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Objective: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning., Methods: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed., Results: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1β were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal., Conclusion: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

Background: Previous meta-analyses have systematically assessed the therapeutic effect of continuous blood purification (CBP) in adult patients with sepsis. Considering infection etiology and host response of sepsis is different in children, this systematic review and meta-analysis aims to evaluate the clinical efficacy of CBP in children with sepsis., Methods: Studies were searched from the Pubmed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and VIP databases. Outcomes included vital signs, coagulation markers, organ function markers, immune markers, inflammatory markers, and prognostic markers. Heterogeneity was evaluated by the I-square statistic (I 2 ), and sensitivity analysis was performed., Results: 24 studies were included in this meta-analysis. Pooled results showed that CBP decreased levels of alanine transaminase (ALT) (weighted mean difference [WMD] = -44.867, 95%CI: 64.809 to -24.926), aspartate aminotransferase (AST) (WMD = -55.373, 95%CI: 73.286 to -37.460), blood urea nitrogen (BUN) (WMD = -2.581, 95%CI: 4.539 to -0.622), and serum creatinine (Scr) (WMD = -11.567, 95%CI: 19.509 to -3.625). The percentage of CD3 + cells (WMD = 8.242, 95%CI: 3.339 to 13.144) and CD4 + cells (WMD = 4.278, 95%CI: 3.252 to 5.303, I 2  = 3.1 %) were increased in the CBP group. C-reaction protein (CRP) (WMD = -20.699, 95%CI: 34.740 to -6.657) and tumor necrosis factor-α (TNF-α) (WMD = -19.185, 95%CI: 34.133 to -4.237) were reduced after CBP treatment. Pediatric critical illness score (PCIS) was increased (WMD = 7.916, 95%CI: 4.317 to 11.516) and the risk of 28-day mortality (risk ratio [RR] = 0.781, 95%CI: 0.632 to 0.965) was lower in the CBP group., Conclusions: CBP reduced the level of inflammatory markers, increased the level of immune markers, and improved organ function and prognosis, which may provide evidence for the use of CBP in sepsis children patients., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this paper is to summarize the blood purification technology applied in patients with severe fever with thrombocytopenia syndrome (SFTS) in the clinical treatment effect., Methods: The medical records of 96 patients with severe SFTS admitted to Weihai Municipal Hospital affiliated to Shandong University from May 2014 to November 2019 were retrospectively analyzed, and they were divided into survival group and death group. The differences in basic data test indexes and treatment method selection during intensive care unit (ICU) admission between the two groups were significantly analyzed, and the indexes with statistically significant differences were included in the multivariate logistic regression analysis related to prognosis., Results: There were no statistically significant differences in age, sex composition, white blood cell count, platelet count, creatine kinase (CK), activated partial thromboplastin time (APTT), serum creatinine and hemofiltration renal replacement therapy between the survival group and the death group. There were statistically significant differences between the two groups in viral load bilirubin and the treatment methods of plasma exchange (PE) or hemoperfusion (HP). Plasma exchange group (78 cases), hemofiltration group (12 cases), hemoperfusion group (6 cases), plasma exchange and hemoperfusion and other blood purification treatment of the prognosis were statistically different., Conclusions: Compared with the three blood purification methods, plasmapheresis has a significant effect on virus removal, improvement of coagulation function and survival rate in patients with severe SFTS. Hemofiltration plays a role in removing inflammatory mediators, replacing renal function, maintaining electrolytes and acid-base balance, but not in removing viruses.

Background: Septic shock poses a significant threat to life safety, with continuous blood purification as a primary treatment modality. Enhancing the therapeutic efficacy of continuous blood purification holds crucial implications for septic shock management., Objective: This study aims to observe the therapeutic efficacy of glucocorticoid-assisted continuous blood purification (CBP) in septic shock patients, providing valuable insights for future clinical treatments., Methods: A total of 200 septic shock patients admitted between October 2020 and January 2023 were selected and categorized into an observation group and a control group. The observation group (n=118) received glucocorticoid-assisted CBP, while the control group (n=82) received standard CBP. Changes in various parameters, including pH, blood urea nitrogen, serum creatinine, bicarbonate, inflammatory cytokines, T lymphocyte subsets, mean arterial pressure, pulmonary vascular permeability index, intrathoracic blood volume index, and cardiac index, were recorded before and after treatment. Complications during treatment were also documented., Results: Post-treatment bicarbonate and cardiac index showed no significant difference between the two groups (P > .05). However, the observation group exhibited higher pH, mean arterial pressure, CD3+, CD4+, and CD8+ levels than the control group, as well as lower blood urea nitrogen, serum creatinine, inflammatory cytokines, and CD4+/CD8+ ratio (P < .05). Moreover, no notable difference in complication rates was identified between the groups (P > .05)., Conclusions: Glucocorticoids-assisted continuous blood purification therapy effectively improves vital signs and immune function in septic shock patients, offering a more reliable guarantee for patient life safety.

