REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery: RELIEF Study (RELIEF)
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.
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.
Other: Liberal fluid therapy
Other: Restrictive fluid therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Supportive Care
|Official Title:||Restrictive Versus Liberal Fluid Therapy in Major Abdominal Surgery|
- Disability-free survival [ Time Frame: 1 year postoperative ] [ Designated as safety issue: No ]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 25% (4-point) or greater increase in the 12-item version of WHODAS to a final score of at least 25.
- Death [ Time Frame: 30 days, then up to 12 months after surgery ] [ Designated as safety issue: No ]
- Sepsis [ Time Frame: 30 days postoperative ] [ Designated as safety issue: No ]using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria, SIRS plus infection (positive blood culture or purulence from any site)
- Surgical site infection [ Time Frame: 30 days postoperative ] [ Designated as safety issue: No ]if associated with purulent discharge and/or a positive microbial culture
- Pneumonia [ Time Frame: 30 Days postoperative ] [ Designated as safety issue: No ]typical x-ray appearance and ≥2 of (i) temperature ≥38 oC, (ii) WCC >12,000, and (iii) positive sputum culture
- Acute kidney injury [ Time Frame: 30 days postoperative ] [ Designated as safety issue: No ]delta creatinine and RIFLE criteria
- Pulmonary oedema [ Time Frame: 30 days postoperative ] [ Designated as safety issue: No ]respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema
- Total ICU stay and mechanical ventilation time [ Time Frame: 30 day postoperative ] [ Designated as safety issue: No ]including initial ICU admission and readmission times
- Hospital stay [ Time Frame: 30 days postoperative ] [ Designated as safety issue: No ]from the start (date, time) of surgery until actual hospital discharge
- Quality of recovery [ Time Frame: day 3 and day 30 postoperative ] [ Designated as safety issue: No ]Quality of recovery score
- Preplanned substudies (for mechanistic understanding) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
We plan several substudies (to be funded from other sources), each of which will have a separate protocol and authorship plan (using an expanded list of contributors). Additional blood tests and other investigations will be done at selected hospitals according to local interest and expertise.
- Cost-effectiveness, to include hospital stay and complications as we have done previously (80)
- Hyperchloraemic acidosis (to measure strong ion difference, Cl-, lactate, albumin …)
- Pulmonary oedema (to measure FiO2/PaO2 ratio, CT/CXR-confirmed atelectasis …)
- Coagulopathy (to measure blood loss, plt count, fibrinogen, INR, APTT, Hb flux, transfusion …)
- Sepsis (to measure fever, WCC, CRP …).
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||November 2018|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
At the commencement of surgery a bolus of Hartmann's balanced salt crystalloid 10 ml/kg followed by 8 ml/kg/h will be administered until the end of surgery. A maintenance infusion will then continue at 1.5 ml/kg/h, for at least 24 hours, but this can be reduced postoperatively if there is evidence of fluid overload and no hypotension, and increased if there is evidence of hypovolaemia or hypotension. Alternative fluid types (crystalloid, dextrose, colloid) and electrolyte supplements will be allowed postoperatively in order to account for local preferences and patient biochemistry, for which we will collect data.
Other: Liberal fluid therapy
Liberal protocol group is designed to provide approximately 6.0L per day.
Will provide less than 2.0 L water and 120 mmol sodium per day. Induction of anaesthesia will limit IV bolus fluid to ≤5 ml/kg; no other IV fluids will be used at the commencement of surgery (unless indicated by goal-directed device [see below]). Hartmann's balanced salt crystalloid 5 ml/kg/h will be administered until the end of surgery, and bolus colloid/blood used intraoperatively to replace blood loss (ml for ml); then an infusion at 1 ml/kg/h until expedited cessation of IV fluid therapy within 24 hours. The rate of postoperative fluid replacement can be reduced if there is evidence of fluid overload and no hypotension, and can be increased if there is hypotension AND evidence of hypovolaemia.
Other: Restrictive fluid therapy
Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01424150
|Contact: Paul S Myles, MB.BS, MPH, MD, FANZCA||+61 3 9076 email@example.com|
|Contact: Sophie KA Wallace, BHS RN, MPH||+ 61 3 9076 3176 ext firstname.lastname@example.org|
|Melbourne, Victoria, Australia, 3004|
|Contact: Sophie Wallace, MPH +61390762651 ext 62651 email@example.com|
|Principal Investigator: Paul S Myles, MB.BS, MPH, MD,FCARCSI,FANZC|
|Study Chair:||Paul S Myles, MB.BS, MPH, MD, FANZCA||Alfred Hospital, Monash University|