Pleural Effusion Evaluation and Management

TONY ABDO, M.D

ASSISTANT PROFESSOR OF MEDICINE

SECTION OF PULMONARY, CRITICAL CARE, AND SLEEP MEDICINE

Disclosures

• None• Ninguna• Aucunال شیئ •

Outline• Background• Pathophysiology• Clinical presentation• Thoracentesis• Pleural Fluid Analysis• Light’s Criteria• Transudates & Exudates Causes• Parapneumonic effusion • Malignant effusion

Background

• Pleural effusion is defined as an abnormal collection of fluid in the pleural space

• It is the most common manifestation of pleural disease

• 1.5 million effusions are diagnosed in the United States each year

• Congestive heart failure, pneumonia, and malignancy are the leading causes of effusions in the United States

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NEJM. 2018 Feb 22;378(8):740-751.

• The pleural space is a potential space between the parietal and visceral pleura

• Only 0.26 ml/kg (15-20 ml) of pleural fluid is contained in each pleural cavity

• The pleural fluid is both produced and absorbed primarily on the parietal surface

• It is dependent on the balance of hydrostatic and oncotic pressures and the rate of resorption by parietal lymphatics

• When this balance is altered → pleural fluid accumulates (effusion)

Pathophysiology

Clinical Presentation• Dyspnea

• Cough

• Chest pain

Symptoms depend on

• Effusion size

• Rate of accumulation

• Underlying cause

• Respiratory reserve/Comorbidities

Evaluation • History – extensive, including occupational history• It frequently identifies the etiology of the effusion•New v/s recurrent effusion

• Imaging – evaluate the size and the appearance of the effusion•CXR, ultrasonography, ± CT chest•Review old imaging when available (? chronicity)

• Thoracentesis ± chest tube insertion

Spleen

Free flowing effusion

Lung

Diaphragm

Image by: Tony Abdo, M.D

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Indications for Thoracentesis• Diagnostic (20-50cc): any new effusion!

• Observation may be warranted in uncomplicated heart failure (i.e. in the absence of atypical features) and viral pleurisy (small)•Atypical features (absence of cardiomegaly, low BNP, normal echo, fever, persistent effusion despite optimization of HF therapy, etc.)

→Thoracentesis

• Therapeutic: mainly for symptomatic relief

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Contraindications for Thoracentesis• No absolute contraindications

• Risk–benefit analysis!

• Relative Contraindications: • INR > 1.5, NOACs, platelets < 50,000,1,2 clopidogrel 3

•< 1cm depth •Skin infection at the site of needle insertion

❖ Non-urgent pleural aspirations and chest drain insertions should be avoided in anticoagulated patients until INR < 1.5 (2010 BTS guidelines – Grade C)

1. CHEST Journal 144.2 (2013): 456-4632. Thorax 70.2 (2015): 127-132.

3. Annals of the American Thoracic Society 11.1 (2014): 73-79

Ultrasound guidance?• Improves safety and accuracy!

• 19% reduction in risk of pneumothorax with US

• BTS Pleural Disease Guidelines 2010 • Thoracic ultrasound guidance is strongly recommended for all pleural procedures for

pleural fluid. (B) • The marking of a site using thoracic ultrasound for subsequent remote aspiration or

chest drain insertion is not recommended except for large pleural effusions. (C)

CHEST 2003; 123: 436

It is 2018!

