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Removal of cephalosporins by continuous arteriovenous ultrafiltration (CAVU) and hemofiltration (CAVH).

Cephalosporins are used with increasing frequency for sepsis treatment in patients receiving CAVU and CAVH. The different cephalosporins share the same basic molecular structure, yet they exhibit varied extent of plasma protein binding. Different amounts of the antibiotics may be removed by the ultrafiltration procedure because of these variations of physicochemical properties. We evaluated the sieving of eight new cephalosporins across the hemofilter membrane using an in vitro model. Bovine blood was perfused through polysulfone membranes at blood and ultrafiltrate flow rates of 100 and 20 ml/min respectively. Arterial plasma, venous plasma and ultrafiltrate drug concentrations were used to determine sieving coefficients. The sieving coefficients correlated well with the ultrafiltrate-arterial plasma drug concentration ratio (r = 0.679-0.972) but poorly with the extent of protein binding. Factors other than protein binding may therefore affect the drug sieving. Based on the findings, it was predicted that 0.2-21.9% of the daily cephalosporin dose may be removed by the CAVU and CAVH treatment. The need to alter drug dosages depends on the techniques of the ultrafiltration and hemofiltration procedure, the kinetics of the cephalosporins in patients, the sensitivity of the pathogen and the nature of the infection.

Animals↗

Serum ultrafiltration for the elimination of endogenous interfering substances in creatinine determination.

Serum, at neutral pH, was submitted to a simple filtration, using centrifugation in the disposable Centrisart. The ultrafiltrate was similar to serum in its creatinine content but was virtually free from proteins, including protein-bound bilirubin, haemoglobin and lipoproteins. The creatinine concentrations of anicteric serum specimens and the corresponding ultrafiltrates as determined with Jaffé and enzymic procedures show a high correlation and are convertible. With icteric sera the negative interference effect of bilirubin in a particular analytical procedure can be quantified using ultrafiltrate as the reference. It is suggested that ultrafiltration is useful in selected cases for eliminating elevated concentrations of bilirubin, haemoglobin and turbidity, which would interfere in the direct creatinine determination. Relative to the continuous flow methods with dialysis of the analyte, direct methods for creatinine are more susceptible to interference by endogenous factors like hyperbilirubinaemia, hypertriglyceridaemia and haemolysis (1). The negative interference by bilirubin is of special importance, since it interferes in some modifications of the kinetic Jaffé method (2) and in the chromogenic enzymatic method (3). As a simple alternative, we evaluated the use of serum ultrafiltrate for the accurate determination of creatinine by the Jaffé and enzymatic methods, free from interfering by the high-molecular serum matrix and compounds bound to it.

Bilirubin↗

Further investigations on serum ultrafiltrate as medium for tissue respiration in vitro.

Serum ultrafiltrate was shown to be able to sustain in vitro the oxygen consumption of various tissue slices, attaining values very close to those reached in vivo. Serum ultrafiltrate also exerted its stimulating effect on homogenate, and maintained this activity for some time, after dilution, after lyophilization and after boiling; finally it was not species-specific. Serum ultrafiltrate was also more efficient than Eagle's Minimum Essential Medium in supporting tissue respiration. Preliminary data, obtained from gel fractionating serum ultrafiltrate, suggested that the metabolic activity should be ascribed to a sum of small single effects due to the single fractions of serum ultrafiltrate.

Animals↗

Prevention of hypoxemia during dialysis by the use of sequential isolated ultrafiltration-diffusion dialysis with bicarbonate dialyzate.

Previous studies have demonstrated that hypoxemia does not occur during isolated ultrafiltration, but does occur during diffusion dialysis with acetate, whether it is performed alone or following a period of isolated ultrafiltration. To determine if the substitution of bicarbonate for acetate in dialyzate could prevent hypoxemia, we studied the effect of sequential isolated ultrafiltration-diffusion dialysis with bicarbonate on arterial oxygen concentration. There was no significant change in pO2 during isolated ultrafiltration or the subsequent period of diffusion dialysis. In addition, excess body fluid could be removed and effective dialysis achieved without marked tachycardia or fluctuation in blood pressure. We conclude that sequential isolated ultrafiltration diffusion dialysis with bicarbonate is a safe and effective way of dialyzing patients without producing hypoxemia or cardiovascular instability.

