3 1-DefinitionPulmonary embolism (PE): is an obstruction of the pulmonary artery or one of its branches by a thrombus (or thrombi) that originates somewhere in the venous system.Infarction : The pathological changes which develop in the lung as a result of pulmonary embolismThe types of emboli :could be a blood clot (most common), air, fat, amniotic, fluid, and septic (from bacterial invasion of the thrombus).
4 2-EpidemiologyPE : The cause of, or a major contributory factor to, death in 7-9% of necropsy cases650,000 cases in the US each year150,000 – 200,000 US deaths each yearMost common preventable cause of hospital death3rd most common acute cardiovascular emergency (MI and stroke)
5 3-PathophysiologySource of Thrombosis (Thrombo-embolic) that originates in the venous system and embolizes to the pulmonary arterial circulationDVT in veins of leg above the knee (>90%)DVT elsewhere (pelvic, arm, calf veins, etc.)Cardiac thrombi
8 3-Pathophysiology Risk factors for deep venous thromboembolism Triad of VirchowEndothelial injury: mainly caused by either direct trauma (severed vein) or local irritation (by chemotherapy, past DVT, phlebitis).Stasis: mainly caused by heart failure, prolonged immobility.Hypercoagulation status: inherited :(AT III def., protein C, S deficiency) or acquired: (malignancy, pregnancy, nephritic syndrome, DIC and liver failure.
9 3-Pathophysiology Risk Factors: Strong Predisposing factors (Odds Ratio>10)Moderate Predisposing factors(Odds Ratio 2-9)Weak Predisposing factors(Odds Ratio <2)Fracture (Hip or Leg)Hip or Knee ReplacementMajor General SurgeryMajor traumaSpinal Cord InjuryArthroscopic Knee SurgeryCentral venous lineChemotherapyChronic heart or respiratory failureHormonal replacement therapyOral Contraceptive PillsParalytic StrokePregnancy/PostpartumPrevious VTEThrombopheliaBed Rest<3 daysImmobility due to sitting(e.g prolonged car or air travel)Increasing AgeLaparoscopic surgery (Cholecystectomy)ObesityVaricose veins
16 4-Clinical Picture Revised Geneva Score (Clinical Prediction) Variable PointsPredisposing Factors:Age>65 yearsPrevious DVT or PESurgery or fracture within 1 monthActive malignancy+1+3+2Symptoms:Unilateral lower limb painHaemoptysisClinical SignsHeart Rate75-94 bpm>95bpmPain on LL deep vein and unilateral edema+5+4Clinical probability:LowIntermidiateHighTotal0-34-10>11
17 4-Clinical Picture Wells Score (Clinical Prediction) Variable Points Predisposing Factors:Previous DVT or PERecent Surgery or immobilizationCancer+1.5+1Symptoms:HaemoptysisClinical SignsHeart Rate>100 bpmClinical signs of DVTClinical JudgementAlternative diagnosis less likely than PE+3Clinical probability:LowIntermidiateHighTotal0-12-6>7
18 4-Clinical PictureMost PE are small embolism will reach the periphery of the lung, sometimes producing wedge shaped shadow (pulmonary infarction) on CxR .A large embolism suddenly obstructing a major pulmonary vessel has marked effects on cardiac function , often associated with anterior chest pain and collapse.Chronic recurrent pulmonary embolism may develop pulmonary hypertension and right ventricular failure
21 Duplex US with compression of the lower extremities 5-Diagnostic ToolsDuplex US with compression of the lower extremitiesNon-invasive test that accurately detects proximal DVT in LE (70-80% of pts with PE have concomitant proximal DVT)Often used in workup of PE before going to more invasive proceduresInvasive test: Venography (definitive diagnosis)
24 5-Diagnostic ToolsLaboratory Investigations (Non Specific): leukocytosis , ESR elevation, LDH, SGOT elevation with normal bilirubin.CK, CK MB or Troponin I should be checked to rule out AMIABGNormal does NOT rule out PEHypoxia, hypocapnia, respiratory alkalosis.D-Dimer: High sensitivity but poor specificityNegative prediction<500 ng /ml is a powerful excluding tool for PE
25 5-Diagnostic Tools Chest X-ray: Abnormal in 88% of acute PE Atelectasis (60-70%): most common finding in PE without infarction.Westermark sign (increased lucency in area of embolus)Hampton Hump (wedge-shaped pleural-based infiltrate)Abrupt cutoff of vesselPleural effusion
26 Westermark Sign: represents a focus of oligemia (vasoconstriction )seen distal to a pulmonary embolism
27 Hampton Hump: Radiologic sign which consists of a shallow wedge-shaped opacity in the periphery of the lung with its base against the pleural surface. Occurs 12 to 36 hours after symptoms begin;usually indicates pulmonary infarction
29 5-Diagnostic Tools ECG: Most common: sinus tachycardia +/- nonspecific ST-segment and T-wave changes“Classic S1-Q3-T3 pattern”Other signs of right heart strain (ie, new RBBB and ST changes ,T wave inversion in V1,2Echocardiography:It may be helpful after a large PE in a compromised patient, as it can show right heart dilatation , occasionally thrombus and increased pulmonary arterial pressure readings if tricuspid regurgitation developed.Convenient and rapidly available
32 Echocardiography Findings Transesophageal echocardiographic shows the reduction in size of the clot (arrow) (PA, pulmonary artery; RA, right atrium; Ao, aorta)Transesophageal echocardiographic findings showing the floating thrombus (arrow) into central pulmonary artery (PA, pulmonary artery; RA, right atrium; Ao, aorta)
33 Helical(Spiral) CTSensitivity 85% (more sensitive for proximal emboli but is less good at detecting peripheral emboli, which may account for up to 30% of PE vessels)Specificity 95%It may be used as a first line investigation when V/Q Scan is delayed and when a large PE is suspected and early diagnosis is needed first-
38 V/Q ScanIdentifies mismatches between areas that are ventilated but not perfusedBest initial test in patients with clear CXRNormal: rules out PEHigh-probability scan: is diagnostic of PE if the clinical suspicion is also highLow-probability scan: rules out PE only in a pt with low pretest clinical probability (because PE is found in roughly 15% of pts with low-probability scans)Intermediate-probability scan: requires further evaluation (16-66% chance of PE depending on pretest probability)
43 Pulmonary Angiography “Gold Standard” but is invasive, time consuming, needs experienced radiologists5% morbidity< 0.5% mortalityIndicated if the diagnosis remains uncertain after noninvasive testing
47 6- Prophylaxis Encourage all patients to ambulate as soon as possible determine patient at risk:Low risk :(<40 years old, ambulating, minor surgery) don't need prophylaxis.Moderate risk: (>40 years old, abdominal, pelvic or thoracic surgery) pneumatic compression, or low dose heparin prophylaxis.High risk: (>60years old, prior DVT or PE malignancy, orthopedic surgery hypercoagulability state) combination of pneumatic compression and low dose heparin prophylaxis or Dextran.Coumadine or IVC filter are considered.
