Buffer metabolism in continuous ambulatory peritoneal dialysis (CAPD): relationship with respiratory dynamics.
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Biomedical subjects
Publications and source records attributed to S Biasioli.
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We investigated the pharmacokinetics of cefuroxime sodium, a new parenteral beta-lactam antibiotic, in 15 patients with stable chronic renal failure during intermittent peritoneal dialysis (IPD). Eight patients were administered 1 g cefuroxime as an intravenous bolus 1 h before the start of dialysis. Mean plasma levels of cefuroxime fell from 80 mcg/ml at 1 h to 40 mcg/ml at 6-8 h. At 24 h, concentrations were higher than 20 mcg/ml. In peritoneal fluid cefuroxime reached 16.7 mcg/ml at 1 h and 7.55 mcg/ml at 6 h. Seven patients received cefuroxime added to the dialysis solution at a dose of 2.5 g/10 liters. After 6 h of dialysis, cefuroxime reached plasma levels of 60 mcg/ml; after 24 h, concentrations were 37.5 mcg/ml. These results demonstrate that cefuroxime, administered by the i.v. route, easily diffuses from blood to peritoneal fluid and, from peritoneal fluid to blood when added to the dialysis solution. In both cases concentrations reached by cefuroxime are sufficient to treat peritoneal infections associated with peritoneal dialysis.
Forty studies of acid-base balance during intermittent peritoneal dialysis (IPD) and during continuous ambulatory peritoneal dialysis (CAPD) were performed on 20 patients who were receiving IPD with acetate buffer (5 patients), IPD with lactate buffer (5 patients), CAPD with acetate buffer (5 patients) and CAPD with lactate buffer (5 patients). Measurements of acetate, lactate and pyruvate levels in blood and dialyzate were taken at different times during dialysis; blood samples for blood gas analysis were drawn at the same times. Calculations of the kinetics of acetate, lactate and bicarbonate during IPD and CAPD were carried out according to the method of Tolchin [1977] but modified for PD. Thus it was possible to quantify the balance of the buffers, their mass transfer rates, bicarbonate generation and the percentage of buffer converted to HCO3. IPD kinetics of acetate and lactate were found to be similar, the main difference being a lower and significant percentage conversion of lactate to bicarbonate (45%) compared to that of acetate to bicarbonate (71%) (P < 0.005). On CAPD the kinetics of the two buffers was quite different: while the serum lactate level was always low (mean 0.97 +/- 0.33 mM/l), the acetate level was always high (mean 5.12 +/- 3.34 mM/l). Thus the utilization of the two buffers during "acute intermittent" treatment (IPD) and "continuous" treatment (CAPD) is different. On IPD there are no important differences between the two buffers, whilst on CAPD lactate seems to be better and safer than acetate; for instance, serum HCO3 values are relatively constant with lactate (27.7 +/- 2.13 mM/l) while with acetate there is a trend to exceed physiological values (29.5 +/- 1.7 mM/l). When acetate is used in the dialyzate for CAPD the concentration must be less than 38.5 mM/l.
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In eighteen months, eleven Sparks mandrils have been implanted in ten patients who presented serious vascular access problems. So far nine mandrils have been anastomosed and six are functioning. In one patient the apparatus, inserted in the right leg, clotted after 108 dialyses and was reinserted in the left arm; after a further forty dialyses the patient died from causes not connected with dialysis. Another patient's Sparks mandril thrombosed from infection on the fourth post-operative day. Using a single needle apparatus, 693 dialyses have been carried out with particular problems either for the patients or the grafts.
