Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) – a pilot randomised controlled trial of conservative fluid administration and deresuscitation in critical illness: study protocol

Background: Intravenous fluid administration is a common intervention in critically ill patients. However, this frequently contributes to a positive fluid balance, which is consistently associated with adverse outcomes including mortality. A conservative or deresuscitative (use of diuretics or renal replacement therapies to remove accumulated fluid) approach to fluid management in critical illness may be beneficial but evidence is limited.

Methods/Design: Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) is an open-label pilot randomised controlled trial of conservative fluid administration and deresuscitation compared with usual care. Mechanically ventilated patients in an adult intensive care unit expected to need critical care beyond the next calendar day and who do not meet any exclusion criteria will be randomised between 24 and 48 hours from intensive care admission. The intervention comprises discontinuation of maintenance intravenous fluids, concentration of intravenous drugs, and a titratedregimen of furosemide, indapamide and spironolactone commenced if fluid balance is greater than2 litres positive from intensive care admission or there is clinical evidence of oedema in more than one anatomical site. The primary feasibility outcome is fluid balance between groups over the 24hour period of study day 2. Secondary outcomes are categorised as feasibility (e.g. cumulative fluid balance, incidence of protocol violations); safety (incidence of adverse events); and clinical efficacy(e.g. change in sequential organ failure assessment scores, mortality). Exploratory mechanistic studies will evaluate cardiac function, cerebral and muscle oximetry and biomarkers of endothelial injury and systemic inflammation.

Discussion: RADAR-2 is a pilot randomised controlled trial comparing a multimodal conservative fluid strategy with usual care in a broad cohort of critically ill patients and will inform future largescale multicentre comparative effectiveness studies.