Pediatrics

Parapneumonic effusion/empyema

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OVERVIEW: What every practitioner needs to know

Are you sure your patient has a parapneumonic effusion or empyema? What are the typical findings for this disease?

Parapneumonic effusion or empyema is a collection of fluid in the pleural space as a result of pneumonia. The diagnosis of parapneumonic effusion or empyema is based on history and physical examination suggesting pneumonia combined with initial laboratory and chest radiography (CXR) indicating a likely bacterial infection with fluid in the pleural space.

The most common symptoms and signs include: fever, cough, chest pain, and decreased breath sounds on the side of the effusion. Symptoms often develop over several days and the effusion may not develop until after antibiotic treatment has been started for the pneumonia.

Parapneumonic effusions

These occur in up to 60% of patients with Streptococcus pneumoniae pneumonias, but can be seen with any pneumonia (usually bacterial, although viral and fungal infections can rarely produce effusions).

Parapneumonic effusions progress through three stages:

  1. Exudative - sterile, free flowing fluid (2-5 days after the onset of pneumonia)

  2. Fibro-purulent - fibrin deposits over the visceral and parietal pleura with fluid becoming loculated (5-10 days after onset of the pneumonia)

  3. Organized - a thick, inelastic pleural peel develops, attached to both pleural surfaces (2-3 weeks after the onset of pneumonia)

Parapneumonic effusions frequently require chest tube drainage if the patient has respiratory distress, is not responding to antibiotic treatment, or when the effusion is >1 cm thick or involves more than 20% of the volume of the chest. A parapneumonic effusion is referred to as a complicated effusion if it requires a procedure to adequately treat.

Empyema

This is a parapneumonic effusion with pus (thick, viscid fluid with high numbers of white blood cells and/or the presence of bacteria) caused by the infection spreading from the lung into the pleural space.

Empyemas always require drainage and are almost always associated with infection of the underlying lung or mediastinum. Occasionally empyemas are a complication of cardiac, mediastinal, or chest wall surgery.

Other symptoms and signs of a parapneumonic effusion or empyema include: shortness of breath, generalized malaise, night sweats, weight loss, dullness to percussion of the chest, crackles, or rarely a friction rub.

What other diseases or conditions share some of these symptoms?

Pneumonia (bacterial) without a pleural effusion - has a similar clinical presentation, but no effusion on CXR.

Lung abscess - has a similar clinical presentation, although an abscess is more likely to occur in children with neurologic abnormalities and be related to an aspiration event. Often lung abscess has a prolonged onset and slow progression.

Hemothorax - can be distinguished by history (trauma or hemoptysis) or findings of abnormal coagulation.

Chest trauma - also distinguishable from a parapneumonic effusion by history.

Malignant effusion - is a pleural effusion due to pleural infiltration of cancerous cells (usually lymphoma or leukemia) and is almost always distinguishable by history.

What other diseases or conditions can result in increased pleural fluid?

Other causes of pleural fluid collections include:

  • Congestive heart failure

  • Tumors, particularly those involving the chest wall or mediastinum, such as lymphoma

  • Chylothorax due to leakage of lymph

  • Pancreatitis

  • Pulmonary embolism

  • Systemic lupus erythematosus (SLE) or rarely other severe inflammatory or auto-immune diseases

These other causes for pleural effusions are distinguished from parapneumonic effusion and empyema based on clinical history and physical findings.

What caused this disease to develop at this time?

Parapneumonic effusion

Infection with streptococcus bacteria is the most frequent cause of a parapneumonic effusion. Both S. pneumoniae and S. pyogenes are associated with complicated pneumonia although S. pneumoniae serotypes 3, 19A, and 7F account for the majority of infections. Frequently the pleural effusion develops after antibiotic therapy for bacterial pneumonia is started and may be related to rapid bacterial killing by the antibiotics. Thus, the development of an effusion does not necessarily indicate that the antibiotic is not effective.

