Continuous Renal Replacement Therapy Initiation Research Articles

Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

Successful Application of a Hemoperfusion Machine in Separated System CRRT: Evaluating Effectiveness and Safety in Critically Ill Patients With AKI in Resource-Limited Settings.

It is imperative to note that integrated system continuous renal replacement therapy (CRRT) necessitates a sophisticated and costly apparatus, potentially limiting its availability within resource-limited settings. The introduction of a separated system for continuous veno-venous hemofiltration (CVVH), characterized by uncomplicated setup procedures with a hemoperfusion machine, holds promise as a feasible alternative to CRRT for critically ill patients with acute kidney injury (AKI). We aimed to retrospectively analyze the effectiveness and safety of separated CRRT applied from a hemoperfusion machine in critically ill patients with AKI during the January 2015 to December 2021 period. We also examine the in-hospital mortality rate and multivariate logistic regression analysis to uncover the factors that affect mortality. We included a total of 129 critically ill patients who received separated system CRRT. The SOFA score at CRRT initiation was 12.6 ± 3.8. The fluid accumulation at the day of CRRT initiation was 3900 mL (622-8172 mL) All patients received pre- and postdilution CVVH. The mean prescribed CRRT dose was 22.4 ± 3.1 mL/kg/h. We found no serious complications including circuit explosion and air embolism. The in-hospital mortality rate was 68.9%. High SOFA score and positive fluid accumulation at CRRT initiation serve as predictors of survival. Separated system CRRT using a hemoperfusion machine provides a simplified system to operate and is proven to be effective and safe in real-life practice, especially in resource-limited areas.

The interaction of net ultrafiltration rate with urine output and fluid balance after continuous renal replacement therapy initiation: A multi-Centre study.

PurposeDuring continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT. MethodsA retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs. ResultsMedian age was 60 years (IQR, 48–70), median APACHE III was 94 (IQR, 76–114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (−1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO. ConclusionA higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. Retrospective cohort. Two large quarternary care pediatric hospitals. Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. None. Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (QE). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, QE intrapatient variability and residual renal function. Retrospective observational cohort study. ICUs within Hartford Hospital (890-bed, acute-care hospital) in Connecticut from 2017 to 2023. Adult ICU patients receiving CRRT for greater than 72 hours. CRRT settings including QE and urine output (UOP) were extracted from the time of CRRT initiation (0 hr) and trends were assessed. To assess the impact on antibiotic dosing, cefiderocol doses were assigned to 0 hour, 24 hours, 48 hours, and 72 hours QE values per product label, and the proportion of antibiotic dose changes required as a result of changes in inpatient's QE was evaluated. Among the 380 ICU patients receiving CRRT for greater than 72 hours, the median (interquartile range) 0 hour QE was 2.96 (2.35-3.29) L/hr. Approximately 9 QE values were documented per patient per 24-hour window. QE changes of greater than 0.75 L/hr were observed in 21.6% of patients over the first 24 hours and in 7.9% (24-48 hr) and 5.8% (48-72 hr) of patients. Approximately 40% of patients had UOP greater than 500 mL at 24 hours post-CRRT initiation. Due to QE changes within 24 hours of CRRT initiation, a potential cefiderocol dose adjustment would have been warranted in 38% of patients (increase of 21.3%; decrease of 16.6%). QE changes were less common after 24 hours, warranting cefiderocol dose adjustments in less than 15% of patients. Results highlight the temporal and variable dynamics of QE and prevalence of residual renal function. Data also demonstrate a risk of antibiotic under-dosing in the first 24 hours of CRRT initiation due to increases in QE. For antibiotics with QE-based dosing recommendations, empiric dose escalation may be warranted in the first 24 hours of CRRT initiation.

