Diagnosis and Management of Parapneumonic Effusions and Empyema

CLINICAL PRACTICE INVITED ARTICLE Ellie J. C. Goldstein, Section Editor Diagnosis and Management of Parapneumonic Effusions and Empyema Steve A. Sahn Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, Charleston Approximately 1 million patients develop parapneumonic effusions (PPEs) annually in the United States. The outcome of these effusions is related to the interval between the onset of clinical symptoms and presentation to the physician, comorbidities, and timely management. Early antibiotic treatment usually prevents the development of a PPE and its progression to a complicated PPE and empyema. Pleural fluid analysis provides diagnostic information and guides therapy. If the PPE is small to moderate in size, free-flowing, and nonpurulent (pH, 17.30), it is highly likely that antibiotic treatment alone will be effective. Prolonged pneumonia symptoms before evaluation, pleural fluid with a pH !7.20, and loculated pleural fluid suggest the need for pleural space drainage. The presence of pus (empyema) aspirated from the pleural space always requires drainage. Fibrinolytics are most likely to be effective during the early fibrinolytic stage and may make surgical drainage unnecessary. If pleural space drainage is ineffective, video-assisted thoracic surgery should be performed without delay. Parapneumonic effusion (PPE; i.e., pleural fluid that results from pneumonia or lung abscess) is the most common cause of an exudative pleural effusion. PPE may be the consequence of either community-acquired or nosocomial pneumonia. Between 20% and 57% of the 1 million patients hospitalized yearly in the United States with pneumonia develop a PPE [1–3]. Although PPEs are relatively common, empyema (i.e., the accumulation of pus in the pleural space) is less common, occurring in 5%–10% of patients who experience PPE [4]. In a review of 14 studies of empyema that involved a total of 1383 patients, 70% of PPEs were secondary to pneumonia (figure 1) [4]. CLASSIFICATION A practical, clinical classification of PPE is as follows: (1) an uncomplicated parapneumonic effusion (UPPE) resolves with antibiotic therapy alone, without pleural space sequelae; (2) a complicated parapneumonic effusion (CPPE) requires pleural space drainage to resolve pleural sepsis and prevent progression Received 4 June 2007; accepted 26 July 2007; electronically published 24 October 2007. Reprints or correspondence: Dr. Steven A. Sahn, Div. of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, 96 Jonathan Lucas St., Ste. 812CSB, PO Box 250630, Charleston, SC 29425 (). Clinical Infectious Diseases 2007; 45:1480–6  2007 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2007/4511-0014$15.00 DOI: 10.1086/522996 1480 • CID 2007:45 (1 December) • CLINICAL PRACTICE to an empyema; and (3) empyema, the end stage of a PPE, occurs. Empyema is defined by its appearance; it is an opaque, whitish-yellow, viscous fluid that is the result of serum coagulation proteins, cellular debris, and fibrin deposition. Empyemas develop primarily because of delayed presentation by the patient with advanced pneumonia and progressive pleural infection and, less often, from inappropriate clinical management. Early antibiotic treatment prevents progression of pneumonia and the development of a PPE. Early antibiotic treatment will prevent development of an UPPE and progression to empyema. Risk factors for empyema include age (empyemas occur most frequently among children and elderly persons), debilitation, male sex, pneumonia requiring hospitalization, and comorbid diseases, such as bronchiectasis, chronic obstructive pulmonary disease, rheumatoid arthritis, alcoholism, diabetes, and gastroesophageal reflux disease [5]. Bacterial pneumonia, pneumonia due to atypical bacteria, and viral pneumonia are all associated with PPE; however, the relative incidence of PPE varies with the organism. Viral pneumonia and Mycoplasma pneumonia cause small pleural effusions in 20% of patients [6]. Streptococcus pneumoniae pneumonia causes PPE in 40%– 57% of cases [3], and cases of pneumonia due to Staphylococcus aureus, gram-negative bacilli, or anaerobes are associated with pleural effusions in ∼50% of cases [9]. The morbidity and mortality of pneumonia increase when the patient presents with a PPE, because this stage correlates with more-advanced pneumonia. Patients with empyema have a reported mortality rate Figure 1. Causes of empyema in 14 prior studies. Of the 1383 patients in the studies, 70% were parapneumonic. For the other 30% of patients, trauma was the cause of empyema in 7%, empyema was postoperative in 6%, and prior tuberculosis was the cause in 4%; 12% of cases were due to other causes. of 5%–30%, with the incidence varying on the basis of comorbid conditions [5]. The mortality rate may be as high as 40% among immunocompromised hosts [7]. Bilateral PPE at the time of hospital admission is associated with increased mortality (relative risk, 2.8) [8]. PATHOPHYSIOLOGY An estimated time course of untreated or inappropriately treated PPE is shown in figure 2. The inciting event in most cases of pneumonia is the aspiration of organisms from the oropharynx. If the organism load is high and the patient’s host defenses are impaired (e.g., as a result of cigarette smoking or alcohol ingestion), the patient is more likely to develop pneumonia. The interval between aspiration of organisms and the development of pneumonia varies from a few days up to 1 week. Pneumonia typically begins in dependent lobes at the periphery of the lung and, if untreated, spreads centripetally towards the hilum. If left untreated for the subsequent 2–5 days, an UPPE will likely develop. The effusion forms because of an increased capillary permeability secondary to endothelial injury induced by activated neutrophils, which release oxygen metabolites, granule constituents, and products of membrane phospholipases. The resultant extravascular lung water increases the interstitial-pleural pressure gradient and promotes a pleural effusion as fluid moves between mesothelial cells into the pleural space [10]. If interstitial fluid formation exceeds the capacity of the lung and pleural lymphatics, a pleural effusion will accumulate. If left untreated for the subsequent 5–10 days, the PPE transitions to the fibrinopurulent stage, which is characterized by the development of fibrinous adhesions, increased neutrophils, and the presence of bacteria. Fibrin forms as intravascular clotting proteins enter the pleural space, with con- comitant inhibition of pleural space fibrinolysis. Fibroblasts enter the pleural space by 2 possible mechanisms: (1) movement of bone marrow fibrocytes to the site of inflammation, and (2) mesothelial cell transformation to fibroblasts by cytokines, such as basic fibroblast growth factor–2 [11]. Later in the fibrinopurulent stage, p (...truncated)