Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock. Issue 176 (April 2019)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Thrombosis research. Issue 176(2019)
• Page Start: 39
• Page End: 45
• Publication Date: 2019-04
• Subjects: aPTT activated partial thromboplastin time -- AT antithrombin -- CFT clot formation time -- CT clotting time -- CVP central venous pressure -- DIC disseminated intravascular coagulation -- Hb haemoglobin -- Hct haematocrit -- LPS lipopolysaccharide -- MAP mean arterial pressure -- MCF maximum clot firmness -- PLT platelets -- PT prothrombin time -- RCC red cell count -- ROTEM rotational thromboelastometry -- TEG thromboelastography -- WCC white cell count; Sepsis -- Thromboelastometry -- Coagulation -- Fibrinogen -- Coagulation factors; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2019.02.015
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: 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. Materials and methods: 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. Results: 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). Conclusions: 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. Highlights: 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.