Plasma neutrophil gelatinase-associated lipocalin independently predicts dialysis need and mortality in critical COVID-19

Neutrophil gelatinase-associated lipocalin (NGAL) is a novel kidney injury and inflammation biomarker. We investigated whether NGAL could be used to predict continuous renal replacement therapy (CRRT) and mortality in critical coronavirus disease 2019 (COVID-19). This prospective multicenter cohort study included adult COVID-19 patients in six intensive care units (ICUs) in Sweden between May 11, 2020 and May 10, 2021. Blood was sampled at admission, days two and seven in the ICU. The samples were batch analyzed for NGAL, creatinine, and cystatin c after the end of the study period. Initiation of CRRT and 90-day survival were used as dependent variables in regression models. Of 498 included patients, 494 were analyzed regarding CRRT and 399 were analyzed regarding survival. Seventy patients received CRRT and 154 patients did not survive past 90 days. NGAL, in combination with creatinine and cystatin c, predicted the subsequent initiation of CRRT with an area under the curve (AUC) of 0.95. For mortality, NGAL, in combination with age and sex, had an AUC of 0.83. In conclusion, NGAL is a valuable biomarker for predicting subsequent initiation of CRRT and 90-day mortality in critical COVID-19. NGAL should be considered when developing future clinical scoring systems.

Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72h) vs. success (no receipt of dialysis for ≥ 72h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Prognostic Factors in Children with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy

Introduction: This study aimed to evaluate prognostic factors and outcomes in a single-center PICU cohort that received continuous renal replacement therapy (CRRT). Methods: This retrospective study analyzed clinical characteristics, laboratory data, and outcomes. Ninety-day mortality and advanced chronic kidney disease (CKD) (eGFR 2) were defined as primary and secondary outcomes, respectively. Results: Seventy-five patients were enrolled, all of whom received CRRT for indications including acute kidney injury with complicated refractory metabolic acidosis, electrolyte derangement, and existed or impending fluid overload. The 90-day mortality and advanced CKD were 53% and 29%, respectively. Multivariate Cox regression analysis demonstrated that only underlying bone marrow transplantation (BMT) (HR 4.58; 95% CI: 2.04–10.27) and a high pSOFA score (HR 1.12; 95% CI: 1.01–1.23) were independent risk factors for 90-day mortality. Among survivors, ten developed advanced CKD on the 90th day, and this group had a higher serum fibrinogen level (OR 1.01; 95% CI: 1.01–1.03) at the start of CRRT. Conclusion: In critically ill children with AKI requiring CRRT, post-BMT and high pSOFA scores are independent risk factors for 90-day mortality. Additionally, a high serum fibrinogen level at the initiation of CRRT is associated with the development of advanced CKD.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. The primary exposure was time to CRRT initiation from intensive care unit admission. The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

Determinants of Urine Output Using Advanced Hemodynamic Monitoring in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy

Introduction: Low cardiac output and hypovolemia are candidate macrocirculatory mechanisms explanatory of de novo anuria in intensive care unit (ICU) patients undergoing continuous renal replacement therapy (CRRT). We aimed to determine the hemodynamic parameters and CRRT settings associated with the longitudinal course of UO during CRRT. Methods: This is an ancillary analysis of the PRELOAD CRRT observational, single-center study (NCT03139123). Enrolled adult patients had severe acute kidney injury treated with CRRT for less than 24 h and were monitored with a calibrated continuous cardiac output monitoring device. Hemodynamics (including stroke volume index [SVI] and preload-dependence, identified by continuous cardiac index variation during postural maneuvers), net ultrafiltration (UF_NET), and UO were reported 4-hourly, over 7 days. Two study groups were defined at inclusion: non-anuric participants if the cumulative 24 h UO at inclusion was ≥0.05 mL kg⁻¹ h⁻¹, and anuric otherwise. Quantitative data were reported by its median [interquartile range]. Results: Forty-two patients (age 68 [58–76] years) were enrolled. At inclusion, 32 patients (76%) were not anuric. During follow-up, UO decreased significantly in non-anuric patients, with 25/32 (78%) progressing to anuria within 19 [10–50] hours. Mean arterial pressure (MAP) and UF_NET did not significantly differ between study groups during follow-up, while SVI and preload-dependence were significantly associated with the interaction of study group and time since inclusion. Higher UF_NET flow rates were significantly associated with higher systemic vascular resistances and lower cardiac output during follow-up. Multivariate analyses showed that (1) lower UO was significantly associated with lower SVI, lower MAP, and preload-independence; and (2) higher UF_NET was significantly associated with lower UO. Conclusions: In ICU patients treated with CRRT, those without anuria showed a rapid loss of diuresis after CRRT initiation. Hemodynamic indicators of renal perfusion and effective volemia were the principal determinants of UO during follow-up, in relation with the hemodynamic impact of UF_NET setting.

