Citra Lock presentation

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DURALOCK C
Catheter Lock Solution
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Duralock C

• protects against catheter related infection

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Duralock C

• protects against catheter related infection
• prevents the formation of biofilm

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Duralock C

• protects against catheter related infection
• prevents the formation of biofilm
• prevents catheter clotting ? use of thrombolytic
  agents

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Duralock C

• protects against catheter related infection

Literature shows catheter related bacteremia
incidence of 3,0 7,0 episodes/1.000 cath.days
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Duralock C

• protects against catheter related infection

Literature shows catheter related bacteremia
incidence of 3,0 7,0 episodes/1.000 cath.days
Tunneled
Non tunneled
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Duralock C

• protects against catheter related infection

• Most cultured microbes
• S. aureus
• Coagulase negative s. aureus
• S epidermidis
• Candida albicans
• E. Agglomerans
• P. aeruginosa
• Enterococcus faecalis

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Duralock C

• protects against catheter related infection

• Consequenses of CRB
• Serious complications in the use of catheters

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Duralock C

• protects against catheter related infection

• Consequenses of CRB
• Serious complications in the use of catheters
• High cost treatment
• catheter exchange
• hospitalization (for example for IV treatment
  with
• antibiotics

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Duralock C

• protects against catheter related infection

• Consequenses of CRB
• Serious complications in the use of catheters
• High cost treatment
• catheter exchange
• hospitalization (for example for IV treatment
  with
• antibiotics
• Interruption of treatment

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Duralock C

• protects against catheter related infection

• Consequenses of CRB
• Serious complications in the use of catheters
• High cost treatment
• catheter exchange
• hospitalization (for example for IV treatment
  with
• antibiotics
• Interruption of treatment
• Increasing problem of antibiotic resistance

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Power of Duralock C

• protects against catheter related infection

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Power of Duralock C

• protects against catheter related infection

Concentrated Sodium Citrate (23) for Catheter
Lock Stephen R. Ash et al, Hemodialysis
International 422-31, 2000

• Protocol
• 40 patients followed for several catheter
  locking solutions
• 1/98-8/98 heparin 5000 units or 10 000 units
• 9/98-11/98 10 sodium citrate (pH 6.5) with
  3 mg/mL gentamicin
• 12/98-3/99 20 sodium citrate with 3 mg/mL
  gentamicin
• 4/99-6/99 46,7 sodium citrate
• 7/99-10/99 heparin 5000 or 10 000 units
• 11/99-3/00 23 sodium citrate
• Study endpoints
• The incidence of symptomatic bactaeremia
  (calculated as the number of episodes per 3000 
  patient-days)
• Use of urokinase

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Power of Duralock C

• protects against catheter related infection

Infection Rate
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Power of Duralock C

• protects against catheter related infection

Heparin 5000 IU/ml
Trisodium citrate 30
M.C. Weijmer, Y.J. Debets-Ossenkopp, F.J. van de
Vondervoort and P.M. ter Wee
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Nephrol Dial Transplant (2002) 17 21892195
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Power of Duralock C
Disk Diffusion Susceptibility Test

• protects against catheter related infection

M.C. Weijmer, Y.J. Debets-Ossenkopp, F.J. van de
Vondervoort and P.M. ter Wee
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Nephrol Dial Transplant (2002) 17 21892195
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Power of Duralock C

• protects against catheter related infection

Heparin 5000 IU/ml
M.C. Weijmer, Y.J. Debets-Ossenkopp, F.J. van de
Vondervoort and P.M. ter Wee
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Nephrol Dial Transplant (2002) 17 21892195
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Study design
Primary endpoint Catheter survival
Secondary endpoints - infection -
bacteremia - exit site infection -
thrombosis - flow problems - use of
urokinase - side effects - bleeding -
thrombocytopenia - systemic reactions after
locking
bacteremia
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291 hemodialysis catheters
citrate 30 heparin total
Catheters tunneled cuffed jugular subclavian femoral untunneled jugular subclavian femoral 148 50 49 1 0 98 77 1 20 143 48 48 0 0 95 69 2 24 291 98 97 1 0 193 146 3 48
Catheter days 8431 8116 16547
Days per catheter tunneled cuffed untunneled 57.0 97.1 36.5 56.8 94.2 37.8 56.9 95.7 37.1
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Power of Duralock C
Why protects a citrate solution against catheter
related infections?
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Power of Duralock C
Why protects a citrate solution against catheter
related infections?
Citrate combined
with citric acid C3H5O(COO)33- binds
double positive ionized molecules Ca / Mg
Na3C6H5O7
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Power of Duralock C
Apart from Mg binding, removal of Ca from the
surrounding milieu can be an explanation for
the antimicrobial properties of TSC. Ca may
regulate several genes responsible for growth and
survival of microbes. Holland et al. 19
demonstrated that cell division in E.coli in
particular appears to be very sensitive to the
level of cellular Ca.
Weijmer MC, Debets-Ossenkopp YJ, Van de
Vondervoort FJ, ter Wee PM Superior
antimicrobial activity of trisodium citrate over
heparin for catheter locking. Nephrol
Dial Transplant 17 21892195, 2002
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Power of Duralock C

