REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial
Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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BioMed Central
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/56712 |
| _version_ | 1848759920312188928 |
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| author | Macdonald, S. Taylor, D. Keijzers, G. Arendts, G. Fatovich, D. Kinnear, F. Brown, S. Bellomo, R. Burrows, S. Fraser, J. Litton, E. Ascencio-Lane, J. Anstey, Matthew McCutcheon, D. Smart, L. Vlad, I. Winearls, J. Wibrow, B. |
| author_facet | Macdonald, S. Taylor, D. Keijzers, G. Arendts, G. Fatovich, D. Kinnear, F. Brown, S. Bellomo, R. Burrows, S. Fraser, J. Litton, E. Ascencio-Lane, J. Anstey, Matthew McCutcheon, D. Smart, L. Vlad, I. Winearls, J. Wibrow, B. |
| author_sort | Macdonald, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Trial registration: Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016. |
| first_indexed | 2025-11-14T10:07:33Z |
| format | Journal Article |
| id | curtin-20.500.11937-56712 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:07:33Z |
| publishDate | 2017 |
| publisher | BioMed Central |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-567122018-08-08T01:26:58Z REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial Macdonald, S. Taylor, D. Keijzers, G. Arendts, G. Fatovich, D. Kinnear, F. Brown, S. Bellomo, R. Burrows, S. Fraser, J. Litton, E. Ascencio-Lane, J. Anstey, Matthew McCutcheon, D. Smart, L. Vlad, I. Winearls, J. Wibrow, B. Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. Trial registration: Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016. 2017 Journal Article http://hdl.handle.net/20.500.11937/56712 10.1186/s13063-017-2137-7 http://creativecommons.org/licenses/by/4.0/ BioMed Central fulltext |
| spellingShingle | Macdonald, S. Taylor, D. Keijzers, G. Arendts, G. Fatovich, D. Kinnear, F. Brown, S. Bellomo, R. Burrows, S. Fraser, J. Litton, E. Ascencio-Lane, J. Anstey, Matthew McCutcheon, D. Smart, L. Vlad, I. Winearls, J. Wibrow, B. REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title | REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title_full | REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title_fullStr | REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title_full_unstemmed | REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title_short | REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial |
| title_sort | restricted fluid resuscitation in sepsis-associated hypotension (refresh): study protocol for a pilot randomised controlled trial |
| url | http://hdl.handle.net/20.500.11937/56712 |