No role for patient body weight on renal function assessment for drug dosing.

Objectives: To evaluate the ability of body-weight-driven renal function assessment (RFA) formulae to predict on-target elimination rate ranges for gentamicin in patients with varying degrees of renal function. Methods: A 6 year retrospective pharmacokinetic study was conducted at a university teaching hospital. Results: A total of 85 patients met the inclusion criteria and 127 pharmacokinetic files were analysed from patients on medical-surgical wards (53%) and medical-surgical ICUs (13%) receiving intravenous gentamicin for treatment, as well as those for patients receiving it for surgical prophylaxis (34%). Each RFA formula was examined against standard dosing tables for gentamicin. A table of acceptable elimination rates was generated using a traditional peak of 8 mg/L and trough between 0.5 and 2 mg/L associated with each of the dosing interval extensions. The ability of each RFA formula to select on-target elimination rates was evaluated. The RFA formula assuming a normalized body weight of 72 kg and a modified creatinine reagent adjustment factor of 90% provided the most accurate on-target elimination rate selection. This method was superior to dosing interval selection based on the Modification in Diet Renal Disease (MDRD) formula, Sanford's guide method, as well as the Cockcroft-Gault formulae using total body weight, ideal body weight or lean body weight ( P < 0.0001). Conclusions: Based on the use of gentamicin as a surrogate guide for renally adjusted drugs, these results support dosing interval selection based on a normalized body weight method and a formula reagent adjustment factor of 90% within the Cockcroft-Gault formula.

The association between geographic proximity to a dialysis facility and use of dialysis catheters.

BACKGROUND: Residing remotely from health care resources appears to impact quality of care delivery. It remains unclear if there are differences in vascular access based on distance of one's residence to dialysis centre at time of dialysis initiation, and whether region or duration of pre-dialysis care are important effect modifiers. METHODS: We studied the association of distance from a patients' residence to the nearest dialysis centre and central venous catheter (CVC) use in an observational study of 26,449 incident adult dialysis patients registered in the Canadian Organ Replacement Registry between 2000-2009. Multivariate logistic regression was used to assess the association between distance in tertiles and CVC use, adjusted for patient demographics and comorbidities. Geographic region and duration of pre-dialysis care were examined as potential effect modifiers. RESULTS: Eighty percent of patients commenced dialysis with a CVC. Incident CVC use was highest among those living > 20 km from the dialysis centre (OR 1.29 (1.24-1.34)) compared to those living < 5 km from centre. The length of pre-dialysis care and geographic region were significant effect modifiers; among patients residing in the furthest tertile (>20 km) from the nearest dialysis centre, incident CVC use was more common with shorter length of pre-dialysis care (< 1 year) and residence in central regions of the country. CONCLUSION: Residing further from a dialysis centre is associated with increased CVC use, an effect modified by shorter pre-dialysis care and the geographic region of the country. Efforts to reduce geographical disparities in pre dialysis care may decrease CVC use.

Initial vancomycin dosing protocol to achieve therapeutic serum concentrations in patients undergoing hemodialysis.

BACKGROUND: Although recent consensus guidelines proposed more aggressive vancomycin troughs of >10 or 15-20 mg/L for complicated Staphylococcus aureus infections, dosing information to achieve these targets in patients undergoing hemodialysis (HD) is scarce. METHODS: We used Monte Carlo simulation (MCS) methods with a previously published population-pharmacokinetic model and relevant patient demographics to evaluate and revise our existing vancomycin dosing protocol (1000-mg load followed by 500-mg maintenance dose, with doses infused during the last hour of dialysis). A new protocol (1000-mg load followed by 500-mg maintenance dose for patients <70 kg, 1250-mg followed by 750-mg for those 70-100 kg, and 1500-mg followed by 1000-mg for those >100 kg) was developed and prospectively validated to achieve therapeutic serum troughs in patients undergoing high-flux HD. RESULTS: MCSs predicted that our existing protocol would be suboptimal in more than one-third of patients. Simulations predicted that the new vancomycin dosing protocol would achieve maintenance (pre-HD) troughs of 10-20 mg/L in 86.0% of cases including 15-20 mg/L in 35.2%. In prospective validation, the observed postload trough (pre-HD session 2) was 13.5 ± 3.4 mg/L with 76.9% of levels (20 of 26) between 10 and 20 mg/L. The observed maintenance trough was 17.3 ± 4.0 mg/L with 65.5% (19 of 29) between 10 and 20 mg/L and 89.7% (26 of 29) within 10% of the upper limit (ie, 10-22 mg/L). CONCLUSIONS: In this study, a practical vancomycin dosing protocol for patients undergoing HD was developed and prospectively validated to achieve therapeutic serum concentrations in the clinical setting.

