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Meta-Analysis
. 2022 Jul 18;7(7):CD008462.
doi: 10.1002/14651858.CD008462.pub4.

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults

Eduardo López-Briz  1 , Vicente Ruiz Garcia  2 , Juan B Cabello  3 , Sylvia Bort-Martí  4 , Rafael Carbonell Sanchis  5
Affiliations
Meta-Analysis

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults

Eduardo López-Briz et al. Cochrane Database Syst Rev. .

Abstract

Background: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency and performance. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% sodium chloride (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to normal saline, to see if the evidence establishes whether one is better than the other. This is an update of an earlier Cochrane Review.

Objectives: To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion.

Search methods: We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021.

Selection criteria: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus normal saline. We excluded studies on infants and children from this review.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were occlusion of CVCs and duration of catheter patency. Our secondary outcomes were CVC-related bloodstream infections and CVC-related colonisation, mortality, haemorrhage, heparin-induced thrombocytopaenia, CVC-related thrombosis, number of additional CVC insertions, abnormality of coagulation profile and allergic reactions to heparin. We used GRADE to assess the certainty of evidence for each outcome.

Main results: We identified one new RCT with 30 participants for this update. We included a total of 12 RCTs with 2422 participants. Data for meta-analysis were available from all RCTs. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Five studies included ICU (intensive care unit) patients, two studies included oncology patients, and the remaining studies included miscellaneous patients (chronic kidney disease, haemodialysis, home care patients, etc.). Primary outcomes Overall, combined results may show fewer occlusions with heparin compared to normal saline but this is uncertain (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; 10 studies; 1672 participants; low-certainty evidence). We pooled studies that used participant or catheter as the unit of analysis. We carried out subgroup analysis by unit of analysis. No clear differences were detected after testing for subgroup differences (P = 0.23). We found no clear evidence of a difference in the duration of catheter patency with heparin compared to normal saline (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; 6 studies; 1788 participants; low-certainty evidence). Secondary outcomes We found no clear evidence of a difference in the following outcomes: CVC-related bloodstream infections (RR 0.66, 95% CI 0.08 to 5.80; 3 studies; 1127 participants; very low-certainty evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; 3 studies; 1100 participants; very low-certainty evidence); haemorrhage (RR 1.54, 95% CI 0.41 to 5.74; 3 studies; 1197 participants; very low-certainty evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; 3 studies; 443 participants; very low-certainty evidence). The main reasons for downgrading the certainty of evidence for the primary and secondary outcomes were unclear allocation concealment, suspicion of publication bias, imprecision and inconsistency.

Authors' conclusions: Given the low-certainty evidence, we are uncertain whether intermittent locking with heparin results in fewer central venous catheter occlusions than intermittent locking with normal saline in adults. Low-certainty evidence suggests that heparin may have little or no effect on catheter patency duration. Although we found no evidence of differences in safety (CVC-related bloodstream infections, mortality, or haemorrhage), the combined studies were not powered to detect rare adverse events such as heparin-induced thrombocytopaenia. Further research conducted over longer periods would reduce the current uncertainties.

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Conflict of interest statement

