Pleural Effusion for Undergraduates

Pleural Effusion, etiology, investigations and management

1. PLEURAL EFFUSION D r . S.Sesha Sai (MD), Pulmonary Medicine

2. Overview Int r o d ucti o n C l assific a tion P a thogen e sis Eti o l o gy C l i n ic a l featur es Investi g ati o ns Management

3. Pleural e f f usion is defined as abnor m al accu m ulation of f luid in the pleural spac e , i.e., the space between parietal and vi s ce r al pleu r a The pleu r al space cont a ins nor m al l y 0.3 m l / kg body weight of pleu r al flui d 1 . There is a cont i nuous ci r cul a t i on of t his fluid and the ly m phat i c vessels can cope wi t h seve r al m i l l i l i tr e s of ext r a fluid per 24hours Fluid accu m ulates in the pleural cavi t y due to ei t her al t ered hydrosta t ic and onco t ic pressu r es or al t er e d per m eab i l i ty of t he pleu r a Introduct i on

4. Mo r e D e finit ions ? P a r apneumon i c E f fus i o n : p leu r al e f fus i o n associ at ed with bac t erial pneu m on ia, b r onch iec t asis, o r l un g a b sces s . Locu l a t ed E f fus i o n : F l u id an a t o m i c ally c o n f i ne d and no t f r eely f l o wi n g in the p leu r al spac e when the r e a r e adhesi on s b e t w een the vi sce r al and the par ie t al p leu r a . Su b - Pu l m o n ic E f fus i on :accumul a ti o n o f f l u id b e t w een the l ung & the d iaph r agm wh i ch gi v es the f al s e imp r ess io n o f an el e v at ed hem i - d iaph r agm

5. Pleural Effusion Parapneumonic effusion Loculated Effusion Subpulmonic Effusion

6. Composition of pleural f l uid Clear ultra f i l t rate of plasma V olume Cell s / m m 3 0.3 mL/ k g 1000 – 5000 60% 30% 5 % 5% 1-2 g/ dL <50% pla s ma leve l (10 5 -333I U /L)  plas m a lev e l ( 9 -120) ≥ plas m a lev e l ( 7. 6 - 7.64) Mesothe l ial cel l s Monocytes L ymphocytes PMN ’ s P r otein L D H G l ucose pH

7. C a n b e un i l ater a l o r b i l atera l an d cl a ssified A)B a sed o n site A p ic a l Int erlo b ar S u b - pu l monic Med i asti n al B)B a sed o n mechan i sm an d type of p l eura l fluid T ransudative (alterat i o n i n hydros t ati c an d onc o tic p r essure) E x ud a tive (alterat i o n i n p l eura l permeabi l ity ) Classification

8. c) B as e d o n mecha n is m a n d type o f p l e u ral flu i d formed Py o ge n ic C h yl o us H a emothorax Ps e ud o chyl o us Hydrothorax Urinothorax

9. Transudative pleural effusions A lteration of hydrostatic and oncotic factors that increase the formation or decrease the absorption of pleural fluid (e.g., increased mean capillary pressure [heart failure] or decreased oncotic pressure [cirrhosis or nephrotic syndrome]).

10. Exudative pleural effusions D amage or disruption of the normal pleural membranes or vasculature (e.g., tumor involvement of the pleural space, infection, inflammatory conditions, or trauma) leads to increased capillary permeability or decreased lymphatic drainage.

11. Pathogenesis Inc reas e d vasc ular pe rmeab i l i ty a l l o w s mi grat i o n o f infla m m atory c el l s (neutrop h i ls, ly m ph ocytes, an d e osin o p h i ls) i nto the p l eu r al s p a c e . The pro c ess is m ediate d by a number of cytok i ne s su c h as inter l eu ki n I L- 1 , IL- 6 , IL- 8 , tumour ne crosi s factor (TNF ) - a l ph a and p l ate let a ctivati n g factor re l ea s e d b y me s o t h el i a l c el l s li n i ng the p l eu r a l s pa c e . The res u lt is the exud ative st ag e o f a p l eu r al e f fusi o n . Th i s progres s e s to t h e fibro- p urule n t st ag e d ue to in c rea s e d f l uid ac c umulati o n an d b ac t eria l i nvasi on a c ross the damage d ep ithel ium. Neut r op hi l migrat i on o c c urs a s we ll a s a ctivati o n o f t he c o ag ulatio n c a s c a d e lea di ng to pr o-co ag ul a n t a ctivity a nd de c reas e d f i br i no l ysi s . Dep os i tio n o f fibrin i n the p l eu r a l s pa c e then lea d s to se ptati o n o r lo c ul atio n . The ple ura l flui d p H and g l u c o s e level fal l s whi l e LDH l evels incr ea s e .

