Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial
To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis.
A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6 h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100 mmHg, after minimum 1000 ml of IV fluid. Primary outcome was total fluid administered within 6 h post randomisation.
There were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6 h in the restricted volume group was 2387 ml [first to third quartile (Q1–Q3) 1750–2750 ml]; 30 ml/kg (Q1–Q3 32–39 ml/kg) vs. 3000 ml (Q1–Q3 2250–3900 ml); 43 ml/kg (Q1–Q3 35–50 ml/kg) in the usual care group (p < 0.001). Median duration of vasopressor support was 21 h (Q1–Q3 9–42 h) vs. 33 h (Q1–Q3 15–50 h), (p = 0.13) in the restricted volume and usual care groups, respectively. At 90-days, 4 of 48 (8%) in the restricted volume group and 3 of 47 (6%) in the usual care group had died. Protocol deviations occurred in 6/50 (12%) in restricted group and 11/49 (22%) in the usual care group, and serious adverse events in four cases (8%) in each group.
A regimen of restricted fluids and early vasopressor in ED patients with suspected sepsis and hypotension appears feasible. Illness severity was moderate and mortality rates low. A future trial is necessary with recruitment of high-risk patients to determine effects on clinical outcomes in this setting.
KeywordsFluid therapy Sepsis Septic shock Emergency medicine Critical care Resuscitation
REFRESH trial investigators and participating sites: Armadale Health Service, WA (David McCutcheon, Ashes Mukherjee, Anton Leonard, Jonathan Burcham); Austin Health, VIC (David Taylor, Rinaldo Bellomo); Fiona Stanley Hospital, WA (Glenn Arendts, Edward Litton); Gold Coast University Hospital, QLD (Gerben Keijzers, Amanda Harley, James Winearls); Royal Hobart Hospital (Juan Carlos Ascencio-Lane, Simon Brown, David Cooper); Royal Perth Hospital/Centre for Clinical Research in Emergency Medicine, WA (Stephen Macdonald [steering committee chair], Daniel Fatovich, Lisa Smart); Sir Charles Gairdner Hospital, WA (Ioana Vlad, Bradley Wibrow, Matthew Anstey); The Prince Charles Hospital, QLD (Frances Kinnear, John Fraser). Trial Management and Coordination: Ellen Macdonald, Sophie Damianopoulos. Data Safety Monitoring Committee: Anthony Brown, Robert Boots, Michael Phillips. Trial endorsed by the Australasian College for Emergency Medicine Clinical Trials Group.
The REFRESH trial was an investigator-initiated study funded in part by a grant from the Emergency Medicine Foundation, Queensland, Australia EMSS-229R24-2015, and supported by the participating institutions.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
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