Annals of Oncology 16: 648 – 654, 2005

Original article doi:10.1093/annonc/mdi111

Published online 27 January 2005

Central venous catheter-related complications in children with

oncological/hematological diseases: an observational study
of 418 devices
G. Fratino1, A. C. Molinari2, S. Parodi3, S. Longo4, P. Saracco4, E. Castagnola5* & R. Haupt3
1
Department of Pediatric Surgery, 2Department of Pediatric Hematology and Oncology, Thrombosis and Hemostasis Unit, 3Epidemiology and Biostatistics Section,
Scientific Directorate, 5Department of Pediatric Hematology and Oncology, Infectious Diseases Unit, G. Gaslini Children’s Hospital, Genoa; 4Department of

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Pediatrics, Regina Margherita Children’s Hospital, Turin, Italy

Received 11 June 2004; revised 15 November 2004; accepted 15 November 2004

Background: The use of indwelling central venous catheters (CVCs) has become commonplace in
the management of children undergoing anticancer treatment. Several types of CVC are available,
while information on complications observed in children is scarce. We describe the experience of
two tertiary care centers in Italy that prospectively followed up three types of CVC used at both
institutions over a 30-month period.
Patients and methods: Between January 2000 and May 2002, double-lumen (DL) or single-lumen
(SL) Hickman – Broviac (HB) catheters, and single-lumen pressure-activated safety valve (PASV)
catheters were used and prospectively evaluated. Four types of possible complication were defined
a priori: mechanical, thrombotic, malfunctioning and infectious.
Results: Four hundred and eighteen CVCs (180 SL-HB, 162 DL-HB and 76 PASV) were inserted in
368 children, for a total of 107 012 catheter days at risk of complication. At least one complication
occurred while using 169 of the devices (40%): 46% of the DL-HB, 46% of the PASV and 33% of
the SL-HB (P = 0.02) catheters. Subjects with hematological malignancies or non-malignant diseases
had significantly more complications than those with solid tumors (P <0.0001). Overall, 234 com-
plications were documented: 93 infectious [complication rate per 1000 catheter days at risk
(CR) = 0.87], 84 malfunctioning (CR = 0.78), 48 mechanical (CR = 0.45) and nine thrombotic
(CR = 0.08). SL-HB had statistically fewer infectious complications, while PASV had more mechan-
ical complications. In a multivariate regression model, the most significant risk factors for having a
CVC complication were hematological disease [relative risk (RR) = 3.0; 95% confidence interval
(CI) 1.8 – 4.8] and age <6 years at CVC insertion (RR = 2.5; 95% CI 1.5 – 4.1). As for the type of
CVC, compared with SL-HB, the DL-HB catheter had a statistically significant two-fold increased
risk of any complication (RR = 2.1; 95% CI 1.2 – 3.6), while the PASV catheter had a borderline RR
of 1.8 (95% CI 1.0 – 3.6). Analysis by tumor type showed a higher risk of any kind of complication
in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB
catheter (RR = 7.2; 95% CI 2.8 – 18.7).
Conclusions: CVCs may cause complications in up to 40% of patients, with type of CVC, under-
lying disease and patient age being the three main factors that affect the incidence of CVC-related
complications. SL-HB catheters have the best performance.
Key words: central venous catheters, infections, surgical complications, thrombosis

*Correspondence to: Dr E. Castagnola, Infectious Diseases Unit,
Department of Pediatric Hematology and Oncology, G. Gaslini Children’s
Hospital, L. go G. Gaslini, 5-16147, Genova, Italy.
Tel: +39-010-5636-301; Fax: +39-010-3777-133;
E-mail: eliocastagnola@ospedale-gaslini.ge.it
Introduction
Indwelling central venous catheters (CVCs) guarantee a
reliable vascular access, and are essential for the management
of children undergoing anticancer chemotherapy or bone mar-
row transplantation [1]. However, they might present disad-
vantages [2], such as the risk of mechanical accidents [3, 4],
thromboses [5] or infections [6], which may interfere with the
course of treatment.

