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Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study

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Abstract

Background

Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population.

Methods

Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality.

Results

A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events.

Conclusions

If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

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References

  1. Bryant R, Salmon C (1996) Pleural empyema. Clin Infect Dis 22:747–764

    Article  CAS  PubMed  Google Scholar 

  2. Kroegel C, Antony VB (1997) Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. Eur Respir J 10:2411–2418

    Article  CAS  PubMed  Google Scholar 

  3. Segura RM, Alegre J, Varela E et al (1998) Interleukin-8 and markers of neutrophil degranulation in pleural effusion. Am J Respir Crit Care Med 157:1565–1572

    Article  CAS  PubMed  Google Scholar 

  4. Idell S, Zwieb C, Kumar A, Koenig K, Johnson A (1992) Pathways of fibrin turnover of human pleural mesothelial cells in vitro. Am J Respir Cell Mol Biol 7:414–426

    Article  CAS  PubMed  Google Scholar 

  5. Hua CC, Chang LC, Chen YC, Chang SC (1999) Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions. Chest 116:1292–1296

    Article  CAS  PubMed  Google Scholar 

  6. Chung CL, Chen CH, Sheu JR, Chen YC, Chang SC (2005) Proinflammatory cytokines, transforming growth factor-beta1 and fibrinolytic enzymes in loculated and free-flowing pleural exudates. Chest 128:690–697

    Article  CAS  PubMed  Google Scholar 

  7. Idell S, Girard W, Koenig K, McLarty J, Fair D (1991) Abnormalities of pathways of fibrin turnover in the human pleural space. Am Rev Respir Dis 144:187–194

    Article  CAS  PubMed  Google Scholar 

  8. Philip-Joët F, Alessi MC, Philip Joët C et al (1995) Fibrinolytic and inflammatory processes in pleural effusions. Eur Resp J 8:1352–1356

    Article  Google Scholar 

  9. Alemán C, Alegre J, Monasterio J et al (2003) Association between inflammatory mediators and the fibrinolysis system in infectious pleural effusions. Clin Sci (Lond) 105:601–607

    Article  Google Scholar 

  10. Davies RJ, Traill ZC, Gleeson FV (1997) Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection. Thorax 52:416–421

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Bouros D, Schiza S, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N (1999) Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study. Am J Respir Crit Care Med 159:37–42

    Article  CAS  PubMed  Google Scholar 

  12. Tuncozgur B, Ustunsoy H, Sivrikoz MC et al (2001) Intrapleural urokinase in the management of parapneumonic empyema: a randomized controlled trial. Int J Clin Pract 55:658–660

    CAS  PubMed  Google Scholar 

  13. Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bolliger CT (2004) Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med 170:49–53

    Article  PubMed  Google Scholar 

  14. Misthos P, Sepsas E, Konstantinou M, Athanassiadi K, Skottis I, Lioulias A (2005) Early use of intrapleural fibrinolytics in the management of postpneumonic empyema. A prospective study. Eur J Cardiothorac Surg 28:599–603

    Article  PubMed  Google Scholar 

  15. Maskell NA, Davies CW, Nunn AJ, First Multicenter Intrapleural Sepsis Trial (MIST1) Group et al (2005) UK controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med 352:865–874

    Article  CAS  PubMed  Google Scholar 

  16. Rahman NM, Maskell NA, West A et al (2011) Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 365:518–526

    Article  CAS  PubMed  Google Scholar 

  17. Janda S, Swiston J (2012) Intrapleural fibrinolytic therapy for treatment of adult parapneumonic effusions and empyemas. Chest 142:401–411

    Article  CAS  PubMed  Google Scholar 

  18. Nie W, Liu Y, Ye J, Shi L, Shao F, Ying K, Zhang R (2014) Efficacy of intrapleural instillation of fibrinolytics for treating pleural empyema and parapneumonic effusions: a meta-analysis of randomized control trials. Clin Respir J. 8:281–291

