Topic Conference7 Jan 2009

Topic Conference7 Jan 2009

Dr. Nattachai Anantasit

Acute Pulmonary Embolism (PE)Acute Pulmonary Embolism (PE)• First report in child was made in 18611

• Annual incidence 0.3-4.2 per 100,000 in USA2

• Pulmonary embolism and deep venousthrombosis spectrum of one disease• Anatomical obstruction is most important cause, vasoactive and bronchoactive agents eg.Serotonin V/Q mismatch • Death results from Rt.ventricular failure

1 Stevenson GF, et al. J Pediatr 1949.2 Heleen C,et al. Thrombosis Research 2006.

PathophysiologyPathophysiology

Risk Factors Risk Factors

Tapson VF. NEJM 2008.

Virchow’s classic triad of risk- Stasis- Venous injury- Hypercoagulability

Hereditary Risk Factors Hereditary Risk Factors

Konstantinides SV, Management of acute pulmonary embolism 2007.

Risk Factors Risk Factors

When we should work up genetic disorder ?

-Recurrent thromboembolism-Young age-Unprovoked thrombotic or thromboembolic episodes-Unusual location(cerebral, portal or hepatic, mesenteric)

1British Thoracic Society's (BTS): Thorax 2003.2Johnson AS, et al. Pediatr Emerg Care 2004.

20% have not risk factors1

but almost all children are found risk factors2

Risk FactorsRisk Factors• More than 95% of child with venous

thromboembolic dz have at least one underlying condition

• Venous thombi in child are often asymptomatic and more likely to involve upper venous system

• Central venous catheters are the most common frequent clinical risk factor

Van Ommen CH., et al. J Pediatr 2001.Derish MT, et al. Pediatr Pulmonol 1995.Pediatric Respirtory Medicine, Taussig 2008.

Clinical Manifestations Clinical Manifestations • Acute or sudden onset • Pleuritic chest pain 84%• Dyspnea 58%• Cough 47%• Hemoptysis 32%

Heleen C,et al. Thrombosis Research 2006Tapson VF. Cardiol Clin 2004.

Clinical ManifestationsClinical Manifestations

Tapson VF. Cardiol Clin 2004.

Clinical ManifestationsClinical Manifestations• Signs and symptom of both DVT and PE

highly suggestive but not sensitive and specific

• Patients who have sudden onset of near syncope or syncope, unexplained dyspnea hypotension, extreme hypoxemia or cardiac arrest should be considered pulmonary embolism

Tapson VF. NEJM 2008.

Laboratory Testing Laboratory Testing

• EKG: • non-specific • ST segment abnormalities, T-wave

changes, Rt.axis deviation • Acute cor pulmonale eg. S1Q3T3

pattern, RBBB, P-pulmonale

ElectrocardiographyElectrocardiography

• The classic S1Q3T3 pattern is described to be present only in 20 % of cases • This pattern had a sensitivity of 54% and a specificity of 62%

Ferrari E, et al. Chest 1997.

Any cause of these EKG: acute bronchospasm, pneumothoraxAnd other acute pulmonary problems

CXRCXR• Often abnormal but non-specific • Pulmonary infiltration (17%), atelectasis (18%),

mild elevation of hemidiaphragm (20%), pleural effusion (23%), and normal (24%)

• Classic pulmonary infarction: Hampton’s hump or decreased vascularity (Westermark’s sign)

Stein PD, et al. chest 1991.

Hampton’s hump

Westermark’s sign

Laboratory TestingLaboratory Testing• ABG: Hypoxemia but may have normal arterial

oxygen tension (PaO2)• ELISA- based D-dimer:

• Elevation• High sensitive but non-specific

• Cardiac troponin levels• elevation but not sensitive

Tapson VF. NEJM 2008.

Imaging Studies Imaging Studies • CT arteriography:

• Greatest sensitive and specific for detecting emboli in main, lobar or segmental pulmonary arteries but subsegmental is less accurate

• Systematic reviews suggest that OPD case with suspected PE and negative CTA have excellent outcomes without therapy1

• False positive CTA is unusual, negative CT may not absolutely rule out smaller emboli

• Multidetector CTA: lead to decreased section thickness, reduced scanning time and markedly improved visualization of segmental and subsegmental vessels

1Moores LK, et al. Ann Intern Med 2004.

Contrast-enhanced CTAContrast-enhanced CTA

Amado AB, et al. The Internet Journal of Emergency Medicine. 2006.

Imaging Studies Imaging Studies • Ventilation-perfusion scanning:

• Most likely to be diagnostic in the absence of cardiopulmonary disease • Normal perfusion scan effectively rule out PE

Retrived from www.imagingpathways.health.wa.gov.au

Imaging StudiesImaging Studies• Pulmonary angiography:

• Standard technique for diagnosis of acute PE• Extremely sensitive, specific test• The Prospective Investigation of Pulmonary Embolism

Diagnosis (PIOPED) review complications in 1,111 patients: death in 0.5% and major nonfatal complications in 1%

• MRA:• Excellent sensitivity and specificity• Safer contrast agents, absence of radiation exposure• Difficulty in transporting and performing in critically ill

patients

Heleen C,et al. Thrombosis Research 2006

Imaging StudiesImaging Studies

• Echocardiography:• Dilation or hypokinesis of Rt.ventricle,

abnormal ventricular septal motion or decreased Lt.ventricular diastolic size may suggest the diagnosis

• In acute PE patients, Echo evidence of Rt. Ventricular dysfunction has been suggested thrombolytic therapy

Tapson VF. Cardiol Clin 2004.Pediatric Respirtory Medicine, Taussig 2008.

