Pulmonary embolism ms

Pulmonary Embolism

MAGDI AWAD SASI1

MAGDI AWAD SASI 2013 PULMONARY EMBOLISM AND DVT

Pulmonary embolism (PE) is a common and potentially lethal condition. Most patients who succumb to pulmonary embolism do so within the first few hours of the event. In patients who survive, recurrent embolism and death can be prevented with prompt diagnosis and therapy. Unfortunately, the diagnosis is often missed because patients with pulmonary embolism present with nonspecific signs and symptoms. If left untreated, approximately one third of patients who survive an initial pulmonary embolism die from a subsequent embolic episode.

The most important conceptual advance regarding pulmonary embolism over the last several decades has been the realization that pulmonary embolism is not a disease; rather, pulmonary embolism is a complication of venous thromboembolism, most commonly deep venous thrombosis (DVT). Virtually every physician who is involved in patient care (eg, internist, family physician, orthopedic surgeon, gynecologic surgeon, urologic surgeon, pulmonary subspecialist, cardiologist) encounters patients who are at risk for venous thromboembolism, and therefore at risk for pulmonary embolism.

DEFINITION:

PE is the obstruction of the pulmonary artery or one of its branches by a thrombus (or thrombi) that originates somewhere in the venous system or in the right side of the heart .

Definition for Massive PE

Acute PE with with at least 1 of the following:

1. Sustained hypotension

SBP <90 mmHg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or LV dysfunction, drugs,etc.

2. Pulselessness

3. Persistent profound bradycardia

Heart rate <40 bpm with signs or symptoms of shock

Definition for Submassive PE

Acute PE without systemic hypotension (SBP >90 mm Hg) but with either RV dysfunction or myocardial necrosis.

2MAGDI AWAD SASI 2013 PULMONARY EMBOLISM AND DVT

• RV dysfunction means the presence of at least 1 of the following:

– Echo: RV dilation (apical 4-chamber RV diameter divided by LV diameter >0.9), or RV systolic dysfunction

•

– CT: RV dilation (4-chamber RV diameter divided by LV diameter > 0.9)

– BNP > 90 pg/mL or N-terminal pro-BNP > 500 pg/mL

– ECG changes: New complete or incomplete RBBB, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion

• Myocardial necrosis is defined as either of the following:

– Troponin I > 0.4 ng/mL, or Troponin T > 0.1 ng/mL

Definition for Low-Risk PE

Acute PE and the absence of the clinical markers of adverse prognosis that define massive or submassive PE.


PREVALENCE

PE is estimated to cause 200,000 deaths each year in the United States . The 2nd leading cause of death among hospitalized patients, unexpected,

nontraumatic death. Most cases are not recognized antemortem, and LESS THAN 10% of

patients with fatal emboli have received specific treatment for the condition.

Management demands a vigilant systematic approach to diagnosis and an understanding of risk factors so that appropriate preventive therapy can be given.

The incidence of PE in USA is 650-900,000 per year.

AETIOLOGYMany substances can embolize to the pulmonary circulation, including

1. AIR (during neurosurgery, from central venous catheters)2. AMNIOTIC FLUID(during active labor), fat (long bone fractures)3. FOREIGN BODIES (talc in injection drug users)4. PARASITE EGGS (schistosomiasis)5. SEPTIC EMBOLI (acute infectious endocarditis)6. TUMOR CELLS(renal cell carcinoma).7. RED EMBOLUS (DVT, atrial fibrillation)

The most common embolus is thrombus, which may arise anywhere in the venous circulation or heart but most often originates in the deep veins of the lower extremities. Thrombi confined to the calf rarely embolize to the pulmonary circulation. However, about 20% of calf vein thrombi propagate proximally to the popliteal and ileofemoral veins, at which point they may break off and embolize to the pulmonary circulation.((50%asymptomatic DVT)). Pulmonary emboli will develop in 50–60% of patients with proximal deep venous thrombosis (DVT); half of these embolic events will be asymptomatic.

DEEP VEIN THROMBOSIS:

50% of all patients with venous thrombosis of the lower extremities have no symptoms. Approximately 50–70% of patients who have symptomatic pulmonary emboli will have lower extremity DVT when evaluated.


