Deep Venous Thrombosis and Pulmonary Embolism : Diagnostic Approach and Current Guidelines in Therapy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow University of Illinois Medical Center at Chicago

DISCLOSURE AND ACKNOWLEDGMENT No relationships to disclose Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

No relationships to disclose

Objective Acute pulmonary embolism Overview Diagnosis Treatment DVT/PE in pregnancy Prevalence of PE in COPD exacerbations Diagnostic vascular ultrasonography Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Acute pulmonary embolism

Overview

Diagnosis

Treatment

DVT/PE in pregnancy

Prevalence of PE in COPD exacerbations

Diagnostic vascular ultrasonography

Acute Pulmonary Embolism : Overview Obstruction of the pulmonary artery or one of its branches by Thrombus Tumor Air Fat Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Obstruction of the pulmonary artery or one of its branches by

Thrombus

Tumor

Air

Fat

Acute Pulmonary Embolism : Overview PE: Acute Symptoms and signs immediately after obstruction of pulmonary vessels Chronic Slowly progressive dyspnea over a period of years due to pulm HTN Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

PE:

Acute

Symptoms and signs immediately after obstruction of pulmonary vessels

Chronic

Slowly progressive dyspnea over a period of years due to pulm HTN

Acute Pulmonary Embolism : Overview Massive PE Hypotension (SBP < 90 mmHg or a drop of ≥ 40 mmHg from baseline for a period >15 minutes) Massive PE > increased (PVR) > decreased RV outflow > reducing LV preload > diminished CO > Hypotension Accompanied by an elevated CVP Submassive PE All acute PE not meeting the definition of massive PE Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Massive PE

Hypotension (SBP < 90 mmHg or a drop of ≥ 40 mmHg from baseline for a period >15 minutes)

Massive PE > increased (PVR) > decreased RV outflow > reducing LV preload > diminished CO > Hypotension

Accompanied by an elevated CVP

Submassive PE

All acute PE not meeting the definition of massive PE

Acute Pulmonary Embolism : Overview Saddle PE Lodges at the bifurcation of the main pulmonary artery Most saddle PE are submassive Retrospective study 546 patients with PE 14 (2.6 %) had a saddle PE Only two of the patients with saddle PE had hypotension Ryu et al. Saddle pulmonary embolism diagnosed by CT angiography: frequency, clinical features and outcome. Respir Med 2007; 101:1537.

Saddle PE

Lodges at the bifurcation of the main pulmonary artery

Most saddle PE are submassive

Retrospective study

546 patients with PE

14 (2.6 %) had a saddle PE

Only two of the patients with saddle PE had hypotension

Acute Pulmonary Embolism : Overview EPIDEMIOLOGY Pulmonary embolism mortality in the United States Over a 20-year duration More than 42 million deaths 600,000 pts (1.5%) were diagnosed with PE Horlander et al. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med 2003; 163:1711.

EPIDEMIOLOGY

Pulmonary embolism mortality in the United States

Over a 20-year duration

More than 42 million deaths

600,000 pts (1.5%) were diagnosed with PE

Acute Pulmonary Embolism : Overview PROGNOSIS Mortality rate of acute PE 30 % without treatment (primarily due to recurrent PE within the first few hours ) 2-8% with anticoagulant therapy Carson et al. The clinical course of pulmonary embolism: One year follow-up of PIOPED patients. N Engl J Med 1992; 326:1240 .

PROGNOSIS

Mortality rate of acute PE

30 % without treatment (primarily due to recurrent PE within the first few hours )

2-8% with anticoagulant therapy

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS INCREASED PE RELATED MORTALITY RV dysfunction RV thrombus Elevated BNP Elevated troponin Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

POOR PROGNOSTIC FACTORS

INCREASED PE RELATED MORTALITY

RV dysfunction

RV thrombus

Elevated BNP

Elevated troponin

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS RV DYSFUCTION Meta-analysis of seven studies (3395 normotensive or hypotensive pts with PE) RV dysfunction was associated with a two-fold increase in PE-related mortality RV dysfunction correlates poorly with PE-related mortality , in normotensive pts Wolde et al. Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism. Arch Intern Med 2004; 164:1685.

POOR PROGNOSTIC FACTORS

RV DYSFUCTION

Meta-analysis of seven studies

(3395 normotensive or hypotensive pts with PE)

RV dysfunction was associated with a two-fold increase in PE-related mortality

RV dysfunction correlates poorly with PE-related mortality , in normotensive pts

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS RV DYSFUCTION Predict recurrent PE or DVT Prospective cohort study 301 patients who had experienced their first PE were categorized: No RV dysfunction RV dysfunction with regression (present at admission but not at discharge) Persistent RV dysfunction (more likely to have a recurrent DVT/PE, or PE-related death) – 3 YRS follow up Grifoni et al. Association of persistent right ventricular dysfunction at hospital discharge after acute pulmonary embolism with recurrent thromboembolic events. Arch Intern Med 2006; 166:2151 .

POOR PROGNOSTIC FACTORS

RV DYSFUCTION

Predict recurrent PE or DVT

Prospective cohort study

301 patients who had experienced their first PE were categorized:

No RV dysfunction

RV dysfunction with regression (present at admission but not at discharge)

Persistent RV dysfunction (more likely to have a recurrent DVT/PE, or PE-related death) – 3 YRS follow up

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS RV THROMBUS Pts with PE and (RV) thrombus have a higher mortality than patients without an RV thrombus 14-day mortality (21 vs. 11 %) Three-month mortality (29 vs. 16 %) Torbicki et al. Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. J Am Coll Cardiol 2003; 41:2245.

POOR PROGNOSTIC FACTORS

RV THROMBUS

Pts with PE and (RV) thrombus have a higher mortality than patients without an RV thrombus

14-day mortality (21 vs. 11 %)

Three-month mortality (29 vs. 16 %)

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS ELEVATED BNP Predicts RV dysfunction and mortality The mortality rate correlates with BNP level Meta-analysis of 16 studies BNP >100 pg/mL Increased short-term mortality X 6 BNP >600 pg/mL Increased short-term mortality X 16 Cavallazzi et al. Natriuretic peptides in acute pulmonary embolism: a systematic review. Intensive Care Med 2008

POOR PROGNOSTIC FACTORS

ELEVATED BNP

Predicts RV dysfunction and mortality

The mortality rate correlates with BNP level

Meta-analysis of 16 studies

BNP >100 pg/mL

Increased short-term mortality X 6

BNP >600 pg/mL

Increased short-term mortality X 16

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS ELEVATED BNP Observational study of 73 pts with acute PE BNP <50 pg/mL Benign clinical course BNP >90 pg/mL a/w cardiopulmonary resuscitation, mechanical ventilation, vasopressor therapy, thrombolysis, and embolectomy, as well as death Kucher et al. Prognostic role of brain natriuretic peptide in acute pulmonary embolism. Circulation 2003; 107:2545.

POOR PROGNOSTIC FACTORS

ELEVATED BNP

Observational study of 73 pts with acute PE

BNP <50 pg/mL

Benign clinical course

BNP >90 pg/mL

a/w cardiopulmonary resuscitation, mechanical ventilation, vasopressor therapy, thrombolysis, and embolectomy, as well as death

Acute Pulmonary Embolism : Overview POOR PROGNOSTIC FACTORS ELEVATED TROPONIN Meta-analysis of 20 observational studies (1985 pts) Elevated troponin I or troponin T level was a/w an increased risk death due to PE (OR 9.44, 95% CI 4.14-21.49) Becattini et al. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116:427.

POOR PROGNOSTIC FACTORS

ELEVATED TROPONIN

Meta-analysis of 20 observational studies (1985 pts)

Elevated troponin I or troponin T level was a/w an increased risk death due to PE (OR 9.44, 95% CI 4.14-21.49)

Acute Pulmonary Embolism : Overview PATHOPHYSIOLOGY Proximal vein thrombi (iliac, femoral, and popliteal vein) are the source of most clinically recognized PE Most distal vein thrombi (calf vein) resolve spontaneously and only 20 -30 % extend into the proximal veins if untreated Weinmann et al. Deep-vein thrombosis. N Engl J Med 1994; 331:1630. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

PATHOPHYSIOLOGY

Proximal vein thrombi (iliac, femoral, and popliteal vein) are the source of most clinically recognized PE

Most distal vein thrombi (calf vein) resolve spontaneously and only 20 -30 % extend into the proximal veins if untreated

Acute Pulmonary Embolism : Overview Pulm HTN in PE Nonhematogenous obstruction (tumor, air, fat) solely due to mechanical obstruction 60-70% of the pulmonary artery must be obstructed to increase PAP PE Due to a combination of mechanical obstruction and vasoconstriction only 25%–30% of the pulmonary artery must be obstructed to increase PAP PE stimulate neutrophils/endothelium/platelets to produce serotonin/histamine..that cause vasoconstriction Stratmann et al. Neurogenic and humoral vasoconstriction in acute pulmonary thromboembolism. Anesth Analg. 2003 Aug;97(2):341-54

Pulm HTN in PE

Nonhematogenous obstruction (tumor, air, fat)

solely due to mechanical obstruction

60-70% of the pulmonary artery must be obstructed to increase PAP

PE

Due to a combination of mechanical obstruction and vasoconstriction

only 25%–30% of the pulmonary artery must be obstructed to increase PAP

PE stimulate neutrophils/endothelium/platelets to produce serotonin/histamine..that cause vasoconstriction

Acute Pulmonary Embolism : Overview RISK FACTORS Immobilization Surgery within the last three months Stroke, paresis, paralysis History of venous thromboembolism Malignancy Central venous instrumentation within the last three months Chronic heart disease Heit, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study Arch Intern Med 2002; 162:1245.

RISK FACTORS

Immobilization

Surgery within the last three months

Stroke, paresis, paralysis

History of venous thromboembolism

Malignancy

Central venous instrumentation within the last three months

Chronic heart disease

Acute Pulmonary Embolism : Overview RISK FACTORS Additional risk factors identified in women Obesity (BMI ≥29 kg/m2) Heavy cigarette smoking (>25 cigarettes per day) Hypertension Goldhaber et al. A prospective study of risk factors for pulmonary embolism in women. JAMA 1997; 277:642. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

RISK FACTORS

Additional risk factors identified in women

Obesity (BMI ≥29 kg/m2)

Heavy cigarette smoking (>25 cigarettes per day)

Hypertension

Acute Pulmonary Embolism : Overview

Acute Pulmonary Embolism : Overview SYMPTOMS / SIGNS Clinical presentation is variable and nonspecific 47 % of pts had symptoms or signs of LE (DVT) edema, erythema, tenderness, or a palpable cord in the calf or thigh Stein et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med 2007; 120:871.

SYMPTOMS / SIGNS

Clinical presentation is variable and nonspecific

47 % of pts had symptoms or signs of LE (DVT)

edema, erythema, tenderness, or a palpable cord in the calf or thigh

Acute Pulmonary Embolism: Diagnosis Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Acute Pulmonary Embolism: Diagnosis LABORATORY Leukocytosis Increased ESR Elevated serum LDH ABGs: hypoxemia, hypocapnia, and respiratory alkalosis Massive PE with hypotension can cause hypercapnia and a combined respiratory and metabolic acidosis (due to lactic acidosis) Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

LABORATORY

Leukocytosis

Increased ESR

Elevated serum LDH

ABGs: hypoxemia, hypocapnia, and respiratory alkalosis

Massive PE with hypotension can cause hypercapnia and a combined respiratory and metabolic acidosis (due to lactic acidosis)

18 % may have normal PaO2 (85-105 mmHg) 6 % may have a normal alveolar-arterial gradient for oxygen Stein et al. Clinical, laboratory, roentgenographic and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991; 100:598 .

18 % may have normal PaO2 (85-105 mmHg)

6 % may have a normal alveolar-arterial gradient for oxygen

Acute Pulmonary Embolism: Diagnosis LABORATORY Elevated BNP Insensitive, nonspecific Case-control study of 2213 hemodynamically stable pts with suspected acute PE BNP had 60% sensitivity and 62% specificity BNP may have a prognostic role in PE Sohne et al. Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. J Thromb Haemost 2006; 4:552.

LABORATORY

Elevated BNP

Insensitive, nonspecific

Case-control study of 2213 hemodynamically stable pts with suspected acute PE

BNP had 60% sensitivity and 62% specificity

BNP may have a prognostic role in PE

Acute Pulmonary Embolism: Diagnosis LABORATORY Elevated Troponin 30-50 % of pts who have a moderate to large PE Due to acute right heart overload Resolve within 40 hrs (more prolonged elevation after acute MI) Muller-Bardorff et al. Release kinetics of cardiac troponin T in survivors of confirmed severe pulmonary embolism. Clin Chem 2002; 48:673.

LABORATORY

Elevated Troponin

30-50 % of pts who have a moderate to large PE

Due to acute right heart overload

Resolve within 40 hrs (more prolonged elevation after acute MI)

Acute Pulmonary Embolism: Diagnosis ELECTROCARDIOGRAPHY 70 % of pts with acute PE had ECG abnormalities Most commonly Sinus tachycardia nonspecific ST-segment and T-wave changes &quot;S 1 Q 3 T 3 &quot; pattern of acute cor pulmonale (acute right heart strain) is classic infrequent during acute PE Common among patients with massive acute PE and cor pulmonale Panos et al. The electrocardiographic manifestations of pulmonary embolism. J Emerg Med 1988; 6:301. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

ELECTROCARDIOGRAPHY

70 % of pts with acute PE had ECG abnormalities

Most commonly

Sinus tachycardia

nonspecific ST-segment and T-wave changes

&quot;S 1 Q 3 T 3 &quot; pattern of acute cor pulmonale (acute right heart strain) is classic

infrequent during acute PE

Common among patients with massive acute PE and cor pulmonale

S1 Q3 T3

Acute Pulmonary Embolism: Diagnosis ELECTROCARDIOGRAPHY The following ECG abnormalities are associated with a poor prognosis Atrial arrhythmias Right bundle branch block Inferior Q-waves Precordial T-wave inversion and ST-segment changes Geibel et al. Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. Eur Respir J 2005; 25:843.

ELECTROCARDIOGRAPHY

The following ECG abnormalities are associated with a poor prognosis

Atrial arrhythmias

Right bundle branch block

Inferior Q-waves

Precordial T-wave inversion and ST-segment changes

Acute Pulmonary Embolism: Diagnosis CHEST RADIOGRAPHY Usually CXR is normal Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

CHEST RADIOGRAPHY

Usually CXR is normal

Stein et al. Clinical, laboratory, roentgenographic and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991; 100:598 .

CXR shows RLL collapse Ventilation perfusion scan showing perfusion defect in right side + corresponding ventilation defect Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

CXR shows RLL collapse

Ventilation perfusion scan showing perfusion defect in right side + corresponding ventilation defect

‘ classical’ appearance of a pulmonary infarction – a wedge-shaped lesion peripherally set against the pleura

‘ classical’ appearance of a pulmonary infarction – a wedge-shaped lesion peripherally set against the pleura

Acute Pulmonary Embolism: Diagnosis VENTILATION-PERFUSION (V/Q) SCAN The PIOPED study Accuracy is greatest when the V/Q scan is combined with clinical probability All patients enrolled in the study were to have a V/Q scan and a pulmonary arteriogram Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753.

VENTILATION-PERFUSION (V/Q) SCAN

The PIOPED study

Accuracy is greatest when the V/Q scan is combined with clinical probability

All patients enrolled in the study were to have a V/Q scan and a pulmonary arteriogram

Acute Pulmonary Embolism: Diagnosis VENTILATION-PERFUSION (V/Q) SCAN Interpretation of V/Q scan for PE as used in PIOPED: Segmental defect (vascular): perfusion abnormality triangular or rectangular shaped periphery based located within one or several vascular segments. Nonsegmental defect (nonvascular) : unlikely to represent PE. (e.g., cardiomegaly, enlarged aorta, enlarged hila, elevated diaphragm) Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753.

VENTILATION-PERFUSION (V/Q) SCAN

Interpretation of V/Q scan for PE as used in PIOPED:

Segmental defect (vascular):

perfusion abnormality

triangular or rectangular shaped

periphery based

located within one or several vascular segments.

Nonsegmental defect (nonvascular) :

unlikely to represent PE. (e.g., cardiomegaly, enlarged aorta, enlarged hila, elevated diaphragm)

Acute Pulmonary Embolism: Diagnosis VENTILATION-PERFUSION (V/Q) SCAN Interpretation of V/Q scan for PE as used in PIOPED: Small defect (small subsegmental): < 25% of a segment Moderate defect (moderate subsegmental): 25%-75% of a segment Large defect (segmental): > 75% of a segment Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753.

VENTILATION-PERFUSION (V/Q) SCAN

Interpretation of V/Q scan for PE as used in PIOPED:

Small defect (small subsegmental): < 25% of a segment

Moderate defect (moderate subsegmental): 25%-75% of a segment

Large defect (segmental): > 75% of a segment

Acute Pulmonary Embolism: Diagnosis VENTILATION-PERFUSION (V/Q) SCAN High Probability (80-100% likelihood for PE) 2 or more large perfusion defects Intermediate Probability (20-80% likelihood for PE) One moderate to 2 large perfusion defects Low Probability (0-19% likelihood for PE) Any number of small perfusion defects with a normal chest radiograph Multiple matched V/Q abnormalities Nonsegmental (nonvascular) perfusion defects (e.g., cardiomegaly, enlarged aorta, enlarged hila, elevated diaphragm). Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753.

VENTILATION-PERFUSION (V/Q) SCAN

High Probability (80-100% likelihood for PE)

2 or more large perfusion defects

Intermediate Probability (20-80% likelihood for PE)

One moderate to 2 large perfusion defects

Low Probability (0-19% likelihood for PE)

Any number of small perfusion defects with a normal chest radiograph

Multiple matched V/Q abnormalities

Nonsegmental (nonvascular) perfusion defects (e.g., cardiomegaly, enlarged aorta, enlarged hila, elevated diaphragm).

No areas of defects in ventilation or perfusion scans; low probability of PE Perfusion

No areas of defects in ventilation or perfusion scans; low probability of PE

Defect in right lung in lateral segment of right middle lobe w/ no match to ventilation study; intermediate probability for PE

Defect in right lung in lateral segment of right middle lobe w/ no match to ventilation study; intermediate probability for PE

A normal V/Q scan virtually excluded PE High-probability V/Q + high clinical probability 95 % likelihood of having PE Low-probability V/Q scan + low clinical probability 4 % likelihood of having PE Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753.

