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Pediatr Blood Cancer 2008;50:826–830
Prevention and Management of Central Venous Catheter Occlusionand Thrombosis in Children With Cancer
Roderick Skinner, PhD, FRCPCH,1* Karin Koller, BSc, PhD,2 Nan McIntosh, RSCN,3
Anthony McCarthy, MB, FRCPCH,4 and Barry Pizer, PhD, FRCPCH5
INTRODUCTION
Central venous catheters (CVCs) provide reliable intravenous
access for blood sampling and administration of drugs, blood
products and parenteral nutrition in children undergoing treatment
for malignancy [1,2]. However, occlusion (CVC-occlusion) may
limits a CVC’s usefulness [3], whilst CVC-associated thrombosis
(CVC-thrombosis) may have serious consequences, including post-
thrombotic syndrome and potentially fatal thromboembolic events
[4–6]. The optimum strategies to diagnose, prevent and treat CVC-
occlusion and CVC-thrombosis/thromboembolism are not known
[4,6], so this survey was performed to document the views and
clinical practice of United Kingdom Children’s Cancer Study Group
(UKCCSG) centres. The intention was to determine the extent of
variation in practice and to stimulate both further research into the
reasons for this, as well as to promote the future development of
clinical practice guidelines.
METHODS
A questionnaire was sent to all 22 UKCCSG centres in 2001
concerning the centres’ opinions about the importance of CVC-
occlusion and CVC-thrombosis/thromboembolism, and their clin-
ical practices regarding prophylaxis, diagnosis and treatment.
The following definitions were used:
. CVC—any tunnelled cuffed catheter or implantable subcuta-
neous vascular port.
. CVC-occlusion (partial)—inability to sample from a CVC
lumen that nevertheless flushes satisfactorily.
. CVC-occlusion (total)—inability to sample blood from and
flush CVC lumen.
. CVC-thrombosis—clinical or imaging evidence of CVC-related
venous thrombosis.
. CVC-thromboembolism—pulmonary embolism, intracardiac
thrombosis, superior vena cava thrombosis, any other venous
thromboembolic event.
. ‘‘Positional’’ difficulty (blood can be sampled, or the lumen
flushed, only in certain positions) was not defined as CVC-
occlusion.
. Persistent ‘‘stiffness’’ in sampling/flushing was defined as partial
CVC-occlusion.
Relevant clinical features of CVC-thrombosis/thromboembo-
lism were suggested, detailed lists of possible investigations and
treatments provided and categorised responses requested. Centres
were asked whether they always, usually (�50% of episodes),
sometimes (<50% episodes) or never employed particular inves-
tigations or treatments. A Chi-squared test was used to compare the
numbers of centres inserting �101 or �100 CVCs per year that
always/usually investigated with the number that sometimes/never
investigated partial CVC-occlusion. Too few centres sometimes/
Background. The views and clinical practice of children’s cancerunits were surveyed regarding management of central venouscatheter (CVC) occlusion (CVC-occlusion), CVC-related thrombosis(CVC-thrombosis) and thromboembolism (CVC-thromboembolism).Procedure. A questionnaire was sent to all 22 United KingdomChildren’s Cancer Study Group centres, requesting informationabout their views of the importance of, and their practices regarding,prophylaxis, diagnosis and treatment of CVC-occlusion/thrombosis.Results. Twenty (91%) centres responded. Eighty percent, 80% and70%, respectively, stated that CVC-occlusion, CVC-thrombosis andCVC-thromboembolism were clinically important concerns. Allcentres used heparinised saline flushes as prophylaxis against CVC-occlusion, with little variation (�30% centres) in frequency, volumeand heparin concentration. Symptoms or signs suggesting partialCVC-occlusion, total CVC-occlusion, or CVC-thrombosis/throm-boembolism were always investigated in 20%, 55% and 85% ofcentres, respectively, but with considerable variability in the nature
and sequence of investigations performed, which included (depend-ing on the clinical scenario) chest X-ray, contrast linography orvenography, ultrasonography, echocardiography and magneticresonance venography. A fibrinolytic lock was administered beforeinvestigation of CVC-occlusion in 75% of centres. Although 45%,60% and 80%, respectively, always treated partial CVC-occlusion,total CVC-occlusion or CVC-thrombosis/thromboembolism, the typeand order of treatments differed greatly between centres, especiallyfor CVC-thrombosis/thromboembolism, in which CVC removal,systemic anticoagulation (heparin or warfarin), local or systemicfibrinolysis, or thrombectomy were performed in at least somecentres. Conclusions. The clinical practice of UKCCSG centresregarding prevention, investigation and treatment of CVC-occlusion/thrombosis varies greatly. Additional trials should facilitate develop-ment of evidence-based guidelines. Pediatr Blood Cancer 2008;50:826–830. � 2007 Wiley-Liss, Inc.
