Management and prognosis of parapneumonic effusion and empyema in children Authors Ibrahim A Janahi, MD Khoulood Fakhoury, MD Section Editors

Gregory Redding, MD Morven S Edwards, MD Deputy Editor Alison G Hoppin, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Dec 2012. | This topic last updated: nov 14, 2012. INTRODUCTION Parapneumonic effusion is defined as pleural effusion associated with lung infection (ie, pneumonia). These effusions result from the spread of inflammation and infection to the pleura. Much less commonly, infections in other adjacent areas, such as the retropharyngeal, vertebral, abdominal, and retroperitoneal spaces may spread to the pleura resulting in the development of effusion. Early in the course of parapneumonic effusion, the pleura becomes inflamed; subsequent leakage of proteins, fluid, and leukocytes into the pleural space forms the effusion. At the time of formation, the pleural effusion is usually sterile with a low leukocyte count. With time, bacteria invade the fluid, resulting in empyema, which is defined as the presence of grossly purulent fluid in the pleural cavity. The development of pleural empyema is determined by a balance between host resistance, bacterial virulence, and timing of presentation for medical treatment [1]. The management of parapneumonic effusion and empyema in children will be reviewed here. The epidemiology, etiology, pathophysiology, clinical presentation, and evaluation of parapneumonic effusion and empyema in children are discussed separately. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children".) The evaluation and management of parapneumonic effusion in adults also are discussed separately. (See "Diagnostic evaluation of a pleural effusion in adults: Initial testing" and "Imaging of pleural effusions in adults" and"Parapneumonic effusion and empyema in adults".) OVERVIEW Despite the improvement in the technology available for diagnosing and treating empyema, the management of empyema in children remains controversial. With limited evidence from controlled studies with random allocation, there is no consensus on the role of medical versus surgical management [2,3]. Data cannot be extrapolated from studies in adults, in whom the morbidity and mortality are increased, often related to underlying lung disorders. Goals The goals of therapy include sterilization of the pleural cavity, resolution of pleural fluid, and reexpansion of the lung [3]. The initial management depends upon the stage of the disease at the time of presentation and the clinical status of the child. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Pathophysiology'.) Hospitalization The decision to hospitalize a given patient with pneumonia depends upon the patient's clinical status, age, and associated conditions. As a general rule, patients with lobar pneumonia who are under six months of age, those with evidence of bacteremia or respiratory compromise, and those who have failed outpatient management, should be admitted to a hospital for intravenous antibiotic therapy and close observation [4]. The majority of patients with complicated pneumonia with parapneumonic effusions will require hospitalization for further management. Occasionally patients with small parapneumonic effusions who are clinically well and are responding to outpatient therapy can be managed without hospitalization, providing that they are followed closely to monitor progress. Transfer to a facility with specialists in pediatric pulmonology, pediatric surgery, and pediatric anesthesia should be considered early in the care of children who may require video-assisted thoracoscopy (VATS) or fibrinolytic therapy [2]. Clinical course Parapneumonic effusion and empyema is a disease process that evolves over time and different management strategies are appropriate at different stages [3]. In cases with mild symptoms of short duration, initial therapy may include broad-spectrum oral antibiotics and close observation with chest radiographs on an outpatient basis. In cases with increased severity, hospitalization and intravenous antibiotics are usually indicated. Children who have effusions that are enlarging and/or compromising respiratory function require drainage of pleural effusion [2,5]. This can be achieved through thoracentesis or chest drain placement. Drainage of loculated or organized pleural effusion usually requires more aggressive therapy. This may include fibrinolytic therapy, or debridement of the pleural space via VATS, or thoracotomy [6,7]. Management options may be limited by the availability of appropriately trained pediatric thoracic surgeons [2]. Early involvement of a surgeon in the decision-making process helps to ensure that timely surgical intervention can occur if it is indicated [2]. The timing for surgical intervention is controversial. Some studies indicate that surgical intervention is seldom needed [8-11], whereas others suggest clear benefits from early pleural debridement or decortication in selected cases [12-14]. Information from these retrospective case series, usually from single institutions, is biased by local practice, and if encompassing long periods of time, influenced by changes in prevalent organisms and evolution of imaging and surgical techniques [2,3,15,16]. Surgical versus medical treatment Whether surgery should be the initial treatment of choice or reserved for failed medical management is not definitively known [2]. A systematic review of 67 studies published between 1981 and 2004 regarding the treatment of empyema in children aggregated the data according to the mode of therapy (nonoperative versus primary operative) [17]. The results are summarized in the table (table 1). Treatment with antibiotics and tube thoracostomy was successful in 76 percent of patients. However, avoidance of surgery appears to occur at the

expense of increased duration of chest tube (10.6 versus 4.4 days), hospital stay (20 versus 10.8 days), and antibiotic therapy (21.3 versus 12.8 days) and mortality (3.3 versus 0 percent). The systematic review is subject to the same limitations as the included studies (eg, local bias, evolution of imaging and surgical techniques over time) as well as the lack of information regarding the method of diagnosis and stage of parapneumonic effusion at the time of treatment. Nonetheless, the conclusions are consistent with clinical experience. Two randomized controlled trials addressing treatment of parapneumonic effusion in children were published after the systematic review [18,19]:

