Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis

Stephen Macdonald; Erika Bosio; Gerben Keijzers; Sally Burrows; Moira Hibbs; Helen O'Donoghue; David Taylor; Ashes Mukherjee; Frances Kinnear; Lisa Smart; Juan-Carlos Ascencio-Lane; Edward Litton; John Fraser; Nathan I Shapiro; Glenn Arendts; Daniel Fatovich; REFRESH Trial Investigators

doi:10.1186/s40635-023-00508-4

Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis

Intensive Care Med Exp. 2023 Apr 17;11(1):21. doi: 10.1186/s40635-023-00508-4.

Authors

Stephen Macdonald^{1

2

3}, Erika Bosio^{4

5}, Gerben Keijzers^{6

7

8}, Sally Burrows^{5

9}, Moira Hibbs¹⁰, Helen O'Donoghue¹⁰, David Taylor¹¹, Ashes Mukherjee¹², Frances Kinnear¹³, Lisa Smart¹⁴, Juan-Carlos Ascencio-Lane¹⁵, Edward Litton¹⁶, John Fraser¹⁷, Nathan I Shapiro¹⁸, Glenn Arendts^{4

5

19}, Daniel Fatovich^{4

5

20}; REFRESH Trial Investigators

Collaborators

REFRESH Trial Investigators:
David McCutcheon, Anton Leonard, Jonathan Burcham, Rinaldo Bellomo, Glenn Arendts, Edward Litton, Amanda Harley, James Winearls, Juan Carlos Ascencio-Lane, Simon Brown, David Cooper, Daniel Fatovich, Ioana Vlad, Bradley Wibrow, Matthew Anstey, Sarah Hazelwood

Affiliations

¹ Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia. [email protected].
² Medical School, University of Western Australia, Perth, WA, Australia. [email protected].
³ Emergency Department, Royal Perth Hospital, Perth, WA, Australia. [email protected].
⁴ Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia.
⁵ Medical School, University of Western Australia, Perth, WA, Australia.
⁶ Emergency Department, Gold Coast University Hospital, Gold Coast, QLD, Australia.
⁷ Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia.
⁸ School of Medicine, Griffith University, Gold Coast, QLD, Australia.
⁹ Research Foundation, Royal Perth Hospital, Perth, WA, Australia.
¹⁰ Research Centre, Royal Perth Hospital, Perth, WA, Australia.
¹¹ Emergency Department, Austin Health, Melbourne, Australia.
¹² Emergency Department, Armadale Health Service, Perth, WA, Australia.
¹³ Department of Medicine, University of Queensland, Brisbane, QLD, Australia.
¹⁴ School of Science, Health Engineering and Education, Murdoch University, Perth, WA, Australia.
¹⁵ Emergency Department, Royal Hobart Hospital, Hobart, TAS, Australia.
¹⁶ Intensive Care, Fiona Stanley Hospital, Perth, WA, Australia.
¹⁷ Critical Care Research Group, The Prince Charles Hospital, University of Queensland, Brisbane, QLD, Australia.
¹⁸ Department of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
¹⁹ Emergency Department, Fiona Stanley Hospital, Perth, WA, Australia.
²⁰ Emergency Department, Royal Perth Hospital, Perth, WA, Australia.

Abstract

Purpose: To investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation.

Materials and methods: A planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation.

Results: Blood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers.

Conclusions: A consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial. Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.

Keywords: Endothelial glycocalyx; Endothelium; Fluid therapy; Inflammation; Sepsis.

Associated data

ANZCTR/ACTRN126160000006448