{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T18:11:56Z","timestamp":1778004716341,"version":"3.51.4"},"reference-count":13,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n Regional anesthesia is widely regarded as one of the safest anesthetic techniques, yet serious complications\u2014such as nerve injury, hematoma, pneumothorax, and local anesthetic systemic toxicity (LAST)\u2014continue to be reported. Their true incidence remains uncertain, as available data are often derived from registry or retrospective studies with heterogeneous definitions and limited sample sizes. Moreover, the mechanisms underlying complications such as nerve injury are incompletely understood and may extend beyond direct mechanical trauma to include factors such as sub-perineural injection, hematoma formation, altered coagulation, and patient-specific vulnerability.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The\n NEURAL<\/jats:italic>\n study, promoted by the Italian Society of Anesthesia, Analgesia and Critical Care (SIAARTI), is a multicenter, prospective, observational study designed to determine the incidence and risk factors for complications following single-shot regional anesthesia of the upper limb, lower limb, and fascial plane. The primary endpoint is the composite incidence of nerve injury, hematoma, pneumothorax, and LAST. Secondary objectives include determining the individual incidence of each complication and identifying patient- and procedure-related risk factors. Data will be collected via the REDCap\u00ae (Research Electronic Data Capture) platform from more than 40 Italian centers. Standardized follow-up will be performed at 24 and 48 hours, 15 and 30 days, and monthly thereafter for unresolved neurological deficits, up to one year. Statistical analyses will include logistic regression modeling to identify independent predictors of complications.\n <\/jats:p>\n <\/jats:sec>\n \n Expected results<\/jats:title>\n Based on an estimated complication rate of 0.5%, a minimum of 3,396 patients will be required to ensure adequate precision of incidence estimates. Nationwide participation is expected to exceed this target.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The\n NEURAL<\/jats:italic>\n study will provide robust, prospective, and standardized data on complications of regional anesthesia. By identifying their true incidence and modifiable risk factors, the findings are expected to inform safer clinical practice, enhance patient counseling, and support the development of updated evidence-based guidelines.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0348493","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:26:16Z","timestamp":1778001976000},"page":"e0348493","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurological events and unanticipated risks after locoregional anesthesia (NEURAL): Protocol for a multicenter prospective observational study"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-1832","authenticated-orcid":true,"given":"Alessandro","family":"De Cassai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Ioppolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Bugada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Tasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Cappelleri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-9177","authenticated-orcid":true,"given":"Vito","family":"Torrano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"issue":"1","key":"pone.0348493.ref001","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3390\/jcm10010102","article-title":"General anesthesia compared to spinal anesthesia for patients undergoing lumbar vertebral surgery: A meta-analysis of randomized controlled trials","volume":"10","author":"A De Cassai","year":"2020","journal-title":"J Clin Med"},{"key":"pone.0348493.ref002","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ajem.2022.06.017","article-title":"Local anesthetic systemic toxicity: A narrative review for emergency clinicians","volume":"59","author":"B Long","year":"2022","journal-title":"Am J Emerg Med"},{"issue":"3","key":"pone.0348493.ref003","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/PRS.0000000000005989","article-title":"Local anesthetic systemic toxicity: A narrative literature review and clinical update on prevention, diagnosis, and management","volume":"144","author":"M Gitman","year":"2019","journal-title":"Plast Reconstr Surg"},{"key":"pone.0348493.ref004","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/anae.14140","article-title":"Peripheral nerve injury arising in anaesthesia practice","author":"DW Hewson","year":"2018","journal-title":"Anaesthesia"},{"key":"pone.0348493.ref005","doi-asserted-by":"crossref","first-page":"111868","DOI":"10.1016\/j.jclinane.2025.111868","article-title":"Morphological findings in the sciatic nerve after intraneural injection","volume":"104","author":"R Boscolo-Berto","year":"2025","journal-title":"J Clin Anesth"},{"key":"pone.0348493.ref006","article-title":"Traumatic needle damage to nerves during regional anesthesia: presentation of a novel mechanotransduction hypothesis","author":"GA McLeod","year":"2022","journal-title":"Reg Anesth Pain Med"},{"issue":"5","key":"pone.0348493.ref007","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/AAP.0000000000000125","article-title":"Pathophysiology and etiology of nerve injury following peripheral nerve blockade","volume":"40","author":"R Brull","year":"2015","journal-title":"Reg Anesth Pain Med"},{"key":"pone.0348493.ref008","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/AAP.0000000000000286","article-title":"The Second ASRA practice advisory on neurologic complications associated with regional anesthesia and pain medicine: Executive summary 2015","volume":"40","author":"JM Neal","year":"2015","journal-title":"Reg Anesth Pain Med"},{"key":"pone.0348493.ref009","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/01621459.1927.10502953","article-title":"Probable inference, the law of succession, and statistical inference","volume":"22","author":"EB Wilson","year":"1927","journal-title":"J Am Stat Ass"},{"issue":"1","key":"pone.0348493.ref010","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1213\/00000539-200301000-00050","article-title":"Neurologic complications of 405 consecutive continuous axillary catheters","volume":"96","author":"BD Bergman","year":"2003","journal-title":"Anesth Analg"},{"key":"pone.0348493.ref011","unstructured":"European Parliament, Council of the European Union. Regulation (EU) 2016\/679 of the European Parliament and of the Council on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95\/46\/EC (General Data Protection Regulation). 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