In the first, surgical therapy (VATS) was compared to conventional medical therapy with antibiotics and chest tube drainage (with or without fibrinolysis in 18 children with large parapneumonic effusion) [18]. As in the systematic review, increased hospital stay and duration of chest tube drainage were noted in the group treated with conventional therapy. The second compared VATS to medical therapy with fibrinolysis and found no difference in clinical outcome [19]. In this trial, 60 children (<16 years) with radiographic evidence of empyema and indications for drainage were randomly assigned to treatment with primary VATS or percutaneous chest tube drainage with intrapleural urokinase. The primary outcome measure was length of hospital stay after intervention and there was no difference between groups (95% CI -2 to 1 day). The median hospital stay after intervention was 6 days for both groups, with a range of 3 to 16 days for those treated with VATS and 4 to 25 days for those with fibrinolysis.

In the aggregate, these studies indicate that the outcome in children who do not have an underlying lung disorder is almost always excellent. However, they also suggest that early surgical intervention with VATS decreases the duration of hospital stay and chest tube drainage. The finding that clinical outcomes are comparable with VATS and fibrinolytic therapy suggests that fibrinolytic therapy is an acceptable alternative to VATS, particularly in institutions where a pediatric surgeon is not readily available. Algorithmic approaches Algorithmic approaches to management of parapneumonic effusion and empyema have been developed by the British Thoracic Society (BTS), the American Pediatric Surgical Association (APSA), and the Pediatric Infectious Diseases Society (PIDS) [2,5,20]. These approaches are similar, treating symptomatic moderate to large simple effusions with drainage and antibiotics, and complicated effusions with either early surgical drainage (VATS or mini-thoracotomy) or fibrinolysis and chest tube drainage. Additional recommendations from the BTS guidelines are shown in the table (table 2). These approaches are described in the algorithm (algorithm 1). At Texas Children's Hospital, the following variation on the algorithm is used:

For patients who present with large effusions requiring drainage, ultrasonography is performed.

If the fluid is free flowing, the patient undergoes thoracentesis with drainage of as much fluid as possible (but no more than 10 to
20 mL/kg). The patient is treated with empiric antibiotics and observed, without drainage, for 48 hours. If fever and fluid collection persist, with evidence of loculation on ultrasonography, then VATS is performed with concurrent insertion of a chest tube (typically a large bore tube to avoid possible blockage by the thick, purulent fluid).

Patients who present with a loculated effusion, documented by ultrasonography, undergo VATS for diagnosis and treatment.
Children with a small effusion (eg, <10 mm on lateral decubitus radiograph or opacifying less than one-fourth of the hemithorax [5]) are treated with broad-spectrum oral antibiotics and close observation with chest radiographs on an outpatient basis (algorithm 2).

This approach has resulted in no major complications, more rapid clinical improvement, and earlier discharge from the hospital than previous management strategies [21]. An alternative approach has been described in which children admitted with a moderate pleural effusion were treated with a trial of empirically selected antibiotics for 24 to 72 hour period before thoracentesis or other drainage procedure; patients who did not respond clinically underwent drainage procedure (chest tube, VATS or thoracotomy) [22]. Antibiotics alone were successful in about half of these children. There are few prospective, randomized trials comparing the various treatment options. Additional trials will be necessary before standards based on high-quality evidence for the treatment of empyema in children can be developed [23]. SUPPORTIVE CARE Supportive care for children with parapneumonic effusion may include antipyretics, analgesia, and early mobilization [2]. Children with empyema are invariably febrile; antipyretics should be used for comfort, with the caveat that resolution of fever is one of the indicators of clinical progress [2]. Analgesia should be administered for pleuritic pain, which may interfere with breathing and affect the child's willingness to cough. Adequate analgesia may prevent secondary scoliosis and will help with early mobilization [2]. Sedatives and agents that may cause central respiratory depression should be used only if needed, and when needed should be used cautiously with close monitoring of respiratory status. Children with parapneumonic effusions may become dehydrated as a result of poor intake and increased losses from fever and tachypnea. Intravenous fluids should be administered if the child refuses oral intake or is unable to drink. However, close attention must be paid to fluid balance since these children also are at risk to develop the SIADH. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)".)

