FOR THE PREVENTION OF CATHETER-RELATED BLOODSTREAM INFECTIONS (CRBSI)
MODERN LOCKING SOLUTIONS
Infection Prevention
Patency
Safety
Infection Prevention
INFECTION PREVENTION
A modern locking solution should be able to prevent Catheter Related Bloodstream Infections (CRBSI) by its antimicrobial activity.
INFECTION PREVENTION
All recently published guidelines state that the use of antimicrobial lock solutions should be preferred to reduce the rate of CRBSI’s.
HYGIENE GUIDELINES COMPLETING ‘GERMAN DIALYSIS STANDARD 2006’ Dialysis Standard 2006, Chapter 2.5.1 Central Venous Catheters Between dialysis treatments the central venous access device may be blocked using a diluted heparin solution. Heparin, however, does not have any antibacterial properties. Antibacterial lock solutions should therefore be preferred, which reduce the rate of catheter-related bacteraemias considerably. The use of antibiotics can not be recommended due to the potential development of resistance. Alternatively, highly concentrated citrate (30% or 45%) or taurolidinecitrate solutions can be used. Due to the risk of severe cardiac arrhythmias highly concentrated citrate must be strictly administered by trained staff according to the instructions of the manufacturer.
NATIONAL KIDNEY FOUNDATION (NKF) KDOQI Guidelines Guideline 7, update 2006 As shown in table 24, silver impregnation of the catheter was ineffective, whereas a gentamycin/citrate solution and a taurolidine solution used as interdialytic antibiotic locks were effective.
EUROPEAN RENAL BEST PRACTICE (ERBP)
Diagnosis, prevention and treatment of haemodialysis catheter-related bloodstream infections (CRBSI): a position statement. R. Vanholder, B. Canaud, R. Fluck, M. Jadoul, L. Labriola, A. Marti-Monros, J. Tordoir, W. Van Biesen NDT Plus (2010) 3: 234-246. Recommendation B.3.1: The preventive use of antimicrobial locks is advocated to reduce the rate of CRBSI.
RENAL ASSOCIATION (UNITED KINGDOM)
Guideline 5.4: Minimising the risk of catheter related infection R. Fluck, M. Kumwenda (2011) We suggest that an antimicrobial or antibiotic lock solution be used to reduce catheter related bacteraemia and other infections. (2B)
LETS REVIEW THE CLINICAL EVIDENCE THAT SUPPORTS THESE GUIDELINES…..
Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution. Betjes et al. - Nephrology Dialysis Transplantation. 2004 Taurolidine-citrate SIGNIFICANTLY reduced CRBSI’s in Haemodialysis patients.
A Meta-analysis of Hemodialysis Catheter Locking Solutions in the Prevention of Catheter-Related Infection. Jaffer et al. - Am J Kidney Dis. 2008 This meta-analysis review confirms that antibiotic locking solutions reduce the frequency of CRI without side effects.
Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-Heparin (TCH), TaurolidineCitrate (TC) and Heparin Catheter Locks in Patients Treated with Hemodialysis. Solomon et al. - Sem Dial 2011 There was a reduction in all cause bactaremia with taurolidine-citrate, with or without the addition of Heparin.
INFECTION PREVENTION
Conclusion Modern guidelines recommend the use of high dose citrate solutions or Taurolidine – citrate solutions to provide antimicrobial effectiveness.
INFECTION PREVENTION
In vitro studies demonstrates that TauroLock™ is more effective at killing organism than other locking solutions.
INFECTION PREVENTION
In vitro studies demonstrates that TauroLock™ is more effective at killing organism than other locking solutions. However there are no clinical studies comparing head to head TauroLock™ & High Concentrated Citrate.
Patency
PATENCY
• A good locking solution should provide patency to the lumen.
• In general it seems that clinical studies tell us that lock solutions which include Heparin are superior regarding patency compared to only citrate solutions that are used as an anticoagulant.
Sodium Citrate Versus Heparin Catheter Locks for Cuffed Central Venous Catheters: A Single-Centre Randomized Controlled Trial. Albert Power et al. - American Journal of Kidney Diseases, Vol 53 (6), 2009
• 232 consenting long-term haemodialysis catheters. • 6 months use of 46.7% Sodium Citrate (citrate) or 5% Heparin. • The use of Urokinase lock was significantly more common in the citrate group, with an increase of 8 versus 4.3/1000 catheter days (P<0.001).
