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Objective: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption integrated with continuous veno‐venous hemofiltration (FPSA‐CVVH) treatment in patients with acute liver failure (ALF). Methods: In this retrospective study, we enrolled patients with ALF (serum total bilirubin >10 mg/dL or Model for End‐Stage Liver Disease [MELD] Score >18) hospitalized between August 2017 and August 2022. All patients had at least two sessions of FPSA‐CVVH. The primary measure of treatment efficacy was the reduction ratios (RRs) of bilirubin after each session of FPSA‐CVVH. Results: Seventy‐eight patients with ALF were enrolled. The MELD score at baseline was 22.9 ± 7.5. The mean total bilirubin was 22.05 ± 5.94 mg/dL, direct bilirubin was 16.33 ± 4.60 mg/dL and indirect bilirubin was 3.43 ± 1.60 mg/dL. One hundred and eighty seven sessions of FPSA‐CVVH treatment lasting 8 hours each were performed. After a single session, serum total bilirubin, direct bilirubin and indirect bilirubin were significantly decreased. RRs were 52.0% ± 7.6% for total bilirubin, 59.4% ± 13.0% for direct bilirubin and 36.9% ± 15.4% for indirect bilirubin. Twenty nine patients (37.2%) survived and were discharged from the hospital, 12 of them recovered their liver function while the remaining 17 patients needed intermittent artificial liver support therapy. Conclusion: FPSA‐CVVH therapy is an effective artificial liver support therapy in patients with ALF. It may be considered as a "bridge technique" to the recovery of liver function in critical ill patients with ALF. [ABSTRACT FROM AUTHOR]

Sepsis is a dysregulated host response to infection that can lead to life‐threatening organ failure. Circulating bacterial toxins, termed pathogen‐associated molecular patterns (PAMPs), and excess cytokines produced by the immune system play a key role in the response that can progress into organ failure. Yet, no therapy is available to effectively remove these PAMPs and cytokines from the circulation or effectively block their action. Macrophage membrane coatings possess a natural blood compatibility, ideal for coating of adsorbent surfaces in extracorporeal blood‐cleansing. Here, the ability of Escherichia coli‐activated macrophage membrane coatings on silicon nanowired (SiNW) surfaces in a microfluidic device to remove PAMPs and cytokines from blood is determined. In vitro, such membrane‐coated SiNW adsorbent surfaces remove significantly more PAMPS or cytokines from spiked human blood than achieved by hemofiltration. Cleansing of plasma from patients with bacterial sepsis using membrane‐coated SiNW adsorbent surfaces reduces cytokine concentrations to healthy levels. In vivo, this coincides with two‐fold better restoration of healthy cytokine levels after 4 h of extracorporeal blood‐cleansing in rats with lipopolysaccharides (LPS)‐induced sepsis and four‐fold higher survival rates. Collectively, blood‐cleansing microfluidic devices using bacterially activate macrophage membrane‐coated SiNW surfaces are more effective than hemofiltration for therapeutic intervention in septic patients. [ABSTRACT FROM AUTHOR]

Treating chronic hyponatremia by continuous renal replacement therapy (CRRT) is challenging because the gradient between a replacement fluid's [sodium] and a patient's serum sodium can be steep, risking too rapid of a correction rate with possible consequences. Besides CRRT, other gains and losses of sodium‐ and potassium‐containing solutions, like intravenous fluid and urine output, affect the correction of serum sodium over time, known as osmotherapy. The way these fluids interact and contribute to the sodium/potassium/water balance can be parsed as a mixing problem. As Na/K/H2O are added, mixed in the body, and drained via CRRT, the net balance of solutes must be related to the change in serum sodium, expressible as a differential equation. Its solution has many variables, one of which is the sodium correction rate, but all variables can be evaluated by a root‐finding technique. The mixing paradigm is proved to replicate the established equations of osmotherapy, as in the special case of a steady volume. The flexibility to solve for any variable broadens our treatment options. If the pre‐filter replacement fluid cannot be diluted, then we can compensate by calculating the CRRT blood flow rate needed. Or we can deduce the infusion rate of dextrose 5% water, post‐filter, to appropriately slow the rise in serum sodium. In conclusion, the mixing model is a generalizable and practical tool to analyze patient scenarios of greater complexity than before, to help doctors customize a CRRT prescription to safely and effectively reach the serum sodium target. [ABSTRACT FROM AUTHOR]

Background: There has been a surge of interest in the preparation of membranes for clinical applications, chiefly for hemodialysis and hemofiltration. Despite numerous benefits, the exploitation of polymeric materials for dialysis membrane preparation remains unsatisfactory due to lack of proper physicochemical properties and biocompatibility. Therefore, this work focuses on the preparation of a ceramic membrane in a tubular configuration using an extrusion method and a clay material mixture. The biocompatibility of the membrane as well as its structural properties were studied. Results: The porosity, permeability and pore size of the membrane were 39 ± 0.88%, 203 ± 0.51 L m−2 h−1 bar−1 and 304 ± 1.20 nm, respectively. The corrosion tolerance of the membrane was found to be better in acidic, alkaline and chlorine solutions. The protein adsorption, hemolysis and platelet adhesion were 2.1 ± 0.03 μg cm−2, 1.02 ± 0.01% and 6856 ± 84 platelets mm−2, respectively. The membrane demonstrated a prolonged blood coagulation time (PT = 18 ± 0.33 s and APTT = 70 ± 0.57 s), a 171 ± 0.57 s whole blood clotting time and complement activation of 805 ± 1.3 mg L−1 for C3 and 247.3 ± 0.98 mg L−1 for C4. During synthetic blood filtration, the membrane had sieving coefficients of 0.98 ± 0.005, 0.97 ± 0.008 and 0.93 ± 0.005 for creatinine, urea and phosphate, respectively. Finally, the membrane revealed a protein rejection of about 56 ± 0.57%. Conclusions: The overall findings indicated that the prepared tubular membrane with excellent biocompatibility and uremic toxin removal can be used for hemofiltration application as an alternative to hemodialysis. © 2022 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Handover, clinical discussion, and care for patients in the Intensive Care Unit (ICU) require visual cues to a verbal "story" in an attempt to quickly understand the patient status. Continuous renal replacement therapy (CRRT) is often associated with sepsis or a toxic cause and "kidney attack" not apparent to the patient; "silent" with no pain, discomfort, or vital sign changes initially. Language, terminology, and definitions for this acute kidney injury (AKI) are a graded classification with guidelines. CRRT and dialysis techniques use the physiological principles of diffusion and or convection for solute removal providing a replacement for the basic kidney functions to sustain life until function returns. When to stop CRRT is based on clinical assessment of the patient overall status and urine production re‐starting. The medical treatment is focused on the key interventions of resuscitation, remove the cause, support with CRRT or dialysis and monitor for recovery of function. CRRT requires a multidisciplinary team and quality process, local policies, education, and competency pathways to promote best outcomes and efficacy. [ABSTRACT FROM AUTHOR]

