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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.)

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.)

Background: This prospective study compared pharmacokinetics (PK) and pharmacodynamics (PD) of linezolid in patients with sepsis receiving continuous venovenous hemofiltration (CVVH) with patients receiving extended daily hemofiltration (EDH)., Methods: Patients with sepsis treated with linezolid and CVVH or EDH were included. Serial blood samples were collected and linezolid concentrations measured. PKs were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement., Results: From 20 patients, 320 blood samples were collected for PK and PD analysis. PK profiles of linezolid were best described by a 2-compartment model. PK parameters were not significantly different between EDH and CVVH groups and were associated with body weight, renal replacement therapy (RRT) duration, and sequential organ failure assessment score. Monte Carlo simulations showed poor fractional target attainment for a minimum inhibitory concentration (MIC) of 2 mg/L with standard 600 mg intravenous administration every 12 hours., Conclusions: Patients with sepsis receiving RRT exhibited variability in PK/PD parameters for linezolid. PK parameters were not significantly different between CVVH- and EDH-treated patients. Higher probability of target attainment would be achievable at a MIC of 2 mg/L in EDH patients. Higher linezolid doses should be considered for patients on RRT to achieve adequate blood levels., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Overseas contingency operations which occur in areas lacking medical infrastructure pose challenges to the stabilization and transportation of critically ill patients. In particular, metabolic derangements resulting from acute kidney injury (AKI) make long-distance aeromedical evacuation risky. Here, we report the first modern use of in-flight continuous veno-venous hemofiltration (CVVH) for intercontinental aeromedical evacuation. Hospital and transport records were reviewed for a 31-yr-old male active duty service member who sustained 40% total body surface area full thickness burns after high-voltage electrical exposure in the southern Philippines. He was evacuated to the Burns Centre at Singapore General Hospital, where CVVH was initiated for anuric AKI secondary to rhabdomyolysis. The United States Army Institute of Surgical Research (USAISR) Burn Flight Team transported the patient to the USAISR Burn Center at Fort Sam Houston, TX, USA. CVVH was performed in-flight for 15 h out of 19.5 h of total flight time. CVVH settings were maintained as follows: blood flow 250 mL/min; replacement fluid rate 3,500 mL/h; and no ultra-filtrate removal. Unfractionated heparin at 500 units/h was utilized for regional anticoagulation. No filter clotting was encountered; a planned filter change was performed during a midway refueling stop. Pre-flight hyperkalemia was managed with low-potassium replacement fluid. No fluid was removed in the setting of large wound insensible losses. The patient remained hemodynamically stable and required no vasoactive medications. Continuous veno-venous hemofiltration can be used safely during high-altitude flight to evacuate casualties with AKI from distant contingency operations. The use of portable hemodialysis equipment in this case also proves the feasibility of deploying renal replacement therapies to more forward facilities than previously considered.

Background: Acute kidney injury is a common complication of both civilian and military trauma. The lack of dedicated resources restrict dialysis in the forward setting. We report a case of a combat polytrauma and renal failure, using continuous arteriovenous hemofiltration to clear uremia and remove volume, allowing for ventilator liberation and safe disposition., Materials and Methods: The patient presented with traumatic lower extremity injuries and abdominal wounds and developed acute post-traumatic renal failure. Using available supplies, the patient was cannulated for continuous arteriovenous hemofiltration. Aggressive fluid and electrolyte management accomplished specific goals of ventilator liberation and clearance of uremia., Results: Over 48 h, blood urea nitrogen was reduced from 101 mg/dL to 63 mg/dL. Creatinine was reduced from 8.2 mg/dL to 4.7 mg/dL. Acute respiratory distress syndrome was improved reducing P:F (PaO2:FiO2) ratio from 142 to 210. The patient was extubated and transferred safely., Conclusions: The ability to perform acute dialysis can be lifesaving. Although resource constrained, we created a dialysis system in the forward environment with a filter and universally available equipment. This represents the first described use of continuous arteriovenous hemofiltration at the NATO Role 3 hospital in Afghanistan. This technique represents another potential tool for deployed trauma teams to improve care., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram., Methods: This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h., Results: The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2)  mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5)  mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013)., Conclusions: By incorporating CVVH intensity into the CIV dosing nomogram, the majority of patients achieved therapeutic concentrations at 24 h and maintained them within range at 48 and 72 h. Additional studies are required to validate this nomogram before widespread implementation may be considered., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The heparin requirement for coupled plasma filtration adsorption (CPFA) is usually high. Heparin administration often cannot be adherent to prescription, leading to a premature clotting of circuit and an insufficient volume of treated plasma. Regional citrate anticoagulation (RCA) could be an attractive alternative; however, no data are available on citrate pharmacokinetics at high levels of circuit citratemia., Methods: Fifteen septic shock patients with acute kidney injury undergoing CPFA with RCA at target circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure predilution (CPFA-HF predilution group, n = 5 patients), or predilution haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients). Citrate pharmacokinetics was carried out through its determination in systemic and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h., Results: The systemic concentrations of citrate in the CPFA-HF predilution group significantly increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h), whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving coefficients of citrate were near the unit in all three groups and unrelated to blood and infusion flow rates in predilution. However, the amount of citrate removed by effluent was ∼40% for the CPFA-HF predilution group and reached 60% for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05). As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to 20 mL/kg/day) was not significantly different among the groups., Conclusions: These results demonstrated that in refractory septic shock patients on CPFA at circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were the best dialysis modalities to maintain a normal systemic citratemia through a high rate of citrate loss in the effluent., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

A significant proportion of patients treated for acute decompensated heart failure (ADHF) suffer from worsening renal function, which is often associated with medical therapy resistance and poor outcome. In this setting, haemofiltration has been used for more than 30 years, despite inconclusive evidence for its advantages. In the last decade, a major technological advances have made available a new technique, ultrafiltration, which works at lower blood flow rates and requires only a venous access. As in a first proof-of-concept study (EUPHORIA), ultrafiltration proved to be efficacious in fluid removal in ADHF patients; this treatment was further investigated in randomized controlled trials. The RAPID-CHF trial demonstrated that ultrafiltration was more effective than medical therapy in fluid removal, even though it did not provide a greater weight loss. The UNLOAD trial thereafter showed a greater weight loss with ultrafiltration compared with diuretic therapy at 48 h after admission and a lower readmission rate at 90 days. Based on these results, the AHA/ACC and ESC guidelines consider ultrafiltration as a reasonable approach in ADHF patients with unresolved congestion notwithstanding optimal medical therapy and/or hyponatremia. However, the recently published CARRESS-HF trial would appear to challenge these recommendations as it failed to demonstrate an advantage of ultrafiltration compared with medical therapy, based on the finding of subtle clinically irrelevant changes in renal function between treatments. This review focused on the current evidence supporting the use of ultrafiltration and on a critical appraisal of the recently published CARRESS-HF trial., (© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported., Summary: A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 μg i.v. (8.2 μg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 μg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy., Conclusion: Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.

