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

Not Applicable

Completed

Conditions: Abdominal Surgery

Registration Number: NCT01424150

Lead Sponsor: Bayside Health

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Disability-free Survival	1 year postoperative	Disability-free survival up to 1 year: survival and freedom from disability. The latter is defined as a persistent (≥6 months) reduction in health status as measured by a 12-item version (12-60 points) of World Health Organisation Disability Assessment Schedule score (WHODAS) of 24 points, reflecting a disability level of at least 25% and being the threshold point between "disabled" and "not disabled" as per WHO guidelines. 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. Further details are provided in the Procedures Manual and the Statistical Analysis Plan.

Secondary Outcome Measures

Name	Time	Method
Composite Septic Outcome or Death	30 days postoperative	composite of 1 or more of:sepsis, surgical site infection, anastomotic leak, death and pneumonia
Pneumonia	30 Days postoperative	The presence of new and/or progressive pulmonary infiltrates on chest radiograph plus two or more of the following: 1. Fever ≥ 38.5°C or postoperative hypothermia \<36°C 2. Leukocytosis ≥ 12,000 WBC/mm3 or leukopenia \< 4,000 WBC/mm3 3. Purulent sputum and/or 4. New onset or worsening cough or dyspnoea.
Total Duration of Time Spend in the ICU or HDU (in Days)	30 day postoperative	including initial ICU admission and readmission times up to 30 days post operatively
Acute Kidney Injury	30 days postoperative	according to The Kidney Disease: Improving Global Outcomes (KDIGO) group criteria, but not urine output - for Stage 2 or worse AKI defined as at least 2-fold increase in creatinine, or estimated GFR decrease \>50%.(73) We also plan to report renal replacement therapy up to 90 days after surgery. Because a restrictive IV fluid regimen may artificially elevate serum creatinine due to a smaller dilutional effect from less IV fluids, we therefore calculated adjusted creatinine by first estimating the volume of distribution for creatinine as equal to total body water (assumed to be 60% of body weight, expressed in mL).
Pulmonary Oedema	30 days postoperative	respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema
Hospital Stay	30 days postoperative	from the start (date, time) of surgery until actual hospital discharge
Quality of Recovery	days 3	15-item Quality of Recovery Score. The score is a patient reported outcome measure to score the individuals recovery following anaesthesia and surgery. Minimum value is 0 and maximum value is 150. The score of 150 is good. The higher the score the better
Anastomotic Leak	30 days postoperative	A defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- an extra luminal compartments.
C-reactive Protein	Day 3 postoperative	plasma C-reactive protein (CRP, using site-specific assay) concentration on Day 3
mmol/L	24 hours post surgery	peak serum lactate within 24 hours of surgery
Total ICU Stay and Unplanned ICU Admission to ICU	30 days postoperative	additive, including initial ICU admission and readmission times up to Day 30
Death	90 days, then up to 12 months after surgery	deceased within 12 months
Sepsis	30 days postoperative	using Centers for Disease Control and Prevention (CDC) with National Healthcare Safety Network (NHSN) criteria, two or more features of the systematic inflammatory response syndrome (SIRS) plus evidence of a source or site of infection (can be positive blood culture or purulence from any site)
Surgical Site Infection	30 days postoperative	using CDC criteria (http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf):