- Email: [email protected]
Central venous lines in critically ill children: Thrombosis but not infection is site dependent
Journal of Pediatric Surgery 54 (2019) 1740–1743
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Central venous lines in critically ill children: Thrombosis but not infection is site dependent S. Christopher Derderian a,⁎, Ryan Good b, Raphael N. Vuille-dit-Bille a, Todd Carpenter b, Denis D. Bensard a,c a b c
Department of Pediatric Surgery, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO Department of Critical Care Medicine at Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO Department of Surgery, Denver Health Medical Center, Denver, CO
a r t i c l e
i n f o
Article history: Received 21 August 2018 Received in revised form 18 October 2018 Accepted 31 October 2018 Key words: Central line Central venous catheter CLABSI VTE Line infection Venous thromboembolism
a b s t r a c t Background: Central venous catheters (CVC) are vital to the management of critically ill children. Despite efforts to minimize complications, central line associated bloodstream infection (CLABSI) and venous thromboembolisms (VTE) still occur. Methods: We performed a retrospective review of a prospectively collected database for children admitted to the pediatric intensive care unit (PICU) between November 2013 and December 2016. Results: In total, 2714 CVC were in place, 979 of which were percutaneous CVC. During the study period, 21 CLABSI (1.6/1000 line days) were identified, of which, nearly half (n = 9, 42.9%) were associated with percutaneous CVC (2.6/1000 line days). Poisson regression analysis did not identify a single risk factor for CLABSI when adjusting for line type, anatomic location and laterality of placement, geographic location of placement, length of PICU admission, presence of gastrostomy tube, concurrent mechanical ventilation, age, weight, and height. Forty clinically significant VTE (2.9/1000 line days) were identified, with percutaneous CVC having the highest incidence (7.5/1000 line days, p b 0.001). Of percutaneous CVC, clinically significant VTE were more often associated with femoral vein cannulation (14.8/1000 line days) compared to internal jugular and subclavian vein (2.5 and 2.4/1000 line days, respectively, p b 0.001). Conclusion: This data suggests that the femoral site may be an important risk factor that should be considered in prevention strategies for catheter-associated VTE in children. Level of Evidence: III. © 2018 Elsevier Inc. All rights reserved.
Central venous catheters (CVC) remain an integral component to the management of critically ill children in the pediatric intensive care unit (PICU). The implementation of bundles and daily assessment of their need has abrogated line-associated complications; however, two commonly recognized sequelae resulting from CVC placement include central line associated bloodstream infections (CLABSI) and venous thromboembolisms (VTE) [1]. Prior to quality improvement initiatives, nearly 50% of adult patients admitted to the intensive care unit had a CVC at one point during their admission [2], but in recent years there has been a paradigm shift with an emphasis on minimizing CVC placement and the number of line days in an effort to reduce associated complications. These efforts have resulted in nearly a 50% reduction in the use of CVC in adults [3]. In pediatrics, the frequency of CLABSI associated with percutaneous CVC approximates 5 per 1000 line days, which is similar to the incidence
⁎ Corresponding author at: Children's Hospital Colorado, University of Colorado School of Medicine, 12631 E 17th Ave, C302, Aurora, CO 80045. Tel.: +1 720 777 6571 (Office). E-mail address: [email protected] (S.C. Derderian). https://doi.org/10.1016/j.jpedsurg.2018.10.109 0022-3468/© 2018 Elsevier Inc. All rights reserved.
