review Annals of Oncology 19: 9–15, 2008

doi:10.1093/annonc/mdm272
Published online 9 September 2007

Management of venous port systems in oncology: a

review of current evidence
S. Vescia1§, A. K. Baumgärtner2§*, V. R. Jacobs2, M. Kiechle-Bahat2, A. Rody3,
S. Loibl1,3 & N. Harbeck2
1
German Breast Group, Neu Isenburg; 2Frauenklinik rechts der Isar, Technische Universität München; 3Frauenklinik, Universitätsklinikum Frankfurt am Main,
Germany

Received 17 March 2007; accepted 30 April 2007

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Background: Over the last decades, many changes have occurred in oncology with new chemotherapy
combinations and more complex application schemes becoming available. Central venous catheters and implantable
venous port systems have become widely used and have facilitated the problem of vascular access. However,
important complications are associated with permanent central venous catheters.

review
Material and methods: This review summarizes evidence on venous port system use published in Medline up to
February 2007. Moreover, recent guidelines for the prevention and management of catheter-related infections issued
by the Infectious Diseases Society of America, the American College of Critical Care Medicine, the Society for
Healthcare Epidemiology of America, the Center for Disease Control and Prevention, Atlanta, and the Infectious
Diseases Working Party of the German Society of Hematology and Oncology are included.
Results: Sterile precautions are essential when implanting and accessing port systems. Infections must be treated
with adequate antimicrobial therapy. Catheter-related thromboembolic complications were found at a rate of 12–64%
in retrospective studies. Five current clinical trials investigated the effect of prophylactic anticoagulation with either low
molecular weight heparin or warfarin in cancer patients with central venous devices. On the basis of these results,
routine anticoagulation cannot be recommended.
Conclusions: This article reviews the current literature on long-term complications of venous port systems, focusing
on infection and thrombosis. In addition, it summarizes the evidence regarding routine maintenance of port systems in
follow-up care.
Key words: central venous catheter, chemotherapy, infection, thrombosis, venous port system

introduction systems have therefore substantially facilitated the problem

of vascular access. To date, safe and easy-to-handle port
In 1973, the first long-term central venous catheter (CVC) systems have become an integral part of daily clinical routine in
was used for parenteral nutrition [1]. In 1979, the Hickman
oncology [4].
catheter, a long-term venous access device, was used for
However, there are several rare but nevertheless important
chemotherapy for the first time [2]. The introduction of totally
complications associated with permanent central venous
implantable port systems started in the early 1980s [3]. Today,
catheters [5]. After immediate perioperative and short-term
these devices provide easy vascular access for delivery of
complications such as accidental arterial puncture, haematoma,
chemotherapy, fluids, medications, blood products and
air embolism, pneumothorax or vessel perforation [6],
parenteral nutrition solutions. Over the last few decades,
clinical oncologists are most often concerned with major
many management changes in oncology have occurred,
long-term complications occurring during the use of catheters
particularly with respect to new chemotherapy combinations
and more complex application schemes. Cancer patients in daily routine care. According to the literature, there is no
usually require repeated venous punctures for treatment uniform definition of long-term complications. Therefore,
monitoring, application of chemotherapy or blood we define long-term complications as complications occurring
transfusions. Central venous catheters and implantable port after the immediate perioperative period following catheter
insertion. A retrospective analysis by Yildizeli et al. of 225
*Correspondence to: Dr A. K. Baumgärtner, Frauenklinik rechts der Isar der Technische catheter and port system implantations detected long-term
Universität München, Ismaninger Str. 22, 81675 München, Germany. complications in 6.6% of cases: infection (2.2%), thrombosis
Tel: +49-(0)894140-6658; Fax: +49-(0)894140-4846; (1.3%), extravasation (1.3%) and catheter fracture (1.8%) [7].
E-mail: annebaumgaertner@web.de
Although reviews about venous catheter-related thrombosis
§
Both authors contributed equally to this manuscript. exist [8], institutional port implantation and maintenance

