ANZICS CTG Endorsed Study

RELIEF

Restrictive versus liberal fluid therapy in major abdominal surgery

Study Description

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 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.

We are thus proposing to study the effects of fluid restriction (vs. liberal), and the possible effect-modification of goal-directed therapy (using either oesophageal Doppler or Flotrac®) and colloid replacement. The first will be randomly assigned; the latter will be measured covariates according to local practices (and beliefs).

Management Committee

Paul Myles (Chair), Rinaldo Bellomo, Thomas Corcoran, Chris Christophi, Andrew Forbes, Philip Peyton, David Story and Sophie Wallace (Project Manager).

Administering Institution

Monash University

Collaborators

University of Queensland

Sample Size

2800 patients

Funding

NHMRC Project Grant 2.38 million
Health Research Council of New Zealand NZ$770,000

Project Status as of June 2018

The project is complete and is now published in the NEJM on Line in May. https://www.nejm.org/doi/full/10.1056/NEJMoa1801601#article_citing_articles Will be available late may in press.  During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.

CONCLUSIONS

Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150.)

Reference

CTG12-002
ClinicalTrials.gov Identifier: NCT01424150

Contact

Paul Myles (email)