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

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• Picked for Pathology and Forensic Medicine (top studies of the week, 6 September 2026): Hydrogel nerve block study, not pathology

Abstract

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 Cmax 5101 nmol/L and median Tmax 0.33 hours), whereas Rop-HG produced a lower and delayed profile (median Cmax 558 nmol/L and median Tmax 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.

Abstract as published, via PubMed.