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Emergent Management of Empyema

Osman Ahmed, M.D. 1 Steven Zangan, M.D. 1
Address for correspondence and reprint requests Osman Ahmed, M.D., Department of Radiology, University of Chicago, 5841 S. Maryland Ave, MC 2026, Chicago, IL 60637 (e-mail: Osmanuddin.ahmed@uchospitals.edu).
1 Department of Radiology, University of Chicago, Chicago, Illinois

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Abstract

Keywords

empyema chest tube brinolytics mucolytics split pleura sign

Empyema is a frankly purulent infection of the pleural space most often occurring secondary to parapneumonic effusion. Imaging, specically contrast-enhanced computed tomography, plays a critical role in diagnosis with a split pleura sign being highly suggestive in the appropriate clinical setting. Diagnostic thoracentesis with culture and Gram stain further guides appropriate antibiotic therapy. Therapeutic drainage with small-bore tube thoracostomy has been shown to be a safe and effective treatment of early stage empyema. Augmentation of tube placement with intrapleural brinolytics and mucolytics facilitates catheter drainage by degrading loculations and decreasing uid viscosity, respectively.

Objectives: Upon completion of this article, the reader should be able to identify classic imaging ndings of empyema, describe in detail the technical approach to chest tube placement, and discuss the role of brinolytics in the management of empyema. Accreditation: Tufts University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credit: Tufts University School of Medicine designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Case Presentation
A 70-year-old man with no signi cant past medical history presented to the emergency department with productive cough, fever, right pleuritic chest pain, and generalized weakness progressing for 3 weeks. Initial vital signs were signi cant for a temperature of 102.5F and a heart rate of 105. Physical examination revealed the patient to be lethargic with decreased breath sounds at the right lung base. Basic laboratory work was remarkable for an elevated white blood cell count of 21,000 106/L. A chest radiograph was subsequently obtained (Fig. 1).

Given the size of the effusion noted on the chest radiograph and the clinical status of the patient, chest computed tomography (CT) with intravenous contrast was obtained for further evaluation (Figs. 2 and 3). The overall clinical presentation and radiological ndings raised high suspicion for pneumonia complicated by an empyema. Broad-spectrum antibiotics were started and the patient was referred to interventional radiology (IR) for drainage of the pleural collection. In the IR department, small-bore tube thoracostomy was performed utilizing the Seldinger technique and uoroscopic guidance, with placement of a 12F pigtail drain into the costophrenic sulcus. The patient tolerated the procedure well without complication. Thick purulent uid was drained and sent for gram staining and culture. Gram-positive cocci in clusters were seen on microscopy, and cultures later grew Staphylococcus aureus. Antibiotics were appropriately adjusted based on the culture sensitivity results. Over the initial 24 hours of catheter drainage, the volume of uid drained decreased dramatically despite radiographic persistence of the effusion. The drain was subsequently injected with 10 mg of tissue plasminogen activator (tPA) and 5 mg deoxyribonuclease (DNase) twice daily for 3 days. The drainage improved dramatically along with clinical and radiographic improvement. As the patients clinical status continued to stabilize over the week, the chest tube was pulled and the patient was discharged from the hospital on short-term antibiotic therapy.

Issue Theme Emergency IR; Guest Editor, Thuong G. Van Ha, M.D.

Copyright 2012 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.

DOI http://dx.doi.org/ 10.1055/s-0032-1326933. ISSN 0739-9529.

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Figure 1 Chest radiograph, posteroanterior projection, demonstrates a large right pleural effusion.

Figure 3 Contrast-enhanced computed tomography, soft tissue window, at the same level as Fig. 2, demonstrates the effusion to be separated by thickened and high-density pleura (open arrow), suspicious for empyema. The consolidated lung can also be better appreciated on this view.

Diagnosis
Parapneumonic effusions are pleural effusions occurring in the setting of bacterial pneumonia, with a reported incidence up to 40%. When a parapneumonic effusion becomes complicated by frank bacterial infection, an empyema results. Empyema is classically described as an exudative effusion containing thick pus and brin products that form septations or loculations.

Figure 2 Contrast-enhanced computed tomography, lung window, demonstrates a consolidation in the right lower lobe. A large effusion can also be seen peripherally.