found in adults [4,5]. Risk factors for CLABSI in children include indwelling duration, underlying non-operative cardiovascular disease or the presence of a gastrostomy tube, parenteral nutrition and blood transfusion [6]. Clinicians have little control over these risk factors; however, in adults, several studies suggest that cannulation of the subclavian vein over the internal jugular and femoral vein results in reduce CLABSI rates [4,7]. In children, however, the evidence for preferential subclavian vein access is limited [8]. Venous thromboembolism is another line-associated complication affecting morbidity, mortality, and hospital cost [9,10]. The reported incidence of CVC associated VTE is variable, ranging from 1.5 to 7.7 per 1000 line days [11,12]. In both children and adults, it has been observed in small series that femoral and subclavian vein CVC have a higher incidence of VTE than the internal jugular vein [13,14]. Whether catheter size and indwelling duration impact the incidence of VTE remains a point of contention [15,16]. Nevertheless, there is little data to support the anatomic location of a percutaneous CVC to minimize the risk of VTE. Given the paucity of data pertaining to complications associated with CVC in children admitted to the PICU, we sought to review our
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743
center's experience with CVC complications, specifically, we risk factors associated with CLABSI and VTE. 1. Methods We performed a retrospective review of all children between the age of 31 days and 17 years admitted to the PICU between November 2013 and December 2016 who had a CVC in place during their PICU admission. We defined CVC as a venous catheter that terminated within the superior or inferior vena cava or the right atrium of the heart. We excluded extracorporeal membrane oxygenation catheters. Line days equaled the difference between CVC placement and removal. If a line was placed while the child was in the PICU and remained in place upon PICU transfer, ‘line days’ was the number of days between placement and PICU transfer. If a child was admitted to the PICU with a CVC in place and it was removed, line days equaled the difference between PICU admission and line removal. If a child was admitted and transferred from the PICU with a line in place, line days equaled PICU length of stay. VTE was defined by evidence of catheter-associated thrombus based on Duplex ultrasonography. Ultrasounds were obtained for clinical suspicion of VTE and thus sub-clinical VTE were not included. Mechanical ventilation was considered a risk factor only if the time of mechanical ventilation overlapped with the time a CVC was in place. We analyzed prospectively collected data from Children's Hospital Colorado electronic medical record (EMR) system, quality improvement reports generated by Children's Hospital Colorado to track CLABSI and VTE, and Virtual Pediatric System (VPS) LLC. No endorsement or editorial restrictions of the interpretation of these data or opinions of the authors has been implied or stated. The charts of children with CLABSI or VTE were reviewed following approval from the Institutional Review Board at Children's Hospital Colorado (Approval # 17–1718). Details pertaining to each case were recorded and analyzed. Poisson regression was used to assess the relationship between CVC type and the number of CLABSI and VTE. The relationship between anatomic site and the number of CLABSI and VTE was also assessed among percutaneous central venous catheters. Regression models were further adjusted for geographic and anatomic location of placement as well as laterality, line duration, gender, age, weight, presence of a gastrostomy tube, and concurrent mechanical ventilation. A p-value of b 0.05 was considered statistically significant. Statistical analyses were performed using Stata 14 (College Park, TX). 2. Results Between November 2013 and December 2016, a total of 2714 lines were in place in patients admitted to the PICU. These included external tunneled catheters, percutaneous CVC, dialysis catheters, peripherally inserted central catheters (PICC), and ports (Table 1). Among children with percutaneous CVC, 408 (42%) were placed in the femoral vein, 385 (39%) in the internal jugular vein, and 186 (19%) in the subclavian vein. The total number of percutaneous CVC days was 3472 with a CLABSI rate of 2.6 per 1000 line days and clinically significant VTE rate of 7.5 per 1000 (Table 2).
1741
In total, 21 CLABSI (1.6/1000 line days) were identified during the study period, of which nine (42.9%) were in children with a percutaneous CVC (2.6/1000 line days); however, regression analysis demonstrated no statistically significant difference between type of line and CLABSI rate (Table 1). A variety of pathogens were responsible and included candida species (5), enterobacter (4), enterococcus (5), Escherichia coli (1), lactobacillus (1), neisseria (1), pseudomonas (3), staphylococcus (4), and stenotrophomas (1). Four cultures grew out polymicrobial organisms with a majority of these organisms coinciding with gastrointestinal flora bacteria. Using Poisson regression analysis adjusting for all confounding variables reported in the methods, we did not find independent risk factors associated with infection rate. The same was true when restricting the analysis to only percutaneous CVC. To account for diaper stool contamination of femoral CVC, we dividing the cohort into those younger than and those equal to or older than 3 years of age (the average age when American children grow out of diapers) and did not find a difference in CLABSI rate (p = 0.54). The median length of time between line insertion and CLABSI was 7.2 (IQR 4.3 and 14.5), at which point seven (33%) were removed. After selecting out percutaneous CVC, we found the incidence of CLABSI with femoral cannulation to be 4.2 per 1000 line days compared to internal jugular (1.7/1000 line days) and subclavian (1.2/1000 line days), but the difference did not reach statistical significance (Table 2). Forty clinically significant VTE (2.9/1000 line days) were identified over the study period. Ports had the lowest incidence at 0.7 per 1000 line days while percutaneous CVC had a 10-fold higher incidence at 7.5 per 1000 line days (p = 0.003). After adjusting for confounding variables reported in the methods, anatomic location was found to be a significant risk factor for clinically significant VTE (p = 0.001). The median time between CVC placement and clinically significant VTE was 5 (IQR 3 and 8.5) days. Eighteen (44%) were occlusive and one was associated with a clinically significant pulmonary embolus. When we selected out percutaneous CVC, femoral vein CVC accounted for 88% of clinically significant VTE with an incidence of 14.8 per 1000 line days compared to internal jugular and subclavian CVC (2.5 and 2.4 per 1000 line days, respectively, p b 0.001).
