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

Abstract

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.

Figure 1. Association between positive, even, and negative FB and mortality

The Kaplan Meier failure plots by FB for probability of death over 1 year from ICU admission in the overall cohort. Red line represents positive FB (≥ 5%), green line represents even FB (0 – < 5%), and blue line represents negative FB (< 0%). The probability of death was highest in the positive FB and lowest in the negative FB, compared with even FB group (Log rank P<0.001).

Figure 2. Association between FB and risk-adjusted mortality using Gray’s model

Figure shows varying adjusted hazard ratios with 95% CIs for risk of death over 365 days estimated from Gray's model using five time nodes and six intervals. A hazard ratio < 1 suggests that FB is associated with lower mortality and a hazard ratio > 1 suggests FB is associated with higher mortality. Models were adjusted for age, race, baseline serum creatinine, body mass index, comorbidities, cardiac disease, heart failure, liver disease and associated sequelae, liver transplantation, malignancy, surgery, admission APACHE III score, vasopressor use, mechanical ventilation use, suspected sepsis, and hypotensive index, oliguria, AKI and RRT use. Negative FB as compared with even FB, is associated with decreased risk for death in the first 21 days after ICU admission, however subsequently, the risk of death is significantly higher from 88 days up to one year (A). Positive FB as compared with even FB, is associated with increased risk of death over one year. This risk was much higher early on and is relatively less from 178 days after ICU admission till the remainder of the year (B). Negative FB as compared with positive FB, was associated with decreased risk of death over the 1 year with the lowest risk upto 11 days after ICU admission (C).