Background: Optimal management of acute kidney injury (AKI) remains controversial, particularly with respect to acutely unwell patients in the intensive care unit (ICU). This is likely to be attributable to the currently poor evidence base. Attempts to introduce guidance and consistency have been made over recent years, such as the AKI Network (AKIN) staging system and, in the UK, recommendations from the 2009 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report into AKI. We wished to ascertain how AKI is investigated and managed in intensive care units in the UK, and whether these recent initiatives have made any difference to clinical practice., Methods: This is an online survey of all general adult UK ICUs between December 2009 and May 2010., Results: One hundred and eighty-eight out of two hundred and thirty-three units (80%) started the survey; 167 (72%) completed it. Only 19.2% of respondents routinely use AKIN or Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria for diagnosis and staging of AKI. A nephrologist is never or rarely consulted about patients with AKI in over 40% of the units. Only 46.4% have 24-h access to a renal ultrasound service. Continuous venovenous haemofiltration (CVVH) is the most commonly used form of renal replacement therapy (RRT) but intermittent haemodialysis (IHD) is used infrequently. Continuous RRTs (CRRTs) are managed almost exclusively by intensivists, whereas IHD is managed predominantly by nephrologists. The most frequently used criteria for initiating RRT are hyperkalaemia, fluid overload and pH. Most units have a standard RRT protocol and 35 mL/kg/h is the most frequently prescribed dose of CVVH. Only 51% of the units assess the delivered dose of RRT., Conclusions: Considerable variation exists in the investigation and management of AKI in UK ICUs. Despite increasing recognition of the importance of AKI, few ICUs are aware of RIFLE and AKIN criteria.

A simple sample preparation method has been developed for the determination of amoxicillin in human plasma by hollow fiber centrifugal ultrafiltration (HF-CF-UF). A 400-μL plasma sample was placed directly into the HF-CF-UF device, which consisited of a slim glass tube and a U-shaped hollow fiber. After centrifugation at 1.25 × 10(3) g for 10 min, the filtrate was withdrawn from the hollow fiber and 20 µL was directly injected into the high-performance liquid chromatography (HPLC) for analysis. The calibration curve was linear over the range of 0.1-20 µg/mL (r = 0.9996) and the limit of detection was as low as 0.025 µg/mL. The average recovery and absolute recovery were 99.9% and 84.5%, respectively. Both the intra-day and inter-day precisions (relative standard deviation) were less than 3.1% for three concentrations (0.25, 2.5 and 10 µg/mL). The sample preparation process was simplified. Only after a single centrifugal ultrafiltration can the filtrate be injected directly into HPLC. The present method is simple, sensitive and accurate. It could be effective for the analysis of biological samples with high protein contents, especially for the biopharmaceutical analysis of drugs that use traditional isolation techniques for sample preparation such as the protein precipitation method.

Background: Existing systems for grading severity of acute kidney injury (AKI) rely on a change of serum creatinine concentration over a defined time interval. The rate of change in serum creatinine increases by degree of reduction in glomerular filtration rate, but is mitigated by low creatinine generation rate (CGR). Failure to appreciate variation in CGR may lead to erroneous conclusions regarding severity of AKI and distorted predictions regarding patient outcomes based on AKI severity., Methods: Cohort study of 103 patients who received continuous venovenous hemodialysis (CVVHD) over a 2-year period in a tertiary care hospital setting. Study participants entered the cohort when they were anuric, receiving a stable and uninterrupted dose of CVVHD with serum creatinine in steady state. They were followed until hospital discharge. CGR was measured based on dialyzate effluent volume and effluent creatinine concentration (prospective cohort) and via effluent volume and serum creatinine concentration (retrospective cohort)., Results: CGR (mean 10.5, range 1.7-22.4 mg/kg/day) was substantially lower in this patient population than what would be predicted from existing equations. Correlates of CGR in multivariable analysis included the length of hospitalization prior to measurement and presence of an oncologic diagnosis. Lower CGR was independently associated with in-hospital mortality in unadjusted analysis and after multivariable adjustment for measures of severity of illness., Conclusions: Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population.

Background: Reduced haemocompatibility and early filter failure during continuous venovenous haemofiltration (CVVH) can be attributed to various aspects from filter engineering to rheological problems. Still, little is known about the impact of acidaemia and hypoxaemia on the haemocompatibility of a CVVH. In a porcine model, we investigated blood and coagulation parameters, filter performance and blockage of filter capillaries to assess the impact of acidaemia and hypoxaemia on haemocompatibility., Methods: Pigs were assigned to three groups (n = 6). One group received mixed acidaemia (pH 7.2) by acid infusion (0.2 M of lactic acid and 0.2 M HCl diluted in normal saline) and low tidal volume ventilation (6-8 mL/kg(-)(1)), one group underwent an additional hypoxaemia (pH 7.2; PaO(2) < 70 mmHg) and another was treated with normal saline and normoventilation (control group; pH 7.4). To accelerate biocompatibility reactions, CVVH was operated with reinfusion of the filtrate to the venous line for 3 h based on standardized heparinization., Results: Acidaemia led to a contradictory pattern with respect to prothrombin time (prolongation), activated partial thrombin time and activated clotting time (acceleration). In comparison to normal pH homeostasis, acidaemia led to increasing activation markers such as terminal complement complex marker sC5b-9, thrombin-anti-thrombin complexes (TAT) and D-dimers. Additional hypoxaemia intensified activation with regard to TAT and complement complex marker sC5b-9. Platelet counts suffered from acidaemia and a tendency for higher rates of blocked hollow fibres was found., Conclusion: Acidaemia led to deteriorated haemocompatibility reactions to a CVVH circuit. The coagulation pattern developed towards complications for the coagulatory state.

