Transcatheter intrapleural urokinase for loculated pleural effusion

Michael L. Cohen

Two patients who had undergone coronary artery bypass graft surgery in the mid-1980s and who had repeat coronary artery bypass graft procedures in 1992 developed loculated, bloody pleural effusions. Percutaneous catheter drainage and installation of intrapleural urokinase led to resolution of these loculated effusions without morbidity. This procedure should reduce the length of hospitalization and treatment for patients with loculated pleural effusions.

Intracavitary urokinase has been successfully utilized in percutaneous abscess drainage[1] and in promoting drainage of both hemorrhagic and fibrinous loculated pleural effusions.[2-4] We present two cases of hemorrhagic loculated effusions occurring after coronary artery bypass grafting procedures. Both were successfully evacuated by transcatheter drainage in conjunction with urokinase infusion.

Case Reports

Case 1

A 74-year-old white man, who had undergone coronary artery bypass graft surgery in 1985, was readmitted to the hospital on December 14, 1992, with accelerating angina and again underwent coronary bypass surgery on December 16, 1992. His postoperative course was complicated by low-grade fever. A chest x-ray film showed patchy basilar atelectasis and increased density in the left pleural space. His WBC count was less than 10,000/[mm.sup.3]. His admission hemoglobin value was 15.2 g/dl but dropped to 8 g/dl by December 25, 1992.

On January 1, 1993, he was seen for a pulmonary consultation. He was complaining of shortness of breath and had a low-grade temperature, a heart rate of 90 beats per minute, and a respiratory rate of 20 breaths per minute. A chest x-ray film, including bilateral decubitus films, showed a subpulmonic right pleural effusion and a large left pleural effusion. Thoracentesis yielded 1,200 ml of port wine-colored bloody fluid from the right and 1,800 ml of similar fluid from the left hemithorax. The patient responded to thoracentesis with decreased shortness of breath. A repeat chest x-ray film show ed a persistent densityin the left hemithorax. Five days later, a computed tomography (CT) scan of the chest with supine and prone imaging was performed. It showed a moderate free-flowing right effusion and a large left effusion that appeared to be loculated within the caudal aspect of the left hemithorax, partially collapsing the left lower lobe (Fig 1, top). The following day, 12F sump catheters were inserted under CT guidance in each pleural fluid collection; 600 ml was drained from the right side of the chest and 1,300 ml was drained from the left side of the chest. Analysis of the pleural fluid showed a few white cells and no growth.

The patient was treated with overnight drainage of both effusions using continuous low suction. The left effusion also was treated with installation of two doses of 250,000 U of urokinase in 50 ml of normal saline solution at 12-h intervals. Following each urokinase infusion, the tube was clamped for 4 h. Another 1,600 ml of fluid was drained f rom the left side of the chest overnight, and a repeat CT the following day. (Fig 1, bottom) showed evacuation of the left pleural effusion. The sump catheters were removed and the patient was discharged, afebrile, and clinically comfortable.

Case 2

A 69-year-old man who had undergone coronary bypass graft surgery in 1983 underwent a repeat coronary artery bypass graft procedure on September 26, 1992, because of increasing angina. His postoperative course was uneventful and he was discharged on a regimen of aspirin and persantine. Over the next few months, he experienced progressively increasing anterior left pleuritic pain and a dry cough. He did not have fever, chills, or sweats. On December 11. 1992. he was readmitted to the hospital with a large left pleural effusion. His WBC count was 7,400/[mm.sup.3]; hemoglobin level, 10.9 g/dl; erythrocyte sedimentation rate, 16 ml in 1 h; and [PaO.sub.2], 54 mm Hg. A thoracentesis yielded 2,000 ml of bloody, nonclotting fluid, with a hematocrit value of 14 percent. A chest tube was inserted for the next 24 h and 800 ml of bloody fluid was drained. A low-grade temperature was noted on the first two hospital days; he was subsequently afebrile. A small right pleural effusion also developed during his hospital stay; and he was believed to have a posteardiotomy syndrome. He was discharged on December 17, 1992, on 40 mg of prednisone a day. His x-ray film showed minimal bibasilar atelectasis.

On January 13, 1993, he was readmitted to the hospital because of increasing left pleuritic pain and recurrent left pleural effusion. A chest CT scan showed a loculated lateral and anterolateral pleural fluid collection, with thickening of the pleural surface. No septations were identified. Under CT guidance, a 12F sump catheter was inserted into the posterior pleural collection device. The fluid was bloody with a specific gravity of 1.025. There was no bacterial growth. At the time of catheter insertion, 250,000 units of urokinase were injected intrapleurally. The pleural effusion was drained as described in case 1 and four further doses of urokinase were administered over the next three days. On the third day of catheter therapy, the catheter was repositioned under fluoroscopic guidance. On the fourth day, there was no further drainage and the catheter was removed. A total of 1,500 ml of fluid had drained from the catheter. A chest x-ray film showed minimal pleural reaction and no free fluid. The patient developed a fever ranging from 38 to 39.5[degrees]C on December 14. He had received two doses of urokinase that day. Three blood cultures taken that day were negative. He was afebrile thereafter despite ongoing urokinase therapy. No medication was given to suppress fever. His hospital course was otherwise uneventful and he was clinically well upon discharge. A follow-up CT scan performed 2 weeks after discharge confirmed clearing of the effusion with a small residual anterior component.