A normal V/Q scan virtually excluded PE

High-probability V/Q + high clinical probability

95 % likelihood of having PE

Low-probability V/Q scan + low clinical probability

4 % likelihood of having PE

Acute Pulmonary Embolism: Diagnosis ULTRASOUND Only 29 % of pts with PE had venous thrombosis detected by compression ultrasound Turkstra, et al. Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med 1997; 126:775.

ULTRASOUND

Only 29 % of pts with PE had venous thrombosis detected by compression ultrasound

Acute Pulmonary Embolism: Diagnosis D-DIMER It can be detected in serum using a variety of different assays Enzyme-linked immunosorbent assay (ELISA) (results in >8 hrs) Quantitative rapid ELISA (results in 30 min) Semi-quantitative rapid ELISA (results in 10 min) Qualitative rapid ELISA (results in 10 min) Quantitative latex agglutination assay (results in 10 to 15 min) Semi-quantitative latex agglutination assay (results in 5 min) Erythrocyte agglutination assay (SimpliRED) (results in 2 min) Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

D-DIMER

It can be detected in serum using a variety of different assays

Enzyme-linked immunosorbent assay (ELISA) (results in >8 hrs)

Quantitative rapid ELISA (results in 30 min)

Semi-quantitative rapid ELISA (results in 10 min)

Qualitative rapid ELISA (results in 10 min)

Quantitative latex agglutination assay (results in 10 to 15 min)

Semi-quantitative latex agglutination assay (results in 5 min)

Erythrocyte agglutination assay (SimpliRED) (results in 2 min)

Acute Pulmonary Embolism: Diagnosis D-DIMER >500 ng/mL is usually considered abnormal Abnormal D-dimer levels being common among hospitalized patients, especially those with malignancy or recent surgery D-dimer levels are abnormal in approximately 90-95 % of all pts with PE D-dimer levels are normal in only 40-68 % of pts without PE Good sensitivity and NPV Poor specificity and PPV D-dimer level <500 ng/mL is sufficient to exclude PE in patients with a low or moderate pretest probability of PE Stein et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140:589.

D-DIMER

>500 ng/mL is usually considered abnormal

Abnormal D-dimer levels being common among hospitalized patients, especially those with malignancy or recent surgery

D-dimer levels are abnormal in approximately 90-95 % of all pts with PE

D-dimer levels are normal in only 40-68 % of pts without PE

Good sensitivity and NPV

Poor specificity and PPV

D-dimer level <500 ng/mL is sufficient to exclude PE in patients with a low or moderate pretest probability of PE

Acute Pulmonary Embolism: Diagnosis ANGIOGRAPHY &quot;gold standard&quot; in the diagnosis of acute PE A negative pulmonary angiogram excludes clinically relevant PE Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

ANGIOGRAPHY

&quot;gold standard&quot; in the diagnosis of acute PE

A negative pulmonary angiogram excludes clinically relevant PE

Pulmonary angiogram in a patient with PE. The clot appears as a filling defect (arrow). Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Pulmonary angiogram in a patient with PE. The clot appears as a filling defect (arrow).

Acute Pulmonary Embolism: Diagnosis CT PULMONARY ANGIOGRAPHY PIOPED II (824 patients) 83 % of pts with PE had a positive CT-PA (sensitivity) 96 % of pts without PE had a negative CT-PA (specificity) Stein, PD et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354:2317.

CT PULMONARY ANGIOGRAPHY

PIOPED II (824 patients)

83 % of pts with PE had a positive CT-PA (sensitivity)

96 % of pts without PE had a negative CT-PA (specificity)

CT-PA requires concomitant pretest clinical probability assessment to be an effective diagnostic tool Stein, PD et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354:2317.

CT-PA requires concomitant pretest clinical probability assessment to be an effective diagnostic tool

What if CTA is Negative? Substantial number of pts with PE may be missed by CT-PA Prospective cohort study of 1041 pts with suspected PE and negative CTA The incidence of PE < 2% Low or intermediate clinical probability 5% High clinical probability CT-PA results should be interpreted with caution if the clinical probability of PE and CT-PA are discordant Musset, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet 2002; 360:1914.

Substantial number of pts with PE may be missed by CT-PA

Prospective cohort study of 1041 pts with suspected PE and negative CTA

The incidence of PE

< 2% Low or intermediate clinical probability

5% High clinical probability

CT-PA results should be interpreted with caution if the clinical probability of PE and CT-PA are discordant

CTA is Not Inferior to V/Q Scanning for Ruling Out PE Randomized, controlled trial 1417 pts with suspected PE Underwent CT-PA or V/Q scanning Similar prevalence of PE in both groups Among patients in whom PE was excluded, the CT-PA and V/Q scans had a similar incidence of PE during the three month follow-up period Anderson et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA 2007; 298:2743.

Randomized, controlled trial

1417 pts with suspected PE

Underwent CT-PA or V/Q scanning

Similar prevalence of PE in both groups

Among patients in whom PE was excluded, the CT-PA and V/Q scans had a similar incidence of PE during the three month follow-up period

Acute Pulmonary Embolism: Diagnosis MRA Limited by respiratory and cardiac motion artifact Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

MRA

Limited by respiratory and cardiac motion artifact

Acute Pulmonary Embolism: Diagnosis ALVEOLAR DEAD SPACE Acute PE the areas of lung with vascular occlusion are ventilated but not perfused Alveolar dead space fraction (ADF) increases 98% pts with PE have an abnormal ADF (defined as >20 %) or a positive D-dimer Common false positive results Difficulty obtaining accurate ADF measurements Rodger et al. Steady-state end-tidal alveolar dead space fraction and D-dimer: bedside tests to exclude pulmonary embolism. Chest 2001; 120:115.

ALVEOLAR DEAD SPACE

Acute PE the areas of lung with vascular occlusion are ventilated but not perfused

Alveolar dead space fraction (ADF) increases

98% pts with PE have an abnormal ADF (defined as >20 %) or a positive D-dimer

Common false positive results

Difficulty obtaining accurate ADF measurements

Acute Pulmonary Embolism: Diagnosis ECHOCARDIOGRAPHY Useful if a rapid diagnosis is required to justify the use of thrombolytic therapy PE related mortality increases with RV dysfunction RV thrombus 35% of pts with RV thrombus have PE only 4 % of pts with PE have an RV thrombus Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

ECHOCARDIOGRAPHY

Useful if a rapid diagnosis is required to justify the use of thrombolytic therapy

PE related mortality increases with

RV dysfunction

RV thrombus

35% of pts with RV thrombus have PE

only 4 % of pts with PE have an RV thrombus

Acute Pulmonary Embolism: Diagnosis ECHOCARDIOGRAPHY Echocardiographic findings in PE RV dilation and dysfunction RV thrombus RA dilation TR Pulm HTN Paradoxical septal movement Increases in RV pressure will displace the septum towards the LV during systole and/or diastole Dilated and invariable IVC McConnell Sign Regional wall motion abnormalities that spare the right ventricular apex 77% sensitivity, 94% specificity Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

ECHOCARDIOGRAPHY

Echocardiographic findings in PE

RV dilation and dysfunction

RV thrombus

RA dilation

TR

Pulm HTN

Paradoxical septal movement

Increases in RV pressure will displace the septum towards the LV during systole and/or diastole

Dilated and invariable IVC

McConnell Sign

Regional wall motion abnormalities that spare the right ventricular apex

77% sensitivity, 94% specificity

Apical 4 chamber view RV triangular shape, less than 60% LV RV size < 60% LV: normal 60-100% LV: moderately dilated RV > LV: severely dilated Normal heart: apex formed by the LV Acute cor pulmonale: apex formed by RV Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

RV triangular shape, less than 60% LV

RV size

< 60% LV: normal

60-100% LV: moderately dilated

RV > LV: severely dilated

Normal heart: apex formed by the LV

Acute cor pulmonale: apex formed by RV

RV pressure overload with septal flattening causes D sign EchoJournal: Echocardiography Videos and Discussions - RV pressure overload causes D sign McConnell’s Sign: Regional wall motion abnormalities that spare the right ventricular apex http://www.echojournal.org/video/132/McConnells-Sign-RV-dysfunction-in-pulmonary-embolus RV dilation (RV > LV), apex formed by RV, Tricuspid regurgitation (RV failure in acute pulmonary embolus ) http://www.echojournal.org/video/133/Huge-Tricuspid-Regurg-Jet http://www.echojournal.org/video/79/Classic-appearance-of-RV-failure-in-acute-pulmonary-embolus-1-of-2 http://www.echojournal.org/video/80/Classic-appearance-of-RV-failure-in-acute-pulmonary-embolus-2-of-2 Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

RV pressure overload with septal flattening causes D sign

EchoJournal: Echocardiography Videos and Discussions - RV pressure overload causes D sign

McConnell’s Sign: Regional wall motion abnormalities that spare the right ventricular apex

http://www.echojournal.org/video/132/McConnells-Sign-RV-dysfunction-in-pulmonary-embolus