Decongestion is a cornerstone therapeutic goal for those presenting with decompensated heart failure. Current approaches to clinical decongestion include reducing cardiac preload, which is typically limited to diuretics and hemofiltration. Several new technologies designed to mechanically reduce cardiac preload are in development. In this review, we discuss the pathophysiology of decompensated heart failure; the central role of targeting cardiac preload; emerging mechanical preload reduction technologies; and potential application of these devices., Competing Interests: Disclosure: N.K.K. has received consulting honoraria and institutional grant support from Abbott Laboratories, Abiomed Inc., Boston Scientific, Medtronic, LivaNova, Getinge, and Zoll. M.K.K. has served on the advisory board for Abiomed Inc., Abbott Laboratories, and CorWave. D.B. has received an unrestricted, educational grant from Abiomed Inc. A.B. is a consultant to Abiomed Inc. The other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Purpose: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients., Methods: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198)., Results: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups., Conclusion: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005)., (© 2024. The Author(s).)

Abstract: We present the case of a 65-year-old patient who was treated with high-dose benzylpenicillin for severe invasive pneumococcal pneumonia, complicated by acute renal failure managed with continuous venovenous hemofiltration. After cessation of continuous venovenous hemofiltration, the patient experienced multiple tonic-clonic seizures. Therapeutic drug monitoring revealed high total serum concentrations of benzylpenicillin, identifying it as the likely cause of the neurotoxicity. This case study presents the first documented total serum benzylpenicillin concentration associated with neurotoxicity., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Background: Regional citrate anticoagulation (RCA) is recommended during continuous renal replacement therapy. Compared to systemic anticoagulation, RCA provides a longer filter lifespan with the risk of metabolic alkalosis and impaired calcium homeostasis. Surprisingly, most RCA protocols are designed for continuous veno-venous hemodialysis or hemodiafiltration. Effective protocols for continuous veno-venous hemofiltration (CVVH) are rare, although CVVH is a standard treatment for high-molecular-weight clearance. Therefore, we evaluated a new RCA protocol for postdilution CVVH., Methods: This is a monocentric prospective interventional study to evaluate a new RCA protocol for postdilution CVVH. We recruited surgical patients with stage III acute kidney injury who needed renal replacement therapy. We recorded dialysis and RCA data and hemodynamic and laboratory parameters during treatment sessions of 72 h. The primary endpoint was filter patency at 72 h. The major safety parameters were metabolic alkalosis and severe hypocalcemia at any time., Results: We included 38 patients who underwent 66 treatment sessions. The mean filter lifespan was 66 ± 12 h, and 44 of 66 (66%) filters were patent at 72 h. After censoring for non-CVVH-related cessation of treatment, 83% of all filters were patent at 72 h. The delivered dialysis dose was 28 ± 5 ml/kgBW/h. The serum levels of creatinine, urea and beta2-microglobulin decreased significantly from day 0 to day 3. Metabolic alkalosis occurred in one patient. An iCa ++ below 1.0 mmol/L occurred in four patients. Citrate accumulation did not occur., Conclusions: We describe a safe, effective, and easy-to-use RCA protocol for postdilution CVVH. This protocol provides a long and sustained filter lifespan without serious adverse effects. The risk of metabolic alkalosis and hypocalcemia is low. Using this protocol, a recommended dialysis dose can be safely administered with effective clearance of low- and middle-molecular-weight molecules., Trial Registration: The study was approved by the medical ethics committee of Heinrich-Heine University Duesseldorf (No. 2018-82KFogU). The trial was registered in the local study register of the university (No: 2018044660) on 07/04/2018 and was retrospectively registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03969966) on 31/05/2019., (© 2024. The Author(s).)

Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the "IL-6-Sieve", wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads-directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended-in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use., (© 2024. The Author(s).)

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients, and often, they contribute to disease progression. Initial treatment encompasses intravenous diuretics although there might be a percentual of patients refractory to this pharmacological approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid overloaded patients. Current equipment allows to perform ultrafiltration in most hospital and acute care settings. Extracorporeal ultrafiltration is then prescribed and conducted by specialized teams, and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials and European and North American practice guidelines suggest that ultrafiltration is indicated for patients with refractory congestion not responding to medical therapy. Close interaction between nephrologists and cardiologists may be the key to a collaborative therapeutic effort in heart failure patients. Further studies are today suggesting that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for the care of chronic heart failure patients. Herein, we provide a state-of-the-art review on extracorporeal ultrafiltration and describe the steps in the development of a new miniaturized system for ultrafiltration, called AD1 (Artificial Diuresis)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Haemodialysis is the most common treatment option for patients with life-sustaining end-stage kidney disease (ESKD). In recent years, haemodiafiltration or haemofiltration has been widely used in patients with ESKD, and there are still conflicting findings as to whether both are superior to traditional haemodialysis. This systematic review and meta-analysis were designed to determine whether haemodiafiltration or haemofiltration is more effective than haemodialysis in reducing all-cause mortality risk in patients with ESKD., Methods and Analysis: We will perform a systematic PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library and Scopus search, including studies published before September 2023. Randomised controlled trials will be included exploring the effects of haemodiafiltration or haemofiltration compared with haemodialysis on prognosis in patients with ESKD. Outcomes of interest include all-cause mortality, cardiovascular events, dialysis adequacy and adverse effects. The Cochrane Collaboration tools (ROB-2) will assess the bias risk. Available data will be used to calculate effect sizes. Heterogeneity between studies will be evaluated with I 2 . The trial sequential analysis will be used to eliminate false-positive results. The certainty of the evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation criteria., Ethics and Dissemination: This systematic review and meta-analysis was deemed exempt from ethics review. Results will be disseminated through publication in peer-reviewed journals and research conferences., Prospero Registration Number: CRD42023464509., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cytokines and endotoxin and improving hemodynamic stability. Despite some very promising results, we conclude that the current evidence does not strongly support these techniques in significantly improving survival rates in septic patients, clearly underlining the need for further research.

