{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:05:42Z","timestamp":1790067942876,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This randomized controlled trial evaluated whether anisodamine hydrobromide reduces 28-day mortality in septic shock and whether this effect is mediated by lactate and lactate clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective randomized controlled trial, 296 patients with septic shock were randomly assigned to receive anisodamine hydrobromide plus standard therapy (n = 148) or standard therapy alone (n = 148). The primary outcome was 28-day all-cause mortality. Causal mediation analyses were performed to assess the mediating roles of lactate and lactate clearance rate at 24, 48, and 72\u00a0h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Anisodamine significantly reduced 28-day mortality compared with control (hazard ratio 0.64, 95% confidence interval 0.43\u20130.95; P = 0.028). Causal mediation analysis revealed that lactate at 24\u00a0h (average causal mediation effect \u22120.0166, P = 0.042) and lactate clearance rate at 24\u00a0h (average causal mediation effect \u22120.0206, P = 0.016) significantly mediated the protective effect, explaining 14.1% and 17.3% of the total effect, respectively. Lactate at 72\u00a0h also showed significant mediation (P = 0.032), with a mediated proportion of 21.6%. Sensitivity analysis using complete cases confirmed the robustness of these findings (hazard ratio 0.60, 95% confidence interval 0.40\u20130.91; P = 0.014), with consistent mediation effects for lactate and lactate clearance at 24\u00a0h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Anisodamine hydrobromide significantly reduces 28-day mortality in patients with septic shock, with effects partially mediated by lactate and lactate clearance at 24\u00a0h. These findings support the integration of anisodamine into sepsis management protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1852584","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:39:11Z","timestamp":1790066351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anisodamine hydrobromide reduces 28-day mortality in septic shock: a randomized controlled"],"prefix":"10.3389","volume":"17","author":[{"given":"Xueting","family":"Yang","sequence":"first","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiong","family":"Peng","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianmeng","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The First People\u2019s Hospital of YiBin","place":["Yibin, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xie","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Deng","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Chen","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Emergency General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Xie","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zeng","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zeng","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Intensive Care Unit, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13054-015-0793-0","article-title":"The original sins of clinical trials with intravenous immunoglobulins in sepsis","volume":"19","author":"Almansa","year":"2015","journal-title":"Crit. 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