12. E tiology E X UD A TIVE Infect ive : Pn eumo n ia, Bron c h i e ctasis, Pan creatitis, TB, L ung ab s ce s s Col l ag e n vasc ular d i s e a s e : S L E, Rh e umato i d art hritis, Polyarteritis Neo p lastic: l e u k emia s an d ly m ph o mas Uremia Drug s: Bromocri ptin e , amio d aro n e , n itofuranto i n , da ntro l en e , INH, P AS Po stradiatio n T raumatic

13. T R A N S U D A TI V E: R e na l cause: N e phroti c synd r o me C a rdiac cause: Con g estiv e cardiac fail u re H e pati c cause: Hep a tic fail u re N ut riti o na l: Protein en e rgy malnutrition H y p o thyroi d ism

14. P Y OGENI C : Lu n g abscess S e pticemia C h es t w a l l i n j uries R u ptur e o f oes o ph a gus R u ptur e o f su b p h ren i c a b sce s s R u ptur e o f l iv e r abscess

15. C H Y L OU S : T rauma to thoracic duct T umou r (m edias t ina l lymphoma) T ub e rculos i s L ymphatic obst r uction

16. H E MOTHO R A X : C h es t w a l l i n j uries B l ee d i n g d i sorders N e op l asm s - l e ukem i a s , lymphoma , mesothel i oma Drugs - antico a gu l a nts P u lmo n ar y i n farct i o n

17. P S E U DO C H Y LO U S: R h eumatoi d p l euritis T ub e rculos i s o r parago n imia s is (l u n g fluke infectio n ) H Y D R OTHORA X : C o ng e stive he art fa i l u re H e p a tic & R e n a l fai l ure

18. Clinical Presentation The underlying cause of the effusion usually dictates the symptoms, although patients may be asymptomatic. Pleural inflammation, abnormal pulmonary mechanics, and worsened alveolar gas exchange produce symptoms and signs of disease .

19. S ymptoms and signs Inflammation of the parietal pleura leads to pain in local (intercostal) involved areas or referred (phrenic) distributions (shoulder). Dyspnea is frequent and may be present and out of proportion to the size of the effusion. Cough can occur.

20. Physical examination Inspection: A b sent o r d imin i shed movements o f a f fect e d si d e Fu l l n es s o f c h es t w it h bu l g i n g i nter costal spaces P a l p ati o n: D i mini s he d breat h sounds ove r th e site o f the e f fusion D e creased o r a bsen t tact i l e f remitus P e rcussion: Sto n y du l l n es s to p e rcuss i on A u scultatio n : A b sence o f b reath soun d s ove r th e e f fusion V oca l resonance abs e nt S i g n s o f p n e u mon i a l i ke bron c h i a l breath i n g , crack l e s etc.

21. Investigations T ota l an d di f ferent ia l le u co c y te c ounts Ac ute p ha s e re a ctant s - whi te c el l c o un t, total n eutr o ph i l c o un t, CR P , ESR, pr o -calc it o n in d istin gu i sh ba cter i a l from viral c au s es Radio l og ical exa m in ation X -ray c h e st P A view do n e i n ere ct p o s i tio n -a tota l of 30 mL o f fl u i d i s n e ed e d to d i ag n o s e p l eur al e f fusi on c l i n ic a l l y an d rad i o l o g ical l y E v e n 50m L o f flui d c a n be d emon strat e d rad i o l o g ical l y in latera l d e c ub i tus

22. Findings Obliteratio n o f c ard i op h ren i c and c ost op h ren i c an gl es Lo c u l ated e f fusi o ns Subpul m on ic e f fus io n -co l le ction o f f l uid be l ow the d i ap h ragm wi ll lead to e l evati o n of d i ap h ragm, c o nf i rmed b y X -ray i n latera l d e c ub i tus La t er al d e c ub i tus o n s i de of e f fusi on wi ll s how a s h ift in the f l uid level T rac he a l an d medi asti n a l s h i f t s a r e s e e n i n ma s s ive e f fusi on