To assess the clinical efficacy of Double Filtration Plasmapheresis (DFAPP), a novel blood purification method, in treating hyperlipidemic moderate/severe pancreatitis (HL-M/SAP). A total of 68 HL-M/SAP patients were enrolled in this study. The observation group, comprising 34 patients, received DFAPP treatment, while the control group underwent CVVH + PA treatment. We compared the efficacy changes between the two groups post-treatment. Patients treated with DFAPP showed significant improvements in clinical outcomes. After 72 h of DFAPP treatment, HL-M/SAP patients exhibited notably lower multiple organ failure scores and a reduced mortality rate compared to those in the CVVH + PA group. Triglyceride levels in HL-M/SAP patients treated with DFAPP for 48 h averaged 3.75 ± 1.95, significantly lower than the 9.57 ± 3.84 levels in the CVVH + PA group (P < 0.05). Moreover, CRP levels decreased markedly, IL-17 levels diminished, IL-10 levels increased, and the decline in IL-35 levels was significantly less pronounced compared to the CVVH + PA group. The recurrence rate of pancreatitis was also significantly lower after 6 months. The early implementation of DFAPP in HL-M/SAP patients effectively reduces triglyceride levels, suppresses pro-inflammatory factors, enhances anti-inflammatory factors, and mitigates cytokine storm-induced sepsis damage. Consequently, this leads to a decrease in the incidence of multiple organ failure, improved patient survival rates, and a reduce the recurrence rate of lipogenic pancreatitis.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076066., (© 2024. The Author(s).)

Introduction: Chloride transfers during continuous renal replacement therapy (CRRT) have not been adequately described and may differ based on CRRT technique. We aimed to measure chloride mass transfer (JS,Cl) during CRRT and identify associated determinants., Methods: We performed a two-centre, prospective, observational study in France and Australia in ICU patients with CRRT initiated for <24 h. Patients received continuous veno-venous hemofiltration (CVVH) or continuous veno-venous haemodialysis (CVVHD, with citrate-CaCl2 regional anticoagulation). Over a 24 h period, plasma and effluent chloride concentrations were measured every 4 h to compute chloride mass transfer (JS,Cl, in mmol.min-1) using a modality-specific model, with negative value indicating chloride transfer towards the patient. Secondary outcomes were the identification of CRRT settings associated with JS,Cl (using multivariate mixed effects regression). Results are presented with median (interquartile range)., Results: Between February 2021 and August 2022, we enrolled 37 patients (64 [56-71] years, 67% male), for a total of 20 CVVHD and 20 CVVH sessions. Over 24 h, plasma chloride concentrations were significantly higher, and JS,Cl significantly lower during CVVHD, compared to CVVH (-0.10 [-0.33 to 0.15] vs. 0.01 [-0.10 to 0.13] mmol.min-1, p < 0.05). With both modalities, net ultrafiltration (QUFNET) and plasma chloride concentrations were the principal determinants of JS,Cl, with higher QUFNET being associated with an increase in JS,Cl during CVVHD. Also, CVVHD sessions demonstrated a concentration gradient between the plasma and the effluent chamber of -6 [-9 to -4] mmol.L-1. Finally, CaCl2 reinjection during CVVHD accounted for 35% [32-60%] of total JS,Cl in sessions with a negative JS,Cl., Conclusion: Compared to CVVH, CVVHD with regional citrate anticoagulation was associated with greater chloride mass transfer to the patient and higher plasma chloride concentrations. This was due to high dialysate chloride concentrations and CaCl2 reinjection. This effect could only be controlled by high net ultrafiltration flow rates., (© 2024 S. Karger AG, Basel.)

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin., Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated., Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min)., Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT., (© 2024 S. Karger AG, Basel.)

In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The ideal modality choice and dialysis prescription during the first renal replacement therapy (RRT) session remain unclear. We conducted a pilot study to determine the safety risk for hemodialysis (HD) versus hemofiltration (HF) and its relationship with neurocognitive assessment on incident RRT patients., Methods: Twenty-four incident RRT patients were included. Patients were randomized to the conventional HD group or post-dilution HF group. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA) tests were applied in all patients before and after session, and brain magnetic resonance image (MRI) was performed in 7 patients from the conventional HD group and 8 patients from the post-dilution HF group before and after the intervention., Results: Baseline characteristics were similar between groups. Compared to conventional HD, post-dilution HF had longer treatment time. There were no significant changes in blood pressure after RRT in both groups. The MMSE test showed no significant differences between groups or within groups. The MOCA test showed an increase in the total score for the post-dilution HF group with no significant changes between groups. The MRI evaluation showed no differences between or within groups., Conclusion: Post-dilution HF is a safe alternative for the first HD session in incident RRT; it allows longer treatment time if ultrafiltration is required and has a similar neurological risk than conventional HD. This is a pilot study and that larger studies are needed to confirm the findings., (© 2023 S. Karger AG, Basel.)

