Net ultrafiltration intensity and mortality in critically ill patients with fluid overload

Abstract

Background: Although net ultrafiltration (UF^NET) is frequently used for treatment of fluid overload in critically ill patients with acute kidney injury, the optimal intensity of UF^NET is unclear. Among critically ill patients with fluid overload receiving renal replacement therapy (RRT), we examined the association between UF^NET intensity and risk-adjusted 1-year mortality.

Methods: We selected patients with fluid overload ≥ 5% of body weight prior to initiation of RRT from a large academic medical center ICU dataset. UF^NET intensity was calculated as the net volume of fluid ultrafiltered per day from initiation of either continuous or intermittent RRT until the end of ICU stay adjusted for patient hospital admission body weight. We stratified UF^NET as low (≤ 20 ml/kg/day), moderate (> 20 to ≤ 25 ml/kg/day) or high (> 25 ml/kg/day) intensity. We adjusted for age, sex, body mass index, race, surgery, baseline estimated glomerular filtration rate, oliguria, first RRT modality, pre-RRT fluid balance, duration of RRT, time to RRT initiation from ICU admission, APACHE III score, mechanical ventilation use, suspected sepsis, mean arterial pressure on day 1 of RRT, cumulative fluid balance during RRT and cumulative vasopressor dose during RRT. We fitted logistic regression for 1-year mortality, Gray's survival model and propensity matching to account for indication bias.

Results: Of 1075 patients, the distribution of high, moderate and low-intensity UF^NET groups was 40.4%, 15.2% and 44.2% and 1-year mortality was 59.4% vs 60.2% vs 69.7%, respectively (p = 0.003). Using logistic regression, high-intensity compared with low-intensity UF^NET was associated with lower mortality (adjusted odds ratio 0.61, 95% CI 0.41-0.93, p = 0.02). Using Gray's model, high UF^NET was associated with decreased mortality up to 39 days after ICU admission (adjusted hazard ratio range 0.50-0.73). After combining low and moderate-intensity UF^NET groups (n = 258) and propensity matching with the high-intensity group (n = 258), UF^NET intensity > 25 ml/kg/day compared with ≤ 25 ml/kg/day was associated with lower mortality (57% vs 67.8%, p = 0.01). Findings were robust to several sensitivity analyses.

Conclusions: Among critically ill patients with ≥ 5% fluid overload and receiving RRT, UF^NET intensity > 25 ml/kg/day compared with ≤ 20 ml/kg/day was associated with lower 1-year risk-adjusted mortality. Whether tolerating intensive UF^NET is just a marker for recovery or a mediator requires further research.

Keywords: Dialysis; Fluid overload; Intensity; Mortality; Net ultrafiltration; Renal replacement therapy.

Fig. 1

a. Association between net ultrafiltration intensity and time to mortality. Kaplan–Meier failure plots by UF^NET intensity for probability of death over 1 year from ICU admission in overall cohort (n = 1075). Red line, low-intensity UF^NET (≤ 20 ml/kg/day); blue line, moderate-intensity UF^NET (> 20 to ≤ 25 ml/kg/day); green line, high-intensity UF^NET (> 25 ml/kg/day). Probability of death highest in low-intensity compared with moderate and high-intensity UF^NET groups (log-rank p < 0.001). b. Association between net ultrafiltration intensity and risk-adjusted 1-year mortality. Shown are adjusted odds ratio with 95% CI for association between UF^NET intensity and mortality. Increasing UF^NET intensity associated with trend toward lower mortality. Odds ratios adjusted for differences in age, sex, race, BMI, history of liver disease and sequela from liver disease, admission for liver transplantation, admission for surgery, baseline glomerular filtration rate, Acute Physiology and Chronic Health Evaluation III score, presence of sepsis, use of mechanical ventilation, percentage of cumulative fluid overload before initiation of RRT, oliguria before initiation of RRT, time to initiation of RRT from ICU admission, MAP on first day of RRT initiation, cumulative vasopressor dose and cumulative fluid balance during RRT, first RRT modality and duration of RRT. ICU intensive care unit

Fig. 2

Association between net ultrafiltration intensity and time to mortality in propensity-matched cohort. Kaplan–Meier failure plots by UF^NET for probability of death over 1 year from ICU admission among patients with UF^NET ≤ 25 ml/kg/day (n = 258) compared with propensity-matched patients with UF^NET > 25 ml/kg/day (n = 258). Red line, UF^NET ≤ 25 ml/kg/day; green line, UF^NET > 25 ml/kg/day. Probability of death lower among patients who received UF^NET > 25 ml/kg/day compared with UF^NET ≤ 25 ml/kg/day (log-rank p < 0.001). ICU intensive care unit