Rebuttal From Drs Colice and Idell
2014; Elsevier BV; Volume: 145; Issue: 1 Linguagem: Inglês
10.1378/chest.13-2357
ISSN1931-3543
Autores Tópico(s)Lung Cancer Diagnosis and Treatment
ResumoDrs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar emphasized that clinical use of a therapeutic agent should be determined by its risk/benefit profile. Let us consider the risk/benefit profile of intrapleural fibrinolytics. Because streptokinase and urokinase are not currently available in the United States, we will focus on the tissue plasminogen activator (tPA). Use of tPA is associated with the risk of bleeding. In a retrospective review, four of 57 patients (7%) treated with intrapleural tPA for a parapneumonic effusion (PPE) or empyema experienced bleeding complications, some of which were serious.2Ben-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: 860-863Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Balanced against the bleeding risk with tPA, clinicians should appreciate that Rahman et al3Rahman NM Maskell NA West A et al.Intrapleural use of tissue plasminogen activator and DNase in pleural infection.N Engl J Med. 2011; 365: 518-526Crossref PubMed Scopus (460) Google Scholar concluded in the second Multicenter Intrapleural Sepsis Trial (MIST2) that intrapleural administration of tPA alone was ineffective. Besides the lack of clinical benefit with tPA in this study, there was no difference in the change in intrapleural opacification between placebo and tPA. This observation indicates that tPA did not effectively cause intrapleural fibrinolysis and pleural drainage when used at an empirical intrapleural dose of 10 mg. With possible risk but no evident benefit, we do not favor routine administration of intrapleural fibrinolytics to adults with a PPE requiring drainage.Drs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar stated that use of intrapleural fibrinolytics in children is firmly established. Although a number of studies support this position, information about clinical practice patterns in the United States does not agree with this point. A large retrospective US database analysis examined treatments and outcomes in 14,936 children hospitalized with empyema or PPE.4Goldin AB Parimi C LaRiviere C Garrison MM Larison CL Sawin RS Outcomes associated with type of intervention and timing in complex pediatric empyema.Am J Surg. 2012; 203: 665-673Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Database analyses provide an invaluable perspective into actual clinical practice. Only 0.1% of these children were treated with intrapleural fibrinolytic therapy, but 8% underwent video-assisted thoracoscopic surgery (VATS). These results indicate that use of VATS, rather than intrapleural fibrinolytics, is firmly established in US management of pediatric patients requiring drainage of a PPE. This clinical approach is supported by outcomes reported in this study. Mortality and length of stay were no different with intrapleural fibrinolytics than with standard treatment with tube thoracostomy alone but were significantly improved with VATS compared with tube thoracostomy.The statement that the outcomes of MIST2 support use of intrapleural tPA with deoxyribonuclease (DNase) is based on results that are not convincing.1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Although change in pleural opacification, a primary outcome in MIST2, significantly favored tPA/DNase over placebo, the difference was modest (mean decrease, 7.9% vs placebo), especially when considering that the chest radiograph measurement strategy predicted only 71% of the exact, CT scan-determined pleural collection.3Rahman NM Maskell NA West A et al.Intrapleural use of tissue plasminogen activator and DNase in pleural infection.N Engl J Med. 2011; 365: 518-526Crossref PubMed Scopus (460) Google Scholar The small amount of additional pleural fluid drainage provided by tPA/DNase did not result in significant differences between the tPA/DNase and placebo groups in the clinically relevant outcomes of death and need for eventual surgery, although length of stay with tPA/DNase was shorter. Although these results are promising, the tPA/DNase approach is based on empirical dosing of both components. Further exploration of the relationship between dose of tPA/DNase and pleural drainage is needed.Drs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar attributed a mortality rate of around 5% to surgical drainage of a PPE, but this statistic is misleading. In the few (small) randomized controlled clinical trials evaluating VATS in patients requiring drainage of a PPE, mortality rates after VATS were very low and similar to control groups5Wait MA Sharma S Hohn J Dal Nogare A A randomized trial of empyema therapy.Chest. 1997; 111: 1548-1551Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 6Bilgin M Akcali Y Oguzkaya F Benefits of early aggressive management of empyema thoracis.ANZ J Surg. 2006; 76: 120-122Crossref PubMed Scopus (78) Google Scholar, 7Sonnappa S Cohen G Owens CM et al.Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.Am J Respir Crit Care Med. 2006; 174: 221-227Crossref PubMed Scopus (254) Google Scholar, 8St Peter SD Tsao K Spilde TL et al.Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial [published correction appears in J Pediatr Surg. 2009;44(9):1865].J Pediatr Surg. 2009; 44: 106-111Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar (Table 1). Farjah et al9Farjah F Symons RG Krishnadasan B Wood DE Flum DR Management of pleural space infections: a population-based analysis.J Thorac Cardiovasc Surg. 2007; 133: 346-351Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar reported a mortality rate of 5.4% after surgical drainage of pleural space infection, but this was significantly lower than the mortality rate for patients not undergoing surgery (16.6%). As we discuss in our counterpoint editorial,10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar recent studies have shown that choosing surgery as the initial pleural drainage procedure after failed tube thoracostomy will result in significantly better outcomes than other pleural drainage approaches. Surgical pleural space drainage can be performed with excellent outcomes even in very elderly patients with significant comorbidity.10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Early use of VATS to drain PPEs has been associated with a shorter hospital length of stay than other drainage approaches.11Marks DJB Fisk MD Koo CY et al.Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre.PLoS ONE. 2012; 7: e30074Crossref PubMed Scopus (72) Google Scholar, 12Suchar AM Zureikat AH Glynn L Statter MB Lee J Liu DC Ready for the frontline: is early thoracoscopic decortication the new standard of care for advanced pneumonia with empyema?.Am Surg. 2006; 72: 688-692PubMed Google ScholarTable 1—Deaths After VATS in Randomized Controlled Clinical Trials in Adults and Children With PPE Requiring DrainageStudyPatient GroupDeaths in VATS GroupDeaths in Control GroupP ValueWait et al5Wait MA Sharma S Hohn J Dal Nogare A A randomized trial of empyema therapy.Chest. 1997; 111: 1548-1551Abstract Full Text Full Text PDF PubMed Scopus (308) Google ScholarAdults1 of 11 (9%)1 of 9 (11%)NSBilgin et al6Bilgin M Akcali Y Oguzkaya F Benefits of early aggressive management of empyema thoracis.ANZ J Surg. 2006; 76: 120-122Crossref PubMed Scopus (78) Google ScholarAdults0 of 35 (0%)1 of 35 (3%)NSSonnappa et al7Sonnappa S Cohen G Owens CM et al.Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.Am J Respir Crit Care Med. 2006; 174: 221-227Crossref PubMed Scopus (254) Google ScholarChildren0 of 30 (0%)0 of 30 (0%)NSSt Peter et al8St Peter SD Tsao K Spilde TL et al.Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial [published correction appears in J Pediatr Surg. 2009;44(9):1865].J Pediatr Surg. 2009; 44: 106-111Abstract Full Text Full Text PDF PubMed Scopus (207) Google ScholarChildren0 of 18 (0%)0 of 18 (0%)NSTotal…1 of 94 (1%)2 of 92 (2%)…NS = not significant; PPE = parapneumonic effusion; VATS = video-assisted thoracoscopic surgery. Open table in a new tab Our recommended approach is straightforward. Evaluate patients with pneumonia for a PPE. If a PPE is present, follow the approach described in our counterpoint editorial10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar to determine whether drainage is recommended. If drainage would provide benefit, perform tube thoracostomy and consult thoracic surgery. If there is clear, rapid clinical improvement in the PPE with tube thoracostomy and antibiotics, no further steps may be needed. If, however, tube thoracostomy does not provide adequate pleural drainage and the clinical picture does not improve, the next step should be VATS to effectively break down loculations and drain the pleural space under direct vision. In patients with limiting comorbid conditions or in whom surgery is not an option, combination tPA/DNase therapy should be considered. Drs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar emphasized that clinical use of a therapeutic agent should be determined by its risk/benefit profile. Let us consider the risk/benefit profile of intrapleural fibrinolytics. Because streptokinase and urokinase are not currently available in the United States, we will focus on the tissue plasminogen activator (tPA). Use of tPA is associated with the risk of bleeding. In a retrospective review, four of 57 patients (7%) treated with intrapleural tPA for a parapneumonic effusion (PPE) or empyema experienced bleeding complications, some of which were serious.2Ben-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: 860-863Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Balanced against the bleeding risk with tPA, clinicians should appreciate that Rahman et al3Rahman NM Maskell NA West A et al.Intrapleural use of tissue plasminogen activator and DNase in pleural infection.N Engl J Med. 2011; 365: 518-526Crossref PubMed Scopus (460) Google Scholar concluded in the second Multicenter Intrapleural Sepsis Trial (MIST2) that intrapleural administration of tPA alone was ineffective. Besides the lack of clinical benefit with tPA in this study, there was no difference in the change in intrapleural opacification between placebo and tPA. This observation indicates that tPA did not effectively cause intrapleural fibrinolysis and pleural drainage when used at an empirical intrapleural dose of 10 mg. With possible risk but no evident benefit, we do not favor routine administration of intrapleural fibrinolytics to adults with a PPE requiring drainage. Drs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar stated that use of intrapleural fibrinolytics in children is firmly established. Although a number of studies support this position, information about clinical practice patterns in the United States does not agree with this point. A large retrospective US database analysis examined treatments and outcomes in 14,936 children hospitalized with empyema or PPE.4Goldin AB Parimi C LaRiviere C Garrison MM Larison CL Sawin RS Outcomes associated with type of intervention and timing in complex pediatric empyema.Am J Surg. 2012; 203: 665-673Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Database analyses provide an invaluable perspective into actual clinical practice. Only 0.1% of these children were treated with intrapleural