q 2005 European Society for Medical Oncology


The most frequently used CVCs in children with cancer are
usually partially implantable, tunneled devices that may be
either valved or not valved. The group of valved CVCs com-
prises those with a valved tip (Groshong) and those with a
pressure-activated safety valve (PASV), which acts as an auto-
matic clamp built into the hub of the catheter. The classical
Hickman–Broviac (HB) catheter is an open-ended (non-
valved), partially implanted device that may be either single
(SL-HB) or double lumen (DL-HB).
To our knowledge, most of the literature on CVC-related
complications refers to studies performed on adults [1, 7], and
the literature that specifically focuses on children usually
refers to studies with <200 devices [3, 4, 8– 15].
In order to quantify the real impact upon the everyday prac-
tice of CVC-related complications observed in tertiary care
centers, we decided to evaluate prospectively the number and
type of complications occurring in partially implanted, indwel-
ling central venous catheters inserted over a 28-month period
in a large cohort of children with onco/hematological diseases
at two pediatric hospitals in Italy.
Patients and methods
All the CVCs consecutively inserted between January 2000 and May 2002
at the G. Gaslini (Genoa) and Regina Margherita (Turin) Children’s
Hospitals, for the management of patients <18 years of age with
hematological or oncological malignancies, or with other diseases requir-
ing allogeneic stem cell transplantation, were considered eligible for this
study.
For the purposes of this study, four groups of possible complications
were defined a priori: (i) mechanical; (ii) symptomatic thrombosis; (iii)
malfunctioning; and (iv) infectious. In particular, a mechanical compli-
cation was defined as a CVC dislocation due to malpositioning of the
catheter tip, or cuff migration, CVC rupture or accidental self-removal by
the patient [4]. If right atrial thrombosis, pulmonary embolism, or deep
venous thrombosis occurred, they were recorded as thrombotic compli-
cations. A malfunctioning event was defined as a difficulty in withdrawing
blood and/or infusing fluids through the catheter that could not be solved
by postural changes or by heparinized saline solution flushes in the
absence of documented thrombosis [16]. Finally, infectious complications
included CVC-related bacteremias, and tunnel or exit-site infections as
defined by internationally accepted definitions [6, 17].
During the study period, three different types of right atrial, indwelling,
partially implanted, tunneled silicone rubber catheters were inserted at the
two hospitals in a non-randomized fashion. In general, subjects scheduled
for stem cell transplantation received DL-HB, while single-lumen cath-
eters (either SL-HB or PASV) were inserted in all other patients. Besides
the specific medical indication of stem cell transplantation, the choice
regarding the type of device to insert was based on the surgeon’s opinion
and the availability of the catheter.
Catheter insertion into the upper venous system was always performed
either by surgical venous cut-down or by the percutaneous technique. In
case of venous cut-down, catheter insertion was accessed by surgical prep-
aration of the external or internal jugular vein. Percutaneous CVC inser-
tion was done using either the subclavian vein by the infraclavicular
approach, or the internal jugular vein. During placement, the correct
position of the distal tip of the catheter (at the superior vena cava–right
atrium junction) was checked by fluoroscopy, and a standard chest radio-
graph with the patient in the upright position was always obtained
649
immediately afterwards [18, 19]. Maintenance procedures were always
performed according to international recommendations [20], and employ-
ing a protocol approved by the Italian Association of Pediatric Hemato-
logy and Oncology (AIEOP). In particular, when not in use HB catheters
were flushed three times a week with a heparinized solution, while PASV
catheters were flushed with normal saline once a week. In any case, no
antibiotic prophylaxis was performed with the flushing. The catheter exit-
site dressing was changed once a week for all devices. Maintenance pro-
cedures were performed by trained pediatric nurses when the patient was
in hospital and by parents when at home. Parents received specific training
during the first weeks after CVC insertion, and were allowed to perform
maintenance procedures only after having reached an adequate level of
skill. Periodic re-evaluations were conducted.
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With regard to each single catheter, data were recorded on type, date of
positioning, age and underlying disease of the patient, date and type of
any complication, date of the last examination, and cause of catheter
removal, if applicable.
Statistical analysis
For each catheter, the total number of catheter days at risk (cdr) was cal-
culated as the total number of days from insertion to last observation (last
examination, removal or patient’s death, whichever occurred first). The
observation period was censored on 31 May 2002. The complication rate
(CR) per 1000 days was calculated as 1000 times the number of compli-
cations divided by the total number of cdr.
Univariate analysis was carried out to determine significant differences
in frequency and type of complications among the three different CVC
types and by the various risk factors that were taken into consideration.
Age at CVC insertion was considered as a dichotomous variable, with 6
years (school age) being the cut-off between the two strata. A separate
analysis has also been performed using age at CVC insertion as a continu-
ous variable. Differences for categorical variables were tested using the
Pearson x2 statistical test, while the Kruskal–Wallis test was used for con-
tinuous variables [21]. The number of complications for each catheter
type was regarded as a Poisson variable and in a multivariate analysis,
results were obtained using the Poisson regression model allowing for
overdispersion and adjusting for age at CVC insertion and underlying dis-
ease [22]. The reasons why underlying disease was considered a risk fac-
tor and stratified accordingly were that treatment protocols for the three
categories considered (i.e. solid tumor, hematological malignancies and
non-malignant diseases) have, in general, different schedules and intensi-
ties, thus requiring different frequencies of catheter manipulation. In this
analysis, the group of children with inborn errors and the group with hem-
atological malignancies were pooled due to the small number of cdr and
of events in the former group. Interaction between type of CVC and
underlying disease was also assessed within the same model.
All parameters were estimated by the maximum likelihood method, and
confidence intervals (CI) were calculated at the 95% level [23]. All stat-
istical tests were two-tailed and the tests were considered significant when
P <0.05.
The cumulative probability of CVC remaining in place with no compli-
cations was calculated using the Kaplan–Meier method, and comparisons
among the three CVC types were carried out using the log-rank test. For
this analysis, only the first complication, if any, was calculated as an
event. With regards to calculation of the overall CVC survival, only
removals due to complications were considered events. All the other
removals, such as those carried out because of other medical decisions
(end of therapy, death of the subject, other), were censored at the date of
removal. Stata and Statistica software packages were used for the
analyses.
650

