Early use of intrapleural fibrinolytics in the management of postpneumonic empyema. A prospective study. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study. The effect of fibrin sealant combined with fibrinolysis inhibitor on reducing the amount of lymphatic leakage after axillary evacuation in breast cancer. A prospective randomized clinical trial. Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions: a prospective, double-blind study. Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery. Use of an antifibrinolytic agent (tranexamic acid) and lateral sutures with laser conization of the cervix. The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study.
A prospective randomized study was conducted in order to analyze the role of fibrinolytics in the treatment of complicated parapneumonic effusion.
                From 2001 to 2004, 127 consecutive patients were managed for thoracic empyema. In all cases the cause was bacterial pneumonia. Seventy patients were managed with sole tube thoracostomy (group A) and 57 with combination of tube thoracostomy and streptokinase instillation (group B). Groups were statistically compared for the age, gender, duration of symptoms, quality of pleural fluid, chest imaging, complete drainage, length of hospital stay and mortality. Multivariate analysis was used in order to define the factors that affect outcome.
                Tube thoracostomy was successful in 47 (67.1%) cases (group A), while fibrinolysis led to a favorable outcome in 50 cases (87.7%) (P<0.05). The length of stay in thoracic surgical department was significantly longer for group A (P<0.001). Mortality rate in group A was significantly higher (P<0.001). Multiple regression analysis disclosed as sole independent favorable factor for pleural drainage, the use of fibrinolysis during the course of chest tube drainage (P=0.006, odds ratio 4.29, 95% CI 1.51-12.14).
                Fibrinolytic agents are a useful adjunct in the management of complicated parapneumonic effusions. Intrapleural fibrinolytics, if used early in the fibrinopurulent stage of a parapneumonic effusion, decrease the rate of surgical interventions (VATS or open decortcation) and the length of hospital stay with minor associated morbidity. 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. One third of women undergoing mastectomy with axillary evacuation for primary breast cancer suffer from postoperative seromas leading to unnecessary costs and complications such as infections and new operations. Different methods to prevent seroma formation have been tried without permanent success. The aim of this prospective randomised study was to examine the effect of fibrin sealant with fibrinolysis inhibitor firstly on the reduction of the amount of lymphatic leakage after axillary evacuation and secondly on the reduction of days with drains and postoperative seroma punctures.
                40 patients with primary breast cancer were prospectively randomised to the treatment group (n = 19) getting fibrin glue combined with fibrinolysis inhibitor (aprotinin) sprayed into the axillary fossa and to the control group (n = 21).
                There were no differences in the incidence of postoperative seromas between the groups. However, the seromas were easier to treat if fibrin clue was used. Total quantity (mean+/-SD) of lymphorrhea and total number of aspirations (mean+/-SD) were almost twice as high in the patients of the control group compared to those having fibrin sealant. In the treatment group seromas resolved after one or occasionally after two aspirations in 71 % of patients, while in the control group 90 % of patients needed three or more aspirations.
                Potentially, fibrin sealant combined with fibrinolysis inhibitor might be used for the treatment of post- axillary evacuation lymphorrhea and seroma. 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. Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.
                One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.
                Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB. One hundred forty patients who underwent laser conization and 220 patients who underwent laser miniconizations were prospectively randomized into two study groups. One treatment group was given antifibrinolytic therapy in the form of tranexamic acid (Cyklokapron, KabiVitrum, Sweden) intraoperatively and for 14 days postoperatively. The other group did not receive antifibrinolytic therapy. In the group of 68 patients with laser conizations who were given antifibrinolytic therapy, no postoperative hemorrhages occurred, whereas there were eight such hemorrhages in 72 conizations (11%) in the untreated patients. This difference is statistically significant (P = .004, Fisher exact test for two proportions). Also, for laser miniconization, the frequency of postoperative hemorrhage was almost halved, from 9.1% in 110 patients not receiving antifibrinolytic therapy to 5.5% in the 110 treated patients. The use of lateral cervical sutures did not reduce the frequency of postoperative hemorrhage at laser conization in the present study. Postoperative air leakage is the most frequent complication after pulmonary surgery. The development of modern surgical techniques has been influenced strongly by the need to manage air leakage effectively during pulmonary resection. This study evaluated the effect of using an autologous fibrin sealant (Vivostat) during lobectomy on morbidity following surgery.
                This was a prospective, blinded, randomised clinical study. Patients undergoing lobectomy were enrolled into two groups (Vivostat or non-treatment control, 20 per group). Air leakage was measured over a 1-h period (using a mechanical suction pump) on the day of operation, and both air leakage and bleeding/exudation (drainage volume) were recorded every morning postoperatively until the chest tubes were removed. Personnel recording these parameters were blinded to the intervention received. Results: Compared with the control group, mean bleeding/exudate volumes were significantly reduced in the Vivostat group (day 1,370 vs. 525 ml; total, 424 vs. 782 ml; both P<0.001), and drains were inserted for a shorter time (medians, 1 vs. 2 days, P=0.07). Significantly fewer patients had air leakage at any time in the Vivostat group (40 vs. 80%, P=0.02), and air leakage volumes were significantly lower compared with the control group (median differences: day of surgery: 0.6l/min, P=0.01; total 0.8l/min, P=0.03). Postoperative hospitalisation time was shorter in the Vivostat group than in the control group but the difference was not significant (0.5 days, P=0.12).
                Vivostat fibrin sealant significantly reduces post-surgical air leakage and drainage volumes following lobectomy in pulmonary surgery and is suitable for routine use in this procedure.
Intrapleural fibrinolytic therapy confers significant benefit in reducing the requirement for surgical intervention for patients in the early studies included in this review but not in the more recently published Maskell study. The reasons for this difference are uncertain. Separate subgroup analysis of proven loculated/septated effusions from the available data in our meta-analysis suggests a potential overall treatment benefit with fibrinolytics, but these results should be treated with caution as the data are incomplete and the benefit is not significant in the subgroup of high quality trials (Cochrane Grade A). Intrapleural fibrinolytics have not been shown to significantly increase adverse events, but the confidence interval is too wide to firmly exclude this possibility.