Imaging StudiesImaging Studies

• Poor prognostic indicators of Echocardiography:• Moderate or severe Rt.ventricular

dysfunction• Persistent pulmonary HT• A patent foramen ovale• Free floating right heart thrombi

More aggressive therapy

Heleen C,et al. Thrombosis Research 2006

Imaging StudiesImaging StudiesTest Sensitivity Specificity

- Pulmonary Angiogram 97 98- V/Q scan - 91- D-dimer

- Rapid ELISA 99 41- Immunoturbidimetric assays 98 40- Whole blood agglutination assay 85 68

- Lower limb venous compression U/S 50 97• Helical CT

• Single-detector row 70 90• Multidetector-row 90 95

Konstantinides SV, Management of acute pulmonary embolism 2007.

Tapson VF. NEJM 2008.

Treatment Treatment • Bed rest is not recommented for DVT but in PE

patients should be initial bed rest for 24-48 hrs • Supportive treatment • Medication therapy:

• Anticoagulation with low-molecular weight heparin(LMWH) or standard heparin

• Thrombolytic therapy

• Surgical therapy:• Inferior vena caval filter• Surgical embolectomy

Anticoagulation Therapy Anticoagulation Therapy • Parenteral anticoagulation with low molecular

weight heparin should be initiated unless contraindicated

• Anticoagulation improves survival in symptomatic PE but risk of recurrent, nonfatal venous thromboembolism is estimated at 5-10% during 1st

year after diagnosis1

• In children, large clinical trials concerning antithrombotic therapy are lacking

1Buller HR, et al. Chest 2005.

Anticoagulation Therapy Anticoagulation Therapy • Subcutaneous LMWH or IV Unfractionated

heparin (UFH) should be administered for at least 5 days

• UFH• Short half life and easily reversible• aPTT should be measured at 6-hr intervals until PTT 1.5-

2.5 times control, achieving within 24hr may reduce risk of recurrence

• LMWH• Subcutaneous administration, fewer side effects and less

frequent monitoring of levels• Anti-Xa is 0.5-1U/ml in sample taken 4-6hr after injection

Tapson VF. NEJM 2008.

Anticoagulation Therapy Anticoagulation Therapy

• Major bleeding in child with treated LMWH occur 0-5.6%, when treated with heparin occur 2%

• Monitoring LMWH by measuring the level of anti-factor Xa may be considered in morbid obesity or very small(<40 kg), pregnant and severe renal insuff.(Cr Cl < 30)

Tapson VF. NEJM 2008.Dix D, et al. J Pediatr 2000.

Anticoagulation Therapy Anticoagulation Therapy

• In acute nonmassive pulmonary embolism, ACCP recommend use LMWH rather than standard heparin (evidence 1A)

• When adequate anticoagulation with heparin, oral warfarin is started and then titrate to obtain INR 2-3

• Warfarin should overlap therapy with heparin

Tapson VF. NEJM 2008.Palareti G, et al. NEJM 2006.

Anticoagulation Therapy Anticoagulation Therapy

• Thromboembolism patients with transient risk factors should be treated for at least 3-6 months but more extended treatment when risk factors persist

• D-dimer levels may help guide decisions about duration of therapy

• Antidote of heparin is protamine

Tapson VF. NEJM 2008.Palareti G, et al. NEJM 2006.

Thrombolytic Therapy Thrombolytic Therapy • Streptokinase, urokinase and rt-PA• Useful adjunct to anticoagulant• Indications in proven PE with:

• Cardiogenic shock• Systemic hypotension without shock

(Massive pulmonary embolism = PE with hemodynamic instability)

Thrombolytic Therapy Thrombolytic Therapy • Contraindication:

• Intracranial, spinal or ocular surgery or disease• Recent major bleeding• Pregnancy• Clinical obvious risk of bleeding

• Directed thrombolytic therapy through pulmonary artery catheter dose not appear to be safer or more effective than through peripheral vein.

Pediatric Respirtory Medicine, Taussig 2008.

Heleen C,et al. Thrombosis Research 2006

Inferior Vena Caval filter Inferior Vena Caval filter • Indication:

• Contraindication to anticoagulation• Major bleeding complications during

anticoagulation • Recurrent embolism while receiving adequate

therapy • Reduced incidence of pulmonary embolism

but increased the subsequent incidence of DVT and have not been shown to increase overall survival

Tapson VF. NEJM 2008.

Inferior Vena Caval filter Inferior Vena Caval filter

Surgical EmbolectomySurgical Embolectomy• Proven massive pulmonary embolism and

hemodynamic instability• Failure of thrombolytic therapy• Absolute contraindication ofthrombolytic therapy

• Risk of death may be high

Tapson VF. NEJM 2008.

Prognosis Prognosis • Received adequate anticoagulant therapy,

3 month overall mortality rate 15-18%• Initial shock is associated with increase in

mortality 3-7 times• Long term sequelae are chronic leg pain or

swelling and chronic pulmonary HT • Recurrent rate of PE is unknown in

children and no information about long term effects on pulmonary function

Tapson VF. NEJM 2008.

Heleen C,et al. Thrombosis Research 2006

Prognosis Prognosis