    Article  CAS  PubMed  Google Scholar 

  19. Schmulling S, Grond M, Rudolf J, Heiss WD (2000) One-year follow-up in acute stroke patients treated with r-TPA in clinical routine. Stroke 31:1552–1554

    Article  CAS  PubMed  Google Scholar 

  20. Morelloni S, Fasciolo L, Freggiaro V et al (1990) A comparative evaluation between streptokinase and r-TPA in limiting the myocardial damage during an acute myocardial infarct. An echocardiographic study. Clin Ter 135:359–365

    CAS  PubMed  Google Scholar 

  21. Thommi G, Shehan JC, Robison KL, Christensen M, Backemeyer LA, McLeay MT (2012) A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med 106:716–723

    Article  CAS  PubMed  Google Scholar 

  22. Weinstein M, Restrepo R, Chait PG, Connoly B, Temple M, Mcarthur C (2004) Effectiveness and safety of tissue plasminogen activator in the management of complicated parapneumonic effusions. Pediatrics 113:e182–e185

    Article  PubMed  Google Scholar 

  23. Goralski JL, Bromberg PA (2009) Intrapleural hemorrhage after administration of tPA: a case report and review of the literature. Ther Adv Respir Dis 3:295–300

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Fidelma Greaves and Roger Mattingly for their linguistic advice. This study was funded by the Instituto de Salud Carlos III (EC07/90479).

Author contributions

The authors take responsibility and vouch for the completeness and accuracy of the data and analyses. Dr. Alemán and Prof Porcel are the guarantors of the entire manuscript. Dr. Alemán contributed to the concept and design of the study, coordination of the acquisition of data, data analysis and interpretation of the data, and writing the article. Dr. Porcel contributed to the concept and design of the study, data acquisition and interpretation, and writing and critically revision of the manuscript. Dr. Alegre contributed to the concept and design of the study, data interpretation, and critical revision of the manuscript. Dr. Ruiz contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Bielsa contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Andreu contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Deu contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Suñé contributed to the concept and design of the study, data acquisition, statistical analysis and interpretation of the data, and critical revision of the manuscript. Dr. Martínez-Sogués contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. López contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Pallisa contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Schoenenberger contributed to the concept and design of the study, data acquisition, and critical revision of the manuscript. Dr. Montoro contributed to the concept and design of the study, data acquisition, statistical analysis and interpretation of the data, and critical revision of the manuscript. Prof Fernández de Sevilla contributed to the concept and design of the study, data interpretation, and critically revision of the manuscript.

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    Authors and Affiliations

    1. Department of Internal Medicine, University Hospital Vall d’Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

      Carmen Alemán, José Alegre, Eva Ruiz & Tomás Fernández de Sevilla

    2. Department of Radiology, University Hospital Vall d’Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

      Jordi Andreu & Esther Pallisa

    3. Department of Thoracic Surgery, University Hospital Vall d’Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

      Maria Deu & Iker López

    4. Department of Pharmacy, University Hospital Vall d’Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

      Pilar Suñé & J. Bruno Montoro

    5. Pleural Medicine Unit, Department of Internal Medicine, Arnau de Vilanova University Hospital, Biomedical Research Institute of Lleida, Lleida, Spain

      José M. Porcel & Silvia Bielsa

    6. Department of Pharmacy, Arnau de Vilanova University Hospital, Biomedical Research Institute of Lleida, Lleida, Spain

      Mireia Martínez-Sogués & Joan Antoni Schoenenberger

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    1. Carmen Alemán
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    Correspondence to Carmen Alemán.

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    The authors report to Lung that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Additional information

    Trial registry: ClinicalTrials.gov; No. NCT01246453; URL:www.clinicaltrial.gov.

    Carmen Alemán and José M. Porcel have contributed equally to the study.

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    Alemán, C., Porcel, J.M., Alegre, J. et al. Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study. Lung 193, 993–1000 (2015). https://doi.org/10.1007/s00408-015-9807-6

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    • DOI: https://doi.org/10.1007/s00408-015-9807-6

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