Alteplase for blood flow restoration in hemodialysis catheters: a multicenter, randomized, prospective study comparing "dwell" versus "push" administration.

AIMS: Catheter-related thrombosis is a frequent complication of providing hemodialysis via central venous catheters. The primary aim of this study was to compare the efficacy of an alteplase "dwell" protocol over 30 minutes (with an additional 90 minutes where necessary) to a new 30 minute "push" protocol in restoring function to occluded hemodialysis catheters. METHODS: This was a prospective, randomized, parallel arm, multicenter study. Participants included hemodialysis patients using central venous catheters for vascular access. A new alteplase push protocol was the intervention and was compared to an alteplase dwell protocol. The primary outcome of this study was the proportion of patients with pre-thrombolytic blood flows less than 200 ml/min achieving a post thrombolytic blood flow ≥ 300 ml/ min. Secondary outcomes included recovery of Kt/V and liters processed per hour at the hemodialysis session following the intervention, time from thrombolytic to future catheter interventions, and the presence of serious adverse events. RESULTS: 82 patients were included in the intention-to-treat analysis. 65% (28/43) of catheters receiving the dwell protocol achieved blood flow ≥ 300 ml/min compared to 82% (32/39) in the push protocol. The difference was not statistically significant despite a 17% separation in the point estimates, p = 0.84. A non-significant result may have been associated with an inability to enrol the required a priori sample size. Kt/V, liters processed per hour and time to next catheter event were not significantly different. There were no serious adverse events attributed to the study medication. CONCLUSIONS: The alteplase push protocol was effective and safe for managing dysfunctional hemodialysis catheters and was more practical than a 2 h dwell.

Long-term effect of an ethanol/sodium citrate locking solution on the mechanical properties of hemodialysis catheters.

PURPOSE: To investigate the effect of a 30% ethanol/4% sodium citrate catheter locking solution on the mechanical properties of hemodialysis (HD) catheters over 36 weeks. METHODS: Twenty-one HD catheters were used in this study. Three catheters, not exposed to locking solutions, underwent mechanical testing to determine baseline properties. Nine of the remaining 18 catheters were filled with normal saline and underwent mechanical testing in groups of three at 12, 24 and 36 weeks. Similarly, nine catheters were filled with the 30% ethanol/4% sodium citrate locking solution and tested in a similar manner. RESULTS: The average force required to break the catheter lumens tended to be smaller in the catheters exposed to 30% ethanol/4% sodium citrate compared to saline controls at 12 and 24 weeks; however, there were no statistically significant differences between the groups after 36 weeks of exposure. The forces required to break these HD catheters are magnitudes greater than forces generated during a typical HD session. CONCLUSIONS: We conclude that the 30% ethanol/4% sodium citrate locking solution had an effect on the mechanical properties of the catheters investigated, but not to the degree that would preclude further in vivo investigation. Further studies are necessary to determine the safety and efficacy of this catheter locking solution.

Effectiveness of a 30% ethanol/4% trisodium citrate locking solution in preventing biofilm formation by organisms causing haemodialysis catheter-related infections.

OBJECTIVES: Antibiotic locks may be used to prevent haemodialysis catheter-related infections (CRIs). This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate lock solution in preventing biofilm formation by the most common pathogens causing haemodialysis CRIs. METHODS: Ten clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli were tested. Bacterial suspensions of each isolate were prepared in a control solution of normal saline/Mueller-Hinton broth (MHB) and in a lock solution of 30% ethanol/4% trisodium citrate and MHB. The bacterial suspensions were placed into the wells of a Calgary Biofilm Device (CBD) and incubated with fresh solution every 24 h for 72 h. The biofilm formation was assessed by removing the CBD pegs, placing them in normal saline and sonicating them for 5 min. The resulting solution was sampled and the colony counts were determined after 24 h of incubation. RESULTS: All controls demonstrated biofilm growth of between 6 x 10(6) and 7.4 x 10(7) cfu/mL over 72 h. In the 30% ethanol/4% trisodium citrate lock solution, no biofilm growth was observed after 72 h of incubation. These results were consistent among duplicates of all isolates. CONCLUSIONS: The 30% ethanol/4% trisodium citrate lock solution prevented the biofilm formation of all isolates of S. aureus, S. epidermidis, P. aeruginosa and E. coli in vitro. Further studies are necessary to determine its efficacy and safety in the haemodialysis population.

