Dealing with a nemesis: Handling cath occlusions
By Lynn Hadaway, MEd, RNC, CRNI
President, Hadaway and Associates
Milner, GA
Occlusions of central venous catheters remain a serious challenge to clinical practice, especially when the catheter must be used for multiple therapies over extended periods of time. Occlusions can be categorized into three major groups — mechanical, precipitate, and thrombus.
Mechanical occlusions include pinch-off syndrome, catheter tips positioned against the vein wall, and numerous external problems, such as tight sutures. Precipitate is caused by contact between drugs or minerals that are incompatible, usually leading to changes in the pH and creating a precipitate inside the lumen. Thrombotic causes include the development of thrombus and fibrin accumulation inside the catheter lumen and around the catheter inside the vein.
The frequency of catheter-related thrombosis ranges from 3% to 70%.1 This wide variation is caused by the lack of standard definitions for assessing and diagnosing the problem. The problem includes occlusion of the blood flow in the vein around the catheter and occlusion of the catheter lumen.
Immediately following the catheter insertion, proteins accumulate on the catheter wall and develop into fibrin. The catheter can become completely encased in a fibrin sheath or have a fibrin tail or flap that acts like a valve closing the lumen on aspiration. Thrombus can form on the vein wall, on the catheter wall, or both. Venous blood flow is slowed, causing edema and discomfort distal to the site of the thrombus. Many studies link vein thrombi with catheter-related infection.2
Proper catheter flushing
Thrombus forms inside the catheter because of blood reflux into the lumen. Reflux occurs from changes in intrathoracic pressure — changes that happen during coughing, sneezing, heavy lifting, or in the presence of congestive heart failure. Reflux also occurs when catheter flushing is performed without the use of positive pressure techniques. Needleless systems leave a small, dead space inside the injection cap. When the system is disconnected from the cap, the fluid flushed into the catheter refluxes to fill this space, causing blood to reflux into the catheter’s internal tip. This reflux does not allow the blood to mix with the heparinized saline solution. Over time, we notice greater resistance when the catheter is flushed.
Many patients with central venous catheters also have hypercoaguable states. Hypercoaguability comes from disease processes such as cancer and diabetes. Pregnancy, use of oral contraceptives, and cigarette smoking also cause hypercoaguability. Your patient may have congenital clotting problems — such as deficiencies of antithrombin III, proteins C and S — plasma proteins that prevent abnormal clotting from occurring. However, the connection between those congenital problems and the incidence of catheter-related thrombus has not been confirmed.
One strategy for managing those problems is removing and replacing the catheter; however, this can be expensive and painful for the patient. Attempts to salvage the catheter or restore its patency are frequently successful. When the problem is caused by thrombus or fibrin, urokinase (Abbokinase, Abbott Laboratories), a drug made from human kidney cells, has become the drug of choice. Over the past year, there has been concern about the potential contamination of urokinase and manufacturing deficiencies. Until those problems are resolved, Abbott can no longer distribute the drug.
New choices
The shortage of urokinase drove the need to look at other drugs to restore catheter and vein patency. Because of clinical experience and published studies, our focus has shifted to streptokinase and alteplase. Although the streptokinase drug literature includes "occlusion of arteriovenous cannulae" as an indication, many question the drug for this use. Streptokinase is made from a protein in the streptococcus bacteria and is known to be an antigen in humans, producing allergic and anaphylactic reactions. Therefore, treatment should not be repeated more than every six months, and there is serious concern about using it in the home care setting.
