Keevin Bernstein

Antibiotic-Heparin Lock: In Vitro Antibiotic Stability Combined with Heparin in a Central Venous Catheter

Long‐term hemodialysis frequently requires vascular access through central venous catheters (CVCs). Infection related to these catheters is a significant complication. The use of an antibiotic‐heparin lock could decrease the risks associated with infected permanent catheters. As an initial step in developing an antibiotic‐heparin lock, we investigated the in vitro stability of antibiotic‐heparin combinations in CVCs. Initially, cefazolin, vancomycin, ceftazidime, ciprofloxacin 10 mg/ml each, and gentamicin 5 mg/ml were incubated separately in glass test tubes in the dark at 37°C for 72 hours. Samples were analyzed spectrophotometrically for stability at 24‐hour intervals. The procedure was repeated with the addition of heparin (final concentration 5000 U/ml in glass test tubes), and the combination was also examined in CVCs. High‐performance liquid chromatography analysis was conducted on the antibiotic‐heparin combinations at 72 hours to confirm the spectrophotometric results. Ciprofloxacin produced an immediate precipitate with the addition of heparin and was not analyzed further. Absorbance values decreased for all antibiotics, with the greatest decreases at 72 hours for cefazolin (27.4%), vancomycin (29.7%), ceftazidime (40.2%), and gentamicin (8%) when combined with heparin. These decreases were postulated to be secondary to adsorption of the antibiotics to the luminal surface of the catheters because submitting the catheters to ultrasound with 1% sodium bicarbonate and analyzing the resulting solution for absorbance revealed that some of the drug was recovered. Although free antibiotic in CVC solution was reduced, the concentration should be sufficient (approximately 5 mg/ml) to decrease the frequency of infections associated with CVCs. We conclude that the concentrations of vancomycin, ceftazidime, cefazolin, or gentamicin used in our study should be sufficient for an antibiotic‐heparin lock.

Production of Tumor Necrosis Factor Alpha and Hemodialysis

The production of TNF alpha by peripheral blood mononuclear cells (PBMC) was determined in 18 hemodialysis (HD) patients. Blood was taken from each patient before and after an HD treatment. Both pre- and post-HD PBMC produced significantly more TNF alpha than controls (TNF alpha units/ml; mean +/- SEM; controls 3.1 +/- 0.7; pre-HD 9.7 +/- 3.9; post-HD 19.8 +/- 7.7, p < 0.05). In addition, post-HD PBMC produced significantly more TNF alpha than pre-HD PBMC suggesting that the HD procedure itself may activate cytokine production. This was true when PBMC were cultured in serum free medium as well as on culture with non-HD sera (human AB) and autologous sera. A positive correlation was also found between the production of TNF alpha and age in HD patients (r = 0.58; p < 0.01). Finally, normal PBMC cultured in post-HD sera produced significantly less TNF alpha than when cultured in the same sera pre-HD (p < 0.02). These findings suggest that PBMC of HD patients are chronically stimulated to produce TNF alpha which may contribute to some of the short-term and long-term complications of HD.

Increased Production of Tumor Necrosis Factor Activity by Hemodialysis but Not Peritoneal Dialysis Patients

The production of tumor necrosis factor alpha (TNF alpha) activity by peripheral blood mononuclear cells (PBMC) was determined in uremic patients on chronic hemodialysis (HD; n = 27), continuous ambulatory peritoneal dialysis (CAPD; n = 19), and in patients with chronic renal failure who were not yet on dialysis (CRF-ND; n = 18). In the HD group blood was taken immediately prior to and immediately following an HD session utilizing a cellulose acetate dialyzer. Post-HD PBMC spontaneously (i.e. in serum free media) produced significantly more TNF alpha activity than the PBMC of all other patient groups as well as those of the normal controls (n = 41) (p < 0.003). Post-HD PBMC produced significantly more TNF alpha activity than pre-HD PBMC both spontaneously and in the presence of nonuremic sera (p < 0.003). PBMC prior to HD also produced significantly more. TNF alpha activity than CAPD PBMC and normal PBMC in the presence of autologous heat inactivated sera (p < 0.03). Under some culture conditions (i.e. in the presence of nonuremic sera) normal PBMC produced significantly (p < 0.003) more TNF alpha activity than CAPD PBMC. Finally, a positive correlation was found between PBMC TNF alpha activity and age for HD patients (r = 0.7, p < 0.004) but not for CAPD or CRF-ND patients. These findings suggest that PBMC of HD but not CAPD or CRF-ND patients are chronically stimulated to produce TNF alpha activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Home Hemodialysis in the Remote Canadian North: Treatment in Manitoba Fly‐in Communities

Manitoba has the highest prevalence of ESRD in Canada. Northern Manitoba is a very sparsely settled area with a high proportion of aboriginal ESRD patients. Relocating to urban areas for dialysis is psychosocially and culturally stressful to patients. Delivering dialysis care in a home setting has demonstrated advantages in both clinical, economic, and health related quality of life domains. Establishing home hemodialysis in very remote communities has significant challenges, including poor and inadequate housing, unreliable water supply, limited community medical backup, and poor road access to communities especially for delivery of supplies. These challenges necessitate the development of strong community partnerships, and well documented processes for contingencies. A dedicated interdisciplinary support and training team at the urban hub is essential.

Erythropoietin-Alpha Dosage Requirements in a Provincial Hemodialysis Population: Effect of Switching from Subcutaneous to Intravenous Administration

Background: The purpose of this initiative was to compare erythropoietin-α doses in hemodialysis patients who changed from subcutaneous to intravenous administration. The Manitoba Renal Program switched routes due to concern about erythropoietin-associated pure red cell aplasia. Methods: We compared the erythropoie tin-α dosage requirements during subcutaneous administration (3 months pre-switch) and intravenous administration (months 4–6 post-switch). We also compared: hemoglobin, transferrin saturation (Tsat%), ferritin, and percent of patients receiving intravenous iron. The same erythropoietin-α regimen was initially used when patients were switched. Results: Of the 628 patients receiving erythropoietin-α, the data were complete for 400. The dose increased 26% (mean ± SD, 10,425 ± 7,330 vs. 13,125 ± 8,638 IU/week; p < 0.0001), despite similar hemoglobin, (mean ± SD, 11.5 ± 1.1g/dl (114.9 ± 11.2 g/l) vs. 11.3 ± 1.0 g/dl (113.5 ± 10.4 g/l); p = 0.0450) and iron parameters (Tsat 30.9%, ferritin 464 ng/ml (µg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (µg/l)). For the subgroup of 84 patients who maintained target hemoglobin (10–11 g/dl or 110–120 g/l) for both periods, the dose increased 26% (mean ± SD, 8,393 ± 6,242 vs. 10,589 ± 7,049 IU/week; p < 0.0001) without a change in hemoglobin, (mean ± SD, 11.5 ± 0.3 g/dl (115.2 ± 3.0 g/l) vs. 11.5 ± 0.3 g/dl (114.9 ± 3.3 g/l); p = 0.5789). When stratified by subcutaneous dose, patients with the lowest dose (<5,000 IU/week) demonstrated the greatest increase (89%), and those with the highest dose (>20,000 IU/week) experienced no increase (–3%). Conclusion: Overall, erythropoietin-α doses increased by 26% when patients were converted from subcutaneous to intravenous administration.