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An observational study fluid balance and patient outcomes in the randomized evaluation of normal vs. augmented level of replacement therapy trial*

The RENAL Replacement Therapy Study Investigators

doi: 10.1097/CCM.0b013e318246b9c6
Clinical Investigations

Objective: To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study.

Design: Statistical analysis of data from multicenter, randomized, controlled trials.

Setting: Thirty-five intensive care units in Australia and New Zealand.

Patients: Cohort of 1453 patients enrolled in the RENAL study.

Interventions: We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models.

Measurements and Main Results: During intensive care unit stay, mean daily fluid balance among survivors was –234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was –1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24–0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models.

Conclusions: In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

*See also p. 1970.

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This study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (grant 352550) and Health Research Council (HRC) of New Zealand (grant 06–357).

Professor Alan Cass was supported by a NHMRC Senior Research Fellowship; and received funding from the Australian National Health and Medical Research Council; and received grant support from Roche and Gambro. Professor Rinaldo Bellomo received consulting fees as an advisor for Gambro; and consulted for Gambro, Biosite, Abbott, and Philipps. Professor Simon Finfer has received travel support to present research results at scientific meetings from Eli Lilly, Cardinal Health, and CSL Bioplasma; and received funding from the Australian government. Dr. Gallagher received honoraria/speaking fees from Roche. Dr. Myburgh received funding from the NHMRC (Australia) and honoraria/speaking fees and grant support from Fresenius. Dr. Scheinkestel received funding from the NHMRC and Health Research Council of New Zealand. The remaining authors have not disclosed any potential conflicts of interest.

The George Institute for International Health, an independent not-for-profit institute affiliated with the University of Sydney, has received reimbursement for Professor Finfer’s time as a steering committee member for studies sponsored by Eli Lilly and Eisai. The George Institute has received research funding from Servier, Novartis, Eisai, Merck, Sharp & Dohme, Pfizer Australia, Fresenius Kabi Deutschland GmbH, and Sanofi Aventis.

The Randomized Evaluation of Normal vs. Augmented Level (RENAL) Replacement Therapy Study is a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) and the George Institute for International Health.

The members of the writing committee (Rinaldo Bellomo, MBBS, MD; Alan Cass MBBS, PhD; Louise Cole, MBBS, PhD; Simon Finfer, MBBS; Martin Gallagher MBBS; Joanne Lee, BMedSc (Hons); Serigne Lo, PhD, MSc, BSc; Colin McArthur, MBBS; Shay McGuiness, MBBS; Robyn Norton, PhD, MP; John Myburgh, MBBS, PhD; and Carlos Scheinkestel, MBBS) take responsibility for the content of this article.

The affiliations of the members of the RENAL Replacement Therapy Study writing committee and the names and affiliations of the Investigators are listed in the Appendix.

For information regarding this article, E-mail: ctg@anzics.com.au

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins