Analisi del Liquido Pleurico

L’analisi del liquido pleurico è utilizzata come supporto alla diagnosi della causa di accumulo di liquido nella cavità pleurica (versamento pleurico). Il pannello di esami iniziale da eseguire include:

• Proteine, albumina, LDH
• Conta cellulare
• Aspetto del liquido

I risultati vengono confrontati con quelli ottenuti da un campione di sangue, per discriminare se il fluido in oggetto è un trasudato o un essudato. 

• Trasudato; tipicamente causato da cirrosi o insufficienza cardiaca congestizia. Se il liquido è identificato come trasudato, generalmente non sono necessari ulteriori esami
• Essudato; per stabilirne la causa possono essere richiesti esami aggiuntivi, quali:
  • Esami per misurare glucosio, lattato, amilasi, trigliceridi, colesterolo, creatinina, NT-proBNP e/o marcatori tumorali quali CEA a livello del liquido pleurico; attualmente, l'utilità clinica di questi esami è ancora dibattuta
  • Esame microscopico del liquido pleurico; per valutare la quantità e l'aspetto di leucociti (WBC), eritrociti (RBC) e microrganismi quali batteri o funghi
  • Citologia; i laboratori possono utilizzare speciali centrifughe (citocentrifughe) per concentrare le cellule del liquido sul fondo della provetta. Il campione viene poi posizionato sul vetrino, trattato con speciali coloranti e valutato per rilevare la presenza di eventuali cellule anomale, come le cellule tumorali
  • Colorazione di Gram; per l’osservazione diretta di batteri o funghi al microscopio. Normalmente, non dovrebbero essere presenti microrganismi nel liquido pleurico
  • Esame micotico; può includere terreni di coltura fungina e test di sensibilità
  • Adenosina-deaminasi; marcatore di tubercolosi nel liquido pleurico

Esami meno comuni sono richiesti per evidenziare malattie infettive, come i test per i virus, per i micobatteri (striscio e coltura per i batteri AFB) e per i parassiti.

L’analisi del liquido pleurico può essere prescritta se si sospetta la presenza di pleurite e/o versamento di liquido pleurico a seguito della conferma con RX del torace. Può essere prescritta quando il paziente manifesta una combinazione dei seguenti segni e sintomi:

• Dolore toracico che peggiora durante i respiri profondi
• Tosse
• Difficoltà respiratorie, respiro affannoso
• Febbre, brividi
• Affaticamento

I risultati degli esami contribuiscono a distinguere tra i vari tipi di liquido pleurico e a stabilire la causa dell’accumulo di liquido. Un pannello di esami iniziale effettuato sul liquido pleurico permette di discriminare se si tratta di un trasudato o un essudato:

Se il liquido in questione è un essudato possono essere eseguiti esami aggiuntivi e le cause associate possono includere:

Caratteristiche fisiche; l’aspetto normale di un campione di liquido pleurico è generalmente paglierino e chiaro. Un aspetto anomalo può suggerire la presenza di condizioni o patologie in atto:

• Il liquido pleurico rossastro può indicare la presenza di sangue
• L'aspetto lattescente può indicare il coinvolgimento del sistema linfatico
• La torbidità può indicare la presenza di infezione e/o di globuli bianchi, oppure la perdita di liquido (linfa) dal sistema linfatico. Il drenaggio del liquido linfatico dal sistema linfatico verso il sistema venoso del torace, un trauma o il linfoma possono determinare la presenza di linfa nel liquido pleurico (chilotorace)

Esami chimici; possono essere effettuati in aggiunta alla misura delle proteine o dell’albumina, anche se la loro utilità clinica è tuttora in discussione. Alcuni esempi includono:

• Glucosio; generalmente la sua concentrazione dovrebbe essere simile a quella del glucosio ematico. Può risultare ridotto in caso di infezione ed artrite reumatoide
• Lattato; può aumentare a seguito di infezione
• Amilasi; aumenta in corso di pancreatite, rottura esofagea o neoplasia
• Trigliceridi; possono essere aumentati in caso di coinvolgimento del sistema linfatico
• Marcatori tumorali, quali il CEA; utili ad identificare il tipo di neoplasia presente
   

Valutazione microscopica; normalmente, il liquido pleurico è caratterizzato da quantità ridotte di globuli bianchi (WBC) ed assenza di eritrociti (RBC) e microrganismi. 

