CADTH RAPID RESPONSE REPORT: REFERENCE LIST

Heparin (5,000 u/0.5 mL) for

Catheter Lock or Flush: An
Update Regarding the
Clinical Effectiveness,
Safety, and Guidelines

Service Line: Rapid Response Service

Version: 1.0
Publication Date: September 7, 2017
Report Length: 7 Pages
 Authors: Sara Khangura, Charlene Argáez

Cite As: Heparin (5,000 u/0.5 mL) for catheter lock or flush: an update regarding the clinical effectiveness, safety, and guidelines. Ottawa: CADTH; 2017 Sep.
(CADTH rapid response report: reference list).

Acknowledgments:

Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders,
and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document,
the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular
purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical
judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and
Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.

While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date
the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the
quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing
this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.

CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or
conclusions contained in or implied by the contents of this document or any of the source materials.

This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by
the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information
contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH
has no responsibility for the collection, use, and disclosure of personal information by third-party sites.

Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal,
provincial, or territorial governments or any third party supplier of information.

This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at
the user’s own risk.

This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and
interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the
exclusive jurisdiction of the courts of the Province of Ontario, Canada.

The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian
Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes
only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.

About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada’s health care decision-makers with objective evidence
to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system.

Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 2
 Research Questions
1. What is the clinical effectiveness and safety of heparin 5,000 u/ 0.5 mL for catheter lock
or flush?

2. What are the evidence-based guidelines associated with the use of heparin for catheter
lock or flush?

Key Findings
Two systematic reviews (both including meta-analyses) were identified regarding heparin
(5,000 u/0.5 mL) for catheter lock or flush.

Methods
A limited literature search was conducted on key resources including PubMed, EMBASE,
The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD)
databases, Canadian and major international health technology agencies, as well as a
focused Internet search. No filters were applied to limit the retrieval by study type. Where
possible, retrieval was limited to the human population. The search was also limited to
English language documents published between January 1, 2008 and August 31, 2017.
Internet links were provided, where available.

Selection Criteria
One reviewer screened citations and selected studies based on the inclusion criteria
presented in Table 1.

Table 1: Selection Criteria

Population Patients with catheters

Intervention Heparin 5,000 u/0.5 mL (alternately stated as 10,000 u/ 1mL)

Comparator Q1: Heparin (at different concentrations);

Sodium citrate (Na3C6H5O7);
Saline;
Standard of care (other preparations)
Q2: No comparator required
Outcomes Q1: Clinical effectiveness, safety (particularly medication errors)
Q2: Guidelines
Study Designs Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-
randomized studies, evidence-based guidelines

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 3
 Results
Rapid Response reports are organized so that the higher quality evidence is presented
first. Therefore, health technology assessment reports, systematic reviews, and meta-
analyses are presented first. These are followed by randomized controlled trials, non-
randomized studies, and evidence-based guidelines.

Two systematic reviews (both including meta-analyses), were identified regarding heparin
(5,000 u/0.5 mL) for catheter lock or flush. No relevant health technology assessments,
randomized controlled trials, non-randomized studies, or evidence-based guidelines were
identified.

Additional references of potential interest are provided in the appendix.

Health Technology Assessments

No literature identified.

Systematic Reviews and Meta-Analyses

1. Zhong L, Wang HL, Xu B, Yuan Y, Wang X, Zhang YY, et al. Normal saline versus
heparin for patency of central venous catheters in adult patients -a systematic review
and meta-analysis. Crit Care. 2017Jan 8;21(1):5.
PubMed: PM28063456
Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219914/pdf/13054_2016_Article_1585.
pdf

2. Wang AY, Ivany JN, Perkovic V, Gallagher MP, Jardine MJ. Anticoagulant therapies for
the prevention of intravascular catheters malfunction in patients undergoing
haemodialysis: systematic review and meta-analysis of randomized, controlled trials.
Nephrol Dial Transplant. 2013 Nov;28(11):2875-88.
PubMed: PM24169613

Randomized Controlled Trials

No literature identified.

Non-Randomized Studies
No literature identified.

Guidelines and Recommendations

No literature identified.

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 4
 Appendix — Further Information
Systematic Reviews and Meta-Analyses
Alternate Heparin Dose (5000U/mL)
3. Han X, Yang X, Huang B, Yuan L, Cao Y. Low-dose versus high-dose heparin locks for
hemodialysis catheters: a systematic review and meta-analysis. Clin Nephrol. 2016
Jul;86(7):1-8.
PubMed: PM27191662

4. Wang Y, Ivany JN, Perkovic V, Gallagher MP, Woodward M, Jardine MJ.

Anticoagulants and antiplatelet agents for preventing central venous haemodialysis
catheter malfunction in patients with end-stage kidney disease. Cochrane Database
Syst Rev. 2016 Apr 4;4:CD009631.
PubMed: PM27039404Randomized Controlled Trials

