Continuous renal replacement therapies in the treatment of acute renal failure in intensive care patients. Part 1. Theoretical aspects and techniques.
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Biomedical subjects
Publications and source records attributed to C Ronco.
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Several patients undergoing chronic renal replacement therapy present problems related to their vascular access. Low blood flows and high rates of recirculation are common in such patients in which, for this reason, it becomes difficult to apply highly efficient techniques or techniques where diffusion and convection are combined as in hemodiafiltration. In these patients we studied the possibility of partially recirculating the blood in the extracorporeal circuit in order to increase the flow rate per single hollow fiber; we defined our system "double pass dialysis". We evaluated the system's efficiency in 12 patients during 24 dialysis sessions: 12 high flux dialysis sessions (without reinfusion) and 12 hemodiafiltration sessions (9 liters reinfusion). Different surfaces of polyacrylonitrile dialyzers were utilized (1.3-1.7-2.1 sqm) at 250 and 350 ml/min of blood flow with or without 100 ml/min of recirculation. During each dialysis session blood and dialysate samples were taken in order to calculate BUN, Creatinine, Phosphate and Inuline clearances from both the blood and dialysate side. The clearances of low molecular weight solutes were not really influenced by the artificial increase of the blood flow, but on the other hand, the clearances of higher molecular weight solutes increased from 10 to 30% during both high flux dialysis and hemodiafiltration with recirculation. This increase was evident mostly in hemodiafiltration suggesting that the cleaning effect on the membrane has a positive impact on the permeability. The good clinical results obtained with the double pass dialysis show that the system is safe and reliable and may become a valid support in critical situations in order to reach adequate dialysis treatment.
The endotoxin transfer across dialysis membranes has been investigated using specific in vitro circuits. Backdiffusion and backfiltration have been analyzed and most dialysis membranes have shown to be permeable to LAL positive substances. Synthetic membranes however display the better capacity of retention of these products despite their higher porosity and permeability. For such reason synthetic polysulfone ultrafilters are used as pyrogen filters to obtain ultrapure dialysate. We have investigated the characteristics of a polysulfone ultrafilter named Diaclean and manufactured by Amicon Ireland. The capacity of endotoxin retention has been investigated both in filtration and backfiltration modes on new and used ultrafilters. The capacity of endotoxin adsorption was investigated as well. Used ultrafilters appeared to maintain the retention capacity and the adsorption capacity up to 4 months of use. Only slight differences were noted from the baseline values (p = n.s.). The best adsorption capacity is always displayed by the outer layer of the membrane suggesting its best utilization in back filtration mode with tangential flow. No morphological changes were observed in the used membrane analyzed by scanning electron microscopy.
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A new blood module for continuous renal replacement therapies has been utilized to perform CVVH in critically ill patients. The features of the new module named (HP300 and manufactured by Medica srl (Medolla, Modena) are the easy installation and transportability to the bedside, the simple and safe management and the continuous measurement of the pre and post filter pressure with automatic calculation of the end-to-end pressure drop inside the filter. The last feature permits to detect early malfunctions of the filter due to fibers clotting or due to the internal coating of the hollow fibers by plasma proteins. In both cases the efficiency of the treatment can be reduced because of a significant reduction of the ultrafiltration rates or a remarkable decay of the membrane permeability and solute sieving coefficients. In many cases this reduction is only detected when important effects on solute removal have already occurred. In our experience, the new module permitted the substitution of the filters when early malfunctions were detected and maximal treatment efficiency was therefore guaranteed over extended periods of time.
First generation asymmetric polysulfone membranes had high hydraulic permeability (kf = 40 ml/h/mmHg/sqm) but a low diffusive permeability due to the hydrophobic nature and wall thickness of 75-100 microns. We have tested a new polysulfone membrane with a wall thickness of 40 microns in a series of in vitro and in vivo dialysis session experiments. The new "Biosulfane" membrane presented a Kf of 45.8 with constant performance up to 240 mins. The koA was 760 and the clearance value at 350 ml/min of Qb in hemodiafiltration was 255 ml/min for urea, 210 for creatinine, 225 for phosphate, 76 for inulin. In high flux dialysis the clearances were similar except for inulin which was 32% lower due to the lower convection amount. Beta-2 microglobulin clearance was 22 ml/min in high flux dialysis and 37 in hemodiafiltration. Solute sieving coefficients were close to 1 for the majority of the studied solutes in a wide range of molecular weights and slight variations were observed for charged solutes due to Donnan's effect. The sieving for Inulin was 0.96 while that for Beta-2 microglobulin was not measurable due to a large molecule adsorption on the inner structure of the fibres. The good performances of this membrane are probably due to reduced wall thickness and a consequent improvement in diffusive permeability to small size solutes.
