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SOE 019: Pulmonary Embolism

Introduction

You are asked to review a 68-year-old woman with shortness of breath on the surgical HDU. She is 48 hours after an anterior resection for bowel cancer. Her blood pressure is 140/89 and she has saturations of 94% on 35% oxygen…

Question No. 2

Q: What are the clinical features that may suggest pulmonary embolism as a cause of a patients deterioration?

Answer No. 2

  • Clinical features are non-specific and have been shown to be of limited value in confirming the diagnosis
  • Features range from being relatively asymptomatic to significant cardiovascular compromise - they can be difficult to identify in the sedated, mechanically-ventilated patient
  • Haemodynamic instability is a rare but important form of clinical presentation, as it indicates central or extensive PE with severely reduced haemodynamic reserve
  • Common features include:
Symptoms
  • Pleuritic chest pain
  • Dyspnea
  • Hemoptysis
Signs
  • Acute onset of tachypnea
  • Hypoxia or increased oxygen requirements
  • Tachycardia
  • Hypotension
  • Unexplained agitation
  • Asymmetric leg swelling
  • Weaning failure
  • Persistent pyrexia without evident source of infection
  • Cardiovascular and respiratory examination findings:
    • Pleural friction rub
    • Small volume arterial pulse
    • Raised jugular venous pressure
    • Gallop rhythm at the left sternal edge
    • Accentuated second heart sound

Question No. 3

Q: How common is pulmonary embolism?

Answer No. 3

  • Common with an annual incidence of 60-70/100,000
    • Half of cases develop VTE whilst in hospital or long term care
    • Sub-massive PEs account for ~20% of diagnosed PEs
  • Often underdiagnosed in critically ill patients
    • May occur in as many as 10% of patients

Question No. 4

Q: What is the mortality associated with pulmonary embolism?

Answer No. 4

  • Mortality rates range in studies range from 6% - 15%
  • In 2004 this equated to 370 000 deaths across Europe
    • 34% died suddenly or within a few hours of the acute event
    • 59% diagnosed after death
      Only 7% who died early were correctly diagnosed with PE before death

Question No. 5

Q: What are the risk factors for VTE in the critically ill?

Answer No. 5

Can be considered according to Virchow’s triad:
Venous Stasis
  • Prolonged bed rest
  • Prolonged air travel (>8 hours)
  • Fracture of lower limbs
  • Hip or knee replacement
  • Spinal cord replacement
  • Varicose veins
Hypercoagulability
  • Malignancy (particularly metastatic disease)
  • Infection (specifically pneumonia, urinary tract infection, and HIV)
  • Specific thrombotic conditions:
    • Previous venous thrombosis
    • Factor V Leiden mutation
    • Protein C or S deficiency
    • Hyperhomocysteinemia
    • Antithrombin III deficiency
    • Antiphospholipid antibodies
    • Thrombotic thrombocytopenic purpura (TTP)
    • High levels of factor VIII
  • Nephrotic syndrome
  • Inflammatory bowel disease
  • Pregnancy
  • Drugs:
    • Hormone replacement therapy
    • Oral contraceptives
    • Tamoxifen
    • Chemotherapy
  • Heart failure or respiratory failure
  • Increasing age
  • Obesity
Endothelial Injury
  • Major surgical procedures
  • Trauma
  • Prior venous thrombosis
  • Venous catheters
  • Smoking
  • Hypertension

Question No. 6

Q: How can the severity of PE be classified?

Answer No. 6

  • Classification of PE severity has traditionally been based on haemodynamic stability:
Massive
  • Cardiovascular compromise with a systolic blood pressure (SBP) <90 mmHg or a drop in systolic pressure of >40 mmHg
Sub-Massive
  • No systemic hypotension but evidence of either RV dysfunction or myocardial necrosis
Mild / Non-Massive
  • Asymptomatic or with mild symptoms and no evidence of RV dysfunction or cardiovascular compromise
  • Newer classifications of severity are based upon early mortality risk (in-hospital or 30-days) using clinical, imaging, and laboratory indicators:
Early Mortality Risk
Early Mortality Risk
Risk Parameters & Scores
Risk Parameters & Scores
Risk Parameters & Scores
Risk Parameters & Scores
Early Mortality Risk
Early Mortality Risk
Shock or hypotension
PESI class III-V
Signs or RV Dysfunction on Imaging
Cardiac Laboratory Biomarkers
High
High
+
(+)
+
(+)
Intermediate
High
-
+
Both positive
Both positive
Intermediate
Low
-
+
Either one (or none) positive
Either one (or none) positive
Low
Low
-
-
-
Assessment optional but negative if assessed

Question No. 7

Q: How is haemodynamic instability defined in the setting of high-risk pulmonary embolism?

