Central Venous Access for Chemotherapy

Michael B. Nicholl

Paul S. Dale

Despite remarkable achievements in cancer prevention, detection, and treatment, cancer is still the second leading cause of death in the United States. In the year 2010, 1.5 million Americans will be diagnosed with cancer.¹ Although patients with early-stage, solid malignancies may not require chemotherapy, those patients with advanced stage disease will often elect to receive therapeutic or palliative chemotherapy. Those patients with hematogenous malignancies are also very likely to require chemotherapy to achieve remission.

The ability to gain and maintain long-term central venous access has been a challenge since the introduction of intravenous (IV) chemotherapy. For many years, the only venous access option was single use peripheral venipuncture, a severe limitation to patient care. Innovations in surgical technique and medical technology have resulted in the ability to administer chemotherapy via long-term central venous access devices (CVAD). Patients receiving chemotherapy also require frequent phlebotomy to monitor treatment-related toxicity. The apprehension and discomfort associated with peripheral blood draws are relieved when central venous access also functions for phlebotomy.²

Short-term peripheral access was the only venous access option until cannulation of the subclavian vein was first described in 1956 by Keeri-Szanto.³ This breakthrough paper demonstrated the feasibility of subclavian vein cannulation in human cadavers and lead to the adoption of the technique for living patients; however, there were many limitations. The technique could be only intermittently and sparingly used because the only vascular access devices were short-term, single-use long stainless steel needles. Access of the subclavian vein required repeated sticks, which were difficult and proved to be uncomfortable for patients. Indwelling, long-term access catheters had not yet been developed.

Long-term central venous access became a reality with the introduction of indwelling silicone catheters. In 1973, Broviac et al.⁴ reported placement of a felt-cuffed, subcutaneously tunneled silicone catheter with its tip placed in the superior vena cava. Silicone, a durable and malleable polymer, was a major advancement in catheter technology. The felt cuff was designed to be left in the subcutaneous fat allowing tissue ingrowth and reducing the chance of accidental removal. The most frequent indication for central venous access in this era was nutritional support via infusion of total parenteral nutrition (TPN). Studies supporting the benefits of TPN resulted in increased utilization of the Hickman catheter.⁵ Tunneled central venous catheters became a lifeline in many patients, but there was a trade-off. These early catheters required frequent nursing care, were intrusive to an active lifestyle, and infection of the catheter and exit site were a common complication requiring catheter removal and replacement.

The feasibility of central venous access for chemotherapy improved when a long-term catheter was introduced by Hickman et al.⁶ This catheter had a larger bore than previously used catheters and had a Dacron cuff located at the exit site of the catheter at the skin. Ingrowths of tissue into the Dacron cuff served as a barrier against skin flora and resulted in a lower infection rate than previous indwelling catheters. The Hickman catheter was a durable long-term option for central venous access. However, care of these catheters required frequent dressing changes and flushing with heparin to keep them patent. Often the patient’s family or caregivers could perform this care after educational instruction. These new large bore catheters were also well-suited for withdrawing blood for laboratory studies, which was an added convenience. The Hickman catheter was the preferred device for central venous access until the introduction of totally implantable devices in the early 1980s.

The first totally implantable port was first described by Niederhuber.⁷ These devices were developed for long-term venous and arterial access. Once implanted, the port was accessed by a needle stick through the skin, perforating the centrally located self-sealing silicone rubber septum. The subcutaneous port was connected to a silastic catheter, which was tunneled to the subclavian vein with the tip in the superior vena cava. These long-term ports were ideal for infusion of chemotherapy, blood, platelets, plasma, and hyperalimentation solutions with minimal complications. Once the infusion was finished, the port was flushed with heparin and the needle was removed, allowing the patient to resume normal activity. These totally implantable subcutaneous ports quickly became the preferred access route for long-term central venous access and remain so even now. Although the basic design remains essentially unchanged, newer port systems have undergone significant improvements with new biomaterials making ports that are smaller, capable of undergoing MRI studies, and can remain in place for indefinite period.

Central venous access has become commonplace in hospitalized patients and in the outpatient setting. Placement of CVADs is relatively safe and allows rapid infusion of large volumes of fluid or medication, which is essential in critically ill patients. Table 27-1 provides a sample of currently available CVADs and their applications.

