Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters

Abstract

Peripherally placed percutaneous central venous catheters (PCVC) are used in neonates to provide long-term vascular access. Major complications associated with these catheters include mechanical complications (catheter thrombosis, occlusion or dislodgement) and infection. Strategies to prevent catheter thrombosis and occlusion include the use of heparin. Systematic review has revealed that heparin is effective in prolonging the umbilical arterial catheter stay in neonates. However, heparin is known to be associated with complications such as bleeding and thrombocytopenia which may result in serious long-term sequelae. The primary objective is to assess the effectiveness of heparin for prevention of catheter related thrombosis. The secondary objectives are to assess the effectiveness of heparin on catheter occlusion, duration of catheter patency, catheter related sepsis and complications associated with the use of heparin. A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) and abstracts from the annual meetings of the Society for Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2005). No language restrictions were applied. Selection criteria applied to the clinical trials were: the population had to be neonates, intervention had to be heparin infusion compared to placebo or no treatment for prevention of any of the complications related to peripherally placed PCVC, the trial had to be randomized or quasi-randomized and at least one of the primary or secondary outcomes reported. The methodological quality of included trials was assessed using criteria for masking of randomization, masking of intervention, completeness of follow-up and masking of outcome measurement. Data on relevant outcomes were extracted and the effect size was estimated by calculating relative risk (95% CI), risk difference (95% CI) and weighted mean difference (95% CI). Two randomized trials on the use of heparin for peripherally placed PCVC were identified . One trial (Kamala et al) of 66 neonates of adequate methodology met the eligibility criteria. There was no statistically significant differences in the incidence of thrombosis (RR 0.79, 95% CI 0.35, 1.79), occlusion (RR 0.63, 95% CI 0.22), catheter related sepsis (RR 0.89, 95% CI 0.06, 13.57), extension of intraventricular hemorrhage (RR 0.87, 95% CI 0.25, 3.03), mortality (RR 0.59, 95% CI 0.18, 1.90) or duration of catheter patency (WMD 1.50 days, 95% CI -1.35 days, 4.35 days) between heparin and no heparin groups. Another trial (Betremieux et al) was excluded due to several methodological issues: 1. randomization was at the time of umbilical catheter placement rather than later PCVC placement 2. multiple PCVC were used in some infants, with reported results based on number of catheters rather than infants. Prophylactic use of heparin for prevention of complications related to peripherally placed PCVC has been examined in only one randomized controlled clinical trial that was eligible for inclusion in this review. No significant differences in the incidence of thrombosis, occlusion, sepsis, mortality and duration of catheter patency were observed. With the current state of knowledge, routine use of heparin for this purpose can not be recommended. Implication for research: Increasing survival of extremely low birth weight infants may be accompanied by prolonged intravenous access for nutrition. Well designed randomized controlled trials of sufficient power to determine the benefits and risks of continuous infusion of heparin in neonates with peripherally inserted PCVC are warranted.