Objective Arterial thrombosis is one of the most reported complications of cardiac catheterisation (CC) in children. The aim of the study was to evaluate the incidence and predictors of arterial thrombosis in children with cardiac diseases (CDs).
Methods During 12 consecutive months, all children aged 0–19 years undergoing CC of the femoral arteries were included in this observational study. After CC, clinical evaluation of impaired limb perfusion was performed according to local guidelines. Doppler ultrasonography was performed when decreased limb perfusion was suspected.
Results 123 children (30% aged <12 months, 70% aged >12 months) underwent CC. Arterial thrombosis occurred in 14 of the 123 children (11.4%). Twelve cases (12/14=86%) of arterial thrombosis occurred in infants aged <12 months and 2 (2/14=14%) in older children. Overall younger age (p<0.01, OR (95% CI) 0.49 (0.28 to 0.86)) and low body weight (p<0.004, OR (95% CI) 0.78 (0.65 to 0.92)) were significantly associated with an increased risk of arterial thrombosis. Cyanotic CD (p=0.07, OR (95% CI) 2.87 (0.90 to 9.15)) showed a trend towards increased thrombotic risk.
Conclusions Arterial thrombosis is a common complication of CC in infants. Diagnosis of CC-related arterial thrombosis remains a challenge. Well-defined clinical monitoring protocols may be valuable methods for timely detection and treatment of arterial thrombosis.
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Cardiac catheterisation (CC) has become a relevant procedure for the diagnosis and for the treatment of several congenital or acquired cardiac diseases (CDs) in children. Avoiding the need for cardiac surgery with long recovery time, congenital atrial or ventricular septal defects can be closed nowadays with devices that are delivered through the cardiac catheter.1 Similarly, congenital obstructed blood vessels and valves can be opened with balloon or stent technology or even replaced by transcatheter valve placement such as the Melody pulmonary valve.2
Although increasing evidence suggests a substantial decrease in procedural-related complications during the past years, arterial thrombosis remains one of the most reported complications of CC in children.3–6 Short-term complications of arterial thrombosis of the femoral arteries may cause skin necrosis and threaten limb viability.7 Despite the lack of long-term outcome data, late complications including leg length difference and claudication have been postulated. It is quite evident that thrombotic occlusion of femoral arteries in children with complex CD may complicate future CCs. Thus, each single CC-related arterial thrombotic complication in these children demands special attention.
The reported incidence of arterial thrombosis after CC varies between 1% and 33%.4–6 ,8–32 This wide difference reflects different study designs and inclusion criteria and the fact that no guidelines for the diagnosis of these thrombotic complications are available, so far. The aim of this observational study was to evaluate the incidence of CC-related arterial thrombosis, to define predictors of these thrombotic complications in children with CD and to provide a broad, critical comparison of the literature.
During 12 consecutive months, all children aged 0–19 years undergoing CC through the femoral arteries for diagnostic or interventional purposes at the University Children's Hospital Zurich were included in this observational study. The catheterisation laboratory at our institution is the largest in Switzerland and performs all procedures currently used to treat children with congenital or acquired CD.
Children undergoing CC are admitted to the hospital 1 day prior to the procedure. At this time, a medical history and clinical examination including vital signs, palpable pulses and Doppler blood pressure measurement of all four extremities are undertaken. CC is performed under full anaesthesia. After arterial puncture, unfractionated heparin (UFH) at a bolus dose of 100 IU/kg is administered intravenously and repeated at a dose of 50 IU/kg after 1 h. Monitoring of anticoagulation is performed every 30 min using the activated clotting time targeting 250 s (Medtronic ACT Plus, Medtronic AG, Münchenbuchsee, Switzerland). Directly after CC, children receive enoxaparin subcutaneously at a dose of 1.5 and 1.0 mg/kg every 12 h in children aged less and more than 2 months, respectively. Administration of enoxaparin is continued for 24 h in children after diagnostic procedures and 48 h in children after interventional procedures. On the evening after interventional procedures, children also receive acetylsalicylic acid at a dose of 3–5 mg/kg/day for 3 or 6 months depending on the performed procedure. To decrease the risk of bleeding from the puncture site during anticoagulation, a compression bandage at the site of the arterial puncture is used in children >1 year. In neonates and infants, a taped low pressure bandage is used for at least 24 h after sheath removal. The pressure of the dressing is chosen in an individual manner that one can still feel an arterial pulse distally to the puncture site.
