{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:14:01Z","timestamp":1792710841650,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare outcomes of phenobarbital\u2010based versus benzodiazepine\u2010based pathways for alcohol withdrawal syndrome (AWS) in critically ill adults and evaluate whether pathway design and timing of phenobarbital use affect treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>\n                      A librarian\u2010led search of MEDLINE, Embase, Cochrane Central, CINAHL, Web of Science, Scopus,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      , and the World Health Organization International Clinical Trials Registry Platform was conducted through July 2024, with updates in December 2024, August 2025, and December 2025. Search concepts included phenobarbital, benzodiazepines, and alcohol withdrawal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction<\/jats:title>\n                    <jats:p>Comparative studies of adults admitted or transferred to an intensive care unit (ICU) with AWS and treated with phenobarbital\u2010based versus benzodiazepine\u2010based pathways were included. Sixteen nonrandomized studies were included in the qualitative synthesis, and 12 treatment\u2010oriented studies were included in the primary meta\u2010analysis. Multiple reviewers independently screened studies, extracted data, and assessed risk of bias using Risk Of Bias In Non\u2010randomized Studies\u2014of Interventions (ROBINS\u2010I).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis<\/jats:title>\n                    <jats:p>\n                      Phenobarbital\u2010based pathways were not associated with significantly different intubation (11 studies; odds ratio (OR), 0.62; 95% confidence interval (CI), 0.20\u20131.87;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200973%) or hospital length of stay (five studies; mean differences [MD], \u22121.75\u2009days; 95% CI, \u22125.07 to 1.56;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200963%) compared with benzodiazepine\u2010based pathways. ICU length of stay was shorter with phenobarbital\u2010based pathways (eight studies; MD, \u22120.60\u2009days; 95% CI, \u22120.79 to \u22120.41;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%). In exploratory subgroup analyses, front\u2010loaded, protocolized phenobarbital\u2010first pathways were associated with lower intubation and shorter hospital length of stay, but certainty of evidence was very low.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance to Patient Care and Clinical Practice<\/jats:title>\n                    <jats:p>This review distinguishes phenobarbital\u2010first, protocolized ICU pathways from adjunctive or mixed phenobarbital strategies, suggesting that implementation design may influence outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although evidence remains very low certainty, these findings suggest that phenobarbital's role in ICU AWS may be pathway dependent. Front\u2010loaded, protocolized phenobarbital\u2010first pathways may be associated with favorable outcomes in exploratory analyses, but these findings should be considered hypothesis\u2010generating and require confirmation in prospective randomized trials.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      CRD42024595819\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70197","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:59:07Z","timestamp":1787551147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenobarbital Versus Benzodiazepine\u2010Based Pathways for Alcohol Withdrawal Syndrome in Critically Ill Adults: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4936-9775","authenticated-orcid":false,"given":"Zeeshan M.","family":"Rizwan","sequence":"first","affiliation":[{"name":"Department of Pharmacy Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Clinical Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6030-321X","authenticated-orcid":false,"given":"Simone","family":"Barry","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Sleep Medicine Royal Adelaide Hospital  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kern","family":"Guppy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Kaiser Permanente  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-3915","authenticated-orcid":false,"given":"Dana J.","family":"Gerberi","sequence":"additional","affiliation":[{"name":"Mayo Clinic Libraries Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4218-0890","authenticated-orcid":false,"given":"Ognjen","family":"Gajic","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-9364","authenticated-orcid":false,"given":"Svetlana","family":"Herasevich","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0261443"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1407298"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ta.0000000000000352"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(81)91179\u20103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.33695"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2023.04.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2023.03.006"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216669183"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1429"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202102\u2010121OC"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_12_14_1","unstructured":"The Cochrane Collaboration \u201cReview Manager (RevMan) v. 7.2.0 \u201d(2024)."},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2017.01.001"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.MR000026.pub2"},{"key":"e_1_2_12_18_1","article-title":"Phenobarbital Versus Diazepam for Delirium Tremens\u2014A Retrospective Study","volume":"57","author":"Michaelsen I. 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