Bronchodilator therapy has no role in treatment of children with parapneumonic effusions and may potentially worsen their V/Q mismatch, exacerbating hypoxemia. Chest physiotherapy is not recommended [2]. ANTIBIOTIC THERAPY Choice of agent All children with parapneumonic effusion should be treated with antibiotic therapy. In children with a small effusion (eg, <10 mm on lateral decubitus radiograph or opacifying less than one-fourth of the hemithorax [5]), this may include broad-spectrum oral antibiotics and close observation with chest radiographs on an outpatient basis (algorithm 2) [5]. Children with moderate to large effusions or empyema should be hospitalized and treated with intravenous antibiotics in doses adequate to ensure pleural penetration [2]. If thoracocentesis or drainage of pleural fluid is indicated, pleural fluid should be sent for culture and analysis prior to beginning antibiotics. (See 'Thoracentesis' below.) The choice of antibiotic(s) should be based upon the suspected causative organism. Empiric coverage should be geared toward the most common organisms causing community acquired or nosocomial pneumonia in the patient's age group in his/her community or hospital, respectively. (See "Inpatient treatment of pneumonia in children", section on 'Empiric therapy'.) Antibiotic therapy should ultimately be modified based upon the sensitivity results if and when they are available. For nonlife-threatening infection, intravenous ceftriaxone or cefotaxime with addition of clindamycin or vancomycin (for suspected communityacquired methicillin-resistant S. aureus [CA-MRSA]) is suggested for empiric therapy, pending the results of cultures. Ampicillin or penicillin G might also be considered as first-line drugs in fully immunized children in areas where local penicillin resistance in invasive strains of pneumococcus is uncommon [5]. The choice of first line antibiotics is mainly determined by the most common bacteriological etiology causing community acquired pneumonia in a given area. For life-threatening infection, vancomycin plus cefotaxime is selected because of the rising prevalence of drug resistant organisms. Antibiotic coverage for children with nosocomial parapneumonic effusion should include coverage of gram-negative organisms. Antibiotic coverage for children in whom aspiration is suspected (ie, those with neuromuscular disease or neurologic impairment) should include coverage of anaerobes. Community-acquired Staphylococcus aureus Methicillin sensitive S. aureus should be treated with beta-lactam antibiotics. However, the number of reported cases of parapneumonic effusions caused by CA-MRSA is increasing [24-28]. Vancomycin remains the drug of choice to treat MRSA. However, other antibacterial agents, such as clindamycin, can be used if the organism is sensitive to them. If the child appears ill and S. aureus is suspected, it is reasonable to initiate therapy with vancomycin pending culture and sensitivity results. The use of newer antiMRSA antibiotics should be reserved for the most resistant cases. (See "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects" and "Treatment of invasive methicillin-resistant Staphylococcus aureus infection in children", section on 'Pneumonia'.) Duration It is the common practice in our institutions, as well as in many centers in the United Kingdom, to continue intravenous antibiotic therapy as long as the child is febrile [2]. The duration of intravenous antibiotic therapy after resolution of fever and toxicity is controversial. There are no data from randomized controlled trials on appropriate length of therapy or whether the duration of therapy should vary depending upon the causative organism [2]. Some clinicians continue intravenous antibiotics for 48 hours after the patient becomes afebrile or after the chest drain is removed [2]. Others continue intravenous therapy for up to two weeks. In our experience, continuation of intravenous antibiotics for five days after resolution of fever is probably adequate. All patients should continue on oral therapy for two to three weeks thereafter. THORACENTESIS If feasible, patients presenting with a moderate or large parapneumonic effusion should undergo a trial of fluid aspiration before starting antibiotic therapy. Cultures and gram stain performed on the aspirated pleural fluid help to direct antibiotic therapy. Additional techniques may be used to increase the yield of microbiologic diagnosis in children who have received antibiotics. These include: direct and enrichment culture for aerobic and anaerobic organisms, pneumococcal antigen detection (latex agglutination) and specific or broad range polymerase chain reaction (PCR). (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Microbial analysis'.) Other characteristics of the pleural fluid, such as pH, glucose, and LDH have been used to predict a need for drainage procedures. The Pediatric Infectious Disease Society (PIDS) does not recommend assessing these characteristics because the results rarely change management of a patient with community-acquired pneumonia [5]. However, these biochemical studies may be useful if the diagnosis of empyema is in doubt or in the setting of an underlying condition that might be responsible for the effusion, such as collagen-vascular disease. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Other studies'.) During thoracentesis, as much fluid as possible should be slowly removed. The aspiration should be limited to 10 to 20 mL/kg because rapid removal of large amounts of pleural fluid has been reported to cause pulmonary edema [29,30] and worsening of respiratory status. If reaccumulation of fluid occurs after the initial thoracentesis, chest tube insertion is warranted. Repeated thoracentesis is not recommended [2]. CHEST TUBES Large amounts of pleural fluid can be slowly drained using chest tubes with underwater seal systems. Chest tube placement should be considered for patients with:

Large amounts of free flowing pleural fluid Compromised pulmonary function (eg, severe hypoxemia, hypercapnia) Evidence of fibrinopurulent effusions (eg, pH <7.0, glucose <40 mg/dL [2.22 mmol/L], LDH >1000 IU [16.67 kat/L], positive gram stain, frank pus) Failure to respond to 48 to 72 hours of antibiotic therapy

The chest tube should be left in place until fluid drainage becomes minimal (less than 10 to 15 mL per 24 hours).

