Thrombolytics for pulmonary embolism: Difference between revisions

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==Overview==
==Overview==
*For most hemodynamically stable patients, thrombolytic therapy is NOT indicated
*'''Major controversy exists regarding thrombolytic therapy in submassive PE.  Therapy should be individualized to patients.'''<ref>Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.</ref><ref>Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7</ref><ref>Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411</ref> ''''The mortality benefit may be greatest in patients with right ventricular dysfunction.''' <ref>Chatterjee. S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311(23):2414-21. PubMed ID: 24938564.</ref>  
*'''Major controversy exists regarding thrombolytic therapy in submassive PE.  Therapy should be individualized to patients.'''<ref>Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.</ref><ref>Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7</ref><ref>Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411</ref> ''''The mortality benefit may be greatest in patients with right ventricular dysfunction.''' <ref>Chatterjee. S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311(23):2414-21. PubMed ID: 24938564.</ref>  



Revision as of 00:45, 21 June 2019

Overview

  • For most hemodynamically stable patients, thrombolytic therapy is NOT indicated
  • Major controversy exists regarding thrombolytic therapy in submassive PE. Therapy should be individualized to patients.[1][2][3] 'The mortality benefit may be greatest in patients with right ventricular dysfunction. [4]
  • Bleeding risk is increased with increasing age especially in the group ≥ 65 yo[5]

Indications

  • Patients with massive PE and acceptable risk of bleeding complications
  • Patient with submassive PE with evidence adverse prognosis + low risk of bleeding complications
    • Hemodynamic instability
    • Worsening respiratory insufficiency
    • Severe Right Ventricular dysfunction
    • Major myocardial necrosis

Evaluation

  • Massive PE[6]
    • Acute with
      • Sustained hypotension (systolic blood pressure <90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction)
      • Pulselessness
      • Or, persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock)
  • Submassive PE[7]
    • Acute without systemic hypotension (see above) but with either RV dysfunction or myocardial necrosis
      • RV dysfunction means the presence of at least 1 of the following:
        • RV dilation (apical 4-chamber RV diameter divided by LV diameter >0.9) or RV systolic dysfunction on echocardiography
        • RV dilation (4-chamber RV diameter divided by LV diameter >0.9) on CT
        • Elevation of BNP (>90 pg/mL)
        • Elevation of N-terminal pro-BNP (>500 pg/mL); or
      • Electrocardiographic changes (new complete or incomplete right bundle-branch block, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion)
      • Myocardial necrosis is defined as either of the following:
        • Elevation of troponin I (>0.4 ng/mL) or
        • Elevation of troponin T (>0.1 ng/mL)

Contraindications

Absolute contraindications

  • Any prior intracranial hemorrhage
  • Known structural intracranial cerebrovascular disease (e.g. AVM)
  • Known malignant intracranial neoplasm
  • Ischemic stroke within last 3 months
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis
  • Recent surgery encroaching on the spinal canal or brain
  • Recent closed-head or facial trauma with radiographic evidence of bony fracture or brain injury

Relative contraindications

  • Age >75 years
  • Current use of anticoagulation
  • PE in Pregnancy
  • Noncompressible vascular punctures
  • Traumatic or prolonged CPR (>10min)
  • Recent internal bleeding (within 2 to 4 weeks)
  • History of chronic, severe, and poorly controlled hypertension
  • Severe uncontrolled hypertension on presentation (sys BP >180 or dia BP >110)
  • Dementia
  • Remote (>3 months) ischemic stroke
  • Major surgery within 3 weeks

Administration

Administration regimens differ widely in the literature, options not in any particular order, include:

  • Alteplase 0.6 - 1 mg/kg or 100 mg with any of the three possibilities
    • Two 50 mg boluses, 30 min apart[8][9]
    • 15 mg bolus, followed by 85 mg over 90 min[10]
    • 100 mg over 15 min[11]
  • Tenecteplase in at 50 mg bolus or 0.5 mg/kg bolus [12][13][14]

Related Instructions

  • Review contraindications (below)
  • After infusion complete measure serial aPTTs
    • Almost all studies of thrombolysis administration included heparin anticoagulation
    • Once value is <2x upper limit restart anticoagulation
  • Ongoing CPR from 2010 AHA Guidelines is not an absolute contraindication, and some studies suggest permiting 15 min of CPR to allow thrombolysis to work[15]
  • Discontinue heparin during infusion

Complications

See Also

Thrombolytics for pulmonary embolism

External Links

References

  1. Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.
  2. Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7
  3. Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411
  4. Chatterjee. S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311(23):2414-21. PubMed ID: 24938564.
  5. EBQ:Thrombolysis_in_Pulmonary_Embolism_Metanalysis#Outcomes
  6. Circulation 2011;123:1788
  7. Circulation 2011;123:1788
  8. Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529-1535.
  9. Ruiz-Bailén M, Aguayo-de-Hoyos E, Serrano-Córcoles M, et al. Thrombolysis with recombinant tissue plasminogen activator during cardiopulmonary resuscitation in fulminant pulmonary embolism. A case series. Resuscitation. 2001;51(1):97-101.
  10. Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529-1535.
  11. Abu-Laban R, Christenson J, Innes G, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med. 2002;346(20):1522-1528.
  12. Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313.
  13. Bozeman W, Kleiner D, Ferguson K. Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation. 2006;69(3):399-406.
  14. Böttiger B, Arntz H, Chamberlain D, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359(25):2651-2662.
  15. Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.