Answer No. 7

Cardiac arrest
  • Need for cardiopulmonary resuscitation
Obstructive shock
  • Systolic BP <90 mmHg or vasopressors required to achieve a BP ≥90 mmHg despite adequate filling status
    and
  • End-organ hypoperfusion (altered mental status; cold, clammy skin; oliguria/anuria; increased serum lactate)
Persistent hypotension
  • Systolic BP <90 mmHg or systolic BP drop ≥40 mmHg, lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolaemia, or sepsis

Case Information

You are arranging a CTPA to be undertaken and ask for an ECG to be performed in the meantime…

Question No. 9

Q: What are the electrocardiographic (ECG) findings seen in PE?

Answer No. 9

  • ECG findings are also variable and neither sensitive or specific
  • A normal ECG is seen in up to 18% of cases
  • Abnormalities seen include:
    • Sinus tachycardia (most common - 44%)
    • Atrial arrhythmias (most frequently atrial fibrillation)
    • Classic S1Q3T3 (10%)
      • Deep S-wave in lead I, Q-wave in III and an inverted T-wave in III
    • Complete or incomplete right bundle branch block (15%): rSR’ in V1
      • Associated with increased mortality
    • Acute right ventricular strain (34%)
      • T-wave inversion in the right precordial leads (V1-4) and the inferior leads (II, III, aVF)
        Associated with high pulmonary artery pressures
    • Right axis deviation (15%):
      • May be extreme deviation - between 0 and -90°
    • Non-specific ST-segment and T-wave changes:
      • ST-elevation and depression
      • T-wave inversion

An ECG in pulmonary embolism demonstrates:

  • S1Q3T3 pattern - an S wave in lead I, Q wave and an inverted T wave in lead III
  • Sinus tachycardia

An ECG in pulmonary embolism demonstrates:

  • Incomplete or complete RBBB (rSR’ in V1)
  • T wave inversion in V1-V3 - mimics anterior ischemia
  • Sinus tachycardia

An ECG in pulmonary embolism demonstrates:

  • Right axis deviation
  • Right bundle branch block (rSR’ in V1)
  • Deep T wave inversion in V1-V3
  • Sinus tachycardia

Case Information

During the performance of the ECG the nurse notices she has become increasingly tachycardic and her blood pressure has fallen to 75/34 mmHg…

Question No. 11

Q: Why do pulmonary emboli cause haemodynamic instability?

Answer No. 11

  • PE can lead to right ventricular (RV) failure due to acute pressure overload:
    • Pulmonary artery pressure (PAP) increases in the presence of obstruction
    • Becomes evident if >30-50% of the total cross-sectional occluded by thromboemboli
    • Obstruction due to:
      • Mechanical obstruction from clot burden
      • Vasoconstriction, mediated by the release of thromboxane A2 and serotonin
  • Results in increased RV afterload and subsequent dilatation:
    • Initial compensation occurs via Frank Starling mechanism with increased myocyte stretch
    • Neurohumoral activation leads to inotropic and chronotropic stimulation.
  • RV adaptation is limited and is unable to generate a mean PAP >40 mmHg
    • Ventricle non-preconditioned and thin-walled
    • Enters cycle of progressive RV failure with imbalanced oxygen supply / demand and decreased contractility
  • Progressive impact on left ventricle (LV) and systemic circulation:
    • Bowing of intraventricular septum impairs LV filling
    • Further exacerbated by development of right bundle branch block
    • Leads to reduced cardiac output and systemic hypotension
    • Exacerbates impaired coronary driving pressure to the overloaded RV and further imbalances myocardial oxygen supply and demand
  • May be a secondary inflammatory response due to massive neurohumoral activation

Question No. 12

Q: How would your diagnostic strategy change now the patient is demonstrating haemodynamic instability?