Table 27-1 Types of Catheter Available

Acute care central lines for short-term inpatient access
	Hohn triple lumen
	Swan-Ganz
	Cordis
	PICCs for short- or long-term access
Implanted ports for long-term central venous access
	Port-a-cath
	Bard ports
Tunneled catheters for long-term outpatient access
	Groshong
	Cook
	Hickman
	Broviac
Central venous catheters for hemodialysis

PATIENT SELECTION

Each patient will present with a unique set of circumstances determining their need for long-term IV access. Applying a team approach with discussion of each among medical oncology, surgery, and nursing staff will provide optimal use of central venous access options. The treatment team must evaluate each patient individually for his or her need of central venous access, giving strong consideration to the most appropriate device and route of access. Not all patients scheduled to undergo chemotherapy will require central venous access. Chemotherapeutic agents with little or no vesicant effect on the peripheral veins can be delivered safely with peripheral venous access, whereas effective orally administered agents are becoming more commonplace.

Active patients requiring frequent or prolonged chemotherapy infusions should be considered for a totally implantable central venous access catheter.⁸ Patients who require outpatient continuous infusion will benefit from tunneled external devices, which allow easy access to the catheter in an outpatient setting. Chemotherapy, cancer-related nausea and emesis, or diarrhea can cause patients to become severely dehydrated or malnourished, requiring long-term fluid replacement. Patients who require repeated blood or blood product transfusion, antibiotics, or other medications in addition to chemotherapy will also benefit from long-term central venous access. Table 27-2 lists common indications for CVAD placement.

CVADs may be safely placed while patients are undergoing concurrent chemotherapy in most cases. However, special consideration should be given to patients receiving antivascular endothelial growth factor therapy, in particular bevacizumab. Bevacizumab has potent effects on wound healing and has been associated with wound dehiscence, failure of wound healing, and skin erosion.⁹^,¹⁰ Implantable CVADs may be contraindi cated in patients actively receiving this drug.

Table 27-2 Common Indications for Central Venous Access

Frequent or prolonged chemotherapy infusion

Continuous infusion chemotherapy

Infusion of chemotherapy caustic for peripheral veins

Hematologic malignancy requiring frequent blood products

Frequent or prolonged IV hydration

Prolonged administration of IV medication

Hyperalimentation

Limited or no peripheral access sites

PERIPHERALLY INSERTED CENTRAL CATHETERS

Peripherally inserted central catheters (PICCs) offer patients the advantage of central venous access without undergoing direct central venous puncture.¹¹ PICC lines are silastic cath eters inserted through a peripheral vein, either at the bedside or in the interventional radiology suite, and advanced into the central venous system. In many institutions, they are placed at the bedside by specialized nursing teams with training in PICC line placement. Patient discomfort during insertion is minimal and insertion complications are rare.

PICC lines are most often used in patients with short or intermediate (2 to 3 weeks) treatment requirements; however, they may be used for long-term care, especially in patients requiring continuous infusion therapy. They may also provide a bridge for long-term central venous access while treating a catheter-related infection. The utilization of PICC lines is most frequent in the pediatric population and patients receiving IV antibiotics.¹² For patients requiring a shorter duration of central venous access or with limited sites of peripheral access, a PICC line is a good option. For patients with clotting abnormalities, which might contraindicate attempts at deep central venous sticks, a PICC line is a good alternative for central venous access.

PICC lines must be used judiciously because there are significant disadvantages and complications associated with their use. The essential requirement for PICC placement is peripheral vein cannulation, which may be very difficult in this group of patients who have likely had numerous previous peripheral sticks. PICC lines require frequent nursing care for dressing change and catheter flushing with heparinized saline solution to maintain patency.⁷ Owing to their smaller lumen, blood withdrawal is difficult through the PICC line and attempts
can result in catheter occlusion. The major complication profile associated with PICC are similar to those associated with long-term CVADs (sepsis, thrombosis, blockage, and leakage); however, rates of these complications may be higher with PICC lines than in long-term central venous access.¹³ Thrombotic complications are a special concern because they may occur in up to 38% of patients with upper extremity PICC lines.¹⁴ The high complication rates have caused some clinicians to recommended caution when PICC lines are placed in patients with solid tumors.¹⁵

SURGICAL INSERTION OF CENTRAL VENOUS ACCESS DEVICES

Temporary central venous access, such as a triple lumen or cordis catheters, can be obtained through a percutaneous approach at the bedside. The surgical insertion of long-term central venous catheters has classically been performed in the operating room by surgeons. For years, patients underwent general anesthesia for central venous device insertion in the operating room. Currently, most patients are able to have insertion with local lidocaine infiltration with or without conscious IV sedation. For more apprehensive patients or patients with comorbid conditions, an anesthesia consultation for monitored anesthesia care or general anesthesia should be considered. An apprehensive, uncooperative patient on the operating table can significantly increase the surgical risks and rescheduling with additional anesthesia is appropriate.