ELB: none known VRG: none known JBC: none known SBM: none known RCS: none known

Figures

1
1
Funnel plot of comparison: 1 Occlusion of CVCs, outcome: 1.1 All studies
2
2
Study flow diagram 2021
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Occlusion of CVCs, Outcome 1: All studies
1.2
1.2. Analysis
Comparison 1: Occlusion of CVCs, Outcome 2: Unit of analysis: line access
2.1
2.1. Analysis
Comparison 2: Duration of catheter patency (days), Outcome 1: All studies
3.1
3.1. Analysis
Comparison 3: Safety, Outcome 1: CVC‐related bloodstream infections
3.2
3.2. Analysis
Comparison 3: Safety, Outcome 2: Mortality
3.3
3.3. Analysis
Comparison 3: Safety, Outcome 3: Haemorrhage from any site
3.4
3.4. Analysis
Comparison 3: Safety, Outcome 4: Heparin‐induced thrombocytopaenia
3.5
3.5. Analysis
Comparison 3: Safety, Outcome 5: CVC‐related thrombosis
4.1
4.1. Analysis
Comparison 4: Sensitivity analysis, Outcome 1: Occlusion of CVCs ‐ good allocation concealment
4.2
4.2. Analysis
Comparison 4: Sensitivity analysis, Outcome 2: Occlusion of CVCs ‐ excluding most weighted study (Goosens 2013)
4.3
4.3. Analysis
Comparison 4: Sensitivity analysis, Outcome 3: Occlusion of CVCs ‐ Z scores by unit of analysis
4.4
4.4. Analysis
Comparison 4: Sensitivity analysis, Outcome 4: Duration of catheter patency ‐ Z scores by unit of analysis
5.1
5.1. Analysis
Comparison 5: Additional subgroup analysis, Outcome 1: Oncology vs non‐oncology participants: occlusion of CVCs
5.2
5.2. Analysis
Comparison 5: Additional subgroup analysis, Outcome 2: One vs more than one lumen (unit of analysis is participant): occlusion of CVCs
5.3
5.3. Analysis
Comparison 5: Additional subgroup analysis, Outcome 3: High vs low heparin concentration: occlusion of CVCs
5.4
5.4. Analysis
Comparison 5: Additional subgroup analysis, Outcome 4: Less than one month vs over one month follow‐up: occlusion of CVCs
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Hendrickx 2001 {published data only}
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Heng 2011 {published data only}
    1. Heng AE, Abdelkader MH, Diaconita M, Nony A, Guerraoui A, Caillot N, et al. Impact of short term use of interdialytic 60% ethanol lock solution on tunneled silicone catheter dysfunction. Clinical Nephrology 2011;75(6):534-41. - PubMed
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IRCT20151228025732N56 {published data only}
    1. IRCT51660. Comparison of the effect of intravenous catheter washing with heparin, normal saline, and taurolock solution on phlebitis severity. www.irct.ir/trial/51660 (first received 20 October 2020). [IRCT20151228025732N56]
IRCT20190325043107N4 {unpublished data only}IRCT20190325043107N4
    1. IRCT20190325043107N4. Comparison of the effect of heparin saline and normal saline on keeping open the pathway of peripheral or peripheral venous catheters in cancer patients. trialsearch.who.int/?TrialID=IRCT20190325043107N4 (first received 21 April 2019). [IRCT20190325043107N4]
IRCT20191218045773N2 {unpublished data only}
    1. IRCT44454. Comparing the effects of flushing and saline lock on phlebitis and patency time of peripheral intravenous catheters in patients admitted to the medical department. irct.ir/trial/44454 (first received 31 January 2020). [IRCT20191218045773N2]
Ishii 2013 {published data only}
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Johnson 2002 {published data only}
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Kankanala 2012 {published data only}
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    1. Liang H, Liu XS, Wu YC, Zhang L, Lin QZ, Jie XN, et al. Ultra-low dose heparin locks perform well on non-tunnelled temporary haemodialysis catheters. Nephrology 2015;20(4):307-8. [PMID: ] - PubMed
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Mortazavi 2011 {published data only}
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NCT00039767 {published data only}
    1. NCT00039767. Heparin vs. lepirudin flushes in preventing withdrawal occlusion of tunneled, open-ended venous access devices: a blinded, randomized, clinical trial. clinicaltrials.gov/ct2/show/NCT00039767 (first received 7 June 2002).
NCT00216866 {published data only}
    1. NCT00216866. A pilot study of central venous catheter survival in cancer patients using low molecular weight heparin (dalteparin) for the treatment of deep vein thrombosis of the upper extremity. clinicaltrials.gov/ct2/show/NCT00216866 (first received 19 September 2005).
NCT00378781 {published data only}
    1. NCT00378781. Prospective, randomized trial comparing heparin and minocycline-EDTA flush for the prevention of catheter-related infections and occlusions. clinicaltrials.gov/ct2/show/NCT00378781 (first received 16 September 2006).
NCT00386451 {published data only}
    1. NCT00386451. Prospective study which compares the use of a closing system without a needle and with positive pressure to a heparin lock with positive pressure for patients with a catheter for chemotherapy. clinicaltrials.gov/ct2/show/NCT00386451 (first received 10 October 2006).
NCT00571259 {published data only}
    1. NCT00571259. Prophylactic antimicrobial catheter lock in hemodialysis patients: a randomized controlled clinical trial. clinicaltrials.gov/ct2/show/NCT00571259 (first received 10 December 2007).
NCT00735813 {published data only}
    1. NCT00735813. A randomised study of taurolock for the locking of tunneled central venous catheters in children with malignant diseases. clinicaltrials.gov/ct2/show/NCT00735813 (first received 14 August 2008).
NCT00749619 {published data only}
    1. NCT00749619. Addition of heparin to taurolock-TM CLS in HD patients with TCC: does it improve catheter patency problems? clinicaltrials.gov/ct2/show/NCT00749619 (first received 7 September 2008).
NCT00862966 {published data only}