Alteplase is a recombinant-tissue plasminogen activator that binds to the fibrin in a blood clot to break it down. In 1994, Haire et al published a study demonstrating the effectiveness of this drug for catheter clearance. Fifty patients with radiographic confirmed occlusions were randomized and treated with urokinase 10,000 units (n = 22) or alteplase 2 mg (n = 28). In the alteplase-treated group, patency was restored in 89% (22/28), while the urokinase group had 59% (13/22) restored.3
Currently, the FDA has approved the use of alteplase (Activase; Genentech) for acute myocardial infarction, acute ischemic stroke, and acute massive pulmonary embolism. Although clearing occluded central venous catheters is not an FDA-approved indication at this time, use of alteplase for this purpose is growing. Dosage for the labeled indications ranges from 50 mg to 100 mg while the dosage being used for catheter clearance is 2 mg. The most common protocol is alteplase 2 mg in 2 ml allowed to remain in the lumen undisturbed for two hours, then aspirated using familiar de-clotting procedures. The drug half-life is between four to six minutes. Small doses, properly instilled into the catheter lumen and aspirated suggest that bleeding problems are unlikely.4
In addition to the challenge from the lack of FDA-approved labeling, there are also limitations from the current packaging of Alteplase. It is a sterile, preservative-free, lyophilized powder in 50 mg or 100 mg vials. Drug wasting, contamination, and costs are major concerns when a small dose is needed. Many pharmacies are now dividing the 50 mg vial into syringes filled with 2 mg in 2 ml and freezing until needed. A recently published study demonstrated bioactivity in polypropylene containers such as syringes at 20° C for up to six months; glass vials at 70° C for up to two weeks; and glass vials at 20° C for up to one month.5
Prevent the problem
Many questions are yet to be answered in clearing catheter occlusions caused by thrombus or fibrin. The return of urokinase to the market is unknown at the present time, so clinical trials are necessary to determine the optimal dose and dwell time of alteplase. We also need to confirm the most appropriate dose and infusion criteria of alteplase to treat venous thrombosis surrounding the catheter. Future studies will lead to the necessary FDA-approved language for using alteplase for catheter clearance and the packaging of alteplase in unit doses.
Rather than finding the best solution to resolve catheter-related thrombi, we must direct our attention to prevention of these problems. Prevention methods fall into four categories:
1. Use of prophylactic warfarin. Studies have shown a decrease in catheter-related thrombus formation when Coumadin 1 mg per day was given.6
2. Proper positioning of central venous catheters. Catheter tips should be positioned in the lower third of the superior vena cava (SVC) to ensure that the catheter will lie parallel to the vein wall and avoid impinging on the wall. Catheter tips placed distal to the SVC, also known as midclavicular catheters, have been associated with a four-fold greater risk of venous thrombosis.7,8
3. Use of appropriate flushing techniques. Positive-pressure flushing techniques prevent blood reflux into the catheter lumen. Perform this procedure by withdrawing the blunt cannula as the last .5 ml of solution is flushed into the injection cap or by closing a clamp on the catheter extension set before disconnecting the flush syringe. Using a push-pause flushing technique creates turbulence in the lumen to aid in removal of blood products. Following blood administration or sampling, flush with 20 ml to 30 ml of preservative-free saline.
4. Use technological advances to overcome blood reflux problems. Valved catheters are designed to prevent the backflow of blood into the catheter lumen. (Groshong, Bard Inc.; PASV Catheters by Catheter Innovations Inc.)
Continuous flushing solutions (One-Step KVO, I-Flow Corp.) eliminate the need for immediate flushing when the drug has infused.
New designs of needleless injection systems overcome the problem of blood reflux by returning a small fluid volume to the catheter tip. (CLC2000 by ICU Medical Inc; Posi-Flow by Becton-Dickinson Inc.; UltraSite by B. Braun Inc.)
Many facilities have chosen to use alteplase for declotting catheter lumens, while others prefer to wait for the appropriate FDA-labeling and more convenient unit-of-use packaging. Appropriate flushing techniques combined with improved technology can decrease the incidence of catheter-related thrombus, although thrombolytic agents will still be needed.
References
1. Lowell J, Bothe A. Central venous catheter-related thrombosis. Surg Oncol Clin N Am 1995; 4:479-492.
2. Raad I, Luna M, Khalil S. The relationship between the thrombotic and infectious complications of central venous catheters. JAMA 1994; 271:1,014-1,016.
3. Haire W, et al. Urokinase vs. recombinant tissue plasminogen activator in thrombosed central venous catheters: A double-blinded, randomized trial. Thromb Haemost 1994; 72:543-547.
4. Calis K, Herbst S, Sidawy E. Management of Central Venous Catheter Occlusions: The Emerging Eole of Alteplase. Littleton, CO: Postgraduate Institute for Medicine; 1999.
5. Calis K, Cullinane A, Horne M. Bioactivity of cryopreserved alteplase solutions. Am J Health Syst Pharm 1999; 56:2,056-2,057.
6. Bern MM, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. Ann Intern Med 1990; 112:423-428.
7. Kearns PJ, Coleman S, Wehner JH. Complications of long arm catheters: A randomized trial of central vs. peripheral tip location. JPEN J Parenter Enteral Nutr 1996; 20:20-24.
8. NAVAN Position Paper. Tip location of peripherally inserted central catheters. JVAD 1998; 3:2.
Need More Information?
Lynn Hadaway, MEd, RNC, CRNI, President, Hadaway and Associates, P.O. Box 10, Milner, GA 30257. Telephone: (770) 358-7861. Fax: (770) 358-6793.
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