Original Article
Prevention of Dialysis Catheter Malfunction with Recombinant Tissue Plasminogen Activator
N Engl J Med 2011; 364:303-312January 27, 2011
- Abstract
Background
The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session (catheter locking solutions) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown.
Methods
We randomly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin (5000 U per milliliter) three times per week or recombinant tissue plasminogen activator (rt-PA) (1 mg in each lumen) substituted for heparin at the midweek session (with heparin used in the other two sessions). The primary outcome was catheter malfunction, and the secondary outcome was catheter-related bacteremia. The treatment period was 6 months; treatment assignments were concealed from the patients, investigators, and trial personnel.
Results
A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%) — an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P=0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P=0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P=0.02). The risk of adverse events, including bleeding, was similar in the two groups.
Conclusions
The use of rt-PA instead of heparin once weekly, as compared with the use of heparin three times a week, as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia. (Funded by Hoffmann–La Roche; Current Controlled Trials number, ISRCTN35253449.)
Media in This Article
Figure 1
Screening, Randomization, and Follow-up.Figure 2
Kaplan–Meier Curves for the Time to Catheter Malfunction, According to Study Group.Article Activity
- Article
Central venous catheters are used for vascular access in the majority of patients undergoing hemodialysis.1-3 The major complications of catheters include thrombosis and infection.4,5, Approximately 50% of hemodialysis catheters fail within 1 year6; up to two thirds of the failures are due to thrombosis. 7,8 Infection related to central venous catheters is also associated with adverse health outcomes and high health care costs; indeed, catheter-related sepsis is one of the most common causes of death in patients undergoing hemodialysis.9
The solution instilled into the central venous catheter lumens after each hemodialysis session and left in the catheter until the next session (catheter locking solution) is used to prevent thrombosis during the period between dialysis sessions and may also prevent catheter-related infection. However, evidence supporting the use of various locking solutions to achieve these objectives is limited. Heparin has been the traditional locking solution. Several small studies have assessed whether citrate and heparin are equally efficacious for maintaining catheter patency,10,11 but the interpretation of the results was limited because the studies had a short follow-up period and included both uncuffed and cuffed central venous catheters. Recombinant tissue plasminogen activator (rt-PA) has been used primarily to treat catheter thrombosis12-14; in one small randomized trial, it was shown to be superior to heparin as a locking solution.15 The relatively high cost of rt-PA and its theoretical potential to cause bleeding, as well as the morbidity and mortality associated with catheter malfunction and infection, justify the need for more definitive evidence of the efficacy of rt-PA as a locking solution.
We performed a multicenter, randomized, blinded, controlled trial involving patients undergoing long-term hemodialysis through a newly inserted, tunneled central venous catheter to determine whether substituting rt-PA (1 mg in each lumen) for heparin once a week as a catheter locking solution, as compared with using heparin three times a week, would decrease the incidence of catheter malfunction and bacteremia.
Methods
Study Oversight
Hoffmann–La Roche funded the trial. The funding body had no role in the design or conduct of the study, in any aspect of data management or analysis, in the reporting of the study results, in the writing of the manuscript, or in the decision to submit the manuscript for publication. The trial was designed and conducted by the investigators in collaboration with the trial's steering committee (for a list of the members of the steering committee, see the Supplementary Appendix, available with the full text of this article at NEJM.org). The investigators and their research staff collected the data at each site. The University of Calgary oversaw data management and analyzed the data according to a prespecified statistical analysis plan. The protocol, including the statistical analysis plan, is available at NEJM.org. The first author and the last (senior) author attest that the study was performed in accordance with the protocol and vouch for the accuracy and completeness of the reported data.
An independent data and safety monitoring board approved the protocol and reviewed the study for safety. A planned interim analysis of safety was performed after one third of the patient-years had been accumulated (at which time 114 patients had undergone randomization) to determine whether the study should be stopped early because of safety issues; stopping the study was deemed not to be necessary.
Study Population
The study design has been described previously.16 Briefly, adults undergoing hemodialysis in whom a tunneled catheter had been newly inserted into the upper central venous system were eligible to be included in the study if they were being treated with hemodialysis three times a week and were expected to continue undergoing hemodialysis with the use of a central venous catheter for 6 months. Major exclusion criteria were long-term receipt of systemic anticoagulant therapy, a central venous catheter inserted by means of guidewire exchange, current use of antibiotics for catheter-related bacteremia, major hemorrhage or intracranial bleeding in the previous 4 weeks, intracranial or intraspinal neoplasm, pregnancy or breast-feeding, and pericarditis. Patients with known catheter-related bacteremia could be eligible for the study once the infection had been treated and the patient had not received antibiotics for a period covering three hemodialysis sessions.