Obstruction of the deep veins of the legs produces edema and swelling of the extremity because the outflow of venous blood is inhibited. The amount of swelling can be determined by measuring extremity circumference at various levels with a tape measure. The skin over the affected leg may become warmer, and superficial veins may become more prominent. Tenderness, which usually occurs later, is produced by inflammation of the vein wall and can be detected by gentle palpation by the extremity. Homan’s Signs, pain in the calf after sharp dorsiflexion of the foot, is not specific for deep venous thrombosis because it can be elicited in any painful condition of the calf. In some cases, signs of a pulmonary embolus are the first indication of a deep venous thrombosis. - Thrombosis of superficial veins produces pain or tenderness, redness, and warmth of the involved area. The risk of dislodgment and embolization of superficial venous thrombi is very low because the majority of them undergo spontaneous lysis; thus, condition can be treated at home with rest, extremity elevation, analgesics, and possibly anti-inflammatory agents.

CAUSES:1. Thrombus 2. Embolism 3. Trauma 4. Surgery 5. Hypercoaguability 6. Heart failure 7. Pregnancy (increase coaguability of BLOOD)8. Older than 50 years 9. Arial fibrillation

RISK FACTORS: PE and DVT are two manifestations of the same disease.((DVT))

► It commonly affects the leg veins, such as the femoral vein or the popliteal vein or the deep veins of the pelvis.


SIGNS AND SYMPTOMS

Pain, Swelling Redness of the leg and dilatation of the surface veinsShinning skin with rednessHotness and tendernessPedal edema may occur.

Pathogenesis:

The risk factors for PE are the risk factors for thrombus formation within the venous circulation.


1. Venous stasis OR turbulence(Venous flow disturbance):

o Immobility leads to local venous stasis by accumulation of clotting factors and fibrin, resulting in thrombus formation.

o The risk of pulmonary embolism increases with prolonged bed rest or immobilization of a limb in a cast.

o Paralysis increases the risk of DVT.o V. stasis leads to accumulation of platelets and thrombin in veins

Bed rest—especially postoperative, Hip replacement, knee replacement, caesarian operation, post delivery, comatose patient in ICU, Fracture of long bones, sitting for hours in work or long trip by car or airplane or bus with out activity, CCU admission, obesity, stroke, comatose patient).Intra-pelvic or intra-abdominal mass impairing venous return from the lower limbs ( ovarian mass, cervix cancer , uterine tumors , prostate cancer , sigmoid cancer).

2. Hypercoagulable state(hyperviscosity)

a. The complex and delicate balance between coagulation and anticoagulation is altered by many diseases, by obesity, after surgery, or by trauma.

b. Concomitant hypercoagulability may be present in disease states where prolonged venous stasis or injury to veins occurs.


Congenital –((inherited gene defects-Protein defects)) Factor (V) Leiden ( 20-40%)

G to A mutation at base pair 1691 results in amino acid 506,Glu instead of Arg Prothrombin 20210 (6%)(G to A) Defect or deficiency of protein C (4%) (outozomal dominant) Defect or deficiency of Protein S (3-4%) ( outozomal dominant)

pregnancy and estrogens reduced protein S Dysfibrinogenemia ( 3% ) Antithrombin deficiency ( 1% ) (outozomal dominant ) acquired deficiency

of it happened in sever obesity , liver disease , chronic renal failer , using oral contraceptive ,immature neonates

Dysplasminogenemia ( <1% ) Reduced Heparin cofactor II Elevation of PAI-1 Elevation of Coagulation factors VII,VIII,IX,X,XI and II Reduction of protein Z

Acquired— Hematologic diseases :

DIC(disseminated intravascular thrombocytopenia),thrombocytosis HIT(heparin induced thrombocytopenia), leukemia Anti phospholipid syndrome TTP(thrombocytopenic thrombotic purpura) HUS(hemolytic uremic syndrome)

Thrombocytosis, leukemia , nephrotic syndrome, Oral contraceptives and

estrogen replacement, antiphospholipid syndrome, Homocysteinemia .

o Malignancy has been identified in 17% of patients with venous thromboembolism.

o The neoplasms most commonly associated with pulmonary embolism, in descending order of frequency, are pancreatic carcinoma; bronchogenic carcinoma; and carcinomas of the genitourinary tract, colon, stomach, and breast.


