REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery: RELIEF Study

Bayside Health

Status: Completed

Conditions: Abdominal Surgery

Treatments: Other: Restrictive fluid therapy; Other: Liberal fluid therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01424150

164/11 Pilot - 544/12 Main

Details and patient eligibility

About

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.

Full description

The investigators have completed a pilot study of 82 subjects to test the feasibility of the trial (2011), and are currently doing a cost-effectiveness substudy (2012-13)

1. AIM OF THE TRIAL To investigate the effectiveness of fluid restriction (vs. liberal), and the possible effect-modification of goal-directed therapy (eg. oesophageal Doppler, Flotrac®). The first will be randomly assigned; the latter will be measured covariates according to local practices and beliefs.

The optimal fluid regimen and haemodynamic (or other) targets 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 plausability regarding tissue oedema, supports a restrictive fluid strategy. There is less (and more contradictory) evidence supporting goal-directed therapy using a flow-directed device and/or dopexamine, and use and choice of colloids. A large, definitive clinical trial evaluating perioperative fluid replacement in major surgery is required.

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 hypotheses: 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.

Enrollment: 3,000 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

1. Adults (≥18 years) undergoing elective major surgery and providing informed consent

2. All types of open or lap-assisted abdominal or pelvic surgery with an expected duration of at least 2 hours, and an expected hospital stay of at least 3 days (for example, oesophagectomy, gastrectomy, pancreatectomy, colectomy, aortic or aorto-femoral vascular surgery, nephrectomy, cystectomy, open prostatectomy, radical hysterectomy, and abdominal incisional hernia repair)

3. At increased risk of postoperative complications, defined as at least one of the following criteria:

   • age ≥70 years

   • known or documented history of coronary artery disease

   • known or documented history of heart failure

   • diabetes currently treated with an oral hypoglycaemic agent and/or insulin

   • preoperative serum creatinine >200 µmol/L (>2.8 mg/dl)

   • morbid obesity (BMI ≥35 kg/m²)

   • preoperative serum albumin <30 g/L

   • anaerobic threshold (if done) <12 mL/kg/min

   • or two or more of the following risk factors:

     • ASA 3 or 4
     • chronic respiratory disease
     • obesity (BMI 30-35 kg/m²)
     • aortic or peripheral vascular disease
     • preoperative haemoglobin <100 g/L
     • preoperative serum creatinine 150-199 µmol/L (>1.7 mg/dl)
     • anaerobic threshold (if done) 12-14 mL/kg/min

Exclusion Criteria

1. Urgent or time-critical surgery
2. ASA physical status 5 - such patients are not expected to survive with or without surgery, and their underlying illness is expected to have an overwhelming effect on outcome (irrespective of fluid therapy)
3. Chronic renal failure requiring dialysis
4. Pulmonary or cardiac surgery - different pathophysiology, and thoracic surgery typically have strict fluid restrictions
5. Liver resection - most units have strict fluid/CVP limits in place and won't allow randomisation
6. Minor or intermediate surgery, such as laparoscopic cholecystectomy, transurethral resection of the prostate, inguinal hernia repair, splenectomy, closure of colostomy - each of these are typically "minor" surgery with minimal IV fluid requirements, generally low rates of complications and mostly very good survival.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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3,000 participants in 2 patient groups

Liberal

Experimental group

Description:

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.

Treatment:

Other: Liberal fluid therapy

Restrictive

Experimental group

Description:

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.

Treatment:

Other: Restrictive fluid therapy