RV dilation (RV > LV), apex formed by RV, Tricuspid regurgitation (RV failure in acute pulmonary embolus )

http://www.echojournal.org/video/133/Huge-Tricuspid-Regurg-Jet

http://www.echojournal.org/video/79/Classic-appearance-of-RV-failure-in-acute-pulmonary-embolus-1-of-2

http://www.echojournal.org/video/80/Classic-appearance-of-RV-failure-in-acute-pulmonary-embolus-2-of-2

RECOMMENDED DIAGNOSTIC APPROACH CT Experienced Institutions: Christopher study

RECOMMENDED DIAGNOSTIC APPROACH CT inexperienced institutions: PIOPED Study

PERC FOR LOW RISK OUTPATIENT POPULATIONS This approach has been best studied in the emergency department Acute PE can probably be excluded without further diagnostic testing if the patient meets all PERC criteria Age < 50 years HR < 100 bpm O2 SAT ≥ 95 % No hemoptysis No estrogen use No prior DVT or PE No unilateral leg swelling No surgery or trauma requiring hospitalization within the past 4 weeks Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

This approach has been best studied in the emergency department

Acute PE can probably be excluded without further diagnostic testing if the patient meets all PERC criteria

Age < 50 years

HR < 100 bpm

O2 SAT ≥ 95 %

No hemoptysis

No estrogen use

No prior DVT or PE

No unilateral leg swelling

No surgery or trauma requiring hospitalization within the past 4 weeks

PERC FOR LOW RISK OUTPATIENT POPULATIONS Multicenter, prospective cohort study 8138 ED pts with suspected PE Chest pain or dyspnea was the chief complaint 1666/8138 pts fulfilled all of the PERC + low clinical suspicion for PE only 15/1666 (< 1 %) developed a DVT or PE within 45 days Kline et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost 2008; 6:772.

Multicenter, prospective cohort study

8138 ED pts with suspected PE

Chest pain or dyspnea was the chief complaint

1666/8138 pts fulfilled all of the PERC + low clinical suspicion for PE

only 15/1666 (< 1 %) developed a DVT or PE within 45 days

Acute Pulmonary Embolism: Treatment Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Mortality rate of acute PE 30 % without treatment (primarily due to recurrent PE within the first few hours ) 2-8% with anticoagulant therapy Acute Pulmonary Embolism: Treatment Carson et al. The clinical course of pulmonary embolism: One year follow-up of PIOPED patients. N Engl J Med 1992; 326:1240 .

Mortality rate of acute PE

30 % without treatment (primarily due to recurrent PE within the first few hours )

2-8% with anticoagulant therapy

ACUTE PULMONARY EMBOLISM: TREATMENT ANTICOAGULATION The goal of anticoagulation Decrease mortality (from 30% to 2-8%) by preventing recurrent PE Its efficacy depends upon achieving a therapeutic level of treatment within the first 24 hours of treatment Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

The goal of anticoagulation

Decrease mortality (from 30% to 2-8%) by preventing recurrent PE

Its efficacy depends upon achieving a therapeutic level of treatment within the first 24 hours of treatment

WHEN SHOULD I INITIATE ANTICOAGULANT THERAPY? Indications High clinical suspicion of PE PE has been confirmed Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Indications

High clinical suspicion of PE

PE has been confirmed

WHICH ANTICOAGULANT SHOULD I INITIATE? IV UFH vs. SC LWMH IV UFH Persistent hypotension (massive PE) The clinical trials that evaluated LMWH in acute PE excluded this patient subgroup Increased risk of bleeding shortest-acting anticoagulant and its activity can be reversed (protamine sulfate) if major bleeding occurs Concern about subcutaneous absorption (morbid obesity, severe anasarca) Thrombolysis is being considered Creatinine clearance is ≤30 mL/min SC LMWH Hemodynamically stable patients with PE Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

IV UFH

Persistent hypotension (massive PE)

The clinical trials that evaluated LMWH in acute PE excluded this patient subgroup

Increased risk of bleeding

shortest-acting anticoagulant and its activity can be reversed (protamine sulfate) if major bleeding occurs

Concern about subcutaneous absorption (morbid obesity, severe anasarca)

Thrombolysis is being considered

Creatinine clearance is ≤30 mL/min

SC LMWH

Hemodynamically stable patients with PE

WHICH ANTICOAGULANT SHOULD I INITIATE? IV UFH vs. SC LWMH Severe renal insufficiency (CrCl <30 mL/minute) UFH should be used instead of LMWH If LMWH is used, there should be an approximately 50 % daily dose reduction (also monitor the anti-Xa activity) Hirsh et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S

Severe renal insufficiency (CrCl <30 mL/minute)

UFH should be used instead of LMWH

If LMWH is used, there should be an approximately 50 % daily dose reduction (also monitor the anti-Xa activity)

THE ADVANTAGES OF USING SC LMWH Meta-analysis of randomized trials In 18 trials (8054 patients), SC LMWH decreased mortality (odds ratio 0.76, 95% CI 0.62-0.92). In 22 trials (8867 patients), SC LMWH decreased recurrent thrombosis (odds ratio 0.68, 95% CI 0.55-0.84). In 12 trials, thrombus size reduction was more common with LMWH (odds ratio 0.69, 95% CI 0.59-0.81). Less major bleeding Fixed dosing that does not require adjustment Decreased likelihood of thrombocytopenia van Dongen et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 2004; :CD001100.

Meta-analysis of randomized trials

In 18 trials (8054 patients), SC LMWH decreased mortality (odds ratio 0.76, 95% CI 0.62-0.92).

In 22 trials (8867 patients), SC LMWH decreased recurrent thrombosis (odds ratio 0.68, 95% CI 0.55-0.84).

In 12 trials, thrombus size reduction was more common with LMWH (odds ratio 0.69, 95% CI 0.59-0.81).

Less major bleeding

Fixed dosing that does not require adjustment

Decreased likelihood of thrombocytopenia

WHAT ABOUT THE USE OF FONDAPARINUX? No studies directly compared SC LMWH and fondaparinux Fondaparinux and IV UFH appear to be equivalent Open-label randomized trial 2213 pts with symptomatic PE Similar rates of recurrent PE, bleeding, thrombocytopenia, and death Dose 5 mg for patients <50 kg 7.5 mg for patients 50 to 100 kg 10 mg for patients >100 kg Contraindicated in patients with severe renal insufficiency (CrCl <30 mL/minute) Buller et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349:1695.

No studies directly compared SC LMWH and fondaparinux

Fondaparinux and IV UFH appear to be equivalent

Open-label randomized trial

2213 pts with symptomatic PE

Similar rates of recurrent PE, bleeding, thrombocytopenia, and death

Dose

5 mg for patients <50 kg

7.5 mg for patients 50 to 100 kg

10 mg for patients >100 kg

Contraindicated in patients with severe renal insufficiency (CrCl <30 mL/minute)

LONG-TERM ORAL ANTICOAGULANT: WARFARIN Suppress production of the vitamin K-dependent clotting factors (II, VII, IX, and X) Long-term vs. short term (1-4 mon) treatment with warfarin Decreased likelihood of recurrent PE or DVT with long-term warfarin (odds ratio 0.18, 95% CI 0.13-0.26) It should NOT be initiated prior to heparin Warfarin alone 3 X higher incidence of recurrent PE or DVT Hutten et al. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006; :CD001367.

Suppress production of the vitamin K-dependent clotting factors (II, VII, IX, and X)

Long-term vs. short term (1-4 mon) treatment with warfarin

Decreased likelihood of recurrent PE or DVT with long-term warfarin (odds ratio 0.18, 95% CI 0.13-0.26)

It should NOT be initiated prior to heparin

Warfarin alone 3 X higher incidence of recurrent PE or DVT

FOR HOW LONG SHOULD WE OVERLAP WORFARIN WITH HEPARIN Minimum of five days and until the (INR) is therapeutic (2.0 to 3.0) for at least 24 hours During the first few days of warfarin therapy, the prolonged PT reflects only the loss of factor VII (which has a half-life of 5-7 hrs) and does not represent adequate anticoagulation because the intrinsic clotting pathway remains intact Pts with known protein C deficiency have an increased risk of warfarin-induced skin necrosis Kearon et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:454S.

Minimum of five days and until the (INR) is therapeutic (2.0 to 3.0) for at least 24 hours

During the first few days of warfarin therapy, the prolonged PT reflects only the loss of factor VII (which has a half-life of 5-7 hrs) and does not represent adequate anticoagulation because the intrinsic clotting pathway remains intact

Pts with known protein C deficiency have an increased risk of warfarin-induced skin necrosis

HOW SHOULD I MONITOR LMWH? LMWH (anti-Xa levels ) Not necessary for most pts Warranted Morbid obesity (BMI >40) Low body weight (<45 kg women, <57 kg men) Severe renal insufficiency (CrCl <30 mL/minute) Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

LMWH (anti-Xa levels )

Not necessary for most pts

Warranted

Morbid obesity (BMI >40)

Low body weight (<45 kg women, <57 kg men)

Severe renal insufficiency (CrCl <30 mL/minute)

Pregnancy

HOW SHOULD I MONITOR UFH? UFH (aPTT) Measures the antithrombotic activity of heparin The therapeutic aPTT is 1.5 to 2.5 times the control aPTT The efficacy depends on achieving a therapeutic level of treatment within the first 24 hours Failure was associated with Higher rate of recurrent DVT or PE (23 vs. 3 %) For at least 3 months, despite ongoing therapeutic anticoagulation Hull et al. Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med 1997; 157:2562. Hull et al. The importance of initial heparin treatment on long-term clinical outcomes of antithrombotic therapy. The emerging theme of delayed recurrence. Arch Intern Med 1997; 157:2317.

