Parapneumonic Pleural Effusions and Empyema Thoracis Treatment & Management

The initial treatment of a patient with pneumonia and pleural effusion involves two major decisions. The first decision involves selection of an appropriate antibiotic that will cover likely pathogens. The second decision involves the need for drainage of pleural fluid and is be guided by the American College of Chest Physicians (ACCP) guideline recommendations for the medical and surgical treatment of parapneumonic effusions. ^[11]

The initial antibiotic selection is usually based on whether the pneumonia is community or hospital acquired and on the severity of the patient's illness. For a patient with community-acquired pneumonia, the recommended agents are second- or third-generation cephalosporins in addition to a macrolide. For patients hospitalized with severe community-acquired pneumonia, initiate treatment with a macrolide plus a third-generation cephalosporin with antipseudomonal activity. Enteric Gram-negative bacilli frequently cause pneumonia acquired in institutions (eg, hospitals, nursing homes). Therefore, initial antibiotic coverage should include an antibiotic effective against pseudomonads. If aspiration is evident or suspected, oral anaerobic micro-organism should also be covered.

Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) consensus guidelines on the management of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, and healthcare-associated pneumonia in adults are published elsewhere. ^{[23, 24]} Also see Bacterial Pneumonia.

Effusions with pleural fluid layering less than 10 mm on decubitus chest radiographs almost always resolve with appropriate systemic antibiotics. Patients with pleural effusions that have a pleural fluid layering greater than 10 mm on lateral decubitus radiographs should have a diagnostic thoracentesis unless there is a contra-indication to the procedure. If the diagnostic thoracentesis yields thick pus, the patient has an empyema thoracis and definitive pleural drainage is absolutely required. If the pleural fluid is not thick pus, then results of pleural fluid Gram stain or culture, pleural fluid pH and glucose levels, and the presence or absence of pleural fluid loculations should guide the course of action as recommended in the guidelines. ^[11]

Of note, the strength of recommendations by the expert panel in this guideline is somewhat limited because of the small number of randomized, controlled trials, and methodological weakness resulted in heterogeneous data. The panel urged review of these recommendations cautiously; they purposefully avoided specific recommendations or preferences on primary management approaches (ie, no drainage, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery [VATS], thoracotomy). Despite these limitations, consistent and possibly clinically meaningful trends formed for the pooled data and the results of the randomized, controlled trials and the historically controlled series on the primary management approach to parapneumonic pleural effusions.

Summary of the recommendations

In all patients with acute bacterial pneumonia, the presence of a parapneumonic pleural effusion should be considered (level C evidence).

In patients with parapneumonic pleural effusions, the estimated risk for poor outcome, using the panel-recommended approach based on pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, should be the basis for determining whether the parapneumonic pleural effusions should be drained (level D evidence). Poor outcomes could result from any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. The 4 risk categories are as follows:

• Category 1 (very low risk): The effusion is small (< 10-mm thickness on decubitus) and free flowing (A₀). Because the effusion is small, no thoracentesis is performed and the bacteriology (B_x) and chemistry (C_x) of the fluid are unknown.

• Category 2 (low risk): The effusion is small to moderate (≥10 mm and less than half the hemithorax) and free flowing (A₁) with negative culture and Gram stain regardless of prior use of antibiotics (B₀); pH is higher than or equal to 7.20 (C₀).

• Category 3 (moderate risk): The effusion meets one of the following criteria: large (greater than or equal to half the hemithorax), loculated effusion, thicken pleura on contrast-enhanced CT scan (A₂), positive Gram stain or culture (B₁), or pH less than 7.20 (C₁).

• Category 4 (high risk): This is when pleural fluid consists of pus.

Patients with category 1 or category 2 risk for poor outcome with parapneumonic pleural effusions may not require drainage (level D evidence).

Drainage is recommended for management of category 3 or 4 parapneumonic pleural effusions based on pooled data for mortality and the need for second interventions with the no-drainage approach (level C evidence).

Based on the pooled data for mortality and the need for second interventions, therapeutic thoracentesis or tube thoracostomy alone appears to be insufficient treatment for treating most patients with category 3 or 4 parapneumonic pleural effusions (level C evidence). However, the panel recognizes that in the individual patient, therapeutic thoracentesis or tube thoracostomy, as planned interim steps before a subsequent drainage procedure, may result in complete resolution of the parapneumonic pleural effusions. Careful evaluation of the patient for several hours is essential in these cases. If resolution occurs, no further intervention is necessary (level D evidence).