Patients were recruited at 11 Canadian sites, within 2 weeks after insertion of the catheter; during the period before recruitment, the catheters were managed according to the usual practice at each center (Table 1 in the Supplementary Appendix). Patients were eligible for randomization after the fourth hemodialysis session if the mean blood flow was at least 300 ml per minute during sessions 3 and 4.
Study Procedures
After providing written informed consent, eligible patients were randomly assigned, in a 1:1 ratio, by a centralized computerized service (Axiom Real-Time Metrics), with the use of a permuted-block design stratified according to center and catheter status (first hemodialysis catheter ever vs. previous use). Patients were assigned to one of two regimens for locking of the catheter after a hemodialysis session: rt-PA (1 mg in each lumen) once a week, at the midweek session, with unfractionated heparin (5000 U per milliliter, full luminal volume) used as a locking solution for the other two dialysis sessions that week, or 5000 U of unfractionated heparin per milliliter (full luminal volume) after each dialysis session. The rt-PA was administered in each lumen initially (1 mg in 1 ml), with saline added to fill the lock to the full luminal volume. The study drug (rt-PA or heparin) was prepared and dispensed by the pharmacy in such a way that concealment of the treatment assignments was ensured, with four syringes prepared per patient for administration of the locking solution. On the days on which heparin was used for all the patients, the heparin was prepared and administered by the hemodialysis nurse according to the usual standard of care.
Patients were followed for 6 months after they underwent randomization. Patients who met the criteria for the primary outcome were followed for at least 1 month after the primary outcome occurred and continued to be followed until one of the following occurred: the patient underwent six consecutive successful hemodialysis sessions (mean blood flow, ≥300 ml per minute during each treatment), 3 months elapsed, or the central venous catheter was no longer used. The follow-up period for these patients was extended so that the natural history of malfunction of the central venous catheter could be documented and the costs associated with maintaining patency could be assessed, for use in the economic analysis. We included six consecutive successful hemodialysis sessions as part of the definition of the extended follow-up period because a second malfunction typically occurs within 2 weeks after the initial malfunction.17
Outcomes
The primary outcome was catheter malfunction, which was defined as the first occurrence of any of the following, after attempts to reestablish patency had been undertaken (see Table 2 in the Supplementary Appendix): peak blood flow of 200 ml per minute or less for 30 minutes during a dialysis treatment, mean blood flow of 250 ml per minute or less during two consecutive dialysis treatments, or inability to initiate dialysis owing to inadequate blood flow. The definition of catheter malfunction was chosen by the study investigators on the basis of published guidelines.18 Catheter malfunction was selected as the primary outcome because of concern that recruitment would be limited if the sole outcome were removal of the central venous catheter and because poor blood flow during dialysis is associated with adverse outcomes.19
Catheter-related bacteremia was defined according to published criteria,16,20 with both “definite” and “probable” infections included in the outcome (Table 3 in the Supplementary Appendix). Bacteremia was treated by the attending nephrologist; patients remained in the study and were followed for the primary outcome. If a new central venous catheter was clinically indicated, the patient's data were censored at the time of removal of the initial central venous catheter.
Bleeding was classified as fatal bleeding, major bleeding (bleeding at a critical site or overt bleeding with a fall in the hemoglobin level of 20 g per liter or more or requiring transfusion of 2 or more units of packed red cells), clinically important nonmajor bleeding (overt bleeding requiring admission to the hospital or a visit to a medical facility or overt bleeding leading to an intervention such as suturing), or minor bleeding (all other episodes of bleeding).
Statistical Analysis
We estimated that with a total of 340 participants (170 in each group), the study would have 80% power to detect approximately a 34% reduction in the incidence of catheter malfunction with rt-PA once weekly, assuming a 1-year rate of catheter malfunction of 95% in the heparin group and an annual dropout rate of 75% (on the basis of data from the University Health Network, Toronto [unpublished data] and Little and Walshe17), at a two-sided alpha level of 0.05.16 Because enrollment was slower than expected, an interim analysis that was based on the overall event rate (with the group assignments concealed) was performed after 197 patients had undergone randomization, to determine what power the study would be expected to have if 225 patients were enrolled. This analysis showed that the study would have 80% power with the event rate at that point and an anticipated effect size of 50%. Therefore, enrollment was halted after 225 patients had undergone randomization.
