Induced normothermia ameliorates the procoagulant host response in human endotoxaemia
Background Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in health...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2021
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| _version_ | 1826272496699047936 |
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| author | Harmon, MBA Heijnen, NFL de Bruin, S Sperna Weiland, NH Meijers, JCM de Boer, AM Schultz, MJ Horn, J Juffermans, NP |
| author_facet | Harmon, MBA Heijnen, NFL de Bruin, S Sperna Weiland, NH Meijers, JCM de Boer, AM Schultz, MJ Horn, J Juffermans, NP |
| author_sort | Harmon, MBA |
| collection | OXFORD |
| description | Background
Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers.
Methods
Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg−1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model.
Results
In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L−1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide.
Conclusion
In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
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| first_indexed | 2024-03-06T22:13:29Z |
| format | Journal article |
| id | oxford-uuid:529cc31e-1e68-4f0f-afec-f930e5d57024 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:13:29Z |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:529cc31e-1e68-4f0f-afec-f930e5d570242022-03-26T16:26:36ZInduced normothermia ameliorates the procoagulant host response in human endotoxaemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:529cc31e-1e68-4f0f-afec-f930e5d57024EnglishSymplectic ElementsElsevier2021Harmon, MBAHeijnen, NFLde Bruin, SSperna Weiland, NHMeijers, JCMde Boer, AMSchultz, MJHorn, JJuffermans, NPBackground Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers. Methods Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg−1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model. Results In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L−1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide. Conclusion In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states. |
| spellingShingle | Harmon, MBA Heijnen, NFL de Bruin, S Sperna Weiland, NH Meijers, JCM de Boer, AM Schultz, MJ Horn, J Juffermans, NP Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title | Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title_full | Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title_fullStr | Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title_full_unstemmed | Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title_short | Induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
| title_sort | induced normothermia ameliorates the procoagulant host response in human endotoxaemia |
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