Empyema

Empyema develops when the infection spreads from the lung into the pleural space. Both aerobic and anaerobic bacteria may be responsible. Anaerobic infections are more common in adults and in patients with neurologic abnormalities or aspiration pneumonia. Anaerobic infections may have a more gradual presentation and include significant weight loss and anemia. Methicillin resistant Staphylococcus aureus (MRSA) has been increasingly identified as a cause of empyema in children. Antibiotics to treat MRSA should be added if gram positive bacteria are present in the pleural fluid.

What are risk factors for parapneumonic effusions and empyema?

Parapneumonic effusion and empyema can develop in previously healthy children and are related to the natural course of community-acquired pneumonias. However, there are some patients where this complication may be more common. Parapneumonic effusion should be suspected in patients with:

  1. Pneumonia requiring hospitalization (i.e., severity of underlying pneumonia)

  2. Varicella or influenza infection

  3. Debilitation and poor nutrition

  4. Severe coincident viral pneumonia such as H1N1 influenza

  5. Co-morbid conditions:

    • Neurologic disability

    • Bronchiectasis (ex. Staphylococcus aureus empyema has been the presenting illness in cystic fibrosis)

    • Rheumatoid arthritis

    • Alcoholism

    • IV drug abuse

    • Diabetes

    • Gastroesophageal reflux

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Initial laboratory studies in patients with suspected pneumonia and parapneumonic effusion or empyema include:

Complete blood cell count (CBC) and differential: Elevated white blood cell count (WBC) >15,000 or increased band neutrophils >1000 are suggestive of bacterial vs. viral pneumonia.

C-reactive protein (CRP): Extremely high levels are suggestive of bacterial vs. viral etiology. Additionally, CRP can serve as a tool for monitoring the course of disease.

Erythrocyte sedimentation rate (ESR): Represents the degree of inflammation and may be used, similar to CRP, for monitoring the course of infection and for follow-up. ESR is not specific for pleural disease versus pneumonia and does not separate bacterial vs. viral etiology.

Blood culture: Blood cultures are not recommended for simple pneumonia because the yield is very low. However the yield may be higher in complicated pneumonias when a parapneumonic effusion or empyema is present.

Diagnosing parapneumonic effusion or empyema

The diagnosis of parapneumonic effusion or empyema is based on history and physical examination suggesting pneumonia, followed by initial laboratory studies and chest radiograph (CXR) indicating a likely bacterial infection plus fluid in the pleural space. If pleural fluid is suspected, a lateral decubitus CXR can be obtained to see if the fluid layers out. If the fluid does not layer out then a chest ultrasound should be obtained to localize the radiographic density seen on CXR.

Once the diagnosis of an effusion is made, diagnostic thoracentesis is indicated to determine if the fluid is infected (i.e., empyema) and/or will require drainage (i.e., complicated effusion). In patients with respiratory distress, diagnostic and therapeutic drainage should be performed as soon as possible to improve the patient’s breathing. Care must be taken when draining large effusions that have been present for a long time, since rapid drainage can produce post-drainage pulmonary edema and worsened respiratory distress.

What history should stimulate further evaluation for parapneumonic effusion or empyema?

Typically, a child with parapneumonic effusion will have a history of developing pneumonia and then, often after starting antibiotic treatment, will worsen with fever, chest pain, increasing tachypnea, and shortness of breath. Physical examination will detect decreased breath sounds on the side where there may have been crackles a few days earlier when the pneumonia was diagnosed. Any child with pneumonia and worsening respiratory difficulty should have a CXR to look for a parapneumonic effusion.

Additional diagnostic studies

Thoracentesis is indicated if the lateral decubitus radiograph shows more than 1 cm of free flowing fluid, or if more than 20% of the hemithorax is occupied by effusion, and to provide relief of respiratory distress caused by large amounts of fluid in the pleural space. The earlier this is done, the better the chance the patient can be treated without surgery.

Pleural fluid should be removed and sent for analysis including:

  • Gram stain (empyema is defined by the presence of bacteria in the pleural fluid)

  • Bacterial culture (both aerobic and anaerobic) to diagnose the cause of the pneumonia

  • Fluid pH (measured on a blood gas machine, not pH indicator strips or meter). Fluid with a pH ≤ 7.2 requires drainage.

