An updated Cochrane review published in 2020 included four randomized controlled trials (RCTs) (N=255) which directly compared the clinical effects of intermittent flushing of normal saline versus heparin in preventing occlusion in long-term central venous catheters (CVCs) in infants and children aged up to 18 years of age. The results showed that the estimated relative risk (RR) for CVC occlusion per 1000 catheter days between the normal saline and heparin groups was 0.75 (95% confidence interval [CI] 0.10 to 5.51; 2 studies, 229 participants; P=0.78; I2 = 92%; very low certainty evidence). This suggested that there was no clear benefit in the outcome of CVC occlusion between flushing with heparin or normal saline. The estimated RR for CVC‐associated bloodstream infection was 1.48 (95% CI 0.24 to 9.37; 2 studies, 231 participants; P = 0.67; I2 = 45%; low‐certainty evidence). Again, the study did not find a clear difference between the use of saline to flush CVCs and the incidence of CVC-associated bloodstream infection. The duration of catheter placement was reported to be similar between the two groups in one study (203 participants; moderate‐certainty evidence), and not reported in the remaining studies. [1]
As noted in the results, not all included studies reported on all outcomes of interest; thus, the pooled analysis was only able to combine the results of the two studies (Cesaro 2009, Goosssens 2013). Of note, a non-inferiority trial by Goossens 2013 did include patients older than 1 year scheduled for insertion of CVC; however, the mean age was 57.9 years (standard deviation [SD] 14.8) and 54.9 years (SD 16.6) in the intervention arm (pulsatile flushing with 10 mL of normal saline) and the control arm (pulsatile flushing with 10 mL of normal saline, followed by 3 mL heparin (100 units/mL)), respectively. A subset of pediatric data (unpublished) was obtained by the study author to assess outcomes in 26 out of 28 children contributed data. However, not all variables were available, and there may be some systematic differences in the characteristics of children in this subset of data. In addition, the study was not powered to analyze this subset of data separately. [1]
Included studies instituted different protocols for the intervention and control arms, different concentrations of heparin, and different frequencies of flushes. Given the high risk of bias for non-blinding, a substantial degree of heterogeneity and inconsistency between the studies, and wide confidence intervals reported in the pooled analysis, the certainty of the evidence largely ranged from very low to low, at best. Based on these results, the authors concluded that there was not enough evidence to determine the effects of intermittent flushing with normal saline versus heparin to prevent occlusion in long‐term CVCs in infants and children. It remains unclear whether heparin is necessary to prevent occlusion, CVC‐associated bloodstream infection, or effects duration of catheter placement. [1]
Though not in the context of the neonate/pediatric population, another updated Cochrane review assessing the effectiveness and safety of intermittent locking of CVCs with heparin vs. normal saline to prevent occlusion in adults (11 studies; N=2,392) conveyed similar findings. The pooled analysis did show fewer occlusions with heparin than with normal saline (RR 0.70, 95% CI 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%), but it is based on a very low-quality of evidence given the differences in methodology, unclear allocation concealment, imprecision, and suspicion of publication bias. Furthermore, low‐quality evidence suggests that heparin may have little or no effect on the catheter patency. The study found no evidence of differences in safety (e.g., sepsis, mortality, or hemorrhage) and was not powered to detect rare adverse events such as heparin‐induced thrombocytopenia (HIT). Based on these findings, the authors concluded that there is uncertainty whether the intermittent locking with heparin results in fewer occlusions than intermittent locking with normal saline. [2]
The authors discussed potential risks associated with heparin use. The exposure of surgical patients to unfractionated heparin for longer than four days implies an overall risk of HIT of 2.6%, and an incidental administration of a heparin bolus through a catheter line intended for heparin locking may pose great harm, as well. From an economic stand of point, flushing with normal saline in place of heparin may yield a substantial saving in associated costs. A systematic review published in 1991 estimated yearly savings of 109 to 218 million dollars when peripheral venous lines were flushed with NS instead of heparin. [2], [3]