Objectives: This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis., Data Sources: We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions., Study Selection: Only randomized controlled trials (RCTs) were selected., Data Extraction: The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement., Data Synthesis: We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy., Conclusions: Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background/aim: Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock., Materials and Methods: The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy., Results: Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05)., Conclusion: The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest., (© TÜBİTAK.)

Background: Regional citrate anticoagulation (RCA) is the preferred modality of anticoagulation used in continuous kidney replacement therapy (CKRT) in adults and less extensively in children. Potential metabolic complications limit widespread use in infants, neonates, and in children with liver failure., Methods: We report our experience with a simplified protocol in 50 critically ill children, infants, and neonates, some of them with liver failure, with commercially available solutions containing phosphorous and higher concentration of potassium and magnesium., Results: RCA allowed attainment of a mean filter lifetime of 54.5 ± 18.2 h, 42.5% of circuits lasted more than 70 h, and scheduled change was the most frequent cause of CKRT interruption. Patient Ca ++ and circuit Ca ++ were maintained in the target range with mean values of 1.15 ± 0.13 mmol/l and 0.38 ± 0.07 mmol/l, respectively. No session had to be stopped because of metabolic complications. The most frequent complications were hyponatremia, hypomagnesemia, and metabolic acidosis mostly related to primary disease and critical illness. No session had to be stopped because of citrate accumulation (CA). Transitory CA occurred in 6 patients and was managed without requiring RCA interruption. No patients with liver failure presented CA episodes., Conclusions: In our experience, RCA with commercially available solutions was easily applied and managed in critically ill children, even in patients with low weight or with liver failure. Solutions containing phosphate and higher concentrations of magnesium and potassium allowed reduction of metabolic derangement during CKRT. Prolonged filter life was ensured with no detrimental effects on patients and reduced staff workload. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background and Objectives: Therapeutic plasma exchange (TPE) is commonly performed using membrane-based TPE (mTPE) and is prone to filter failure., Design, Setting, Participants, & Measurements: We report on 46 patients, with a total of 321 mTPE treatments using the NxStage machine. This was a retrospective study with an aim to evaluate the effect of heparin, pre-filter saline dilution and the impact of total plasma volume exchanged (< 3 L vs. ≥3 L) on the rate of filter failure. Primary outcome was the overall rate of filter failure. Secondary outcomes included factors that may have indirectly influenced the rate of filter failure, including hematocrit, platelet count, replacement fluid (Fresh Frozen Plasma vs. albumin), and access type., Results: We found that treatments that received both pre-filter heparin and saline had a statistically significant decrease in filter failure rate as compared to those that received neither (28.6% vs. 5.3%, P = .001), and compared to the treatments that received pre-filter heparin alone (14.2% vs. 5.3%, P = .015). In treatments that received both pre-filter heparin and saline predilution, we noted a significantly higher filter failure rate when the plasma volume exchanged was ≥3 L as compared to those that had <3 L exchanged (12.2% vs. 0.9%, P = .001)., Conclusions: Rate of filter failure in mTPE can be reduced by implementing several therapeutic interventions including pre-filter heparin and pre-filter saline solution. These interventions were not associated with any clinically significant adverse events. Despite the above-mentioned interventions, large plasma volume exchanges of ≥3 L can negatively impact filter life., (© 2023 Wiley Periodicals LLC.)

Background: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium., Methods: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate., Results: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation., Conclusions: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation., Trial Registration: NCT03976440 (registered 6 June 2019)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

MB-102 is a novel fluorescent tracer agent that is exclusively removed from the body by glomerular filtration. This agent can be detected transdermally to provide a real-time measurement of glomerular filtration rate at the point-of-care and is currently in clinical studies for such. MB-102 clearance during continuous renal replacement therapy (CRRT) is unknown. Its plasma protein binding (~0%), molecular weight (~372 Da) and volume of distribution (15-20 L) suggest that it may be removed by renal replacement therapies. To determine the disposition of MB-102 during CRRT, an in vitro study assessing the transmembrane clearance (CL TM ) and adsorptive clearance of MB-102 was conducted. A validated in vitro bovine blood continuous hemofiltration (HF) and continuous hemodialysis (HD) models were performed using two types of hemodiafilters to evaluate CL TM of MB-102. For HF, three different ultrafiltration rates were evaluated. For HD, four different dialysate flow rates were evaluated. Urea was used as a control. No MB-102 adsorption to the CRRT apparatus or either of hemodiafilters was observed. MB-102 is readily removed by HF and HD. Dialysate and ultrafiltrate flow rates directly influence MB-102 CLTM. Hence MB-102 CLTM should be measurable for critically ill patients receiving CRRT., Competing Interests: Disclosure: The authors have no conflict of interest to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (S v ) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH)., Methods: In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.v. undergoing CVVH were included. Patients received a zanamivir loading dose of 600 mg i.v., 12 h later followed by maintenance dosages two times daily according to the treating physician. Per patient, nine CFT plasma and nine ultrafiltrate samples were drawn on day 2 of treatment and analysed with a validated HPLC-MS/MS method., Results: Four patients were included in the study. The zanamivir elimination half-life was prolonged with 5.6-9.9 h, compared to patients with normal renal function. A S v of approximately 1.0 was identified, with unrestricted transport of zanamivir to the ultrafiltrate., Conclusions: Zanamivir is well cleared by CVVH. In absence of the possibility for therapeutic drug monitoring, the ultrafiltration rate seems as a good surrogate parameter to estimate the CL CVVH and may help guide the dosing of zanamivir.

