Alain Tremblay Medical Grand Rounds November 30 th, 2010
Top Ten Countdown - Objectives Through a case based approach, to review Diagnostic approach for pleural effusions Common and uncommon causes of pleural effusions Incorporate recent BTS pleural disease guidelines
Outline The Borderline (exudative) Patient The Girl who Collapsed (her lung) The Man with the Rotten Tooth The Man who Played with Asbestos The Undiagnosed Exudate The Wedding Planner The Patient with an Upset Stomach The Woman with a Hornet s nest in Her Belly The Lady with Milky Fluid in the Chest The Lady with No Kidneys The Man with Bilateral Empyema
The Borderline (exudate) Patient 72 yo y.o. man History of Coronary disease Decrease LV function and mildmoderate renal insufficiency Admitted d for treatment t t of volume overload / pulmonary edema Overall improving, i but pleural l effusions persistent
The Borderline (exudate) Patient Thoracentesis is performed LDH 105/200 (0.52) PTN 35/67 (0.52) Cultures, cytology negative Exudate / lymphocytic What do you do?
Criteria for Exudative vs. Transudative Effusions Light s Criteria for exudates LDH > 2/3 upper limit serum PF LDH / Serum LDH >0.6 PF PTN / Serum PTN >0.5 Cutoffs selected for high sensitivity for Cutoffs selected for high sensitivity for exudates (>95%)
Criteria for Exudative vs. Transudative Effusions Some transudates will be misclassified as exudates (up to 25%) Usually just barely meet exudate criteria Borderline exudates Usually not LDH > 2/3 upper limit serum Usually receiving diuretics Can be sorted out by looking at additional markers Albumin gradient >12g/L suggest transudate NT-proBNP >1500 pg/ml suggest CHF No better than serum measurement No better then albumin gradient
The Borderline (exudate) Patient Additional fluid analysis requested Serum albumin: 40g/L Pleural albumin: 25g/L Albumin gradient 15 Likely a misclassified transudate
The Girl who Collapsed (her lung) 55 y.o. Woman History of Breast Cancer localized 2 years prior Sought nonconventional treatment Increased breathlessness for 4 weeks Thoracentesis in ER
The Girl who Collapsed (her lung) Pneumothorax on post tap CXR Why? Entrained Air Iatrogenic Lung Injury Trapped lung
Pneumothorax Post Thoracentesis Pneumothorax - 6%-30% cases OR 0.3 with ultrasound guidance X marks the spot does not work 15% chosen sites inappropriate US 10% organ punctures avoided US 26% increase in appropriate site
Trapped Lung Ex-vacuo PTX Usually in patient with malignant disease Un-expandable lung underlying effusion Removal of fluid in pleural space leads to negative pleural pressure Air fills the space (lung tear or through drainage system) Insertion of chest tube will not resolve the PTX
The Girl who Collapsed (her lung) Symptoms better post tap despite PTX Chest tube deferred Cytology +adenocarcinoma Eventual TPC / good re expansion
The Man with the Rotten Tooth 70 y.o. Male Cough / Fever / Right pleuritic pain RLL infitrate on CXR, elevated WBC Gets CT PE (negative) RLL infiltrate, 2cm effusion Started on PO antibiotics
The Man with the Rotten Tooth F/U 2 days later... Sent home
The Man with the Rotten Tooth F/U with his GP 5 days later Abx extended to 10 days F/U Chest CT done Day 17 F/U GP Day 24 suggest tback kto ER Still not well, loosing weight Chest pain still present To ER Day 27
Parapneumonic effusions and Empyemas Over 1700 people each year are admitted to hospital with empyemas Mortality up to 20% One of civilization s oldest and severest diseases If an empyema does not rupture, death will occur Hippocrates "the most fatal of all acute diseases -Osler
Pleural effusion in setting of pneumonia / infection Uncomplicated parapneumonic p capillary permeability Production of pro-inflammatory cytokines IL-8 8, TNFα Free flowing exudate, normal ph, sterile Complicated parapneumonic Bacterial invasion / increased inflammation Coagulation cascade / fibrin deposition ph 7.2, glucose 2.2 mmol/l & LDH 1000 Empyema Frank pus, positive cultures Fibrous pleural peel ABx DRA AIN
How can you tell which is present? You can t
How can you tell which is present? Can observe if Fluid <10mm on lat decubitus <20mm? Considered in a recent retrospective study
SEND: LDH, PTN, Glucose (yellow top) ph (ABG, call RT) C&S (bottles + sterile container) Cell count & diff (purple top) Cyto (Any, bottle, >100ml)
The Man with the Rotten Tooth Thoracentesis is performed PUS Anaerobic cultures Strep milleri Chest tube placed Abx (3-6 weeks) Dentistry referral!!!