23. U l tras o n o gr a m Us e ful i n di f fer e nti a ting b e t w e e n l o cu l at e d p l e u ral e f fusi o n a n d tum o ur C T Sc a n H e l p ful i f the e f fusi o n i s mi n im a l o r l o cu l at e d P leu r a l fl u i d a s p ir a ti o n ( T ho r a c o c en tes i s) D i a g n ostic: H e l p s to d i f fer e nti ate b e t w e e n e x u d at e s a n d tra n su d at e s Th e ra p e utic: Mass i ve co l l e ction o r ra p i d co l l e ction o f p l e u ral flu i d S e v e re res p ir a tory d istr e ss S u sp e cted em p y ema Mass i ve me d i a stin a l sh i ft

24. Gross appearance Stra w -co l o u red B l oo d stained P u rule nt C h yl o us

25. T ransu d ate & Exudate Fe a tures T r a nsu d at e s E x u d at e s A p p e ar a nce C l e a r/S t raw co l o u red C l o u d y , p u ru l e n t, o p a l asc e nt Prot e in < 3 g/ 1 mL >3g/ 1 mL pH >7.2 <7.2 Gluc o se >40m g / dL <40m g / dL L D H L o w , <20 IU/L H i g h , > 2 0IU/L C e l l s <10 0/m m 3 >10 0/m m 3

26. L IGHT’S CRITERIA: At l e a st o n e o f the fol l o w i n g criteria s h o u l d be satisfied to i d entif y e x ud ates : P l eura l fluid to s e rum total p r otei n rati o - more than 0.5 P l eura l fluid to s e rum L D H rati o - more tha n 0.6 P l eura l fluid L D H- more than two -third o f s eru m L D H N o n e o f these criteria sh o u l d b e satisfi e d i n a t rans u dativ e e f fusion

27. Pleural fluid appearance Most transudates are clear, straw colored, nonviscid, and without odor Red-tinged pleural effusions indicate the presence of blood .

28. Bloody pleural fluid If the blood is due to thoracentesis, the degree of discoloration should clear during the aspiration. Bloody pleural fluid usually indicates the presence of malignancy, pulmonary embolism (PE), or trauma.

29. Hemothorax The presence of gross blood should lead to the measurement of a pleural fluid hematocrit. Hemothorax is defined as a pleural fluid to blood hematocrit ratio of >0.5 , and chest tube drainage should be considered.

30. Eosinophilia (>10% of total nucleated cell count) is suggestive of air or blood in the pleural space . If air or blood is not present in the pleural space, consideration should be given to fungal and parasitic infection, drug- induced disease, PE, asbestos-related disease, and Churg-Strauss syndrome.

31. Lymphocytosis (>50% of the total nucleated cell count) is suggestive of malignancy or tuberculosis. Mesothelial cells argues against the diagnosis of tuberculosis. Plasma cells suggest a diagnosis of multiple myeloma.

32. Glucose concentration A glucose concentration of <60 mg/ dL is probably due to tuberculosis, malignancy, rheumatoid arthritis, or parapneumonic effusion. For parapneumonic pleural effusions with a glucose of <60 mg/dL, tube thoracostomy should be considered.

33. Pleural fluid with a low pH A pH of <7.3 is seen with empyema, tuberculosis, malignancy, collagen vascular disease, or esophageal rupture.

34. Amylase An elevation of amylase suggests that the patient has pancreatic disease, malignancy, or esophageal rupture. Malignancy and esophageal rupture have salivary amylase elevations and not pancreatic amylase elevations.

35. Turbid or milky fluid After it is centrifuged. If the supernatant clears, the cloudiness is likely due to cells and debris. If the supernatant remains turbid, pleural lipids should be measured. Elevation of triglycerides (>110 mg/dL) suggests that a chylothorax is present, usually due to disruption of the thoracic duct from trauma, surgery, or malignancy (i.e., lymphoma).

36. Cyto l ogy Cytology is positive in approximately 60% of malignant effusions. The volume of pleural fluid analyzed does not impact the yield of cytologic diagnosis. Repeat thoracentesis increases the diagnostic yield.

