PULMONARY THROMBOEMBOLISM DR.SUDHA RANI PANEM

PE IS IMPORTANT IN ICU PATIENTS WHERE DIAGNOSIS IS DIFFICULT AND PE MAY BE LIFE THREATENING WITH MORTALITY RATE IN HEMODYNAMICALLY UNSTABLE PATIENTS BEING 30%.

AETIOLOGY DVT AND PE ARE SINGLE DISEASE TERMED VENOUS THROMBOEMBOLISM. EMBOLISATION OF DVT TO PULMONARY ARTERIES LEADS TO PE. MOST PE RESULTS FROM DVT OF LOWER LIMBS,PELVIC VEINS OR INFERIOR VENA CAVA ALSO DVT FROM UPPER LIMBS,RIGHT ATRIUM OR VENTRICLE.

40% DVT PATIENTS DEVELOP PE.

PREDISPOSING RISK FACTORS FOR VTE INVOLVE ONE OR MORE COMPONETS OF VROCHOW’S TRIAD: 1.VENOUS STASIS 2.VEIN WALL INJURY AND 3.HYPERCOAGULABILITY OF BLOOD

RISK FACTORS VENOUS THROMBOEMBOLISM PRIMARY HYPERCOAGULABLE STATES(THOMBOPHILIA) -ANTITHROMBIN III DEFICIENCY -PROTIEN C DEFICIENCY -PROTIEN S DEFICIENCY RESISTANCE TO ACTIVATED PROTIEN C (INHERITED FACTOR V LEIDEN MUTATION) HYPERHOMOCYTEINNNAEMIA LUPUS ANTICOAGULANT(ANTIPHOSPHOLIID AB)

SECONDARY HYPERCOAGULABLE STATES * IMMOBILITY SURGERY TRAUMA MALIGNANCY PREGNANCY AND THE PERPURIUM OBESITY SMOKING OCPS INDWELLING CATHERS IN GREAT VEINS AND THE RIGHT HEART BURNS PATIENTS WITH LIMB PARALYSIS HEART FAILURE INCREASING AGE

PATHOPHSIOLOGY PULMONARY ARTERIAL OBSTRUCTION AND THE SUBSEQUENT RELEASE OF VASOACTIVE SUBSTANCES SUCH AS SEROTONIN AND THROMBOXANE A2 FROM PLATELETS LEAD TO ELEVATED PULMONARY VASCULAR RESISTANCE AND ACUTE PULMONARY HYPERTENSION. cont…...

Pulmonary Embolism Pulmonary Embolus is a fragment of the thrombus that breaks off and travels In the blood until it lodges at the pulmonary vasculature.

Cont… AC PULMONARY HTN INCREASES RV AFTERLOAD AND RV WALL TENSION,WHICH LEADS TO RV DYSFUNCTION WITH CORONARY ISCHEMIA BEING A MAJOR CONTRIBUTING MECHANISM.IN MASSIVE PE,THE COMBINATION OF CORONARY ISCHEMIA, RV SYSTOLIC FAILURE,PARADOXICAL INTERVENTRICULAR SEPTAL SHIT PERICARDIAL CONSTRAINT LEADS TO LV DYSFUNCTIONAND OBTRUCTIVE SHOCK. PATIENTS WITH UNDERLYING RESPIRATORY DISEASE,A SMALL PE CAN HAVE PROFOUND CONSEQUENCES

THERE IS VENTILATION PERFUSION MISMATCHWHICH LEADS TO HYPOXAEMIA. THERE IS INCREASED DEAD SPACE AND INCREASE IN END TIDAL TO ARTERIAL CO2 GRADIENT. ALVEOLAR HYPERVENTILATION CAUSES HYPOCAPNEA. INCREASED RIGHT ATRIAL PRESSURE CAN OPEN A PATENT FORAMEN OVALE,RIGHT TO LEFT SHUNTING MANIFESTED AS REFRACTORY HYPOXEIMIA OR PARODOXICAL ARTERIAL EMBOLISATION COMMONLY TO THE BRAIN,LEADING TO CEREBRAL INFARCTION.