Effect of an ethanol/trisodium citrate hemodialysis catheter locking solution on isolates of Candida albicans.

We conducted an in vitro study to assess the effect of a 30% ethanol/4% trisodium citrate (TSC) catheter locking solution on isolates of Candida albicans. Twelve isolates obtained from human blood cultures were tested in control solutions composed of broth and normal saline, and a test solution of 30% ethanol, 4% TSC, and broth. Colony counts were determined for control and test solutions at baseline and after 1, 24, and 48 hours of exposure. After 48 hours, the remaining test solution was filtered through a sterile filter funnel and rinsed with 10 mL of sterile water. Filters were aseptically transferred to agar plates and incubated for 24 hours. Control solutions grew well over the incubation period, as expected. In contrast, no viable growth was observed in test solutions 1 hour after instillation of the ethanol/TSC locking solution, or throughout the 48-hour study duration. Additionally, filters from test solutions displayed no growth. We conclude that a 30% ethanol/4% TSC catheter locking solution eradicated all isolates of C. albicans within 1 hour of exposure in this in vitro study, and shows promise as a new hemodialysis catheter locking solution.

Conversion from epoetin alfa to darbepoetin alfa within the Manitoba Renal Program: evaluation of dose ratios.

We sought to describe dose conversion ratios between epoetin alfa and darbepoetin alfa for patients with anemia of chronic kidney disease (CKD) in a large provincial renal program. Hemodialysis (HD), peritoneal dialysis (PD) and pre-dialysis patients with CKD were included. Laboratory parameters and darbepoetin alfa doses were compared to epoetin alfa doses (same route). In 2005, 857 patients received darbepoetin alfa and were compared to 746 patients who received epoetin alfa in 2003-2004. Mean dose conversion ratios were 12,939 IU, 53.1 microg, 244:1 for HD; 9,273 IU, 41.8 microg, 222:1 for PD; and 5,516 IU, 25.2 microg and 219:1 for CKD patients. The mean hemoglobin and iron parameters were within K/DOQI targets on both drugs. Conversion ratios in HD, PD and CKD patients using erythropoietic therapies was greater than 200:1 with both intravenous and subcutaneous dosing. Renal programs across Canada should consider dosage conversion ratios in addition to drug acquisition costs when considering a formulary decision about erythropoiesis stimulating agents.

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-alpha 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 erythropoietin-alpha 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-alpha regimen was initially used when patients were switched. RESULTS: Of the 628 patients receiving erythropoietin-alpha, 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 (microg/l) vs. Tsat 28.7%, ferritin 538 ng/ml (microg/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-alpha doses increased by 26% when patients were converted from subcutaneous to intravenous administration.

An ethanol/sodium citrate locking solution compared to heparin to prevent hemodialysis catheter-related infections: a randomized pilot study.

PURPOSE: The objective of this study was to compare the initial safety and efficacy of a novel 30% ethanol/4% sodium citrate catheter-locking solution to heparin in a hemodialysis population. METHODS: This was a prospective, randomized, pilot study of 40 hemodialysis patients randomized to a 30% ethanol/4% sodium citrate or heparin 1000 units/mL locking solution. The primary outcome was identification of any serious adverse events over the study duration. Secondary outcomes included the rate per 1000 catheter days for catheter-related bloodstream infections (CRBSI), alteplase use, catheter dysfunction, and catheter removal. RESULTS: Three serious adverse events were reported as possibly related to the catheter solutions. Only one CRBSI was observed during the study in the heparin arm. The rate of alteplase use was 1.5/1000 catheter days in the heparin arm compared to 2.8/1000 catheter days in the ethanol/citrate arm (rate ratio = 1.85, 90% CI 0.48, 7.07, p value = 0.45), while the rate of catheter dysfunction was 6.8/1000 catheter days in the heparin arm compared to 1.9/1000 catheter days in the ethanol citrate arm (rate ratio = 0.27, 90% CI 0.10, 0.74, p value = 0.04). Catheter survival to first catheter outcome was longer in the ethanol/citrate group compared to heparin and there were no catheter removals due to bacteremia or thrombosis. CONCLUSIONS: The ethanol/sodium citrate locking solution was safely used in this study. It appears to prevent CRBSI and may improve catheter survival compared to heparin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01394458.