Over the last 40 years, acute renal replacement therapy (RRT) in the intensive care units (ICUs) of high‐income countries has transitioned from the predominant use of intermittent hemodialysis (and the much less common use of peritoneal dialysis) to the almost exclusive use of continuous renal replacement therapy (CRRT). Accordingly, CRRT has become the most common form of vital organ support delivered to critically ill patients. A series of clinical and technical advances has enabled the transformation of basic CRRT machines into highly sophisticated and customized devices. Recent work has focused on using evidence from clinical trials to enhance the application of CRRT with regard to timing of initiation, choice of modality, dose, and anticoagulation. However, many questions remain unanswered. Uncertainty surrounding volume control and the utility of strategies to minimize circulatory stress are key areas for future development. Advances in membrane technology, combination with other extracorporeal therapies, and personalization of CRRT delivery may provide additional benefit to certain subgroups. Development of quality metrics and use of data analytics to audit and benchmark could provide important insight into practice, while biofeedback and automated CRRT prescription could increase safety. In this review, we summarize the evolution of CRRT and highlight several future areas for development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The high mobility group box 1 protein (HMGB1) is recognized as a prototypical endogenous danger cytokine in sepsis. We previously reported that a polyacrylonitrile (AN69ST) membrane rapidly adsorbed HMGB1. Herein, an in vitro hemofiltration system was designed to assess the HMGB1 adsorption capacity, adsorption sites, and adsorption mechanism of the AN69ST membrane. HMGB1 was repeatedly added seven times during hemofiltration. A rapid decrease in circulating HMGB1 was observed after every addition with no sign of saturation. Presence of HMGB1 on the filter membrane was observed on both membrane surfaces and within the bulk layer using a high concentration of HMGB1 by immunoelectron microscopy. We hypothesized that the addition of heparin to the membrane surface or filtration rate would contribute to the adsorption mechanism. We could not measure the influence of heparin and filtration. Although the membrane was too large to saturate under the μg/mL HMGB1 conditions, our results show that the AN69ST membrane has a robust absorption capacity that could be used to treat sepsis. [ABSTRACT FROM AUTHOR]

Convection‐based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion‐based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD‐HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD‐HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady‐state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin. [ABSTRACT FROM AUTHOR]

A critically ill patient requiring continuous venovenous hemofiltration therapy received parenteral nutrition through the same commonly used intravascular device. The inclusion of injectable lipid emulsion had an adverse effect on hemofilter function. This was successfully managed first by using lipid-free parenteral nutrition and then by administering the total nutrient admixture via a separate central venous access device. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate extended‐infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD). Design: Prospective, open‐label, PK study. Setting: Intensive care units at a large, academic, tertiary‐care medical center. Patients: Ten critically ill adults who were receiving cefepime 2 g intravenously every 8 hours as a 4‐hour infusion while receiving CVVH (eight patients) or CVVHD (two patients). Intervention: Two sets of five serum cefepime concentrations were collected for each patient to assess pharmacokinetics before and during presumed steady state. Concurrent serum and CRRT effluent samples were collected at hours 1, 2, 3, 4, and 8 after the first cefepime dose and after either the fourth, fifth, or sixth (steady‐state) cefepime doses. Measurements and Main Results: Reversed‐phase high‐performance liquid chromatography was used to determine free cefepime concentrations. PK analyses included CRRT clearance, half‐life, and sieving coefficient or saturation coefficient. Cefepime peak (4 hrs) concentrations, trough (8 hrs) concentrations (Cmin), and minimum inhibitory concentration breakpoint of 8 µg/ml for the pathogen (MIC8) were used to evaluate attainment of pharmacodynamic targets: 100% of the dosing interval that free drug remains above MIC8 (100% fT > MIC8), 100% fT > 4 × MIC8 (optimal), percentage of time fT > 4 × MIC8 (%fT > 4 × MIC8) at steady state, and ratio of Cmin to MIC8 (fCmin/MIC8). Total CRRT effluent flow rate was a mean ± SD of 30.1 ± 5.4 ml/kg/hr, CRRT clearance was 39.6 ± 9.9 ml/min, and half‐life was 5.3 ± 1.7 hours. Sieving coefficient or saturation coefficient were 0.83 ± 0.13 and 0.69 ± 0.22, respectively. First and steady‐state dose Cmin were 23.4 ± 10.1 µg/ml and 45.2 ± 14.6 µg/ml, respectively. All patients achieved 100% fT > MIC8 on first and steady‐state doses. First and steady‐state dose 100% fT > 4 × MIC8 were achieved in 22% (2/9 patients) and 87.5% (7/8 patients) of patients, respectively. The mean %fT > 4 × MIC8 at steady state was 97.5%. The fCmin/MIC8 was 2.92 ± 1.26 for the first dose and 5.65 ± 1.83 at steady state. Conclusion: Extended‐infusion cefepime dosing in critically ill patients receiving CRRT successfully attained 100% fT > MIC8 in all patients and an appropriate fCmin/MIC8 for both first and steady‐state doses. All but one patient achieved 100% fT > 4 × MIC8 at steady state. No significant differences were observed in PK properties between first and steady‐state doses among or between patients. It may be reasonable to initiate an empiric or definitive regimen of EI cefepime in critically ill patients receiving concurrent CRRT who are at risk for resistant organisms. Further research is needed to identify the optimal dosing regimen of EI cefepime in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Vancomycin pharmacokinetics are affected by renal replacement therapy and physiologic changes in critically ill patients. Literature regarding vancomycin removal and pharmacokinetics during accelerated venovenous hemofiltration (AVVH), a form of prolonged intermittent renal replacement therapy, is limited., Objective: To describe the removal and pharmacokinetics of vancomycin during AVVH., Methods: Eighteen critically ill adults receiving vancomycin and AVVH were included. Vancomycin serum concentrations were obtained within 4 h before and 2-6 h after the AVVH session. Patients' serum concentrations were plotted against time, and individual pharmacokinetic parameters were determined by a one-compartmental analysis. Continuous data are reported as a median (interquartile range [IQR]) and categorical data as a percentage., Results: The median AVVH effluent rate was 39.3 mL/kg/h (IQR 35.5-48 mL/kg/h) for a duration of 9 h (IQR 8-9.75 h). AVVH decreased vancomycin concentrations by 29.8% (IQR 24.9%-35.9%), at a rate of 3.4% per hour (IQR 3.1%-4.3% per hour) of AVVH. The vancomycin elimination rate constant and half-life were 0.039 h -1 (IQR 0.036-0.053 h -1 ) and 17.6 h (IQR 13.1-18.8 h), respectively. The area under the curve during AVVH was 171.7 mg*h/L (IQR 149.1-190 mg*h/L). The volume of distribution in 10 patients was 1 L/kg (IQR 0.73-1.1 L/kg). After AVVH, vancomycin 1000 mg (IQR 750-1000 mg) was needed to maintain a serum trough concentration ≥15 mg/L., Conclusion: Vancomycin is significantly removed by AVVH, which requires supplemental dosing after completion of the AVVH session to maintain desired serum concentrations. Therapeutic drug monitoring of vancomycin serum concentrations is recommended for patients undergoing AVVH., (© 2023 Pharmacotherapy Publications, Inc.)