Solute Clearance Evaluation and Filter Clotting Prediction in Continuous Renal Replacement Therapy.

Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This single-center, retrospective, observational study aimed to determine whether reduced solute clearance of low- and medium-molecular-weight molecules in CRRT can predict filter clotting. Solute clearances of urea and myoglobin (Mb) were measured at 24 h after initiation of continuous hemodiafiltration (CHDF). Clearance per flow (CL/F) was calculated. The primary outcome was clotting of the filter in the subsequent 24 h, and 775 CHDF treatments conducted on 230 patients for at least 24 consecutive hours in our ICU were analyzed. Filter clotting was observed in 127 treatments involving 39 patients. Urea and Mb CL/F at 24 h were significantly lower in the patients who experienced clotting. Further analysis was limited to the first CHDF treatment of each patient to adjust for confounding factors. Multivariate logistic regression analysis revealed that both urea CL/F < 94% and Mb CL/F < 64% were significant predictors of clotting within the next 24 h. Lower urea and Mb CL/F measured at 24 h after CRRT initiation were associated with filter clotting in the next 24 h. Further study is necessary to ascertain whether measurement of urea and MB CL/F will help with avoiding unexpected filter clotting.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19: A Single-Center Study.

Coronavirus disease 2019 (COVID-19) can lead to acute respiratory failure, which frequently necessitates invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, the limited availability of ECMO resources poses challenges to patient selection and associated decision-making. Consequently, this retrospective single-center study was undertaken to evaluate the characteristics and clinical outcomes of patients with COVID-19 receiving ECMO. Between March 2020 and July 2022, 65 patients with COVID-19 were treated with ECMO and were subsequently reviewed. Patient demographics, laboratory data, and clinical outcomes were examined, and statistical analyses were performed to identify risk factors associated with mortality. Of the patients studied, 15 (23.1%) survived and were discharged from the hospital, while 50 (76.9%) died during their hospitalization. The survival group had a significantly lower median age, at 52 years (interquartile range [IQR], 47.5-61.5 years), compared to 64 years (IQR, 60.0-68.0 years) among mortality group (p=0.016). However, no significant differences were observed in other underlying conditions or in factors related to intervention timing. Multivariable analysis revealed that the requirement of a change in ECMO mode (odds ratio [OR], 366.77; 95% confidence interval [CI], 1.92-69911.92; p=0.0275) and the initiation of continuous renal replacement therapy (CRRT) (OR, 139.15; 95% CI, 1.95-9,910.14; p=0.0233) were independent predictors of mortality. Changes in ECMO mode and the initiation of CRRT during management were associated with mortality in patients with COVID-19 who were supported by ECMO. Patients exhibiting these factors require careful monitoring due to the potential for adverse outcomes.

