Thrombolysis in Massive Pulmonary Embolism

Aka: Thrombolysis in Massive Pulmonary Embolism, Pulmonary Embolism Thrombolysis, PE Thrombolysis

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II. Indications

  1. Massive Pulmonary Embolism (absolute indications)
    1. Hypotension
      1. Systolic Blood Pressure <90 mmHg or
      2. Systolic Blood Pressure drops >40 mmHg from baseline for at least 15 minutes
    2. Systemic hypoperfusion
    3. Cardiac Arrest with dilated right ventricle on Bedside Ultrasound (suggestive of PE)
      1. Thrombolytics are not indicated in undifferentiated Cardiac Arrest
  2. Submassive Pulmonary Embolism with significant cardiopulmonary findings (relative indications, treatment is controversial)
    1. Evidence does not support as of 2017 (see below)
    2. Right ventricular dysfunction (RV Strain)
      1. Serum Troponin elevation or
      2. ntBNP >900 pg/ml or (BNP >90 pg/ml) or
      3. Echocardiogram with right ventricular dilation or hypokinesis
    3. Right Ventricle diameter to Left Ventricle Diameter Ratio (axial views) >1.5
      1. Associated with increased risk of ICU admission and death in hemodynamically stable patients
      2. Ghaye (2006) RadioGraphics 26:23-39 [PubMed]
    4. Pulmonary Hypertension
    5. Extensive Deep Vein Thrombosis
    6. Prevent recurrent Pulmonary Embolism
    7. Markers of significant cardiopulmonary strain (may risk stratify sub-massive PE to Thrombolysis)
      1. Shock Index >1
      2. Non-sustained Hypotension
      3. Significant Tachycardia
      4. Significant Tachypnea
      5. Increased serum Lactic Acid
      6. Hypoxia despite nasal cannula Supplemental Oxygen

III. Contraindications

  1. See Thrombolytic Contraindication

IV. Efficacy

  1. Local or directed Thrombolysis has had mixed efficacy in massive Pulmonary Embolism
    1. Early studies demonstrated no benefit over intravenous Thrombolysis
    2. However, as of 2015, catheter placement within the PE appears effective
      1. Piazza (2015) JACC Cardiovasc Interv 8(10): 1382-92 +PMID: 26315743 [PubMed]
      2. Kuo (2015) Chest 148(3):667-73 [PubMed]
  2. Only significant benefit for Thrombolysis may be in massive Pulmonary Embolism
    1. Thrombolysis offers faster clot lysis than Heparin
    2. Short-term better pulmonary artery perfusion
    3. Benefit is in first 24-48 hours
  3. Thrombolysis longterm outcomes are similar to Heparin in non-massive PE (intermediate risk PE)
    1. No difference in mortality
    2. No difference in Pulmonary Embolism resolution
    3. No difference in recurrent PE
    4. Dyspnea at 3 year follow-up is similar for those treated with Thrombolysis and those not treated
      1. Konstantinides (2017) J Am Coll Cardiol 69(12): 1536-44 +PMID:28335835 [PubMed]
    5. Exception: Right ventricular dysfunction may be less with Thrombolysis (see below)
  4. Quality of life may be improved with Thrombolysis for non-massive PE (intermediate risk PE)
    1. Right ventricular dysfunction and functional outcome may be improved with Thrombolysis (esp. younger patients)
    2. Lower risk of Pulmonary Embolism recurrence (less residual nidus)
    3. Weigh quality of life following submassive PE versus the bleeding risk (see below)
    4. Orman and Kline in Herbert (2015) EMRap 15(9):14-17
    5. Kline (2014) J Thromb Haemost 12(4):459-68 +PMID:24484241 [PubMed]
  5. Adverse effects of bleeding are substantial and likely to outweigh the benefits in intermediate risk PE
    1. Studies of patients with RV dysfunction but hemodynamically stable
    2. Number Needed to Treat (NNT) was 59 to prevent one death and 53 to prevent recurrence
    3. Number needed to harm (NNH) for major bleeding was 18 (NNH was 11 if over age 65)
    4. Number needed to harm (NNH) for Intracranial Hemorrhage was 78
    5. Chatterjee (2014) JAMA 311(23): 2414-21 [PubMed]
  6. References
    1. (1974) JAMA 229:1606-13 [PubMed]
    2. Levine (1990) Chest 98:1473-9 [PubMed]
    3. Dalla-Volta (1992) J Am Coll Cardiol 20:520-6 [PubMed]

V. Protocol

  1. General
    1. Indicated within 14 days of severe Pulmonary Embolism onset
    2. Outcomes between agents are similar at 24 hours (however tPA is typically used)
    3. Meyer (1992) J Am Coll Cardiol 19:239-45 [PubMed]
  2. Agents
    1. T-PA (Alteplase) - preferred agent
      1. Pulse present (standard protocol)
        1. First: 10 mg IV bolus over 1-2 minutes, then
        2. Next: 90 mg IV over 2 hours
      2. Pulse present (low dose protocol)
        1. Consider in sub-massive PE with positive marker of significant cardiopulmonary strain)
        2. Alteplase 50 mg IVover 2 hours OR
        3. Alteplase 25 mg IV over 6 hours (experimental low dose protocol)
          1. Aykan (2023) Clin Exp Emerg Med 10(3): 280-6 +PMID: 37188358 [PubMed]
      3. Pulse absent
        1. tPA 50 mg IV bolus and continue CPR for at least 30 minutes (to allow for tPA circulation)
      4. Restart Heparin when PTT less than twice normal
    2. Streptokinase
      1. Load: 250,000 units over 30 minutes
      2. Maintenance: 100,000 units per hour for 24 hours
    3. Urokinase
      1. Load: 4400 units/kg over 10 minutes
      2. Maintenance: 4400 units/kg per hour for 12-24 hours
  3. Monitoring
    1. Obtain PTT after Thrombolytic infusion and q4 hours
    2. Most protocols stop Heparin while TPA is infusing (lowering major bleeding risk)
    3. Restart Heparin when PTT falls below 2x to 2.5x normal (typically <80 seconds)
      1. Fibrinogen levels may also direct timing of Heparin restart
      2. Maintain PTT 1.5 to 2.5 times normal
      3. Standard Unfractionated Heparin is typically used (over LMWH) to allow for rapid stopping in case of bleeding

VI. Complications

  1. See Complications in Thrombolysis
  2. Major Bleeding: 9.24% of cases (compared with 3.42% of cases with Anticoagulation alone)
  3. Intracranial Hemorrhage: 1.45% of cases (compared with 0.19% of cases with Anticoagulation alone)
  4. Chatterjee (2014) JAMA 311(23): 2414-21 [PubMed]

VII. References

  1. (2000) Eur Heart J 21(16): 1301-36 [PubMed]
  2. Almoosa (2002) Am Fam Physician 65(6):1097-1102 [PubMed]
  3. Condliffe (2014) Thorax 69(2): 174-80 [PubMed]
  4. Jaff (2011) Circulation 123: 1788-830 [PubMed]

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