Pulmonary embolism Paweł Balsam
Venous thromboembolism (VTE) Pulmonary embolism (PE) and deep vein thrombosis (DVT) are two clinical presentations of veonus thromboembolism
Pulmonary embolism A pulmonary embolism is a blockage in one of the blood vessels in your lungs. It can be fatal if the obstruction is very large and blocks the main blood supply to the lungs.
Pulmonary embolism
CLOT
Pulmonary embolism Virchow's Triad - Causes of Thrombosis Changes in the blood vessel wall Changes in the blood flow Changes in the blood composition 2012-10-25
Changes in the blood flow The first category, alterations in normal blood flow, refers to several situations. These includeturbulence, stasis, mitral stenosis, and varicose veins. The equivalence of Virchow's version and the modern version has been disputed.
Changes in the blood vessel wall The second category, injuries and/or trauma to endothelium includes damage to the veins arising from shear stress or hypertension.
Changes in the blood composition The last category, alterations in the constitution of blood, has numerous possible risk factors such as hyperviscosity, deficiency of antithrombin III, nephrotic syndrome, changes after severetrauma or burn, disseminated cancer, late pregnancy and delivery, race, age, whether the patient is a smoker, and obesity. All of these risk factors cause the situation called hypercoagulability.
Pulmonary embolism
Pulmonary embolism Pulmonary embolism (PE) is cardiovascular emergency. Occlusion of pulmonary artery may lead to life threatning but potientially reversible right ventricle failure.
Epidemology The prevalence of PE among hospitalized patients is 0.4% It gives about 600 000 patients cases/year in USA
Mortality 2-8% treated (diagnosed) 30% non-treated (non-diagnosed)
Predisposing factors Strong predisposing factors: -fractu re (hip or leg) -hip or knee replacement -major general surgery -major trauma -spinal cord injury
Predisposing factors Moderate predisposing factors: -arthroscopic knee surgery -central venous lines -chemotherapy -chronic heart or respiratory failure -hormone replacement therapy -malignancy -oral contraceptive therapy -paralytic stroke -pregnancy -previous VTE -thrombofilia 2012-10-25
Predisposing factors Weak predisposing factors: - Bed rest > 3 days - Immobility due to sitting (prolonged trip) - Increasing age - Laparoscopic surgery - Obesity - Varicose veins 2012-10-25
Primary risk factors AT III deficiency factor V Leiden (APC-R) mutation of protromine gene 20210A dysfibrynogenemia hiperhomocysteinemia anticardiolipin a-bodies protein C deficiency plasminogen deficiency protein S deficiency
PE Risk factors - secondary CHF immobilization older age neoplasm stroke obesity surgery central iv lines smoking pregnancy/peripartum oral contraceptives long distance travels 2012-10-25
Pathophysiology Key consequences of pulmonary embolism are hemodynamic. Large and mutiple emobli may increase pulmonary vascular resistance to a level of afterload which cannot be matched by a right ventricle (RV)
Pathophysiology Sudden death occurs mainly in the mechanism of electromechanical dissociation.
Pathophysiology Movie: http://www.youtube.com/watch?v=ggrdagn5p C0
Severity of PE Markers of severity: 1. Clinical markers: Shock and Hypotension 2. Markers of RV dysfunction: dilation, hypokinesis or pressure overload on echocardiography RV dilation on spiral computed tomography BNP or NT-proBNP elevation Elevated right heart pressure on RHC 3. Markers of myocardial injury: cardiac troponin T or I 2012-10-25
Risk stratification P E r e l a t e d E A R LY M O R TA L I T Y R I S K C L I N I C A L R I S K M A R K E R S R V d y s f u n t i o n M y o c a r d i a l i n j u r y Tr e a t m e n t i m p l i c a t i o n s H I G H ( 1 5 % ) + ( + ) * ( + ) * Thrombolysis or embolectomy N O N H I G H I n t e r m e d i a t e (3-1 5 % ) - Low <1% + + + - - + - - - H o s p i t a l a d m i s s i o n E a r l y d i s c h a r g e or h o m e t r e a t m e n t 2012-10-25
Prognostic assesment Shock and hypotension are principal markers of high risk of early death in acute PE
Prognostic assesment RV dysfunction is related to intermediate risk of short-term mortality Its prognostic value is limited by the lack of universally accepted criteria. 2012-10-25
Prognostic assesment Myocardial injury is related to intermediate risk of short-term mortality Its prognostic value is limited by the lack of universally accepted criteria.
