Determinants of overall state of illness in patients with empyema.
The diagnosis is a progressive clinical picture beginning with pneumonia. Patients with an empyema demonstrate some degree of respiratory distress, malaise, persistent fever, and pleuritic chest pain [10–13]. Physical exam reveals diminished breath sounds with dullness to percussion on the affected side indicative of substance within the pleural space.
Laboratory studies can play a role in the diagnosis of empyema. Serum studies often nonspecifically reflect an infectious process, such as a leukocytosis and elevated inflammatory markers. Pleural fluid findings can be useful. In addition to revealing an exudative process, they have been found to correlate with staging of parapneumonic processes. The Light criteria for complicated parapneumonic effusions include a pH <7.2, lactate dehydrogenase >1000 units, glucose <40 mg/dl or <25 % blood glucose, and Gram stain or culture positive along with loculations or septations proven by imaging . As stages progress from simple to complex, pleural fluid reveals a decrease in glucose and pH while lactate dehydrogenase rises. Multivariate logistic analysis of a retrospective dataset found that pH less than 7.27 in pleural fluid was the only significant factor for the formation of fibrin with/without septations . Similarly, a pleural fluid pH less than 7.1 has been found to result in a sixfold increase in the likelihood of surgical intervention based on retrospective data . Regardless of the findings, in practice once pleural fluid becomes symptomatic, drainage is required.
Imaging is key in diagnostic evaluation of pleural space disease. Chest X-ray (CXR) is often the initial study and reveals poor penetration on the affected side. It is difficult to distinguish between parenchymal consolidation and pleural fluid using plain radiographs . In a retrospective review of over 300 adult patients, CXR missed all effusions significant enough to warrant drainage by subsequent computed tomography (CT) scans . Decubitus films, however, may be helpful to distinguish between free-flowing and loculated effusion . While CXRs are readily available, adjunct studies are often required.
Ultrasonography (US) is portable, is relatively inexpensive, and involves no radiation. Bedside US assesses both the pleural space, revealing effusions of varying complexity, and the pleura itself (Kearney). Some authors suggest that US is superior to CT in the identification of pleural debris or loculations [19, 20]. It can reliably differentiate between parenchymal and pleural based processes . A post hoc analysis of a prospective trial of pediatric patients studying fibrinolysis against operative debridement revealed 31 children who underwent both CT and US and found that CT offered no diagnostic benefit over US . Two independent series reviewed the implementation of an algorithm using US first in children with complicated pneumonia. Both demonstrated a significant reduction in length of stay as well as a decrease in the use of CT without an increase in the rate of operative management or pleural drainage [21, 22]. In addition to providing accurate, real-time imaging, it can be used to guide percutaneous drainage and catheter placement [23, 24]. The main disadvantages include availability and operator dependence. Regardless, US has been demonstrated as an effective diagnostic tool for empyema management.
Radiation exposure from CT has raised the concern for overall lifetime cancer risk. This is of great concern in the pediatric population, in whom repeat imaging significantly compounds their risk. Nevertheless, CT scans may still be utilized; CT with intravenous contrast effectively differentiates between parenchymal and pleural processes . A small retrospective review comparing US and CT suggested that CT should be used in complex cases only, such as patients undergoing surgery or considered to have parenchymal abscesses or bronchopleural fistulae . Consensus statements are clear; the use of CT should be limited to only when necessary, such as in preoperative planning at surgeon discretion [7, 8].
Empyema management is multifold. The ultimate aim is to return normal thoracic physiology by allowing for full expansion of the lung with the removal of infectious components of the pleural cavity. Treatment options are varied and include antibiotics with or without pleural drainage, intrapleural fibrinolytics via chest drains, or operative debridement via video-assisted thoracoscopic surgery (VATS).
Historically, the most common causative pathogen in pediatric empyema has been Streptococcus pneumoniae [26–29]. While the overall incidence of pediatric community-acquired pneumonia has decreased with the initiation of heptavalent pneumococcal conjugate vaccine (PCV-7), pediatric empyema rates have increased. This has been found to be due to a multitude of organisms, including non-serotype Streptococcus pneumoniae, other Streptococcus spp., Staphylococcus aureus, and unspecified pathogens . Understanding the source will also help reveal the underlying pathogen, e.g., mixed aerobic and anaerobic flora in esophageal rupture cases and subdiaphragmatic sources or Staphylococcus spp. in infected posttraumatic or postoperative hemothoraces.
