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

Zou, Zhi-ye; Huang, Jia-jia; Luan, Ying-yi; Yang, Zhen-jia; Zhou, Zhipeng; Zhang, Jingjing; Yao, Yong-ming; Wu, Ming

doi:10.1093/burnst/tkac029

Cited by 11 publications

(14 citation statements)

References 41 publications

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“…Therefore, unfractionated heparin has been widely used in clinical practice Systematic reviews have documented that treatment with a low dose of heparin is associated with a significant reduction 28-day mortality among patients with sepsis ( Wang et al, 2014 ; Zarychanski et al, 2015 ). Our previous results study manifested an association between heparin administrationand decreased risk-adjusted mortality in septic patients (HR 0.70, 95% CI 0.56–0.87, p < 0.001) ( Zou et al, 2022 ). Unfortunately, in update surviving sepsis campaign 2021, there were no recommendations on anticoagulation in patients with sepsis, only recommend using low molecular weight heparin over unfractionated heparin for venous thromboembolism prophylaxis ( Evans et al, 2021 ).…”

Section: Introductionmentioning

confidence: 87%

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Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy

et al. 2023

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Background: This study aimed to investigate whether early unfractionated heparin (UFH) administration provides a survival advantage for patients with sepsis-induced coagulopathy (SIC).Methods: Patients hospitalized with sepsis-induced coagulopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database were identified. Patients were divided into two groups, who received unfractionated heparin (UFH) subcutaneously within 24 h after intensive care unit (ICU) admission, and the control group, who received not. The primary endpoint was intensive care unit mortality, the secondary outcomes were 7, 14, and 28-day and hospital mortality. Propensity score matching (PSM) the marginal structural Cox model (MSCM) and E-value analysis were used to account for baseline differences, time-varying and unmeasured confounding factors.Results: A total of 3,377 patients with sepsis-induced coagulopathy were enrolled in the study, of which 815 in unfractionated heparin group and 2,562 in control group. There was significant effect on primary and secondary outcomes with unfractionated heparin after propensity score matching (intensive care unit mortality, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.52–0.92; 7-day, HR 0.70, 95% CI 0.49–0.99; 14-day, HR 0.68.95% CI 0.50–0.92; 28-day, HR 0.72, 95% CI 0.54–0.96; hospital mortality, HR 0.74, 95% CI 0.57–0.96), marginal structural Cox model manifested unfractionated heparin associated with decreased intensive care unit mortality in all populations (HR 0.64, 95% CI 0.49–0.84), and stratification with the marginal structural Cox model indicated analysis further indicated the survival advantage only among patients with an sepsis-induced coagulopathy score of 4 (HR 0.56, 95% CI 0.38–0.81). Further analysis showed that treatment with 6,250–13750 IU/day of unfractionated heparin associated with a decreased risk of intensive care unit mortality. Similar results were replicated in subgroup analysis with propensity score matching only for patients with an sepsis-induced coagulopathy score of 4 (intensive care unit mortality, HR 0.51, 95% CI 0.34–0.76).Conclusion: This study found early unfractionated heparin therapy to patients with sepsis-induced coagulopathy appears to be associated with improved outcomes. Subgroup analysis further demonstrates heparin therapy decreased intensive care unit mortality primarily in patients only with SIC score of 4.

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Section: Introductionmentioning

confidence: 87%

“…Using Structured Query Language, the MIMIC-IV database was populated with data. The database was searched using techniques described previously, and the extracted patient data were then analyzed ( Shen et al, 2019 ; Zou et al, 2022 ). Patients with multiple hospitalizations were only counted for their initial hospitalization.…”

Section: Methodsmentioning

confidence: 99%

Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy

et al. 2023

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“…Nevertheless, systematic reviews have documented that treatment with a low dose of heparin is associated with a signi cant reduction in 28-day mortality among patients with sepsis [9,10]. Our previous study found an association between early prophylactic heparin administration to septic patients and decreased risk-adjusted mortality (HR 0.70, 95% CI 0.56-0.87, P < 0.001) [11]. Therefore, the indications for and timing and dosage of heparin administration to patients with sepsis are still unclear.…”

Section: Introductionmentioning

confidence: 94%

“…Data were extracted from the MIMIC-IV database through Structured Query Language [19]. We used the methods described in previous studies to search this database (sepsis) and analyse the extracted patient data [11,20]. For patients with multiple hospitalizations, only the rst hospitalization was included.…”

