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: Ibrahim A Janahi, MD Nothing to disclose. Khoulood Fakhoury, MD Nothing to disclose. Gregory Redding, MD Nothing to disclose. Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer Inc. [Group B Streptococcus]. Consultant/Advisory Boards: Novartis Vaccines [Group B Streptococcus]. Alison G Hoppin, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2015. | This topic last updated: Jul 20, 2015.

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 areas adjacent to the pleura, 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”.)

DEFINITIONS

●Parapneumonic effusion is defined as pleural effusion associated with lung infection (ie, pneumonia). Early in the disease course, the effusion usually is free-flowing (also known as a “simple” effusion) and sterile.

●Loculated parapneumonic effusion refers to the presence of septations (separate compartments) within the effusion, which interfere with free flow of fluid. Loculation usually is detected by imaging (ultrasonography or computerized tomography [CT]). Loculation is caused by accumulation of proteinaceous debris in the fluid as the disease progresses.

●Empyema is defined as the presence of bacterial organisms on gram stain and/or grossly purulent fluid in the pleural cavity.

●Complicated parapneumonic effusion refers to changes in the pleural fluid due to bacterial invasion into the pleural space. Because bacteria are cleared rapidly after antibiotic therapy, cultures of fluid from complicated parapneumonic effusions are often negative. In clinical practice, the term is often used to refer to either loculated effusion or empyema, with or without complicated pneumonia (eg, necrotizing pneumonia).

OVERVIEW — Both medical and surgical interventions have a role in the management of parapneumonic effusion in children [2,3]. The goals of therapy include sterilization of the pleural cavity, resolution of pleural fluid, and reexpansion of the lung. Selection of treatment depends upon factors including the patient’s respiratory function and the size and loculation of the fluid collection, as well as the response to initial interventions. With appropriate treatment, outcomes are generally excellent.

Caution should be used when extrapolating from experience and studies of parapneumonic effusion in adults, in whom underlying lung disorders are more common and the morbidity and mortality are higher than in children.

Hospitalization — The majority of patients with pneumonia complicated by parapneumonic effusions will require hospitalization for further management. 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 thoracoscopic surgery (VATS) or fibrinolytic therapy [2].

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. As for any patient with pneumonia, additional indications for hospitalization include ages younger than six months, evidence of bacteremia or respiratory compromise, and failure of outpatient management [4]. (See “Pneumonia in children: Inpatient treatment”, section on ‘Hospitalization’.)

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 early stages, children tend to have small effusions and are in no respiratory distress; such patients usually can be managed as outpatients, with broad-spectrum oral antibiotics and close observation with chest radiographs on an outpatient basis. (See ‘Small parapneumonic effusion’ below.)

●Later in the evolution of the process, the effusion may become large and/or compromise respiratory function. Patients with these characteristics require hospitalization, intravenous (IV) antibiotics, and drainage of pleural effusion, which can be achieved with thoracentesis or chest tube placement [2,5]. (See ‘Moderate or large simple effusion (not loculated)’ below.)

●Subsequently, the effusion may become loculated or organized, and/or frankly infected (empyema). This stage usually requires more aggressive therapy, including fibrinolytic therapy, or surgical debridement of the pleural space [6,7]. Expert opinion on the optimal type and timing of drainage and surgical intervention continues to evolve, and management remains somewhat controversial [2]. (See‘Loculated effusion or empyema’ below.)

Children with pneumonia-associated pleural disease can present initially with an effusion that is in any one of these stages of evolution. Management depends on the stage of evolution of the parapneumonic process and what therapy has already been provided. In some cases, oral antibiotics may have already been initiated in the outpatient setting before the effusion became apparent.

Supportive care — Supportive care for children with parapneumonic effusion may include antipyretics, analgesia, and early ambulation [2]. Children with empyema are invariably febrile; antipyretics should be used for comfort as needed, with the caveat that their use may mask the resolution of fever, which is one of the indicators of clinical progress. Analgesia should be administered for pleuritic pain, which may interfere with breathing and affect the child’s willingness to cough. Adequate analgesia will also help with early ambulation and other measures to encourage lung expansion. However, analgesia should be tailored to the patient’s symptoms rather than regularly scheduled, to permit monitoring of clinical improvement. 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. IV 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 for developing syndrome of inappropriate antidiuretic hormone secretion (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 ventilation-perfusion (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, this may include broad-spectrum oral antibiotics and close observation on an outpatient basis [5].