3. Discussion Our experience with CLABSI and VTE in the PICU is rare with rates of 1.6 per 1000 and 2.9 per 1000 line days, respectively, which is slightly lower than that reported in the literature [4,5,11]. We found that PICC lines are associated with the lowest rate of CLABSI and VTE and percutaneous CVC carry the highest rate of VTE. Among percutaneous CVC, anatomic location did not significantly impact CLABSI rate but did affect clinically significant VTE rate with nearly a 6-fold increase risk with femoral vein access compared to subclavian or internal jugular access. The reduced incidence of CLABSI and VTE is undoubtedly a reflection of “target zero” type measures including health care worker training, hand hygiene, ultrasound guidance, aseptic insertion techniques, catheter site care with a transparent dressing, and ethanol cleansing prior to access [17,18]. As a result, the number of catheter-associated complications is significantly reduced; however, when they do occur,
Table 1 Central venous catheter associated CLABSI and VTE. Type of Line
Total Number Placed
Line Days
CLABSI
CLABSI/1000 Line Days
P-value1
VTE
VTE/1000 Line Days
P-value1
External Tunneled Catheter Percutaneous CVC Dialysis Catheter PICC Port Combined
307 979 86 913 429 2714
1441 3472 491 5948 1527 12,879
4 9 0 5 3 21
2.8 2.6 0 0.8 2.0 1.6
0.261 0.108 0.999 0.049 0.731
1 26 2 10 1 40
0.7 7.5 4.1 1.7 0.7 2.9
0.116 b0.001 0.695 0.010 0.102
CVC: Central venous catheter; PICC: Peripherally inserted central catheter; CLABSI: Central line associated bloodstream infections; VTE: venous thromboembolism. 1 Poisson regression.
1742
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743
Table 2 Percutaneous central venous catheters associated CLABSI and VTE by anatomic site. Anatomic Site
Total Number Placed
Line Days
CLABSI
CLABSI/1000 Line Days
P-value1
VTE
VTE/1000 Line Days
P-value1
Femoral Vein Internal Jugular Vein Subclavian Vein Combined
408 385 186 979
1421 1211 840 3472
6 2 1 9
4.2 1.7 1.2 2.6
0.134 0.433 0.377
21 3 2 26
14.8 2.5 2.4 7.5
b0.001 0.021 0.068
CLABSI: Central line associated bloodstream infection; VTE: venous thromboembolism. 1 Poisson regression.
they can result in increased morbidity, mortality and health care dollars. Thus, measures to reduce complications further are warranted. Extrapolating data from the adult literature, we expected to find a higher rate of CLABSI associated with percutaneous CVCs placed within the femoral vein. Presumably, the increased incidence of CLABSI with femoral vein cannulation in adults is related to CVC colonization by skin flora. In an adult randomized control trial by Parienti et al., dialysis catheters placed within the femoral vein were only found to have a higher CLABSI rate than internal jugular catheterization among patients with a high body mass index [19]. As children rarely have redundant skin folds in the groin, it is theoretically easier to maintain cleanliness with the use of CVC bundles. Compared to the general pediatric population, PICU patients are at a higher risk of developing VTE, particularly those with a CVC [20,21]. Multiple variables may influence the risk of VTE and include hypercoagulable states, often seen in children with burns and malignancy, age, weight, catheter size, length of stay greater than 3 days, and significant infection but these variables have not been well studied in the PICU population [22]. Venous thromboembolism chemoprophylaxis decreases the risk of asymptomatic VTE in adults who are at risk for line associated VTE [23]. Some institutions, including ours, advocate a scoring system to stratify those at high risk for VTE who may benefit form VTE prophylaxis but the benefit is yet to be validated [22]. It is also unclear if the anatomic site of CVC insertion is a risk factor for VTE. We found that clinically significant VTE were more frequently associated with percutaneous CVC compared to other line types, and that among percutaneous CVC, femoral vein CVC had the highest frequency of clinically significant VTE with a 6-fold increase compared to subclavian and internal jugular vein. This observation may be a reflection of increased collateralization around the subclavian and internal jugular veins compared to the femoral vein and consequently we may be missing occult VTE. Alternatively, proximity to the heart and a larger catheter-to-vessel ratio may affect VTE rate but we were unable to account for these variables due to infrequent abdominal radiographs to assess femoral CVC positioning and inconsistent catheter size recordings. We did not find any other risk factors associated with VTE in our study group. It has been reported that among children admitted to the PICU, independent risk factors for VTE include age less than 1 year of age, mechanical ventilation, cardiac catheterization, and percutaneous CVC placement [21]. Given our low incidence of CVC related CLABSI and VTE, it is feasible that our sample