Solomon et al 2010.
Solomon et al 2011.
• Solomon also found that there was an increased requirement for Urokinase in the Taurolidine-citrate. • However in his follow up study (2011) he concluded that the addition of Heparin to Taurolidine-citrate was equivalent to Heparin 5000 units/ml.
PATENCY
In conclusion Studies suggest that without Heparin we have increased flow problems, by adding Heparin we can reduce these flow problems.
Safety
SAFETY
A modern lock solution should be safe to the patient.
SAFETY
Cardiac risks of high concentrated citrate solutions • FDA safety warning issued. • This product is banned from the American market and the FDA encourage their users switch to 4% Citrate solutions.
Letter to the Editor. C.D. Punt & W.E. Boer - Clinical Nephrology, Vol. 69 – No. 4/2008 • Whole 5ml ampoule was used (2.5ml for each port). • Immediately after a cardiac arrest occurred, it lasted 10 seconds. • “it was realized that a similar incident occurred the day before”. • Over injection of 1.9ml.
Embolic Complications From Central Venous Hemodialysis Catheters Used With Hypertonic Citrate Locking Solution. M K Willicombe, K Vernon, A Davenport - American Journal Kidney Disease 55:348-351. 2010 • Reported 8 patients developed symptomatic emboli from catheter associated thrombus. • Documented pulmonary and cerebral emboli in 3 cases.
• “This may be exacerbated by the use of hypertonic citrate lock.”
This theory was further supported by Schilcher et al (2012). He theorised that Tri-Sodium Citrate caused protein precipitation in HD catheters and studied this both in-vivo & in-vitro.
Trisodium citrate induced protein precipitation in haemodialysis catheters might cause pulmonary embolism Schilcher et al. - Nephrology Dialysis Transplantation. 2012. • The density difference between high concentration citrate and whole blood caused further seepage of the locking solution. • Results - Protein precipitation capable of causing filter occlusion was seen above a concentration of 12%. • Conclusion - Precipitated protein may have contributed to the pathophysiology of reported embolism.
HOW TO MITIGATE THIS RISK?
• Staff Training. • Selecting a low risk locking solution.
CONCLUSION
In Summary: TauroLock™ Hep 500 provides good infection/prevention, patency & safety features – all the requirements of a modern locking solution. In addition the TauroLock™ Urokinase 25,000 compliments the range providing a proven anti-thrombolytic (when required), without the loss of antimicrobial cover.
REFERENCES LIST Hygiene Guidelines Completing ‘GERMAN DIALYSIS STANDARD 2006‘ German Workgroup for Clinical Nephrology in Cooperation with the Verband Deutsche Nierenzentren der DD nÄ e.V. and the Society for Pediatric Nephrology: Hygiene Guidelines 2008 completing the German Dialysis Standard 2006, Chapter 2.5.1 Central Venous Catheters Diagnosis, prevention and treatment of haemodialysis catheter-related bloodstream infections (CRBSI): a position statement of European Renal Best Practice (ERBP) R. Vanholder, B. Canaud, R. Fluck, M. Jadoul, L. Labriola, A. Marti-Monros, J. Tordoir, W. Van Biesen, NDT Plus (2010) 3: 234-246. Vascular Access for Haemodialysis Renal Association (United Kingdom), R. Fluck, M. Kumwenda (2011) National Kidney Foundation (NKF): KDOQI Guidelines KDOQI Guideline, Guideline 7, update 2006. A Meta-analysis of Hemodialysis Catheter Locking Solutions in the Prevention of Catheter-Related Infection Y. Jaffer, N. M. Selby, M. W. Taal, R. J. Fluck, and C. W. McIntyre, American Journal Kidney Disease 51:233-241.
Prevention of dialysis catheter-related sepsis with a citrate–taurolidine-containing lock solution M. G. H. Betjes and M. van Agteren, Nephrology Dialysis Transplantation, 2004, 19:1546-1551. Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-Heparin (TCH), Taurolidine-Citrate (TC) and Heparin Catheter Locks in Patients Treated with Hemodialysis L. R. Solomon, J. S. Cheesbrough, R. Bhargava, N. Mitsides, M. Heap, G. Green, P. Diggle, Seminars in Dialysis 2011.