Children with moderate to large effusions or empyema should be hospitalized and treated with intravenous (IV) 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 antibiotic sensitivity analysis. The culture should be performed prior to beginning antibiotics if this does not delay treatment. However, cultures can still be helpful even if the patient has been on antibiotics prior to the sampling of pleural fluid. (See ‘Thoracentesis’ below.)

The initial choice of antibiotic(s) should be empiric, informed by considerations of the most common organisms causing community-acquired or nosocomial pneumonia in the patient’s age group in his/hercommunity or hospital, respectively. Antibiotic therapy should be modified based upon the sensitivity results if and when they are available.

Community-acquired infection

●For outpatients (ie, those with a small effusion who are clinically well), empiric antibiotic regimens are the same as for all children with pediatric community-acquired pneumonia. The considerations are summarized in the table (table 1) and detailed in a separate topic review. (See “Community-acquired pneumonia in children: Outpatient treatment”.)

●For inpatients, suggested empiric therapy is IV ceftriaxone or cefotaxime, PLUS clindamycin or vancomycin if Staphylococcus aureus or anaerobes are a consideration. The choice of first-line antibiotics is mainly determined by the most common bacteriological etiology causing community-acquired pneumonia in a given area. Antibiotic selection is summarized in the table (table 2) and detailed in a separate topic review. (See “Pneumonia in children: Inpatient treatment”, section on ‘Complicated CAP’.)

For ill-appearing children, it is particularly important to include vancomycin or clindamycin in the regimen because of the increasing frequency of parapneumonic effusions caused by community-associated methicillin-resistant S. aureus (CA-MRSA) [8-12]. 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. The use of newer anti-MRSA antibiotics should be reserved for the most resistant cases. (See “Methicillin-resistant Staphylococcus aureus in children: Treatment of invasive infections”, section on ‘Pneumonia’.)

Hospital-acquired infection — Antibiotic coverage for children with hospital-acquired (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. (See “Pneumonia in children: Inpatient treatment”, section on ‘Nosocomial pneumonia’.)

Duration — The duration of antibiotic therapy should be individualized, depending on the adequacy of drainage and clinical response of the patient [5]. Common practice is to continue antibiotics for at least 10 days after resolution of fever; antibiotics may be changed from the IV to oral route when the child has been afebrile and without a chest drain for two to five days, or possibly sooner if close clinical follow-up is assured [2]. For most cases of parapneumonic effusion or empyema, a total antibiotic course of two to four weeks is adequate [5]. Infections caused by certain pathogens, including CA-MRSA, may require a longer course of treatment.

SMALL PARAPNEUMONIC EFFUSION — A small pleural effusion is generally defined by its appearance on chest radiograph, as fluid occupying <1 cm on lateral decubitus radiograph or opacifying less than one-fourth of the hemithorax [5]. Children with effusions of this size who are in no respiratory distress usually can be managed as outpatients, with broad-spectrum oral antibiotics and close observation with chest radiographs (algorithm 1) [5]. (See ‘Antibiotic therapy’ above.)

Even if the effusion is small, hospital admission and intravenous (IV) antibiotics are appropriate for patients with respiratory compromise or distress, age under six months, evidence of bacteremia, or failed outpatient management. (See ‘Hospitalization’ above.)

MODERATE OR LARGE SIMPLE EFFUSION (NOT LOCULATED) — Recommendations for 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) [2,5,13]. These approaches are similar, as summarized in the algorithm (algorithm 2):

A moderate or large pleural effusion is generally defined by its radiographic appearance, as fluid occupying >1 cm on lateral decubitus radiograph or opacifying more than one-fourth of the hemithorax [5]. Such patients should be further evaluated with ultrasonography to determine whether the fluid is free-flowing (simple effusion) or loculated.

●Patients with simple effusions (free-flowing fluid) can be treated with drainage and antibiotics.

•In our practice, we generally perform the initial drainage with thoracentesis, provided that the patient has little or no respiratory compromise. We drain as much fluid as possible (up to a maximum of 10 to 20 mL/kg) and send a fluid sample for bacterial culture. We then treat the patient with empirically selected intravenous (IV) antibiotics while observing for 48 hours without further drainage. Further intervention including chest tube or surgical intervention may be needed if the patient’s condition worsens (eg, respiratory distress or sepsis). We adjust antibiotic coverage based on the culture results and antibiotic sensitivity testing. (See ‘Thoracentesis’ below.)

•We insert a pigtail catheter (small bore catheter) for continuous drainage if there is no clinical improvement by 48 hours and repeat ultrasonography demonstrates reaccumulation or loculation of fluid. We also insert a chest tube initially (rather than perform thoracentesis) if the patient has significant respiratory compromise or if the effusion is very large (eg, occupying more than one-half of the hemithorax). (See ‘Chest tubes’ below.)

●Complicated effusions (loculated effusion or empyema) are treated with either fibrinolysis with chest tube drainage, or early surgical drainage, as discussed below, in addition to IV antibiotics. (See‘Loculated effusion or empyema’ below.)

An alternative approach has been described in which children admitted with a moderate or large pleural effusion were treated with a trial of empirically selected antibiotics for a 24 to 72 hour period before thoracentesis or other drainage procedure; patients who did not respond clinically underwent drainage procedure (chest tube or surgical drainage) [14]. Antibiotics alone were successful in about half of these children.

Thoracentesis — Moderate or large simple effusions can be drained by thoracentesis, which can be therapeutic and diagnostic. 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 [15,16] and worsening of respiratory status. Insertion of a pigtail catheter or chest tube is warranted if reaccumulation of fluid occurs after the initial thoracentesis, or if the effusion is very large (eg, occupying more than one-half of the hemithorax). Repeated thoracentesis is not recommended [2]. (See ‘Chest tubes’ below.)

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’.)

Measurement of other characteristics of the pleural fluid, such as pH, glucose, and lactate dehydrogenase (LDH) may be helpful 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. Routine measurement of these characteristics is not recommended. Although they have been used to predict a need for drainage procedures, the results rarely change management of a patient with community-acquired pneumonia [5]. (See “Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children”, section on ‘Other studies’.)

Chest tubes — Large amounts of pleural fluid can be slowly drained using chest tubes with underwater seal systems. Indications for chest tube placement include:

●Large amounts of free-flowing pleural fluid – Chest tube insertion is an appropriate alternative to simple thoracentesis in large effusions, even in the absence of respiratory compromise.

●Compromised pulmonary function – eg, respiratory distress, severe hypoxemia, hypercapnia.

●Evidence of fibrinopurulent effusions – eg, positive gram stain, frank pus, or pH <7.0, glucose <40 mg/dL [2.22 mmol/L], lactate dehydrogenase [LDH] >1000 international units [16.67 kat/L], if these characteristics were measured [17].

●Lack of clinical improvement – eg, fever that fails to respond to 48 to 72 hours of antibiotic therapy, with reaccumulation or increase of pleural fluid after thoracentesis.

●Loculation of fluid on initial or follow-up imaging. (See ‘Loculated effusion or empyema’ below.)

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

Size of tube — Smaller chest tubes (eg, <14F, including pigtail catheters) are now generally recommended over large bore tubes, to minimize patient discomfort [2,13]. In the past, smaller tubes were often avoided because they were thought to be more prone to obstruction by fibrinopurulent exudate, but clinical studies have failed to substantiate this concern, especially when fibrinolytics are used in addition to chest tube drainage [18,19].

Furthermore, 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 [20]. 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 with thoracotomy in terms of duration of fever, parental report of clinical improvement, and length of hospital stay [21].

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 [22-25]. 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 of the chest tube, to ensure that there is no pneumothorax and to verify position [2]. However, an effectively functioning chest tube should not be repositioned solely on the basis of a radiograph [26].

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 underwater 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).

Very rapid drainage of fluid should be avoided. We suggest clamping the drain for one hour after drainage of the initial 10 mL/kg of pleural fluid. In large children and adolescents, some experts suggest that no more than 1500 mL of fluid should be drained at one time, and that drainage should be limited to 500 mL/hour, although there is no specific evidence on which to base this suggestion [2,27]. These precautions are suggested because very rapid drainage of pleural fluid occasionally causes pulmonary edema (known as “reexpansion pulmonary edema”). This complication has been reported after drainage of large effusions in adults [15] and in children with malignant lymphoma [16], but is otherwise rare in children.

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].

A bubbling chest drain should never be clamped, for the same reason [2,27]. Continuous bubbling from a chest drain suggests a continued visceral pleural air leak, which may develop into a tension pneumothorax if the chest drain is clamped. In chest tubes that are on suction, continuous bubbling may indicate that the drain is partly out of the thorax and one of the tube’s drainage holes is open to the atmosphere [2]. In a child with necrotizing pneumonia, a bubbling chest drain might indicate the development of bronchopleural fistula, a complication that sometimes requires surgical intervention.