48 IVC Filter: if anticoagulation is contraindicated (e. g IVC Filter: if anticoagulation is contraindicated (e.g., active GI bleed, intracranial neoplasm, Ophthalmology patient , known bleeding diathesis), if thrombus formed despite adequate anticoagulation, or with a large burden of thrombosis in the LE that could be fatal if embolized.
51 6- Prophylaxis Rivaroxaban (Oral factor X a inhibitor) New Drug that provide a simple, fixed-dose regimen for treating acute DVT and for continued treatment, without the need for lab. Monitoring.Approved (FDA) for prophylaxis in post-operative period after knee & hip replacement and chronic AF.Nearly it will approved for treatment of acute PE.Antidote: Thrombin Complex Concentrate.
52 7-Treatment Primary Treatment: Supplemental oxygen for hypoxemia. If the PE is large, supportive treatments for hypotension or reduced CO should be given IVF , Levophed , or Dopamine/Mechanical Ventilatory SupportSpecific treatment is with intravenous unfractionated heparin infusion following an initial bolus dose 80 U/kg bolus, then 18 U/kg/hra PTT should be monitored 6 hours after initiation, 6 10 hours after any dosage change, then daily with a target of seconds.Heparin does not reduce acute mortality but significantly reduces further events
53 7-TreatmentLMWH: Current guidelines for patients with acute nonmassive pulmonary embolism recommend LMWH over UFH.LMWHs have many advantages over UFH:These agents have a greater bioavailability,can be administered by subcutaneous injections,and have a longer duration of anticoagulant effect.- A fixed dose of LMWH can be used ( 30mg, sc, bid), and laboratory monitoring of a PTT is not necessaryChest. Jun 2008;133(6 Suppl):454S-545S
54 7-Treatment Oral Anticoagulation: Oral Warfarin can be given with the initiation of Heparin keep INR between 2- 3 with initial dose of 5mg/day for 2 days (The peak effect does not occur until hours after drug administration) .An overlap of 4- 5 days with a therapeutic INR and a PTT is recommended .Persistent oral Warfarin should be prescribed for 3 months till the absence of risk factorsLMWH can be used when Warfarin is contraindicated (e.g. pregnancy) .
55 7-Treatment Long-term anticoagulation 1st event with reversible risk factors: 3-6 months Warfarin.Idiopathic PE/DVT: 6 months Warfarin.2nd event, cancer, preexisting irreversible risk factors, such as deficiency of antithrombin III, protein S and C Deficiency: 12 month to life long Warfarin.BMJ. Mar ;334(7595):674
56 7-TreatmentPotential indications for THROMBOLYTIC THERAPY in venous thromboembolism (acceptable risk of bleeding complications) :significant cardiac compromise , RV strain (Dysfunction) .presence of hypotension related to PE not responding to IVF and vasopressor resuscitation.Presence of severe hypoxemia.Substantial perfusion defect.Extensive DVT.Thrombolytic therapy achieves faster resolution of the thrombus and more rapid recovery of normal vascular flow than simple anticoagulation.
57 7-Treatment Regimens for thrombolysis in Pulmonary Embolism: Drug RegimenStreptokinase IU in min followed by IU/Hour up to 24 Hourst-PA MG IV over 1-2 min followed by an infusion of 90 MG over 2 HoursCerebral hemorrhage can occur in up to 1% of casesIt has been used successfully and safely in a pregnant woman and this is not a contraindication unless immediately postpartum
58 7-Treatment Pulmonary Embolectomy: This is reserved for severe cardiac compromise where thrombolysis has either failed or is contraindicated.It requires an experienced team to be successful and, although used infrequently, small studies (Doerge et al, 1999) have shown favorable outcomes.
59 8-ConclusionUntreated PE is associated with high mortality ,Suspected PE demands prompt diagnostic testing & assessment of risk factors & clinical probability, with empirical clinical assessment & a validated clinical prediction score when possible.