  • Cell count and differential to further define the effusion (i.e., there are a high number of neutrophils when the effusion is related to bacteria)

  • Additional pleural fluid analysis (NOTE: these tests are generally not indicated in patients with pneumonia and parapneumonic effusion or empyema, but may be helpful if the etiology of the pleural effusion is not known and other diagnoses are suspected):

    • additional cultures if clinically indicated (mycobacteria, fungus)

    • antigen tests (PCR) in difficult to diagnose pneumonia

    • cytology if clinically a lymphoma or other cancer is suspected

    • protein to separate a transudate (heart failure, liver or renal disease) from exudate (parapneumonic effusion or empyema)

    • glucose to support the possibility of empyema

    • LDH to separate a transudate (heart failure, liver or renal disease) from exudate (ex. parapneumonic effusion or empyema)

    • triglycerides if chylothorax is suspected or the fluid is a milky color

In older children thoracentesis is best performed with the patient sitting and leaning forward with support. Following percussion of the chest, the needle is inserted over the rib, one intercostal space below the line of dullness.

For younger children, thoracentesis is performed with the patient lying supine and their arm raised. The location is generally in the 4th intercostal space, mid-axillary line, paying attention to avoid the nipple. Again percussion can be used to determine the level of fluid accumulation and ultrasound guidance may be helpful.

Following cleaning the skin with an antiseptic solution and preparing a sterile field, local anesthetic is used to infiltrate the skin and underlying tissues down to the level of the pleura.

After a brief delay to allow the anesthetic to become effective, a larger needle (frequently a standard 20- or 22-gauge IV catheter over a needle is used) with an attached syringe is inserted over the rib (to avoid the blood vessels running under the rib). Gentle aspiration on the syringe will return fluid once the needle enters the pleural space. If free air is seen without fluid, the needle and catheter should be withdrawn. Once fluid is flowing into the syringe, the catheter can be advanced over the needle and into the pleural space. The needle can then be withdrawn and another syringe can be attached to the catheter, allowing fluid to be withdrawn. Placing a three-way stopcock in line can allow large amounts of fluid to be removed if desired.

Once the procedure is complete, the catheter is removed and an occlusive dressing is applied. A follow-up CXR is only necessary if a complication, such as pneumothorax, is suspected.

Would imaging studies be helpful? If so, which ones?

Radiologic studies for children with suspected pneumonia and parapneumonic effusion or empyema should begin with a chest radiograph (CXR). Additional studies are based on the findings of the CXR.

  • Chest radiograph

    • Always get an upright AP view. A lateral view is not always necessary.

    • Localized increased lung density suggests pneumonia.

    • Blunting of the costo-phrenic angle suggests fluid in the pleural space and necessitates further evaluation.

    • Used for estimating the amount of fluid in the pleural space.

  • Lateral decubitus CXR can be obtained if the plain CXR has evidence of pleural fluid

    • Obtain with the side of the suspected effusion in the dependent position (down).

    • Evaluate if there is free flowing fluid in the pleural space (i.e., fluid layers out when the child is lying on their side).

    • In addition to the upright AP view it can be helpful to estimate the volume of fluid in the pleural space.

  • Chest ultrasound

    • If the AP and lateral decubitus CXRs are not diagnostic, ultrasound is the evaluation of choice to estimate the size of the effusion.

    • To assure accuracy, ultrasound should be performed by an experienced person.

  • Chest CT scan

    • Much higher radiation dose than a lateral decubitus radiograph and not needed if fluid layers out when the child is lying on their side.

    • May be helpful if the fluid is not free flowing on lateral decubitus radiograph and ultrasound evaluation is not available.

    • Can be used to demonstrate damage to the lung parenchyma (i.e., lung abscess).

If you are able to confirm that the patient has a parapneumonic effusion or empyema, what treatment should be initiated?

Antibiotics should always be started to treat bacterial pneumonia. Initial options to treat the parapneumonic effusion include: observation, thoracentesis only, chest tube drainage, chest tube drainage combined with fibrinolytic therapy, video-assisted thoracoscopic surgery (VATS), or open thoracotomy.

Observation can be used in patients with minimal pleural fluid (<1 cm on lateral decubitus chest radiograph and no respiratory distress) or if thoracentesis cannot safely be performed.