REFERENCES LIST A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Locks (vs. Heparin (5000 IU/mL) for the Prevention of Bacteremia in Patients Treated With Hemodialysis L. R. Solomon, J. S. Cheesbrough, L. Ebah, T. Al-Sayed, M. Heap, N. Millband, D. Waterhouse, S. Mitra, A. Curry, R.Saxena, R. Bhat, M. Schulz, P. Diggle, American Journal of Kidney Disease, Vol 55, No 6 (June), 2010; pp 1060 Sodium Citrate Versus Heparin Catheter Locks for Cuffed Central Venous Catheters: A single Center Randomized Controlled trial A. Power, N. Duncan, S.K. Singh, W.Brown, E. Dalby, C. Edwards, K. Lynch, V. Prout, T. Cairns, M. Griffith, A. McLean, A. Palmer, D. Taube American Journal of Kidney Diseases, Vol 53 (6), 2009, 1034-10415. Trisodium citrate induced protein precipitation in haemodialysis catheters might cause protein embolism G. Schilcher, H. Scharnagl, J.H. Horina, W. Ribitsch, A.R.Rosenkranz, T. Stojakovic, H.D. Polaschegg Nephrology Dialysis Transplantation (2012) 0; 1-5. FDA Warning Letter, April 2000. Letter to the Editor C.D.Punt , W.E. Boer Clinical Neprhology, 69, 2008, 317-318. Embolic Complications From Central Venous Haemodialysis Catheters Used With Hypertonic Citrate Locking Solution M.K. Willicombe, K.Vernon, A. Davenport American Journal of Kidney Diseases, Vol. 55, 2009, pp. 348-351.
FOR THE PREVENTION OF CATHETER-RELATED BLOODSTREAM INFECTIONS (CRBSI)
Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution. Betjes et al. - Nephrology Dialysis Transplantation. 2004 • Haemodialysis patients. • Randomized prospective trial.
• 76 catheters, 58 patients. • Heparin = 4/1000 catheter days. • Taurolidine-citrate = 0/1000 catheter days. • P<0.05.
Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-Heparin (TCH), Taurolidine-Citrate (TC) and Heparin Catheter Locks in Patients Treated with Hemodialysis. Solomon et al. - Sem Dial 2011
The bacteraemia rates from all causes were 1.33, 1.22, and 3.25 per 1000 catheter days (p < 0.001) in the TCH, TC and Heparin groups respectively.
Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-Heparin (TCH), Taurolidine-Citrate (TC) and Heparin Catheter Locks in Patients Treated with Hemodialysis. Solomon et al. - Sem Dial. 2011 • “Addition of 500iu/ml heparin to TC reduces the need for thrombolysis” • “…may achieve patency comparable to heparin 5000iu/ml”.
A Meta-analysis of Hemodialysis Catheter Locking Solutions in the Prevention of Catheter-Related Infection. Jaffer et al. - Am J Kidney Dis. 2008
• Meta analysis. • Antibiotic and/or antimicrobial catheter locking solution. • 7 studies. • Conclusion: This meta-analysis review confirms that antibiotic locking solutions reduce the frequency of CRI without side effects.
Trisodium citrate induced protein precipitation in haemodialysis catheters might cause protein embolism.
Schilcher et al. - Nephrology Dialysis Transplantation. 2012. IN-VIVO • 10 catheters, each filled with 4%,20% or 46.7% citrate. • Protein precipitation was seen in all 10 catheters filled with 20% & 46.7% citrate. • No precipitates were seen in those catheters filled with 4% citrate.
Trisodium citrate induced protein precipitation in haemodialysis catheters might cause protein embolism.
Schilcher et al. - Nephrology Dialysis Transplantation. 2012. IN-VITRO Pumped whole blood/citrate solution with different citrate concentrations pushed through 20Âľm mesh (simulating pulmonary vessels). Pressure of pump increased and eventually blocked filter, when checked protein precipitates were found, predominantly from ‘Albumin’.
A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Lock for the Prevention of Bacteremia in Patients Treated with Hemodialysis Solomon et al 2010. • Double-blind randomized controlled trial.
• Taurolidine-Citrate Catheter vs. Heparin locks. • 110 adult haemodialysis patients. • “…taurolidine was associated with a greater need for thrombolytic treatment.”