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New Options for Catheter Occlusion
Barbara McKinnon, PharmD
For individuals living with a “lifeline” or vascular access device (VAD), catheter occlusion is among the most frequent complications encountered. Until recently, most home care consumers and clinicians knew just what to do: after ruling out mechanical complications, urokinase for catheter clearance was the drug of choice for empiric treatment of catheter occlusion. All that changed last year when the Food and Drug Administration (FDA) removed urokinase for catheter clearance from distribution due to manufacturing-related issues. While no FDA-approved drug is currently available for treating catheter occlusions, new treatment options are emerging. Commercially available products approved for other uses are being specially prepared for use in catheter occlusion, and preliminary clinical observations are very promising.
Although the drugs used for catheter occlusion have changed, the basic process of assessing the occlusion to identify clues as to its possible cause is still an essential component of appropriate treatment. Catheter obstruction can be detected by the inability to infuse TPN or other solutions through the catheter without undue pressure.
If the catheter is occluded, the first step should be to rule out any obvious external causes. Mechanical occlusions are caused by physical factors that occlude the flow of fluid. Causes can be as simple as leaving the tubing clamped, kinks or knots in the tubing, or sitting or standing on the tubing. Don’t forget to check the pump, as pump malfunction and catheter occlusion are easily confused, especially when trying to explain the problem to a clinician over the phone. Many a home care company has sent out a replacement pump after repeated “high pressure” or “occlusion” alarms occurred, only to find out later that the problems were caused by an occluded catheter. Internal causes of mechanical obstruction include internal malposition of the catheter, internal kinks in the tubing course, or catheter pinch-off syndrome. In general, catheters that are completely occluded and will not permit the infusion of fluids, are likely to be obstructed mechanically; however, extensive precipitates or clot cannot be ruled out (1).
Precipitates are caused by the incompatibility of drugs, minerals, or other substances, causing the formation of particles. These particles, or precipitates, can clump and accumulate in the catheter, blocking the flow of fluid. Clues that precipitates may be the cause of an occlusion include occlusions that occur shortly after the infusion of a drug, or the appearance of particles of solid material in the solution bag or tubing. Treatment for precipitates should be discussed with your physician.
Thrombotic (blood clot) occlusion
Immediately following the insertion of a central venous catheter, thrombus and fibrin begin to accumulate inside the catheter lumen and around the outside of the catheter inside the vein. The outside of the catheter can become completely enclosed in fibrin. (Also known as a fibrin sheath, this sheath may extend beyond the tip of the catheter like a soft extension of the tube or pseudo catheter). Thrombus forms inside the catheter due to blood backup into the lumen or inner catheter space. This is more likely if the catheter is used for routine blood drawing.
Many HomePN consumers have experienced situations when solutions infuse just fine through the catheter, but blood cannot be withdrawn. This is known as a withdrawal occlusion. Usually we can’t tell clinically whether a withdrawal occlusion is due to a collapse of the soft walls of the catheter or obstruction by the fibrin extension wafting over the catheter tip. In the majority of cases, withdrawal occlusion is the result of a fibrin sheath(1).
If an obvious cause of the occlusion is detected, treatment should be directed at correcting the problem. However, in most cases, treatment of catheter occlusion is empiric, meaning we try the treatment which has the best chance for success and see if it works. Because thrombosis is the most common cause of catheter occlusion, initial treatment is directed at dissolving clot. While this can be accomplished by replacing the device, restoring its patency without removing the line is the preferred approach for most homePN patients who depend on their lifeline for fluids and nutrients, and want to preserve all access sites for as long as possible.
Thrombolytics are drugs that dissolve the thrombus and can restore the catheter’s function. Urokinase for catheter clearance is the only drug approved by the FDA for the treatment of occluded catheters. However, since its distribution has been halted, alternative agents must be used. Three other commercially available thrombolytic agents, streptokinase, alteplase, and reteplase, have been used to treat occluded central venous catheters.
Streptokinase is a thrombolytic agent that is made from a protein secreted by the streptococcus bacteria; for this reason, some humans who have previously experienced a streptococcal infection such as a strep throat may experience allergic reactions to this product. To minimize the risk of reactions, treatment should not be repeated more than once every six months. Because homePN consumers may experience catheter occlusion more frequently than every six months, and because of the risk of a reaction in the home, streptokinase is not recommended for use except in the hospital setting. Recently, the manufacturer of streptokinase has issued a letter reporting a number of serious adverse events associated with the use of streptokinase in catheter clearance. The letter urges health care providers to consider the risk before using the product for the management of occluded central venous catheters(2).
Alteplase (tissue plasminogen activator, TPA)
Alteplase is a recombinant tissue plasminogen activator that binds to the fibrin in the bloodstream to break it down. As early as l990, investigators reported that doses of 2 mg/2cc of alteplase were effective in the treatment of occluded central venous catheters that failed treatment with urokinase(3). In 1994, Haire et. al. treated thrombosed central venous catheters with doses of either 2 mg. alteplase or 10,000 units of urokinase. In the alteplase treated group, 89% of catheters (22/28) were successfully cleared, while in the urokinase group, 59% (13/22) of catheter occlusions resolved(4).
