Thrombolytics for pulmonary embolism

Overview

For most hemodynamically stable patients, thrombolytic therapy is NOT indicated
Major controversy exists regarding thrombolytic therapy in submassive PE. ^[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]

There is no evidence suggesting administering thrombolytics within a certain window of time improves outcomes ^[6]

There is no evidence suggesting administering thrombolytics empirically during cardiac arrest improves outcomes
- In patients with PEA secondary to confirmed PE, administration of thrombolytics may be indicated^[7]

Indications

Patients with massive PE (i.e. persistent hypotension SBP <90 for ≥15 mins or requiring inotropic support) and acceptable risk of bleeding complications^[8]
Can be considered in initially hemodynamically stable patients (i.e. submassive PE) who acutely decompensate despite anticoagulation
- develop persistent hypotension (massive PE)
- increasing heart rate
- JVD or worsening right heart failure
- worsening gas exchange
- signs of shock

Evaluation

See Pulmonary Embolism (PE)
Massive PE^[9]
- 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^[10]
- 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^[11]^[12]
- 15 mg bolus, followed by 85 mg over 90 min^[13]
- 100 mg over 15 min^[14]
Tenecteplase in at 50 mg bolus or 0.5 mg/kg bolus ^[15]^[16]^[17]

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^[18]
Discontinue heparin during infusion

Complications

External Links

http://emcrit.org/emcrit/aha-pulmonary-embolism-guidelines-2011/

References

↑ Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.
↑ Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7
↑ Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411
↑ 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.
↑ EBQ:Thrombolysis_in_Pulmonary_Embolism_Metanalysis#Outcomes
↑ Daniels L et al. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol. 1997 Jul 15;80(2):184-8
↑ 15. Sharifi M et al. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the “PEAPETT” study). Am J Emerg Med. 2016 Oct;34(10):1963-1967. doi: 10.1016/j.ajem.2016.06.094
↑ ACCP 9th Edition of the Antithrombotic Therapy Guidelines: Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2012;141:e419s – e494s. doi: 10.1378/chest.11-2301.
↑ Circulation 2011;123:1788
↑ Circulation 2011;123:1788
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313.
↑ 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.
↑ 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.
↑ Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.

Authors:

[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] Daniels L et al. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol. 1997 Jul 15;80(2):184-8

[7] 15. Sharifi M et al. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the “PEAPETT” study). Am J Emerg Med. 2016 Oct;34(10):1963-1967. doi: 10.1016/j.ajem.2016.06.094

[8] ACCP 9th Edition of the Antithrombotic Therapy Guidelines: Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2012;141:e419s – e494s. doi: 10.1378/chest.11-2301.

[9] Circulation 2011;123:1788

[10] Circulation 2011;123:1788

[11] 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.

[12] 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.

[13] 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.

[14] 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.

[15] Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313.

[16] 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.

[17] 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.

[18] Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.

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Thrombolytics for pulmonary embolism

Contents

Overview

Indications

Evaluation

Contraindications

Absolute contraindications

Relative contraindications

Administration

Related Instructions

Complications

See Also

Thrombolytics for pulmonary embolism

External Links

References