Thrombolytics for pulmonary embolism: Difference between revisions
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==Indications== | ==Indications== | ||
*Patients with [[Pulmonary_embolism#Massive:_High-risk|massive PE]] (i.e. persistent hypotension SBP <90 for ≥15 mins or requiring inotropic support) and acceptable risk of bleeding complications<ref>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.</ref> | *Patients with [[Pulmonary_embolism#Massive:_High-risk|massive PE]] (i.e. persistent [[hypotension]] SBP <90 for ≥15 mins or requiring inotropic support) and acceptable risk of bleeding complications<ref>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.</ref> | ||
*Can be considered in initially hemodynamically stable patients (i.e. submassive PE) who acutely decompensate despite anticoagulation | *Can be considered in initially hemodynamically stable patients (i.e. submassive PE) who acutely decompensate despite anticoagulation | ||
**develop persistent hypotension (massive PE) | **develop persistent [[hypotension]] (massive PE) | ||
**increasing heart rate | **increasing [[tachycardia|heart rate]] | ||
**JVD or worsening right heart failure | **JVD or worsening right [[heart failure]] | ||
**worsening gas exchange | **worsening gas exchange | ||
**signs of shock | **signs of [[shock]] | ||
===Evaluation=== | ===Evaluation=== | ||
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*'''Massive PE'''<ref>Circulation 2011;123:1788</ref> | *'''Massive PE'''<ref>Circulation 2011;123:1788</ref> | ||
**Acute with | **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) | ***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) - ACCP 2016 | ||
*** | ***Other definitions include pulselessness or persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock) | ||
*'''Submassive PE'''<ref>Circulation 2011;123:1788</ref> | *'''Submassive PE'''<ref>Circulation 2011;123:1788</ref> | ||
**Acute without systemic hypotension (see above) but with either RV dysfunction or myocardial necrosis | **Acute without systemic hypotension (see above) but with either RV dysfunction or myocardial necrosis | ||
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****Elevation of BNP (>90 pg/mL) | ****Elevation of BNP (>90 pg/mL) | ||
****Elevation of N-terminal pro-BNP (>500 pg/mL); or | ****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) | ***[[EKG|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: | ***Myocardial necrosis is defined as either of the following: | ||
****Elevation of troponin I (>0.4 ng/mL) or | ****Elevation of troponin I (>0.4 ng/mL) or | ||
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===Absolute contraindications=== | ===Absolute contraindications=== | ||
*Any prior [[intracranial hemorrhage]] | *Any prior [[intracranial hemorrhage]] | ||
*Known structural intracranial cerebrovascular disease (e.g. AVM) | *Known structural intracranial cerebrovascular disease (e.g. [[AVM]]) | ||
*Known malignant intracranial neoplasm | *Known malignant [[brain tumor|intracranial neoplasm]] | ||
*Ischemic stroke within last 3 months | *[[Ischemic stroke]] within last 3 months | ||
*Suspected aortic dissection | *Suspected [[aortic dissection]] | ||
*Active bleeding or bleeding diathesis | *Active [[hemorrhage|bleeding]] or [[coagulopathy|bleeding diathesis]] | ||
*Recent surgery encroaching on the spinal canal or brain | *Recent surgery encroaching on the spinal canal or brain | ||
*Recent closed-head or [[facial trauma]] with radiographic evidence of bony fracture or brain injury | *Recent closed-[[head trauma|head]] or [[facial trauma]] with radiographic evidence of bony [[facial fracture|fracture]] or brain injury | ||
===Relative contraindications=== | ===Relative contraindications=== | ||
*Age >75 years | *Age >75 years | ||
*Current use of anticoagulation | *Current use of [[anticoagulation]] | ||
*[[PE in Pregnancy]] | *[[PE in Pregnancy]] | ||
*Noncompressible vascular punctures | *Noncompressible vascular punctures | ||
*Traumatic or prolonged [[CPR]] (>10min) | *Traumatic or prolonged [[CPR]] (>10min) | ||
*Recent internal bleeding (within 2 to 4 weeks) | *Recent internal bleeding (within 2 to 4 weeks) | ||