3. Endothelial injury INJURY TO ENDOTHELIUM CAN BE CAUSED BY

1. ATHEROSCLEROSIS2. HYPERTENSION3. HYPERCHOLESTEROLEMIA4. RADIATION INJURY5. SMOKING 6. Thrombophlebitis -Vascular disease7. -Foreign bodies (IV/central venous catheters)

Pathophysiology

When a thrombus completely or partially obstructs a pulmonary artery(massive embolus) or its branches in diseased lung or heart,

The alveolar dead space is increased. The area, although continuing to be ventilated, receives little or no blood flow. Thus, gas exchange is impaired or absent in this area.


Regional blood vessels and bronchioles constrict.

More than 50% of the vascular bed has to be occluded before PAP becomes substantially elevated

In patients without cardiopulmonary disease, occlusion of 25-30 % of the vascular bed .

Causes an increase in pulmonary vascular resistance. Impaired gas exchange

A . Ventilation/perfusion mismatch

B. Release of inflammatory mediators leads to surfactant dysfunction, atelectasis, alveolar hemorrhage ,Intrapulmonary shunting

PVR from 1. The regional vasoconstriction

2. Reduced size of the pulmonary vascular bed.

An increase in pulmonary arterial pressure

An increase in right ventricular work to maintain pulmonary blood flow.

When obstruction approaches 75%, the RV must generate systolic pressure in excess of 50mmHg to preserve pulmonary circulation.

When the work requirements of the right ventricle exceed its capacity, right ventricular failure occurs, leading to a decrease in cardiac output followed by a decrease in systemic blood pressure and the development of shock.(fatigue , syncopy, dizziness).


SYMPTOMOLOGY:

Clinical clues cannot make the diagnosis of PE; their main value lies in suggesting the diagnosis.The symptoms are quite variable according to the heart and lung situation whether they are healthy or diseased and degree of damage.Most of the cases are missed as no specific symptom that the symptoms can be explained by other diagnosis by most of doctors which can lead to lose of the patients.Signs and symptoms are highly variable, nonspecific, and common in patients without PE.

Fatal PE typically leads to death within one to two hours of the event.

Small PE in healthy pt= asymptomatic.

Dyspnea (80%) – usually acute onset

Pleuritic chest pain (44%)

Calf pain/swelling (41-44%)

Orthopnea (28%)

Wheezing (21%)

Cough (20%)

Syncope (14%)

Hemoptysis (7%)

1.Dyspnea is the most frequent symptom; all of a SUDDEN in high risk patients , while in bed or moving from resting state, NEVER GRADUAL, The duration and intensity of the dyspnea depend on the extent of embolization ,heart and lung status.


2. Chest pain is common and is usually sudden and pleuritic. It may be substernal and misdiagnosed with angina pectoris or a myocardial infarction. It is severe from the first minute in high risk patient.

3. All chest symptoms may occur and all of sudden onset in absence of other possibilities(( acute pneumothorax , acute left ventricular failure, acute dissection of ascending aorta)).

97% with PE have at least one of the following:

1. Dyspnea

2. Tachypnea

3. Pleuritic pain

Presence of DVT should trigger initial suspicion.

OTHERS may present with low cardiac out put symptoms such as dizziness, syncopy, profuse sweating, sudden fatigability in suspected high risk patient with dyspnea mimicking vasovagal attacks.

OTHERS may present with sudden vomiting with epigastric pain and diarrhea with fatigue and right hypochondrial discomfort or heaviness due to right side congestion in massive/submassive P.E. WITH HYPOTENSION.

Other symptoms include anxiety, fever, tachycardia, apprehension, cough, diaphoresis, hemoptysis, unexplained fatigue or palpitation/shivering.