UFH (aPTT)

Measures the antithrombotic activity of heparin

The therapeutic aPTT is 1.5 to 2.5 times the control aPTT

The efficacy depends on achieving a therapeutic level of treatment within the first 24 hours

Failure was associated with

Higher rate of recurrent DVT or PE (23 vs. 3 %)

For at least 3 months, despite ongoing therapeutic anticoagulation

HOW SHOULD I MONITOR COUMADIN? Target an INR of 2.5 (range 2.0 to 3.0) INR <2.0 is associated with an increased likelihood of recurrent PE or DVT INR > 3.0 is associated with bleeding Kearon et al. Comparison of Low-Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism. N Engl J Med 2003; 349:631 .

Target an INR of 2.5 (range 2.0 to 3.0)

INR <2.0 is associated with an increased likelihood of recurrent PE or DVT

INR > 3.0 is associated with bleeding

WHAT ARE THE COMMON COMPLICATIONS? Major bleeding Intracranial hemorrhage Retroperitoneal hemorrhage Bleeding that led directly to death, hospitalization, or transfusion The frequency of major bleeding IV UFH <3% Fondaparinux < 3% Warfarin < 3% SC LMWH (significantly lower rate ) Management Protamine sulfate Vitamin K and fresh frozen plasma Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Major bleeding

Intracranial hemorrhage

Retroperitoneal hemorrhage

Bleeding that led directly to death, hospitalization, or transfusion

The frequency of major bleeding

IV UFH <3%

Fondaparinux < 3%

Warfarin < 3%

SC LMWH (significantly lower rate )

Management

Protamine sulfate

Vitamin K and fresh frozen plasma

WHAT ARE THE COMMON COMPLICATIONS? Heparin-induced thrombocytopenia (HIT) Risk factors for developing HIT Previous episode of HIT Less common after the use of LMWH compared to UFH Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Heparin-induced thrombocytopenia (HIT)

Risk factors for developing HIT

Previous episode of HIT

Less common after the use of LMWH compared to UFH

FOR HOW LONG SHOULD I TREAT? First episode of PE / DVT Reversible risk factor (immobilization, surgery, and trauma): warfarin for at least three months 6 months therapy : no additional benefit < 3 months therapy: more recurrent PE or DVT (11 VS. 4 %) Unprovoked (idiopathic): conflicting data 2 Randomized trials enrolled patients with DVT or PE : 3 months therapy vs. long term ( 2 years) therapy: fewer recurrent PE or DVT Another randomized trial enrolled patients with PE only : 3 months therapy vs. > 3 months: no difference in the rate of recurrent DVT or PE, or mortality Kearon et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:454S.

First episode of PE / DVT

Reversible risk factor (immobilization, surgery, and trauma): warfarin for at least three months

6 months therapy : no additional benefit

< 3 months therapy: more recurrent PE or DVT (11 VS. 4 %)

Unprovoked (idiopathic): conflicting data

2 Randomized trials enrolled patients with DVT or PE :

3 months therapy vs. long term ( 2 years) therapy: fewer recurrent PE or DVT

Another randomized trial enrolled patients with PE only :

3 months therapy vs. > 3 months: no difference in the rate of recurrent DVT or PE, or mortality

FOR HOW LONG SHOULD I TREAT? Recurrent PE / DVT (two or more episodes) Indefinite warfarin therapy Randomized trial of 227 pts with recurrent PE or DVT Therapy for 6 months vs. indefinitely 4 years follow up Fewer recurrent PE or DVT (3 vs. 21 %) Higher major bleeding (9 vs. 3 %) Kearon et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:454S.

Recurrent PE / DVT (two or more episodes)

Indefinite warfarin therapy

Randomized trial of 227 pts with recurrent PE or DVT

Therapy for 6 months vs. indefinitely

4 years follow up

Fewer recurrent PE or DVT (3 vs. 21 %)

Higher major bleeding (9 vs. 3 %)

Acute Pulmonary Embolism: Treatment A 58-year-old man is evaluated in the emergency department because of dyspnea and hypotension of 3 hours’ duration. Three weeks ago, he fractured his right tibia in a motor vehicle accident, requiring open reduction and fixation. A cast was placed that included ankle and knee joints. On physical examination, his pulse rate is 120/min and blood pressure is 95/55 mm Hg (preoperative blood pressure was 135/85 mm Hg). Chest radiography shows no infiltrates. The SaO 2 when the patient is breathing room air is 89%. Ventilation-perfusion scanning shows two unmatched lobar defects and two segmental defects. A Doppler study shows a deep venous thrombosis in the femoral vein of the right leg. Which of the following therapies is most likely to restore hemodynamic stability within the first 24 hours? ( A ) Unfractionated heparin ( B ) Low-molecular-weight heparin ( C ) Tissue plasminogen activator (t-PA) followed by heparin ( D ) Unfractionated heparin plus an inferior vena cava filter ( E ) Warfarin

A 58-year-old man is evaluated in the emergency department because of dyspnea and hypotension of 3 hours’ duration. Three weeks ago, he fractured his right tibia in a motor vehicle accident, requiring open reduction and fixation. A cast was placed that included ankle and knee joints. On physical examination, his pulse rate is 120/min and blood pressure is 95/55 mm Hg (preoperative blood pressure was 135/85 mm Hg). Chest radiography shows no infiltrates. The SaO 2 when the patient is breathing room air is 89%. Ventilation-perfusion scanning shows two unmatched lobar defects and two segmental defects. A Doppler study shows a deep venous thrombosis in the femoral vein of the right leg.

Which of the following therapies is most likely to restore hemodynamic stability within the first 24 hours?

( A ) Unfractionated heparin ( B ) Low-molecular-weight heparin ( C ) Tissue plasminogen activator (t-PA) followed by heparin ( D ) Unfractionated heparin plus an inferior vena cava filter ( E ) Warfarin

SHOULD I ADMINISTER THROMBOLYTIC THERAPY? Only pts in whom the diagnosis of (PE) has been confirmed Accelerates clot lysis and is a/w short-term physiologic benefits (RV function and pulmonary perfusion) No mortality benefit Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Only pts in whom the diagnosis of (PE) has been confirmed

Accelerates clot lysis and is a/w

short-term physiologic benefits (RV function and pulmonary perfusion)

No mortality benefit

Large saddle PE 24 hours after IV TPA therapy resolution of the saddle embolus Fam, NP, Verma, A. Thrombolysis of a massive pulmonary embolism. N Engl J Med, 2002; 347:1161. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Large saddle PE

24 hours after IV TPA therapy

resolution of the saddle embolus

Thrombolytic Therapy Does Not Improve Mortality Meta-analysis of 9 randomized trials (461 pts) Thrombolytic therapy followed by heparin vs. heparin alone No statistically significant effect on mortality (relative risk 0.63, 95% CI 0.32-1.23) No statistically significant effect on recurrence of PE (relative risk 0.59, 95% CI 0.30-1.18) Increase risk of major hemorrhage (relative risk 1.76, 95% CI 1.04-2.98) Thabut et al. Thrombolytic therapy of pulmonary embolism: a meta-analysis. J Am Coll Cardiol 2002; 40:1660. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Meta-analysis of 9 randomized trials (461 pts)

Thrombolytic therapy followed by heparin vs. heparin alone

No statistically significant effect on mortality

(relative risk 0.63, 95% CI 0.32-1.23)

No statistically significant effect on recurrence of PE

(relative risk 0.59, 95% CI 0.30-1.18)

Increase risk of major hemorrhage

(relative risk 1.76, 95% CI 1.04-2.98)

Thrombolytic Therapy Improves Important Physiologic Parameters LONG TERM IMPROVEMENT Randomized study of 40 pts with acute PE Anticoagulation plus thrombolysis vs. anticoagulation alone After 2 wks More complete resolution of emboli Longer-term follow-up (7 yrs) Lower pulmonary artery pressure and pulmonary vascular resistance Sharma et al. Effect of thrombolytic therapy on pulmonary-capillary blood volume in patients with pulmonary embolism. N Engl J Med 1980; 303:842. SHORT TERM IMPROVEMWNT Prospective study of 40 pts with acute PE Thrombolytic therapy plus anticoagulation vs. anticoagulation alone 12 hours Improved right ventricular function One week later No difference in RV function Konstantinides et al. Comparison of alteplase versus heparin for resolution of major pulmonary embolism. Am J Cardiol 1998; 82:966.

LONG TERM IMPROVEMENT

Randomized study of 40 pts with acute PE

Anticoagulation plus thrombolysis vs. anticoagulation alone

After 2 wks

More complete resolution of emboli

Longer-term follow-up (7 yrs)

Lower pulmonary artery pressure and pulmonary vascular resistance

Sharma et al. Effect of thrombolytic therapy on pulmonary-capillary blood volume in patients with pulmonary embolism.

N Engl J Med 1980; 303:842.

SHORT TERM IMPROVEMWNT

Prospective study of 40 pts with acute PE

Thrombolytic therapy plus anticoagulation vs. anticoagulation alone

12 hours

Improved right ventricular function

One week later

No difference in RV function

Konstantinides et al. Comparison of alteplase versus heparin for resolution of major pulmonary embolism.

