Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions: a prospective, double-blind study.

Abstract

Intrapleural administration of fibrinolytics has been shown in small numbers of patients with complicated parapneumonic effusions (CPE) and pleural empyema to be effective and relatively safe. Although streptokinase (SK) is recommended as the fibrinolytic of choice, there are no comparative studies among fibrinolytics. We therefore compared the efficacy, safety, and the cost of treatment two of the most used thrombolytics, SK and urokinase (UK). Fifty consecutive patients with CPE or empyema were randomly allocated to receive either SK (25 patients) or UK, in a double-blind fashion. All patients had inadequate drainage through chest tube (< 70 ml/24 h). Both drugs were diluted in 100 ml normal saline and were infused intrapleurally through the chest tube in a daily dose of 250,000 IU of SK or 100,000 IU of UK. The chest tube was clamped for 3 h after instillation. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasound, and/or computed tomography. Clinical and radiologic improvement was noted in all but two patients in each group, who required surgical intervention. The mean volume drained during the first 24 h after instillation was significantly increased; 380 +/- 99 ml for the SK group (p < 0.001) and 420.8 +/- 110 ml for the UK group (p < 0.001). The total volume (mean +/- SD) of fluid drained after treatment was 1,596 +/- 68 ml for the SK group, and 1,510 +/- 55 ml for the UK group (p > 0.05). The SK instillations (mean +/- SD) were 6 +/- 2.16 (range, 3 to 10) and those of UK 5.92 +/- 2.05 (range, 3 to 8). High fever as adverse reaction to SK was observed in two patients. The total cost of the drug in the UK group was two times higher than that of SK ($180 +/- 47 for SK and $320 +/- 123 for UK). The mean total hospital stay after beginning fibrinolytic therapy was 11.28 +/- 2.44 d (range, 7 to 15) for the SK group and 10.48 +/- 2.53 d (range, 6 to 18) for the UK group (p = 0.32). We conclude that intrapleural SK or UK is an effective adjunct in the management of parapneumonic effusions and may reduce the need for surgery. UK could be the thrombolytic of choice given the potentially dangerous allergic reactions to SK and relatively little higher cost of UK.

U.K. Controlled Trial of Intrapleural Streptokinase for Pleural Infection

“…Such therapy is intended to lyse the fibrinous septations within infected pleural-fluid collections and is supported by management guidelines. 6,7 Small trials [8][9][10][11][12] and case series 13 have suggested that these agents improve drainage of pleural fluid, as quantified radiographically, and may also reduce the need for surgery, 12 with few adverse effects. These studies have had low statistical power, 14 however, and have therefore been unable to assess accurately whether these benefits translate into a reduction in mortality or in the frequency with which patients require surgical drainage.…”

Randomised trial of intrapleural urokinase in the treatment of childhood empyema

“…not cause significant activation of systemic fibrinolysis. 15 Allergic reactions have been reported with the use of intrapleural streptokinase with an incidence ranging from 12.5% 16 to less than 5% (R J Davies, personal communication). Urokinase is of human origin and allergic reactions have not been reported.…”

It is reasonable to recommended intrapleural alteplase for loculated pleural effusions

“…These studies are split between one large trial (N = 454) that concludes that thrombolytics should not be used in the treatment of pleural effusion 1 and several smaller studies (N ≤ 100) in favor of the use of thrombolytics in the treatment of pleural effusion [2][3][4][5][6][7][8][9][10] . There are also three meta-analyses of the randomized, placebo-controlled trials written on this topic, all of which conclude that intrapleural thrombolytics likely reduce the need for surgical intervention in some patients, but that the data are heterogenous [11][12][13] .…”

“…Of the nine studies that support the use of thrombolytic therapy, five had no control arm; two were retrospective reviews of cases of intrapleural alteplase treatment [2][3] ; two were single-arm prospective studies of similar cases [4][5] ; one was a randomized trial comparing the efficacies of intrapleural streptokinase and intrapleural urokinase, without a control group 6 ; two were single-center, randomized, placebo-controlled trials, using inclusion criteria that were too broad for this situation (patients were grouped together if they had either empyema or a complicated parapneumonic effusion, and only a subset of these patients had loculations) [7][8] ; and the remaining two papers were both double-blind, randomized studies that included patients who had been diagnosed with multiloculated pleural effusions based on ultrasound and/or CT evidence [9][10] . Both of these last studies also required participants to have failed simple tube drainage, which may indicate a blockage of free flow.…”