Abstract: Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof‐of‐concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin‐leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large‐pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis. [ABSTRACT FROM AUTHOR]

Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory response by removal of circulating cytokines and therefore improve cardiac function in patients with heart failure (HF). We hypothesized that patients with developed cardiorenal syndrome and treated with CVVH have lower risk for mortality than other patients treated with slow continuous ultrafiltration (SCUF). This was a prospective, longitudinal follow-up study for 24 months duration. In total, 120 patients were recruited from the intensive care units. Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and 23 SCUF patients survived. Mean survival time was longer in CVVH group with cardiomyopathy than in the SCUF group. When we compared patients with cardiomyopathy and hourly urine output <10 mL/h, mean survival time was significantly longer in patients treated with CVVH. This is the first study to analyze the impact of different CRRT modalities (CVVH vs. SCUF) on survival of patients with HF and who developed cardiorenal syndrome. Better survival in patients treated with CVVH, which is mostly pronounced in patients with cardiomyopathy, is a consequence of a better preserved hourly urine output. Longer survival in patients with cardiomyopathy is most probably related to cytokine removal by CVVH with smaller UF rates and longer duration of each treatment. Slow continuous ultrafiltration remains the method of choice in patients with HF and preserved renal function but in cases of developed cardiorenal syndrome is much inferior to CVVH. [ABSTRACT FROM AUTHOR]

The efficacy and safety of certoparin in the prophylaxis of clotting during hemodialysis have recently been proven. Different to other low-molecular weight heparins ( LMWHs), certoparin does not accumulate in maintenance dialysis patients for unknown reasons. The purpose of the present study was to examine the impact of the dialysis procedure on the removal of certoparin. In a subgroup of the MEMBRANE study consisting of 12 patients, the pharmacokinetics of certoparin during hemodialysis was determined by means of the anti- Xa activity. In addition, the elimination of certoparin into continuously collected dialysate was assessed. Further, in vitro experiments with human blood-simulating high-flux hemodialysis and hemofiltration were performed to quantify the elimination and the sieving coefficients S K of the two LMWHs certoparin and enoxaparin compared with unfractionated heparin ( UFH). The surrogate marker middle molecules inulin and myoglobin served as reference solutes during the experiments. Finally, the adsorption of 125iodine-radiolabeled certoparin onto the synthetic dialysis membrane was quantified. The clinical study reconfirmed the absence of bioaccumulation of certoparin with anti- Xa activities between <0.01 and 0.02 IU/mL after 24 h. A short plasma half-life time of 2.0 ± 0.7 h was determined during hemodialysis. Of the total certoparin dose injected intravenously prior to hemodialysis, only 2.7% was eliminated into dialysate. The in vitro experiments further revealed only 6% of certoparin to be adsorbed onto the dialysis membrane. The anti- Xa activities of certoparin and enoxaparin slowly declined during in vitro hemofiltration to 87.3 ± 5.5 and 82.5 ± 9.4% of baseline, respectively, while inulin and myoglobin concentrations rapidly decreased. The anti- Xa activity of UFH remained unchanged. The S K of both LMWH and UFH was very low in hemofiltration and particularly in hemodialysis with values ≤0.1. The elimination kinetics during hemodialysis suggests strong protein-binding of certoparin. Different from LMWH significantly cleared by the kidneys, the relatively short half-life time of certoparin of only 2 h during hemodialysis allows a more reliable control of the anti-coagulatory effects and decreases the risk of bleeding complications. Dialytic removal does not significantly contribute to the clearance of certoparin in maintenance dialysis patients. [ABSTRACT FROM AUTHOR]

Whilst prolonging hemofilter (circuit) life, heparin increases bleeding risk. The impact of achieved activated partial thromboplastin time ( APTT) on circuit life and bleeding risk has not been assessed in a modern critically ill cohort. Lowering filtration fraction may be an alternative means of prolonging circuit life, but is often overlooked in critical care. An observational study of 309 consecutive circuits in a general intensive care unit was conducted using a wide target APTT range. Multilevel modeling was used to predict circuit life and bleeding according to achieved APTT and filtration fraction. Independent predictors of circuit failure (i.e. unplanned ending of treatment) included filtration fraction ( P < 0.001, HR 1.07 per 1% increase), peak APTT ( P < 0.001, HR 0.8 per 10 s increase or 0.3 APTR increase) and baseline PT ( P = 0.014, HR 0.91 for every 50% increase). The only significant predictor of bleeding was peak APTT ( P = 0.017, OR 1.05 per 10 s increase). Every 10 s APTT increase was associated with a 20% reduction in circuit failure, but a 5% increase in hemorrhage. A 3% reduction in filtration fraction was associated with the same improvement in circuit life as a 10 s increase in APTT. Increasing APTT prolongs circuit life but carries a substantial risk of bleeding even in modern practice. Filtration fraction has a large impact on circuit life in the critically ill: a 3% reduction in filtration fraction, e.g. by increasing blood flow or delivering some of the clearance via dialysis, would be expected to reduce circuit failure as much as a 10 s increase in APTT. [ABSTRACT FROM AUTHOR]

Avian influenza A ( H7N9) is a severe disease with high mortality. Hypercytokinemia is thought to play an important role in the pathogenesis. This study was to investigate the efficiency of plasma exchange ( PE) + continuous veno-venous hemofiltration ( CVVH) on the removal of inflammatory mediators and their benefits in the management of fluid overload and metabolic disturbance. In total, 40 H7N9-infected patients were admitted to our hospital. Sixteen critically ill H7N9-infected patients received combination of PE and CVVH. Data from these 16 patients were collected and analyzed. The effects of PE + CVVH on plasma cytokine/chemokine levels and clinical outcomes were examined. H7N9-infected patients had increased plasma levels compared to healthy controls. After 3 h of PE + CVVH treatment, the cytokine/chemokine levels descended remarkably to lower levels and were maintained thereafter. PE + CVVH also benefited the management of fluid, cardiovascular dysfunction and metabolic disturbance. Of the 16 critically ill patients who received PE + CVVH, 10 patients survived. PE + CVVH decreased the plasma cytokine/chemokine levels significantly. PE + CVVH were also beneficial to the management of severe avian influenza A ( H7N9). [ABSTRACT FROM AUTHOR]

Current fluconazole dosing strategies can be described using either standardized doses (800 or 400 mg) or as weight-based dosing recommendations (12 mg/kg loading dose followed by 6 mg/kg maintenance dose). The ideal method of fluconazole dosing is still unclear for certain patient populations, such as those receiving renal replacement therapy or the morbidly obese. We describe a 48-year-old man with a body mass index of 84 kg/m2 who was receiving continuous venovenous hemofiltration (CVVH) and was treated with fluconazole by using a weight-based dose determined by lean body weight, infused at a rate of 200 mg/hour. Blood samples were collected at hour 0 (i.e., ~24 hrs after the loading dose was administered) and at 3.5, 6.8, and 11.3 hours after the start of the 600-mg maintenance dose, infused over 3 hours. Pharmacokinetic parameters calculated were maximum serum concentration 9.64 mg/L, minimum serum concentration 5.98 mg/L, area under the serum concentration-time curve from 0-24 hours (AUC0-24) 184.75 mg/L•hour, elimination rate constant 0.0199 hour−1, elimination half-life 34.8 hours, and total body clearance 3.25 L/hour. Our data, when combined with previously published literature, do not support using a linear dose-to-AUC approximation to estimate drug dosing needs in the critically ill patient population receiving CVVH. In addition, our results suggest that morbidly obese patients are able to achieve pharmacodynamic goals defined as an AUC:MIC ratio higher than 25 by using a lean body weight for fluconazole dosing calculations. [ABSTRACT FROM AUTHOR]

