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Thrombolytic Therapy in Fulminant Pulmonary Thromboembolism V. Tilsner Department ofBloodcoagulation Disordersin the Department of Surgery, University Hospital Hamburg-Eppendorf, Germany

For the treatment of massive pulmonary embolism thrombolytic therapy is efficient in reducing late mortality and complications from chronic pulmonary hypertension. Best results are achieved if treatment is started as soon as possible . Even after days or weeks after pulmonary thromboembolism, however, thrombolytic therapy is beneficial. In life threatening conditions due to right heart failure an initial bolus of 200 000 Uurokinase should be adm inistered. The number of contraindications can be markedly reduced due to the well controlled thrombolysis with urokinase. Keywords Pulmonary thromboembolism Urokinase

Thr ombolytic therapy -

Introduction Pulmonary thromboembolism has an acute mortality of 11 % 0 ,56) and may cause severe long-term complications due to pulmonary hypertension (35,36,39,40,44,45,47, 49). Well-documented studies have demonstrated that the early mortality within the first two hours can only be influenced under certain circumstances, i. e. in hospitalised patients (38, 48, 49, 52, 53). Therefore, the major goal of treatment, i, e. thrombolytic therapy or surgical embolectomy, is to influence late mortality and to prevent the longterm complications of resulting hypertension. Well-conducted clinical studies require diagnosis of pulmonary thromboembolism by pulmonary angiography or recentl y by echocardiography. Perfusion lung scan is a sensiti ve, non-in vasive test to demonstrate perfusion defects but has a specifity of only 44 % without addit ional ventilation scan. With only few exceptions therapy is restricted to the treatment of massive pulmonary thromboembolism with occlusion of one or both pulmonary arteries or at least one major artery. In most cases occlusions' of minor arteries resolve spontaneously and ra ther quickly and therefore do not lead to long-term complications (42, 43). In our hospital, thrombolytic therapy for pulmonary embolism is coordinated with the department of cardiovascular surgery. In this study 93 patients with pulmonary thromboembolism confirmed by

Thorac. cardiovasc. Surgeon 39 (1991) 357-359 © Georg Thieme Verlag Stuttgart· NewYork

Thrombolytische Therapie der fuliminanten pulmonalen Thrombembolie Die thrombolytische Behandlung der mass iven Lungenembolie redu ziert die Spatmortalitat und vermindert die Komplikationen des chron ischen pulmonalen Hypertonus. Die besten Ergebniss e werd en erzielt, wenn mit der Behandlung moglichst friihzeitig begonn en wird. Jedoch auch Tage und Wochen nach einer akut en Lungenembolie kann die thrombolytische Thera pie noch erfolgreich sein . In lebensb edrohli chen Situation en mit Rechtsh erzversagen sollte ein initialer Bolus von 2 Mio E. Urokinase gegeben werden, welcher haufig zu einer raschen Reduzierung des pulmonalen Hypertonus fiihrt . Die Zahl der Kontra indikationen wird durch die sehr gut kontrollierte Thrombolyse mit Urokinase deutlich vermindert.

angiography were included. Additional diagnostic tests such as ECG, analysis of blood gases and of bloodcoagulation , and determination of pulmonary artery pressure were performed prior to and after thrombolytic therapy. Urokinase has been used almost exclusively as the thrombolytic drug since its dosage can be controlled most accurately and side-effects are comparatively rare (6,1 8,33,41 ,42,46,53, 54,55).

Patients and Methods The patient population consisted of 51 males and 42 female s, their age in the range 22 to 86 years (mean = 49 years), who were referr ed to our department from 1984 to 1990 for treatment of pulmonary thromboembolism . In 82 patients deep vein thrombosis and in 5 patients varicosis were identified as the pr obable cause of thromboembolism. In 6 patients the reason for thromboembolism rema ined unclear. Coagulation tests revealed signs ofhypercoagulation in only 5 of 93 patients . All patients were given heparin intrav enously in a high-dose regimen with prolongation of thrombin time to 60sec (18-25 sec) and ofPTT to 55-60 sec (38- 55 sec). 250000 U urokinas e were applied as an initial bolus with a subsequent maint enance dose of 60000 to 80000 Wh. 10 patients with acute right-heart failure received an initial bolus of 2000000 U urokinas e. In 30 patien ts with relat ive contraindications (surgery within the last three days, hypertension, age over 75 years) the maint enance dose was reduced to 40000 to 60000 U.