Fibrinolytics, VATS, and surgery are acceptable approaches for managing patients with category 3 and category 4 parapneumonic pleural effusions based on cumulative data across all studies that indicate that these interventions are associated with the lowest mortality and need for second interventions (level C evidence).

Chest tubes (tube thoracostomy)

Insert chest tubes immediately after a complicated parapneumonic pleural effusion or empyema thoracis is diagnosed (see the image below). The key to resolution involves prompt drainage of pleural fluid because delay leads to the formation of loculated pleural fluid.

Position the chest tube in a dependent part of the pleural effusion. Previously, large-bore (38-32F) tubes were recommended, but smaller tubes are similarly effective, and at least a 28F tube should be placed. These can be placed either using a guidewire-assisted serial dilatation technique or the more traditional cut-down approach.

Smaller pigtail catheters (8-14F) can also be placed under ultrasound or CT guidance. Consider these in smaller, difficult-to-access, multiple-loculated effusions and nonloculated, nonpurulent effusions. These catheters have also been successful in draining empyemas. The variation in success rates for these catheters (72–82%) is associated with patient selection, operator expertise, and the stage of the parapneumonic pleural effusions. The major advantage of small-bore catheters is better patient tolerance and avoidance of major complications. ^[2]

Continue closed-tube drainage as long as clinical and radiologic improvement are observed. The chest tube can be removed once the volume of the pleural drainage is less than 100 mL/24 h, with clearance of the pleural fluid turbidity seen in complicated pleural effusions.

If the patient does not demonstrate clinical or radiologic improvement with declining pleural fluid drainage, perform a pleural space ultrasound examination or chest CT scanning to look for pleural fluid loculations and ensure proper tube placement.

Undrained pleural fluid may respond to intrapleural thrombolytic therapy or may require placement of another tube. Closed chest tube drainage yields satisfactory results in approximately 60% of patients with aerobic infections and 25% of patients with anaerobic infections.

Intrapleural thrombolytic agents

Since the 1970s, several studies have reported success of thrombolytic therapy for loculated complicated parapneumonic pleural effusions. ^{[25, 26, 27, 28, 29, 30, 31, 32, 33]} The thrombolytic agents used in parapneumonic pleural effusions are more effective if administered in the early fibrinopurulent stage of parapneumonic pleural effusions.

With thrombolytic therapy, success rates of 70-90% have been reported. Streptokinase has been used in a dose of 250,000 IU in 100 mL of normal saline once or twice a day. Urokinase was also effective and in a randomized trial of patients with multiloculated pleural effusions. Subjects in the urokinase group drained significantly more pleural fluid, required less surgical intervention, and required fewer days in the hospital.

Important to note is that streptokinase and urokinase are no longer available in the United States.

Following instillation, the chest tube is clamped for 2-4 hours. These agents may be administered daily for as many as 14 days. Streptokinase may lead to sensitization with production of an antibody response and subsequent allergic reaction if used for systemic thrombolysis.

Streptokinase and urokinase are probably equally effective, although neither has been compared to each other in a research trial. The potential for developing antibodies to streptokinase has generally favored urokinase as a pleural thrombolytic.

While thrombolytic agents may facilitate and increase pleural fluid drainage, their effect on improving patient outcomes and avoiding surgical intervention has not been established.

A prospective randomized trial of intrapleural thrombolytic agent streptokinase (MIST1 group) was conducted on the drainage of infected pleural fluid collections. In this double-blind trial, 454 patients with pleural infection (either purulent pleural fluid or pleural fluid with a pH < 7.20 with signs of infection) received either intrapleural streptokinase (250,000 IU bid for 3 d) or placebo. Among the 427 patients who received streptokinase or placebo, no benefit was reported for streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of hospital stay; serious adverse events (chest pain, fever, or allergy) were more common with streptokinase. ^[29]

Tokuda et al performed a meta-analysis of all properly randomized trials, comparing intrapleural thrombolytic agents with placebo in adult patients with empyema thoracis and complicated parapneumonic pleural effusions. The outcome of primary interest was the reduction of death and surgical intervention. Five trials totaling 575 patients were included. ^[30]

The MIST1 trial constituted the bulk of patients in the meta-analysis, and its non-beneficial findings contributed significantly to the final conclusion. The meta-analysis did not support the routine use of thrombolytic therapy for all patients who required chest tube drainage for empyema thoracis or complicated parapneumonic pleural effusions. Note that the meta-analysis described a nonsignificant reduction in death and surgery even despite including the MIST1 trial. Because of significant heterogeneity of the treatment effects, selected patients might benefit from thrombolytic treatment. ^[30]

The reason the MIST1 caused a significant heterogeneity could have been the differences in patient population studied and their study design. First, the proportion of loculated pleural effusions enrolled was low (70%). Second, unlike other studies, only plain chest radiography, and not ultrasonography or CT imaging, was used to document radiographic improvement. Third, the median size of the chest tube used was smaller, only 12F, and there was no mention whether ultrasound guidance was used for placement. Lastly, the criteria for surgical intervention were more subjective and were based on clinical judgment of the physicians, whereas other studies had more objective criteria.

