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Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study.

OBJECTIVE: A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease. METHODS: Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines. RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS: Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.

Cardiopulmonary Bypass↗

Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting.

OBJECTIVE: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients. DESIGN: Randomized and controlled. SETTING: University-affiliated heart center. PARTICIPANTS: Forty-three patients scheduled for elective CABG. INTERVENTIONS: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed. MEASUREMENTS AND MAIN RESULTS: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05). CONCLUSION: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

Blood Pressure↗

Changes in blood volume during dialysis are dependent upon the rate and amount of ultrafiltrate.

Actual circulating blood volume during dialysis therapy can be monitored by continuous hemoglobinometry. Using this method in 15 stable, clinically nonoverhydrated dialysis patients, blood volume was recorded applying different modes of ultrafiltration: constant ultrafiltration (less than 500 ml/hr); high initial (greater than 1,500-2,000 ml/hr), subsequently decreasing ultrafiltration; and intermittently high (greater than 1,500 ml/hr) ultrafiltration. Mean amount of ultrafiltrate in all patients was 3,400 ml. Mean decrease in blood volume by 20% was generally tolerated without a decrease in blood pressure. Irrespective of the different modes of ultrafiltration, a decrease in blood volume was dependent only on the amount of ultrafiltered fluid. A constant, low ultrafiltration rate was not superior to a high ultrafiltration rate. In stable dialysis patients, decrease in blood volume is dependent only on the amount of ultrafiltrate. Up to a 20% decrease in blood volume, fluid can be removed from the patient even at a rate of 2,000 ml/hr.

Blood Flow Velocity↗

Effect of high and low ultrafiltration volume during hemodialysis on relative blood volume.

Achieving an optimal post-hemodialysis hydration status may be difficult because objective criteria for dry weight are lacking. Both relative blood volume changes (DeltaRBV) at the end of hemodialysis and DeltaRBV normalized for ultrafiltration volume (DeltaRBV/UF ratio) have been reported to indicate post-hemodialysis volume status. A parameter for volume status should not be influenced by variations in ultrafiltration volume. However, if the volume that has to be ultrafiltrated to reach dry weight varies as a result of variations in pre-hemodialysis weight, either DeltaRBV or the DeltaRBV/UF ratio (or both) must change. To elucidate the relation between intradialytic ultrafiltration volume versus DeltaRBV and its derivative, the DeltaRBV/UF ratio, we studied the effect of a relatively high (mean+/- SD, 2.7+/- 0.5 l) and low (1.5+/- 0.3 l) intradialytic ultrafiltration volume on these parameters in eight patients. Post-hemodialysis weight was comparable in low and high ultrafiltration volume sessions. The average end-hemodialysis DeltaRBV did not differ between high (-6.7+/- 2.5%) and low ultrafiltration volume sessions (-7.3+/- 1.0%; NS), but the intraindividual variation was considerable. The DeltaRBV/UF ratio differed markedly (p<0.001) between high (-2.4+/- 0.8 %/l) and low (-4.9+/- 1.3 %/l) ultrafiltration volume sessions. In conclusion, the considerable random intraindividual variation of DeltaRBV and the systematic change of the DeltaRBV/UF ratio with variations in intradialytic ultrafiltration volume limit the use of these parameters as an aid to assess hydration status in hemodialysis patients.

Aged↗

A comparative study of serum ultrafiltrable, ionized, and total calcium in the diagnosis of primary hyperparathyroidism in patients with intermittent or no elevation in total calcium.