ª 2007 European Society for Medical Oncology. For Permissions, please email: journals.permissions@oxfordjournals.org
review Annals of Oncology

guidelines tend to vary substantially. Therefore, this article Occurring at a rate of 13–14%, bloodstream infections are
reviews the current literature on long-term complications of the third most frequent type of nosocomial infection in the
venous port systems, focusing on infection and thrombosis as USA and Europe [18, 19]. A large multicentre European study
well as on their routine maintenance in follow-up care. The reported that 71% of all sepsis patients had central lines
important complication of extravasation that still exists with of different types [20]. Catheter-related infections are thus
the widespread use of port systems has been extensively an important problem in the hospital or outpatient setting,
discussed in other current reviews [9]. contributing to an increased patient morbidity and mortality
rate [21]. Therefore, clinicians need to know about prevention,
diagnosis and therapy of port system infections. In 2001,
method the Infectious Diseases Society of America (IDSA), the
Guidelines, recommendations and clinical trials concerning venous port American College of Critical Care Medicine, the Society for
systems and their complications such as thrombosis and infection were Healthcare Epidemiology of America and the Center for
searched and reviewed. These data were identified by a Medline search Disease Control and Prevention (CDC), Atlanta,
comprising all articles published in English in international journals up to implemented evidence-based guidelines for the prevention
February 2007. The main search terms included ‘central venous catheter’, and management of intravascular catheter-related infections
‘venous port systems’, ‘thrombotic complications’, ‘thromboses’, [10, 22]. The 2003 guidelines of the Infectious Diseases
‘infection’, ‘chemotherapy’ and ‘cancer’. Working Party (AGIHO) of the German Society of Hematology

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and Oncology (DGHO) cover diagnosis, management and
prophylaxis of CVC-related infections in neutropenic patients
discussion [23]. The definition of ‘catheter-related infections’ varies
characteristics and use of venous port systems considerably among authors and studies: as thoroughly
discussed by Faetkenheuer et al., it is necessary to differentiate
Port systems are permanently implantable venous access
strictly between catheter colonization (i.e. the presence of
devices consisting of a port body with silicone membrane and
bacteria on the catheter surface without bacteraemia or
the catheter line itself. Port catheters may be inserted into
clinical signs of inflammation) and true catheter infections,
a number of peripheral veins adhering to maximum sterile
which are subdivided into local infection (i.e. clinical signs
precautions and using a cap, mask, sterile gown, sheet and
of infection at the catheter site without systemic infection),
gloves [10, 11]. Implantation is usually possible under local
bacteraemia/fungaemia (where the same microorganisms are
anaesthesia. The port system must be placed in a vessel with
found at the catheter site and in peripheral blood cultures),
a large enough lumen in order to dilute chemotherapeutic
septic thrombophlebitis and tunnel or pocket infections
drugs and minimize venous damage. Most frequently, the
(defined as spread of the infection into the subcutaneous part
internal jugular or subclavian veins as well as the brachial veins
of an implanted port system) [23]. In the following we discuss
are used [12]. The advantage of implantation in brachial veins
true catheter infections only.
is the easy vascular access and a lower risk of immediate
According to a comprehensive review by Bouza et al.,
complications such as pneumothorax. Kuriakose et al. reported
catheter infections may be promoted by the following
more frequent thrombogenic complications in arm ports than
mechanisms: contamination at insertion, which can be avoided
in chest ports (11.4% versus 4.8% respectively) [6, 13]. After
by strict antiseptic procedures; migration of skin organisms
implantation, radiological control of the venous port system
along the external catheter surface, a pathway less important
position is mandatory.
in port systems than in short-term catheters; contamination
The port system is accessed using a special non-coring Huber
of the catheter hub by substances brought into or passing
needle. The silicone port membrane needs to be punctured
through the catheter lumen, which constitutes the most
vertically in order to avoid bending the tip and care must be
frequent way of pathogenesis of infection in port systems;
taken to observe strictly aseptic precautions (i.e. wearing sterile
contamination by infusate; and finally haematogenous
gloves and disinfecting the skin). It has been shown that
infection from a distant site [17]. Depending on the type of
2% chlorhexidine-based preparations reduce catheter-related
patient and catheter, the main microorganisms responsible
infections most effectively [14]; however a 70% alcohol
for catheter-related infections are coagulase-negative
solution, an iodophor or a tincture of iodine can be used
staphylococci, Staphylococcus aureus and Candida species
alternatively [15, 16]. The needle can be kept in place for
[17, 23–25].
72 hours, but should be replaced after 24 hours when used
Diagnosis of a catheter-related infection might be difficult in
for administering blood products or lipid emulsions [10].
the absence of local signs of inflammation [17]. In case of fever,
Using a non-coring Huber needle, more than 2000 punctures
all other aetiologies must be ruled out by thorough clinical
are possible [10].
examination as well as blood and imaging work-up of the
Infections. According to the literature, the rate of catheter- patient in order to confirm catheter-related infection as
related infections in long-term central venous access catheters a diagnosis. Paired blood cultures (aerobic and anaerobic)
ranges from 0.6 to 27% [7], depending on the catheter type and from a peripheral vein and the central catheter should be
location and the patient’s constitution. Immunosuppressed obtained. If the culture from the central catheter turns
patients with port systems were found to have a median of positive before the peripheral sample (diagnostic cut-off
0.2 infections per 1000 catheter-days (range 0–2.7 per 1000 2 hours), this so-called differential time to positivity (DTTP)
catheter-days) [17]. can help to make the diagnosis of catheter-related infection [17,