Conversion from subcutaneous to intravenous erythropoietin in a hemodialysis population.

The purpose of this study was to compare erythropoietin dosage requirements during subcutaneous versus intravenous administration in a hemodialysis population. Hemodialysis patients receiving subcutaneous epoetin alfa were switched to the intravenous route using a prospective, crossover design. Baseline anemia parameters were measured at months -2, -1, and 0 when patients were receiving subcutaneous dosing and compared to months 4, 5, and 6 after the switch to intravenous dosing. Ninety-eight patients were enrolled into the study with an average age of 54.8 years. Over the course of the study, 34 patients were excluded from analysis, leaving 64 patients with complete hemoglobin and erythropoietin dosing data throughout the subcutaneous and intravenous evaluation periods. In these patients, the dose of erythropoietin increased significantly from the subcutaneous to the intravenous period (7567.7 to 10229.2 IU/wk). The conversion of hemodialysis patients from the subcutaneous to the intravenous route of administration significantly increased epoetin alfa dosage requirements.

Bayesian pharmacokinetics of gentamicin in a haemodialysis population.

BACKGROUND: Aminoglycosides are commonly used in the haemodialysis population. Standard pharmacokinetic approaches require multiple sampling to describe the parameters of drug distribution and elimination in the intra- and interdialytic periods. OBJECTIVE: To characterise the pharmacokinetics of gentamicin in a haemodialysis population by using Bayesian pharmacokinetic methods and only two plasma concentrations. DESIGN AND PARTICIPANTS: Prospective case series of 13 adult (aged 36-70 years) haemodialysis patients (Fresenius F80 dialysers were used) receiving gentamicin. METHODS: Patients with suspected or confirmed Gram-negative infections were given gentamicin. At 48 hours after receiving the dose (at the next haemodialysis session), patients provided two blood samples, one immediately before the dialysis session and another 1 hour after haemodialysis. Data on dosage, timing and plasma concentrations for all subjects were analysed with PASTRX version 10.6 and Bayesian pharmacokinetic analysis. Volume of distribution (Vd), interdialytic elimination rate constant (k(inter)), interdialytic elimination half-life (t1/2beta, inter)) and interdialytic clearance (CL(inter)) were determined from a single predialysis plasma concentration. Elimination rate constant (k(dial)), elimination half-life (t1/2beta, dial)) and clearance (CL(dial)) during 3.5-4 hours of dialysis were also determined from the pre- and post-plasma concentrations. RESULTS: Pharmacokinetic parameters (mean +/- SD) were: Vd 0.288 +/- 0.002 L/kg, k(inter) 0.015 +/- 0.004h(-1), t1/2beta, inter) 48 +/- 11h, CL(inter) 5.9 +/- 2.4 mL/min, k(dial) 0.25 +/- 0.05 h(-1), t1/2beta, dial) 3.0 +/- 1.0h and CL(dial) 91 +/- 24 mL/min. CONCLUSIONS: The rate of elimination of gentamicin was 17-fold greater (95% CI 13.7-20.7) on haemodialysis with a Fresenius F80 than off haemodialysis. All of the pharmacokinetic parameters of interest were determined using Bayesian pharmacokinetic procedures and only two plasma gentamicin concentrations.

The ketolides: a critical review.