Intrapleural recombinant tissue plasminogen activator (r-TPA) or alteplase has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion and pleural empyema. Some authors have suggested that r-TPA might be a more effective therapeutic agent than streptokinase.

A small, noncomparative study of consecutive adult patients using r-TPA or alteplase administered intrapleurally in a single daily dose of 25 mg reported the treatment was well tolerated and effective. ^[31] Another retrospective review of 22 consecutive patients also demonstrated improved drainage of pleural fluid with alteplase, with 2 mg administered into the pleural space 3 times a day for 3 days.

This has led to a prospective, randomized comparison of alteplase with placebo in the management of complicated pleural effusions and empyema. The study has been completed, and the final report of this experience is pending.

The Cochrane Database systematic review on this topic published in 2008 had identified 7 studies and 761 patients. ^[33] A significant reduction in the need for surgical intervention was identified, but the authors also noted the discrepancy between this conclusion and results of the MIST1 trial. The authors note subgroup analysis that suggests the greatest benefit is in patients with loculated effusions, but the data are very limited and due caution is advised. No increase in adverse events was noted with thrombolytic therapy.

An r-TPA study that came out later in 2011, the MIST2 trial, included a comparison with intrapleural recombinant human DNase, a potential treatment for pleural infection that may help prevent biofilm formation and increased viscosity by destroying extracellular DNA. The blinded 2-by-2 factorial trial randomly assigned 210 patients with pleural infection to receive a 3-day study treatment using double placebo, r-TPA (alteplase) and placebo, DNase and placebo, or r-TPA and DNase. The combined intrapleural r-TPA and DNase therapy reduced hospital stay length, decreased the need for thoracic surgery, and produced a greater improvement in pleural opacity on day 7 relative to double placebo. Stay length and pleural opacity change for DNase alone and for r-TPA alone did not significantly differ from those for double placebo.

The possible explanation could be that the fibrinolytics help lyse the pleural fibrinous septation and the DNase is required to reduce the viscosity of the pus. This study suggested that DNase monotherapy should be avoided because it increases the need for thoracic surgery. ^[34]

After the MIST2 study, no other randomized trial has been performed in this field. The latest systematic review with meta-analysis of fairly good–quality trials was published by Janda and Swiston in 2012. This study analyzed 7 randomized controlled trials, total of 801 patients, comparing fibrinolytic therapy with placebo, including the MIST1 and MIST2 trials. The results showed significant reduction of treatment failure (surgical intervention or death) and surgical intervention alone but not for death alone or hospital length of stay. ^[35] The MIST1 was also the one that caused significant heterogeneity in this meta-analysis. The authors also addressed potential publication bias due to missing large positive studies, as well as small and large negative studies.

Thus, the conclusion by the authors was not quite different from previous meta-analyses that although fibrinolytic therapy cannot be routinely recommended, it could be considered in patients with loculated pleural effusions because it may prevent the need for surgical intervention. More randomized controlled trials with adequate power are needed. However, pleural thickening greater than two mm on CT scan might predict failure of intrapleural fibrinolytic therapy. ^[36]

Thoracoscopy

Thoracoscopy is an alternate therapy for multiloculated empyema thoracis. In patients with multiloculated parapneumonic pleural effusions, the loculations in the pleural space can be disrupted with a thoracoscope, and the pleural space can be drained completely. If extensive adhesions are present or thick pleural peel entraps the lung, the procedure may be converted to open thoracostomy and decortication.

Luh et al published their experience in the treatment of complicated parapneumonic pleural effusions and empyema thoracis by VATS in 234 patients (108 women, 126 men). More than 85% (200 patients) received preoperative diagnostic or therapeutic thoracentesis, tube thoracostomy, or fibrinolytics. Of 234 patients, 202 patients (86.3%) achieved satisfactory results with VATS. Only 40 patients required open decortication or repeat procedures. VATS is safe and effective for treatment; earlier intervention with VATS can produce better clinical results. ^[37]

Hope et al reviewed outcomes of surgical treatment for parapneumonic empyema thoracis. The use of VATS was compared with thoracotomy. Morbidity and mortality rates were similar among all groups. The conversion rate to open thoracotomy was 21%. Based on a shorter postoperative length of stay with similar morbidity and mortality in patients operated on within 11 days of admission, early aggressive surgery treatment for complicated parapneumonic effusions or empyema thoracis is recommended. ^[38]

