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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.

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.

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 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.

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.

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.

Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear. To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration. The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019. Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight. Risk-adjusted 90-day survival. Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (β = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08). Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings. ClinicalTrials.gov identifier: NCT00221013.

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.

IntroductionDespite the acknowledged advantage of continuous renal replacement therapy (CRRT) in maintaining stable haemodynamics compared with intermittent haemodialysis, hypotension remains a common complication, affecting up to 43% of patients immediately following CRRT. This issue can precipitate serious adverse events and is associated with increased mortality. The significant reduction in blood volume during the withdrawal process for machine processing, combined with the rapid elimination of urea during purification, can cause a precipitous decline in plasma osmotic pressure, both of which may serve as triggers for early hypotension during CRRT. Currently, conventional strategies, such as priming the pipeline with normal saline combined with double connections, have failed to significantly reduce the incidence of early hypotension. To prevent this complication, some researchers have turned to the use of human albumin, plasma and colloid fluids instead of normal saline for pipeline priming. Nevertheless, evidence favouring this approach over traditional crystalloid priming is still lacking. This study aims to investigate whether colloid priming is superior to crystalloid priming in reducing the incidence of early hypotension and all-cause mortality, as well as shortening the duration of hospitalisation in intensive care unit and reducing the dialysis dependence in critically ill patients undergoing CRRT.Methods and analysisA single-centre, prospective, randomised controlled trial will be conducted at West China Hospital of Sichuan University, China. A total of 216 participants who met the inclusion and exclusion criteria will be recruited and divided into either the experimental or control group at a ratio of 1:1 via a central randomisation system. In the experimental group, succinyl gelatin will be used to prime the pipeline prior to the connection with the CRRT machine, whereas the control group will use normal saline. The primary outcome is the incidence of early hypotension during CRRT. The outcome assessors and data analysts will be blinded. All the data will be analysed based on randomly assigned groups unless data for the primary outcomes are missing.Ethics and disseminationThe trial protocol was approved by the Ethics Review Committee of West China Hospital of Sichuan University (2023.2084), and the results will be published in peer-reviewed journals.Trial registration numberChiCTR2400082835.

IntroductionIn addition to various techniques involved in catheter insertion, catheter placement location, lumen diameter and operation and management during continuous renal replacement therapy (CRRT), the design of the tip and side holes, as well as the position of the tip of the catheter, can also impact catheter function. Side-hole and step-tip catheters are commonly used during CRRT. However, there is insufficient evidence comparing their efficacy for CRRT in critically ill patients. And the optimal position of the tip of catheters is not well studied and remains controversial. This study was conducted to assess whether using a step-tip catheter could reduce the rate of catheter dysfunction compared with a side-hole catheter and whether inserting a longer catheter could reduce the incidence of catheter dysfunction and increase catheter survival time.Methods and analysisA prospective, open-label, three-arm, parallel-group, single-centre randomised controlled trial will be conducted at West China Hospital of Sichuan University in China. An estimated sample of 378 participants receiving CRRT treatment will be recruited. Eligible patients will be randomly assigned to three groups to receive different dialysis catheters for the initiation of CRRT at a 1:1:1 ratio via a central randomisation system: group A, side-hole catheters (11Fr, 200 mm; GDHK‐1120; Baxter International Inc., Deerfield, Illinois); group B, step-tip catheters (13Fr, 200 mm; GDHK‐1320; Baxter International Inc.) and group C, step-tip catheters (13Fr, 250 mm; GDHK‐1325; Baxter International Inc.). The femoral vein is the only vascular access. All catheters will be inserted under the guidance of ultrasound using the Seldinger method to reduce complications and trauma related to catheter insertion. The primary outcomes are the occurrence of catheter dysfunction and catheter survival time. Outcome assessors and data analysts will be blinded. All data will be analysed according to the group randomly assigned by an intention-to-treat analysis, in which catheters with missing data for the primary outcomes would be excluded.Ethics and disseminationThe trial protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2023.1221). And the results will be published in peer-reviewed journals.Trial registration numberChiCTR2300075107.