The Man who Played with Asbestos 70 yo y.o. male History of occupational asbestos exposure Dyspnea / Right chest pain Several non-diagnostic thoracentesis
The Man who Played with Asbestos Most recent results LDH 612/125 (4.9) TP 31 Glucose 1.1 mmol/l Lymph (64%) RF 5 (same as serum) Cyto negative
The Man who Played with Asbestos Concerning features Pain Asbestos Thickened pleura / Nodularity / Mediastinal
The Man who Played with Asbestos Closed pleural biopsy Fibrinous pleuritis Thoracoscopy Sarcomatoid mesothelioma Trapped lung
The Undiagnosed Exudate 42 yo y.o. Woman Cough, bilat chest discomfort and increasing dyspnea over weeks
The Undiagnosed Exudate Thoracentesis LDH 153/137 (1.1) PTN 42/66 (0.64) Glucose 6.9, ph 7.43 WBC 1.2x10 9 /L 32%L, 12%N Cyto, cultures, TG, flow cytometry TSH, ANA, RF, anti CCP, C3C4 normal Small amount of pericardial fluid
What to do when an Exudate remains unexplained? Review existing basic information & Tests Is it really an exudate List for transudate is short CHF, Cirrhosis, Nephrotic, TSH, Urino, CSF Have basic test been sent (WBC diff. cultures, cyto) CT chest
What to do when an Exudate remains unexplained?
What to do when an Exudate remains unexplained? Review history Review physical Previous cancer Asbestos TB risks Sub-diaphragmatic process Cardiac surgery / injury Procedures (urologic or spinal) Systemic findings (CTDs) Drugs Nitrofurantoin, Dantrolene, Bromocriptine, Amiodarone Adenopathy Breast / Gyne exam Abdominal process Pericardial rub / Kussmaul sign Joints Yll Yellow nails
What to do when an Exudate remains unexplained? Blood tests Albumin & NT-BNP, Urinalysis for protein Creat / BUN (Uremic effusion) CTD serology (RF, ANA, dsdna, ENA) Hypothyroidism (TSH) Consider additional fluid testing ADA Flow cytometry Cholesterol and TG Creatinine, Amylase Imaging CT (PE protocol) PE, Thickening/nodularity, adenopathy, lung lesions, pericardial, liver, pancreas, ascites, subdiaphragmatic abcess
What to do when an Exudate unexplained? Closed pleural biopsy / CT pleural Bx (if thick pleura) Best for TB Some additional yield for malignancy as well Consider thoracoscopy Especially if TB / Malignancy / Asbestos What if still do not know? About 20% of exudates Finding of non-specific pleuritis on biopsy (30%) Eventual diagnosis of malignancy in ~10% Specific cause eventually found in ~30% Ongoing f/u required, but most follow a benign course
The Undiagnosed Exudate Thoracoscopy performed Non-specific pleuritis Pericardial effusion regressed?element of constriction Placed on NSAIDS
The Undiagnosed Exudate F/U 4 months later... Echo also normal
The Wedding Planner 62 yo y.o. Woman Hx SLE for 20 years Low dose azathioprine, hydroxychloroquine Admitted with several days of increasing Admitted with several days of increasing dyspnea, dry cough and fevers
The Wedding Planner Fails to improve after 2 weeks of escalating IV antibiotics Thoracentesis LD 153/203 (0.75) PTN 40/69 (0.58) Glucose 6.1, ph 7.47 WBC 1.1x10 9 /L (45% lymphs) Cultures negative ANA 1:640 speckled, homogenous dsdna +
