Pleural Effusion Treatment & Management

Transudative effusions are managed by treating the underlying medical disorder. However, regardless of whether transudative or exudative, large, refractory pleural effusions causing severe respiratory symptoms can be drained to provide symptomatic relief.

The management of exudative effusions depends on the underlying etiology of the effusion. Pneumonia, malignancy, and TB cause most exudative pleural effusions, with the remainder typically deemed idiopathic. Complicated parapneumonic effusions and empyemas should be drained to prevent development of fibrosing pleuritis. Malignant effusions are usually drained to palliate symptoms and may require pleurodesis to prevent recurrence.

Medications cause only a small proportion of all pleural effusions and are associated with exudative pleural effusions. However, early recognition of this iatrogenic cause of pleural effusion avoids unnecessary additional diagnostic procedures and leads to definitive therapy, which is discontinuation of the medication. Implicated drugs include medications that cause drug-induced lupus syndrome (eg, procainamide, hydralazine, quinidine), nitrofurantoin, dantrolene, methysergide, procarbazine, and methotrexate.

A meta-analysis and systemic review of 19 observational studies determined that pleural effusion drainage in patients on mechanical ventilation is safe and appears to improve oxygenation. ^[46] No data supported or refuted claims of beneficial effects on clinical outcomes, such as duration of ventilation or length of stay.

Parapneumonic effusions  ^[47]

Of the common causes for exudative pleural effusions, parapneumonic effusions have the highest diagnostic priority. Even in the face of antibiotic therapy, infected pleural effusions can rapidly coagulate and organize to form fibrous peels that might require surgical decortication. Therefore, quickly assess pleural fluid characteristics predictive of a complicated course to identify parapneumonic effusions that require urgent tube drainage. These are observed more commonly in indolent anaerobic pneumonias than in typical community-acquired pneumonia.

Indications for urgent drainage of parapneumonic effusions include (1) frankly purulent fluid, (2) a pleural fluid pH of less than 7.0-7.1, (3) loculated effusions, and (4) bacteria on Gram stain or culture. ^[48]

Patients with parapneumonic effusions who do not meet the criteria for immediate tube drainage should improve clinically within one week with appropriate antibiotic treatment.

Reassess patients with parapneumonic effusions who do not improve or who deteriorate clinically, using chest CT scanning and/or ultrasonography to evaluate the pleural space, and direct further drainage attempts, if needed.

Malignant pleural effusions

Malignant pleural effusions usually signify incurable disease with considerable morbidity and a dismal mean survival of less than one year. For some patients, drainage of large, malignant effusions relieves dyspnea caused by distortion of the diaphragm and chest wall produced by the effusion. Such effusions tend to recur in more than 90% of patients, necessitating repeated thoracentesis, pleurodesis, or placement of indwelling tunneled catheters. ^[44] Drainage systems using tunneled catheters allow patients to drain their effusions as needed at home.

For patients with lung entrapment from malignant effusions indwelling tunneled catheter drainage systems are the preferred treatment and provide good palliation of symptoms. ^[49] In patients without lung entrapment, pleurodesis (also known as pleural sclerosis) is another option to prevent recurrence of symptomatic effusions. In a 2012 non-randomized study, 34 patients choosing placement of indwelling catheters for malignant effusions had significantly fewer days spent in the hospital, less recurrence of effusion, and more rapid improvement in quality of life, compared with 31 patients choosing talc pleurodesis. ^[50]

Tuberculous pleuritis

Tuberculous pleuritis is typically self-limited. However, because 65% of patients with primary tuberculous pleuritis reactivate their disease within five years, empiric anti-TB treatment is usually begun pending culture results when sufficient clinical suspicion is present, such as an unexplained exudative or lymphocytic effusion in a patient with a positive PPD finding.

Chylous effusions

Chylous effusions are usually managed by dietary and surgical modalities. However, studies suggest that somatostatin analogues also may help in reducing the efflux of chyle into the pleural space.

Surgical treatment

Surgical intervention is most often required for parapneumonic effusions that cannot be drained adequately by needle or small-bore catheters. Surgery may also be required to establish a diagnosis and for pleural sclerosis therapy of exudative effusions.

Pleurodesis by insufflating talc directly onto the pleural surface using video-assisted thoracoscopy is an alternative to using talc slurries.

Decortication is usually required for trapped lungs to remove the thick, inelastic pleural peel that restricts ventilation and produces progressive or refractory dyspnea. In patients with chronic, organizing parapneumonic pleural effusions, technically demanding operations may be required to drain loculated pleural fluid and to obliterate the pleural space.

Surgically implanted pleuroperitoneal shunts are another treatment option for recurrent, symptomatic effusions, most often in the setting of malignancy, but they are also used for management of chylous effusions. However, the shunts are prone to malfunction over time, can require surgical revision and are poorly tolerated by patients.

In unusual cases, surgery might be required to close diaphragmatic defects (thereby preventing recurrent accumulation of pleural effusions in patients with ascites) and to ligate the thoracic duct to prevent reaccumulation of chylous effusions.

