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Intensive Care Medicine

, Volume 44, Issue 12, pp 2070–2078 | Cite as

Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial

  • Stephen P. J. Macdonald
  • Gerben Keijzers
  • David McD Taylor
  • Frances Kinnear
  • Glenn Arendts
  • Daniel M. Fatovich
  • Rinaldo Bellomo
  • David McCutcheon
  • John F. Fraser
  • Juan-Carlos Ascencio-Lane
  • Sally Burrows
  • Edward Litton
  • Amanda Harley
  • Matthew Anstey
  • Ashes Mukherjee
  • for the REFRESH trial investigators
Original

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Fluid therapy Sepsis Septic shock Emergency medicine Critical care Resuscitation 

Notes

Acknowledgements

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.

Funding

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.

Supplementary material

134_2018_5433_MOESM1_ESM.pdf (672 kb)
Supplementary material 1 (PDF 672 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature and ESICM 2018

Authors and Affiliations

  • Stephen P. J. Macdonald
    • 1
    • 2
    • 3
  • Gerben Keijzers
    • 4
    • 5
    • 6
  • David McD Taylor
    • 7
    • 8
  • Frances Kinnear
    • 9
  • Glenn Arendts
    • 1
    • 2
    • 10
  • Daniel M. Fatovich
    • 1
    • 2
    • 3
  • Rinaldo Bellomo
    • 11
  • David McCutcheon
    • 1
    • 2
    • 3
    • 12
  • John F. Fraser
    • 13
  • Juan-Carlos Ascencio-Lane
    • 14
  • Sally Burrows
    • 2
  • Edward Litton
    • 15
  • Amanda Harley
    • 4
  • Matthew Anstey
    • 16
  • Ashes Mukherjee
    • 12
  • for the REFRESH trial investigators
  1. 1.Centre for Clinical Research in Emergency MedicineHarry Perkins Institute of Medical ResearchPerthAustralia
  2. 2.Medical SchoolUniversity of Western AustraliaPerthAustralia
  3. 3.Emergency DepartmentRoyal Perth HospitalPerthAustralia
  4. 4.Emergency DepartmentGold Coast University HospitalGold CoastAustralia
  5. 5.School of MedicineBond UniversityGold CoastAustralia
  6. 6.School of Medical SciencesGriffith UniversityGold CoastAustralia
  7. 7.Emergency DepartmentAustin HospitalMelbourneAustralia
  8. 8.Department of MedicineUniversity of MelbourneMelbourneAustralia
  9. 9.Emergency DepartmentThe Prince Charles HospitalBrisbaneAustralia
  10. 10.Emergency DepartmentFiona Stanley HospitalPerthAustralia
  11. 11.Department of Intensive CareAustin HospitalMelbourneAustralia
  12. 12.Emergency DepartmentArmadale-Kelmscott Memorial HospitalPerthAustralia
  13. 13.Critical Care Research GroupThe Prince Charles HospitalBrisbaneAustralia
  14. 14.Emergency DepartmentRoyal Hobart HospitalHobartAustralia
  15. 15.Department of Intensive CareFiona Stanley HospitalPerthAustralia
  16. 16.Department of Intensive CareSir Charles Gairdner HospitalPerthAustralia

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