In a systematic review of 67 studies regarding treatment of empyema in children published between 1981 and 2004, data were aggregated according to mode of therapy (nonoperative versus primary operative) [17]. Among children treated with antibiotics and chest tube drainage, 23.6 percent eventually required operative intervention. The aggregate mortality rate was 3.3 percent. The average duration of chest tube, antibiotic therapy, and hospital stay was 10.6 days, 21.3 days, and 20 days, respectively. Size of tube There is controversy regarding the optimum size of chest tube. Good data to recommend one size of chest tube over another are lacking. The British Thoracic Society (BTS) guidelines suggest that in the absence of evidence that large bore tubes confer any advantage over smaller tubes, smaller tubes (including pigtail catheters) should be used whenever possible to minimize patient discomfort [2]. Practices vary among institutions. The size and type of chest tubes generally depend upon the type of fluid in the pleural cavity. Free flowing fluid can be adequately drained by flexible small-bore drains (ie, pigtails), whereas thick pus may require large bore drains with holes of increased diameter. Even large bore drains are usually inadequate once loculations develop because the holes become obstructed by the fibrinous material. In such cases, more aggressive therapy is required (eg, VATS or fibrinolytic therapy, which is discussed below). Many pediatric surgeons prefer to use large tubes after the VATS procedure to provide adequate drainage and less chance of tube blockage during the recovery period. When combined with fibrinolytic therapy, the use of small chest tubes may provide some advantages over large tubes. In post-hoc analysis of one of the studies evaluating fibrinolytic therapy in children, the use of a smaller drain was associated with a shorter hospital stay [31]. In addition, one retrospective case series noted that the use of pigtail catheters and fibrinolytic therapy for loculated effusion was superior to surgical stiff drains and comparable to thoracotomy in terms of duration of fever, parental report of clinical improvement, and length of hospital stay [32]. Placement Ultrasonography can be used to guide chest tube placement. The procedure can be performed with ultrasonography or the skin can be marked to indicate the optimum site for drain insertion [33-36]. If the skin is marked, chest tube insertion must be performed with the child in the same position as he or she was when the skin was marked [2]. Care must be taken to ensure that the child will be able to lie down without discomfort once the drain is in place. Adequate analgesia and/or sedation with appropriate monitoring should be employed [2]. Chest radiographs should be obtained after insertion to ensure that there is no pneumothorax and to verify position [2]. However, an effectively functioning tube should not be repositioned solely on the basis of a radiograph [37]. Management All chest tubes should be connected to a unidirectional drainage system, which must be kept below the level of the patient's chest at all times [2]. The underwater seal system is frequently used. This system is comprised of a tube placed under water at a depth of approximately 1 to 2 cm, and a side vent, which either permits escape of air or is connected to a suction pump [2]. The system should be assessed daily for the amount of drainage, the presence of bubbling, and the presence of swing in the fluid with respiration (which confirms tube patency and appropriate position in the pleural cavity). Reexpansion pulmonary edema has been reported after drainage of large effusions in adults [29] and in children with malignant lymphoma [30], but is otherwise rare in children. Nonetheless, to prevent this complication, the drain should be clamped for one hour after drainage of the initial 10 mL/kg of pleural fluid. In large children and adolescents, although there is no high-quality evidence on which to base this recommendation, it is suggested that no more than 1500 mL of fluid be drained at one time, or that drainage should be slowed to 500 mL/hour [2,38]. Clamped drains must be immediately unclamped if there are any signs of clinical deterioration (eg, breathlessness, chest pain). This is because tension pneumothorax may develop in patients with air leak (which may be subclinical) [2]. Air in the pleural space is indicated by air bubbles in the water. Continuous bubbling suggests a continued visceral pleural air leak or, in patients on suction, that the drain is partly out of the thorax and one of the tube's drainage holes is open to the atmosphere [2]. Because of the risk of developing a tension pneumothorax, a bubbling chest drain should never be clamped [2,38]. Troubleshooting Sudden cessation of fluid drainage may indicate kinking or blockage of the tube by thick exudative fluid, pus, or debris [2]. Small soft drains are prone to kinking at the exit site, particularly in young mobile children. Obstruction of the tube by pus may be relieved by carefully flushing with normal saline (10 mL should be adequate in a small bore drain) [2]. A drain that cannot be unblocked should be removed and replaced if significant pleural fluid remains [2]. In addition, drainage may cease if the fluid becomes loculated or the suction holes of the tube are outside the pleural space [6]. Removal The chest tube should be removed once there is clinical resolution and minimal chest tube drainage (less than 10 to 15 mL per 24 hours) [2,5,6]. It is not necessary to wait for complete resolution of drainage since the tube itself may act as a stimulus for pleural exudative reaction [8,39] and increases the risk of secondary infection. There is no need to clamp the chest tube before its removal [2]. Factors to consider in clinical resolution are discussed below. (See 'Monitoring response to therapy' below.) They include [2]:

The child's temperature and well-being Chest radiographic and ultrasonographic appearance Fall in white blood cell count and acute phase reactants

During chest tube removal, analgesia should be used, and sedation may be necessary in young children [2]. Local anesthetic cream applied to the adjacent skin three hours before chest tube removal may be as effective as intravenous morphine for pain control [40]. The chest tube should be removed with a brisk firm movement while the child performs the Valsalva maneuver or during expiration [2]. A chest radiograph should be taken shortly after chest tube removal to check for pneumothorax. Complications Complications of chest tubes include bleeding, failure to drain adequately, wound infection at the exit site, development of bronchopleural fistula, persistent atelectasis, and laceration of the lung [36,41].

FIBRINOLYTIC THERAPY The use of fibrinolytic drugs to lyse the fibrinous strands in loculated parapneumonic effusions has been described in adults and children. These drugs include urokinase, streptokinase, andalteplase (tissue plasminogen activator, tPA). The British Thoracic Society (BTS) guidelines and a position paper by the American Pediatric Surgical Association suggest fibrinolytic therapy as a component of the medical option for patients in whom the pleural fluid is thick or loculated [2,20]. We agree that fibrinolytic therapy is a reasonable alternative to VATS, and suggest it as an alternative for children with loculated parapneumonic effusion who are hospitalized at institutions lacking a pediatric surgeon who is trained in VATS. (See 'Algorithmic approaches' above.) Efficacy The efficacy of fibrinolytic therapy in complicated parapneumonic effusion and empyema has been studied in adults. A metaanalysis of five trials comparing intrapleural fibrinolytic therapy versus placebo revealed a reduction in death and need for surgery among patients who received fibrinolytic therapy that was not statistically significant (pooled risk ratio 0.55, 95% CI 0.28-1.07) [42]. (See "Parapneumonic effusion and empyema in adults", section on 'Empyema'.) The use of fibrinolytic therapy in the management of parapneumonic effusion in children also has been described, primarily in case series [4354]. These reports suggest that children treated with fibrinolytic therapy have increased pleural drainage and often have successful outcomes without surgery. Controlled trials of fibrinolytic therapy versus saline in children have had inconsistent results [31,55], which may be related to differences in disease stage [52] or in the fibrinolytic agent, as illustrated below:

In one trial, 60 children with parapneumonic effusion were randomly assigned to receive either intrapleural urokinase or saline, but otherwise managed at the discretion of the managing pediatrician [31]. Children in the urokinase group had a shorter hospital stay (7.4 versus 9.5 days after entry into the study) with no major adverse effects. However, by chance, children in the placebo group had longer duration of illness before entry into the study and marginally lower oxygen saturation. In the second trial, 40 children with advanced stage empyema were randomly assigned to receive intrapleural streptokinase or normal saline in addition to intercostal drainage [55]. There was no difference in clinical or ultrasonographic outcome between the groups.

Another randomized study, comparing fibrinolytic therapy with urokinase to VATS, found no difference in length of hospital stay after intervention between groups [56]. This study is discussed in greater detail above. (See 'Surgical versus medical treatment' above.) Choice of agent Evidence from controlled studies that any one of the fibrinolytic agents is more effective than the others is lacking. Only urokinase has been studied in a controlled fashion in children, and thus is recommended by the BTS [2]. However, urokinase is no longer available in North America. The one study comparing urokinase and streptokinase in adults found them to be equally effective [57]. However, in the BTS/MRC multicenter intrapleural streptokinase trial, streptokinase had no beneficial effect in adult empyema [58]. In addition, the riskto-benefit ratio for streptokinase is higher than for the other fibrinolytics [2]. In one retrospective case series, thoracostomy tube drainage was increased with alteplase compared to urokinase [48]. The choice of agent depends upon availability, with urokinase being preferred if it is available, followed by alteplase (recombinant tissue plasminogen activator) and streptokinase. (See "Parapneumonic effusion and empyema in adults", section on 'Empyema'.) Technique and dose Administration of fibrinolytic therapy, which is performed by instilling the drug through the chest tube, or irrigation at the time of thoracoscopy, may cause discomfort. Adequate sedation and or analgesia should be provided. A number of different doses of these agents have been used in various studies. The following technique and dose for urokinase is recommended in the BTS guidelines [2] and is also included in the PIDS guidelines [5]:

Urokinase 40,000 units in 40 mL 0.9 percent saline for children one year and older, and 10,000 units in 10 mL 0.9 percent saline for children younger than 1 year. This dose should be administered twice daily (with a four-hour dwell time) for three days; additional doses can be administered if the response is incomplete after six doses. Intrapleural bupivacaine (0.5 to 1.0 mL/kg of a 0.25 percent solution) can be administered with urokinase if the child finds it uncomfortable [2].