Clinical assessment after CC
During the first 6 h after CC, pedal pulses (dorsalis pedis and/or tibialis posterior artery) are palpated every hour. Thereafter, pulses are palpated every 8 h during 24 h. If pulses on the punctured leg are absent or weaker, as compared with the contralateral pulses, pulses are verified with Doppler. In this case, bilateral blood pressure measurement of the lower extremities is performed by Doppler method every hour to detect increasing blood pressure discrepancy. As soon as suspicious of decreased perfusion is detected even after removing of compression bandage, defined as cold and pale lower extremity, persistent decreased or absent palpable pedal pulses, persistent lack of signal with Doppler or Doppler blood pressure difference of the limbs of >20 mm Hg, Doppler ultrasonography is performed by a paediatric-experienced radiologist to exclude arterial thrombosis.
After diagnosis of arterial thrombosis, children are treated with low-molecular weight heparin or UFH until clinical and radiological resolution of thrombosis occurs and for a maximal duration of 3–4 weeks. In children with persistent thrombosis after 3–4 weeks therapy, heparin is changed to aspirin for 3–6 months.
Children are seen at follow-up 3 months after first diagnosis and then yearly. Follow-up visits include both clinical and ultrasound examinations. Clinical examination includes history of symptoms, such as pain, cool or pale limb, and claudication, palpation of femoral, popliteal and ankle pulses as well as Doppler-derived systolic blood pressure measurement of the upper (brachial) and lower extremities (ankle). In addition, leg circumference and length are measured.
Demographic data and information on CC for each child were collected at the time of the procedure using a predefined protocol. Data recorded included age and weight of patient at the time of procedure, haematocrit, type of CD (cyanotic, non-cyanotic) and CC (diagnostic, interventional), size of cardiac catheter sheath, number of puncture attempts, duration of CC and duration of compression bandage.
Data are presented as frequencies, mean and medians with ranges where appropriate. Significant differences between groups were assessed using Mann–Whitney and χ2 test as appropriate. To determine predictors of CC-related arterial thrombosis, multivariate logistic regression analyses were performed and results presented as ORs with their 95% CIs. Statistical significance was defined as p value of <0.05. Statistical analyses were performed using SPSS software (Statistical Package for the Social Sciences, V.18; SSPS, Chicago Illinois, USA).
During the 12-month study period, 123 children with CD underwent CC with cannulation of femoral arteries. Of these 123 children, 37 (30%) were infants aged <12 months and 86 (70%) were children aged >12 months. Depending on the interventional procedure, cannulation of a femoral vein was also needed and performed in a total of 87 (71%) children, of whom 32 (37%) were infants and 55 (63%) were older children. Characteristics of infants and older children and CC procedures are depicted in table 1. None of the patients required any kind of invasive interventions to restore blood supply for life-threatening limb.
Incidence and predictors of arterial thrombosis
Arterial thrombosis occurred in 14 of the 123 children reflecting an overall incidence of 11.4%. Of these 14 arterial thrombotic events, 12 occurred in infants and two in older children, reflecting a relative incidence of 32.4% and 2.3%, respectively (p<0.0001; table 1). When considering only patients aged ≤4 weeks, arterial thrombosis occurred in four of seven cases, reflecting a relative incidence of 57%.
Overall, younger age and low body weight were significantly associated with an increased risk of arterial thrombosis. When using logistic regression analyses in infants only, younger age was still significantly associated with an increased thrombotic risk. Although not statistically significant, a trend towards increased risk of thrombosis in children with cyanotic CD (p=0.07) was observed (table 2).