Measurement of serum ionized calcium has been shown to be more sensitive a method of diagnosing primary hyperparathyroidism than total calcium in patients with subtle or intermittent elevations of total calcium. The measurement of ionized calcium, however, is technically difficult. The measurement of serum ultrafiltrable calcium would circumvent technical difficulties because atomic absorption spectroscopy would be used to measure the calcium of a filtrate produced by passing serum through a filter which excludes protein-complexed calcium (Worthington ultrafree filter). The normal range for ultrafiltrable calcium (4.7 to 6.8 mg/dl) was determined in 138 patients by nonlinear least-squares analysis and chart review. The serum concentration of ultrafiltrable calcium correlated well with ionized calcium (r = 0.91). Previous studies have demonstrated no benefit in measuring ionized calcium, as opposed to total calcium, in the diagnosis of primary hyperparathyroidism unless there was subtle, intermittent, or no elevation of the total calcium. This comparative study of ultrafiltrable, ionized, and total calcium was, therefore, done in six patients with primary hyperparathyroidism who exhibited intermittent, minimal, or no elevations in serum total calcium. All six patients had symptoms referrable to hyperparathyroidism. All six underwent parathyroid surgery, and a parathyroid adenoma was found in each case. These six patients had a total of 24 concurrent preoperative determinations of ionized, ultrafiltrable, and total calcium levels. The total calcium value was elevated in only 9 of these 24 determinations (38%), ultrafiltrable calcium was elevated in 15 (63%), and ionized calcium was elevated in 23 (96%). The values of ionized calcium were elevated more frequently than both total calcium (p less than 0.0005) and ultrafiltrable calcium (p less than 0.025). The values for ultrafiltrable calcium were more frequently elevated than those for total calcium; this difference, however, was not significant. This study confirms our previous reports showing that ionized calcium is a more sensitive indicator of primary hyperparathyroidism in patients with intermittent or borderline elevation of the total calcium and extends those observations to show that ionized calcium is also a more sensitive indicator of primary hyperparathyroidism than ultrafiltrable calcium in this group of patients.

Calcium↗

Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration.

BACKGROUND: In human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin. METHODS: A method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin. RESULTS: The recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (r(s)=0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (r(s)=0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration. CONCLUSIONS: Ultrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.

Adolescent↗

Ultrafiltration behavior of major ions (Na, Ca, Mg, F, Cl, and SO4) in natural waters.

Aquatic colloids, including macromolecules and microparticles, with sizes ranging between 1 nm to 1 micron, play important roles in the mobility and bioavailability of heavy metals and other contaminants in natural waters. Cross-flow ultrafiltration has become one of the most commonly used techniques for isolating aquatic colloids. However, the ultrafiltration behavior of chemical species remains poorly understood. We report here the permeation behavior of major ions (Na, Ca, Mg, F, Cl, and SO4) in natural waters during ultrafiltration using an Amicon 1 kDa ultrafiltration membrane (S10N1). Water samples across a salinity gradient of 0-20@1000 were collected from the Trinity River and Galveston Bay. The permeation behavior of major ions was well predicted by a permeation model, resulting in a constant permeation coefficient for each ion. The value of the model-derived permeation coefficient (Pc) was 0.99 for Na, 0.97 for Cl, and 0.95 for F, respectively, in Trinity River waters. Values of Pc close to 1 indicate that retention of Na, Cl, and F by the 1 kDa membrane during ultrafiltration was indeed minimal (< 1-5%). In contrast, significant (14-36%) retention was observed for SO4, Ca, and Mg in Trinity River waters, with a Pc value of 0.64, 0.82, and 0.86 for SO4, Ca and Mg, respectively. However, these retained major ions can further permeate through the 1 kDa membrane during diafiltration with ultrapure water. The selective retention of major ions during ultrafiltration may have important implications for the measurement of chemical and physical speciation of trace elements when using cross-flow ultrafiltration membranes to separate colloidal species from natural waters. Our results also demonstrate that the percent retention of major ions during ultrafiltration decreases with increasing salinity or ionic strength. This retention is largely attributed to electrostatic repulsion by the negatively charged cartridge membrane.

Anions↗

Modified ultrafiltration in surgical correction of congenital heart disease with cardiopulmonary bypass.