37. Urinothorax Due to obstructive uropathy Urine arrives in the pleural space either retroperitoneally under the posterior diaphragm, or via the retroperitoneal lymphatics Pleural fluid smells of urine. Pleural fluid Creatinine ≈ Serum Creatinine

38. Other investigations S u spected TB A d en o si n e de a minase (> 50 IU/L) B e ta2 - microglo b u l in L yso z yme I I I (> 2 mcg/mL) P C R ( S e n s 10 % , S p ec 95%) • AFB ( smear 10 - 20% ; cx 2 5 - 50 %) S u spected R h eumatoid P l eura l RF L o w g l uc o se S u spected S L E S e rum Complement P l eura l A N A L E cells S u spected P n eumon i a pH S u spected P a ncreatitis P l e u ral Amy l ase

39. P l e u ral B i o p sy Ca n b e don e a t ma x imu m dullnes s o n pe rcussion or at a m a x imum t hickening of p l eura. Abra m ’ s pleural biops y needl e i s use d fo r biopsy Most h e l p ful i n ev a l u ati n g for TB Limi t e d u tilit y fo r C A ( 4 - 50 % pos i tive) Repea t cy t olog y x 3 Sarc oi d , funga l : might b e helpful

40. Management S U P P O R TIVE T R E A TM E NT O x ygen i s neces s ar y i f S pO 2 <92% F l u i d therapy i f ch i l d de h ydrated o r u na b l e /unwilli ng i n drink i n g w a ter Initiate I V anti b i o tics A n a l ges i cs an d anti pyret ics C h es t radi o graph y & U/S

41. Medical T re a t the c a u s e Pneu m oni a - initia l a n tibiotic tr e atm e nt A) Follow in g c o mmunity a c qui r e d pne u monia C efuroxime Co- amoxiclav P enicilli n & f l ucloxacillin Amo x icilli n & flucloxa x illin Clin d amycin B ) Ho s pi t a l acq u ire d pneumonia Broader s p e c tr u m antibiotic s that c o ver ae r obi c g r a m neg a ti v e ro ds

42. T u b erc u losi s - C a tegory I tr e a tment 2 H R Z E+4 H RE Predn i sol o n e 1 - 2 m g / kg or a ll y 4 - 6week s pr om o tes rap i d a b sorpti o n o f the p l e u ral flu i d a n d prev e nts fibrosis C o nge s t iv e cardia c fai lur e - t r ea t w it h diure t ic s and othe r a n t i -fai l ur e med i cati o ns

43. Su r gical Pleural f l uid as p irat i o n i s d on e by us i n g a wid e b ore ne e d l e . If the flui d i s th i ck an d c a nn ot b e dr ai n e d b y a ne e d l e , a n i nterc o stal dr ai n ag e (un de r wate r s e a l) a t the most dependant pa rt s ho ul d b e d o ne .

44. Tube Thoracostomy Pneumothorax Pleural fluid loculat ed Recurrent Pleural effusion - malignancy Effusion filling more than half the hemithorax Air fluid level – Hydro/ Pyopneumothorax Pus in the pleural space - Empyema Hemothorax / Chylothorax Para pneumonic effusion Positive stain for microorganisms Positive pleural fluid cultures Pleural fluid pH <7.2 Pleural fluid glucose <60 mg/ dL

45. Underwater seal bag is used as one way valve mechanism. The air or fluid/pus from the pleura enters the underwater drainage bag, but the atmospheric air cannot enter pleura due to under water seal

46. Failure to drain with a single small-bore tube should also lead to thoracic surgery consultation to avoid delays in case video assisted thoracoscopy (VATS) becomes necessary. VATS

47. Chemical pleurodesis Chemical pleurodesis is an effective therapy for recurrent effusions . This treatment is recommended in patients whose symptoms are relieved with initial drainage but who have rapid reaccumulation of fluid . Talc slurry - Effective and inexpensive . Doxycycline or minocycline can also be instilled into the pleural space via a chest tube. Pain is more prevalent and severe following doxycycline and minocycline than following talc.

48. Chronic indwelling pleural catheters Provide good control of effusion-related symptoms via intermittent drainage .

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