Exudative Pleural Effusion in the Course of Bacterial Pneumonia

Definition, Etiology, PathogenesisTop

Exudative pleural effusions are relatively common (up to 20%-40% of hospitalized patients may have parapneumonic effusion) but the development of empyema following a parapneumonic effusion is much less common with prompt antibiotic therapy and fluid drainage used as needed. Classification of pleural disease secondary to bacterial pneumonia:

1) Uncomplicated parapneumonic effusion is purely exudative and accompanies bacterial pneumonia, lung abscess, or infected bronchiectasis. In the course of a lung infection an increase in the pulmonary interstitial fluid volume is observed. This fluid moves across the adjacent visceral pleural to accumulate as an effusion. The effusion fluid is clear and has a pH >7.2, lactate dehydrogenase (LDH) levels <1000 IU/L, and glucose levels >2.2 mmol/L. No bacteria are observed in cultures or Gram-stained specimens. Cell counts typically demonstrate an intense neutrophilic reaction, although a tuberculosis-related effusion can be associated with lymphocytosis.

2) Complicated parapneumonic effusion corresponds to bacterial invasion across the damaged pleural lining, which leads to an intense inflammatory response that results in fibrin deposition and the development of loculations in the pleural space. The pleural fluid, however, is not yet distinctly purulent. The effusion may be clear or cloudy, with a pH <7.2, LDH levels >1000 IU/L, and glucose levels <2.2 mmol/L. Bacteria may be observed by direct smear or in cultures. Pleural drainage is usually necessary.

3) Pleural empyema: The effusion is purulent (cloudy and often foul smelling). Biochemical analysis results are similar to those of complicated parapneumonic effusion (pH may be <7.0). Bacteria may be sometimes observed by direct smear or in cultures (these are predominantly aerobic gram-positive [streptococci and Staphylococcus aureus] or gram-negative bacteria [Escherichia coli, Pseudomonas, Haemophilus, and Klebsiella]; the prevalence of anaerobic infections has been increasing). Causes include complicated parapneumonic effusions and, less commonly, complications of thoracic surgery, chest trauma, esophageal perforation, thoracentesis, and subdiaphragmatic infection. Persistent purulent effusions lead to the formation of septa within the empyema and to fibrosis of the visceral pleura, which impairs lung expansion; they may also result in the formation of bronchopleural fistulas and lead to the development of sepsis, malnutrition, and cachexia.

TreatmentTop

The goals of treatment are reduction in mortality and preventing progression to the organizing phase of the effusion, that is, to the development of fibrothorax necessitating surgical decortication. Medical treatment alone has a 70% chance of recovery.

1. Antibiotic treatment: Empiric antibiotic therapy is indicated for most patients as soon as a diagnosis of parapneumonic effusion or empyema is suspected. Antibiotics should not be routinely delayed while awaiting thoracentesis. The exception to this rule includes only stable patients with chronic effusions, as the microbial nature of such infections often differs from those associated with an acute pneumonic process.

Initial antibiotic therapy should include an agent that targets anaerobic species, which are commonly the culprit. Therapy can be tailored on the basis of drug susceptibility results. Empiric therapy usually involves administration of antibiotics that are active against bacteria typically causing community-acquired infections and against anaerobes, for instance, ceftriaxone 1 g daily combined with metronidazole 500 mg tid. Alternative regimens include a combination of a beta-lactam and beta-lactamase inhibitor (piperacillin/tazobactam 4.5 g tid) or monotherapy with a carbapenem (meropenem 1 g tid). For patients with a penicillin allergy, ciprofloxacin 400 mg bid with metronidazole is also usually satisfactory. Aminoglycosides should be avoided due to their poor penetration into the pleural space. Antimicrobial treatment used alone is effective only in small uncomplicated parapneumonic effusions.

2. Pleural drainage is indicated when the risk of developing complications is deemed not low. Purulent fluid, pleural pH (<7.4, intermediate risk; <7.2 high risk [measured by an arterial blood gas analyzer machine]), LDH (>900), glucose (<2.2 mmol/L), imaging findings (septation on ultrasonography, contrast enhancement on computed tomography [CT]) may assist in determining risk. In the first line drainage should be done with a small bore (12-14 F) chest drain connected to a water seal.

3. Intrapleural administration of tissue plasminogen activator (tPA) 10 mg with deoxyribonuclease (DNase) 5 mg bid for 3 days using a sterile technique (local protocols differ and guide how much volume should be used to dilute the above-mentioned medications. Usually tPA will be diluted in 30 mL of 0.9% saline, and DNase, in 30 mL of water for injection) is indicated for patients with complicated parapneumonic effusion or empyema if the antibiotic therapy and initial drainage have failed. It is important to administer both agents in combination rather than as monotherapy, as guided by randomized controlled trial data.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness of some outcome measures. Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740. PMID: 21830966.

4. Surgical treatment (videothoracoscopic procedures, open pleural drainage, thoracotomy, decortication) should be considered in symptomatic patients with persistent pleural fluid collections who had no adequate response to attempts of drainage, antimicrobial therapy, and a treatment course of tPA/DNase. Video-assisted thoracoscopic surgery (VATS) is preferred to open thoracotomy given the associated reduction in hospital stay.