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Acute management of PE and Thrombolysis RCP Acute Medicine Conference Simon Bax Consultant Chest Physician SASH

Acute management of PE and Thrombolysis

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Page 1: Acute management of PE and Thrombolysis

Acute management of PE and ThrombolysisRCP Acute Medicine Conference

Simon Bax

Consultant Chest Physician

SASH

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Whatrsquos new in the world of PE

NCEPOD ndash Key findings

One delay or more in management was present in 383 of encounters

An avoidable delay in commencing treatment was found in 187

PE Severity assessment was not performed in 903

Wide variation in patient selection for ambulatory pathways

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 2: Acute management of PE and Thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Whatrsquos new in the world of PE

NCEPOD ndash Key findings

One delay or more in management was present in 383 of encounters

An avoidable delay in commencing treatment was found in 187

PE Severity assessment was not performed in 903

Wide variation in patient selection for ambulatory pathways

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 3: Acute management of PE and Thrombolysis

Whatrsquos new in the world of PE

NCEPOD ndash Key findings

One delay or more in management was present in 383 of encounters

An avoidable delay in commencing treatment was found in 187

PE Severity assessment was not performed in 903

Wide variation in patient selection for ambulatory pathways

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 4: Acute management of PE and Thrombolysis

NCEPOD ndash Key findings

One delay or more in management was present in 383 of encounters

An avoidable delay in commencing treatment was found in 187

PE Severity assessment was not performed in 903

Wide variation in patient selection for ambulatory pathways

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 5: Acute management of PE and Thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 6: Acute management of PE and Thrombolysis

Diagnostic algorithm in patients with suspected PE

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 7: Acute management of PE and Thrombolysis

NICE recommend use of the two level Wells score

What proportion have a PE

~30~12

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 8: Acute management of PE and Thrombolysis

Age-adjusted D-dimer

bull The specificity of D-dimer decreases with age

bull A multinational prospective study evaluated a previously validated age-adjusted cut-off

bull (age x 10 microgramsL in gt50s)

bull 3346 patients (PE prevalence 19)

bull Patients with a normal age adjusted D-dimer did not undergo imaging

bull Use of the age adjusted D-dimer increased the number of patients where PE could be safely excluded from 64 to 30

Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism the ADJUST-PE studyRighin et al JAMA 2014 Mar 19 311 (11) 1117-24

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 9: Acute management of PE and Thrombolysis

Case 1

bull 52 Female presented by blue light

bull Collapse while walking with shopping

bull Bipolar Obesity Smoker

bull BP ndash 8842 HR 122 RR 30 O2 88 (15LO2)

bull GCS ndash E2 V4 M5 ndash 11

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 10: Acute management of PE and Thrombolysis

PEA Arrest

bull Adrenaline

bull Alteplase 50mg bolus

bull Intubated and Ventilated

bull Lost output a further 4 times until instigated on Adrenaline infusion

bull ITU ndash Persistent high inotrope requirement despite thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 11: Acute management of PE and Thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 12: Acute management of PE and Thrombolysis

Factors causing haemo-dynamic collapse

2019 ESC ERS Guidelines for the diagnosis and management if acute PE

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 13: Acute management of PE and Thrombolysis

Massive PE ndash Acute high risk

PE

Need for CPR

bull Systolic BPlt90mmHg or systolic ge40mmHg lasting more than 15 minutes in absence of other cause

Persistent hypotension

bull Systolic BP (lt90mmHg) or vasopressors

bull And

bull End-organ hypoperfusion

bull Confusion Increased lactate Cold and clammy

Obstructive Shock

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 14: Acute management of PE and Thrombolysis

Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism A Randomized Controlled Trial

bull 8 patients

bull 4 received heparin alone

bull 4 received heparin and streptokinase

bull Heparin group all died

bull Streptokinase group all survived

Jerjes-Sanchez et al J Thomb Thrombolysis 1995 2 (3)227-229

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 15: Acute management of PE and Thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 16: Acute management of PE and Thrombolysis

Risk stratification in all patients with PE ndash PESI sPESI

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 17: Acute management of PE and Thrombolysis

RV Dysfunction

bull RV dysfunction means the presence of at least 1 of the following

ndash RV dilation (apical 4-chamber RV diameter divided by LV diameter gt09) or RV systolic dysfunction on echocardiography

ndash RV dilation (4-chamber RV diameter divided by LV diameter gt09) on CT

ndash Elevation of BNP (gt90 pgmL)

ndash Elevation of N-terminal pro-BNP (gt500 pgmL) or

ndash Electrocardiographic changes (new complete or incomplete right bundle-branch block anteroseptal ST elevation or depression or anteroseptal T-wave inversion)

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 18: Acute management of PE and Thrombolysis

Assessing RV dysfunction at CTPA

Right Ventricular to Left Ventricular Ratio at CT Pulmonary Angiogram Predicts Mortality in Interstitial Lung DiseaseBax et al Chest 2019 Jul 24 [Epub ahead of print]

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 19: Acute management of PE and Thrombolysis

BNP

BNP if elevated 10 risk of early death and a 23 risk of an adverse clinical outcome2

In normotensive patients with PE the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low3

In a prospective multicentre cohort study that included 688 patients NT-proBNP plasma concentrations of 600 pgmL were identified as the optimal cut-off value for the identification of elevated risk4

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 20: Acute management of PE and Thrombolysis

Troponin

A meta analysis showed that elevated Troponin was associated with an increased risk of mortality (OR 52 CI 33-84)

The risk remained in those who were haemodynamically stable (OR 59 CI 27-130)5

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 21: Acute management of PE and Thrombolysis

