Overview
Massive Pulmonary Embolism
Quick Reference
Critical Alerts
- Hemodynamic instability defines massive PE: SBP <90 or drop ≥40 mmHg for >15 min
- Thrombolytics are indicated for massive PE: Despite bleeding risk
- RV dysfunction predicts mortality: Assess with bedside echo
- Anticoagulation should not be delayed: Start heparin immediately
- ECMO as a bridge: For refractory shock or peri-arrest
- PEA arrest with PE history: Consider thrombolytics during CPR
Key Diagnostics
| Test | Finding | Significance |
|---|---|---|
| CT Pulmonary Angiography | Filling defect in pulmonary arteries | Gold standard for diagnosis |
| Bedside Echo | RV dilation, McConnell's sign | Supports diagnosis; prognostic |
| Troponin | Elevated | RV strain; adverse prognosis |
| BNP/NT-proBNP | Elevated | RV dysfunction; adverse prognosis |
| D-dimer | Elevated | Sensitive but not specific |
| ECG | S1Q3T3, RV strain pattern | Classic but often absent |
Emergency Treatments
| Condition | Treatment | Dose |
|---|---|---|
| Anticoagulation | Heparin IV | 80 units/kg bolus, then 18 units/kg/hr |
| Thrombolysis (first-line) | Alteplase (tPA) | 100 mg IV over 2 hours |
| Accelerated lysis | Alteplase | 50 mg IV over 15 min (if hemodynamic collapse) |
| Shock support | Norepinephrine | Titrate to MAP >5 |
| Fluid-cautious | Small bolus 250-500 mL | Avoid RV overload |
Definition
Overview
Massive pulmonary embolism (also termed "high-risk PE") is a life-threatening condition in which a large clot burden in the pulmonary arteries causes acute right ventricular failure and hemodynamic collapse. It requires immediate diagnosis and treatment with anticoagulation and often systemic thrombolysis.
Classification (ESC/AHA)
| Category | Hemodynamics | RV Dysfunction | Biomarkers | Mortality |
|---|---|---|---|---|
| High-risk (Massive) | Unstable (SBP <90, shock, arrest) | Yes | Usually elevated | 30-50% |
| Intermediate-high (Submassive) | Stable | Yes | Elevated | 3-15% |
| Intermediate-low | Stable | Yes OR biomarker+ | One positive | ~3% |
| Low-risk | Stable | No | Normal | <1% |
Hemodynamic Instability Criteria:
- Cardiac arrest
- Obstructive shock requiring vasopressors
- Persistent SBP <90 mmHg OR drop ≥40 mmHg for >15 minutes
Epidemiology
- PE incidence: 600,000-900,000 per year in US
- Massive PE: 5-10% of all PE
- Mortality without treatment: 30-50% for massive PE
- Mortality with treatment: 15-30% (thrombolysis); 50%+ without reperfusion
- Third leading cause of cardiovascular death: After MI and stroke
Etiology
Risk Factors (Virchow's Triad):
| Category | Risk Factors |
|---|---|
| Stasis | Immobility, paralysis, long travel, hospitalization |
| Hypercoagulability | Cancer, pregnancy, thrombophilia, OCP/HRT |
| Endothelial injury | Surgery (especially ortho), trauma, catheter |
Major Risk Factors:
- Recent surgery (especially hip/knee, pelvic)
- Active malignancy
- Prior VTE
- Immobilization >3 days
- Pregnancy/Postpartum
- Trauma
Pathophysiology
Mechanism of Shock in Massive PE
- Clot occlusion: Large clot burden obstructs pulmonary arteries
- Increased RV afterload: Acute rise in pulmonary vascular resistance
- RV dilation: RV cannot overcome afterload
- Septal shift: RV pushes septum leftward (D-sign on echo)
- LV underfilling: Reduced preload to left ventricle
- Systemic hypotension: Low cardiac output
- RV ischemia: Elevated RV wall stress → ischemia
- Obstructive shock: Death if untreated
Right Ventricular Failure Cascade
- RV dilatation → tricuspid regurgitation → further RV volume overload
- Septal bowing impairs LV filling
- Coronary perfusion pressure falls (RV ischemia)
- Spiral to PEA arrest
Changes in Pulmonary Circulation
- Dead space increases (ventilation without perfusion)
- Hypoxemia from V/Q mismatch
- Catecholamine surge initially maintains BP before decompensation
Clinical Presentation
Symptoms
Classic Triad (Dyspnea + Pleuritic Chest Pain + Hemoptysis): Present in <20%
History
Key Questions:
Physical Examination
Vital Signs:
| Finding | Significance |
|---|---|
| Tachycardia | Very common (>00 in 50%) |
| Hypotension | Defines massive PE |
| Tachypnea | Common |
| Hypoxia | Variable; may have normal SpO2 initially |
| Fever | Low-grade possible |
Cardiovascular:
Pulmonary:
Leg Examination:
Dyspnea
Sudden onset (most common)
Chest pain
Often pleuritic
Syncope or presyncope
Suggests massive PE
Palpitations
Common presentation.
