Different unfractionated heparin doses for preventing arterial thrombosis in children undergoing cardiac...

The role of cardiac catheterization in pediatrics has progressed significantly over the last two decades, evolving from a primary diagnostic tool to a primary treatment modality in children with congenital heart disease. Vascular complications, particularly arterial thrombosis, are among the most common unwanted post-cardiac catheterization events. In 1974, unfractionated heparin proved to be superior to placebo in decreasing the incidence of arterial thrombosis in pediatric patients. However, the optimal dose of unfractionated heparin to be utilized in this setting remains a matter of controversy.

To evaluate the use of low-dose (< 100 units/kg) versus high-dose (≥ 100 units/kg) unfractionated heparin administered as an intravenous bolus at the time of initiation of cardiac catheterization (that is, immediately after arterial puncture), with or without subsequent heparin maintenance doses, for the prevention of post-procedural arterial thrombosis in children.

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). The authors searched MEDLINE, EMBASE, and the Virtual Health Library. Clinical trials databases and sources of grey literature were searched. No language restrictions were applied.

Randomized or quasi-randomized trials that compared low dose to high dose unfractionated heparin administered prior to cardiac catheterization were included. We selected studies conducted in children aged 0 to 18 years.

The first screening of potentially eligible studies was conducted by one of the authors (MLA). The second screening, quality assessment and data extraction were independently conducted by two authors (MLA, LRB). Outcomes (thrombotic events, bleeding complications, other complications) were treated as dichotomous variables. The effect measures used were risk ratio (RR), risk difference (RD) and number needed to treat (NNT), with 95% confidence intervals (CI).

Two studies with a total of 492 participants were eligible for inclusion. Risk of bias was low for all domains in one of the studies and unclear for the other. One of the trials was stopped early. The quality of evidence for our key outcomes was moderate. The CI for the risk of arterial thrombotic events was compatible with benefits of either high or low unfractionated heparin dose regimens (RR low-dose versus high-dose 1.06, 95% CI 0.58 to 1.92). Only one of the studies reported the frequency of bleeding events for the cohort of patients and found no statistically significant difference in the incidence of major and minor bleeding events between arms (RR low-dose versus high-dose 1.38, 95% CI 0.46 to 4.13 for minor bleeding; RR low-dose versus high-dose 2.96, 95% CI 0.12 to 71.34 for major bleeding events). This study also reported on the incidence of deep vein thrombosis when comparing the high versus low dose of heparin and reported a non-significant difference (RR low-dose versus high-dose 0.34, 95% CI 0.01 to 8.28). The other study lacked information about bleeding. Side effects of heparin other than bleeding complications were not reported in either of the studies.

Due to the limitations of the current evidence, small number of included studies, and lack of details reported in one study, we are unable to determine the effects of different dosing regimens of unfractionated heparin for the prevention of vascular thrombosis during cardiac catheterization in children. A further adequately powered, randomized clinical trial is needed.