Continuous venovenous hemofiltration ( CVVH) is an important organ supportive technique. This study aimed to evaluate the impact of early classic CVVH on the outcomes of severe acute pancreatitis ( SAP) patients with early organ failure ( EOF). Between 2008 and 2012, a total of 44 SAP patients with EOF were admitted to our department. The 44 patients were classified into two groups according to whether they received early classic CVVH (2 L/h, initiated within 24 h after admission): 25 patients received early CVVH ( ECVVH group), and 19 patients did not receive early CVVH (control group). The two groups were matched for age and Acute Physiology and Chronic Health Evaluation II scores. The severity of organ dysfunctions was evaluated by Sequential Organ Failure Assessment ( SOFA) scores. Each group included 19 patients. The baseline characters between the two groups were balanced. The SOFA scores in the ECVVH group increased compared with those in the control group. The time to weaning from mechanical ventilation was significantly longer in the ECVVH group (log-rank test: χ2 = 4.007, P = 0.045). Renal support was also significantly prolonged in the ECVVH group (the number of patients receiving CVVH 72 h after admission: 10 vs. 3, respectively, P = 0.038). Nine patients died in the ECVVH group versus six patients in the control group ( P = 0.508). In conclusion, our study failed to prove that early classic CVVH had any benefits on the outcomes of SAP patients with EOF. Unexpectedly, early classic CVVH worsened organ functional capacity. However, it is possible that CVVH using advanced techniques may be beneficial in SAP patients with EOF. [ABSTRACT FROM AUTHOR]

Intensive therapy demanding diseases (organ failure or sepsis) are assumed to be the etiology behind a decreased biocompatibility of extracorporeal systems for renal replacement therapy ( RRT). There are also potential interactions between different components of the overall therapy. Volume substitutes are known to influence hemorheology and coagulation. To define a potential net effect of volume substitutes on the hemocompatibility of an RRT, we chose an animal model without interfering pathophysiologies. According to the problem of early filter failure and coagulation disorders in critically ill patients, we focused on the hypothesized interaction between RRT and different volume substitutes with respect to blood cell counts, coagulation parameters and required heparin dose. Forty-eight pigs were assigned to four groups of fluid therapy with either normal saline ( NaCl), 6% HES130kD/0.4 ( HES130), 6% HES200kD/0.5 ( HES200) or 4%gelatin ( GEL). Six pigs of each fluid group underwent continuous venovenous hemofiltration ( CVVH), the remaining six served as the control group. Anticoagulation was performed with continuous heparin infusion. CVVH was run in a recirculation-mode for 4.5 h to force hemocompatibility reactions, thereafter in a standard-mode for 2 h. During the CVVH-treatment GEL reduced platelet counts and fibrinogen concentration and additionally lowered ATIII levels. Heparin requirements did not differ between different volume substitutes or CVVH and control groups. Severe pathophysiologies are not the only reason for a reduced hemocompatibility of CVVH treatment. Interaction of a particular volume substitute with CVVH should be considered when interpreting study results and evolving new strategies. [ABSTRACT FROM AUTHOR]

Our aim was to investigate the efficacy of continuous venovenous hemofiltration ( CVVH) in treating severe acute pancreatitis ( SAP). A literature search was performed using Pub Med (1992-present), and all studies investigating the efficacy of CVVH in treating SAP were included. Four comparative studies and seven case series comprising a total of 354 patients were included. The overall mortality rate of patients receiving CVVH was 20% (55/275). A decreased mortality rate and decreased serum cytokine levels were reported in the CVVH groups in only two studies. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of CVVH varied among the studies, and the impact of these parameters on the efficacy of CVVH was poorly reported. High-volume CVVH, when started early, was demonstrated to be more effective in eliminating cytokines in only one study. After the application of CVVH, the patient conditions started to improve between the 6th and 72nd hours. In conclusion, no solid clinical evidence has proven the efficacy of CVVH in treating SAP. High-volume CVVH that is started early and sustained for at least 72 h may be adopted to investigate the efficacy of CVVH for treating SAP. [ABSTRACT FROM AUTHOR]

