Surgery should be the first line of treatment for empyemaresp_1677

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1 PRO/CON DEBATE Surgery should be the first line of treatment for empyemaresp_1677 IOANNIS E. PETRAKIS, 1 JOHN E. HEFFNER 2 * AND JEFFREY S. KLEIN 3 1 Department of General and Thoracic Surgery, University Hospital of Heraklion, University of Crete, Heraklion Crete, Greece, 2 Department of Medicine, Providence Portland Medical Center, Oregon Health and Science University, Portland, Oregon, and 3 Department of Radiology, Fletcher Allen Health Care and the University of Vermont College of Medicine, Burlington, Vermont, USA ABSTRACT Few thoracic conditions present such considerable challenges as pleural space infections, herein termed empyema as a general term. Patients may present with free-flowing infected pleural effusions that readily drain by catheter or, at the other extreme, with organized intrapleural collections of pus with thick pleural peels that require open decortication. In the transition from a simple to complex empyema, patients pass through the intermediary, or fibrinopurulent stage. Such patients require careful assessment to determine the ideal management approach. Although existing trials provide insufficient evidence to standardize drainage approaches, an accepted principle directs clinicians to drain empyemas promptly and completely.in this pro-con presentation, two recognized experts on empyema a thoracic surgeon and an interventional radiologist approach management from decidedly opposite perspectives. The surgeon prefers videoassisted thoracoscopic surgery as primary therapy for fibrinopurulent empyemas. The radiologist counters that imaging-guided, small-bore catheters, sometimes with adjunctive fibrinolytic drugs, provide effective therapy for select patients. In the absence of highquality data to settle this debate, both experts present *Moderator. Dr Ioannis E Petrakis, MD, PhD is Consultant Surgeon in the Department of General and Thoracic Surgery Department of the University Hospital of Heraklion, University of Crete, Heraklion, Crete, Greece and President of the Hellenic Society of Geriatric Surgery. Dr John E Heffner, MD, FCCP is Garnjobst Chair of the Department of Medicine at Providence Portland Medical Center, Professor of Medicine at Oregon Health & Science University, and a member of the Respirology editorial board. Dr Jeffrey Klein, MD, FACR, FCCR serves as Chief of Thoracic Radiology at Fletcher Allen Health Care in Burlington, Vermont. He has been a practicing thoracic radiologist for 20 years, and has a special interest in image-guided thoracic interventional procedures. Correspondence: Ioannis E. Petrakis, Department of General and Thoracic Surgery, University Hospital of Heraklion, University of Crete, GR 71110, Heraklion Crete, Greece. petrakis@post.com. Jeffrey S. Klein, Department of Radiology, Fletcher Allen Health Care and the University of Vermont College of Medicine, 111 Colchester Avenue, Patrick 105, Burlington, Vermont 05401, USA. Jeffrey.klein@vtmednet.org Received 20 October 2009; invited to revise 22 October 2009; revised 29 October 2009; accepted 29 October 2009 (Associate Editor: Y.C. Gary Lee). reasoned and thoughtful approaches, which produce superior clinical outcomes in their own institutions. So readers should recognize that controversy exists in empyema management and carefully review each expert s comments. Within each are essential elements of care that can be integrated into a multidisciplinary approach. Readers may conclude from this debate that each institution should develop a collaborative model for managing empyemas that integrates differing expertise to customize care for individual patients and continuously measure and improve their patients outcomes. Key words: chest tube, empyema, spiral computed tomography, ultrasonography, thorcoscopic surgery. PRO Ioannis E. Petrakis, MD, PhD In the 5th Century BCE, Hippocrates described empyema thoracis to the medical community and proposed surgical drainage as appropriate treatment. 1 Since then, our understanding and recognition of empyema have expanded along with advances in diagnostic and therapeutic technologies. But the need for early and effective surgical drainage remains a fundamental principle. During the 1990s, case series demonstrated an important role for video-assisted thoracic surgery (VATS) for draining empyemas in the early fibrinopurulent stage. 2 6 Although some surgeons report favourable outcomes with VATS for organized empyemas equivalent to open surgical decortication, 7 the ability of VATS to adequately decorticate the lung in this advanced empyema stage remains controversial. 8,9 It is observed, however, that delayed referral of patients with empyema for VATS increases the need for conversion to open thoracotomy and consequently increases morbidity and mortality. 5 So appropriate timing of drainage procedures has fundamental importance for decreasing mortality, which remains 1 19% for empyema. 5,10 The VATS debridement offers an elegant, minimally invasive approach for patients with early fibrinopurulent empyemas. Open surgical drainage can also effectively drain this early stage of disease, but doi: /j x

