Ultrasound assessment of thrombotic complications in pediatric patients with tunneled central venous catheters.

Central venous access consists in inserting a vascular catheter to the vena cava and placing its tip in the vicinity of the opening to the right atrium. In the patients of the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdańsk, such implantation procedures are conducted 40-50 times in a year using Broviac/Hickman catheters that are placed in the subclavian vein. In the Ultrasound and Biopsy Laboratory at the clinic mentioned above, approximately 200-250 examinations have been conducted since 2005 to assess the central venous access. Implantation of a catheter considerably increases the comfort of patients who require a long-term venous access. Nevertheless, it is an invasive procedure, burdened with a risk of numerous, early and late complications. The late complications are associated with implanted catheters and include catheter-related thrombosis. The aim of this paper was to present three patients of the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdańsk, in whom thrombotic complications occurred as a result of long-term central venous catheters. The paper also discusses the possibilities of using sonography in the assessment of such complications. In the presented patients, it was possible to determine the size and localization of a thrombus which enabled effective treatment in two cases. The pathomechanism of catheter-related thrombosis was explained and the risk factors of such complications were discussed. The attention was paid to the necessity of conducting ultrasound examinations in pediatric patients with inserted catheters as soon as the first symptoms of thrombosis appear. Based on own observations and despite the lack of validation of ultrasound imaging in the assessment of central catheters, we believe that this method is highly promising and can be recommended for the assessment of thrombotic complications in pediatric patients with central venous catheters.

Introduction

Central venous access consists in inserting a vascular catheter to the vena cava (usually the superior one) so as to place its tip in the vicinity of the opening to the right atrium. Depending on the manner of insertion and the placement of the peripheral part of the catheter, the following types are distinguished:

non-tunneled catheters – introduced directly to the vein (for short-term usage);

tunneled catheters – partially introduced in a tunnel created in the subcutaneous tissue of the chest wall, Broviac/ Hickman types (fig. 1).

Fig. 1

Patient after central venous catheter placement (biluminal Broviac/Hickman catheter). A dashed line marks the fragment of the catheter which runs in the subcutaneous tunnel

implanted ports – consist of a catheter and the main part of the port which is placed subcutaneously(.

In the patients of the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdańsk, such implantation procedures are conducted 40–50 times in a year using Broviac/Hickman catheters that are placed in the subclavian vein (left or right).

Insertion of a central catheter considerably increases the comfort of patients who require a long-term venous access. Initially, in the 1970s, catheters were used in patients fed parenterally. At present, they are usually used in hematooncological patients as well as in surgery and intensive care. The indications for a central venous access in pediatric patients from hematology and oncology departments include: the necessity to administer chemotherapy, anticipated long-term fluid therapy, parenteral nutrition, administration of agents with high osmolarity and frequent blood draws(.

Central catheter implantation is an invasive procedure, burdened with a risk of numerous, early and late complications. The early complications are direct consequences of cannulation itself: e.g. subcutaneous hematoma, subcutaneous emphysema, pneumothorax, air embolism, arrhythmias, damage to the thoracic duct, brachial plexus, the vessel's wall or cardiac wall (tamponade) and mediastinal bleeding. The late complications are associated with implanted catheters and include mechanical complications such as: accidental removal of the catheter, spontaneous retraction of the catheter, catheter fracture or translocation of its tip as well as infections and thrombotic complications(.

Initially, the procedure of catheter implantation and the assessment of complications were conducted with the use of X-ray techniques (conventional chest X-ray, venography). The application of sonography (US) in the assessment of central venous catheters initially concerned the localization of the catheter in the venous system(. In the subsequent years, as the technical possibilities developed and the method became more common, the range of its application became wider. Currently, it is used both in the initial assessment of the venous return anatomy and during catheter implantation as well as in the assessment of early and late complications(. In the Ultrasound and Biopsy Laboratory at the Clinic of Pediatrics, Hematology and Oncology at the Academic Clinical Centre of the Medical University in Gdańsk, approximately 200–250 US examinations have been conducted since 2005 to assess the central venous access.

The aim of this paper was to present three patients, in whom thrombotic complications occurred as a result of long-term indwelling central venous catheters and to present the possibilities of sonography in the assessment of such consequences and in treatment monitoring.

Examination technique

The examinations were conducted with the use of the Logiq 7 ultrasound system (GE Medical Systems, Waukesha, WI, USA, produced in 2005) with the following transducers: 7 S sector probe (4.0–8.0 MHz), 3 S sector probe (2.8–3.8 MHz), convex probe (2.0–5.5 MHz) and M12 linear probe (7–14 MHz), as well as with the use of the SPARQ system (Philips Healthcare, Bothell, WA, USA, produced in 2012) with sector (2.0–4.0 MHz), convex (2.0–5.5 MHz) and linear probes (4.0–12.0 MHz). The examinations were performed in two-dimensional as well as color Doppler modes and a “contrast” agent in the form of a 0.9% NaCl solution was used(. The basic projection for the assessment of the central catheter was the suprasternal one (fig. 2).