Results complications; and 0.08 (n = 9) for thrombotic complications

During the study period, 418 indwelling central venous cath-
eters (180 SL-HB, 162 DL-HB and 76 PASV) were consecu-
tively inserted in 368 children (212 males, 156 females) with
hemato-oncological diseases; 51 had more than one CVC
inserted. Among them, 190 had solid tumors, 162 had acute
leukemia or lymphoma, and 16 had non-malignant disease
requiring stem cell transplantation. Patients’ age at CVC inser-
tion ranged between 21 days and 17 years, with a mean age of
7.3 years (95% CI 6.8– 7.8); 203 CVC (49%) were inserted in
children <6 years of age. The overall length of observation
(Table 2).
Differences existed among the three types of CVC with
regard to the frequency of the various complications observed
(Table 2). In fact, infections were most frequently reported
among DL-HB catheters (56 of 114; 49% of all complications
in this type of CVC), while malfunctioning was more frequent
among SL-HB (35 of 75; 47%) and mechanical complications
occurred more frequently in PASV catheters (16 of 45; 36%)
(P = 0.0074). Thrombotic complications were rare (only nine
events overall), with no differences in incidence among the
three types of CVC that were taken into consideration. The

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ranged between 3 and 868 days for a total of 107 012 catheter
days. Table 1 reports on the number, type of CVC and length
of observation, by underlying disease, of patients enrolled into
the study.
Overall, 234 complications were observed in 169 devices
(40% of all devices) with a maximum of six complications in
two CVCs. The overall complication rate was 2.2 (95% CI
1.92 –2.48): it was 0.87 (n = 93) for infectious complications;
0.78 (n = 84) for malfunctioning; 0.45 (n = 48) for mechanical
cause-specific complication rates were also different among
the three types of CVC (Table 2). In fact, infections were less
frequent among SL-HB catheters (infection rate = 0.46), with a
statistically significant difference only as compared with
DL-HB ones (infection rate = 1.40) (P <0.001). The CR for
mechanical complications was higher among PASV catheters
(0.96), with a statistically significant difference only as com-
pared with SL-HB ones (0.28) (P <0.001). No differences
among the three CVC types were observed for rates of

Table 1. Number and type of CVC inserted in 368 children with hematological or oncological malignancies, or undergoing
allogeneic bone marrow transplant (some children may have had more than one CVC inserted)

