Background
Pleural effusions are a common finding in patients with pneumonia. More than 40% of patients with bacterial pneumonia and 60% of patients with pneumococcal pneumonia develop parapneumonic effusions. While treatment with antibiotics leads to resolution in most patients, some patients develop a more fibrinous reaction, with the presence of frank pus in the most severe cases. The latter is referred to as an empyema or empyema thoracis. [1]
Parapneumonic pleural effusions are classified into three broad groups based on fluid characteristics, which, in turn, provides a reflection on both the severity and natural history of the pleural effusion.
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Uncomplicated parapneumonic effusions: These are exudative, predominantly neutrophilic effusions reflecting increasing passage of interstitial fluid as a result of inflammation associated with pneumonia. The fluid may be slightly cloudy or even clear, without any organisms noted on Gram stain or culture. They resolve with appropriate antibiotic treatment of the pneumonia.
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Complicated parapneumonic effusions: These occur as a result of bacterial invasion into the pleural space that leads to an increased number of neutrophils, decreased glucose levels, pleural fluid acidosis, and an elevated lactic dehydrogenase (LDH) concentration. These effusions often are sterile because bacteria are usually cleared rapidly from the pleural space. The fluid is typically cloudy and is classified as complicated because it requires drainage for resolution.
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Empyema thoracis: This develops as frank pus accumulates in the pleural space. Laboratory studies indicate that preexisting pleural fluid is required for the development of an empyema because empyema is not seen after direct inoculation into a "dry" pleural space. The pus is seen after thoracentesis or any drainage procedure of the pleural space and is generally characterized as thick, viscous, and opaque.
Empyema thoracis has been recognized as a serious problem for centuries. In approximately 500 BCE, Hippocrates recommended treating empyema with open drainage. The treatment of empyema remained essentially unchanged until the middle of the 19th century. In 1876, Hewitt described a method of closed drainage of the chest in which a rubber tube was placed into the empyema cavity to drain via a water seal drainage method. In the early 20th century, surgical therapies for empyema (eg, thoracoplasty, decortication) were introduced. More recently, video-assisted thoracoscopic surgery (VATS) has played a major role in the treatment of patients with empyema thoracis.
Etiology
Virtually any type of pneumonia (eg, bacterial, viral, atypical) can be associated with a parapneumonic pleural effusion. However, the relative incidence of parapneumonic pleural effusions varies with the organism. Viral pneumonia and Mycoplasma pneumonia cause small pleural effusions in 20% of patients. For thoracic empyema, bacterial pneumonia is the cause in 70%. [2] Increasingly, empyema thoracis is a complication of previous surgery, which accounts for 30% of cases. Trauma may also be complicated by infection of the pleural space. In the absence of trauma or surgery, the infecting organism may spread from blood or other organs into the pleural space. These can develop into subdiaphragmatic abscesses, a ruptured esophagus, mediastinitis, osteomyelitis, pericarditis, cholangitis, and diverticulitis, among others.
Bacteriology
Bacteriologic features of culture-positive parapneumonic pleural effusions have changed over time. Prior to the antibiotic era, Streptococcus pneumoniae was the most common. S pneumoniae and Staphylococcus aureus now account for approximately 70% of aerobic Gram-positive cultures. Presently, aerobic organisms are isolated slightly more frequently than anaerobic organisms. Streptococcus milleri has also become more common. [3, 4, 5] Klebsiella, Pseudomonas, and Haemophilus species are the three most commonly isolated aerobic Gram-negative organisms. Bacteroides and Peptostreptococcus species are the 2 most commonly isolated anaerobic organisms. Currently, empyema thoracis is most often associated with aspiration pneumonia with mixed bacterial florae containing aerobic and anaerobic bacteria. [6] The usual organism isolated in empyema thoracis complicating previous surgery is S aureus.
Pathophysiology
The evolution of a parapneumonic pleural effusion, as shown in the image below, can be divided into 3 stages, including exudative, fibrinopurulent, and organization stages. [2]
Left pleural effusion developed 4 days after antibiotic treatment for pneumococcal pneumonia. Patient developed fever, left-sided chest pain, and increasing dyspnea. During thoracentesis, purulent pleural fluid was removed, and the Gram stain showed gram-positive diplococci. The culture confirmed this to be Streptococcus pneumoniae.
During the exudative stage, sterile pleural fluid rapidly accumulates in the pleural space. The pleural fluid originates in the interstitial spaces of the lung and in the capillaries of the visceral pleura because of increased permeability. The pleural fluid has a low white blood cell (WBC) count and a relatively low LDH level. The pleural fluid glucose and pH levels are within the reference range. These effusions resolve with antibiotic therapy, and chest tube insertion is not required. This stage takes approximately 2-5 days from the onset of pneumonia.
In the second stage, or fibrinopurulent stage, bacterial invasion of the pleural space occurs, with accumulation of polymorphonuclear leukocytes, bacteria, and cellular debris. A tendency toward loculation and septation exists, pleural fluid pH (< 7.20) and glucose levels are lower (< 60 mg/dL), and the LDH levels increase. At this stage, bacteriological stains and/or cultures of the pleural fluid can be positive for microorganisms. This stage takes approximately 5-10 days after pneumonia onset.
In the last, or organization stage, fibroblasts grow into the exudates from both the visceral and parietal pleural surfaces, and they produce an inelastic membrane called a pleural peel. Pleural fluid is thick. In an untreated patient, pleural fluid may drain spontaneously through the chest wall (ie, empyema thoracis necessitatis). Empyema thoracis may arise without an associated pneumonic process, such as from esophageal perforation, trauma, a surgical procedure in the pleural space, or septicemia. This last stage may take 2-3 weeks to develop.
Etiology
See Background for details on the etiology and bacteriology of these pleural infections.