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 and increases the risk of secondary infection. There is no need to do a trial of clamping the chest tube before its removal [2].

Factors to consider in determining clinical resolution include the child’s fever and general well-being, chest imaging, and fall in white blood cell count, as discussed below. (See ‘Monitoring response to therapy’below.)

Analgesia should be used for chest tube removal, 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 IV morphine for pain control [28]. 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, wound infection at the exit site, development of bronchopleural fistula, persistent atelectasis, and laceration of the lung [25,29].

LOCULATED EFFUSION OR EMPYEMA — Patients who have evidence of loculated fluid on the initial ultrasound require more aggressive intervention to drain the fluid and clear the infection. Expert opinion regarding the optimal type and timing of drainage and surgical intervention continues to evolve, and management remains somewhat controversial. The main options are fibrinolytic therapy and surgical debridement of the pleural space.

Management approaches described below are consistent with guidelines from the American Pediatric Surgery Association (APSA) and British Thoracic Society (BTS) [2,13]. Additional recommendations from the BTS guidelines are shown in the table (table 3).

Medical versus surgical treatment — Either medical or surgical treatment is acceptable as first-line therapy for children with loculated effusions. However, we suggest a trial of medical therapy (chemical debridement with fibrinolysis) as the initial treatment of choice for children with loculated effusions, followed by surgical therapy (typically video-assisted thorascopic surgery [VATS]) for those failing medical therapy, consistent with BTS and APSA guidelines [2,13]. This suggestion is based on limited evidence, and most experts agree that either approach is reasonable. The choice may be influenced by available expertise, cost considerations, and patient preferences.

Medical therapy with fibrinolysis is successful in approximately 83 percent of children; the remaining 17 percent who fail medical therapy will require VATS, as shown in the following randomized trials:

●A randomized trial in Europe compared VATS to medical therapy with fibrinolysis and found no difference in clinical outcome [30]. 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 randomized to fibrinolysis. Hospital costs were 25 percent higher for the group treated with primary VATS versus those randomized to primary fibrinolysis.

●Similar findings were shown in a randomized trial from the United States, in which 36 children were randomized to initial treatment with primary VATS or fibrinolysis with alteplase (recombinant human tissue plasminogen activator [tPA]) [31]. The failure rate of fibrinolysis was 16.6 percent (3 of 18 subjects), and two patients treated with primary VATS required ventilator support after surgery. There was no difference in median hospital stay after intervention, but hospital costs were substantially lower for the group treated with primary fibrinolysis (USD $11,700 versus $7,600).

Thus, long-term outcomes are excellent for either primary medical or surgical therapy, but surgical therapy is associated with higher treatment costs, and possibly greater short-term morbidity. Before these randomized trials were published, many institutions preferred to use primary surgical therapy because this approach appeared to reduce duration of therapy with 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), based on a systematic review of observational studies summarized in the table (table 4) [32].

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, alteplase (tPA) or streptokinase.

Efficacy — The evidence supporting fibrinolysis as a component of medical therapy for complicated parapneumonic effusion comes from randomized trials and meta-analyses comparing various fibrinolytic therapies with normal saline, and weakly favors fibrinolytic therapy:

●A meta-analysis in adults with loculated effusions or empyema found a nonsignificant improvement in outcomes with fibrinolytic therapy compared with saline (pooled risk ratio, 0.55; 95% CI 0.28-1.07) [33]. A separate meta-analysis analyzing the same trials using different methods found that fibrinolytics reduced the need for surgical intervention (pooled risk ratio 0.63, 95% CI 0.46-0.85) [34]. (See“Parapneumonic effusion and empyema in adults”, section on ‘Empyema’.)

●A randomized study in children examined the effect of intrapleural alteplase versus normal saline on 17 children with parapneumonic effusion (>20 percent of pleural cavity or >2 cm thickness on computerized tomography [CT] scan) who underwent chest tube placement [35]. Nine subjects received alteplase on day 1 and 3 and saline on day 2 and 4, and eight patients received the alteplase on day 2 and 4 with saline on the alternate days. Pleural drainage was increased on the days that alteplase was administered, compared with days when normal saline was used.

