Reduction of biofilm formation with trisodium citrate in haemodialysis catheters: a randomized controlled trial.

BACKGROUND: Formation of an intraluminal microbial biofilm is noted to play a significant role in the development of catheter-related infections (CRIs). Recently, it has been demonstrated that trisodium citrate (TSC) has superior antimicrobial effects over heparin for catheter locking. In this randomized controlled trial, we compared the influence of catheter locking with heparin and TSC on the in vivo intraluminal biofilm formation in haemodialysis catheters. METHODS: Six patients were studied from the time of catheter insertion for haemodialysis treatment. They were randomly assigned to TSC 30% or heparin 5000 U/ml for catheter locking for the duration of 1 month. After elective guidewire exchange of the catheter, the locking solution was also changed. After removal, catheters were dissected in three segments and examined by standardized scanning electron microscopy (SEM) to assess quantitative biofilm formation. Furthermore, standardized cultures of all segments were performed to identify any microorganisms. RESULTS: In catheters filled with TSC, the average coverage by biofilm was 16% versus 63% in the heparin group (P < 0.001). A total of eight subsegments were associated with local catheter infection in the patients who were randomized to heparin locking versus three subsegments who were assigned to TSC (P < 0.05). CONCLUSIONS: Our study demonstrates that using TSC 30% for catheter locking reduces the formation of microbial biofilm in haemodialysis catheters and culture-positive colonization. It is likely that this is the explanation for the observed prevention of CRIs by TSC locking.

Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters: A retrospective cohort study.

BACKGROUND: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters. MATERIALS AND METHODS: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight non-tunnelled catheter. RESULTS: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70-1.19, p = 0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 95% confidence interval, 0.46-0.93; p = 0.02). A trend for less infections and catheter malfunctions was seen in precurved jugular non-tunnelled catheters compared to straight non-tunnelled catheters (hazard ratio, 0.60; 95% confidence interval, 0.24-1.50; p = 0.28) and were removed less often (hazard ratio, 0.41; 95% confidence interval, 0.18-0.93; p = 0.03). CONCLUSION: Tunnelled central venous catheters and precurved non-tunnelled central venous catheters showed no difference in reaching the combined endpoint of catheter-related infections and catheter malfunction. Tunnelled catheters get removed less often because of infection/malfunction than precurved non-tunnelled catheters.

Prospective follow-up of a novel design haemodialysis catheter; lower infection rates and improved survival.

BACKGROUND: Untunnelled straight jugular catheters (USC) are uncomfortable for patients and cannot be well fixated. This could be a reason for the high incidence of catheter-related complications. METHODS: We prospectively analysed the outcome of a novel designed untunnelled precurved catheter (UPC) with better fixation properties and compared it with the outcome of USC. The outcome was also related to data on tunnelled cuffed catheters (TCC). RESULTS: The outcome of USC was documented over a 32-month period. Thereafter, we switched to an UPC. The same catheter care protocol was used and not changed over time. A total of 104 USC and 65 UPC were inserted. Compared to USC, less UPC had to be removed for a complication (53 versus 15%; P < 0.001) and less periods of catheter-related bacteraemia were observed in UPC compared to USC [0 versus 5.6 per 1000 catheter days (cd); P < 0.01]. Removal for flow problems was similar. Compared to 64 TCC, inserted in the same period, UPC had more flow problems. Other outcomes and complication rates were similar. Complication rates for TCC inserted before and after the switch from USC to UPC were similar. CONCLUSIONS: UPC have better patency rates and a lower risk for bacteraemia and exit-site infection compared to USC.

The influence of blood volume-controlled ultrafiltration on hemodynamic stability and quality of life.