Thoracentesis should be performed in all patients where adequate fluid is present (i.e., ≥ 1 cm on upright AP or lateral decubitus CXR or the effusion occupies at least 20% of the involved hemithorax). Drainage may not be necessary if the patient is not in respiratory distress and the fluid has a pH>7.2 and no bacteria are present.

Chest tube drainage alone can be performed if the parapneumonic effusion is treated in the exudative phase (i.e., free flowing). This can be determined with the lateral decubitus CXR.

Chest tube drainage combined with the fibrinolytic therapy is probably superior to chest tube drainage alone and should be started within 24 hours if the parapneumonic effusion does not resolve.

VATS can also be used for non-resolving effusions and the child is not improving with other therapy. Proceeding directly to VATS rather than chest tube drainage may be indicated when the pleural effusion has been present for more than 10 days and is organized.

Open thoracotomy is rarely indicated in patients with complications, or if the surgeon has limited experience with VATS.

General therapy for parapneumonic effusion and empyema

Antibiotics

Initial treatment for community-acquired pneumonia generally includes ampicillin (amoxicillin) or a second- or third-generation cephalosporin (cefuroxime, cefotaxime). A macrolide (clarithromycin or azithromycin) should be added when Mycoplasma pneumonia is suspected. Ampicillin plus clindamycin can be used when aspiration pneumonia is suspected or in younger children. This combination is also highly effective with S. pneumoniae infection, the most common cause of parapneumonic effusions in children. Vancomycin or linezolid should be added if methicillin resistant Staphylococcus aureus (MRSA) empyema is suspected (i.e., large gram positive bacteria present in the pleural fluid). Choice of antibiotics should be guided by local microbiology and antibiotic resistance patterns.

Chest tube drainage

Patients with pneumonia and a >1 cm thick effusion should have pleural drainage. Small tubes or "pig-tail" catheters produce less pain and are better tolerated than larger drains. Drainage is always indicated in patients with respiratory distress, empyema (bacteria present in the pleural fluid), complicated parapneumonic effusion (ex. pH <7.2) and large volumes of fluid (>50% of hemithorax).

Supportive care includes:

  • adequate fluids – may need IV fluids if not taking oral. Replace any deficit and use maintenance amounts. Do not overhydrate, as this may worsen the effusion.

  • nutrition – good calorie intake is important for recovery.

  • anti-pyretics and analgesics – for fever and pain. Non-steroid anti-inflammatory analgesics are particularly helpful given the degree of pleural inflammation.

Specific therapy for parapneumonic effusion and empyema

There is no proven therapeutic advantage of VATS over chest tube drainage with fibrinolytics, however local experience and comfort with different approaches should be considered in management decisions.

There is no proven therapeutic advantage of VATS over chest tube drainage with fibrinolytics, however local experience and comfort with different approaches should be considered in management decisions.

Fibrinolytic therapy (tissue plasminogen activator [tPA] or urokinase) in addition to chest tube drainage is used to treat empyema (bacteria in pleural fluid) or complicated parapneumonic effusion (pH <7.2 or poor clinical response within 24 hours). Although no standard protocol exists for the use of tPA, one evidence-based approach used 4 mg tPA diluted in 40 mL sterile normal saline instilled directly into the chest tube. After a 1-hour period with the tube clamped, drainage was restarted with -20 cm suction. This was repeated at 24 and 48 hours. Other studies have used a dose of 0.1 mg/kg/dose (minimum 1 mg in 10 mL) and have instilled every 12 hours for up to 72 hours. The dose of urokinase (difficult to obtain in the US) is 40,000 units in 40 ml normal saline instilled into the chest tube every 12 hours for 72 hours.

VATS should be considered if there has been a delayed diagnosis of greater than 10 days, for effusions with underlying necrotic lung tissue, and for effusions that fail to improve with drainage and fibrinolytic therapy.

Open thoracotomy is only indicated when VATS is not available.

