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| Journal of Vascular Access 2002; 3: 147 - 153 |
| Valved central venous catheter connected to subcutaneous port: A multicenter phase IV study based on a cohort of 50 oncology patients |
R. Biffi1, M. Pittiruti2, J.P. Gillet3, D. Fobe3, J.P. Hermanne3, M. Pescio4, A. Gourlia5, K. Collet6, C. Battelli7, S. Cenciarelli1
1Division of General Surgery, European Institute of Oncology, Milano - Italy
2Shock Pathophysiology Research Centre, Catholic University, Rome – Italy
3Departments of Surgery and Oncology, Centre Hospitalier Régional de Namur, Namur - Belgium
4Department of Anesthesiology, Hôpital Régional de Pontoise, Pontoise - France
5Department of Anesthesiology, Clinique Claude Bernard de Metz, Metz - France
6Department of Anesthesiology, Clinique Victor Hugo de Boulogne/Billancourt, Boulogne - France
7Departments of Surgery and Oncology, Catholic University, Rome - Italy
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Search Medline for articles by:
 R. Biffi
M. Pittiruti
J.P. Gillet
D. Fobe
J.P. Hermanne
M. Pescio
A. Gourlia
K. Collet
C. Battelli
S. Cenciarelli
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ABSTRACT
Purpose: Since technical aspects and clinical features of central venous valved catheters are far from being completely understood, a multinational group of investigators has decided to assess a new distally-valved catheter connected to a port, in the clinical setting of oncology patients undergoing chemotherapy, in an attempt to verify its safety and viability, while also investigating its practical features.
Methods: Our project was structured as a phase IV multicenter study. Hospitalized adults (ages 18-80 years) who had solid tumors and were candidate for intravenous chemotherapy met the criteria to enter the study. One single type of port was used (made of titanium, plastic and silicone) connected to a silicone, distally valved catheter (as manufactured by B. Braun Aesculap). A case report form was provided for each treated case; all relevant data regarding implantation and follow-up were entered into the form, mailed to a coordinating center (G. Chevillon, B. Braun Medical, France) and stored in a software database for statistical analysis.
Results: 50 patients (from 6 participating centers) were included in this study. No major complications occurred at insertion. The most frequent clinical problem during follow-up was inability to draw blood samples (9% during the first chemotherapy cycle; 8% after the second cycle); blood obtained from the device was defined “unsuitable for hematology test” in 9% of the cases at first chemotherapy cycle and in 23% of the cases after the second cycle. No catheter obstruction occurred.
Conclusion: The distally valved catheter port tested in this study was reliable, safe and practical for long-term treatment of an oncology patients’ population undergoing chemotherapy. As most other reports and clinical trials dealing with other types of distally valved catheters pointed out, inability to draw viable blood samples (so called withdrawal occlusion) is a major concern in their clinical use. Mechanisms underlying this technical problem are still unclear. (The Journal of Vascular Access 2002; 3: 147-53)
Key Words. Central venous catheters, Ports, Valved intravenous catheters, Chemotherapy
INTRODUCTION
Technical aspects and clinical features of central venous valved catheters are far from being completely understood and investigated. The “gold standard” for these catheters is surely the Groshong valved catheter, until a few years ago the sole commercially available. Developed in 1978, the Groshong catheter has the unique feature of a three-position, pressure sensitive valve – close to its distal tip – which opens only with positive or negative pressures, thus effectively preventing spontaneous reflux of blood or inadvertent air embolism (1, 2). More recently, new valved devices have been developed, with different types of valves, positioned distally or proximally (PASV and others) (3). A multinational group of investigators has decided to clinically assess a new distally-valved catheter, connected to a totally implantable device (Celsite, from B. Braun Aesculap), in a group of oncology patients undergoing chemotherapy, so to verify its safety and viability, as well as its clinical performance. Our paper presents the main results of this phase IV study.
Material, patients and methods
Patients
This project was structured as a phase IV multicenter study. Hospitalized adults (ages 18-80 years) who had solid tumors and were candidate for intravenous chemotherapy were considered eligible for the study. The only criteria for exclusion were: evidence of ongoing infection, coagulation abnormalities (defined as a platelet count lower than 50,000 ml, and/or prothrombin time longer than 18 seconds), or inability to provide an informed consent.
Catheters
One single type of port was used (built of titanium, plastic and silicone rubber) attached to a silicone distally valved catheter (both manufactured by B. Braun Aesculap). The valve – positioned just at the tip of the catheter – is an original, specific 4-sided valve, completely different from the 3-position Groshong valve, which is laterally positioned, closed to the tip.
Insertion and maintenance of ports
Each investigator was allowed to adopt different approaches to central vein access, in agreement with the local institutional policy and/or personal experience. Upright chest X-ray was routinely performed after implantation and a hard copy was included in each case report form; all relevant data regarding implantation and follow-up were also entered into the form, which was mailed to a coordinating center (G. Chevillon, B. Braun Medical, France) and stored in a software database for statistical analysis.