Dialysis hypotension occurs frequently and is associated with increased morbidity, mortality, and may influence quality of life. We investigated the influence of blood volume (BV)-controlled ultrafiltration on hemodynamic stability and quality of life in a prospective multiple crossover study. Nineteen patients were consecutively treated with standard hemodialysis (HD), BV-controlled ultrafiltration, and again with standard ultrafiltration during 3-week phases, during which different hemodynamic parameters, ultrafiltrate quantities, dry weight, and quality of life were measured. Blood volume-controlled ultrafiltration resulted in increased hemodynamic stability: systolic blood pressure was significantly higher after treatment with BV-controlled HD compared with both standard treatments (p=0.018 and 0.043, respectively). Also, systolic blood pressure reduction, as a measure of blood pressure stability, was significantly smaller during the BV-controlled phase (-3.9 mmHg) compared with both standard phases (-13.7 and -11.0 mmHg): p=0.003 and 0.035, respectively. No difference was found in the occurrence of large decreases of blood pressure (>30 mmHg), decreases below 90 mmHg systolic pressure, or subjective complaints during treatment or after treatment between both treatment modalities. During the course of the study, the dry weight decreased significantly from mean 73.3 to mean 70.9 kg, and the amount of ultrafiltrate was significantly larger using BV-controlled HD compared with standard treatment (mean 2407 vs. mean 2266 mL; p=0.035). Quality of life, measured by visual analog scales (VAS), showed discrete but no consistent differences between study phases. We conclude that BV-controlled HD increases hemodynamic stability and ultrafiltrate amount compared with a standard treatment. No consistent change in quality of life is found between both treatment modalities.

Improvement of radiocephalic fistula maturation: rationale and design of the Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study - a randomized controlled trial.

BACKGROUND: Non-maturation is a frequent complication of radiocephalic arteriovenous fistulas (RCAVF). In an animal model, liposomal prednisolone improved maturation of experimental fistulas. The Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT) study investigates if liposomal prednisolone improves RCAVF maturation. METHODS AND RESULTS: The LIPMAT study is an investigator-initiated, multicenter, double-blinded, placebo-controlled randomized controlled trial with 1:1 randomization to liposomal prednisolone or placebo. Eighty patients receiving an RCAVF will be included. The primary outcome is the cephalic vein diameter six weeks after surgery, measured by ultrasound. The LIPMAT study started in May 2016. Enrollment is expected to be completed by the end of 2017. CONCLUSIONS: The LIPMAT study is the first to evaluate the efficacy of liposomal prednisolone to enhance RCAVF maturation.

Initiating CAPD with a regimen low in glucose and glucose degradation products, with icodextrin and amino acids (NEPP) is safe and efficacious.

BACKGROUND: The high Levels of glucose, glucose degradation products (GDPs), and lactate buffer present in standard peritoneal dialysis (PD) solutions contribute to peritoneal damage, malnutrition, and dyslipidemia. Therefore, we studied the feasibility of a PD regimen as low as possible in glucose and GDPs. METHODS: In a prospective 30-week study, patients new to continuous ambulatory PD (CAPD) were randomized to either a standard PD regimen (SPD; 4 dwells glucose-/lactate-based) or a low glucose-GDP regimen (NEPP; 1 dwell amino acids, 1 dwell icodextrin, and two dwells bicarbonate/lactate-buffered glucose-based solution). RESULTS: Results obtained during a 30-week study period for 63 new CAPD patients (30 NEPP, 33 SPD) were analyzed. Intraperitoneal glucose load was lower in the NEPP group (111 +/- 76 vs 159 +/- 40 g/day at 30 weeks, p < 0.001). Dialysis efficacy, ultrafiltration, weight, blood pressure, and laboratory results were similar in the groups, whereas, in the NEPP group, cancer antigen 125 in dialysate effluents decreased less but dialysate-to-plasma ratios were slightly higher. CONCLUSION: Short-term treatment of new CAPD patients with a PD regimen low in glucose and GDPs is feasible. Dialysis efficacy, ultrafiltration, and metabolic consequences are similar to those during a standard glucose-lactate-based regimen, whereas peritoneal transport seems slightly higher and preservation of mesothelial cell mass better during NEPP.

Hemodialysis vascular access management in the Netherlands.

PURPOSE: In the Netherlands, 86% of patients start renal replacement therapy with chronic intermittent hemodialysis (HD). Guidelines do indicate predialysis care and maintenance of a well-functioning vascular access (VA) as critical issues in the management of the renal failure patient. Referral to the surgeon and time to VA creation are important determinants of the type and success of the VA and HD treatment. METHODS AND RESULTS: Data from a national questionnaire showed that time from referral to the surgeon and actual access creation is <4 weeks in 43%, 4 to 8 weeks in 30% and >8 weeks in 27% of the centers. Preoperative ultrasonography and postoperative access flowmetry are the diagnostic methods in the majority of centers (98%). Most facilities perform rope-ladder cannulation with occasionally the buttonhole technique for selected patients in 87% of the dialysis units. Endovascular intervention for thrombosis is practiced by 13%, surgical thrombectomy by 21% and either endovascular or surgery by 66% of the centers. Weekly multidisciplinary meetings are organized in 57% of the units. Central vein catheters are inserted by radiologists (36%), nephrologists and surgeons (32%). CONCLUSIONS: We conclude that guidelines implementation has been successful in particular regarding issues as preoperative patient assessment for VA creation and postoperative surveillance in combination with (preemptive) endovascular intervention, leading to very acceptable VA thrombosis rates.

