The RELIEF trial
The optimal fluid regimen, haemodynamic (or other) targets and fluid choice (colloid or crystalloid) for patients undergoing major surgery are based on rationales that are not supported by strong evidence. Practices vary substantially, guidelines are vague, small trials and meta-analyses are contradictory. The strongest and most consistent evidence, and biological plausibility because of tissue edema, supports a restrictive fluid strategy. But other evidence supports goal-directed therapy, requiring additional IV fluid. There is no good evidence that use and choice of colloids improves outcome. RELIEF will study the effects of fluid restriction, and the possible effect-modification of goal-directed therapy and colloids. The first will be randomly assigned; the latter will be measured covariates dictated by local practices and beliefs.
Study Hypotheses: A restrictive fluid regimen for adults undergoing major abdominal surgery leads to reduced complications and improved disability-free survival when compared with a liberal fluid regimen.
This will be a large, randomized, parallel-group, controlled trial. After stratification by centre
and planned ICU/HDU admission (or not), patients will be randomly assigned from a
computer-generated list (1:1) to either a Restrictive or Liberal fluid Group.
Group 1 = Restrictive fluid regimen (intraoperative and 1st 24 h ≈2.5 L)
Group 2 = Liberal fluid regimen (intraoperative and 1st 24 h ≈5.5 L)
Sample Size: 2800 patients
Study Duration: 3 years
Primary Endpoint :
Disability-free survival up to 1 year: survival and freedom from new-onset disability, the latter being a persistent (>6 months) reduction in functional status as defined by a 4-point or greater reduction in the 12-item version of WHODAS. Disability will be assessed by the participant, but if unable then we will use the proxy’s report. The date of onset of new disability will be recorded.
Funding: Australian NHMRC Project Grant
Registration: ClinicalTrials.gov Identifier: NCT01424150
Secondary hypothesis: The effects of fluid restriction are similar whether or not goal-directed therapy is used (assessed as a statistical test of interaction). A restrictive fluid regimen will reduce a composite of 30-day septic complications and mortality.