Survival curves for the primary and secondary outcomes were prepared with the use of the Kaplan–Meier method and were compared with the use of a two-sided log-rank test. Cox proportional-hazards models were used to compare event-free survival in the rt-PA and heparin groups, stratified according to center and catheter status. The results of analyses with models that included terms for the interaction between treatment and the stratification variables were nonsignificant; therefore, the results for the overall study population are presented. Comparisons of primary and secondary outcomes were based on the treatment assignments, irrespective of adherence to the intervention. We also performed a secondary analysis according to the actual treatment received. Follow-up data were censored at the end of the study (January 15, 2010) or at the time of death, a switch to an alternative form of renal-replacement therapy, removal of the central venous catheter or use of an alternative dialysis access, or the patient's transfer to a clinical center that was not involved in the trial — whichever came first. Statistical analyses were performed with the use of SAS, version 9.2 (SAS Institute) or Stata, version 11.1 (Stata) software. All reported P values are two-sided and have not been adjusted for multiple testing.
Although a full economic evaluation for this trial is not yet complete (administrative data on the cost of hospitalizations are not yet available), we provide a preliminary analysis of cost-effectiveness, on the basis of the cost (in Canadian dollars, as of 2010) of the interventions ($64 for 2 mg of rt-PA and $1.25 for 10,000 U of heparin) and the estimated cost of treating patients in whom bacteremia develops or catheter malfunction occurs. The cost of removal and replacement of a catheter ($1,228), and the mean cost of outpatient and inpatient treatment for catheter-related bacteremia ($485 and $6,040, respectively) were estimated from a detailed cost analysis of hemodialysis vascular access.21
Results
Study Population
We assessed 2325 patients for eligibility, of whom 225 underwent randomization; 110 patients were assigned to receive rt-PA, and 115 were assigned to receive heparin only (Figure 1Figure 1
Screening, Randomization, and Follow-up.). All the patients received their assigned intervention except for one patient in the rt-PA group, who underwent emergency surgery before the first dose of the study drug was administered. The baseline characteristics of the two groups were similar (Table 1Table 1
Baseline Characteristics of the Study Patients., and Table 4 in the Supplementary Appendix).A total of 58 patients in the rt-PA group (52.7%) and 56 in the heparin group (48.7%) discontinued the study medication before the end of the 6-month study period. The median duration of follow-up was 115.5 days in the rt-PA group and 89.0 days in the heparin group. No patients were lost to follow-up.
Primary Outcome
The primary outcome occurred in 62 patients — 22 (20.0%) in the rt-PA group and 40 (34.8%) in the heparin group (hazard ratio with heparin vs. rt-PA, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P=0.02) (Figure 2Figure 2
Kaplan–Meier Curves for the Time to Catheter Malfunction, According to Study Group.). There was no significant interaction between catheter status (first hemodialysis catheter ever vs. previous use) and treatment assignment (P=0.84) or between clinical center and treatment assignment (P=0.46). The results were unchanged in a model adjusted for catheter status and clinical center (hazard ratio with heparin, 1.88; 95% CI, 1.11 to 3.19) and in a sensitivity analysis with a composite outcome of catheter malfunction or early discontinuation of the study intervention (Figure 1 in the Supplementary Appendix). A total of 31 patients (50.0%) met the criteria for the primary outcome because of a peak blood flow of 200 ml per minute or less for 30 minutes, 19 patients (30.6%) because of an inability to initiate dialysis, and 12 patients (19.4%) because of a mean blood flow of 250 ml per minute or less for two consecutive sessions.The results were similar in a secondary analysis that was performed according to the actual treatment received. The primary outcome occurred in 54 participants: 18 (16.4%) in the rt-PA group and 36 (31.3%) in the heparin group (hazard ratio with heparin, 2.13; 95% CI, 1.20 to 3.76).
Among patients in whom the primary outcome occurred, immediate management of the central venous catheter included reversal of catheter lines (in 13 of 22 patients in the rt-PA group [59.1%] and 14 of 40 in the heparin group [35.0%]; P=0.07) and use of rt-PA (in 4 of 22 patients in the rt-PA group [18.2%] and 20 of 40 in the heparin group [50.0%]; P=0.01). One patient in the heparin group underwent an immediate exchange of the central venous catheter.