Key words: cancer; central venous catheter; children; occlusion; thromboembolism; thrombosis
� 2007 Wiley-Liss, Inc.DOI 10.1002/pbc.21332
——————This article contains Supplementary Material available at http://www.
interscience.wiley.com/jpages/1545-5009/suppmat.
1Royal Victoria Infirmary, Newcastle upon Tyne, UK; 2UKCCSG Data
Centre, Leicester, UK; 3Royal Hospital for Sick Children, Glasgow,
UK; 4Royal Hospital for Sick Children, Belfast, UK; 5Royal Liverpool
Children’s Hospital, Liverpool, UK
On behalf of the United Kingdom Children’s Cancer Study Group
(UKCCSG)/Paediatric Oncology Nursing Forum (PONF) Supportive
Care Group.
*Correspondence to: Roderick Skinner, Department of Paediatric and
Adolescent Oncology, Paediatric Oncology Day Unit, Royal Victoria
Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust,
Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.
E-mail: [email protected]
Received 31 January 2007; Accepted 6 July 2007
never investigated or treated the other clinical scenarios to permit
statistical analysis.
RESULTS
Twenty centres (91%) responded. Results are expressed as
percentages (of responding centres), unless stated otherwise. The
questionnaire was completed by at least one consultant (paediatric
oncologist, haematologist, surgeon) in 75% centres, in collaboration
with a senior nurse (ward sister, clinical nurse specialist) in 20%,
and by at least one senior nurse in 25%. Medical and nursing staff
both contributed in 35% centres. Ten percent of centres inserted
>200 CVCs per year, 20% inserted 101–200, 55% inserted 51–100,
10% inserted 26–50 and only 5% placed �25.
Importance of CVC-Occlusion, CVC-Thrombosisor CVC-Thromboembolism
Most centres considered these complications to be clinically
important or major concerns (Table I). However, only two centres
(10%) had experienced any deaths (one each from cerebral sagittal
venous thrombosis and pulmonary embolism) due to CVC-
thrombosis/thromboembolism during the previous 5 years.
Written Protocols for Prevention,Investigation and Treatment
Although 80% of centres had a written protocol for prevention of
CVC-occlusion, only 40% had one for investigation and 55% for
treatment. 45%, 20% and 25% of centres had protocols for
prevention, investigation and treatment of CVC-thrombosis, whilst
20%, 15% and 10% had protocols for prevention, investigation and
treatment of CVC-thromboembolism.
Prophylaxis
Tunnelled external CVCs. Eighty-five percent of centres
flushed tunnelled external CVCs weekly, and 15% twice weekly.
All centres used heparinised saline flushes, most commonly 5 ml
(70% centres) of 10 U/ml solution (90%). A minority used different
volumes (range 2–15 ml) or heparin concentrations (1–100 U/ml).
Some centres varied flush frequency, volume or type according to
CVC type (25%), size (20%) or number of lumens (30%).
Subcutaneous vascular ports. Seventeen centres used sub-
cutaneous vascular ports, with the flush interval ranging from
fortnightly (6%) to monthly (82%), using 2–6 (71%) to 10–15 ml
(24%) of heparinised saline (100 U/ml in 88%, 10 U/ml in 12%).
Few centres varied the flush frequency, volume or type according to
the port type (6%) or size (18%).
Other methods of prophylaxis. Twenty-five percent of centres
used systemic low molecular weight (LMW) heparin and 15% low
dose warfarin in selected high-risk patients.
Diagnosis
Twenty percent centres always, 25% usually and 50% sometimes
investigated partial CVC-occlusion. The corresponding figures
were 55%, 35% and 10% for total CVC-occlusion. Eighty-five
percent centres always and 10% usually investigated patients with
clinical features of CVC-thrombosis or CVC-thromboembolism
(Table II). One centre never investigated partial CVC-occlusion, but
no centre stated that it never investigated the other three clinical
scenarios. The responses do not add up to 100% for CVC-
thrombosis or CVC-thromboembolism since one centre reported
no experience of these complications. Whether a centre always/
usually or sometimes/never investigated partial CVC-occlusion was
not related to the number of CVCs the centre inserted per year
(P¼ 0.1).