Two approaches for treatment with alteplase were described in the PIDS guidelines, based on clinical studies in which these regimens were safe and effective in children older than three months [5]:

Alteplase 4 mg in 40 mL 0.9 percent saline, intrapleural. The first dose is given at time of chest tube placement with 1 hour dwell time, repeat every 24 hours for 3 days (total of 3 doses) [59]. Alteplase 0.1 mg/kg (maximum: 3 mg) in 10-30 mL 0.9 percent saline, intrapleural. The first dose is given after pigtail catheter (or chest tube) placement, with a 45 minute to 1 hour dwell time, and repeated every 8 hours for 3 days (total of 9 doses) [60].

Contraindications Fibrinolytic therapy should not be performed in patients who have bronchopleural fistula or chest tubes that are bubbling, suggestive of an air leak, since clamping of the chest tube in such a patient could result in tension pneumothorax. In addition, chest tubes that are clamped must be immediately unclamped if the child has any signs of clinical deterioration (eg, breathlessness, chest pain). Adverse effects Adverse effects of fibrinolytic therapy include fever, discomfort, bleeding, and anaphylaxis [31,48,61]. In the pediatric trials using urokinase and/or alteplase described above, minor side effects included discomfort during intrapleural injection and transient blood staining of the drainage fluid [31,48]. Rare immediate hypersensitivity reactions to urokinase have been reported in adults [62]. Intrapleural

administration of streptokinase generates a systemic antibody response similar to that when the drug is administered intravenously [63]; fever has been reported and other immunologic responses are possible. SURGICAL THERAPY Surgical therapy is usually required in late presenting cases (ie, those with symptoms for more than one week), particularly those with multiple loculations, and in those with concomitant medical conditions [64,65]. However, accurate prediction of the need for surgical intervention is not possible [2]. Early involvement of a surgeon in the decision-making process helps to ensure that timely surgical intervention can occur if it is indicated [2]. Whether surgery should be the initial treatment of choice or reserved for failed medical management is not definitively known [2]. (See 'Surgical versus medical treatment' above.) Indications Situations in which surgical intervention is usually necessary include [2]:

Lack of clinical and radiologic response to initial medical management (eg, antibiotics, chest tube drainage, fibrinolytic therapy) Persistent sepsis in association with persistent pleural collection, despite chest tube drainage and antibiotics Complex empyema with significant lung pathology (eg, delayed presentation with a significant peel and trapped lung) Bronchopleural fistula with pyopneumothorax

