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 categorised UFNET into tertiles of mean UFNET in the first 72 hours and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 hours. Results: We studied 1218 patients; 154,712 hours and 9,282,729 minutes of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46 to 1.57) mL/kg/hr. Early UFNET tertiles were similar to previously reported values at 0.00-1.20 mL/kg/hr, 1.21 to 1.93mL/kg/hr and >1.93mL/kg/hr. UFNET values were similar whether evaluated at 24 or 72 hours 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 to 1.37), independent of admission diagnosis, weight, age, sex, presence of ESKD and severity of illness. Conclusion: Early UFNET practice reflects known tertiles but 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.

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.

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.

Objective: To determine whether contemporaneous practices are adequately represented in recent critical care comparative effectiveness research studies. Design: All critical care comparative effectiveness research trials published in the New England Journal of Medicine from April 2019 to March 2020 were identified. To examine studies published in other high impact medical journals during the same period, such trials were subsequently also identified in the Journal of the American Medical Association and The Lancet. All cited sources were reviewed, and the medical literature was searched to find studies describing contemporary practices. Then, the designated control group or the comparable therapies studied were examined to determine if they represented contemporaneous critical care practices as described in the medical literature. Results: Twenty-five of 332 randomised clinical trials published in these three journals during this 1-year period described critical care comparative effectiveness research that met our inclusion criteria. Seventeen characterised current practices before enrolment (using surveys, observational studies and guidelines) and then incorporated current practices into one or more study arm. In the other eight, usual care arms appeared insufficient. Four of these trials randomly assigned patients to one of two fixed approaches at either end of a range of usually titrated care. However, due to randomisation, different subgroups within each arm received care that was inappropriate for their specific clinical conditions. In the other four of these trials, common practices influencing treatment choice were not reflected in the trial design, despite a prior effort to characterise usual care. Conclusion: One-third of critical care comparative effectiveness research trials published in widely read medical journals during a recent year did not include a designated control arm or comparable therapies representative of contemporary practices. Failure to incorporate contemporary practices into critical care comparative effectiveness trials appears to be a widespread design weakness.

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.

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.