December 2008, Volume 12, Number 6



Restoring Patency to Central Venous Access Devices

Cynthia Cummings-Winfield, BScN, CON(C), and Tayreez Mushani-Kanji, RN, BScN, CON(C), CHPCN(C)



In September 2006, the Oncology Nursing Advisory Board met to discuss the current management of central venous access device (CVAD) occlusions for patients receiving cancer treatment in centers across Canada. The board found inconsistency in practice across the country and advocated for the development of evidence-based, standardized guidelines for the use of thrombolytic agents to clear thrombotic occlusions. PubMed was searched for articles related to catheter occlusion, catheter patency, and catheter complications published from 1997–2007. The board compared institutional and published protocols for thrombolytic treatment of occluded CVADs, in light of a systematic, evidence-based review of the literature on CVAD-related complications. Restoration of CVAD patency, when appropriate, represents a safe, effective, and cost-effective alternative to device replacement and improves patient quality of life. The treatment algorithm presented in this article reflects the board’s consensus recommendations for managing thrombotic CVAD occlusions in adult patients with cancer.


At a Glance


·         Central venous access is critical for many patients with cancer for delivery of treatment and supportive care.

·         Replacing dysfunctional central venous access devices (CVAD) is expensive and invasive; therefore, steps to prevent or resolve thrombotic occlusions are essential.

·         Evidence-based guidelines for managing thrombotic CVAD occlusions support oncology nursing practice, promote positive patient outcomes, and reduce costs associated with device replacement.


Access to venous circulation is critical for many patients with cancer. Treatment regimens can be complicated, often requiring repeated and reliable venous access. In oncology practice, the most common indication for placing a central venous access device (CVAD) is the delivery of chemotherapeutic medications. However, the same device may be used for the administration of supportive therapies (e.g., antibiotics, antiemetics), blood products, and nutritional supplementation (Wingerter, 2003). CVADs also may be used for withdrawal of blood samples (Wingerter).


Medications and nutrients instilled directly through wide-bore catheters into the superior vena cava can be delivered more efficiently and in larger volumes than would be possible via the peripheral circulation. Fluids instilled into the major veins become diluted rapidly as they emerge from the catheter lumen. This allows for safe and comfortable administration of concentrated solutions, vesicants, or irritants without pain or damage to the vessel wall and with minimal risk of extravasation and chemical phlebitis (Dudrick, 2006). However, CVADs have the potential for complications such as thrombotic occlusion, which can lead to treatment delays and affect patient quality of life (Moureau, Poole, Murdock, Gray, & Semba, 2002).


Patients With Cancer and Central Venous Access Devices


According to the World Health Organization, cancer prevalence is increasing globally, and cancer now is classified under the framework of chronic diseases (Cancer Care Ontario, 2007; Grunfeld, 2006). Given the complexity and intensity of cancer treatment, long-term central vascular access is a priority for an increasing number of patients. Indeed, an estimated five million CVADs are placed every year in the United States alone (Maki, Stolz, Wheeler, & Mermel, 1997). Although that statistic includes other patient groups that require long-term venous access (e.g., individuals with renal failure requiring hemodialysis), the number of patients with cancer with CVADs is undoubtedly large.


CVADs are inserted with the expectation that they will function until the need for central venous access has passed. Some classes of CVAD can be expected to last more than 18 months (Galloway & Bodenham, 2004); however, many devices are removed prematurely because of a variety of common complications (Galloway & Bodenham).


Replacing a dysfunctional CVAD is an expensive and, in many cases, invasive procedure with some inherent risk to the patient. Replacement usually requires a new venous access site and may necessitate surgical or radiologic consultation and sedation, as well as the risk of complications associated with central venous cannulation (Jacobs, Haygood, & Hingl, 2001). Salvaging a device may be quicker than replacing it and may avoid delays in treatment. The cost of device replacement (estimated at $850–$1,500, depending in part on the type of CVAD) greatly exceeds that of salvage (Kokotis, 2005). Although the cost of salvage can encompass chair time, a declotting agent, and nursing time, those things intuitively pale in comparison to the cost of replacing a CVAD, which can include interventional radiology time, diagnostic imaging, nursing time, and the price of a new access device. In addition to financial costs, catheter replacement can pose a clinical risk and affect patients’ quality of life.  Therefore, nurses and physicians should take appropriate steps to prevent CVAD complications and to salvage dysfunctional CVADs when possible. In particular, thrombolytic treatment is recommended for restoring the patency of devices occluded by fibrin or blood clots.


