medical grandrounds odessa tolentino-wilson, md october 25, 2007

Medical Grandrounds

Odessa Tolentino-Wilson, MDOctober 25, 2007

Objectives:

• To present a case of TB Pericarditis

• To discuss the pathogenesis, diagnosis, and management of TB pericarditis

• To discuss updates in the management of TB Pericarditis

Identifying Data

• R.T.• 51 y/o, male • Filipino• Married• Quezon City

Chief Complaint

• Shortness of breath

History of Present Illness

1 month PTA generalized body

weaknessundocumented fever Right upper back pain

with radiation to the left

History of Present Illness

17 days PTA easy fatigability

shortness of breath 3 pillow orthopnea

History of Present Illness

Consult 2D Echo: Large to massive

circumferential pericardial effusion with no evidence of tamponadeEjection Fraction: 76%

History of Present Illness

admitted Diagnostic

pericardiocentesis: 580 cc red turbid fluid

• Gram stain: no microorganisms seen• Direct AFB stain: no acid fast bacilli

seen• Routine culture: pending• Fungal culture: pending• AFB culture: pending• Final cytopathologic diagnosis:

Pericardial fluid; smears and cell block showing lymphocytes, macrophages, and some mesothelial cells

History of Present Illness

1 week PTA easy fatigability, shortness of breath, orthopnea

History of Present Illness

1 day PTA progressive shortness of breath follow up

History of Present Illness

2 d echo: Large organized fluid with thickened pericardium but no evidence of constriction or tamponade. Ejection Fraction: 64%

advised admission

Review of systems

(-)headache(-)dizziness(-)fever(-)cough(-)hemoptysis(-)vomiting(-)chest pain(-)palpitations

(-)dysuria(-)polyuria (-)nocturia(-)oliguria(-)abdominal

pain(-)constipation(+)weight loss

Past Medical History• Hypertension x 10 years

– Metoprolol 50 mg BID– Nifedipine 30 mg OD

• Diabetes Mellitus x 1 year – Gliclazide 30 mg 2 tablets daily

• CKD x 1 year– Ketosteril 2 tablets TID – Epoeitin alpha 4000 units SC 1x/week

• No Bronchial Asthma• No Pulmonary TB

Family History

(+) Diabetes Mellitus(+) Hypertension

Personal/Social History

• Previous smoker (10 pack years)

• Previous alcoholic beverage drinker

Physical examination

• Conscious, coherent, weak looking, not in distress

• BP 150/90 HR 87 RR 19 T37.2C• Pale palpebral conjunctivae,

anicteric sclearae, no tonsillopharyngeal congestion, no neck vein distention, no cervical lymphadenopathy

• Symmetric chest expansion, decreased tactile fremitus, both bases, decreased breath sounds both bases, more on the right

Physical examination

• Adynamic precordium, normal rate, regular rhythm, muffled heart sounds, AB 5th ICS LMCL, (-)murmur

• Flabby, normoactive bowel sounds, tympanitic, soft, no tenderness, no organomegaly

• Grade 2 bipedal edema, full and equal pulses

Salient Features• 51 y/o, Filipino, male • Progressive shortness of breath• Generalized body weakness,

undocumented fever, easy fatigability, 3 pillow orthopnea, weight loss

• Decreased breath sounds, both bases, more on the right

• Muffled heart sounds, pericardial friction rub

• Bipedal edema• Recurrent pericardial effusion• Hypertension, diabetes, CKD

Admitting Impression

• Recurrent Pericardial Effusion, etiology to be determined

• Hypertensive Cardiovascular Disease

• Diabetes Mellitus Type 2, NIR• Chronic Kidney Disease

secondary to Diabetic vs Hypertensive Nephrosclerosis

Pericardial Effusion / Pleural Effusion

Malignancy

Uremic Pericarditis

Infectious Pericarditis

Viral/Idiopathic Bacterial Tuberculous

Course in the wards

On Admission

• Oxygen at 2-3 lpm via nasal cannula

pO2 72.8

pH 7.4

pCO2 27.3

HCO3 16.8

O2 Sat 95

Base excess

-6.1

TCO2 17.7

RR 26

2-3 lpm

Hgb 8.9

Hct 27.4

WBC 7490

Seg 76

Lym 13

Mono 10

Eos 1

Plt Ct 538,000

K 3.4

Crea 2.8

Alb 1.9

Protime

Act 58.4%

INR 1.4

• Yellow, hazy, acidic 5.0, ph 1.025, sugar trace, CHON trace, ketones negative, nitrites negative, leucocyte esterase neg, blood trace, rbc 1.4, wbc 8.1, epithelial cells 3.2, Bact 1151.7