size was not large enough to identify other risk factors. There are limitations to this study. As our practice is to only obtain Duplex ultrasonography for patients with a clinical suspicion for a VTE, it is likely that sub-clinical VTE were not identified. Nevertheless, we believe that symptomatic VTE are more relevant to clinical practice and therefore worthy of reporting. Additionally, VTE may be more common in younger children with a lower vessel to catheter size ratio but as we did not have consistent catheter size recordings to reliably assess this risk and it remains a question worth further research. In summary, we found that among children with percutaneous CVC in place during their PICU admission, femoral cannulation was associated with an increased frequency of VTE but not CLABSI. This data suggests that femoral cannulation may be an independent risk factor
for catheter-associated VTE in children. Furthermore, PICC lines were found to have the lowest incidence of CLABSI and VTE and may be the line of choice if time permits for placement. CRediT authorship contribution statement S. Christopher Derderian: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. Ryan Good: Conceptualization, Data curation. Raphael N. Vuille-dit-Bille: Formal analysis, Writing – original draft. Todd Carpenter: Conceptualization, Data curation, Writing – review & editing. Denis D. Bensard: Formal analysis, Writing – original draft, Writing – review & editing. References [1] Edwards JD, Herzig CT, Liu H, et al. Central line-associated blood stream infections in pediatric intensive care units: longitudinal trends and compliance with bundle strategies. Am J Infect Control 2015;43(5):489–93. [2] Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000;132(5):391–402. [3] Prevention CfDCa. Bloodstream infection event (central line-associated bloodstream infection and non-central line associated bloodstream infection). National Healthcare Safety Network (NHSN) Patient Safety Component Manual; 2018. [4] Ramritu P, Halton K, Cook D, et al. Catheter-related bloodstream infections in intensive care units: a systematic review with meta-analysis. J Adv Nurs 2008;62 (1):3–21. [5] Smith MJ. Catheter-related bloodstream infections in children. Am J Infect Control 2008;36(10):S173 e1–3. [6] Wylie MC, Graham DA, Potter-Bynoe G, et al. Risk factors for central line-associated bloodstream infection in pediatric intensive care units. Infect Control Hosp Epidemiol 2010;31(10):1049–56. [7] Parienti JJ, Mongardon N, Megarbane B, et al. Intravascular complications of central venous catheterization by insertion site. N Engl J Med 2015;373(13):1220–9. [8] Committee HICPA. In: Prevention CfDCa, editor. Guidelines for the prevention of intravascular catheter-related infections; 2011. [9] Goudie A, Dynan L, Brady PW, et al. Costs of venous thromboembolism, catheterassociated urinary tract infection, and pressure ulcer. Pediatrics 2015;136(3):432–9. [10] Mahajerin A, Croteau SE. Epidemiology and risk assessment of pediatric venous thromboembolism. Front Pediatr 2017;5:68. [11] Amankwah EK, Atchison CM, Arlikar S, et al. Risk factors for hospital-associated venous thromboembolism in the neonatal intensive care unit. Thromb Res 2014; 134(2):305–9. [12] Bonizzoli M, Batacchi S, Cianchi G, et al. Peripherally inserted central venous catheters and central venous catheters related thrombosis in post-critical patients. Intensive Care Med 2011;37(2):284–9. [13] Male C, Chait P, Andrew M, et al. Central venous line-related thrombosis in children: association with central venous line location and insertion technique. Blood 2003; 101(11):4273–8. [14] Saber W, Moua T, Williams EC, et al. Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies. J Thromb Haemost 2011;9(2):312–9. [15] Beck C, Dubois J, Grignon A, et al. Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study. J Pediatr 1998;133(2):237–41. [16] Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286(6):700–7. [17] Band J, Gaynes R. Intravascular catheter-related infection: Prevention. UpToDate Retrieved October 3, 2018, from https://www.uptodate.com/contents/intravascularcatheter-relatedinfectionprevention?search=clabsi%20prevention&source=search_ result&selectedTitle=1~94&usage_type=default&display_rank=1. [18] Centers for Disease C, Prevention. Vital signs: central line-associated blood stream infections–United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep 2011;60(8):243–8. [19] Parienti JJ, Thirion M, Megarbane B, et al. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial. JAMA 2008;299(20):2413–22.
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743 [20] Higgerson RA, Lawson KA, Christie LM, et al. Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 2011;12(6):628–34. [21] Tran M, Shein SL, Ji X, et al. Identification of a "VTE-rich" population in pediatrics – critically ill children with central venous catheters. Thromb Res 2018;161:73–7.