Selection of a Central Venous Access Device


CVADs all share a common characteristic of terminating in the distal third of the superior vena cava. The devices fall into multiple categories, distinguished by whether they allow one or more solutions to be administered separately (single-, double-, or multiple-lumen catheters) and by other aspects of their designs that determine how and where they are inserted into the venous circulation and how the devices are used. For instance, catheters, which allow for external access through one or more exposed lumens, should be distinguished from ports, which are implanted under the skin and must be accessed via a special noncoring needle. The type of CVAD used should be chosen based on a variety of considerations, including prescribed therapy, duration of therapy, physical assessment, patient health history, support system and resources, device availability, and patient preference (Registered Nurses Association of Ontario [RNAO], 2004).


CVADs used in oncology include implanted ports and nonimplanted catheters. The latter group of devices includes central venous catheters, which usually are tunneled through subcutaneous tissue, and peripherally inserted central catheters (PICCs), which are inserted into the major veins of the arm (Galloway & Bodenham, 2004).


Implanted Ports


Implanted ports consist of a fluid reservoir with a puncturable septum implanted subcutaneously (see Figure 1) and are best suited to long-term therapy (Galloway & Bodenham, 2004). The devices require surgical or radiologic placement and removal.


Nonimplanted Central Venous Access Devices


Nonimplanted CVADs may be tunneled or nontunneled. Tunneled CVADs (see Figure 2) are placed through subcutaneous tissue, with an exit site on the chest or abdominal wall and the tip resting in the superior vena cava (RNAO, 2004). The device contains a dacron cuff, which allows for stabilization of the catheter in the subcutaneous tissue and prevents superficial infection (Galloway & Bodenham, 2004). Such catheters require surgical or radiologic insertion, typically into the jugular or subclavian vein or inferior vena cava, and are appropriate for longer-term therapy.

Nontunneled CVADs (PICCs) typically are placed via the cephalic, basilic, or median cubital veins, sparing other sites of venous access (Galloway & Bodenham, 2004) (see Figure 3). PICCs are the least invasive of all CVADs but contain a narrow lumen, which is associated with a greater risk of occlusion than other CVADs. PICCs are associated with a relatively low risk of infection (RNAO, 2004).


Complications Related to Central Venous Access Devices


Numerous complications can arise directly from central vein cannulation; however, the incidence of such complications is difficult to ascertain. Acute complications include pneumothorax, hemothorax, embolization, and cardiac tamponade. Healthcare professionals must recognize such complications by their signs and symptoms and take necessary action, should they occur.

Common complications associated with CVADs include, but are not limited to, infection at the insertion site or within the bloodstream (bacteremia or sepsis, the most severe complication), phlebitis (mechanical or chemical), or extravasation (Hamilton, 2006a). Mechanical obstruction may occur, including pinch-off syndrome, in which the catheter tunneled between the first rib and the clavicle becomes compressed between those bones or the catheter kinks or is improperly positioned (Galloway & Bodenham, 2004; Jacobs, 2003; Kerner, Garcia-Careaga, Fisher, & Poole, 2006). In addition, the device itself may malfunction or be obstructed by a retaining suture that is too tight.


Catheter occlusion can result from extraluminal or intraluminal complications. Extraluminal complications include persistent withdrawal occlusion such that infusion of solutions is possible but aspiration of blood is not possible because of a fibrin sheath. Sluggish infusion of solution and sluggish withdrawal of blood may be caused by an extraluminal fibrin tail. In addition, a mural thrombus can form when fibrin from the injured vessel wall binds to fibrin covering the catheter surface (Forauer & Theoharis, 2003). Intraluminal occlusions may be the result of drug precipitates when incompatible medications are infused through the same catheter lumen without proper flushing. Lipid residues also can build up in an internal catheter lumen. Finally, intraluminal thrombotic occlusions can occur.


