Explore the vast range of titles available.

Background Continuous renal replacement therapy (CRRT) is a widely used standard therapy for critically ill patients with acute kidney injury (AKI). Despite its effectiveness, treatment is often interrupted due to clot formation in the extracorporeal circuits. Anticoagulation is a crucial strategy for preventing extracorporeal circuit clotting during CRRT. While various anticoagulation options are available, there were still no studies synthetically comparing the efficacy and safety of these anticoagulation options. Methods Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to October 31, 2022. All randomized controlled trials (RCTs) that examined the following outcomes were included: filter lifespan, all-cause mortality, length of stay, duration of CRRT, recovery of kidney function, adverse events and costs. Results Thirty-seven RCTs from 38 articles, comprising 2648 participants with 14 comparisons, were included in this network meta-analysis (NMA). Unfractionated heparin (UFH) and regional citrate anticoagulation (RCA) are the most frequently used anticoagulants. Compared to UFH, RCA was found to be more effective in prolonging filter lifespan (MD 12.0, 95% CI 3.8 to 20.2) and reducing the risk of bleeding. Regional-UFH plus Prostaglandin I2 (Regional-UFH + PGI2) appeared to outperform RCA (MD 37.0, 95% CI 12.0 to 62.0), LMWH (MD 41.3, 95% CI 15.6 to 67.0), and other evaluated anticoagulation options in prolonging filter lifespan. However, only a single included RCT with 46 participants had evaluated Regional-UFH + PGI2. No statistically significant difference was observed in terms of length of ICU stay, all-cause mortality, duration of CRRT, recovery of kidney function, and adverse events among most evaluated anticoagulation options. Conclusions Compared to UFH, RCA is the preferred anticoagulant for critically ill patients requiring CRRT. The SUCRA analysis and forest plot of Regional-UFH + PGI2 are limited, as only a single study was included. Additional high-quality studies are necessary before any recommendation of Regional-UFH + PGI2. Further larger high-quality RCTs are desirable to strengthen the evidence on the best choice of anticoagulation options to reduce all-cause mortality and adverse events and promote the recovery of kidney function. Trial registration The protocol of this network meta-analysis was registered on PROSPERO ( CRD42022360263 ). Registered 26 September 2022.

Background Citrate accumulation (CA) is a feared complication in critically ill patients undergoing regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT). This study aimed to describe the characteristics of patients presenting CA within a large cohort of unselected critically ill patients receiving RCA-CRRT depending on the time of occurrence of CA after CRRT initiation. Methods This retrospective, multicenter observational study performed in nine intensive care units (ICU) in Lyon, France, included patients treated with RCA-CRRT between January 2020 and January 2022. CA was defined by a total to ionized calcium ratio (tCa/iCa) ≥ 2.3 associated with hypocalcemia and metabolic acidosis. Results Among 2080 patients, 76 (3.7%) developed CA: 69 (91%) experienced CA within 24 h after CRRT initiation (initial CA) and 7 (9%) after 24 h (late-onset CA). Only lactate levels at CRRT initiation differed between patients with initial CA and those with late-onset CA (10 mmol/l [4.6–16] vs 1.4 mmol/l [1–3.8], p = 0.006 respectively). In the initial CA group, 39 (57%) exhibited signs of CA within 6 h or less (immediate CA) and 30 (43%) showed signs of CA between 6 and 24 h. Over the first 24 h, patients with initial CA presented a marked increase in lactate levels, worsening norepinephrine requirements, persistent elevation of the tCa/iCa ratio, decrease in prothrombin time, and increase in transaminases. Patients with immediate CA showed higher lactate concentration and more severe metabolic acidosis at CRRT initiation compared to patients with early CA whereas other markers did not differ significantly between the two groups. The area under the Receiver Operating Characteristic curve of lactate and pH for predicting immediate citrate accumulation were 0.75 [0.62 – 0.87] and 0.74 [0.62 – 0.85] respectively, with optimal cutoff values of 10.6 mmol/L and 7.14 respectively. The ICU mortality rate among patients with CA was 97% compared to 55% in the whole cohort. Conclusions CA is a rare phenomenon in patients under RCA-CRRT. Severe metabolic acidosis with hyperlactatemia at CRRT initiation is the most relevant marker to identify patients at risk of immediate CA and should encourage close monitoring of tCa/iCa ratio.