Randomized Controlled Trials

Alternate Heparin Dose (5000 U/mL)
5. Chu G, Fogarty GM, Avis LF, Bergin S, McElduff P, Gillies AH, et al. Low dose heparin
lock (1000 U/mL) maintains tunnelled hemodialysis catheter patency when compared
with high dose heparin (5000 U/mL): a randomised controlled trial. Hemodial Int. 2016
Jul;20(3):385-91.
PubMed: PM26833752

6. Kanaa M, Wright MJ, Akbani H, Laboi P, Bhandari S, Sandoe JA. Cathasept line lock
and microbial colonization of tunneled hemodialysis catheters: a multicenter randomized
controlled trial. Am J Kidney Dis. 2015 Dec;66(6):1015-23.
PubMed: PM26141306

7. Ward DR, Moist LM, MacRae JM, Scott-Douglas N, Zhang J, Tonelli M, et al. Risk
factors associated with hemodialysis central venous catheter malfunction; a
retrospective analysis of a randomized controlled trial. Can J Kidney Health Dis.
2014;1:15. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424538
PubMed: PM25960883

8. Hryszko T, Brzosko S, Mysliwiec M. Low concentration of heparin used for permanent

catheters canal locking is effective and diminishes the risk of bleeding. Int Urol Nephrol.
2013 Jun;45(3):825-9. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689468
PubMed: PM22418764

9. Hu HH, Hsu CY, Fang HC, Lee PT, Chen CL, Chang TY, et al. Low-dose heparin
retention in temporary hemodialysis double-lumen catheter does not increase catheter
occlusion and might reduce risk of bleeding. Blood Purif. 2011;32(3):232-7.
PubMed: PM21829015

10. Maki DG, Ash SR, Winger RK, Lavin P, AZEPTIC Trial Investigators. A novel
antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center,
controlled, randomized trial. Crit Care Med. 2011 Apr;39(4):613-20.
PubMed: PM21200319

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 5
 11. Thomson PC, Morris ST, Mactier RA. The effect of heparinized catheter lock solutions
on systemic anticoagulation in hemodialysis patients. Clin Nephrol. 2011 Mar;75(3):212-
7.
PubMed: PM21329631

12. Malo J, Jolicoeur C, Theriault F, Lachaine J, Senecal L. Comparison between standard

heparin and tinzaparin for haemodialysis catheter lock. ASAIO J. 2010 Jan;56(1):42-7.
PubMed: PM20051836

13. Maya ID, Smith T, Allon M. Does the heparin lock concentration affect hemodialysis
catheter patency? Clin J Am Soc Nephrol. 2010;5(8):1458-62.
PubMed: PM20498241

14. Solomon LR, Cheesbrough JS, Ebah L, Al-Sayed T, Heap M, Millband N, et al. A
randomized double-blind controlled trial of taurolidine-citrate catheter locks for the
prevention of bacteremia in patients treated with hemodialysis. Am J Kidney Dis. 2010
Jun;55(6):1060-8.
PubMed: PM20207458

15. MacRae JM, Dojcinovic I, Djurdjev O, Jung B, Shalansky S, Levin A, et al. Citrate 4%
versus heparin and the reduction of thrombosis study (CHARTS). Clin J Am Soc
Nephrol. 2008 Mar;3(2):369-74. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390935
PubMed: PM18308996

Non-Randomized Studies
Alternate Heparin Dose (5000 U/mL)
16. Bong YC, Walsham J. Systemic anticoagulation related to heparin locking of non-
tunnelled venous dialysis catheters in intensive care patients. Anaesth Intensive Care.
2016 Jul;44(4):474-6.
PubMed: PM27456177

17. Renaud CJ, Lim EK, Tho SJ, Yeoh LY. Effect of ultra-low dose and standard heparin
locks on early tunnelled dialysis catheter outcomes in low-risk dialysis patients.
Nephrology (Carlton). 2015 Feb;20(2):85-90.
PubMed: PM25346031

18. Ivan DM, Smith T, Allon M. Does the heparin lock concentration affect hemodialysis
catheter patency? Clin J Am Soc Nephrol. 2010 Aug;5(8):1458-62. Available from:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924411
PubMed: PM20498241

19. Brzosko S, Hryszko T, Malyszko J, Malyszko JS, Mazerska M, Mysliwiec M. Femoral

localization and higher ultrafiltration rate but not concentration of heparin used for canal
locking of hemodialysis catheter are negative predictors for its malfunction. Am J
Nephrol. 2008;28(2):298-303.
PubMed: PM18025778

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 6
 Clinical Practice Guidelines – Unspecified Methodology
20. Ho A, Bravery K. Central venous access devices (CVADs): flush volumes [Internet].
London (UK) : Great Ormond Street Hospital for Children (GOSH); 2016 [cited 2017
Sep 06]. Available from: http://www.gosh.nhs.uk/health-professionals/clinical-
guidelines/central-venous-access-devices-cvads-flush-volumes

Position Paper
21. Moran JE, Ash SR, ASDIN Clinical Practice Committee. Locking solutions for
hemodialysis catheters; heparin and citrate--a position paper by ASDIN. Semin Dial.
2008 Sep;21(5):490-2.
PubMed: PM18764795

REFERENCE LIST Heparin (5,000 u/0.5 mL) for Catheter Lock or Flush 7