthesia but have a relatively short duration of action. This motivates the development of sustained-release delivery systems. The aim of this study was to evaluate whether an in situ-forming hydrogel composed of poloxamers and alginate could prolong the duration of ropivacaine-induced sensory and motor blockade. Methods In this randomized and blinded two-period cross-over study, 10 female sheep received ultrasound-guided sciatic nerve injections of either 200 mg ropivacaine poloxamer-alginate hydrogel (Rop-HG) or 200 mg, as a control, plain ropivacaine solution (Rop-C). Sensory and motor functions were assessed repeatedly using a standardized clinical scoring system. Plasma ropivacaine concentrations were measured over time, and postmortem histopathological evaluation of the sciatic nerve and surrounding tissues was performed. Results Rop-HG markedly prolonged block duration compared with Rop-C, increasing the median (IQR) sensory block from 24 hours (IQR 16–36) to 60 hours (IQR 60–72) and the median motor block from 16 hours (IQR 16–18) to 60 hours (IQR 36–72). Pharmacokinetic analysis showed a sharp early peak for Rop-C (median C max 5101 nmol/L and median T max 0.33 hours), whereas Rop-HG produced a lower and delayed profile (median C max 558 nmol/L and median T max 8 hours). Histopathology revealed more pronounced and persistent local tissue reactions in Rop-HG-treated limbs, characterized by degeneration, necrosis, and inflammation. Conclusion Ultrasound-guided perineural injections of 200 mg Rop-HG substantially prolonged the clinical duration of sciatic nerve block and reduced early systemic exposure compared with a 200 mg plain ropivacaine solution. However, the formulation was associated with severe local tissue degeneration, necrosis, and inflammation. Consequently, it remains unclear whether the prolonged clinical effect resulted from a sustained pharmacological release of ropivacaine or from the local tissue toxicity. Further optimization of the formulation is required before clinical translation.