Excerpt from Empyema

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Background

Bacterial pneumonia with associated pleural empyema is the most common cause of pleural effusion found in the pediatric population. Parapneumonic effusions are predominately exudative and occur in as many as 50-70% of patients admitted with a complicated pneumonia. The pulmonary infections of these patients extend into the pleural space and require more extensive therapy, with associated increased morbidity and extended hospital stay.

Involvement of the pleural space with pulmonary infections has been recognized since ancient times. Aristotle identified the increased morbidity and mortality associated with empyema and described drainage of empyema fluid with incision. The practice of surgical drainage as part of therapy for empyema has continued into the era of modern medicine. In his 1901 text, The Principles and Practice of Medicine, Sir William Osler, MD, stated that empyema should be treated as an ordinary abscess, "with incision and drainage." Of note, Osler underwent a rib resection for his own postpneumonic empyema, from which he ultimately expired.

Complicated parapneumonic effusions are appearing more frequently by most accounts, with reported increases in incidence rates in both in Europe and the United States. In England, the rate of admission with a diagnosis of empyema increased over the last decade, most notably in children aged 1-4 years. In addition, the identification of Streptococcus pneumoniae as the primary pathogen has also been reported, both in both the United States and abroad.

Pathophysiology

The definition of a parapneumonic effusion is a pleural effusion associated with either bacterial pneumonia or lung abscess or, rarely, external introduction of organisms associated with chest wall trauma. The development of parapneumonic effusions is gradual, with the pleural fluid collection most commonly divided into 3 stages. The progression of pleural fluid collection evolves from stage 1-3.

In stage 1, the exudative stage, the pleural inflammation from a contiguous infection results in increased permeability and a small fluid collection. At this stage, the effusion is thin and amenable to thoracentesis alone, contains mostly neutrophils, and is often sterile. Stage 2, the fibrinopurulent stage, is characterized by invasion of the organism into the pleural space, progressive inflammation and polymorphonuclear (PMN) leukocyte invasion, and the formation of fibrin membrane deposition, which forms partitions or loculations within the pleural space. Inflammation is characterized by progressive decreases in the pleural fluid glucose and pH and increased protein and lactate dehydrogenase (LDH). The last stage, stage 3, is the organizing stage, in which a pleural peel is created by the resorption of fluid and is associated with fibroblast proliferation that can result in parenchymal entrapment.

Empyema is defined by the presence of intrapleural pus and, for definition purposes, represents an advanced parapneumonic effusion. Complicated parapneumonic effusions (CPE) refer to those fluid collections that require tube thoracostomy or surgery for their resolution.

The accumulation of pleural effusions can rapidly occur in the presence of infection. The pleural surface is a mesothelial membrane that covers the lungs and chest wall. The resultant pleural space is a potential space, containing only small volumes of transudative fluid, with a protein content of less than 1.5 g/dL. This fluid is normally composed of lymphocytes, macrophages, and mesothelial cells, with an absence of neutrophils. Interaction of the mesothelium with the invading bacteria, PMNs, and resultant inflammatory mediators can increase pleural permeability. Further PMN recruitment ensues, which results in the increased production of neutrophil chemotactic mediators, ultimately leading to significant pleocytosis.

Activation of the coagulation cascade is common with pleural empyema. The pleural inflammatory response favors increased procoagulant activity, as well as depressed fibrinolytic activity, which favors fibrin deposition. Loculations result with these fibrin strands covered rapidly by a meshwork of fibroblasts that both proliferate and deposit basement membrane proteins onto the surface of the pleura. These proteins obscure the separation of the visceral and parietal pleura and lead to the formation of the pleural peel.

Following initiation of appropriate therapy, the inflammatory cellular and cytokine production recedes, and the PMN predominance of the parapneumonic effusion decreases. An influx of macrophages assists in the clearance of PMNs, with resolution of the inflammatory process. Migration of pleural mesothelial cells into areas of denuded mesothelium results in the reepithelialization of the pleura and recovery of normal function; however, following exuberant pleural inflammation, the potential for pleural fibrosis and restrictive lung disease is enhanced. The mechanisms that lead to either the development of pleural fibrosis or pleural repair with normal recovery are not well understood and need further investigation and characterization.

Frequency

United States

Parapneumonic effusions are predominately exudative and occur in as many as 50-70% of patients admitted with a complicated pneumonia. These patients have extension of their pulmonary infection into the pleural space and require more extensive therapy, with associated increased morbidity and extended hospital stay.

International

With an increased incidence of pneumonia and tuberculosis worldwide, the frequency of CPE is likely to be even higher.

Mortality/Morbidity

Early recognition of pneumonia with parapneumonic effusion, effective intervention to identify the infecting organism, and initiation of definitive therapy reduce the morbidity and complications associated with this process.

Age

The bacteriology of the infection varies with patient age. In the pediatric population, the most commonly implicated organisms are S pneumoniae, Staphylococcus aureus, and group A streptococci. The latter may be observed as a complication of an infectious skin disorder, such as varicella, impetigo, or infectious eczema. Haemophilus influenzae is rarely encountered since the advent of the H influenzae B vaccine.

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