SIGNS:

Tachypnea (53%) Tachycardia (24%)

Rales (18%) Decreased breath sounds (17%)

Accentuated P2 (15%) JV distension (14%)

Signs of DVT


Physical examination findings are quite variable in pulmonary embolism and, for convenience, may be grouped into 4 categories as follows:

Massive pulmonary embolism o The patient in SHOCK. (( systemic hypotension, poor perfusion of

the extremities, tachycardia, and tachypnea , drowzy)).o Additionally, signs of pulmonary hypertension such as palpable P2

second left intercostal space, loud P2, right ventricular S3 gallop, and (tricuspid regurgitation) may be present.

Acute pulmonary infarction o These patients have decreased excursion of the involved

hemithorax, palpable or audible pleural friction rub, and even localized tenderness.

o Signs of pleural effusion, such as dullness to percussion and diminished breath sounds, may be present.

Acute embolism without infarction o These patients have nonspecific physical signs that may easily be

secondary to another disease process.o Tachypnea and tachycardia frequently are detected, pleuritic pain

sometimes may be present, crackles may be heard in the area of embolization, and local wheeze may be heard rarely.

Multiple pulmonary emboli or thrombi o Physical signs of pulmonary hypertension and cor pulmonale.o Patients may have elevated jugular venous pressure, right

ventricular heave, palpable P2 , right ventricular S3 gallop, TR, hepatomegaly, ascites, and dependent pitting edema.

o These findings are not specific for pulmonary embolism and require a high index of suspicion for pursuing appropriate diagnostic studies.

LUNG EXAMINATION- collapse, consolidation where there is 2ry pneumonia which may delay the diagnosis, elevation of diaphragm, cavitating lung cavity with missed diagnosis mimicking lung abscess, pleural effusion , pleural rub , localized wheezing ,basal inspiratory fine crepiataion .


Assessment and Diagnostic Findings:

No single noninvasive test is sufficiently sensitive or specific to diagnose or exclude PE in all patients.

No single test can reliably rule out PE.

Yep, that includes CT Angio (right?)

THEY ARE HELPFUL IN MASSIVE /SUBMASSIVE PE NOT SMALL .

The clinical priorities in the investigation of patients with suspected PE include:

1. Diagnosis of extensive PE

2. Diagnosis of PE in patients with severe symptoms and/or poor cardiopulmonary reserve

3. Diagnosis of any PE when associated with symptomatic or asymptomatic proximal DVT

4. Diagnosis in patients presenting with possible recurrent PE

1.ABG-arterial blood gases:

¯ pO2 ¯ pCO2

Increased A-a gradient


2.D-dimer:

This blood screening test relies on the principle that most patients with PE have ongoing endogenous fibrinolysis that is not effective enough to prevent PE but that does break down some of the fibrin clot to d-dimers .

Although elevated plasma concentrations of d-dimers are sensitive for the presence of PE, they are not specific.

patients with a low clinical probability of PE who had negative d-dimer results, additional diagnostic testing was not necessary

Different assays have different sensitivities

PE in low-risk patients with a negative D-dimer…

o Thrombus formation >72 hrs before blood draw (circulating dimer t1/2 = 8 hrs)

o Subsegmental PE

False-positives = age >70, pregnancy, active malignancy, recent surgery, liver disease, RA, infections, trauma

False-negatives = Coumadin use, symptoms >5days, small clots or infarction, isolated calf vein thrombosis.

Therefore, the plasma d-dimer assay is ideally suited for outpatients or emergency department patients who have suspected PE but no coexisting acute systemic illness OR history of venous thromboembolism and whose symptoms are of short duration.

This test is generally not useful for acutely ill hospitalized inpatients because their D-dimer levels are usually elevated. A normal d-dimer assay appears to be as diagnostically useful as a normal lung scan to exclude PE.

D-dimer test should not be used when the clinical probability of pulmonary embolism is high, because the test has low negative predictive value in such cases.


3.Electrocardiographic Signs:

Sinus tachycardia( THE COMMENEST ) Incomplete or complete right bundle branch block Right-axis deviation T wave inversions in leads III and aVF or in leads V1-V4

S wave in lead I and a Q wave and T wave inversion in lead III (S1Q3T3) QRS axis greater than 90 degrees or an indeterminate axis Atrial fibrillation or atrial flutter


4.Chest Radiography:

A near-normal radiograph in the setting of severe respiratory compromise is highly suggestive of massive PE.(AHA)

Major chest radiographic abnormalities are uncommon.

