{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:17:51Z","timestamp":1792808271081,"version":"4.5.0"},"reference-count":18,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Canerector Foundation"},{"DOI":"10.13039\/100031571","name":"Libin Cardiovascular Institute, University of Calgary","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031571","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL142583-01A1"],"award-info":[{"award-number":["R01 HL142583-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["UL1 TR000445"],"award-info":[{"award-number":["UL1 TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,2,23]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Ehlers-Danlos syndromes (EDS) are a collection of heritable connective tissue disorders. Local anesthetic resistance is commonly reported by patients with EDS, but there is little clinical evidence to support this finding. We hypothesized that patients with EDS would have increased anesthetic resistance using lidocaine compared with healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An interventional study design was used. Participants (total N=135: EDS n=91, healthy n=44) completed a series of sensation tests using a standardized 10\u2009g monofilament following subcutaneous injection with saline or lidocaine at two separate sites on the right forearm in a randomized order. Participants rated their sensation at each site relative to non-anesthetized skin. Sensation was used as a surrogate measure of anesthetic effect. Participant ratings were converted into two measures: (1) a dichotomous variable to represent adequate anesthesia and (2) a delta sensation score. This study was registered on ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05603741\">NCT05603741<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Delta sensation scores were not different at 5\u2009min post-injection between EDS and healthy participants (p=0.2), but were significantly different at 15\u2009min (1 (0\u20132) arbitrary units (a.u.) vs 2 (1\u20132) a.u; p=0.002) and 30\u2009min (1 (0\u20132) a.u. vs 2 (1\u20132) a.u.; p=0.003) post-injection. There was no difference in categorical \u201canesthesia\u201d at 5\u2009min between EDS and controls (p=0.2). A smaller proportion of EDS experienced \u201canesthesia\u201d at 15 min (60% vs 84%, p=0.006) and 30 min (53% vs 80%, p=0.003) post-injection compared with healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with EDS experienced increased sensation with lidocaine, suggesting shorter duration of effect of lidocaine local anesthetic. This evidence validates previous patient reports and small case studies suggesting this phenomenon. Healthcare providers should be aware of this reduced effectiveness experienced by patients with EDS, to adjust care accordingly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05603741\">NCT05603741<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2025-107416","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:40:14Z","timestamp":1772552414000},"page":"rapm-2025-107416","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Patients with Ehlers-Danlos syndrome experience reduced effectiveness of lidocaine local anesthetic: a randomized cross-over clinical trial"],"prefix":"10.1136","clinical-trial-number":[{"clinical-trial-number":"nct05603741","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05603741","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04036305","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05603741","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-0002","authenticated-orcid":false,"given":"Kate M","family":"Bourne","sequence":"first","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serra","family":"Thai","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy Y","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Black","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Peltier","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Paranjape","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndya A","family":"Shibao","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Diedrich","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Gamboa","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Sheldon","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish R","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada"},{"name":"Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University 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