• protects against catheter related infection

We conclude that in our in vitro study using
standardized antimicrobial susceptibility tests
we demonstrated that TSC 30 was the most potent
antimicrobial locking solution and that its
hyperosmolality was of minor importance to
explain the inhibitory effects of TSC on
microbial growth.
M.C. Weijmer, Y.J. Debets-Ossenkopp, F.J. van de
Vondervoort and P.M. ter Wee
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Nephrol Dial Transplant (2002) 17 21892195
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Power of Duralock C

• protects against catheter related infection

Randomized, Clinical Trial Comparison of
Trisodium Citrate 30 and Heparin as
Catheter-Locking Solution in Hemodialysis
Patients Marcel C. Weijmer, Marinus A. van den
Dorpel, Peter J.G. Van de Ven, Pieter M. ter Wee,
Jos A.C.A. van Geelen, Johannes O. Groeneveld,
Brigitte C. van Jaarsveld, Marjon G. Koopmans,
Caatje Y. le Poole, Anita M. Schrander-Van der
Meer, Carl E.H. Siegert, Koen J.F. Stas for the
CITRATE Study Group
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Catheter survival
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Bacteremia free survival
73
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Infection related admissions
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Mortality
P0.35
20
18
18
16
14
12
13
heparin
10
8
citrate 30
6
4
2
0
overall
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Duralock C

• Prevents formation of biofilm

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Duralock C

• Prevents formation of biofilm

Micro organisms
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Duralock C

• Prevents formation of biofilm

Biofilm grows under the influence of poly
sacharides, produced by micro organisms.
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Duralock C

• Prevents formation of biofilm

Biofilm grows under the influence of poly
sacharides, produced by micro organisms. Heparin
is a poly sacharide combined with an anti
thrombin
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Duralock C

• Prevents formation of biofilm

Biofilm grows under the influence of poly
sacharides, produced by micro organisms. Heparin
is a poly sacharide combined with an anti
thrombin Heparin induces the growth of biofilm
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Duralock C
Crit Care Med. 1992 May20(5)665-73.
Biofilms on indwelling vascular catheters,
Passerini. L, Lam K, Costerton JW, King EG
Method examined 42 arterial and 26 central
venous catheters that had been in place in ICU
patients between 1 and 14 days for the presence
of bacterial biofilms by scanning electron
microscopy, transmission electron microscopy, and
a special scraping/sonication bacterial recovery
technique.
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Duralock C

• Prevents formation of biofilm

Crit Care Med. 1992 May20(5)665-73.
Biofilms on indwelling vascular catheters,
Passerini. L, Lam K, Costerton JW, King EG

• Conclusion
• Extensive biofilm formation on all 42 arterial
  and 26 central venous catheters.
• Bacteria within the biofilms on 69 (29/42) of
  the arterial and 88 (23/26) of the central
  venous catheters.

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Power of Duralock C

• Prevents formation of biofilm

Catheter lock solutions influence staphylococcal
biofilm formation on abiotic surfaces Robert M.
Q. Shanks1, Jennifer L. Sargent1, Raquel M.
Martinez1, Martha L. Graber2 and George A.
OToole1 1Department of Microbiology and
Immunology, Dartmouth Medical School, Hanover, NH
03755 and 2Department of Medicine, Section of
Hypertension and Nephrology, Dartmouth Hitchcock
Medical Center, Lebanon, NH 03766, USA
Nephrol Dial Transplant (2006) 1 of
9 doi10.1093/ndt/gfl170
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Power of Duralock C

• Prevents formation of biofilm

Catheter lock solutions influence staphylococcal
biofilm formation on abiotic surfaces
This in vitro study demonstrates that heparin
alternatives, sodium citrate and sodium EDTA, can
prevent the formation of S. aureus biofilms,
suggesting that they may reduce the risk of
biofilm-associated complications in indwelling
catheters.
Nephrol Dial Transplant (2006) 1 of
9 doi10.1093/ndt/gfl170
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Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

Catheter related thrombosis is often the cause of
low catheter blood flows.
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Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

Catheter related thrombosis is often the cause of
low catheter blood flows. Low blood flow ?
inefficient treatment ? low Kt/V
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Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