On Admission

• Referred to TCVS

• Hgb 8.9; Hct 27.4• Transfused with 1 unit PRBC• Hgb 10.9 ; Hct 33 • Fecal Occult Blood Test:

negative

• Epoietin alpha 4000 units SQ 1x week

• Metoprolol 50 mg BID• Amlodipine 5 mg OD

1st Hospital Day

• Pericardiostomy tube insertion with Pericardial biopsy

• Chest tube insertion, Right lung

• Cefuroxime 750 mg IV q8

• Pericardial Fluid analysis:– No microorganisms seen,

pus cells 0-1, epithelial cells 1-2– Negative AFB– Culture: No growth in 5 days

• Pleural fluid analysis:– Negative AFB– Culture: oxacillin resistant

coagulase negative staphylococcus

• Linezolid 600 mg IV q12

2nd Hospital Day

• CT scan of the chest and the abdomen

Impression:CT scan of the chest: • S/P placement of the right thoracotomy and

pericardostomy drainage catheters• Subsegmental atelectasis organizing

consolidation pneumonia, right lower lobe• Moderate pleural effusion, left hemithorax

with complete atelectasis of the left lower lobe.

• Mild cardiomegaly• Residual pericardial effusion with minimal

pericardial emphysema which may be post surgical in nature

• Nonspecific mediastinal lymphadenopathy• Minimal subcutaneous emphysema, right

lateral chest wall.

CT scan of the Abdomen: No oral or intravenous contrast were given

• Minimal ascites. • Consider gastric ileus. • Perinephric fat stranding which

may be due to an inflammatory/infectious process.

• Mild atherosclerotic disease, coronary vessels, abdominal aorta and common iliac arteries.

Pericardial Effusion / Pleural Effusion

Malignancy

Uremic Pericarditis

Infectious Pericarditis

Viral/Idiopathic Bacteria Tuberculous

Course in the Wards

• Referred to Endocrinology service– CBG monitoring– Repaglinide 0.5 mg TID ac

meals

0

200

400

600

800

1000

1200

1400

1600

D1 D2 D3 D4 D5 D6

CTT

Pericardios-tomy

Figure 1. CT tube and Pericardiostomy tube drain

6th Hospital Day

• Pericardiostomy tube pulled out

• Right Chest tube was hooked to Heimlich valve

• Iberet Folic BID

Hgb 10.1

Hct 32.4

WBC 9840

Seg 85

Lym 6

Mono 9

Plt Ct 515,000

• Pericardial biopsy: caseating granuloma consistent with tuberculosis– Referred to Infectious Disease

• Ethambutol HCL 275mg/tab 4 tablets/day

• Rifampicin 150mg/tab 4 tablets/day

• INH 75 mg/tab 4 tablets/day• Pyrazinamide 400 mg/tab 4

tablets/day

Pericardial Effusion / Pleural Effusion

Malignancy

Uremic Pericarditis

Infectious Pericarditis

Viral/Idiopathic Bacteria Tuberculous

Clinical Outcome

• Discharged improved on the 8th hospital day

• Readmitted for Pericardiectomy

FINAL DIAGNOSIS:TB pericarditis, pericardial effusion

secondaryHypertensive Atherosclerotic

Cardiovascular DiseaseDiabetes Mellitus, type 2, poorly

controlled, NIRChronic Kidney Disease secondary to

Diabetic Nephropathy vs Hypertensive Nephrosclerosis, Acute Kidney Injury, resolved

Hypoalbuminemia, multifactorial Hyponatremia, multifactorial

Discussion

Tuberculosis

In 1993, the World Health Organization (WHO) declared TB to be a global public health emergency

Most common cause of infection-related death worldwide

..”nearly 2 billion people, one-third of the world's population, have Tuberculosis..”