Duration of therapy and long-term follow-up

Duration of therapy is determined by clinical response. Patients should be monitored for improving fever and clinical activity. In general patients with respiratory distress rapidly improve once drainage is accomplished, although it may take many days for the fever and chest pain to resolve. As long as the patient is clinically improving, therapy can be assumed to be effective. Following CRP (or ESR) every few days or weekly may be an objective biochemical marker of disease course in patients who are slow to improve clinically.

Antibiotics

Intravenous (IV) antibiotics are indicated initially until the patient is clinically improving. Antibiotic choice is the same as for bacterial pneumonias. Oral antibiotics (based on the identification of the organism and antibiotic sensitivities) can be used if the patient is clinically improving on IV antibiotics and should be continued for at least 14 days. Group A streptococcal infections should be treated for at least 21 days. IV antibiotics for 14 days or more may be indicated if the causative bacteria cannot be identified, the patient is slow to clinically improve, or the patient clinically worsens when changed to oral antibiotics.

Chest tube drainage

Repeat CXR one day after beginning chest drainage should be obtained to evaluate the size of the effusion. If there is no improvement with drainage, a chest CT scan may be helpful to see if the chest tube needs to be repositioned or if there is underlying necrotic lung tissue. The chest tube should be removed when it is draining less than 20 mL per day, the effusion is smaller, and the patient is clinically improving.

Long-term follow-up

Patients with complicated parapneumonic effusions or empyema should have a CRP (or ESR) obtained prior to changing to oral antibiotics and prior to stopping antibiotics so that a baseline is established for comparison if the patient experiences a clinical deterioration. No additional laboratory follow-up is needed for patients with a clinically uncomplicated recovery. A follow-up CXR may be obtained in 3-6 months to assure complete recovery. Additional CXRs and chest CT scans are not indicated. Residual cystic changes or other complications can be monitored with a CXR if necessary.

What are the adverse effects associated with each treatment option?

Observation is reasonable if the effusion is small. Progression with increasing effusion and respiratory distress occurs occasionally.

Thoracentesis alone will clarify the diagnosis (i.e., is bacteria present in the fluid?), however, if the effusion is increasing in size, repeated thoracentesis will be needed to avoid respiratory compromise. If repeated thoracentesis is expected, then a chest tube should be inserted.

Chest tube drainage is generally the treatment of choice, however, chest tubes produce pain. Large tubes should be avoided.

Fibrinolytic therapy aids in draining the pleural fluid and is generally recommended whenever a chest tube is used for treating parapneumonic effusions or empyemas. Adverse effects include minor pain, occasional fever, and failure of the effusion to resolve. Systemic absorption is not a problem and significant bleeding is rarely seen. Care must be taken to ensure that all chest tube ports are within the pleural space as fibrinolytics can cause skin necrosis if instilled into the dermis.

VATS can be complicated by bronchopleural fistula due to injury to the lung during debridement. Only experienced surgeons should perform this procedure and patients should be referred if local expertise is not available.

Open thoracotomy, while performed by general surgeons, is frequently complicated by pain and prolonged recovery. Occasionally long term disability is seen if a bronchopleural fistula develops or there is a chest wall complication (muscle or nerve injury). Open thoracotomy is not recommended and the patient should be referred for VATS if not available locally.

What are the possible outcomes of parapneumonic effusion/empyema?

Parapneumonic effusions and empyema are rarely life threatening if treated early. Delaying management, particularly for patients with respiratory distress, should never occur. With proper management, most effusions will resolve within 2-5 days and even complicated effusions will resolve with time. While patients occasionally have prolonged disease with fever and respiratory symptoms resolving gradually over several weeks, this is rare.

In general, thoracentesis for diagnosis and chest tube drainage drainage with fibrinolytic therapy is the treatment of choice. Performing VATS early in the disease has no added value and rarely is necessary. However, when therapy is delayed the effusion can organize and surgical intervention may be needed.

What causes this disease and how frequent is it?

Parapneumonic effusion and empyema have had changing incidence over the last several decades due to changing bacteria responsible for community-acquired pneumonia. Two additional changes since the mid-1990s have been the introduction of pneumococcal conjugate vaccine and the increasing frequency of methicillin resistant Staphylococcus aureus (MRSA) bacteria.