Ketolides are a new class of macrolides designed particularly to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A, and retain the erythromycin macrolactone ring structure as well as the D-desosamine sugar attached at position 5. The defining characteristic of the ketolides is the removal of the neutral sugar, L-cladinose from the 3 position of the ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. The ketolides presently under development additionally contain an 11, 12 cyclic carbamate linkage in place of the two hydroxyl groups of erythromycin A and an arylalkyl or an arylallyl chain, imparting in vitro activity equal to or better than the newer macrolides. Telithromycin is the first member of this new class to be approved for clinical use, while ABT-773 is presently in phase III of development. Ketolides have a mechanism of action very similar to erythromycin A from which they have been derived. They potently inhibit protein synthesis by interacting close to the peptidyl transferase site of the bacterial 50S ribosomal subunit. Ketolides bind to ribosomes with higher affinity than macrolides. The ketolides exhibit good activity against Gram-positive aerobes and some Gram-negative aerobes, and have excellent activity against drug-resistant Streptococcus pneumoniae, including macrolide-resistant (mefA and ermB strains of S. pneumoniae). Ketolides such as telithromycin display excellent pharmacokinetics allowing once daily dose administration and extensive tissue distribution relative to serum. Evidence suggests the ketolides are primarily metabolised in the liver and that elimination is by a combination of biliary, hepatic and urinary excretion. Pharmacodynamically, ketolides display an element of concentration dependent killing unlike macrolides which are considered time dependent killers. Clinical trial data are only available for telithromycin and have focused on respiratory infections including community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis and streptococcal pharyngitis. Bacteriological and clinical cure rates have been similar to comparators. Limited data suggest very good eradication of macrolide-resistant and penicillin-resistant S. pneumoniae. As a class, the macrolides are well tolerated and can be used safely. Limited clinical trial data suggest that ketolides have similar safety profiles to the newer macrolides. Telithromycin interacts with the cytochrome P450 enzyme system (specifically CYP 3A4) in a reversible fashion and limited clinically significant drug interactions occur. In summary, clinical trials support the clinical efficacy of the ketolides in upper and lower respiratory tract infections caused by typical and atypical pathogens including strains resistant to penicillins and macrolides. Considerations such as local epidemiology, patterns of resistance and ketolide adverse effects, drug interactions and cost relative to existing agents will define the role of these agents. The addition of the ketolides in the era of antibacterial resistance provides clinicians with more options in the treatment of respiratory infections.

Use of an alteplase algorithm for the management of hemodialysis catheter dysfunction.

Hemodialysis (HD) catheter dysfunction compromises HD adequacy and increases the cost of patient care. Repeated administration of alteplase in HD catheters typically produces only short-term benefits. The purpose of this study was to design, implement, and evaluate the efficacy of an experimental alteplase algorithm to manage HD catheter dysfunction. This was a two-part prospective nonrandomized study. Baseline data of alteplase use and catheter exchange were collected during part 1 of the study. Part 2 consisted of the alteplase algorithm implementation and repeat collection of catheter data. Rates of alteplase use and catheter exchange per 1000 catheter-days were the primary and secondary outcomes of the study. One hundred and seventy-two catheters in 131 patients were followed prospectively during the course of the study. The adjusted relative rate (RR) of alteplase use showed no significant difference between both parts of the study, adjusted RR: 1.10, 95% confidence interval (CI) (0.73-1.65). Similarly, catheter exchange rates were not significantly different over the duration of the study (1.12 vs. 1.03 per 1000 catheter-days). However, waiting time for catheter exchange increased from 20.36 ± 14 days in part 1 to 38.42 ± 28 days in part 2 (P < 0.05). The alteplase algorithm did not significantly reduce alteplase use. This may be partially explained by repeated use of alteplase in part 2, due to longer waiting times for catheter exchange procedures.

Antibiotic lock: in vitro stability of gentamicin and sodium citrate stored in dialysis catheters at 37 degrees C.

Catheter-related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis. Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution for prophylaxis of CRB. The objective of this study was to evaluate the stability of gentamicin and sodium citrate in hemodialysis catheters as an interdialytic lock. Solutions containing gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) were prepared individually and in combination. The solutions were instilled into dialysis catheters and stored at 37 degrees C for 96 h. Samples were withdrawn randomly from catheter lumens at 24-hour intervals for 4 days and stored at -20 degrees C until analysis. The samples were analyzed with validated, stability-indicating HPLC assays. The luminal concentration of gentamicin 2.5 mg/mL, sodium citrate 40 mg/mL (4%), and the combination was determined on study days 0, 1, 2, 3, and 4. When gentamicin was combined with sodium citrate and stored at 37 degrees C in dialysis catheters, the solution showed no decrease in either the gentamicin or the sodium citrate concentrations over the 96-hour study period. The percent of the original concentration at 96 h was 102.4+/-1.03 for gentamicin and 102.9+/-1.25 for citrate (P=0.5556). The combination of gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) can be retained in hemodialysis catheters for at least 96 h at 37 degrees C with no evidence of degradation.