The clinical presentation of empyema depends on the patients immune status and timing of presentation for evaluation. In this case, delayed admission to the emergency department with a prolonged duration of fever and pleuritic chest pain should heighten the suspicion for pneumonia complicated by parapneumonic effusion or empyema. Aside from the clinical history, physical examination can be helpful in identifying the presence of uid in the pleural space. This is often noted by diminished breath sounds and decreased tactile fremitus on the side of the effusion. Despite the importance of history and physical examination, imaging plays a vital role in the accurate diagnosis of an empyema. Plain radiographs are often the initial imaging test of choice because they demonstrate areas of consolidation in the lung with or without an accompanying effusion. Furthermore, decubitus radiographs can help delineate whether an effusion is loculated by demonstrating a lack of uid shift with a change in positioning. Another quick and inexpensive way for imaging the pleural space is ultrasonography. It remains the most sensitive method to visualize septations in an effusion. Additionally, in most cases it is used as the initial imaging modality to guide thoracentesis. In most institutions, however, ultrasonography is not commonly performed as a purely diagnostic tool. Contrast-enhanced CT (CECT) is the most optimal form of imaging to diagnose empyema. As in this case, CECT shows a low-density lentiform-shaped effusion with thickening and enhancement of the adjacent pleural layers. The thickening and enhancement of the inner visceral and outer parietal pleura separated by an effusion has been dubbed the split pleura sign (Fig. 4).1 Although nonspeci c, the clinical history of fever and additional ndings of pneumonia make this sign highly suggestive of empyema. Additionally, CECT is
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discouraged and considered suboptimal. The appropriate duration of therapy is speci c to the individual patients case but typically can be continued for 2 to 4 weeks following defervescence and/or radiographic improvement. A frankly purulent collection noted on thoracentesis indicates the need for therapeutic drainage. If the uid is not clearly infected, laboratory analysis can be helpful. Generally, pleural uid pH <7.2, glucose level <60 mg/dL, and lactate dehydrogenase (LDH) >1000 units/L indicates an empyema or complicated parapneumonic effusion that requires therapeutic drainage. Tube thoracostomy with the usage of brinolytics is often required because empyema is a brinopurulent process characterized by multiloculation. Ultrasound (for needle placement) with uoroscopy (for wire and catheter exchanges) is the preferred method for this procedure, with CT guidance reserved for collections requiring multiple tubes in separate or dif cult to reach loculations. A lateral approach is used to minimize tube kinking when the patient is supine; in addition, the intercostal space tends to be wider more laterally, decreasing the risk of inadvertent neurovascular injury. Local anesthetic is in ltrated into the skin followed by accessing the pleural space with a 21- or 18-gauge needle under ultrasound guidance. The Seldinger technique is then used to place a 12F or 14F small-bore pigtail drain over a stiff guidewire. Alternatively, trocar technique can be substituted for larger collections that pose a smaller risk of pneumothorax. Fluoroscopy is used to con rm optimal placement of the pigtail, often in the dependent costophrenic sulcus where most uid collects. As mentioned earlier, the use of brinolytics is advocated for adjuvant therapy to tube thoracostomy. In the development of an empyema, brin is deposited in a sheet over the pleura and in a honeycomb-like network through the effusion. tPA is a commonly used intrapleural agent for enzymatic debridement of these loculations. Additionally, the use of DNase is advised to decrease viscosity of the uid being drained. A common regimen includes 10 mg of tPA and 5 mg DNase injected via the tube thoracostomy twice daily for 3 days. Volume of the injectate depends on the size of the pleural uid collection; 10 to 50 mL total volume is typical.

Figure 4 Split pleura sign. Contrast-enhanced computed tomography, soft tissue window, demonstrates a left basilar multiloculated effusion with visibly thickened and enhancing pleura (open arrows). This appearance of the pleural layers separated by an effusion describes the split pleura sign and is highly suggestive of empyema in the appropriate clinical context.

nearly 100% accurate in its ability to distinguish an empyema from an intraparenchymal lung abscess.

Treatment
An empyema is the nal, most severe type of a three-stage continuum that includes parapneumonic and complicated parapneumonic effusions. When an empyema is suspected clinically or radiographically, broad-spectrum antibiotics are typically initiated. Ultimately, sampling of the pleural uid is required to tailor antibiotic therapy. The uid should be sent for Gram stain and culture to identify the pathogen and obtain appropriate antibiotic sensitivities. Once results are available, antibiotic treatment can be altered to a more narrow-spectrum option to prevent microbial resistance and hasten clinical improvement. In most cases, the infective organism causing the pneumonia is responsible for its associated empyema. S. aureus is the most common cause of empyema, although anaerobes and other strains of Staphylococcus and Streptococcus are not uncommonly seen. Most antibiotics cross the pleural space and are thus safe to use, with the exception of aminoglycosides (due to their inactivation in low pH environments). Unsuccessful culture of organisms from a frankly infected collection can be observed due to the initial empirical treatment begun prior to diagnostic evaluation. Anaerobic organisms are also dif cult to culture and should be suspected in the setting of a negative culture. Appropriate empirical agents for empyema include -lactam with -lactamase inhibitors (e.g., amoxicillin-clavulanate or piperacillin-tazobactam) and carbapenems (e.g., imipenem or meropenem). The use of single-agent antibiotics such as penicillin or metronidazole is
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Discussion
Empyema is a condition that often results from an infected parapneumonic effusion. Alternatively, it can be seen following trauma, surgery, esophageal perforation, or secondary to local spread from an adjacent subphrenic abscess or osteomyelitis. Speci cally de ned as an infected exudative effusion containing pus, the uid of an empyema is often free owing in the rst 48 hours. However, the following stage is hallmarked by a brinopurulent process that covers the pleural layers in brin and creates a network of loculations within the exudative uid. Although the viscosity of uid and extent of loculation varies, the degree of each increases with the severity of infection. CECT is the most helpful imaging tool because it can demonstrate effusion with thickening and enhancement of

