Early Net Ultrafiltration during Continuous Renal Replacement Therapy: Impact of Admission Diagnosis and Association with Mortality.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality. METHODS: We studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h. RESULTS: We studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46-1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00-1.20 mL/kg/h, 1.21-1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13-1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness. CONCLUSION: Early UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association.

Continuous Renal Replacement Therapy during Extracorporeal Membrane Oxygenation: Circuit Haemodynamics and Circuit Failure.

INTRODUCTION: Treatment with continuous renal replacement therapy (CRRT) is common during extracorporeal membrane oxygenation (ECMO). Such ECMO-CRRT has specific technical characteristics, which may affect circuit life. Accordingly, we studied CRRT haemodynamics and circuit life during ECMO. METHODS: ECMO and non-ECMO-CRRT treatments in two adult intensive care units were compared using data collected over a 3-year period. A potential predictor of circuit survival identified in a 60% training data subset as a time-varying covariate within a Cox proportional hazard model was subsequently assessed in the complementary remaining data (40%). RESULTS: Median [interquartile range] CRRT circuit life was greater when associated with ECMO (28.8 [14.0-65.2] vs. 20.2 [9.8-40.2] h, p < 0.0001). Access, return, prefilter, and effluent pressures were also greater during ECMO. Higher ECMO flows were associated with higher access and return pressures. Classification and regression tree analysis identified an association between high access pressures and accelerated circuit failure, while both first access pressures ≥190 mm Hg (HR 1.58 [1.09-2.30]) and patient weight (HR 1.85 [1.15-2.97] third tertile vs. first tertile) were independently associated with circuit failure in a multivariable Cox model. Access dysfunction was associated with a stepwise increase in transfilter pressure, suggesting a potential mechanism of membrane injury. CONCLUSION: CRRT circuits used in conjunction with ECMO have a longer circuit life than usual CRRT despite exposure to higher circuit pressures. Markedly elevated access pressures, however, may predict early CRRT circuit failure during ECMO, possibly via progressive membrane thrombosis as evidenced by increased transfilter pressure gradients.

Circuit haemodynamics during non-citrate and regional citrate continuous renal replacement, and impact of blood flow on filter life.

BACKGROUND: During continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA), blood flow (Qb) might affect vascular access dysfunction (AD) and, thereby, circuit life. METHODS: Circuit life and circuit haemodynamics were studied in three intensive care units (ICUs) by analysing hemofilter device data (Prismaflex®, Baxter, Chicago, IL). The three sites shared similar RCA protocols but differed in Qb (120-130 vs 150-200 mL/h). Non-RCA circuits were compared with RCA circuits in which the impact of Qb was also assessed. RESULTS: About 3,981,906 min of circuit pressures were analysed in 2568 circuits in 567 patients. High-Qb RCA was associated with more extreme pressures, and greater AD (IRR 3.7 (1.93-7.08) as well as reduced filter life 21.1 (10.2-42.6) vs 27.0 (14.8-41.6) h). AD in high-Qb RCA circuits was associated with a 49% reduction in filter life, versus 24% reduction in low-Qb RCA, associated with a rise in the rate of increase in transfilter pressure. CONCLUSIONS: High-Qb RCA-CRRT was associated with greater access dysfunction, earlier filter loss and increased haemodynamic impacts of access dysfunction, suggesting low-Qb RCA-CRRT may improve circuit mechanics, function and longevity.

The relationship between commencement of continuous renal replacement therapy and urine output, fluid balance, mean arterial pressure and vasopressor dose.

Background and objectives: The effect of initiating continuous renal replacement therapy (CRRT) on urine output, fluid balance and mean arterial pressure (MAP) in adult intensive care unit (ICU) patients is unclear. We aimed to evaluate the impact of CRRT on urine output, MAP, vasopressor requirements and fluid balance, and to identify factors affecting urine output during CRRT. Design: Retrospective cohort study using data from existing databases and CRRT machines. Setting: Medical and surgical ICUs at a single university-associated centre. Participants: Patients undergoing CRRT between 2015 and 2018. Main outcome measures: Hourly urine output, fluid balance, MAP and vasopressor dose 24 hours before and after CRRT commencement. Missing values were estimated via Kaplan smoothing univariate time-series imputation. Mixed linear modelling was performed with noradrenaline equivalent dose and urine output as outcomes. Results: In 215 patients, CRRT initiation was associated with a reduction in urine output. Multivariate analysis confirmed an immediate urine output decrease (-0.092 mL/kg/h; 95% confidence interval [CI], -0.150 to -0.034 mL/kg/h) and subsequent progressive urine output decline (effect estimate, -0.01 mL/kg/h; 95% CI, -0.02 to -0.01 mL/kg/h). Age and greater vasopressor dose were associated with lower post-CRRT urine output. Higher MAP and lower rates of net ultrafiltration were associated with higher post-CRRT urine output. With MAP unchanged, vasopressor dose increased in the 24 hours before CRRT, then plateaued and declined in the 24 hours thereafter (effect estimate, -0.004 µg/kg/ min per hour; 95% CI, -0.005 to -0.004 µg/kg/min per hour). Fluid balance remained positive but declined towards neutrality following CRRT implementation. Conclusions: CRRT was associated with decreased urine output despite a gradual decline in vasopressor and a positive fluid balance. The mechanisms behind the reduction in urine output associated with commencement of CRRT requires further investigation.