Procedures Three surgical procedures have been described in the management of children with parapneumonic effusion: video-assisted thoracoscopy (VATS), minithoracotomy, and decortication [2]. A chest drain is left in place after each of these procedures for continued drainage of fluid or pus. Provided that there is an appropriately trained pediatric surgeon, VATS is the preferred procedure because it is less invasive than open thoracotomy. Video-assisted thoracoscopy (VATS) Video-assisted thoracoscopy (VATS) can be used to remove the thick fibrinous septations that prevent adequate drainage of pleural fluid via thoracentesis or chest tube. VATS permits debridement of fibrinous pyogenic material, breakdown of loculations [14,66,67], and drainage of pus from the pleural cavity under direct vision [2,68-70]. There are no randomized controlled trials to show that VATS is more effective and/or safer than the existing operative techniques [2]. However, there appears to be an international trend toward early surgical intervention with video-assisted thoracoscopy (VATS), with some centers advocating VATS as first-line therapy for empyema [14]. At Texas Children's Hospital, VATS is used as the ultimate therapy in approximately 70 percent of children with complicated parapneumonic effusions [71]. A review of the 10-year experience (1993-2002) with VATS at that institution suggested that early (<48 hours after admission) compared with late VATS (>48 hours after admission) significantly decreased the length of hospitalization (11.5 versus 15.2 days) [21]. A similar finding was reported in a systematic review of English- and Spanish-language articles on the treatment of empyema in children published between 1987 and 2002 [23]. Although it requires general anesthesia, VATS is otherwise safe and much less invasive than open thoracotomy with decortication, which is discussed below [14,56,66,72]. VATS leaves two to three small scars [2,73]. The use of VATS depends to a large extent upon the availability of the equipment and appropriately trained pediatric thoracic surgeons [2]. However, it is commonly performed in children in many centers [14,66,74-76]. Proponents of early VATS suggest if general anesthesia is necessary for simple drain insertion, the procedure may as well be combined with VATS if an appropriately trained surgeon is available [68]. Early VATS is reported to enhance the chance of full expansion of the collapsed lung [68-70]. The failure rate increases in late presenting cases [69,72], and in patients who undergo VATS after failure of urokinase therapy [73,77,78]. One nonrandomized study compared VATS and conventional thoracotomy after failure of medical treatment (antibiotics with or without drainage) in 39 children over a two-year period [79]. Children admitted during the first year (n = 17) were treated with conventional thoracotomy; those admitted during the second (n = 22) were treated with VATS. Children in the VATS group had shorter duration of analgesia use, postoperative length of hospital stay, time to normothermia, and duration of postoperative chest drains, as well as better cosmesis. Two children in the VATS group required conversion to open thoracotomy for resection of lung parenchyma (for severe necrosis and bronchopleural fistula). Similarly, in a small randomized controlled trial comparing primary VATS and conventional thoracostomy drainage in children with large parapneumonic effusion, children in the VATS group had shorter length of hospital stay and duration of chest tube drainage [18]. Medical thoracoscopy has been used as an alternative to VATS in adults with pleural diseases including empyema; this procedure is performed by pulmonologists rather than surgeons and is usually done under light sedation. Medical thoracoscopy is not generally used in children because of lack of safety data and technical difficulties including trocar size. The use of this procedure in adults is discussed separately. (See "An overview of medical thoracoscopy".) Contraindications to VATS include inability to develop a pleural window to access the pleural cavity, the presence of thick pyogenic material, and/or fibrotic pleural rinds [2]. Minithoracotomy Minithoracotomy achieves debridement and evacuation in a manner similar to VATS [2]. However, minithoracotomy is an open procedure that leaves a small linear scar along the rib line. Decortication Decortication involves an open posterolateral thoracotomy and excision of the thick fibrous pleural rind with evacuation of pyogenic material. This is a longer and more complicated procedure than minithoracotomy and leaves a larger linear scar along the rib line [2].

Decortication is rarely necessary in children with empyema, since most, if not all, ultimately return to baseline lung function. The BTS guidelines suggest that decortication should be reserved for children with late presenting empyema and significant fibrous pleural rind, complex empyema, and chronic empyema [2,80]. MONITORING RESPONSE TO THERAPY With appropriate therapy, children with symptomatic parapneumonic effusion can be expected to improve within the first few days of treatment [6,81]. Those with empyema, particularly empyema caused by S. aureus, anaerobic, or group A streptococcus (S. pyogenes), typically have a more protracted recovery [6]. The response to therapy is characterized by gradual decrease in temperature, white blood cell count, respiratory rate, and heart rate, and improvement in air entry and sense of well being. In patients in whom a chest tube has been placed, diminished chest tube drainage usually also indicates recovery, provided the above-mentioned parameters also are improving. If the child remains febrile or tachypneic, and aeration does not improve, the chest tube may be obstructed or failing to drain because of the development of loculations [6,7,82-84]. (See 'Troubleshooting' above.) There is no indication for routine daily chest radiographs since radiographic findings lag behind clinical status [3]. Chest radiographs should be repeated as indicated by changes in clinical status or after interventions (ie, removal of suction or clamping). OUTPATIENT FOLLOW-UP Children with parapneumonic effusion or empyema should have chest radiographs (PA and lateral) one to two months after discharge from the hospital. These children should continue to be followed until they have recovered completely and their chest radiograph has returned to near normal, which usually occurs by three to six months [2,6,85-87], but may take as long as 16 months [88]. They may have residual dullness to percussion and quiet breath sounds over the affected areas related to pleural thickening [2,89-92]. Evaluation for underlying predisposing conditions, such as immunodeficiency or cystic fibrosis, should be considered in children who have a history of recurrent bacterial infections or poor growth [2,15,93]. Cystic fibrosis should particularly be considered in young children in whom S. aureus or Pseudomonas aeruginosa was the infecting organism [94]. (See "Cystic fibrosis: Clinical manifestations and diagnosis".) PROGNOSIS AND OUTCOME Despite the marked abnormalities at the time of presentation, and the variety of treatment approaches, the majority of children make a complete recovery [17,95]. In retrospective reviews, the percentage of patients who require closed chest tube drainage or other surgical procedures ranges from 62 to 80 percent [10,81,90,96,97]. There is no evidence that cases caused by antibiotic resistant organisms are associated with poorer outcomes [71], although length of stay may be increased [21]. Most children improve with antibiotic therapy and simple drainage [17]. However, early active therapy (ie, chest tube placement plus or minus fibrinolytic therapy or video-assisted thoracoscopy (VATS)) may result in shorter duration of illness and length of hospital stay [2,17]. Complications such as bronchopleural fistula and tension pneumothorax are rare, but if these complications occur, recovery is prolonged. In the systematic review comparing primary operative and nonoperative therapy described above, the mortality rate for children treated with antibiotics and chest tubes was 3.3 percent; no deaths were reported in the smaller studies of children treated with fibrinolytic therapy, VATS, or thoracotomy [17]. Mortality is higher for children younger than one to two years of age [10,90,96]. Mortality also is increased in patients with underlying disease (eg, aspiration, malnutrition), particularly if treatment is delayed. Long-term follow-up studies suggest that fewer than 10 percent of children have residual symptoms [8,88,98,99]. The rate of residual radiologic or pulmonary function abnormalities is higher, but these abnormalities are usually mild [8,98,100,101]. Patients with residual abnormalities in lung function are usually asymptomatic and have normal exercise tolerance [8,98,99]. SUMMARY AND RECOMMENDATIONS General overview