DL-HBa [n (%)] SL-HB [n (%)] PASV [n (%)] Total [n (%)]

b
Solid tumors 66 (30.9) 113 (53.1) 34 (16.0) 213 (100)
Hematological malignanciesc 80 (43.0) 65 (35.0) 41 (22.0) 186 (100)
d
Non-malignant diseases 16 (84.2) 2 (10.5) 1 (5.3) 19 (100)
Total 162 (38.8) 180 (43.1) 76 (18.1) 418 (100)
Mean length of observation 247 (217–276) 279 (248– 311) 219 (173–266) 256 (236–276)
[days (95% confidence interval)]
Catheter days at risk 39 986 50 342 16 684 107 012

a
All patients with DL-HB catheters underwent stem cell transplantation.
b
Solid tumors: neuroblastoma (65), brain tumors (50), bone tumors (43), Wilms’ (20), soft tissue sarcomas (17), other (18).
c
Hematological malignancies: acute lymphoblastic leukemia (121), other leukemias (34), lymphomas (31).
d
Non-malignant diseases: bone marrow failure syndrome (eight), hemoglobinopathies (seven), other (four).
CVC, central venous catheter; DL-HB, double-lumen Hickman–Broviac; SL-HB, single-lumen Hickman–Broviac;
PASV, pressure-activated safety valve.

Table 2. Distribution and complication rates of CVC-related complications among different types of CVC

DL-HB (cdr = 39 986) SL-HB (cdr = 50 342) PASV (cdr = 16 684) Overall (cdr = 107 012)
n (%) CR (95% CI) n (%) CR (95% CI) n (%) CR (95% CI) n (%) CR (95% CI)
Infectious 56 (49) 1.40 (1.06–1.82) 23 (31) 0.46 (0.29 –0.69)a 14 (31) 0.84 (0.46–1.41) 93 (40) 0.87 (0.70 –1.06)
Malfunctioning 36 (32) 0.90 (0.63–1.25) 35 (47) 0.69 (0.48 –0.97) 13 (29) 0.78 (0.41–1.33) 84 (36) 0.78 (0.63 –0.97)
Mechanical 18 (16) 0.45 (0.27–0.71) 14 (19) 0.28 (0.15 –0.47) 16 (35) 0.96 (0.55–1.56)b 48 (20) 0.45 (0.33 –0.59)
Thrombotic 4 (3) 0.10 (0.03–0.26) 3 (4) 0.06 (0.01 –0.17) 2 (4) 0.12 (0.01–0.43) 9 (4) 0.08 (0.04 –0.16)
Total 114 2.85 (2.35–3.40) 75 1.49 (1.17 –1.87)a 45 2.70 (1.97–3.61) 234 2.2 (1.92 –2.48)

a
RR in comparison to DL-HB catheters (P <0.0001).
b
RR in comparison to SL-HB catheters (P <0.05).
CVC, central venous catheter; DL-HB, double-lumen Hickman–Broviac; SL-HB, single-lumen Hickman–Broviac; PASV, pressure-activated safety valve;
cdr, catheter days at risk; CR, complication rate; CI, confidence interval; RR, relative risk.
 651

Table 3. Multivariate Poisson regression model: risk estimates for any

type of CVC complication in all patients (left part) and stratified by tumor
type (right part)

Variables in All patients Solid tumors Hematological or

the model non-malignant
disease
RR (95% CI) RR (95% CI) RR (95% CI)
CVC type
SL-HB 1 (ref) 1 (ref) 1 (ref)
DL-HB 2.1 (1.2–3.6) 7.2 (2.8– 18.7) 0.9 (0.5–1.8)
PASV 1.8 (1.0–3.6) 1.3 (0.4– 4.2) 1.8 (0.8–4.2)