Answer No. 12

Question No. 13

Q: What are the echocardiographic findings seen in PE?

Answer No. 13

  • Dilatation of the right ventricle
  • Impaired right ventricular function 
  • Flattened intraventricular septum
  • Distended inferior vena cava with diminished inspiratory collapsibility 
  • Tricuspid regurgitation
  • Mobile thrombus in the right heart

Dilatation of the right ventricle

  • Basal RV/LV > 1.0 
  • RV >4cm at the base in the 40 chamber view

Impaired right ventricular function

  • Tricuspid annular plane systolic excursion (TAPSE) <16 mm
  • May be evident on visual evaluation

McConnel's sign

  • Normokinesia and/or hypokinesia of the apical segment of the RV free wall despite hypokinesia and/or akinesia of the remaining parts of the RV free wall

Flattened intraventricular septum

Distended inferior vena cava with diminished inspiratory collapsibility

Tricuspid regurgitation

  • Velocity greater than 2.7 m/sec by colour doppler flow imaging

Mobile thrombus in the right heart

Question No. 14

Q: What are the indications for thrombolysis in PE?

Answer No. 14

  • High-risk (massive) PE
  • Selected cases of intermediate-risk (sub-massive) PE:
    • Currently not routinely recommended by ESC guidance
    • Some evidence it improves long term outcomes

Question No. 15

Q: What is the role for thrombolysis in sub-massive PE?

Answer No. 15

  • Some argue in favour of thrombolysis given improved longer-term outcomes:
    • Reduced burden of chronic RV failure or thrombus-related pulmonary hypertension
  • Others argue against thrombolysis given:
    • Relatively low mortality rates even with standard treatment (heparin)
    • Lack of proven mortality benefit (PEITHO trial used composite endpoint of mortality and haemodynamic instability)
    • Known potential for serious morbidity/ mortality with thrombolytics (mainly due to intracranial bleeding)
    • Increased cost
  • European Society of Cardiology guidelines do not currently recommend thrombolysis for intermediate-risk (sub-massive) pulmonary embolism

Question No. 16

Q: What is the evidence for thrombolysis in intermediate-risk (sub-massive) PE?

Answer No. 16

Study
Intervention
Population
Conclusion

RCT: PEITHO


Meyer et al
JAMA (2014)

View Paper
  • Thrombolysis (tenecteplase 30-50mg & heparin) vs. no thrombolysis (placebo & heparin) in patients with intermediate-risk/sub-massive pulmonary embolism
  • 1006 patients across 76 sites in 13 countries
  • PE confirmed by V/Q, CT or pulmonary angiogram with RV dysfunction confirmed by echo or CT and raised troponin
  • Primary outcome: Death or haemodynamic decompensation (composite endpoint) within 7 days significantly lower in thrombolysis group than placebo group (2.6%5.6%)
  • Secondary outcomes:
    • No significant difference in mortality (1.2% vs. 1.8%)
    • Both major extracranial bleeding (6.3% vs. 1.2%) and haemorrhagic stroke (2% vs 0.2%) significantly higher in thrombolysis group
    The Bottom Line Review

RCT: TOPCOAT


Kline et al
J Thromb Haem (2014)

View Paper
  • Thrombolysis (tenecteplase & heparin) vs. no thrombolysis (heparin alone) in patients with intermediate-risk/sub-massive pulmonary embolism
  • 83 patients across 8 sites in the USA
  • PE confirmed by V/Q, CT or pulmonary angiogram with RV dysfunction confirmed by echo, troponin or BNP
  • Composite primary outcome of death, intubation and major bleeding at 5 days or recurrent PE or impaired functional capacity at 90 days
  • Significantly reduced adverse outcomes in thrombolysis group (15% vs. 37% had at least 1 adverse outcome)
The Bottom Line Review

RCT: MOPPET


Sharifi et al
Am J Card (2013)

View Paper
  • Thrombolysis with half standard dose thrombolysis (tPa & enoxaparin) vs. anticoagulation alone in 'moderate PE'
  • 121 patients in single centre in the USA
  • 'Moderate PE' defined as haemodynamically stable PE with >70% involvement of thrombus in ≥2 lobar or left or right main pulmonary arteries
  • Primary outcome of development of pulmonary hypertension (pulmonary artery systolic pressure ≥ 40mmHg) significantly lower in thrombolysis group than control group(16% vs. 57%)
The Bottom Line Review

Question No. 17

Q: What surgical and catheter reperfusion therapies are available and what are their roles?

