Intrapleural Urokinase versus Normal Saline in the Treatment of Complicated Parapneumonic Effusions and Empyema

Abstract

Intrapleural administration of fibrinolytic agents has been shown to be effective and safe in the treatment of loculated parapneumonic pleural effusions. However, controlled studies of the possible role of the activity of urokinase (UK) through the volume effect are lacking. We therefore investigated the hypothesis that UK is effective through the lysis of pleural adhesions and not through the volume effect. Thirty-one consecutive patients with multiloculated pleural effusions were randomly assigned to receive either intrapleural UK (15 patients) or normal saline (NS) (16 patients) for 3 d, in a double-blind manner. All patients had inadequate drainage through a chest tube (< 70 ml/24 h). UK was given daily through the chest tube in a dose of 100.000 IU diluted in 100 ml of NS. Controls were given the same volume of NS intrapleurally. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasonography (US) and/or computed tomography (CT). Clinical and radiographic improvement was noted in all but two patients in the UK group but in only four in the control group. The net mean volume drained during the 3-d treatment period was significantly greater in the UK group (970 +/- 75 ml versus 280 +/- 55 ml, p < 0.001). Pleural fluid drainage was complete in 13 (86.5%) patients in the UK group (two patients were treated through video-assisted thoracoscopy) but in only four (25%) in the control group. Twelve patients in the control group were subsequently treated with UK and six of them had complete drainage; the remaining six patients had complete drainage after video-assisted thoracoscopy. Our results suggest that UK is effective in the treatment of loculated pleural effusions through the lysis of pleural adhesions and not through the volume effect.

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project

“…Thus, intrapleural fibrinolytic therapy to lyse pleural loculations has attracted ongoing interest since 1949(6) with small studies (7,8) demonstrating reductions in surgical intervention rates. Subsequently, the MIST (Multi-Centre Intrapleural Sepsis Trial)-1, the largest randomised controlled trial of intrapleural fibrinolytics (streptokinase) failed to demonstrate any benefits over placebo for pleural infection.…”

Effectiveness and Safety of Tissue Plasminogen Activator in the Management of Complicated Parapneumonic Effusions

“…Although the clinical relevance of pleural fluid drainage (rate and volume) as an outcome measure is unclear, the majority of published studies have used this variable as a primary outcome. 5,6 In addition, no local or systemic bleeding events were associated with the use of tPA in this patient population. Last, early instillation of tPA (within 24 hours) was associated with a shorter duration of chest tube placement, particularly when compared with late administration of tPA.…”

“…4 Two small sample randomized controlled trials in adults have shown that pleural fluid drainage is increased with fibrinolytics and that significant activation of systemic fibrinolysis does not occur. [5][6][7] Both streptokinase and urokinase have been used as intrapleural fibrinolytics in children. A recent placebo-controlled trial of intrapleural urokinase in children with complicated parapneumonic effusions demonstrated a reduced length of hospital stay in children who were treated with urokinase compared with the placebo group.…”

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.…”