The surgical correction of congenital heart disease using haemodilution and hypothermia with cardiopulmonary bypass (CPB) may expose patients to tissue ischaemia and initiate a systemic inflammatory response, increasing the total body water and inducing impairment, especially of heart, lung and brain function. It is possible to use ultrafiltration during CPB in the rewarming phase to remove water accumulation in the third space (conventional ultrafiltration). The reduced volume of prime used in children and the ability only to filter the reservoir blood during CPB led the Great Ormond Street Group to modify the method of ultrafiltration with regards to the placement of the filter and the timing of filtration (post-CPB). The main advantage of the modified technique is the ultrafiltration of the patient. A prospective nonrandomized study has been conducted to compare conventional with conventional + modified ultrafiltration. From January 1996 to March 1998, 41 patients underwent correction of congenital heart disease and were submitted to a comparative study (homogeneous groups), using either the conventional or the conventional + modified ultrafiltration techniques. There were no technical complications, no patient required mediastinal re-exploration due to bleeding and it was possible to close all the chests. There were significant differences in the ultrafiltrate volume balance (143.3 +/- 54.3 versus 227 +/- 71.4 mL; P < 0.001) but there were no significant differences in clinical postoperative evolution between the conventional and the conventional + modified ultrafiltration.

Blood Transfusion↗

Assays of ligand-human serum albumin binding using pulsed ultrafiltration and liquid chromatography-mass spectrometry.

Two approaches were utilized to increase the throughput of pulsed ultrafiltration assays of ligand binding to human serum albumin, reducing the volume of the ultrafiltration chamber and combining pulsed ultrafiltration with high performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-MS). Affinity constants for binding of ligands to human serum albumin were determined using pulsed ultrafiltration with ultraviolet absorbance detection. The first affinity constants (Ka1) were measured for the binding of dansylsarcosine, dansylamide, 7-anilinocoumarin-4-acetic acid and warfarin, and were determined to be 1.8 x 105, 5 x 104, 8 x 104, and 2.0 x 105 M-1, respectively. The throughput of pulsed ultrafiltration analyses was tripled compared to previous pulsed ultrafiltration measurements by reducing the volume of the chamber. In addition, the use of LC-MS with pulsed ultrafiltration permitted the simultaneous comparison and rank ordering of ligand mixtures for binding to serum albumin. For example, the throughput of these pulsed ultrafiltration measurements was tripled by analyzing three ligands as a mixture.

Chromatography, Liquid↗

The effects of ultrafiltration on e-aminocaproic acid: an in vitro analysis.

Blood conservation strategies have become a standard of practice in cardiac surgery, with the use of antifibrinolytic agents and ultrafiltration two popular techniques. The purpose of this study was to evaluate the effects of continuous ultrafiltration on e-aminocaproic acid (EACA) utilizing functional coagulation analysis. A fibrinolytic assay was developed to detect EACA using the thromboelastograph (TEG) and urokinase (0.138 units 0.360 mL(-1)). Fresh bovine blood (23 +/- 1% hematocrit) was pumped (100 mL min(-1)) through an ultrafiltrator (HPH 400) at 37 degrees C with a transmembrane pressure of 280 mmHg. EACA (0.065 mg mL(-1)) was circulated for 10 minutes before initiating ultrafiltration. Samples (pre- and postultrafiltrator) were obtained at baseline, 5, and 10 min of ultrafiltration and analyzed via the fibrinolytic assay for EACA determination. TEG profiles significantly decreased from concentrations of 0.065 mg to 0.0325 mg of EACA mL(-1) blood (maximum amplitude MA, 75.4 +/- 4.0 versus 63.3 +/- 2.9, p < .05, TEG index 5.4 +/- 0.7 versus 4.0 +/- 0.3, p < .05). Fibrinolysis at 30 min increased as EACA concentrations declined (0.065 mg, 0% versus 0.032 mg, 16.4 +/- 2.8%, p < .05). During ultrafiltration the MA increased significantly from baseline to 10 min postultrafiltrator (68.2 +/- 3.0 versus 75.8 +/- 10.0, p < .05) and from 5 min pre- to 10 min postultrafiltrator (69.7 +/- 4.2 versus 75.8 +/- 10.0, p < .05). The TEG index showed no significant change, and no fibrinolysis was detected at 30 min from any datapoint during ultrafiltration. In conclusion, this study demonstrates that the antifibrinolytic properties of EACA are maintained during ultrafiltration with a 25% reduction in total circulating volume.

