Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock
Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coa...
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| Veröffentlicht in: | Thrombosis research 2019-04, Vol.176, p.39-45 |
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| creator | Passmore, Margaret R. Obonyo, Nchafatso G. Byrne, Liam Boon, Ai-Ching Diab, Sara D. Dunster, Kimble R. Fung, Yoke L. Spanevello, Michelle M. Fauzi, Mohd H. Pedersen, Sanne E. Simonova, Gabriela Anstey, Chris M. Shekar, Kiran Tung, John-Paul Maitland, Kathryn Fraser, John F. |
| description | Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.
Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups.
Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.
•Fluid resuscitation results in prolonged prothrombin time and aPTT.•Fluid resuscitation results in decreased levels of antithrombin and Protein C.•ROTEM clotting time and clot formation time are prolonged with fluid resuscitation. |
| doi_str_mv | 10.1016/j.thromres.2019.02.015 |
| format | Article |
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Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups.
Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.
•Fluid resuscitation results in prolonged prothrombin time and aPTT.•Fluid resuscitation results in decreased levels of antithrombin and Protein C.•ROTEM clotting time and clot formation time are prolonged with fluid resuscitation.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/j.thromres.2019.02.015</identifier><identifier>PMID: 30776686</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Animals ; Blood Pressure - drug effects ; Coagulation ; Coagulation factors ; Disease Models, Animal ; Endotoxemia - blood ; Endotoxemia - physiopathology ; Endotoxemia - therapy ; Female ; Fibrinogen ; Fluid Therapy ; Hemostasis - drug effects ; Resuscitation ; Saline Solution - therapeutic use ; Sepsis ; Sheep ; Thromboelastometry</subject><ispartof>Thrombosis research, 2019-04, Vol.176, p.39-45</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-6fe7998ad96830d5b0fb76f0b0ed8b9c53af10eb154b596f48c61b5ee376e7aa3</citedby><cites>FETCH-LOGICAL-c471t-6fe7998ad96830d5b0fb76f0b0ed8b9c53af10eb154b596f48c61b5ee376e7aa3</cites><orcidid>0000-0002-0859-8882</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.thromres.2019.02.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30776686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Passmore, Margaret R.</creatorcontrib><creatorcontrib>Obonyo, Nchafatso G.</creatorcontrib><creatorcontrib>Byrne, Liam</creatorcontrib><creatorcontrib>Boon, Ai-Ching</creatorcontrib><creatorcontrib>Diab, Sara D.</creatorcontrib><creatorcontrib>Dunster, Kimble R.</creatorcontrib><creatorcontrib>Fung, Yoke L.</creatorcontrib><creatorcontrib>Spanevello, Michelle M.</creatorcontrib><creatorcontrib>Fauzi, Mohd H.</creatorcontrib><creatorcontrib>Pedersen, Sanne E.</creatorcontrib><creatorcontrib>Simonova, Gabriela</creatorcontrib><creatorcontrib>Anstey, Chris M.</creatorcontrib><creatorcontrib>Shekar, Kiran</creatorcontrib><creatorcontrib>Tung, John-Paul</creatorcontrib><creatorcontrib>Maitland, Kathryn</creatorcontrib><creatorcontrib>Fraser, John F.</creatorcontrib><title>Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.
Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups.
Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.