Background: Cardiogenic dysfunction with acute renal failure (ARF) and diuretic drug resistance increases mortality after cardiac surgery with cardiopulmonary bypass (CPB) in adults. Until few years ago, intermittent renal replacement therapy (IRRT) was the only therapeutical strategy proposed to such patients. Few data are available in the literature regarding the use of continuous veno-venous haemofiltration (CVVH) in this clinical context. The aim of our observational study was to evaluate the impact of CVVH strategy on ARF in conjunction with cardiogenic shock after cardiac surgery and on its well-known associated poor outcome., Methods: During the period 2005-2006, we prospectively collected data from our database as we controlled the renal replacement therapy using CVVH (n=73). We also retrospectively collected data from our computerised database on patients who were treated with IRRT (n=68, period 2002-2003). Among CVVH-treated patients, a multivariate analysis of the data aimed to identify risk factors associated with 30-day mortality., Results: In patients who presented with ARF in conjunction with cardiogenic shock after cardiac surgery, 30-day mortality rate was 59% for the IRRT group and 42% for the CVVH group. Within the CVVH group, the logistic regression and multivariate analyses reported that some variables were associated with higher mortality risk: a score F concerning the urinary output criteria of the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification (for scores R or I: odds ratio (OR): 0.01, 95% confidence interval (95% CI): 0.02-0.59; p=0.01), plasma bilirubin (OR: 1.44, 95% CI: 1.12-1.84; p=0.04), total CVVH duration <50h over 72 h (>50h; OR: 0.009, 95% CI: 0.04-0.93; p=0.01), the need of catecholamine support (OR: 12.88, 95% CI: 1.95-84.96; p=0.01), tachycardia in the intensive care unit (ICU; OR: 1.64, 95% CI: 1.02-2.65; p=0.04), surgery duration (<300 min; OR: 0.11, 95% CI: 0.02-0.71; p=0.02) and combined cardiac surgery (OR: 7.00, 95% CI: 1.29-37.88; p=0.02)., Conclusion: In patients with ARF in conjunction with cardiogenic shock after cardiac surgery, renal replacement therapeutic strategy based on long-lasting CVVH could improve patients' outcome. The identification of risk factors associated with a poor outcome would help to better manage such patients in the ICU. Low total duration of CVVH within the first 72 h was one criteria related to poor outcome. This suggests that CVVH must be initiated as soon as possible when ARF with diuretic resistance occurs in patients after cardiac surgery and continued as long as possible for the first 3 days.

Various forms of renal replacement therapies (RRT) are available to treat acute kidney injury (AKI) after cardiac surgery. The objective of this review is to assess the incidence of postoperative AKI that necessitates the application of haemofiltration in adult patients undergoing cardiac operations with cardiopulmonary bypass (CPB), to determine the factors that influence the outcome in these patients. In addition, the review aims to assess the outcomes of postoperative early haemofiltration as compared to late intensive haemofiltration. Different forms of RRT such as intermittent haemodialysis, continuous haemofiltration, or hybrid forms which combine advantages of both are now available for application in cardiac surgery patients, and will be discussed in this article. The underlying disease, its severity and stage, the aetiology of AKI, clinical and haemodynamic status of the patient, the resources available, and different costs of therapy may all influence the choice of the RRT strategy. AKI, with its risk of uraemic complications, represents an independent risk factor for adverse outcomes in critically ill patients after cardiac surgery. Whether early initiation of RRT is associated with improved survival is unknown, and also clear guidelines on RRT durations are still lacking. In particular, it remains unclear whether haemodynamically unstable patients who develop septic shock pre- and postoperatively can benefit from early RRT initiation. In addition, it is not known whether in AKI patients undergoing cardiac surgery RRT modalities can eliminate significant amounts of clinically relevant inflammatory mediators. This review gives an update of information available in the literature on possible mechanisms underlying AKI and the recent developments in continuous renal replacement treatment modalities.

Background: Although different on-line convective removal strategies are available, there are no studies comparing the efficiency of solute removal for the three main options [post-dilution haemodiafiltration (post-HDF), pre-dilution haemodiafiltration (pre-HDF) and pre-dilution haemofiltration (pre-HF)] in parallel., Methods: In this study, we compared post-HDF (Polyflux 170), pre-HDF (Polyflux 170) and pre-HF (Polyflux 210) in 14 patients. Parallelism of the evaluation protocols consisted in applying the same blood flow, dialysis time and effective convection (22.9 +/- 1.7 versus 22.2 +/- 2.0 L, P = NS) in pre-HDF versus post-HDF, and the same blood flow and dialysis time while comparing pre-HDF and pre-HF (1:1 dilution). With pre-HF, ultrafiltration was maximized and resulted in an effective convective volume of 28.5 L. We studied water-soluble compounds (urea, creatinine, uric acid), protein-bound compounds (hippuric acid, indole acetic acid, indoxylsulfate and p-cresylsulfate) and beta(2)-microglobulin (beta(2)M)., Results: Post-HDF was superior to pre-HDF for water-soluble compounds and beta(2)M, whereas there was no difference for protein-bound compounds. Pre-HDF was superior to pre-HF for water-soluble compounds and protein-bound compounds. In contrast, removal of beta(2)M for pre-HF was higher than for pre-HDF, but it did not differ from that obtained with post-HDF., Conclusions: It is concluded that post-dilution is superior to pre-dilution HDF under conditions of similar convective volume, and that HDF is superior to HF in pre-dilution, with the exception of removal of beta(2)M. Overall, post-HDF is the most efficient convective strategy among those tested.

Background: High-volume haemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock due to its capacities to remove from blood both pro- and anti-inflammatory mediators involved in the sepsis syndrome. Adsorption properties of some haemofiltration membranes are also interesting with this indication because inflammatory mediators are caught in the membrane itself. The aim of this study was to determine the haemodynamic and immunological effects of a new haemofiltration membrane, which has enhanced adsorption properties due to a special surface treatment, allowing the adsorption of endotoxins., Methods: We compared this membrane to a standard haemofiltration membrane both in vitro and in 20 sepsis-induced pigs, randomized in two groups. One group was haemofiltered with the treated membrane and the other with the standard haemofiltration membrane during 6-h HVHF sessions., Results: At the end of the experiment, mean +/- SD crystalloids requirements (5937 +/- 1588 versus 7587 +/- 1456 ml, P = 0.026), colloids requirements (1437 +/- 320 versus 1912 +/- 538 ml, P = 0.027), lactic acidosis (pH = 7.20 +/- 0.11 versus 7.10 +/- 0.07, P = 0.026) and pulmonary arterial hypertension (MPAP = 24 +/- 7 versus 34 +/- 8 mmHg, P = 0.008) were less pronounced when HVHF was performed with the treated membrane. In addition, mean +/- SD endotoxins levels were lower in the treated membrane group after 1 hour of HVHF (1.91 +/- 1.19 versus 11.07 +/- 10.64 EU/ml, P = 0.035). Cytokines levels were not different between groups except for IL-1beta, which was slightly lower in the treated membrane group., Conclusions: The use of a membrane with enhanced adsorption properties during a 6-h HVHF session in septic pigs improves haemodynamics compared to a standard haemofiltration membrane. These results are probably due to an efficient endotoxins and cytokines adsorption. A human study using this membrane is now necessary to confirm these results.

