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Abdominal SurgeryRELIEFNCT01424150

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

A study testing Liberal fluid therapy and Restrictive fluid therapy in people with Abdominal Surgery, run by Bayside Health at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Abdominal Surgery
What is being tested?
Liberal fluid therapy and Restrictive fluid therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,000 participants
Where
1 siteAustralia
Study dates
Jul 2013to 22 Oct 2017
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site
  • Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: Restrictive Versus Liberal Fluid Therapy in Major Abdominal Surgery

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.

Read the 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.

Being tested
Liberal fluid therapy, Restrictive fluid therapy
Keywords
Postoperative fluid, surgery, anaesthesia, fluid, mortality, morbidity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Liberal fluid therapyOther

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

  • Restrictive fluid therapyOther

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

Study groups in NCT01424150
Study groupRoleWhat they receive
LiberalExperimentalAt 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.
Receives: Other: Liberal fluid therapy
RestrictiveExperimentalWill 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.
Receives: Other: Restrictive fluid therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year postoperative

Secondary outcomes (14)
  1. Death

    deceased within 12 months

    Measured: 90 days, then up to 12 months after surgery

  2. Composite Septic Outcome or Death

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

    Measured: 30 days postoperative

  3. 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)

    Measured: 30 days postoperative

  4. Surgical Site Infection

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

    Measured: 30 days postoperative

  5. 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.

    Measured: 30 Days postoperative

  6. 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).

    Measured: 30 days postoperative

  7. Pulmonary Oedema

    respiratory distress or impaired oxygenation AND radiological evidence of pulmonary oedema

    Measured: 30 days postoperative

  8. 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

    Measured: 30 day postoperative

  9. Hospital Stay

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

    Measured: 30 days postoperative

  10. 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

    Measured: days 3

  11. 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.

    Measured: 30 days postoperative

  12. C-reactive Protein

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

    Measured: Day 3 postoperative

  13. mmol/L

    peak serum lactate within 24 hours of surgery

    Measured: 24 hours post surgery

  14. Total ICU Stay and Unplanned ICU Admission to ICU

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

    Measured: 30 days postoperative

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2011 (estimated)
  2. Study startJul 2013
  3. Primary completionSep 2017
  4. Study completion22 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
3,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01424150
Sponsor's protocol ID
164/11 Pilot - 544/12 Main
Acronym
RELIEF
Status last verified
Aug 2017
First submitted
25 Aug 2011
Last updated
20 Jan 2026
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • McIlroy DR, Wallace SK, Forbes A, Peyton P, Story DA, Corcoran T, Neto AS, Myles PS. Perioperative intravenous fluid and chronic kidney disease: long-term follow-up of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) randomised trial. Br J Anaesth. 2026 Aug;137(2):479-489. doi: 10.1016/j.bja.2026.05.010. Epub 2026 Jun 23.

    PubMed 42331645
  • 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.

    PubMed 33521643
  • 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.

    PubMed 31774526
  • 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.

    PubMed 30916001
  • 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.

    PubMed 29742967
  • 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.

    PubMed 28259855

Questions about this trial

What is this clinical trial studying?

A study testing Liberal fluid therapy and Restrictive fluid therapy in people with Abdominal Surgery, run by Bayside Health at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disability-free Survival (time frame: 1 year postoperative). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01424150, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.

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