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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., (© 2023 S. Karger AG, Basel.)

Introduction: Renal replacement therapy (RRT) is associated with hypotension. However, its impact on cardiac output (CO) is less understood. We aimed to describe current knowledge of CO monitoring and changes during RRT., Methods: We searched MEDLINE, Embase, and Cochrane from January 1, 2000, to January 31, 2023, using Covidence for studies of intermittent hemodialysis (IHD) and continuous RRT (CRRT) with at least three CO measurements during treatment. Two independent reviewers screened citations, and a third resolved disagreements. The findings did not allow meta-analysis and are presented descriptively., Results: We screened 3,285 articles and included 48 (37 during IHD, nine during CRRT, and two during both). Non-invasive devices (electrical conductivity techniques and finger cuff pulse contour) were the most common CO measurement techniques (21 studies). The median baseline cardiac index in IHD studies was 3 L/min/m2 (95% CI, 2.7-3.39). Among the 88 patient cohorts studied, a decrease in CO occurred in 63 (72%). In 16 cohorts, the decrease was severe (>25%). Changes in blood pressure (BP) were not concordant in extent or direction with changes in CO. The decrease in CO correlated weakly with ultrafiltration rate (r = -0.3, p = 0.05) and strongly with changes in systemic vascular resistance (SVR) (r = -0.6, p < 0.001)., Conclusion: There are limited data on CO changes during RRT. However, a decrease in CO appeared common and was marked in 1 of 5 patient cohorts. Such decreases often occurred without BP changes and were associated with increased SVR., (© 2023 S. Karger AG, Basel.)

Introduction: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV., Methods: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome., Results: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013)., Conclusions: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The effect of continuous renal replacement therapy (CRRT) on renal function is poorly understood. However, the initiation of CRRT may induce oliguria. We aimed to investigate the impact of CRRT commencement on urine output (UO)., Methods: This was a retrospective cohort study in two intensive care units. We included all patients who underwent CRRT and collected data on hourly UO and fluid balance before and after CRRT commencement. We performed an interrupted time series analysis using segmented regression to assess the relationship between CRRT commencement and UO., Results: We studied 1,057 patients. Median age was 60.7 years (interquartile range [IQR], 48.3-70.6), and the median APACHE III was 95 (IQR, 76-115). Median time to CRRT was 17 h (IQR, 5-49). With start of CRRT, the absolute difference in mean hourly UO and mean hourly fluid balance was -27.0 mL/h (95% CI: -32.1 to -21.8; p value < 0.01) and - 129.3 mL/h (95% CI: -169.2 to -133.3), respectively. When controlling for pre-CRRT temporal trends and patient characteristics, there was a rapid post-initiation decrease in UO (-0.12 mL/kg/h; 95% CI: -0.17 to -0.08; p value < 0.01) and fluid balance (-78.1 mL/h; 95% CI: -87.9 to -68.3; p value < 0.01), which was sustained over the first 24 h of CRRT. Change in UO and fluid balance were only weakly correlated (r -0.29; 95% CI: -0.35 to -0.23; p value < 0.01)., Conclusion: Commencement of CRRT was associated with a significant decrease in UO that could not be explained by extracorporeal fluid removal., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2023 S. Karger AG, Basel.)

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., (© 2021 S. Karger AG, Basel.)

Introduction: Higher net ultrafiltration (UFNET) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT)., Objective: The aim of the study was to discover whether UFNET rates are associated with renal recovery and independence from renal replacement therapy (RRT)., Methods: Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UFNET rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UFNET rate was defined as the volume of fluid removed per hour adjusted for patient body weight., Results and Conclusions: Median age was 67.3 (interquartile range [IQR], 57-76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84-118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UFNET rates, 3 groups were defined: high, >1.75; middle, 1.01-1.75; and low, <1.01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0%; p = 0.01. Using competing risk regression, higher UFNET rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66-0.95; subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67-0.97) and lower (csHR, 0.69, 95% CI, 0.56-0.85; sHR, 0.78, 95% CI 0.64-0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74-0.89; and sHR, 0.87, 95% CI, 0.80-0.95). Using the joint model, longitudinal increases in UFNET rates were also associated with a lower renal recovery (β = -0.29, p < 0.001). UFNET rates >1.75 mL/kg/h compared with rates 1.01-1.75 and <1.01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UFNET rate-outcome relationship., (© 2021 S. Karger AG, Basel.)

Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment., Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected., Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ., Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction., (© 2021 S. Karger AG, Basel.)

Background: Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery., Methods: This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days., Results: Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66-0.91) and in those with >50% platelet decrease (HR 0.84, CI 0.72-0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90-0.97) and >50% platelet decrease (OR 0.91, CI 0.88-0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small., Conclusions: Platelet nadir <100 × 103/µL and platelet decrease by >50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT., (© 2021 S. Karger AG, Basel.)

Introduction: Continuous renal replacement therapy (CRRT) can be used to treat hyperammonaemia. However, no study has assessed the effect of different CRRT techniques on ammonia clearance., Methods: We compared 3 different CRRT techniques in adult patients with hyperammonaemia, liver failure, and acute kidney injury. We protocolized CRRT to progressively deliver continuous veno-venous haemofiltration (CVVH), haemodialysis (CVVHD) or haemodiafiltration (CVVHDF). Ammonia was simultaneously sampled from the patient's arterial blood and effluent fluid for each technique. We applied accepted equations to calculate clearance., Results: We studied 12 patients with a median age of 47 years (interquartile range [IQR] 25-79). Acute liver failure was present in 4 (25%) and acute-on-chronic liver failure in 8 (75%). There was no significant difference in median ammonia clearance between CRRT technique; CVVH: 27 (IQR 23-32) mL/min versus CVVHD: 21 (IQR 17-28) mL/min versus CVVHDF: 20 (IQR 14-28) mL/min, p = 0.32. Moreover, for all techniques, ammonia clearance was significantly less than urea and creatinine clearance; urea 50 (47-54) mL/min versus creatinine 42 (IQR 38-46) mL/min versus ammonia 25 (IQR 18-29) mL/min, p = 0.0001., Conclusion: We found no significant difference in ammonia clearance according to CRRT technique and demonstrated that ammonia clearance is significantly less than urea or creatinine clearance., (© 2022 S. Karger AG, Basel.)

Aim: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT)., Methods: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data., Results: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was -288 mL (-904 to 261) with 20% HAS only versus 245 mL (-248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77-1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84-1.30; p = 0.70) compared to those who received 4% HAS only., Conclusions: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction: In continuous renal replacement therapy (CRRT)-treated patients, a net ultrafiltration (NUF) rate >1.75 mL/kg/h has been associated with increased mortality. However, there may be heterogeneity of effect of NUF rate on mortality, according to patient characteristics., Methods: To investigate the presence and impact of heterogeneity of effect, we performed a secondary analysis of the "Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy" (RENAL) trial. Exposure was NUF rate (weight-adjusted fluid volume removed per hour) stratified into tertiles (<1.01 mL/kg/h; 1.01-1.75 mL/kg/h; or >1.75 mL/kg/h). Primary outcome was 90-day mortality. Patients were clustered according to baseline characteristics. Heterogeneity of effect was assessed according to clusters and baseline edema and related to the additional impact of baseline cardiovascular Sequential Organ Failure Assessment (SOFA) score. We excluded patients with missing values for baseline weight and/or treatment duration., Results: We identified 2 clusters. The largest (cluster 1; n = 941) included more severely ill patients, with more sepsis, more edema, and more vasopressor therapy (all p < 0.001). Compared to the middle tertile, the probability of harm was greater with the high tertile of NUF rate in patients in cluster 1 and in patients with baseline edema (probability of harm, cluster 1: 99.9%; edema: 99.1%). Moreover, higher baseline cardiovascular SOFA score also increased mortality risk with both high and low compared to middle NUF rates in cluster 1 patients and in patients with edema., Conclusions: In CRRT patients, both high and low NUF rates may be harmful, especially in those with edema, sepsis, and greater illness severity. Cardiovascular SOFA scores modulate this association. Additional studies are needed to test these hypotheses, and targeted trials of NUF rates based on risk stratification appear justified., Trial Registration: ClinicalTrials.gov identifier: NCT00221013., (© 2020 S. Karger AG, Basel.)