1743
[22] Arlikar SJ, Atchison CM, Amankwah EK, et al. Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery. Thromb Res 2015;136(4):717–22. [23] Lloyd NS, Douketis JD, Moinuddin I, et al. Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis. J Thromb Haemost 2008;6(3):405–14.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Central venous lines in critically ill children: Thrombosis but not infection is site dependent S. Christopher Derderian a,⁎, Ryan Good b, Raphael N. Vuille-dit-Bille a, Todd Carpenter b, Denis D. Bensard a,c a b c
Department of Pediatric Surgery, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO Department of Critical Care Medicine at Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO Department of Surgery, Denver Health Medical Center, Denver, CO
a r t i c l e
i n f o
Article history: Received 21 August 2018 Received in revised form 18 October 2018 Accepted 31 October 2018 Key words: Central line Central venous catheter CLABSI VTE Line infection Venous thromboembolism
a b s t r a c t Background: Central venous catheters (CVC) are vital to the management of critically ill children. Despite efforts to minimize complications, central line associated bloodstream infection (CLABSI) and venous thromboembolisms (VTE) still occur. Methods: We performed a retrospective review of a prospectively collected database for children admitted to the pediatric intensive care unit (PICU) between November 2013 and December 2016. Results: In total, 2714 CVC were in place, 979 of which were percutaneous CVC. During the study period, 21 CLABSI (1.6/1000 line days) were identified, of which, nearly half (n = 9, 42.9%) were associated with percutaneous CVC (2.6/1000 line days). Poisson regression analysis did not identify a single risk factor for CLABSI when adjusting for line type, anatomic location and laterality of placement, geographic location of placement, length of PICU admission, presence of gastrostomy tube, concurrent mechanical ventilation, age, weight, and height. Forty clinically significant VTE (2.9/1000 line days) were identified, with percutaneous CVC having the highest incidence (7.5/1000 line days, p b 0.001). Of percutaneous CVC, clinically significant VTE were more often associated with femoral vein cannulation (14.8/1000 line days) compared to internal jugular and subclavian vein (2.5 and 2.4/1000 line days, respectively, p b 0.001). Conclusion: This data suggests that the femoral site may be an important risk factor that should be considered in prevention strategies for catheter-associated VTE in children. Level of Evidence: III. © 2018 Elsevier Inc. All rights reserved.
Central venous catheters (CVC) remain an integral component to the management of critically ill children in the pediatric intensive care unit (PICU). The implementation of bundles and daily assessment of their need has abrogated line-associated complications; however, two commonly recognized sequelae resulting from CVC placement include central line associated bloodstream infections (CLABSI) and venous thromboembolisms (VTE) [1]. Prior to quality improvement initiatives, nearly 50% of adult patients admitted to the intensive care unit had a CVC at one point during their admission [2], but in recent years there has been a paradigm shift with an emphasis on minimizing CVC placement and the number of line days in an effort to reduce associated complications. These efforts have resulted in nearly a 50% reduction in the use of CVC in adults [3]. In pediatrics, the frequency of CLABSI associated with percutaneous CVC approximates 5 per 1000 line days, which is similar to the incidence
⁎ Corresponding author at: Children's Hospital Colorado, University of Colorado School of Medicine, 12631 E 17th Ave, C302, Aurora, CO 80045. Tel.: +1 720 777 6571 (Office). E-mail address: [email protected] (S.C. Derderian). https://doi.org/10.1016/j.jpedsurg.2018.10.109 0022-3468/© 2018 Elsevier Inc. All rights reserved.
found in adults [4,5]. Risk factors for CLABSI in children include indwelling duration, underlying non-operative cardiovascular disease or the presence of a gastrostomy tube, parenteral nutrition and blood transfusion [6]. Clinicians have little control over these risk factors; however, in adults, several studies suggest that cannulation of the subclavian vein over the internal jugular and femoral vein results in reduce CLABSI rates [4,7]. In children, however, the evidence for preferential subclavian vein access is limited [8]. Venous thromboembolism is another line-associated complication affecting morbidity, mortality, and hospital cost [9,10]. The reported incidence of CVC associated VTE is variable, ranging from 1.5 to 7.7 per 1000 line days [11,12]. In both children and adults, it has been observed in small series that femoral and subclavian vein CVC have a higher incidence of VTE than the internal jugular vein [13,14]. Whether catheter size and indwelling duration impact the incidence of VTE remains a point of contention [15,16]. Nevertheless, there is little data to support the anatomic location of a percutaneous CVC to minimize the risk of VTE. Given the paucity of data pertaining to complications associated with CVC in children admitted to the PICU, we sought to review our
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743
