Continuous Renal Replacement Therapy Membrane Research Articles

The influence of continuous renal replacement therapy on 1,3-β-d-glucan levels in critically ill patients: a single-center retrospective propensity score study

1,3-β-d-Glucan (BDG) is commonly used for diagnosing invasive fungal infections (IFIs). While exposure to cellulose-based hemodialyzers is known to cause false-positive BDG results, the impact of modern hemofilters used in continuous renal replacement therapy (CRRT) remains unclear. This retrospective, single-center cohort study aimed to evaluate the effect of CRRT on BDG levels in critically ill patients. We included adult intensive care unit (ICU) patients with ≥1 BDG measurement between December 2019 and December 2020. The primary outcome was the rate of false-positive BDG results in patients exposed to CRRT compared to unexposed patients. Propensity score analysis was performed to control for confounding factors. A total of 103 ICU patients with ≥1 BDG level were identified. Most (72.8%) were medical ICU patients. Forty patients underwent CRRT using hemofilter membranes composed of sodium methallyl sulfonate copolymer (AN 69 HF) (82.5%) and of polyarylethersulfone (PAES) (17.5%). Among the 91 patients without proven IFI, 31 (34.1%) had false-positive BDG results. Univariable analysis showed an association between CRRT exposure and false-positive BDG results. However, the association between CRRT exposure and false-positive BDG results was no longer significant across three propensity score models employed: 1:1 match (n = 32) (odds ratio (OR) 1.65, p = .48), model-adjusted (n = 91) (OR 1.75, p = .38), quintile-adjusted (n = 91) (OR 1.78, p = .36). In this single-center retrospective analysis, exposure to synthetic CRRT membranes did not independently increase the risk of false-positive BDG results. Larger prospective studies are needed to further evaluate the association between CRRT exposure and false-positive BDG results in critically ill patients with suspected IFI.

Clinical Effect of the Acrylonitrile-Co-Methallyl Sulfonate Surface-Treated Membrane as a Cytokine Adsorption Therapy for Sepsis due to Acute Panperitonitis: A Retrospective Cohort Study

Introduction: Sepsis is a systemic inflammatory response syndrome caused by infectious diseases, with cytokines possibly having an important role in the disease mechanism. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve the outcomes of patients with sepsis through cytokine adsorption. Objective: This study aimed to investigate the clinical effect of the AN69ST membrane in comparison to standard continuous renal replacement therapy (CRRT) membranes for panperitonitis due to lower gastrointestinal perforation. Methods: Using the Diagnosis Procedure Combination database, we identified adult patients with sepsis due to panperitonitis receiving any CRRT. Propensity score matching was used to compare patients who received CRRT with the AN69ST membrane (AN69ST group) and those who received CRRT with other membranes (non-AN69ST group). The primary outcome measure was in-hospital mortality. Results: A total of 528 and 1,445 patients were included in the AN69ST group and in the non-AN69ST group, respectively. Propensity score matching resulted in 521 pairs. There was no significant difference in in-hospital mortality (32.1 vs. 35.5%; p = 0.265) and 30-day mortality (41.3 vs. 42.8%, p = 0.074) between the AN69ST group and the non-AN69ST group. Conclusion: There is no significant difference in-hospital mortality between CRRT with the AN69ST membrane and CRRT with standard CRRT membranes for panperitonitis due to lower gastrointestinal perforation. These results indicate that the AN69ST membrane is not superior to the standard CRRT membrane.

Membranes and Sorbents.

For continuous renal replacement therapy (CRRT), the extracorporeal filter provides solute depuration, fluid removal, and control of electrolyte and acid-base balance in critically ill patients with acute kidney injury (AKI). The membranes comprising CRRT filters are almost exclusively based on hollow fiber designs and, while adapted from the chronic hemodialysis field, have features that are specific to the requirements of CRRT nevertheless. In addition, these devices have evolved through the 40 years of CRRT in response to changes in clinical practice and the desire to extend the solute removal spectrum. For some critically ill patients, more targeted removal of specific compounds poorly cleared by standard CRRT can be attempted with techniques based on adsorption. Sorbent hemoperfusion is now being applied more broadly in critically ill patients, especially in those with sepsis and systemic inflammation. In this review, the manner in which CRRT membranes and extracorporeal sorbents have evolved over the past 40 years for the treatment of critically ill patients with AKI and other disorders is described.

AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study

BackgroundIn Japan, nafamostat mesylate (NM) is frequently used as an anticoagulant during continuous renal replacement therapy (CRRT). The dialyzer membrane AN69ST has been reported to adsorb NM and affect the management of anticoagulant therapy. However, the adsorbed amount has not yet been quantitatively assessed. Therefore, in this study, we evaluated the pre- and post-hemofilter prolongation of the activated clotting time (ACT) in patients with AN69ST and PS membranes. We also measured the adsorption of NM in three types of CRRT membranes using an experimental model.MethodsIn a study of patients who underwent CRRT using AN69ST or PS membranes in 2015 at the Advanced Emergency and Critical Care Center, Okayama University Hospital, pre- and post-hemofilter ACT measurements were extracted retrospectively, and the difference was calculated. In addition, AN69ST (sepXiris100), PS (HEMOFEEL SHG-1.0), and PMMA membranes (HEMOFEEL CH-1.0N) were used in an in vitro model of a dialysis circuit, and the concentrations of NM were measured in pre- and post-hemofilter membranes and filtrates.ResultsThe ACT difference was significantly lower in the group using AN69ST membranes (p < 0.01). In the in vitro model (n = 4) with adsorption and filtration, the post-hemofilter and filtrate concentrations of NM in AN69ST membranes were significantly lower than those in the PS and PMMA membranes (p < 0.01). The NM adsorption clearance of the AN69ST membrane was significantly higher than that of the PS and PMMA membranes.ConclusionsThe AN69ST membrane had higher NM adsorption than the PS and PMMA membranes. This may have resulted in the lower ACT difference in patients undergoing CRRT using the AN69ST membrane than in patients undergoing CRRT using PS or PMMA membranes.

Consumptive Coagulopathy after Commencement of Continuous Renal-Replacement Therapy in Patients with Decompensated Cirrhosis: A Case Series

Over a four-month period, three patients with ascites and hyponatraemia secondary to decompensated cirrhosis were admitted to the Intensive Care unit (ICU) of a quaternary referral centre for liver disease and transplantation for further management. Each had a stable documented coagulopathy without bleeding on ICU admission. Following commencement of anticoagulant-free continuous renal replacement therapy (CRRT), a severe bleeding diathesis developed in all three patients necessitating transfusion of large volumes of blood products. The clinical presentation and results of detailed coagulation profiles and thromboelastography (TEG) were consistent with the development of disseminated intravascular coagulation (DIC) with hyperfibrinolysis. The onset of DIC in all three cases was associated with significant morbidity. One patient went on to receive an orthotopic liver transplant (OLT) and death was the end result in the subsequent two cases. Due to the temporal relationship, we hypothesise that the initiation of CRRT may have contributed to the derangement in coagulation status in these patients. Though the exact mechanism is uncertain, it may be related to a higher rate of adsorption of high molecular weight kinins or the CRRT membrane’s ability to bind endogenous heparinoids. These cases highlight the precarious nature of the coagulation cascade in patients with decompensated cirrhosis. Initiation of CRRT may profoundly disrupt that tenuous balance and should be preceded by careful consideration of the potential complications including DIC and its associated morbidity.

Newly Designed CRRT Membranes for Sepsis and SIRS—A Pragmatic Approach for Bedside Intensivists Summarizing the More Recent Advances

