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Background and aims Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes. Methods In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb ( n  = 67) or CRRT alone ( n  = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics. Results At the start of therapy, CytoSorb-treated patients had higher lactate levels ( p  < 0.001), lower mean arterial pressure ( p  = 0.007) and higher levels of noradrenaline ( p  < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 ( n  = 67) was 75% (95%CI 71–79%), while the actual 28-day mortality rate was 48% (mean difference − 27%, 95%CI − 38 to − 15%, p  < 0.001). For CRRT, based on a SOFA of 12.8 ( n  = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference − 16.9% [95%CI − 32.6 to − 1.2%, p  = 0.035]). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p  = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio [aOR] 5.47, p  = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p  = 0.031) and older age (aOR per 10 years 1.67, p  = 0.034). Conclusions CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.

PurposeNet ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0 ml·h−1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care.MethodsIn this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24 h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72 h a UFNET ≥ 100 ml·h−1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25 ml·h−1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population.ResultsBetween June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was −2650 [−4574; −309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736–6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms.ConclusionIn patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

Endotoxin induces an inflammatory response, with secondary release of cytokines, which can progress to shock and multiple organ failure. We explored whether continuous renal replacement therapy (CRRT) using a modified membrane (oXiris) capable of adsorption could reduce endotoxin and cytokine levels in septic patients. Sixteen patients requiring CRRT for septic shock-associated acute renal failure and who had endotoxin levels >0.03 EU/ml were prospectively randomized in a crossover double-blind design to receive CRRT with an oXiris filter or with a standard filter. Endotoxin and cytokine levels were measured at baseline and 1, 3, 8, 16 and 24 hours after the start of CRRT. Norepinephrine infusion rate and blood lactate levels were monitored. During the first filter treatment period, endotoxin levels decreased in 7 of 9 (77.8%) oXiris filter patients, but in only 1 of 6 (16.7%) standard filter patients (P = 0.02). Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and interferon (IFN)γ decreased more with the oXiris filter than with the standard filter. Lactate concentration decreased with oXiris (-1.3[-2.2 to -1.1] mmol/l, P = 0.02), but not with the standard filter (+0.15[-0.95 to 0.6]). The norepinephrine infusion rate was reduced during oXiris CRRT, but not during standard filter CRRT. In the second filter treatment period, there was no significant reduction in endotoxin or cytokine levels in either group. CRRT with the oXiris filter seemed to allow effective removal of endotoxin and TNF-α, IL-6, IL-8 and IFNγ in patients with septic shock-associated acute renal failure. This may be associated with beneficial hemodynamic effects.

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.

Up to 14 % of critically ill patients receive renal replacement therapy (RRT) during their ICU stay and are treated with intermittent hemodialysis (IHD) or one of the continuous renal replacement therapy (CRRT) techniques. The choice of a modality (IHD or CRRT) and technique (continuuous veno-venous -hemodialysis (CVVHD), −hemofiltration (CVVH), or - hemodiafiltration (CVVHDF)), and the way it is delivered, may have an impact on outcomes but only few studies addressed this question. We aimed to survey the availability, settings, and clinicians' preferences regarding RRT modalities and techniques in critically ill patients. Between July 2021 and March 2022, we conducted an open online worldwide survey targeting ICU clinicians and consisting of 31 questions. Among the 1174 participants from 73 countries, 94 % indicated their ability to initiate RRT at any time. CRRT was more widely available than IHD (97 % vs 85 %). CVVHDF was the most frequently used CRRT technique (59 %), followed by CVVHD (26 %) and CVVH (16 %). Most participants (70 %) reported having access to at least two CRRT techniques in their unit. Preference for IHD or CRRT varied greatly, depending on the clinical situation. Among CRRT techniques, CVVHD was preferred for removal of small-sized molecules, better hemofilter lifespan and reduced nursing workload. The preferential indications for CVVH included septic shock, removal of middle-sized molecules and fluid overload. The technical settings for CVVH and CVVHDF were very heterogeneous. This international survey underscores the large diversity in RRT practices wordlwide, as well as heterogeneity in beliefs and preferences among intensivists. These data highlight the need for robust comparative trials to identify the optimal RRT modality and technique to improve outcomes in specific clinical situations. •The best RRT modality (intermittent or continuous) and technique (diffusion or filtration) in ICU are still unclear and debated.•CVVHDF remains the most used technique, although CVVHD is increasingly adopted.•CVVHDF and CVVH settings (filtration/dialysis ratios, pre/post dilution) vary considerably.•Clinician agreement on the best RRT modality/technique varies by context, from strong consensus to marked uncertainty.•RRT is not viewed as one-size-fits-all; clinicians aim to tailor it, underscoring need for research.

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.