Fig. 2

Suprasternal examination with a convex probe

Case reports

Case 1

A 7-year-old patient with acute lymphoblastic leukemia. On the 5th day of the therapy, a central venous catheter (VYGON, Lifecath Biflux 7F) was implanted in the right subclavian vein. Due to infection (Empedobacter brevis, Enterobacter agglomerans, Pseudomonas sp.), a properly working catheter was removed in the 8th month of chemotherapy (II protocol according to the ALLIC 2002 regimen). The second central catheter (VYGON, Lifecath Biflux 7F) was inserted to the left subclavian vein. On the 19th day following the implantation, difficulty in drawing blood appeared but it was still possible to administer fluids through both openings of the catheter. A 2D US examination in the suprasternal view conducted with the use of a sector probe demonstrated a fragment of the catheter in the left brachiocephalic vein and a mural thrombus with the size of 11.7 × 7.4 mm in the right brachiocephalic vein (fig. 3). Subsequently, a color Doppler examination was conducted with the use of a convex probe in the same projection (fig. 4). A clear outline of the thrombus located opposite to the implanted catheter was obtained. Additionally, it was possible to assess the degree to which the right brachiocephalic vein was narrowed. The 2D examination conducted with the sector probe revealed a fragment of the catheter in the left brachiocephalic vein. For more accurate localization of its tip, a US examination with prior intravenous administration of 0.9% NaCl solution was conducted (figs. 5, 6). In a subsequent examination performed on the first day after the 24-hour infusion with Actylise, a reduction in the size of the thrombus was observed. The treatment with low-molecular-weight heparin was initiated which resulted in restoring complete patency of the vein. The maintenance therapy with heparin was continued until the removal of the catheter after the completed chemotherapy.

Fig. 3

Case 1. Suprasternal view. 2D examination conducted with a sector probe. Asterisk – a mural thrombus with the size of 11.7 × 7.4 mm in the right brachiocephalic vein. A fragment of the catheter (arrow head) is visible in the left brachiocephalic vein

Fig. 4

Case 1. Suprasternal view. Color Doppler examination with a convex probe. S – the thrombus in the right brachiocephalic vein; SVC – superior vena cava

Fig. 5

Case 1. Suprasternal view. 2D examination with a sector probe following contrast administration (a bolus of 0.9% NaCl solution). The catheter (arrow head) is visible in the left brachiocephalic vein. Triangles mark a contrast-enhanced tip of the catheter

Fig. 6

Case 1. Diagram presenting the pathogenesis of thrombus formation resulting from endothelial damage of the vein located opposite to the catheter

Case 2

A 12-year-old patient with non-Hodgkin lymphoma. On the 7th day of the patient's stay in hospital, a central venous catheter (VYGON, Lifecath Biflux 7F) was implanted in the right subclavian vein. Following 4 weeks of chemotherapy (BFM 04 III), a properly working catheter was removed due to infection (coagulase-negative Staphylococcus). The second central catheter (VYGON, Lifecath Biflux 7F) was inserted to the left subclavian vein. In the 7th week following the implantation, difficulty in drawing blood and administering fluids through both openings appeared. A suprasternal US examination with a sector probe was conducted and revealed a thrombus in the left brachiocephalic vein localized in the region of the catheter's tip. The thrombus occluded the vessel's lumen nearly completely. A color Doppler examination revealed peripheral flow in two narrow streams (fig. 7). In a suprasternal examination with a convex probe aiming to examine the left brachiocephalic vein, an outline of the thrombus with the size of 27 × 8 mm was visualized (figs. 8, 9). Actylise was started and in a follow-up US examination performed on the first day following a 24-hour infusion, complete patency of the vein was observed. Subsequently, low-molecular-weight heparin was administered in a prophylactic dose and such a treatment was continued until the catheter was removed after the completed chemotherapy.

Fig. 7

Case 2. Suprasternal view. Color Doppler examination with the use of a convex probe. Two narrow peripheral streams of blood flow are detected. A thrombus is seen in the region of the catheter's tip (triangle)

Fig. 8

Case 2. Suprasternal view. Color Doppler examination with the use of a convex probe. Measurement of the thrombus in the left brachiocephalic vein – 26.9 × 8.0 mm

Fig. 9

Case 2. Diagram illustrating the localization of the thrombus around the catheter's tip

Case 3

A 7-year-old patient with an inoperative tumor of the central nervous system, treated palliatively at home. The difficulty in drawing blood with continued possibility to administer fluids through one of the catheter's openings (VYGON, Lifecath Biflux 7F) was an indication for a US examination. In suprasternal examinations performed with sector and convex probes, no blood flow was observed in the left brachiocephalic vein due to a complete obstruction caused by a thrombus. Moreover, with the help of a linear probe, an image of an extensive thrombus in the internal jugular vein was obtained (with the size of 9.0 × 5.9 mm, in a transverse plane) which occluded the vein nearly completely (figs. 10, 11). In order to restore patency, the continuous treatment with low-molecular-weight heparin was initiated. The patient died 2 months later due to the progression of the neoplastic disease.