Choice of agent — No controlled studies are available to determine whether any one of the fibrinolytic agents is more effective than the others. The choice of agent depends upon availability, with urokinase being preferred if it is available, followed by alteplase (tPA) and streptokinase. Addition of the mucolytic agent deoxyribonuclease (DNase, eg, dornase alpha) to the fibrinolytic regimen appears to enhance treatment in adults [36], but has not been studied in children and is therefore not recommended in the pediatric age group. (See “Parapneumonic effusion and empyema in adults”, section on ‘Empyema’.)

Only urokinase has been studied in a placebo-controlled fashion in children, and thus is recommended by the BTS [2]. In North America, urokinase is no longer available so alteplase is usually used. This approach is supported by a retrospective case series showing similar outcomes and increased thoracostomy tube drainage with alteplase compared with urokinase [37]. Streptokinase is generally considered a third-line choice because of limited efficacy in one large trial and reports of occasional allergic reactions [2,38].

Technique and dose — Fibrinolytic therapy is administered by instilling the drug through the chest tube, or via irrigation at the time of thoracoscopy. In most cases, we administer fibrinolytic therapy through a pigtail catheter, inserted under ultrasound guidance using light sedation. The treatment may cause discomfort, and adequate sedation and or analgesia should be provided.

A number of different doses of these agents have been used in various studies. Two approaches for treatment with alteplase were described in the Pediatric Infectious Diseases Society (PIDS) guideline, based on clinical studies in which these regimens were shown to be safe and effective in children older than three months of age [5]:

●Alteplase 4 mg in 40 mL 0.9 percent saline, intrapleural. The first dose is given at time of chest tube placement with one hour dwell time, repeat every 24 hours for three days (total of three doses) [13,31].

●Alteplase 0.1 mg/kg (maximum: 3 mg) in 10 to 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 eight hours for three days (total of nine doses) [39].

The following technique and dose for urokinase is recommended in the BTS guidelines [2] and is also included in the PIDS guideline [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 one 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].

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). (See ‘Management’ above.)

Adverse effects — Adverse effects of fibrinolytic therapy include fever, discomfort, intrapleural bleeding, and anaphylaxis [20,37,40]. 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 [20,37]. Rare immediate hypersensitivity reactions to urokinase have been reported in adults [41]. Intrapleural administration of streptokinase generates a systemic antibody response similar to that when the drug is administered intravenously [42]; fever has been reported and other immunologic responses are possible.

Surgical therapy — Surgical intervention may be used as primary drainage for patients with loculated effusions or empyema, or a secondary therapy for those failing fibrinolytic therapy. Most experts agree that either approach is reasonable, and the choice may be influenced by available expertise, cost considerations, and patient preferences. In either case, early involvement of a surgeon in the decision-making process helps to ensure that timely surgical intervention can be performed if it is indicated [2]. (See ‘Medical versus surgical treatment’ above.)

Indications — Situations in which surgical intervention usually is necessary include [2]:

●Lack of clinical and radiologic response to initial medical management (eg, antibiotics, chest tube drainage and fibrinolytic therapy for three to four days).

●Persistent sepsis in association with persistent pleural collection, despite chest tube drainage and antibiotics.

●Complex empyema with significant lung pathology (eg, development of a thick fibrous pleural rind, sometimes termed a “peel,” which may “trap” the lung and prevent lung re-expansion).

●Bronchopleural fistula with pyopneumothorax.

Procedures — Three surgical procedures have been described in the management of children with parapneumonic effusion: VATS, minithoracotomy, and open thoracotomy with decortication [2]. A chest drain is left in place after each of these procedures for continued drainage of fluid or pus. VATS is the preferred procedure in typical patients if expertise in this technique is available because it is less invasive than open thoracotomy.

Video-assisted thoracoscopic surgery (VATS) — 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 [43-45], and drainage of pus from the pleural cavity under direct vision [2,46-48]. 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].

Observational studies and case series suggest that VATS has good outcomes in efficacy and safety, and the procedure is commonly performed in children with empyema in centers where appropriate expertise is available [2,43,44,49-53]. Compared with open thoracotomy, VATS is less invasive and is associated with shorter duration of analgesia, chest tubes, and postoperative length of stay [17,43,44,54,55]. VATS leaves two to three small scars [2,56]. The use of VATS depends to a large extent upon the availability of the equipment and appropriately trained pediatric thoracic surgeons [2].