The optimal timing for renal replacement therapy initiation in septic acute kidney injury (AKI) remains controversial. This study investigates the impact of early versus late initiation of continuous renal replacement therapy (CRRT) on organ dysfunction among patients with septic shock and AKI. Patients were dichotomized into 'early' (simplified RIFLE Risk) or 'late' (simplified RIFLE Injury or Failure) CRRT initiation. Patients with chronic kidney disease stage 5 or those on long-term dialysis were excluded. Organ dysfunction was quantified by Sequential Organ Failure Assessment (SOFA) score. From January 2008 to June 2011, 120 patients fulfilled the inclusion criteria. Thirty-one (26%) underwent 'early' while 89 (74%) had 'late' CRRT. No significant difference was noted between groups on improvement of total SOFA/non-renal SOFA score or noradrenaline equivalent in the first 24 and 48 h after CRRT initiation. Dialysis requirement and mortality (at 28 days, 3 months and 6 months) did not differ. In conclusion, improvement of non-renal SOFA score 48 h after CRRT correlated with SOFA score on CRRT initiation ( P = 0.040) and APACHE IV risk of death ( P = 0.000), but not estimated glomerular filtration rate on CRRT initiation ( P = 0.377). Improvement of non-renal SOFA score correlated with SOFA score on CRRT initiation and APACHE IV risk of death. However, this retrospective review cannot identify any significant clinical benefit of early CRRT initiation in patients presenting with septic shock and AKI. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that the expression of tumor necrosis factor-α (TNF-α) in myocardium correlates with the severity of cardiac dysfunction in septic shock. The aim of this study was to investigate the impact of high-volume hemofiltration (HVHF) on the expression of TNF-α in myocardium in septic shock pigs. Sixteen male Landrace pigs weighing 31 ± 5 kg were randomly assigned to control group ( n = 4), septic shock group ( n = 6), and HVHF group (septic shock + HVHF, n = 6). All animals were anesthetized and mechanically ventilated. After baseline examinations, septic shock group and HVHF group underwent induction of peritonitis. One hour later, the animals in HVHF group received treatment with HVHF and the treatment was continued for 12 h. As the control of HVHF group, the animals in septic shock group received the same support but hemofiltration. Twelve hours after HVHF therapy, all the animals were sacrificed. TNF-α and nitric oxide (NO) levels in both circulation and myocardium were measured. Compared with those of septic shock animals, the levels of cardiac output, stroke volume, and mean arterial pressure were better maintained in HVHF group. The expression of TNF-α in myocardium in HVHF group was lower than that in septic shock group (44.17 ± 18.70 vs. 92.50 ± 33.89 pg/mg protein, P = 0.015). The difference of TNF-α in circulation between HVHF group and septic shock group was no significance at different time. However, circulating NO in HVHF group was lower than that in septic shock group. These results suggest that HVHF improves hemodynamics and heart dysfunction in septic shock pigs, which may be attributed to reduction of TNF-α in myocardium but not in circulation. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine whether early high-dose continuous venous-venous hemofiltration (CVVH) alleviates the alterations in CD4 + T lymphocyte subsets in septic patients combined with acute kidney injury., Methods: Enrolled septic patients combined with acute kidney injury were randomized into CVVH (n = 50) and conventional treatment (non-CVVH, n = 53) groups. Healthy volunteers (n = 21) were enrolled. CVVH was initiated within 12 h of intensive care unit (ICU) admission with doses of 35~60 ml/kg/h and maintained for at least 72 h. Th1, Th2, Th17, and T reg were measured by flow cytometry on days 1, 3, and 7 of ICU admission. Sequential organ failure assessment (SOFA) scores were calculated., Results: Th1 percentages and Th1/Th2 ratios were lower, and Th2, Th17, and T reg percentages and Th17/T reg ratios were higher in septic patients compared to healthy volunteers. CVVH significantly increased Th1 percentages and Th1/Th2 ratios, and significantly decreased Th2, Th17, and T reg percentages and Th17/T reg ratios compared to non-CVVH. Th1 percentages and Th1/Th2 ratios were negatively correlated with SOFA scores, while Th2, Th17, and T reg percentages and Th17/T reg ratios were positively correlated with SOFA scores. Patients with CVVH had significantly lower SOFA scores on day 7 of ICU admission and a shorter ICU stay compared to those with non-CVVH., Conclusions: Septic patients combined with acute kidney injury exhibit different alterations of CD4 + T lymphocyte subsets. Early high-dose CVVH alleviates the alterations, which may be one of the factors associated with improved sepsis severity., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m2, large-pore (78 Å) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY), a potent vasoconstrictor released from the sympathetic nerves, has been suggested to counterbalance sepsis-induced vasodilation. Thus, the changes in plasma and tissue NPY concentrations in relation to hemodynamic variables and inflammatory markers in a porcine model of moderate septic shock were investigated. Susceptibility of NPY to be removed by continuous hemofiltration in two settings has been also studied. Thirty-four domestic pigs were divided into five groups: (i) control group; (ii) control group with conventional hemofiltration; (iii) septic group; (iv) septic group with conventional hemofiltration; and (v) septic group with high-volume hemofiltration. Sepsis induced by fecal peritonitis continued for 22 h. Hemofiltration was applied for the last 10 h. Hemodynamic and inflammatory parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-α, interleukin-6, and NPY) were measured before and at 12 and 22 h of peritonitis. NPY tissue levels were determined in the left ventricle and mesenteric and coronary arteries. Sepsis induced long-lasting increases in the systemic NPY levels without affecting its tissue concentrations. Continuous hemofiltration at any dose did not reduce sepsis-induced elevations in NPY plasma concentrations, nor did it affect the peptide tissue levels. The increases in NPY systemic levels were significantly correlated with changes in the systemic vascular resistance. The results support the hypothesis of NPY implication in the regulation of the vascular resistance under septic conditions and indicate that NPY clearance rate during hemofiltration does not exceed the capacity of perivascular nerves to release it. [ABSTRACT FROM AUTHOR]

The most common method of controlling acidemia during lung-protective ventilation is CO removal with an extracorporeal lung assist (ECLA) system. Another possibility to prevent acidemia is based on intravenous (i.v.) application of tris-hydroxymethyl-aminomethane (3 mol/L, THAM) buffer, which can bind hydrogen protons and which can be removed from the body via renal replacement therapy (RRT). We investigated whether RRT combined with predilutional (prefilter) THAM-application provides an alternative to ECLA for a rescue situation. For this, anesthetized pigs, 40 kg of body weight, six animals per group, underwent 5 h of acidemia (pH 7.19-7.24) induced by acid infusion and permissive hypercapnia (low tidal volume ventilation, PaCO 80-90 mm Hg). Isovolemic, high-volume hemofiltration (HVHF) was operated with predilutional THAM-infusion for treatment. To evaluate adverse effects of this approach, we set up further groups: HVHF with postdilutional (post-filter) THAM-application; i.v.-THAM without HVHF; normal pH homeostasis with HVHF. Acid-base parameters, hemodynamics, renal function, and lung morphology were investigated. HVHF with predilutional THAM-infusion of 8 mmol/kg/h allowed fast pH normalization, significant reduction in PaCO to 56 mm Hg and tolerable hemodynamics. HVHF alone or lower dose i.v. THAM (2 mmol/kg/h) failed to produce a comparable result. A postdilutional THAM infusion reduced hemodynamic tolerability and increased lung edema formation. HVHF in pigs with normal acid-base status resulted in a decreased base excess and urine acidification. In conclusion, predilutional THAM-application and HVHF corrected the acid-base disorder and improved pulmonary hemodynamics. Further studies are necessary to optimize the protocol including the dosage. [ABSTRACT FROM AUTHOR]

High-dose vasopressor use is associated with increasing mortality in patients with septic shock. We conducted this study to determine if the high-dose of vasopressor used before the initiation of continuous renal replacement therapy (CRRT) is associated with increasing mortality in critically ill patients. We retrospectively reviewed all patients who underwent CRRT in the medical intensive care unit of China Medical University Hospital between 2003 and 2007. The association between mortality and highest vasopressors (dopamine and norepinephrine [NE]) dose used were analyzed using Kaplan-Meier analysis and multivariate Cox regression. A total of 279 patients (170 men and 109 women) treated with CRRT in medical intensive care were reviewed and 237 (84.9%) died. In Kaplan-Meier analysis with log-rank test, dopamine dose of ≥20 µg/kg/min and NE dose of ≥0.3 µg/kg/min were significantly linked to mortality ( P = 0.007 and <0.001). In multivariate Cox proportional hazards regression, NE dose of ≥0.3 µg/kg/min, Acute Physiology and Chronic Health Evaluation II score, and low platelet count were independently linked to mortality. The hazard ratios and 95% confidence interval (CI) were 1.771 (95% CI: 1.247-2.516, P = 0.001), 1.035 (95% CI: 1.012-1.058, P = 0.003), and 0.997 (95% CI: 0.996-0.999, P = 0.003), respectively. Critically ill patients treated with very high dose of NE before the initiation of CRRT have a very high mortality rate regardless of the acute kidney injury stage. [ABSTRACT FROM AUTHOR]

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 μg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 μg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occurred at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation. [ABSTRACT FROM AUTHOR]