Consultations

Drainage of complicated effusions usually requires consultation with a pulmonologist, interventional radiologist, or thoracic surgeon, depending on the location of the effusion and the clinical situation.

Therapeutic thoracentesis is used to remove larger amounts of pleural fluid to alleviate dyspnea and to prevent ongoing inflammation and fibrosis in parapneumonic effusions. In addition to the precautions listed previously for diagnostic thoracentesis, note three additional considerations when performing therapeutic thoracentesis.

First, to avoid producing a pneumothorax during the removal of large quantities of fluid, remove fluid during therapeutic thoracentesis with a catheter, rather than with a needle, introduced into the pleural space. Various specially designed thoracentesis trays are available commercially for introducing small catheters into the pleural space. Alternatively, newer systems using spring-loaded, blunt-tip needles that avoid lung puncture are also available.

Second, monitor oxygenation closely during and after thoracentesis because arterial oxygen tension might worsen after pleural fluid drainage due to shifts in perfusion and ventilation in the re-expanding lung. Consider use of empiric supplemental oxygen during the procedure.

Third, remove only moderate amounts of pleural fluid to avoid reexpansion pulmonary edema and to avoid causing a pneumothorax. Removal of 400-500 mL of pleural fluid is often sufficient to alleviate shortness of breath. The recommended limit is 1000-1500 mL in a single thoracentesis procedure. Preventive strategies include monitoring pleural pressure with a manometer.

Larger amounts of pleural fluid can be removed if pleural pressure is monitored by pleural manometry and is maintained above -20 cm water. ^[51] However, this monitoring is rarely used by most proceduralists.

The onset of chest pressure or pain during the removal of fluid indicates a lung that is not freely expanding, and the procedure should be stopped immediately to avoid reexpansion pulmonary edema. ^[51] In contrast, cough frequently occurs during removal of fluid, and this is not an indication to stop the procedure, unless the cough is causing the patient discomfort.

Mediastinal position and lung entrapment

The position of the mediastinum on the chest radiograph may predict whether a patient is likely to benefit from the procedure. A mediastinal shift away from the pleural effusion indicates a positive pleural pressure and compression of the underlying lung that can be relieved by thoracentesis. (See the images below.)

In contrast, a mediastinal shift towards the side of the effusion indicates an endobronchial obstruction that prevents re-expansion of the lung when the pleural fluid is removed or lung trapped by encasement by chronic pleural thickening. Lung entrapment with malignant effusions is most common with mesothelioma and primary lung cancer.

Attempts at therapeutic thoracentesis usually do not improve dyspnea in patients with lung entrapment, due to the inability of the lung to re-expand. In fact, attempts at drainage of fluid in these patients usually results in a hydropneumothorax. (See the image below.)

Although small, freely flowing parapneumonic effusions can be drained by therapeutic thoracentesis, complicated parapneumonic effusions or empyemas require drainage by tube thoracostomy.

Traditionally, large-bore chest tubes (20-36F) have been used to drain the thick pleural fluid and to break up loculations in empyemas. However, such tubes are not always well tolerated by patients and are difficult to direct correctly into the pleural space. On the other hand, small-bore tubes (7-14F) inserted at the bedside or under radiographic guidance have been demonstrated to provide adequate drainage. ^[52] These tubes cause less discomfort and are more likely to be placed successfully within a pocket of pleural fluid. Using 20-cm water suction and flushing the tube with normal saline every 6-8 hours may prevent occlusion of small-bore catheters.

Insertion of additional pleural catheters, usually under radiographic guidance, or instilling fibrinolytics (eg, streptokinase, urokinase, or alteplase) through the pleural catheter can help to drain multiloculated pleural effusions.

A randomized trial of 210 participants with pleural infection documented that instillation of alteplase and DNase produced significantly greater drainage of pleural effusion, less need for surgical referral or surgical intervention, shorter hospital stays, and a decrease in pleural fluid inflammatory markers compared with placebo. ^[53]

Pleurodesis (also known as pleural sclerosis) involves instilling an irritant into the pleural space to cause inflammatory changes that result in bridging fibrosis between the visceral and parietal pleural surfaces, effectively obliterating the potential pleural space. Pleurodesis is most often used for recurrent malignant effusions, such as in patients with lung cancer or metastatic breast or ovarian cancer. Given the limited life expectancy of these patients, the goal of therapy is to palliate symptoms while minimizing patient discomfort, hospital length of stay, and overall costs. ^{[54, 55]}

Patients with poor performance status (Karnofsky score < 70) and a life expectancy of less than 3 months should not be treated with pleurodesis, and can be treated with repeated outpatient thoracentesis as needed to palliate symptoms. ^[56] Unfortunately, pleural effusions can reaccumulate rapidly, and the risk of complications increases with repeated drainage.

