{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:06:06Z","timestamp":1790258766429,"version":"4.1.0"},"reference-count":20,"publisher":"BMJ","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,9,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The use of mixtures of local anaesthetics and\/or adjuvants is a common practice in regional anaesthesia, aimed at optimising onset time and prolonging block duration. However, several previous in vitro studies have demonstrated that mixing local anaesthetics may lead to crystallisation. A major barrier to understanding their potential physiological effects has been the lack of imaging techniques capable of detecting crystal formations beyond conventional microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this in vitro study, ropivacaine 0.75%, lidocaine 2%, chloroprocaine 2% and mepivacaine 2%, as well as six commonly used local anaesthetic or local anaesthetic-adjuvant mixtures, were imaged by high-resolution ultrasound in liquid medium, using two high-resolution probes of 24 MHz and 33 MHz over a maximum duration of 40\u2009min. The sonographic grade of crystallization was assessed on a scale from 0 to 3\u2009based on the number and size of visible precipitates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two pure local anaesthetics\u2014lidocaine and chloroprocaine\u2014demonstrated minimal crystallization. All mixtures produced precipitates immediately after mixing, with mild to moderate increases in crystallization quantities over time. The mixture of ropivacaine, lidocaine, and sodium bicarbonate exhibited the highest tendency to crystallise, reaching a sonographic grade of crystallization of 1 at baseline, increasing to 3 at 20\u201340\u2009min.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>All investigated mixtures demonstrated precipitation detectable by high-resolution ultrasound; the combination of ropivacaine, lidocaine and sodium bicarbonate showed the most pronounced effect. Ultrasound imaging proved to be a suitable method for detecting and grading crystalline structures in vitro and may represent a possible technology for future in vivo diagnostics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2026-108294","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:45:11Z","timestamp":1790257511000},"page":"rapm-2026-108294","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Crystal precipitates of local anaesthetic and adjuvant mixtures can be visualised and graded using ultrahigh-frequency ultrasound imaging"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0326-557X","authenticated-orcid":false,"given":"Anna","family":"Seisl","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Gasteiger","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottokar","family":"Stundner","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria"},{"name":"Department of Anesthesiology, Paracelsus Medical University, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Skalla","sequence":"additional","affiliation":[{"name":"Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Oberherber","sequence":"additional","affiliation":[{"name":"Canon Medical Systems GesmbH, Wiener Neudorf, Lower Austria, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Gasteiger","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"2026092406450704000_rapm-2026-108294v1.1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/AAP.0b013e31819a9528","article-title":"Bicarbonate plus epinephrine shortens the onset and prolongs the duration of sciatic block using chloroprocaine followed by bupivacaine in sprague-dawley rats","volume":"34","author":"Yung","year":"2009","journal-title":"Reg Anesth Pain Med"},{"key":"2026092406450704000_rapm-2026-108294v1.2","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/anae.14966","article-title":"Choice of local anaesthetic for epidural caesarean section: a Bayesian network meta-analysis","volume":"75","author":"Reschke","year":"2020","journal-title":"Anaesthesia"},{"key":"2026092406450704000_rapm-2026-108294v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aet417"},{"key":"2026092406450704000_rapm-2026-108294v1.4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/anae.15641","article-title":"Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review","volume":"77","author":"Nestor","year":"2022","journal-title":"Anaesthesia"},{"key":"2026092406450704000_rapm-2026-108294v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31823c1030"},{"key":"2026092406450704000_rapm-2026-108294v1.6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/ALN.0000000000005683","article-title":"Is