[Acute theophylline poisoning treated with combined hemoperfusion and hemodialysis].
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Biomedical subjects
Publications and source records attributed to H Asaba.
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Plasma concentrations of middle molecule (MM) fractions were quantitatively assessed by use of combined gel filtration and ion exchange chromatography in 82 non-dialyzed azotemic patients. "Sick" patients exhibiting uremic symptoms were compared with symptom-free azotemic patients with regard to plasma levels of individual MM fractions. The patients with edema, pericarditis and intercurrent infections had significantly higher plasma concentration of MM fraction 7c than symptom-free controls. The results confirm our earlier anecdotic observations that high plasma concentration of fraction 7c often associated with uremic symptoms. In the symptom-free group, the patients with polycystic kidney disease showed a significantly lower concentration of fraction 7b in plasma than those with pyelonephritis; the patients on protein restricted diet had higher plasma concentrations of fractions 7b and 7c than those on diets with daily protein intake of 60 g or more. Slight correlations between some biochemical parameters and MM fractions in plasma were found in the total patient material; the highest correlation between albumin and fractions 7c (r = -0.36), and 7d (r = 0.36), respectively. Statistical analysis of this survey has shown that the accumulation of MM fractions, especially fraction 7c, is associated with uremic "sickness", i.e. edema, pericarditis and intercurrent infection.
In this communication we present a case of fulminating anti-A autoimmune hemolysis with anuria occurring during the postoperative course after a successful renal transplantation. The patient was treated with repeated plasma exchange in an effort to remove antibodies directed against the red cells and also to eliminate the products of hemolysis known to cause acute renal failure. Subsequently the hemolysis receded and the patient regained graft function. Repeated plasma exchange, in addition to immunosuppression, appeared to have contributed to the ultimate recovery of the patient.
In order to monitor heparin activity during hemodialysis, were evaluated three commonly used methods; measurement of whole blood activated coagulation time (WBACT), whole blood thrombin time (WBTT) and heparin concentration in plasma, determined with a chromogenic substrate. Studies were performed on six regular dialysis patients during 4-hour dialysis sessions, employing three different heparin regimens; a single intravenous loading dose only, priming of the dialyzer with heparin followed by a heparin infusion and a pharmaco-kinetic model. Efficacy of heparinization was assessed by determination of fibrinopeptide A (FPA) which is a peptide split product of the fibrinogen molecule formed during thrombin-induced conversion to fibrin. There was a linear correlation (r = 0.95) between FPA-production in the dialyzer and the FPA content of the blood at the inlet to the dialyzer; the slope of the correlation line indicates that at least 65% of FPA formed in the dialyzer is disposed during passage through the patient. Considerably higher production of FPA was noted when the heparin concentration was below 0.5 IU/ml than at a higher level. This was a common finding at the end of a dialysis, regardless of regimen. No consumption of antithrombin (AT III) occurred during a dialysis with any of the heparin regimens. Good correlations were found between WBACT, WBTT and heparin concentration. Heparin activity during a dialysis may be monitored with any of these three methods with equal reliability. However, from a practical point of view, WBACT appears most attractive because of its simplicity. FPA generation, frequency of visible clots in the dialyzer and hemorrhagic manifestations were essentially the same for each of the heparin dose regimens. The simple administration of a single loading dose was as safe as the more complicated infusion technique.
Anticoagulation effects were studied during a 4-hr hemodialysis in 6 patients using 3 different heparin regimens: I. Intravenous loading dose only; II. priming of the dialyzer and continuous infusion of heparin for 2 hr; III. intravenous loading dose and continuous infusion of heparin based on anticoagulation kinetics. In all regimens the difference of fibrinopeptide A (delta FPA) between the blood inlet and outlet of the dialyzers increased at the end of the dialyses, indicating increased fibrin formation. There was a good correlation between delta FPA and the fibrin deposition on the membranes measured with I-125-fibrinogen. delta FPA increased when heparin concentration in plasma was less than 0.5 IU/ml. The anticoagulation kinetic regimen offered no advantage over the single loading dose regimen with regard to the formation and deposition of fibrin in the dialyzers.