Low Blood Flow Continuous Veno-Venous Haemodialysis Compared with Higher Blood Flow Continuous Veno-Venous Haemodiafiltration: Effect on Alarm Rates, Filter Life, and Azotaemic Control.

TITLE: Low blood flow continuous veno-venous haemodialysis (CVVHD) compared with higher blood flow continuous veno-venous haemodiafiltration (CVVHDF): effect on alarm rates, filter life, and azotaemic control. INTRODUCTION: Continuous renal replacement therapy (CRRT) can be delivered via convective, diffusive, or mixed approaches. Higher blood flows have been advocated for convective clearance efficiency and promotion of filter life. It is unclear whether a lower blood flow predominantly diffusive approach may benefit filter life and alarm rates. MATERIALS AND METHODS: Sequential cohort study of 284 patients undergoing 874 CRRT circuits from January 2015 to August 2018 in a single university-associated tertiary referral hospital in Australia. Patients underwent a protocol of either CVVHDF at blood flow 200-250 mL/min or CVVHD at blood flow 100-130 mL/min. Machine and patient data were analysed. Outcomes of azotaemic control, filter life, and warning alarm rates were log transformed and analysed with mixed linear modelling with patient as a random effect. RESULTS: Both groups had similar azotaemic control (effect estimate on log creatinine CVVHD vs. CVVHDF 1.04 [0.87-1.25], p = 0.68) and median filter life (CVVHDF 16.8 [8.4-90.5] h and CVVHD 16.4 [9.4-82.3] h, p = 0.97). However, circuit pressures were less extreme with a narrower distribution during CVVHD. Multivariate analysis showed CVVHD had a reduced risk of warning alarms (incidence risk ratio [IRR] 0.51 [0.38-0.70]) and femoral access placement also had a reduced risk of alarms (IRR 0.55 [0.41-0.73]). CONCLUSION: Low blood flow CVVHD and femoral vascular access reduce alarms while maintaining azotaemic control and circuit patency thus minimizing bedside clinician workload.

Circuit Hemodynamics and Circuit Failure During Continuous Renal Replacement Therapy.

OBJECTIVES: To study hemodynamic changes within continuous renal replacement therapy circuits and evaluate their relationship with continuous renal replacement therapy longevity. DESIGN: Analysis of downloaded variables recorded by continuous renal replacement therapy machines during multiple episodes of clinical care. SETTING: Tertiary ICU in Melbourne, Australia. PATIENTS: Cohort of 149 ICU patients: 428 episodes of continuous renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Indices of continuous renal replacement therapy function representing 554,991 minutes were assessed including blood flow, access pressure, effluent pressure, prefilter pressure, and return pressure. We defined three patterns of artificial kidney failure: early (≤ 12 hr), intermediate (> 12-24 hr), and late (> 24 hr) in 35%, 31%, and 34% of circuits, respectively. Mean access pressure in late artificial kidney failure was 7.5 mm Hg (7.1-7.9 mm Hg) less negative than early failing circuits and pressures demonstrated lower variability in such late failing circuits. Access dysfunction, defined as access pressure less than or equal to -200 mm Hg occurred in the first 4 hours in 118 circuits (27%) which had a shorter (median [interquartile range]) life at 12.9 hr [5.5-21.3 hr]) hours than access dysfunction-free circuits (18.8 hr [10.1-33.4 hr]; p < 0.0001). Multivariate analysis found the first occurrence of access dysfunction (as a time-varying covariate) was independently associated with increased hazard of subsequent failure (hazard ratio, 1.75; 1.36-2.26). Classification and regression tree analysis of summary pressure indices in the first 2 hours confirmed minimum access pressure to be a significant predictor, as well as indices of transmembrane pressure and return pressure. A pressure-based predictor correctly identified early and late failing circuits (86.2% and 93.6% specificity, respectively). CONCLUSIONS: Access dysfunction is a predictor of continuous renal replacement therapy circuit failure. Future monitoring of continuous renal replacement therapy hemodynamics may facilitate remedial actions to improve circuit function.