Etiology Three primary influences predispose a patient to thrombus formation; these form the so-called Virchow triad, which consists of the following: Endothelial injury Stasis or turbulence of blood flow Blood hypercoagulability

Virchow’s Triad Stasis Vascular Injury Hypercoag- ulability Thrombosis Stasis Hypercoag- ulability Vascular Injury Rudolph Virchow Why does blood clot? IN 1862 Rudolf Virchow (pronounced fer kho), a German physician, known as the father of pathology, formulated “Virchow’s triad” – Stasis, Vascular injury, and hypercoagulability – as the basis of what we now know as thrombosis. Since then, a deepening understanding of the risk factors for venous thrombosis have been developed base on his pioneering studies. Virchow’s Triad as it is called describes three factors, that cause thrombosis. They are: Vascular Injury, Stasis and Hypercoagulability.

Thrombosis usually originates as a platelet nidus on valves in the veins of the lower extremities. Further growth occurs by accretion of platelets and fibrin and progression to red fibrin thrombus, which may either break off and embolize or result in total occlusion of the vein. The endogenous thrombolytic system leads to partial dissolution; then, the thrombus becomes organized and is incorporated into the venous wall.

Pulmonary emboli usually arise from thrombi originating in the deep venous system of the lower extremities; however, they may rarely originate in the pelvic, renal, or upper extremity veins or the right heart chambers. After traveling to the lung, large thrombi can lodge at the bifurcation of the main pulmonary artery or the lobar branches and cause hemodynamic compromise

Smaller thrombi typically travel more distally, occluding smaller vessels in the lung periphery. These are more likely to produce pleuritic chest pain by initiating an inflammatory response adjacent to the parietal pleura. Most pulmonary emboli are multiple, and the lower lobes are involved more commonly than the upper lobes.

The causes for pulmonary embolism are multifactorial and are not readily apparent in many cases. The causes described in the literature include the following: Venous stasis Hypercoagulable states Immobilization Surgery and trauma Pregnancy Oral contraceptives and estrogen replacement Malignancy Hereditary factors Acute medical illness

Additional risk factors Risk factors for pulmonary embolism also include the following: Drug abuse (intravenous [IV] drugs) Drug-induced lupus anticoagulant Hemolytic anemias Heparin-associated thrombocytopenia Homocystinemia Homocystinuria Hyperlipidemias

Phenothiazines Thrombocytosis Varicose veins Venography Venous pacemakers Venous stasis Warfarin (first few days of therapy) Inflammatory bowel disease Sleep-disordered breathing

In the PIOPED II study, 94% of patients with pulmonary embolism had 1 or more of the following risk factors: Immobilization Travel of 4 hours or more in the past month Surgery within the last 3 months Malignancy, especially lung cancer Current or past history of thrombophlebitis contd……

Contd… Trauma to the lower extremities and pelvis during the past 3 months Smoking Central venous instrumentation within the past 3 months Stroke, paresis, or paralysis Prior pulmonary embolism Heart failure Chronic obstructive pulmonary disease

SYMPTOMS DYSPNOEA PLURITIC CHEST PAIN AND HEMOPTYSIS ARE CLASSIC SYMPTOMS OF PE. PLURITIC CHEST PAIN AND HEMOPTYSIS ARE LATE PRESENTATION WHERE PULMONARY INFARCTION HAS OCCURRED. IF SYNCOPY OCCURS,IT IS A MASSIVE PE.

PHYSICAL SIGNS TACHYCARDIA FEVER AND SIGNS OF RV DYSFUNTION(RAISED JVP,PARASTERNAL HEAVE AND LOUD PULMONARY COMPONENTS OF THE 2ND HEART SOUND)> IN MASSIVE PE,HYPOTENTION,PALE MOTTELED SKIN AND PERIPHERAL OR CENTRAL CYANOSIS. IT IS IMPORTANT TO EXAMINE SIGNS OF DVT ESPLY IN LEGS.

