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Crit Care Nurse 2002 Jun; 22(3): 57-63
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Cardiovascular Medicine

Reteplase: Nursing Implications for Catheter-Directed Thrombolytic Therapy for Peripheral Vascular Occlusions

Michelle E. Bussard, RN, MSN, CCRN

Michelle E. Bussard is an adult clinical nurse specialist. She currently works in a medical-surgical intensive care unit at St. John West Shore Hospital in Westlake, Ohio. She has been a registered nurse for 6 years.

To purchase reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 809-2273 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, reprints{at}aacn.org.

Athrombus is defined as an accumulation of platelets, fibrin, and other clotting factors that lodges in an artery or a vein and occludes blood flow.1(p1193),2 Blood coagulation occurs via both intrinsic and extrinsic pathways (Figure 1Go). Four conditions can cause a thrombus: venous stasis, vessel damage or injury, inflammation, and hypercoagulability.2,5 Deep venous thrombosis causes pain and swelling in the affected extremity, and the thrombus can dislodge and can lead to a potentially fatal pulmonary embolism.2,6 Arterial occlusion can lead to pain and ischemia and potentially to amputation because of the lack of arterial blood flow distal to the occlusion.2



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  		Figure 1 Blood coagulation pathways.3(p586),4

 
Because of the seriousness of peripheral vascular occlusions, prompt treatment is critical. Traditionally, patients with deep venous thrombosis have been treated with intravenous infusions of heparin and then with oral warfarin after discharge from the hospital.7 Patients with arterial occlusions have undergone surgery for removal of the clot or been treated with the thrombolytic agents urokinase or streptokinase.8 The Food and Drug Administration (FDA) recently rescinded approval for use of urokinase in the United States because of difficulties in manufacturing the drug.2,8–15 Consequently, streptokinase is now the only thrombolytic agent approved by the FDA for treatment of peripheral vascular occlusion. However, because of the low efficacy, poor predictability, and potential for hemorrhagic complications of streptokinase, physicians use other thrombolytic agents such as alteplase and reteplase to treat peripheral vascular occlusion.14 The nursing literature provides little information about these medications. In this article, I review catheter-directed thrombolytic therapy with reteplase (Retavase) for peripheral arterial and venous occlusions. Brief descriptions of alteplase and streptokinase are also provided.

The traditional agents used for arterial and venous thrombolysis are streptokinase, urokinase, and alteplase; the primary drug of choice is urokinase.9,10,14 In 1999, as mentioned earlier, the FDA rescinded approval of urokinase because the screening for viral vectors was inadequate.9

Streptokinase is currently the only FDA-approved thrombolytic agent for treatment of peripheral vascular occlusion.14 Streptokinase is a plasminogen activator; cleavage (or activation) of plasminogen by the enzyme produces plasmin,2 the enzyme needed for clot lysis.14 Because the predictability of lysis with streptokinase is low, and the drug tends to cause substantial bleeding and is less effective than are other thrombolytic agents, it is not often used to treat peripheral vascular occlusion.12 The half-life of streptokinase is 25 minutes, and its lytic action can last 6 hours.2

Alteplase is a thrombolytic agent currently being used to treat peripheral vascular occlusion; however, it is not FDA approved. Success has been reported for use of alteplase for catheter-directed therapy,8 but optimal dosing is unknown. Alteplase is a weak plasminogen activator when fibrin is absent. However, with increased doses of alteplase, plasmin is formed from the circulating plasminogen. The increased levels of plasmin lead to fibrin breakdown and, therefore, clot lysis.14 The half-life of alteplase is 4 to 6 minutes, with elimination in approximately 35 minutes.14

Reteplase has been used to treat coronary thrombosis for several years, and its use in the treatment of peripheral vascular occlusion has recently been investigated.9,14 Laird et al10 studied 2 patients with occlusions of peripheral arteries. After catheter-directed thrombolytic therapy with reteplase, 1 patient had complete thrombolysis (full clot lysis), and the other patient had partial thrombolysis (partial clot lysis).

Comerota et al16 compared the health-related quality of life between patients who received catheter-directed thrombolytic therapy and patients who received heparin therapy to treat iliofemoral deep venous thrombosis. The patients who received catheter-directed thrombolytic therapy had a better quality of life than did the patients who received heparin therapy.