• Conta delle cellule totali; l’incremento dei WBC può essere osservato in corso di infezioni ed altre cause di pleurite. L’aumento dei RBC può indicare la presenza di traumi, tumori o infarto polmonare
• Conta differenziale dei WBC; consente di determinare la percentuale dei diversi tipi di globuli bianchi. L'aumento dei neutrofili può essere osservato in seguito ad infezioni batteriche; l'incremento dei linfociti in seguito a tumori e tubercolosi
• Citologia; il campione viene sottoposto a centrifugazione, trattato con speciali colorazioni ed esaminato al microscopio per valutare la presenza di eventuali cellule anomale; soprattutto se si sospetta la presenza di mesotelioma o tumore metastatico. Il riscontro di cellule anomale, quali cellule tumorali o cellule del sangue immature, può indicare la forma tumorale coinvolta.
   

Esami di malattie infettive:

• Colorazione di Gram; non dovrebbero essere presenti microrganismi nel liquido pleurico
• Coltura batterica e test di sensibilità; se sono presenti batteri, il test di suscettibilità può essere effettuato per individuare la corretta terapia antimicrobica da prescrivere. Se non sono presenti batteri, non è comunque possibile escludere l’infezione; essi potrebbero essere presenti in numero ridotto oppure la loro crescita può risultare inibita da una terapia antibiotica effettuata in precedenza
• Esame micotico; se la coltura è positiva, è possibile effettuare il test di sensibilità per identificare il/i fungo/i causa dell'infezione
• Adenosina-deaminasi; un livello marcatamente elevato nel liquido pleurico in presenza di sintomi riconducibili alla tubercolosi indica la probabile presenza di infezione da Mycobacterium tuberculosis. Il sospetto è rafforzato in pazienti che vivono in aree con alta prevalenza della tubercolosi (per maggiori informazioni a riguardo, consultare l'articolo sul test dell'Adenosina Deaminasi).

Altri test meno comunemente utilizzati per le malattie infettive permettono di identificare, come causa dell’accumulo di liquido, un’infezione virale, da micobatteri (come i micobatteri che causano la tubercolosi) o da parassiti.

Possono essere richiesti glucosio, proteine, albumina o LDH su sangue, per compararne le concentrazioni con quelle del liquido pleurico

La toracentesi consiste nella raccolta del liquido pleurico dalla cavità pleurica tramite l'utilizzo di una siringa. Il paziente deve trovarsi in posizione seduta con le braccia sollevate. Viene applicato un anestetico locale e successivamente inserito l’ago nella cavità pleurica per aspirare il campione. Può essere utilizzata una guida ecografica per facilitare la procedura. È importante non muoversi durante tutta la procedura. Raramente, la toracentesi comporta effetti collaterali. Tuttavia, alcune delle complicanze potenzialmente associate includono pneumotorace, nel caso in cui l'ago perfori il polmone, con conseguente accumulo di aria nello spazio pleurico e collasso polmonare, emorragie, infezioni, edema polmonare, lesioni epatiche o spleniche, nel caso in cui il fegato o alla milza vengano erroneamente perforate dall’ago durante la procedura.

Sì; talvolta viene eseguita per drenare un eccesso di liquido pleurico e rilevare la pressione nei polmoni. É possibile utilizzare un catetere per drenare grandi quantità di liquido e gli accumuli ricorrenti dello stesso.

Sì; se la quantità di liquido accumulata è ridotta, il versamento può risolversi senza trattamento.

Il versamento pleurico può rivelarsi grave se il liquido in eccesso esercita una pressione a livello polmonare, con conseguenti difficoltà respiratorie. L’accumulo di liquido nello spazio pleurico non è mai fisiologico e deve essere valutato per determinarne la causa. Inoltre, le cause del versamento possono essere gravi e richiedere un approccio terapeutico specifico. Alcuni esempi di cause includono: insufficienza cardiaca, polmonite ed altre infezioni, tumore, ostruzione dell'arteria polmonare (embolia polmonare) e patologie epatiche.

A.D.A.M. Medical Encyclopedia. Creatinine blood test. Updated July 4, 2019. Accessed January 10, 2022. https://medlineplus.gov/ency/article/003475.htm

A.D.A.M. Medical Encyclopedia. Empyema. Updated August 25, 2019. Accessed January 11, 2022. https://medlineplus.gov/ency/article/000123.htm

A.D.A.M. Medical Encyclopedia. Pleural fluid analysis. Updated October 14, 2019. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003624.htm

A.D.A.M. Medical Encyclopedia. Pleural fluid smear. Updated October 14, 2019. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003721.htm

A.D.A.M. Medical Encyclopedia. Pleural fluid culture. Updated November 9, 2019. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003725.htm

