Jonathan A Silversides1,2, Ross McMullan3, Lydia M Emerson4, Ian Bradbury5, Jonathan Bannard-Smith6,7, Tamas Szakmany8,9, John Trinder10, Anthony J Rostron11,12, Paul Johnston13, Andrew J Ferguson3, Andrew J Boyle3,14,13, Bronagh Blackwood14, John C Marshall15,16, Daniel F McAuley3,14. 1. Department of Critical Care, Belfast Health and Social Care Trust, Belfast, UK. j.silversides@qub.ac.uk. 2. Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK. j.silversides@qub.ac.uk. 3. Department of Critical Care, Belfast Health and Social Care Trust, Belfast, UK. 4. School of Health Sciences, City, University of London, London, UK. 5. Independent Consulting Statistician, Aviemore, UK. 6. Department of Critical Care, Manchester University NHS Foundation Trust, Manchester, UK. 7. Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK. 8. Critical Care Directorate, Aneurin Bevan University Health Board, Newport, UK. 9. Department of Anaesthesia, Intensive Care and Pain Medicine, Cardiff University, Cardiff, UK. 10. Intensive Care Unit, South-Eastern Health and Social Care Trust, Dundonald, UK. 11. Integrated Critical Care Unit, South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK. 12. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. 13. Intensive Care Unit, Northern Health and Social Care Trust, Antrim, UK. 14. Wellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK. 15. Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, Canada. 16. Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada.
Abstract
PURPOSE: Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness. METHODS: Open-label, parallel-group, allocation-concealed randomised clinical feasibility trial. Mechanically ventilated adult patients expected to require critical care beyond the next calendar day were enrolled between 24 and 48 h following admission to the intensive care unit (ICU). Patients were randomised to either a 2-stage fluid strategy comprising conservative fluid administration and, if fluid overload was present, active deresuscitation, or usual care. The primary endpoint was fluid balance in the 24 h up to the start of study day 3. Secondary endpoints included cumulative fluid balance, mortality, and duration of mechanical ventilation. RESULTS: One hundred and eighty patients were randomised. After withdrawal of 1 patient, 89 patients assigned to the intervention were compared with 90 patients assigned to the usual care group. The mean plus standard deviation (SD) 24-h fluid balance up to study day 3 was lower in the intervention group (- 840 ± 1746 mL) than the usual care group (+ 130 ± 1401 mL; P < 0.01). Cumulative fluid balance was lower in the intervention group at days 3 and 5. Overall, clinical outcomes did not differ significantly between the two groups, although the point estimate for 30-day mortality favoured the usual care group [intervention arm: 19 of 90 (21.6%) versus usual care: 14 of 89 (15.6%), P = 0.32]. Baseline imbalances between groups and lack of statistical power limit interpretation of clinical outcomes. CONCLUSIONS: A strategy of conservative fluid administration and active deresuscitation is feasible, reduces fluid balance compared with usual care, and may cause benefit or harm. In view of wide variations in contemporary clinical practice, large, adequately powered trials investigating the clinical effectiveness of conservative fluid strategies in critically ill patients are warranted.
PURPOSE: Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness. METHODS: Open-label, parallel-group, allocation-concealed randomised clinical feasibility trial. Mechanically ventilated adult patients expected to require critical care beyond the next calendar day were enrolled between 24 and 48 h following admission to the intensive care unit (ICU). Patients were randomised to either a 2-stage fluid strategy comprising conservative fluid administration and, if fluid overload was present, active deresuscitation, or usual care. The primary endpoint was fluid balance in the 24 h up to the start of study day 3. Secondary endpoints included cumulative fluid balance, mortality, and duration of mechanical ventilation. RESULTS: One hundred and eighty patients were randomised. After withdrawal of 1 patient, 89 patients assigned to the intervention were compared with 90 patients assigned to the usual care group. The mean plus standard deviation (SD) 24-h fluid balance up to study day 3 was lower in the intervention group (- 840 ± 1746 mL) than the usual care group (+ 130 ± 1401 mL; P < 0.01). Cumulative fluid balance was lower in the intervention group at days 3 and 5. Overall, clinical outcomes did not differ significantly between the two groups, although the point estimate for 30-day mortality favoured the usual care group [intervention arm: 19 of 90 (21.6%) versus usual care: 14 of 89 (15.6%), P = 0.32]. Baseline imbalances between groups and lack of statistical power limit interpretation of clinical outcomes. CONCLUSIONS: A strategy of conservative fluid administration and active deresuscitation is feasible, reduces fluid balance compared with usual care, and may cause benefit or harm. In view of wide variations in contemporary clinical practice, large, adequately powered trials investigating the clinical effectiveness of conservative fluid strategies in critically ill patients are warranted.
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