Pleural Effusions in SLE In SLE Pleural effusions common (30-50% of pts) More common than in other CTDs 5-10% this can be presenting manifestation Pleuritic chest pain (pleurisy) Effusions typically small / bilateral Exudative, lymph/pmns, lowish glucose Fluid low compl / +ANA / LE cells NSAIDS, low dose steroids
Pleural Effusions in SLE In this case, effusions not an isolated finding Fever / Dyspnea / Hypoxemia / Alveolar infitrates / + dsdna Acute Lupus Pneumonitis Severe complication of SLE (50% mortality) R/O infection High dose steroids (1 15 1.5mg.kg/d) Pulse 1g x 3 day if not responding Consider additional drugs (cyclophosphamide)
The Wedding Planner Bronchoscopy performed y No infection Steroids initiated
The Man with an Upset Stomach 77 yo y.o. male, CAD/HTN/CHOL Feels unwell with nausea, retching A few hours later develops acute L chest pain and dyspnea
PTX Fluid
The Man with an Upset Stomach Chest tube placed Dark brownish fluid LDH 1140/283 (4.0) PTN 17/75 (0.23) Glucose 11.1 WBC Diff: degenerated cells Gram stain: Heavy yeast, G-ves, G+ves
The Man with an Upset Stomach
The Man with an Upset Stomach Hydropneumothorax Post procedure Infection Broncho-pleural fistula Esophageal perforation
Boerhaave s syndrome Spontaneous (non-iatrogenic) rupture of distal esophagus Uncommon Will often lead to sepsis / death Mortality lowest if repaired <24hrs Diagnosis via CT / Esophagram
The Man with an Upset Stomach Surgical repair performed Post OP ICU Ventilatory support Vasopressors Eventual recovery
The Lady with a Hornet s Nest in Her Belly Increasing SOB over weeks Chronic abdominal pain Thoracentesis LDH 490/326 (1.5) PTN 33/57 (0.58) WBC 1.7x10 9 /L 59%N Glucose 4.8mmol/l
The Lady with a Hornet s Nest in Her Belly CT Chest / Abdo Pancreatic pseudocysts Dilated pancreatic duct Fluid / thickening tracking near crux of diaphragm Pleural fluid amylase 759 U/l (N 30-110)
Pleural effusion 2ry chronic Pancreatitis Development of sinus track between pancreas / pleural space Abdominal symptoms may improve with decompression into the chest Patient may look chronically ill Elevated Amylase (>1000 U/L) in pleural fluid Treatment directed towards pancreatitis and pseudocysts Don t forget subdiaphragmatic processes Subphrenic / hepatic abscesses Meigs syndrome
The Woman with Milky Fluid 46 yo y.o. woman progressively more SOB over 2-3 months Large Pleural Effusion
The Woman with Milky Fluid Thoracentesis / chest tube LDH 141/216 (0.65) TP 45/70 (0.64) Glucose 5.6, ph 7.38 WBC 71% Lymph Pus? Chyle? Cholesterol? TG 3.48 mmol/l
Chylothorax Interruption of Thoracic Duct Diagnosed Not all exudates TG >1.24 mmol/l Borderline 0.62-1.24 Chylomicrons in fluid Oil red O stain
Chylothorax Traumatic Iatrogenic (Surgery, Lines) Non-iatrogenic (chest trauma, coughing) Malignancy Others Lymphatic disorders Congenital, Yellow nail, LAM Thoracic duct obstruction ti Increased CVP Chylous ascites
The Woman with Milky Fluid Cyto/Flow Atypical lymphocyte population CT Mediastinal / paraspinal mass Mediastinoscopy Follicular Lymphoma
The Lady with no Kidneys 56 yo y.o. woman ESRD on hemodialysis DM / CAD / CABG (1 year) / r BKA Dyspnea for a few weeks Mild left chest discomfort Weight stable No fluid overload on exam No Hx cancer/asbestos/tb