Does warfarin safely prevent clotting of hemodialysis catheters? a review of efficacy and safety.

This article reviews the efficacy and safety of warfarin to prevent tunneled cuffed catheter (TCC) thrombosis in the hemodialysis population. Literature searches of PubMed, EMBASE, the Cochrane Library and Google Scholar were performed until April 1, 2007. Bibliographies of relevant articles were reviewed for additional publications. Minidose (1 mg/day) warfarin is ineffective in preventing TCC malfunction. Warfarin titrated to an international normalized ratio (INR) of 1.5-2.0, 1.8-2.5, and 2.0-3.0 was found to decrease the rate of thrombosis in selected patients. Early initiation of warfarin after catheter placement may be advantageous. Despite evidence of efficacy, safety is of greater concern. There were no major bleeds reported at an INR range of 1.5-2.5 specifically in catheter studies. However, an increase in major bleeding episodes has been reported with INR ranging from 1.4 to 3.0 in patients receiving warfarin for other indications (e.g., graft patency or cardiovascular indications). There is insufficient evidence to recommend the routine use of warfarin to prevent TCC thrombosis in all patients, primarily because of safety concerns. There is an increased risk of bleeding associated with warfarin use in the hemodialysis population. If a decision is made to use warfarin on a case-by-case basis, literature to date suggests that an INR target of 1.5-2.5 should suffice. Bleeding must be monitored carefully in this population, especially in patients using antiplatelet medications for concurrent conditions.

Alteplase versus urokinase for occluded hemodialysis catheters.

BACKGROUND: The use of central venous catheters as a source of vascular access in patients undergoing hemodialysis may be complicated by thrombosis. Frequently, thrombolytics are used in an attempt to reestablish blood flow through partially or completely occluded catheters. OBJECTIVE: To compare the efficacy of alteplase (recombinant tissue plasminogen activator) versus urokinase in reestablishing adequate blood flow through partially or completely occluded vascular catheters. METHODS: Part 1 of the study prospectively investigated the effect of alteplase in reestablishing adequate blood flow through partially or completely occluded vascular catheters in 30 hemodialysis patients. Part 2 of the trial compared the efficacy of alteplase with that of urokinase in 14 of 30 patients who had also previously received urokinase. A 30-minute push-protocol was used to administer thrombolytics in both parts of the study. The primary endpoint was the proportion of patients with partially or completely occluded catheters achieving post-thrombolytic blood flow of > or =200 mL/min. RESULTS: Part 1 showed a large proportion of partially or completely occluded catheters achieving post-alteplase blood flows > or =200 mL/min (70/76, 92.1% vs. 34/40, 85%, respectively). In Part 2 of the study, the proportion of partially occluded catheters achieving post-thrombolytic blood flows > or =200 mL/min was not significantly different between the alteplase and urokinase groups, (36/41, 87.8% vs. 21/28, 75%, respectively; p = 0.205). The proportion of completely occluded catheters achieving post-thrombolytic blood flows > or =200 mL/min was significantly better with alteplase compared with urokinase (15/17, 88.2% vs. 6/14, 42.8%, respectively; p =.018). CONCLUSIONS: Alteplase, administered via the 30-minute push-protocol, is an effective thrombolytic for restoring hemodialysis catheter patency. In our study sample, alteplase was generally more effective than urokinase in restoring blood flow through catheters, especially those that were completely occluded.

An in vitro evaluation of the antibiotic/heparin lock to sterilize central venous haemodialysis catheters.

This in vitro study investigated the ability of antibiotic/heparin locks to sterilize central venous haemodialysis catheters (CVCs) inoculated with methicillin-resistant Staphylococcus epidermidis (MRSE). Isolates of MRSE were incubated in broth inside CVCs. The catheters were then drained and filled with either vancomycin/gentamicin/heparin (VGH), cefazolin/gentamicin/ heparin (CGH) or control locks for 48 h. The catheters were drained, filled with fresh broth and again incubated. The final catheter solutions were sampled and the remaining volumes filtered. The samples, filters and catheter segments were examined for growth. For two isolates, both the VGH and CGH locks sterilized the catheters. Bacterial counts of the remaining two isolates were significantly reduced by >99%, but the catheters were not sterilized after the instillation of a single-antibiotic/heparin lock.