ANNE ARUNDEL MEDICAL CENTER CRITICAL CARE MEDICATION MANUAL DEPARTMENT OF NURSING AND PHARMACY Guidelines for Use of Intravenous Tissue Plasminogen Activator (tPA), Activase® in the Treatment of ACUTE PULMONARY EMBOLISM

Major Indications

Acute Ischemic Stroke (see section in this manual titled Guideline for Use of tPA in the Treatment of Acute Ischemic Stroke). Acute Myocardial Infarction (see section in this manual titled Guidelines for Use of tPA in the Treatment of Acute Myocardial Infarction) Acute Pulmonary Embolism tPA is indicated in the treatment of acute management of confirmed massive pulmonary embolism (PE) in adults: • lysis of acute pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments of the lungs • lysis of pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Mechanism of Action tPA acts as a thrombolytic agent by promoting the direct conversion of plasminogen to plasmin which then acts directly on fibrin in clots to promote clot dissolution.

Patient Selection Guidelines for TPA in Acute Pulmonary Embolism tPA is recommended for treatment in patients with symptoms consistent with acute massive pulmonary embolism who have: • • • •

confirmed massive pulmonary embolism clinical right sided heart failure or pulmonary hypertension secondary to acute pulmonary embolism OR arterial hypotension/cardiogenic shock/circulatory collapse related to acute pulmonary embolism no contraindications to thrombolytic therapy (see below)

Contraindications • • • • • •

Active internal bleeding History of cerebrovascular accident Recent intracranial or intra-spinal surgery or trauma Intracranial neoplasm, arteriovenous malformation, or aneurysm Known bleeding diathesis Severe uncontrolled hypertension

Precautions / Relative Contraindications Risk of bleeding may be increased in the following situations: • Hypertension (SBP>175, DBP>110) • Recent GI or GU bleed (within previous 21 days) • Recent major surgery (6 weeks) • Recent trauma • Age > 77 yrs • Cerebrovascular disease • Likelihood of left heart thrombus • Subacute bacterial endocarditis • Acute Pericarditis • Hemostatic defects • Significant Hepatic Dysfunction • Pregnancy • Septic thrombophlebitis • Hemorrhagic ophthalmic conditions • Oral anticoagulation • Any condition where bleeding represents a hazard or is at a difficult location to manage

Adverse Reactions 1. Bleeding, both internal, including intracranial hemorrhage, and superficial. The risk of bleeding can be minimized by careful patient selection, following monitoring guidelines below, and using the nursing guidelines for the care of anticoagulated patients. 2. Cholesterol embolization 3. Phlebitis

Special Administration and Monitoring Guidelines for TPA in PE 1. Proper patient selection is essential - see Patient Selection Guidelines. Each patient being considered for therapy with tPA should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. 2. Follow general nursing guidelines for care of the anticoagulated patient 3. Insert 2 saline locks for rapid IV access. 4. Venipuncture, if needed, should be done with as 22 or 23 gauge needle; compress all venipuncture sites for at least 10 minutes. 5. No arterial punctures, invasive procedures, intramuscular injections, or puncture of non-compressible vessels for the first 24 hours following tPA infusion. Should an arterial puncture be necessary during an infusion of tPA, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding. 6. As fibrin is lysed during tPA therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cut-down sites, and needle puncture sites). 7. Intramuscular injections and nonessential handling of the patient should be avoided during treatment with tPA.

Dosage Recommended dosing of tPA in the treatment of acute pulmonary embolism is: 100 mg tPA infused over 2 hours** **

Some clinicians have reported the use of a front-loading regimen for tPA in the treatment of pulmonary embolism. Clinical trials have failed to show any improvement in outcomes when a front-loading regimen is used, however a higher incidence of bleeding was noted in these patients. Based on these results, it is not recommended to accelerate the dosing regimen of tPA in patients with acute pulmonary embolism.

Comments 1. tPA for PE is available in the Emergency Department's Pyxis machine. 2. Treatment of PE with tPA does not provide adequate treatment of underlying deep venous thrombosis. There is an associated risk of re-embolization due to possible lysis of underlying deep venous thrombosis. 3. The concomitant use of heparin anticoagulation may contribute to bleeding. Some of the hemorrhage episodes occurred 1 or more days after the effects of tPA had dissipated, but while heparin therapy was continuing.

Preparation Sheet TPA Infusion for Acute Pulmonary Embolism 1. Obtain 100 mg tPA vial with diluent from Pyxis machine in Emergency Department (or STAT from Pharmacy via Med Need request in conjunction with a phone call to alert the pharmacy). 2. Using aseptic technique throughout: a. remove flip top caps on both TPA 100 mg vial and the 100 cc vial of SWFI diluent provided. b. open the package containing the transfer device by peeling back label c. remove protective cap from one end of the transfer device and, keeping the vial of SWFI upright, insert the piercing pin into center of the stopper on the vial of SWFI d. remove the protective cap from the other end of the transfer device (do not invert the vial of SWFI) e. hold the vial of TPA upside-down , position it so that the center is directly over the exposed piercing pin, and push the vial of TPA down so that the piercing pin is inserted through the stopper in the TPA vial. f. invert the two vials so that the TPA vial is on the bottom and the SWFI vial is on the top allowing the entire contents of the SWFI vial to enter the TPA vial (this takes approx 2 mins) remove the transfer device and empty SWFI vial from the TPA vial. g. swirl or gently roll the vial to dissolve (DO NOT SHAKE) h. the resulting concentration is 1 mg/cc. 3. Spike vial with vented infusion set using the same hole made by the transfer device. 4. Attach infusion set to pump. 5. Set pump to deliver 2 hour infusion a. Press primary b. Enter amount of “infusion dose” (100 mg or 100 ml) c. Enter time of 2:00 (2 hours)