Background The tip design and length of catheter impact catheter function. Two types of catheters with different tips, side-hole catheters and step-tip catheters, are commonly used during continuous renal replacement therapy (CRRT). However, there is insufficient evidence comparing their efficacy and safety in CRRT. In addition, whether the insertion of a longer catheter could enhance catheter function remains poorly studied and controversial. Methods In this open-label, three-arm, randomized trial, critically ill patients receiving CRRT were randomized to three groups. Group A received 20 cm side-hole catheters (GDHK‐1120), group B received 20 cm step-tip catheters (GDHK‐1320) and group C received 25 cm step-tip catheters (GDHK‐1325). The primary outcomes were the incidence of catheter dysfunction and catheter survival time. Results A total of 351 patients were enrolled, with 116 in group A, 117 in group B, and 118 in group C. The incidence of catheter dysfunction in group A (35.7%, 51/143) was significantly higher than that in group B (17.7%, 22/124) ( P  = 0.001). However, there was no difference between group B and group C (15.6%, 23/147) ( P  = 0.744). The catheter survival time was comparable between group A (5.5 days, IQR 2.5–9.3) and group B (5.0 days, IQR 3.0–10.0) ( P  = 0.626). In contrast, group C (6.4 days, IQR 3.9–12.0) demonstrated a significantly longer catheter survival time compared to group B ( P  = 0.019). Cox regression analysis identified BMI (HR 1.052, 95% CI 1.003–1.103, P  = 0.036) as an independent risk factor for catheter dysfunction. Results were not consistent across BMI tertiles, with similar results observed only in patients with a lower BMI (BMI < 24.2) (chi-square 13.65, P  = 0.001). There was also a trend that patients in group C have a longer filter lifespan (36.5 h, IQR 16.9–68.1, P  = 0.001) and a lower incidence of catheter-related thrombosis (10.40 per 1000 catheter-days, 95% CI 5.93, 17.83, P  = 0.019). Other secondary outcomes were not significantly different among groups. Conclusions Step-tip catheters may be preferable for CRRT, particularly for patients in the lower BMI tercile. Longer femoral vein catheterization demonstrated enhanced benefits in CRRT, especially among obese patients. Further high-quality, multicenter RCTs are essential to strengthen the evidence guiding catheter selection during CRRT. Trial registration : ChiCTR2300075107. Registered 25 August 2023.

Renal replacement therapy (RRT) is vital for managing acute kidney injury (AKI), with continuous renal replacement therapy (CRRT) and intermittent hemodialysis (iHD) as primary modalities. CRRT is preferred for critically ill patients due to gradual fluid and solute removal, whereas iHD is used for stable patients. Outcomes among AKI patients requiring RRT vary widely, with some recovering kidney function while others progress to end-stage renal disease (ESRD). This study evaluates the risk of dialysis dependence and ESRD within 90 days among AKI patients receiving RRT. Retrospective cohort study analyzed inpatient admissions from the MarketScan database (2005-2021) with an AKI diagnosis requiring RRT, identified using ICD-10 codes. Logistic regression compared CRRT and iHD groups, adjusting for age, sex, length of stay, and calendar year. Compared to iHD, CRRT was associated with 67% lower odds of dialysis dependence at discharge (OR = 0.33; 95% CI: 0.28-0.39) and 80% lower odds at 90 days (OR = 0.20; 95% CI: 0.16-0.27). Patients receiving both iHD and CRRT had higher odds of dialysis dependence at discharge (OR = 1.41; 95% CI: 1.27-1.57) but 46% lower odds at 90 days (OR = 0.54; 95% CI: 0.45-0.64). CRRT also reduced the risk of ESRD within 90 days by 88% (OR = 0.12; 95% CI: 0.10-0.14). Our study demonstrates that compared to iHD, CRRT is associated with a significantly lower risk of dialysis dependence and progression to ESRD in patients with AKI. CRRT may prevent further kidney injury and promote improved renal recovery.

PurposeContinuous 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.MethodsThe 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 0–25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h 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 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation.ResultsA 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]).ConclusionsInability 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.

Acute kidney injury (AKI) is common in critically ill patients, optimal timing for initiation of renal replacement therapy (RRT) for AKI but without life-threatening indications is unclear. A retrospective study was performed using the medical information mart for intensive care (MIMIC-IV), including AKI patients identified based on kidney disease improving global outcomes (KDIGO) definition. The time to initiate CRRT was defined as the interval from first diagnosis of AKI to the initiation of CRRT, analyzed as a continuous variable. The primary outcome was 28-day mortality, restricted cubic splines (RCS) to assess the relationship between CRRT initiation timing intervals and clinical outcomes. The study included 673 patients, with a 28-day mortality rate of 38.78%. RCS analysis revealed no significant association between variations in CRRT timing intervals and 28-day mortality (P > 0.05). In the subgroup of patients with non-renal SOFA scores < 8, observed an increase in 28 day mortality (OR 1.011 [95% CI 1.001–1.021], P < 0.05), along with a greater likelihood of reduced 28-day CRRT, mechanical ventilation (MV), and ICU-free days for each 1-h delay in CRRT initiation (OR − 0.037 [95% CI − 0.064 to − 0.010], P < 0.05; OR − 0.051 [95% CI − 0.078 to − 0.024], P < 0.05; OR − 0.056 [95% CI − 0.082 to − 0.003], P < 0.05). The findings indicate that while no significant relationship exists between mortality and the timing of CRRT initiation, patients with lower non-renal SOFA scores who initiate RRT promptly may experience improved clinical outcomes. Further exploration and validation require the adoption of novel research methodologies and more pertinent clinical studies.