Parapneumonic effusion and empyema occur in all age groups. While younger children have been reported to have higher rates, the median age is 4-6 years. Since this is a complication of bacterial pneumonia, the seasonal frequency reflects that of community-acquired pneumonia. In most studies S. pneumoniae is the most frequent pathogen, with parapneumonic effusions occurring in up to 60% of hospitalized patients.

Following the introduction of pneumococcal conjugate vaccine, the frequency of community-acquired pneumonia decreased, although pneumonia attributed to serotypes not included in the original vaccine increased. Now with the expanded vaccine, the frequency of pneumonia caused by Streptococcus once again seems to be decreasing.

Haemophilus influenzae infection was a common cause of parapneumonic effusion and empyema prior to the widespread use of H. influenzae B vaccines in the 1980's.

Other organisms reported to cause parapneumonic effusions and empyema in children include: Klebsiella spp, Pseudomonas spp, anaerobic bacterial, Mycoplasma, and some viruses (especially adenovirus).

The estimated population incidence of parapneumonic effusion and empyema requiring hospitalization is roughly estimated at 1-5 per 100,000 children <19 years old. There are no associated genetic risk factors, although infection with varicella virus during the month prior to hospitalization is associated with empyema.

How do these pathogens/genes/exposures cause the disease?

S.pneumoniae is the most frequent cause of parapneumonic effusion, most likely related to the bacteria's ability to produce streptokinase and cause leakage of fluid from the lung. The recent increase in MRSA as a pathogen represents the increasing virulence and prevalence of this organism.

What complications might you expect from the disease or treatment of the disease?

Acute complications requiring immediate therapy include:

  • Respiratory distress due to compression of the adjoining lung by a large amount of fluid. These patients need drainage as soon as possible in order to avoid potential respiratory arrest or need for assisted ventilation.

  • Hypoxemia, often manifested by respiratory distress.

  • Bacteremia and sepsis.

  • Hemolytic uremic syndrome.

Other complications which may be delayed or persist over a longer time, but generally do not require surgical intervention in children include:

  • Pneumatocele

  • Bronchopleural fistula (rare)

  • Pleural thickening

  • Reduced lung function

  • Anemia, due to chronic inflammation.

How can parapneumonic effusion/empyema be prevented?

While there are no preventative therapies for parapneumonic effusion or empyema, infection with S. pneumoniae can be dramatically reduced with the use of the polyvalent vaccine. Newer versions of this vaccine, covering greater numbers of serotypes that produce parapneumonic effusions, have been accompanied by an overall decreasing rate of this diagnosis over the last few years.

What is the evidence?

Hendaus, MA, Janahi, IA. "Parapneumonic effusion in children: An up-to-date review". Clin Pediatr. vol. 55. 2016. pp. 10-8.

(This is an excellent review of the pediatric literature and provides clear and concise recommendations.)

Islam, S, Calkins, CM, Goldin, AB. "The diagnosis and management of empyema in children: a comprehensive review from the APSA Outcomes and Clinical Trials Committee". J Pediatr Surg. vol. 47. 2012. pp. 2101-10.

(Guidelines from the American Pediatric Surgical Association for diagnosis and management of parapneumonic effusions and empyema.)

Rahman, NM, Maskell, NA, Davies, CWH, Hedley, EL, Nunn, AJ, Gleeson, FV, Davies, RJO. "The relationship between chest tube size and clinical outcome in pleural infection". Chest. vol. 137. 2010. pp. 536-43.

(This large study shows a clear association with improved recovery if smaller chest tubes are used. While it was conducted in adults, the findings apply equally to children.)

Sonnappa, S, Cohen, G, Owens, CM, van Doorn, C, Cairns, J, Stanojevic, S, Elliott, MJ, Jaffe, A. "Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema". Am J Respir Crit Care Med. vol. 174. 2006. pp. 221-7.

(Randomized trial of chest tube drainage with urokinase compared with VATS. Shows no clinical advantage of either technique, particularly if used early in the course of illness.)

St. Peter, S, Tao, K, Harrison, C. "Thoracoscopic decortications vs. tube thoracostomy with fibrinolysis in empyema in children: a prospective, randomized trial". J Pediatr Surg. vol. 44. 2009. pp. 106-11.