Hemoptysis
Less common
Anxiety
Common presentation.
Cough
Common presentation.
Red Flags
Life-Threatening Presentations
| Finding | Concern | Action |
|---|---|---|
| SBP <90 mmHg | Massive PE | Immediate thrombolysis considered |
| Cardiac arrest | PE as cause | tPA during CPR if suspected |
| Syncope | Large clot burden, RV failure | Rapid evaluation |
| Severe hypoxia | V/Q mismatch, cardiovascular collapse | High-flow O2, prepare for intubation |
| RV failure signs on echo | Intermediate-high or massive | Close monitoring, consider escalation |
| Refractory shock | ECMO or surgical embolectomy | Transfer to appropriate center |
Features Suggesting Massive PE
- Syncope as presenting symptom
- Profound hypoxia
- Shock or near-shock at presentation
- Pulseless electrical activity (PEA) cardiac arrest
Differential Diagnosis
Must-Consider Alternatives
| Diagnosis | Distinguishing Features | Evaluation |
|---|---|---|
| Acute coronary syndrome | ST changes, troponin, no hypoxia initially | ECG, troponin |
| Tension pneumothorax | Absent breath sounds, tracheal deviation | CXR, clinical |
| Cardiac tamponade | Distended neck veins, muffled sounds | Bedside echo |
| Aortic dissection | Tearing pain, BP differential, wide mediastinum | CT angiography |
| Septic shock | Fever, infection source, warm initially | Cultures, lactate |
| Cardiogenic shock (other causes) | Known CHF, acute MI | Echo, troponin |
Diagnostic Approach
Pre-Test Probability
Wells Score for PE:
| Criteria | Points |
|---|---|
| Clinical signs of DVT | 3 |
| PE is #1 diagnosis or equally likely | 3 |
| Heart rate >00 | 1.5 |
| Immobilization ≥3 days or surgery in past 4 weeks | 1.5 |
| Previous VTE | 1.5 |
| Hemoptysis | 1 |
| Active cancer | 1 |
| Score | Probability |
|---|---|
| ≤4 | PE unlikely |
| > | PE likely |
Note: In massive PE with shock, proceed directly to imaging or empiric treatment
Imaging
CT Pulmonary Angiography (CTPA):
- Gold standard
- Sensitivity 83-98%, Specificity 94-98%
- Shows filling defects in pulmonary arteries
- May show RV enlargement (RV:LV ratio >0.9)
- Issue: Patient must be stable enough for scanner
Bedside Echocardiography (Critical in Massive PE):
| Finding | Significance |
|---|---|
| RV dilation (RV:LV >:1) | RV failure |
| RV hypokinesis | RV strain |
| McConnell's sign | Apical sparing of RV (wall motion) |
| Septal flattening/bowing (D-sign) | RV pressure overload |
| Tricuspid regurgitation | Elevated RV pressures |
| Direct visualization of thrombus | Rare but diagnostic |
V/Q Scan: Alternative if CTPA contraindicated; less useful in ICU settings
Lower Extremity Doppler: If DVT found, supports diagnosis and anticoagulation
Laboratory Studies
| Test | Purpose | Findings |
|---|---|---|
| D-dimer | Rule out if low probability | Elevated but non-specific |
| Troponin | RV strain, prognosis | Elevated = higher risk |
| BNP/NT-proBNP | RV dysfunction | Elevated = higher risk |
| ABG | Hypoxemia, A-a gradient | May be normal initially |
| CBC, CMP | Baseline | Variable |
| Coagulation studies | Baseline, anticoagulation | Baseline |
| Type and screen | Blood availability | For procedures |
ECG Findings (Often Non-Specific)
- Sinus tachycardia (most common)
- S1Q3T3 (classic but <20%)
- Right axis deviation
- Right bundle branch block (new)
- T-wave inversions V1-V4 (RV strain)
- Atrial fibrillation (new)
Risk Stratification
PESI Score (Pulmonary Embolism Severity Index):
| Variable | Points |
|---|---|
| Age | +years |
| Male | +10 |
| Cancer | +30 |
| Heart failure | +10 |
| Chronic lung disease | +10 |
| HR ≥110 | +20 |
| SBP <100 | +30 |
| RR ≥30 | +20 |
| Temp <36°C | +20 |
| AMS | +60 |
| SpO2 <90% | +20 |
| Class | Points | 30-day Mortality |
|---|---|---|
| I | ≤65 | 0-1.6% |
| II | 66-85 | 1.7-3.5% |
| III | 86-105 | 3.2-7.1% |
| IV | 106-125 | 4-11.4% |
| V | >25 | 10-24.5% |
Simplified PESI (sPESI): 1 point each for age >80, cancer, chronic cardiopulmonary disease, HR ≥110, SBP <100, SpO2 <90%
- 0 points = low risk
- ≥1 point = higher risk
Treatment
Principles of Management
- Hemodynamic support: Careful fluids, vasopressors
- Anticoagulation immediately: Heparin
- Reperfusion for massive PE: Systemic thrombolysis first-line
- Respiratory support: Oxygen, careful intubation if needed
- Advanced therapies: Catheter-directed lysis, surgical embolectomy, ECMO
Hemodynamic Support
Fluids:
- Cautious fluids only: 250-500 mL bolus MAX
- RV is already volume-overloaded; excess fluid worsens septal bowing
- Avoid aggressive fluid resuscitation
Vasopressors:
| Agent | Dose | Notes |
|---|---|---|
| Norepinephrine | 0.1-0.3 mcg/kg/min | First-line |
| Dobutamine | 2-20 mcg/kg/min | If low cardiac output (consider after norepinephrine) |
| Epinephrine | 0.1-0.5 mcg/kg/min | If refractory |
Oxygen:
- High-flow nasal cannula or non-rebreather
- Target SpO2 ≥94%
Intubation Caution:
- Positive pressure ventilation can worsen RV failure
- If intubation necessary: Use ketamine or slow induction
- Prepare for post-intubation arrest
Anticoagulation (All Patients)
Initial Therapy:
| Agent | Dose |
|---|---|
| Unfractionated heparin | 80 units/kg bolus → 18 units/kg/hr infusion |
| Enoxaparin | 1 mg/kg SC every 12h (if stable) |
- UFH preferred in massive PE (short half-life, reversible)
- Do NOT delay anticoagulation while awaiting definitive imaging if high clinical suspicion
Systemic Thrombolysis (Massive PE)
Indication: Hemodynamically unstable massive PE without absolute contraindications
Regimens:
| Agent | Standard Dose | Accelerated (Cardiac Arrest) |
|---|---|---|
| Alteplase (tPA) | 100 mg IV over 2 hours | 50 mg IV bolus over 15 min |
| Tenecteplase | Weight-based bolus | Off-label for PE |
Monitoring:
- Hold heparin during tPA infusion (restart when PTT <80)
- Monitor for bleeding (especially intracerebral)
- Expected improvement in 30-60 minutes
Contraindications:
| Absolute | Relative |
|---|---|
| Prior intracranial hemorrhage | Recent surgery (10 days - 3 weeks) |
| Known structural cerebral lesion | Recent bleeding (2-4 weeks) |
| Ischemic stroke within 3 months | Traumatic CPR |
| Active bleeding | Pregnancy |
| Suspected aortic dissection | Uncontrolled HTN |
Advanced Therapies
Catheter-Directed Thrombolysis (CDT):
- Lower systemic dose
- May reduce bleeding risk
- Requires interventional radiology capability
- Consider if systemic lysis contraindicated or intermediate-high risk
Surgical Embolectomy:
- Cardiothoracic surgery with cardiopulmonary bypass
- For patients with contraindication to lysis
- Or failed medical therapy
ECMO (Extracorporeal Membrane Oxygenation):
- VA-ECMO for refractory cardiogenic shock
- Bridge to recovery or definitive therapy
- Transfer to ECMO center if not available
IVC Filter:
- Only if anticoagulation contraindicated
- Retrievable filter preferred
- Consider if recurrent PE despite anticoagulation
Cardiac Arrest and PE
PEA Arrest with Suspected PE:
- Consider empiric thrombolysis during CPR
- Alteplase 50 mg IV bolus (accelerated regimen)
- Continue CPR for 60-90 minutes after lysis
- Survival possible with aggressive management
Disposition
ICU Admission Criteria
- Massive PE (hemodynamically unstable)
- Post-thrombolysis monitoring
- Need for vasopressor support
- Respiratory failure
- Intermediate-high risk with close monitoring needs
Step-Down/Floor
- Intermediate-low risk PE
- Hemodynamically stable
- No significant hypoxia
Discharge (Rarely from ED for Massive)
- Does not apply to massive PE
- Low-risk PE may be considered for outpatient treatment
Transfer Considerations
- Transfer to higher level of care if:
- Interventional cardiology/radiology for catheter-directed therapy
- Cardiothoracic surgery capability
- ECMO capability
Follow-Up
| Timeframe | Purpose |
|---|---|
| Inpatient | Transition to oral anticoagulation |
| 1-2 weeks | Hematology/Pulmonology follow-up |
| 3-6 months | Duration of therapy assessment |
| Long-term | Thrombophilia workup if unprovoked, cancer screening |
Patient Education
Condition Explanation
- "You have a large blood clot in the arteries of your lungs. This is very serious because it's making it hard for your heart to pump blood."