There is no consensus on the optimal renal replacement treatment in intensive care units. Among intermittent dialysis methods, hemofiltration (HF) is preferred by some because of better hemodynamic stability and cytokine removal. We report our experience with regional citrate anticoagulation for intermittent predilution online HF. Forty-one patients (age 69 ± 10 years, 73% male) with acute renal failure and an increased bleeding risk in intensive care units were included in this retrospective analysis. Citrate anticoagulation was performed with 4% citrate (starting at 400 mL/h) and 1 mol/L calcium chloride (starting at 7 mL/h). Calcium-containing (1.25 mmol/L) infusate, prepared online, was used. Anticoagulation was assessed visually after HF in a subgroup of 36 procedures using a score of 5 (no clotting) to 1 (total occlusion). The duration of the 94 HF sessions performed was 4 h 50 min ± 47 min, and the infusate volume reached was 77 ± 9 L. During HF, ionized calcium increased (1.01 ± 0.14 to 1.13 ± 0.09 mmol/L, P < 0.001), and the increases in sodium (141 ± 5 to 143 ± 3 mmol/L, P < 0.001) and bicarbonate (23 ± 6 to 25 ± 4 mmol/L, P < 0.01) were significant, but small. There were two cases of metabolic alkalosis (pH > 7.5) not requiring any intervention. None of the circuits clotted. The mean anticoagulation assessment scores were 4.6 ± 0.6 at the arterial bubble trap, 4.2 ± 1.0 at the dialyzer, and 4.2 ± 0.9 at the venous bubble trap. To conclude, regional citrate anticoagulation for predilution online hemofiltration with calcium-containing infusate provides a good anti-thrombotic effect and has rare metabolic side effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize vancomycin adsorption by polyacrylonitrile (PAN), polyamide, and polysulfone hemofilters using an in vitro model of hemofiltration. Vancomycin (36 mg) was added to a blood-crystalloid mixture of known volume (target concentration of 50 mg/L) and pumped around a closed circuit. Adsorption, which was calculated from the fall in concentration over 120 min, was significantly greater by 0.6-m2 PAN filters (10.08 ± 2.26 mg) than by 0.6-m2 polyamide (5.20 ± 1.82 mg) or 0.7-m2 polysulfone (4.80 ± 2.40 mg) filters ( P < 0.05). Cumulative adsorption was not changed by the addition of 500-mL lactated Ringer's solution (to reduce the circulating vancomycin concentration). These data show that although adsorption of vancomycin by PAN, polyamide, and polysulfone hemofilters occurs, the absolute adsorption is small. Adsorption is dependent on filter material and is not reversed by a decrease in circulating concentration. [ABSTRACT FROM AUTHOR]

A three-valve, pulsatile tubular pump was used in 24 pigs weighing 10.2 ± 3.2 kg; the pump was connected to a neonatal hemofiltration circuit. Ninety-two periods of 30 min were studied to analyze the efficacy of the system with variations in the percentage time in diastole, the diastolic speed, the systolic speed, and the percentage time in systole during which the postfilter valve was closed. System efficacy was determined by the blood flow through the filter, the ultrafiltrate volume, the vascular overload measured by the inlet aspiration pressure, and the filter overload measured by the cross-filter pressure drop and the transmembrane pressure. The variations in the pump parameters did not lead to significant differences in the efficacy of the system or in the vascular or filter overload. The parameters must be adjusted in each case to obtain the best yield with the lowest vascular and filter overload. [ABSTRACT FROM AUTHOR]

In hemofiltration (HF) and hemodiafiltration (HDF), removal of medium and high-molecular-weight solutes is greatly enhanced by convective mechanisms as compared with simple diffusion; increasing convective flows may allow greater removal rates of these solutes. Use of “predilution” (pre-H[D]F) may allow higher ultrafiltration rates than the “postdilution” mode (post-H[D]F); yet, the dilution of plasma water may have unpredictable effects on “endogenous” water convection. We have applied a mathematical analysis to evaluate and compare endogenous water convective flow rates in pre-H(D)F vs. post-H(D)F. Endogenous plasma water recovered in ultrafiltrate was calculated according to patient (hematocrit, total protein level) and session parameters (blood flow, ultrafiltration rate, programmed weight loss), in absolute terms and as a fraction of endogenous plasma water delivery to the filter. Maximally efficient post-H(D)F was modelled according to a preset postfilter hematocrit or filtration fraction. Nomograms were constructed expressing endogenous water convective fluxes in relation to parameters of interest (ultrafiltration rate, blood flow, hematocrit) with both post-H(D)F and pre-H(D)F, and “efficiency” of pre-H(D)F vs. post-H(D)F (as the ratio of endogenous water convective flow rate with the 2 techniques) as a function of the ultrafiltration/reinfusion rate. In post-H(D)F, the model predicts maximal ultrafiltration rates within the limits of a preset hemoconcentration at the filter outlet; additionally, the model allows to calculate ultrafiltration/reinfusion quantities to be set in pre-H(D)F to equal and overcome maximal convective efficiency of post-H(D)F. This “equivalence” ultrafiltration rate may greatly vary according to patient's hematocrit and blood flow, so that the ultrafiltrate-reinfusate volume available in the system dictates, in any patient, which mode of reinfusion may attain higher “endogenous” convective flow rates. Pre-H(D)F may allow higher fractional and absolute “endogenous” convective flow rates as compared with post-H(D)F, provided that adequate amounts of reinfusate are available. For lower reinfusate volumes than “equivalence” values, post-H(D)F remains a better option. [ABSTRACT FROM AUTHOR]

Hemodynamic improvement in patients suffering from both septic shock and renal failure who received hemofiltration suggested that an extrarenal epuration technique could be of interest in patients with septic shock alone. However, most of the studies using continuous venovenous hemofiltration (CVVH) in this setting evidenced neither cytokine clearance nor significant reduction in their plasma level. Lack of significant clearance was explained in part by the small size of the membrane pores. Therefore, we investigated the effects of large-pore membrane hemofiltration (LPHF) during endotoxic shock in pigs on interleukin 6 (IL-6) and interleukin 10 (IL-10) clearances, and on right ventricular (RV)–vascular coupling. Thirteen anesthetized healthy pigs weighing 20–30 kg were divided into two groups. In the Endo group ( n = 6), the pigs received a 0.5-mg/kg endotoxin infusion over a period of 30 mins from T0 to T30. In the EndoHF group ( n = 7), LPHF (cutoff = 80 kDa) and an ultrafiltration rate of 45 mL/kg/h were started 30 mins after the end of the endotoxin infusion, from T60 to T240. In this model of porcine endotoxic shock, LPHF was responsible for a significant clearance of IL-6 (20 mL/min) and Il-10 (14 mL/min), and for an improvement in RV–vascular coupling. [ABSTRACT FROM AUTHOR]

There is a need to develop artificial means of liver replacement and/or assistance with the aim of either supporting patients with borderline functional liver cell mass until their liver regenerates, or until a donor liver becomes available for transplantation. Selective plasma filtration is a novel approach to blood purification therapy designed to reduce the level of circulating toxins of hepatic and renal failure, mediators of inflammation and inhibitors of hepatic regeneration. The results of preclinical studies indicate that treatment of pigs with experimentally-induced fulminant hepatic failure is safe and effective in extending survival time and arresting brain swelling. In addition, the amount of ammonia, aromatic amino acids, IL6, TNFα and C3a removed during the 6-h treatment in the present study was higher by 34% to 175% than the total plasma content of those substances at the start of therapy. [ABSTRACT FROM AUTHOR]