10 | Vescia et al. Volume 19 | No. 1 | January 2008

Annals of Oncology review
23, 25–27]. Quantitative blood cultures and swabs from as catheter-related bloodstream infections that recur despite
the catheter hub are not recommended as routine measures optimal aseptic catheter maintenance [10, 23, 25]. Figure 1
in the current guidelines. Should catheter removal be presents an algorithm for the approach to catheter-related
necessary, a microbiological examination of the catheter tip is infections according to current guidelines as outlined above
necessary. Different standard techniques for this have been [10, 17, 22, 23, 25].
comprehensively discussed elsewhere [23].
According to the literature, routine device removal cannot be Thromboembolic complications. Another major long-term
recommended in every patient. Port systems must be removed problem of catheter use in cancer patients is thromboembolic
in case of persistent sepsis/bacteraemia or relapse of infection complications. Both infection and thrombosis may lead to
after antibiotic treatment, signs of port or catheter tunnel significant morbidity and impairment of patients’ quality of
infection, unstable patients, systemic complications (e.g. septic life. Cancer patients are in general at increased risk of venous
thrombosis/embolism, osteomyelitis, abscess formation or thrombosis [33], and placement of a catheter or venous port
endocarditis) or detection of certain microorganisms such as system further increases this risk. Increased venous stasis,
S. aureus or Candida species, as these are often associated with endothelial injury, prothrombotic effects of malignancy and
systemic complications and low success rates with catheter chemotherapy itself are among the factors implicated as causes
salvage. If none of the mentioned criteria is present, catheter of thrombosis in cancer patients. Catheter-associated
salvage may be tried [10, 17, 23, 25, 28]. The conditions for thrombosis manifests itself either as thrombosis of the vein in