Answer No. 17

  • Should be considered:
    • Where there are absolute contraindications to thrombolysis
    • Where thrombolytic therapy has failed and the patient is critically ill
  • Options include:
Percutaneous Catheter-Directed Thrombolysis / Embolectomy
  • Involves insertion of a catheter into the pulmonary arteries via the femoral route
  • Different approaches involve one or a combination of:
    • Mechanical fragmentation
    • Ultrasound fragmentation
    • Thrombus aspiration
    • In situ reduced-dose thrombolysis
  • Overall procedural success rates in small studies have reached 87%
Surgical Embolectomy
  • Carried out with cardiopulmonary bypass, with aortic cross-clamping and cardioplegic cardiac arrest
  • Involves incision of the two main pulmonary arteries with the removal or suction of fresh clots
  • Has favourable outcomes in small studies:
    • Similar 30-day mortality to thrombolytic therapy
    • Lower risk of stroke or re-intervention

Question No. 18

Q: What are the options for anticoagulation for a patient presenting with pulmonary embolism?

Answer No. 18

Acute Management
Parenteral, weight-adjusted anticoagulation should be used:
  • Low-molecular weight heparin (LMWH) SC
  • Fondaparinux SC
  • Unfractionated heparin (UFH) IV
    • Generally second line due to higher bleeding risk and HIT risk
    • Preferred agent in the setting of:
      • Overt haemodynamic instability or imminent haemodynamic decompensation in whom primary reperfusion treatment will be necessary (short half life and easy reversal)
      • Increased risk of bleeding
      • Serious renal impairment (creatinine clearance <30 mL/min)
Longer-Term Management
Started when the patient's condition is stable and no invasive procedures are planned
  • Non-vitamin K oral anticoagulant (NOAC)
  • Warfarin international normalized ratio (INR) is 2.0 to 3.0:

Question No. 19

Q: When should anticoagulation be commenced?

Answer No. 19

  • Anticoagulation should be initiated without delay, while diagnostic workup in progress, in patients with:
    • Suspected PE with haemodynamic instability
    • Suspected PE without haemodynamic instability with a high or intermediate clinical probability

Question No. 20

Q: When should intubation be considered in pulmonary embolism?

Answer No. 20

  • Patients at high risk of deterioration during induction of anaesthesia, intubation, and positive-pressure ventilation:
    • Effect of drugs on hypotensive patient
    • Positive intrathoracic pressure reduces venous return and exacerbates RV dysfunction
  •  Intubation should be performed only if the patient is unable to tolerate or cope with non-invasive ventilation or high-flow oxygen therapy

Question No. 21

Q: How should right ventricular failure be managed in pulmonary embolism?

Answer No. 21

Fluid Therapy
  • Cautious fluid therapy may improve haemodynamic status:
    • Small fluid boluses (500ml) have been shown to improve cardiac output
  • Aggressive volume expansion should be avoided:
    • Potential to over distend the RV and lead to reduced systemic cardiac output
    • Not shown to be of benefit in studies and may be harmful
    • If signs of elevated CVP, further volume loading should be withheld
Vasopressors & Inotropes
  • Noradrenaline considered as first line therapy:
    • Increases RV inotropy and systemic blood pressure
    • Restores coronary perfusion gradient and improves ventricular interactions
  • Dobutamine may be considered useful for patients with PE, a low cardiac index and normal:
    • Potential to aggravate ventilation/perfusion mismatch
    • Can worsen circulatory failure given vasodilatory effect
Pulmonary Vasodilators
  • May be useful in in patients with PE and pulmonary hypertension, though anecdotal evidence only
  • Options include inhaled nitric oxide and aerosolised prostacyclin
Mechanical Circulatory Support
  • May be useful in the setting of circulatory collapse or cardiac arrest:
    • VA-ECMO most frequently used:
    • Associated with a high incidence of complications, even when used for short periods
    • Effectiveness depends upon centre experience and patient selection

Review:

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