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Age
>
_ 6 years 1 (ref) 1 (ref) 1 (ref)
<6 years 2.6 (1.6–4.3) 3.9 (1.6– 9.6) 2.4 (1.4–4.4)
Tumor type
Solid tumor 1 (ref) – –
Hematological or 3.0 (1.9–4.9) – –
non-malignant
disease
CVC, central venous catheter; DL-HB, double-lumen Hickman–Broviac;
SL-HB, single-lumen Hickman–Broviac; PASV, pressure-activated safety
valve; RR, relative risk; ref, reference value.
malfunctioning or for thrombotic complications. The overall
catheter-specific CR was 2.85 for DL-HB, 2.70 for PASV, and
1.49 for SL-HB. The difference among the three types of
CVC was statistically significant for SL-HB compared both
with DL-HB (P <0.001) and with PASV (P = 0.002). If the
type of underlying disease was taken into consideration, the
complication rate was 3.6 (95% CI 3.02 –4.19) among chil-
dren with hematological malignancies (n = 143), 2.0 (95% CI
1.01 –3.60) among those with non-malignant disease (n = 11),
and 1.3 (95% CI 1.03 –1.62) among those with solid tumors
(n = 80) (P <0.001) (likelihood ratio test). In a Poisson’s multi-
variate regression model that took into consideration the type
of CVC, age at CVC insertion, and the underlying disease of
the subject (Table 3), the most significant risk factors for CVC
complications were having a hematological disease [relative
risk (RR) 3.0] and being <6 years of age at CVC insertion
(RR = 2.6). In a separate analysis, for which age was treated as
a continuous variable, the results did not change substantially
and the risk of complications decreased by 7% with each extra
year of age (data not shown). Regarding the CVC type, as
compared with SL-HB, the DL-HB catheter had a statistically
significant two-fold increased risk of any complication
(RR = 2.1; 95% CI 1.2–3.6), while PASV had a borderline RR
of 1.8 (95% CI 1.0– 3.6). This observational study was not
randomized, and as it occurs in clinical practice, some types
of catheters (e.g. DL-HB) were inserted more frequently under
particular conditions (e.g. stem cell transplantation recipients).
Therefore, further analysis was performed to evaluate any
possible interaction between the type of underlying disease
and type of CVC in the risk of developing any complications,
using age at insertion as a confounder. A statistically signifi-
cant interaction was observed between CVC type and tumor
Figure 1. Overall catheter survival in three different central venous
catheter types (only removals due to irresolvable complication are
considered as events). CVC, central venous catheter.
type (P = 0.0003, likelihood ratio test). Thus the same analysis
was performed, stratifying by type of underlying disease
(Table 3), and a significant effect was observed (P <0.001,
likelihood ratio test) in DL-HB catheters inserted in children
with solid tumors, with a seven-fold increased risk compared
with SL-HB catheters (RR = 7.2; 95% CI 2.8–18.7).
The complication could not be resolved in 72 (31%) epi-
sodes, thus leading to catheter removal. In particular, it was
required in 52% (25 of 48) of the mechanical complications,
in 44% (41 of 93) of the infections, in 44% (four of nine) of
thrombotic complications, and in 2% (two of 84) of malfunc-
tioning. At the end of the present study, besides the 72 CVCs
that had been removed due to complications, 164 further
devices were no longer in place: 97 because of end of treat-
ment, 51 because of death of the subject and 16 because of
replacement with another type of CVC due to other medical
indications. It should be noted that even though CVC abduc-
tion after death is not routinely performed in our centers, no
death certificates referred to any CVC-related complication as
the cause of death. Figure 1 reports the overall probability of
survival of the CVC. In this analysis, only removals that were
needed due to irresolvable complications were considered
events. Overall, CVC survival after >800 days was estimated
at 74.9% for SL-HB, 53.2% for PASV and 52.4% for DL-HB
catheters. The difference among the three types of CVC was
significant only with regard to the comparison between
DL-HB and SL-HB (P = 0.01), while there was no significant
difference between PASV and SL-HB (P = 0.06), or between
PASV and DL-HB (P = 0.9).
CVCs with at least one complication
As mentioned before, the 234 complications were observed in
169 CVCs. Considering the catheter type, 45 of 162 (46%)
DL-HB catheters, 35 of 76 (46%) PASV catheters, and 59 of
180 (33%) SL-HB catheters had at least one complication
(P = 0.02). If the underlying disease was taken into consider-
ation, at least one complication was observed in 95 of 168
(51%) CVCs inserted in patients with hematological malig-
nancies, in nine of 19 (47%) of those inserted in children with
652
Figure 2. Catheter survival without any complication in three different
central venous catheter types. PASV, pressure-activated safety valve;
CVC, central venous catheter.
non-malignant diseases, and in 65 of 213 (30%) of those
inserted in patients with solid tumors (P <0.001). Finally, 94
of the 203 CVCs inserted in children <6 years of age (46%)