Bicarbonates↗

Hematologic studies during isolated ultrafiltration.

The effect of negative-pressure isolated ultrafiltration on leucocytes, platelets, and clotting factors was evaluated in maintenance hemodialysis patients. A significant decrease in the number of leucocytes was observed during the first 45 minutes of ultrafiltration. However, by one hour, leucocyte counts had returned to pre-ultrafiltration values. A slight, of haptoglobin, free hemoglobin, or fibrinogen after one hour of isolated ultrafiltration. Levels of fibrin degradation products and fibrin monomers similarly showed no change. Heparin administration alone had no effect on the above hematologic values. We suggest that isolated ultrafiltration, as clinically practised, has little acute effect on the coagulation system, and does not cause detectable hemolysis. The transient decrease in leucocyte count, and the modest fall in platelet count that were found are in keeping with changes previously reported to occur during hemodialysis.

Blood↗

Haemodynamics of isolated versus dialytic ultrafiltration in the unanaesthetised, non-uraemic dog.

Ten alert, non-uraemic, splenectomised dogs were subjected to isolated ultrafiltration until mean arterial pressure decreased to less than 80mmHg. On a separate occasion, in the same dogs, ultrafiltration was performed in the course of haemodialysis. Whether or not dialysate was circulated, ultrafiltration resulted in marked increases in total peripheral vascular resistance, and large increases in plasma concentrations of vasoactive hormones, including norepinephrine. Our results suggest that, in the non-uraemic dog, the haemodynamic responses to ultrafiltration during dialysis and to isolated ultrafiltration are similar.

Animals↗

Estimation of the percentage of free steroid in undiluted serum by centrifugal ultrafiltration-dialysis.

A new method is described for the estimation of the percentages of free steroids in undiluted serum or plasma. Samples were incubated with 3H-steroid and [14C]glucose, and duplicate aliquots of the mixture were subjected to centrifugal ultrafiltration through a dialysis membrane at 37 degrees C. The percentages of free estradiol, testosterone, and progesterone in serum were estimated by comparing the ratio of 3H-steroid to [14C]glucose in the ultrafiltrate with the corresponding ratio in the serum retained by the dialysis membrane. In addition to being highly reproducible, the present method affords several advantages over existing methods. The use of [14C]glucose to monitor the movement of unbound serum components obviates measurement of the ultrafiltrate volume, and because the ultrafiltrate remains in contact with the dialysis membrane, small molecular weight components are able to pass through the dialysis membrane in either direction during centrifugal ultrafiltration. This latter feature, which could be described as "isodialysis," allows the estimation of the percentage of free steroid under conditions which closely approximate the in vivo situation.

Blood Glucose↗

Measurement of ultrafiltrable calcium in serum with use of the "Worthington Ultrafree Anticonvulsant Drug Filter".

We describe a method for ultrafiltrable calcium involving the use of Worthington Ultrafree Anticonvulsant Drug Filters. When measured at 37 degrees C, with mineral oil covering the sample to prevent loss of CO2, values for ultrafiltrable calcium correlated reasonably well (r = 0.91) with those for ionized calcium as measured with an ion-selective electrode. All patients' samples with significantly high or low values for ionized calcium were identified by the ultrafiltration method, including one specimen for which the McLean-Hastings protein correction could not explain the discrepancy between ionized and total calcium. The method requires about 2 mL of serum, yields about 100 microL of protein-free ultrafiltrate, and with it any laboratory with a semi-micro calcium method can measure ultrafiltrable calcium.

Anticonvulsants↗

Sample preparation for HPLC by Centricon ultrafiltration.

Peptides and other bioactive materials can be purified from complex biological sources by reverse-phase high-performance liquid chromatography (RP-HPLC), provided the mixture is suitably prepared before injection onto an HPLC system. Ultrafiltration offers a convenient and rapid sample preparation technique with numerous advantages over alternative methods such as conventional gel filtration chromatography. We demonstrate the use of ultrafiltration as an HPLC sample preparation step in the purification of peptides bound to class I major histocompatibility complex (MHC-I) membrane proteins. When ultrafiltration was performed with a Centricon-10 ultrafiltration device, peptides were efficiently separated from the alpha (45 kDa) and beta 2m (12 kDa) chains of MHC-I proteins and could be subjected to HPLC without further treatment. Furthermore, even samples as crude as whole cell lysates or supernatants could be prepared for HPLC in a single ultrafiltration step, affording a remarkably straightforward route to the purification of biologically important peptides.

