Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis.

The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis. Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX. Multiple blood and dialysate samples were collected during the 72-h period after drug administration. The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v. administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively. No significant differences were observed in these parameters after i.p. administration. The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v. administration. The bioavailability of CTX after i.p. instillation was 74.6 +/- 21.3%. Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p. dosing. Administration (i.v.) of 2 g every 12 h or i.p. instillation of 2 g every 24 h may be used for the treatment of i.p. infections with highly susceptible organisms (MIC less than 1.0 microgram/ml).

Dialytic therapy in the management of chronic renal failure.

The maintenance of life after the development of end-stage renal disease can be achieved by the use of dialytic therapy, either alone as permanent replacement therapy or in conjunction with transplantation. The imperfections of all forms of dialytic therapy leave the nephrologist with the responsibility of recommending to the patient the treatment(s) considered most suitable. Hemodialysis, hemofiltration, and peritoneal dialysis are discussed in this article.

Opsonic deficiency of peritoneal dialysis effluent in continuous ambulatory peritoneal dialysis.

Staphylococcus epidermidis peritonitis frequently complicates the clinical course of patients treated with continuous ambulatory peritoneal dialysis (CAPD). Since bacterial opsonization is critical to the effective defense of the peritoneal cavity by phagocytic cells, we prospectively evaluated the opsonic activity of peritoneal dialysis effluent obtained from 17 CAPD patients during 102 patient months. Samples of peritoneal dialysis effluent contained concentrations of opsonins against S. epidermidis that were less than 2% of that observed in serum. Moreover, heat-labile opsonic activity against Escherichia coli was absent from all dialysis effluents. During the study, there were ten episodes of peritonitis in nine CAPD patients (1 per 10.2 patient months). S. epidermidis was isolated in seven episodes, a gram-negative bacillus in one, and two episodes were culture negative. the incidence of S. epidermidis peritonitis was 1 per 62 patient months in the patients with "high" peritoneal dialysis effluent opsonic activity against S. epidermidis but was nearly tenfold greater in patients with "low" opsonic activity (1 per 6.7 patient months). We conclude that peritoneal dialysis effluent opsonic activity predicts which CAPD patients are at an increased risk to develop S. epidermidis peritonitis.

Peritoneal transport of vancomycin in 4 patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin have been studied in 4 chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis. Patients received 1 g of vancomycin in 2 liters of dialysate during an initial phase, and serum and dialysate samples were collected for vancomycin determination. 54% of the amount introduced into the peritoneal cavity were absorbed systemically during a 6-hour cycle. Peak serum concentrations averaged 23.7 microgram/ml. Mean elimination half-life was calculated to be 66.9 h, and dialysis clearance averaged 2.4 ml/min.

Pharmacokinetics of gentamicin in patients undergoing continuous ambulatory peritoneal dialysis.

Teh pharmacokinetics of gentamicin were studied in seven chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis. Patients received 100 mg of gentamicin in 2 liters of dialysate during an initial pass, and serum and dialysate samples were collected for gentamicin determination. Approximately 49% of the amount introduced into the peritoneal cavity was absorbed systemically during a 6-h cycle. Subsequent clearance of gentamicin from the serum occurred slowly with an elimination half-life of 36 h. Dialysis clearance of gentamicin during continuous ambulatory peritoneal dialysis was 2.94 ml/min.

Quinidine pharmacokinetics in continuous ambulatory peritoneal dialysis.

The clearance of quinidine was evaluated in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The dialysis clearance of quinidine was 0.793 ml/min which represented only 0.61% of the total body clearance (154.21 ml/min) of the drug. The elimination half-life of quinidine was 5.44 hours. Based on our results, dosage adjustment of quinidine does not appear to be necessary for patients undergoing CAPD.

Cardiac operation and end-stage renal disease.

From 1972-1979, 22 patients with end-stage renal disease underwent 23 cardiac operations involving the pump oxygenator. Fourteen patients had coronary artery bypasss, 2 had aortic valve replacement, 2 had mitral valve replacement (MVR), 2 had MVR with coronary artery bypass, and 2 had ascending aortic root replacement with a composite graft. One patient underwent successful reoperation for a false aneurysm of the left ventricle after MVR. There were 2 postoperative deaths, for a mortality of 9.1%. The patients undergoing coronary artery bypass had an average of 2.7 grafts and an average Functional Class improvement from New York Heart Association Class III or IV to Class I to II. Eighteen patients required preoperative and postoperative dialysis to control blood volume, potassium, and uremia. Four patients had functioning renal transplants, and 4 patients underwent subsequent successful renal transplantation. We conclude that: (1) patients who have transplants and require dialysis can be successfully managed for cardiac operation in spite of their complex associated medical problems; (2) functional and symptomatic improvement simplifies continued management of the patient needing dialysis; and (3) improvement of a cardiac disability can allow favorable renal transplantation in selected patients.