Background: A number of medical, mostly immune-mediated conditions call for a combination therapy consisting of plasmapheresis and haemodialysis. While the two treatments are most commonly applied separately, we describe here the technical details of providing a combined 'tandem' treatment. Method. The components of a dialyzer (polysulfon membrane) and plasma filter are serially connected by a continuous arteriovenous haemofiltration (CAVH) system. In an extracorporeal circulation, using a blood pump the patient's blood is led first to the plasma filter and then into the dialyzer. The substituate connection is located behind the plasma filter and before the dialyzer. At the beginning it is obligatory to carry out an inspection of tubing system leakages. Afterwards, the system is flushed with a heparinized (5000 IE) sodium chloride solution that is removed thereafter. During the treatment, a blood flow of 150-200 ml/min is possible. In each case, the plasmafiltration and the ultrafiltration should not exceed 25% of the blood flow. The whole time, an intermittent check of blood pressure and heart rate is necessary. The total procedure does not take longer than a routine haemodialysis (3-4 h)., Results: In 82 patients we performed 483 tandem treatments during the last 16 years. None of the patients had volume disturbances caused by plasma shifts and derangements of electrolytes and acid-base balance were immediately equalized. There were no episodes of hypotension or bleeding. Back-filtration did not occur., Conclusion: Providing both haemodialysis and plasmapheresis at the same time reduces treatment time and thus, overall cost of the treatment. This retrospective analysis shows the tandem treatment to be safe and effective.

Background: The aim of our study was to evaluate whether convective (haemofiltration, Hf) and diffusive (haemodialysis, Hd) dialysis techniques induce different patterns of long- and short-term autonomic adjustments in haemodynamically stable dialysis patients., Methods: Ten haemodynamically stable Hd patients were studied. Each patient underwent a block of six Hd sessions, then was switched to six Hf. During the last session of each dialytic treatment, continuous beat to beat measurements of systolic arterial pressure (SAP) and heart rate (HR) were performed. Spectral analysis of heart rate variability (HRV) was made before and during the treatment to evaluate the modification of autonomic nervous system activity., Results: Baseline values of plasma sodium, body weight, HR and SAP were not different for the two considered methods of dialysis, while the baseline values of normalized LF were significantly higher in Hf as compared to Hd and the opposite was observed for HF powers (P < 0.001). Sodium balance and body weight loss per hour did not differ between Hd and Hf while body temperature was kept constant in all sessions. Throughout the dialytic procedures, with both techniques, SAP was constant, while HR diminished from the first hour till the end of the procedure (P < 0.05). An increase in LF (and decrease in HF) was noticed only in the case of Hd, considering normalized units (P < 0.05). These selective changes were maintained also during the recovery after the procedure., Conclusions: The spectral analysis of RR interval variability during Hd and Hf suggests a potential autonomic advantage with Hf, to be added to the well-recognized intrinsic greater haemodynamic stability.

Background: Apart from their standard applications, haemofiltration (HF) and plasmafiltration (PF) may provide helpful therapy for sepsis, multiple organ- and acute liver-failure. Some colloids cause either decreases or increases in blood cell agglomeration. We hypothesized that solutions which reduce cell aggregability may lead to both improved filter clearance and better haemocompatibility due to decreasing rates of clogged hollow fibres., Methods: Heparinized porcine blood (5 IU/ml) was used in an in vitro circuit. The filter types tested were from GAMBRO: HF66D (effective membrane surface: 0.6 m2) and PF1000N (effective membrane surface: 0.15 m2). Albumin (ALB), hydroxyethyl starch (HES) 200/0.5, HES 130/0.4, gelatin (GEL) or normal saline (0.9%) were added to the blood (n = 6/group). Recirculation systems were run for 2 h. Spontaneous haemolysis and filter resistance >420 mmHg were selected as indications of maximal flow rates. Sieving coefficients were determined for 17 parameters at the lowest and highest blood flows and filtration rate., Results: Based on the filter types used, supplementation of ALB and HES130/0.4 led to an improved filter clearance without increasing the number of clogged capillary membranes or causing impaired haemocompatibility. Sieving coefficients for most solutes were independent of volume substitute and flow rate. Haemocompatibility and filter clearance deteriorated after addition of HES200 or GEL to the blood., Conclusions: Under standardized in vitro conditions, we found that colloids which reduce cell aggregability cause improved HF- and PF-performance. This phenomenon may provide new options for higher clearances and may lead to new concepts in low dose anticoagulation.

Background: Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF)., Methods: The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized., Results: After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change., Conclusions: No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state.

Background: The risk of developing cardiovascular diseases is higher in patients on haemodialysis than in the general population. These patients may develop arrhythmias that depend on the extra- and intracellular concentrations of potassium. ECG findings, particularly the QT interval and its dispersion (QT(d)) and the QT(c) (QT interval corrected for heart rate according to Bazett's formula) and its dispersion (QT(cd)), may be direct indicators of the risk of developing arrhythmia., Methods: Our cohort comprised 28 patients who were dialysed for 3.5-4 h three times per week, first with haemodiafiltration with a constant potassium concentration (HDF) in the dialysis bath then with haemodiafiltration with variable concentrations of potassium (HDF(k)). ECGs were done at different time intervals: at the start of dialysis (T(0)), at 15 (T(15)), 45 (T(45)), 90 (T(90)) and 120 min (T(120)) after the beginning of the session, and at the end of treatment (T(end)). ECG-derived data (QT, QT(d), QT(c) and QT(cd)) were measured. At the same time points, plasma electrolytes, intra-erythrocytic potassium and the electrical membrane potential at rest (REMP) of the erythrocytic membrane were measured., Results: Plasma potassium concentration diminished more gradually in HDF(k) than in HDF, the difference being statistically significant at T(15) and T(45) (P<0.05), and T(90) (P<0.01). The intra-erythrocytic potassium concentration remained constant throughout the observation period. In both HDF and HDF(k), REMP was lower at all points after T(0) (P<0.05), but the reduction was greater and more significant in HDF than in HDF(k) at T(15) and T(120) (P<0.05). ECG revealed a statistically significant diminution in HDF(k) vs HDF in the measures of dispersion of QT and QT(c) at T(15), T(90), T(120) and T(end) (P<0.01) and of QT(cd) at T(45) (P<0.05). The mean of QT(d), adjusted for plasma potassium, increased over time in HDF with large alternate mean increase and decrease peaks and error intervals. In HDF(k), instead, there was a progressive and constant diminution with minor error intervals. QT(cd) adjusted for plasma potassium had the same trend. A marked difference was found between the final values in standard HDF and those in HDF(k)., Conclusions: HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.

