Abstract
Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear. To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration. The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019. Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight. Risk-adjusted 90-day survival. Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (β = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08). Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings. ClinicalTrials.gov identifier: NCT00221013.
Highlights
Fluid overload is a frequent complication present in more than two-thirds of critically ill patients with acute kidney injury and is independently associated with mortality.1,2 When fluid overload is resistant to treatment with diuretics, international practice guidelines recommend net ultrafiltration (NUF).3,4 These recommendations are supported by studies suggesting that NUF could reduce the number of deaths.5,6 uncertainty exists about the optimal rate of NUF in critically ill patients.A slower NUF rate is associated with prolonged exposure to tissue edema and organ dysfunction, whereas a faster rate is associated with hemodynamic stress.7,8 Both complications could decrease survival
A single-center observational study of critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF) and hemodialysis9 found that an NUF rate less than 20 mL/kg/d was associated with higher mortality compared with an NUF rate greater than 25 mL/kg/d
Emerging evidence from outpatients with end-stage renal disease receiving hemodialysis suggests that an NUF rate greater than 13 mL/kg/h per session compared with an NUF rate of 10 mL/kg/h or less is associated with mortality
Summary
Fluid overload is a frequent complication present in more than two-thirds of critically ill patients with acute kidney injury and is independently associated with mortality. When fluid overload is resistant to treatment with diuretics, international practice guidelines recommend net ultrafiltration (NUF). These recommendations are supported by studies suggesting that NUF could reduce the number of deaths. uncertainty exists about the optimal rate of NUF in critically ill patients.A slower NUF rate is associated with prolonged exposure to tissue edema and organ dysfunction, whereas a faster rate is associated with hemodynamic stress. Both complications could decrease survival. When fluid overload is resistant to treatment with diuretics, international practice guidelines recommend net ultrafiltration (NUF).. When fluid overload is resistant to treatment with diuretics, international practice guidelines recommend net ultrafiltration (NUF).3,4 These recommendations are supported by studies suggesting that NUF could reduce the number of deaths.. A slower NUF rate is associated with prolonged exposure to tissue edema and organ dysfunction, whereas a faster rate is associated with hemodynamic stress.. A slower NUF rate is associated with prolonged exposure to tissue edema and organ dysfunction, whereas a faster rate is associated with hemodynamic stress.7,8 A single-center observational study of critically ill patients receiving continuous venovenous hemodiafiltration (CVVHDF) and hemodialysis found that an NUF rate less than 20 mL/kg/d was associated with higher mortality compared with an NUF rate greater than 25 mL/kg/d. Emerging evidence from outpatients with end-stage renal disease receiving hemodialysis suggests that an NUF rate greater than 13 mL/kg/h per session compared with an NUF rate of 10 mL/kg/h or less is associated with mortality. the implications and generalizability of these study findings to patients undergoing continuous NUF are unclear
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