Thrombolysis in Massive Pulmonary Embolism

See Also

Thrombolysis contraindications
Pulmonary Embolism
Pulmonary Embolism Management
Thrombolytic
Thrombolysis in Cerebrovascular Accident
Thrombolysis in ST Elevation Myocardial Infarction
t-PA (Alteplase)

Indications

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
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

Contraindications

See Thrombolytic Contraindication

Efficacy

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]
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
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)
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]
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]
References

Protocol

General
1. Original use was within 14 days of severe Pulmonary Embolism onset
2. Outcomes between agents are similar at 24 hours (however tPA is typically used)
  1. Meyer (1992) J Am Coll Cardiol 19:239-45 [PubMed]
Agents
1. T-PA (Alteplase) - preferred agent
  1. Restart Heparin when PTT less than twice normal
  2. Low Dose (for Submassive PE Category D and E1)
    1. Low dose Alteplase (tPA) 18-25 mg administered via peripheral IV over 6 hours
    2. Aykan (2023) Clin Exp Emerg Med 10(3): 280-6 +PMID: 37188358 [PubMed]
  3. Half Dose (for Massive PE Category E2, requiring Vasopressors, possible pulmonary vasodilators)
    1. Half dose Alteplase (tPA) with 10 mg IV bolus, then 40 mg IV over 30 minutes
    2. May continue to full dose infusion (additional 50 mg IV over 90 min) if worsening
  4. Full Dose (Peri-Arrest or Cardiac Arrest)
    1. Full dose Alteplase (tPA) with 10 mg IV bolus over 1-2 minutes, then 90 mg IV over 2 hours
    2. In Cardiac Arrest, a single Alteplase (tPA) 50 mg IV bolus may be given
      1. Continue CPR for at least 30 minutes (to allow for tPA circulation)
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
4. Tenectaplase (TNK-tPA)
  1. See Tenectaplase (massive PE uses same Tenectaplase dosing as for STEMI)
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

Complications

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

References