*History of chronic, severe, and poorly controlled hypertension | *History of chronic, severe, and poorly controlled [[hypertension]] | ||
*Severe uncontrolled hypertension on presentation (sys BP >180 or dia BP >110) | *Severe uncontrolled [[hypertension]] on presentation (sys BP >180 or dia BP >110) | ||
*Dementia | *[[Dementia]] | ||
*Remote (>3 months) ischemic stroke | *Remote (>3 months) [[ischemic stroke]] | ||
*Major surgery within 3 weeks | *Major surgery within 3 weeks | ||
==Administration== | ==Administration== | ||
*Standard dose: [[Alteplase]] 100mg over 2 hours <ref>Martin C et al. Systemic thrombolysis for pulmonary embolism: a review. P T. 2016 Dec; 41(12):770-775.</ref><ref>Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11026</ref> | |||
*Alternative dose: [[Alteplase]] 50mg over 2 hours | |||
**Half-dose regimen can be considered in patients >65yo, higher bleeding risk, or submassive PE (see [[EBQ:MOPETT_Trial| MOPETT trial]]) | |||
** | *Systemic therapy is recommended over catheter-directed therapy | ||
* | *Cardiac arrest dose:<ref>Scott Weingart. EMCrit 261 – Thrombolysis during Cardiac Arrest. EMCrit Blog. Published on December 12, 2019. Accessed on December 13th 2019. Available at https://emcrit.org/emcrit/thrombolysis-cardiac-arrest/ </ref> | ||
*[[Tenecteplase]] | **[[Tenecteplase]] (not FDA approved for PE) - 50 mg bolus or 0.5 mg/kg bolus has been used for PEA arrest | ||
<ref>Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313.</ref><ref>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.</ref><ref>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.</ref>'''OR''' | |||
**[[Alteplase]] - 50 mg of by IV Push over ~60 seconds | |||
**Continue CPR for 30-60 minutes after lytic administration. | |||
===Related Instructions=== | ===Related Instructions=== | ||
*Review contraindications ( | *Review [[Thrombolytics_for_pulmonary_embolism#Contraindications| contraindications]] | ||
* | *Several trials continued unfractionated heparin (UFH) to target aPTT 1.5-2.5x baseline during thrombolytic administration so this would be standard <ref>Konstantinides S et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50.</ref><ref>Meyer G et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.</ref> | ||
** | **However, discontinuing anticoagulation can be considered while administering thrombolytics | ||
*Always obtain serial aPTT every 4 hours after completion of thrombolytic | |||
*Ongoing CPR from 2010 AHA Guidelines is not an absolute contraindication, and some studies suggest | **If heparin was discontinued during thrombolysis, resume heparin without a loading dose when aPTT <2x upper limit of normal | ||
*Ongoing CPR from 2010 AHA Guidelines is not an absolute contraindication, and some studies suggest permitting 15 min of CPR to allow thrombolysis to work<ref>Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.</ref> | |||
==Complications== | ==Complications== | ||
*Major bleeding<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 Jun 18;311(23):2414-21. doi: 10.1001/jama.2014.5990.</ref> | |||
**Major bleeding OR 2.73 (9.24% vs 3.42%) compared to anticoagulant alone | |||
**[[Intracranial hemorrhage]] OR 4.63 (1.46% vs 0.19%) | |||
**'''There was no statistically significant increase in major bleeding risk in patients 65yo or younger''' | |||
*No standard or evidence-based reversal regimen exists but general guidelines include: <ref> Yaghi S, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplace in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the AHA/ASA. Stroke. 2017;48:e343–e361</ref> | |||
**Supportive care (e.g. [[transfusion]]) | |||
**[[Cryoprecipitate]] (contains fibrinogen) 10 units or more to achieve fibrinogen level >150 mg/dL | |||
**[[TXA]] or aminocaproic acid are antifibrinolytics, but limited data | |||
**[[PCC]] or [[FFP]] can be considered, but generally as adjuncts to cryoprecipitate | |||
**Consider [[vitamin K]] | |||
**[[Platelets]] controversial (theoretical benefit, but a small study showed worsening ICH with platelets) | |||
**Consider neurosurgical intervention if large ICH is found on CT | |||
==See Also== | ==See Also== | ||
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==External Links== | ==External Links== | ||