2 Empyema management pro-con 203 Table 1 Randomized controlled trials of VATS as primary intervention Authors (publication year, reference), treatment group Cases (n) Stage Conversion rate (n) Primary treatment success (%) Hospital stay days (mean) Wait et al VATS 11 Mixed Chest tube with streptokinase 9 Mixed Bilgin et al VATS 35 Mixed Chest tube 35 Mixed represents unnecessarily invasive management. VATS is also more effective than chest tube drainage for fibrinopurulent pleural infections To achieve a high success rates with VATS, early referral for surgical evaluation is required to select the appropriate drainage approach Such referrals should not be delayed by waiting too long to assess outcomes of chest tube drainage. The fibrinopurulent stage of empyema formation represents a transition phase between the exudative and the organized stages of the disease and may lapse as only a brief interlude. Unfortunately, no clinical sign, laboratory test or imaging results clearly distinguish the transition from a fibrinopurulent to an organized empyema. Consequently, decision-making for appropriate treatment (surgical or non-surgical) requires careful patient selection and recognition of the importance of urgently applying what appears to be the most effective drainage procedure based on each patient s unique circumstances. 15,16 To do so, clinicians should recall that the probability of conversion thoracotomy in patients undergoing VATS for presumed fibrinopurulent empyemas increases from 22% to 86% between day 12 to day 16 of presentation. 5 Once established, pleural thickening and signs of lung restriction on CT scan characterize organized empyemas. Open thoracotomy and decortication in this stage of empyema are the conventional approach to free the trapped lung and prevent empyema recurrence and late restriction. Unfortunately, open thoracotomy often causes substantial postoperative pain and morbidity. 16 Despite these risks, conversion thoracotomy should be used when necessary for organized empyemas, especially for patients with delayed referrals (>2 weeks) and when other methods have failed to resolve the problem. 5,16 A meta-analysis of largely retrospective cohort studies and histologically controlled case series demonstrate lower early mortality (2 5% vs 9 10%) and re-intervention rates (0 11% vs 40 46%) for primary operative versus non-operative drainage of empyemas. 17 Different patient characteristics among the treatment groups, however, may have influenced these outcomes. Only two randomized trials in adults compare operative (primary VATS) with nonoperative therapy (standard large-bore tubes placed without imaging guidance) and report that patients undergoing primary VATS experienced fewer treatment failures and shorter hospital stays (Table 1). 18,19 Unfortunately, significant methodological flaws exist with these small studies. In our series, VATS was more effective when applied primarily for patients with fibrinopurulent empyemas who were promptly referred for surgery as compared with secondary VATS after failure of initial chest tube drainage with fibrinolytic therapy. 12,14 The incidence of empyema and the proportion of patients undergoing surgery have increased during the last 20 years with surgery applied to an increasingly younger age group. 20 Patients surgically drained experience a lower risk of early death as compared with non-surgical care. 20 The optimally aggressive treatment modality should be tailored to the condition of the patient and to the anticipated healing potential of the postoperative pleural space. Decision-making involves three considerations: the aetiology of empyema (i.e. primary vs secondary), general condition of the patient and tri-phasic stage of the disease. Current selection concepts are based mainly on expert opinion. Flexibility and patience on behalf of the surgeon, nursing staff, patient and hospital management, as well as a good understanding of the complexity of this condition, are the cornerstones of treatment. No exclusive sequence of procedures leading to a uniformly predictable successful outcome is available. Individualized approaches can be recommended based on institutional practice and local protocols. Empyema in general remains a complex entity that does not fit well into standardized, evidence-based medical approaches and still requires expert-based decision-making. 21 When VATS is applied in the earlier stages of empyema (Table 2), generally within the fibrinopurulent stage up to four or maximum 5 weeks from symptom onset, patients experience higher success rates with the best outcomes occurring with VATS performed 14 days ( 2 days) after onset of disease. VATS delayed beyond the fibrinopurulent stage is associated with decreasing success rates, more complications, increased conversion rates, and more recurrences and re-operations. Thoracic surgeons can use these findings to better inform their patients that a 19-year experience in the state of Washington, USA 20 indicates that surgery should be the first-line treatment for empyema and is safe and effective for selected patients. Surgeons should better educate clinicians about the importance of early referral for thoracic surgical consultation.