Catheter related thrombosis is often the cause of
low catheter blood flows. Low blood flow ?
inefficient treatment ? low Kt/V Treatment
Expensive thrombolitic agents (TpA, Urokinase,
Streptokinase)
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Power of Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

Under influence of Ca So...
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Power of Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

Under influence of Ca So... Binding Ca
inthe catheter environment, stops the proces of
clotting
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Flow problems
getunneld ongetunneld
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Power of Duralock C

• prevents catheter clotting ? use of thrombolytic
  agents

medCOMP
Ash SR, et al. ASN 1999 A1375
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Leakage lock solution
Duralock C
Bleeding complications
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Bayes B et al, Nephrol Dial Transpl 1999 14 2532
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Power of Duralock C

• protects against catheter related infection

Sodium citrate for filling haemodialysis
catheters We recommend filling the catheter
with sodium citrate 46,7
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Bayes B et al, Nephrol Dial Transpl 1999 14 2532
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Duralock C
Bleeding complications
Risk of heparin lock-related bleeding when using
indwelling venous catheters in haemodialysis,
Hüseyin Karaaslan et al, Service de Néphrologie
CHU Dupuytren, Limoges, France Nephrol Dial
Transpant, (2001) 16 2072-2074
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Consequences of leakage lock solution
Bleeding complications during citrate-trial
P0.005
20
heparin
18
19
citrate 30
16
14
12
10
8
6
6
4
2
0
After insertion
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DURALOCK C
The injected concentration Citra-Locktm
decreases 30 in the inter dialytic periode in
jugular and subclavian catheters. Femoral
catheters show a decrease of 90.
Cornelius J. Doorenbos, Marjo Van den
Elsen-Hutten, Margret J. M. Heuven and Jan
Hessels, Estimation of trisodium citrate
(Citra-LockTM) remaining in central venous
catheters after the interdialytic interval,
Nephrology Dialysis Transplantation 2006
21(2)543-545
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DURALOCK C
The injected concentration Citra-Locktm
decreases 30 in the inter dialytic period in
jugular and subclavian catheters. Femoral
catheters show a decrease of 90.
46,7
Anti microbial protection, Weijmer)
30
30
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Duralock C
Literature reviews 1. Beathard GA Management of
bacteremia associated with tunneled-cuffed
hemodialysis catheters. J Am Soc Nephrol 10
10451049, 1999 2. Weijmer MC, ter Wee PM
Temporary vascular access for hemodialysis
treatment. Current guidelines and future
directions. Contrib Nephrol 137 3845, 2002 3.
Costerton JW, Stewart PS, Greenberg EP Bacterial
biofilms A common cause of persistent
infections. Science 28413181322, 1999 4. Raad
I Intravascular-catheter-related infections.
Lancet 351 893898, 1998 5. Bayes B, Bonal J,
Romero R Sodium citrate for filling
haemodialysis catheters. Nephrol Dial Transplant
14 25322533, 1999 6. Karaaslan H, Peyronnet P,
Benevent D, Lagarde C, Rince M, Leroux-Robert C
Risk of heparin lock-related bleeding when using
indwelling venous catheter in haemodialysis.
Nephrol Dial Transplant 16 20722074, 2001 7.
Dogra GK, Herson H, Hutchison B, Irish AB, Heath
CH, Golledge C, Luxton G, Moody H Prevention of
tunneled hemodialysis catheter-related infections
using catheter-restricted filling with gentamicin
and citrate A randomized controlled study. J Am
Soc Nephrol 13 21332139, 2002 8. Weijmer MC,
Debets-Ossenkopp YJ, Van de Vondervoort FJ, ter
Wee PM Superior antimicrobial activity of
trisodium citrate over heparin for catheter
locking. Nephrol Dial Transplant 17 21892195,
2002 9. Ash SR, Mankus RA, Sutton JM, Criswell
ER, Crull CC, Velasquez KA, Smeltzer BD, Ing TS
Concentrated sodium citrate (23) for catheter
lock. Hemodial Int 4 2231, 2000 10. Stas KJ,
Vanwalleghem J, Moor BD, Keuleers H Trisodium
citrate 30 vs heparin 5 as catheter lock in the
interdialytic period in twin- or double-lumen
dialysis catheters for intermittent
haemodialysis. Nephrol Dial Transplant
1615211522, 2001 11. Twardowski ZJ High-dose
intradialytic urokinase to restore the patency of
permanent central vein hemodialysis catheters. Am
J Kidney Dis 31 841847, 1998 12. Buturovic J,
Ponikvar R, Kandus A, Boh M, Klinkmann J,
Ivanovich P Filling hemodialysis catheters in
the interdialytic period Heparin versus citrate
versus polygeline Aprospective randomized study.
Artif Organs 22 945947,1998 13. Betjes MG, Van
Agteren M Prevention of dialysis
catheterrelatedsepsis with a citrate-taurolidine-c
ontaining lock solution. Nephrol Dial Transplant
19 15461551, 2004 14. De Wachter DS, Weijmer
MC, Kausylas M, Verdonck PR Do catheter side
holes provide better blood flows? Hemodial Int 6
4046, 2002 15. Twardowski ZJ The clotted
central vein catheter for haemodialysis. Nephrol
Dial Transplant 13 22032206, 1998 16. FDA
Issues Warning on triCitrasol Dialysis Catheter
Anticoagulant.FDA Talk Paper T00-16, Rockville,
MD, US Food and Drug Administration, 2000
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Duralock C