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Pleural effusion

Ascites

Image by: Tony Abdo, M.D

Pleural Fluid Analysis• Gross appearance

• Chemical and biochemical analysis:•Protein, LDH, glucose, and PH in all patients•Cholesterol, triglycerides, amylase, creatinine, adenosine deaminase, etc. in specific patients

• Cell Count

• Microbiology

• Cytology

Gross Appearance• Fluid color:•Pale yellow – transudate•Red (bloody) – malignancy, pulmonary infarction, and hemothorax •White (milky) – chylothorax, and pseudochylothorax•Black – aspergillus niger, chronic hemothorax, and melanoma•Dark green – biliothorax• Enteral tube feeding or CVC infusate ☹

• Fluid characteristic: pus, turbid, anchovy paste (amebic liver abscess)

• Fluid odor: putrid (anaerobic empyema), ammonia (urinothorax)

Images by: Tony Abdo, M.D & Jad Kebbe, M.D

Transudate v/s Exudate• Light's Criteria: if at least one of the following criteria is fulfilled → exudate•Pleural fluid protein/serum protein > 0.5, or•Pleural fluid LDH/serum LDH > 0.6, or•Pleural fluid LDH > 2/3 the upper limits of the laboratory's normal serum LDH

• These criteria identify almost all exudates but misclassify 25% of the transudates as exudates (CHF patients on diuretics)

• (Serum protein - pleural fluid protein) > 3.1 g/dL or (serum albumin - pleural fluid albumin) > 1.2 g/dL may help identify those misclassified transudates

Ann Intern Med. 1972;77(4):507Chest 2002; 122: 1524-9

BTS Pleural Disease Guideline 2010. Thorax. 2010 Aug 1;65(Suppl 2):ii4-17.

3-10% of malignant effusions are transudates!

Cell Count

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DISEASE DIAGNOSTIC PLEURAL FLUID TESTS

Empyema Pus, putrid odor, positive cultureMalignancy Positive cytologyTuberculous pleurisy Positive AFB stain, cultureEsophageal rupture High amylase, low pH (often as low as 6), food particlesFungal-related effusions Positive fungal stain, cultureChylothorax Triglycerides >110 mg/dL, chylomicrons by lipoprotein electrophoresisCholesterol effusion Cholesterol >200 mg/dL with a cholesterol/triglyceride >1Hemothorax PF/S hematocrit > 0.5Urinothorax PF/S creatinine > 1.7Peritoneal dialysis Protein < 0.5 mg/dL and PF/S glucose > 1 Extravascular migration of a CVC PF/S ratio >1, PF gross appearance mirrors infusateRheumatoid pleurisy Typical cytology (multinucleated giant cells + elongated macrophages)Glycinothorax Measurable glycine after bladder irrigation with glycine-containing solutionsCSF leakage into pleural space Detection of beta-2 transferrinParasite-related effusions Detection of parasites

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“Assiniboine hunting buffalo", painting by Paul Kane

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Buffalo Chest

Parapneumonic Effusion

Parapneumonic Effusion• Found in ~ 40% of bacterial pneumonia• ~ 300,000 cases/year in the United States• Incidence is on the rise• High morbidity/mortality• Distinctive microbiology • Usual effusions are small and resolves with antibiotherapy (uncomplicated)• The development of empyema is a progressive process:

simple exudate → fibrinopurulent stage → organizing scar tissue formation

BTS pleural disease guideline 2010. Thorax. 2010 Aug 1;65(Suppl 2):ii41-53.

BTS pleural disease guideline 2010. Thorax. 2010 Aug 1;65(Suppl 2):ii41-53.

Courtesy of Najib M. Rahman, BM BCh, MA, MRCP

Classification

1. Uncomplicated parapneumonic effusion

2. Complicated parapneumonic effusion

3. Empyema

Complicated Parapneumonic Effusion

ACCP Criteria:

• Pleural fluid pH < 7.2

• Pleural fluid glucose < 60mg/dL

• Positive culture

• Effusion > ½ of hemithorax, loculated effusion, thick parietal pleura

BTS Criteria

• Pleural fluid pH <7.2,

• Pleural fluid glucose < 40 mg/dL

• Positive Culture

• Pleural fluid LDH > 1000 IU/L

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Thorax 2003;58(Suppl 2):ii18.

Early identification of complicated parapneumonic effusion is key since antibiotherapy alone is not enough, and chest tube drainage is required.