Davidian et al9 studied 15 patients with acute peripheral arterial occlusions. Catheter-directed thrombolytic therapy with reteplase had a 73% success rate for thrombolysis. One patient died of a retroperitoneal hemorrhage. Ouriel et al13 studied 37 patients with venous and arterial peripheral occlusions. Catheter-directed thrombolytic therapy with reteplase resulted in complete thrombolysis in 33 patients (89%) and partial thrombolysis in 4 patients (11%). Patients in that study experienced no adverse effects.

The studies just cited included a total of 54 patients with peripheral vascular occlusions. Total lysis (success) occurred in 83% of the patients, and the complication rate was 11%. All of these studies were limited by the small sample sizes. Further medical and pharmacotherapeutic research must be done to determine the optimal dosage of reteplase, the optimal duration of reteplase infusion, and whether concurrent peripheral infusion of heparin is necessary . None of the published studies described nursing interventions or actions for catheter-directed thrombolytic therapy with reteplase (Table 1Go).


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  		Table 1 Summary of published studies related to use of reteplase for peripheral vascular occlusions

 
RETEPLASE

Reteplase is a plasminogen activator that generates plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus.2,9,13,4 Unlike other thrombolytic agents, which bind to the fibrin matrix and accumulate on the surface of the thrombus, reteplase penetrates the thrombus and destroys the fibrin matrix, steps that enhance lytic action2 (Figure 2Go). The half-life of reteplase is 13 to 16 minutes, with a terminal half-life of approximately 170 minutes.19



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  		Figure 2 Pathways to thrombosis.

 
Reteplase infusions are given at a rate of 0.5 to 2 U/h, for a mean duration of 21 hours.13 The infusion is given via a catheter that is inserted in the extremity opposite the thrombus during angiographic studies. This technique is called catheter-directed thrombolytic therapy. The catheter is threaded through the opposite extremity to the affected extremity (eg, if the thrombus is in the right popliteal artery, the catheter is threaded through the left femoral artery and is positioned directly above the thrombus). With this placement, the thrombolytic agent can be injected directly into the thrombus, facilitating lysis of the clot. With the catheter-directed approach, the systemic concentration of the thrombolytic agent and the dosage required are decreased, thus decreasing hemorrhagic complications.7

The catheter may be a single-lumen or a coaxial (double-lumen) system. The dose of reteplase depends on the type of catheter used . With a single - lumen CDDT indicates catheter-directed thrombolytic therapy. catheter, a full dose of reteplase is infused , where as with the coaxial system, the dose is split equally between the lumens. A continuous infusion of a low dose or a full dose of heparin may also be used during the reteplase infusion. Many studies7,9,10,12–14,17 have shown that use of heparin facilitates clot lysis and continued lysis after the reteplase infusion is completed. The cost of a 2 0 - unit vial of reteplase is approximately $2150.14 Contraindications to the use of reteplase are listed in Table 2Go.


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  		Table 2 Contraindications for thrombolytic therapy with reteplase16,19

 
NURSING CONSIDERATIONS

Patients undergoing catheter-directed thrombolytic therapy with reteplase are admitted to the intensive care unit for monitoring for hemorrhagic complications. A nurse begins the continuous infusion of reteplase via the catheter immediately after the patient is admitted. A bolus of heparin is given, and a peripheral intravenous infusion of heparin is started.

Because intracranial hemorrhage is a major complication of thrombolytic therapy (with an overall risk of 1%),7 a neurological examination must be done every hour. Maintaining a blood pressure less than 180/110 mm Hg helps prevent intracranial hemorrhage.19 Retroperitoneal hemorrhage is also a complication that can lead to hypotension and/or death (with an overall risk of 0.3%).7 A physician should be notified immediately if the patient complains of severe back pain.

Heparin and reteplase are not compatible and thus should not be administered via the same tubing.20 Currently, neither the optimal duration nor the optimal dose of reteplase in catheter-directed therapy is known. Table 3Go indicates nursing interventions for many of the potential adverse reactions that can occur during catheter-directed thrombolytic therapy with reteplase. Figure 3Go is an example of a hospital’s standard order set for patients undergoing catheter-directed thrombolytic therapy with reteplase.


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  		Table 3 Nursing considerations for patients receiving catheter-directed thrombolytic therapy with reteplase acute lower extremity arterial occlusions.