Aminocaproic Acid↗

Measurement of free desipramine in serum by ultrafiltration with immunoassay.

We developed an ultrafiltration method for assaying free desipramine (DMI) in serum. An ultrafiltrate of DMI-containing serum was prepared by centrifugation through an Amicon Centrifree micropartition filter. Syva DMI solid-phase extraction (SPE) columns were used to extract the DMI from the serum and ultrafiltrate. The Syva monoclonal EMIT assay was used to quantify the DMI in the extract. In some experiments, the percent free DMI was quantified with radioactivity. Nonspecific losses of DMI in serum to the ultrafilter system were low (recoveries > 91%). Extraction of [3H]DMI from phosphate-buffered saline (to mimic serum ultrafiltrate) with the Syva SPE system was quantitative (recoveries of 98.4% +/- 4.6%). Free DMI concentrations, derived from serum containing 2.5-2500 micrograms/L DMI, were determined by ultrafiltration; results agreed well with values determined by equilibrium dialysis, the average percent of free DMI being 18.4% +/- 0.25% and 15.9% +/- 0.51%, respectively. To increase the sensitivity of the free DMI assay in the therapeutic range (total DMI 125-300 micrograms/L), we increased fourfold the ultrafiltrate volume applied to the SPE column. For free DMI at 11-130 micrograms/L, the within-run and between-run CVs for the ultrafiltration method were < 9% and < 15%, respectively. Binding of DMI to serum proteins decreased over the pH range 6.0-8.0, although temperatures between 20 and 28 degrees C did not affect binding. The ultrafiltration assay is fast, accurate, simple, and adaptable to standard laboratory instrumentation.

Desipramine↗

[Effects of salivary ultrafiltrates on the production of phenol from tyrosine by oral microorganisms].

The metabolism of oral microorganisms is known to correlate with oral diseases. Protein degradation by oral microorganisms is usually followed by the production of phenol from tyrosine. The purpose of this study is to clarify the effect of salivary ultrafiltrates [MW: less than 10,000, 1,000-10,000 (intermediate fraction), less than 1,000, less than 500] on the production or the decomposition of phenol by oral microorganisms. Salivary sediment and salivary ultrafiltrate, the molecular weight of which is less than 10,000 unless otherwise stated, were incubated at 37 degrees C for 24 hours with tyrosine or phenol at a final concentration of 2.5 mg/100 ml. After incubation, the phenol produced (or remained) was extracted with ether and determined spectrophotometrically. Phenol production by oral microorganisms was not seen in the non-dialyzable fraction of saliva even when tyrosine was added. It was confirmed that the presence of the salivary ultrafiltrates was essential for the production of phenol by oral microorganisms. Phenol production in the salivary ultrafiltrate was further increased with the addition of tyrosine or non-dialyzable fraction of saliva. Phenol disappeared within 48 or 72 hours after the salivary sediment was incubated with phenol. The decomposition of phenol was inhibited with the salivary ultrafiltrate. Phenol production was enhanced with the addition of Good's buffer. Optimum pH of phenol production by oral microorganisms in the ultrafiltrate of saliva was within the range from 6.5 to 7.0 in the presence of Good's buffer (MOPS). Phenol production decreased with the reduction of the molecular weight of the salivary ultrafiltrates. The phenol production was increased when the intermediate fraction was added to the ultrafiltrate (MW: less than 1,000). The increase of the phenol production was considered to be due to the peptides in the intermediate fraction.

Bacteria↗

Indications for ultrafiltration in the cardiac surgical patient.

