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An imbalance in oxygen supply to cardiac tissues or formation of thrombus leads to deleterious results like pulmonary embolism, coronary heart disease and acute cardiac failure. The formation of thrombus requires clinical encounter with fibrinolytic agents including streptokinase, urokinase or tissue plasminogen activator. Irrespective to urokinase and tissue plasminogen activator, streptokinase is still a significant agent in treatment of cardiovascular diseases. Streptokinase, being so economical, has an important value in treating cardiac diseases in developing countries. This review paper will provide the maximum information to enlighten all the pros and cons of streptokinase up till now. It has been concluded that recent advances in structural/synthetic biology improved SK with enhanced half-life and least antigenicity. Such enzyme preparations would be the best thrombolytic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Despite the common occurrence of streptokinase-induced hypotension among patients with acute myocardial infarction, the underlying pathophysiology remains obscure and poorly understood. Our study aimed to pool clinical evidence on the potential mechanism of streptokinase-induced hypotension through a systematic review of the literature. Material and methods: We conducted literature search from Medline, Scopus and Web of Science on clinical studies related to streptokinase-induced hypotension. Results: Our search yielded 972 citations. After removal of duplicates, 878 articles were screened for eligibility, of which 856 papers were excluded due to various reasons. Of the remaining 22 articles retrieved with full texts, eight relevant articles were selected for final analysis. Three themes emerged as the proposed mechanisms of streptokinase-induced hypotension, including (i) reduction in total peripheral resistance, (ii) complement activation, and (iii) dismissal of hypotheses involving other intermediaries. Conclusions: Our findings suggest that the underlying mechanism of streptokinase-induced hypotension lies primarily in the reduction in total peripheral resistance. [ABSTRACT FROM AUTHOR]

Objectives: The purposes of this paper are to study clinicobacteriological profile, treatment modalities and outcome of pediatric empyema thoracis and to identify changes over a decade., Design: This is a retrospective study., Setting: Department of Pediatrics of a tertiary care hospital in North India., Patients: We enrolled 205 patients (1 month-12 years) of empyema thoracis admitted over 5 years (2007-11) and compared the profile with that of a previous study from our institute (1989-98)., Results: Pleural fluid cultures were positive in 40% (n = 82) cases from whom 87 isolates were obtained. Staphylococcus aureus was the most common isolate (66.7%). Methicillin-sensitive S. aureus accounted for 56%, Methicillin-resistant S. aureus (MRSA) 10% and gram-negative organisms 18.3% of isolates. Intercostal drainage tube (ICDT) was inserted in 97.5%, intrapleural streptokinase was administered in 33.6%, and decortication performed in 27.8% cases. Duration of hospital stay was 17.2 (±6.3) days, duration of antibiotic (intravenous and oral) administration was 23.8 (±7.2) days and mortality rate was 4%. In the index study (compared with a previous study), higher proportion of cases received parenteral antibiotics (51.7% vs. 23.4%) and ICDT insertion (20.5% vs. 7%) before referral and had disseminated disease (20.5% vs. 14%) and septic shock (11.2% vs. 1.6%), less culture positivity (40% vs. 48%), more MRSA (10.3% vs. 2.5%) and gram-negative organisms (18.4% vs. 11.6%), increased use of intrapleural streptokinase and surgical interventions (27.8% vs. 19.7%), shorter hospital stay (17 vs. 25 days) and higher mortality (3.9% vs. 1.6%)., Conclusions: Over a decade, an increase in the incidence of empyema caused by MRSA has been noticed, with increased use of intrapleural streptokinase and higher number of surgical interventions., (© The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The paper describes synthesis and testing of novel biodegradable polylactide-based polymer membranes with desired mechanical properties, which are capable of sustained and directed release of biomacromolecules with high molecular weight (in particular, streptokinase; m.w. 47 kDa). Streptokinase is a pharmaceutical agent, possessing a pronounced thrombolytic activity. The membranes synthesized had a percentage elongation of 2–11% and tensile strength of 25–85 MPa. They were biodegradable – yet being stored in aqueous media in the absence of biological objects, would be dissolved by no more than 10% in 6 months. The synthesized membranes were capable of controlled release of streptokinase into the intercellular space, with the enzyme retaining more than 90% of its initial activity. The rate of streptokinase release from the membranes varied from 0.01 to 0.04 mg/day per cm2 of membrane surface. The membrane samples tested in the work did not have any short-term toxic effects on the cells growing de novo on the membrane surface. The mitotic index of those cells was approximately 1.5%, and the number of non-viable cells on the surface of the polymer films did not exceed 3–4% of their total amount. The implantation of the synthesized polymers – as both individual films and coatings of nitinol stents – was not accompanied by any postoperative complications. The subsequent histological examination revealed no abnormalities. Two months after the implantation of polymer films, only traces of polylactide were found in the implant-surrounding tissues. The implantation of stents coated with streptokinase-containing polymers resulted in the formation of a mature and thick connective-tissue capsules. Thus, the polylactide membranes synthesized and tested in this work are biodegradable, possess the necessary mechanical properties and are capable of sustained and directed release of streptokinase macromolecules. [ABSTRACT FROM AUTHOR]