fibrinolytic therapy, but 8% underwent video-assisted thoracoscopic surgery (VATS). These results indicate that use of VATS, rather than intrapleural fibrinolytics, is firmly established in US management of pediatric patients requiring drainage of a PPE. This clinical approach is supported by outcomes reported in this study. Mortality and length of stay were no different with intrapleural fibrinolytics than with standard treatment with tube thoracostomy alone but were significantly improved with VATS compared with tube thoracostomy. The statement that the outcomes of MIST2 support use of intrapleural tPA with deoxyribonuclease (DNase) is based on results that are not convincing.1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Although change in pleural opacification, a primary outcome in MIST2, significantly favored tPA/DNase over placebo, the difference was modest (mean decrease, 7.9% vs placebo), especially when considering that the chest radiograph measurement strategy predicted only 71% of the exact, CT scan-determined pleural collection.3Rahman NM Maskell NA West A et al.Intrapleural use of tissue plasminogen activator and DNase in pleural infection.N Engl J Med. 2011; 365: 518-526Crossref PubMed Scopus (460) Google Scholar The small amount of additional pleural fluid drainage provided by tPA/DNase did not result in significant differences between the tPA/DNase and placebo groups in the clinically relevant outcomes of death and need for eventual surgery, although length of stay with tPA/DNase was shorter. Although these results are promising, the tPA/DNase approach is based on empirical dosing of both components. Further exploration of the relationship between dose of tPA/DNase and pleural drainage is needed. Drs Corcoran and Rahman1Corcoran JP Rahman NM Point: should fibrinolytics be routinely administered intrapleurally for management of a complicated parapneumonic effusion? Yes.Chest. 2014; 145: 14-16Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar attributed a mortality rate of around 5% to surgical drainage of a PPE, but this statistic is misleading. In the few (small) randomized controlled clinical trials evaluating VATS in patients requiring drainage of a PPE, mortality rates after VATS were very low and similar to control groups5Wait MA Sharma S Hohn J Dal Nogare A A randomized trial of empyema therapy.Chest. 1997; 111: 1548-1551Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 6Bilgin M Akcali Y Oguzkaya F Benefits of early aggressive management of empyema thoracis.ANZ J Surg. 2006; 76: 120-122Crossref PubMed Scopus (78) Google Scholar, 7Sonnappa S Cohen G Owens CM et al.Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.Am J Respir Crit Care Med. 2006; 174: 221-227Crossref PubMed Scopus (254) Google Scholar, 8St Peter SD Tsao K Spilde TL et al.Thoracoscopic decortication vs tube thoracostomy with fibrinolysis for empyema in children: a prospective, randomized trial [published correction appears in J Pediatr Surg. 2009;44(9):1865].J Pediatr Surg. 2009; 44: 106-111Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar (Table 1). Farjah et al9Farjah F Symons RG Krishnadasan B Wood DE Flum DR Management of pleural space infections: a population-based analysis.J Thorac Cardiovasc Surg. 2007; 133: 346-351Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar reported a mortality rate of 5.4% after surgical drainage of pleural space infection, but this was significantly lower than the mortality rate for patients not undergoing surgery (16.6%). As we discuss in our counterpoint editorial,10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar recent studies have shown that choosing surgery as the initial pleural drainage procedure after failed tube thoracostomy will result in significantly better outcomes than other pleural drainage approaches. Surgical pleural space drainage can be performed with excellent outcomes even in very elderly patients with significant comorbidity.10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Early use of VATS to drain PPEs has been associated with a shorter hospital length of stay than other drainage approaches.11Marks DJB Fisk MD Koo CY et al.Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre.PLoS ONE. 2012; 7: e30074Crossref PubMed Scopus (72) Google Scholar, 12Suchar AM Zureikat AH Glynn L Statter MB Lee J Liu DC Ready for the frontline: is early thoracoscopic decortication the new standard of care for advanced pneumonia with empyema?.Am Surg. 2006; 72: 688-692PubMed Google Scholar NS = not significant; PPE = parapneumonic effusion; VATS = video-assisted thoracoscopic surgery. Our recommended approach is straightforward. Evaluate patients with pneumonia for a PPE. If a PPE is present, follow the approach described in our counterpoint editorial10Colice GL Idell S Counterpoint: should fibrinolytics be routinely administered intrapeurally for management of a complicated pleural effusion? No.Chest. 2014; 145: 17-20Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar to determine whether drainage is recommended. If drainage would provide benefit, perform tube thoracostomy and consult thoracic surgery. If there is clear, rapid clinical improvement in the PPE with tube thoracostomy and antibiotics, no further steps may be needed. If, however, tube thoracostomy does not provide adequate pleural drainage and the clinical picture does not improve, the next step should be VATS to effectively break down loculations and drain the pleural space under direct vision. In patients with limiting comorbid conditions or in whom surgery is not an option, combination tPA/DNase therapy should be considered.
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