center's experience with CVC complications, specifically, we risk factors associated with CLABSI and VTE. 1. Methods We performed a retrospective review of all children between the age of 31 days and 17 years admitted to the PICU between November 2013 and December 2016 who had a CVC in place during their PICU admission. We defined CVC as a venous catheter that terminated within the superior or inferior vena cava or the right atrium of the heart. We excluded extracorporeal membrane oxygenation catheters. Line days equaled the difference between CVC placement and removal. If a line was placed while the child was in the PICU and remained in place upon PICU transfer, ‘line days’ was the number of days between placement and PICU transfer. If a child was admitted to the PICU with a CVC in place and it was removed, line days equaled the difference between PICU admission and line removal. If a child was admitted and transferred from the PICU with a line in place, line days equaled PICU length of stay. VTE was defined by evidence of catheter-associated thrombus based on Duplex ultrasonography. Ultrasounds were obtained for clinical suspicion of VTE and thus sub-clinical VTE were not included. Mechanical ventilation was considered a risk factor only if the time of mechanical ventilation overlapped with the time a CVC was in place. We analyzed prospectively collected data from Children's Hospital Colorado electronic medical record (EMR) system, quality improvement reports generated by Children's Hospital Colorado to track CLABSI and VTE, and Virtual Pediatric System (VPS) LLC. No endorsement or editorial restrictions of the interpretation of these data or opinions of the authors has been implied or stated. The charts of children with CLABSI or VTE were reviewed following approval from the Institutional Review Board at Children's Hospital Colorado (Approval # 17–1718). Details pertaining to each case were recorded and analyzed. Poisson regression was used to assess the relationship between CVC type and the number of CLABSI and VTE. The relationship between anatomic site and the number of CLABSI and VTE was also assessed among percutaneous central venous catheters. Regression models were further adjusted for geographic and anatomic location of placement as well as laterality, line duration, gender, age, weight, presence of a gastrostomy tube, and concurrent mechanical ventilation. A p-value of b 0.05 was considered statistically significant. Statistical analyses were performed using Stata 14 (College Park, TX). 2. Results Between November 2013 and December 2016, a total of 2714 lines were in place in patients admitted to the PICU. These included external tunneled catheters, percutaneous CVC, dialysis catheters, peripherally inserted central catheters (PICC), and ports (Table 1). Among children with percutaneous CVC, 408 (42%) were placed in the femoral vein, 385 (39%) in the internal jugular vein, and 186 (19%) in the subclavian vein. The total number of percutaneous CVC days was 3472 with a CLABSI rate of 2.6 per 1000 line days and clinically significant VTE rate of 7.5 per 1000 (Table 2).
1741
In total, 21 CLABSI (1.6/1000 line days) were identified during the study period, of which nine (42.9%) were in children with a percutaneous CVC (2.6/1000 line days); however, regression analysis demonstrated no statistically significant difference between type of line and CLABSI rate (Table 1). A variety of pathogens were responsible and included candida species (5), enterobacter (4), enterococcus (5), Escherichia coli (1), lactobacillus (1), neisseria (1), pseudomonas (3), staphylococcus (4), and stenotrophomas (1). Four cultures grew out polymicrobial organisms with a majority of these organisms coinciding with gastrointestinal flora bacteria. Using Poisson regression analysis adjusting for all confounding variables reported in the methods, we did not find independent risk factors associated with infection rate. The same was true when restricting the analysis to only percutaneous CVC. To account for diaper stool contamination of femoral CVC, we dividing the cohort into those younger than and those equal to or older than 3 years of age (the average age when American children grow out of diapers) and did not find a difference in CLABSI rate (p = 0.54). The median length of time between line insertion and CLABSI was 7.2 (IQR 4.3 and 14.5), at which point seven (33%) were removed. After selecting out percutaneous CVC, we found the incidence of CLABSI with femoral cannulation to be 4.2 per 1000 line days compared to internal jugular (1.7/1000 line days) and subclavian (1.2/1000 line days), but the difference did not reach statistical significance (Table 2). Forty clinically significant VTE (2.9/1000 line days) were identified over the study period. Ports had the lowest incidence at 0.7 per 1000 line days while percutaneous CVC had a 10-fold higher incidence at 7.5 per 1000 line days (p = 0.003). After adjusting for confounding variables reported in the methods, anatomic location was found to be a significant risk factor for clinically significant VTE (p = 0.001). The median time between CVC placement and clinically significant VTE was 5 (IQR 3 and 8.5) days. Eighteen (44%) were occlusive and one was associated with a clinically significant pulmonary embolus. When we selected out percutaneous CVC, femoral vein CVC accounted for 88% of clinically significant VTE with an incidence of 14.8 per 1000 line days compared to internal jugular and subclavian CVC (2.5 and 2.4 per 1000 line days, respectively, p b 0.001).
