Prophylactic Enoxaparin Against Catheter-Associated Thrombosis in Postoperative Cardiac Children: An Interrupted Time Series Analysis

Abstract

The effectiveness of pharmacologic prophylaxis against catheterassociated thrombosis in children is unclear. We evaluated the compliance and outcomes associated with a prophylactic enoxaparin protocol in postoperative cardiac children. DESIGN:The protocol was implemented as a quality improvement initiative and then analyzed using interrupted time series method. Data collected from November 2014 to December 2018 were divided into preprotocol (period 1), protocol implementation (period 2), and protocol revision (period 3). SETTING:A 12-bed academic pediatric cardiac ICU. PATIENTS:Children less than or equal to 18 years old with congenital heart disease admitted postoperatively with central venous catheter in situ for greater than or equal to 1 day. INTERVENTIONS:Before 2016, prophylactic enoxaparin was administered according to physician preference. In January 2016, an enoxaparin protocol was implemented with a goal anti-Xa range of 0.25-0.49 international units/mL. Protocol was revised in February 2017 to increase the starting dose by 25% for infants less than 1 year old. MEASUREMENTS AND MAIN RESULTS:We analyzed 780 hospitalizations from 636 children. Median percentage of catheter-days on prophylactic enoxaparin was 33% (interquartile range [IQR], 23-47%), 42% (IQR, 30-51%), and 38% (IQR, 35-52%) in periods 1-3, respectively. Percentage of catheter-days on enoxaparin showed immediate increase of 90% (95% CI, 17-210%) between periods 1 and 2 and sustained increase of 2% (95% CI, 0.3-4%) between periods 2 and 3. Median rates of thrombosis per 1,000 catheter-days were 5.8 (IQR, 0-9.3), 3.8 (IQR, 0-12), and 0 (IQR, 0-5.3) in periods 1-3, respectively. Rate of thrombosis showed immediate decrease of 67% (95% CI, 12-87%) between periods 1 and 2 and sustained decrease of 11% (95% CI, 2-18%) between periods 1 and 3. CONCLUSIONS:The temporal association between increase in percentage of catheter-days on enoxaparin and decrease in rate of thrombosis suggests the effectiveness of prophylactic enoxaparin. KEY WORDS: anticoagulation agents; central venous catheter; intensive care units; pediatric; venous thrombosis C hildren with congenital heart disease (CHD) admitted postoperatively to the cardiovascular ICU (CVICU) are at high risk of venous thromboembolism (VTE) (1, 2). Placement of central venous catheter (CVC) constitutes an important risk factor for VTE (3). Peripherally inserted central catheter (PICC)

Enoxaparin to Prevent Catheter-Associated Thrombosis: Effective, But Is This a Tool We Need?*

“…Additionally, if (when) we can answer the question of who should receive therapy, we may then be able to start the process of addressing the clinical significance of CADVT. Although studies, including the current study by Centers et al (6), suggest the benefit of anticoagulant therapy, the effectiveness of these agents is not so strong that alternative antithrombotic therapy when pharmacologic intervention is warranted should be precluded from study. Although current anticoagulation interventions interrupt the pathways that result in the formation of a fibrin clot, they do nothing, or at least very little, to affect the processes that involve the interaction of platelets and endothelial cells (ECs) in thrombus formation.…”

“…In this issue of pediatric Critical Care Medicine , Centers et al (6) report the results of a retrospective analysis of the use of prophylactic enoxaparin for the prevention of postcardiac surgery CADVT in children. The study by Centers et al (6) was designed and carried out as a quality improvement process and conducted over three time periods from 2014 to 2018: pre study (November 2014 to December 2015), study (January 2016 to January 2017), and study revision (February 2017 to December 2018). A total of 780 hospitalizations in 636 unique patients were analyzed using Interrupted Time Series Analysis (ITSA).…”

“…Centers et al (6) have identified another tool for our toolbox, and now our task is to determine whether this is the right tool and when to use it. A recent survey of pediatric intensivists has already demonstrated that equipoise on the issue of treatment of CADVT has been established (15).…”

Editor’s Choice Articles for October

“…Centers GI, Hege KM, Nitu ME, et al: Prophylactic Enoxaparin Against Catheter-Associated Thrombosis In Postoperative Cardiac Children: An Interrupted Time Series Analysis (2). My next Editor's Choice article looks at protocol implementation using enoxaparin prophylaxis in over 600 postoperative congenital heart disease patients (before versus during implementation, versus after protocol revision) and the temporal association between catheter days on enoxaparin and decrease in rate of thrombosis (2). Read the accompanying editorial and its insightful approach as to what should now follow regarding clinical investigation (5).…”

“…Robert C. Tasker, MBBS, MD, FRCP [1][2][3] Editor's Choice Articles for October My third Editor's Choice article is a feature systematic review and meta-analysis of nine articles (a total of more than 750 patients) and asks whether early initiation of peritoneal dialysis is associated with beneficial postoperative outcomes after infant cardiac surgery (3). The accompanying editorial helps us to better understand the context of these data and to think about patient selection, timing of intervention, and methodology of peritoneal dialysis (6).…”