Too much of a good thing: does fluid resuscitation worsen septic shock?

Grant ID: EMPJ-358R25-2016

Lay Summary

Patients with infections are a leading cause of presentations to the Emergency Department (ED), with severe sepsis and infection causing an estimated 20,000 deaths each day across the world. Treatment is aimed at eradicating the infection and supporting the patient while recovery can take place. Frequently patients develop low blood pressure as a result of immune response that can ultimately result in further organ injury (termed septic shock). Intravenous fluids are recommended by international guidelines as the first line therapy in the ED to treat low blood pressure of sepsis with the hope of preventing organ injury and death.

Despite 50 years of use in sepsis, the rationale for fluids remains based in theory rather than clear evidence it is effective in saving lives. Disconcertingly, there is now increasing evidence that fluids in sepsis are ineffective and may actually worsen patient survival. Despite this fluids continue to be recommended and used liberally in the ED resulting in conflict between our historical practice and the best evidence. We have developed an animal model of septic shock and resuscitation in order to test the effectiveness of fluid resuscitation. This will allow us to both understand the true effect but also investigate the underlying physiological mechanisms of any harms.


Leveraged Funds

- NHMRC grant: $AUD 980,810.56 (Understanding tissue responses to fluid resuscitation and blood transfusion during ovine sepsis to improve outcomes [ 2014 - 2017 ] Also known as: Resuscitation in Endotoxaemic Shock - Understanding Sepsis (RESUS))
- In-kind: $230,000


Dissemination

- Byrne, L., Obonyo, N.G., Diab, S., Dunster, K., Passmore, M., Boon, A.C., Hoe, L.S., Pedersen S., Fauzi M.H., Pimenta L.P., Hay, K., Van Haren, F., Antsey C.M., Cullen, L., Tung J-P., Shekar, K., Maitland, K., and Fraser, J., “Unintended Consequences; Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia”, American Journal of Respirator and Critical Care Medicine, 2018 June [in press]. doi.org/10.1164/rccm.201801-0064OC
- Byrne, L., Obonyo, N.G., Diab, S., Dunster, K., Passmore, M., Boon, A.C., Hoe, L.S., Hay, K., Van Haren, F., Tung, J.P. and Cullen, L., 2017. "An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism", 'Shock', 2018;49(1):99-107. doi: 10.1097/SHK.0000000000000904.


SHARE

Amount Awarded
$77,233


Program


Grant Scheme


Status
Active


Principal Investigator:
Prof Louise Cullen


Co Investigators:
Prof John Fraser
Prof Kathryn Maitland
A/Prof Kiran Shekar
Dr Liam Bryne
Dr Obonyo Nchfatso
Dr Louise See Ho
Margaret Passmore
Dr Ai Chin Boon


Institution


Collaborating Institutions


Links

  • Linked EMF funding: Developing animal model that underpins this research
  • Fluid bolus therapy Fluid bolus therapy by Chris Nickson, Last updated December 13, 2017
  • Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review

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