By using high speed gel filtration combined with ion exchange gradient elution chromatography, the concentrations of plasma (p) middle molecules (MM) were determined in 126 samples from 90 non-dialyzed azotemic patients and in 210 pre-dialysis samples from 53 regular hemodialysis and 24 intermittent peritoneal dialysis patients. Samples were taken, when the patients were free from major uremic symptoms (controls) and when they presented symptoms or signs of complication, i.e., intercurrent infection, edema, vomiting, pericarditis--in hemodialysis patients also malnutrition. Compared with the symptom-free controls, the patients with infection and malnutrition revealed higher p-MM fraction 7c. In patients with edema 7a and 7b were elevated. Vomiting was not associated with accumulation of MM. In non-dialyzed patients with symptoms, p-urea was higher than in the controls. No such difference was found in dialyzed patients. The p-creatinine concentrations did not differ between the groups studied. The results of this survey imply that uremic "sickness" is more often associated with high p-MM concentrations than with high urea or creatinine, whether the accumulation of MM is cause-effect related to uremic symptomatology or an epiphenomenon remains as an open question.
Haemodynamic studies were made in eight patients before and during isovolaemic dialysis with five different dialysis solutions which varied with regard to concentration of sodium, acetate, bicarbonate and urea. Low sodium (133mmol/L) in the dialysate induced a fall in blood pressure both with and without urea removal, but no significant fall in peripheral vascular resistance. Acetate in the dialysate at higher sodium concentration (140mmol/L) resulted in peripheral vasodilation but no fall in blood pressure due to a compensatory increase in heart rate and cardiac output. We conclude that a fall in plasma tonicity (sodium) is the most important pathogenetic factor in dialysis associated hypotension; fall in total osmolality (mainly urea) is of no importance and acetate vasodilation can be compensated for haemodynamically provided that tonicity is kept stable.
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Four patients with rapidly progressive crescentic glomerulonephritis were treated with repeated plasma exchanges, using a disposable plasma filter (PLASMAFLO), combined with immunosuppression and anticoagulation. A definite improvement of renal function was observed in two patients and complete recovery of the severe lung changes of Goodpasture's syndrome was seen in one of them. In another patient rapid progression of renal insufficiency was arrested. One patient with anuria at the start of treatment remained anuric. The filter was capable of removing as large a molecule as IgM, and the plasma concentrations of immunoglobulins and complement factors declined successively after each treatment. Plasma exchange with the filter technique is readily accessible and safe in hands of the hemodialysis staff. Easy availability and simplicity are important advantages over the centrifuge methods, considering that prompt commencement of the treatment is a key issue in success.
Seven patients on regular dialysis were studied to elucidate the hemodynamic changes during ultrafiltration and dialysis, performed sequentially, the period of ultrafiltration (1 hour) either preceding or following dialysis (3 hours). During dialysis ultrafiltration was prevented by applying positive pressure in the dialysate compartment. Cardiac index (dye dilution: indocyanine green), heart rate, stroke volume index, blood pressure, and total peripheral vascular resistance index were measured. During ultrafiltration, cardiac index and stroke volume index decreased, but heart rate was not significantly changed. Total peripheral vascular resistance increased, resulting in unchanged blood pressure. During dialysis, the total peripheral vascular resistance decreased, but cardiac index and heart rate increased. BP decreased when the increase in cardiac index was insufficient to compensate for the decrease in total peripheral vascular resistance. PRA increased during ultrafiltration due to hypovolemia and decreased during dialysis, presumably due to decreased sympathetic activity which may also be a cause of dialysis-induced vasodilation.
In four regular dialysis patients, the removal of uremic middle molecules was studied during a three-hour hemoperfusion using a column containing 300 gm of activated carbon encapsulated with cellulose. Middle molecules in plasma were determined by high-speed gel filtration followed by gradient elution chromatography. Different adsorption characteristics were shown for the four middle molecule fractions measured. The initial clearances for middle molecule fractions were about 120 ml/min; clearances were 20-50 ml/min after two hours, and less than 25 ml/min, with release of some middle molecule fractions from the column, after three hours. The findings suggest that saturation of the column occurs after two to three hours of perfusion. Thus, prolongation of the perfusion time beyond two hours appears to be of little benefit. The reduction of middle molecules in plasma by a three-hour hemoperfusion was in magnitude, similar to that obtained by three-hour dialysis with a large surface area dialyzer or high-flux membrane.