A variety of medical and surgical therapies are available to treat parapneumonic effusions. Although approaches vary, there is a growing consensus that simple effusions should be treated with drainage and antibiotics, and complicated effusions with either early surgical drainage (VATS or mini-thoracotomy) or fibrinolysis and chest tube drainage (algorithm 1). (See 'Overview' above.) Children with loculated parapneumonic effusion who may require further intervention (ie, VATS or fibrinolytic therapy) should undergo transfer to a facility with specialists in pediatric pulmonology, pediatric surgery, and pediatric anesthesia. Early involvement of the surgeon in the decision-making process is beneficial. (See 'Overview' above.)

Antibiotics

We recommend that all children with parapneumonic effusion be treated with antibiotic therapy (Grade 1A). The choice of antibiotic initially is based upon the suspected causative organism and subsequently tailored according to the results of microbiologic testing. (See "Inpatient treatment of pneumonia in children", section on 'Empiric therapy' and "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children".) We suggest that intravenous antibiotics be continued for five days after resolution of fever and oral therapy be continued for at least two weeks thereafter (Grade 2C). (See 'Antibiotic therapy' above.)

Free-flowing fluid There are a number of approaches to the management of children with parapneumonic effusion and free-flowing fluid, none of which has been proven superior to the others in controlled trials. (See 'Algorithmic approaches' above.)

We suggest that children who present with moderate or large amounts of free fluid documented by chest radiograph and ultrasonography undergo thoracentesis with drainage of as much fluid as possible (but no more than 10 to 20 mL/kg) and

observation (with antibiotic therapy) for 48 hours. (Grade 2C). Those patients who improve clinically are continued on antibiotic therapy as described above. (See 'Thoracentesis' above and 'Antibiotic therapy' above.) If the fever and fluid collection persists and repeat ultrasound shows evidence of loculation, we suggest video-assisted thoracoscopy (VATS) with concurrent insertion of a chest tube (Grade 2B). (See 'Video-assisted thoracoscopy (VATS)' above and 'Chest tubes' above.)

Loculated fluid There are a number of approaches to the management of children with parapneumonic effusion and loculated fluid, none of which has been proven superior to the others in controlled trials. (See 'Surgical versus medical treatment' above and 'Algorithmic approaches' above.)

We suggest that patients who present with loculated fluid, documented by ultrasonography, undergo primary VATS, with concurrent insertion of a chest tube for diagnosis and treatment (Grade 2B). Fibrinolytic therapy is an alternative for children hospitalized at institutions lacking a pediatric surgeon who is trained in VATS. (See 'Video-assisted thoracoscopy (VATS)' above and 'Fibrinolytic therapy' above.)

Chest tube removal

Chest tube removal is indicated once there is clinical resolution and minimal chest tube drainage. Clinical resolution is indicated by decreased temperature, white blood cell count, respiratory rate, and heart rate, and improved air entry and sense of well being. (See 'Removal' above and 'Monitoring response to therapy' above.)

Follow-up

We suggest that children who have been treated for parapneumonic effusion undergo chest radiograph one to two months after discharge from the hospital and continue to be followed until they have recovered completely and their chest radiograph has returned to near normal (Grade 2C). (See 'Outpatient follow-up' above.) We suggest that children with parapneumonic effusion who have a history of recurrent bacterial infections, poor growth, or had S. aureus or P. aeruginosa as the infecting organism undergo evaluation for cystic fibrosis and immunodeficiency (Grade 2C). (See "Cystic fibrosis: Clinical manifestations and diagnosis" and "Approach to the child with recurrent infections", section on 'Laboratory evaluation'.) Use of UpToDate is subject to the Subscription and License Agreement.

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