(Randomized trial of chest tube drainage with tPA compared with VATS. Shows no clinical advantage of VATS, although costs were significantly higher.)

Hanson, SJ, Havens, PL, Simpson, PM, Nugent, ML, Wells, RG. "Intrapleural alteplase decreases parapneumonic effusion volume in children more than saline irrigation". Pediatr Pulmonol. vol. 50. 2015. pp. 1328-35.

(Randomized trial of early (day 1) vs. late (day 2) treatment with tPA. Earlier treatment had better outcomes.)

Gasior, AC, Knott, EM, Sharp, SW, Ostlie, DJ, Holcomb, GW, St. Peter, SD. "Experience with an evidence-based protocol using fibrinolysis as the first line treatment for empyema in children". J Pediatr Surg. vol. 48. 2013. pp. 1312-5.

(Report of 102 pediatric patients treated with tPA and chest tube drainage. 15.7% required subsequent VATS.)

Shah, SS, Hall, M, Newland, JG. "Comparative effectiveness of pleural drainage procedures for the treatment of complicated pneumonia in children". J Hosp Med. vol. 6. 2011. pp. 256-63.

(Large epidemiologic review of pleural drainage for complicated pneumonia suggesting there is little advantage, and no cost benefit, of VATS compared to other medical approaches.)

Schultz, KD, Fan, LL, Pinsky, J, Ochoa, L, O'Brian Smith, E, Kaplan, SL, Brandt, ML. "The changing face of pleural empyemas in children: epidemiology and management". Pediatrics. vol. 113. 2004. pp. 1735-40.

(Discusses both epidemiology and management. Although their increased incidence of MRSA caused empyema has not been reported elsewhere, due to the increasing frequency of MRSA in the community, the experience of these authors is important.)

Slinger, R, Hyde, L, Moldovan, I, Chan, F, Pernica, JM. "Direct Streptococcus pneumoniae real-time PCR serotyping from pediatric parapneumonic effusions". BMC Pediatrics. vol. 14. 2014. pp. 189-94.

(Serotyping of parapneumonic effusions in 35 children demonstrated 54% positive for serotype 3 and 26% positive for serotype 19A.)

Byington, CL, Spencer, LY, Johnson, TS. "An epidemiological investigation of a sustained high rate of pediatric parapneumoninc empyema: risk factors and microbiological associations". Clin Infect Dis. vol. 34. 2002. pp. 434-40.

(This is an excellent study reporting the epidemiology and increasing incidence of empyema in Utah during the 1990's.)

What are ongoing controversies regarding etiology, diagnosis, treatment?

Choice of antibiotics and duration of treatment remain highly variable and no ideal protocol has been developed. While treatment of less than 2 weeks is adequate for the majority of patients, longer treatment is required in some cases. Various monitoring tools, such as ESR and CRP have not been adequately studied to know if they can predict the point at which antibiotics can be stopped.

While surgical management of complicated effusions was controversial, recent controlled and comparative effectiveness studies have all shown superior outcomes with the use of chest tube drainage combined with fibrinolytic therapy. A small percentage of patients fail this approach and VATS may be secondarily necessary. Additionally, recent studies indicate that avoiding VATS will actually reduce the length of hospital stay and possibly the length of antibiotic therapy, although this may be related to a bias in choice of initial therapy during these studies. Shah et al. also reported that VATS resulted in higher costs based on a large epidemiologic study.

The best approach to fibrinolytic therapy is mildly controversial, although urokinase is not available in the US and tPA is the therapy of choice. Some evidence suggests tPA is at least as effective and may have fewer side effects than urokinase. Additional therapies, including the combination of intrapleural recombinant DNase with fibrinolytics, are being investigated.

Bradley, JS, Byington, CL, Shah, SS, Alverson, B. "Executive Summary: The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the pediatric infections disease society and the infections diseases society of America". Clinical Infectious Diseases. vol. 53. 2011. pp. 617-30.

(This executive summary includes antibiotic recommendations and treatment guidelines for community-acquired pneumonia, parapneumonic effusion, and empyema.)
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