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Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database

Abstract Background Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in...

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Published in:Burns and trauma 2022-01, Vol.10, p.tkac029
Main Authors: Zou, Zhi-ye, Huang, Jia-jia, Luan, Ying-yi, Yang, Zhen-jia, Zhou, Zhi-peng, Zhang, Jing-jing, Yao, Yong-ming, Wu, Ming
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creator Zou, Zhi-ye
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Zhou, Zhi-peng
Zhang, Jing-jing
Yao, Yong-ming
Wu, Ming
description Abstract Background Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68–0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68–0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71–0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56–0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p
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This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68–0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68–0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71–0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56–0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p <0.001). E-Value analysis suggested robustness to unmeasured confounding. Conclusions This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality. A prospective randomized-controlled study should be designed to further assess the relevant findings.]]></description><identifier>ISSN: 2321-3868</identifier><identifier>ISSN: 2321-3876</identifier><identifier>EISSN: 2321-3876</identifier><identifier>DOI: 10.1093/burnst/tkac029</identifier><identifier>PMID: 36168402</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Anticoagulants ; Bacterial infections ; Emergency medical care ; Intensive care ; Mortality ; Sepsis ; Value analysis</subject><ispartof>Burns and trauma, 2022-01, Vol.10, p.tkac029</ispartof><rights>The Author(s) 2022. Published by Oxford University Press. 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-f467e450109787aad249f293817554393832f8af73b1abdfd098b3bfb4fddd193</citedby><cites>FETCH-LOGICAL-c452t-f467e450109787aad249f293817554393832f8af73b1abdfd098b3bfb4fddd193</cites><orcidid>0000-0002-0800-5506</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501718/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501718/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1604,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36168402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zou, Zhi-ye</creatorcontrib><creatorcontrib>Huang, Jia-jia</creatorcontrib><creatorcontrib>Luan, Ying-yi</creatorcontrib><creatorcontrib>Yang, Zhen-jia</creatorcontrib><creatorcontrib>Zhou, Zhi-peng</creatorcontrib><creatorcontrib>Zhang, Jing-jing</creatorcontrib><creatorcontrib>Yao, Yong-ming</creatorcontrib><creatorcontrib>Wu, Ming</creatorcontrib><title>Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database</title><title>Burns and trauma</title><addtitle>Burns Trauma</addtitle><description><![CDATA[Abstract Background Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68–0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68–0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71–0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56–0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p <0.001). E-Value analysis suggested robustness to unmeasured confounding. Conclusions This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality. A prospective randomized-controlled study should be designed to further assess the relevant findings.]]></description><subject>Anticoagulants</subject><subject>Bacterial infections</subject><subject>Emergency medical care</subject><subject>Intensive care</subject><subject>Mortality</subject><subject>Sepsis</subject><subject>Value analysis</subject><issn>2321-3868</issn><issn>2321-3876</issn><issn>2321-3876</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNqFkU1v1DAQhiMEolXplSOyxAUOaf2RxAkHpGrVlpVacQGu1iSxGxdvHGxnUf4NP5VBWVbAhYs99jzz-WbZS0YvGG3EZTuHMabL9BU6ypsn2SkXnOWiltXTo13VJ9l5jI-UUiZ4yWX5PDsRFavqgvLT7Mc1BLeQKfhpWBx0yXYERjw9PMwOkvUj-W7TQAY9QbAjAef03kLSkex8SOBsWgj-d8FiFHrx5RyZMFSPKa7BUU_RxncESNAp-DhpLLTXWAncgh5igt-RNGhyv73fbvLtF9JDghaifpE9M-CiPj_cZ9nnm-tPmw_53cfb7ebqLu-KkqfcFJXURUlxL7KWAD0vGsMbUTNZloVAQ3BTg5GiZdD2pqdN3YrWtIXp-5414ix7v-ad5nan-w6bD-DUFOwOwqI8WPW3Z7SDevB71WBRyWpM8OaQIPhvs45J7WzstHMwaj9HxRFqKiEaiejrf9BHj1LieEhxyqUQtETqYqU63FgM2hybYVT90l-t-quD_hjw6s8RjvhvtRF4uwJ-nv6X7CeVA8Ef</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Zou, Zhi-ye</creator><creator>Huang, Jia-jia</creator><creator>Luan, Ying-yi</creator><creator>Yang, Zhen-jia</creator><creator>Zhou, Zhi-peng</creator><creator>Zhang, Jing-jing</creator><creator>Yao, Yong-ming</creator><creator>Wu, Ming</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0800-5506</orcidid></search><sort><creationdate>20220101</creationdate><title>Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database</title><author>Zou, Zhi-ye ; Huang, Jia-jia ; Luan, Ying-yi ; Yang, Zhen-jia ; Zhou, Zhi-peng ; Zhang, Jing-jing ; Yao, Yong-ming ; Wu, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-f467e450109787aad249f293817554393832f8af73b1abdfd098b3bfb4fddd193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anticoagulants</topic><topic>Bacterial infections</topic><topic>Emergency medical care</topic><topic>Intensive care</topic><topic>Mortality</topic><topic>Sepsis</topic><topic>Value analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zou, Zhi-ye</creatorcontrib><creatorcontrib>Huang, Jia-jia</creatorcontrib><creatorcontrib>Luan, Ying-yi</creatorcontrib><creatorcontrib>Yang, Zhen-jia</creatorcontrib><creatorcontrib>Zhou, Zhi-peng</creatorcontrib><creatorcontrib>Zhang, Jing-jing</creatorcontrib><creatorcontrib>Yao, Yong-ming</creatorcontrib><creatorcontrib>Wu, Ming</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Burns and trauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zou, Zhi-ye</au><au>Huang, Jia-jia</au><au>Luan, Ying-yi</au><au>Yang, Zhen-jia</au><au>Zhou, Zhi-peng</au><au>Zhang, Jing-jing</au><au>Yao, Yong-ming</au><au>Wu, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database</atitle><jtitle>Burns and trauma</jtitle><addtitle>Burns Trauma</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>10</volume><spage>tkac029</spage><pages>tkac029-</pages><issn>2321-3868</issn><issn>2321-3876</issn><eissn>2321-3876</eissn><abstract><![CDATA[Abstract Background Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68–0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68–0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71–0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56–0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p <0.001). E-Value analysis suggested robustness to unmeasured confounding. Conclusions This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality. A prospective randomized-controlled study should be designed to further assess the relevant findings.]]></abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>36168402</pmid><doi>10.1093/burnst/tkac029</doi><orcidid>https://orcid.org/0000-0002-0800-5506</orcidid><oa>free_for_read</oa></addata></record>
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subjects Anticoagulants
Bacterial infections
Emergency medical care
Intensive care
Mortality
Sepsis
Value analysis
title Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database
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