Case information was divided into 4 main sections:
1. General information and catheter implantation;
2. First treatment cycle;
3. Second treatment cycle;
4. Subsequent treatment cycle and end of follow-up.
Information included: patients’ population characteristics, implantation technique, procedure-related events, position of the catheter tip (as documented by X-ray), comments regarding catheter implantation, chemotherapy treatment protocols (drugs and duration), details about the device use (needles, infusion, blood sampling, rinsing of the port after infusion), and final comments of the investigators on overall device features and performance.
Statistics
Data were stored by simple entry (data entry performed and visually controlled by an experienced medical doctor) on Microsoft AccessTM and analyzed with UNISTAT 5.0 statistical package (4 Shirland Mews, London, UK). Data were descriptively presented: percentages for categorical parameters, means, median, standard deviation and extremes for continuous variables. No statistical comparison or subgroup analysis were performed.
RESULTS
General information and implantation procedure. Fifty patients were included in this study by 6 participating centers during a 11-month period (October 2000 to September 2001). Milano (Italy), Namur (Belgium) and Pontoise (France) enrolled 10 patients each, whereas Rome (Italy), Metz (France) and Boulogne (France) studied 9, 8 and 3 patients respectively. Characteristics of patients’ population and underlying diseases are detailed in Table I and II.
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Table I
Characteristics of patients’ population
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Table II
Underlying disease
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Indication for device implantation was chemotherapy in all cases but one (non-malignant esophageal stricture, Tab. II). Forty devices were implanted in the operating theatre; one case was treated in an outpatient clinic setting; in nine cases, the port was implanted in a day-hospital setting. The most frequently used entry sites were the left (26%) and the right (20%) subclavian vein (Tab. III).
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Table III
Entry sites for central venous cannulation
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With regards to the implantation technique, Seldinger’s method was applied in 40 cases (80%), while a surgical cut-down approach was used in the remaining 10 cases (20%). Catheter was considered easy to place through the peelable sheath and to connect to port in 44 cases out of 50 (88%); intraoperative fluoroscopic control of catheter positioning was adopted in 35 cases.
Clinically-relevant complications during insertion were reported in 5 patients (10%); two of these were catheter-related (Tab. IV), while two others were puncture problems and the last one was a rhythm disturbance observed during implantation (atrial fibrillation; heart rate = 200 bpm).
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Table IV
Complications during insertion
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Catheter tip position – as esteemed by postoperative upright chest X-ray – was at the junction of the superior vena cava (SVC) and right atrium in 48 cases (96%); in two cases, the tip was positioned in the middle third of the SVC. Relevant comments from the investigators regarding the device’s features and implantation-related problems are detailed in Table V.
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Table V
Comments of the investigators regarding catheter’s features during implantation
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Treatment cycles
First treatment
In most cases (68%), the port was used within 1 week after implantation. In all patients, the skin around the port pocket was normal. Blood sampling through the device was attempted in 43 patients; in 39 cases (91%), it appeared to be easy and suitable for hematological test. Investigators from different centers reported 4 cases of inability to draw blood samples for absence of venous return (so called ‘withdrawal occlusion’), and 4 cases of intermittent difficult aspiration. No catheter occlusion occurred.
Second treatment
The interval between the first and the second cycle was 4-30 days. One patient complained of pain at the port location, without further details. In all cases, the skin around the port pocket was normal. Blood sampling through the device was attempted in 39 patients; blood withdrawal was easy in 36 cases (92%) and suitable for hematological test in 30 (77%). Investigators reported 3 cases of inability to draw blood samples for absence of venous return, and 4 cases of intermittent difficult aspiration. Again, no catheter occlusion was detected.
Subsequent treatment cycle
Since the first use of the device, 2 to 3 treatments have been administered in 90% of the cases (mean: 2.8 ± 0.7). The interval between cycles was 1-30 days (21 days in 50% of the cases). One patient complained of pain at the port location, without further details. In all cases but one, the skin around the port pocket was reported as normal. Blood sampling through the device was attempted in 37 patients; sampling was easy in 34 cases (92%) and suitable for hematological test in 29 (78%). Investigators reported 3 cases of inability to draw blood samples for absence of venous return, and 2 case of intermittent difficult aspiration. No catheter occlusion occurred.
End of follow-up
Duration of follow-up was documented in 31 cases; ranging from 28 to 155 days (mean 84.9 ± 29.2 days), and one to 7 treatment cycles were administered. Table VI summarizes the management problems faced during ports’ use.
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Table VI
Problems in ports’ management during follow-up
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DISCUSSION
Many patients suffering from malignant diseases require long-term central venous access for safe administration of chemotherapy, transfusion of blood products, parenteral nutrition and/or for blood testing. In most patients, totally implantable access ports are a trouble-free, well functioning device, since: a) they do not require external dressing; b) do not interfere with patient’s social activities, and c) require minimal maintainance – monthly flushes of heparinized saline – to keep the catheter patent (4, 5).
A subcutaneous port can be connected to either an open-ended or a valved catheter. The valve is usually located at or near the distal tip, and its main theoretical advantage is to avoid blood reflux and inadvertent air embolism. Obviously this feature is more likely to improve the patient’s safety when the catheter is externally tunneled than when connected to a subcutaneous port. Nevertheless, a three-position, pressure-sensitive valve is theoretically able to positively affect the performance of a totally implantable device, as it may avoid spontaneous blood reflux, thus limiting the occurrence of blood deposits inside the catheter and catheter obstruction.
