ANZICS CTG Endorsed Study
Australasian Resuscitation in Sepsis Evaluation: Fluids
We propose a pivotal multicentre, randomised clinical trial comparing a strategy of intravenous (IV) fluid sparing resuscitation with early introduction of vasopressors to the current recommended practice of a larger volume of IV fluid and later vasopressors in patients presenting to the Emergency Department (ED) with septic shock: The Australasian Resuscitation In Sepsis Evaluation: FLUid or Vasopressors In Emergency Department Sepsis (ARISE FLUIDS).
Sepsis is a major public health issue, recognised as a Global Health Priority by the World Health Organisation. Sepsis affects over 18,000 patients per year in Australia, with a burden of death more than 3 times the annual national road toll. Current standard care of patients with septic shock includes the initial administration of a large volume of intravenous fluid, with vasopressor medication reserved for those with persistent hypotension. Recent evidence suggests this approach may be associated with harm, and a fluid-sparing strategy with earlier introduction of vasopressors may be better.
Building on the success of the ARISE trial and the REFRESH pilot study, we propose to randomise patients presenting to the ED with sepsis, a lactate >2mmol/L and hypotension (SBP<90mmHg) after receiving 1000ml of IV fluid, to receive either a ‘vasopressor first’ strategy with sparing use of IV fluids, or current standard ‘fluid first’ management with later introduction of vasopressors. Allocation will be concealed and the primary outcome (90-day mortality) robust. We will randomise 3000 patients, a sample size that will allow us to detect a clinically important reduction in mortality. Given the high mortality rate of sepsis, this may lead to hundreds of lives saved per year in our country and thousands worldwide. A study aimed at resolving the uncertainty about fluid and vasopressor use in patients with septic shock Australia is, therefore, of the highest priority.
Sandra Peake (Chair), Glenn Arendts, Rinaldo Bellomo, Louise Cullen, Anthony Delaney, Daniel Fatovich, John Fraser, Amanda Harley, Peter Jones, Gerben Keijzers, Stephen MacDonald, David Taylor, Andrew Udy, Julian Williams, and Trish Williams.
Project Status as of June 2019
The NHMRC funding application for 2018 was unsuccessful.
The investigator team are focusing on completing the ARISE-FLUIDS Observational study prior to re-submitting a grant application. This will provide crucial contemporary data concerning fluid and vasopressor use in septic hypotensive patients in the ED. Similarly, we are seeking greater consumer engagement, so as to inform the study question. This will be through great collaboration with the Australian Sepsis Network, and via community forums.
Andrew Udy (email)