Pneumonia is the leading cause of parapneumonic effusions and empyema thoracis.
Increasingly, empyema is also a complication of previous cardiothoracic surgery, which accounts for 30% of cases. The usual organisms are Staphylococcus species and Gram-negative bacteria.
Trauma can also lead to inoculation and superinfection of the pleural space.
In the absence of trauma or surgery, the infecting organism may have spread from blood or other organs into the pleural space. These causes include extension of infections from adjacent or distant sites (eg, ruptured esophagus, mediastinitis, osteomyelitis, pericarditis, cholangitis, diverticulitis, pericarditis) or subdiaphragmatic abscesses.
Risk factors
Risk factors for empyema thoracis include age (children and elderly persons), debilitation, pneumonia requiring hospitalization, and comorbid diseases, such as bronchiectasis, rheumatoid arthritis, alcoholism, diabetes, and gastroesophageal reflux disease. [2]
A large prospective observational study in the United Kingdom, using multivariate regression analysis, identified 7 clinical factors predicting the development of complicated parapneumonic pleural effusions or empyema thoracis. They identified an albumin value of less than 30 g/L, a serum sodium value of less than 130 mmol/L, a platelet count of greater than 400 X 109/L, a C-reactive protein level of greater than 100 mg/L, and a history of alcohol abuse or intravenous drug use as independently associated with the development of complicated parapneumonic pleural effusions or empyema thoracis, while a history of chronic obstructive pulmonary disease (COPD) was associated with a decreased risk. [7]
Epidemiology
Frequency
United States
Based on hospital discharge data, approximately 1.3 million patients are hospitalized each year with pneumonia in the United States. The prevalence of parapneumonic effusions is dependent, in part, on the organism involved. Overall, pleural effusions are seen in approximately 35-40% of patients with bacterial pneumonia or anaerobic pneumonia, with a prevalence in pneumococcal pneumonia approaching 60%. Complicated pleural effusions are more commonly seen with anaerobic pleuropulmonary infections. This results in an estimated 500,000-750,000 patients with parapneumonic effusions annually. No good estimates are available regarding the fraction of these patients that proceed to complicated effusions or empyema, but in small series, approximately 5-10% require a drainage or a surgical procedure.
A study of United States hospitalization data found that in 1996, the national hospitalization rate for parapneumonic empyema-related diagnoses was 3.04 per 100,000; by 2008, it had increased to 5.98 per 100,000, a 2-fold increase. Pneumococcal empyema rates remained stable, but staphylococcal empyema rates tripled. Hospitalization rates for empyemas of other or unknown etiology (62.4% of empyema hospitalizations) doubled, as did rates for nonpneumococcal streptococcal empyemas. [8]
International
No good estimates are available on the international incidence of pneumonia. The World Health Organization has reported the burden of disease related to deaths from lower respiratory tract infections in 2004 at 4.2 million. One can extrapolate the incidence of pleural effusions and empyema using a US estimate, but caution is advised because the lack of treatment and delayed treatment in underdeveloped countries may skew the international incidence upward.
Race
No specific ethnic predisposition is recognized for empyema; however, a larger number of ethnic minorities have limited financial resources, limited access to healthcare, and more comorbidities, which, in turn, may increase their risk of pneumonia, pleural effusions, and empyema.
Sex
Empyema has no known sexual predilection.
Age
No specific age predisposition is recognized for empyema, although increasing age and associated comorbidities increase the risk for pneumonia and, subsequently, pleural effusions and empyema. Also recognized is that differences exist in empyema that occurs in children compared with adults. The most striking differences include the development of empyema in previously healthy children (as opposed to adults who usually have some underlying comorbidity) and the lower threshold for treatment with thrombolytics and surgical drainage in children compared with adults. See Empyema for more details.
Prognosis
Most patients recover, but the mortality rate remains approximately 10%. Appropriate antibiotic therapy and early drainage of pleural fluid are crucial for recovery. Approximately 15-25% of patients require surgical intervention, including decortication and/or an open drainage procedure.
Mortality/morbidity
Mortality rates from empyema have been reported to be 11-50% range. The wide difference is due in part to limited data, with mortality rates being higher (in the 50% range) at a time when current diagnostic imaging, antibiotics, and drainage options were not readily available. Other complicating factors include cardiac and respiratory comorbidities, immunosuppressive states related to medications or human immunodeficiency virus (HIV) infection, and age. Death rates related to pneumonia are higher in elderly persons and in those with the outlined underlying comorbidities. More recent reports estimate deaths in patients with pneumonia and complicated pleural effusions in the 7-10% range.
Patient Education
For patient education resources, visit the Lung Disease and Respiratory Health Center. Also, see the patient education article Bacterial Pneumonia.
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Left pleural effusion developed 4 days after antibiotic treatment for pneumococcal pneumonia. Patient developed fever, left-sided chest pain, and increasing dyspnea. During thoracentesis, purulent pleural fluid was removed, and the Gram stain showed gram-positive diplococci. The culture confirmed this to be Streptococcus pneumoniae.
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Left lateral chest radiograph shows a large, left pleural effusion.
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A right lateral decubitus chest radiograph shows a free-flowing pleural effusion, which should be sampled with thoracentesis for pH determination, Gram stain, and culture.
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CT scan of thorax shows loculated pleural effusion on left and contrast enhancement of visceral pleura, indicating the etiology is likely an empyema.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, showing a thickened contrast-enhanced pleural rind, high-density pleural effusion, loculation, and septation. Thoracentesis yielded foul-smelling pus.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, 3 days following thoracostomy and intrapleural fibrinolysis (Reteplase).
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Chest CT scan with intravenous contrast (axial, coronal, and sagittal views) of an alcoholic male patient with an anaerobic empyema demonstrating the split pleura sign.