had at least one complication, compared with only 75 of the
215 inserted in patients >
_ 6 years (34%; P = 0.017).
The interval between insertion and the first complication
ranged between 0 and 724 days (median 52 days). Considering
the three different CVC types, the median interval was 31
days (range 1– 724) for PASV, 77 days (range 0–665) for
DL-HB, and 62 days (range 1–565) for SL-HB; there were
significant differences among them. The estimated probability
of CVC survival without any complications after >800 days
following CVC positioning was 55.8% for SL-HB, 36.6% for
DL-HB and 32.6% for PASV catheters (Figure 2). The differ-
ence among the three CVC types was statistically significant
(P = 0.004). In particular the SL-HB catheter performed sig-
nificantly better compared with the PASV (P = 0.012) and
DL-HB catheters (P = 0.006), while no differences in the
probability of developing a complication were observed
between the SL-HB and PASV catheters.
Finally, 44 CVCs (11%) had more than one complication
[24 DL-HB (15%), 12 SL-HB (7%), eight PASV (11%)], and
in 20 the same type of complication occurred at least twice. In
particular, 16 CVCs had more than one episode of malfunc-
tioning or thrombosis for a total of 18 extra episodes, and
eight CVCs had more than one infection, for a total of 11
extra infectious episodes. Among the 51 patients with more
than one CVC inserted, only two had both CVCs with more
than two identical complications (both infections).
Discussion
In this prospective, observational study of 418 partially
implanted CVCs, for a total of >100 000 days of observation,
we demonstrated that even by adopting internationally
approved procedures for CVC management, complications
occur in 40% of devices inserted in children with oncohemato-
logical diseases, with an overall CR of 2.2. SL-HB catheters
perform best (33% of complications, overall CR = 1.49), and
catheters inserted in children with solid tumors and of school
age (>_ 6 years) have the fewest complications.
Infections represent the most frequently reported compli-
cation, showing a rate of 0.87, which is lower than the mean
1.2 and 3.9 values reported in two literature reviews [24, 25].
The fact that DL-HB catheters had the highest rate of infec-
tious complications is not unexpected, since these devices
require a greater number of CVC manipulations, which has
been shown to be strictly related to the risk of infections [26].
However, the rate of 1.4 for infectious complications that we
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observed among DL-HB catheters is lower than that reported
in two retrospective studies on adults for this type of CVC
[27, 28], which describe an infection rate up to 2.02. We
believe that these satisfactory results may be, at least in part,
due to the routine use of internationally approved standards
for CVC maintenance, and to continuous surveillance of the
hospital and home care of the devices. However, we cannot
rule out that different study designs and populations may have
had some influence on the results.
Catheter removal for complete resolution of the infection
was required in 44% of the episodes. This percentage of
removal is between the 29% and 67% reported in two other
retrospective studies in children with cancer [29, 30]. These
differences might in fact reflect different policies with respect
to the definition and management of catheter-related infec-
tions. However, it should be emphasized that in our insti-
tutions we adopted the guidelines for the diagnosis and
management of CVC-related infections implemented by the
Infectious Disease Society of America [6]. Therefore, it is
reasonable to assume that the percentage of CVC removals
due to infection that we observed represents what would be
expected under these conditions.
Malfunctioning events were the second most frequently
reported complication, with no significant differences among
the three types of CVC evaluated. This type of complication,
however, has little impact on CVC life since it was solved in
98% of cases by the salvage protocols that employ urokinase,
as previously reported [16], thereby leading to only 2% of
CVC removals. Symptomatic thrombotic complications were
rare, occurring in 2% of CVCs (nine of 418 events). This
result confirms another of our previous retrospective studies
[16]. Pooled together, thrombotic or malfunctioning events
were recorded in 22% of CVCs (93 complications in 418
CVCs); this value is lower than the 25% –40% reported in the
literature [31, 32].
We acknowledge that our definition of thrombotic compli-
cation is more restrictive than that used in other reports since
it is based on clinical criteria alone. However, our strategy,
which promptly calls for urokinase in malfunctioning catheters
[16], likely prevented clot progression from becoming sympto-
matic. Therefore, we believe that the prompt use of urokinase
in the management of a malfunctioning CVC that is refractory
to postural changes and heparin flushes, is a safe and cost-
effective approach which may have prevented the progression