INVESTIGATIONS D-DIMER ELEVATED WHEN ACUTE THROMBUS OCCURS IT IS SENSITIVE. NEGATIVE D-DIMER USING ELISA , ELFA AND LATEX QUANTITATIVE ASSAYS ARE HIGHLY PREDICTIVE OF ABSENCE OF BOTH DVT AND PE.

HIGH D-DIMER IS OFTEN ELEVATED IN ICU PTS INCLUDING INFECTION,INFLAMMATION,CANCER,SURGERY AND TRAUMA,ACUTE CORONARY SYNDROME,STROKE,PERIPHERAL ARTERY DISEASE OR RUPTURED ANEURYSM.

RAISED TROPONIN IS ASSOCIATED WITH HEMODYNAMIC INSTABILITY IN PATIENTS WITH NON-MASSIVE PE INDEPENDENTLY OF CLINICAL,ECHOCARDIOGRAPHIC AND LABORATORY FINDINGS. LOW BNP AND NT-PRO BNP HAVE BEEN SHOW TO HAVE UNEVENTFUL COURSE IN PATIENTS WITH KNOWN CASE OF PE

ABG HYPOXIA (with widened alveolar-arterial oxygen gradient) HYPOCAPNIA INCREASED END TIDAL CO2 SUSPECT PE EVEN IF IT IS COMMON FINDINGS IN CRITICALLY ILL PTS. METABOLIC ACIDOSIS WITH SHOCK =>LARGE PE.

ECG NON SPECIFIC SINUS TACHYCARDIA, NON SPECIFIC S-T DEPRESSION AND T-WAVE INVERSION IN ANTERIOR LEAD INDICATES RIGHT HEART STRAIN. S1 Q3T3 IS CLASSICAL BUT INFREQUENT. ECG IS USEFUL IN EXCLUDING ACUTE MI AND PERICARDITIS.

CHEST X-RAY FOCAL OLIGEMIA AND WEDGE SHAPED DENSITY ABOVE THE DIAPHRAGM AND ENLARGED DESCENDING PULMONARY ARTERY ARE USUALLY UNCOMMON.

Diagnostic Testing Echocardiography Consider in every patient with a documented pulmonary embolism EKG maybe helpful in demonstrating right heart strain Early fibrinolysis can reduce mortality 50%! Diagnosing of early right ventricular strain is important because it is a strong predictor of subsequent death Important to recommend echocardiogram with your admitting internist if a pattern of right heart strain is suggested by EKG. Studies have documented that lives are saved with early fibrinolysis is considered in these patients.

Diagnostic Testing ECG= Most Common Findings: Tachycardia or nonspecific ST/T-wave changes Acute cur pulmonale or right strain patterns Tall peaked T-waves in Lead II. Right axis deviation. RBBB S1-Q3-T3 (occurs in only 20% of PE patients) A brief mention about the classic S1-Q3-T3, its appearance on the EKG may suggest PE, but study after study has shown it has no predictive value what so ever! But you got to know it because question writers for the boards love it!

CTPA SCAN ESPECIALLY MULTIDETECTOR SCANNER(MD-CTPA) HAS LAGLY REPLACED LUNG VENTILATION PERFUSION SCANNING. ADVANTAGES:GREATER ACCURACY,AND READY AVAILABILITY AT MOST HOSPITALS. WHEN COMPARED WITH CONVENTIONAL ANGIOGRAPHY IT APPEARS RELIABLE WITH EXCELLENT SENSITIVITY,SPECIFICITY AND ACCURACY.

CTPA CAN DETECTSMALL PERIPHERAL EMBOLI IN SUBSEGMENTAL PULMONARY ARTERIES DUE TO BETTER VISUALISATION CAN ALSO BE USED TO ASSES THE SEVERITY OF PE. INCREASED RV/LV RATIO AND CLOT IN THE PROXIMAL BRANCHES OF THE PULMONARY ARTERY CORRELATE WITH THE CLINICAL SEVERITY OF PE. CTPA CAN ALSO IDENTIFY THE CAUSATIVE DVT IN THE VEINS OF THE LEGS,PELVIS AND THE ABDOMEN OR DETECT ALTERNATIVE OR ADDITIONAL DIAGNOSES SUCH AS A PULMONARY MASS,EMPHYSEMA OR MEDIASTINAL ADENOPATHY.