Aims: To study the impact of early human albumin solution (HAS) in continuous renal replacement therapy (RRT) patients., Methods: Analysis of Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data., Results: Of 1,464 patients, 500 (34%) received early albumin. These patients had higher illness severity scores, greater use of mechanical ventilation, and 90-day mortality (51 vs. 41%; p < 0.001). However, early albumin carried similar RRT dependence risk among survivors at day 90 (4.9 vs. 5.8%; p = 0.62). On Cox proportional hazards regression, with standardized inverse probability of treatment weighting, early albumin was not associated with increased mortality (hazard ratio [HR]: 1.23, 95% CI: 0.97-1.55; p = 0.09) or recovery to RRT independence (HR: 0.92, 95% CI: 0.78-1.10; p = 0.38)., Conclusions: Early albumin was administered to one-third of RENAL trial patients and in those with greater illness severity. Early albumin was not independently associated with mortality risk or rate of recovery to RRT independence., (© 2020 S. Karger AG, Basel.)

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials., (© 2020 S. Karger AG, Basel.)

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems., Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients., Methods: Observational study in a tertiary care hospital in Milan, Italy., Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients., Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality., (© 2020 S. Karger AG, Basel.)

Introduction: Little is known about early (first 48 h) hourly and cumulative fluid balance (FB) during continuous renal replacement therapy (CRRT)., Objectives: To study the characteristics and outcome associations of early hourly and cumulative FB., Methods: We studied FB in CRRT patients (2016-2018)., Results: Among 350 patients, mean hourly FB became negative after 20 CRRT hours, but within 6 CRRT hours in patients with baseline fluid overload. A negative early FB was never achieved in patients receiving vasopressor therapy (p < 0.001). Mortality was 31%. The percentage of hourly negative FB was independently associated with decreased ICU mortality. A time-weighted hourly FB between 18.5 and -33 mL/h was also significantly and independently associated with decreased mortality., Conclusions: In CRRT patients, an early FB conservative approach is possible, modulated by patient characteristics, and associated with a low mortality. Moreover, avoidance of an early positive FB is associated with decreased mortality., (© 2019 S. Karger AG, Basel.)

Background: Continuous renal replacement therapy (CRRT) technique may affect circuit lifespan. A shorter circuit life may reduce CRRT efficacy and increase costs., Methods: In a before-and-after study, we compared circuit median survival time during continuous venovenous hemofiltration (CVVH) versus continuous venovenous hemodialysis (-CVVHD). We performed log-rank mixed effects univariate analysis and Cox mixed effect regression modeling to define predictors of circuit lifespan., Results: We compared 197 -CVVHD and 97 CVVH circuits in 39 patients. There was no overall difference in circuit lifespan. When no anticoagulation was used, median circuit survival time was shorter for CVVH circuits (5 h, 95% CI 3-7 vs. 10 h, 95% CI 8-13, p < 0.01). Moreover, CVVHD, lower platelets levels, and longer activated partial thromboplastin time independently predicted longer circuit median survival time., Conclusions: CVVHD is associated with longer circuit median survival time than CVVH when no anticoagulation is used and is an independent predictor of circuit survival., (© 2020 S. Karger AG, Basel.)