Acute kidney injury (AKI) is associated with high death rates and unfavorable outcomes. Previous studies evaluating the effect of the timing of CRRT therapy on the prognosis of patients with AKI have shown inconsistent results. Consequently, we aimed to assess the impact of continuous renal replacement therapy (CRRT) initiation on the outcomes of patients with AKI. This meta-analysis identified eligible randomized controlled trials (RCTs) via comprehensive searches of PubMed, Embase, and the Cochrane databases from their creation until June 1, 2024. Outcomes, including 28-, 60-, and 90-day mortality and adverse event incidence, were compared between the early and delayed CRRT groups post-randomization. Twelve RCTs (n = 1,244) were included. Meta-analysis indicated that early initiation of CRRT did not significantly affect 28-day mortality (RR 0.91 [0.79, 1.06]; p = 0.23; I 2 = 0). Early CRRT initiation correlated with a shorter length of ICU stay [MD -3.24 (-5.14, -1.35); p = 0.0008; I 2 = 36%] but did not significantly affect hospital stay duration [MD -7.00 (-14.60, 0.60); p = 0.07; I 2 = 38%]. The early initiation of CRRT was associated with a significant reduction in RRT dependency at discharge [RR 0.57 (0.32, 0.99); P = 0.05; I 2 = 0%; P = 0.47]. Compared to delayed CRRT, early CRRT was associated with higher incidence rates of hypotension [RR 1.26 (1.06, 1.50); p = 0.008; I 2 = 0%], thrombocytopenia [RR 1.53 (1.11, 2.10); p = 0.009; I 2 = 0%], and hypophosphatemia [RR 3.35 (2.18, 5.15); p < 0.00001; I 2 = 11%]. Our findings suggest that although early CRRT initiation is associated with short intensive care unit stays and reduced RRT dependence, it has no significant effect on mortality and is in fact associated with higher incidence rates of hypotension, thrombocytopenia, and hypophosphatemia. Therefore, early CRRT should be used clinically with caution and consideration of potential adverse effects.

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion : In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes . • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT . What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality . • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes .

Introduction During continuous renal replacement therapy (CRRT), preload-independent patients risk of becoming preload-dependent in case of excessive net ultrafiltration (UF NET ). We aimed to evaluate the ability of a UF NET challenge to identify de novo preload-dependence in preload-independent patients undergoing CRRT. Materials and methods We conducted a single-center, randomized, cross-over trial, enrolling adult patients with CRRT, calibrated continuous cardiac index (CCI) monitoring, and preload-independent at time of enrolment. The diagnostic test consisted of 250-ml UF NET removal over 15 (fast challenge) or 30 min (slow challenge), preceded and followed by a postural maneuver (PM) evaluating preload-dependence using CCI relative variations. Patients underwent both types of challenges, starting with either fast or slow challenges as determined by randomization, separated by a wash-out period of 24 h. We evaluated the performance of UF NET challenges to diagnose de novo preload-dependence using the area under the receiver operating curve (AUROC) of the relative change in calibrated cardiac index between before and after the challenge (∆CI UFC ), based on the result of the PM performed after the challenge (responder if positive, non-responder if negative). NCT05214729. Results We included 20 patients, comprising 36 UF NET challenges (19 fast and 17 slow challenges). In intention-to-treat (ITT), the rate of preload-dependence after the challenge was 33% (12/36, 95% confidence interval: 19% to 51%). In ITT, the AUROC of ∆CI UFC to identify de novo preload-dependence was 0.74 (95% confidence interval: 0.58–0.88), with the respective AUROCs of fast and slow challenges not reaching statistical significance. After exclusion of 5 challenges a posteriori identified as being preload-dependent before challenge start (modified intention-to-treat [mITT], N = 31), the AUROC of ∆CI UFC was 0.83 (0.66–0.99), with ∆CI UFC not significantly differing between fast and slow challenges. In mITT, CCI variation during the PM preceding the challenge predicted de novo preload-dependence with an AUROC of 0.82 (0.65–0.98), at an optimal threshold of + 5%. Conclusions A 250-ml UF NET challenge had acceptable diagnostic performance to identify preload-independent patients becoming preload-dependent during CRRT, with no detectable difference between fast and slow challenges. A CCI variation ≥ 5% during a PM in preload-independent patients may help identify those at risk of becoming preload-dependent.