Background: Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD)., Methods: This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality., Results: In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65-0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4-45.3) and was 26.6 (13.0-63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups., Conclusions: Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD., Trial Registration: ClinicalTrials.gov, NCT04762524. Registered 02/21/21-Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Continuous renal replacement therapies (CRRTs) are frequently used in critically ill patients; however, there are scarce in vitro and in vivo studies showing the extracorporeal elimination of ceftaroline and avibactam. The aim of this study was to assess, through an in vitro model, the extracorporeal elimination of ceftaroline and avibactam by continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodiafiltration (CVVHDF), and continuous veno-venous hemodialysis (CVVHD), using a polysulfone hemofilter., Methods: Simulated in vitro experiments were performed using a multiFiltrate machine with a 1.4 m2 Ultraflux® AV600S polysulfone hemofilter. Isofundin® without or with bovine serum albumin was circulated as vehicle for ceftaroline or avibactam. Pre-filter, post-filter, and effluent samples were taken over a period of 60 min, and they were immediately stored at 4°C until processed in the same day. The quantification of ceftaroline and avibactam in the samples was performed by high-performance liquid chromatography with ultraviolet detection. Protein binding, extraction coefficient (EC), and extracorporeal clearance (CLCRRT) were calculated., Results: The elimination of both ceftaroline and avibactam during the three extracorporeal modalities followed first-order pharmacokinetics. Regardless of the CRRT technique, EC values for both molecules were around 1, similar to the unbound fraction of avibactam (0.96) and higher than the unbound fraction of ceftaroline (0.79). CLCRRT of ceftaroline ranged from 15.63 to 17.66 mL/min when CVVH and CVVHD were used with a flow rate of 1,000 mL/h, and from 29.25 to 32.95 mL/min for the CVVHDF modality with a flow rate of 2,000 mL/h. For avibactam, CLCRRT ranged from 15.07 to 18.82 mL/min for CVVH and CVVHD, and from 33.74 to 34.13 mL/min for CVVHDF., Discussion: Avibactam and ceftaroline are extensively removed through the polysulfone membrane, and a dose adjustment may be recommended for patients under CRRT to ensure pharmacodynamic target achievement., (© 2023 S. Karger AG, Basel.)

Introduction: Electrolyte derangements, acidosis, and volume overload remain life-threatening emergencies in people with acute kidney injury in austere environments. A single-lumen alternating micro-batch (SLAMB) dialysis technique was designed to perform renal replacement therapy using a single-lumen access, low-cost disposable bags and tubing, widely available premade fluids, and a dialysis filter. A manual variation (mSLAMB) works without electricity, battery, or a pump. We modeled mSLAMB dialysis and predicted it could achieve adequate small solute clearance, blood flow rates, and ultrafiltration accuracy., Methods: A 25- to 30-kg pediatric patient's blood volume was simulated by a 2-L bag of expired blood and spiked with 5 g of urea initially, then with 1-2 g between experiments. Experiments had 8 cycles totaling prescription volumes of 800-2,400 mL and were conducted with different ratios of hemofiltration fluid to blood volume. Concentrations of urea and potassium, final effluent volumes, and cycle duration were measured at the end of each cycle to determine clearance, ultrafiltration accuracy, and blood flow rates., Results: Each cycle lasted 70-145 s. Experiments achieved a mean urea reduction ratio of 27.4 ± 7.1% and a mean potassium reduction of 23.4 ± 9.3%. The largest urea and potassium reduction percentage occurred with the first cycle. Increased hemofiltration fluid to blood volume ratio did not increase clearance. Mean (+/- standard deviation) blood flow ranged from 79.7 +/- 4.4 mL/min to 90.8 +/- 6.5 mL/min and increased with larger batch volume and height difference between reservoirs. Ultrafiltration accuracy ranged from 0 to 2.4% per cycle., Discussion: mSLAMB dialysis is a simple, manual, cost-effective mode of dialysis capable of providing clearance and accurate ultrafiltration. With further refinement of technique, we believe this can be a potentially lifesaving treatment in austere conditions and low-resource settings., (© 2022 S. Karger AG, Basel.)

After initial tentative steps with bioincompatible sorbents, hemoadsorption is making a comeback. This has been fueled by improved coating technology and improved sorbent technology. Both have markedly increased the safety, biocompatibility, and efficiency of hemoadsorption. Despite such development and an emerging body of evidence, the research agenda for hemoadsorption is substantial and, in most ways, unfulfilled. In this chapter, we highlight the need for more extensive and sophisticated work to understand the biological effect of hemoadsorption in key areas (especially sepsis). We also explain why more technical research needs to be conducted ex vivo and in large animals to understand the performance characteristics of hemoadsorption sorbent cartridge, including optimal blood flow, optimal anticoagulation, and optimal duration of application. Finally, we focus on the need to develop registries of the use of this technique so that more extensive information can be obtained about current use and real-world performance., (© 2023 S. Karger AG, Basel.)