Ultrafiltration is an extracorporeal technique that employs the principle of convective solute transport across a semipermeable membrane and by which plasma water is removed from blood. Ultrafiltration has been employed in 74 cardiac surgical patients intraoperatively, preoperatively, and postoperatively. In 55 patients with clinical evidence of excess body water, the ultrafilter was employed at the start of cardiopulmonary bypass. The amount of ultrafiltrate removed was 2,914 +/- 1,662 ml (SD), and the fluid balance was -219 +/- 1,298 ml (SD). In 17 patients the ultrafilter was inserted during bypass because of excess reservoir volumes, low hematocrit, or prolonged bypass time. The amount of ultrafiltrate removed was 1,450 +/- 898 ml (SD), and the fluid balance was 1,296 +/- 2,161 ml (SD). One patient with cardiopulmonary failure and nutritional depletion underwent slow continuous ultrafiltration preoperatively along with intravenous alimentation, producing a positive nitrogen balance and improvement in cardiorespiratory failure. One patient underwent slow continuous ultrafiltration for severe, diuretic-resistant congestive heart failure postoperatively. After 9 days of ultrafiltration, there was an 8 kg weight loss, an improvement in congestive heart failure, and a return of the response to diuretics. From this experience my colleagues and I have developed the following indications for ultrafiltration in the cardiac surgical patient: during cardiopulmonary bypass to prevent further fluid accumulation in the patient with clinical evidence of excess body water; during bypass to prevent excess fluid balance in a patient whose bypass time will be greater than 2 hours; during bypass when the pump reservoir volumes are excessive and/or the hematocrit is less than 18%; preoperatively or postoperatively to increase caloric intake in the fluid-overloaded patient; and preoperatively or postoperatively to reverse severe congestive heart failure in the diuretic-resistant patient.

Aged↗

Improved ultrafiltration method for simultaneous measurement of free thyroxin and free triiodothyronine in serum.

We describe a new ultrafiltration method for measuring concentrations of free thyroxin (FT4) and free triiodothyronine (FT3). Serum containing [131I]T4 and [125I]T3 is diluted 10-fold in phosphate buffer (500 mmol/L, pH 7.4 at 37 degrees C), then passed through a YMT membrane in an Amicon MPS-1 centrifugal ultrafiltration device. Radioactive iodide and protein-bound thyronines are separated from FT4 and FT3 in the ultrafiltrate by use of a Sephadex G-25 microcolumn. In normal controls, the fraction of T4 that passes into the ultrafiltrate is 0.021 +/- 0.006% (mean +/- SD), FT4 is 19.6 +/- 6.5 ng/L, the fraction of T3 that passes into the ultrafiltrate is 0.18 +/- 0.5%, and the FT3 is 2.03 +/- 0.50 ng/L. Intra-assay precision (CV) is 5.4% for FT4 and 4.2% for FT3; the respective interassay CVs are 10.1% and 8.0%. In various groups of patients with thyroid disease and other conditions that influence serum T4 and T3 concentrations, FT4 by ultrafiltration correlated with FT4 measured by equilibrium dialysis (r = 0.84, p less than 0.001) and FT3 by ultrafiltration correlated with FT3 measured by the Diagnostic Products RIA kit (r = 0.87, p less than 0.001). The accuracy, reproducibility, speed, and simplicity of the ultrafiltration method compared favorably with the more cumbersome method of equilibrium dialysis.

Adult↗

Adjuvant spleen ultrafiltrate immunotherapy in unresectable advanced non small cell lung cancer.