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catheter removal or salvage as outlined by the CDC and DGHO which the catheter is situated or as an occlusion of the catheter
guidelines and the comprehensive reviews by Hall et al. and lumen. Venous thrombosis may be asymptomatic or present
Bouza et al. are summarized in Table 1 [10, 17, 23, 25]. with ipsilateral arm or neck pain and swelling. Thrombotic
All authors of the different guidelines and comprehensive occlusion of the catheter lumen may be partial or complete;
reviews recommend empirical antimicrobial therapy, based on it may cause restrictions of the catheter’s utility and be
the therapy principles for patients with fever of unknown origin a starting point for infections or vice versa [34]. The incidence
and taking into consideration clinical situation, suspected of catheter-associated thrombosis in cancer patients varies
microorganisms involved and the patient’s underlying disease. considerably between studies and patient or cancer type (Table 2).
Antibiotic treatment should include an aminoglycoside and Four prospective studies of catheter-associated thrombosis in
vancomycin plus aztreonam or a third-generation patients with solid tumours and haematological malignancies
cephalosporin. Therapy must be modified once the report rates of thromboembolic events between 37% and 66%
microorganisms are identified according to susceptibility. [35–38]. The incidence of catheter-associated thrombosis in
Faetkenheuer et al. provide a differentiated therapeutic retrospective studies varies even more widely (12% to 64%)
approach depending on the causative microorganisms, [39–43].
especially stressing the vital importance of adequate treatment Table 3, adapted from Agnelli and Verso [8], shows different
of S. aureus-related infections [17, 22, 23, 25]. clinical trials of thrombosis prophylaxis in cancer patients with
Another therapeutic option for catheter-related bloodstream central venous catheters. In one trial conducted by Monreal
infections, especially in port systems, is an antibiotic lock. A et al., cancer patients with central venous catheters were
high-concentration solution of an antimicrobial substance plus randomized to either low molecular weight heparin once daily
heparin/normal saline is instilled into the catheter when it is for 90 days or no prophylaxis. One of 16 patients in the heparin
not in use [17]. This method showed promising effects in group (6%) and eight of 13 patients in the control group (62%)
therapy of infections and prevention of catheter colonization developed a thromboembolic event (P = 0.002) [38]. Similarly,
[29–32]. However, it is not recommended as a routine measure Bern et al. showed a benefit of the use of 1 mg warfarin for
and should thus remain reserved for special situations such 90 days in cancer patients with central venous catheters. Four
out of 42 patients (9.5%) in the warfarin group and 15 of
40 patients (37.5%) in the control group developed thrombosis
(P < 0.001) [35]. In the majority of patients, there was no
Table 1. Conditions for catheter removal or salvage in case of catheter-
increased risk of bleeding associated with warfarin or low
related infections
molecular weight heparin. According to these two studies,
cancer patients with central catheters should routinely receive
Salvage approach possible Catheter removal
thromboprophylaxis. Yet the fact that in some patients the
if all criteria present necessary in case of:
prothrombin time was excessively prolonged due to the
Absence of local infection Local complications, e.g. concurrent use of chemotherapeutic drugs was not
signs tunnel or port infection separately discussed. Furthermore, neither of the trials was
Absence of metastatic Metastatic complications placebo-controlled or double-blind and both analysed only
complications
a small number of patients.
Sterile blood cultures Relapse of infection during/
Recently, three study groups tried to answer the question
after antibiotic treatment
of thromboprophylaxis with two prospective, double-blind,
Clinically stable patient Unstable patient
placebo-controlled trials. In one trial by Verso et al.,
Persistent sepsis/bacteraemia
310 patients received either low molecular weight heparin for
Certain microorganisms:
S. aureus, Candida species
6 weeks or placebo. Thrombosis was diagnosed by
phlebography in 14.1% in the heparin group compared with

Volume 19 | No. 1 | January 2008 doi:10.1093/annonc/mdm272 | 11

review Annals of Oncology

Suspected catheter-related infection

(local signs/systemic manifestation)

Rule out other causes of fever

Initially empirical antibiotic Paired blood cultures from catheter

treatment and peripheral vein

Catheter salvage possible ?

