REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trial
Abstract 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 inju...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Trials |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13063-017-2137-7 |
| _version_ | 1818190070553772032 |
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| author | Stephen P. J. Macdonald David McD Taylor Gerben Keijzers Glenn Arendts Daniel M. Fatovich Frances B. Kinnear Simon G. A. Brown Rinaldo Bellomo Sally Burrows John F. Fraser Edward Litton Juan Carlos Ascencio-Lane Matthew Anstey David McCutcheon Lisa Smart Ioana Vlad James Winearls Bradley Wibrow |
| author_facet | Stephen P. J. Macdonald David McD Taylor Gerben Keijzers Glenn Arendts Daniel M. Fatovich Frances B. Kinnear Simon G. A. Brown Rinaldo Bellomo Sally Burrows John F. Fraser Edward Litton Juan Carlos Ascencio-Lane Matthew Anstey David McCutcheon Lisa Smart Ioana Vlad James Winearls Bradley Wibrow |
| author_sort | Stephen P. J. Macdonald |
| collection | DOAJ |
| description | Abstract 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 | 2024-12-11T23:52:52Z |
| format | Article |
| id | doaj.art-ec2ae4ed092a4d67b6114e8670624850 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-11T23:52:52Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-ec2ae4ed092a4d67b6114e86706248502022-12-22T00:45:27ZengBMCTrials1745-62152017-08-0118111510.1186/s13063-017-2137-7REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trialStephen P. J. Macdonald0David McD Taylor1Gerben Keijzers2Glenn Arendts3Daniel M. Fatovich4Frances B. Kinnear5Simon G. A. Brown6Rinaldo Bellomo7Sally Burrows8John F. Fraser9Edward Litton10Juan Carlos Ascencio-Lane11Matthew Anstey12David McCutcheon13Lisa Smart14Ioana Vlad15James Winearls16Bradley Wibrow17Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchEmergency Department, Austin HospitalEmergency Department, Gold Coast University HospitalCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchEmergency and Children’s Services, The Prince Charles HospitalCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchDepartment of Intensive Care, Austin HospitalSchool of Medicine and Pharmacology, University of Western AustraliaSchool of Medicine, Bond UniversityDepartment of Intensive Care, Fiona Stanley HospitalEmergency Department, Royal Hobart HospitalDepartment of Intensive Care, Sir Charles Gairdner HospitalCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchCentre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical ResearchEmergency Department, Sir Charles Gairdner HospitalSchool of Medical Sciences, Griffith UniversityDepartment of Intensive Care, Sir Charles Gairdner HospitalAbstract 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.http://link.springer.com/article/10.1186/s13063-017-2137-7SepsisFluid therapyHypotension |
| spellingShingle | Stephen P. J. Macdonald David McD Taylor Gerben Keijzers Glenn Arendts Daniel M. Fatovich Frances B. Kinnear Simon G. A. Brown Rinaldo Bellomo Sally Burrows John F. Fraser Edward Litton Juan Carlos Ascencio-Lane Matthew Anstey David McCutcheon Lisa Smart Ioana Vlad James Winearls Bradley Wibrow REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trial Trials Sepsis Fluid therapy Hypotension |
| 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 |
| topic | Sepsis Fluid therapy Hypotension |
| url | http://link.springer.com/article/10.1186/s13063-017-2137-7 |
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