Biotechnology↗

Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs.

We previously showed a beneficial effect of hemofiltration on hemodynamics of endotoxic shock pigs. To test the hypothesis that this effect of hemofiltration is caused by convective removal of factors that adversely affect hemodynamics during endotoxemia, we infused ultrafiltrate from endotoxic shock pigs into healthy pigs. Their hemodynamics were compared with those of pigs who were infused with ultrafiltrate from healthy pigs. Twelve anesthetized and ventilated pigs were hemodynamically monitored for 150 minutes following the infusion of 2 L of ultrafiltrate from 12 donor pigs. The acceptor pigs were randomly divided into two groups; group 1 received ultrafiltrate from pigs who were hemofiltered after the infusion of 0.5 mg/kg endotoxin over 30 minutes; group 2 served as a control group, receiving ultrafiltrate from healthy donor pigs. Group 1 showed a decrease in mean arterial pressure of 28 +/- 7 mm Hg (mean +/- SEM) versus an increase of 17 +/- 3 mm Hg in group 2 (P < 0.4). Mean pulmonary artery pressure increased more in group 1 than in group 2 (9 +/- 2 mm Hg versus 1 +/- 1 mm Hg, P < .04). The decrease in cardiac output in group 1 was greater than in group 2 (3.3 +/- 0.2 L/min v 0.3 +/- 0.3 L/min, P < .02) and was due to a decrease in stroke volume. The decrease in right ventricular ejection fraction was also greater (0.15 +/- 0.02 v 0.01 +/- 0.00, P < .01). Systemic vascular resistance, right atrial pressure, right ventricular end-diastolic volume, pulmonary wedge pressure and heart rate did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children.

Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25.5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 micrograms/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

Ultrafiltration attenuates cardiopulmonary bypass-induced acute lung injury in a canine model of single-lung transplantation.

OBJECTIVE: The purpose of this study was to investigate the effects of cardiopulmonary bypass and ultrafiltration on graft function in a canine single-lung transplantation model. METHODS: Fifteen left single-lung transplantations were done in weight-mismatched canine pairs. The animals were divided into 3 groups: group 1, in which transplantation was done without cardiopulmonary bypass; group 2, in which transplantation was done with cardiopulmonary bypass and in which the cardiopulmonary bypass flow was decreased slowly with controlled pulmonary artery pressure; and group 3, in which transplantation was done with cardiopulmonary bypass and ultrafiltration. Hemodynamic parameters and lung function were monitored for 6 hours after reperfusion. The grafts were harvested for histologic studies, myeloperoxidase assay, and real-time quantitative reverse transcription-polymerase chain reaction of mRNA encoding interleukin 6. RESULTS: The hemodynamic parameters were similar among the 3 groups. In group 1 PaO2 and alveolar to arterial gradient for O2 levels were excellent throughout the 6-hour observation period, but in group 2 they progressively deteriorated. However, ultrafiltration significantly (P = .02) improved the PaO2 level in group 3. On histology, interstitial edema and polynuclear cell infiltration were most marked in group 2 and significantly worse than in groups 1 and 3. Myeloperoxidase assay and real-time quantitative reverse transcription-polymerase chain reaction showed increased myeloperoxidase activity and interleukin 6 gene expression in group 2 grafts compared with group 1 grafts. Myeloperoxidase activity and interleukin 6 gene expression were suppressed with ultrafiltration. CONCLUSIONS: Cardiopulmonary bypass had negative effects on the graft, but ultrafiltration attenuated acute lung dysfunction by reducing the inflammatory response.

Animals↗

Fouling mechanisms in the integrated system with softening and ultrafiltration.

Softening is designed to remove hardness ions, but it can also remove NOM and particles, yielding the possibility to use the process as a pretreatment for ultrafiltration. The objectives of this research were to understand the nature of the fouling mechanisms for ultrafiltration when used for waters that either require softening or have been softened, and to use that understanding to determine promising options for the use of softening as a pretreatment before ultrafiltration. To understand fouling mechanisms in the integrated system with softening and ultrafiltration, three different levels of softening performance in terms of removal of inorganics and organic matter were selected. Experiments were performed with both natural waters and synthetic waters with similar (but separable) inorganic, organic, and particulate characteristics. The synthetic waters were used to distinguish among inorganic fouling by precipitates, organic fouling, particulate fouling, and combined fouling by particles and organic matter. The results showed that organic matter played a major role in fouling, either by itself or by adsorption onto particles, and that softening pretreatment effectively reduced the foulants prior to ultrafiltration.