3 204 IE Petrakis et al. Table 2 VATS in the treatment of Empyema relative to empyema stage Authors (publication year, reference) Cases (n) Stage Conversion rate (%) Chest tube days (mean) Hospital stay days (mean) Postoperative complications (%) Landreneau et al Mixed Striffeler et al Early Angelillo et al Early Cassina et al Mixed Waller and Rengarajan Late 41 Kim et al Mixed Petrakis Early Petrakis et al Late Luh et al Early Luh et al Late Lardinois et al Mixed 44 9 Wurnig et al Early Solaini et al Mixed In conclusion, VATS has been established as a safe and effective alternative approach for many thoracic procedures in addition to empyema, offering visual inspection of the entire pleural cavity, visual guidance for surgical manoeuvres, better cosmetic results, shorter hospital stay, lower cost, reduced pain and morbidity, and a lower demand on medical personnel by avoiding formal and mini-thoracotomies and their complications. The precise role and timing of VATS, however, are incompletely defined. Future investigations should better define the proportion of patients undergoing primary surgical therapy, control for confounders and measure post-treatment quality of life and functional status to evaluate the comparative effectiveness of competing therapies. CON Jeffrey S. Klein, MD, FACR, FCCP Although cross-sectional imaging of the chest with multi-detector CT and real-time ultrasound have become integral for detecting and characterizing infected pleural effusions, the role of image-guided catheter placement in the management of patients with complicated parapneumonic effusions remains less well defined. Nevertheless, small-bore catheters, with adjunctive intrapleural fibrinolytics when needed, placed under image guidance can benefit select patients, even though existing literature and clinical guidelines on the use of image-guided catheters are somewhat limited. As detailed in the American College of Chest Physicians consensus statement on the medical and surgical management of parapneumonic effusions, considerations of the anatomy of infected pleural fluid collections have prognostic importance in predicting patient morbidity and mortality. 27 Ultrasonography is extremely sensitive for the detection of small effusions and helps guide diagnostic sampling of parapneumonic collections. Moreover, sonographic characterization of parapneumonic collections can predict the likelihood of successful closed drainage. For instance, findings of non-loculated collections lacking internal echoes or septations correspond to early exudative stage empyemas and suggest a high likelihood of success using catheter drainage. Alternatively, sonographic evidence of septated collections indicates a need for longer durations of chest tube drainage, prolonged hospital stays and intrapleural instillation of fibrinolytics. For such patients, early surgical intervention may be warranted. 28 Patients with extensive and complex empyemas require evaluation by contrast-enhanced multidetector CT to assess the extent of the pleural fluid collection, which may extend along the mediastinum, and to characterize underlying lung and adjacent chest wall disease. Chest CT makes available axial, sagittal and coronal reformatted images that provide important information when considering therapeutic options for empyema. Early-stage exudative or fibrinopurulent effusions characterized on CT as dependent meniscoid or unilocular collections are best suited to small-bore image-guided catheter placement, with case series reporting success rates as high as 93%. 29 Selected patients with unilocular empyemas or those with multi-loculated collections who are poor surgical candidates for VATS or open surgical drainage can be successfully managed with one or more imageguided catheters either as definitive therapy or as a bridge to later definitive surgical treatment. For free-flowing or unilocular, non-septated parapneumonic collections, we place small-bore imageguided catheters by a trocar technique using a 14- or 16-French drainage catheter (All Purpose Drainage Catheter, Cook Inc., Bloomington, IN, USA). Ideal candidates for this approach have empyemas with an area of contact with the costal pleural surface of sufficient breadth to allow safe placement of the sharp-tipped trocar/catheter combination into the dependent part of the collection. For treatment of frank empyemas or collections with multiple loculations or septations as determined by cross-sectional imaging in non-operative patients,

