{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:26:54Z","timestamp":1791318414795,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,24]],"date-time":"2024-03-24T00:00:00Z","timestamp":1711238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["associationofanaesthetists-publications.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anaesthesia"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta\u2010analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all\u2010cause mortality. Fifty\u2010six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti\u2010inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1\u2010month follow\u2010up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events,\u00a0based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90\u20131.00), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll\u2010like receptor 4 antagonists (RR (95%CI) 1.18 (1.04\u20131.34), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1\u2010month mortality (RR (95%CI) 0.88 (0.78\u20130.98), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200957%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti\u2010tumour necrosis factor \u03b1 interventions (RR (95%CI) 0.93 (0.87\u20130.99), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). Anti\u2010inflammatory drugs had the largest apparent effect on mortality at 2\u2009months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51\u20130.80), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%) and at 3\u2009months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55\u20130.81), I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). These data indicate that, except for toll\u2010like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short\u2010term mortality benefit for selected drugs.\n                  <\/jats:p>","DOI":"10.1111\/anae.16263","type":"journal-article","created":{"date-parts":[[2024,3,24]],"date-time":"2024-03-24T23:09:05Z","timestamp":1711321745000},"page":"869-879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Immunomodulatory drugs in sepsis: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-4923","authenticated-orcid":false,"given":"R. C.","family":"Robey","sequence":"first","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences University of Manchester, Manchester Academic Health Science Centre  Manchester UK"},{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Logue","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Caird","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hansel","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences University of Manchester, Manchester Academic Health Science Centre  Manchester UK"},{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. P.","family":"Hellyer","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Dark","sequence":"additional","affiliation":[{"name":"University of Manchester Manchester Academic Health Science Centre  Manchester UK"},{"name":"Critical Care Unit, Northern Care Alliance NHS Foundation Trust Salford Care Organisation  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. G.","family":"Mathioudakis","sequence":"additional","affiliation":[{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"},{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences University of Manchester, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Felton","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences University of Manchester, Manchester Academic Health Science Centre  Manchester UK"},{"name":"Wythenshawe Hospital, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1707170"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01926"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.6.1644"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520360048038"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510470040032"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.36"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1751143718765407"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.628302"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-019-05704-z"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.01.007"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82224"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100433"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00734-z"},{"key":"e_1_2_6_17_1","unstructured":"HigginsJPT ThomasJ ChandlerJ et\u00a0al.Cochrane Handbook for Systematic Reviews of Interventions version 6.3. 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