Pleural Effusion

Pathophysiology

• Systemic factors (eg. T PCWP. i oncotic pressure) — transudate effusion

• Local factors (ie. A pleural surface permeability) — exudative effusion

Transudates

• Congestive heart failure (40%): 80% bilateral, usually cardiomegaly on CXR

occasionally exudative (especially after aggressive diuresis or if chronic), but 75% of exudative effusions in CHF Pts found to have non-CHF cause (Owa 2001122:1518)

• Constrictive pericarditis

• Cirrhosis ("hepatic hydrothorax"): diaphragmatic defect w/ passage of ascitic fluid often right-sided (2/3) & massive (even w/o marked ascites)

• Nephrotic syndrome: usually small, bilateral, asymptomatic (r/o PE b/c hypercoag)

• Other: PE (usually exudate), malignancy (lymphatic obstruction), myxedema. CAPO

Exudates

• Lung parenchymal infection (25%)

bacterial (parapneumonic): can evolve along spectrum of exudative (but sterile) -»

fibropurvlent (infected fluid) • organization (fibrosis & formation of rigid pleural peel) mycobacterial: 50% lymphs 80% of the time. ADA -40. pleural bx 70% Se fungal, viral (usually small), parasitic (eg. amebiasis, echinococcosis, paragonimiasis)

• Malignancy (15%): primary lung cancer most common, metastases (especially breast.

lymphoma, etc.). mesothelioma (✓ serum osteopontin levels: nejm 2005:353:15)

• Pulmonary embolism (10%): effusions in 40% of PEs: exudate (75%) > transudate

(25%): hemorrhagic—must have high suspicion b/c presentation highly variable

• Collagen vascular disease: RA (large). SLE (small). Wegener's. Churg-Strauss

• Gastrointestinal diseases: pancreatitis, esophageal rupture, abdominal abscess

• Hemothorax (HcWHctt^ood ^50%): trauma. PE. malignancy, coagulopathy, leaking aortic aneurysm, aortic dissection, pulmonary vascular malformation

• Chylothorax (triglycerides >110): thoracic duct damage due to trauma, malignancy. LAM

Post-CABG: left-sided: initially bloody, clears after several wks

Dressler's syndrome (pericarditis & pleuritis post-MI), uremia, post-radiation therapy

Asbestos exposure: benign; ® eosinophils

Drug-induced (eg. nitrofurantoin, methysergide. bromocriptine, amiodarone): © eos. Meigs's syndrome benign ovarian tumor -» ascites & pleural effusion Yellow-nail syndrome: yellow nails, lymphedema, pleural effusion, bronchiectasis

Diagnostic studies

• Thoracentesis

Indications: all effusions >1 cm in decubitus view if suspect due to CHF. can diurese and see if effusions resolve (75% do so in 48 h) asymmetry, fever, chest pain. or failure to resolve -»thoracentesis parapneumonics should be tapped ASAP (cannot exclude infxn clinically) Diagnostic studies: ✓ total protein. LDH. glucose, cell count w/ differential, gram stain &

culture. pH; remaining fluid for additional studies as dictated by clinical scenario Complications: PTX (5-10%). hemothorax ( 1%). re-expansion pufm. edema (rf > T.5 L removed), spleen/liver lac.; post-tap CXR not routinely needed (annofc 1996,124:816)

• Transudate vs. exudate (Awwh 1972:77 507)

Light's criteria exudate TP^TP^ -0.5 or LDH^LDH^ >0.6 or LDH*

•2/3 ULN of LDH*™: 98% Se. 83% Sp; best Se of all methods (Chat 1995:107:1604); however will misidentify 25% of transudates as "exudates";if clinically suspect transudate but meets criterion for exudate, confirm w/ test w/ higher Sp exudative criteria w/ better Sp: serum-effusion alb gradient - 1.2; Se 87%. Sp 92%

choU -45 mg/dl and LDHe« 200; 90% Se. 98% Sp (no serum required) CHF effusions: TP may T with diuresis or chronicity -* "pseudoexudate"; use albumin gradient 1.2.choU >60 md/dl (Se 54%. Sp 92%). or clinical judgment to help distinguish (Oat 2002:122:1524)

• Complicated vs. uncomplicated parapneumonic (Chat 1995:108 299)

complicated " © gram stain or culture or pH <7.2 or glucose 60

complicated parapneumonic effusions usually require drainage to achieve resolution empyema frank pus. also needs drainage to achieve resolution