Diagnosis The diagnosis is often difficult to obtain and it is frequently missed
Diagnosis Clinical presentation D-dimer Compression ultrasonography and computed tomographic venography Ventilation-perfusion scintigraphy Computed tomography Pulmonary angiography Echocardiography 2012-10-25
Clinical presentation Symptoms: -dyspnoea 80% -chest pain 52% -cough 20% -hemoptysis -cyanosis -collapse 2012-10-25
Clinical presentation Signs: -Tachypnoea (>20/min) 70% -Tachycardia (>100/min) 26% -Pulmonary component of the second tone -Raised jugular venous pressure 2012-10-25
Assesment of clnical probability of Variable PE Wells score Predisposing factors: Previous DVT or PE Recent surgry or immobilization Cancer Points +1.5 +1.5 +1 Symptoms Hemoptysis +1 Clinical signs Heart rate >100 beats/min Clinical signs of DVT +1.5 +3 Clinical judgement Alternative diagnosis less likely than PE +3
Assesment of clnical probability of PE Wells score Clinical probability (3 level) Low Intermediate High Clinical probability (2 level) PE unlikely PE likely Total 0-1 2-6 7 0-4 >4
Differential diagnosis of PE: Pneumonia or bronchitis Asthma Exacerbation of chronic obstructive disease MI Pulmonary edema Anxiety
Differential diagnosis of PE: Dissection of the aorta Pericardial tamponade Lung cancer Primary pulmonary hipertension Rib fracture Pneumothorax
D-dimer The product of a cross-linked fibrin. Very high negative predictive value. Very low positive predictive value increased level: cancer, inflamation, necrosis, dissection of the aorta Negative D-dimer result in a higly sensitive assay safely excludes the PE in a patientns with low or moderate clinical risk 2012-10-25
Compression ultrasonography (CUS) 90% of PE is due to DVT in lower limb. CUS has 90% sensitivity and 95% specificity for diagnosing proximal DVT Thus finding a proximal DVT in patients with suspected PE is sufficient to start anticoagualnt treatment 2012-10-25
Ventilation-perfusion scintigraphy Combination of perfusion and ventilation scans. In case of PE the perfusion scan is abnormal but the ventilation scan is normal There is perfusion-ventilation mismatch
Ventilation-perfusion scintigraphy Normal perfusion scan is very safe to exclude PE Combination of non-diagnostic V/Q in a patient with low clinical probability of PE i acceptable for excluding PE. High probability ventilation-perfusion scans establish the diagnosis of PE with a high degree of probability, but further tests are required. 2012-10-25
Computed tomography SDCT single detector computed tomography SENSITIVITY 70%; SPECIFICITY 90% Negative SDCT test is not safe for ruling out PE In association with absence of proximal DVT is a good method for ruling out the PE 2012-10-25
Computed tomography MDCT multi detector computed tomography has high spatial and temporal resolution. SENSITIVITY 83%; SPECIFICITY 96% MDCT showing a thrombus up to the segmental level can be adequate evidence of PE. In a patient with non-high clinical probability of PE, negative MDCT may be used as a stand alone test to exclude PE. 2012-10-25
Pulmonary angiography Is an invasive method associated with some risk. Currently it is useful when the results of noninvasive methods are equivocal.
Echocardiography In the presence of shock and hypotension the lack of echocardiographic signs of RV overload or dysfunction excludes PE as the cause of hemodynamic compromise. It also helps to find the reason of such a condition: tamponade, acute valvular dysfunction, acute myocardial infarction.
Diagnostic strategies Suspected high-risk PE Suspected non-high risk PE
Diagnostic strategies Suspected high-risk PE CT immediately available no yes Echo RV overload no yes CT available CT stable patient positive negative Search for No other test available other causes or patient unstable PE-specific Search for other causes treatment justified 2012-10-25
Diagnostic strategies Suspected non-high-risk PE Asses clinical probability of PE Low/intermediate clinical probability of PE D dimer High clinical probability of PE negative positive Multidetector CT (no treatment) Multidetector CT No PE PE No PE PE No treatment TREATMENT!!! No treatment TREATMENT!! Investigate further 2012-10-25
Treatment The scheme of treatment depends on severity of PE.