In recent years, after all the attention has been focused on the dose for continuous renal replacement therapy (CRRT) in sepsis and systemic inflammation response syndrome (SIRS), the relatively negative results of all those studies did urge our expectations on new approaches regarding CRRT in sepsis and SIRS. So far, after the failure of the major randomized studies on dose, attention is now drawn to new membranes that could better eliminate massive amounts of unbound mediators in wider spectrum and also in greater magnitude Nevertheless, for septic acute kidney injury, the recommended dose will remain 35 ml/kg/h until the IVOIRE (hIgh VOlume in Intensive Care) study will be published. In this new armamentarium, we have distinguished the first tools that can still be called membranes ranging from AN69 Surface Treated (ST), SEPTEX, polymethylmetacrylate, to Oxiris that can still run with a CRRT device. Polymyxin B is still a kind of membrane although it has a larger surface, but it can run in a hemoperfusion system and is also much more selective. Adsorptive columns and sorbents are not anymore membranes but are seen as cartridges as the surface is extremely huge when compared with that of membranes (more than 500 m). They can still run in a hemoperfusion device. At the very end, we do have apheresis or selective plasma exchange (also very close to sorbents and columns) but we have very few data up to now regarding sepsis. Regarding spectrum, CytoSorb seems to be very promising although it is not able to capture endotoxin and IL-10. Oxiris is also promising as it can capture endotoxin and cytokines. AN69 ST is very powerful to capture numerous cytokines and especially high-mobility group box 1 protein (a very upstream cytokine). Polymethylmetacrylate has also the power to capture endotoxin and numerous other cytokines probably with a larger magnitude than Oxiris although this is not proven. Lastly, high-porosity membranes (Septex) may play a role especially when used in continuous venovenous hemodialysis mode. At the end, if we look for a more enlarged spectrum and a higher magnitude, CytoSorb might be seen as the most promising although not having the ability to fix endotoxin. Future studies will tell us which membrane or sorbent will be most useful in the adjunctive treatment for sepsis.

Meropenem and Continuous Renal Replacement Therapy: In Vitro Permeability of 2 Continuous Renal Replacement Therapy Membranes and Influence of Patient Renal Function on the Pharmacokinetics in Critically Ill Patients

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Cefepime and continuous renal replacement therapy (CRRT): In vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients

Cefepime is a fourth-generation cephalosporin with a broad spectrum of antimicrobial activity against gram-positive and gram-negative micro-organisms. It is a useful option for treating infections in critically ill patients in intensive care due to its high degree of activity and its tolerability. The aim of this study was to characterize in vitro the permeability to cefepime of 2 membranes frequently used in continuous renal replacement therapies (CRRTs). An in vivo study was also carried out to determine the pharmacokinetics of cefepime in critically ill patients undergoing CRRT. In vitro procedures were conducted in 3 different fluids using polyacrylonitrile (AN69) or polysulfone (PS) membranes. Continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) were simulated. Four male patients undergoing CVVH or continuous venovenous hemodiafiltration, who received 2000 mg of cefepime intravenously every 8 hours, entered the in vivo study. Prefilter and ultrafiltrate samples were collected, and concentrations of cefepime were measured using high-performance liquid chromatography. The sieving coefficient (Sc), defined as the fraction of drug eliminated across the membrane, and the saturation coefficient (Sa), defined as the fraction of drug diffused through the membrane to the dialysate fluid, were analyzed. Pharmacokinetic parameters were determined according to a noncompartmental analysis. The patients ranged in age from 18 to 75 years and weighed from 65 to 80 kg. By analyzing Sc and Sa values in the in vitro procedures, no differences were detected in the permeability of AN69 or PS membranes to cefepime in CVVH or CVVHD. Sc/Sa values were between 0.93 and 1.03 in Ringer's lactate and in bovine albumin-containing Ringer's lactate samples, but Sc/Sa values were lower in plasma samples (0.82-0.95). In the in vivo portion of the study, the patients' mean (SD) Sc/Sa value was 0.76 (0.21) and correlated well with the fraction unbound to proteins (0.79 [0.09]). Clearance by CRRT (mean [SD]) was 29.0 (16.8)% of the total clearance. Serum elimination t(1/2) was 4.6 (0.9) hours, and the volume of distribution at steady state was 0.6 (0.3) L/kg (mean [SD] values). Cefepime was significantly removed by CRRT. No significant differences were found in the Sc or Sa of cefepime between AN69 and PS membranes used in the CVVH or CVVHD procedures. The clearance of cefepime by CRRT must be considered when dosing critically ill patients.

Hemofiltration: From the origin to the new wave

A brief historical review of the major developments for continuous renal replacement therapy (CRRT) is given, followed by several observations on present CRRT membrane design characteristics and transport performance. It is projected that evolution of the CRRT methodology will eventually lead to the “holy grail” of artificial kidney therapy, namely, a continuously operating wearable device.