Additional pleural fluid studies (nejm 2002.346: 1971) WBC & diff. exudates tend to have IWBC vs. transudates but nonspecific neutrophils -• parapneumonic. PE. pancreatitis lymphocytes (>50%) — cancer.TB. rheumatologic eos (>10%) -♦ blood, air, drug rxn. asbestos, paragonimiasis. Churg-Strauss. PE RBC: Hctrf 1-20% — cancer. PE. trauma; Hct.ft/Hctfcioo.j >50% -» hemothorax AFB: yield in TB 0-10% w/ stain. 11-50% w/ culture. 70% w/ pleural bx adenosine deaminase (ADA): seen w/ granulomas. >70 suggests TB. <40 excludes TB cytology: yield is 55% w/1 sample. 70% w/ 3 samples; 1 sample volume — no A Se glucose: ' 60 mg/dl — malignancy, infection, RA

amylase: seen in pancreatic disease and esophageal rupture (salivary amylase) rheumatoid factor, Ch50,ANA limited utility in dx collagen vascular disease triglycerides: >110 — chylothorax.50-110 ✓ lipoprotein analysis for chylomicrons cholesterol: >60; seen in chronic effusions (eg. CHF, RA) creatinine: effusion/serum ratio >1 -» urinothorax Chest CT; pleural biopsy;VATS

Characteristics of Pleural Fluid (not diagnostic criteria)

Etiology

Appear

WBC

RBC

pH

Glc

Comments

diff

CHF

clear, straw

<1,000

<5,000

normal

-serum

bilateral.

lymphs

cardiomegaly

Cirrhosis

clear, straw

<1.000

5.000

normal

»•serum

light-sided

Uncomplicated

turbid

5-40.000

<5.000

normal

» serum

parapneumonic

polys

to 1

(>40)

Complicated

turbid to

5-40.000

<5,000

U

U

need drainage

parapneumonic

purulent

polys

(-40)

Empyema

purulent

25-100.000

<5,000

Ui

U

need drainage

polys

Tuberculosis

serosang.

5-10.000

<10.000

normal

normal

•»AFB

lymphs

to .

to 1

® ADA

Malignancy

turbid to

1-100.000

100.000

normal

normal

@ cytology

bloody

lymphs

toi

toi

Pulmonary

sometimes

1-50.000

100.000

normal

-serum

no infarct —

embolism

bloody

polys

transudate

Rheumatoid

turbid

1-20.000

<1,000

i

RA iU

T RF. 1 C«50

Arthritis/SLE

variable

SlEnl

T ¡mm. complex

Pancreatitis

serosang.

1-50.000

<10.000

normal

-serum

left-sided.

to turbid

polys

t amylase

Esophageal

turbid to

■ 5.000

<10.000

a

left-sided.

rupture

purulent

■50.000

• Symptomatic effusion: therapeutic thoracentesis, treat underlying disease process

• Parapneumonic effusion (Chest 2000.118:11S8)

uncomplicated -» antibiotics for pneumonia

>1/2 hemithorax or complicated or empyema -* tube thoracostomy

(o/w risk of organization and subsequent need for surgical decortication) loculated — tube thoracostomy or VATS; intrapleural lytics w/o dear benefit (although largest trial used lytics late and w/ small-bore chest tubes, nejm 2005.351865)

• Malignant effusion: serial thoracenteses vs. tube thoracostomy • pleurodesis (success rate 80-90%) (Cochrane database 200«. CD002916); pleurodesing agent (talc, bleo, doxy) controversial; systemic steroids and pH <7.2 assoc. w/1 likelihood to fail pleurodesis

• TB effusions: effusion will often resolve spontaneously; however, treat Pt for active TB

• Hepatic hydrothorax

Rx: A pressure gradient (ie, i ascitic fluid volume. NIPPV)

avoid chest tubes; prn thoracenteses. pleurodesis.TIPS or VATS closure of diaphragmatic defects if medical Rx fails; NIPPV for acute short-term management spontaneous bacterial empyema (SBEM) can occur (even w/o SBP being present).

.. thoracentesis if suspect infection transplant is definitive treatment and workup should begin immediately

VENOUS THROMBOEMBOLISM (VTE)

Definitions

• Caif-vein thrombosis: less likely to cause significant thromboembolism, 80% resolve spont.

• Proximal deep venous thrombosis (DVT): thrombosis of popliteal, femoral, or iliac veins

(nb. "superificiar' femoral vein is part of the deep venous system)

• Pulmonary embolism (PE): thrombosis that originates in the venous system and embolizes to the pulmonary arterial circulation: 600.000 cases per yr

• Virchow's triad for thrombogenesis alterations in blood flow (ie. stasis): bed rest, inactivity. CHF. CVA w/in 3 mos.

air travel 8 h (NE¡M 2001:345:779) injury to endothelium: trauma, surgery, prior DVT

thrombophilia (50% ©): APC resistance, protein C or S deficiency. APS. prothrombin gene mutation, hyperhomocysteinemia OCP. HRT. tamofixen, raloxifene

• Malignancy (12% of "idiopathic" DVTÍPE)

• History of thrombosis

Clinical manifestations (Ctai 1991:100598 s Am/Corf 1991.^8 1723)

• DVT: calf pain, edema, venous distention, pain on dorsiflexion. asx phlegmasia cerúlea do/ens: stagnant blood — edema, cyanosis, pain

• PE: dyspnea (73%). pleuritic chest pain (66%). cough (37%). hemoptysis (13%). asx massive PE with acute cor pulmonale — syncope, hypotension, PEA