• Heparin
• Anticoagulant
• Systemic effect
• Generates bleeding risks
• Promotes bacterial growth, poly sacharide is feed
  for micro organisms

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Duralock C

• Heparin
• Anticoagulant
• Systemic effect
• Generates bleeding risks
• Promotes bacterial growth, poly sacharide is feed
  for micro organisms
• Promotes formation of biofilm

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Power of Duralock C
Conclusions

1. Trisodium citrate, in a concentration of at least
   30 shows an antimicrobial effect (Weijmer et
   al)
2. Trisodium citrate 30 shows a decrease of CRB of
   75 in a randomized controlled multi centre trial
   (Weijmer et al).
3. Trisodium citrate 30 doesnt effect positively
   on blood flow and use of thrombolytic agents
   (Weijmer et al)
4. Trisodium citrate 46,7 does show in In vivo
   studies a decrease in CRB and use of thrombolytic
   agents like Urokinase.
5. There is leakage of catheter lock solutions in
   the inter dialytic period, resulting in hight
   ATTP results, constantly measurable gentamycin
   levels or decreased trisodium citrate levels.
6. Catheter lock solutions based on antibiotics
   promote the risk of anti biotic resistance.

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DURALOCK C

• No formation of biofilm
• Anti microbial effect without anti biotics
• No drug-resistant bacterial strains
• No bleeding complications
• Proven anticoagulant
• Bio-compatible without systemic effects

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Action plan- february
22.26.2 15-19.2 8-12.2 1-5.2
????? ????????? ??????? ?????????? ???? ????? ??? ??????? ????? ?? ??????? ?????? ?? ????? ?????? ?????????? ?????? ?? ????? ?????? ??????????
????? ????????? ??????? ?????????? ????? ????????? ??????? ?????????? ???? ????? ??? ??????? ????? ?? ???????  
????? ????????? ??????? ?????????? ???? ????? ?????????? ??????? ??????- ???? 1400-1700 ???? ????? ??? ??????? ????? ?? ??????? ???? ????? ?????????? ??????? ??????- ???? 1400-1700
????? ????????? ??????? ?????????? ???? ????? ?????????? ??????? ??????- ???? 1400-1700 ???? ????? ?????????? ??????? ??????- ???? 1400-1700
???? ????? ?????????? ??????? ??????- ???? 1400-1700 ???? ????? ?????????? ??????? ??????- ???? 1400-1700 ???? ????? ?????????? ??????? ??????- ???? 1400-1700
57
Action plan- january
25-29.1 .118-22
???? ?????? ????? ???- 26.1.09 ???? ???? ???- 22.1.09
???? ?? ???? ???? ???- 26.1.09 ???? ????? ?????????? ??????? ??????- ???? 800-1200
????? ?????? ?? ??????? ?????????- 29.1 ???? ????? ?????????? ??????? ??????- ???? 800-1200
???? ????? ?????????? ??????? ??????- ???? 800-1200 ???? ????? ?????????? ??????? ??????- ???? 800-1200
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Action plan- march
22.26.3 15-19.3 8-12.3 1-5.3
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???? ??? ?????? ????? ??? ?????? ???? ????? ????? ???? ?????? ?????? ?????????? ????? ????? ???? ?????? ?????? ?????????? ????? ????????? ??????? ??????????
???? ??? ?????? ????? ??? ?????? ???? ????? ?????? ????? ??? ?????? ???? ????? ????? ???? ?????? ?????? ?????????? ????? ????????? ??????? ??????????
???? ??? ?????? ????? ??? ?????? ???? ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????. ????? ????? ???? ?????? ?????? ?????????? ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????.
???? ??? ?????? ????? ??? ?????? ???? ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????. ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????.
??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????. ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????. ??????? ??????? ?????? ?????????? ?????? ?? ????? ???????? ?? ????? ???????.
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DURALOCK C
Q A
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