- "We are giving you medicines to dissolve the clot and support your heart."
- "You will need blood thinners for several months to prevent new clots."
Long-Term Anticoagulation
- Importance of medication adherence
- Signs of bleeding to watch for
- Dietary considerations (if on warfarin)
- Medical alert identification
Prevention of Recurrence
- Mobilization after surgery
- Compression stockings during long travel
- Adequate hydration
- Discussion of VTE prophylaxis for future surgeries
Warning Signs
- Return of shortness of breath
- Leg swelling or pain
- Chest pain
- Lightheadedness or syncope
Special Populations
Pregnancy
- Pregnancy is a VTE risk factor
- LMWH is anticoagulation of choice
- Thrombolytics used in life-threatening situations (limited data)
- Multidisciplinary decision-making
Cancer Patients
- Higher risk of VTE and bleeding
- LMWH or DOACs preferred over warfarin
- Consider duration based on ongoing cancer
Elderly
- Higher bleeding risk with thrombolytics
- Higher mortality from massive PE
- May still benefit from lysis in true massive PE
- Careful risk-benefit discussion
Cardiac Arrest
- Empiric tPA if PE suspected
- Continue CPR for extended period post-lysis
- ECMO as bridge if available
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Develop in 2-4% after PE
- Screen for symptoms at follow-up
- Pulmonary endarterectomy may be treatment
Quality Metrics
Performance Indicators
| Metric | Target | Rationale |
|---|---|---|
| CTPA or definitive imaging within 1-2h | 100% (unstable) | Rapid diagnosis |
| Anticoagulation initiated in ED | 100% | Prevent clot extension |
| Thrombolysis for massive PE (no contraindications) | >0% | Evidence-based treatment |
| RV function documented (echo or CT) | 100% for unstable | Prognosis and treatment |
| ICU admission for massive PE | 100% | Close monitoring |
| 30-day mortality tracking | <30% (massive PE) | Outcome measure |
Documentation Requirements
- Hemodynamic status (BP, HR, shock)
- Risk stratification (PESI or sPESI)
- RV function assessment
- Thrombolysis decision and rationale
- Anticoagulation initiated
- Complications monitored
Key Clinical Pearls
Diagnostic Pearls
- Shock + hypoxia + clear lungs = think massive PE
- Bedside echo is invaluable: RV dilation highly suggestive
- S1Q3T3 is classic but insensitive: Don't rely on it
- D-dimer is NOT useful in high-probability shock: Go straight to imaging or empiric treatment
- CTPA is gold standard: But echo may be enough to start thrombolysis if too unstable
- DVT supports diagnosis: Positive leg ultrasound = treat as PE
Treatment Pearls
- Fluids can kill in massive PE: RV is already overloaded
- Anticoagulate immediately: Heparin while awaiting imaging
- Thrombolyse if unstable: Benefits outweigh risks
- Accelerated lysis for arrest: 50 mg tPA over 15 min
- Intubation is dangerous: Positive pressure worsens RV
- ECMO is a bridge: Transfer to capable center if refractory
Disposition Pearls
- Massive PE = ICU: No exceptions
- Intermediate-high = close monitoring: May escalate quickly
- Long-term anticoagulation: At least 3-6 months, possibly lifelong
- Screen for cancer if unprovoked: First episode warrants workup
- CTEPH screen at follow-up: Persistent dyspnea after PE
References
- Konstantinides SV, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2020;41(4):543-603.
- Jaff MR, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension. Circulation. 2011;123(16):1788-1830.
- PEITHO Investigators. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med. 2014;370(15):1402-1411.
- Kearon C, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352.
- Kucher N, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486.
- Vieillard-Baron A, et al. Echo-Doppler demonstration of acute cor pulmonale at the bedside in the medical intensive care unit. Am J Respir Crit Care Med. 2002;166(10):1310-1319.
- Truhlář A, et al. European Resuscitation Council Guidelines 2021: Cardiac arrest in special circumstances. Resuscitation. 2021;161:152-219.
- UpToDate. Treatment, prognosis, and follow-up of acute pulmonary embolism in adults. 2024.