The results of this single centre study show that thrombosis of the femoral artery after CC in children is still a frequent postprocedural complication with an overall incidence of 11% in children aged 0–19 years and a relative incidence of 32% in infants aged <12 months.
Several previous studies have reported the incidence of arterial thrombosis after CC in children. These studies, summarised in table 3, show an incidence varying between 0% and 33%. Several reasons account for the wide range of incidence. First of all, available studies have different study designs. Independent on whether diagnosis was established clinically or radiologically, retrospective studies have reported a lower incidence (median 1.1%, range 0.32%–28%) than prospective studies (median, 8.7%, range 1%–33%; table 3). Several studies were focused on arterial thrombosis and on overall complications of CC.4 ,5 ,9 ,16 ,29 ,30 Other studies were designed to evaluate diagnostic tools to detect thrombosis or the effect of prophylactic administration of heparin to prevent arterial thrombosis or to evaluate the effect of different thrombolytic agents to dissolve arterial thrombosis after CC.8 ,10 ,12 ,13 ,18 ,19 ,21–23 ,25–28 ,32–34
Second, reported studies have used different inclusion criteria. Whether the study population includes infants and older children or even young adults will determine the incidence of arterial thrombosis. In line with previously reported data, our study clearly shows that arterial thrombosis after CC predominantly affects neonates and infants aged <12 months.4–6 ,9 ,11 ,21 ,25 ,26 ,31 An overall analysis of patients with a large range of age may therefore underestimate the incidence of thrombosis.4 ,8 ,10 ,12 ,15 ,18 ,20 ,21 ,23 ,26 ,33
Third, available studies have used different clinical and radiological diagnostic criteria to detect arterial thrombosis, which is a consequence of the lack of generally accepted guidelines for the diagnosis of this complication in children. Several studies have recommended the use of ultrasound screening after CC to detect arterial thrombosis.10 ,12 ,13 In the study by Hanslik et al,13 all included patients were screened with ultrasound after CC and the reported incidence was low (3%). This study has showed that of the six patients with arterial thrombosis, two had absent pulses defined as a clinical sign for arterial thrombosis, while the other four patients had weak pulses, defined as a non-clinical sign. The authors conclude that clinical examination only is insufficient to detect arterial thrombosis. In the study by Kocis et al,10 arterial thrombosis after CC was detected in 32% of infants. Of the seven infants with arterial thrombosis on ultrasound, only four had clinical signs of femoral artery compromise, which are not specified in the manuscript. A more recent, multicentre study has evaluated both clinical diagnosis and routine Doppler ultrasound for the diagnosis of CC-related arterial thrombosis in two groups of infants.12 In the first group, diagnosis of arterial thrombosis was made first clinically and subsequently confirmed by Doppler ultrasound. In this group, two (1.7%) of the four (3.4%) infants with clinical signs of arterial thrombosis had radiologically confirmed thrombosis. In the second group, Doppler ultrasound was performed as a routine procedure the day after CC independent of the presence or absence of clinical signs of arterial thrombosis. In this group, clinical signs of arterial thrombosis were present in four (7.4%) infants, whereas 10 (18.5%) infants showed arterial thrombosis on Doppler ultrasound. The authors conclude that Doppler ultrasound should be performed routinely the day after CC. In our opinion, these data have to be interpreted cautiously. Indeed, authors declared no randomisation of the patient groups and it is not evident, if the two groups were investigated parallel or serial. The fact that only 57 of the 171 patients had undergone routine Doppler ultrasound suggests major bias in the recruitment of patients. Although ultrasound was not performed routinely in our patients, using clearly defined clinical diagnostic criteria, the incidence of arterial thrombosis in our study was similar to the incidence reported by Kocis et al and significantly increased compared with the ones reported by Hanslik et al12 and Knirsch et al.1,3 As long as no validation data are available on the use of Doppler ultrasound as compared with angiography, which is still considered the gold standard for the diagnosis of arterial thrombosis, our data indicate that a well-defined and intensive clinical monitoring of children after CC can be considered a valuable diagnostic tool.