Continuous renal replacement therapies are extensively utilized for the treatment of acute renal failure in the critically ill patient. The arterio-venous circulation has been partially substituted by the veno-venous pump driven circulation. Diffusion has been added to convection in order to increase the small solutes clearance even though sometimes the pure convection is still advantageously utilized. Hemofilters have been changed in hemodiafilters with the possibility of countercurrent dialysate circulation. The blood path geometry has been specifically designed to operate under conditions of low pressure and flow. Therefore lower amounts of heparin are required to maintain the extracorporeal anticoagulation with a reduced risk of bleeding. New techniques and new materials permit us today to carry out continuous therapies with a low rate of complications and an increased percentage of survival among the treated patients. The improved understanding of the multiple organ failure syndrome and the pathophysiology of the septic syndrome, suggest today newer indications for continuous renal replacement therapies. The proposed mechanisms of action of the therapy should be the removal of chemical mediators such as platelet activating factor, interleukin-1 and tumor necrosing factor alfa, not only by a filtration process, but also by the adsorption on the surface and structure of the artificial membrane. These new mechanisms may in part be responsible for the beneficial effects of continuous therapies in the patients affected by acute renal failure and other organ dysfunctions.
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Ultrafiltration and pressure profiles in hollow fiber dialyzers with different hydraulic permeabilities have been investigated with a new scintigraphic method. Radiolabelled albumin macroaggregates, used as a nondiffusible marker molecule, were added to the blood in an in vitro circuit and circulated through cuprophan and polysulphon dialyzers. Since the marker molecule was too big to cross the dialysis membrane, its changes in concentration were assumed to occur in response to the variation of the blood water content (filtration or back-filtration). These changes in concentration, recorded by a gamma camera, were evaluated to establish the cumulative values of filtration and back-filtration and their relevant profiles along the length of the dialyzer. The achieved data were compared with the experimental values of ultrafiltration empirically measured and with the theoretical values predicted by a classic linear method. Two conditions were analyzed: A) the minimal filtration rate necessary to avoid back-filtration (critical filtration); and B) the condition of zero net filtration in which filtration equals back-filtration. The nuclear method proved to be extremely precise in predicting the ultrafiltration values and significantly more precise than the linear method, especially for the highly permeable dialyzer. The reason for that probably depends on the non-linear pressure and ultrafiltration profile observed with the scintigraphic pattern of the dialyzer. Viscosity changes and local variations in blood flow may in fact interfere with the pressure drop inside the hollow fibers and result in such a complex behavior. The other interesting aspect of this method is the possibility of accurate measurement of the amount of back-filtration that wouldn't be possible with simple calculations. In conclusion, the complex nature of the phenomena regulating the water fluxes in hollow fiber dialyzers requires more complex calculation than a simple linear model to achieve an accurate range of predictability.
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The dynamic catheterography is an image technique that allows to study the peritoneal solution inflow and outflow phases in case of catheter malfunction. The examination is carried out in three subsequent steps: 1) direct examination without contrast media in order to define the position of the catheter inside the abdomen; 2) low speed catheterography by normal injection of 10 ml of hydrosoluble contrast medium to verify the patency of the cannula; 3) high speed catheterography by 30 ml hydrosoluble dye injected with an automateds high pressure system to study the inflow phase, the fluid distribution in the peritoneal cavity and the patency of the catheter holes. Different radiographic patterns can be found: dislocation of the catheter tip, KinKing, one way obstruction, inner lumen obstruction. The procedure is simple, safe and reliable for a correct diagnosis and for the choice of a successful therapeutic approach to peritoneal catheter malfunction.
The effect of differing dialysate and substitution fluid buffer types and concentrations on acid-base balance have not been assessed in patients treated with hemodiafiltration for ESRD. To determine bicarbonate, acetate, lactate and total buffer flux, mass balance studies were performed in patients treated with hemodiafiltration using four different combinations of dialysate and substitution fluids. Driving force for bicarbonate flux was assessed in all treatments. Bicarbonate flux depended on bicarbonate driving force and ultrafiltration rate. Bicarbonate flux was negative in all treatment combinations, even when the driving force was positive. Acetate flux was positive in all treatment combinations, but the net magnitude was small. Lactate flux, when lactate containing substitution fluid was used, varied with dialysate buffer employed during treatment. Overall buffer flux depended on the bicarbonate driving force, ultrafiltration rate, and varied with the type of substitution and dialysate buffer employed. The types and concentrations of buffer used in dialysate and substitution fluid have important effects on the acid-base balance of patients treated with hemodiafiltration. The long-term implications of different therapeutical choices in these patients is unknown.
Paired filtration dialysis (two-chamber haemodiafiltration) was evaluated as a short, highly efficient renal replacement therapy in 35 uraemic subjects belonging to three different dialysis centres. The study period was 1 year. Patients were divided into two groups according to their body-weight and drinking habits. The smaller patients underwent 150-min dialysis sessions three times weekly. The larger patients underwent 3-h treatments thrice weekly. The treatment was adequate in all patients according to the KT/V criteria of adequacy. The intradialytic symptomatology was remarkably low and the treatments were well tolerated in all patients. The study confirms the reliability of paired filtration dialysis as a short dialysis technique. In some patients 150 min may be insufficient to achieve an adequate dialysis efficiency and 180 min may be required for the majority of the population.
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