Background: An important advantage of convective therapies is improved vascular reactivity. However, it is not well known whether the vascular response during convective therapies remains superior when compared to haemodialysis (HD) with an adjusted temperature of the dialysate. It has also been suggested that convective therapies may impair small electrolyte removal through an effect on the Donnan equilibrium. In the present study, we compared the haemodynamic response and small electrolyte removal between pre-dilution on-line haemofiltration (HF) and HD procedures., Methods: Cardiac output (CO), central blood volume (CBV) and peripheral vascular resistance (PVR) were assessed, using the saline dilution technique, in 12 stable patients during HF and HD with two different temperatures of the dialysate [36.5 and 35.5 degrees C (HD(36.5) and HD(35.5))]. Balances for sodium, potassium, calcium and conductivity were assessed using total dialysate/filtrate collections. Target filtration volume for HF was 1.2 times body weight. The temperature of the infusate was 36.5 degrees C., Results: The change (Delta) in CBV was less during HD with a dialysate temperature of 35.5 degrees C (-0.03+/-0.14 l; P<0.05) compared to HF (-0.16+/-0.05 l) and HD(36.5) (-0.11+/-0.14 l), but the other haemodynamic parameters did not differ between the studied techniques. DeltaPVR was significantly related to DeltaCBV (r = -0.46; P<0.01), whereas DeltaCBV was related to ultrafiltration rate (r = -0.34; P = 0.05). DeltaCO was related to DeltaCBV (r = 0.62; P<0.001). Solute balances did not differ between HF and HD., Conclusion: Using the saline dilution method, no difference in the change in CO and PVR was observed between on-line HF vs HD(36.5) and HD(35.5). Only CBV declined to a significantly lesser degree during HD(35.5), although absolute differences were small. Changes in the other haemodynamic variables appeared more dependent upon the degree and rapidity of fluid removal than upon the treatment modality. No difference in small electrolyte balance was observed between HF and HD, suggesting that ionic removal is not impaired during on-line HF.

Background: A number of haemodialysis studies have demonstrated beneficial effects of cooler dialysates on global haemodynamics in chronic dialysis patients. However, the effects of continuous venovenous haemofiltration (CVVH)-induced cooling on regional perfusion and energy metabolism in critically ill septic patients have not been well defined., Methods: Nine septic mechanically ventilated patients (age 40-69 years) were investigated during CVVH (ultrafiltration 30-35 ml/kg/h). Baseline data (=WARM 1) were collected when core temperature (Tc) was >37.5 degrees C; the second data set (=COLD) was obtained after 120 min of 'cooling'; and a third set (=WARM 2) was obtained after 120 min of 'rewarming'. During 'warming' (WARM 1 and 2, respectively), both substitution fluids (SFs) and 'returned' blood (RB) were warmed (37 degrees C), whereas during 'cooling', the SFs were at 20 degrees C and RB was not warmed. We measured hepatic venous (HV) haemoglobin oxygen saturation (ShvO(2)), blood gases, lactate and pyruvate. Gastric mucosal PCO(2) (PgmCO(2)) was measured by air tonometry and the gastric mucosal - arterial PCO(2) difference (PCO(2) gap) was calculated. Haemodynamic monitoring was performed with arterial and pulmonary arterial thermodilution catheters., Results: Tcs were significantly altered [WARM 1, 37.9 degrees C (37.6, 38.3); COLD, 36.8 degrees C (36.3, 37.1); WARM 2, 37.5 degrees C (37.0, 38.0); P<0.001; data are median, 25th and 75th percentiles, respectively]. Systemic vascular resistance significantly increased during cooling. As a result, mean arterial pressure increased. Cooling was associated with significant decreases in heart rate, cardiac output, systemic oxygen delivery and consumption. ShvO(2) did not change [WARM 1, 51.0% (44.0, 59.5); COLD, 49.0% (42.0, 58.0); WARM 2, 51.0% (46.0, 57.0); P = NS]. The splanchnic oxygen extraction ratio, the HV lactate to pyruvate ratio, HV acid base status and PCO(2) gap remained unchanged., Conclusion: Mild core cooling induced by CVVH may not affect hepatosplanchnic oxygen and energy balance in septic critically ill patients, even though it affects global haemodynamics.

Background: Treatment with trisodium citrate provides an effective means of regional anticoagulation during continuous renal replacement therapy (CRRT). We evaluated the efficacy, safety and cost of a regional citrate anticoagulation protocol using commercial solutions in 17 critically ill patients treated with continuous venovenous haemodiafiltration (CVVHDF). We performed a total of 22 sessions., Methods: We delivered an A.C.D-A(541(R)) solution containing 112.9 mmol/l disodium citrate (3.22%) at a median rate of 260 (190-280) ml/h via the pre-filter port of a COBE PRISMA with an AN-69 dialyser, while adjusting the rate to maintain post-filtered ionized calcium (iCa(2+)) between 0.25 and 0.4 mmol/l. Plasma iCa(2+) was maintained at >1.1 mmol/l by infusion of calcium chloride at a median rate of 1.70 (1.36-2.27) mmol/h. The dialysate was easily modified according to the acid-base status of each patient. Both replacement and dialysate solutions were delivered at 1200 ml/h. Each session was scheduled for 48 h and biological parameters were assessed every 6 h., Results: The mean dialyser survival was 39 +/- 11 h (median 41.5 h; range 13-48 h). We observed dialyser clotting in four cases (18%). There were no bleeding events or modifications of coagulation parameters. The citrate solution, replacement solution and dialysate were obtained as commercial products. Both the replacement and dialysate solutions contained calcium. The extra cost of this technique was 25 euro;/day as compared to anticoagulation with heparin., Conclusions: We designed an efficient method of regional citrate anticoagulation for CVVHDF by using commercial solutions. The monitoring of patients was as intensive as during heparin anticoagulation for CRRT. Because of the higher cost of this method, it should be proposed only for patients with high bleeding risk.