• Philippines has the ninth highest burden of tuberculosis in the world

– World Health Organization (WHO) Global TB Report 2006

Discussion

TB in the Philippines

• TB is the sixth greatest cause of morbidity and mortality

• Approximately 78 Filipinos die from the disease every day

• By 2004, the country achieved a TB case detection rate of 73 %, exceeding the national and global target of 70 %

• The National TB treatment success rate is currently at 88 % above the national target of 85 %World Health Organization (WHO) Global TB Report 2006

Tuberculosis

TB Pericarditis

• Inflammation of the pericardium caused by Mycobacterium tuberculosis

• rare but life-threatening form of extrapulmonary tuberculosis

Incidence

• TB has been reported to be the cause of acute pericarditis in 4% of patients in the developed world and 60% to 80% of the patients in the developing world

• TB pericarditis has been estimated to occur in 1-8% patients with pulmonary tuberculosis

Clinical Manifestations

• Symptoms:– nonspecific:

•fever, weight loss, and night sweats.

•Symptoms depend upon the stage of infection, the degree of pericardial involvement, and the degree of extrapericardial tuberculous disease

In one series, the following frequency of symptoms was noted: •Cough — 94 percent •Dyspnea — 88 percent •Chest pain —76 percent •Night sweats — 56 percent •Orthopnea — 53 percent •Weight loss — 48 percent

TB Pericarditis• “Definite”

– tubercle bacilli in pericardial fluid or on a histological section of the pericardium

• “Probable" – proof of tuberculosis elsewhere in a

patient with otherwise unexplained pericarditis

– a lymphocytic pericardial exudate with elevated adenosine deaminase levels

and/or – appropriate response to a trial of

antituberculosis chemotherapy

• Acute pericarditis• Chronic pericardial effusion• Cardiac tamponade• Pericardial constriction

Routes of Spread

• Retrograde lymphatic spread of M tuberculosis from peritracheal, peribronchial, or mediastinal lymph nodes

• Hematogenous spread from primary tuberculous infection

• Direct extension of infection from adjacent mediastinal lymph nodes

Four pathological stages of tuberculous pericarditis:

(1) fibrinous exudation with initial polymorphonuclear leukocytosis, relatively abundant mycobacteria, and early granuloma formation with loose organization of macrophages and T cells

(2) serosanguineous effusion with a predominantly lymphocytic exudate with monocytes and foam cells

(3) absorption of effusion with organization of granulomatous caseation and pericardial thickening caused by fibrin, collagenosis, and ultimately, fibrosis

(4) constrictive scarring the fibrosing visceral and parietal pericardium contracts on the cardiac chambers and may become calcified, encasing the heart in a fibrocalcific skin that impedes diastolic filling and causes the classic syndrome of constrictive pericarditis.

Integrated Etiologic Approach to the Patient With Suspected

Tuberculous Pericardial Effusion

• Chest radiograph – may reveal changes suggestive of

pulmonary tuberculosis in 30% of cases

• Electrocardiogram– Low voltage QRS, inverted T waves

• Echocardiogram– evidence of pericardial effusion

Mayosi et.al.Tuberculous Pericarditis. Circulation. 2005;112:3608-3616

Integrated Etiologic Approach to the Patient With Suspected

Tuberculous Pericardial Effusion

•  CT scan and/or MRI of the chest – evidence of pericardial effusion and

thickening (>5 mm) and typical mediastinal and tracheobronchial lymphadenopathy (>10 mm, hypodense centers, matting), with sparing of hilar lymph nodes.

Mayosi et.al.Tuberculous Pericarditis Circulation. 2005;112:3608-3616

Integrated Etiologic Approach to the Patient With Suspected

Tuberculous Pericardial Effusion

• Culture of sputum, gastric aspirate, and/or urine

• Right scalene lymph node biopsy if pericardial fluid is not accessible and lymphadenopathy is present    

Mayosi et.al.Tuberculous Pericarditis Circulation. 2005;112:3608-3616

Integrated Etiologic Approach to the Patient With Suspected

Tuberculous Pericardial Effusion

• Pericardiocentesis    – Therapeutic pericardiocentesis

• indicated in the presence of cardiac tamponade.    

– Diagnostic pericardiocentesis • considered in all patients with

suspected tuberculous pericarditis

– Mayosi et.al.Tuberculous Pericarditis Circulation. 2005;112:3608-3616

Integrated Etiologic Approach to the Patient With Suspected

Tuberculous Pericardial Effusion

• Pericardial biopsy  • Diagnostic biopsy:

– Not required in areas in which TB is endemic before commencing empirical antituberculosis treatment.

