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Coagulopathy, encephalopathy, sepsis and other comorbidities complicate care. Liver failure lowers albumin and \u03b11-acid glycoprotein and slows hepatic clearance, increasing the unbound fraction and effective exposure to amide local anesthetics. Risks are magnified by acidosis, low cardiac output, low body mass index, sepsis, and concurrent renal dysfunction. Neuraxial options are often limited by coagulopathy and the risk of catastrophic neurologic complications while superficial, compressible peripheral blocks are generally considered safer than deep plexus targets. Safe practice includes the use of ultrasound guidance, incremental injection with frequent aspirations, avoidance of unnecessary high-dose multiple-site injections, and conservative dosing and infusion strategies. Regional anesthesia is feasible in patients with hepatic failure when dose and technique are adjusted to disease biology and when local anesthetic systemic toxicity (LAST) preparedness is routine. Catheters should run at lower concentrations and rates with scheduled reassessment and clearly communicated stop times. Teams should keep 20% lipid emulsion immediately available for treatment of neurologic or cardiovascular signs of LAST. We provide a practical pathway to select the block, choose the agent, and set doses that keep a reasonable safety margin for local anesthetics.<\/jats:p>","DOI":"10.1177\/08850666261444973","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:58:05Z","timestamp":1779299885000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Regional Anesthesia in Patients with Hepatic Failure: How Risky is it to Administer Local Anesthetic?"],"prefix":"10.1177","author":[{"given":"Montather O.","family":"Taheer","sequence":"first","affiliation":[{"name":"University of North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Kleiman","sequence":"additional","affiliation":[{"name":"University of Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari K.","family":"Kalagara","sequence":"additional","affiliation":[{"name":"Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-5611","authenticated-orcid":false,"given":"Bryant W.","family":"Tran","sequence":"additional","affiliation":[{"name":"University of North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"issue":"2","key":"e_1_3_3_2_2","first-page":"239","article-title":"Perioperative evaluation and management of patients with cirrhosis: Risk assessment, surgical outcomes, and future directions","volume":"270","author":"Newman KL","year":"2019","unstructured":"Newman KL, Johnson KM, Cornia PB, et al. 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