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Chronic heart failure (HF) is considered to be refractory when persisting despite an intensive drug regimen, or intractable when requiring "artificial" supports. Among them, hemofiltration (HE) has been used frequently, but only on an "acute" basis, to induce fast and safe water removal. Since 1985 the authors have treated refractory and intractable HF first by means of acute CAVH (continuous arteriovenous HE: 11 patients) and then (1988-1992) with IVVH (intermittent venovenous HE), initially done on an "acute" basis (13 patients) and then an a chronic basis (CIVVH): 8 subjects (6M, 2F; mean age, 60.8 years), 3 with RCHF and 5 with ICHF. This report deals with our experience in CIVVH. All patients were in severe failure. During a follow-up period of 63 months (range, 1-17/patient), 82 IVVH treatments (10.2/patient) were carried out, using this schedule: permanent Tesio catheter in superior vena cava, 0.6 m2 filter, double blood pump (blood flow = 80-250 ml/min); transmembrane pressure = 50-150 mmHg; mean ultrafiltration = 19 ml/min; replacement fluid = 8.6 ml/min; and session time = 340 +/- 88 min, according to individual dry weight (bioimpedance system). Six patients died (1-13 months after IVVH began); four of six had ICHF and two of six had RCHF; five of eight patients showed a significant amelioration of functional state, changing from fourth to third, to second and first degree failure, but this was after heart transplantation. In all cases a marked reduction in the drug regimen and in hospitalization was the rule.
The defenses against the production of free radicals and reactive oxygen species (ROS) are to be found in plasma (ascorbate, urate, alpha tocopherol) and in erythrocytes (superoxide dismutase or SOD; catalase or CAT; glutathione peroxidase or GPx). In chronic renal failure, an increased lipid peroxidation and a reduced antioxidant activity seem to be present, but previous reports are conflicting. To clarify the peroxidative status and the defense mechanisms taking place in patients on dialysis, in 30 patients on dialysis (15 men, 15 women) and in 20 control subjects (10 men, 10 women), the following parameters were measured: plasma 4-hydroxinonenal (4-HNE) and erythrocyte reduced glutathione (GSH), SOD, GPx, and glucose-6-phosphate dehydrogenase (G-6-PD). Patients on dialysis, in comparison with control subjects, had 1) increased levels of 4-HNE (p < 0.001); 2) a significant increase in erythrocyte-GSH (p < 0.05); and 3) significant decreases in erythrocyte-SOD (p < 0.001), erythrocyte-G-6-PD (p < 0.005), and the erythrocyte-SOD/GPx ratio (p < 0.001). The dialysis procedure induced a certain reduction in plasma 4-HNE, an increase in erythrocyte-SOD activity, and an important consumption of erythrocyte-GSH, while the erythrocyte-SOD/GPx ratio changed. The current study supports the view that 1) erythrocytes act as small detoxifying packets; 2) in chronic renal failure, the antioxidant system is largely inadequate; and 3) in patients on dialysis, the antioxidant mechanism of erythrocytes in scavenging ROS is effectively exerted during dialysis but remains largely inadequate, as signs of lipid peroxidation persist with time.
In patients with chronic renal failure who undergo hemodialysis (HD), the antioxidant system is inadequate to correct the imbalance between the generation and scavenging of reactive oxygen species. To clarify the role of six different membranes on oxidative stress, the authors measured plasma lipid peroxidation and erythrocyte (E) concentrations of several antioxidant enzymes in 30 HD patients: 20 on bicarbonate HD, 4 on paired filtration dialysis, 3 on acetate free biofiltration, and 3 on hemodiafiltration. Before, during, and after the first session of the week (at times 0, 30, 60, and 120 min, end, and 30 min after end of HD), several blood samples were drawn. Plasma (P) homocysteine (HCY), cysteine (CYS), malondialdehyde (MDA), E-glutathione (GSH), glucose-6-phosphodehydrogenase, glutathione reductase (GR), glutathione peroxidase (GP), catalase (CAT), and superoxide dismutase (SOD) were determined. All six membranes (Hemophan [HEMO]; cellulose diacetate [DIAC]; acrylonitrile-69 [AN69]; polymethylmethacrylate [PMMA]; cuprammonium rayon [CURAY]; polysulfone plus hemophan [PS + HEMO]) induced a significant decrease in plasma lipid peroxidation (p < 0.001) and an increase in E-GSH, GR, GR + flavinadenine dinucleotide, GP, and SOD (p < 0.001). Some membranes, however, showed some peculiar effects on reactive oxygen species: HEMO is better than DIAC, as far as P-MDA and P-HCY are concerned; PMMA induces higher changes in E-GR and P-CYS than does HEMO; and patients chronically using PMMA and PS + HEMO membranes show the lowest P-HCY levels both before and after dialytic sessions. Based on these changes, implications as to the effects on vascular disorders could be derived.
Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.
To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.
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