A large-scale study analyzed complications of CVADs used for outpatient home infusion therapy in patients with varying diagnoses, including a small percentage of patients with cancer. Among approximately 50,000 patients (> 2.5 million catheter days), the most common complication observed was loss of patency (CVAD dysfunction from blockage). In particular, nonthrombotic blockage was the single most common cause of loss of patency observed (Moureau et al., 2002), followed by thrombotic blockage and infection. However, not all kinds of CVADs were at equal risk of the different complications. For instance, tunneled CVADs were at relatively high risk of infection but low risk of thrombosis compared with PICCs (Moureau et al.) (see Figure 4).


Astute nursing assessment strategies are required to determine the probable causes of CVAD complications. Once a nurse has identified the cause, he or she must take appropriate actions to salvage venous access. If mechanical and chemical causes are ruled out, empirical treatment with a thrombolytic agent should be attempted. Published guidelines from the Oncology Nursing Society (2004) and the RNAO (2005) support the practice of early intervention to troubleshoot and resolve CVAD occlusions. The guidelines presented in this article are directed specifically at the management of thrombotic occlusions in CVADs.


Causes and Consequences of Thrombotic Occlusions


Thrombotic occlusions occur when blood or blood elements accumulate within, surrounding, or at the tip of catheters (Jacobs, 2003). Patients may be at heightened risk of thrombosis because of hypercoagulability because of “tumor cell activation of clotting, vessel wall injury, and stasis” (Prandoni, Piccioli, & Griolami, 1999, p. 437) or because of their chemotherapeutic regimens (Jacobs). As well, blood may reflux into a catheter tip as a result of changes in intrathoracic pressure during violent sneezing, coughing, or vomiting (Wingerter, 2003). However, in many cases, CVAD occlusion can be attributed directly to poor infusion technique, specifically to failure to flush lines properly or to use a locking solution appropriate to the device. Incorrect procedure when disconnecting a positive or negative displacement device from a line can have the same effect (Hadaway, 2005).


After blood withdrawal, a CVAD must not be allowed to stand without fluid flow or minimal infusion rates (keep the vein open) (Wingerter, 2003) but must be actively flushed with a solution such as 0.9% saline. Push-pause instillation, involving frequent stopping-staring of the flushing solution, should be used to create turbulent flow within the line (Hamilton, 2006b; RNAO, 2005).


In general, thrombi can cause three distinct forms of occlusion that impair fluid instillation, withdrawal, or both. In a withdrawal (ball-valve) occlusion, fluids can be instilled but blood cannot be withdrawn without resistance. Withdrawal occlusions occur because of insoluble proteins (thrombi or fibrin tails) extending from the catheter tip (see Figure 5). They are pulled over and cover the catheter tip as blood flows into the catheter—a so-called ball-valve effect. Partial or incomplete occlusion results in sluggish instillation or withdrawal of blood. A complete catheter occlusion restricts fluid instillation and blood withdrawal. Figure 6 shows different classes of thrombotic occlusion.


Finally, thrombotic material can accumulate inside a port to create a so-called reverse ball-valve effect, blocking instillation while allowing withdrawal.


Safety and Efficacy of Thrombolytic Treatment


The first report showing that a thrombolytic agent could be used to clear an occluded CVAD (Hurtubise, Bottino, Lawson, & McCredie, 1980) employed streptokinase, an enzyme that is no longer widely used for that purpose (Valji, 2000). For some time, urokinase-type plasminogen activator (u-PA) became the standard of care for that indication. Because of concerns about possible contaminating pathogens in the u-PA available at the time, however, the agent was withdrawn from the market in 1999 (Valji). In its place, clinics now use a different recombinant enzyme, tissue-type plasminogen activator (t-PA, or alteplase, marketed for that purpose as Cathflo® Activase® [Genentech, Inc.]). Unlike the other agents, t-PA binds avidly and specifically to fibrin, one of the major components of a blood clot. t-PA causes thrombolysis by activating plasminogen (present in the circulation and the clot) to generate plasmin, which breaks apart the fibrin protein, thus dissolving the clot (see Figure 7). Anticoagulant agents such as heparin are ineffective against existing clots and cannot be used to restore patency to occluded CVADs (Fedan, 2003).


Clinical Evidence


In a head-to-head trial, t-PA (alteplase) was shown to be more effective at clearing thrombotic occlusions than nonrecombinant u-PA (Haire, Atkinson, Stephens, & Kotulak, 1994). A newer, recombinant form of u-PA (Abbokinase®, Microbix Biosystems Inc.) has been developed and is expected to be similar to the nonrecombinant form but without the potential contamination risks (Haire et al., 2004). Other agents that could be used for that purpose are being studied (Liu, Jain, Shields, & Heilbrun, 2004; Moll et al., 2006). Alteplase is approved in Canada and the United States for restoring CVAD patency (Genentech, Inc., 2003). Therefore, all recommendations for thrombolytic treatment in this article relate to alteplase.