    1. NCT00862966. Randomized control trial on citrate as the central venous catheter lock solution. clinicaltrials.gov/ct2/show/NCT00862966 (first received 13 March 2009).
NCT00951574 {published data only}
    1. NCT00951574. Prevention of venous and arterial thromboembolism in cancer patients undergoing chemotherapy, with a low molecular weight heparin (nadroparin calcium). A randomized, placebo-controlled, double-blind, multicenter phase III study. clinicaltrials.gov/ct2/show/NCT00951574 (first received 31 July 2009).
NCT01097031 {published data only}
    1. NCT01097031. Continuous or intermittent for keeping arterial catheter in children: a randomized clinical trial. clinicaltrials.gov/show/NCT01097031 (first received 30 March 2010).
NCT01131754 {published data only}
    1. NCT01131754. Heparin in prophylaxis of peripheral venous catheters thrombosis: randomized clinical trial [Studio clinico randomizzato sull'utilizzo di eparina per la profilassi della tromboflebite da catetere venoso periferico]. clinicaltrials.gov/ct2/show/NCT01131754 (first received 26 May 2010).
NCT01229592 {published data only}
    1. NCT01229592. Clinical study of ethanol lock-therapy in the prevention of non-tunnelled, short term central venous catheter associated infections. clinicaltrials.gov/ct2/show/NCT01229592 (first received 18 October 2012).
NCT01243710 {published data only}
    1. NCT01243710. A randomised controlled trial of taurolidine with heparin for prevention of recurrence of catheter related bacteraemia in haemodialysis patients. clinicaltrials.gov/ct2/show/NCT01243710 (first received 18 November 2010).
NCT01472965 {published data only}
    1. NCT01472965. A double-blind, randomized, placebo-controlled trial of ethanol lock therapy for treatment and secondary prophylaxis of central line associated bloodstream infection (CLABSI) in children and adolescents. clinicaltrials.gov/show/NCT01472965 (first received 14 November 2011).
NCT01483872 {published data only}
    1. NCT01483872. Phase II trial of a novel catheter lock solution for adjunctive treatment of hemodialysis catheter-associated bacteremia. clinicaltrials.gov/ct2/show/NCT01483872 (first received 26 November 2011).
NCT01522846 {published data only}
    1. NCT01522846. Influence by heparinized flush solution of the radial artery catheter: INTEM and HEPTEM analysis. clinicaltrials.gov/ct2/show/NCT01522846 (first received 9 January 2012).
NCT01592032 {published data only}
    1. NCT01592032. Concentration and antibiotic activity in antibiotic lock solutions. clinicaltrials.gov/ct2/show/NCT01592032 (first received 24 April 2012).
NCT01820962 {published data only}
    1. NCT01820962. Concentrated citrate locking to reduce the incidence of central venous catheter-related infections and thrombosis: a randomized phase III study in a hematological patient population. clinicaltrials.gov/ct2/show/NCT01820962 (first received 12 March 2013).
NCT01948245 {published data only}
    1. NCT01948245. A double blinded, randomized, controlled investigation of taurolidine-citrate/heparin catheter lock solution versus heparin in patients on home parenteral nutrition with previously proven high risk of catheter related blood stream infections. clinicaltrials.gov/ct2/show/NCT01948245 (first received 16 September 2013).
NCT01962116 {published data only}
    1. NCT01962116. Citrate versus heparin for the lock of non-tunneled hemodialysis catheters in patients hospitalised in ICU. Multicentre, controlled, randomised superiority trial. clinicaltrials.gov/ct2/show/NCT01962116 (first received 27 August 2013).
NCT01989091 {published data only}
    1. NCT01989091. Multi-center, prospective, randomized, open-label, sponsor-blinded, active-control (heparin) clinical investigation to evaluate the safety and effectiveness of B-Lock™ as an antimicrobial catheter lock solution in dialysis patients with a central venous catheter. clinicaltrials.gov/ct2/show/NCT01989091 (first received 30 October 2013).
NCT02923830 {published data only}
    1. NCT02923830. Maintaining patency in BioFlo implanted port catheters with saline only flushes. clinicaltrials.gov/ct2/show/NCT02923830 (first received 30 September 2016).
NCT03114722 {published data only}
    1. NCT03114722. Citrate 4% versus heparinised saline in preventing peripherally inserted central catheter (PICC) occlusions. clinicaltrials.gov/show/NCT03114722 (date first received 14 April 2017).
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Rijnders 2005 {published data only}
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References to ongoing studies

ChiCTR1800018391 {published data only}
    1. ChiCTR1800018391. The effect of different concentrations of heparin sealing liquid on thrombosis after peripherally inserted central catheter catheterization in malignant tumor patients: a prospective, single-blind, randomized, controlled study. chictr.org.cn/showproj.aspx?proj=30808 (first received 14 September 2018). [DOI: 10.21203/rs.2.54/v1] - DOI
CTRI/2021/04/033007 {published data only}
    1. CTRI/2021/04/033007. A randomized controlled trial on comparison of normal saline with heparin for maintaining patency of central venous catheters in intensive care unit patients. trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/04/033007 (first received 22 April 2021). [033007]
IRCT20190905044704N1 {published data only}
    1. IRCT20190905044704N1. The effect of intermediate dose of heparin solution in the prevention of central vein catheter occlusion on ICU admitted patients. irct.ir/trial/57908 (first received 19 August 2021). [IRCT20190905044704N1]
JPRN‐UMIN000033713 {published data only}
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NCT02354118 {published data only}
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NCT05029596 {published data only}
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References to other published versions of this review

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