Background: Critically ill patients with COVID-19 may develop multiple organ dysfunction syndrome, including acute kidney injury (AKI). We report the incidence, risk factors, associations, and outcomes of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients. Methods: We performed a retrospective cohort study of adult patients with COVID-19 diagnosis admitted to the intensive care unit (ICU) between March 2020 and May 2020. Multivariable logistic regression analysis was applied to identify risk factors for the development of AKI and use of RRT. The primary outcome was 60-day mortality after ICU admission. Results: 101 (50.2%) patients developed AKI (72% on the first day of invasive mechanical ventilation [IMV]), and thirty-four (17%) required RRT. Risk factors for AKI included higher baseline Cr (OR 2.50 [1.33–4.69], p = 0.005), diuretic use (OR 4.14 [1.27–13.49], p = 0.019), and IMV (OR 7.60 [1.37–42.05], p = 0.020). A higher C-reactive protein level was an additional risk factor for RRT (OR 2.12 [1.16–4.33], p = 0.023). Overall 60-day mortality was 14.4% {23.8% (n = 24) in the AKI group versus 5% (n = 5) in the non-AKI group (HR 2.79 [1.04–7.49], p = 0.040); and 35.3% (n = 12) in the RRT group versus 10.2% (n = 17) in the non-RRT group, respectively (HR 2.21 [1.01–4.85], p = 0.047)}. Conclusions: AKI was common among critically ill COVID-19 patients and occurred early in association with IMV. One in 6 AKI patients received RRT and 1 in 3 patients treated with RRT died in hospital. These findings provide important prognostic information for clinicians caring for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Hyperammonemia is a life-threatening condition. However, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. Methods: We searched EMBASE and MEDLINE databases. We included all publications reporting ammonia clearance by extracorporeal treatment in adult and pediatric patients with clearance estimated by direct dialysate ammonia measurement or calculated by formula. Two reviewers screened and extracted data independently. Results: We found 1,770 articles with 312 appropriate for assessment and 28 studies meeting eligibility criteria. Most of the studies were case reports. Hyperammonemia was typically secondary to inborn errors of metabolisms in children and to liver failure in adult patients. Ammonia clearance was most commonly reported during continuous renal replacement therapy (CRRT) and appeared to vary markedly from <5 mL/min/m2 to >250 mL/min/m2. When measured during intermittent hemodialysis (IHD), clearance was highest and correlated with blood flow rate (R2 = 0.853; p < 0.001). When measured during CRRT, ammonia clearance could be substantial and correlated with effluent flow rate (EFR; R2 = 0.584; p < 0.001). Neither correlated with ammonia reduction. Peritoneal dialysis (PD) achieved minimal clearance, and other extracorporeal techniques were rarely studied. Conclusions: Extracorporeal ammonia clearance varies widely with sometimes implausible values. Treatment modality, blood flow, and EFR, however, appear to affect such clearance with IHD achieving the highest values, PD achieving minimal values, and CRRT achieving substantial values especially at high EFRs. The role of other techniques remains unclear. These findings can help inform practice and future studies. [ABSTRACT FROM AUTHOR]

Aims: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. Methods: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. Results: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). Conclusions: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Aims: The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. Methods: Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. Results: The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). Conclusions: Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. [ABSTRACT FROM AUTHOR]