Safety of Alteplase Treatment of Occluded Central Venous Access Devices


When alteplase is used for CVAD clearance (as with Cathflo), the concentration in the circulation does not reach pharmacologic levels. Any alteplase released into the circulation is metabolized rapidly by the liver (plasma half-life less than five minutes). Therefore, systemic complications such as bleeding and intracranial hemorrhage are not anticipated. In clinical trials of adult and pediatric patients, no such events have been attributed to alteplase treatment (Blaney et al., 2006; Deitcher et al., 2002). Two cases of major hemorrhage were observed but were not considered to be related to t-PA treatment (Deitcher et al.). Alteplase has not been studied in patients known to be at risk for bleeding.


Therefore, alteplase should be used with caution in patients with known or suspected CVAD infection. In situ decontamination of CVADs has been reported, but device removal should be considered when evidence of CVAD-related infection exists, particularly Staphylococcus aureus bacteremia or candidemia (Galloway & Bodenham, 2004).


Alteplase should be used with caution in patients with thrombocytopenia, other hemostatic defects, or any condition for which bleeding constitutes a significant hazard or would be particularly difficult to manage, as well as with patients who are at high risk for embolic complications. Caution should be exercised with patients who have active internal bleeding or who have had any of the following within 48 hours: surgery, obstetrical delivery, percutaneous biopsy of viscera or deep tissues, or puncture of noncompressible vessels (Middleton & Ruzevick, 2004). Alteplase is contraindicated in patients with known hypersensitivity to the drug or any component of its formulation (e.g., alteplase, L-arginine, phosphoric acid, polysorbate-80) (Genentech, Inc., 2003).


Efficacy in Central Venous Access Device Clearance


The efficacy of alteplase in clearing occluded CVADs has been reported to be 87%–90% (Deitcher et al., 2002; Journeycake & Buchanan, 2006; Ponec et al., 2001). In the various efficacy studies, treatment was applied as many as two times, for one to two hours at each application. The largest of the studies was the Cardiovascular Thrombolytic to Open Occluded Lines–2 (COOL-2) interventional trial (N = 995), which showed 87% efficacy (Deitcher et al.). A subanalysis of the COOL-2 data focusing on the 242 patients with PICCs showed still higher levels of treatment success—93% on a cumulative basis when treated as many as two times (see Figure 8) (Ng, Li, Tu, & Semba, 2004).


The published clinical trials with alteplase have excluded patients with complete CVAD occlusions, when instilling the specified volume of fluid to treat the occlusion was not possible. However, a recent trial of recombinant u-PA has been reported in which totally occluded lines were treated successfully with a variation on the normal CVAD instillation procedure (Haire et al., 2004; Horne, 2004; Kerner et al., 2006). The alternate procedure, requiring a three-way stopcock, is used widely in infusion clinics and has been described extensively (Hamilton, 2006b; Infusion Nurses Society, 2006; Ottawa Hospital, 2006). The standard instillation method (for partial occlusions) and alternate (stopcock) method (for total occlusions) are described in Figures 9 and 10.


Restoration of Patency


Institutional Protocols for Treatment of Thrombotic Occlusions


Depending on institutional policies, RNs may require competency validation to manage occluded CVADs. Institutional policies also direct whether a physician’s order or a medical directive is required to proceed with a CVAD clearance protocol. An institutional protocol should outline the procedure for the number of instillations and dwell times and whether diagnostic imaging is required.


Reconstituting Alteplase


Alteplase is provided in sterile vials and must be reconstituted immediately before use. When stored at 2°C–30°C (36°F–86°F), it may be used for intracatheter instillation within eight hours of reconstitution. To reconstitute Cathflo, inject 2.2 ml of sterile water for injection, USP, into the vial, directing the diluent stream into the alteplase powder. Slight foaming is not unusual. Let the vial stand undisturbed to allow large bubbles to dissipate. Mix by gently swirling until the contents are completely dissolved. Complete dissolution should occur within three minutes. Do not shake. The reconstituted preparation results in a colorless to pale yellow transparent solution containing 1 mg/ml alteplase at a pH of approximately 7.3 (Genentech, Inc., 2003).