Retrospective evaluation of 2 different surgical procedures (decortication vs debridement) and approaches (VATS vs thoracotomy) were analyzed by Casali and colleagues. The study included 119 patients; 51 patients had debridement (52% through VATS, 48% through thoracotomy) and 68 patients had decortications through thoracotomy. VATS debridement had a lower postoperative hospital stay and shorter duration of chest drainage and greater improvement in a subjective dyspnea score. The long-term spirometric evaluation was normal in 58 patients (56%). Age older than 70 years old was the only variable associated with poor long-term results (forced expiratory volume in 1 second [FEV₁] < 60% and/or dyspnea Medical Research Council grade ≥2) at multivariate analysis. VATS is associated with less postoperative mortality and shorter postoperative hospital stay. ^[39]

Two other studies that support the use of VATS as a primary drainage procedure are those by Potaris et al ^[40] and Chan et al. ^[41]

Wang and colleagues proposed a new technique using an electronic endoscope (bronchoscope or gastroscope) inserted through the chest tube to directly visualize, irrigate, and break down the loculation effectively in various pleural diseases, including 13 cases of empyema thoracis. ^[42]

In a prospective, randomized study comparing VATS and thrombolytic therapy in children with empyema, no differences in outcomes were noted between the 2 methods in a small study involving 36 patients. ^[43] Thrombolytic therapy consisted of 4-mg doses administered 3 times over a 48-hour period. Three (16.7%) of the patients treated with thrombolytic therapy eventually required VATS for management.

Rib resection and open drainage of pleural space

Open drainage of the pleural space may be used when closed-tube drainage of the pleural infection is inadequate and the patient does not respond to intrapleural thrombolytic agents. This procedure is recommended only when the patient is too ill to tolerate decortication. The resection of one to three ribs overlying the lower part of the empyema thoracis cavity is performed, a large-bore chest tube is inserted into the empyema thoracis cavity, and the tube is drained into a colostomy bag.

Patients treated by open drainage have an open chest wound for a prolonged period. In one series, the median time for healing the drainage site was 142 days. With decortication, the period of convalescence is much shorter, although patients who are markedly debilitated do not tolerate decortication.

In decortication, all the fibrous tissue is removed from the visceral pleural peel, and all pus is evacuated from the pleural space. Decortication is a major thoracic operation requiring full thoracotomy; therefore, decortication is not tolerated by critically ill patients. Decortication is the procedure of choice for patients in whom pleural sepsis is not controlled by closed-tube thoracostomy, intrapleural thrombolytic agents, and, possibly, thoracoscopy. Mortality rates as high as 10% have been described with this procedure. Decortication should not be performed solely to remove the thickened pleural peel; the thickened pleural peel usually resolves over several months. If the pleura remains thickened with symptom-limiting reduction in pulmonary function after approximately 6 months, decortication can be considered.

Postpneumonectomy empyema thoracis, an uncommon but life-threatening complication, is often associated with a bronchopleural fistula. Treatment of bronchopleural fistula depends on several factors, including the extent of dehiscence, degree of pleural contamination, and general condition of the patient. Early diagnosis and aggressive therapeutic strategies for controlling infection, closing the fistula, and sterilizing the closed pleural space are mandatory. Repeated debridement, VATS, endoscopic application of tissue glue, and stenting may be additional management strategies. ^[44]

Most patients can be treated by pulmonary and/or infectious diseases specialists.

An interventional radiologist may be needed to place small-bore drainage catheters for difficult-to-access loculated effusions.

Patients with persistently loculated effusions or unresolving empyema thoracis may require surgery and should be seen by a thoracic surgeon.

No dietary restrictions are recommended for patients with parapneumonia effusions and empyema, other than what is dictated by comorbidities.

No specific activity restrictions are recommended for patients with parapneumonic effusions and empyema. Their activity level may be limited by comorbidities and any interventions required to treat their infection.

Complications are related to adverse events related to incomplete drainage of infected pleural fluid. These include chronic, indolent infections, chest tube site infections, trapped lung, bronchopleural fistulas, and pneumothoraces.

Untreated infections may lead to sepsis, septic shock, and death.

Early diagnosis and intervention (thoracentesis and/or drainage procedure), may obviate the need for surgical treatment.

Often, prolonged antibiotic therapy is required, particularly in patients who have anaerobic infections. The length of antibiotic therapy is generally dictated by the response to antibiotics and clinical and radiologic resolution.