The Lady with No Kidneys Left thoracentesis serosanguinous fluid LDH 238/147 (1.62) PTN 49/75 (0.65) WBC lymphocyte y 40% ph 7.25 Cultures / cytology negative
Uremic pleuritis? Effusions common in dialysis patients As high as 20% in a hospitalized cohort Degree of uremia does not correlate with occurrence of effusions Mechanism remains unknown Need to consider other causes Fluid overload / CHF Infection / parapneumonic TB Malignancy
The Lady with No Kidneys Discussion regarding g clinical f/u vs. Additional work-up Repeat thoracentesis Pleural biopsies (increased risk) Fibrinous pleuritis No specific treatment known to be effective for uremic pleuritis ASA prescribed (one year post CABG) No change in effusion on f/u 2 months later
The Man with Bilateral Empyema 66 yo y.o. male several months SOB Rheumatoid arthritis (etanercept, hydroxychloroquine, leflunomide)
The Man with Bilateral Empyema Left Thoracentesis Purulent appearance LDH >2500 PTN 50/ Glucose <0.5 mmol/l WBC 3.7 x109/l 86% Neuts Cyto (infl cells), cultures -ve
Pleural disease in RA Pleurisy Pleural thickening (very common) Pneumothorax Pleural effusion Older male patients with high RF Almost never presenting problem (unlike SLE) Unilateral Exudate, LDH, glucose Fluid RF > Serum RF Fluid can be milky / greenish yellow Pseudochylothorax (high h cholesterol) l) Sterile empyema Trapped lung
Pseudochylothorax / Chyliform effusion Another cause of milky fluid Cholesterol >5.18 mmol/l Cholesterol crystals Chronic effusions associated with TB Rheumatoid arthritis Paragonimiasis
Management of Pleural Effusion in RA Thoracentesis R/o infection R/o malignancy Pleural biopsy Especially if TB / Cancer risks Treatment Limited evidence Tap Steroids systemic, intrapleural Surgical decortication
The Man with Bilateral Empyema Additional fluid RF 36/393 Fluid cholesterol 3.89 mmol/l TG 0.49 mmol/l Not chylothorax / not pseudochylothorax Infection vs. sterile empyema
The Man with Bilateral Empyema Right Thoracentesis Almost identical results Anti-histone Ab negative Improvement with high dose prednisone Unable to wean without worsening No impact of bilat IP steroids No impact of Humera (adalimumab) Vital Capacity 70% - 47% Considering rituximab
Conclusions Most exudates will be parapneumonic or malignant Negative cytology does not r/o cancer Parapneumonic effusions need to be sampled/drained In some cases, rapid assement and management is critical to susccesful outcomes Use ultrasound for pleural procedures
Conclusions History / Physical and basic investigations (Blood / Fluid / CT) will often lead to narrow DDx Use the fluid appropriately! Transudates are transudates, but not all exudates are exudates! Don t forget TB, uremia, PE, CABG, esophageal/sub-diaphragmatic processes, asbestos and CTDs as causes of exudates But the list is long
Conclusions Involve Resp/Thoracics Complicated parapneumonic / empyema Malignant Unexplained exudate after first tap Pleural biopsy / thoracoscopy required to make diagnosis in some cases Some cases will remain unexplained despite extensive w/u Clinical f/u important