Lactate

Serum lactate gt 2 associated with a higher risk of adverse outcome

The combination of RV dysfunction elevated troponin and increased lactate predicted a 66 fold of adverse short term PE related adverse events6

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 22: Acute management of PE and Thrombolysis

Clinical laboratory and echo parameters predicting 30-day PE-related mortality in normotensive patients (adapted from Jimenez et al)

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismJimenez et al Thorax 2011 Jan66(1)75-81

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 23: Acute management of PE and Thrombolysis

Classification of patients with acute PE based on early mortality risk

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 24: Acute management of PE and Thrombolysis

Case 2

bull 80 Male Severe breathlessness

bull Collapsed the previous night

bull Very minor Left sided chest pain

bull Exercise tolerance 5-10m

bull BP 13577 HR 115

bull O2 ndash 92 ra RR 22

Prognosticationbull sPESI ndash 3 (109)bull PESI ndash 140 (10-24)bull Troponin (+ive) 63bull Echo ndash Septum deviation

D shaped LV Dilated RV PASP ndash 70mmHg

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 25: Acute management of PE and Thrombolysis

Management

bull LMWH

bull Thrombolysis discussed (Pietho)

bull Good improvement ndash Ex tolerance improved

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 26: Acute management of PE and Thrombolysis

Day of discharge

bull Collapseshellipagain

bull BP- 9576 HR 120 O₂ 95

bull ldquoIrsquom finerdquo

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 27: Acute management of PE and Thrombolysis

Pre and post thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 28: Acute management of PE and Thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

bull 1006 patients multi-centre double blind placebo controlled

bull Randomized to receive a single dose of tenecteplase plus heparin or to receive placebo plus heparin

bull Onset of symptoms 15 days or less before randomization

bull Right ventricular dysfunction (echo ct) and positive trop

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 29: Acute management of PE and Thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 30: Acute management of PE and Thrombolysis

Pulmonary Embolism Thrombolysis trial (PEITHO)

Primary outcomes

bull Death or hemodynamic de-compensation within 7 days after randomization

Safety outcomes

bull Extra-cranial major bleeding within 7 days after randomization

bull Ischemic or hemorrhagic stroke within 7 days

bull Serious adverse events within 30 days

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 31: Acute management of PE and Thrombolysis

Results

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 32: Acute management of PE and Thrombolysis

Safety

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 33: Acute management of PE and Thrombolysis

Compromise

Fibrinolysis for Patients with Intermediate-Risk Pulmonary EmbolismMeyer et al N Engl J Med 2014 370 1402-1411

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 34: Acute management of PE and Thrombolysis

Approach to Thrombolysis in intermediate high risk

bull RISK STRATIFY - PESIbull Check Trop BNP and review CT for signs of R heart

strainbull Intermediate high risk patients should be in a high

visibility environment with Thrombolytics to hand and frequently re-evaluate

bull Consider thrombolysisndash Clinical worseningndash DVT presentndash Increasing Lactatendash RA thrombusndash lt75 years of age with no prior cerebrovascular disease

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 35: Acute management of PE and Thrombolysis

How to dose in Thrombolysis

bull High risk

ndash Alteplase

ndash 10mg over 1-2 minutes

ndash 90mg over 2 hours (If over 65Kg)

ndash Total dose 15mgKg if lt65Kg

bull In cardiac arrest

ndash 50mg bolus ndash continue resuscitation for 30minutes to one hour

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 36: Acute management of PE and Thrombolysis

What risks should you quote if taking about thrombolysis

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality Major Bleeding and Intracranial Haemorrhage A Meta-analysisChatterjee et al JACC 2014311 (23) 2414-2421

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 37: Acute management of PE and Thrombolysis

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

bull Retrospective evaluation of 9703 patients thrombolysed between 2003 ndash 2012 ndash Clinical risk score with validation

bull Peripheral vascular disease (1 point)bull Age gt 65 (1 point)bull Prior hx of MI (1 point)bull CVA with residual deficit (5 points)

bull Score of 0 (12)bull Score of 1 (19)bull Score of 2 (24)bull Score ge 5 (178)

bull C-statistic only 066 (060-072)

Chatterjee S Thromb Haemost 2017 Jan 26 117(2) 246-251

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 38: Acute management of PE and Thrombolysis

Topics

bull Whatrsquos new in the world of PE

bull Is this a PE

bull Front door management in suspected massive PE

bull Can I predict which patients with PE are at a high risk of early deterioration

bull Should I thrombolyse to prevent future morbidity

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 39: Acute management of PE and Thrombolysis

Impact of Thrombolytic Therapy on the Long-Term Outcome ofIntermediate-Risk Pulmonary Embolism

J Am Coll Cardiol 2017691536ndash4

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 40: Acute management of PE and Thrombolysis

References

bull 1 Goldhaber SZ Bounameaux H Pulmonary embolism and deep vein thrombosis Lancet 2012 May 12379(9828)1835-46 Epub 2012 Apr 10

bull 2 Klok FA Mos IC Huisman MV Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism a systematic review and meta-analysis Am J Respir Crit Care Med 2008178(4)425ndash430

bull 3 Kucher N Goldhaber SZ Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism Circulation 2003108(18)2191ndash2194

bull 4 Lankeit M Jimenez D Kostrubiec M Dellas C Kuhnert K Hasenfuss G Pruszczyk P Konstantinides S Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism Eur Respir J 201443(6)1669ndash1677

bull 5 Becattini C Vedovati MC Agnelli G Prognostic value of troponins in acute pulmonary embolism a meta-analysis Circulation 2007116427433

bull 6 Short term clinical outcome of normotensive patients with acute pe and high plasma lactate Simone Vanni Thorax April 2015 Volume 70 issue 4

Page 41: Acute management of PE and Thrombolysis