Elevated strong ion gap: A predictor of the initiation of continuous renal replacement therapy in acute kidney injury

BackgroundThere is no optimal timing for continuous renal replacement therapy (CRRT) in acute kidney injury (AKI). AKI is a reason for the increased unmeasured anions, which refers to the increased organic acids in the blood, and they can be detected by calculating strong ion gap (SIG). SIG level at the moment of the AKI diagnosis may be a predictor for the initiation of CRRT. MethodsPatients who were diagnosed with AKI in the first week of the intensive care unit (ICU) period were included in this prospective observational study. At the moment of the AKI diagnosis, blood gas samples were recorded, and SIG was calculated. ResultsThe median level of SIG at the moment of the AKI diagnosis of CRRT (+) patients was significantly higher than CRRT (-) patients (7.4 and 3.2 mmol L−1, respectively). In the multivariate Cox regression analysis, the likelihood of the initiation of CRRT was increased 1.16-fold (1.01-1.33) and 4.0-fold (1.9-8.7) by only 1 mmol L−1 increases in SIG and SIG ≥6 mmol L-1 at the moment of AKI diagnosis, respectively (p = 0.035 and p < 0.001). ConclusionsIncreased SIG at the moment of the AKI diagnosis in patients with AKI may be a predictive marker to initiate CRRT.

Risk factors of hemodialysis catheter dysfunction in patients undergoing continuous renal replacement therapy: a retrospective study

BackgroundContinuous renal replacement therapy is a relatively common modality applied to critically ill patients with renal impairment. To maintain stable continuous renal replacement therapy, sufficient blood flow through the circuit is crucial, but catheter dysfunction reduces the blood flow by inadequate pressures within the circuit. Therefore, exploring and modifying the possible risk factors related to catheter dysfunction can help to provide continuous renal replacement therapy with minimal interruption.MethodsAdult patients who received continuous renal replacement therapy at Seoul National University Hospital between January 2019 and December 2021 were retrospectively analyzed. Patients who received continuous renal replacement therapy via a temporary hemodialysis catheter, inserted at the bedside under ultrasound guidance within 12 h of continuous renal replacement therapy initiation were included.ResultsA total of 507 continuous renal replacement therapy sessions in 457 patients were analyzed. Dialysis catheter dysfunction occurred in 119 sessions (23.5%). Multivariate analysis showed that less prolonged prothrombin time (adjusted OR 0.49, 95% CI, 0.30–0.82, p = 0.007) and activated partial thromboplastin time (adjusted OR 1.01, 95% CI, 1.00–1.01, p = 0.049) were associated with increased risk of catheter dysfunction. Risk factors of re-catheterization included vascular access to the left jugular and femoral vein.ConclusionsIn critically ill patients undergoing continuous renal replacement therapy, less prolonged prothrombin time was associated with earlier catheter dysfunction. Use of left internal jugular veins and femoral vein were associated with increased risk of re-catheterization compared to the right internal jugular vein.

Hepcidin Removal during Continuous Renal Replacement Therapy

Introduction: Patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) may require continuous renal replacement therapy (CRRT) as a supportive intervention. While CRRT is effective at achieving solute control and fluid balance, the indiscriminate nature of this procedure raises the possibility that beneficial substances may similarly be removed. Hepcidin, an antimicrobial peptide with pivotal roles in iron homeostasis and pathogen clearance, has biochemical properties amenable to direct removal via CRRT. We hypothesized that serum hepcidin levels would significantly decrease after initiation of CRRT. Methods: In this prospective, observational trial, we enrolled 13 patients who required CRRT: 11 due to stage 3 AKI, and 2 due to critical illness in the setting of ESKD. Plasma was collected at the time of enrollment, and then plasma and effluent were collected at 10:00 a.m. on the following 3 days. Plasma samples were also collected from healthy controls, and we compared hepcidin concentrations in those with renal disease compared to normal controls, evaluated trends in hepcidin levels over time, and calculated the hepcidin sieving coefficient. Results: Plasma hepcidin levels were significantly higher in patients initiating CRRT than in normal controls (158 ± 60 vs. 17 ± 3 ng/mL respectively, p < 0.001). Hepcidin levels were highest prior to CRRT initiation (158 ± 60 ng/mL), and were significantly lower on day 1 (102 ± 24 ng/mL, p < 0.001) and day 2 (56 ± 14 ng/mL, p < 0.001) before leveling out on day 3 (51 ± 11 ng/mL). The median sieving coefficient was consistent at 0.82–0.83 for each of 3 days. Conclusions: CRRT initiation is associated with significant decreases in plasma hepcidin levels over the first 2 days of treatment regardless of indication for CRRT, or presence of underlying ESKD. Since reduced hepcidin levels are associated with increased mortality and our data implicate CRRT in hepcidin removal, larger clinical studies evaluating relevant clinical outcomes based on hepcidin trends in this population should be pursued.