3. Discussion Our experience with CLABSI and VTE in the PICU is rare with rates of 1.6 per 1000 and 2.9 per 1000 line days, respectively, which is slightly lower than that reported in the literature [4,5,11]. We found that PICC lines are associated with the lowest rate of CLABSI and VTE and percutaneous CVC carry the highest rate of VTE. Among percutaneous CVC, anatomic location did not significantly impact CLABSI rate but did affect clinically significant VTE rate with nearly a 6-fold increase risk with femoral vein access compared to subclavian or internal jugular access. The reduced incidence of CLABSI and VTE is undoubtedly a reflection of “target zero” type measures including health care worker training, hand hygiene, ultrasound guidance, aseptic insertion techniques, catheter site care with a transparent dressing, and ethanol cleansing prior to access [17,18]. As a result, the number of catheter-associated complications is significantly reduced; however, when they do occur,
Table 1 Central venous catheter associated CLABSI and VTE. Type of Line
Total Number Placed
Line Days
CLABSI
CLABSI/1000 Line Days
P-value1
VTE
VTE/1000 Line Days
P-value1
External Tunneled Catheter Percutaneous CVC Dialysis Catheter PICC Port Combined
307 979 86 913 429 2714
1441 3472 491 5948 1527 12,879
4 9 0 5 3 21
2.8 2.6 0 0.8 2.0 1.6
0.261 0.108 0.999 0.049 0.731
1 26 2 10 1 40
0.7 7.5 4.1 1.7 0.7 2.9
0.116 b0.001 0.695 0.010 0.102
CVC: Central venous catheter; PICC: Peripherally inserted central catheter; CLABSI: Central line associated bloodstream infections; VTE: venous thromboembolism. 1 Poisson regression.
1742
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743
Table 2 Percutaneous central venous catheters associated CLABSI and VTE by anatomic site. Anatomic Site
Total Number Placed
Line Days
CLABSI
CLABSI/1000 Line Days
P-value1
VTE
VTE/1000 Line Days
P-value1
Femoral Vein Internal Jugular Vein Subclavian Vein Combined
408 385 186 979
1421 1211 840 3472
6 2 1 9
4.2 1.7 1.2 2.6
0.134 0.433 0.377
21 3 2 26
14.8 2.5 2.4 7.5
b0.001 0.021 0.068
CLABSI: Central line associated bloodstream infection; VTE: venous thromboembolism. 1 Poisson regression.
they can result in increased morbidity, mortality and health care dollars. Thus, measures to reduce complications further are warranted. Extrapolating data from the adult literature, we expected to find a higher rate of CLABSI associated with percutaneous CVCs placed within the femoral vein. Presumably, the increased incidence of CLABSI with femoral vein cannulation in adults is related to CVC colonization by skin flora. In an adult randomized control trial by Parienti et al., dialysis catheters placed within the femoral vein were only found to have a higher CLABSI rate than internal jugular catheterization among patients with a high body mass index [19]. As children rarely have redundant skin folds in the groin, it is theoretically easier to maintain cleanliness with the use of CVC bundles. Compared to the general pediatric population, PICU patients are at a higher risk of developing VTE, particularly those with a CVC [20,21]. Multiple variables may influence the risk of VTE and include hypercoagulable states, often seen in children with burns and malignancy, age, weight, catheter size, length of stay greater than 3 days, and significant infection but these variables have not been well studied in the PICU population [22]. Venous thromboembolism chemoprophylaxis decreases the risk of asymptomatic VTE in adults who are at risk for line associated VTE [23]. Some institutions, including ours, advocate a scoring system to stratify those at high risk for VTE who may benefit form VTE prophylaxis but the benefit is yet to be validated [22]. It is also unclear if the anatomic site of CVC insertion is a risk factor for VTE. We found that clinically significant VTE were more frequently associated with percutaneous CVC compared to other line types, and that among percutaneous CVC, femoral vein CVC had the highest frequency of clinically significant VTE with a 6-fold increase compared to subclavian and internal jugular vein. This observation may be a reflection of increased collateralization around the subclavian and internal jugular veins compared to the femoral vein and consequently we may be missing occult VTE. Alternatively, proximity to the heart and a larger catheter-to-vessel ratio may affect VTE rate but we were unable to account for these variables due to infrequent abdominal radiographs to assess femoral CVC positioning and inconsistent catheter size recordings. We did not find any other risk factors associated with VTE in our study group. It has been reported that among children admitted to the PICU, independent risk factors for VTE include age less than 1 year of age, mechanical ventilation, cardiac catheterization, and percutaneous CVC placement [21]. Given our low incidence of CVC related CLABSI and VTE, it is feasible that our sample size was not large enough to identify other risk factors. There are limitations to this study. As our practice is to only obtain Duplex ultrasonography for patients with a clinical suspicion for a VTE, it is likely that sub-clinical VTE were not identified. Nevertheless, we believe that symptomatic VTE are more relevant to clinical practice and therefore worthy of reporting. Additionally, VTE may be more common in younger children with a lower vessel to catheter size ratio but as we did not have consistent catheter size recordings to reliably assess this risk and it remains a question worth further research. In summary, we found that among children with percutaneous CVC in place during their PICU admission, femoral cannulation was associated with an increased frequency of VTE but not CLABSI. This data suggests that femoral cannulation may be an independent risk factor