Diaphragm

Loculated effusion

Liver

Image by: Tony Abdo, M.D & Houssein Youness, M.D

Abdo T, Bhardwaj H, Keddissi J, Youness H. Pleural Fluid Glucose Testing Using a Finger Stick Glucometer; a Novel Bedside Test with Potential for a Prompt Diagnosis and Decision. American Thoracic Society; 2018. p. A4222-A.

Excellent correlation → A low pleural fluid glucose measured by glucometer allows the clinician to make bedside decision about the need for chest tube insertion.

Pleural Fluid Glucose Testing Using a Finger Stick Glucometer?

A chest physician or thoracic surgeon should beinvolved in the care of all patients requiring chesttube drainage for pleural infection. (C)

Delay to pleural drainage is probably associated with increased morbidity, duration of hospital stay, and may lead to increased mortality

BTS pleural disease guideline 2010. Thorax. 2010 Aug 1;65(Suppl 2):ii41-53.

Outcome Prediction (RAPID Score)

N Rahman et al. Chest. , 2014, Vol.145(4), p.848-855

Chest Tube Size?

Moderate/severe pain54% (≥ 15F) v/s 27% (<15F)

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Chest Tube Size? BTS pleural disease guidelines 2010

• A small-bore catheter 10-14 F will be adequate for most cases of pleural infection. However, there is no consensus on the size of the optimal chest tube for drainage. (C)

• If a small-bore flexible catheter is used, regular flushing is recommended to avoid catheter blockage. (C)

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Fibrinolytic Therapy• Small trials and case series suggested that instillation of a fibrinolytic agent into the pleural space improved outcomes

• A large RCT trial (MIST1) did not show a benefit with streptokinase•No difference in mortality, need for surgery, radiographic outcome, or length of

hospitalization

• Limited success with intrapleural fibrinolytic agents + the thought that DNA is a main contributor to the viscosity of empyema fluid → Benefit of intrapleural administration of the enzyme deoxyribonuclease (DNase) ?

MIST1. N Engl J Med 2005; 352:865-874

Fibrinolytic + Mucolytic Agents

→ MIST2 trial, RCT

210 patients with complicated parapneumonic effusion/empyema

Patients randomized into 4 groups:•10 mg intrapleural TPA twice daily for 3 days•5 mg intrapleural DNase twice daily for 3 days•Both TPA and DNase twice daily for 3 days•Double placebo

MIST2. N Engl J Med 2011;365:518-26.

MIST2. N Engl J Med 2011;365:518-26.

Surgical Treatment• VATS is often used to debride empyemas that fail to resolve with antibiotics and chest tube drainage

• Thoracoscopic debridement ± decortication ± open thoracotomy

• In a cochrane review; when compared with tube thoracostomy, (VATS) did not result in a mortality benefit but may have reduced the length of hospital stay

• VATS performed later in the course of the disease → a higher conversion rate to thoracotomy and more complications than when it is performed early

• Early VATS v/s t-PA/DNase? → we may have an answer in few years!

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Management of Parapneumonic Effusions.

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Courtesy of Yathin S Krishnappa

Malignant Pleural Effusion

Malignant Pleural Effusion (MPE)• Second leading cause of exudative effusions. Can be a transudate (~ 5%)

• MPE accounts for > 125,000 hospital admissions/year in the US, with inpatient mortality ~ 11.6%

• Majority of MPEs arise from lung cancer, breast cancer, and lymphoma

• Poor prognosis. Median survival of 4 to 7 months from the time of diagnosis

• Survival depends on tumor subtype

• Paramalignant effusion is associated with malignancy but cytology is negative

• LENT score has been shown to accurately stratify patients into high, moderate, and low risk groups

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Survival curves according to the LENT score.