Clinical effects of a peritoneal dialysis regimen low in glucose in new peritoneal dialysis patients: a randomized crossover study.

Standard glucose-based peritoneal dialysis (PD) solutions have unfavorable effects on the peritoneum and contribute to metabolic abnormalities. A PD regimen in which solutions with an alternative osmotic agent (icodextrin, amino acids) and solutions with a bicarbonate/lactate buffer are combined may reduce those effects. In a prospective crossover study, we randomized new continuous ambulatory peritoneal dialysis (CAPD) patients to one of two groups. One group used 4 exchanges of standard PD (SPD) solution (Dianeal: Baxter Healthcare BV, Utrecht, Netherlands) daily. The second group used 1 exchange of Nutrineal (Baxter Healthcare BV), 1 exchange of Extraneal (Baxter Healthcare BV), and 2 exchanges of Physioneal (Baxter Healthcare BV) daily (NEPP). After 30 weeks of treatment, each group switched over to the other regimen for 24 weeks. Statistical analysis used analysis of variance (ANOVA) for repeated measurements. Of the 74 patients enrolled into the study, 50 completed the full study period (24 NEPP-SPD, 26 SPD-NEPP). With regard to daily ultrafiltration and dialysis efficacy (Kt/V), the NEPP regimen was as efficacious as the standard regimen. The NEPP regimen was found to be safe: body weight, blood pressure, decline in urine volume, residual creatinine clearance, and laboratory measurements did not differ statistically significantly from those measured in the standard regimen. The NEPP regimen was well tolerated and was not accompanied by serious side effects. During the NEPP regimen, bicarbonate was found to be significantly higher in both groups. The NEPP regimen is a feasible treatment schedule for patients starting CAPD.

Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients.

Interdialytic hemodialysis catheter-locking solutions could contribute to a reduction of catheter-related complications, especially infections. However, they can cause side effects because of leakage from the tip of the catheter. Recently, trisodium citrate (TSC) has been advocated because of its antimicrobial properties and local anticoagulation. In a multicenter, double-blind, randomized, controlled trial, TSC 30% was compared with unfractionated heparin 5000 U/ml for prevention of catheter-related infections, thrombosis, and bleeding complications. The study was stopped prematurely because of a difference in catheter-related bacteremia (CRB; P < 0.01). Of 363 eligible patients, 291 could be randomized. The study included 98 tunneled cuffed catheters and 193 untunneled. There were no significant differences in patient and catheter characteristics on inclusion. In the heparin group, 46% of catheters had to be removed because of any complication compared with 28% in the TSC group (P = 0.005). CRB rates were 1.1 per 1000 catheter-days for TSC versus 4.1 in the heparin group (P < 0.001). For tunneled cuffed catheters, the risk reduction for CRB was 87% (P < 0.001) and for untunneled catheters was 64% (P = 0.05). Fewer patients died from CRB in the TSC group (0 versus 5; P = 0.028). There were no differences in catheter flow problems and thrombosis (P = 0.75). No serious adverse events were encountered. Major bleeding episodes were significantly lower in the TSC group (P = 0.010). TSC 30% improves overall patency rates and reduces catheter-related infections and major bleeding episodes for both tunneled and untunneled hemodialysis catheters. Flow problems are not reduced.

Compared to tunnelled cuffed haemodialysis catheters, temporary untunnelled catheters are associated with more complications already within 2 weeks of use.