Fig. 10

Case 3. 2D examination conducted with a linear probe in a transverse view of the left internal jugular vein. A thrombus (asterisk) with the size of 9.0 × 5.9 mm nearly completely occludes the vein

Fig. 11

Case 3. Color Doppler examination conducted with a linear probe in a longitudinal view of the left internal jugular vein. The thrombus (asterisks) occludes the vein nearly completely; blood flow is detectable only on its periphery

Discussion

Central venous catheter thrombosis (catheter-related thrombosis) is a formation of a blood clot in the region of the catheter's tip, which partially or completely occludes the vein(. The incidence of thrombotic events in pediatric patients amounts to 50%(. A thrombus is formed in several phases: first of all, a fibrin sheath forms around the tip of the catheter. Such a pericatheter thrombus may result in its partial occlusion in the valve mechanism – administration of medicines or fluids is possible, but blood withdrawal is not. Subsequently, the thrombus partially occludes the vein along its wall (mural thrombosis) and then blocks blood flow completely (venous thrombosis)(. As a consequence, progressing venous thrombosis may encompass e.g. the internal jugular vein – as it happened in the patient 3.

The pathogenesis of catheter-related thrombosis is complex. The damage to the vascular endothelium resulting from mechanical injury is believed to be the prime cause. In the case 1 presented above, the thrombus was found in the vein opposite to the catheter inserted, which suggests such a mechanism of its formation. Another important factor predisposing to catheter-related thrombus formation is a concomitant infection. In two patients presented above, in whom thrombosis appeared after the implantation of the second catheter, the first one had been removed due to infection. Other risk factors are: use of cytostatic agents (L-asparaginase), steroids and antibiotics as well as parenteral nutrition and positive family history of coagulation disorders (thrombophilia)(.

Thrombosis of the superior vena cava drainage may be manifested with the following symptoms: edema of the face and upper part of the body, reddening, cyanosis, pain in the upper extremity at the side of the catheter and dilation of the superficial veins. Pediatric patients, however, rarely manifest all symptoms of such complications (2% according to Fratino(). This causes delayed diagnosis and progression of thrombosis. Therefore, it is recommended to conduct regular ultrasound check-up examinations of the venous return in pediatric patients with a central catheter. The first examination is conducted at the patient's bedside several hours after catheter implantation. Such a strategy is in line with one of the new directions of ultrasound imaging, i.e. bedside ultrasound imaging. Such examinations are performed according to a specified model and their aim is to provide quick explanations to given clinical problems (point of care ultrasound). Following catheter implantation, a CVC sono model may be applied. It was created by Matsushima in 2010(. According to the model, the following steps should be taken: C – excluding mechanical complications, such as pneumothorax and hemothorax (mechanical complication screen); V – assessment of the intravenous placement of the catheter's tip (intravenous tip screen); and C – assessment of the intracardiac placement of the catheter's tip (intracardiac tip screen). In the case of any doubts concerning the catheter, further examinations are conducted immediately. Usually, one-way loss of patency, i.e. difficulty in drawing blood with continued possibility to administer fluids, is the first alarming sign. Such a situation may result from improper placement of the catheter's tip which adheres to the vein's wall. In such a situation, changing the body position (positioning the patient in the supine or lateral positions), deeper respiration or the Valsalva manoeuvre are sufficient to restore patency. The aim of these actions is to dilate the venous vessel and to place the catheter's tip in a right position in relation to the vein's wall. Unfortunately, one-way loss of patency may also indicate the initial stage of a thrombotic complication, e.g. a slight clot in the region of the catheter's tip which acts as a valve – it opens the catheter during fluid administration but closes it during blood withdrawal. Such a phenomenon was observed in two patients presented above.

Sonography has been used for the assessment of thrombotic complications in patients with central catheters for many years( but so far, the genuine value of this method has not been determined. The reports of various authors are ambiguous. Gatini claims that sensitivity of color Doppler sonography in the diagnosis of upper limb thrombosis ranges from 78% to 100% and specificity – from 82% to 100%(. However, in Male's study of pediatric patients with leukemia, the level of sensitivity in detecting thrombosis of the subclavian vein was only 37%(. On the one hand, the accessibility and non-invasiveness of sonography are emphasized, on the other, attention is drawn to the possibility of obtaining false negative images in the case of small thrombi(. The majority of authors agree that venography is the gold standard in catheter-related thrombosis and sonography is given the role of a screening examination(.

In our ultrasound laboratory, US examinations with the use of various types of transducers (sector, convex and linear) and various techniques (2D, color Doppler) as well as with the administration of a 0.9% NaCl solution have been the basis of assessment in catheter dysfunctions for 8 years.

Conclusions

Despite the lack of validation for ultrasound imaging in the assessment of central catheters, it is a highly promising method and can be recommended for the assessment of thrombotic complications in pediatric patients with central venous catheters.