4 Empyema management pro-con 205 we typically use either a 16-French catheter or, for large collections, a 28-French tube (Thal-Quick Drainage Set, Cook Inc., Bloomington, IN, USA), which is placed using a Seldinger technique. Multiple catheters or tubes can be employed if necessary to drain separate locules within the chest as detected on CT. 30 Once catheters and tubes have been placed under imaging guidance, the patient s clinical status, tube output and radiological studies are reviewed daily to determine the effectiveness of drainage. The tube/ catheter should be flushed with saline three times daily to maintain patency of the lumen and prevent occlusion by fibrin and debris of the drainage holes located in the distal aspect of the device. 31 An inadequate response to treatment warrants either a re-evaluation of the patient with consideration of additional manoeuvres to improve drainage or a decision to proceed to surgical management. An inadequate response is defined by: (i) a lack of improvement in fever, peripheral white blood cell count or oxygenation; (ii) persistent dyspnea or pain; or (iii) a persistent or enlarging collection on radiography or CT. Assuming that radiological evaluation and management demonstrate adequate positioning and functioning of the drainage catheter/tube within the collection(s), inadequate drainage may require upsizing the tube and/or instillation of intrapleural fibrinolytic drugs to promote drainage. In those who have failed to improve following proper placement of tubes, contrast-enhanced chest CT is helpful to detect undrained locules and to guide tube exchange when necessary. CT can also assess the status of the underlying pneumonia or abscess to determine if lack of clinical improvement is more a result of progressive pulmonary infection rather than inadequate pleural drainage. Once there has been clinical and radiographical resolution of the pleural collection and drainage has diminished to <100 ml/day, the catheter is removed. We believe that intrapleural fibrinolytic drugs can promote drainage of loculated empyemas, particularly in the early fibrinopurulent stage, if state-of-theart imaging techniques guide catheter placement with daily monitoring of drainage. Small case series assessing the use of intrapleural streptokinase, urokinase or recombinant tissue plasminogen activator have shown efficacy in obviating the need for surgical drainage and in the radiographical resolution of infected pleural fluid collections. 32,33 Given allergic reactions to streptokinase and limited availability of urokinase, most centres, including ours, currently use recombinant tissue plasminogen activator for intrapleural fibrinolysis. Although a randomized trial found no benefits from intrapleural strepotokinase in terms of survival, length of hospital stay or need for open surgical drainage, the study failed to use advanced imaging techniques to anatomically stage the pleural space or guide chest catheter insertion. We and others find in select patients managed with accurate catheter placement into the dependent regions of a parapneumonic collection that daily administration of intrapleural fibrinolytics for effusions that do not initially drain completely can promote drainage and avoid surgery (Fig. 1). 33,34 Residual pleural thickening in successfully treated empyemas, regardless of the drainage procedure used, resolves within 6 months, so primary surgery does not have any advantages in preventing respiratory restriction even when initial pleural thickening is severe. Regardless of the algorithm employed to manage patients with infected pleural fluid collections, timely diagnosis and accurate characterization using contrast-enhanced CT and ultrasonography combined with a multidisciplinary, staged approach to treatment are critical to minimize the morbidity and mortality from this condition. In our experience, using CT and ultrasonography to triage patients and guide accurate catheter placement, with adjunctive use of fibrinolytics when appropriate and daily monitoring of response to treatment, a significant subset of patients with complicated parapneumonic effusions can be managed with image-guided catheter or tube drainage. Only a minority of properly selected patients require surgical drainage. MODERATOR S COMMENTS John E. Heffner, MD, FCCP Empyema represents a complex clinical condition that has defied randomized controlled trials and efforts to define best clinical practices because of the multitude of patient factors that determine treatment outcomes. These factors include age, comorbidities, functional status, underlying lung and pleural disease, immune status, socioeconomic setting, underlying virulence and antibiotic susceptibility of the aetiological pathogen(s), empyema stage and delays in presentation for care, to name only a few. Definitive management trials would require tens of thousands of patients to control for these many variables, and no sufficient funding sources exist for empyema research. 