A.D.A.M. Medical Encyclopedia. Lactate dehydrogenase test. Updated February 6, 2020. Accessed January 10, 2022. https://medlineplus.gov/ency/article/003471.htm

A.D.A.M. Medical Encyclopedia. CT angiography – chest. Updated April 5, 2020. Accessed January 11, 2022. https://medlineplus.gov/ency/article/007676.htm

A.D.A.M. Medical Encyclopedia. Brain natriuretic peptide test. Updated June 25, 2020. Accessed January 10, 2022. https://medlineplus.gov/ency/article/007509.htm

A.D.A.M. Medical Encyclopedia. Cytology exam of pleural fluid. Updated August 3, 2020. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003866.htm

A.D.A.M. Medical Encyclopedia. Pleural effusion. Updated August 3, 2020. Accessed January 4, 2022. https://medlineplus.gov/ency/article/000086.htm

A.D.A.M. Medical Encyclopedia. Thoracentesis. Updated August 3, 2020. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003420.htm

A.D.A.M. Medical Encyclopedia. Pleural fluid Gram stain. Updated November 27, 2020. Accessed January 4, 2022. https://medlineplus.gov/ency/article/003722.htm

A.D.A.M. Medical Encyclopedia. Enzyme. Updated January 16, 2021. Accessed January 10, 2022. https://medlineplus.gov/ency/article/002353.htm

A.D.A.M. Medical Encyclopedia. Amylase – blood. Updated January 24, 2021. Accessed January 10, 2022. https://medlineplus.gov/ency/article/003464.htm

Akinfemiwa O, Muniraj T. Amylase. In: StatPearls. Updated July 31, 2021. Accessed January 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK557738/

Boka K. Pleural effusion workup. In: Soo Hoo GW, ed. Medscape. Updated October 15, 2021. Accessed January 10, 2022. https://emedicine.medscape.com/article/299959-workup#showall

D’Agostino HP, Edens MA. Physiology, pleural fluid. In: StatPearls. Updated September 1, 2021. Accessed January 4, 2022. https://www.ncbi.nlm.nih.gov/books/NBK513353/

Dezube R. How to do thoracentesis. Merck Manuals Professional Edition. Updated September 2019. Accessed January 4, 2022. https://www.merckmanuals.com/professional/pulmonary-disorders/how-to-do-pulmonary-procedures/how-to-do-thoracentesis

Dezube R. Needle biopsy of the pleura or lung. Merck Manuals Consumer Edition. Updated May 2021. Accessed January 4, 2022. https://www.merckmanuals.com/home/lung-and-airway-disorders/diagnosis-of-lung-disorders/needle-biopsy-of-the-pleura-or-lung

Dezube R. Pleural biopsy. Merck Manuals Professional Edition. Updated May 2021. Accessed January 4, 2022. https://www.merckmanuals.com/professional/pulmonary-disorders/diagnostic-and-therapeutic-pulmonary-procedures/pleural-biopsy

Dezube R. Thoracentesis. Merck Manuals Consumer Edition. Updated May 2021. Accessed January 4, 2022. https://www.merckmanuals.com/home/lung-and-airway-disorders/diagnosis-of-lung-disorders/thoracentesis

Farhana A, Lappin SL. Biochemistry, lactate dehydrogenase. In: StatPearls. Updated May 7, 2021. Accessed January 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK557536/

Hantzidiamantis PJ, Lappin SL. Physiology, glucose. In: StatPearls. Updated September 20, 2021. Accessed January 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK545201/

Heffner JE. Patient education: Thoracentesis (beyond the basics). In: Maldonado F, ed. UpToDate. Updated April 14, 2021. Accessed January 4, 2022. https://www.uptodate.com/contents/thoracentesis-beyond-the-basics

Heffner JE, Mayo P. Ultrasound-guided thoracentesis. In: Broaddus VC, ed. UpToDate. Updated June 29, 2021. Accessed January 4, 2022. https://www.uptodate.com/contents/ultrasound-guided-thoracentesis

Heffner JE. Diagnostic evaluation of a pleural effusion in adults: Initial testing. In: Maldonado F, ed. UpToDate. Updated September 16, 2021. Accessed January 4, 2022. https://www.uptodate.com/contents/diagnostic-evaluation-of-a-pleural-effusion-in-adults-initial-testing

Janahi IA, Fakhoury K. Epidemiology, clinical presentation, and evaluation of parapneumonic effusion and empyema in children. In: Redding G, Kaplan SL, eds. UpToDate. Updated November 3, 2021. Accessed January 11, 2022. https://www.uptodate.com/contents/epidemiology-clinical-presentation-and-evaluation-of-parapneumonic-effusion-and-empyema-in-children