Secondary Outcome
Catheter-related bacteremia (which was classified as definite, according to the published criteria used, in 45.0% of the cases) occurred in 5 patients (4.5%) assigned to receive rt-PA and 15 patients (13.0%) assigned to receive heparin alone (hazard ratio with heparin, 3.30; 95% CI, 1.18 to 9.22; P=0.02) (Figure 3Figure 3
Kaplan–Meier Curves for the Time to a First Episode of Bacteremia, According to Study Group.). This corresponded to rates of 0.40 and 1.37 episodes of bacteremia per 1000 patient-days in the rt-PA and heparin groups, respectively (P=0.02).Follow-up after the Primary Outcome
Patients who met the criteria for the primary outcome were followed for up to 3 months or until removal of the catheter, with a median follow-up period that covered 11.5 and 10.0 dialysis sessions in the rt-PA and heparin groups, respectively. Treatment with rt-PA (outside the study protocol) for repeat malfunction of the original catheter occurred in 8.8% of the sessions (32 of 364 sessions) in the rt-PA group and 12.8% of the sessions (101 of 792 sessions) in the heparin group (P=0.06) (see also Table 5 in the Supplementary Appendix).
Adverse Events
Serious adverse events were reported in 23 patients (20.9%) receiving rt-PA and 34 (29.6%) receiving heparin (P=0.14) (Table 2Table 2
Adverse Events.). The rate of adverse events was similar in the two groups: 70.0% (77 of 110 patients) in the rt-PA group and 68.7% (79 of 115 patients) in the heparin group (P=0.83). Most patients had multiple events, with the result that there was a total of 454 adverse events and 68 serious adverse events. Neither the frequency nor the severity of bleeding events was greater among patients in the rt-PA group than among patients in the heparin group. There were 4 intracranial bleeding episodes, all in patients in the heparin group; 1 episode was a fatal brain-stem hemorrhage. There were no intracranial bleeding episodes or deaths caused by bleeding in the rt-PA group.Cost-Effectiveness Analysis
For each patient who received therapy for 6 months, the mean costs (in Canadian dollars) of rt-PA and heparin were $1,794 and $195, respectively; the cost of managing complications associated with catheter malfunction and catheter-related bacteremia per patient was $156 with rt-PA and $582 with heparin. Thus, the incremental cost of caring for patients with rt-PA as compared with heparin was $1,173 per patient, or $13,956 per episode of catheter-related bacteremia prevented.
Discussion
As compared with the use of unfractionated heparin three times a week, the use of rt-PA as a catheter locking solution once a week (with heparin used the other two times) significantly decreased the incidence of catheter malfunction and bacteremia among patients with a newly inserted hemodialysis catheter. The findings were consistent between patients for whom this was the first use of a catheter and those who had had previous catheters. The frequency of bleeding or other serious adverse events was not increased with the use of rt-PA.
Catheter thrombosis occurs at a frequency of 0.5 to 3.0 events per 1000 catheter-days,4,22 resulting in shortened dialysis treatments, less-than-adequate dialysis, and increased morbidity and mortality.19 Thrombolytic agents are used to treat catheter malfunction in both nondialysis catheters23,24 and dialysis catheters.12,13 Thrombolytic agents such as rt-PA preferentially bind to fibrin and activate plasminogen in close proximity to the clot to form plasmin, which dissolves the fibrin in the clot and prevents fibrinogen from forming more fibrin. The binding of rt-PA to fibrin confines fibrinolysis to the thrombus, theoretically averting systemic activation and justifying the use of this drug for the treatment and prevention of catheter malfunction.
Evidence to guide the use of locking solutions for the primary prevention of catheter malfunction has been based on studies in the critical care and oncology settings.25-27 It was uncertain whether these results could be generalized to catheters used for hemodialysis, which are larger, are used for longer periods, and require locking solutions to remain in place for up to 72 hours. A single randomized, crossover trial involving 12 patients undergoing hemodialysis showed that locking with 2 mg of rt-PA in each catheter lumen was superior to locking with heparin.15 Our results are consistent with these findings and indicate that the use of rt-PA as a locking solution at a reduced dose (1 mg in each lumen) and a reduced frequency (once a week) decreases the rates of catheter malfunction and bacteremia, although the number of catheters removed because of malfunction was small.