Antibiotic regimens have been classically tailored to what organism is grown on a case-by-case basis, with initial recommendations for broad coverage, particularly for gram-positive organisms. There is little consensus on the duration of agents, particularly once interventions have been done. A retrospective review found that those transitioned to an oral antibiotic regimen after being afebrile, stable from a respiratory perspective and without evidence of loculations, resulted in a decreased hospital stay and financial burden. These patients still underwent approximately 7–14 days of parenteral therapy and, ultimately, were placed on additional 2–4 weeks of enteral therapy . The British Thoracic Society recommended in adult patients a minimum of 3 weeks of oral therapy when the patient showed clinical improvement . The most recent guidelines state a treatment for 10 days after resolution of fever in children treated for empyema complicating community-acquired pneumonia [8, 32]. A prospective, observational study for 7 days of therapy with oral antibiotics after afebrile, off oxygen, and completion of fibrinolysis is underway to help guide future management.
After identifying the presence of pleural fluid, the next step in management relies on understanding the nature of the fluid itself—free flowing versus frankly purulent. The need for intervention is dictated by size, symptoms, and presence of septations.
Size classification is difficult to precisely define. In general, small effusions have <1 cm rim of fluid, moderate effusions have 1–2 cm rim, and large effusions have >2 cm rim as seen on decubitus CXR. One pediatric study classified effusions as small, moderate, and large based on the degree of opacification on upright films, <¼ opacification, ¼–½ opacification and >½ opacification, respectively . The authors found small and most moderately sized parapneumonic effusions that could be effectively managed with antibiotics and without drainage procedures without an increase in the length of stay or other complications, suggesting that interventions be based on symptomology versus size criteria alone .
Effusion size typically correlates with symptoms. Symptoms precipitating intervention generally include poor feeding intolerance, worsening tachypnea, and increasing oxygen requirement. A retrospective case series in children found respiratory distress on presentation was related to a prolonged stay and higher likelihood for intervention . When symptoms seem to progress, further action is required to manage pleural disease.
Loculated pleural fluid indicates a later pathologic stage of empyema formation. In 2000, the American College of Chest Physicians stated the need for interventional therapy as the stage of parapneumonic effusion increased . This is likely due to disrupted normal fibrinolytic properties in infected pleural fluid. Thus, resolution of septated fibrin matrices or thick pleural peel is unlikely without further intervention past antibiotic treatment [10, 21].
The decisional tree for fluid drainage includes the options of single or multiple thoracentesis versus tube thoracostomy. Single thoracentesis can be utilized in the drainage of free-flowing effusions. A prospective, nonrandomized series compared pediatric empyemas treated with repeated US-guided needle aspirations to tube thoracostomy. Thirty-five children underwent repeated needle thoracentesis every other day with an average of 2.4 drainage procedures per patient. This cohort had an overall similar length of stay to those managed with a traditional chest tube . Although less invasive, there is still a requirement for local anesthesia and sedation with each drainage procedure. Practically speaking, while an older child may endure thoracenteses, it is arguable whether this would be tolerable in younger children.
The British Thoracic Surgery guidelines recommend chest tube placement when initial thoracentesis fails to adequately drain an effusion to avoid multiple attempts . A retrospective series compared children who underwent chest tube placement on the basis of effusion size and fluid analysis versus those placed only for mediastinal shift or progressively worsening symptoms. The study revealed no difference in hospital stay, suggesting judicious use of chest tubes . Studies evaluating chest tube caliber have revealed catheters as small as 12 French may be used for adequate drainage purposes and for administration of fibrinolytics [38, 39].
