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Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial

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A Correction to this article was published on 29 August 2023

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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.

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Raw data are available on request from the corresponding author.

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Acknowledgements

The authors are grateful to Catriona McGarvey, Amanda Scappaticci, Ian Adair, Paul Caddell, and John Conlon for technical assistance; to Chris Wright, Aisling O’Neill, Kathryn Ward, and Gerard Quinn for study delivery and co-ordination; and to Damian Downey and Chris Nutt for contributions to the data monitoring committee.

Funding

The study was funded by the Public Health Agency, Northern Ireland (EAT.5103.14); and by project grants from the British Journal of Anaesthesia/Royal College of Anaesthetists (WKR0-2017-0019) and the National Institute of Academic Anaesthesia. Edwards Lifesciences provided equipment and consumables for near-infrared spectroscopy.

Author information

Authors and Affiliations

  1. Department of Critical Care, Belfast Health and Social Care Trust, Belfast, UK

    Jonathan A. Silversides, Ross McMullan, Andrew J. Ferguson, Andrew J. Boyle & Daniel F. McAuley

  2. Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University of Belfast, Lisburn Road, Belfast, BT9 7BL, UK

    Jonathan A. Silversides, Andrew J. Boyle, Bronagh Blackwood & Daniel F. McAuley

  3. School of Health Sciences, City, University of London, London, UK

    Lydia M. Emerson

  4. Independent Consulting Statistician, Aviemore, UK

    Ian Bradbury

  5. Department of Critical Care, Manchester University NHS Foundation Trust, Manchester, UK

    Jonathan Bannard-Smith

  6. Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK

    Jonathan Bannard-Smith

  7. Critical Care Directorate, Aneurin Bevan University Health Board, Newport, UK

    Tamas Szakmany

  8. Department of Anaesthesia, Intensive Care and Pain Medicine, Cardiff University, Cardiff, UK

    Tamas Szakmany

  9. Intensive Care Unit, South-Eastern Health and Social Care Trust, Dundonald, UK

    John Trinder

  10. Integrated Critical Care Unit, South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK

    Anthony J. Rostron

  11. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Anthony J. Rostron

  12. Intensive Care Unit, Northern Health and Social Care Trust, Antrim, UK

    Paul Johnston & Andrew J. Boyle

  13. Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, Canada

    John C. Marshall

  14. Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada

    John C. Marshall

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  1. Jonathan A. Silversides
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Contributions

Conception and design: JS, JM, AF and DM; acquisition of data: JS, LE, RM, JBS, TS, JT, AR, PJ, AF, and AB; statistical analysis: IB; drafting of manuscript: JS; critical revision of manuscript: JS, RM, LE, IB, JBS, TS, JT, AR, PJ, AJF, AB, BB, JM, and DM.

Corresponding author

Correspondence to Jonathan A. Silversides.

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Conflicts of interest

The authors have no conflict of interest to declare.

Ethics approval

Ethical approval for the study was provided by the Office of Research Ethics Committees Northern Ireland.

Consent to participate

Written approval for enrolment was obtained from patient representatives.

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Not applicable.

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The original online version of this article was revised: the denominator for 180-day mortality was incorrectly calculated, leading to an erroneously high percentage mortality in both treatment arms being reported in Table 2 (Outcomes). 180-day mortality was reported as 25 (54.4%) for the intervention arm, and 21 (52.5%) for the usual care arm. The numerators are correct, but the relevant percentages are not, so that the correct numbers are 25 of 88 (28.4%) and 21 of 88 (23.9%) respectively. The associated P-value for this outcome should be 0.61 rather than 0.86.

Additionally, the N in the left-hand column for the outcomes of anxiety, depression and PTSD is incorrect by 1. For anxiety N is reported as 34 when the correct number is 33; for depression we have reported 37 rather than 36, and for PTSD we have reported N = 35 when the correct number is 34. All significance testing was carried out using the correct data, so all reported P-values are correct.

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Silversides, J.A., McMullan, R., Emerson, L.M. et al. Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial. Intensive Care Med 48, 190–200 (2022). https://doi.org/10.1007/s00134-021-06596-8

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