for catheter-associated VTE in children. Furthermore, PICC lines were found to have the lowest incidence of CLABSI and VTE and may be the line of choice if time permits for placement. CRediT authorship contribution statement S. Christopher Derderian: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. Ryan Good: Conceptualization, Data curation. Raphael N. Vuille-dit-Bille: Formal analysis, Writing – original draft. Todd Carpenter: Conceptualization, Data curation, Writing – review & editing. Denis D. Bensard: Formal analysis, Writing – original draft, Writing – review & editing. References [1] Edwards JD, Herzig CT, Liu H, et al. Central line-associated blood stream infections in pediatric intensive care units: longitudinal trends and compliance with bundle strategies. Am J Infect Control 2015;43(5):489–93. [2] Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000;132(5):391–402. [3] Prevention CfDCa. Bloodstream infection event (central line-associated bloodstream infection and non-central line associated bloodstream infection). National Healthcare Safety Network (NHSN) Patient Safety Component Manual; 2018. [4] Ramritu P, Halton K, Cook D, et al. Catheter-related bloodstream infections in intensive care units: a systematic review with meta-analysis. J Adv Nurs 2008;62 (1):3–21. [5] Smith MJ. Catheter-related bloodstream infections in children. Am J Infect Control 2008;36(10):S173 e1–3. [6] Wylie MC, Graham DA, Potter-Bynoe G, et al. Risk factors for central line-associated bloodstream infection in pediatric intensive care units. Infect Control Hosp Epidemiol 2010;31(10):1049–56. [7] Parienti JJ, Mongardon N, Megarbane B, et al. Intravascular complications of central venous catheterization by insertion site. N Engl J Med 2015;373(13):1220–9. [8] Committee HICPA. In: Prevention CfDCa, editor. Guidelines for the prevention of intravascular catheter-related infections; 2011. [9] Goudie A, Dynan L, Brady PW, et al. Costs of venous thromboembolism, catheterassociated urinary tract infection, and pressure ulcer. Pediatrics 2015;136(3):432–9. [10] Mahajerin A, Croteau SE. Epidemiology and risk assessment of pediatric venous thromboembolism. Front Pediatr 2017;5:68. [11] Amankwah EK, Atchison CM, Arlikar S, et al. Risk factors for hospital-associated venous thromboembolism in the neonatal intensive care unit. Thromb Res 2014; 134(2):305–9. [12] Bonizzoli M, Batacchi S, Cianchi G, et al. Peripherally inserted central venous catheters and central venous catheters related thrombosis in post-critical patients. Intensive Care Med 2011;37(2):284–9. [13] Male C, Chait P, Andrew M, et al. Central venous line-related thrombosis in children: association with central venous line location and insertion technique. Blood 2003; 101(11):4273–8. [14] Saber W, Moua T, Williams EC, et al. Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies. J Thromb Haemost 2011;9(2):312–9. [15] Beck C, Dubois J, Grignon A, et al. Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study. J Pediatr 1998;133(2):237–41. [16] Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286(6):700–7. [17] Band J, Gaynes R. Intravascular catheter-related infection: Prevention. UpToDate Retrieved October 3, 2018, from https://www.uptodate.com/contents/intravascularcatheter-relatedinfectionprevention?search=clabsi%20prevention&source=search_ result&selectedTitle=1~94&usage_type=default&display_rank=1. [18] Centers for Disease C, Prevention. Vital signs: central line-associated blood stream infections–United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep 2011;60(8):243–8. [19] Parienti JJ, Thirion M, Megarbane B, et al. Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial. JAMA 2008;299(20):2413–22.
S.C. Derderian et al. / Journal of Pediatric Surgery 54 (2019) 1740–1743 [20] Higgerson RA, Lawson KA, Christie LM, et al. Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 2011;12(6):628–34. [21] Tran M, Shein SL, Ji X, et al. Identification of a "VTE-rich" population in pediatrics – critically ill children with central venous catheters. Thromb Res 2018;161:73–7.
1743
[22] Arlikar SJ, Atchison CM, Amankwah EK, et al. Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery. Thromb Res 2015;136(4):717–22. [23] Lloyd NS, Douketis JD, Moinuddin I, et al. Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis. J Thromb Haemost 2008;6(3):405–14.