DESPITE THE INCREASED USE OF CTPA V/Q SCAN IS USEFUL IN PATIENTS IF CTPA IS CONTRAINDICATED.

ECHOCARDIOGRAPHY MOST COMMON ARE RV DILATATION,RV HYPH OKINESIS,PARADOXICAL INTERVENTRICULAR SEPTAL MOTION TOWARD THE LV,TRICUSPID REGURGITATION AND PULMONARY HYPERTENSION. PRESENCE OF RV DYSFUNTION CORELATES WITH MORTALITY. TRANSTHORACIC ECHOCARDIOGRAPHY ALLOW ESTIMATION OF PULMONARY ARTERIAL PRESSURE,IDENTIFICATION OF INTRACARDIAC THROMBI AND AIDS IN DIFFERENTIAL DIAGNOSIS BY EXCLUDING AORTIC DISSECTION AND PULMONARY TAMPONADE

TRANSTHORACICECHO HAS ADDITIONAL BENEFIT OF DIRECTLY IDENTIFYING EMBOLUS IN THE PROXIMAL PULMONARY ARTERIES WHICH IS COMMON IN HEMODYNAMICALLY STABLE PATIENTS.

IN HEMODYNAMICALLY UNSTABLE PATIENTS TRANSTHORACIC ECHO IS PREFERABLE.

MANAGEMENT MANAGEMENT PRINCIPLES ALL PATIENTS AT ALL LEVELS OF SEVERITY SHOULD RECEIVE ANTICOAGULATION WITH EITHER UNFRACTIONATED OR LOW MOLECULAR WEIGHT OF HEPARIN TO PREVENT FURTHER EMBOLISATION.

IN HEMODYNAMICALLY UNSTABLE PATIENTS IF CPR IS REQUIRED MORTALITY IS 65%.THESE PATIENTS HAVE THE BENFIT FROM A STRATEGY THAT INCLUDES URGENT EMBOLUS DESTRUCTION(WITH THROMBOLYTIC THERAPY OR EMBOLECTOMY),CONCURRENT HEMODYNAMIC SUPPORT AND PREVENTION OF FURTHER EMBOLISATION.

MAJOR PRINCIPLES OF MANAGEMENT ARE : PREVENTION OF FUTHER EMBOLISATION (ALL MASSIVE, SUBMASSIVE AND MILD PE) EMBOLUS DESTRUCTION (MASSIVE AND SUBMASSIVE PE). CONCURENT HEMODYNAMIC SUPPORT(IN MASSIVE PE)

PREVENTION OF FURTHER EMBOLISATION:ANTICOAGULANT THERAPY Unfractionated heparin therapy Initial bolus of 80 U/kg or 5000 U followed by an infusion of 18 U/kg/h or 1300 U/h should be given, with the goal of rapidly achieving and maintaining the aPTT at levels that correspond to therapeutic heparin levels. Fixed-dose and monitored regimens of subcutaneous UFH are available and are acceptable alternatives.

APTT DOSE CHANGE (UNITS/KG/HR) ADDITIONAL ACTION NEXT <35 SECS +4 REBOLUS OF 80 UNITS/KG 6HRS 35-45 SECS +2 REBOLUS OF 40UNITS/KG 46-70SECS NIL NOTHING 71-90SECS >90SECS -2 -3 STOP INFUSION FOR 1HR

Low-molecular-weight heparin therapy Current guidelines for patients with acute PE recommend LMWH over IV UFH (grade 2C) and over SC UFH (grade 2B).[5] In patients being treated with LMWH, once-daily regimens are preferred over twice-daily regimens (grade 2C). The choice between fondaparinux and LMWH should be based on local considerations to include cost, availability, and familiarity of use.