Loculated pleural effusions may be treated by thoracentesis, thoracoscopy, thoracostomy tube drainage, open drainage, or thoracotomy and decortication. We favored CT-guided tube placement as a means of insuring proper catheter positioning. Single lumen or sump catheters in the range of 1OF to 14F generally are adequate to drain all but the most viscous fluid collections.[5-7] Loculated effusions may prove refractory to catheter drainage even when catheter placement is appropriate due to fibrinous debris or septations within the collection.[6] Urokinase converts plasminogen to plasmin, which degrades fibrin and produces a local chemical milieu that lyses septations. Both streptokinase[8,9] and urokinase have been used in the treatment of loculated pleural effusions, but urokinase has supplanted streptokinase as the preferred thrombolytic agent because it produces no antibody response. It has been used in the treatment of infected intra-abdominal hematomas[10] and in the percutaneous drainage of septated and multiloculated abdominal abscesses.[1] The ideal dose of urokinase, frequency of treatments, and time of initiation of treatment remain to be determined. The reported doses of intrapleural urokinase range from 80,000 to 450,000 U and the length of treatment ranges from 3 to 8 days. In treating abdominal abscesses, Lahorra et al[1] based the dose upon the size of the collection (1,000 to 5,000 U/cm of abscess diameter). The intrapleural dose could be adjusted based on the size of the effusion. The length of treatment can be determined by the quantity of fluid, its age, and the size of any residual fluid collection as measured by plain radiography or CT. We favor the early administration of urokinase following percutaneous catheter drainage to reduce the length of hospitalization and prevent progressive fibrosis of the pleural surfaces.

Local urokinase therapy has not been reported to produce any significant complications. Lahorra et al[1] measured hematocrit level, prothrombin time, partial thromboplastin time, platelet count, and serum fibrinogen and fibrin degradation products in 26 patients and found no significant change without urokinase therapy. We believe that urokinase therapy can be considered for hemorrhagic effusions in the immediate postoperative period or in the setting of trauma, but serial hematocrit values should be obtained despite the evidence suggesting that local infusion does not produce systemic fibrinolysis. We would also postpone this therapy in a patient with known active bleeding.

The transient fever in case 2 may have represented a systemic response to absorbed urokinase, although similar doses given subsequently produced no febrile reaction. Nonhemorrhagic systemic reactions to urokinase have been reported. These include rigor, hypotension, and anaphylactoid reaction.[11,12] Such complications have been noted following intravascular administration of urokinase but have not been reported in conjunction with localized therapy where systemic absorption is much less.


[1] Lahorrajm, Haaja Jr, Stellatot, Flanigan T, Graham R. Safety of intracavity urokinase with percutaneous abscess drainage. AJR 1993; 160:171-74 [2] Moulton JS, Moore PT, Mencini RA. Treatments of loculated pleural effusion with transeatheter intracavity urokinase. AJR 1989; 153:941-45 [3] Brule JF, Winnoch S, Dabadie P, Dardel E, Maurette P, Janvier G. Decaillotage pleural et fibrolytiques: thrombolytic treatment of intrapleural clots. Ann Fr Anesth Reamin 1985; 4:298-300 [4] Couser JI jr, Berley J, Timm EG. Intrapleural urokinase for loculated effusion. Chest 1992; 101:1467-69 [5] Silverman SG, Mueller PR, Saini S, Hahn PF, Simeone JF, Formon BH, et al. Thoracie empyema: management with image-guided catheter drainage. Radiology 1988; 169:5-9 [6] Merriam MA, Cronan JJ, Dorfman GS, Lambiase RE, Haas RA. Radiographically guided percutaneous catheter drainage of pleural fluid collections. AJR 1988; 151:1113-16 [7] vanSonnenberg E, Nakamoto SK, Mueller PR, Casola S, Neff CC, Friedman PJ, et al. CT and ultrasound-guided catheter drainage of empyemas after chest-tube failure. Radiology 1984; 151:349-53 [8] Bergh NP, Ekroth R, Larsson S, Nagy P. Intrapleural streptokinase in the treatment of hemothorax and empyema. Scand J Thorac Cardiovasc Surg 1977; 11:265-68 [9] Bershin E, Ekroth R, Teger-Nilsson AC, William-Olsson G. Intrapleural instillation of streptokinase: effects on systemic fibrinolysis. Thorac Cardiovasc Surg 1981; 29:265-66 [10] Vogelzang RL, Tobin RS, Borstein S, Anschertz SL, Marzano M, Kozlowski JM. Transeatheter intracavity fibrolysis of infected extravascular hematomas. AJR 1987; 148:378-80 [11] Vidovich RR, Heiselman DE, Hudock D. Treatment of urokinase-related anaphylactoid reaction with intravenous famotidine. Ann Pharmacother 1992; 26:782-83 [12] Goldhaber SZ, Kessler CM, Heit JA, Elliott CG, Friedenberg WR. Heiselman DE, et al. Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. J Am Coll Cardiol 1992; 20:24-30

COPYRIGHT 1994 American College of Chest Physicians

COPYRIGHT 2004 Gale Group

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