It Time to Reassess Local Anesthetic and Adjuvant Mixtures? A Narrative Review of Practice, Evidence, and Risks","volume":"144","author":"Gasteiger","year":"2026","journal-title":"Anesthesiology"},{"key":"2026092406450704000_rapm-2026-108294v1.7","doi-asserted-by":"crossref","unstructured":"Siddique Z , Nestor CC . Letter to the editor: Dexamethasone and ropivacaine - Potential for physiochemical incompatibility. J Clin Anesth 2022;82. doi:10.1016\/j.jclinane.2022.110934","DOI":"10.1016\/j.jclinane.2022.110934"},{"key":"2026092406450704000_rapm-2026-108294v1.8","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31819237f8"},{"key":"2026092406450704000_rapm-2026-108294v1.9","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2023-105229"},{"key":"2026092406450704000_rapm-2026-108294v1.10","doi-asserted-by":"crossref","unstructured":"Gasteiger E , Schwarz B , Harder M , et al . Crystallization of local anesthetic and adjuvant mixtures: a chemical analysis of the crystal precipitate composition. Reg Anesth Pain Med 2025. doi:10.1136\/rapm-2025-106981","DOI":"10.1136\/rapm-2025-106981"},{"key":"2026092406450704000_rapm-2026-108294v1.11","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2023-104398"},{"key":"2026092406450704000_rapm-2026-108294v1.12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5535\/arm.2016.40.1.21","article-title":"Crystallization of Local Anesthetics When Mixed With Corticosteroid Solutions","volume":"40","author":"Hwang","year":"2016","journal-title":"Ann Rehabil Med"},{"key":"2026092406450704000_rapm-2026-108294v1.13","doi-asserted-by":"crossref","unstructured":"Zhu A , Pei L , Liu W , et al . Neurologic Complication Due to Crystallization After Drug Interaction Between Alkalized Lidocaine and Ropivacaine: A Case Report and in vitro Study. Front Med (Lausanne) 2022;9. doi:10.3389\/fmed.2022.919911","DOI":"10.3389\/fmed.2022.919911"},{"key":"2026092406450704000_rapm-2026-108294v1.14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/AAP.0b013e31820d4235","article-title":"Combined versus sequential injection of mepivacaine and ropivacaine for supraclavicular nerve blocks","volume":"36","author":"Roberman","year":"2011","journal-title":"Reg Anesth Pain Med"},{"key":"2026092406450704000_rapm-2026-108294v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/bjaceaccp\/mkr030"},{"key":"2026092406450704000_rapm-2026-108294v1.16","doi-asserted-by":"publisher","DOI":"10.11613\/BM.2012.031\/FULLARTICLE"},{"key":"2026092406450704000_rapm-2026-108294v1.17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1034\/j.1399-6576.2001.450106.x","article-title":"Neurologic sequelae after caesarean section","volume":"45","author":"Rorarius","year":"2001","journal-title":"Acta Anaesthesiol Scand"},{"key":"2026092406450704000_rapm-2026-108294v1.18","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00101-013-2179-5","article-title":"Bupivacaine crystal deposits after long-term epidural infusion","volume":"62","author":"Balga","year":"2013","journal-title":"Anaesthesist"},{"key":"2026092406450704000_rapm-2026-108294v1.19","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2656"},{"key":"2026092406450704000_rapm-2026-108294v1.20","doi-asserted-by":"crossref","unstructured":"Gasteiger E , Seisl A , Hegen H , et al . Local Anesthetic and Adjuvant Mixtures Show Unexpected pH-Dependent Crystallization Patterns in Human Cerebrospinal Fluid: A Semiquantitative In Vitro Trial. Anesth Analg 2026. doi:10.1213\/ANE.0000000000008193","DOI":"10.1213\/ANE.0000000000008193"}],"container-title":["Regional Anesthesia &amp; Pain Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rapm-2026-108294","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:45:15Z","timestamp":1790257515000},"score":1,"resource":{"primary":{"URL":"https:\/\/rapm.bmj.com\/lookup\/doi\/10.1136\/rapm-2026-108294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":20,"alternative-id":["10.1136\/rapm-2026-108294"],"URL":"https:\/\/doi.org\/10.1136\/rapm-2026-108294","relation":{},"ISSN":["1098-7339","1532-8651"],"issn-type":[{"value":"1098-7339","type":"print"},{"value":"1532-8651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}