{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:16:28Z","timestamp":1788448588179,"version":"build-2803163510"},"reference-count":40,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,8,3]]},"abstract":"\n Background<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Rop-HG markedly prolonged block duration compared with Rop-C, increasing the median (IQR) sensory block from 24 hours (IQR 16\u201336)\u2009to 60 hours (IQR 60\u201372)\u2009and the median motor block from 16 hours (IQR 16\u201318)\u2009to 60 hours (IQR 36\u201372). Pharmacokinetic analysis showed a sharp early peak for Rop-C (median C\n max<\/jats:sub>\n 5101 nmol\/L and median T\n max<\/jats:sub>\n 0.33\u2009hours), whereas Rop-HG produced a lower and delayed profile (median C\n max<\/jats:sub>\n 558 nmol\/L and median T\n max<\/jats:sub>\n \u20098 hours). Histopathology revealed more pronounced and persistent local tissue reactions in Rop-HG-treated limbs, characterized by degeneration, necrosis, and inflammation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/rapm-2026-108092","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:30:07Z","timestamp":1788445807000},"page":"rapm-2026-108092","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Prolonging peripheral ropivacaine nerve block with an in situ-formed hydrogel carrier: randomized controlled trial in an ovine model"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0573-0033","authenticated-orcid":false,"given":"Hans Vangsnes","family":"Vingen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Helse M\u00f8re og Romsdal HF, Alesund, Norway"},{"name":"Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"\u0106uk","sequence":"additional","affiliation":[{"name":"Section for Pharmaceutics and Social Pharmacy, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-8143","authenticated-orcid":false,"given":"Axel R","family":"Sauter","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav","family":"Spigset","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway"},{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Helse M\u00f8re og Romsdal HF, Alesund, Norway"},{"name":"Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-806X","authenticated-orcid":false,"given":"Fredrik Strebel","family":"Skedsmo","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, \u00c5s, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hiorth","sequence":"additional","affiliation":[{"name":"Section for Pharmaceutics and Social Pharmacy, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1316-1139","authenticated-orcid":false,"given":"Marija T","family":"Garvin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor \u00c5","family":"Myklebust","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, M\u00f8re og Romsdal Hospital Trust, Alesund, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audun","family":"Stubhaug","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6796-3219","authenticated-orcid":false,"given":"Henning A","family":"Haga","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Norwegian University of Life Sciences, \u00c5s, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"2026090307202072000_rapm-2026-108092v1.1","article-title":"New formulations of local anaesthetics-part I","volume":"2012","author":"Shipton","year":"2012","journal-title":"Anesthesiol Res Pract"},{"key":"2026090307202072000_rapm-2026-108092v1.2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.actbio.2021.09.008","article-title":"An injectable mesoporous silica-based analgesic delivery system prolongs the duration of sciatic nerve block in mice with minimal toxicity","volume":"135","author":"Wang","year":"2021","journal-title":"Acta Biomater"},{"key":"2026090307202072000_rapm-2026-108092v1.3","first-page":"e101","article-title":"Advances in regional anaesthesia and acute pain management: a narrative review","volume":"75 Suppl 1","author":"Albrecht","year":"2020","journal-title":"Anaesthesia"},{"key":"2026090307202072000_rapm-2026-108092v1.4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137312","article-title":"Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review","volume":"10","author":"Kirksey","year":"2015","journal-title":"PLoS One"},{"key":"2026090307202072000_rapm-2026-108092v1.5","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/anae.15245","article-title":"Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review","volume":"76 Suppl 1","author":"Desai","year":"2021","journal-title":"Anaesthesia"},{"key":"2026090307202072000_rapm-2026-108092v1.6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/pm\/pnac119","article-title":"Extended Release of Bupivacaine from Temperature-responsive Hydrogels Provides Multi-day Analgesia for Postoperative Pain","volume":"24","author":"Heffernan","year":"2023","journal-title":"Pain Med"},{"key":"2026090307202072000_rapm-2026-108092v1.7","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2021-102726"},{"key":"2026090307202072000_rapm-2026-108092v1.8","doi-asserted-by":"crossref","DOI":"10.1038\/natrevmats.2016.71","article-title":"Designing