Adjust regimen according to
susceptibility pattern
no yes

Antibiotic lock
(certain cases)

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Catheter removal Salvage attempt

Catheter tip culture

Figure 1. Algorithm for the approach to catheter-related infections

Table 2. Incidence of venous catheter-related thrombosis in cancer respectively) is reminiscent of the endpoint controversy in trials
patients evaluating antithrombotics in orthopaedic surgery [46]. It may
be that, in trials evaluating antithrombotic prophylaxis in
Reference No. of Method of Catheter-
patients with central vein catheters, symptomatic thrombosis
patients diagnosis related
is associated with a better outcome because the natural history
(n) thrombosis of an asymptomatic thrombus on a screening venogram
(%) remains unclear. In the trial by Couban et al., patients received
1 mg of warfarin or placebo for 9 weeks. The rate of
Bern et al. [35] 42 Phlebography 37.5
symptomatic thrombosis in the warfarin patients was 4.6%
De Cicco et al. [36] 127 Phlebography 66.0
Balestieri [37] 57 Phlebography 56.0
compared with 4.0% in the placebo patients (hazard ratio, 1.20;
Monreal et al. [38] 29 Phlebography 62.0 95% CI, 0.37 to 3.94). Once again, the event rate was much
Newman et al. [39] 690 Clinical diagnosis 63.5 lower than expected [47]. Both of these prospective trials show
Drakos et al. [40] 480 Phlebography 57.2 that the rate of catheter-associated thrombosis is relatively low,
Lokich and Becker [41] 53 Clinical diagnosis 41.5 independent of whether it is measured clinically or
Koksoy et al. [42] 44 Clinical diagnosis 40.0 radiographically. Moreover, it is necessary to mention
Cortelezzi et al. [43] 416 Clinical diagnosis 12.0 complications such as heparin-induced thrombocytopenia
(HIT), which is potentially life-threatening in cancer patients
[48]. Thus, balancing reasons for and against
thromboprophylaxis is essential.
Another prospective, double-blind, placebo-controlled,
18% in the placebo group (P = 0.35). The rate of symptomatic multicentre study published recently evaluated whether
thrombosis was only 2.1% [44]. Therefore, the authors prophylactic treatment with a low molecular weight heparin
speculated that low molecular weight heparin as used in the (dalteparin) could prevent clinically relevant catheter-related
trial may be ineffective and that a higher dose might have thrombosis. In this study 439 cancer patients with a central
resulted in a positive result. Although this is plausible, the venous catheter were randomized 2:1 to receive either
40 mg daily dose of enoxaparin is considered to be an dalteparin (5000 IU) or placebo once daily for 16 weeks. The
effective prophylactic dose used after orthopaedic surgery. dalteparin prophylaxis did not reduce the frequency of
Moreover, an increased dose could well be associated with an thromboembolic complications [49].
increased risk of bleeding, which was not observed in this A literature search on prophylactic treatment in tumour
trial [45]. patients with central venous catheters or receiving
Couban et al. chose to use clinical outcome rather than chemotherapy did not present evidence to support the use of
phlebography as the primary endpoint. The choice of two routine prophylactic anticoagulation for these patients [50].
different primary endpoints in the trials by Verso et al. and Chew et al. merged the California Cancer Registry with the
Couban et al. (phlebography versus clinical outcome American Patient Discharge Data Set and identified breast

12 | Vescia et al. Volume 19 | No. 1 | January 2008

Annals of Oncology review
Table 3. Clinical trials of thrombosis prophylaxis in cancer patients with central venous catheters

Reference Total no. of patients (n) Method of Therapeutic regimen Catheter-related P value
(therapy vs diagnosis thrombosis (%)
control group)
Bern et al. [35] 82 (42 vs 40) Phlebography Warfarin 1 mg/day vs nil 9.5 vs 37.5 <0.001
Monreal et al. [38] 29 (16 vs 13) Phlebography Dalteparin 2500 IU/day vs nil 6.0 vs 62.0 0.002
Verso et al. [44] 310 (155 vs 155) Phlebography Enoxaparin 40 mg/day vs placebo 14.1 vs 18.0 0.35
Couban et al. [47] 255 (130 vs 125) Clinical diagnosis Warfarin 1 mg/day vs placebo 4.6 vs 4.0 n.s.
Karthaus et al. [49] 439 (293 vs 146) Clinical diagnosis Dalteparin 5000 IU/day vs placebo 3.7 vs 3.4 0.9

cancer patients diagnosed with thrombosis between 1993 and the increased risk of relapse within this period, in particular in
1999 to evaluate the incidence of thrombosis and risk high-risk patients. Similarly, in metastatic patients with current