•Fluid resuscitation results in prolonged prothrombin time and aPTT.•Fluid resuscitation results in decreased levels of antithrombin and Protein C.•ROTEM clotting time and clot formation time are prolonged with fluid resuscitation.</description><subject>Animals</subject><subject>Blood Pressure - drug effects</subject><subject>Coagulation</subject><subject>Coagulation factors</subject><subject>Disease Models, Animal</subject><subject>Endotoxemia - blood</subject><subject>Endotoxemia - physiopathology</subject><subject>Endotoxemia - therapy</subject><subject>Female</subject><subject>Fibrinogen</subject><subject>Fluid Therapy</subject><subject>Hemostasis - drug effects</subject><subject>Resuscitation</subject><subject>Saline Solution - therapeutic use</subject><subject>Sepsis</subject><subject>Sheep</subject><subject>Thromboelastometry</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhL1S-IHFJGCfx1wWBKgpIlbjAFcuxJ8RLEhfbWcq_J6ttKzhxmsP7MaN5CLlgUDNg4vW-LmOKc8JcN8B0DU0NjD8iO6akrppONo_JDqDTVas6dUae5bwHYJJp_pSctSClEErsyLeraQ2ebj1rdqHYEuJCf4UyUqj1S5rtFBakdiqYMh0tzjEXm0OmYaF2ofFwlOfocaJxoLj4WOItzsHRPEb34zl5Mtgp44u7eU6-Xr3_cvmxuv784dPlu-vKdZKVSgwotVbWa6Fa8LyHoZdigB7Qq1473tqBAfaMdz3XYuiUE6zniK0UKK1tz8mbU-_N2s_oHS4l2cncpDDb9NtEG8y_yhJG8z0ejBSs5Q1sBa_uClL8uWIuZg7Z4TTZBeOaTcNUKzquG7FZxcnqUsw54fCwhoE5wjF7cw_HHOEYaMwGZwte_H3kQ-yexmZ4ezLg9qpDwGQ2Jrg49CGhK8bH8L8dfwCf1Kbn</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Passmore, Margaret R.</creator><creator>Obonyo, Nchafatso G.</creator><creator>Byrne, Liam</creator><creator>Boon, Ai-Ching</creator><creator>Diab, Sara D.</creator><creator>Dunster, Kimble R.</creator><creator>Fung, Yoke L.</creator><creator>Spanevello, Michelle M.</creator><creator>Fauzi, Mohd H.</creator><creator>Pedersen, Sanne E.</creator><creator>Simonova, Gabriela</creator><creator>Anstey, Chris M.</creator><creator>Shekar, Kiran</creator><creator>Tung, John-Paul</creator><creator>Maitland, Kathryn</creator><creator>Fraser, John F.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0859-8882</orcidid></search><sort><creationdate>20190401</creationdate><title>Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock</title><author>Passmore, Margaret R. ; 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The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.
Twenty-one adult female sheep were randomly divided into no endotoxemia (n = 5) or endotoxemia groups (n = 16) with an escalating dose of lipopolysaccharide (LPS) up to 4 μg/kg/h administered to achieve a mean arterial pressure below 60 mmHg. Endotoxemia sheep received either no bolus fluid resuscitation (n = 8) or a 0.9% saline bolus (40 mL/kg over 60 min) (n = 8). No endotoxemia, saline only animals (n = 5) underwent fluid resuscitation with a 0.9% bolus of saline as detailed above. Hemodynamic support with vasopressors was initiated if needed, to maintain a mean arterial pressure (MAP) of 60-65 mm Hg in all the groups.
Rotational thromboelastometry (ROTEM®) and conventional coagulation biomarker tests demonstrated sepsis induced derangements to secondary haemostasis. This effect was exacerbated by saline fluid resuscitation, with low pH (p = 0.036), delayed clot initiation and formation together with deficiencies in naturally occurring anti-coagulants antithrombin (p = 0.027) and Protein C (p = 0.001).
Endotoxemia impairs secondary haemostasis and induces changes in the intrinsic, extrinsic and anti-coagulant pathways. These changes to haemostasis are exacerbated following resuscitation with 0.9% saline, a commonly used crystalloid in clinical settings.
•Fluid resuscitation results in prolonged prothrombin time and aPTT.•Fluid resuscitation results in decreased levels of antithrombin and Protein C.•ROTEM clotting time and clot formation time are prolonged with fluid resuscitation.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>30776686</pmid><doi>10.1016/j.thromres.2019.02.015</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-0859-8882</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Thrombosis research, 2019-04, Vol.176, p.39-45 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Blood Pressure - drug effects Coagulation Coagulation factors Disease Models, Animal Endotoxemia - blood Endotoxemia - physiopathology Endotoxemia - therapy Female Fibrinogen Fluid Therapy Hemostasis - drug effects Resuscitation Saline Solution - therapeutic use Sepsis Sheep Thromboelastometry |
| title | Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock |
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