Background: To evaluate the efficacy and safety of continuous renal replacement therapy (CRRT) modalities with regional sodium citrate anticoagulation (RCA) in children., Methods: This retrospective study was conducted at the paediatric intensive care unit of Hunan Children's Hospital in China. Medical records of paediatric patients hospitalised for RCA-CRRT between April 2017 and March 2021 were reviewed. Patients received continuous venovenous haemodialysis, continuous venovenous haemofiltration (CVVH), or continuous venovenous haemodiafiltration (CVVHDF)., Results: Patients on continuous venovenous haemodialysis ( n  = 2) were excluded because of their small sample size. The remaining participants were divided into CVVH and CVVHDF groups; 80 patients received CRRT, with 40 and 62 sessions in the CVVH and CVVHDF groups, respectively. The filtre lifespan was longer in the CVVHDF group than in the CVVH group (median value [interquartile range]; 47 [15] hours vs. 35 [17.5] hours; p  = 0.029). Compared with the CVVHDF group, the hazard ratio for filtre lifespan in the CVVH group was 3.023 (95% confidence interval 1.820-5.023, p  < 0.001). There were no significant differences in ionised calcium levels of the circuits between the two groups at different time points ( p  < 0.05). Metabolic alkalosis, hyperlactataemia, hypocalcaemia, and hypercalcaemia occurred in both groups, with metabolic alkalosis being the most common complication. No patients in either group experienced sodium citrate accumulation or hypernatraemia. Inter-group differences in the incidence of these complications were not statistically significant ( p  > 0.05)., Conclusions: Our results suggest that CVVHDF is a better option for RCA-CRRT than CVVH.

Sepsis is a leading cause of morbidity and mortality worldwide. Dysregulated immune response to infection is a hallmark of sepsis, leading to life-threatening organ dysfunction or even death. Advancing knowledge of the complex pathophysiological mechanisms has been a strong impetus for the development of therapeutic strategies aimed at rebalancing the immune response by modulating the excess of both pro- and anti-inflammatory mediators. There is a wealth of preclinical data suggesting clinical benefits of various extracorporeal techniques in an attempt to modulate the exaggerated host inflammatory response. However, the evidence base is often weak. Owing to both an advancing comprehension of the pathophysiology and the increased quality of clinical trials, progress has been made in establishing extracorporeal therapies as part of the general therapeutic canon in sepsis. We aim for a comprehensive overview of the technical aspects and clinical applications in the context of the latest evidence concerning these techniques., (© 2022 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Sepsis represents a serious risk to the life of any patient, which is why it is crucial to start an effective treatment in all its extremes as soon as possible, that is, the chosen antibiotics must have activity against the pathogen that produces the condition and, in addition, they must be dosed considering the patient's situation in all its extremes. It should be considered that it will be necessary to adjust the dose when there is edema (drugs with reduced volume of distribution), hypoproteinemia (drugs bound to proteins in a high proportion), obesity, and also when they require the use of external techniques such as ECMO or any of the different types of hemodialysis and hemofiltration., (©The Author 2022. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Antibiotic dosing in critically ill patients undergoing continuous renal replacement therapy is considered challenging. This study aimed to analyse the population pharmacokinetics of polymyxin B in patients receiving continuous venovenous haemofiltration (CVVH), and to optimize individual dosing regimens in specific clinical scenarios. Patients treated with CVVH and polymyxin B for multi-drug-resistant Gram-negative bacterial infections were enrolled from two hospitals. Blood samples were collected during and outside CVVH, and assayed using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Phoenix NLME software. In total, 53 patients were included. The area under the concentration curve across 24 hours at steady state (AUC ss,24h ) of polymyxin B during CVVH was 27.94 ± 10.92 mg‧h/L, which was significantly lower than that outside CVVH (77.89 ± 35.66 mg‧h/L) (P=1.65 × 10 -8 ). The population pharmacokinetic model revealed that CVVH significantly increased the clearance of polymyxin B. Monte Carlo simulations showed that for patients on CVVH, a loading dose of 200 mg plus a fixed maintenance dose of 150 mg every 12 h had a high probability of achieving AUC ss,24h of 50-100 mg•h/L and the pharmacokinetic/pharmacodynamic target with a minimum inhibitory concentration ≤0.5 mg/L. For patients undergoing CVVH, high doses of polymyxin B and a dose-adjustment regimen based on therapeutic drug monitoring should be considered to improve efficacy., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Pediatric burns are life-threatening injuries due to the acute injury and secondary complications. In acute-phase burns, hypovolemia and vasoconstriction cause renal impairment. Sepsis and multiorgan failure compound the problem resulting in morbidity and mortality. This paper outlines 5 years' experience using hemofiltration in major pediatric burns, and a review of the current literature. Retrospective patient data collection was undertaken identifying relevant pediatric burns undergoing Continuous Veno-Venous Hemofiltration. Data were analyzed to identify demographics, indication, duration of therapy, and outcomes. A systematic review was also performed using PRISMA principles. PubMed, Science Direct, and OVID databases were explored and relevant papers were included. From January 2015 to December 2019, hemofiltration was utilized in five cases. Age range 3 to 15 years (mean: 12), four males/one female, and mean weight 56 kg (12-125 kg). TBSA 21% to 61% (mean: 37.6%), mechanism of injury was scald-60%, flame-40%. Overall survival was 100%. Three patients were filtered for a brief period during the first 24 hours to correct metabolic acidosis and control temperature. Two patients required prolonged therapy. All patients recovered without further long-term renal support. A total of 3814 papers were identified for systematic review. Three were considered relevant for inclusion. This paper reflects the benefits of hemofiltration in the management of severe pediatric burns. Renal replacement therapy is useful in managing metabolic acidosis, temperature control, and renal failure. The current literature supports judicious use on a patient-by-patient basis. Given the lack of evidence in the literature, further studies are required to establish guidelines for the use of hemofiltration in pediatric burns., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb ® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb ® interval and its intensity on the outcome., Methods: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA., Results: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59-76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb ® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS., Conclusions: In this group of septic shock patients, the earlier initiation of Cytosorb ® , its longer duration and the higher volume of blood processed were associated with a better survival.