– in areas in which TB is not endemic, a diagnostic biopsy is recommended in patients with >3 weeks of illness and without etiologic diagnosis having been reached by other tests.

Mayosi et.al.Tuberculous Pericarditis Circulation. 2005;112:3608-3616

• Empirical antituberculosis chemotherapy    – In tuberculosis endemic population: trial of

empirical antituberculous chemotherapy is recommended for exudative pericardial effusion, after other causes such as malignancy, uremia, and trauma have been excluded.   

– If tuberculosis is not endemic in the population: when systematic investigation fails to yield a diagnosis of tuberculous pericarditis, there is no justification for starting antituberculosis treatment empirically

Mayosi et.al.Tuberculous Pericarditis Circulation. 2005;112:3608-3616

Treatment

• Randomized controlled trials:– suggests that 6- to 9-month regimens that

include INH and RIF are effective– Therefore, among patients with

extrapulmonary tuberculosis, a 6- to 9-month regimen (2 months of INH, RIF, PZA, and EMB followed by 4--7 months of INH and RIF) is recommended as initial therapy unless the organisms are known or strongly suspected of being resistant to the first-line drugs. If PZA cannot be used in the initial phase, the continuation phase must be increased to 7 months, as described for pulmonary tuberculosis.

American Journal of Respiratory and Critical Care Medicine (2003;167:603--62)

Evidence-based guidelines for the treatment of extrapulmonary tuberculosis

Site Length of therapy (mo)

Rating (duration)

Lymph node 6 A1

Bone and joint 6-9 A1

Pleural disease 6 A11

Pericarditis 6 A11

CNS tuberculosis including meningitis

9-12 B11

Disseminated disease

6 A11

Genitourinary TB 6 A11

Peritoneal 6 A11American Journal of Respiratory and Critical Care Medicine (2003;167:603--62)

• Antibiotic treatment is the same as for pulmonary tuberculosis.

• On antituberculous drugs, resolution occurs in 2 to 3 months in 80% of patients.

• In 20%, subacute constriction develops, and in half of these patients it resolves over a few months, leaving 10% in whom pericardiectomy is required.

Cardiac Tamponade as a manifestation of tuberculosis. South Med J 94(5):525-528, 2001. © 2001 Southern Medical Association

• Corticosteroid treatment is a useful adjunct in treating some forms of extrapulmonary tuberculosis, specifically meningitis and pericarditis caused by drug-susceptible organisms.

American Journal of Respiratory and Critical Care Medicine

(2003;167:603--62)

Evidence-based guidelines for adjunctive use of corticosteroids in the treatment of extrapulmonary TB

Site Corticosteroids Rating (corticosteroids)

Lymph node Not Recommended D111

Bone and joint Not Recommended D111

Pleural disease Not Recommended D1

Pericarditis Strongly Recommended

A1

CNS tuberculosis including meningitis

Strongly Recommended

A1

Disseminated disease

Not Recommended D111

Genitourinary TB Not Recommended D111

Peritoneal Not Recommended D111American Journal of Respiratory and Critical Care Medicine (2003;167:603--62)

• Corticosteroid treatment reduces the need for repeated pericardiocentesis for control of fluid accumulation (9% vs 23%) and control of hemodynamically threatening effusion.

• In one study, treatment with corticosteroids in fairly large doses (60 mg/day for 4 weeks and 15 mg/day for 2 weeks) decreased mortality from 11% in control cases to 4% in treated cases.

Cardiac Tamponade as a manifestation of tuberculosis. South Med J 94(5):525-528, 2001. © 2001 Southern Medical Association

• Pericardiectomies were less frequently necessary in patients given corticosteroids (30% in control patients vs 11% in steroid-treated patients)

• One-year follow-up of patients with tuberculous pericarditis revealed that constriction developed in 18% of steroid-treated patients vs 83% who did not receive steroids

Cardiac Tamponade as a manifestation of tuberculosis. South Med J 94(5):525-528, 2001. © 2001 Southern Medical Association

THANK YOU!!!

Sept 8

Sept 9

Sept 11

Sept 14

Sept 15

Sept 16

Na 133 131 125 123 128

K 3.4 3.7 3.7 4 4

BUN

52 47

Crea

2.8 2.6 2.6 1.7