Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Intrapleural Fibrinolysis with Urokinase versus Alteplase in Complicated Pleural Effusions and Empyema: A Prospective Randomized Controlled Trial

  • Sudipt Adhikari (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Vikas Marwah (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Robin Choudhary (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Indermani Pandey (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Tentu Ajai Kumar (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Virender Malik (Department of Radiology, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Arpita Pemmaraju (Department of Pathology, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Shrinath Vasudevan (Department of Pulmonary, Critical Care and Sleep Medicine, Army Institute of Cardiothoracic Sciences (AICTS)) ;
  • Suraj Kapoor (Department of Community Medicine, Armed Forces Medical College (AFMC))
  • Received : 2023.01.10
  • Accepted : 2024.02.27
  • Published : 2024.07.31
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Abstract

Background: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. Methods: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. Results: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean±standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. Conclusion: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

Keywords

References

  1. Malhotra P, Aggarwal AN, Agarwal R, Ray P, Gupta D, Jindal SK. Clinical characteristics and outcomes of empyema thoracis in 117 patients: a comparative analysis of tuberculous vs. non-tuberculous aetiologies. Respir Med 2007;101:423-30. https://doi.org/10.1016/j.rmed.2006.07.016
  2. Kundu S, Mitra S, Mukherjee S, Das S. Adult thoracic empyema: a comparative analysis of tuberculous and nontuberculous etiology in 75 patients. Lung India 2010;27:196-201. https://doi.org/10.4103/0970-2113.71939
  3. Barthwal MS, Marwah V, Chopra M, Garg Y, Tyagi R, Kishore K, et al. A five-year study of intrapleural fibrinolytic therapy in loculated pleural collections. Indian J Chest Dis Allied Sci 2016;58:17-20.
  4. Tillett WS, Sherry S. Streptococcal enzymatic debridement. Ann Surg 1950;131:12-22. https://doi.org/10.1097/00000658-195001000-00002
  5. Bergh NP, Ekroth R, Larsson S, Nagy P. Intrapleural streptokinase in the treatment of haemothorax and empyema. Scand J Thorac Cardiovasc Surg 1977;11:265-8.
  6. Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bolliger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Respir Crit Care Med 2004;170:49-53. https://doi.org/10.1164/rccm.200312-1740OC
  7. Simpson G, Roomes D, Heron M. Effects of streptokinase and deoxyribonuclease on viscosity of human surgical and empyema pus. Chest 2000;117:1728-33. https://doi.org/10.1378/chest.117.6.1728
  8. Maskell NA, Batt S, Hedley EL, Davies CW, Gillespie SH, Davies RJ. The bacteriology of pleural infection by genetic and standard methods and its mortality significance. Am J Respir Crit Care Med 2006;174:817-23. https://doi.org/10.1164/rccm.200601-074OC
  9. Light RW, Nguyen T, Mulligan ME, Sasse SA. The in vitro efficacy of varidase versus streptokinase or urokinase for liquefying thick purulent exudative material from loculated empyema. Lung 2000;178:13-8. https://doi.org/10.1007/s004080000002
  10. Ben-Or S, Feins RH, Veeramachaneni NK, Haithcock BE. Effectiveness and risks associated with intrapleural alteplase by means of tube thoracostomy. Ann Thorac Surg 2011;91:860-4. https://doi.org/10.1016/j.athoracsur.2010.10.082
  11. Popowicz N, Bintcliffe O, De Fonseka D, Blyth KG, Smith NA, Piccolo F, et al. Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection: the Alteplase Dose Assessment for Pleural Infection Therapy project. Ann Am Thorac Soc 2017;14:929-36. https://doi.org/10.1513/AnnalsATS.201609-673OC
  12. Vaudaux P, Waldvogel FA. Gentamicin inactivation in purulent exudates: role of cell lysis. J Infect Dis 1980;142:586-93. https://doi.org/10.1093/infdis/142.4.586
  13. Colice GL, Curtis A, Deslauriers J, Heffner J, Light R, Littenberg B, et al. Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline. Chest 2000;118:1158-71. https://doi.org/10.1378/chest.118.4.1158
  14. Nie W, Liu Y, Ye J, Shi L, Shao F, Ying K, et al. Efficacy of intrapleural instillation of fibrinolytics for treating pleural empyema and parapneumonic effusion: a meta-analysis of randomized control trials. Clin Respir J 2014;8:281-91. https://doi.org/10.1111/crj.12068
  15. Aleman C, Porcel JM, Alegre J, Ruiz E, Bielsa S, Andreu J, et al. Intrapleural fibrinolysis with urokinase versus alteplase in complicated parapneumonic pleural effusions and empyemas: a prospective randomized study. Lung 2015;193:993-1000. https://doi.org/10.1007/s00408-015-9807-6
  16. Rahman NM, Maskell NA, Davies CW, Hedley EL, Nunn AJ, Gleeson FV, et al. The relationship between chest tube size and clinical outcome in pleural infection. Chest 2010;137:536-43. https://doi.org/10.1378/chest.09-1044
  17. Bouros D, Schiza S, Patsourakis G, Chalkiadakis G, Panagou P, Siafakas NM. Intrapleural streptokinase versus urokinase in the treatment of complicated parapneumonic effusions: a prospective, double-blind study. Am J Respir Crit Care Med 1997;155:291-5. https://doi.org/10.1164/ajrccm.155.1.9001327
  18. Skeete DA, Rutherford EJ, Schlidt SA, Abrams JE, Parker LA, Rich PB. Intrapleural tissue plasminogen activator for complicated pleural effusions. J Trauma 2004;57:1178-83. https://doi.org/10.1097/01.TA.0000141879.67441.52
  19. Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 2011;365:518-26. https://doi.org/10.1056/NEJMoa1012740
  20. Idell S. Update on the use of fibrinolysins in pleural disease. Clin Pulm Med 2005;12:184-90. https://doi.org/10.1097/01.cpm.0000163392.76738.84
  21. Altmann ES, Crossingham I, Wilson S, Davies HR. Intra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema. Cochrane Database Syst Rev 2019;2019:CD002312.