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

NCT01424150 | Completed Results DMC

• 1 other identifier: 164/11 Pilot - 544/12 Main
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Surgery

Keywords

Postoperative fluid; surgery; anaesthesia; fluid; mortality; morbidity

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year postoperative

Secondary Outcomes (14)

• Death

  90 days, then up to 12 months after surgery

• Composite Septic Outcome or Death

  30 days postoperative

• Sepsis

  30 days postoperative

• Surgical Site Infection

  30 days postoperative

• Pneumonia

  30 Days postoperative

Other Outcomes (1)

• Preplanned Substudies (for Mechanistic Understanding)

  5 years

Study Arms (2)

Liberal

EXPERIMENTAL

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

Restrictive

EXPERIMENTAL

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

Interventions

Liberal fluid therapy OTHER

Liberal protocol group is designed to provide approximately 6.0L per day.

Liberal

Restrictive fluid therapy OTHER

Restrictive protocol group is designed to provide less than 2.0 L water and 120 mmol sodium per day.

Restrictive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Urgent or time-critical surgery
• 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)
• Chronic renal failure requiring dialysis
• Pulmonary or cardiac surgery - different pathophysiology, and thoracic surgery typically have strict fluid restrictions
• Liver resection - most units have strict fluid/CVP limits in place and won't allow randomisation
• 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.

Sponsors & Collaborators

• Bayside Health: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Related Publications (5)

• Bihari S, Dixon DL, Painter T, Myles P, Bersten AD. Understanding Restrictive Versus Liberal Fluid Therapy for Major Abdominal Surgery Trial Results: Did Liberal Fluids Associate With Increased Endothelial Injury Markers? Crit Care Explor. 2021 Jan 25;3(1):e0316. doi: 10.1097/CCE.0000000000000316. eCollection 2021 Jan.

  PMID: 33521643 DERIVED

• Gurunathan U, Rapchuk IL, Dickfos M, Larsen P, Forbes A, Martin C, Leslie K, Myles PS. Association of Obesity With Septic Complications After Major Abdominal Surgery: A Secondary Analysis of the RELIEF Randomized Clinical Trial. JAMA Netw Open. 2019 Nov 1;2(11):e1916345. doi: 10.1001/jamanetworkopen.2019.16345.

  PMID: 31774526 DERIVED

• Myles PS, McIlroy DR, Bellomo R, Wallace S. Importance of intraoperative oliguria during major abdominal surgery: findings of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery trial. Br J Anaesth. 2019 Jun;122(6):726-733. doi: 10.1016/j.bja.2019.01.010. Epub 2019 Feb 16.

  PMID: 30916001 DERIVED

• Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D, Christophi C, Leslie K, McGuinness S, Parke R, Serpell J, Chan MTV, Painter T, McCluskey S, Minto G, Wallace S; Australian and New Zealand College of Anaesthetists Clinical Trials Network and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery. N Engl J Med. 2018 Jun 14;378(24):2263-2274. doi: 10.1056/NEJMoa1801601. Epub 2018 May 9.

  PMID: 29742967 DERIVED

• Myles P, Bellomo R, Corcoran T, Forbes A, Wallace S, Peyton P, Christophi C, Story D, Leslie K, Serpell J, McGuinness S, Parke R; Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial. BMJ Open. 2017 Mar 3;7(3):e015358. doi: 10.1136/bmjopen-2016-015358.

  PMID: 28259855 DERIVED

Results Point of Contact

• Title: Professor Paul Myles
• Organization: Alfred Health

p.myles@alfred.org.au

61 3 9076 3176

Study Officials

• Paul S Myles, MB.BS, MPH, MD, FANZCA

  Alfred Hospital, Monash University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 26, 2011
• Study Start: July 1, 2013
• Primary Completion: September 1, 2017
• Study Completion: October 22, 2017
• Last Updated: January 20, 2026
• Results First Posted: January 24, 2025

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)