In spite of thousands of clinical applications and a 20-year experience, technical aspects and clinical features of central venous valved catheters are far from being completely understood and investigated. The “gold standard” for these catheters is surely the Groshong’s device, until a few years ago the sole commercially available. Developed in 1978, it has been investigated by a number of research groups in the world (6- 8).
The results of these studies about Groshong valved catheters are substantially confirmed by the present report, in which a non-Groshong valved catheter was investigated.
In our multicenter study, we noted very few insertion-related complications; as expected, they were not related to the specific type of device implanted. No major intraoperative complications occurred. Some minor problems related to catheter’s handling were noted but it is most likely that they could be minimized after a proper learning curve completion (the device was absolutely new to all investigators).
On the other hand, follow-up of catheter performance detected a small but significant incidence of catheter malfunction.
Catheter malfunction may be considered one of the worst complications for the patients undergoing chemotherapy, significantly affecting their quality of life, as it can lead to undesired events, such as: a) multiple venipunctures for blood testing; b) use of peripheral catheters for hydration or drug administration, and possibly c) positioning of a new central venous access. Early catheter malfunction is almost always a progressive inability to draw blood for laboratory test or for confirmation of the intravascular tip placement (so called withdrawal occlusion, which may be persistent or transient), and it is related to the presence of a fibrin sleeve adhering to the catheter’s tip. If the fibrin sheath progresses and completely encompasses the catheter, it may lead to complete catheter obstruction. Though in our present study complete occlusion of the line never occurred, still we detected a significant incidence of withdrawal occlusion, particularly after 2 cycles of treatment, so that blood withdrawal for hematology tests was inadequate in 23% of cases. These figures are similar to those reported in a previous randomized trial of central venous ports connected to open-ended vs. Groshong catheters in adult oncology patients (9). From this and other reports in the literature, it is clear that a major problem of any distally valved catheter is inability to draw blood samples (in about 20% of cases), particularly when the catheter is left in situ for prolonged time. This complication is not unique of valved devices, since it occurs – even if less frequently – also in open-ended catheters.
The cause of withdrawal occlusion is unclear: It may be secondary to dysfunction of the valve (“ball-valve effect”) (10, 11); however, recent experimental studies do not entirely support this contention (12). Based on laboratory tests and ultrastructural analysis of 16 explanted Groshong catheters, Campisi and co-workers showed that the withdrawal occlusion cannot be related to a single cause and certainly not to abnormality of silicone bio-stability or valve morphology. They found that the inability to obtain blood samples is more probably related to the presence of intraluminal deposits (clots were present in all the catheters examined) and/or fibrin sleeve on the external catheter surface. The laterally placed Groshong valve could in fact promote the formation of fibrin links between the catheter and vein wall, thus realizing an external flap-valve. For this reason, these authors recommended that the catheter tip should be positioned in the right atrium, one centimeter below the junction with the superior vena cava (SVC). This advice is in agreement with many clinical observations, suggesting that a higher position of the catheter’s tip in the SVC is related to much higher incidence of long-term catheter dysfunction (13).
Nonetheless, such explanation is not easily applied to the catheter malfunction we observed in the present study, since we were dealing with a 4-sided, non-Groshong valve placed just at the tip of the catheter. Nonetheless, it is possible that intraluminal clots or extensive fibrin sleeve might affect the function even of this kind of valve.
It is interesting to stress that in this study there was no correlation between position of the tip and catheter malfunction. Two catheters had their tip in the middle third of the superior vena cava, i.e. higher than usually recommended, but they showed no malfunction.
Also, there were two cases of early malfunction of the valve (inability to draw blood), detected during insertion: in one of these cases, the malfunction was transient, in the other it was persistent for the whole length of the follow-up. In such cases, other explanations – such as some structural problem of the valve or an abnormal position of the valve in relation to the venous wall – should be taken into consideration.
In conclusion, this phase IV study shows that the tested port, attached to a distally valved catheter, is reliable, safe and practical for long-term treatment of an oncology patients’ population undergoing chemotherapy. Nonetheless, persistent or transient withdrawal occlusion, with consequent inability to draw viable blood samples, was a major concern in its clinical use: this was in agreement with other reports and clinical trials, mostly investigating other types of valved catheters, such as the Groshong device. The explanation for catheter malfunction is unclear: fibrin sleeve, intraluminal clots, position of the tip of the catheter, as well as structural features of the valve, may all play a role. Despite significant recent advances, further studies are required for a better understanding of the underlying mechanism of this clinical problem.
ACKNOWLEDGEMENTS
Devices have been provided by B.Braun Medical-France. Authors gratefully thank G. Chevillon – Director of Clinical Research B. Braun Medical – for his assistance and technical support.
Reprint requests to:
Roberto Biffi, MD
Department of Surgery
European Institute of Oncology
Via Ripamonti, 435
20141 Milano, Italy
e-mail: Roberto.Biffi@ieo.it
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