of an undetectable thrombosis [33], and which also avoids
the widespread use of more invasive diagnostic approaches in
children [34, 35].
Mechanical complications represented 20% of all the events
we observed, with a complication rate of 0.45, but in 52% of
cases the catheter had to be removed. PASV catheters per-
formed the worst in this respect, as shown by the sharp
decline in CVC survival shortly after insertion (Figure 2). A
possible explanation for this finding is that the size of the cuff
in this type of catheter does not favor adhesion to the subcu-
taneous tissue. After this problem was first observed, the man-
ufacturer provided a silicone device to place around the CVC
to suture to the skin as an anchorage, but this did not prove to
be as effective as expected (data not shown). Recently, Cesaro
et al. reported mechanical complications to be the main cause
of premature loss of CVC, especially in younger children [14].
In our experience, young age at CVC insertion has also been
associated with a higher incidence of any complication. The
observation that the younger the patient with the CVC, the
greater the probability of a complication, could be at least par-
tially due to a higher incidence of malfunctioning events
linked to the small size of the CVC and to the increased risk
of self-removal.
This study has also documented different complication rates
between children with solid tumors and those with hemato-
logical diseases. This observation is not surprising since, at
least with regard to infections, patients with acute leukemia
have a higher incidence of CVC-related infections as com-
pared with patients with solid tumors because they require a
greater number of CVC manipulations for the treatment and
management of chemotherapy-induced side-effects [36, 37].
As this prospective, non-randomized observational study
allowed us to collect a sizable number of catheters and days
of observation, we used multivariate analysis to study the role
and interaction of some possible risk factors in the develop-
ment of CVC-related complications. This analysis confirms
that the most significant risk factors for developing any type
of CVC-related complication include having a hematological
disease, being <6 years of age at CVC insertion and having a
DL-HB catheter inserted. However, since there are inter-
actions between CVC type and the underlying disease of the
patients, the stratified analysis by tumor and catheter type
showed a significant, increased risk of any complications
among DL-HB catheters inserted in children with solid
tumors. This fact is probably due to our previous policy of
inserting DL-HB catheters, even for the management of chil-
dren with solid tumors scheduled for autologous stem cell
transplantation. Since supportive care following this procedure
is much less intensive compared with that required after allo-
geneic transplant, after the preliminary analysis of this study
we decided not to routinely implant DL-HB catheters in chil-
dren scheduled for autologous stem cell transplantation.
We agree that totally implanted devices have an overall
lower risk of complications. In particular, the risk of self-
removal in toddlers is absent, and infections are by far lower
because of the need for fewer maintenance procedures when
653
not in use. However, we believe that the psychological reasons
(fear of needles) that drive all Italian pediatric cancer centers
to use partially implanted CVCs allow acceptance of this
increased risk.
Caution should be taken considering these results when
dealing with smaller and less experienced institutions than
those that contributed to this study. We believe that continu-
ous medical education should also consider the management
of possible CVC-related complications.
Finally, the design of this study was catheter-oriented and
not patient-oriented. We acknowledge that the repeated com-
plications occurring in some CVCs, or in different CVCs
Downloaded from https://academic.oup.com/annonc/article-abstract/16/4/648/173530 by guest on 21 August 2019
inserted in the same child, could be at least partially due to
the patient’s predispositions (e.g. hypercoagulability, immuno-
deficit, low socio-economic status). However, we believe that
in order to analyze the role of these variables, the study should
have been planned differently, in particular acquiring data on
the presence of possible ‘genetic’ risk factors at diagnosis, and
on the occurrence of other risk factors (e.g. type of drugs
administered, course of the underlying disease) throughout the
course of therapy. Such a study might in fact yield valuable
additional information, but should be designed specifically.
Acknowledgements
This manuscript is dedicated to the memory of Carlina Haupt.
The authors wish to thank Dr Cinzia Mazzola for data collec-
tion and Mr Felice Savelli for software development. This
study was partially funded by grants from the G. Gaslini
Children’s Hospital and by the Italian Ministry of Health.
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