Coronary-artery surgery in patients with end-stage renal disease.

Between 1975 and 1979 we performed coronary arteriography on 15 patients with end-stage renal failure and clinical evidence of severe ischemic heart disease. One patient died after the procedure of severe pump failure. Ten patients subsequently received coronary-artery bypass grafts, and two of these patients also received mitral-valve replacement. One patient, a diabetic, died of sepsis after surgery. Eight of the nine surviving patients, including the two patients who had undergone mitral-valve replacement, are markedly improved as a result of surgery. Our experience indicates that these patients can undergo angiography and coronary-artery bypass surgery at an increased but acceptable risk, provided dialysis is done before and after cardiac catheterization and surgery to control extracellular volume overload and hyperkalemia. The operation benefits patients with end-stage renal failure and severe ischemic heart disease by relieving angina and improving their level of activity. It is unclear whether survival is improved for these patients.

Dietary management of patients with diabetes treated by hemodialysis.

Early experience with the treatment of patients with insulin-dependent diabetes and renal failure by chronic hemodialysis indicated a high mortality and increased incidence of medical complications. Since 1972, a marked improvement in survival and reduction in incidence of complications has been attributed to more rigorous control of fluid overload, hypertension, and blood sugar levels by insulin therapy and careful dietary management. A diet has been developed which combines the diet used by dialysis patients with suitable modifications for the insulin-dependent patient with diabetes. The importance of patient education is stressed in an attempt to improve patient compliance.

The metabolic effects of hemodialysis with and without glucose in the dialysate.

The present study compares some of the metabolic effects of hemodialysis of fasting patients with and without glucose in the dialysate bath. Unlike glucose dialysis, glucose-free dialysis caused marked decreases in blood levels of glucose, insulin, lactate, and pyruvate along with profound increases in acetoacetate and beta-hydroxybutyrate. It is concluded that oxidation of fatty acids increases to meet energy demands and that the combined processes of glycogenolysis and gluconeogenesis serve to prevent critical hypoglycemia during glucose-free dialysis.

A clinical study of anti-NDP in the sera of patients in a large repetitive hemodialysis program.

Anti-NDP has been detected in the sera of 38 of 430 patients on regular hemodialysis at the Regional Kidney Disease Program in Minneapolis. It developed in these patients from 7 to 58 months after commencement of dialysis. Bacterial infection appeared temporally related to the development of anti-NDP in 12 patients. Hemolytic episodes, possibly related to anti-NDP, occurred in 11. Fifty-five percent of the patients never reused dialyzers. The antibody preceded the insertion of a bovine graft in seven. We postulate that anti-NDP is recognizing an antigenic site similar to that recognized by Vicia graminea lectin, and that this site might become immunogenic by alteration of M and N antigens on red blood cell surfaces. Though formaldehyde might be involved in this alteration, dialysis membrane reuse does not seem to be required for the formation of anti-NDP.

A reassessment of the prognosis of diabetic patients treated by chronic hemodialysis (CHD).

Our early results in 25 diabetics treated by CHD prior to 1972, compared to results in a further 66 diabetics starting CHD since 1972, show an improvement in survival related to a reduction in deaths from myocardial infarction and sepsis. There has been a reduction in complications requiring hospital admission, related to a lower incidence of sepsis. Access survival has been markedly improved since the introduction of the bovine fistula.

Depressed in vitro aggregation of platelets of chronic hemodialysis patients (CHDP): a role for cyclic AMP.

1) On log-log-coordiantes a direct correlation has bee shown to exist between plasma cyclic AMP and plasma Cr levels. 2) hemodialysis results in a significant reduction in the arterial plasma cyclic AMP levels, but a return of plasma cyclic AMP to pre-dialysis levels is seen within 30 mins post-dialysis. 3) the dialyzer clearance of cyclic AMP, both in vitro and vivo, is commensurate with its M.W. 4) In vitro platelet aggregation responses, to ADP, EPI, and COLL are not influenced by PRP cell counts between 150,000 and 300,000/mm3. 5) the BT of NC and CHDP are not significantly different, indicating that the in vivo hemostatic properties of the CHDP are otherwise intact. 6)the CHDP have PVPC significantly lower than the NC, a finding commensurate with the usual mold thrombocytopenia of renal failure. 7)the aggreation responses of the CHDP to COLL and to both Lo and Hi concentrations of ADP and EPI are significantly less than those of the NC. 8)A statistically significant inverse correlation between aggregation response and plasma cyclic AMP is observed.