Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery

Myles, Paul S. M.P.H., D.Sc.
Bellomo, Rinaldo M.D.
Corcoran, Tomas M.D.
Forbes, Andrew Ph.D.
Peyton, Philip M.D., Ph.D.
Story, David M.D.
Christophi, Chris M.B., B.S.
Leslie, Kate M.D.
McGuinness, Shay M.B., Ch.B.
Parke, Rachael M.P.H.
Serpell, Jonathan M.D.
Chan, Matthew T.V. M.B., B.S.
Painter, Thomas M.B., Ch.B.
McCluskey, Stuart M.D., Ph.D.
Minto, Gary M.B., Ch.B.
Wallace, Sophie M.P.H.

From Alfred Hospital (P.S.M., J.S., S.W.), Monash University (P.S.M., R.B., T.C., A.F., K.L., J.S., S.W.), and the University of Melbourne (R.B., P.P., D.S., C.C., K.L.), Melbourne, VIC, Austin Hospital, Heidelberg, VIC (R.B., P.P., D.S., C.C.), Royal Perth Hospital and the University of Western Australia, Perth (T.C.), Royal Melbourne Hospital, Parkville, VIC (K.L.), and Royal Adelaide Hospital and Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA (T.P.) — all in Australia; Auckland City Hospital, Auckland, and the Medical Research Institute of New Zealand, Wellington — both in New Zealand (S. McGuinness, R.P.); the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); University Health Network, Toronto (S. McCluskey); and Derriford Hospital, Plymouth, United Kingdom (G.M.).

A list of participating centers and investigators in the RELIEF trial is provided in the Supplementary Appendix, available at NEJM.org.

Address reprint requests to Dr. Myles at the Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Rd., Melbourne, VIC 3004, Australia, or at [email protected].

Supported by a grant (ID1043755) from the Australian National Health and Medical Research Council (NHMRC), the Australian and New Zealand College of Anaesthetists, Monash University, a grant (ID14/222) from the Health Research Council of New Zealand, and the United Kingdom National Institute of Health Research. Drs. Myles and Bellomo are supported by Australian NHMRC Practitioner Fellowships.

Disclosure forms provided by the authors are available at NEJM.org.

This article was published on May 10, 2018, at NEJM.org.

We thank Adam Meehan for data management, construction of the Web-accessed electronic database, and provision of the Web-based randomization service; Monty Mythen and David McIlroy and all the members of the committees overseeing the trial; and the Australian and New Zealand College of Anaesthetists Clinical Trials Network.

New England Journal of Medicine 378(24):p 2263-2274, June 14, 2018. | DOI: 10.1056/NEJMoa1801601

ABSTRACT

BACKGROUND

Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion.

METHODS

In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.

RESULTS

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.)