Compared with medical therapy (antibiotics and drainage, with or without fibrinolysis), VATS is more invasive and costly but has a lower failure rate. These competing considerations lead to ongoing controversy as to the relative benefits of medical therapy versus early VATS in children with parapneumonic effusion and empyema:

●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 [46]. Early VATS is reported to enhance the chance of full expansion of the collapsed lung [46-48]. Some data suggest that the failure rate increases in late-presenting cases [47,54] and in patients who undergo VATS after failure of urokinase therapy [56-58].

Compared with medical therapy without fibrinolysis, early VATS appears to decrease the length of hospitalization. As an example, one study concluded that early VATS (<48 hours after admission) compared with late VATS (>48 hours after admission) significantly decreased the length of hospitalization (11.5 versus 15.2 days) [50]. Similar findings have been reported in other retrospective studies [51,59].

●Proponents of a trial of medical therapy point out that this approach is successful in a majority of patients, thus avoiding the need for surgery. When medical therapy includes fibrinolysis, it is effective in more than 80 percent of children, with similar length of stay and lower costs compared with early VATS. As a result, a trial of fibrinolysis is suggested for most patients with loculated effusion or empyema; supporting data and rationale are discussed above. (See ‘Medical versus surgical treatment’ above.)

Other techniques

●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 and involves incision of chest wall muscles as opposed to spreading the muscles.

●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 and may promote subsequent development of scoliosis [2,60].

Decortication is rarely necessary in children with empyema, since most, if not all, ultimately return to baseline lung function. The procedure may be necessary for children with late-presenting empyema and significant fibrous pleural rind (“peel”), complex empyema, and chronic empyema, and/or if VATS fails [2,61].

●Medical thoracoscopy – 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”.)

MONITORING RESPONSE TO THERAPY — With appropriate therapy, children with symptomatic parapneumonic effusion can be expected to improve within the first few days of treatment [6,62]. Those with empyema, particularly empyema caused by S. aureus, anaerobic bacteria, or group A streptococcus (S. pyogenes), typically have a more delayed recovery [6].

A response to therapy is indicated by gradual resolution of fever, with decreasing white blood cell count and C-reactive protein (CRP), decreasing respiratory and heart rates, and improvement in appetite 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 other parameters mentioned above 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 [6,7,63-65]. (See ‘Troubleshooting’ above and‘Loculated effusion or empyema’ above.)

There is no indication for routine daily chest radiographs since radiographic findings lag behind clinical status [3]. Repeat chest radiographs should be considered as indicated by changes in clinical status or after interventions (ie, removal of suction or clamping).

OUTPATIENT FOLLOW-UP — After hospital discharge, children with parapneumonic effusion or empyema should be seen in follow-up to ensure full recovery and complete resolution of symptoms. We perform chest radiography (posteroanterior [PA] and lateral) at this point for patients with residual symptoms or those who had particularly severe disease at presentation. Patients should be followed until they have recovered completely and their chest radiograph has returned to near normal, which usually occurs by three to six months [2,6,66-68], but may take as long as 16 months [69]. They may have residual dullness to percussion and quiet breath sounds over the affected areas because of pleural thickening [2,70-73].

Evaluation for underlying predisposing conditions, such as immune disorders, should be considered in children who have a history of recurrent bacterial infections or poor growth [2,74,75]. (See “Cystic fibrosis: Clinical manifestations and diagnosis” and “Approach to the child with recurrent infections”.)

PROGNOSIS AND OUTCOME — Despite the marked abnormalities at the time of presentation, and the variety of treatment approaches, the majority of children with parapneumonic effusion or empyema make a complete recovery [32,76,77]. There is no evidence that cases caused by antibiotic-resistant organisms are associated with poorer outcomes [49], although length of hospital stay may be increased [50].

Most children improve with antibiotic therapy and simple drainage (thoracentesis) [32]. Several studies suggest that early active therapy (ie, chest tube placement with or without fibrinolytic therapy or video-assisted thoracoscopy [VATS]) for selected patients may result in shorter duration of illness and length of hospital stay [2,32]. If necrotizing pneumonia develops, this may be complicated by bronchopleural fistula and tension pneumothorax. These complications are rare, but if they occur, recovery is prolonged.