Am J Cardiol 1998; 82:966.

Kearon, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 Suppl 6:454.

Thrombolytic Therapy in Patients Undergoing CPR due to PE-induced Cardiac Arrest Case reports Insufficient data Successful in PE-induced Cardiac Arrest?!? No outcome improvement when the cardiac arrest manifests as PEA Bailen et al. Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: A review. Crit Care Med 2001; 29:2211. Abu-Laban et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med 2002; 346:1522.

Case reports

Insufficient data

Successful in PE-induced Cardiac Arrest?!?

No outcome improvement when the cardiac arrest manifests as PEA

Adverse Effect Associated with Thrombolysis Bleeding Intracranial hemorrhage occurs in up to 3 % of pts who receive thrombolytic therapy for PE SK: allergic reactions and hypotension (anaphylaxis <0.5 %) Particularly with repeat administration Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Bleeding

Intracranial hemorrhage occurs in up to 3 % of pts who receive thrombolytic therapy for PE

SK: allergic reactions and hypotension (anaphylaxis <0.5 %)

Particularly with repeat administration

Thrombolytic Therapy in DVT Not recommended Catheter-directed thrombolysis, rather than systemic thrombolysis (Grade 2B) Massive iliofemoral or proximal femoral DVT with a high risk of limb gangrene Within 2 wks of the onset of symptoms Alternative therapies catheter extraction catheter fragmentation surgical thrombectomy WEAK RECOMMENDATION, JUST A SUGGESTION Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Not recommended

Catheter-directed thrombolysis, rather than systemic thrombolysis (Grade 2B)

Massive iliofemoral or proximal femoral DVT with a high risk of limb gangrene

Within 2 wks of the onset of symptoms

Alternative therapies

catheter extraction

catheter fragmentation

surgical thrombectomy

WEAK RECOMMENDATION, JUST A SUGGESTION

Systemic vs. Catheter-directed Thrombolysis: Which One is Better? Randomized trial on 32 pts with iliofemoral DVT Catheter-directed vs. systemic thrombolysis followed by anticoagulation Lower doses of thrombolytics, resulting in fewer bleeding complications Normal valve function preserved in more patients!!! Laiho et al. Preservation of venous valve function after catheter-directed and systemic thrombolysis for deep venous thrombosis. Eur J Vasc Endovasc Surg 2004; 28:391

Randomized trial on 32 pts with iliofemoral DVT

Catheter-directed vs. systemic thrombolysis followed by anticoagulation

Lower doses of thrombolytics, resulting in fewer bleeding complications

Normal valve function preserved in more patients!!!

Kearon, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 Suppl 6:454.

The ATTRACT Trial A large, randomized, multicenter trial In progress Pharmacomechanical catheter-directed thrombolysis This approach combines thrombolytic therapy with a catheter-mounted clot removal device Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

A large, randomized, multicenter trial

In progress

Pharmacomechanical catheter-directed thrombolysis

This approach combines thrombolytic therapy with a catheter-mounted clot removal device

Acute Pulmonary Embolism: Treatment A 35-year-old woman is evaluated for treatment of a pulmonary thromboembolism. Four days ago she was involved in an automobile accident resulting in fractures of the left lower ribs and required an emergency splenectomy. Two hours ago she developed pleuritic chest pain and dyspnea. Noninvasive ultrasound and Doppler studies of the leg veins show a deep venous thrombosis in the right leg extending beyond the femoral vein into the iliac system. Ventilation-perfusion lung scanning shows two segmental unmatched perfusion defects in the right lung and a similar defect in the left lung. On physical examination, her heart rate is 120/min, respiration rate is 24/min, and blood pressure is 95/60 mm Hg. Arterial blood gases when the patient is breathing room air are PaO 2 , 58 mm Hg; PaCO 2 , 28 mm Hg; and pH, 7.44. Which of the following is the most appropriate next step? ( A ) Tissue plasminogen activator ( B ) Pulmonary angiography ( C ) Unfractionated heparin ( D ) Inferior vena cava filter ( E ) Warfarin

A 35-year-old woman is evaluated for treatment of a pulmonary thromboembolism. Four days ago she was involved in an automobile accident resulting in fractures of the left lower ribs and required an emergency splenectomy. Two hours ago she developed pleuritic chest pain and dyspnea. Noninvasive ultrasound and Doppler studies of the leg veins show a deep venous thrombosis in the right leg extending beyond the femoral vein into the iliac system. Ventilation-perfusion lung scanning shows two segmental unmatched perfusion defects in the right lung and a similar defect in the left lung. On physical examination, her heart rate is 120/min, respiration rate is 24/min, and blood pressure is 95/60 mm Hg. Arterial blood gases when the patient is breathing room air are PaO 2 , 58 mm Hg; PaCO 2 , 28 mm Hg; and pH, 7.44.

Which of the following is the most appropriate next step?

( A ) Tissue plasminogen activator ( B ) Pulmonary angiography ( C ) Unfractionated heparin ( D ) Inferior vena cava filter ( E ) Warfarin

SHOULD AN IVC FILTER BE PLACED? Indications: Absolute contraindication to anticoagulation active bleeding Major surgery Recurrent PE despite adequate anticoagulant therapy Complication of anticoagulation severe bleeding Hemodynamic or respiratory compromise (another PE may be lethal ) Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Indications:

Absolute contraindication to anticoagulation

active bleeding

Major surgery

Recurrent PE despite adequate anticoagulant therapy

Complication of anticoagulation

severe bleeding

Hemodynamic or respiratory compromise (another PE may be lethal )

IVC FILTERS: OUTCOME Randomized trial 400 pts with proximal DVT Anticoagulation alone vs anticoagulation plus an IVC filter Decrease recurrent PE Increase recurrent DVT No reduction in mortality Decousus et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med 1998; 338:409 .

Randomized trial

400 pts with proximal DVT

Anticoagulation alone vs anticoagulation plus an IVC filter

Decrease recurrent PE

Increase recurrent DVT

No reduction in mortality

IVC FILTERS: COMPLICATIONS Complications related to the insertion process (bleeding, venous thrombosis at the insertion site) Filter misplacement Filter migration Filter erosion and perforation of the IVC wall IVC obstruction due to filter thrombosis Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Complications related to the insertion process (bleeding, venous thrombosis at the insertion site)

Filter misplacement

Filter migration

Filter erosion and perforation of the IVC wall

IVC obstruction due to filter thrombosis

LONG-TERM vs. RETRIEVABLE IVC FILTERS Permanent IVC filter placement is discouraged Investigation of their effectiveness and adverse effects is still in its early stages Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Permanent IVC filter placement is discouraged

Investigation of their effectiveness and adverse effects is still in its early stages

EMBOLECTOMY Persistent hypotension due to PE Thrombolytic therapy fails or is contraindicated Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Persistent hypotension due to PE

Thrombolytic therapy fails or is contraindicated

Catheter Embolectomy Rheolytic embolectomy (AngioJet embolectomy ) Injecting pressurized saline through the catheter The saline and fragments of clot are then sucked back into the catheter Rotational embolectomy Rotating device to fragment the thrombus, while continuously aspirating the fragments. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Rheolytic embolectomy (AngioJet embolectomy )

Injecting pressurized saline through the catheter

The saline and fragments of clot are then sucked back into the catheter

Rotational embolectomy

Rotating device to fragment the thrombus, while continuously aspirating the fragments.

Normal inferior pulmonary artery and peripheral reperfusion immediately and one month after thrombectomy Huge thrombus in the right inferior pulmonary artery Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Surgical Embolectomy Experienced surgeon Cardiopulmonary bypass Small observational cohort study on pts failed the initial thrombolysis Surgical embolectomy vs repeat thrombolysis Fewer recurrent PE Fewer deaths and fewer major bleeding But not statistically significant Meneveau et al. Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest 2006; 129:1043.

Experienced surgeon

Cardiopulmonary bypass

Small observational cohort study on pts failed the initial thrombolysis

Surgical embolectomy vs repeat thrombolysis

Fewer recurrent PE

Fewer deaths and fewer major bleeding

But not statistically significant

Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy The incidence is higher during in pregnancy ( x 4-50) Incidence rate of 1 / 500 - 2000 Maternal Mortality PE 20 % Maternal hemorrhage 17 % Pregnancy-associated hypertension 16 % Chang et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ 2003; 52:1.

The incidence is higher during in pregnancy ( x 4-50)

Incidence rate of 1 / 500 - 2000

Maternal Mortality

PE 20 %

Maternal hemorrhage 17 %

Pregnancy-associated hypertension 16 %

Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy More common in the postpartum period DVT is 2 X higher after cesarean delivery than vaginal birth Antepartum DVT/PE is equally distributed across trimesters Simpson et al. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001; 108:56.

More common in the postpartum period

DVT is 2 X higher after cesarean delivery than vaginal birth

Antepartum DVT/PE is equally distributed across trimesters

DVT is more common in the left than the right leg 60 pregnant women with a first episode DVT 58 left lower extremity DVTs 2 bilateral DVTs No isolated right lower extremity DVTs Increased venous stasis in the left leg Compression of the left iliac vein by the right iliac artery Compression of the IVC by the uterus Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Ginsberg et al. Venous thrombosis during pregnancy: Leg and trimester of presentation. Thromb Haemost 1992; 67:519.

