Eight centers participated in a study in which intrapulmonary and intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) were compared in 34 patients with acute massive pulmonary embolism. All patients received intravenous heparin in a bolus of 5000 IU followed by 1000 LU/hr. After 50 mg rt-PA given over 2 hr the severity of embolism, determined from pulmonary angiograms, declined by 12% in the intrapulmonary drug group (p < .005) and 15% in the intravenous drug group (p < .005); mean pulmonary arterial pressure fell from 31 7 to 22 + 6 mm Hg (p < .005) and from 31 + 12 to 21 ± 9 mm Hg (p < .005) in the respective groups. After a further 50 mg given over 5 hr (22 patients), the angiographically determined severity of embolism had decreased by 38% from baseline in the intrapulmonary drug group and by 38% in the intravenous drug group. The mean pulmonary arterial pressure further declined to 18 ± 7 and 12 ± 5 mm Hg in the respective groups. Fibrinogen levels dropped to 48% of baseline after 50 mg and to 36% of baseline after 100 mg rt-PA. Some degree of bleeding at puncture and/or operation sites was noted in 16 patients, including four who required a transfusion of two or more units of blood and had been operated on an average of 7.5 days (range 2 to 13) before thrombolytic treatment was started. In seven other patients thrombolytic treatment was initiated an average of 8.5 days (range 3 to 15) after surgery and only very minor or no bleeding was observed. This trial indicates that the intrapulmonary infusion of rt-PA does not offer a significant benefit over the intravenous route and suggests that a prolonged infusion of rt-PA over 7 hr (100 mg) is superior to a single infusion of 50 mg over 2 hr. Circulation 77, No. 2, 353-360, 1988. A NUMBER of studies 1-13 has demonstrated the accelerated resolution of pulmonary emboli that can be obtained with thrombolytic therapy and in 1980 a National Institutes of Health consensus conference14 concluded that". . ideal therapy for pulmonary embolism requires either the surgical removal or lysis of the thrombus or embolus." Despite the established superiority of thrombolytic over heparin treatment for hemodynamically compromised patients with massive pulmonary embolism, such therapy has not been universally adopted and there remains a significant group of patients to whom thrombolytic agents are not given. Such patients include those in whom the risk of bleeding induced by streptokinase or urokinase is thought to outweigh the benefit, particularly postsurgical patients,
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