1. The ultrafiltration causes a reduction of blood pressure and minute output of the heart which is compensated by vasoconstriction and thus a decrease of blood pressure is prevented. 2. Changes in the salt concentrations with reduction of the osmolarity during the dialysis without simultaneous ultrafiltration lead to vasodilation and hypotension despite increase of the minute output of the heart. 3. During a usual haemodialysis (i.e. dialysis with simultaneous ultrafiltration) the vasodilating effect of the dialysis may abolish the vasoconstrictive effect of the ultrafiltration and thus may be the cause of the hypotension.
Uremic plasma and dialysis fluid were separated by high speed gel filtration followed by gradient elution ion exchange chromatography into several UV-absorbing fractions containing middle molecules (MM) (7a, b, c, etc.), which were quantitated by integrating the peak areas of the chromatograms. Dialyzer clearance of MM was determined in vivo for two dialyzers, Gambro Optima and RP-6, but no difference could be found in spite of far better in vitro MM clearance of RP-6 than of Gambro Optima. Nor was there any difference in post-dialysis decrease in MM between the two dialyzers, or between them and two dialyzers with larger surface areas (Gambro Major and Dow HK-5). In 45 determinations of MM in blood obtained before and after dialysis, using different dialyzers, the mean decrease in MM was significantly larger than for creatinine, suggesting a much smaller distribution volume immediately available for exchange. Ultrafiltration without dialysis in 7 patients induced a significant decrease in plasma MM (7a, b, c, and g) in spite of stable osmolality, urea, creatinine, and sodium concentrations in plasma, suggesting that the reduction in body water affected the net production rate of these MM. In 5 studies, using RP-6 and a 75 l recirculating dialyzate, a rapid post-dialysis rebound was observed for MM in plasma, sometimes followed by a secondary decrease in plasma concentration. The volume of distribution of dialyzed MM, assessed from pre- and post-plasma concentrations and concentrations in the dialyzate, appeared to be much smaller than for urea and creatinine. In a stable dialysis population of 17 patients, significant negative correlations were found between pre-dialysis plasma concentrations of some MM (7a, 7b, 7f, 7g) and dialysis index or endogenous renal creatinine clearance. No such correlations were found for peaks 7c and 7d. The good correlation between 7b and dialysis index (r = 0.73) suggests that plasma determination of 7b may be used as a measure of the efficiency of MM removal.
We have estimated the degree of fibrin deposition as well as changes in dialyzer efficiency of Gambro Optima 13.5 mu dialyzers, re-used up to six times in six regular dialysis patients. After each dialysis the dialyzer was rinsed and left filled with formaldehyde. The patients were given I-125-fibrinogen before the study. The radioactivity from the dialyzer was continuously measured during each dialysis and rinsing procedure. Urea and creatinine clearances were determined 30 min after start of each dialysis. After the last re-use the dialyzer membranes were removed and divided into sections and the radioactivity of each section was measured. Twice as much fibrin deposition was found near the blood inlet of the dialyzer as near the outlet. A higher fibrin deposition was found after each re-use than after the initial dialysis. The clearances of urea and creatinine were scarcely influenced by the re-use. The half-life of fibrinogen in the patients was in the same range as in normal subjects.
Nine patients with diuretic-resistant edema, secondary to congestive heart failure, liver cirrhosis, or nephrotic syndrome, were treated with ultrafiltration using high water flux dialyzers. Access to the blood stream was obtained by femoral vein catheterization. As much as 8.3 kg of fluid were removed in 3--4 hours with only transient decline in blood pressure. The procedure was well tolerated and yielded immediate symptomatic relief. The potential for restoration of an edema-free state in patients with diuretic-resistant edema suggests that further experience with this technique is justified.
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