Only 15% of centres had a protocol that defined a specific
sequence of tests. Seventy-five percent of centres instilled a
fibrinolytic agent into the CVC (fibrinolytic lock) as treatment
before investigating CVC-occlusion, employing urokinase (65%),
streptokinase (5%) or recombinant tissue plasminogen activator
(rtPA; 5%).
Table II also shows the nature of the investigations used by
centres providing detailed information, including both first line
investigation and those employed at any stage. The results are
expressed as percentages of centres providing information about
each specific clinical scenario. A wide range of investigations was
performed, with marked variability between centres. Chest X-rays
were the most commonly performed investigation in all four clinical
scenarios, being the first-line investigation in 60–100% of centres
and performed at any stage in 73–100% (varying with each
scenario). Depending on the specific scenario, other investigations
performed included linograms (radiological imaging as radio-
opaque contrast material is flushed into CVC, used in CVC-
occlusion/thrombosis by 50–60% of centres), Doppler ultrasound
and echocardiography (used in CVC-thrombosis/thromboembolism
by 53–60% of centres), and radioisotope ventilation perfusion (V/
Q) scans (in CVC-thromboembolism in 53% of centres). Less
commonly performed investigations included magnetic resonance
venograms (MRVs) and investigation of coagulation pathways or of
pro-thrombotic factors (in CVC-thrombosis/thromboembolism in
13–20% of centres). There was no consistent pattern in the order in
which these investigations were performed.
TreatmentForty-five percent of centres always and 50% usually treated
partial, and 60% and 35%, total CVC-occlusion. Likewise 70–80%
Pediatr Blood Cancer DOI 10.1002/pbc
TABLE I. Importance of CVC-Occlusion, CVC-Related Thrombosis and Thromboembolism
CVC-occlusion CVC-thrombosis CVC-thromboembolism
(1) It is not a significant problem 0 1 (5%) 6 (30%)
(2) It is a nuisance for patients and/or staff but not usually clinically important 4 (20%) 3 (15%) 0
(3) It is a clinically important concern 7 (35%) 9 (45%) 8 (40%)
(4) It is a major clinical concern and is important enough to merit efforts to
improve current practice
9 (45%) 7 (35%) 6 (30%)
Results expressed as number (percentages) of responding centres.
CVC Occlusion and Thrombosis 827
always and 5–20% usually treated patients with clinical features of
CVC-thrombosis/thromboembolism. There was no relationship
between centre experience and the centre’s likelihood of starting
treatment. Three centres stated that they had not recognised any
clinical problems due to CVC-thrombosis/thromboembolism (Sup-
plemental Table I). None of these three centres had a written
treatment protocol, although they inserted 26–50, 51–100 and
101–200 CVCs respectively per year. The form was completed by a
consultant in two of these centres and senior nurse in the other. Two
of these centres and one other centre graded the relative importance
of CVC-occlusion and CVC-thrombosis/thromboembolism as
neither significant nor clinically important, but there was no
apparent difference between these 3 and the other 17 centres in the
frequency or manner of treatment (except for those complications
that were not reported by 2 centres, when no further details were
provided). Only two centres (10%) had a protocol with a specific
sequence of treatment.
Supplemental Table I shows the nature of the treatments used by
those centres providing detailed information, including both first
line treatment, and that used at any stage of management. Several
different treatments were used, with wide variability between
centres in the nature of treatments and the order in which they were
employed. First line treatment of CVC-occlusion comprised a
fibrinolytic lock in 44–57% of centres, whilst the remainder used a
fibrinolytic infusion (6–29% of centres) or flushed the CVC with
crystalloid or heparin solution (14–50%).
CVC removal was performed more frequently as first line
treatment in the presence of signs (e.g. facial or limb oedema) of
CVC-thrombosis (35% of centres), symptoms (e.g. chest pain) or
signs of CVC-thromboembolism (44%), and where investigation
had revealed either CVC-thrombosis or CVC-thromboembolism
(17–19%), most commonly as a closed procedure (i.e. ‘‘pulling the
line’’ without direct visualisation of the venous incision). Systemic
anticoagulation (with either standard or LMW heparin) was also
used commonly in these scenarios (34–50% of centres), whilst
fibrinolytic locks and infusion were used less frequently (0–11%
and 0–33%, respectively).
Other treatments employed less frequently included warfarin
anticoagulation (for CVC-thrombosis, or symptoms or signs of
CVC-thromboembolism, in 35–50% of centres), systemic fibrinol-
ysis (rtPA infusion) (for CVC-thromboembolism in 31–38% of
centres, and confirmed CVC-thrombosis in 17%), and thrombec-
tomy (for CVC-thrombosis in 6–11% of centres, and CVC-
thromboembolism in 13–19%). Open CVC removal at thoracotomy
(with direct visualisation of the venous incision) was performed for
confirmed CVC-thromboembolism in 6% of centres.
