Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial
Open accessAbstract
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.
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The current evidence evaluating a restrictive IV fluid strategy in septic patients varies in inclusion criteria, definitions of restrictive and liberal strategies, criteria for additional fluids, and duration of interventions.
“The current evidence evaluating a restrictive IV fluid strategy in the management of septic patients varies with respect to the inclusion criteria, the definition of restrictive and liberal fluid strategies, the criteria guiding the administration of additional IV fluids (e.g., perfusion parameters vs. haemodynamic variables), and the duration of the interventions [397–401].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [400]
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- Authors
- Macdonald, S. P. J., Keijzers, G., Taylor, D. M., Kinnear, F., Arendts, G., Fatovich, D. M., Bellomo, R., McCutcheon, D., Fraser, J. F., Ascencio-Lane, J.-C., Burrows, S., Litton, E., Harley, A., Anstey, M., Mukherjee, A., & for the REFRESH trial investigators
- Affiliations
- The University of Western Australia (AU)
- Griffith University (AU)
- The University of Melbourne (AU)
- Prince Charles Hospital (AU)
- Austin Hospital (AU)
- Royal Hobart Hospital (AU)
- Fiona Stanley Hospital (AU)
- Gold Coast Hospital (AU)
- Sir Charles Gairdner Hospital (AU)
- Armadale Health Service (AU)
- Corresponding author
- Macdonald, Stephen P. J.
- ORCID
- Venue
- Intensive Care Medicine
- Published
- 2018-10-31
- Volume
- 44
- Issue
- 12
- Pages
- 2070-2078
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2898967013
- Cited by
- 129
- References
- 33
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 25 · 2022: 17 · 2021: 28 · 2020: 17 · 2019: 9
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- eSpace (Curtin University) (submittedVersion)
- Bond University Research Portal (Bond University) (submittedVersion, other-oa)
- Griffith Research Online (submittedVersion)
- Funders
- Queensland Emergency Medicine Research Foundation (EMSS-229R24-2015)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Abdominal Surgery and Complications
- Keywords
- sepsis, septic shock, hypotension, fluid resuscitation, emergency department, protocol feasibility, mortality, protocol adherence
- MeSH terms
- Aged, Blood Pressure, Drug Administration Schedule, Emergency Service, Hospital, Feasibility Studies, Female, Fluid Therapy, Humans, Hypotension, Male, Middle Aged, Pilot Projects, Prospective Studies, Resuscitation, Vasoconstrictor Agents, Sepsis
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