Fourth, available studies differ in the time point of diagnosis of arterial thrombosis after CC. Recovery of arterial pulses over time has been previously described and is possibly related to the process of angiogenesis.3 During this process, increased shear stress leads to remodelling of collateral vessels into larger vessels with increased blood transport capacity immediately after occlusion of a major artery.
These findings clearly suggest that a well-defined clinical diagnostic tool may be more sensitive than a routinely performed Doppler ultrasound the day after the CC, when remodelled vessels are possibly and, in our experience, often mistaken for the femoral artery in the case of small infants, depending on the experience of the radiologist. In addition, mobilisation of the patient, removal of compression bandage, resorption of the haematoma, thrombus resolution and/or remodelling of small dissection flaps may also contribute to the recovery of arterial pulses.
Finally, catheterisation techniques have changed over time. Originally, the arterial catheterisation in paediatric patients was performed by exposure and cutdown of the brachial or femoral artery.35 The incidence of arterial thrombotic complications of this technique may be possibly different from the one derived from the newest percutaneous technique. In addition, technique evolution has also included the use of antithrombotic prophylaxis with UFH. Whether the use of UFH can reduce arterial thrombosis in children after CC is still unclear.5 ,6 ,8 ,10 ,11–13 ,18–28 ,30 ,31 ,33 ,34
In the present study, younger age as well as low body weight and height were overall significant risk factors for developing arterial thrombosis after CC. Considering infants only aged <4 weeks and body weight <4 kg were still significantly associated with an increased thrombotic risk. These findings are in line with previous data.4–6 ,9 ,11 ,21 ,25 ,26 ,31 Because of the small vessel size, smaller and younger children are at higher risk for vascular injury. Often a vasospasm occurs after puncturing the small vessels increasing the risk for injuring the intima by the catheter movements which predispose for developing a thrombus. A trend towards increased thrombotic risk in children with cyanotic CD was also observed in our cohort and supports the results of Glatz et al31 In the study of Saxena et al,25 prolonged duration of procedure was also a significant risk factor. Vitiello et al5 and Kulkarni and Naidu8 could not confirm these results as neither could we.
In conclusion, arterial thrombosis is still a most common complication of CC affecting, in particular, newborns and infants with a small body weight. Diagnosis of CC-related arterial thrombosis remains a challenge and urgently requires further studies comparing timely and well-defined clinical monitoring protocols along with Doppler ultrasound guidelines.
What is already known on this subject?
Vascular complications are frequent in children after cardiac catheterisation (CC). Thrombotic occlusion of femoral arteries in children with complex cardiac disease cause short-term and long-term complications and may complicate future cardiac catheterisations.
What might this study add?
This study provides further information on the incidence and risk factors of arterial thrombosis in children with cardiac disease undergoing CC. Diagnosis of these arterial complications remains a challenge. Our study provides new insights on clinical diagnostic modality as compared with ultrasounds. Well-defined clinical monitoring protocols may be valuable methods for timely detection and treatment of arterial thrombosis.
How might this impact on clinical practice?
It is important to diagnose arterial thrombosis shortly after CC to start with heparinisation to restore blood flow in the affected vessel. Defined clinical monitoring protocols are helpful to diagnose arterial thrombosis timely after the procedure.
We dedicate this work to the memory of Professor Urs Bauersfeld who was a paediatric interventional cardiologist at our institution and prematurely passed away in October 2010.
Contributors BB: Coordinated data collection, drafted the initial manuscript and approved the final manuscript as submitted. MIH: Helped in data collection and critically reviewed the manuscript and approved the final manuscript as submitted. OK: Performed cardiac catheterisation of the included patients and critically reviewed the manuscript and approved the final manuscript as submitted. MR: Helped analysing data and critically reviewed the manuscript and approved the final manuscript as submitted. MA: Designed the study, supervised data collection, analysed data, reviewed and revised the manuscript and approved the final manuscript as submitted.
Competing interests None.
Ethics approval Research Ethics Boards of the University Children's Hospital Zurich.
Provenance and peer review Not commissioned; externally peer reviewed.
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