Treatment In high risk patients the respiratory and hemodynamic support is necessary. Hemodynamic support: dopamine, dobutamine, epinephrine, norepinephrine
Treatment High risk patients Thrombolytic therapy is the first line treatment in high-risk patients presenting with cardiogenic shock and/or persistent arterial hypotension with a very few absolute cantraindications.
Treatment High risk patients Routine use of thrombolysis in non-high risk patients is not recomended. It may be considered in intermediate risk patients after thorough consideration of conditions increasing the risk of bleeding.
Thrombolysis contraindications Absolute: -Haemorrhagic stroke or stroke of unkown origin at any time -Ishemic stroke in preceding 6 months -Central nervous system damage or neoplasms -Recent major trauma/surgery/head injury (within preceding 3 weeks) -Gastrointestinal bleeding within the last month -Known bleeding 2012-10-25
Thrombolysis contraindications Relative contraindications: -transient ischaemic attack in preceding 6 months -oral anticoagulant therapy -pregnancy or within 1 week post partum -non-compressible punctures -traumatic resuscitation -advanced liver disease -infective endocarditis -active peptic ulcer -refractory hypertension 2012-10-25
Thrombolytic regimens for PE treatment Streptokinase: -250000 IU as a loading dose over 30 minutes -followed by 100000 IU/h over 12-24h Urokinase: -4400IU/kg as a loading dose over 10min -followed by 4400IU/kg/h over 12-24h 2012-10-25
Thrombolytic regimens for PE treatment rtpa 100mg over 2h or 0.6 mg/kg over 15 min (maxium dose 50mg)
Surgical pulmonary embolectomy With current surgical techniques, pulmonary emobolectomy is a valuable therapeutic option in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.
Percutaneous catheter embolectomy and fragmentation Catheter embolectomy or fragmentation of proximal pulmonary clots may be considered as an alternative to surgical treatment in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.
Anticoagulant therapy Anticoagulant therapy with unfractioned heparin, LMWH or fondaparinux should be initiated without delay in patients with confirmed PE and those with high or intermediate risk clinical probability of PE while diagnostic workup is still ongoing.
Anticoagulant therapy Except for patients at high risk of bleeding and those with severe renal dysfunction, subcutaneous LMWH or fondaparinux rather than intravenous unfractioned heparin should be considered for initial treatment
Anticoagulant therapy 2012-10-25 Unfractioned heparin: -bolus of 80U/kg, followed by infusion at the rate of 18U/kg/h. -subsequent doses should be adjusted using the activated partial thromboplastin time(aptt). -reach and maintain the prolongation of aptt between 1.5 and 2.5 -aptt should be measured 3-4 hours after bolus and 3 hours after each dose adjustment
Anticoagulant therapy - UFH aptt Change of dosage <35 s (<1.2 times control) 80 U/kg bolus; increase infusion rate by 4U/kg/h 35-45s (1.2 1.5 times control) 46-70s (1.5-2.3 times control) 71-90s (2.3 3.0 times control) 40 U/kg bolus; increase infusion rate by 2U/kg/h No change Reduce the infusion rate by 2 U/kg >90s (>3.0 times) Stop infusion for 1 hour then reduce infusion rate by 3 U/kg/h
Anticoagulant therapy In patients at high risk of bleeding (non-high risk PE) and in those with severe renal dysfunction, unfractioned heparin with an aptt target range of 1.5-2.5 times normal is a recommended form of initial treatment.
Anticoagulant therapy LMWH enoxaparin -dose: 1.0 mg/kg every 12h -contraindicated in severe renal failure (creatinine clearance <30 ml/min) Fondaparinux selective factor Xa inhibitor -dose: 5mg body weight <50g 7.5mg body weight 50-100kg 10mg body weight > 100kg 2012-10-25
Anticoagulant therapy Parenteral anticoagulation should be continued for at least 5 days VKA a should be initiated as soon as possible and preferably on the same day as initial anticoagulant. Parenteral anticoagulant should be stopped when the INR lies between 2.0 and 3.0 for at least 2 consecutive days. 2012-10-25
Class o recomedation
Level of evidence
Oral anticoagulant therapy
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