Venous thrombosis in children : the roles of vascular access and critical illness

Venous thromboembolism (VT) is a rare event in the general pediatric population. However, the incidence in hospitalized children is higher and has increased dramatically reaching 58 per 10 000 children. The single most important risk factor for pediatric VT is the presence of a central venous catheter. The overall aim of this thesis was to achieve a better knowledge and understanding of risk factors for VT in children, specifically related to the use of vascular catheters and to critical illness

The studies in this thesis were performed at the department of Pediatric Perioperative Medicine and Intensive care at Karolinska University Hospital, Stockholm. All patients studied were under 18 years of age.

In study I the incidence of CVC-related VT was prospectively investigated in 211 non-tunneled pediatric CVCs using doppler ultrasonography. CVC-related VT occurred in 30% of cases. Risk factors for any CVC-related VT were internal jugular vein insertion, multiple lumen CVCs and male sex. However, risk factors for small asymptomatic VTs differed from risk factors for VTs with larger thrombotic mass that were symptomatic and/ or occluded vein blood flow. Symptomatic and/or occlusive VT was more likely to occur with femoral vein insertion, a catheter/vein diameter ratio >0.33, PICU admission, and young age.

In study II, the risk for VT related to vascular access catheters used for pediatric CRRT was retrospectively evaluated. Patients with vascular access used for CRRT for at least 48 hours were included. In this study, 5.7% (95% CI: 2-12%) of vascular catheters used for CRRT were complicated by a VT event. Five out of six patients with thromboembolic complications were neonates.

In study III, the incidence of VTs not related to a vascular catheter was prospectively investigated in 70 PICU patients considered to be at high risk of VT. Patients admitted to PICU for ≥72 hours and with at least two risk factors for VT were eligible for inclusion. The incidence of symptomatic VT or asymptomatic not related to a vascular catheter was 0% (95% CI: 0-5.1%). This corresponds to a VT incidence of 0% (95% CI: 0–5.1%).

In study IV the frequency of catheter-related VT and other complications related to the use of pediatric midline catheters was prospectively evaluated. One hundred patients who received a midline catheter at Astrid Lindgren Children´s Hospital were included. Midline catheter-related VT was found in 30% (95% CI 21-40%) of catheters. Mechanical complications occurred in 33 (33%, 95% CI 24-43%) midline catheters but no midline-related bloodstream infection was found. 78% of patients completed iv therapy without the need for additional iv access.

The main conclusions of this thesis are: - VT is a common complication of pediatric CVCs. Risk factors for smaller, asymptomatic VTs are different from risk factors for VTs with larger thrombotic mass; - VT is a clinically relevant complication of pediatric CRRT. Neonates seem to be at the highest risk for this complication; - The risk for VT not related to a venous catheter is low in PICU patients; - Based on the incidences of clinical complications and the observed dwell-time, midline catheters could be alternative to CVCs for short-term iv therapy in selected patients.

List of scientific papers

I. Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters. Åsa Östlund, Urban Fläring, Åke Norberg, Ann Dahlberg, Jonas Berner, Sylvie Kaiser, Lena Vermin, Anna Svenningsson, Tony Frisk, Peter Larsson, Andreas Andersson. British Journal of Anaesthesia. 123(3):316-324(2019).
https://doi.org/10.1016/j.bja.2019.04.055

II. Thromboembolic complications of vascular catheters used for pediatric continuous renal replacement therapy; prevalence in a single-center, retrospective cohort. Isabelle Szeps, Åsa Östlund, Åke Norberg, Urban Fläring, Andreas Andersson. Pediatric Critical Care Medicine. 8(22):743-752(2021).
https://doi.org/10.1097/PCC.0000000000002754

III. Incidence of thromboembolic events not related to vascular catheters in a prospective cohort of critically ill children. Åsa Östlund, Urban Fläring, Peter Larsson, Sylvie Kaiser, Lena Vermin, Tony Frisk, Ann Dahlberg, Jonas Berner, Åke Norberg, Andreas Andersson. European Journal of Pediatrics. 181(8):3031-3038(2022).
https://doi.org/10.1007/s00431-022-04487-8

IV. A prospective study on complications of pediatric midline catheters. Åsa Östlund, Urban Fläring, Åke Norberg, Sylvie Kaiser, Tony Frisk, Peter Larsson, Andreas Andersson. Anesthesia & Analgesia. [Accepted]
https://doi.org/10.1213/ANE.0000000000006328