CVADs can also be inserted in the interventional radiology suite by trained interventional radiologists. This was first described in 1993, and since that time studies have confirmed that this approach is as safe as and may be more cost effective than placement in the operating room.¹⁶^,¹⁷ Whether central venous access is obtained in the operating room or the radiology suite can vary according to radiology availability, local standards, and patient choice. Patient comfort and safety should be the primary concern, guiding the placement of CVADs.

Classically, the preferred site for central venous access was the subclavian vein. The left subclavian vein has a direct approach to the superior vena cava with a gentle arch through the innominate vein. The pleura of the left lung is anatomically more superior to the right and may be associated with an increased risk of pneumothorax. Subclavian vein placement may also be associated with catheter pinch-off syndrome and catheter fracture.¹⁸ Now, with improved safety of venipuncture introduced with ultrasound guidance, the internal jugular (IJ) vein is strongly recommended.¹⁹ Sarzo et al.²⁰ described their experience with totally implantable devices utilizing the surgical cut-down technique through the cephalic vein in 105 oncology patients. The cephalic vein can be localized at the deltoid-pectoral groove with minimal dissection in most patients. Utilizing this cut-down approach might be of benefit in patients with clotting abnormalities, which contraindicate deep central venous sticks. More recent randomized data derived exclusively from cancer patients suggest that the site of placement has little effect on early or late complications.²¹

Those patients with known superior cava thrombosis will not be candidates for either the subclavian, IJ, or cephalic vein approach, and alternative approaches to the central venous system must be sought. Patients with chest wall disease, a thrombosed superior vena cava, scaring from prior ports or surgical procedures, or planned surgical procedures involving the upper torso or head and neck should also be considered for alternative routes of access. The most common alternative for central venous access is the femoral vein. The femoral vein can be cannulated through a percutaneous stick or a cut-down approach through the saphenous vein. Wolosker et al.²² reported their experience with totally implantable femoral vein catheters in their cancer patients. This approach was only required in 20/560 (3.5%) patients undergoing totally implanted catheter insertion. The subcutaneous ports were implanted in the lower abdominal wall tissue. Only two devices required removal because of infection. The rest were utilized for the full course of therapy and removed or the patient expired during therapy. Bertoglio et al.²³ reported their experience with femoral vein catheters in 465 cancer patients. Forty-one (8.8%) patients were not candidates for subclavian or jugular vein cannulation because of the extent of disease or other indications. They reported no difference in complication rates between the two groups and also concluded that the femoral vein approach is a good alternative for central venous access in patients who are not candidates for upper torso access. For patients with limited access to the central venous system, the femoral vein approach is a safe and convenient alternative.

A particularly challenging situation is encountered in those patients with caval occlusion limiting central venous access through the more accessible central venous approaches. Kenney et al.²⁴ first reported utilizing the lumbar veins for central venous access in an adult in 1985. In this original report, the lumbar veins were accessed by the percutaneous approach and the catheter was then threaded into the patent inferior vena cava (IVC). Direct percutaneous cannulation of the IVC was performed and described by Denny et al.²⁵ with access obtained in the L2-3 region of the IVC. More recent reports, especially in the pediatric population, describe the percutaneous cannulation of the lumbar or hepatic portion of the IVC for long-term venous access. Azizkhan et al.²⁶ reported their experience with 11 pediatric patients who had their IVC percutaneously accessed in the angiography suite utilizing ultrasonography to identify the patient portion of the IVC. Their complication rates relating to placement was minimal, and the catheters performed similar to those with standard placement approaches. The right gonadal vein has also been described as a viable route of central venous cannulation.²⁷^,²⁸ A laparotomy is required to access the gonadal vein. Fortunately, most patients are candidates for the more traditional approaches of central venous access; however, knowledge of these alternative approaches is beneficial.

The technical approach for the insertion of a CVAD can vary according to the device being used, tunneled versus implanted, and the operating surgeon’s or radiologist’s personal preference. Insertion should be performed under sterile conditions.
Most vascular access devices are packaged with all of the instrumentation required for insertion. This improvement in packaging reduces intraoperative confusion and storage space.

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