Section: Research Procedures and De Nitionsmentioning

confidence: 99%

Association of prophylactic heparin therapy and outcomes in critically ill patients with sepsis-induced coagulopathy: A marginal structural Cox model cohort study

Huang

Zou

Zhou

et al. 2022

Preprint

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BackgroundSepsis-induced coagulopathy (SIC) is defined as infection-induced organ dysfunction and coagulopathy. Although anticoagulation with heparin has been widely used in practice, its effectiveness for treating SIC remains controversial. This study aimed to investigate whether prophylactic heparin administration would provide a survival advantage for patients with SIC.Methods Patients with SIC were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was ICU mortality, and the secondary outcomes were 7-day, 14-day, and 28-day mortality as well as hospital mortality. A Cox proportional hazards model and propensity score matching (PSM) were used to account for baseline differences in the probability of using prophylactic heparin. The marginal structural Cox model (MSCM) was employed to adjust for both baseline and time-varying confounding factors. E-value analysis was used for unmeasured confounding.Results A total of 6498 septic patients with SIC were enrolled in the study, with 1284 in the heparin group and 5124 in the nonheparin group. There was no significant effect on ICU mortality in the overall population (prematched, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.77-1.14, P=0.517, postmatched, HR 0.89, 95% CI 0.70-1.12, P=0.323). Interestingly, the MSCM identified a significant effect on ICU mortality in the overall population (HR 0.77, 95% CI 0.60-0.98, P=0.032). Stratification analysis with the MSCM showed that prophylactic heparin administration was associated with decreased ICU mortality only among patients with a SIC score of 4 (HR 0.63, 95% CI 0.45-0.89, P=0.009). Similar results were replicated with PSM only for patients with a SIC score of 4 (ICU mortality HR 0.68, 95% CI 0.49-0.95, P=0.025; 7-day mortality HR 0.59, 95% CI 0.36-0.98, P=0.040; 14-day mortality HR 0.66, 95% CI 0.44-0.98, P=0.040; Hospital mortality HR 0.77, 95% CI 0.58-1.03, P=0.074; 28-day mortality HR 0.77, 95% CI 0.54-1.10, P=0.147). E-value analysis indicated robustness to unmeasured confounding.Conclusions: Prophylactic heparin administration to patients with a SIC score of 4 appears to be associated with improved survival outcomes, including ICU mortality and 7-day and 14-day mortality, but not with improvement in hospital or 28-day mortality. These results need to be verified in prospective randomized controlled trials.

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“…The second similar propensity analysis also reported reduced in-hospital and 60-day mortality by prophylactic use of UFH or LMWH. 25 In these studies, UFH was administered for thrombosis prophylaxis rather than treating sepsis-associated DIC. Therefore, UFH administration was initiated within 48 hours of ICU admission.…”

Section: Effectiveness Of Heparins On Sepsis-associated Dicmentioning

confidence: 99%

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

Iba,

Helms,

Totoki

et al. 2024

Semin Thromb Hemost

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Historically, heparin has had the longest historical use as an anticoagulant and continues this day to be the primary therapeutic option for preventing thrombosis and thromboembolism in critically ill hospitalized patients. Heparin is also used to treat sepsis and sepsis-associated disseminated intravascular coagulation (DIC) in various countries. However, the efficacy and safety of heparin for this indication remains controversial, as adequately powered randomized clinical studies have not demonstrated as yet a survival benefit in sepsis and sepsis-associated DIC, despite meta-analyses and propensity analyses reporting improved outcomes without increasing bleeding risk. Further, activated protein C and recombinant thrombomodulin showed greater improvements in outcomes compared with heparin, although these effects were inconclusive. In summary, further research is warranted, despite the ongoing clinical use of heparin for sepsis and sepsis-associated DIC. Based on Japanese guidelines, antithrombin or recombinant thrombomodulin may be a preferable choice if they are accessible.

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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

Cited by 11 publications

References 41 publications

Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy

Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy

Association of prophylactic heparin therapy and outcomes in critically ill patients with sepsis-induced coagulopathy: A marginal structural Cox model cohort study

Heparins May Not Be the Optimal Anticoagulants for Sepsis and Sepsis-Associated Disseminated Intravascular Coagulation

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