DVT is more common in the left than the right leg

60 pregnant women with a first episode DVT

58 left lower extremity DVTs

2 bilateral DVTs

No isolated right lower extremity DVTs

Increased venous stasis in the left leg

Compression of the left iliac vein by the right iliac artery

Compression of the IVC by the uterus

PATHOGENESIS AND RISK FACTORS Virchow's triad Venous stasis Endothelial injury Hypercoagulable state Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

PATHOGENESIS AND RISK FACTORS

Virchow's triad

Venous stasis

Endothelial injury

Hypercoagulable state

PATHOGENESIS AND RISK FACTORS VENOUS STASIS Progesterone induced dilation of veins Venous pooling Valvular incompetence Compression of large veins by the gravid uterus Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Goodrich et al. Peripheral venous distensibility and velocity of venous blood flow during pregnancy or during oral contraceptive therapy. Am J Obstet Gynecol 1964; 90:740.

PATHOGENESIS AND RISK FACTORS

VENOUS STASIS

Progesterone induced dilation of veins

Venous pooling

Valvular incompetence

Compression of large veins by the gravid uterus

PATHOGENESIS AND RISK FACTORS ENDOTHELIAL INJURY At the uteroplacental surface Probably accounts for the frequency of DVT/PE in the immediate postpartum period Forceps, vacuum extraction, or surgical delivery can exaggerate vascular intimal injury and amplify this phenomenon Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Marik et al. Venous thromboembolic disease and pregnancy. N Engl J Med 2008; 359:2025. Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

PATHOGENESIS AND RISK FACTORS

ENDOTHELIAL INJURY

At the uteroplacental surface

Probably accounts for the frequency of DVT/PE in the immediate postpartum period

Forceps, vacuum extraction, or surgical delivery can exaggerate vascular intimal injury and amplify this phenomenon

PATHOGENESIS AND RISK FACTORS HYPERCOAGULABLE STATE Increase coagulation factors, such as factors I, II, VII, VIII, IX, and X Decrease in protein S Increase in resistance to activated protein C Inherited thrombophilias Antiphospholipid antibodies Deep Vein Thrombosis and Pulmonary Embolism in Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

PATHOGENESIS AND RISK FACTORS

HYPERCOAGULABLE STATE

Increase coagulation factors, such as factors I, II, VII, VIII, IX, and X

Decrease in protein S

Increase in resistance to activated protein C

Inherited thrombophilias

Antiphospholipid antibodies

Marik et al. Venous thromboembolic disease and pregnancy. N Engl J Med 2008; 359:2025

Diagnosis of DVT/PE During Pregnancy can be a Challenge Lower extremity swelling and discomfort are common in advanced pregnancy Dyspnea (the most frequent symptom of PE) occurs at some point in up to 70 % of normal pregnancies Respiratory alkalosis is a very common feature of both pregnancy and PE Wells Score, have not been validated in pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Lower extremity swelling and discomfort are common in advanced pregnancy

Dyspnea (the most frequent symptom of PE) occurs at some point in up to 70 % of normal pregnancies

Respiratory alkalosis is a very common feature of both pregnancy and PE

Wells Score, have not been validated in pregnancy

Diagnosis of DVT/PE During Pregnancy can be a Challenge D-Dimer is elevated in uncomplicated pregnancy Increases with gestational age and peaks at the time of delivery and in the early postpartum period Kline et al. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005; 51:825.

D-Dimer is elevated in uncomplicated pregnancy

Increases with gestational age and peaks at the time of delivery and in the early postpartum period

The recommended initial test in the workup of DVT Doppler ultrasound Should be done with the pt in the left lateral decubitus position If U/S results are equivocal then contrast venography with abdominal-pelvic shielding The delivered radiation to the fetus is small (<500 mcGy) with shielding shielding renders the test relatively insensitive to isolated iliofemoral thrombosis In cases of contraindications of contrast, or strong clinical suspicion of pelvic thrombosis MRI Diagnosis of DVT During Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

The recommended initial test in the workup of DVT

Doppler ultrasound

Should be done with the pt in the left lateral decubitus position

If U/S results are equivocal then

contrast venography with abdominal-pelvic shielding

The delivered radiation to the fetus is small (<500 mcGy) with shielding

shielding renders the test relatively insensitive to isolated iliofemoral thrombosis

In cases of contraindications of contrast, or strong clinical suspicion of pelvic thrombosis

MRI

The recommended initial test in the workup of PE LE’s Doppler ultrasound The diagnostic test of choice in the workup of PE in pregnancy CT angiography Mean radiation dose to the fetus is 3 to 131 mcGy In case of contraindication to radiocontrast: (V/Q) scan Pulmonary angiography Diagnosis of PE During Pregnancy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

The recommended initial test in the workup of PE

LE’s Doppler ultrasound

The diagnostic test of choice in the workup of PE in pregnancy

CT angiography

Mean radiation dose to the fetus is 3 to 131 mcGy

In case of contraindication to radiocontrast:

(V/Q) scan

Pulmonary angiography

There are no systematic differences in the diagnostic strategies for DVT and PE in the pregnant and the non-pregnant pt Avoiding radiation-requiring studies in pregnant pts may result with greater harm to the pt and the fetus from the failure to detect VTE Fetal radiation exposure from the combination of a chest radiograph, V/Q scanning, and pulmonary arteriography is less than 5000 mcGy Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21:1301.

There are no systematic differences in the diagnostic strategies for DVT and PE in the pregnant and the non-pregnant pt

Avoiding radiation-requiring studies in pregnant pts may result with greater harm to the pt and the fetus from the failure to detect VTE

Fetal radiation exposure from the combination of a chest radiograph, V/Q scanning, and pulmonary arteriography is less than 5000 mcGy

Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD 30% of all exacerbations of COPD do not have a clear etiology COPD pts are at a high risk for PE Limited mobility Inflammation Comorbidities Rizkallah et al. Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD: A Systematic Review and Meta-analysis CHEST March 2009 vol. 135 no. 3 786-793

30% of all exacerbations of COPD do not have a clear etiology

COPD pts are at a high risk for PE

Limited mobility

Inflammation

Comorbidities

Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD Systematic review and metaanalysis 5 cross-sectional or prospective studies Used CT scanning or pulmonary angiography for PE diagnosis Sample size 550 patients Rizkallah et al. Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD: A Systematic Review and Meta-analysis CHEST March 2009 vol. 135 no. 3 786-793

Systematic review and metaanalysis

5 cross-sectional or prospective studies

Used CT scanning or pulmonary angiography for PE diagnosis

Sample size 550 patients

One of four COPD patients who require hospitalization for an acute exacerbation may have PE Rizkallah et al. Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD: A Systematic Review and Meta-analysis CHEST March 2009 vol. 135 no. 3 786-793

One of four COPD patients who require hospitalization for an acute exacerbation may have PE

Diagnostic Vascular Ultrasonography Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Should we Perform our Own Compression Studies? Bedside procedure Progressively practiced by Intensivists Easy to learn Available 24/7 Fast and safe Can be repeated Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Bedside procedure

Progressively practiced by Intensivists

Easy to learn

Available 24/7

Fast and safe

Can be repeated

Lower Extremity Deep Venous Anatomy Great Saphenous Vein (GSV) Superficial vein GSC thrombosis is not cause for anticoagulation With the exception of the most proximal portion of the vein Proximal Distal Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Great Saphenous Vein (GSV)

Superficial vein

GSC thrombosis is not cause for anticoagulation

With the exception of the most proximal portion of the vein

Why Do we Ignore Calf DVT? Most distal vein thrombi (calf vein) resolve spontaneously 20-30 % of calf DVTs extend proximally if untreated If left untreated 80% become symptomatic 50% then become PE So, from 100 calf DVTs, there will be 8 PE’s From 100 proximal DVTs, there will be 50 PE’s Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Most distal vein thrombi (calf vein) resolve spontaneously

20-30 % of calf DVTs extend proximally if untreated

If left untreated

80% become symptomatic

50% then become PE

So, from 100 calf DVTs, there will be 8 PE’s

From 100 proximal DVTs, there will be 50 PE’s

Why Do we Ignore Calf DVT? Most distal vein thrombi (calf vein) resolve spontaneously 20-30 % of calf DVTs extend proximally if untreated If left untreated 80% become symptomatic 50% then become PE So, from 100 calf DVTs, there will be 8 PE’s From 100 proximal DVTs, there will be 50 PE’s Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Most distal vein thrombi (calf vein) resolve spontaneously

20-30 % of calf DVTs extend proximally if untreated

If left untreated

80% become symptomatic

50% then become PE

So, from 100 calf DVTs, there will be 8 PE’s

From 100 proximal DVTs, there will be 50 PE’s

Incidence of DVT in ICU High incidence of DVT in the ICU (8%-18% first wk) Cook , Crit Care Med, 2005 261 MICU/SICU pts (expected stay > 72hrs) Ultrasound done within 48hrs and 2x/week All on ppx 2.7% prevalence of proximal DVT 9.6% incidence of proximal DVT Ibrahim, Crit Care Med 2002 MICU pts on vent > 7 days Duplex done every 7 days All on ppx 18% with proximal LE DVT, 5 % with UE DVT Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

High incidence of DVT in the ICU (8%-18% first wk)