*Example of decision making guide factoring in size of PE and lytics contraindications: https://emcrit.org/ibcc/pe/#algorithm | |||
*http://emcrit.org/emcrit/aha-pulmonary-embolism-guidelines-2011/ | *http://emcrit.org/emcrit/aha-pulmonary-embolism-guidelines-2011/ | ||
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[[Category:Procedures]] | [[Category:Procedures]] | ||
[[Category:Pharmacology]] | [[Category:Pharmacology]] | ||
[[Category:Critical Care]] |
Revision as of 22:41, 3 November 2020
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) - ACCP 2016
- Other definitions include pulselessness or persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock)
- Acute with
- 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)
- RV dysfunction means the presence of at least 1 of the following:
- Acute without systemic hypotension (see above) but with either RV dysfunction or myocardial necrosis
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
- Standard dose: Alteplase 100mg over 2 hours [11][12]
- Alternative dose: Alteplase 50mg over 2 hours
- Half-dose regimen can be considered in patients >65yo, higher bleeding risk, or submassive PE (see MOPETT trial)
- Systemic therapy is recommended over catheter-directed therapy
- Cardiac arrest dose:[13]
- Tenecteplase (not FDA approved for PE) - 50 mg bolus or 0.5 mg/kg bolus has been used for PEA arrest
- Alteplase - 50 mg of by IV Push over ~60 seconds
- Continue CPR for 30-60 minutes after lytic administration.
Related Instructions
- Review contraindications
- Several trials continued unfractionated heparin (UFH) to target aPTT 1.5-2.5x baseline during thrombolytic administration so this would be standard [17][18]
- However, discontinuing anticoagulation can be considered while administering thrombolytics
- Always obtain serial aPTT every 4 hours after completion of thrombolytic
- If heparin was discontinued during thrombolysis, resume heparin without a loading dose when aPTT <2x upper limit of normal
- Ongoing CPR from 2010 AHA Guidelines is not an absolute contraindication, and some studies suggest permitting 15 min of CPR to allow thrombolysis to work[19]
Complications
- Major bleeding[20]
- Major bleeding OR 2.73 (9.24% vs 3.42%) compared to anticoagulant alone
- Intracranial hemorrhage OR 4.63 (1.46% vs 0.19%)
- There was no statistically significant increase in major bleeding risk in patients 65yo or younger
- No standard or evidence-based reversal regimen exists but general guidelines include: [21]
- Supportive care (e.g. transfusion)
- Cryoprecipitate (contains fibrinogen) 10 units or more to achieve fibrinogen level >150 mg/dL
- TXA or aminocaproic acid are antifibrinolytics, but limited data
- PCC or FFP can be considered, but generally as adjuncts to cryoprecipitate
- Consider vitamin K
- Platelets controversial (theoretical benefit, but a small study showed worsening ICH with platelets)
- Consider neurosurgical intervention if large ICH is found on CT
See Also
- Thrombolytics
- Pulmonary embolism (main)
Thrombolytics for pulmonary embolism
- Clinical Page
- Research summary page: EBQ:Thrombolysis in Pulmonary Embolism Metanalysis
External Links
- Example of decision making guide factoring in size of PE and lytics contraindications: https://emcrit.org/ibcc/pe/#algorithm
- 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
- ↑ Martin C et al. Systemic thrombolysis for pulmonary embolism: a review. P T. 2016 Dec; 41(12):770-775.
- ↑ Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11026
- ↑ Scott Weingart. EMCrit 261 – Thrombolysis during Cardiac Arrest. EMCrit Blog. Published on December 12, 2019. Accessed on December 13th 2019. Available at https://emcrit.org/emcrit/thrombolysis-cardiac-arrest/
- ↑ 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.
- ↑ Konstantinides S et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50.
- ↑ Meyer G et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
- ↑ Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.
- ↑ Chatterjee S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. doi: 10.1001/jama.2014.5990.
- ↑ Yaghi S, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplace in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the AHA/ASA. Stroke. 2017;48:e343–e361