Patients with lung entrapment from malignant effusions are not good candidates for repeated thoracentesis, because they may not relieve dyspnea in such patients, nor for pleurodesis, as the visceral and parietal pleural surfaces cannot stay apposed to allow the bridging fibrosis. The best treatment for effusions in such patients may be the insertion of an indwelling tunneled catheter, which allows patients to remove pleural fluid as needed at home. ^[57]

A 2006 systematic review found that in pleurodesis, rotating the patient through different positions did not appear necessary to ensure distribution of soluble sclerosing agents throughout the pleural space. In addition, neither protracted drainage after instillation of sclerotics nor the use of larger-bore chest tubes increased the effectiveness of pleurodesis. ^[58]

Pleurodesis is likely to be successful only if the pleural space is drained completely before pleurodesis and if the lung is fully re-expanded to appose the visceral and parietal pleura after sclerosis. Animal studies suggest that systemic corticosteroids can reduce inflammation during sclerosis and can cause pleurodesis failures.

Sclerosing agents

Various agents, including talc, doxycycline, bleomycin sulfate (Blenoxane), zinc sulfate, and quinacrine hydrochloride, can be employed to sclerose the pleural space and effectively prevent recurrence of the malignant pleural effusion.

Talc is the most effective sclerosing commercially available agent and can be administered as slurry through chest tubes or pleural catheters. Although a systematic review suggested that direct insufflation of talc via thoracoscopy was more effective than talc slurry, both were equally effective in a 2005 prospective trial of malignant effusions. ^[59] Importantly, talc particles tend to occlude the small drainage holes in small pleural catheters. Therefore, pleural catheters should be at least 10-12F if intended for talc pleurodesis.

Doxycycline and bleomycin are also effective in most patients and can be administered more easily through small-bore catheters, although they are somewhat less effective and substantially more expensive than talc.

All sclerosing agents can produce fever, chest pain, and nausea. Talc rarely causes more serious adverse effects, such as empyema and acute lung injury. The latter appears to be related to the particle size and the amount of talc injected for pleurodesis.

Injection of 50 mL of 1% lidocaine hydrochloride prior to instillation of the sclerosing agent has been advocated help to alleviate pain ^{[21, 44]} but is not universally used. Additional analgesia might be required in some cases. Clamp chest tubes for approximately two hours after instillation of the sclerosing agent.

Tunneled pleural catheters (TPC) were approved by the FDA in 1997 and are a valid alternative for pleurodesis in malignant and some benign effusions. ^[60] TPC can be inserted as an outpatient procedure and can be intermittently drained at home, minimizing the amount of time spent in the hospital for patients with short prognoses. In contrast to pleurodesis, they can be used for patients with effusions and trapped lungs. ^[57]

Both talc pleurodesis and TPC improve dyspnea when used for malignant effusions, but talc pleurodesis requires significantly more days spent in the hospital and more pleural procedures. ^{[50, 61]} Consequently, TPC is the most cost-effective approach for patients with malignant effusions with expected survival of greater than 3 months. ^[62] The combined use of thoracoscopic talc poudrage and simultaneous placement of TPC for rapid pleurodesis has been reported to have a 92% success rate and 1.79 days median hospitalization stay following the procedure. ^[63]

TPC has also been shown to palliate refractory symptoms from recurrent effusions due to class III or IV heart failure, with effectiveness similar to thoracoscopic talc pleurodesis and with significantly fewer hospital days, operative morbidity, and readmissions. ^[64]

Complications reported from use of TPC include malfunction of the catheter (9.1%), clogging (3.7%), and pain (5.6%). ^[60] Less common but serious complications associated with TPC are infection (2.8%) or, when used for malignant effusions, tumor invasion of the catheter track (less than 1%). Notably, systemic chemotherapy does not increase the risk of pleural infection and can be used in these patients. ^[56]

Restriction of fat intake may help in the treatment of chylous effusions, although management remains controversial. Ongoing drainage of these effusions can rapidly deplete patients of fat and protein stores and lymphocytes. Limiting oral fat intake may slow the accumulation of chylous effusions in some patients. Hyperalimentation or total parenteral nutrition can preserve nutritional stores and limit accumulation of the chylous effusion but probably should be restricted to patients in whom definitive therapy for the underlying cause of the chylous effusion is possible.

Record the amount and quality of fluid drained and monitor for an air leak (bubbling through the water seal) at each shift. Large air leaks (steady streams of air throughout the respiratory cycle) may be indications of loose connectors or of a drainage port on the catheter that has migrated out to the skin. Consequently, dressings should be taken down and the position of the catheter inspected at the puncture site. Alternatively, they may indicate large bronchopleural fistulae.

Briefly clamping the catheter at the skin helps to determine whether the air leak is originating from within the pleural cavity (in which case, it stops when the tube is clamped) or from outside the chest (in which case, the leak persists).

Repeat the chest radiographs when drainage decreases to less than 100 mL/day to evaluate whether the effusion has been fully drained. If a large effusion persists radiographically, reevaluate the position of the chest catheter using chest CT scanning to ensure that the drainage ports are still positioned within the pleural collection. If the catheter is positioned appropriately, consider injecting thrombolytics through the chest tube to break up clots that may be obstructing drainage. Alternatively, chest CT scanning may reveal lung entrapment/trapped lung, which is unlikely to respond to further drainage.