Key message
We did not find clear evidence of a difference between heparin and normal saline solution (sterile solution of salt in water) in preventing central venous catheter blockages (occlusions), or in the length of time catheters remained unblocked, or in the number of side effects such as infections, death, bleeding, etc. Further well-designed, large-scale studies are required to reduce uncertainties.
Why is this question important?
Central venous catheters are tubes (also called 'lines') that must be temporarily placed into the veins of patients whose veins need to be accessed regularly for medical reasons. These are inserted into the great vessels leading to the heart. While not in use, a fluid is injected into the catheter until it is next used to avoid blood clots that can block the catheter. This is called locking catheters. Replacement of catheters adds to the cost of care, may delay treatment, and poses an additional risk of catheter-related adverse events to the patient. The catheter may also become infected, resulting in bloodstream infections. Fluids used for locking are heparin or normal saline. Heparin, which is an anticoagulant, is used to prevent clotting of the blood. It may also help to prevent the catheters from blocking; however, it can also cause bleeding, allergic reactions, and a drop in the number of platelets in the blood. This has raised the question whether heparin is better than saline to avoid blockages, and how safe each method is.
What did we do?
We searched for randomised controlled trials that assessed whether locking catheters with heparin was more effective in reducing the risk of blocking and infections compared to normal saline. In randomised controlled trials, the treatments people receive are decided at random and these give the most reliable evidence about treatment effects.
What we did find?
We found one new study for this update. In total, we included 12 studies with 2422 people. Five studies included ICU patients, two studies included cancer patients, and the remaining studies included miscellaneous patients (haemodialysis, home care patients, etc.). We cannot conclude that locking catheters with heparin prevents blocking better than flushing with normal saline. We saw little or no difference in the length of time the catheter remained unblocked or in the numbers of side effects between heparin or saline use.
How certain are we with the evidence?
When comparing heparin with saline, the certainty of the evidence of the results ranged from very low to low due to the design of the studies and because the overall result included the likelihood of both benefit and harm.
How up to date is the evidence?
This Cochrane review updates our previous evidence. The evidence is current to 20 October 2021.
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.
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.
To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion.
We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021.
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.
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.
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.