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Summary

V. Tilsner

Thom e. ea rdiovas e. Surgeon 39 (1991)

Table 1 Results of Urokinase Therapy in 93 patients withangiographicallycontrolled Massive Pulmonary Embolism group

urokinase dosage initia l maintenance

age of thrombus

mortalitis

residual occlusions complete reopening

a) 57 patients

250000 u

4 (older emboli)

53

250000 u

6 hours to 2 month 6 hours to 2 month

0

b) 26 patients withcontraindications (hypertonia,age, operation inthe last 3 days) c) 10 patients in shock

60000 to 80000 u 40000 to 60000 u

21

40000 to 80000 u

2 hours to 4 days

2 3 (older emboli) (90 min.after beginningof the rapy) 4 0 (60 min.to 3 h. after beginningof therapy)

2 million u

Results

The results are shown in Table 1. In the course of therapy the pulmonary occlusion resolved nearly completely in 80 of 93 patients. 6 of 7 patients with residual occlusions after therapy showed signs of pulmonary hypertension in a follow-up examination 12 months later, in 4 only after physical exercise. These patients, however, had recurrent thromboembolism with 2 to 15 months old occlusions. Complications due to bleeding were found in only4 of93 patients. One patient (1.07 %) developed a retroperitoneal hematoma requiring blood transfusion . 3 patients (3.2 %) developed hematoma after venous puncture without decrease of hemoglobin concentration. In all cases the angiographic catheter was left until the end of thrombolytic therapy to monitor the therapeutic effects. Therefore, no bleedings were observed from these puncture sites . The shortest time interval between preceding surgery and subsequent thrombolytic therapy for thromboembolism was 32 hours . The overall mortality of 6.5 % (6 patients) is low, especially taking into consideration that 4 of thes e patients were treated in shock and died within 3 hours of start of therapy. The other two patients, whose thromboembolisms were 3 and 6 weeks old, died within 3 hours after start of therapy due to right-heart failure. Discussion It should be stated explicitly that no patient died due to complications caused by thrombolytic therapy. As demonstrated in Table I, the relative contraindications have to be weighed against the life-threatening risk of pulmonary embolism. Our data clearly indicate that the risk of bleeding under thrombolytic therapy is much lower than generally assumed. As stated above, therapy for pulmonary thromboembolism is coordinated with the department of cardiovascularsurgery(14,15 ,19, 22, 32). Surgical embolectomy which leads to a quick reduction of pulmonary artery pressure was always considered as an alternative to thrombolytictherapy in massive pulmonary thromboembolism. In the same time interval from 1984 to 1990 surgical embolectomy was necessary in only 5 patients due to acute right-heart failure in the course of massive thromboembolism. These patients did not receive thrombolytic therapy and therefore are not included in this study . The administration of 2 000 000 U urokinase, however, can also lower the pulmonary artery pressure within 2 to 4 hours, although the complete lysis requires up to 6 days. An unsuccessful thrombolytic therapy, which is rather seldom, is a further indicat ion for

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surgical embolectomy. In addition, in a hospital with the possibility to carry out surgery using extracorporeal circulation patients can be treated immediate ly with surgical embolectomy. These, however, are a minority. Our results are in good agreement with previously pub lished data (2-5 ,7-13,16,17,20-32,37,38,50,51,56). Death occurred only in patients who decompensated with acute heart failure or who were treated too late. Treatment for patients with pulmonary thromboembolism in shock has been considerably improved by an initial bolus of 2 000 000 Uurokinase. Prior to this investigation only a few retrospective studies have demonstrated a beneficial effect ofthrombolytic therapy in regard to development ofchronic pulmonary hypertension (10,11,36,45,47 ,56). To this end the results of thrombo lytic therapy can be improved when the treatment is continued until all thrombotic material is resolved as assessed not only clinically but also anglographically. References 1

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Prof Dr. med . V. Tilsn er

Depar tm ent of Surgery University Hospit al Hamburg-Eppend orf Martinistr . 52 D-2000 Hamburg Germ any

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Thora c. cardiovas c. Surgeon 39 (1991)

Thrombolyti c Th erapy in Fulminant Pulmonary Thromboembolism