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.

Initiation of continuous renal replacement therapy versus intermittent hemodialysis in critically ill patients with severe acute kidney injury: a secondary analysis of STARRT-AKI trial.

There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.

Left Ventricular Unloading With Impella Versus IABP in Patients With VA-ECMO: A Systematic Review and Meta-Analysis

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I2 were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I2=71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I2=82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2=66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.

Hemodynamic and Homeostasis Changes after Continuous Renal Replacement Therapy in Septic Shock Children at Vietnam National Children’s Hospital

Objectives: This study aims to describe changes in hemodynamics and homeostasis after continuous renal replacement therapy (CRRT) in septic shock children without acute kidney injury. Methods: An observational study was conducted in the pediatric intensive care unit (PICU) at Vietnam National Children’s Hospital from January 2018 to June 2022. Children aged under 18 years old with septic shock and without acute kidney injury who required CRRT were analyzed on demographic factors, baseline clinical and laboratory results, changes in hemodynamics and homeostasis at 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 4 days and 5 days after CRRT initiation. Results: A total of 125 children (male, 57.6%) were enrolled in the study. The median age was 11.5 months (IQR: 5 – 29). Overall PICU mortality rate at day 28 was 40.8%. Among survivors, there was a statistically significant improvement in heart rate, mean blood pressure, vasoactive inotropic score (VIS), and pH at all mentioned periods after CRRT initiation. Lactatemia statistically significantly decreased after 24 hours of CRRT initiation (p &lt; 0.05). Among non-survivors, there was a statistically significant improvement in heart rate at all the periods and in mean blood pressure at 6 hours and 12 hours, while there was no improvement in VIS, pH, and lactatemia. Conclusion: CRRT played an important role in stabilizing hemodynamics and homeostasis in septic shock children without acute kidney injury.&#x0D; &#x0D; &#x0D; &#x0D;

Real-Time Acute Kidney Injury Risk Stratification–Biomarker Directed Fluid Management Improves Outcomes in Critically Ill Children and Young Adults

Critically ill admitted patients are at high risk of acute kidney injury (AKI). The renal angina index (RAI) and urinary biomarker neutrophil gelatinase-associated lipocalin (uNGAL) can aid in AKI risk assessment. We implemented the Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2; TF2) to personalize fluid management and continuous renal replacement therapy (CRRT) initiation based on AKI risk and patient fluid accumulation. We compared outcomes pre-TF2 and post-TF2 initiation. Patients admitted from July 2017 were followed-up prospectively with the following: (i) an automated RAI result at 12 hours of admission, (ii) a conditional uNGAL order for RAI≥8, and (iii) a CRRT initiation goal at 10% to 15% weight-based fluid accumulation. A total of 286 patients comprised 304 intensive care unit (ICU) RAI+ admissions; 178 patients received CRRT over the observation period (2014-2021). Median time from ICU admission to CRRT initiation was 2 days shorter (P< 0.002), and≥15% pre-CRRT fluid accumulation rate was lower in the TF2 era (P< 0.02). TF2 ICU length of stay (LOS) after CRRT discontinuation and total ICU LOS were 6 and 11 days shorter for CRRT survivors (both P< 0.02). Survival rates to ICU discharge after CRRT discontinuation were higher in the TF2 era (P= 0.001). These associations persisted in each TF2 year; we estimate a conservative $12,500 health care cost savings per CRRT patient treated after TF2 implementation. We suggest that automated clinical decision support (CDS) combining risk stratification and AKI biomarker assessment can produce durable reductions in pediatric CRRT patient morbidity.