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Debridement: Surgical Versus Chemical
The definitive management for empyema has traditionally been surgical debridement. While this may be done via open procedures, the current gold standard employs the minimally invasive approach of VATS [40–44]. VATS has resulted in earlier and more complete resolution of empyema than chest tube drainage alone in both retrospective and prospective studies, resulting in shorter hospitalization lengths with primary VATS [45–48]. A retrospective series of 89 children undergoing primary VATS found that only 12 % had a risk of subsequent procedures for ongoing disease or complications . In recent years, the standard of thoracoscopy is being increasingly challenged by chemical debridement as the definitive management for fibrinopurulent pleural space disease.
Chemical fibrinolysis takes advantage of the underlying pathophysiology of empyema formation. Infected pleural fluid allows for increased fibrin deposition, which later forms loculations in complicated effusion. Simply stated, fibrinolytics break down fibrin within the pleural space. Examples include urokinase, streptokinase, and tissue plasminogen activator (tPA). With local instillation, these agents target and liquefy the matrices of pleural debris in empyema and have been shown to be effective in promoting resolution of empyema in multiple series [46–57].
Fibrinolytics have been shown to be superior in chest tube drainage alone in both retrospective and prospective studies by both direct comparison and when used in patients who failed primary chest tube drainage only [50, 51, 54, 56, 57]. Moreover, empyema treatment with fibrinolytics via chest tube has been shown to be more cost effective than solely with chest tube .
There is still speculation over the efficacy of one fibrinolytic over another in pleural disease management. In a rabbit model comparing urokinase to streptokinase, there was found to be no overall difference in effect of pus viscosity after treatment . An adult prospective randomized trial comparing these same two agents with empyema demonstrated no difference in disease resolution. Severe allergic reactions were seen in the streptokinase arm, and, thus, the authors concluded favorably for the use of urokinase . As urokinase is no longer available in the United States, tPA has become the most commonly used chemical fibrinolytics. Comparison studies of fibrinolytics have not been done in the pediatric population.
The operative treatment involves placing the patient in lateral position. Lung isolation is not required and the lung will usually be adherent to the chest wall regardless. An initial 5 or 10 mm port is placed below the tip of the scapula and the camera is used to initiate the dissection by sweeping between the lung and chest wall to create enough working space for additional instrument sites. One or two additional ports can be placed with adequate triangulation to get around the entire chest. Through a 10 mm incision, a handheld curved ring tipped grasper can be placed straight into the chest without the port in place to remove large fibrinous chunks. The goal of the operation is to remove or break down the solid components in the pleural space which allows suction of the purulent fluid. It is not advisable to try to remove peel from the lung itself as there can be necrotic and friable areas of lung resulting in a persistent air leak or worse.
There have been three prospective randomized clinical trials comparing fibrinolysis to primary VATS for empyema management in children [61–63]. Two single institution series compared the instillation of three intrapleural doses of fibrinolytic agents to VATS at diagnosis [61, 62]. One utilized urokinase while the other used tPA. Results were highly concordant. Both revealed no difference in hospital length of stay and found VATS to be more expensive. One of these two reported no difference in days of tube drainage, days of fever, and doses of analgesics or oxygen requirements. Failure rates after fibrinolysis requiring salvage VATS was 16.6 % in both studies and is similar to previous studies [61, 62, 64, 65].
More recently, a multicenter randomized clinical trial comparing urokinase to VATS was conducted in 103 children specifically with complicated, septated parapneumonic effusions. Intrapleural urokinase was instilled for 3 days every 12 h. The surgical protocol did not include debridement of the pleural peel of the lung. They found no significant difference in overall hospitalization length or postoperative length of stay. Failure rates were similar, 15 % in VATS patients and 10 % in urokinase; only 5 of these 13 total patients requiring salvage thoracoscopy and 8 were treated successfully with repeat fibrinolytics. Three-month radiologic follow-up was considered normal in 66.7 % of VATS and 59.5 % of urokinase patients, again revealing no difference. Overall, urokinase was demonstrated to be as effective as VATS as first-line therapy in treatment of complicated empyema .
Based on these studies, there is growing evidence in the efficacy of first-line administration of fibrinolytics in the management of empyema regardless of level of complexity. Current American Pediatric Surgical Association guidelines support this and suggest operative management should be reserved for failure after fibrinolysis . Based on a comprehensive review of the literature, we propose an empyema management algorithm in the pediatric population (Fig. 17.2).
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