Contraindications to regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) have recently been challenged. We aimed to assess the safety of the generalization of RCA to all CRRT sessions. We reviewed all CRRT sessions performed in our ICU during two periods (P1:2018–2019 and P2:2020–2022). RCA was considered as contraindicated in situations at risk of citrate accumulation (lactate >4 mmol/L and/or prothrombin time < 40 %) during P1 but not P2. We reviewed CRRT modality, filter lifespan, and therapy-associated complications including citrate accumulation, electrolyte and acid/base disturbances, and blood transfusion requirements. CRRT efficacy was assessed by serum creatinine and urea kinetics across circuits' lifespan. We studied 1877 circuits in 467 (P1:245, P2:222) patients. The proportion of patients with risk factors for citrate accumulation was similar between both periods (P1:35 %, P2:32 % p = 0.61). During P2, RCA was used in more circuits (93 vs 66 %, p < 0.001) and filter lifespan was longer (44 vs 32 h, p < 0.001). CRRT efficacy was similar between the two periods. Although risk factors for citrate accumulation were present at first circuit initiation in more RCA circuits during P2 (25 vs 11 %, p = 0.002), the rate of citrate accumulation remained similar (0.3 vs 0.4 %, p = 0.72). There was no increase in the rates of electrolyte disturbances or significant bleeding. There was, however, a higher rate of metabolic acidoses during P2 (13 vs. 9 %, p = 0.01). In an experienced team, generalization of RCA to nearly all patients requiring CRRT extended median filter lifespan without increasing the rate of significant complications. •Generalized utilization of RCA was associated with an increased circuit lifespan.•It was not associated with an increased rate of serious complications.•A “low citrate” protocol with reduced citrate delivery is safe in patients at risk.•Shock and liver failure should not be considered contraindications to RCA.

Non-anticoagulation is a commonly used strategy in continuous renal replacement therapy (CRRT) among patients with high-bleeding risk. However, the optimal blood flow rate (BFR) to maximize filter and circuit life remains uncertain. This study is designed to elucidate the impact of different BFRs on the durability of filters and circuits in CRRT without anticoagulation. This single-center, prospective, three-arm, single-blind, randomized controlled trial (RCT) will involve adult patients requiring non-anticoagulation continuous veno-venous hemodiafiltration (CVVHDF). A total of 486 filters and circuits will be enrolled and randomly assigned to one of three BFR groups: low (150 mL/min), medium (200 mL/min), or high (250 mL/min) BFR group. The outcomes will be analyzed by both intention-to-treat analysis and per-protocol analysis. The primary outcome is filter and circuit life, which is defined as the time from CRRT initiation to CRRT termination due to extracorporeal circuit clotting or other reasons, alongside the proportion of patent circuits at 24, 48, and 72 hours. Secondary outcomes encompass clinical outcomes and potential adverse events such as bleeding and hemodynamic alterations. This study is aiming at comparing the filter and circuit life under different BFR levels during CVVHDF without anti-coagulation. The results may add knowledge to the optimal BFR to prevent extracorporeal circulation clotting and prolong filter and circuit life in non-anticoagulation CRRT. The study has been registered at https://www.chictr.org.cn (ChiCTR2400087819).

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.

BackgroundContinuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients’ clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates.MethodsA 7-year single-center retrospective study in a tertiary NICU.ResultsThirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT.ConclusionsCKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation.

Regional citrate anticoagulation (RCA) is recommended for critically ill patients at high bleeding risk undergoing continuous renal replacement therapy (CRRT). Nafamostat mesylate (NM), a short-half-life serine protease inhibitor, is a popular alternative in East Asia. Direct comparisons of their efficacy and safety are limited. This retrospective single-center study included 81 critically ill patients receiving CRRT with either NM (  = 31) or RCA (  = 50) from January 2022 to January 2023. The primary outcome was filter lifespan. Secondary outcomes included circuit patency, bleeding events, and metabolic complications. The median filter lifespan was significantly shorter in the NM group compared to the RCA group (23.4 29.6 h,  = 0.02). The NM group also had a higher rate of unplanned circuit discontinuation (52.3 39.1%,  = 0.03). Multivariable analysis confirmed RCA was independently associated with a lower risk of circuit failure (HR = 0.44,  = 0.03). Although not statistically significant, trends favored NM regarding metabolic safety, with lower incidences of severe metabolic alkalosis (16.1 36.0%,  = 0.09) and hypocalcemia (9.7 26.0%,  = 0.13). RCA demonstrated superior anticoagulation efficacy in prolonging filter survival, while NM may offer a more favorable metabolic safety profile. The choice of anticoagulant should be individualized based on efficacy priorities and metabolic risk.