In a systematic review comparing primary operative and nonoperative therapy in 3418 children with empyema, the mortality rate for children treated with antibiotics and chest tubes was 3.3 percent; no deaths were reported among the 363 children treated with fibrinolytic therapy, VATS, or thoracotomy [32]. Mortality is higher for children younger than one to two years of age [71,78,79]. 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 [69,77,80,81]. The rate of residual radiologic or pulmonary function abnormalities is higher, but these abnormalities are usually mild, and most of these patients are asymptomatic and have normal exercise tolerance. As an example, among 51 children examined at least two years after recovery from parapneumonic effusion, there were small abnormalities in lung function and exercise capacity, which were of no clinical importance [82]. All of the children in this report had been managed with medical therapy alone; 73 percent with chest tube drainage and 33 percent with drainage and fibrinolysis.

SUMMARY AND RECOMMENDATIONS

General overview

●Although approaches vary, there is a growing consensus that simple parapneumonic effusions should be treated with drainage and antibiotics, and complicated effusions with either fibrinolysis and chest tube drainage, or early surgical drainage (video-assisted thoracoscopic surgery [VATS]) (algorithm 2). (See ‘Overview’ above.)

●The majority of patients with pneumonia complicated by parapneumonic effusions will require hospitalization for further management. Transfer to a facility with specialists in pediatric pulmonology, pediatric surgery, and pediatric anesthesia should be considered early in the care of children with large or effusions because they may require VATS or fibrinolytic therapy. (See ‘Hospitalization’ above.)

Antibiotics

●All children with parapneumonic effusion should be treated with antibiotic therapy. The choice of antibiotic initially is based upon the suspected causative organism based on characteristics of the patient and local population and subsequently tailored according to the results of microbiologic testing. (See ‘Choice of agent’ above.)

●The duration of antibiotic therapy should be individualized, depending on the adequacy of drainage and clinical response of the patient. A common approach is to continue intravenous (IV) antibiotics for two to five days after resolution of fever, followed by oral therapy to complete total antibiotic course of two to four weeks. (See ‘Duration’ above.)

Free-flowing fluid — Management of parapneumonic effusion with free-flowing fluid depends on the size of the collection and clinical course of the patient.

●Children with small pleural effusions (eg, occupying <1 cm on lateral decubitus radiograph or opacifying less than one-fourth of the hemithorax) who are in no respiratory distress usually can be managed as outpatients, with broad-spectrum oral antibiotics and close observation with chest radiographs (algorithm 1). (See ‘Small parapneumonic effusion’ above.)

●We suggest that children who present with moderate or large amounts of free fluid documented by chest radiograph and ultrasonography undergo thoracentesis and observation (with antibiotic therapy) for 48 hours, rather than immediate placement of chest tube (Grade 2C). We drain off as much fluid as possible but no more than 10 to 20 mL/kg. Those patients who improve clinically are continued on antibiotic therapy as described above. Insertion of chest tube for large effusions is an acceptable alternative and is preferred by some clinicians. (See ‘Thoracentesis’ above and ‘Antibiotic therapy’ above.)

●A chest tube should be inserted for continuous drainage if the patient has severe respiratory compromise, or if there is no clinical improvement by 48 hours and repeat ultrasonography demonstrates reaccumulation or loculation of fluid (algorithm 2). (See ‘Chest tubes’ above and ‘Loculated fluid’ below.)

Loculated fluid — Patients who have loculated pleural fluid, documented by ultrasonography, can be treated with either medical or surgical therapy (algorithm 2).

●We suggest medical therapy (chemical debridement with fibrinolysis) as the initial treatment of choice for children with loculated effusions, followed by surgical therapy (VATS) for those failing medical therapy (Grade 2C). Early VATS is an acceptable alternative. Medical therapy with fibrinolysis is successful in approximately 80 percent of children; the remainder who fail medical therapy will require VATS. (See ‘Medical versus surgical treatment’ above and ‘Fibrinolytic therapy’ above.)

●Long-term outcomes are excellent for either primary medical or surgical therapy, but surgical therapy is associated with higher treatment costs and possibly greater short-term complications. (See ‘Medical versus surgical treatment’ above and ‘Video-assisted thoracoscopic surgery (VATS)’ above.)

Chest tube removal

●Chest tube removal is indicated once there is clinical resolution and minimal chest tube drainage. Clinical resolution is indicated by resolution of fever, with decreased 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

●Children who have been treated for parapneumonic effusion should continue to be followed until they have recovered completely. Follow-up chest radiographs are appropriate for patients with residual symptoms or those who had particularly severe disease at presentation. (See ‘Outpatient follow-up’ above.)

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