Cook , Crit Care Med, 2005

261 MICU/SICU pts (expected stay > 72hrs)

Ultrasound done within 48hrs and 2x/week

All on ppx

2.7% prevalence of proximal DVT

9.6% incidence of proximal DVT

Ibrahim, Crit Care Med 2002

MICU pts on vent > 7 days

Duplex done every 7 days

All on ppx

18% with proximal LE DVT, 5 % with UE DVT

Do we Need to Utilize Doppler and Color Modalities? Lensing, Ann Int Med, 1997 Added color Doppler to simple compression study, found to result in no added sensitivity or specificity Blaivas, Acad Emerg Med, 2000 17% DVT had normal augmentation 12% normal studies had poor augmentation Color doppler decreased “indeterminate” diagnoses Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Lensing, Ann Int Med, 1997

Added color Doppler to simple compression study, found to result in no added sensitivity or specificity

Blaivas, Acad Emerg Med, 2000

17% DVT had normal augmentation

12% normal studies had poor augmentation

Color doppler decreased “indeterminate” diagnoses

Do we Need to Scan Every 2 cm from CFV to PV? Poppitti 1995 2 site compression vs. complete doppler exam No additional proximal DVT with complete study Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Poppitti 1995

2 site compression vs. complete doppler exam

No additional proximal DVT with complete study

Can We Accurately Perform Compression Studies Magazzini, Acad Emerg Med, 2006 ED physicians took 30 hr ultrasound course, performed LE ultrasound on ED pts, discharge pt if results normal Radiologist did “formal” study within 24-48hrs 399 pts scanned, mean time for study was 13 min PPV 96%, NPV 100%, only 2% “uncertain” No pts died or developed DVT within 1 month Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Magazzini, Acad Emerg Med, 2006

ED physicians took 30 hr ultrasound course, performed LE ultrasound on ED pts, discharge pt if results normal

Radiologist did “formal” study within 24-48hrs

399 pts scanned, mean time for study was 13 min

PPV 96%, NPV 100%, only 2% “uncertain”

No pts died or developed DVT within 1 month

Can We Accurately Perform Compression Studies Jang T, Acad Emerg Med, 2004 8 ED residents , PGY 1-3 Training: One week general introductory course One hour PowerPoint lecture on DVT U/S with images, performed tow practice studies on normal volunteers 72 pts, full compression study performed Results compared to venography, vasc lab U/S, or CTV 100% SENSETIVITY, 92% SPECIFICITY Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Jang T, Acad Emerg Med, 2004

8 ED residents , PGY 1-3

Training:

One week general introductory course

One hour PowerPoint lecture on DVT U/S with images, performed tow practice studies on normal volunteers

72 pts, full compression study performed

Results compared to venography, vasc lab U/S, or CTV

100% SENSETIVITY, 92% SPECIFICITY

Can We Accurately Perform Compression Studies Blaivas 2000 – ED physician study ED physicians experienced in ultrasound (but not for DVT) Training 2 hrs didactics 3 hrs hands-on training 103 high risk ED pts with signs and symptoms 2 site compression + color augmentation Then duplex done by vascular laboratory 30% of pts found with DVT 1 false positive ED finding 1 true positive ED (negative by vasc lab, + on venography) Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Blaivas 2000 – ED physician study

ED physicians experienced in ultrasound (but not for DVT)

Training

2 hrs didactics

3 hrs hands-on training

103 high risk ED pts with signs and symptoms

2 site compression + color augmentation

Then duplex done by vascular laboratory

30% of pts found with DVT

1 false positive ED finding

1 true positive ED (negative by vasc lab, + on venography)

Can We Accurately Perform Compression Studies Trottier, CHEST 1996 Investigator with no prior experience Training 35 practice studies 100 med-surg hospitalized pts Compression study done with 1-2 cm intervals, compared to vas lab duplex 94% sensitivity, 99% specificity Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Trottier, CHEST 1996

Investigator with no prior experience

Training

35 practice studies

100 med-surg hospitalized pts

Compression study done with 1-2 cm intervals, compared to vas lab duplex

94% sensitivity, 99% specificity

Can We Accurately Perform Compression Studies in Acutely Ill Medical Patients? Tomkowski WZ, Haematoligica, 1999 Moderate risk hospitalized pts (CHF, COPD exac, PNA/UTI) Screening compression U/S on day 6-16 of hospital Venography performed same day 3.2% proximal DVT Sensitivity 60%, specificity 99% PPV 75%, NPV 98% Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Tomkowski WZ, Haematoligica, 1999

Moderate risk hospitalized pts (CHF, COPD exac, PNA/UTI)

Screening compression U/S on day 6-16 of hospital

Venography performed same day

3.2% proximal DVT

Sensitivity 60%, specificity 99%

PPV 75%, NPV 98%

Can We Accurately Perform Compression Studies in High Risk Patients? Lensing, Arch Int Med, 1997 204 post-op knee/hip ortho surgery pts Screened for asymptomatic DVT Compression with color compared to contrast venography 60% sensitivity , 71% specificity Color added no additional DVT accuracy Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Lensing, Arch Int Med, 1997

204 post-op knee/hip ortho surgery pts

Screened for asymptomatic DVT

Compression with color compared to contrast venography

60% sensitivity , 71% specificity

Color added no additional DVT accuracy

Summary Slide Simple compression study is sufficient No need for doppler color/ augmentation maneuver Compression studies can be accurately performed by clinicians with minimal training Has only been shown in ED and medical ward patients Not sensitive in high risk or acutely ill medical pts Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Simple compression study is sufficient

No need for doppler color/ augmentation maneuver

Compression studies can be accurately performed by clinicians with minimal training

Has only been shown in ED and medical ward patients

Not sensitive in high risk or acutely ill medical pts

Performance of Compression Study Vascular “linear” transducer (7.5 MHz) Pt in supine position with slight external rotation Position transducer just distal to inguinal ligament, marker at 9 o’clock Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5

Vascular “linear” transducer (7.5 MHz)

Pt in supine position with slight external rotation

Position transducer just distal to inguinal ligament, marker at 9 o’clock

Compression Technique Apply pressure until vein collapses If artery starts to deform and vein is not collapsing, this suggests possibility of a thrombus in lumen If a DVT is found, mark most proximal location This allows eval of progression or treatment failure Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5 Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Apply pressure until vein collapses

If artery starts to deform and vein is not collapsing, this suggests possibility of a thrombus in lumen

If a DVT is found, mark most proximal location

This allows eval of progression or treatment failure

Compression Points Femoral Compressions Start on CFV just distal to inguinal ligament Then q 1 cm until the medial entry of the GSV (the bean sign) Then q 1 cm until CFV splits into DFV and SFV Then continue 1-2 cm Then may go straight to PV Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5 1 2 3 4 5 Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Femoral Compressions

Start on CFV just distal to inguinal ligament

Then q 1 cm until the medial entry of the GSV (the bean sign)

Then q 1 cm until CFV splits into DFV and SFV

Then continue 1-2 cm

Then may go straight to PV

BEAN SIGN CFV GSV

Compression Points Popliteal Compressions Locate PA and PV behind knee Compress last 2 cm of PV and just distal to it’s trifurcation Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5 1 2

Popliteal Compressions

Locate PA and PV behind knee

Compress last 2 cm of PV and just distal to it’s trifurcation

PA PV PA

PA PA PV PV

How to Distinguish Acute from Chronic Thrombus Consider MRI to distinguish acute from chronic DVT Acute DVT Anechoic (black) but may be echogenic Confirm with compression Chronic DVT (organized thrombus) Organization occur between 5-10 days More echogenic (brighter) More irregular Recannulize centrally Blood flow can be seen through or around the thrombus Thickened venous walls Collateral may be present Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5 Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Consider MRI to distinguish acute from chronic DVT

Acute DVT

Anechoic (black) but may be echogenic

Confirm with compression

Chronic DVT (organized thrombus)

Organization occur between 5-10 days

More echogenic (brighter)

More irregular

Recannulize centrally

Blood flow can be seen through or around the thrombus

Thickened venous walls

Collateral may be present

Important Hints Do not compress a free-floating thrombus Risk for embolization Echogenic lumen not specific for clot. An acute thrombus can be anechoic Confirm patency by complete apposition of the anterior and posterior walls of the vessel Differentiate a lymph node or Baker's cyst from DVT The transducer can be moved proximally and distally to identify the edges of the lymph node or cyst LN usually oval and encapsulated If the vein seems to be only partially filled, a long axis view is warranted Blaivas M. Ultrasound in the detection of venous thromboembolism. Crit Care Med 2007 Vol. 35 No. 5 Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Do not compress a free-floating thrombus

Risk for embolization

Echogenic lumen not specific for clot. An acute thrombus can be anechoic

Confirm patency by complete apposition of the anterior and posterior walls of the vessel

Differentiate a lymph node or Baker's cyst from DVT

The transducer can be moved proximally and distally to identify the edges of the lymph node or cyst

LN usually oval and encapsulated

If the vein seems to be only partially filled, a long axis view is warranted

Integrating bedside ultrasound for thromboembolic disease into an ICU-based protocol for DVT prophylaxis, screening, and diagnosis holds promise for decreasing deadly sequelae such as PE Bassel Ericsoussi, MD Pulmonary and Critical Care Fellow

Integrating bedside ultrasound for thromboembolic disease into an ICU-based protocol for DVT prophylaxis, screening, and diagnosis holds promise for decreasing deadly sequelae such as PE