Guidelines for diagnosis and management of acute pulmonary embolism By Dr. Ahmed Zaghloul M.D. Anesthesia & Critical Care 2014
Predisposing factors for VTE Predisposing factor Strong predisposing factors Fracture (hip or leg) Major surgery Moderate predisposing factors Malignancy Central venous lines Weak predisposing factors Bed rest >3 days Pregnancy/antepartum
Symptoms and signs Pollack CV et ai Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report ofemperor(multicenter Emergency Medicine PulmonaryEmbolism in the RealWorld Registry). J Am Coll Cardiol 2011;57(6):700 706.
Assessment of clinical probability: Use of prediction rule, makes it possible to discriminate suspected P.E. patients in categories of clinical or pretest probability to an increasing prevalence of P.E.
Clinical prediction rules Wells PS et alfurther validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thromb Haemost 2008;99(1):229 234.
Initial Risk Stratification a) SBP <90 mmhg or a pressure drop of >40 mmhg for >15 min (If not caused by new onset arrhythmia, hypovolemia or sepsis) b) risk of early (in-hospital or 30 day) PE- related mortality
Diagnostic Assessment (1) Suspected high-risk PE i.e. with shock or hypotension NO CT immediately available YES Available Echo ( RV overload) CT CT available(stabilized patient) NO YES No other tests available or patient unstable Positive Negative Search for other causes thrombolysis/ embolectomy not justified PE specific treatment justified consider thrombolysis or embolectomy Search for other causes thrombolysis/ embolectomy not justified
Diagnostic Assessment (2) Suspected non- high-risk PE i.e. without shock or hypotension Assess clinical probability of PE (prediction rule) Low/intermediate clinical probability or PE unlikely High clinical probability or PE likely D-dimer CT angiography Negative (No treatment) Positive (CT angiography) NO PE (No treatment or investigate further) PE treatment
Diagnostic Assessment
Risk- and Severity Adjusted Strategy Severity of PE should be understood as an individual estimate of PE related early mortality risk, rather than anatomic burden, shape and distribution of intrapulmonary emboli. Therefore current guidelines suggest replacing potentially misleading terms such as massive, sub- massive, non-massive with the estimated levels of risk of PE-related early death.
Original and simplified PESI
Original and simplified PESI
Classification of patients with acute PE based on early mortality risk
Principal markers useful for risk stratification Clinical markers Markers of RV Dysfunction Shock Hypotension RV dilatation, hypokinesis or pressure overload on echocardiography RV dilatation on spiral computed tomography BNP or NT-proBNP elevation Elevated right heart pressures at right heart catheterization Markers of myocardial injury Cardiac troponin T or I positive SBP <90 mmhg or a pressure drop of >40 mmhg for >15 min
Recommendations for PE with shock or hypotension Recommendations for high risk Class level Anticoagulation with UFH should be initiated without delay in patients with high-risk PE I C Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE Vasopressive drugs are recommended for hypotensive patients with PE I C I A Dobutamine may be used in patients with PE low cardiac output and normal blood pressure IIa B Aggressive fluid challenge is not recommended III B Oxygen should be administered to patients with hypoxaemia I C Thrombolytic therapy should be used in pts with high risk PE with cardiogenic shock and/or persistent art. Hypotension Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high risk PE in whom thrombolysis is absolutely contraindicated or has failed Catheter embolectomy or fragmentation of proximal P. arterial clots may be considered as an alternative to surgical treatment in high-risk patient when thrombolysis is absolutely contraindicated or has failed Meneveau et al Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest 2006;129(4):1043 1050 Wan S et al Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation 2004;110(6):744 749. I I I B C C
Approved thrombolytic regimens for pulmonary embolism Streptokinase 250,000 IU as a loading dose over 30min, followed by 100,000 IU/h over 12-24h Accelerated regimen: 1.5 million IU over 2h Urokinase 4,400 IU/kg as a loading dose over 10min, followed by 4,400 IU/kg/h over 12-24h Accelerated regimen: 3 million IU over 2h rtpa 100mg over 2h; or 0.6mg/kg over 15min (maximum dose 50mg)
Contra-indications to thrombolytic therapy Absolute contra-indications Haemorrhage stroke or stroke of unknown origin at any time Ischaemic stroke in preceding 6 months Central nervous system damage or neoplasms Recent major trauma/surgery/head injury within preceding weeks Gastro-intestinal bleeding within the last month Known bleeding Relative contra-indications Transient ischaemic attack in preceding 6 months Oral anticoagulant therapy Pregnancy or within 1 week post partum Non-compressible punctures Traumatic resuscitation Refractory hypertension (systolic blood pressure > 180 mmhg) Advanced liver disease Infective endocarditis Active peptic ulcer
Recommendations PE without shock or hypotension Recommendations for non-high risk Class Level Anticoagulation: combination combination of of parenteral parenteral treatment treatment with with VKA VKA should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic work-up is still ongoing Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk those with severe renal dysfunction UFH with an aptt target range of 1.5-2.5 times normal is a recommended form of initial treatment Initial treatment with UFH, LMWH or fondaparinux should be continued for at least 5 days and may be replaced by VKA only after achieving target INR levels for at least 2 consecutive days Anticoagulation: new oral anticoagulants Rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) I B I I I I C A C B Thrombolysis Routine use of thrombolysis in non-high-risk patients is not recommended, but it may be considered in selected patients with intermediate-risk PE IIb B Buller HR et al Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. NEngl J Med 2012;366(14);1287-129
Buller HR et al Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. NEngl J Med 2012;366(14);1287-1297
LMW heparins and fondaparinux approved for treatment of P.E.
Recommendations for venous filters Recommendations Class Level IVC filters should be considered in patients with acute PE and absolute contraindications to anticoagulation IIa C IVC filters should be considered in case of recurrence of PE, despite therapeutic levels of anticoagulation IIa C Routine use of IVC filters in patients with PE is not recommended. III A PREPIC StudyGroup. Eight-year follow-up of patients with permanent vena cava ilters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d Embolie Pulmonaire par Interruption Cave) randomized study. Circulation2oo5;112(3):416-422
Duration of anticoagulation after pulmonary embolism Recommendations Class Level For patients with PE secondary to a transient (reversible) risk factors, treatment when a VKA is recommended for 3 months For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months I I B A Pts with a first episode of unprovoked PE and low bleeding risk, and in whom stable anticoagulation can be achieved, may be considered for long-term oral Anticoagulation For patients with a second episode of unprovoked PE, long-term treatment is recommended New oral anticoagulants should be considered as an alternative to VKA (except for patients with severe renal impairment) IIa I IIa B A B