Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: A European multicenter double-blind trial

Abstract

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h. At 2 h, total pulmonary resistance decreased by 18 +/- 22% in the urokinase group and by 36 +/- 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h. After 12 h, the decrease in total pulmonary resistance was 53 +/- 19% in the urokinase group compared with 48 +/- 17% in the alteplase group and the reduction in the angiographic severity score was 30 +/- 25% compared with 24 +/- 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinase-treated patients experienced hematomas at puncture sites.

A critical review of thromboembolic complications associated with central venous catheters

“…47,48 Recombinant tissue plasminogen activator is typically infused over two hours, compared to a 12-hr infusion with streptokinase and up to 24 hr of administration with urokinase. Evidence from RCTs, reporting on patients with massive [49][50][51][52][53][54] and submassive 52,55 PE, favour thrombolysis over heparinization. Randomized controlled trials comparing streptokinase and alteplase, in massive PE, 56,57 and urokinase and rTPA 58 failed to demonstrate superiority of one thrombolytic over another.…”

Terapia trombolítica en TEP submasivo/riesgo intermedio: Evidencias y sugerencias post estudio Pulmonary Embolism Thrombolysis (PEITHO)

“…Así, reteplase posee mayor rapidez y duración de acción 16 , tenecteplase tiene bajo clearance y mayor especificidad por fibrina [17][18][19][20] , desmoteplase posee vida media más larga y es dos veces más potente 21 . El riesgo de los trombolíticos son las hemorragias, con tasas de hemorragia mayor de 13% y letal de 1,8% 11,[22][23][24][25][26][27][28][29][30][31] . En pacientes inestables los trombolíticos reducen la mortalidad (19 La controversia para el uso de los trombolíticos se centra en los pacientes hemodinámicamente estables 35 .…”

“…Así, si la trombolisis está indicada, pero existe alto riesgo de sangrado, podría considerarse el uso de media dosis. Así, en caso de estar indicada la terapia, el tratamiento es en infusión continua y se debe utilizar en media dosis del bolo en caso de paro, debido a la distribución limitada de la droga cuando la perfusión se encuentra comprometida 28,29 . En definitiva, en TEP, para maximizar los beneficios de la trombolisis, se sugiere utilizar HNF con trombolítico 28,30,58 , reiniciando la infusión de HNF en pacientes con TEP submasivo cuando TTPa es menor que 60 a 80 segundos 59 .…”

“…Así, en caso de estar indicada la terapia, el tratamiento es en infusión continua y se debe utilizar en media dosis del bolo en caso de paro, debido a la distribución limitada de la droga cuando la perfusión se encuentra comprometida 28,29 . En definitiva, en TEP, para maximizar los beneficios de la trombolisis, se sugiere utilizar HNF con trombolítico 28,30,58 , reiniciando la infusión de HNF en pacientes con TEP submasivo cuando TTPa es menor que 60 a 80 segundos 59 . Los pacientes mayores de 65-70 años, procedimientos invasivos recientes, presión arterial diastólica elevada (> 90 mmHg), peso menor 65 kg o IMC menor que 24, presentan mayor riesgo de sangrado a dosis estándar de trombolítico 21,[60][61][62][63] .…”

Thrombolytic treatment given at the and of the first week of stroke due to pulmonary embolism in a patient with middlee cerebral artery infarction

“…Pulmoner embolide onay alan trombolitik rejimler streptokinaz (SK), ürokinaz (UK), rt-PA dır ve birbirlerine üstünlükleri gösterilememiştir. Çalışmalarda intrakraniyal kanama oranı %1,8 olarak bildirilmiştir (8)(9)(10)(11). İntrakraniyal kanama riski trombolitik tedavi ile %1,8 olmakla birlikte, bu oran serebravasküler hastalık öyküsü olan olgularda yükselmektedir.…”