35 It is not surprising therefore that we have so little high-quality evidence to guide clinical practice. In such circumstances of insufficient knowledge, strong opinions usually reign. I am delighted therefore that our two pro-con experts acknowledge the limitations of existing evidence and present reasonable and well-tempered opinions based on fundamental principles of care. Both experts identify areas of differences to help us flesh out the topic, yet appear to agree on common ground. As for differences, Dr Petrakis emphasizes the definitive effectiveness of VATS for fibrinopurulent pleural infections and its occasional role for more established organized empyemas. He emphasizes that VATS should supersede chest tube/catheter drainage, which may delay application of VATS thereby worsening clinical outcome. Even short delays for surgery may increase morbidity and mortality. Dr Klein describes a role for advanced chest imaging CT and ultrasonography to select appropriate patients for catheter drainage, which in his institution rarely requires later conversion to surgical drainage, and to guide catheter placement. Certain imaging features establish a need for primary surgical

5 206 (a) IE Petrakis et al. Figure 1 Frontal chest radiograph (a) and coronal reformatted contrast-enhanced CT at the level of the descending aorta (b) in a 64-year-old man shows a multi-loculated parapneumonic right pleural effusion with both posteromedial (P in b) and fissural (F in b) components. Repeat chest radiograph 5 days later following placement of a 16-French drainage catheter and daily intrapleural recombinant tissue plasminogen activator (r-tpa) shows virtually complete resolution of the collection with good re-expansion of the underlying lung (c). The patient recovered completely and surgical management was not necessary. (b) (c) drainage for patients who appear unlikely to benefit from catheter drainage. In some settings, limited operating room and/or surgeon availability may delay surgical drainage wherein imaging-guided catheters can stabilize patients until surgery can be performed. Considering that we selected our two experts based on their institutions demonstrated success in managing empyemas, some common ground must exist. And it does their discussions share a belief that pleural infections must be quickly diagnosed with sensitive imaging techniques, properly staged and promptly drained by the most effective method available tailored for the individual patient at hand. Both would agree that blind insertion of standard chest tubes without imaging guidance is no longer adequate, although it may remain routine in regions without access to VATS and advanced imaging techniques. As with lung cancer, only a multidisciplinary team of pulmonary physicians, radiologists and surgeons working closely together and sharing their unique expertise can customize care and effectively advance the Hippocratic principle that pus must be drained quickly and effectively. The specific approach for achieving this goal in the absence of high-quality data should be institution-specific based on available expertise and resources. 36 An ideal collaboration would combine the high expertise represented by Drs Klein s and Petrakis s comments in a coordinated program. To continuously improve patient outcomes, whatever approach an institution adopts should be continuously monitored for outcomes and modified to ensure proper patient selection for either catheter drainage, which must maintain a low failure rate, or for primary surgical drainage, which ensures a high rate of success but pays the price of greater invasiveness. REFERENCES 1 Hippocrates AF. The Genuine Works of Hippocrates. Williams & Wilkins, Baltimore, Angelillo-Mackinlay T, Lyons GA, Piedras MB et al. Surgical treatment of postpneumonic empyema. World J. Surg. 1999; 23: Lawrence DR, Ohri SK, Moxon RE et al. Thoracoscopic debridement of empyema thoracis. Ann. Thorac. Surg. 1997; 64: Striffeler H, Gugger M, Im Hof V et al. Video-assisted thoracoscopic surgery for fibrinopurulent pleural empyema in 67 patients. Ann. Thorac. Surg. 1998; 65:

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