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Background Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. Methods We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité—Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO 2 -adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. Results From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO 2 -adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p  < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group ( p  = 0.26). Conclusion Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. Trial registration The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

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.

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 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.

Background The KDIGO recommendation in acute kidney injury (AKI) patients requiring kidney replacement therapy is to deliver a Urea Kt/V of 1.3 for intermittent thrice weekly hemodialysis, and an effluent volume of 20–25 ml/kg/hour when using continuous renal replacement therapy (CRRT). Considering that prior studies have suggested equivalent outcomes when using CRRT-prolonged intermittent renal replacement therapy (PIRRT) effluent doses below 20 mL/kg/h, our group investigated the possible benefits of low effluent volume CRRT-PIRRT (12.5 ml/Kg/hour). Methods Thirty-six AKI patients that had been treated in the previous 12 months by CRRT-PIRRT with low effluent volume were included in the present retrospective observational study. The total effluent volume, derived from the formula [25 (or 12.5 ml) × kg body weight × 24], was administered over 24 h in CRRT and over 10 h in daily PIRRT. The control group consisted of the last 36 AKI patients previously treated with standard effluent volume CRRT (25 ml/kg/hour). Mortality within 90 days, shift from low effluent volume to standard effluent volume due to dialysis inadequacy, and remission of AKI were the end points. The two groups were homogeneous for age, sex, and sequential organ failure assessment (SOFA) score. Patients with AKI caused by metformin-induced lactic acidosis were excluded because they were treated with standard effluent volume CRRT until the lactic acidosis was corrected by subsequently reducing the effluent volume to 12.5 ml/kg/hour. Results The two groups were homogeneous as for baseline features. The UKt/V in the low effluent volume group was 0.51 ± 0.04 in CRRT and 0.50 ± 0.07 in PIRRT per session (Table 3 ). The UKt/V in the standard effluent volume group was 1.00 ± 0.02 in CRRT and 0.95 ± 0.05 in PIRRT per session. No differences were observed between the 2 groups regarding death from any cause at 90 days, and recovery of renal function. No patient was switched from low effluent volume to standard effluent volume due to inadequate control of uremic toxins. Serum creatinine at discharge from the hospital in patients with no KRT dependence was 2.1 ± 0.6 mg/dl in standard effluent volume and 1.9 ± 0.5 in low effluent volume ( p  = 0.37). All low effluent volume patients showed adequate metabolic, electrolyte, and acid–base profile control. In the low effluent volume group, the incidence of hypophosphatemia was lower than in the standard effluent volume group (5 vs 15, p  = 0.003). Conclusions In this single-center retrospective study, low effluent volume CRRT-PIRRT was associated with similar outcomes to standard effluent volume CRRT-PIRRT, which is consistent with the results of prior observational studies. Randomized controlled studies comparing low effluent volume with standard effluent volume are needed. Graphical abstract

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.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Background Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients. Methods We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review. Results After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD − 65.82 [− 194.19, 62.55]), lactate (MD 0.49 [− 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [− 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD − 0.04 [− 0.13, 0.05]), serum lactate level (MD 0.69 [− 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [− 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h. Conclusions Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.

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).

Background:Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as the first modality affects survival of patients with severe AKI.Methods:This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient’s modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting.Results:A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan–Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01–1·60). In a complementary analysis of less severely ill patients (SOFA score: 3–10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01–3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients.Conclusion:Compared to IHD, CRRT as the first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.