Focal oligemia (Westermark sign) indicates massive central embolic occlusion.

A peripheral wedge-shaped density above the diaphragm (Hampton hump) usually indicates pulmonary infarction.

Subtle abnormalities suggestive of PE include enlargement of the descending right pulmonary artery, elevated diaphragm,collapse.

The vessel often tapers rapidly after the enlarged portion. PE.


5.Echocardiographic Signs:

Right ventricular enlargement or hypokinesis, especially free wall hypokinesis, with sparing of the apex (the McConnell sign). Interventricular septal flattening and paradoxical motion toward the left ventricle, resulting in a D-shaped left ventricle in cross section.

Tricuspid regurgitation.

Pulmonary hypertension with a tricuspid regurgitant jet velocity >2.6 m/sec.

Loss of respiratory-phasic collapse of the inferior vena cava with inspiration.

Dilated inferior vena cava without physiologic inspiratory collapse.

Direct visualization of thrombus (more likely with transesophageal echocardiography)

Overview of Imaging Modalities for Pulmonary Embolism:

Lower extremity venous ultrasonography

Multidetector helical CT pulmonary angiography

MRI

Ventilation-perfusion scintigraphy (V/Q scan)

6. Computed Tomography

1. Size, location, and extent of thrombus

2. Other diagnoses that may coexist with PE or explain PE symptoms: Pneumonia, Atelectasis, Pericardial effusion, Pneumothorax, abscess, Left ventricular enlargement

3. Pulmonary artery enlargement === pulmonary hypertension Age of thrombus: acute, subacute, chronic


4. Location of thrombus: pulmonary arteries , deep leg veins,

5.Right ventricular enlargement

6.Contour of the interventricular septum: whether it bulges toward the left ventricle, thus indicating right ventricular pressure overload

7.Incidental masses or nodules in lung

7. CT pulmonary Angiography

CT angiography (CTA) is the initial imaging modality of choice for stable patients with suspected pulmonary embolism(low risk).

Sensitivity/Specificity ~90%

withholding anticoagulation after negative pulmonary CTA results appears to be safe.

CTPA use increased 10-fold from 1998-2006


Incidence increased 81% from 1998-2006 (112/100,000) with only 3% mortality reduction

o Increased in-hospital antigcoagulation complications during that same time period

8. Spiral CT- can visualize main, lobar, and segmental pulmonary emboli with a reported sensitivity of greater than 90%. Spiral CT scanning can help detect emboli as small as 2 mm that are affecting up to the seventh border division of the pulmonary artery. A further benefit of spiral CT scanning is that the results may suggest an alternative diagnosis in up to 57% of patients. A significant limitation of spiral CT scanning is that small subsegmental emboli may not be detected.

o The technique is as follows: Spiral CT examination is performed immediately after infusion

of 150-200 mL of 30% contrast material. Scanning is performed from the level of the aortic arch to

approximately 2 cm below the level of the inferior pulmonary vein while the patient is holding his or her breath at full inspiration.

If the patient is not able to hold his or her breath for 20-30 seconds, scanning may be performed during gentle breathing.

Positive findings on CT imaging include a central intravascular filling defect within the vessel lumen, eccentric tracking of contrast material around a filling defect, and complete vascular occlusion. Smooth filling defects making an obtuse angle with a vessel wall may represent chronic thrombi or recent recanalization. In the lung parenchyma, signs of pulmonary embolism include oligemia, pulmonary hemorrhage (ground-glass attenuation), and pulmonary infarction (peripheral wedge-shaped pleural-based opacification.

9. Ventilation-perfusion (V/Q) scanning of the lungs:

This is an important diagnostic modality for establishing the diagnosis of pulmonary embolism.


However, V/Q scanning should be used only 1.when CT scanning is not available or 2. If the patient has a contraindication to CT scanning or intravenous contrast material.

