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Both Positive and Negative Fluid Balance May Be Associated With Reduced Long-Term Survival in the Critically Ill

Balakumar, Vikram MD1,2; Murugan, Raghavan MD, MS, FRCP, FCCM1,3; Sileanu, Florentina E. MS1; Palevsky, Paul MD1,4; Clermont, Gilles MD, MSc3; Kellum, John A. MD, MCCM1,3

doi: 10.1097/CCM.0000000000002372
Online Clinical Investigations

Objectives: Among critically ill patients with acute kidney injury, exposure to positive fluid balance, compared with negative fluid balance, has been associated with mortality and impaired renal recovery. However, it is unclear whether positive and negative fluid balances are associated with poor outcome compared to patients with even fluid balance (euvolemia). In this study, we examined the association between exposure to positive or negative fluid balance, compared with even fluid balance, on 1-year mortality and renal recovery.

Design: Retrospective cohort study.

Setting: Eight medical-surgical ICUs at the University of Pittsburgh Medical Center, Pittsburgh, PA.

Patients: Critically ill patients admitted between July 2000 and October 2008.

Interventions: None.

Measurements and Main Results: Among 18,084 patients, fluid balance was categorized as negative (< 0%), even (0% to < 5%), or positive (≥ 5%). Following propensity matching, positive fluid balance, compared with even or negative fluid balance, was associated with increased mortality (30.3% vs 21.1% vs 22%, respectively; p < 0.001). Using Gray’s model, negative fluid balance, compared with even fluid balance, was associated with lower short-term mortality (adjusted hazard ratio range, 0.81; 95% CI, 0.68–0.96) but higher long-term mortality (adjusted hazard ratio range, 1.16–1.22; p = 0.004). Conversely, positive fluid balance was associated with higher mortality throughout 1-year (adjusted hazard ratio range, 1.30–1.92; p < 0.001), which was attenuated in those who received renal replacement therapy (positive fluid balance × renal replacement therapy interaction (adjusted hazard ratio range, 0.43–0.89; p < 0.001). Of patients receiving renal replacement therapy, neither positive (adjusted odds ratio, 0.98; 95% CI, 0.68–1.4) nor negative (adjusted odds ratio, 0.81; 95% CI, 0.43–1.55) fluid balance was associated with renal recovery.

Conclusions: Among critically ill patients, exposure to positive or negative fluid balance, compared with even fluid balance, was associated with higher 1-year mortality. This mortality risk associated with positive fluid balance, however, was attenuated by use of renal replacement therapy. We found no association between fluid balance and renal recovery.

1The Center for Critical Care Nephrology, CRISMA, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

2The Department of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

3The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

4Renal Section, Veterans Affairs Pittsburgh Healthcare System, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Drs. Balakumar and Murugan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Balakumar and Murugan contributed in study concept and design. Drs. Clermont and Kellum contributed in acquisition of data. Drs. Balakumar, Murugan, Sileanu, Palevsky, Clermont, and Kellum contributed in analysis and interpretation of data. Drs. Balakumar and Murugan contributed in drafting of the article. Drs. Murugan, Palevsky, Clermont, and Kellum contributed in critical revision of the article for important intellectual content. Drs. Balakumar and Sileanu contributed in statistical analysis. Drs. Balakumar, Murugan, Sileanu, and Kellum contributed in administrative, technical, or material support. Drs. Murugan and Kellum contributed in study supervision.

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Supported, in part, by the National Institutes of Health through Grant Number UL1-TR-000005 awarded to Univeristy of Pittsburgh’s Clinical and Translational Science Institute.

Dr. Murugan received support for article research from the National Institutes of Health (NIH). Dr. Sileanu disclosed work for hire. Dr. Palevsky disclosed government work, and he received funding from Complexa, Stealth Biotherapeutics, and Baxter. Dr. Clermont received funding from Astute Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: muruganr@upmc.edu

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