The purpose of this study was to assess the possible benefit of adjuvant spleen ultrafiltrate immunotherapy in advanced lung cancer patients on chemotherapy. Twenty-six patients with inoperable non-small cell lung carcinoma were eligible to this study and randomised divided into two groups. The two groups received additionally to standard chemotherapy--three times once a month--placebo or spleen ultrafiltrate (Prosplen), respectively, given to the patients for 14 days beginning from the 7th day after each chemotherapy. To evaluate the effects of spleen ultrafiltrate, the time of haematological recovery and profile of peripheral blood lymphocytes and clinically number of days with fever and oncological response were documented. During the observation time patients receiving spleen ultrafiltrate had a higher number of leukocytes (p = 0.01) and higher counts (p = 0.03) and percentage of granulocytes (p < 0.001) including nadir values (p = 0.05) in blood. The positive effect was also seen in natural killer cells (p = 0.005) but not in T cells compartment. This could be of clinical significance because patients receiving spleen ultrafiltrate presented less frequently febrile episodes than patients in the placebo group (75 vs. 127 days with body temperature > 38 degrees C, p = 0.007) and had less frequently highly elevated serum C-reactive-protein levels (p = 0.02). Notably, 2 out of 12 patients receiving in addition to chemotherapy spleen ultrafiltrate and 7 out of 14 lacking this adjuvant treatment showed tumor progression during the treatment. Serum C3 levels were associated with progression of disease in both groups (p = 0.03). Overall, spleen ultrafiltrate receiving patients had lower serum C3 values than placebo receiving patients. Serum IgM levels were rather high in the placebo group (p = 0.033). Spleen ultrafiltrate is thought to benefit patients on palliative chemotherapy in advanced metastatic cancers.

Adjuvants, Immunologic↗

Effects of ultrafiltration and peritoneal dialysis on proinflammatory cytokines during cardiopulmonary bypass surgery in newborns and infants.

OBJECTIVES: To assess the impact of balanced ultrafiltration and peritoneal dialysis (PD) on plasma and urinary cytokines and renal dysfunction after cardiopulmonary bypass (CPB) surgery in newborns and infants. METHODS: Twenty-three newborns and infants weighing less than 7 kg and scheduled for operation on congenital malformation were enrolled in this descriptive open clinical study. All patients received conventional ultrafiltration in the CPB rewarming period. Eleven newborns underwent Tenckhoff-catheter implantation in the operation theatre as a routine institutional procedure and received PD after admission to the ICU (the PD [+] group). No PD was used in another 12 patients (the PD [-] group). Interleukins (IL) 6 and 8 were measured four times pre- and post-operatively. Kidney function was assessed by creatinine clearances and urine protein and enzyme analyses. RESULTS: All patients had an uneventful clinical course. Age (10+/-2 days, PD [+] vs. 96+/-19 days, PD [-]), CPB duration (215+/-23 vs. 143+/-20 min), and degree of hypothermia (26+/-1.3 vs. 31+/-0.1 degrees C) differed significantly between the groups. Age, CPB duration and ultrafiltration influenced post-operative IL-levels in an analysis of variance. While there were few differences immediately after the end of ultrafiltration, post-operative levels of IL-6 and IL-8 were higher and more sustained in the newborns (PD [+]) than in the older infants (PD [-]). The median amount of IL-6 and IL-8 removed by ultrafiltration came to 28 and 59% compared to the amount of IL-6 and IL-8 remaining in the blood at the end of CPB. IL-clearance by ultrafiltration was more than 1000-fold and by PD more than 100-fold as effective as IL-clearance by the kidney. While the kidneys showed an unselective mixed glomerular and tubular pattern of injury, during CPB higher serum IL-concentrations correlated with lower urinary IL-clearances in both study groups. CONCLUSIONS: Ultrafiltration and PD are highly effective in removing proinflammatory cytokines. Impaired kidney function was associated with proinflammatory IL-serum concentrations. Thus, we raise the hypothesis that glomerular-filtered proinflammatory ILs damage the proximal tubular cells of the kidney in newborns and infants, thus contributing to post-operative renal dysfunction. Conversely, we conclude that removing proinflammatory ILs by ultrafiltration and PD acts renoprotectively. A future prospective randomised study could demonstrate whether this can indeed improve clinical outcome.

Cardiopulmonary Bypass↗

Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failure.

OBJECTIVES: We sought to investigate the possibility that lung diffusing capacity reduction observed in chronic heart failure is reversible in the short term. BACKGROUND: Mechanical properties of the lung usually ameliorate with antifailure treatment including drugs, ultrafiltration and heart transplantation, whereas lung diffusion rarely improves. METHODS: We studied the mechanical properties of the lung (pulmonary function tests with determination of alveolar volume, extravascular lung fluids and lung tissue), lung diffusion for carbon monoxide (DLco), including membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc) and pulmonary hemodynamics, in 28 patients with stable chronic heart failure, before a single session of extracorporeal ultrafiltration (3,973 +/- 2200 ml) and four days thereafter. Lung mechanics and diffusion were also evaluated in 18 normal subjects. RESULTS: Vital capacity, forced expiratory volume (1 s) and maximal voluntary ventilation were lower in patients when compared with normal subjects, and increased after ultrafiltration from 2.1 +/- 0.7 to 2.5 +/- 0.7(1)*, 1.7 +/- 0.5 to 2.0 +/- 0.6(1)* and 67 +/- 25 to 79 +/- 26 (1/min)*, respectively (* p < 0.02 vs. pre-ultrafiltration). Post-ultrafiltration alveolar volume was augmented, while lung tissue, body weight (approximately 6 kg), chest X-ray extravascular lung water score and pulmonary vascular pressure were reduced. Heart dimensions (echocardiography) remained unchanged. DLco, Dm and Vc were 29.0 +/- 5.0 ml/min/mm Hg, 47.0 +/- 11.0 ml/min/mm Hg, 102 +/- 20 ml in normal subjects and 17.1 +/- 4.0#, 24.1 +/- 6.5#, 113 +/- 38 and 17.0 +/- 5.0#, 24.8 +/- 7.9#, 100 +/- 39 in patients before and after ultrafiltration, respectively (# = p < 0.01 vs. controls). CONCLUSIONS: In chronic heart failure, ultrafiltration improves volumes and mechanical properties of the lung by reducing lung fluids. Diffusion is unaffected by ultrafiltration, suggesting that, in chronic heart failure, the alveolar-capillary membrane abnormalities are fluid-independent.

Chronic Disease↗

Modified ultrafiltration improves global left ventricular systolic function after open-heart surgery in infants and children.

OBJECTIVES: Modified ultrafiltration increases blood pressure and cardiac index following open-heart surgery in children, but it is unclear if this is secondary to an improvement in global left ventricular function. A previous report has suggested that left ventricular systolic function as assessed in a single chord is improved by ultrafiltration (Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1998;115:361--370). The prominent vascular actions of modified ultrafiltration necessitate left ventricular assessment using load-independent indices of systolic and diastolic function. METHODS: In 22 consecutive infants and children undergoing open-heart surgery, left ventricular function was assessed following bypass and then 10 min later. Sixteen children (median weight 8.1 kg) underwent modified ultrafiltration during this period, the remainder (median weight 7.3 kg) were controls for spontaneous recovery without ultrafiltration. Real-time pressure-volume loops, with transient inferior caval vein snaring were generated from conductance and microtip pressure catheters inserted through the LV apex. From these, load-independent (slope of the end-systolic pressure-volume [Ees] and end-diastolic pressure-volume [Eed] relationships) and load-dependent (Pmax, maximum LV pressure; Ped, end-diastolic LV pressure; maximum [dP/dtmax] and minimum [dP/dtmax] time derivatives of LV pressure; tau, time constant of isovolumic relaxation) indices of left ventricular function were measured. RESULTS: Haemoconcentration was achieved in all modified ultrafiltration patients, median increase in haematocrit 34% (interquartile range 21%, 42%), final haematocrit 0.40 (0.35, 0.41). Ees increased 58% (9, 159, P = 0.005). The changes in Eed, Pmax, Ped, dP/dtmax, dP/dtmin, and tau were not significantly different from the control group. CONCLUSION: Modified ultrafiltration improves global left ventricular systolic function in infants and children following open-heart surgery.

Cardiac Surgical Procedures↗