Instillation Procedure


In adult patients, as much as 2 ml of the reconstituted alteplase should be instilled per occluded catheter lumen. However, ascertaining the fill volume for the particular CVAD requiring alteplase instillation is essential. The appropriate method for instillation should be determined by whether the CVAD is partially or completely occluded. For an incomplete occlusion, follow the standard protocol for treating incomplete or withdrawal occlusions (see Figure 9). In the case of a complete catheter occlusion, follow the alternate (stopcock) protocol (see Figures 10 and 11).


Figure 12 presents an algorithm for restoring CVAD patency. The procedure is technically simpler as well as more effective if applied before a CVAD is fully occluded (Shen et al., 2003). Clots that persist for more than seven days become relatively resistant to thrombolytic treatment (Steiger, 2006). Therefore, thrombotic occlusions should be treated as soon as they are identified.


Introducing Standardized Procedures to an Oncology Practice


Institutions are encouraged to adopt these guidelines for managing thrombotic CVAD occlusions. Implementing new clinical practice guidelines can be complex, in part because of the number of multidisciplinary groups that may be affected in a particular practice setting (RNAO, 2002). In general, the process requires commitment at multiple levels within an institution to establish “buy-in” from administrators and patient educators, as well as nurses and physicians in different clinical practice groups. The range of existing practices must be determined, along with the educational and skill-development needs of team members, followed by the design of appropriate educational materials and training to support the integration of clinical practice guidelines. The authors suggest evaluating parameters of change resulting from implementation of clinical practice guidelines, including quality of patient care, patient satisfaction, nursing satisfaction, and cost of care.


Evaluation of clinical practice guidelines should be based on objective, quantifiable measures when possible. Thus, in a review of the effects of implementing the guidelines discussed in this article, changes from baseline should be determined for the number of partial and complete CVAD occlusions, thrombolytic agent dwell time, the number and severity of CVAD-related infections, the number and type of CVADs replaced or removed prematurely, the number of consultations with staff pharmacists, nursing time and costs related to materials, and surgery and clinical consultation time. The outcomes should be revisited at regular intervals as infusion nursing practices evolve.


Implications for Nursing Practice


Nurses require astute assessment skills and sound clinical judgment to identify and successfully manage CVAD complications. They are in a unique position to advocate for and adopt into practice evidence-based clinical practice guidelines to support the management of CVADs. As members of a multidisciplinary team, nurses are important links in the chain of patient care. Economic exigencies, the current nursing shortage, the chronicity of cancer, and the ever-increasing complexity of treatment are driving forces that compel nurses to develop in-depth knowledge of CVAD management. Positive patient outcomes are demonstrated by completion of therapy free of complications and patient satisfaction with care (RNAO, 2005).  Table 1 provides a summary of recommendations regarding CVAD occlusions.




Central venous access is crucial to the delivery of cancer therapy. Proper assessment, use, and maintenance of CVADs prevent treatment delays, as well as potentially life-threatening complications. Restoration of CVAD patency, when appropriate, represents a cost-effective alternative to device replacement and improves patient quality of life. Thrombotic occlusion, a common complication of CVAD use, can be resolved safely and effectively with the thrombolytic treatment procedures described in this article. The procedures, based on best clinical evidence, should be standardized in oncology practice so that they can be implemented consistently and evaluated regularly at all centers where CVADs are used.




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Cynthia Cummings-Winfield, BScN, CON(C), is the coordinator for nursing research and professional practice development, and Tayreez Mushani-Kanji, RN, BScN, CON(C), CHPCN(C), is a staff development instructor, both at Cross Cancer Institute in Edmonton, Canada. The authors gratefully acknowledge Hoffman La-Roche Ltd., manufacturers of Alteplase/Cathflo®. The company’s support was instrumental in identifying clinical leaders in oncology to develop these guidelines and for securing John Ashkenas, PhD, Script Medical Writing, to assist in manuscript development. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. (Submitted July 2008. Accepted for publication July 23, 2008.)


Author Contact: Cynthia Cummings-Winfield, BScN, CON(C), can be reached at, with copy to editor at


Digital Object Identifier:10.1188/08.CJON.925-934