 


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  		Figure 3 Sample thrombolytic orders

 
SUMMARY

Several studies since 1998 have shown the efficacy of catheter-directed thrombolytic therapy with reteplase. Reteplase is a plasminogen activator that penetrates the thrombus and causes lysis.2,9,13,14 This catheter-directed approach has been used to treat both arterial and venous occlusions, with a success rate of 72% to 88%. The most serious complication associated with thrombolytic therapy is intracranial hemorrhage. Patients should be admitted to the intensive care unit for monitoring of neurological status, vital signs, laboratory values (hematocrit, hemoglobin level, activated partial thromboplastin time, and fibrinogen concentration), and bleeding or oozing at puncture sites. Staff nurses in the intensive care unit must be aware of this important thrombolytic therapy, its indications, and its implications for nursing interventions.

References

  1. Anderson K, Anderson L . Mosby’ s Pocket Dictionary of Medicine, Nursing, and Allied Health. 3rd ed. St Louis, Mo: Mosby-Year Book; 1998.
  2. Curzen N, Haque R, Timmis A. Applications of thrombolytic therapy. Intensive Care Med. 1998;24:756–768.[Medline]
  3. Urban N, Greenlee K, Krumberger J, et al. Guidelines for Critical Care Nursing. St Louis, Mo: CV Mosby; 1995.
  4. Brockington C, Lyden P. Criteria for selection of older patients for thrombolytic therapy. Clin Geriatr Med. 1999; 15:721–739.[Medline]
  5. Gorman P, Davis K, Donnelly R. Swollen lower limb: general assessment and deep vein thrombosis. BMJ. 2000;320: 1453–1456.[Free Full Text]
  6. Catalano J. American Nursing Review for Critical Care Nursing Certification. 2nd ed. Springhouse, Pa: Springhouse Corp; 1998.
  7. Kandarpa K. Catheter-directed thrombol-ysis of peripheral arterial occlusions and deep vein thrombosis. Thromb Haemost. 1999;82:987–996.[Medline]
  8. Semba C, Murphy TP, Bakal CW, Calis KA, Matalon TA. Thrombolytic therapy with use of alteplase (rt-PA) in peripheral arterial occlusive disease: review of the clinical literature. J Vasc Interv Radiol. 2000;11:149–161.[Medline]
  9. Davidian MM, Powell A, Benenati JF, Katzen BT, Becker GJ, Zemel G. Initial results of reteplase in the treatment of J Vasc Interv Radiol. 2000;11:289–294.[Medline]
  10. Laird JR, Dangas G, Jaff M, Satler LF, Mehran R, Leon MB. Intra-arterial reteplase of the treatment of acute limb ischemia. J Invasive Cardiol. 1999;11: 757–762.[Medline]
  11. Ouriel K, Gray B, Clair DG, Olin J. Complications associated with the use of urokinase and recombinant tissue plasminogen activator for catheter-directed peripheral arterial and venous thrombolysis. J Vasc Interv Radiol . 2000;11:295–298.[Medline]
  12. Ouriel K. Initial experience with Retavase (reteplase) for arterial and venous applications. Paper presented at: International Symposium on Endovascular Therapy; January 23–27, 2000; Miami, Fla.
  13. Ouriel K, Katzen B, Mewissen M, et al. Reteplase in the treatment of peripheral arterial and venous occlusions: a pilot study. J Vasc Interv Radiol. 2000;11:849–854.[Medline]
  14. Valji K. Evolving strategies for thrombolytic therapy of peripheral vascular occlusions. J Vasc Interv Radiol. 2000; 11:411–420.[Medline]
  15. Laird JR. Pharmacologic therapies in the treatment of peripheral vascular disease: clinical experience with reteplase, a third-generation thrombolytic. J Invasive Cardiol. 2000;12(suppl B);27B–32B.
  16. Comerota AJ, Throm RC, Mathias SD, Haughton S, Mewissen M. Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life. J Vasc Surg. 2000;32:130–137.[Medline]
  17. Fischer S, Kohnert U. Major mechanistic differences explain the higher clot lysis potency of reteplase over alteplase: lack of fibrin binding is an advantage for bolus application of fibrin-specific thrombolytics. Fibrinolysis Proteolysis. 1997;11:129–135.
  18. Colman RW, Marder VJ, Salzman EW, et al. Overview of hemostasis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed. Philadelphia, Pa: JB Lippincott; 1994.
  19. Clinical Pharmacology, 2000. Gold Standard Multimedia Network Web site. Customized monograph: reteplase. Available at: http://www.gsm.com. Accessed January 28, 2001.
  20. Reteplase. Dimens Crit Care Nurs. November-December 1999;18:23.




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