BACKGROUND: Comparison of outcome of untunnelled catheters (UCs) and tunnelled cuffed catheters (TCCs) is difficult because they are usually used for different patients and conditions. The aim of the present study is to compare the outcome of TCCs with UCs limiting as much as possible the influence of confounding factors. The second purpose was to see whether our results support the time recommendations for maximum use of UCs outlined in the NKF-DOQI guidelines. METHODS: Catheter and patient characteristics, catheter-related complications and all cultures taken from haemodialysis catheters inserted during a 3 year period were collected. RESULTS: We analysed the outcome of 272 catheters (149 patients, 11 612 catheter-days, 37 TCC and 235 UC). Patients with an UC suffered more often from acute renal failure (40 vs 8% for TCCs, P<0.001), their hospitalization rates were higher (54 vs 14%, P<0.001) and coumarins were used less (11 vs 27%, P<0.01). Rates of preliminary removal were 1.8 per 1000 catheter-days for TCCs, 35.3 for untunnelled femoral catheters (UFCs) and 17.1 for untunnelled jugular catheters (UJCs). Infection rates were 2.9 per 1000 catheter-days for TCCs, 15.6 for UJCs and 20.2 for UFCs. Hospitalization was an independent risk factor for an adverse outcome and more apparent in patients with an UC. After correction for patient differences, the strongest risk factor for preliminary removal (RR 9.69, P<0.001) and infection (RR 3.76, P<0.001) was having an UC inserted. Already, within 2 weeks actuarial and infection-free survival were better for TCCs (P<0.05 vs all separate groups). CONCLUSIONS: According to our results, a TCC should be used whenever it can be foreseen that a haemodialysis catheter is needed for more than 14 days.

Do Catheter Side Holes Provide Better Blood Flows?

Four catheters (Ash Split Cath, Tesio, Duo-Split, and Duo--Flow; Medcomp, Harleysville, PA, U.S.A.) were tested in a temperature-controlled in vitro setup filled with 50% aqueous glycerin solution to determine hydraulic resistance at different flow rates. All these catheters have side holes; hydraulic resistance was determined with these holes open and closed. Due to extra pressure losses near the catheter tip, the pressure-flow relationship deviates from Poiseuillian theory and is generally quadratic in nature. An equivalent diameter was derived from the data. This equivalent diameter can be used to evaluate performance using a single number. Permanent catheters can easily deliver 300 mL/minute under optimal circumstances, but acute catheters are, in practice, limited to 200 mL/minute, and even somewhat less in the coaxial Duo-Flow type. Permanent catheters have larger equivalent internal diameters (1.8 vs 1.45 mm). Covering the side holes does not influence hydraulic resistance to a great degree, except in the arterial limb of acute catheters. These results indicate that, especially in acute catheters, obstruction of the side holes or fibrin sleeve/thrombus formation over the inlet holes may severely impact the available blood flow rate during dialysis. On the other hand, side holes in permanent catheters or venous limbs seem to be superfluous for performance reasons.

Superior antimicrobial activity of trisodium citrate over heparin for catheter locking.

BACKGROUND: Haemodialysis catheters used for vascular access are frequently complicated by infection and catheter-related thrombosis. Improvement of interdialytic locking solutions could reduce these problems. Trisodium citrate (TSC) has been advocated in recent years because it might have antimicrobial qualities. METHODS: Antimicrobial efficacy of four concentrations of TSC (2.2, 7.5, 15 and 30%) was compared with three equi-osmolal sodium chloride (NaCl) concentrations, unfractionated heparin 5000 IU/ml and a solution of gentamicin 1 mg/ml in TSC 7.5%. We analysed antimicrobial properties by two classical in vitro susceptibility tests. All tests were performed in triplicate by incubation of test fluids with Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. RESULTS: Increasing TSC concentrations effectively killed the staphylococcal strains in both assays. For E.coli and P.aeruginosa complete killing was achieved only with TSC 30%. TSC 30% was also the only solution that significantly inhibited growth of C.albicans. Heparin manifested no antimicrobial effect of any significance. Adding gentamicin to TSC provided superior bacterial growth inhibition but had no effect on yeast growth. TSC solutions manifested superior antimicrobial activity compared with iso-osmolal NaCl solutions in both assays. CONCLUSION: This in vitro study demonstrates superior antimicrobial activity of TSC, especially in higher concentrations, in contrast to heparin. The mechanism seems to differ from hyperosmolality. Ca(2+) and Mg(2+) chelating effects are probably more important. Adding gentamicin provided the most potent antimicrobial solution. However, for reasons concerning development of bacterial resistance and sensitization of the patient, continuous exposition to aminoglycosides seems not advisable.