Lee YCG. Diagnostic evaluation of pleural effusion in adults: Additional tests for undetermined etiology. In: Maldonado F, ed. UpToDate. Updated May 12, 2020. Accessed January 4, 2022. https://www.uptodate.com/contents/diagnostic-evaluation-of-pleural-effusion-in-adults-additional-tests-for-undetermined-etiology

Light RW. Pleural effusion. Merck Manuals Consumer Edition. Updated January 2021. Accessed January 4, 2022. https://www.merckmanuals.com/home/lung-and-airway-disorders/pleural-and-mediastinal-disorders/pleural-effusion

Light RW. Pleural effusion. Merck Manuals Professional Edition. Updated January 2021. Accessed January 4, 2022. https://www.merckmanuals.com/professional/pulmonary-disorders/mediastinal-and-pleural-disorders/pleural-effusion

Mayo Clinic Laboratories. Cell count and differential, body fluid. Date unknown. Accessed January 4, 2022. https://www.mayocliniclabs.com/test-catalog/overview/8419

Mayo Clinic Laboratories. Protein, total, body fluid. Date unknown. Accessed January 10, 2022. https://www.mayocliniclabs.com/test-catalog/overview/606619

MedlinePlus: National Library of Medicine. ADA gene. Updated July 1, 2013. Accessed January 10, 2022. https://medlineplus.gov/genetics/gene/ada/

MedlinePlus: National Library of Medicine. Lymphatic diseases. Updated September 3, 2014. Accessed January 11, 2022. https://medlineplus.gov/lymphaticdiseases.html

MedlinePlus: National Library of Medicine. Abscess. Updated May 2, 2016. Accessed January 11, 2022. https://medlineplus.gov/abscess.html

MedlinePlus: National Library of Medicine. Triglycerides. Updated January 23, 2017. Accessed January 10, 2022. https://medlineplus.gov/triglycerides.html

MedlinePlus: National Library of Medicine. Cholesterol levels: What you need to know. Updated December 4, 2017. Accessed January 10, 2022. https://medlineplus.gov/cholesterollevelswhatyouneedtoknow.html

MedlinePlus: National Library of Medicine. Pleural fluid analysis. Updated September 9, 2021. Accessed January 4, 2022. https://medlineplus.gov/lab-tests/pleural-fluid-analysis/

Mercer RM, Corcoran JP, Porcel JM, Rahman NM, Psallidas I. Interpreting pleural fluid results. Clin Med (Lond). 2019;19(3):213-217. doi:10.7861/clinmedicine.19-3-213

National Heart, Lung, and Blood Institute. Pleural disorders. Updated October 15, 2019. Accessed January 4, 2022. https://www.nhlbi.nih.gov/health-topics/pleural-disorders

Philips JB III. Approach to the neonate with pleural effusions. In: Martin R, ed. UpToDate. Updated June 24, 2020. Accessed January 11, 2022. https://www.uptodate.com/contents/approach-to-the-neonate-with-pleural-effusions

UpToDate. Patient education: Pleural effusion (the basics). Date unknown. Accessed January 4, 2022. https://www.uptodate.com/contents/pleural-effusion-the-basics

Wiederhold BD, Amr O, Modi P, O’Rourke MC. Thoracentesis. In: StatPearls. Updated July 31, 2021. Accessed January 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK441866/

(2020 February 26, Updated). Pleural Fluid Analysis. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/lab-tests/pleural-fluid-analysis/. Accessed July 2020.

Light, R. (2019 July, Updated). Pleural Effusion. Merck Manual Consumer Version. Available online at https://www.merckmanuals.com/home/lung-and-airway-disorders/pleural-and-mediastinal-disorders/pleural-effusion. Accessed July 2020.

(2019 October 31, Updated). Cardiopulmonary Syndromes (PDQ) – Patient Version. National Cancer Institute. Available online at https://www.cancer.gov/about-cancer/treatment/side-effects/cardiopulmonary-pdq#section/_210. Accessed July 2020.

Hadjiliadis, D. et al (2018 July 28, Updated). Pleural effusion. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/000086.htm. Accessed July 2020.

(2019 March 1). Management of Malignant Pleural Effusions Clinical Practice Guidelines (2019). Medscape Clinical Practice Guidelines. Available online at https://reference.medscape.com/viewarticle/909652. Accessed July 2020.

Bracey, A. and Goldenberg, W. (2017 July 17, Updated). Emergent Management of Pleural Effusion. Medscape Emergency Medicine. Available online at https://emedicine.medscape.com/article/807375-overview. Accessed July 2020.