Emergent Management of Empyema

Table 1 Algorithm to Determine Need for Tube Thoracostomy Based on Pleural Fluid Characteristics Pleural Space Anatomy Pleural Fluid Bacteriology AND Culture and Gram stain results unknown Negative culture and Gram stain Positive culture or Gram stain Pus AND Pleural Fluid Chemistry pH unknown Category

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Risk of Poor Outcome Very low

Drainage

Minimal, free owing (<10 mm on lateral decubitus lm) Small to moderate free owing effusion (>10 mm and <1/2 hemithorax) Large, free owing (>1/2 hemithorax) or loculated effusion or thickened parietal pleura

No

AND

AND

pH >7.2

Low

No

AND

OR

pH <7.2

3 4

Moderate High

Yes Yes

Adapted from Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest 2000:118(4):11581171.

the pleura. These ndings, termed the split pleura sign, are highly suggestive of empyema in the febrile patient. Additional ndings seen on CECT include a lentiform collection that does not shift with decubitus positioning, and foci of air from gas-forming organisms or bronchopleural stulization. Although most clinically relevant loculations and septations of pleural uid are manifest on CECT, ultrasound remains the most sensitive means of detection. The approach to treatment for empyema varies and is still a topic of discussion for optimal management. Although antibiotic therapy is suf cient in the treatment of pneumonia with a small parapneumonic effusion, there is general consensus that an empyema requires additional thoracentesis or drainage. For more dif cult cases where the need for drainage is indeterminant, laboratory analysis of pleural uid can be helpful. As stated earlier, a pH <7.2, glucose <60 mg/dL, and LDH >1000 units/L are all values that drainage is indicated. A simple algorithm for tube thoracostomy is presented in Table 1. Image-guided placement of small- or medium-bore (8F to 14 F) pleural drainage catheter has been reported as a reasonable initial step in the management of early stage empyema. Data from the Multi-Center Intrapleural Streptokinase Trial (MIST1) showed that small-bore catheters are equally as effective as larger surgical-size catheters (>21F) in draining a uniloculated empyema. In this study, small-bore catheters were also tolerated with much less discomfort, particularly during tube placement.2 Following successful chest tube placement, chest CT is obtained within the rst 24 hours to assess drainage and document adequate positioning. Optimal management of chest tubes requires a rm understanding of intrapleural dynamics. Normally containing a thin layer of serous uid, the pleural space acts as a negative pressure space that serves as a hydrostatic coupling agent to counteract the balance between the lungs tendency to collapse inwardly and the outward recoil of the chest wall. When air or uid accumulates within the space, this protective feature is lost and the lungs normal ability to expand is