A three-valve pulsatile tubular pump was used in 10 pigs weighing 9.9 ± 0.3 kg, connected to a neonatal hemofiltration (HF) circuit to analyze the parameters to determine the ultrafiltration effectiveness for venovenous continuous renal replacement therapy. Forty 30-min periods were studied to analyze the influence of the catheter diameter, purification technique (HF or hemodiafiltration), pump pulsation frequency, percentage time in diastole, percentage time in diastole in which the postpump valve was closed, and percentage time in systole in which the postfilter valve was closed, on ultrafiltrate volume and blood flow through the filter. A higher ultrafiltrate flow was achieved with a frequency of 60 bpm than with 30 bpm, a diastolic time of 65% of the total cycle versus 50%, and a blood flow of greater than 20 mL/min versus less than 20 mL/min. The ultrafiltrate flow increases in relation to the blood flow, the frequency of the pump, and the diastolic time. [ABSTRACT FROM AUTHOR]

Convective treatments (high-flux hemodialysis (HD), hemodiafiltration and hemofiltration) are characterized by enhanced removal of middle and large molecular weight solutes compared with conventional low-flux HD. As these molecules are claimed to play an important role in the genesis of many complications of chronic HD, the availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of HD patients. Here we will critically review the most important published studies comparing convective treatments with low-flux HD on chronic morbidity, preservation of residual renal function, and long-term survival. [ABSTRACT FROM AUTHOR]

Acute hypotension is a frequent hemodialysis complication. Intratreatment vascular instability is a multifactorial process in which procedure-related and patient-related factors may influence the decrease in plasma volume and induce an impairment of cardiovascular regulatory mechanisms. Identification of the most susceptible patients and of the various risk factors may contribute to significantly improve cardiovascular stability during dialysis. In some high-risk patients, monitoring and biofeedback of the various hemodynamic variables, together with an extensive use of convection, can prevent the appearance of symptomatic hypotension and help in averting its onset. [ABSTRACT FROM AUTHOR]

When introduced in the 1970s, convective dialysis therapies were considered an attractive alternative to hemodialysis (HD), but technical and economical limitations prevented wide clinical application. Today, these therapies (i.e. hemofiltration and hemodiafiltration) are receiving renewed interest from the renal community. The main reason is the disappointment with current chronic dialysis therapy, which despite continuous integration of technical and pharmaceutical progress, has not provided significantly improved survival. The recent HEMO study showed that HD, even when administered at high dose and with high-flux membranes, has reached the limit of benefit for a representative dialysis population. At the same time there is new evidence supporting convective therapies. The extended range of solutes that is removed by convection as opposed to diffusion includes many molecules associated with uremic symptoms and complications. The hemodynamic stability characteristic of convective therapies is confirmed also in comparison with modern HD. Observational data indicates a survival benefit for patients treated with large volumes of convection. Continuously applied convective therapies are the preferred choice in severe cases of acute renal failure, and new membrane development may take these therapies to new applications of blood purification in the intensive care unit. [ABSTRACT FROM AUTHOR]

In critically ill patients with acute renal failure and continuous renal replacement therapy (CRRT), the elimination of antimycotic agents is influenced by many factors; these include not only the nature and dose of the renal replacement therapy but also the properties of the medicine. High protein binding, a high molecular weight and little or no renal elimination even in subjects with normal renal function suggest that a substance is not eliminated by CRRT. This is the case with amphotericin B, caspofungin, itraconazole and voriconazole, but not with fluconazole. In the case of fluconazole, an increase in dose than that used in patients with normal renal function may be required according to the nature and dose of CRRT, because the clearance of fluconazole can be substantially higher under CRRT than in subjects with normal renal function. Daily doses of 800 mg or more may be necessary. As a result of the diverse influences on elimination in patients receiving CRRT, the determination of fluconazole through concentrations cannot be dispensed with, in order to avoid underdosing and a failure of the antimycotic therapy. [ABSTRACT FROM AUTHOR]

To introduce and investigate the application, efficacy, and potential clinical complications of a continuous renal replacement therapy (CRRT) in a feline acute renal failure (ARF) patient.A domestic short-haired cat presented for continued management of ARF of a presumed toxic etiology. Severe azotemia and uremic complications had been identified on initial presentation to a local urgent care facility, and the cat had been referred for renal replacement therapy following approximately 9 hours of conservative management. Continuous venovenous hemodiafiltration was performed over an approximately 25-hour period, and a significant resolution of the cat's uremic derangements was obtained. Major complications included significant hypothermia and a single episode of hypocalcemia associated with utilization of citrate anticoagulation. All complications identified were readily managed. Following hospital discharge, long-term medical support was not required, and no evidence of significant illness was noted 6 months following therapy.CRRT represents a collection of extracorporeal blood purification techniques that utilize extended treatment periods for gradual, physiologically balanced correction of uremic toxicity. These therapies demonstrate significant promise in the treatment of ARF cats with actual or potential hemodynamic compromise, and prior advances in therapeutic administration have made these techniques readily accessible within the intensive care unit setting. [ABSTRACT FROM AUTHOR]

Although hemodialysis remains the primary treatment modality for the management of patients with end-stage renal disease (ESRD), its clearance of relatively large-sized uremic toxins is limited due to its primarily diffusive nature. Moreover, recent studies suggesting conventional, diffusion-based therapies may be limited in their ability to influence outcome in ESRD patients indicate the need for alternative chronic dialysis approaches, an example of which is convective therapies. In an analogous manner, a reassessment of the dialytic management of critically ill patients with acute renal failure (ARF) has also occurred recently based on clinical evidence that high-dose continuous hemofiltration improves survival. These recent clinical results suggest the utilization of convective therapies in both ARF and ESRD will increase in the future. This article provides a review of convective therapies, with an initial discussion of the determinants of convective solute removal. This is followed by a comprehensive overview of the manner in which hemofiltration and hemodiafiltration are applied clinically. [ABSTRACT FROM AUTHOR]

Increasing attention is being paid to quantifying the dose of dialysis prescribed and delivered to critically ill patients with acute renal failure (ARF). Recent trials in both the intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) realms have suggested that a direct relationship between dose and survival exists for both of these therapies. The purpose of this review, first, is to analyze critically the above-mentioned dose/outcome studies in acute dialysis. Subsequently, the factors influencing dose prescription and delivery are discussed, with the focus on continuous venovenous hemofiltration (CVVH). Specifically, differences between postdilution and predilution CVVH will be highlighted, and the importance of blood flow rate in dose delivery for these therapies will be discussed. [ABSTRACT FROM AUTHOR]

Background: DALI (direct adsorption of lipids) is the first LDL-apheresis technique able to adsorb low-density lipoprotein (LDL) and lipoproteina) directly from whole blood. In the standard procedure, acid citrate dextrose (ACD-A) is used as anticoagulation and the adsorber is rinsed with a specially manufactured priming solution (PS). Using neutral trisodium citrate (TSC) instead of ACD-A might improve the acid-base homeostasis during DALI apheresis; moreover, applying wholesale hemofiltration solutions instead of the special PS might avoid the use of two separate solutions for both priming before and reinfusion after the treatment, thus simplifiying the procedure. Aim: The present study was performed to test the effect of neutral (TSC) anticoagulation and of two different commercially available hemofiltration (HF) priming solutions on the efficacy and biocompatibility of DALI apheresis. Materials and Methods: Five hypercholesterolemic chronic DALI patients were treated prospectively, on a weekly or biweekly basis, 3 times each by standard DALI-apheresis (A), by DALI using 4% TSC and bicarbonate-buffered HF BIC35-210 priming (B), as well as by DALI using 4% TSC and lactate-buffered HF 23 priming (C). After the sessions, the extracorporeal circuit (ECC) was rinsed with saline in study arm A and with the corresponding HF solutions in study arms B and C, respectively. Results: Acute LDL-cholesterol reductions in the study arms A/B/C averaged 64/64/63%, for Lp(a) 62/64/62%, respectively (n=15). Clinically, all sessions were essentially uneventful and no clots were observed in the ECC. No major differences were found between the 3 study arms with respect to biocompatibility (elastase, C3a, thrombin-antithrombin, β-thromboglobulin, bradykinin). Conclusion: DALI apheresis using TSC anticoagulation and HF solutions for both priming and reinfusion proved to be as safe and effective as the standard DALI apheresis. These modifications, however, further simplify the procedure. [ABSTRACT FROM AUTHOR]