Malignant Effusion• Symptoms: dyspnea, orthopnea, and cough → impact QOL

• Asymptomatic MPEs do not need to be treated

• Given poor prognosis with MPE, treatment focuses on palliation

• Options mainly include:1. Repeated thoracentesis2. Tube thoracostomy3. Chemical or biological pleurodesis4. Tunneled pleural catheters

Pleurodesis• Process of obliterating the pleural space by causing extensive adhesion of visceral & parietal pleural surfaces by chemically or mechanically induced inflammation of the pleura

• Different sclerosing agents act by inducing the pleural mesothelial cells to start the cascade of inflammation/fibrosis• Talc (preferred), doxycycline (++ pleuritic pain), tetracycline derivatives, and

bleomycin

• Talc pleurodesis• Talc slurry (through chest tube)• Talc poudrage (aerosolized talc) accomplished with VATS or medical thoracosocpy

(higher success, but less likely performed in MPE– short life expectancy)

Pleurodesis/Chest Tube Size? • No convincing evidence. •Questionable inferiority of small bore chest tubes to achieve pleurodesis. •More discomfort with large tubes.

TIME1 Trial

• Objective = to assess effect of chest tube size & analgesia (NSAID vs opiates) on pain & clinical efficacy related to pleurodesis in MPE

• Main outcomes = pain while chest tube in place & pleurodesis efficacy at 3 months

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TIME1 Trial

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• Small bore chest tube failed to meet non-inferiority criteria for pleurodesis efficacy• Pain scores were lower in the 12F chest tube groups• No significant difference in pain score or pleurodesis between NSAIDs and Opiates groups

Indwelling pleural catheter (IPC)• Indwelling (tunneled) pleural catheter: soft silicone tube inserted percutaneously under local anesthesia ± minimal analgesics/sedation

• Patients/caregivers manage drainage → patients can be managed at home

• Spontaneous pleurodesis often occur over time (~ 50% over ~ 2 months)

• IPC v/s chest tube with pleurodesis?

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PleurX™ (Becton Dickinson - CareFusion , NJ, USA)

Rocket® IPCRocket Medical plc., UK

Aspira® BardMERITMEDICAL, UT, USA

TIME2 Trial• Unblinded RCT from 7 centers across UK (106 pts with MPE)

• IPC vs talc pleurodesis (talc slurry via chest tube)

• Primary outcome •Dyspnea at 6 weeks (daily 100 mm line visual analog scale)

• Secondary outcomes• Included among others; dyspnea at 3 & 6 months, serious adverse events, quality of life, and length of hospital stay

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• Primary outcome: no significant difference at 6 weeks. Dyspnea improved in both groups.

• Secondary outcomes:✓ Statistically significant improvement in dyspnea in IPC group at 6 months✓ Length of hospital stay was significantly shorter in IPC group

JAMA. 2012;307(22):2383-2389.

IPC v/s chest tube with pleurodesis?

1. Is the lung expandable? ➢ Trapped/non-expandable lung (+++ pleurodesis failure) → IPC

2. Patient’s overall prognosis, functional status, and social/financial situation

Management of Malignant Pleural Effusions

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• RCT, 18 centers in UK

• IPC inserted → regular drainage on an outpatient basis → At 10 days, if no significant lung entrapment, patients were randomized to receive either 4 g of talc slurry or placebo

• Primary outcome: successful pleurodesis at day 35 after randomization• 43% (IPC + talc) v/s 23% (IPC + placebo)

IPC for Non Malignant Pleural Effusion• Use of IPCs for non-malignant effusions is increasing • Complication rate comparable to that in the more established MPE population• Spontaneous pleurodesis rate is lower (~ 30%) • Main target population•Refractory cardiac effusion (after maximal therapy)•Refractory hydrothorax (w/ contraindication for TIPS)

• This should only be in select cases when maximal medical therapy has failed to control symptomatic recurrent pleural effusions• Goal: mostly palliation

Bhatnagar R, et al. Thorax 2013;0:1–3

Involve patient’s cardiologist/ hepatologist

Questions?