Feller-Kopman, D. et al. (2018 October 1). Management of Malignant Pleural Effusions An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med Vol 198, Iss 7, pp 839–849. Available online at https://www.atsjournals.org/doi/pdf/10.1164/rccm.201807-1415ST. Accessed July 2020.

Skok, K. et. al. (2019 August). Malignant Pleural Effusion and Its Current Management: A Review. Medicina (Kaunas). 2019 Aug; 55(8): 490. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723530/. Accessed July 2020.

(June 9, 2019) University of Michigan Medicine. Pleural Effusion. Available online at https://www.uofmhealth.org/health-library/abs2938. Accessed July 2020.

Arup Laboratories. Body Fluid Reference Intervals and/or Interpretive Information for Select Analytes. Available online at https://www.aruplab.com/bodyfluids. Accessed July 2020.

Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 904-909.

Wu, A. (2006).  Tietz Clinical Guide to Laboratory Tests, Fourth Edition.  Saunders Elsevier, St. Louis, Missouri. Pp 868-869, 1535-1536.

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. pp 1496.

Forbes, B. et. al. (© 2007). Bailey & Scott's Diagnostic Microbiology, Twelfth Edition: Mosby Elsevier Press, St. Louis, Missouri. Pp 904 – 913.

Schriber, A. (2007 November 12). Pleural fluid analysis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003624.htm. Accessed on 6/21/08.

Kaufman, D. (2006 August 7, Updated). Thoracentesis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003420.htm. Accessed on 6/21/08.

Kaufman, D. (2006 August 7, Updated). Pleural effusion. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000086.htm. Accessed on 6/21/08.

Kaufman, D. (2006 May 3, Updated). Pulmonary actinomycosis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000074.htm. Accessed on 6/21/08.

Garlipp, C. et. al. (2008 January 18). Pleural Effusions: Stability of Samples for White Blood Cell and Differential Counts. Medscape from Laboratory Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/568386. Accessed on 6/21/08.

Lababede, O. (2007 August 10). Effusion, Pleural. eMedicine [On-line information]. Available online at http://www.emedicine.com/radio/TOPIC233.HTM. Accessed on 6/21/08.

(2007 August). What Are Pleurisy and Other Disorders of the Pleura?. NHLBI [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/pleurisy/pleurisy_whatare.html. Accessed on 6/28/08.

Knight JA, Kjeldsberg CR: Cerebrospinal, synovial, and serous body fluids. In Henry's Clinical Diagnosis and Laboratory Management by Laboratory Methods, 21sted. MCpHerson RA & Pincus MR, eds. Saunders:New York, pp 426-454, 2006.

Rubins, J. and Mosenifar, Z. (Updated 2012 May 21). Pleural Effusion. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/299959-overview. Accessed June 2012.

Blaivas, A. (2011 December 15). Pleural fluid analysis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003624.htm. Accessed June 2012.

Light, R. (Revised 2012 May). Pleural Effusion. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed June 2012.

(2011 September 21). How Are Pleurisy and Other Pleural Disorders Diagnosed? National Heart Lung and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/health-topics/topics/pleurisy/diagnosis.html. Accessed June 2012.

Crawford Mechem, C. (Updated 2011 July 8). Emergent Management of Pleural Effusion. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/807375-overview. Accessed June 2012.

Rodriguez-Panadero, F. and Romero-Romero, B. (2011 August 31). Management of Malignant Pleural Effusions. Medscape News from Curr Opin Pulm Med. 2011;17(4):269-273 http://www.medscape.com/viewarticle/745553. Accessed June 2012.

Dugdale, D. (2010 September 15). Thoracentesis. MedlinePlus Medical Encyclopedia. [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003420.htm. Accessed June 2012.

Rubins, J. (2014 September 5, Updated). Pleural Effusion. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/299959-overview. Accessed 11/15/15.

Michelson, P. (2014 December 3, Updated). Pediatric Empyema. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/1001747-overview. Accessed 11/15/15.

Hadjiliadis, D. (2014 August 25, Updated). Pleural effusion. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000086.htm. Accessed 11/15/15.

Hadjiliadis, D. (2013 December 3, Updated). Pleural fluid analysis. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003624.htm. Accessed 11/15/15.

Limsukon, A. and Soo Hoo, G. (2014 March 13, Updated). Parapneumonic Pleural Effusions and Empyema Thoracis. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/298485-overview. Accessed 11/15/15.

Brauner, M. and Bailey, R. (2013 December 6, Updated). Thoracentesis. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/80640-overview#showall Accessed 11/15/15.