Margaret R Passmore1, Nchafatso G Obonyo2, Liam Byrne3, Ai-Ching Boon4, Sara D Diab5, Kimble R Dunster6, Yoke L Fung7, Michelle M Spanevello8, Mohd H Fauzi9, Sanne E Pedersen10, Gabriela Simonova11, Chris M Anstey12, Kiran Shekar13, John-Paul Tung14, Kathryn Maitland15, John F Fraser16. 1. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; University of Queensland, Brisbane, Australia. Electronic address: M.Passmore@uq.edu.au. 2. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; KEMRI-Wellcome Trust Research Programme, Kenya. Electronic address: gnchafatso@gmail.com. 3. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; Intensive Care Unit, The Canberra Hospital, Canberra, Australia. Electronic address: liambyrne.syd@gmail.com. 4. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; University of Queensland, Brisbane, Australia. Electronic address: c.boon0207@gmail.com. 5. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia. Electronic address: sara_diab5@hotmail.com. 6. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; Queensland University of Technology, Brisbane, Australia. Electronic address: Kimble.Dunster@health.qld.gov.au. 7. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, Australia. Electronic address: ylfung@usc.edu.au. 8. University of Queensland, Brisbane, Australia; Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia. Electronic address: mmspanevello@gmail.com. 9. School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kelantan, Malaysia. Electronic address: hashairi@usm.my. 10. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia. Electronic address: sanne.pedersen.work@gmail.com. 11. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; University of Queensland, Brisbane, Australia; Research and Development, Australian Red Cross Blood Service, Brisbane, Australia. Electronic address: GSimonova@redcrossblood.org.au. 12. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; Sunshine Coast University Hospital Intensive Care, Birtinya, Australia. Electronic address: Chris.Anstey@health.qld.gov.au. 13. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia. Electronic address: kiran.shekar@health.qld.gov.au. 14. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; Research and Development, Australian Red Cross Blood Service, Brisbane, Australia. Electronic address: JTung@redcrossblood.org.au. 15. KEMRI-Wellcome Trust Research Programme, Kenya; Wellcome Trust Centre for Clinical Tropical Medicine and Department of Paediatrics, Faculty of Medicine, Imperial College, London, UK. Electronic address: kathryn.maitland@gmail.com. 16. Critical Care Research Group, Prince Charles Hospital, Brisbane, Australia; University of Queensland, Brisbane, Australia. Electronic address: j.fraser@uq.edu.au.
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.
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.
Authors: Mervyn Singer; Clifford S Deutschman; Christopher Warren Seymour; Manu Shankar-Hari; Djillali Annane; Michael Bauer; Rinaldo Bellomo; Gordon R Bernard; Jean-Daniel Chiche; Craig M Coopersmith; Richard S Hotchkiss; Mitchell M Levy; John C Marshall; Greg S Martin; Steven M Opal; Gordon D Rubenfeld; Tom van der Poll; Jean-Louis Vincent; Derek C Angus Journal: JAMA Date: 2016-02-23 Impact factor: 56.272
Authors: Paul Young; Michael Bailey; Richard Beasley; Seton Henderson; Diane Mackle; Colin McArthur; Shay McGuinness; Jan Mehrtens; John Myburgh; Alex Psirides; Sumeet Reddy; Rinaldo Bellomo Journal: JAMA Date: 2015-10-27 Impact factor: 56.272
Authors: Liam Byrne; Nchafatso G Obonyo; Sara Diab; Kimble Dunster; Margaret Passmore; Ai Ching Boon; Louise See Hoe; Karen Hay; Frank Van Haren; John-Paul Tung; Louise Cullen; Kiran Shekar; Kathryn Maitland; John F Fraser Journal: Shock Date: 2018-01 Impact factor: 3.454
Authors: David S Sparks; Siamak Saifzadeh; Flavia Medeiros Savi; Constantin E Dlaska; Arne Berner; Jan Henkel; Johannes C Reichert; Martin Wullschleger; Jiongyu Ren; Amaia Cipitria; Jacqui A McGovern; Roland Steck; Michael Wagels; Maria Ann Woodruff; Michael A Schuetz; Dietmar W Hutmacher Journal: Nat Protoc Date: 2020-02-14 Impact factor: 13.491
Authors: Mohamad Hakam Tiba; Brendan M McCracken; Robert P Dickson; Jean A Nemzek; Carmen I Colmenero; Danielle C Leander; Thomas L Flott; Rodney C Daniels; Kristine E Konopka; J Scott VanEpps; Kathleen A Stringer; Kevin R Ward Journal: PLoS One Date: 2020-12-11 Impact factor: 3.240