Extracorporeal support has been advocated for patients with acute and chronic liver failure. Patients with acute liver failure and those with decompensated cirrhosis can be broadly divided into two groups. The first group comprises those with acute liver failure and ongoing hepatic necrosis, and the second, those with long-standing chronic decompensation admitted with one or more complications of liver failure, such as encephalopathy without any evidence of a precipitating factor or accompanying acute deterioration of liver function. This second group includes patients with acute liver failure, where the insult causing hepatic necrosis has been resolved, and those patients with chronic decompensation who suffer another insult to the liver, such as acute infection or variceal hemorrhage that causes further liver injury in the setting of multiorgan failure. These two groups are likely to have different outcomes and may need to be managed differently. In the first group, liver transplantation is the only possible long-term therapeutic option, whereas in the second group, other possibilities such as extracorporeal liver support systems and/or medical therapy may allow these patients to return to their previous state before the acute insult. Over time extracorporeal support has expanded from simple peritoneal dialysis and hemodialysis, to the development of circuits designed primarily to remove both water and lipid-soluble toxins and, in addition, bioartificial devices to provide replacement synthetic hepatic function. Because many of the patients with an acute liver insult have ongoing chronic liver disease and develop hepatorenal syndrome, this group of patients has been targeted by several groups to study the role of liver support systems. [ABSTRACT FROM AUTHOR]

We designed a membrane culture unit on which 2 different cell lines were co-cultured to achieve selective and active transport of toxins. Hepatic origin HepG2 and renal origin multidrug-resistant gene-transduced proximal convoluted tubular cell line (PCTL-MDR) were cultured on the opposite sides of an expanded polytetrafluoroethylene membrane. The activity of testosterone hydroxylation by original HepG2 was very low; however, the cytochrome P450 (CYP) 3A4–transduced recombinant HepG2 metabolized the substrate efficiently. Testosterone added into the outer medium was hydrolyzed by HepG2, and the metabolites were preferentially transported to the inner medium by PCTL-MDR. [3 H]-digoxin and [ 14 C]-inulin were added to the outer medium; the digoxin was transported from the outer to inner space through the cell monolayer but the inulin was not, suggesting that the membrane actively transported only the substrate of the channel protein, MDR. The cells were irradiated (10 Gy) to prevent a membrane leak due to overgrowth. The irradiation did not induce apoptosis but resulted in long-lasting membrane function without leakage. The membrane co-cultured with hepatic and renal origin cells will enable a novel hemofiltration system with selective and active transport activities. [ABSTRACT FROM AUTHOR]

Many kinds of blood purifying technologies have been applied to the treatment of critically ill patients since 1979 when plasma exchange with hollow fiber membranes was developed. These technologies have been applied not only to the removal of toxic substances, but also to the treatment of objective diseases and the removal of the factors relating to the associated inflammation. This article briefly summarizes these methods and their efficacies for critically ill patients, especially those with severe sepsis. Attempts have been made to remove endotoxin, the main cause of sepsis from the circulation, using polymyxin B-immobilized fiber, charcoal hemoperfusion, and plasma or whole blood exchange. Attempts have also been made to remove proinflammatory cytokines, eicosanoids, and coagulative factors from the circulation in the human body. Continuous hemofiltration or hemodiafiltration is representative technology. The efficacy of these methods has been established, but several issues remain unresolved. All methods of the treatment of severe sepsis are discussed with reference to treatment indications, efficacy, and outcome parameters. In particular, the clinical results of endotoxin removal with polymyxin B-immobilized fiber are summarized in this article. [ABSTRACT FROM AUTHOR]

Sespis, the leading cause of mortality in intensive care units, is a complex series of interrelated effects caused by the overproduction of multiple mediators and their unrestrained biological activity. Both proinflammatory and antiinflammatory mediators participate in the high complexity of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as therapeutic options and as tools for blood purification in sepsis. Along these lines and in order to achieve higher clearances and mass removal rates, we studied the effects of plasmafiltration coupled with adsorption and provided in vitro and in vivo evidence that adsoprtion of multiple cytokines, activated complement components, and lipid mediators such as the platelet-activating factor occurs. We also showed that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics, reduced norepinephrine dose, and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma, as a modular device to conventional hemofiltration, may pave the way to innovative approaches in the extracorporeal treatment of septic patients. [ABSTRACT FROM AUTHOR]

Abstract: To study gas exchange in the filter during continuous venovenous hemodiafiltration (CVVHDF), an air-tight heated mixing chamber with adjustable CO2 supply was constructed and connected to a CVVHDF monitor. Bicarbonate-free crystalloid (Part 1) and packed red blood cell (Part 2) solutions were circulated at 150 ml · min-1. Gas exchange expressed as pre-postfilter difference in CO2 and O2 contents was measured at different CVVHDF settings and temperatures of circulating and dialysis solutions. Ultrafiltration was most efficacious for CO2 removal (at 1,000 ml · h-1 ultrafiltration CO2 losses reached 13% of prefilter CO2 content). Addition of dialysis (1,000 ml · h-1) increased CO2 loss to 17% and at maximal parameters (filtration 3,000 ml · h-1, dialysis 2,500 ml · h-1), the loss of CO2 amounted to 35% of prefilter content. Temperature changes of circulating and/or dialysis fluids had no significant impact on CO2 losses. The O2 exchange during CVVHDF was negligible. Currently used CVVHDF is only marginally effective in CO2 removal. Higher volume ultrafiltration combined with dialysis can be expected to reach clinical significance. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the impact of the addition of calcium to bicarbonate solutions for continuous renal replacement therapy (CRRT). We tested single bag (bicarbonate and calcium mixed 24 h before testing) and double bag solutions (mixed immediately before) with and without the addition of 4 mEq/L of acetate. Prescribed calcium varied from 0 to 5 mEq/L. All test solutions containing calcium showed crystallization at light microscopy. The double bag solutions decreased but did not prevent crystallization. The addition of acetate did not interfere with crystallization. Crystallization, as measured by the weight of the crystals after filtration of the solutions, showed a significant positive correlation with the calcium deficit (prescribed minus measured) and with partial pressure of carbon dioxide. The measured level of calcium was lower than expected and correlated with crystallization. Our results suggest that the use of bicarbonate solutions containing calcium as replacement fluids for CRRT is a potentially unsafe procedure. [ABSTRACT FROM AUTHOR]