Pleural effusion is one of the most common presentations of the post-COVID-19 sequela of the pandemic. It is also a common pathology associated with a lot of bacterial, fungal, malignant, and non-infective conditions. The following article ponders on the treatment and management of untappable pleural effusion.

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What is pleural effusion?

Among the causes of pleural effusion, pleural infection (bacterial, fungal), heart failure and malignancy are the most common. The former two of the causes are managed separately as “Non-malignant Pleural effusion (NMPE)”. As very little has been known about the exact intervention for evaluating NMPEs, most of the strategies depend on evidence derived from the management of malignant pleural effusion (MPE).

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Common causes of pleural effusion

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Symptoms of pleural effusion

Most of the times there are no active symptoms and pleural effusion is detected incidentally on chest X-ray done for another reason. Along with unrelated symptoms due to the disease that has caused the effusion, specific symptoms associated with this pathology include:

• Pleuritic chest
• Dry, non-productive cough
• Decreased exercise capacity
• Dyspnoea (shortness of breath, or difficult, laboured breathing)
• Orthopnoea (difficulty breathing when lying down)

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Importance of history taking

A developing nation like India known for overcrowding has increased cases of tuberculosis among the population. It is also the most common cause of pleural effusion among third-world countries. And thus, as a physician in a government setup, infectious causes of pleural effusion almost always takes precedence.

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Tuberculous causes of effusion: Questions to ask your patient

• Do you have any evening rise of fever?
• Have you lost any weight recently?
• What do you think about your appetite?
• Do you have any complaints of cough with or without expectoration?
• Do you have chest pain? *
• Does your chest pain increase with activity and deep inspiration? *
• Does the pain increase when you are lying down and improves while you are sitting upright? *

*Questions specific to NMPE

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Algorithm for management of NMPE

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Treatment of non-tappable/tappable tuberculous pleural effusion

Once tuberculosis as a diagnosis is confirmed based on pleural fluid analysis, which is exudative, lymphocyte-predominant pleural effusion, usually with the following characteristics is observed:

• Colour: Straw coloured
• Protein concentration: >3.0 g/dL (30 g/L)
• LDH: Elevated in approximately 75 per cent of cases, with levels commonly exceeding 500 international units/L
• pH: <7.40
• Glucose: Usually between 60 and 100 mg/dL
• ADA >40 units/L
• Acid-fast bacilli seen

The above mentioned pleural fluid interpretation along with interferon-gamma release assay (IGRA), clinical history and a tuberculin skin test (TST) confirms the diagnosis. The patient can then be started on anti-tuberculous medications such as Isoniazid, Rifampicin, Ethambutol and Pyrazinamide.

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Treatment of non-tappable bacterial pleural effusion

1. The patient should be started with empirical antibiotics (aerobic and anaerobic coverage) for 7 consecutive days:
   1. Third-generation cephalosporin (ceftriaxone or cefotaxime) + metronidazole
   2. Beta-lactam/beta-lactamase inhibitor combination: ampicillin-sulbactam
   3. Carbapenem monotherapy (imipenem, meropenem) (if the patient is allergic to penicillin/cephalosporins)
   4. +/- Respiratory fluroquinolone (levofloxacin, moxifloxacin) + metronidazole
   5. Clindamycin (covers most of the anaerobes, but due to consistently exceeding resistance rates, its usage as an empiric method of intervention has been prohibited)
2. Once there is clinical resolution, intravenous antibiotics are shifted to oral dosages.

A generalised dictum for the duration of therapy is:

• Empyema – 4 to 6 weeks
• Complicated parapneumonic effusion – 2 to 3 weeks
• Uncomplicated parapneumonic effusion – 1 to 2 weeks

While we take radiographic response into account when determining the duration of therapy, complete radiographic resolution may take many weeks or months and residual pleural thickening can persist for longer periods. Thus, treating with the goal of a complete radiographic resolution is not necessary.

The initial IV antibiotic regimen can be switched to an oral regimen with a similar treatment spectrum when the clinical response is clear (e.g. the patient is afebrile, haemodynamically stable, clinically improving), no further drainage procedures are needed, and when the patient is able to tolerate oral medications.

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Post-resolution management

Patients who clinically resolve along with radiological evidence for the same usually present with pleural thickening and sometimes even atelectasis. The only remnant symptom the patient presents with is decreased exercise capacity and infrequent complaints of breathlessness. The following intervention has been found effective:

• Bronchodilators [Metered dosage inhalers (MDIs) or nebulisation] **
• Incentive spirometry

**Beta-agonists like (salbutamol, albuterol, etc.) and muscarinic antagonist (tiotropium) are the drugs of choice with or without adding inhalational corticosteroids (as the pathophysiology is not inflammatory bronchoconstriction but residual bronchoconstriction due to the insult from the disease).

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.