When flushing, infusing or locking an occluded CVC, most centres
(85%) treated only the affected lumen, whereas 15% treated all lumens.
DISCUSSION
Occlusion and thrombosis/thromboembolism remain frequent
and potentially serious complications of CVCs in patients with
Pediatr Blood Cancer DOI 10.1002/pbc
TABLE II. Investigation of CVC-Occlusion, CVC-Related Thrombosis and Thromboembolism
Clinical scenario
Number ofcentres providing
information First line investigation Investigation at any stage
(1) Partial CVC-occlusion 14 Chest X-ray 79% Chest X-ray 79%Linogram 7% Linogram 50%Not specified 14% Contrast venogram 14%
MRV 7%Doppler ultrasound 7%Echocardiogram 7%
(2) Total CVC-occlusion 15 Chest X-ray 100% Chest X-ray 100%Linogram 60%Echocardiogram 33%Contrast venogram 7%Doppler ultrasound 7%MRV 7%
(3) Signs of CVC-thrombosis 15 Chest X-ray 73% Chest X-ray 87%Doppler ultrasound 13% Linogram 60%Investigation of coagulation pathways 13% Doppler ultrasound 60%
Echocardiogram 53%Contrast venogram 40%MRV 20%Investigation of coagulation pathways 13%Investigation of pro-thrombotic factors 13%
(4) Symptoms or signs of 15 Chest X-ray 60% Chest X-ray 73%CVC-thromboembolism Doppler ultrasound 20% Doppler ultrasound 60%
Full blood count 7% Echocardiogram 53%V/Q scan 7% V/Q scan 53%Investigation of coagulation pathways 7% Linogram 33%
Contrast venogram 33%MRV 20%Investigation of coagulation pathways 20%Investigation of pro-thrombotic factors 20%Pulmonary angiogram 13%
See Methods Section for definitions; Linogram¼ radiological study where radio-opaque contrast material is flushed into CVC; MRV¼magnetic
resonance venogram; V/Q¼ radioisotope ventilation perfusion scan.
828 Skinner et al.
malignancy [2–4,6–12]. An early report of 1,019 children with
malignancy described 1141 CVCs of which 284 were removed non-
electively (39% of all removals), including 27 (10%) due to CVC-
occlusion [2]. More recently, a prospective study of 418 CVCs in
368 children with malignancy or undergoing haemopoietic stem cell
transplantation, observed for a mean of 256 days each, reported 84
episodes of CVC-occlusion (0.20 per CVC) and 9 of CVC-
thrombosis (0.02 per CVC) [11]. CVC removal was required in 44%
of CVC-thrombosis episodes [11]. These data may underestimate
the frequency of CVC-thrombosis since many episodes are
clinically silent. A recent review suggested that CVC-thrombosis
may occur in about 40% of patients, with only about 12% being
symptomatic [12]. A study of 24 children with malignancy under-
going removal of subcutaneous vascular ports (at completion of
therapy in 15 patients) demonstrated that 12 had venographic evidence
of CVC-thrombosis. Nine of these patients had no clinical features of
CVC-thrombosis [10]. Studies in adults have revealed venographic
evidence of CVC-thrombosis in up to 60% of patients [13,14]. The
long-term outcome of CVC-thrombosis is unknown [6], but CT
angiography demonstrated residual deep venous abnormalities 10–
30 months after CVC removal in 3 (12%) of 25 children previously
treated for malignancy [15]. Moreover, CVC-thrombosis/throm-
boembolism may have fatal consequences. The Canadian Childhood
Thrombophilia Program reported that 9 (3.7%) of 244 consecutive
children with CVC-thrombosis died as a result of pulmonary
embolism (7 children) or obstructive intracardiac thrombosis (2) [4].
The relatively small proportion of UKCCSG centres with
specific protocols for the management of CVC-occlusion and
especially CVC-thrombosis/thromboembolism, and the consider-
able variability in the clinical practice of centres, reflects the lack of
high quality evidence to guide practice. Furthermore, although most
centres believed CVC-occlusion/thrombosis to be an important
issue, a minority did not. Although the absence of experience with
CVC-thrombosis/thromboembolism reported by three centres was
not related to centre size, participation in a comprehensive
surveillance programme (analogous to the Canadian Childhood
Thrombophilia Program [4]) might generate greater awareness of
the potential importance of this complication.