A few trials have evaluated other strategies for the primary prevention of catheter malfunction. A fixed dose (1 mg) of warfarin was shown to be ineffective for the prevention of catheter malfunction.28 The rates of catheter malfunction with 30% trisodium citrate were similar to those with heparin, although there was a reduction in catheter-related bacteremia in the citrate group.11
Catheter-related bacteremia is a serious complication, with an incidence of 2.5 to 6.5 episodes per 1000 catheter-days.5,29 Furthermore, septicemia is responsible for more than 75% of deaths from infection among patients undergoing dialysis.9 Several mechanisms may contribute to catheter-related bacteremia, including the formation of an intraluminal thrombosis, which may act as a nidus for the development of bacterial biofilm.30,31 Although antibiotic locking solutions have been proposed for the treatment32 or prevention33,34 of bacteremia, side effects limit their widespread use.35 Although the interpretation of our results is limited by the small number of events, we found that the risk of bacteremia was increased by a factor of 3 in the heparin-only group as compared with the rt-PA group. Furthermore, the number of central venous catheters that were removed in both groups owing to an episode of presumed or confirmed bacteremia was not inconsequential. Although an earlier trial suggested that there was a reduction in the rate of bacteremia with 30% trisodium citrate as compared with heparin,11 two recent trials of 46.7% sodium citrate36 and taurolidine–citrate37 did not show any significant difference. Since management of catheter-related bacteremia is expensive and often requires replacement of central venous catheters, our finding that rt-PA reduces the risk of this complication without increasing the risk of bleeding is potentially very important.
Though our study is a relatively large, multicenter trial with complete follow-up data, it has several limitations. First, although our primary outcome was defined according to published guidelines,18 it was a surrogate outcome that was based on measurement of blood flow. Ongoing evidence of catheter malfunction after the primary outcome provides support for the validity of this definition. Second, we discontinued enrollment early, owing to difficulties with patient recruitment. However, even the smaller sample had adequate power to detect a significant difference in both primary and secondary outcomes. Third, because of protocol-mandated selection criteria, we were not able to perform analyses in potentially important subgroups, such as patients in whom the expected duration of use of a central venous catheter was less than 6 months. Finally, a large proportion of patients discontinued the study medication during the course of the study (often because of a switch to arteriovenous access or hospitalization), as has been observed in previous trials involving patients undergoing hemodialysis.38
In conclusion, we found that among patients undergoing hemodialysis, rt-PA administered once a week as a catheter locking solution (with heparin administered the other two times), as compared with heparin administered three times a week, led to a significant reduction in the incidence of both catheter malfunction and bacteremia.
Supported by Hoffmann–La Roche. Drs. Hemmelgarn, Manns, and Tonelli were supported by awards from the Alberta Heritage Foundation for Medical Research and the Canadian Institutes of Health Research.
Drs. Hemmelgarn, Manns, Tonelli, Scott-Douglas, and Holden report receiving grant support from Amgen; Drs. Hemmelgarn and Manns, grant support from Merck; Dr. Tonelli, grant support from Abbott Laboratories; and Dr. Scott-Douglas, board membership fees from Amgen and lecture fees and travel expenses from Novartis.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
No other potential conflict of interest relevant to this article was reported.
We thank Anita Kozinski for her contribution to the study and the members of the data and safety monitoring board — Drs. Denis Geary (chair), George Pylypchuk, and Philip McFarlane — for their input.
Source Information
From the Departments of Medicine (B.R.H., B.J.M., J.Z., N.S.-D.) and Community Health Sciences (B.R.H., B.J.M., P.F.), University of Calgary; the Alberta Kidney Disease Network (B.R.H., M.T., B.J.M., N.S.-D.); the Department of Medicine, University of Alberta, Edmonton (M.T.); and Alberta Health Services, Calgary (P.F.) — all in Alberta; London Health Sciences Center, University of Western Ontario, London (L.M.M.); University Health Network–Toronto General Hospital, University of Toronto, Toronto (C.E.L.); and the Department of Medicine, Queen's University, Kingston (R.M.H.) — all in Ontario; and the Department of Medicine, Maisonneuve–Rosemont Hospital, University of Montreal (M.L.); and the Department of Medicine, McGill University (P.B.) — both in Montreal.
Address reprint requests to Dr. Hemmelgarn at the Division of Nephrology, Foothills Medical Centre, 1403 29th St. NW, Calgary, AB T2N 2T9, Canada, or at brenda.hemmelgarn@albertahealthservices.ca.