Introduction: Endotoxin or lipopolysaccharide (LPS) is one of the components of the wall of gram-negative bacteria, which, when in contact with blood, stimulates the immune system and causes fever and even serious adverse effects or death. Removing endotoxin is one of the most daunting challenges presented to the purification process in the production of recombinant biological drugs. Bacterial endotoxin (LPS) is resistant to heat and passes through sterilizing filters, and due to its dangerous side effects in living organisms, part of the target protein purification process is always related to removing this disturbing factor from the product. Materials & Methods: The affinity matrix S3E3-S-Sepharose, which was produced by immobilizing the improved variant of antimicrobial peptide S3 called S3E3 peptide on Sepharose chromatography resin, was used to remove endotoxin from active pharmaceutical ingredient (API) of streptokinase, and the performance of this matrix was compared with the performance of a disposable commercial matrix (containing S3 peptide as its ligand) and with ion exchange chromatography resin. Results: The statistical analysis of the results revealed that compared to commercial S3 matrices and ion exchange chromatography, the S3E3-S-Sepharose matrix had higher protein recovery (84.07% compared to 81.50 and 75.31%, respectively) and higher streptokinase biological activity recovery (81.95% vs. 27 76.76 and 61.54%, respectively). Conclusion: As evidenced by the obtained results, the S3E3-S-Sepharose matrix seems to be a suitable candidate for use in the purification processes of Streptokinase API and other recombinant biopharmaceuticals. [ABSTRACT FROM AUTHOR]

A kinetic study is made of plasminogen activation to plasmin catalyzed by streptokinase. The goal of the present paper is the resolution of the mechanism corresponding to the activation process by a global way, considering the mechanism as a whole and under less restrictive assumptions that those used by other authors. The kinetic equations describing the evolution with time of species involved in the system have been obtained. These equations are valid for both the transient phase and the steady state of the reaction. A kinetic data analysis procedure to evaluate the kinetic parameters, based on the derived kinetic equations has been suggested, for the first time, in the present paper. The validity of the results obtained has been checked by using simulated progress curves of the species involved. Finally, we have demonstrated that the time course equations obtained can be applied directly to different mechanisms of zymogen activation that could be considered to be particular cases of the general studied mechanism. [ABSTRACT FROM AUTHOR]

To report a case of femoral artery thrombosis and its medical management in a young dog.A 13-week-old, female Boxer puppy presented with hind limb paralysis after an abdominal crush injury. A left femoral artery thrombus was identified on ultrasound. No spinal trauma was visualized in imaging studies. Clinical management of arterial thrombosis in a 13-week-old puppy with streptokinase and dalteparin therapy is described.This paper describes an unusual presentation of arterial thrombosis. The medical management with streptokinase and dalteparin is also out of the ordinary. Images that document the development of compensatory circulation around the thrombosed vessel are included. Additionally, this paper also documents the altered development that occurred in this immature dog after the thrombotic event. [ABSTRACT FROM AUTHOR]

Acute Myocardial Infarction (AMI) is the immediate cessation of the blood supply to the heart muscle and occurs due to lack of oxygen and is one of the most frequent medical emergencies. ST-Elevation Acute Myocardial Infarction (STEMI)is one of the major cardiological emergencies which is associated with complications of heart failure, arrhythmia, and high mortality. The main treatment is coronary artery recanalization of the involved artery in the shortest time possible. Percutaneous transluminal coronary angioplasty has shown the best results of AMI treatment. Reperfusion of the ischemic myocardium can be achieved by pharmacologic methods (thrombolysis) and PCI (Percutaneous Coronary-arteries Intervention). Purpose of the study: The study is of cohort-prospective type. It is a study for the coronary-angiography evaluation of the current treatment of STEMI at the University Hospital Center in Tirana in patients undergoing thrombolysis with streptokinase or reteplase (choice is based on the specific case), and the effect of predisposing factors upon the mortality of STEMI. Materials and methods: this study included all patients admitted to the department of cardiologic resuscitation, from 01 Feb 2013, until 05 Jul 2013 (56 patients, of whom 26 were females and 30 were males, with an identical average age of 56.0 ±10.0 years old) diagnosed with STEMI in whom thrombolysis with reteplase or streptokinase has been performed according to previously tested protocols, respecting the absolute contraindications for the application of reperfusion procedure. Thrombolysis was performed in patients who presented within 6 hours since the onset of pain. Follow-up includes days of hospitalization (cardiology resuscitation + cardiology clinic I or II). Results: Data analysis showed Thrombolysis in Myocardial Infarction (TIMI) 3 in 82% of the total cases; The group of patients treated with streptokinase showed TIMI 3 of 70% and the group of patients treated with reteplase showed TIMI 3 of 91%. The total mortality rate was 6.9% (3 patients) and these were part of the group treated with reteplase. Predisposing factors for high mortality in patients undergoing thrombolysis such as age, sex, diabetes mellitus (DM) type II (prevalence of DM type II was 33.9% of all patients, of whom 41% of the patients treated with RP and 22% of patients treated with ST, p=0.0001) and TIMI had a statistical significantly higher risk factors in the group treated with reteplase. Conclusion: Thrombolysis of STEMI patients presents an effective recanalizing alternative when the patient presents within the first few hours since the onset of pain onset, a conclusion achieved by TIMI-based coronary angiography assessment. Mortality in thrombolysis is related to factors such as: age, gender, high blood pressure (BP), DM, and other comorbid factors. [ABSTRACT FROM AUTHOR]

Purpose: PLGA nanoparticles (NPs) have been extensively investigated as carriers of different drug molecules to enhance their therapeutic effects or preserve them from the aqueous environment. Streptokinase (SK) is an important medicine for thrombotic diseases. Methods: In this study, we used electrospray to encapsulate SK in PLGA NPs and evaluate its activity. This is the first paper which investigates activity of an electrosprayed enzyme. Effect of three input parameters, namely, voltage, internal diameter of needle (nozzle) and concentration ratio of polymer to protein on size and size distribution (SD) of NPs was evaluated using artificial neural networks (ANNs). Optimizing the SD has been rarely reported so far in electrospray. Results: From the results, to obtain lowest size of nanoparticles, ratio of polymer/enzyme and needle internal diameter (ID) should be low. Also, minimum SD was obtainable at high values of voltage. The optimum preparation had mean (SD) size, encapsulation efficiency and loading capacity of 37 (12) nm, 90% and 8.2%, respectively. Nearly, 20% of SK was released in the first 30 minutes, followed by cumulative release of 41% during 72 h. Activity of the enzyme was also checked 30 min after preparation and 19.2% activity was shown. Conclusion: Our study showed that electrospraying could be an interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles. However, further works are required to assure maintaining the activity of the enzyme/protein after electrospray. [ABSTRACT FROM AUTHOR]

The article presents an overview of some of the key topics presented at the British Thoracic Society Winter Meeting held in London, England, from December 5-7, 2001. It states that the winter meeting of the British Thoracic Society covered a wide range of respiratory topics. Over 300 papers were presented and internationally renowned speakers delivered a number of lively symposia. Some of those topics were on asthma, chronic obstructive pulmonary disease and pleural disease. Initial data from the first 150 patients enrolled in the multicentre intrapleural streptokinase versus placebo in empyema trial was presented at the meeting. Emphasis was placed on the importance of obtaining blood cultures for microbiological diagnosis.

Streptokinase is being successfully used as a thrombolytic agent for restoring the blood flow following thromboembolism and myocardial infarction. However, high immunogenicity of the drug has limited its use in clinics. To overcome this limitation, several approaches including PEGylation, use of polymeric particles and liposomes have been suggested. Here, an overview of options for encapsulating the streptokinase has been provided. The suggested options in the literature include PEGylation, polymeric nano/micro-capsules and liposomes. In each approach, efficacy, side effect(s) and pharmacokinetic profile of streptokinase has been evaluated. The data show that while efficacy of streptokinase does not appear to change importantly, side effects and pharmacokinetics have been improved. [ABSTRACT FROM AUTHOR]

Introduction: Modern pharmacological reperfusion in ST segment elevation acute myocardial infarction means the application of fibrin specific thrombolytics combined with modern antiplatelets therapy--dual antiplateles therapy, acetylsalicylic acid and clopidogrel, and enoxaparin. The contribution of each agent has been widely examined in large clinical studies, but not sufficiently has been known about the effects of a combined approach, where the early angiography and percutaneous coronary intervention is added during hospitalization, if necessary., Objective: The aim of the paper is to compare the effects of streptokinase and alteplase, together with the standard modern adjuvant antiplatelets and anticoagulation therapy (aspirin, clopidogrel, enoxaparin) in patients with ST segment elevation acute myocardial infarction, on electrocardiographic and angiographic signs of the achieved myocardial reperfusion., Method: The prospective study included 127 patients with the first ST segment elevation acute myocardial infarction who were treated with a fibrinolytic agent in the first 6 hours from the chest pain onset. The examined group included 40 patients on the alteplase reperfusion therapy, while the control 87 patients were on the streptokinase therapy. All the patients received the same adjuvant therapy and all were examined by coronary angiography on the 3rd to 10th day of hospitalization. Reperfusion effects were estimated on the basis of the following: ST segment resolution at 60, 90 and 120 minutes, the appearance of reperfusion arrhythmias at the electrocardiogram, percentage of residual stenosis at the "culprit" artery, TIMI coronary flow at the "culprit" artery and the appearance of new major adverse coronary events in the 6-month-follow-up period., Results: By analysing the resolution of the sum of ST segment elevation in infarction leading 60 minutes after the beginning of the medication application, we received a statistically significantly higher resolution of ST segment in the group of patients who received alteplase (p < 0.05). 60 minutes after the application of thrombolytics, 64% of patients at streptokinase showed the absence of ST segment resolution (<30%), and 32% of patients at alteplase (p < 0.0001). Reperfusion arrhythmias as the sign of successful myocardial reperfusion were present in 62.5% of patients at alteplase and in 57.4% of patients at streptokinase, but the difference is not statistically significant.There was no statistically significant difference in the degree of residual stenosis at the,culprit" artery in the compared groups of patients. TIMI 3 flow was achieved in 75% of patients at alteplase and in 38% of patients at streptokinase (p < 0.0001). There was no statistically significant difference in the frequency of major adverse coronary events in the 6-month-follow-up period after acute myocardial infarction., Conclusion: Alteplase with modern adjuvant therapy of ST segment elevation acute myocardial infarction shows the earlier achievement of coronary perfusion as well as better coronary flow compared to streptokinase. There is no statistically significant difference in the frequency of reperfusion arrhythmias, degree of residual stenosis at the"culprit"artery and the frequency of new coronary events in the 6-month-follow-up period after acute myocardial infarction.

Background: Left ventricular mobile thrombi carry high risk of embolism and need early treatment in which the appropriate treatment is still controversial. Because most patients with mobile thrombi have low ejection fraction and also accompanying heart failure symptoms, decision of surgical treatment is not always easy and thus effective medical treatment is crucial., Method: In this paper we present, treatment and follow-up of seven patients with mobile thrombi who underwent fibrinolytic treatment between 2002 and 2006., Results: In four cases, mobile thrombi disappeared completely while echocardiographically regressed to lower size with decreased mobility in the other three patients. On 6th month follow-up, complete lysis of the thrombi in six patients was observed with warfarin treatment. No major complications were seen in the patients., Conclusion: In case of mobile left ventricular thrombi with concomitant low ejection fraction and heart failure fibrinolytic treatment might be a therapeutic option.

The downstream processing of recombinant streptokinase (rSK), a protein used for dissolution of blood clots has been investigated employing Escherichia coli inclusion bodies obtained after direct chemical extraction followed by expanded bed adsorption chromatography (EBAC). Streptokinase was over-expressed using high cell density (final OD(600)=40) culture of recombinant E. coli, and an SK protein concentration of 1080 mg l(-1) was achieved. The wet cell pellet after centrifugation was re-suspended in 8M urea containing buffer resulting in direct extraction of almost 97% of cellular proteins into solution. Compared to mechanical disruption using sonication, the direct extraction helped in simultaneous cell lysis and inclusion body (IB) solubilization in a single integrated step. The post-extraction solution containing cell debris and cellular proteins was diluted and directly loaded on to an EBAC column containing Streamline phenyl, without clarification. By passing the solution four times through the column and using 1M NaCl during loading, 82.7% rSK activity could be recovered in the 10mM sodium phosphate buffer used for elution. A 3-fold increase in specific activity of rSK, from 0.18 x 10(5) in cell lysate to 0.53 x 10(5)IU mg(-1) resulted after this step. rSK was further purified to near-homogeneity (specific activity=0.96 x 10(5)IU mg(-1)) by a subsequent ion-exchange step operated in packed bed mode. An overall downstream recovery of 63% rSK was achieved after EBAC and ion exchange chromatography. The paper thus describes the purification of rSK using a three-step regime involving simple, efficient and highly facile steps.

Background: Portal vein thrombosis in adults is usually related to cirrhosis. There are several possible therapies. including anticoagulation, transjugular intrahepatic portosystemic shunt, balloon dilatation, local and systemic fibrinolytics agents. Hypercoagulable states are also reported in association with this disease entity. Eosinophilia may activate platelets and promote thrombosis due to proteins contained in intracytoplasmic granules, such as eosinophil cationic protein and major basic protein. There is only one paper in the medical literature linking eosinophilia and portal vein thrombosis., Case Report: We present here the case of a middle-age woman with idiopathic eosinophilia and acute portal vein thrombosis with massive venous thrombosis, involving the mesenteric, splenic, inferior cava, iliac and femoral veins, successfully treated with systemic streptokinase., Conclusions: Acute portal vein thrombosis with associated mesenteric and splenic vein thrombosis is a potentially lethal coagulation disorder that can be treated successfully with systemic streptokinase.

Background and Objectives: Valvular thrombosis is a serious complication in patients with prosthetic heart valves. Traditional treatment is emergency surgery, but thrombolysis provides a non invasive alternative. In this paper we evaluate the efficacy and safety of thrombolysis in prosthetic heart valve thrombosis., Methods: Data of 68 patients diagnosed of prosthetic valve thrombosis, treated at the Institute of Cardiology and Cardiovascular Surgery, Havana during a 6-years period were analyzed. They received thrombolysis with a recombinant streptokinase infusion at 250,000 IU in 30 minutes followed by 100,000 IU/hour during 72 hours or less if the thrombosis resolved before. The evaluation was based on clinical and echocardiographic findings., Results: Affected sites were mitral (50 cases), tricuspid (9), and aortic (9). Mean time of prosthesis implantation was 6.8 years. The presentation form was generally heart failure (NYHA functional class III-IV) in 64 (94.1%) patients. Mean time interval between onset of symptoms and diagnosis was 10.6 days. There was total response to treatment in 58 (85.3%) patients, partial in 4 (5.9%) and failure in 6 (8.8%). Recombinant streptokinase overall dose was 5.1 x 10(6) IU and mean infusion time 50 hours. Major hemorrhagic complications were observed in two patients. Five embolic events occurred during thrombolysis. Four patients died. Rethrombosis was noted in 11 patients; 10 were retreated successfully with thrombolysis., Conclusions: Thrombolysis with recombinant streptokinase is efficacious and safe for the treatment of prosthetic heart valve thrombosis. It does not contraindicate surgical treatment if there is no total response, because patient goes to surgery in better hemodynamic conditions with lower risk. Nowadays it can be considered as first-line treatment in all patients with prosthetic heart valve thrombosis regardless of functional class unless specific contraindications exist.

The paper evaluates the intensity of peritoneal adhesions induced by talc administration on Wistar rats, alone and in association with different other substances. The comparative study was performed on 40 rats, separated in 5 groups: group A was injected intraperitoneally with talc, group B with talc and streptokinase, group C with talc and heparin, group D with talc and dexamethasone and group E with talc and dextran. The adherence syndrome was evaluated after 3 weeks, scoring 5 parameters: number, density, strength, vascularization, topography and granulomas. The sum of these 5 parameters was defined as the adherence score. The best results in preventing adhesion formation are obtained with the intraperitoneal administration of dextran and streptokinase.

Aim: The aim of this paper was to compare the efficacy of adjunctive intrapleural fibrinolygic agents (streptokinase, urokinase) on fibrinopurulent stage empyema and chronic stage empyema., Methods: In our clinic, we used intrapleural fibrinolytic agents in 78 pediatric patients (36 fibrinopurument stage empyemas, 42 chronic stage empyemas) between December 1994 and September 2002. Pleural biopsy was done for staging. Streptokinase 250,000 units in 100 ml 0.9% saline solution (62 patients) and 125000 units in 100 ml 0.9% saline solution (16 patients) was instilled daily to the chest tube, and the tube was clamped for 4 h followed by suction. This treatment was continued daily for 2 to 8 days until resolution was demonstrated by chest radiograms and/or computed chest tomography., Results: The treatment was discontinued due to allergic reaction and pleural hemorrhage in 1 patient with fibrinopurulent empyema. This patient died 1 day later in a septic condition. The regimen was completely successful in 24/36 (66.6%) fibrinopurulent empyemas, and partially successful in other 11/36 (30.55%). Treatment was ineffective in 38 of 42 patients with chronic empyemas (90.6%). Two cases in chronic phase empyema completely recovered and 2 other patients had a partial response. Success of the treatment was 91.66% (35/36) (complete response: 24/36' partial response 11/36) in the fibropurulent stage and 9.4% (2/42 complete response, 2/42 partial response in chronic cases., Conclusions: Our study suggests that intrapleural fibrinolytic treatment is an effective and safe therapy in children with fibrinopurulent phase thoracic empyema.

Background: Effusions and empyema may complicate lower respiratory tract infections. Loculation of fluid is a major problem with this condition and treatments have included surgical drainage and the use of intra-pleural fibrinolysis to break down fibrin bands that may cause loculation., Objectives: To conduct a systematic review of the benefit of adding intrapleural fibrinolytic therapy to intercostal tube drainage in the treatment of complicated para pneumonic effusions and empyema., Search Strategy: The Cochrane Controlled Trials Register was initially searched for relevant RCT's. Trial authors were contacted for further information and details regarding the possibility of unpublished trials was requested. The most recent search was conducted in July 2003., Selection Criteria: All studies in the review were Randomised Controlled Trials in adult patients with empyema or complicated para pneumonic effusions who had not had prior surgical intervention or trauma. The intervention was an intrapleural fibrinolytic agent (streptokinase or urokinase) versus control or a comparison of the two., Data Collection and Analysis: All identified studies were reviewed independently by two reviewer and all data collected. Reviews were scored according to the Cochrane assessment of allocation concealment and the Jadad scale of methodological quality. Disagreements between reviewers were referred to a third reviewer. Where further information was required, authors of trial papers were contacted for further details., Main Results: Four studies were included, one which directly compared the fibrinolytics streptokinase and urokinase. Three small RCTs (total 104 patients) compared streptokinase or urokinase versus normal saline control. The pooled data showed significant benefits in terms of hospital stay, time to defervescence, improvement in chest radiograph, requirement for surgery, but the results were not always consistent across studies. Complications attributable to therapy were not observed., Reviewers' Conclusions: The numbers of patients in the controlled trials are small. In meta-analysis of these trials, intrapleural fibrinolytic therapy confers significant benefit when compared with normal saline control. Although lesser levels of evidence suggest that intrapleural fibrinolysis can be considered as an important adjunctive therapy to intercostal tube drainage in these conditions, on the basis of RCT evidence alone, we cannot recommend the routine use of fibrinolysis in their management as the trial numbers are too small. Both streptokinase and urokinase are equally efficacious but streptokinase has a slightly higher non-fatal complication rate. Life-threatening complications are rare and were not seen in the RCTs.

Background: Effusions and empyema may complicate lower respiratory tract infections. Loculation of fluid is a major problem with this condition so treatments have included surgical drainage and the use of intra-pulmonary fibrinolysis to break down fibrin bands that may cause loculation., Objectives: To conduct a systematic review of the benefit of adding intrapleural fibrinolytic therapy to intercostal tube drainage in the treatment of complicated parapneumonic effusions and empyema., Search Strategy: The Cochrane Controlled Trials Register was initially searched for relevant RCT's. The search terms were Streptokinase OR Urokinase AND Pleural Effusion OR Intrapleural OR Pleur* OR Parapneumonic Or Empyema. Bibliographies and review articles identified herein were searched for further citations and RCT's. MEDLINE, EMBASE were searched and, where relevant, Index Medicus was hand searched. Trial authors were contacted for further information and details regarding the possibility of unpublished trials was requested., Selection Criteria: Types of Studies All studies in the review were Randomised Controlled Trials in adult patients empyema or complicated parapneumonic effusions who had not had prior surgical intervention or trauma. The intervention was an intrapleural fibrinolytic agent (streptokinase or urokinase) vs control or a comparison of the two., Data Collection and Analysis: All identified studies were reviewed independently by two reviewer and all data collected. Reviews were scored according to the Cochrane assessment of allocation concealment and the Jadad scale of methodological quality. Disagreements between reviewers were referred to a third reviewer. Where further information was required, authors of trial papers were contacted for further details., Main Results: Three studies were identified, one which directly compared the fibrinolytics streptokinase and urokinase. Two small RCTs (total 58 patients) compared streptokinase or urokinase vs normal saline control. The pooled data showed small benefits in terms of hospital stay, time to defervescence, improvement in chest radiograph, requirement for surgery, but the results were not always consistent across studies. Complications attributable to therapy were not seen., Reviewer's Conclusions: There is currently insufficient evidence to support routine use of intrapleural fibrinolytic therapy in the treatment of parapneumonic effusion and empyema. The results of a large multi-centre study, currently underway, are awaited.

Intrapleural fibrinolytic treatment is increasingly used in patients with loculated empyema. In this paper, we report our experience with fibrinolytic therapy in eight patients with empyema not responding to drainage and antibiotics. Mean patient age was 47 (range 3-76), and mean duration of symptoms 14 weeks (range 1-24). The patients were treated with 250,000 IU streptokinase in four hours, 1-6 intrapleural instillations (except 50,000 IU for the child). Between 500 and 4,500 cc fluid was drained. Mean drainage time was 14 days (range 6-20). Mean time spent in hospital was 20 days (range 15-25). No microbiological agent was isolated in three patients. All patients recovered. One patient experienced a hypersensitivity reaction following streptokinase treatment for more than one week. Fibrinolysis with streptokinase should be used in patients with loculated empyema when drainage and antibiotics fail.