Background: Continuous veno-venous haemofiltration (HF) with high permeability (HP) haemofilters is a novel approach in the adjuvant therapy of septic patients. HP haemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether HP-HF has an impact on peripheral blood mononuclear cell (PBMC) proliferation and whether ultrafiltrate can alter PBMC function in isolates from healthy volunteers., Methods: Twenty-eight septic patients with acute renal failure were randomly allocated to either HP-HF or conventional HF (C-HF). HP-HF was performed with a newly developed high-flux polyamide membrane (P2SH) with a nominal cut-off point of 60 kDa. For C-HF, a high-flux polyamide haemofilter (Polyflux 11S; cut-off, 30 kDa) was used., Results: Septic patients demonstrated a significantly reduced proliferation of anti-CD3-stimulated PBMCs compared to healthy controls (P = 0.016). Initiating HF led to a restoration of the PBMC proliferation in HP-HF but not in C-HF. Exposing PBMCs isolated from healthy donors to ultrafiltrates from patients with sepsis demonstrated a significant suppressive effect of HP ultrafiltrates on the anti-CD3-stimulated PBMC proliferation (P = 0.011). Ultrafiltrate from patients with sepsis who received C-HF had no impact on PBMC proliferation., Conclusion: HP-HF restores PBMC proliferation in septic patients probably by eliminating immunomodulatory mediators. HP-HF may represent a new renal replacement therapy able to modulate PBMC function in sepsis.

Background: Cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. Post-dilution haemofiltration has been reported to be a method for improving cardiovascular stability; however, the limited removal of small molecular weight solutes together with the need for high blood flow from the fistula greatly restrict the use of this treatment. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in post-dilution mode, can be administered in pre-dilution mode. A high vascular stability has also been observed for pre-dilution haemofiltration. Since the lower morbidity may be due to less sodium removal when compared with haemodialysis, it would be important to characterize the sodium transport in this kind of treatment., Methods: Nine patients underwent nine pre-dilution haemofiltration treatments (one for each patient) with on-line prepared substitution fluid., Results: As mean values, total (NaF(pw)) and ionized (NaE(pw)) plasma water sodium concentrations increased from 149.4 +/- 2.8 mEq/l to 151.1 +/- 2.4 mEq/l, and from 143.1 +/- 2.8 to 144.5 +/- 1.2 mEq/l, respectively, during the treatment, suggesting a hypotonic concentration of net ultrafiltrate. Plotting the difference between final and initial ionized plasma water concentrations (fNaE(pw) - iNaE(pw)) against the difference between initial plasma water values and ionized sodium concentration in the reinfusate (iNaE(pw) - NaE(R)), a significant negative correlation was found, with the regression line that intercepts the abscissa at the (iNaE(pw) - NaE(R)) value of 8.8 mEq/l; this means that to avoid changes in NaE(pw) in our patients, the NaE(R) should be lower than the iNaE(pw) by this amount. This is quite different from the theoretical value of approximately 4 mEq/l necessary to avoid changes in NaE(pw) during haemodialysis. The ratio between the total sodium concentration in the ultrafiltrate (NaF(uf)) and NaF(pw) (alpha) at the post-reinfusion site was 0.96 and decreased to 0.94 when NaF(pw) values at the pre-reinfusion site were considered. This last value is quite close to the theoretical alpha value of post-dilution haemofiltration., Conclusion: As for post-dilution haemofiltration, less sodium removal, compared with haemodialysis, can partly explain the improved cardiovascular stability during pre-dilution haemofiltration.

The concept of dialysis adequacy has to be widened to include medium size and large molecule removal in addition to urea kinetics. The HEMO study found a non-significant trend toward a beneficial effect on mortality of high-flux dialysis compared with low-flux dialysis. In that study, the beneficial effect of convection could have been attenuated by the fact that 'internal filtration' in high-flux haemodialysis (HD) is lower than that expected by convection in haemofiltration (HF) or haemodiafiltration (HDF). To explore the putative beneficial effect of convection, this Italian multicentre study was planned, comparing on-line convective treatments (HF and HDF) with standard, low-flux HD. The enrolled patients will be evaluated prospectively on their usual treatment for 2 months (baseline period) and subsequently randomized to continue either with low-flux HD (50%) or to start on-line convective treatment (50%), HF or HDF according to a 1:1 ratio. The primary end point of the study will be cardiovascular stability and blood pressure control. As secondary aims of the study, the impact on symptoms, morbidity and mortality will be assessed. Feasibility and patient compliance during HF and HDF treatments will also be evaluated. The experimental phase of the study, of at least 2 years, is divided into a 3-month adaptation period and a subsequent evaluation period. A recruitment period of 1 year is planned. The study design has adequate power to detect an absolute reduction of 3% hypotensive episodes with the experimental convective treatments compared with standard low-flux HD.

The cornerstone of renal replacement therapy in critically ill patients with acute renal failure (ARF) in our hospital, was intermittent bicarbonate dialysis with synthetic membranes, prescribed daily for anuric patients. Filling of the extracorporeal circuit with 5% human albumin or saline solution before the start of dialysis, as well as hypernatraemic dialysis with profiling, lower dialysate temperature and higher ionized calcium concentration have been used to prevent harmful hypotensive episodes either at the start or during dialysis. Continuous renal replacement therapy (CRRT) in adults was used primarily for anuric, hypotensive patients who might not tolerate standard haemodialysis. All newborns and infants in whom peritoneal dialysis was not possible were treated by continuous procedures. Sustained low efficiency dialysis (SLED) or extended daily dialysis (EDD) were an acceptable compromise between intermitent haemodialysis and CRRT. However, in our opinion, the most promising approach to intensive care unit (ICU) patients with ARF would be the combination of CRRT in the anuric patient followed by intermittent daily dialysis thereafter. Although the mortality rate of ARF patients was as high as 88% in adults and 73% in small children due to the lack of reliable criteria for the selection of patients with poor or good prognosis, aggressive treatment for all patients who needed dialysis was recommended recently. Apheresis has dramatically improved the prognosis and outcome in patients with myasthenia gravis, Guillain-Barré syndrome, Goodpasture syndrome and thrombotic thrombocytopenic purpura. The mortality rate of patients with septic shock and fulminant hepatic failure was still very high, and the role of apheresis and dialysis, in spite of some encouraging results, remains controversial.