impaired. Chest tube drainage systems restore this unique balance by draining the uid without allowing air to reenter the space inadvertently. A drainage catheter connected to a three-chamber system is often used to achieve this task. The rst chamber is a uid collection chamber that collects the drained pleural uid. The second chamber is a water seal that contains a sufcient amount of water to seal the tube and prevent ow of air into the pleural space; bubbling of air within the water seal chamber alerts the clinician toward this possible complication. Finally, the third chamber acts as a suction control. This chamber can be lled with 20 to 25 cm of water to create adequate suction of most pleural uid collections. When gentle bubbling is seen in this chamber, one can infer that adequate suction is being applied to the pleural space.3 Clinicians should not confuse bubbling in this third compartment, which is desired, with air bubbling in the second chamber that represents an air leak into the pleural space. Over the course of management, follow-up radiographs can document a decrease in the size of the effusion, resolution of the pneumonia, and lung reexpansion. Clinical parameters for tube removal include radiographic improvement, <50 to 100 mL output per day, defervescence, and resolving leukocytosis. The use of brinolytics such as tPA is often administered as an adjuvant to tube thoracostomy to break up loculations and increase the volume of uid drained. Although controversial, its use has been reported to reduce morbidity and mortality by sparing the need for a thoracotomy in up to 69% of patients with empyema.4 A different study showed 86% successful treatment with the use of tPA after initial drainage failed.5 The combination of tPA augmented with a mucolytic-like deoxyribonuclease (DNase) can further help by decreasing the viscosity of infected uid, helping to increase volume drained and prevent tube thoracostomy failure. A common dosage includes 10 mg of tPA with 5 mg of DNase twice daily for 3 days; volume of the instillate varies depending on the size of the empyema.6 Each dosage should be instilled with the tube clamped for at least 60 minutes to allow adequate time for enzymatic degradation.
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6. When feasible, a lateral approach utilizing the Seldinger or trocar technique under ultrasound/ uoroscopic guidance is preferred. 7. Fibrinolytic agents such as 10 mg tPA can be instilled twice a day for a total of 3 days to break loculations and improve the effectiveness of catheter drainage. 8. Mucolytic agents like 5 mg DNase are combined with brinolytics to decrease the viscosity of the infected uid. 9. Surgical consultation for thoracotomy or VATS should be sought in cases of more advanced stage empyema with multiple loculations and/or thick pleural peel.

Other Treatment Options

In the presence of an advanced stage empyema with multiple loculations and/or thick pleural peel, surgical consultation for video-assisted thorascopic surgery (VATS), decortication, or open thoracotomy should be sought. The reported ef cacy of VATS is variable, with small studies documenting failure rates (de ned as conversion to open thoracotomy) between 29% and 44%79 However, decortication has been shown to have outcomes at least as good as open thoracotomy; one nonrandomized study of 420 patients showed decreased mortality in patients undergoing decortication as opposed to open thoracotomy (8% versus 16%, respectively).10 Additionally, surgical consultation should be considered in cases when tube thoracostomy with brinolytics fails. Early debridement or thoracotomy in good surgical candidates has been shown to reduce morbidity and mortality in the event of tube thoracostomy failure.2 Referral to VATS or thorascopic debridement should be performed as early as reasonably possible; negative predictive factors for conversion to open thoracotomy include >2 weeks delayed referral and infection with gram-negative organisms.7

References
1 Kraus GJ. The split pleura sign. Radiology 2007;243(1):297298 2 Huang H-C, Chang H-Y, Chen C-W, Lee C-H, Hsiue T-R. Predicting

3 4

Teaching Points/Pearls
1. An empyema is an infected exudative pleural effusion containing pus. 2. Although typically resulting from a parapneumonic effusion, empyema can occur secondary to trauma, surgery, esophageal perforation, or spread from adjacent abscess or osteomyelitis. 3. The split pleura sign is seen on CECT and is highly suggestive of empyema in the febrile patient. 4. Staphylococcus aureus is the most common organism. 5. Small-bore catheters can be used just as effectively as larger ones when drainage of an early stage empyema is performed.

10

factors for outcome of tube thoracostomy in complicated parapneumonic effusion for empyema. Chest 1999;115(3):751756 Braun MA. Interventions in the pleural space. J Vasc Interv Radiol 1997;8:154160 Temes RT, Follis F, Kessler RM, Pett SB Jr, Wernly JA. Intrapleural brinolytics in management of empyema thoracis. Chest 1996; 110(1):102106 Gervais DA, Levis DA, Hahn PF, Uppot RN, Arellano RS, Mueller PR. Adjunctive intrapleural tissue plasminogen activator administered via chest tubes placed with imaging guidance: effectiveness and risk for hemorrhage. Radiology 2008;246(3):956963 Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 2011;365(6):518526 Lardinois D, Gock M, Pezzetta E, et al. Delayed referral and gramnegative organisms increase the conversion thoracotomy rate in patients undergoing video-assisted thoracoscopic surgery for empyema. Ann Thorac Surg 2005;79(6):18511856 Lawrence DR, Ohri SK, Moxon RE, Townsend ER, Fountain SW. Thoracoscopic debridement of empyema thoracis. Ann Thorac Surg 1997;64(5):14481450 Striffeler H, Gugger M, Im Hof V, Cerny A, Furrer M, Ris HB. Videoassisted thoracoscopic surgery for brinopurulent pleural empyema in 67 patients. Ann Thorac Surg 1998;65(2):319323 Tong BC, Hanna J, Toloza EM, et al. Outcomes of video-assisted thoracoscopic decortication. Ann Thorac Surg 2010;89(1): 220225

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