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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Bayside Health
Sponsor:
Collaborator:
Australian and New Zealand College of Anaesthetists
Information provided by (Responsible Party):
Bayside Health
ClinicalTrials.gov Identifier:
NCT01424150
First received: August 25, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Abdominal Surgery
Other: Liberal fluid therapy
Other: Restrictive fluid therapy
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Bayside Health:

Primary Outcome Measures:
  • Disability-free survival [ Time Frame: 1 year postoperative ] [ Designated as safety issue: No ]
    survival and freedom from new-onset disability, defined as a 4-point or greater persistent decrement in the 12-item WHODAS score The date of onset of new disability will be recorded.


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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.

    1. Cost-effectiveness, to include hospital stay and complications as we have done previously (80)
    2. Hyperchloraemic acidosis (to measure strong ion difference, Cl-, lactate, albumin …)
    3. Pulmonary oedema (to measure FiO2/PaO2 ratio, CT/CXR-confirmed atelectasis …)
    4. Coagulopathy (to measure blood loss, plt count, fibrinogen, INR, APTT, Hb flux, transfusion …)
    5. Sepsis (to measure fever, WCC, CRP …).


Estimated Enrollment: 2800
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)
Arms Assigned Interventions
Experimental: Liberal
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.
Experimental: Restrictive
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.

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424150

Contacts
Contact: Paul S Myles, MB.BS, MPH, MD, FANZCA +61 3 9076 3176 p.myles@alfred.org.au
Contact: Sophie KA Wallace, BHS RN, MPH + 61 3 9076 3176 ext 2651 s.wallace@alfred.org.au

Locations
Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Sophie Wallace, MPH    +61390762651 ext 62651    s.wallace@alfred.org.au   
Principal Investigator: Paul S Myles, MB.BS, MPH, MD,FCARCSI,FANZC         
Sponsors and Collaborators
Bayside Health
Australian and New Zealand College of Anaesthetists
Investigators
Study Chair: Paul S Myles, MB.BS, MPH, MD, FANZCA Alfred Hospital, Monash University
  More Information

No publications provided

Responsible Party: Bayside Health
ClinicalTrials.gov Identifier: NCT01424150     History of Changes
Other Study ID Numbers: 164/11
Study First Received: August 25, 2011
Last Updated: January 29, 2014
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Bayside Health:
Postoperative fluid
surgery
anaesthesia
fluid
mortality
morbidity

ClinicalTrials.gov processed this record on July 20, 2014