Background: In continuous venovenous haemofiltration (CVVH), high ultrafiltration rates provide survival benefits in acute renal failure. This study measured clearances obtained at ultrafiltration rates of up to 4.5 l/h., Methods: Clearances of small solutes (urea, creatinine, phosphate and urate) and of beta(2)-microglobulin (beta(2)-M) were measured during CVVH. Five preset Multiflow-100 (M-100) and five HF1000 hollow-fibre filters were compared. For the M-100, clearances obtained by haemofiltration were compared with those obtained by haemodiafiltration at similar total effluent rates from a previous study., Results: For small solutes, the effluent to plasma ratio (E/P) remained close to 1.0 at all ultrafiltration rates; filter clearances were thus equal to Quf for both filters. Increasing Quf from 1.0 to 4.5 l/h did not significantly modify E/P. Convective clearances of beta(2)-M were lower than those obtained for small solutes. For the M-100, average beta(2)-M E/P was 0.62+/-0.10 and did not significantly change while increasing Quf. For the HF1000, average beta(2)-M E/P were significantly lower compared with the M-100 (0.42+/-0.09 at 1.0 l/h) and decreased progressively to 0.26+/-0.06 while increasing Quf to 4.5 l/h. With pre-dilution, progressive decreases in clearances delivered to patients were observed reaching 40% at a Quf rate of 4.5 l/h. There was no clinically significant adsorption of beta(2)-M. For the M-100, at similar total effluent flow rates, clearances delivered to patients using haemodiafiltration were significantly higher for small solutes but lower for beta(2)-M in comparison to haemofiltration only., Conclusions: Filter clearance for small solutes equalled Quf at evaluated rates. At high ultrafiltration rates there was significant loss of clearances with pre-dilution. At similar total effluent rates with the use of pre-dilution, haemodiafiltration is superior to haemofiltration for small solute clearance but inferior for beta(2)-M.

Background: Thrice-weekly haemofiltration affords excellent outcome when it is used to treat chronic renal failure patients. Daily haemofiltration (DHF) has recently been proposed as a more intensive therapy option, but the total ultrafiltration or exchange volume (replacement volume plus net ultrafiltration volume) requirements for adequate solute clearances during this novel therapy are unknown., Methods: We calculated theoretical solute kinetic profiles during six times per week DHF for comparison with those during thrice-weekly haemodialysis using a high-flux dialyser (HFHD) or during continuous ambulatory peritoneal dialysis (CAPD). HFHD and CAPD were chosen for comparison because K/DOQI guidelines have defined adequate treatment doses for these therapies. Steady-state concentrations were calculated using a two-compartment model of an anuric patient with 35 l of total body water for five solutes: urea, creatinine, vitamin B(12), inulin and beta(2)-microglobulin. Solute distribution volumes and generation rates were taken from the literature, and excess fluid (1 l/day) was assumed to accumulate in and be removed from the extracellular fluid compartment. Theoretical predictions of solute clearance were compared for a 15-l exchange volume/session during DHF, urea Kt/V of 3.6/week during HFHD and urea Kt/V of 2.0/week during CAPD as solute-specific values of the equivalent renal clearance (EKR) and standard Kt/V (stdKt/V) recently defined by Gotch. Additional comparisons of solute clearances were performed between DHF and other daily therapies including six times per week short daily haemodialysis (SDHD) and six times per week nocturnal haemodialysis (NHD)., Results: The calculated results predict that: (i) urea clearance during DHF with an exchange volume of 90 l/week (6x15 l) is equivalent to those during HFHD and CAPD based on urea stdKt/V; and (ii) middle molecule clearances during DHF exceed those achieved during HFHD and CAPD based on either EKR or stdKt/V. As expected, DHF therapy was inferior regarding the clearance of urea and other small solutes to SDHD and NHD; however, DHF therapy was superior to SDHD regarding the clearance of larger middle molecules, approaching the clearances achieved by NHD., Conclusions: We predict that an exchange volume of approximately 40% of total body water (15/35 l=43%) per session will provide adequate clearance of small solutes and substantial clearance of middle molecules during six times per week DHF therapy. These theoretical predictions require clinical validation.

Objectives: The pharmacokinetics of lipid-formulated amphotericin B (AMB), and of AMB that has dissociated from its lipid moiety and bound to lipoproteins in plasma, were separately determined in critically ill patients., Patients and Methods: Eleven patients required continuous veno-venous haemofiltration (CVVH). Five of them were treated with liposomal AMB (AmBisome) and seven with AMB colloidal dispersion (Amphocil). Six of the critically ill were not undergoing CVVH (three of them treated with liposomal AMB and three with AMB colloidal dispersion)., Results: Significant amounts of AMB are liberated from liposomes or colloidal dispersion during circulation in plasma, where pharmacokinetics mimic that of AMB deoxycholate. Elimination of the remaining lipid-formulated fraction is different and differentially affected by CVVH. Plasma levels of lipid-formulated AMB were significantly higher in patients treated with liposomal AMB than in those treated with AMB colloidal dispersion; clearance of liposomal AMB is enhanced by haemofiltration, whereas elimination of AMB colloidal dispersion is not significantly affected., Conclusions: The pharmacokinetics of AMB that has been liberated from its lipid moiety is similar under treatment with either liposomal AMB or AMB colloidal dispersion. Since no significant influence of haemofiltration on the pharmacokinetics of liberated AMB has been found, a standard dose of lipid-formulated AMB can be recommended for patients on haemofiltration.

Published recommendations for the optimal dosing regimen of ceftazidime in critically ill patients with continuous venovenous haemofiltration (CVVH) differ. The aim of this prospective study was to analyse the pharmacokinetic and pharmacodynamic parameters of ceftazidime during CVVH with a high-flux polysulphone membrane, and derive a dosage recommendation. Twelve critically ill patients (five female, seven male) with acute renal failure undergoing CVVH using a 0.7 m(2) polysulphone high-flux membrane were investigated. All patients received ceftazidime 2 g i.v. q8h. Peak ceftazidime concentrations were 58.2 +/- 11.6 mg/L, with trough concentrations 14.0 +/- 3.2 mg/L at the arterial port. The elimination half-life, haemofiltration clearance, volume of distribution and total removal were 4.3 +/- 0.6 h, 32.1 +/- 7.9 mL/min, 36.4 +/- 6.4 L and 74.5 +/- 6.5%, respectively. Based on these pharmacokinetic parameters and that maximal killing is at 4 x MIC we recommend at least ceftazidime 2 g i.v. q8h.