hydrogels for controlled drug delivery","volume":"1","author":"Li","year":"2016","journal-title":"Nat Rev Mater"},{"key":"2026090307202072000_rapm-2026-108092v1.9","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13111953","article-title":"Advances in Injectable In Situ-Forming Hydrogels for Intratumoral Treatment","volume":"13","author":"Shin","year":"2021","journal-title":"Pharmaceutics"},{"key":"2026090307202072000_rapm-2026-108092v1.10","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/1440-1681.13492","article-title":"Population pharmacokinetic analysis of ropivacaine extended-release from a temperature-responsive hydrogel in rats","volume":"48","author":"Bang","year":"2021","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2026090307202072000_rapm-2026-108092v1.11","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/7300098","article-title":"Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation","volume":"2021","author":"Mariano","year":"2021","journal-title":"Biomed Res Int"},{"key":"2026090307202072000_rapm-2026-108092v1.12","doi-asserted-by":"crossref","DOI":"10.3390\/ph15030371","article-title":"Current and Future Prospective of Injectable Hydrogels-Design Challenges and Limitations","volume":"15","author":"Almawash","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"key":"2026090307202072000_rapm-2026-108092v1.13","doi-asserted-by":"crossref","first-page":"121291","DOI":"10.1016\/j.ijpharm.2021.121291","article-title":"Injectable thermosensitive lipo-hydrogels loaded with ropivacaine for prolonging local anesthesia","volume":"611","author":"Li","year":"2022","journal-title":"Int J Pharm"},{"key":"2026090307202072000_rapm-2026-108092v1.14","first-page":"101158","article-title":"Development of an injectable, in situ formed hydrogel for controlled delivery of local anesthetics by exploiting synergism between thermoresponsive block copolymers and alginate, chitosan, or hyaluronate","volume":"14","author":"\u0106uk","year":"2026","journal-title":"Carbohydr Polym Technol Appl"},{"key":"2026090307202072000_rapm-2026-108092v1.15","article-title":"Ultrasound Landmarks in the Approach to the Common Peroneal Nerve in a Sheep Model-Application in Peripheral Nerve Regeneration","volume":"13","author":"Alvites","year":"2023","journal-title":"Life (Basel)"},{"key":"2026090307202072000_rapm-2026-108092v1.16","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22031401","article-title":"Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve","volume":"22","author":"Alvites","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026090307202072000_rapm-2026-108092v1.17","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"2026090307202072000_rapm-2026-108092v1.18","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2022.830689","article-title":"The Median Effective Analgesic Concentration of Ropivacaine in Sciatic Nerve Block Guided by Ultrasound After Arthroscopic Anterior Cruciate Ligament Reconstruction: A Double-Blind Up-Down Concentration-Finding Study","volume":"9","author":"Xu","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"2026090307202072000_rapm-2026-108092v1.19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.52973\/rcfcv-e32102","article-title":"Distribution of the Sciatic nerve in hind limb of Hasmer sheep breed: an anatomical study","volume":"XXXII","author":"Balkaya","year":"2021","journal-title":"RC FCV-LUZ"},{"key":"2026090307202072000_rapm-2026-108092v1.20","doi-asserted-by":"crossref","first-page":"9603271231173382","DOI":"10.1177\/09603271231173382","article-title":"Establishment of an animal model of sciatic nerve injury induced by local anesthetics","volume":"42","author":"E","year":"2023","journal-title":"Hum Exp Toxicol"},{"key":"2026090307202072000_rapm-2026-108092v1.21","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1177\/0310057X0903700612","article-title":"Repeated intrathecal administration of ropivacaine causes neurotoxicity in rats","volume":"37","author":"Zhong","year":"2009","journal-title":"Anaesth Intensive Care"},{"key":"2026090307202072000_rapm-2026-108092v1.22","doi-asserted-by":"crossref","first-page":"120748","DOI":"10.1016\/j.ijpharm.2021.120748","article-title":"Injectable thermoresponsive gels offer sustained dual release of bupivacaine hydrochloride and ketorolac tromethamine for up to two weeks","volume":"604","author":"Abdeltawab","year":"2021","journal-title":"Int J Pharm"},{"key":"2026090307202072000_rapm-2026-108092v1.23","doi-asserted-by":"crossref","DOI":"10.3390\/gels11020131","article-title":"Advanced Hydrogel Systems for Local Anesthetic Delivery: Toward Prolonged and Targeted Pain Relief","volume":"11","author":"Jeong","year":"2025","journal-title":"Gels"},{"key":"2026090307202072000_rapm-2026-108092v1.24","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/ALN.0000000000003630","article-title":"Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain","volume":"134","author":"Ilfeld","year":"2021","journal-title":"Anesthesiology"},{"key":"2026090307202072000_rapm-2026-108092v1.25","doi-asserted-by":"publisher","DOI":"10.1097\/AAP.0000000000000772"},{"key":"2026090307202072000_rapm-2026-108092v1.26","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1517\/17425241003767383","article-title":"Review of prolonged local anesthetic action","volume":"7","author":"Weiniger","year":"2010","journal-title":"Expert Opin Drug Deliv"},{"key":"2026090307202072000_rapm-2026-108092v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpa.2014.02.001"},{"key":"2026090307202072000_rapm-2026-108092v1.28","doi-asserted-by":"crossref","first-page":"119703","DOI":"10.1016\/j.ijpharm.2020.119703","article-title":"Entrapping bupivacaine-loaded emulsions in a crosslinked-hydrogel increases anesthetic effect and duration in a rat sciatic nerve block model","volume":"588","author":"Davis","year":"2020","journal-title":"Int J Pharm"},{"key":"2026090307202072000_rapm-2026-108092v1.29","doi-asserted-by":"crossref","first-page":"4904","DOI":"10.7150\/thno.74845","article-title":"Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"key":"2026090307202072000_rapm-2026-108092v1.30","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1177\/08853282251387512","article-title":"Development and evaluation of a ropivacaine-loaded hydrogel for prolonged nerve blockade and local anesthesia","volume":"40","author":"Zhang","year":"2026","journal-title":"J Biomater Appl"},{"key":"2026090307202072000_rapm-2026-108092v1.31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/00000542-200601000-00017","article-title":"Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: comparison of in vitro, in vivo, and effect kinetics","volume":"104","author":"S\u00f6derberg","year":"2006","journal-title":"Anesthesiology"},{"key":"2026090307202072000_rapm-2026-108092v1.32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4155\/tde.14.95","article-title":"Pain management via local anesthetics and responsive hydrogels","volume":"6","author":"Bagshaw","year":"2015","journal-title":"Ther Deliv"},{"key":"2026090307202072000_rapm-2026-108092v1.33","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1213\/ANE.0000000000001581","article-title":"Continuous Peripheral Nerve Blocks: An Update of the Published Evidence and Comparison With Novel, Alternative Analgesic Modalities","volume":"124","author":"Ilfeld","year":"2017","journal-title":"Anesth Analg"},{"key":"2026090307202072000_rapm-2026-108092v1.34","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ijpharm.2019.01.011","article-title":"Preclinical studies of ropivacaine extended-release from a temperature responsive hydrogel for prolonged relief of pain at the surgical wound","volume":"558","author":"Oh","year":"2019","journal-title":"Int J Pharm"},{"key":"2026090307202072000_rapm-2026-108092v1.35","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-023-01803-8","article-title":"Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration","volume":"21","author":"Zhao","year":"2023","journal-title":"J Nanobiotechnology"},{"key":"2026090307202072000_rapm-2026-108092v1.36","doi-asserted-by":"crossref","DOI":"10.1002\/mabi.202300005","article-title":"Development of a Supramolecular Hydrogel for Intraperitoneal Injections","volume":"24","author":"Wintjens","year":"2024","journal-title":"Macromol Biosci"},{"key":"2026090307202072000_rapm-2026-108092v1.37","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.actbio.2025.11.005","article-title":"A solvent-free ropivacaine-loaded composite hydrogel assembled from pH-sensitive micelles and a thermosensitive injectable hydrogel for prolonged local anesthesia","volume":"208","author":"Li","year":"2025","journal-title":"Acta Biomater"},{"key":"2026090307202072000_rapm-2026-108092v1.38","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1016\/j.biomaterials.2012.12.035","article-title":"A chitosan thermogel for delivery of ropivacaine in regional musculoskeletal anesthesia","volume":"34","author":"Foley","year":"2013","journal-title":"Biomaterials"},{"key":"2026090307202072000_rapm-2026-108092v1.39","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp130336"},{"key":"2026090307202072000_rapm-2026-108092v1.40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/vms3.1049","article-title":"Effect of temperature-responsive hydrogel on femoral and sciatic nerve blocks using bupivacaine in Beagle dogs","volume":"9","author":"Kim","year":"2023","journal-title":"Vet Med Sci"}],"container-title":["Regional Anesthesia & Pain Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rapm-2026-108092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:30:13Z","timestamp":1788445813000},"score":1,"resource":{"primary":{"URL":"https:\/\/rapm.bmj.com\/lookup\/doi\/10.1136\/rapm-2026-108092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":40,"alternative-id":["10.1136\/rapm-2026-108092"],"URL":"https:\/\/doi.org\/10.1136\/rapm-2026-108092","relation":{},"ISSN":["1098-7339","1532-8651"],"issn-type":[{"value":"1098-7339","type":"print"},{"value":"1532-8651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}