Adsorption↗

Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease.

BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. The optimal target population for MUF needs to be defined. This prospective, randomized study attempted to identify the best candidates for MUF during operations for congenital heart disease. METHODS: Informed consent was obtained from 100 consecutive patients with complex congenital heart disease undergoing operations with CPB. They were randomized into a control group (n = 50) of conventional ultrafiltration during bypass and an experimental group using dilutional ultrafiltration during bypass and venovenous modified ultrafiltration after bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of ventilatory support, transfusion requirements, hematocrit, chest tube output, and time to chest tube removal were compared between the groups stratified by age and weight, CPB technique, existence of preoperative pulmonary hypertension, and diagnosis. RESULTS: There were no MUF-related complications. In patients with preoperative pulmonary hypertension, MUF significantly improved postoperative oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002), shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/- 131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/- 18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors: 5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to earlier chest tube removal. In neonates (< or =30 days), MUF significantly reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control: 39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/- 36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant differences were observed between MUF and control patients for any parameter in the presence of ventricular septal defect without pulmonary hypertension, tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration after CPB is safe and decreases the need for homologous blood transfusion, the duration of ventilatory support, and chest tube placement in selected patients with complex congenital heart disease. The optimal use of MUF includes patients with preoperative pulmonary hypertension, neonates, and patients who require prolonged CPB.

Blood Loss, Surgical↗

Investigation of conventional membrane and tangential flow ultrafiltration artifacts and their application to the characterization of freshwater colloids.

Artifacts associated with the fractionation of colloids in a freshwater sample were investigated for conventional membrane filtration (0.45 microm cutoff), and two tangential flow ultrafiltration cartridges (0.1 microm cutoff and 3000 MW cutoff). Membrane clogging during conventional filtration removed some colloids smaller than 0.1 microm in diameter, much smaller than the nominal size of the filter. For certain constituents (e.g., Fe), filter clogging had a significant effect on filtrate concentrations, while artifacts associated with tangential flow ultrafiltration using a 0.1 microm cutoff were minimal. Artifacts occurred during tangential flow ultrafiltration with a 3000 MW cutoff, but did not deviate from predicted changes in concentration based on a standard permeation model. Comparison of filtrate concentrations for membrane filtration (at 1.0 and 0.45 microm) and tangential flow ultrafiltration (at 0.1 microm) for a large number of samples from Connecticut rivers shows that significant and consistent differences exist between their separation characteristics. Results for organic carbon, Fe, Mn, Al, Cu, and Pb demonstrate the magnitude of the effects of the fractionation technique on filtrate element concentration, show variability by element and flow condition, and highlight the importance of larger colloids to freshwater metal speciation. One implication of the research is that tangential flow ultrafiltration with large size cutoff membranes (e.g., approximately 0.1 microm) may be superior to conventional filtration with filters in the same size discrimination range, and potentially more appropriate for the fractionation of natural water samples.

Artifacts↗

Determination of ultrafiltrable zinc in human milk by electrothermal atomic absorption spectrometry.

Percentages of non-protein-bound zinc in human milk have been reported by different workers, but ultrafiltration and zinc determination in human milk have not been comprehensively examined. However, zinc contamination and zinc membrane binding have been described for the determination of non-protein-bound zinc in serum. In this work, ultrafiltration was studied in terms of zinc contamination and zinc membrane binding. An MPS-1 micropartition system fitted with a YMT membrane was used. Zinc contamination was found to be less than 276 nmol dm-3 and the zinc recovery was 85 +/- 4%. The conditions for electrothermal atomic absorption spectrometry were also studied. The detection limit was found to be 26.4 nmol dm-3 and the upper linear range was 4 mumol dm-3. The precision varied from 3% (within-run) to 17% (between-run). The recovery of standard additions was 95 +/- 7% (n = 30, different human milk ultrafiltrate samples). Physiological values varied from 0.46 to 84 mumol dm-3 (4-56% of zinc in whole human milk). Expressed in mumol dm-3, zinc in human milk ultrafiltrate decreased slightly through the lactation period, whereas expressed as a percentage of the total zinc in milk, zinc in human milk ultrafiltrate remained constant from day 2 to day 69 post partum.