Although it has long been recognized that alteplase is an effective treatment for occluded catheters, it never became popular because of the impracticalities associated with using it. Alteplase requires refrigerated storage, and it must be reconstituted prior to use. Additionally, since catheter clearance required only a 2 mg. dosage, the 50 mg. vial size it was distributed in was costly and wasteful for this purpose. (In contrast, when urokinase for catheter clearance was available, it came in a vial size tailored for use in catheter clearance, and it could be reconstituted easily by pressing the top of its specially designed vial. Urokinase could also be stored at room temperature, making it ideal to keep in the home for TPN consumers who periodically required treatment for catheter occlusion.)
Once urokinase for catheter clearance was no longer available, clinicians re-examined the existing data about the use of alteplase and came up with a new way of using it. Since alteplase is not available in a size appropriate for catheter clearance doses, pharmacists began reconstituting the product and making multiple doses out of each 50 mg. vial and freezing them for later use. Alteplase 1 mg/mL may be stable for up to six months when stored in polypropylene tubes at -20°C(5). When stored in plastic syringes and frozen, 2 mg/ml doses have been reported to be stable for 30 days(6). Once thawed to room temperature, the alteplase doses should be used within 24 hours(6).
Currently, clinicians are investigating the optimal use of alteplase for catheter clearance. Various doses from 0.5 mg. to 2 mg., and dwell times from 30 minutes to several hours have been used anecdotally. Additionally, the Genentech company is currently conducting a randomized, double-blind, placebo controlled trial of the efficacy and safety of a 2 mg/mL alteplase dose for catheter clearance.
Reteplase is a recombinant thrombolytic agent that has been used for clearance of central venous access catheters. Doses of 0.5 to 1.0 U of reteplase have been instilled into the catheter with dwell times of 15 minutes. Reconstituted reteplase solutions have been frozen in Becton Dickinson Tuberculin syringes in doses of 0.5 mg/0.5 mL at -8°C. No significant changes in activity or physical characteristics of the product were noted with frozen storage for up to 5 weeks. After thawing to room temperature, the reteplase solution should be used within 4 hours(7). Centocor, a manufacturer of reteplase, reports that doses of 0.25 to 0.4 U are being investigated for catheter clearance.
Until an FDA-approved product is available for treatment of catheter occlusion, we must continue to try to prevent catheter occlusion whenever possible(8). Several prevention strategies may be helpful.
Warfarin, also known as Coumadin®, is a blood-thinning drug that helps to prevent clots from forming. Low doses of warfarin, such as 1 mg. per day, have been shown to be effective in preventing thrombosis of central venous catheters(9,10). This small dose does not prolong clotting tests and therefore does not require frequent blood test monitoring.
Positive pressure flushing
Positive pressure flushing techniques prevent blood reflux into the catheter lumen, and can help minimize the risk of thrombus forming within the catheter. This can be accomplished by either withdrawing the cannula as the last 0.5 mL of solution is flushed into the injection cap, or by closing the clamp on the catheter extension set before disconnecting the flush syringe. Flushing with 20-30 mL of saline following blood draws may be helpful as well, since blood draws cause fibrin and platelets to accumulate on the inside of the catheter(8).
A number of new products have been designed to minimize problems with blood backup into the catheter. These include special valved catheters, continuous flushing solutions, and new designs of needleless systems(8).
As our experience grows with using new drugs and products to prevent and treat catheter occlusion, we hope homePN consumers will be able to use these new advances to manage their catheters independently (at home) with the goal of minimizing complications and enhancing their quality of life.
1. Stevens LC, Haire WD, Kotulak GD. Are clinical signs accurate indicators of the cause of central venous catheter occlusion? J Parenteral Enteral Nutrition. 1995; 19: 75-79.
2. Neil G. Important safety information. http://www.fda.gov/medwatch/safety/1999/strept.htm.
3. Atkinson JB, Bagnall HA, Gomperts E. Investigational use of tissue plasminogen activator (t-PA) for occluded central venous catheters. J Parenteral Enteral Nutrition. 1990; 14: 310-1.
4. Haire WD, Atkinson JB, Stephens LC, et al. Urokinase versus recombinant tissue plasminogen activator in thrombosed central venous catheters: a double-blinded, randomized trial. Thrombosis and Haemostasis. 1994: 72: 543-7.
5. Calis KA, Cullinane AM, Horne MK. Bioactivity of cryopreserved alteplase solutions. Am J Health-System Pharmacy. 1999; 56: 2056-7.
6. Grewing R, Mester U, Low M. Clinical experience with tissue plasminogen actovator stored at -20¡ C. Ophthalmic Surgery. 1992: 23: 780-1.
7. Data on file, Centocor, Inc.
8. Hadaway L. Dealing with a nemesis: handling cath occlusions. Home Infusion Therapy Management. 2000; 8: 6-8.
9. Bern MM, Bothe A, Bistrian B, et al. Prophylaxis against central vein thrombosis with low-dose warfarin. Surgery. 1986; 99: 216-20.
10. Bern MM, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. Ann Intern Med. 1990; 112: 423-8.
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