New criteria for V/Q scanning diagnosis of pulmonary embolism, from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II trial:

High probability criteria are as follows: Two large (>75% of a segment) segmental perfusion defects

without corresponding ventilation or chest x ray defects. One large segmental perfusion defect and 2 moderate (25-

75% of a segment) segmental perfusion defects without corresponding ventilation or radiographic abnormalities.

Four moderate segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities


Intermediate probability criteria are as follows: One moderate to fewer than 2 large segmental perfusion

defects without corresponding ventilation or chest radiographic abnormalities

Corresponding V/Q defects and radiographic parenchymal opacity in lower lung zone

Single moderate matched V/Q defects with normal chest radiographic findings

Corresponding V/Q and chest radiography small pleural effusion

Difficult to categorize as normal, low, or high probability Low probability criteria are as follows:

Multiple matched V/Q defects, regardless of size, with normal chest radiographic findings

Corresponding V/Q defects and radiographic parenchymal opacity in upper or middle lung zone

Corresponding V/Q defects and large pleural effusion Any perfusion defects with substantially larger radiographic

abnormality Defects surrounded by normally perfused lung (stripe sign) More than 3 small (<25% of a segment) segmental perfusion

defects with normal chest radiographic findings Nonsegmental perfusion defects (cardiomegaly, aortic

impression, enlarged hila) Very low criterion is 3 small (<25% of a segment) segmental

perfusion defects with normal chest radiograph findings.

Advantage

1. a normal V/Q scan rules out PE>99% negative predictive value

2. the radiation dose is low3. iodine-based contrast is not used

other investigations:

1.MRI


2.PULMONARY ANGIOGRAPHY

3. Multidetector helical CT pulmonary angiography


0-2 = PE unlikely , 3-7 = PE likely

Prevention

Prevent deep venous thrombosis.

1. Active leg exercises 2. The intermittent pneumatic leg compression device ( venous stasis). 3. Use of elastic compression stockings 4. Anticoagulant therapy

Medical Management

• General measures to improve respiratory and vascular status

• Anticoagulation therapy

• Thrombolytic therapy

• Surgical intervention


GENERAL MANAGEMENT

Oxygen therapy is administered to correct the hypoxemia, relieve the pulmonary vascular vasoconstriction, and reduce the pulmonary hypertension.

Thrombolytics

Evidence of circulatory/respiratory insufficiency

Hypotension (SBP <90)

Hypoxia (SpO2 <95%)

Evidence of RV dysfunction

RV dilation/hypokinesis

Elevated troponin-I (>0.4) or proBNP (>900)

EKG changes

FDA-recommended dose: Alteplase 100mg over 2hrs


Therapeutic anticoagulation with subcutaneous LMWH, intravenous or subcutaneous UFH with monitoring, unmonitored weight-based subcutaneous UFH, should be given to patients with objectively confirmed PE and no contraindications to anticoagulation.

UFH=Weight-based dosing (nomogram)IV bolus – 80mg/kg IV bolus, then 18mg/kg/hrMonitor PTT (1.5-2.0 x), CBCContinue ³4-5d and therapeutic on Warfarin for 2d (INR>2.0)

LMWH

Alternative regimen Lovenox – 1mg/kg SC q12h

Better bioavailability, longer half-life, more predictable effect

No monitoring of PTT (follow CBC)

Contraindications: renal failure (CrCl<30), weight extremes

Warfarin

Start when therapeutic on Heparin

Monitor INR daily

Goal: INR 2.0-3.0 for 3-6 months

Identified precipitant 3 mos

First idiopathic episode 6 mos

Prolonged/indefinite:

³ 2 thrombotic episodes

1 spont. life-threatening episode

Anti-phospholipid antibody syndrome, ATIII deficiency


Catheter embolectomy

Surgical embolectomy

Reasonable for…

Massive PE if still unstable after fibrinolysis

Massive/Submassive PE if fibrinolysis is contra-indicated or there is evidence of adverse prognosis

o Three General Categories of Percutaneous InterventionAspiration thrombectomy Thrombus fragmentationRheolytic thrombectomy



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Pulmonary embolism ms