It is possible that the results of this survey do not reflect current
practice in UK centres since it was performed in 2001/2002, but it
seems unlikely that practice has become more uniform subsequently
since no national guidelines have been developed during this time.
Moreover, marked inter-centre variability in practice was still
apparent when the Supportive Care Group reviewed CVC care
protocols used in UKCCSG centres in 2004/2005 in order to
evaluate the feasibility of developing consensus guidelines (A.
McCarthy, unpublished work). Another potential limitation of the
survey is that the questionnaire was completed by one respondent
only in 65% of centres. However, all replies were completed by at
least one experienced staff member (consultant or senior nurse)
involved in the use and care of CVCs. Medical and nursing staff
work together closely in paediatric oncology multidisciplinary
teams in the UK, suggesting that the survey should be representative
of UK practice.
Despite the frequency of CVC-occlusion and the potential severity
of CVC-thrombosis/thromboembolism, there is little agreement
about how to diagnose, prevent and treat them [6]. Considerable
uncertainty persists about the optimum choice of ‘‘flushing’’ protocol.
No large controlled study has been performed in children [16], leading
tovariability in practice [17]. Several prophylactic strategies to reduce
the frequency of CVC-occlusion/thrombosis have been studied [17],
including low dose warfarin [18–20], infused conventional [21] or
subcutaneous LMW heparin [13], but the overall risk-benefit balance
of these treatments remains unclear [12,22]. Relatively few studies
have included children [19,20].
Less invasive imaging modalities (e.g. MRV) [23] have been
used to detect CVC-thrombosis, but have not been shown to be
superior to contrast venography and ultrasonography [6,24]. One
study suggested that MRV several months after CVC removal
overemphasised venous stenoses in children [23].
CVC-occlusion is usually treated by infusing or ‘‘locking’’ a
fibrinolytic drug (urokinase [25,26], streptokinase or rtPA [27–31])
into the affected lumen. One study in adults found that rtPA was
more effective than urokinase in restoring function and clearing
thrombotic CVC-occlusion [32], but paediatric data are lacking. It is
agreed that the optimum treatment for CVC-thrombosis is CVC
removal, this is often impractical. Full dose anticoagulation with
warfarin or LMW heparin is usually employed [33], but the best
approach in children is not clear. An alternative strategy to use the
CVC itself to direct fibrinolytic treatment [34] may reduce the risk of
systemic toxicity, but this has not been studied in children. Finally,
uncertainty persists about how asymptomatic CVC-thrombosis
should be managed [6].
Although it is unclear how frequently CVC-occlusion heralds
the onset of CVC-thrombosis [6], it is possible that prevention of
CVC-occlusion may retard the subsequent development of CVC-
thrombosis [35].
The results of this survey demonstrate the need for further
research into several aspects of the management of CVC-occlusion
and CVC-thrombosis. For example, does the use of systemic LMW
heparin in addition to a conventional heparin CVC flush reduce the
frequency of CVC-thrombosis, especially in high-risk scenarios?
Although the 7th AACP Conference on Antithrombotic and
Thrombolytic Therapy did not recommend this strategy, this was
due to insufficient evidence [22]. Likewise, there is a need for a well-
designed comparative trial of urokinase and rtPA in the treatment of
CVC-occlusion in children.
Nevertheless, several professional groups have produced guide-
lines for the use of CVCs in children in an attempt to reduce the risk
of thromboembolic complications (including occlusion), especially
in children dependent on long-term CVCs for continued treatment.
Some of these documents have been published [36,37], but most are
based largely on a combination of low quality published evidence
(e.g. case series, descriptive studies), ‘‘expert opinion’’ and
institutional practice and/or experience. Unfortunately, it has not
been possible to develop guidelines based on rigorous systematic
review since there is a paucity of high quality clinical trials [6].
However, a formal critical appraisal of published paediatric
literature would identify knowledge gaps with the ultimate aim of
stimulating future research that would then facilitate the develop-
ment of evidence-based guidelines.
In conclusion, this survey of UKCCSG centres has demonstrated
considerable variability in clinical practice in the prevention,
diagnosis and therapy of CVC-occlusion and CVC-thrombosis/
thromboembolism in children with malignancy, and highlighted the
lack of consistency in those written protocols that are available. The
lack of high quality evidence makes it imperative to address
variability in care by designing studies and controlled trials of these
elements of CVC care, thereby enabling the development of
rigorous evidence-based guidelines.
Pediatr Blood Cancer DOI 10.1002/pbc
CVC Occlusion and Thrombosis 829
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