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

Bayside Health3,000 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Disability-free Survival

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.

Time frame: 1 year postoperative

Secondary Outcomes

Death

deceased within 12 months

Time frame: 90 days, then up to 12 months after surgery

Composite Septic Outcome or Death

composite of 1 or more of:sepsis, surgical site infection, anastomotic leak, death and pneumonia

Time frame: 30 days postoperative

Sepsis

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)

Time frame: 30 days postoperative

Surgical Site Infection

using CDC criteria (http://www.cdc.gov/nhsn/PDFs/pscManual/9pscSSIcurrent.pdf):

Time frame: 30 days postoperative

Pneumonia

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.

Time frame: 30 Days postoperative

Acute Kidney Injury

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).

Time frame: 30 days postoperative

Pulmonary Oedema

respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema

Time frame: 30 days postoperative

Total Duration of Time Spend in the ICU or HDU (in Days)

including initial ICU admission and readmission times up to 30 days post operatively

Time frame: 30 day postoperative

Hospital Stay

from the start (date, time) of surgery until actual hospital discharge

Time frame: 30 days postoperative

Quality of Recovery

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

Time frame: days 3

Anastomotic Leak

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.

Time frame: 30 days postoperative

C-reactive Protein

plasma C-reactive protein (CRP, using site-specific assay) concentration on Day 3

Time frame: Day 3 postoperative

mmol/L

peak serum lactate within 24 hours of surgery

Time frame: 24 hours post surgery

Total ICU Stay and Unplanned ICU Admission to ICU

additive, including initial ICU admission and readmission times up to Day 30

Time frame: 30 days postoperative

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes