Urokinase Instillation Research Articles

A case of single cervical tuberculous cold abscess associated with multi-loculated tuberculous pleurisy

Although the incidence of pulmonary tuberculosis is declining, the number of extrapulmonary tuberculosis has remained constant. Tuberculous Lymphadenitis accounts for over 50% of total inflammatory lymphadenitis and the most common site is cervical lymph node. We report a case of single cervical tuberculous cold abscess associated with multiloculated and septated tuberculous pleurisy. Intracavitary urokinase instillation via percutaneous catheter is indicated in loculated and septated pleural effusion. And our result was satisfactory without complication.

Treatment of Complicated Pleural Fluid Collections With Image-Guided Drainage and Intracavitary Urokinase

We report the results of image-guided catheter drainage with adjunctive enzymatic pleural debridement in the treatment of empyemas and other complicated pleural fluid collections. Retrospective review. One hundred eighteen patients with complicated pleural fluid collections were treated with image-guided drainage. There were 79 empyemas, 27 sterile loculated parapneumonic effusions, 10 sterile hemothoraces, and 2 sterile postoperative exudative effusions. Forty-one patients had failed prior large-bore thoracostomy drainage. The estimated age of the effusions at the time of image-guided drainage ranged from 1 to 175 days with a mean estimated age of 13 days. Patients were treated with image-guided placement of one or more 12F to 16F chest drains. Adjunctive urokinase instillation was used in 98 cases. Urokinase (100,000 to 250,000 U/mL) was instilled in 20 to 240-mL aliquots and reaspirated in 1 to 4 h. One to four instillations were performed per day until drainage was complete. Drainage was successful in 111 cases (94%). Two patients died of sepsis with incomplete drainage. Five patients underwent decortication (three recovered and two died postoperatively). Fifty-three patients (45%) required placement of more than one drain. The mean duration of drainage was 6.3 days. Patients treated with pleurolysis required a mean of five instillations of urokinase. The mean total dose of urokinase used per case was 466,000 U. There were no complications. Image-guided drainage with adjunctive pleural urokinase therapy is a safe and effective method of closed thoracostomy drainage of complicated pleural fluid collections and can obviate surgery in most cases.

Morbidity using subcutaneous ports and efficacy of vancomycin flushing in cancer.

An evaluation of totally implanted venous access systems inserted in 163 consecutive children with cancer is reported. From 1988 to 1994, 180 subcutaneous ports were inserted in children more than 1 year old. Initial diagnosis was acute leukaemia (n = 79), non-Hodgkin's lymphoma (n = 33), and solid tumour (n = 51). Median age was 85 months. All venous procedures were performed through the device. Chemotherapy was either moderate (n = 13) or intensive (n = 119) or very intensive (n = 48), including 16 patients undergoing marrow transplantation. Cumulative venous access totalled 55,770 patient days with a mean of 305 days/subcutaneous port. The cause of device removal was, end of treatment (n = 111), death due to malignancy (n = 20), catheter related infection (n = 7), and occlusion of the system (n = 4). Mechanical complications occurred in 19 ports; 16 were due to clots, of which 14 were cleared with instillation of urokinase. Documented infectious episodes occurred in 47 ports, recurred once in 14, and twice in five cases. Among these infections, 47 were septicaemic; 31 due to Staphylococcus epidermidis. Twenty seven of initial septic episodes were considered to be catheter related; the rate was 15%/subcutaneous port or 0.05/100 catheter days. Risk factors for the development of a first infection were age below 4 years and the time of use. Since February 1993, vancomycin (50 micrograms/ml) has been given and this has reduced the rate of S epidermidis infection from 26/83 subcutaneous port to 4/97. Life table analysis showed that the infection free interval for staphylococcus was significantly better after this technique ws initiated (log rank rest=0.02). Time saved was approximately 30minutes/patient/week compared with external catheters, or 45 hours/month for the cohort of children treated. Subcutaneous ports in paediatric cancer patients are reliable, safe, and durable and may offer an attractive alternative to external catheters for prolonged venous access and intensive treatment.

Transcatheter Instillation of Urokinase into Loculated Pleural Effusion: Analysis of Treatment Effect

Transcatheter Instillation of Urokinase into Loculated Pleural Effusion: Analysis of Treatment Effect

Intrapleural instillation of urokinase in the treatment of loculated pleural effusions in children

The authors report on the use of intrapleural instillation of urokinase in the treatment of loculated pleural effusions in two pediatric patients. Urokinase helps to lyse fibrin by converting plasminogen to plasmin. The intrapleural instillation of urokinase is safe and effective for promoting drainage of loculated intrapleural effusions, and it proved a useful option in the treatment of persistent loculations.

Acute Hypoxemic Respiratory Failure Following Intrapleural Thrombolytic Therapy for Hemothorax

Intrapleural instillation of thrombolytic agents has been useful in the treatment of hemothorax when thoracostomy tube drainage is unsuccessful. We present a patient who developed acute hypoxemic respiratory failure following the intrapleural instillation of both streptokinase and urokinase 24 h apart. Hypoxemia most likely resulted from a direct effect of the products of fibrinolysis on the pulmonary circulation.

Intrapleural Urokinase in the Treatment of Loculated Pleural Effusions

The purpose of this study was to assess the value of intrapleural urokinase (UK) instillations in enhancing tube drainage of loculated, complex pleural effusions. Tube thoracostomy has variable success in the treatment of complex pleural effusions, with limitations because of viscous fluid, improper tube position or kinking, and, most importantly, loculation. In the past, intrapleural administration of streptokinase has been used to lyse locules. In this study, eight patients with nine loculated pleural processes were treated with intrapleural instillations of UK. Six patients had previously undergone unsuccessful conventional tube drainage. Loculation was suggested by persistent fluid despite an adequate trial of simple drainage, radiographic demonstration of septation, or drainage of a volume of fluid far less than expected by a computed tomography scan. After instillation of a UK solution, the tubes were clamped for 30 to 180 min and then placed back to suction. Five pleural cavities with disease 6 to 18 days old showed complete resolution, and clinical improvement occurred. Three pleural processes showed improvement and one showed no improvement, with disease ranging from 23 days to 3 months. No complications were seen. These results suggest that UK instillations may enhance tube drainage of loculated pleural fluid in the early phase, before fibrosis has developed.

A new look at intraoperative completion arteriography: Classification and management strategies for intraluminal defects

Completion arteriography is widely regarded as an essential component of infrainguinal bypasses. However, the significance of various intraluminal filling defects is poorly defined, and strategies for managing these defects are unclear. Completion arteriography was performed by a standard technique in 78 infrapopliteal bypasses and were evaluated prospectively for the presence of angiographic defects. Thirty-nine arteriograms (50%) had no visible abnormality (grade O). Six arteriograms (8%) had minimal (grade I) defects, i.e., round lucencies (bubbles) or valve leaflets. Eighteen arteriograms (23%) had moderate (grade II) defects, i.e., uniform smooth tapering (up to 90% of luminal diameter) of the graft or outflow artery, irregular intraluminal filling defect (less than 60% of luminal diameter) within the distal graft or its adjacent outflow artery, or incomplete or faint graft opacification. Fifteen arteriograms (19%) had severe (grade III) defects, i.e., total cutoff of graft or outflow artery opacification or irregular intraluminal filling defect (greater than 60%) in the distal graft or adjacent outflow artery. Completion arteriograms were further stratified for type of bypass and outflow characteristics. All 24 bypasses with grade I or grade II defects on completion arteriography had no further surgical treatment. However, the 18 bypasses with grade II defects on completion arteriography had minimal nonsurgical manipulations consisting of repeat arteriography without or with papaverine infusion or urokinase instillation. In all 18, repeat arteriography showed improvement in the defect. The 15 bypasses with grade III defects had further surgical intervention (graftotomy, thrombectomy, vein patching, interposition graft, or graft extension). One-month and 1-year patency rates for grafts with grade I and grade II defects (87% and 79%, respectively) were not significantly worse than those for the 39 grafts with no arteriographic abnormalities (87% and 82%, respectively). In contrast, grafts with grade III defects had significantly worse (p < 0.01) 1-month and 1-year patency rates (33% and 20%, respectively) despite aggressive surgical correction of the arteriographic defects. These results emphasize the value of repeat completion arteriography and minimal interventional strategies when grade I or II defects are seen on arteriography. The poor outcome with surgical correction of grade III defects suggests that completion arteriography may not always define the full extent of the problem or that the corrective surgical maneuvers were either incomplete or detrimental.

Prospective analysis of urokinase in the treatment of catheter sepsis in pediatric hematology-oncology patients

Use of right atrial catheters (RACs) in children with cancer improves the comfort and efficacy of therapy. However, catheter-related infections are responsible for significant morbidity leading to the removal of approximately 20% of implanted RACs. Sepsis has been linked to thrombus and fibrin sheath formation within the RAC. Gram-negative and fungal infections appear to be particularly resistant to antibiotic therapy alone and most of these infections have required catheter removal. Urokinase has been effectively used for reopening thrombus occluded RACs. Theoretically, thrombolytic agents could improve the treatment of catheter-related infections by removing luminal sites of bacterial/fungal colonization. We prospectively monitored the use of urokinase and antibiotics for catheter-related sepsis in our pediatric hematology/oncology population from 1985 to 1991. Sepsis episodes were treated with 2 doses of urokinase and antibiotics (10 to 42 days) infused through the RAC. One to 2 mL of urokinase (5,000 U/mL) was instilled in the RAC for 1 hour, then removed and repeated 24 hours later. During the study, 224 RACs were placed in 177 children. RACs were in place for a total of 71,134 days (median, 274 days). There were 67 blood culture-positive sepsis episodes occurring in 50 RACs. Fifty-nine sepsis episodes were treated with urokinase and antibiotics and all responded by clearance of organisms from the blood. Three patients (5.1% of urokinase treated) had recurrent sepsis with the same organism within 2 months, were considered treatment failures and had RACs removed. Only 1 of 16 episodes of multiple organism/ Candida sepsis led to RAC removal due to inability to cure the infection. An additional patient died of leukemia and Candida pancreatic abscess. Two other RACs in the urokinase group were removed for subsequent exit site infections and one was removed due to a mechanical complication. A smaller subgroup of patients with 8 catheter sepsis episodes were treated with antibiotics alone. In this group, one RAC required removal due to persistent infection, 2 patients died with infection and disease relapse, and 2 catheters were removed before completing antibiotic therapy. The remaining 3 patients retained their RAC. Isolated exit site or tunnel infections without bacteremia were observed on 8 occasions and lead to the removal of 6 RACs. Overall, only 13 of 224 RACs (5.8%) were removed due to all catheter-related infections. No adverse effects of urokinase instillation were observed. The concomitant use of urokinase and antibiotics can effectively and safely treat catheter-related sepsis leading to salvage of over 90% of infected RACs. This protocol is not designed for improvement of RAC exit site infection therapy.

Treatment of thoracic multiloculated empyemas with intracavitary urokinase: a prospective study.

The authors prospectively treated 10 consecutive patients with multiloculated empyemas with intracavitary instillation of urokinase via a percutaneous drainage catheter. Urokinase (100,000 IU) in 100 mL of 5% dextrose in water was instilled into the pleural cavity via a percutaneous drainage catheter. After overnight clamping, the catheter was opened and the empyema drained with use of negative suction (20 cm H2O). Intermittent irrigation of the catheter with normal saline was performed to prevent clogging of the catheter. Complete drainage of multiloculated empyemas was accomplished in nine patients by means of intracavitary instillation of urokinase via a single 8-F catheter. One patient showed complete drainage of multiloculated empyema, but recurrent empyema appeared in the site of a previous tube thoracostomy. A total of 100,000-700,000 IU (mean, 400,000 IU) of urokinase were needed for complete drainage in all patients. Plasminogen and fibrin degradation product levels in empyema fluid were determined before instillation of urokinase to demonstrate any fibrinolytic action. No complications occurred.

Intraperitoneal Thrombolytic Agents in Relapsing or Persistent Peritonitis of Patients on Continuous Ambulatory Peritoneal Dialysis

Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis.

Use of a Silicone Dual-Lumen Catheter With a Dacron Cuff as a Long-Term Vascular Access for Hemodialysis Patients

We evaluated our experience over a 4-year period with a silicone dual-lumen catheter with a Dacron cuff (SDLCDC) to determine if the catheter represents an alternative to the polytetrafluoroethylene graft for long-term vascular access for hemodialysis patients. Records of 131 patients who used 168 catheters were reviewed for catheter function, duration of use, and occurrence and response to treatment of complications. Eighty-five percent of catheters functioned adequately until their use was no longer required or the end of the study. One-year catheter survival estimate was 65% and median survival estimate was 18.5 months. Mean blood flow rate achieved was 243 mL/min and recirculation was 7.5%. Exit-site infection occurred in 21% of patients and bacteremia in 12%. There were significantly more exit-site infections in diabetics than nondiabetics (33% v 11%, P less than 0.02). Exit-site infections resolved with parenteral antibiotic therapy in 90% and bacteremia in 25% of cases without catheter removal. Unresolved bacteremia was the most common cause of catheter removal and led to the loss of 7% of catheters. Thrombotic complications occurred in 46% of catheters. Urokinase instillation successfully treated catheter occlusion in 81% of cases. When urokinase instillation failed, streptokinase infusion restored catheter patency 97% of the time. The literature on the polytetrafluoroethylene (PTFE) graft was reviewed, and the SDLCDC was found to be similar to the graft in function, duration of use, and frequency of infectious and thrombotic complications. We conclude that the catheter represents an alternative to the graft for long-term vascular access in hemodialysis patients. Because of the frequent complications with both accesses, neither should be considered optimal. Further research is required to improve vascular access for patients in whom placement of an arteriovenous fistula is not possible.

The use of Dual Lumen Jugular Venous Catheters as Definitive Long Term Access for Haemodialysis

We describe the long term use for haemodialysis of the PermCath (Quinton, Seattle, Washington) dual lumen, jugular venous catheter (DLJVC) in 21 patients who had no apparent alternative means of access. The nineteen patients maintained in this manner for periods of 30 to 600 days (mean 233.2) included 6 patients dialyzed for over 12 months. Blood flows exceeded 250 mls/min and recirculation rates averaged 5.9%. Infection and insufficiency due to thrombosis were the major problems. In 8 patients (38.1%) infection required DLJVC removal; in three the catheter was immediately replaced over a guidewire along the same track under antibiotic cover and infection has not recurred. Insufficiency occurred in 10 patients (47.6%) and was successfully managed with oral anticoagulants, local instillation of urokinase (4 cases), systemic streptokinase (2 cases) or by changing the DLJVC over a guidewire (2 cases). We believe that the DLJVC is the long term access method of choice for patients in whom conventional access cannot be constructed.

Treatment of loculated pleural effusions with transcatheter intracavitary urokinase.

Surgical thoracostomy tube placement and radiologically guided catheter drainage are standard therapy for loculated pleural fluid collections. Treatment may fail if the catheter is not placed optimally within the loculation or if the fluid is hemorrhagic or fibrinous. We studied the value of transcatheter urokinase instillation in facilitating drainage of hemorrhagic or fibrinous nonhemorrhagic loculated pleural collections in 11 patients with 13 loculated pleural collections. Eight of the fluid collections were hemorrhagic, five were nonhemorrhagic. Five patients had had a thoracostomy tube placed surgically and all had had radiologically guided placement of single lumen drainage catheters managed with suction, saline irrigation, and mechanical guidewire manipulation. This therapy had failed to drain the loculations completely over an average of 10 days (range, 1-22 days). Urokinase (1000 units/ml) was instilled into the drainage catheters in 80- to 150-ml aliquots. After 1-2 hr, suction was reinstituted and the procedure was repeated. Twelve (92%) of the 13 collections were drained completely after an average of 4.3 instillations (range, three to eight instillations). Successful urokinase therapy required an average of 28 hr (range, 8-75 hr). In one case, therapy was discontinued after partial resolution for unrelated clinical reasons. There were no complications. These results suggest that transcatheter intracavitary urokinase therapy is a safe and effective method to facilitate drainage of loculated hemorrhagic or fibrinous nonhemorrhagic pleural fluid collections.

Prospective Evaluation of a Dacron Cuffed Hemodialysis Catheter for Prolonged Use

Double lumen subclavian venous hemodialysis catheters are in wide use in the United States to provide temporary vascular access. The disadvantages of these catheters include a high infection rate and short use-life (2 to 3 weeks). We evaluated a felt cuffed tunnelled jugular venous hemodialysis catheter (PermCath) to determine its ability to overcome these shortcomings and compared it with standard noncuffed double lumen dialysis catheters. Eighty PermCaths were inserted during this prospective study in patients needing temporary vascular access in excess of 1 month. Median use-life of these catheters was 8 weeks with a use range of 3 weeks to 5.4 months. Only four functioning catheters failed before elective removal. Despite the prolonged use-life there was only one episode of catheter mediated bacteremia. Seven catheters (9%) failed to function immediately after insertion. These failures were caused by catheter kinking in the region of the felt cuff. Thrombosis of the catheter lumen was the most frequent complication (137 episodes) but resolved in over 95% of the instances with urokinase instillation. Exit site infections (23 instances) were successfully treated conservatively. We conclude that the PermCath (Quinton Instrument Co, Seattle) is a safe and reliable new device with a low complication rate and a longer use-life than standard subclavian dialysis catheters. This longer use-life allows more time for maturation of primary arteriovenous (AV) fistulas and Tenckhoff peritoneal dialysis catheters, and provides time for the healing of infected vascular access grafts. Its primary disadvantage is the need for surgical insertion.

Hickman catheter for haemodialysis in paediatric patients.

Twelve Hickman catheters were inserted in nine children in order to establish access for haemodialysis or plasmapheresis. Catheters were implanted either through the external or internal jugular vein and the tip located in the right atrium or superior vena cava. Mean blood flow was 25-55 ml/min with single lumen catheters and 83-100 ml/min with double lumen catheters. Three catheters had to be removed because of obstruction, whilst seven remained in situ until an arteriovenous fistula had matured or renal function was restored. Infection in two cases was successfully treated with antibiotics and transient obstruction by urokinase instillation. Following catheter removal, angiographic studies showed that with one exception all catheterized vessels were obstructed, but this did not prevent from ipsilateral arteriovenous fistulas to mature satisfactorily.

Lysis of Intraventricular Blood Clot with Urokinase in a Canine Model: Part 1

To test the safety and feasibility of using direct instillation of urokinase to induce rapid lysis of intraventricular clots, an animal model of intraventricular blood cast is required. Injections of 11 ml of fresh, unclotted autologous blood into the ventricles of adult mongrel dogs did not produce a solid blood cast in the ventricular system, suggesting that the adult dogs have an unusual ability to clear uncoagulated whole blood from the ventricles and subarachnoid space. Injection of 9 ml of preclotted blood resulted in a subtotal cast of the ventricles, leaving only portions of the occipital horns free of solid clots. This volume of injected clots incurred no mortality and minimal morbidity, whereas injection of 10 to 12 ml resulted in a mortality of 42% and formidable morbidity. The technique of producing this intraventricular blood cast model, as well as that of implanting an indwelling ventricular catheter-reservoir system useful in chronic urokinase administration, is described.

Urokinase in the treatment of occluded central venous catheters in children

Urokinase was used to clear occluded silastic central venous catheters in 14 pediatric patients. The catheters, which had been placed into a neck vein and tunnelled out through the skin of the anterior chest wall, were being used for either long-term parenteral nutrition or chemotherapy. Occluded catheters that could not be cleared by simple flushing with heparinized saline were filled with a solution of urokinase, which was left in place for 2 hours before the catheter was flushed a second time. Twenty-one occluded catheters were managed in this way over a period of 14 months. There were no allergic reactions or bleeding complications. Twelve of the 21 occluded catheters were immediately cleared. Three catheters ruptured during attempted flushing maneuvers but were patent after repair. Two catheters remained partially occluded. Only four catheters were removed because of persistent occlusion. When simpler techniques fail, urokinase instillation appears a safe and effective alternative to the more common practice of removing occluded central venous catheters in children.

The Prophylactic Use of Thio-Tepa and Urokinase in Transitional Cell Carcinoma of the Bladder: A Preliminary Report

The prevention of recurrences of bladder cancer was attempted in 48 patients by means of the combined intravesical instillation of thio-tepa and urokinase and in 28 patients through the instillation of thio-tepa alone. The recurrence rates of both therapies for the postoperative 18 months were 7.9 and 32.6 per cent, respectively, indicating a significant drop in the recurrence rate in the group subjected to the combined therapy. No significant difference was found between the 2 instillation groups in terms of the blood transmission of 32P thio-tepa. Serious leukopenia was found in 2 of the 48 patients receiving the combined instillation therapy but we concluded that this was not attributable to the use of urokinase.

Serosal hypofibrinolysis: A cause of postoperative adhesions

1. 1. Fibrinolytic activator activity is present in canine and human gastrointestinal serosa and is decreased after trauma. 2. 2. Massive adhesion formation occurred when the serosal fibrinolytic activity was decreased at least 50 per cent. 3. 3. Intraperitoneal urokinase was effective in preventing adhesions in 80 per cent of the animals. 4. 4. No wound healing or anastomotic difficulties were encountered and there were no hemorrhagic complications from the intraperitoneal instillation of urokinase.