COMPLICATIONS WITH BOTH HEPARIN AND LMWH:PEPTIC ULCER, STROKE, RETROPERITONIAL HEMATOMA, POST SURGICAL WOUND HEMORRHAGES AND HITTS-HEPARIN INDUCED THROMBOTIC THROMBOCYTOPENIA.

Treatment Warfarin (Coumadin) Interferes with the action of Vit-K dependent factors: II, VII, IX, and X, as well as protein C & S Causes temporary hypercoagulable state in first 5 days of treatment Patient is anticoagulated with heparin before initiating warfarin therapy Target INR is 2.5 – 3.0 This is because the anticoagulants protein C and S have short half-lives compared with the procoagulant vitamin K-dependent proteins. So, this gives rise to the clinical importance that heparin must be continued for at least five days after beginning Coumadin The incidence of progressive thrombosis and embolization is 40% when starting warfarin directly, compared to only 8% when beginning after a patient has been anticoagulated with heparin. Treatment is usually for 6 months, but may continue lifelong

NEWER ANTICOAGULANTS INCLUDE RIVAROXABAN(COMPETITIVELY BINDS ACTIVATED FACTOR X) DABIGATRON (DIRECT INHIBITOR OF THROMBIN)

IVC FILTERS ABSOLUTE INDICATIONS INCLUDE: NEW OR RECURRENT PE DESPITE ANTOCOAGULATION CONTRAINDICATIONS TO ANTICOAGULATION COMPLICATIONS RESULTING FROM ANTICOAGULATION OTHERS: PATIENTS WITH EXTENSIVE DVT PATIENTS FOLLOWING SURGICAL EMBOLECTOMY PATIENTS FOLLOWING THROMBOLYTIC THERAPY

THRMBOLYTIC THERAPY

RECOMMENDE DOSES OF THROMBOLYTICS FOR PE UROKINASE:4400 UNITS/KG BOLUS OVER 10 MIN 4400 UNITS/KG /HR FOR 12HRS. STREPOKINASE:2,50,000UNITS BOLUS FOR 15 MIN FOLLOWED BY 1,00,000UNITS/HR FOR 24HRS. ALTEPLASE 10MG F/B 90mg OVER 2HRS. RETEPLASE 10 UNITS BOLUSES 30MIN APART.

Treatment Embolectomy Prefibriniolytic therapy this was only therapy for Massive Pulmonary Embolism. Carries a 40% operative mortality. Alternative is Transvenous Catheter Embolectomy. This is a procedure where a suction tip catheter is placed in contact with the thrombus under fluoroscopy and sucked out while catheter is withdrawn

CONCURRENT HEMODYNAMIC SUPPORT IV FLUIDS TO IMPROVE HEMODYNAMIC STATUS BUT CAUTIOUSLY AS OVER LOAD MAY WORSEN RV FUNCTION WHICH MAY WORSEN LV FUNCTION

VASOPRESSORS FOR ELEVATION OF THE BLOOD PRESSURES AND REDUCTION INPULMONARY AND RV PRESSURES BASED ON RATIONALE THAT THE RV CORONARY PERFUSION PRESSURE CAN BE SEVERELY IMPAIRED IN MASSIVE PE. ECMO IS EXTREME BUT ALTERNATE FORM OF MECHANICAL ASSISTANCE THAT MAY BE AVAILABLE IN MORE SPECIALISED INSTITUTIONS.

INHALED NITRIC OXIDE MAY BE USEFUL IN PATIENTS WITH MASSIVE PE BY SELECTIVELY DECREASING PUL.A .PRESSURE WITH MINIMAL EFFECT ON SYSTEMIC HEMODYNAMICS.

OXYGEN FOR ADEQUATE OXYGEN SATURATION. HIGH FLOW REQUIRED BECAUSE OF HYPERVENTILATION AND INCREASED DEAD SPACE. INTUBATION AND MECHANICAL VENTILATION ARE OFTEN NECESSARY FOR MASSIVE PE PATIENTS.

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