The elimination of the piperacillin/tazobactam combination was studied in six patients with acute renal failure undergoing either continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) at 1 L/h and 2 L/h for 12 h. Piperacillin 4 g/tazobactam 0.5 g was given iv on three successive treatment periods and their concentrations in plasma, ultrafiltrate/dialysate and urine were determined for 12 h after each dose. The elimination half-life of piperacillin during CVVH (7.7 +/- 2.3 h; mean +/- s.d.) was significantly longer than during CVVHDF 1 L/h (6.7 +/- 1.9 h) or 2 L/h (6.1 +/- 2.0 h) (P< 0.05). Corresponding values for tazobactam were 13.9 +/- 3.9, 11.6 +/- 3.3 and 9.4 +/- 2.4 h, respectively (P< 0.05). Total piperacillin clearance during CVVH (3.89 +/- 1.23 L/h) was significantly lower than during CVVHDF 1 L/h (5.06 +/- 1.68 L/h) or 2 L/h (5.48 +/- 2.11 L/h) (P< 0.05). The corresponding tazobactam clearance values were 2.42 +/- 0.75, 3.13 +/- 0.66 and 3.75 +/- 1.43 L/h, respectively. The mean 12 h elimination of piperacillin and tazobactam in ultrafiltrate/dialysate was 29% and 37% during CVVH, 42% and 57% during CVVHDF (1 L/h), and 46% and 69% during CVVHDF (2 L/h). We recommend 8 hourly dosing of patients with renal failure on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.

Background: The potential superiority of various renal replacement treatment modalities consisting largely of convective mass transfer as opposed to primarily diffusive mass transfer, is still a matter of debate. The objective of the present study was to evaluate acute and long-term clinical effects of varying degrees of convection and diffusion in a group of 24 clinically stable patients with end-stage renal disease., Methods: The patients were prospectively assigned to three consecutive treatment schedules of 6 months each: phase I (HF1) (on-line predilution haemofiltration)-->phase II (HD) (high-flux haemodialysis)-->phase III (HF2; as phase I). We used the AK100/200 ULTRA monitor (Gambro), which prepares ultrapure dialysis fluid for HD and sterile, pyrogen-free substitution solution for HF. The membrane (polyamide), fluid composition, and treatment time were the same on HF and HD. The targeted equilibrated Kt/V was 1.2 for both treatment modes, creating a similar urea clearance., Results: Fifteen patients, mean age 62.8+/-8.4 years, completed the study according to the above conditions. Urea kinetics, nutritional parameters, and dry weight were similar in the three periods. The frequency of intra-treatment episodes of hypotension/patient/month was significantly lower on HF1 (1.24) and HF2 (1.27) than on HD (1.80) (P<0.04). It decreased progressively on HF1, then increased on HD, and decreased again during HF2. Patients had fewer muscular cramps on HF than on HD (P<0.03) and required significantly less saline and plasma expander during HF than HD sessions. The prevalence of inter-treatment symptoms, including fatigue and hypotension, was lower on HF than on HD (score difference P=0.04). Quality of life, determined by the Laupacis method in all three periods, showed a tendency towards improvement during the study, reaching the best values during HF2., Conclusions: HF has a progressive stabilizing haemodynamic effect, producing a more physiological cardiovascular profile than HD. This long-term effect, observed in stable patients treated under strictly identical conditions, is probably due to the mechanism of convection, and is different from the acute effect observed mainly in unstable patients.

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) results in expression of cytokines and adhesion molecules (AM) with subsequent inflammatory response. The purpose of the study was to evaluate the clinical impact of modified ultrafiltration (MUF) and its efficacy in reducing cytokines and AM following coronary artery bypass grafting (CABG) in adults., Methods: A prospective randomized study of 97 patients undergoing elective CABG was designed. Fifty patients were operated on using normothermic and 47 patients using hypothermic CPB. The normothermic group was subdivided into a group with modified ultrafiltration (n = 30) and a group without MUF (n = 20). In the hypothermic group 30 patients received MUF compared to 17 patients serving as controls. MUF was instituted after CPB for 15 min through the arterial and venous bypass circuit lines. Cytokines (IL-6, IL-8, TNF-alpha, IL-2R) and adhesion molecules (sE-selectin, sICAM-1) were measured preoperatively, pre-MUF, in the ultrafiltrate, 24 h, 48 h and 6 days after surgery by chemiluminescent enzyme immunometric assay or enzyme-linked immunosorbent assay (ELISA). Clinical parameters were collected prospectively until discharge., Results: In all patients AM and cytokines were significantly elevated after normothermic and hypothemic CPB. AM and cytokines were significantly higher in hypothermia compared to normothermia. In hypothermic CPB sE-selectin was decreased after 24 h by 37% (P < 0.0063) and by 40% (P < 0.0027) after 48 h postoperatively. ICAM-1 was reduced by 43% (P < 0.0001) after 24 h and by 60% (P < 0.0001) after 6 days. Similar results were seen in cytokines with reduction up to 60% after 24 h. Changes after 48 h were noticeable but not significant. Reduction of AM and cytokines after normothermic CPB was minimal. Neither in normothermia, nor in hypothermia has sIL-2R been effectively removed from the circulation. There were no significant differences in the clinical variables between the patients with or without MUF., Conclusion: AM and cytokines are significantly elevated after hypothermic CPB compared to normothermic CPB. MUF led to a significant reduction in cytokine and AM levels after hypothermic CPB, except for IL-2R. MUF showed minimal effect in normothermia. We conclude that MUF is an efficient way to remove cytokines and AM. However, we were unable to demonstrate any significant impact of MUF in outcome of adults after elective CABG.

Background: Sepsis is associated with enhanced cytokine production. Here, we examined the in vitro removal of plasma cytokines during continuous plasmafiltration coupled with sorbent adsorption., Methods: Proinflammatory (tumour necrosis factor-alpha, interleukins-1, -8) and anti-inflammatory (interleukin 1 receptor antagonist, soluble tumour necrosis factor receptor type I and II) cytokines in whole blood spiked with Escherichia coli endotoxin were determined during 2-h recirculation in the ultrafiltrate (condition A), plasma filtrate (condition B), before and after different sorbents (of the Amberlite-, Amberchrome- Ambersorb -type and charcoal). We studied the maximal adsorbing capacity, the 1% leakage test for cytokines and C3a des Arg and the adsorption of complement-dependent leukocyte chemiluminescence. Plasma proteins eluted from the resins were examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting with an anti-human alpha2-macroglobulin., Results: In condition B, we observed a 40- and 121-fold % increase (vs condition A) in the removed mass and clearance of tumour necrosis factor-alpha. For all other cytokines, the removed mass and the clearance increased from 2.3- up to 6-fold. The Amberchrome but not the Amberlite or Ambersorb resins could remove the highest amount of cytokines and could reduce complement-dependent chemiluminescence. Two protein bands of approximately 400,000 D and 200,000 D were eluted only from Amberchrome resins and immunoprecipitated by anti-human alpha2-macroglobulin and anti-human C3c antibodies, respectively., Conclusions: These studies suggest an efficient removal of cytokines in continuous plasmafiltration with sorbent adsorption. The binding of alpha2-macroglobulin, a carrier of cytokines in plasma, might be a additional mechanism in the removal of cytokines from plasma.