Adult↗

Effect of ultrafiltration during cardiopulmonary bypass for pediatric cardiac surgery.

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)-6 and IL-8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL-6 concentration increased to 128.4+/-20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1+/-48.2 pg/ml, p < 0.02). The blood IL-8 concentration was not significantly different than that of adults. The total amounts of excreted IL-6 in the ultrafiltrate and urine during CPB were 11.5+/-0.32 pg/kg and 0.32+/-0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL-8 in the ultrafiltrate and urine were 4.64+/-0.69 pg/kg and 1.92+/-0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone.

Cardiopulmonary Bypass↗

The effect of sodium and ultrafiltration modelling on plasma volume changes and haemodynamic stability in intensive care patients receiving haemodialysis for acute renal failure: a prospective, stratified, randomized, cross-over study.

BACKGROUND: Haemodynamic stability in intensive care unit (ICU) patient with acute renal failure (ARF) during intermittent dialytic support has been the focus for several variations to dialysis delivery. Indeed this has been noted by many as a possible cause for prolonged renal dysfunction created by repeated hypotensive renal insult, as well as a reason for the lower delivered dialysis dose afforded. End-stage renal failure patients supported by intermittent dialysis have benefitted from variable sodium dialysate and variable ultrafiltration rate protocols. The current study has focused upon the response to these dialysis variations in the ICU ARF patient. METHODS: Successive ICU patients with defined characteristics of ARF requiring dialytic support were entered into a prospective, stratified (by Cleveland Clinic Foundation ARF Acuity Score), randomized, crossover designed study to evaluate haemodynamic effects and need for interaction during dialysis therapy delivering a fixed dialysis dose based upon area kinetic analysis. Subjects were supported either by a fixed dialysate sodium (140 meq/dl) and fixed ultrafiltration rate (Protocol A), or a variable sodium dialysate (160-140 meq/dl) and variable ultrafiltration (50% UF during the first third of treatment time, 50% UF over the last two thirds treatment time) (Protocol B). After three sessions, the patients were crossed to the other protocol, and if continued, after three sessions returned to the original protocol. Mean arterial pressures, Cardiac output, serum electrolytes, serum albumin, and relative blood volume changes were measured. Frequency of nursing intervention, quantity and type of volume replacements as well as pressor agent use was standardized, documented and compared. RESULTS: Ten ARF patients (age: 64.2 +/- 13.7 years), CCF acuity score (13.3 +/- 3.9), APACHE II score (28.7 +/- 4.7). MAP (VNA: 82.8 +/- 16.9; FNA: 86.2 +/- 18.9 mmHg), CO, cardiac index, pressor support interventions required (VNA: 16%: FNA: 48.4%, P < 0.001), blood volume changes (Critline) (VNA: -6.6 +/- 5.2; FNA: -7.59 +/- 6.7, P < 0.05), S. albumin (VNA: 2.4 +/- 0.6; FNA: 2.81 +/- 0.9 g/dl, ns) pre/post S.Na (VNA: 138.7 +/- 5.1/141.7 +/- 2.3; FNA: 136.6 +/- 5.96/139.1 +/- 3.71 mmol/dl), osmolality, Urea (VNA: 69.5 +/- 0.6; FNA: 70.5 +/- 0.6%, ns) and Creatinine (VNA: 56.6 +/- 0.5: FNA: 59.6 +/- 0.5%, ns) Reduction ratio, dialysis time (VNA: 4.8 +/- 0.5: FNA: 4.6 +/- 0.45 h) and achieved UF (VNA: 2.0 +/- 1.2; FNA: 1.56 +/- 1.3 L, P < 0.05) were measured. CONCLUSION: Haemodynamic stability was greater during Protocol B than during Protocol A in all patients. Significantly less intervention was noted during Protocol B, despite the same dialysis delivery during both Protocols. Relative Blood volume changes were less during Protocol B, despite a greater total ultrafiltration. Variable sodium dialysate coupled with a variable ultrafiltration rate seems to be the preferred dialysis prescription for ICU ARF patients undergoing intermittent haemodialysis.

Acute Kidney Injury↗