Background: The continuous renal replacement therapy (CRRT) bubble trap chamber is a frequent site of clotting. Aims: To assess clot formation when comparing our standard 'vertical' blood entry chamber (BEC) with a new 'horizontal' BEC. Methods: Adult ICU patients requiring CRRT were treated with the vertical BEC and then a similar subsequent cohort with the horizontal BEC in continuous veno-venous haemofiltration mode. Results: 40 chambers were assessed for each design. Circuit life was 13.9 ± 9.5 h for the vertical and 17.7 ± 15.9 h for the horizontal BEC (p = 0.33). APTT, however, was higher for the horizontal BEC (55.7 ± 34.7 vs. 37.4 ± 9.0, p < 0.002) and no difference in circuit life was found after multivariable analysis. A clotting score ≥3 was observed in 85% of all chambers. There was no difference in chamber clotting score (vertical 3.6 ± 1.03 vs. horizontal 3.8 ± 1.0, p = 0.5). In addition, no difference was found when scores were divided into two groups using a 'likelihood' to clot analysis (p = 1.0). Conclusion: CRRT horizontal BEC were not associated with less clotting compared to our standard vertical BEC. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: To examine biochemical effects of phosphate-containing replacement fluid (Phoxilium®) for continuous venovenous hemofiltration (CVVH). Methods: Retrospective comparison of respective serum biochemistry with sequential use of Accusol™ and Phoxilium, each over 48 h of CVVH. Results: We studied 15 critically ill patients. Accusol was switched to Phoxilium after 5 (4-8) days of CVVH. Respective serum biochemistry after 36-42 h of Accusol versus Phoxilium were: phosphate 1.02 (0.82-1.15) versus 1.44 (1.23-1.78) mmol/l, ionized calcium 1.28 (1.22-1.32) versus 1.12 (1.06-1.21) mmol/l, bicarbonate 24 (23-25) versus 20 (19-22) mmol/l, base excess 0 (-2 to 1) versus -4 (-6 to -3) mmol/l (p < 0.001). Cumulative phosphate intakes during respective periods were 69.6 (56.6-76.6) versus 67.2 (46.6-79.0) mmol (p = 0.45). Plasma strong ion differences were narrower with Phoxilium (p < 0.05), with similar strong ion gaps. No additional intravenous phosphate was given during Phoxilium use. Seven patients had serum phosphate >1.44 mmol/l. Conclusions: Phoxilium versus Accusol use during CVVH effectively prevented hypophosphatemia but contributed to mild hyperphosphatemia, and is associated with relative hypocalcemia and metabolic acidosis. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims: Attempts at achieving cytokine homeostasis include blood purification to deliver cytokine removal. Assessment of ex vivo studies for optimal operating conditions is a vital step. Methods: We conducted a systematic search for ex vivo studies on cytokine removal using known modalities of extracorporeal circulation. We selected 29 articles and analyzed data according to clearance, sieving coefficient, ultrafiltrate concentration and percentage removal. Results: We identified four main techniques for cytokine removal: standard techniques, high cut-off (HCO) techniques, adsorption techniques and combined plasma filtration adsorption. HCO hemofiltration (HCO/HF) showed greatest consistency in cytokine removal among all approaches. Mean albumin clearance with HCO filters was 3.74 ml/min. Conclusion: Ex vivo data support the view that HCO/HF is the most consistently effective approach in terms of sieving and clearance. Further investigation of HCO/HF in randomized controlled trials in animal models and humans seems desirable. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Aims: In vasopressor-dependent patients, we evaluated the impact of a slow blood flow protocol on hypotension when starting continuous renal replacement therapy (CRRT). Methods: Retrospective observational study in tertiary ICU of a slow blood flow protocol at the start of CRRT circuits. Results: 205 circuits in 52 patients were studied. No significant changes in mean arterial pressure (MAP) and norepinephrine dose were found. Only 16 circuit starts in 13 patients were associated with a decrease in MAP >20%. In 23 filters and 11 patients, norepinephrine dose was >50 μg/min at baseline and also did not change significantly. There were no cardiac arrests or ventricular arrhythmias and CRRT was not discontinued because of hypotension. Conclusions: Implementation of a CRRT slow blood flow protocol in vasopressor-dependent patients enabled the initiation of CRRT circuits with limited hemodynamic consequences and no cardiac arrest or ventricular arrhythmia. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Choice of insertion side and patient position during continuous renal replacement therapy (CRRT) with femoral vein vascular access may affect circuit life. We investigated if there is an association between choice of insertion side and body position and its changes and circuit life during CRRT with femoral vein access. Methods: We studied 50 patients receiving CRRT via femoral vein access with a sequential retrospective study in a tertiary intensive care unit. We defined two groups: patients with right or left femoral vein access. We then obtained information on age, gender, circuit life, total heparin dose, hemoglobin concentration and coagulation variables (platelet count, international normalized ratio, and activated partial thromboplastin time) and percentage of time each patient spent in the supine, left lying, right lying, and sitting position during treatment. Results: We studied 341 circuits in 50 patients. Mean circuit life was 13.9 h. Of these circuits, 251 (73.6%) were treated with right femoral vein access. Mean circuit life in this group was significantly longer compared with left femoral vein access (15.0 ± 14.3 vs. 10.6 ± 7.4; p = 0.019). Percentage spent in a particular position during CRRT was not significantly different between two groups. On multivariable linear regression analysis, mean circuit life was significantly and positively correlated with right vascular access site (p = 0.03) and lower platelet count (p = 0.03), but not with patient position. Conclusions: Right-sided insertion but not time spent in a particular position significantly affects circuit life during CRRT with femoral vein access. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Failure of extracorporeal circuit (EC) function during continuous renal replacement therapy (CRRT) appears most likely due to progressive circuit clotting or, in some cases, most likely due to mechanical problems that affect flow. We aimed to study the incidence of such likely mechanical circuit failure (MCF). Design and Setting: Retrospective observational study in an adult ICU of a tertiary hospital. Patients and Measurements: We studied 30 patients treated with CRRT via femoral vein vascular access. We obtained information on age, gender, diagnosis, mode of CRRT, circuit life, and blood chemistry. We defined MCF as 'likely' if there was a reduction of between 60 and 80% in circuit life compared to the previous or following circuit life and 'very likely' if such a reduction was between 81 and 100%. Results: We studied 166 circuits in 30 different patients. Of these 26 were electively disconnected leaving 140 circuits with unplanned cessation of function. Among these circuits, likely MCF affected 10 circuits (7.1%) and very likely MCF affected 9 circuits (6.4%) for a total of 19 (13.6%) circuits. Conclusion: Mechanical circuit failure appears to affect approximately 1 in 8 circuits. Prospective studies are needed to understand why MCF occurs. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]