REstrictive Versus LIbEral Fluid Therapy in Major Abdominal Surgery: RELIEF Study - Full Text View

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:

MedlinePlus related topics: Edema

U.S. FDA Resources

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:	February 2013
Estimated Study Completion Date:	November 2016
Estimated Primary Completion Date:	November 2015 (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.

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:

Adults (18 years) undergoing elective major surgery and informed consent
All types of open abdominal or pelvic surgery with an expected duration of at least 2 hours, and a hospital stay of at least 3 days. For example, oesophagectomy, gastrectomy, pancreatectomy, colectomy (including lap-assisted), aortic or aorto-femoral vascular surgery, nephrectomy (including lap-assisted), cystectomy, prostatectomy, radical hysterectomy, and incisional hernia repair
At increased risk of postoperative complications, defined as any of:
- known or documented history of coronary artery disease
- known or documented history of heart failure
- diabetes currently treated with an oral hypoglycaemic agent or insulin
- renal impairment >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:
  - age ≥70 years
  - ASA 3 or 4
  - chronic respiratory disease
  - obesity (BMI ≥30 kg/m2)
  - aortic or peripheral vascular disease
  - preoperative haemoglobin <100 g/L
  - preoperative serum creatinine >150 µmol/L (>1.7 mg/dl)
  - anaerobic threshold (if done) <14 mL/kg/min

Exclusion Criteria:

Urgent or time-critical surgery
ASA physical status 5
Pulmonary or cardiac surgery
Liver resection
Minor or intermediate surgery, such as laparoscopic cholecystectomy, transurethral resection of the prostate, inguinal hernia, splenectomy, closure of colostomy
Pre-existing (preoperative) sepsis (any of: temp >37.5 C, WCC >15,000 109/L, proven site of infection, peritonism)

Contacts and Locations

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	Not yet recruiting
Melbourne, Victoria, Australia, 3004
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:	February 5, 2013
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 May 16, 2013