Determining the Incidence and Risk Factors for Central Venous Catheter Related Thrombosis in Children
Authors: Jaffray Julie , Witmer Char , Vasquez Brian , Diaz Rosa , Malvar Jemily , Young Guy 
Published: October 2019

Abstract
Introduction: Venous thromboembolism (VTE) rates in children are increasing, largely due to the improved care of critically ill children and the placement of central venous catheters (CVCs). There is limited evidence regarding risk factors for CVC-associated thrombosis, and there are no guidelines for pediatric patients on choosing catheter type, insertion technique or consideration for prophylaxis. This study aims to be the first prospective, observational, multi-center, pediatric study to compare the VTE incidence between peripherally inserted central catheters (PICCs) and centrally inserted tunneled lines (TLs), as well as identify additional risk factors for CVC-associated thrombosis.
Methods: This prospective, observational cohort study enrolled patients aged 6 months to <18 years from 3 large pediatric hospitals, Children's Hospital Los Angeles, Children's Hospital of Philadelphia and Texas Children's Hospital between September 2013 to April 2016 who either had a PICC or TL placed. Data regarding subject demographics and medical history (cancer, congenital heart disease, history of VTE, current infection, etc.) were collected via electronic medical record (EMR) review. Details specific to the CVC (reason for insertion, CVC size, number of lumens, brand and CVC material) and insertion technique (length of CVC, vein accessed, number of attempts) were also collected. Subjects were then prospectively monitored for the occurrence of a VTE and other CVC-related complications (infection, malfunction, use of tissue plasminogen activator) via EMR review for up to 6 months after their CVC was placed or after diagnosis of a VTE. Univariable and multivariable logistic regression was utilized to examine the association of patient and CVC characteristics on VTE incidence. All significant predictors (p < 0.10) in the univariable analyses were entered into a multivariable model where each predictor's contribution was assessed.
Results: Interim analysis includes 789 subjects [53% male, median age 6 years (0.5, 18)] who had 883 CVCs placed (Table 1). PICCs were placed in 570 (65%) subjects and 313 (35%) had TLs placed. There were a total of 43 CVC-related VTEs (4.9%) and the majority, 37 (86%), were in subjects with PICCs. The median time to develop a PICC-associated VTE after placement was 37 days (1, 215). Twenty-four predictors were analyzed in separate logistic regression models. Univariable analysis of twenty-four possible predictors revealed a statistically significant increased risk of VTE incidence in subjects with a history of VTE with an odds ratio (OR) of 2.9 [95% confidence interval (CI), 1.3-6.6] or congenital heart disease OR=2.8 (CI 1.3-6.0), subjects with PICCs (vs. TLs) OR=3.8 (CI 1.6-9.1), multiple lumen CVCs (TL or PICC) OR=3.2 (CI 1.7-6.0) or in CVCs with a malfunction OR=2.1 (1.1-3.9). Male gender, on the other hand, was associated with a reduced risk of VTE OR=0.46 (0.2-0.9). Type of CVC (PICC vs. TL) OR=3.4 (CI 1.4-8.2), number of lumens OR=2.7 (CI 1.5-5.3), and history of VTE OR=2.8 (CI 1.2-6.5) remained significant positive predictors of VTE incidence in the setting of a multivariable model. Male gender remained to be inversely associated with VTE incidence (Table 2).
Conclusions: This is the first prospective pediatric study comparing VTE incidence in PICCs versus TLs. This interim analysis of nearly 800 subjects revealed a significantly higher risk of VTE in subjects who have had a PICC placed versus a TL. Due to their ease of insertion, PICCs are being placed at increasing rates in some pediatric centers, thus this finding may be the leading factor for the increasing pediatric VTE incidence. Other significant risk factors for VTE were patients with multiple lumen CVCs and a history of VTE. For children who require a new CVC, practitioners should consider avoiding PICCs and multiple lumen CVCs if possible. Consideration should also be made to give prophylactic anticoagulation for children with a CVC and a history of VTE. Further analysis will be performed concerning the decreased VTE rate in male patients.
The identification of these risk factors is the first step to creating CVC selection and insertion guidelines for all children to prevent VTE. Continued subject recruitment, with the recent addition of Nationwide Children's Hospital, is occurring to complete this evaluation.

Disclosures
Young: Biogen: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Kedrion: Consultancy; Baxter: Consultancy.