Clinical studies have suggested that use of bicarbonate-containing substitution and dialysis fluids during continuous kidney replacement therapy may result in excessive increases in the carbon dioxide concentration of blood; however, the technical parameters governing such changes are unclear. The current work used a mathematical model of acid-base chemistry of blood to predict its composition within and exiting the extracorporeal circuit during continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration (CVVHDF). Model predictions showed that a total substitution fluid infusion rate of 2 L/h (33% predilution) with a bicarbonate concentration of 32 mEq/L during CVVH at a blood flow rate of 200 mL/min resulted in only modest increases in plasma bicarbonate concentration by 2.0 mEq/L and partial pressure of dissolved carbon dioxide by 4.4 mmHg in blood exiting the extracorporeal circuit. The relative increase in bicarbonate concentration (9.7%) was similar to that in partial pressure of dissolved carbon dioxide (8.2%), resulting in no significant change in plasma pH in the blood exiting the CVVH circuit. The changes in plasma acid-base levels were larger with a higher infusion rate of substitution fluid but smaller with a higher blood flow rate or use of substitution fluid with a lower bicarbonate concentration (22 mEq/L). Under comparable flow conditions and substitution fluid composition, model predicted changes in acid-base levels during CVVHDF were similar, but smaller, than those during CVVH. The described mathematical model can predict the effect of operating conditions on acid-base balance within and exiting the extracorporeal circuit during continuous kidney replacement therapy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Background: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival., Materials and Methods: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients)., Results: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up., Conclusions: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation., (© 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Introduction: In critically ill patients requiring intermittent renal replacement therapy (RRT), the benefits of convective versus diffusive clearance remain uncertain. We conducted a systematic review and meta-analysis to determine the safety, clinical efficacy, and clearance efficiency of hemofiltration (HF) and hemodiafiltration (HDF) compared to hemodialysis (HD) in patients with acute kidney injury (AKI) receiving intermittent RRT., Method: We searched Medline, Embase, Cochrane Library, and PROSPERO. We included clinical trials and observational studies that reported the use of intermittent HF or HDF in adult patients with AKI. The following outcomes were included: mortality, renal recovery, clearance efficacy, intradialytic hemodynamic stability, circuit loss, and inflammation modulation., Results: A total of 3,169 studies were retrieved and screened. Four randomized controlled trials and 4 observational studies were included (n: 615 patients). Compared with conventional HD, intermittent convective therapies had no effect on in-hospital mortality (relative risk, 1.23; 95% confidence interval (CI), 0.76-1.99), renal recovery at 30 days (RR, 0.98; 95% CI, 0.82-1.16), time-to-renal recovery (mean difference [MD], 0.77; 95% CI, -6.56 to 8.10), and number of dialysis sessions until renal recovery (MD, -1.34; 95% CI, -3.39 to 0.72). The overall quality of included studies was low, and dialysis parameters were suboptimal for all included studies., Conclusion: This meta-analysis suggests that there is no significant difference in short-term mortality and renal recovery in patients with severe AKI when treated with intermittent HF or HDF compared to conventional HD. This systematic review emphasizes the need for further trials evaluating optimal convective parameters in AKI patients treated with intermittent dialysis., (© 2021 S. Karger AG, Basel.)

Background: Limited previous studies had proved that oXiris-continuous veno-venous hemofiltration (CVVH) could decrease endotoxins and inflammatory factors, thereby improving circulation's stability. However, conclusive data are lacking regarding the comparison between oXiris membrane (with the function of removing endotoxins and decreasing inflammatory factors) and AN69 filters (with the only function of decreasing inflammatory) on the mortality of patients with septic shock. The potential mechanisms of oXiris that might influence the mortality of septic shock patients remain unexplored., Methods: This is a single-center, retrospective cohort study. The experimental group (30 patients with septic shock) was treated with oXiris-CVVH, and the control group (46 patients with septic shock) was treated with AN69 filter-CVVH. We employed the inverse probability of treatment-weighting method (IPTW), doubly robust estimation, and mediating effect analysis to analyze those clinical outcomes, with a special focus on the results of 28-day mortality, 72-h lactate, the need for norepinephrine (NE) in the next 72 h., Results: A total of 76 patients with septic shock who received blood purification therapies were enrolled. After IPTW, differences in patient characteristics have been minimized. The 28-day mortality in the control group is higher than in the treatment group (73.3% vs. 47.3%, p < 0.001; median survival time: 10 vs. ≥28 days, log-rank p = 0.0366). And the 25% decrease and the 50% decrease in demand for NE in the next 72 h are different between the treatment and control groups (median time of 25% decrease in demand: 24 vs. >72 h, log-rank p = 0.0126; median time of 50% decrease in demand: 24 vs. >72 h, log-rank p = 0.0322). The 72-h lactic acid level and white blood cell (WBC) counts in the oXiris group are lower than in the control group. The 72-h lactate fully mediated the effects of oXiris on 28-day mortality after confounds adjustment., Conclusions: For septic shock patients, the use of oXiris-CVVH was associated with lower mortality and appeared to reduce lactate, NE dosage, PCT, and WBC counts, as compared to AN69-CVVH., (© 2022 S. Karger AG, Basel.)

Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment., Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected., Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ., Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction., (© 2021 S. Karger AG, Basel.)

This study aimed to investigate the efficiency, safety and cost-efficiency of blood purification (BP) in treating patients with severe-acute pancreatitis (SAP). A literature search was conducted using PubMed, OVID, International Clinical Trials Register (ICTRP), and Cochrane Central Register of Controlled Trials (CENTRAL). A total of 11 prospective studies and 6 retrospective studies, which reported the mortality of 1279 SAP patients, were included for analysis. Decreased short-term mortality and incidence rate of infection were observed in the high-volume hemofiltration (HVHF) group, but not in patients treated with other types of BP. There was no significant difference in the incidence of multiple-organ dysfunction (MODS), duration of hospital stay, or cost of hospitalization between the BP and non-BP groups. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of BP varied across studies. In conclusion, HVHF may reduce the short-term mortality (<4 weeks), not long-term mortality, of SAP patients by decreasing the incidence of infection, while other types of BP did not show a significant beneficial effect. Neither HVHF nor other BP patterns affect the duration of hospital stay, cost of hospitalization, or incidence of MODS in SAP patients., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation., Methods: This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors., Results: Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors., Conclusions: The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Patients with acute respiratory distress syndrome and acute kidney injury (AKI) treated by kidney replacement therapy may also require treatment with extracorporeal carbon dioxide removal (ECCO 2 R) devices to permit protective or ultraprotective mechanical ventilation. We developed a mathematical model of acid-base balance during extracorporeal therapy using ECCO 2 R and continuous venovenous hemofiltration (CVVH) devices applied in series for the treatment of mechanically ventilated AKI patients. Published data from clinical studies of mechanically ventilated AKI patients treated by CVVH at known infusion rates of substitution fluid without ECCO 2 R were used to adjust the model parameters to fit plasma levels of arterial partial pressure of carbon dioxide (PaCO 2 ), arterial plasma bicarbonate concentration ([HCO 3 ]), and plasma pH (as well as certain other unmeasured physiological variables). The effects of applying ECCO 2 R at an unchanged and a reduced tidal volume on PaCO 2 , [HCO 3 ] and plasma pH were then simulated assuming carbon dioxide removal rates from the ECCO 2 R device measured in the clinical studies. Agreement of such model predictions with clinical data was good whether the ECCO 2 R device was positioned proximal or distal to the CVVH device in the extracorporeal circuit. Although carbon dioxide removal rates from the ECCO 2 R device measured in one previous clinical study were higher when it was placed proximal to the CVVH device, suggesting that such in-series positioning was optimal, the current mathematical model demonstrates that proximal positioning of the ECCO 2 R device also results in lower bicarbonate (and, therefore, total carbon dioxide) removal from the distal CVVH device. Thus, the removal of total carbon dioxide by such extracorporeal circuits is relatively independent of the position of the in-series devices. It is concluded that the described mathematical model has quantitative accuracy; these results suggest that the overall acid-base balance when using ECCO 2 R and CVVH devices in a single extracorporeal circuit will be similar, independent of their in-series position., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Continuous venovenous hemofiltration (CVVH) is a life-sustaining procedure in patients with severe burns and acute kidney injury. Physiologic changes from burn injury and use of CVVH may alter imipenem pharmacokinetics (PK). We aimed to compare imipenem clearance (CL) in burn patients with and without CVVH, determine the effect of burn on imipenem volume of distribution (CVVH, n = 12; no CVVH, n = 11), in combination with previously published models. Model qualification was performed with standard diagnostics and comparing predicted PK parameters/time-concentration profiles with those in the existing literature. Monte Carlo simulations were conducted to evaluate the probability of target attainment. A 2-compartment model best described the data. Utilizing albumin as a covariate on volume parameters and leveraging the clearance model from prior literature, our model predicted imipenem central volume and CL within a 10% margin of error across healthy, renally impaired, and burn populations. We provide direct comparison of imipenem CL in burn patients with and without CVVH. Notably, there was no significant difference. Large imipenem V d in patients with severe burns is likely explained by increased capillary permeability, for which serum albumin may be a reasonable surrogate. Dosing 500 mg every 6 hours is adequate for burn patients on renally dosed CVVH; however, suspicion of augmented renal clearance or patients placed on CVVH without renal impairment may necessitate dosing of 1000 mg every 6 hours., (© Published 2021. This article is a U.S. Government work and is in the public domain in the USA. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high-flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high-flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high-flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high-flow HDF would be desirable., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients., Methods: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients., Results: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m 2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication., Conclusion: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success., (© 2021 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)