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- Citing Articles (20)
Citing Articles
1
Hemender Singh Vats. (2012) Complications of Catheters: Tunneled and Nontunneled. Advances in Chronic Kidney Disease 19:3, 188-194
CrossRef2
Angela L. Hewlett, Mark E. Rupp. (2012) New Developments in the Prevention of Intravascular Catheter Associated Infections. Infectious Disease Clinics of North America 26:1, 1-11
CrossRef3
Joseph A. Vassalotti, William C. Jennings, Gerald A. Beathard, Marianne Neumann, Susan Caponi, Chester H. Fox, Lawrence M. Spergel, . (2012) Fistula First Breakthrough Initiative: Targeting Catheter Last in Fistula First. Seminars in Dialysisno-no
CrossRef4
Laure Hermite, Jean-Pierre Quenot, Abdelouaid Nadji, Saber David Barbar, Pierre-Emmanuel Charles, Maël Hamet, Nicolas Jacquiot, François Ghiringhelli, Marc Freysz. (2012) Sodium citrate versus saline catheter locks for non-tunneled hemodialysis central venous catheters in critically ill adults: a randomized controlled trial. Intensive Care Medicine 38:2, 279-285
CrossRef5
John Moran, Sumi Sun, Ishrag Khababa, Alexander Pedan, Sheila Doss, Brigitte Schiller. (2012) A Randomized Trial Comparing Gentamicin/Citrate and Heparin Locks for Central Venous Catheters in Maintenance Hemodialysis Patients. American Journal of Kidney Diseases 59:1, 102-107
CrossRef6
Ahmed S. Abdelmoneim, Lisa M. Miller, Sean Armstrong, Manish M. Sood, Lori Wazny, Dan Chateau, Lavern M. Vercaigne. (2012) Use of an alteplase algorithm for the management of hemodialysis catheter dysfunction : Alteplase for occluded hemodialysis catheters. Hemodialysis International 16:2, 298
CrossRef7
, Wesley N. Hayes, Alan R. Watson, Nichola Callaghan, Elizabeth Wright, Constantinos J. Stefanidis. (2011) Vascular access: choice and complications in European paediatric haemodialysis units. Pediatric Nephrology
CrossRef8
Philip Kam-Tao Li, Kai Ming Chow. (2011) Infectious complications in dialysis—epidemiology and outcomes. Nature Reviews Nephrology 8:2, 77-88
CrossRef9
Vandana Dua Niyyar. (2011) Catheter Dysfunction: The Role of Lock Solutions. Seminars in Dialysisno-no
CrossRef10
Chidi Okafor, Kambiz Kalantarinia. (2011) Vascular Access Considerations for Therapeutic Apheresis Procedures. Seminars in Dialysisno-no
CrossRef11
Samir Parikh, Ruba Nijmeh, Sheri Van Cleef, Sue Timmerman, Udayan Y. Bhatt, Anil K. Agarwal. (2011) Catheter Outcomes in the Short-term Inpatient Setting: A Controlled Quality Improvement Study Comparing Citrate and Heparin Lock. Seminars in Dialysisno-no
CrossRef12
Peter G. Kerr. (2011) International Differences in Hemodialysis Delivery and Their Influence on Outcomes. American Journal of Kidney Diseases 58:3, 461-470
CrossRef13
Laurie R. Solomon, John S. Cheesbrough, Ramya Bhargava, Nicos Mitsides, Michael Heap, Gerwyn Green, Peter Diggle. (2011) Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-Heparin, Taurolidine-Citrate and Heparin Catheter Locks in Patients Treated with Hemodialysis. Seminars in Dialysisno-no
CrossRef14
Richard A. Sherman. (2011) Briefly Noted. Seminars in Dialysis 24:4, 469-470
CrossRef15
Anatole Besarab, Carol L. Moore. (2011) Dialysis: Two for the price of one: is rt-PA ready for prime time?. Nature Reviews Nephrology 7:6, 310-311
CrossRef16
(2011) Dialysis Catheters and Recombinant Tissue Plasminogen Activator. New England Journal of Medicine 364:18, 1779-1780
Full Text17
(2011) Journal Club. Kidney International 79:8, 800-801
CrossRef18
Winkelmayer, Wolfgang C., . (2011) Tackling the Achilles' Heel of Hemodialysis. New England Journal of Medicine 364:4, 372-374
Full Text19
Jean-François Timsit, Yohann Dubois, Clémence Minet, Agnès Bonadona, Maxime Lugosi, Claire Ara-Somohano, Rebecca Hamidfar-Roy, Carole Schwebel. (2011) New materials and devices for preventing catheter-related infections. Annals of Intensive Care 1:1, 34
CrossRef20
T.G. Walker. (2011) Prevention of Dialysis Catheter Malfunction with Recombinant Tissue Plasminogen Activator. Yearbook of Diagnostic Radiology 2011, 260-265
CrossRef
- Letters