• 50% of Pts with symptomatic DVT have asx PE: 60% of patients with PE have DVT

Physical exam (Owst 1991:100:598« 2000:117:39; Am I Cord 1991:68:17231

• DVT (Se 60-88%. Sp 30-72%.¡AMA 1998:279 1094): lower extremity swelling ( -3 cm c/w unaffected side), edema, erythema, warmth, tenderness, palpable cord. ' Homan's sign (calf pain on dorsiflexion, seen in <5% of patients)

• PE: tachypnea ( -70%). crackles (51%). tachycardia (30%), fever, cyanosis, pleural friction rub, loud Pi: submossive/mossrve: t JVP. R-sided Si. Graham Steed's (PR) murmur

Pretest Probability of DVT

Major points

Minor points

• Active cancer

• Paralysis, paresis, immobilization of foot

• Localized tenderness along veins

• Swelling of thigh and calf

• © FHx of DVT (.-2 1° relatives)

• Trauma to symptomatic leg w/in 60 d

• Pitting edema in symptomatic leg

• Dilated superficial veins (nonvaricose)

in symptomatic leg only

• Hospitalization w/in previous 6 mos

• Erythema

High probability ( 85% < DVT) 2=3 major * no alternative dx -2 major • -2 minor • no alternative dx Intermediate prob ( 33% © DVT) neither high nor low probability

Low probability ( 5% © DVT) 1 major + a 2 minor - alternative dx 1 major s 1 minor no alternative dx 0 major +■ a3 minor • alternative dx 0 major • &2 minor + no alternative dx

(Lancet 1995:345:1326: NifM 1996:335:18161 Diagnostic studies (DVT)

• Compression ultrasonography -95% Se & Sp (Bfiy 1998:316:17); U/S © in 60% Pts w/ PE

Figure 2-3 Approach to tmpcctcd DVT

Low_I Prelesl probability | Intermedíale or High ^

Ultrasound repeat U/S in 1 wk

DVT excluded

DVT confirmed

(Baled on diu from loncet 1995:345:1326 S 1997:350:1795; NijM 1996:335:1816 & 2003:349:13.)

"Modified Wells" Pretest Probability Scoring of PE

Variable Point Score

• PE as likely or more likely than alternate dx; din. s/s of DVT 3 each

• Immobilization (bed rest d) or surgery w/in 4 wks 1.5

• Hemoptysis; malignancy 1 each

"Modified Wells" Pretest Probability Assessment (Use for V/Q)

Low probability Intermediate probability High probability

"Dichotomized Wells" Pretest Probability Assessment* (Use for CTA)

Score - 4: PE "Unlikely" Score -4: PE "Likely"

(Ann /nt Med 2001:135:98) ('JAMA 2006:295:172) Diagnostic studies (PE)

• CXR (limited Se & Sp): 12% nl. atelectasis, effusion. T hemidiaphragm. Hampton hump.

(wedge-shaped density abutting pleura); Westermark sign (avascularity distal to PE)

• ECG (limited Se & Sp): sinus tachycardia. AF; signs of RV strain -» RAD. P pulmonale.

RBBB.TWI V,-V< (McGinn-White pattern; Chest 1997; 111:537). SiQinTui

• ABG: hypoxemia, hypocapnia. respiratory alkalosis. T A-a gradient (Chest 1996:109:78)

18% w/ room air P.Oj 85-105 mmHg, 6% w/ nl A-a gradient (Che« 1991:100598)

• D-dimer: high Se. poor Sp ( 25%); ELISA has -99% NPV and can be used to r/o PE in

Pts w/"unlikely" pretest prob. (see below) (.iama 2006:295:172)

• Echocardiography: useful for risk stratification (RV dysfxn).but not dx (Se <50%)

• V/Q scan: use at CTA-inexperienced institutions or if contraindication to CTA

• CT angiography (CTA): Se. 90% & Sp 95% w/ MDCT. • CTV. and experienced readers (pioped ii.n£/ai 2006.354 2317); PPV & NPV -95% if imaging concordant w/ clinical suspicion. 80% if discordant ( need to consider both); CT may also provide other dx

• Pulmonary angiography: ? gold-standard (morbidity 5%. mortality <0.5%)

• MR angiography: Se 84% (segmental) to 100% (lobar) (lone« 2002:359:1643)

• Diagnostic algorithms: CTA-experienced institutions use CTA algorithm (fig. 2-4);

CTA inexperience, contraindic., or inconclusive CTA use V/Q algorithm (fig. 2-5)

Figure 2-4 Approach to wnpcctcd PE uimg CTA

Figure 2-4 Approach to wnpcctcd PE uimg CTA

Based on data from NEJM 200S:3S2 1760 & 2006:354:22: JAMA 2005:293:2012 & 2006:295:172

Figure 2-5 Approach to impectcd PE using V/Q ion

"Modified Wells" clinical PE probability

Intormodiate

or High

Low prob dm & scan All other combos High prob din & scan 4% PE 16-88% PE 96% PE

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