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factors. Approximately 1% of breast cancer patients interruption of their chemotherapy treatment due to good
developed thrombosis within the first 2 years. Metastases response or stable clinical situation, the port systems will
and comorbidities were the strongest predictors for eventually be needed again.
thrombosis [51]. Most manufacturers recommend heparin flushing of the port
In conclusion, all of these recent studies fail to support the systems at 4-week intervals [10]. However, according to the
routine use of prophylactic anticoagulation in cancer patients literature and our own experience, patients show poor
with venous catheters to prevent catheter-induced thrombosis. compliance with these inconvenient, time-consuming and
Institutions should assess their rates of catheter-associated expensive monthly appointments. Kuo et al. demonstrated
thrombosis and the indication for prophylaxis should be in a retrospective study of 73 patients with gynaecologic
individualized for each patient accordingly. If institutional rates malignancies that a 3-monthly protocol for flushing port
seem to be higher than the rates reported in contemporary systems was equally safe and well-accepted. None of their
trials, institutions may need to re-evaluate how their catheters patients was on any anticoagulant therapy. No complications
are inserted and maintained. Central catheters and venous port were observed in this study apart from catheter tip thrombosis
systems are a mainstay of chemotherapy administration, and in seven patients. There was no significant correlation between
thousands of catheters are inserted annually. When accession intervals and the development of this complication
symptomatic thrombosis occurs in association with a catheter, (P > 0.05) [52]. Up to now, the paper by Kuo et al. is the only
it definitely complicates further clinical care of the patient available publication investigating timing of port flushing in the
because of the need for anticoagulant therapy and potential follow-up setting. Again, to fully answer the question of how
catheter-removal. So far, routine prophylactic anticoagulation often a permanent indwelling device should be accessed during
cannot be recommended based on the available evidence. a therapy pause, prospective trials will be necessary.
Large-scale trials like that of Chew et al. using symptomatic
thrombosis as an outcome measure are still urgently needed
[51]. conclusion
In addition, there are no data in the literature concerning
Port systems play an important role in daily care of oncology
frequency and management of mere catheter tip thrombosis,
patients. Several relevant long-term complications exist, namely
where the port system is flushable but no aspiration of blood is
catheter-related thrombosis, infection, occlusion and skin
possible due to a small thrombus occluding the catheter tip. In
penetration. Several researchers evaluated the benefit of
our institutions, we administer 5000 IU heparin over 24 hours
anticoagulant prophylaxis in patients with permanent venous
into the port system via a perfusor system, after which
access devices; however, routine anticoagulation cannot be
treatment the port system often becomes patent again.
recommended so far. Infections can be avoided by careful and
However, no further evidence from clinical trials exists to
strict antiseptic handling, thus minimizing contamination. In
validate this protocol. Moreover, it remains unclear whether
the follow-up setting, 3-monthly intervals of catheter flushing
catheter tip thrombosis needs to be treated at all since any
with heparin seem to be sufficient to keep port systems usable
therapeutic approach is of a merely empirical nature given the
and to prevent thromboembolic complications. Important
lack of any published evidence so far.
aspects regarding the care of port catheters and the
port maintenance in the follow-up setting. With permanent management of potential complications are summarized in
venous access devices becoming more widely used, it remains Table 4.
an open question how to manage port systems and maintain Although clinical management of cancer patients has been
their function once they are no longer used for chemotherapy facilitated by venous port systems, critical analysis and
or total parenteral nutrition. In our institutions, we discuss standardization of port system care on the basis of prospective
with our patients the option to keep their port systems for trials are still necessary to reduce the morbidity and mortality
as long as 2 years after adjuvant breast cancer therapy owing to of cancer patients caused by venous port system complications.

Volume 19 | No. 1 | January 2008 doi:10.1093/annonc/mdm272 | 13

review Annals of Oncology

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