Pulmonary embolism: Difference between revisions

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***80 units/kg bolus; then 18 units/kg/hr
***80 units/kg bolus; then 18 units/kg/hr
****Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
****Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
**Direct thrombin inhibitors
***[[Dabigatran]]
****Approved by the FDA in 2014 for the treatment of DVT and PE
****Dabigatran was noninferior to warfarin in reducing DVT and PE<ref>Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361(24):2342-52. </ref><ref>Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014; 129(7):764-72.</ref>
**Factor Xa inhibitors
***[[Rivaroxaban]]
****Approved by the FDA in November 2012 for the treatment of DVT or PE
****Associated with less bleeding, particularly in elderly patients and those with moderate renal impairment compared to standard treatments<ref>Hughes S. Rivaroxaban Stands up to standard anticoagulation for VTE treatment. Medscape Medical News. December 13, 2012.</ref><ref>Buller HR, on behalf of the EINSTEIN Investigators. Oral rivaroxaban for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN DVT and EINSTEIN PE studies [abstract 20]. Presented at: 54th Annual Meeting and Exposition of the American Society of Hematology; December 8, 2012; Atlanta, Ga.</ref>
***[[Apixaban]]
****Approved for treatment of PE in August 2014
****Studies show 16% reduction in VTE related death compared to standard therapy<ref>Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013; 369(9):799-808.</ref><ref>Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013; 368(8):699-708.</ref>


===Thrombolysis===
===Thrombolysis===

Revision as of 11:23, 6 September 2015

See Pulmonary Embolism in Pregnancy for pregnancy specific information.[1]

Background

Clinical Spectrum of Venous thromboembolism

Only 40% of ambulatory ED patients with PE have concomitant DVT[2][3]

Types

Pulmonary Embolism Categorization[4]

Massive: High-risk

Hemodynamically unstable with symptoms of shock

  • ACCP 2016 CHEST Guidelines: Sustained hypotension ONLY criteria (systolic BP <90 for at least 15min or requiring inotropic support)
  • Previous definitions (e.g. AHA 2011) include cardiac arrest/pulselessness or persistent profound bradycardia (HR <40 with signs of shock)

Submassive: Intermediate-risk

Right ventricular dysfunction (RVD) and/or myocardial necrosis in the absence of persistent hypotension or shock (SBP >90)[5]

  • RV dysfunction
    • RV dilation or dysfunction on TTE
      • "D Sign" on bedside echo (LV takes on a "D" shape due to RV dilation)
    • RV dysfunction on CT defined as RV/LV ratio >0.9[6]
    • Elevation of BNP (>90)
    • ECG findings of right heart strain (see diagnosis below)
  • Myocardial necrosis: Troponin I >0.4

Non-Massive: Low-risk

No hemodynamic compromise and no RV strain

Sub-Segmental

  • Limited to the subsegmental pulmonary arteries

Symptoms

According to the PIOPED II study, these are the most common presenting signs[7]

Signs

  • Tachypnea (54%)
  • Calf or thigh swelling, erythema, edema, tenderness, palpable cord (47%)
  • Tachycardia (24%)
  • Rales (18%)
  • Decreased breath sounds (17%)
  • Accentuated pulmonic component of the second heart sound (15%)
  • JVD (14%)
  • Fever (3%)

Differential Diagnosis

Chest pain

Critical

Emergent

Nonemergent

Acute dyspnea

Emergent

Non-Emergent

Diagnostic Evaluation

Wells Criteria

  • Symptoms of DVT - 3pts
  • No alternative diagnosis better explains the illness - 3pts
  • HR > 100 - 1.5 pts
  • Immobilization within prior 4wks - 1.5pts
  • Prior history of DVT or PE - 1.5pts
  • Active malignancy - 1pt
  • Hemoptysis - 1pt

Wells Score

  • 0-1 point: Low probability (3.4%)
  • 2-6 points: Moderate probability (27.8%)
  • 7-12 points: High probability (78.4%)

Workup by Probability

Low Probability

  • Avoid CT pulmonary angiography in low probability pts that are either PERC rule negative or have a negative d-dimer
  • If low prob and PERC Rule negative, then no workup
  • If low prob and PERC Rule positive, then d-dimer
  • Age-adjusted D-Dimer in patients <50 yrs old (Age x 10) has increased specificity without changing sensitivity[8][9]

Moderate Probability

  • D-dimer
    • However, it is unclear whether d-dimer alone is sufficient to rule-out PE[10]

High Probability

  • Consider anticoagulation before imaging!
  • CTA if GFR >60
  • V/Q if GFR <60

Bedside Ultrasound

  • Ultrasound can help diagnosis in equivocal cases
  • Assess for right ventricular strain (RVS) and McConnell's sign
  • RVS is associated with statistically significant worse outcome[11]

Treatment

Supportive care

  • Give IVF to increase preload

Anticoagulation

  • Indicated for all patients with confirmed PE or high clinical suspicion (don't wait for imaging)
  • Treatment options:
    • LMWH SC
      • 1st line for most hemodynamically stable pts
      • contraindicated in renal failure
      • Enoxaparin 1 mg/kg SC q12h
      • Dalteparin 200 IU/kg SC q24h, max 18,000 IU
    • Unfractionated Heparin
      • Consider in pts w/:
        • Persistent hypotension
        • Increased risk of bleeding
        • Recent sx/trauma
        • Renal failure (GFR <30)
        • Morbid obesity or anasarca (poor sc absorption)
        • Thrombolysis is being considered
      • 80 units/kg bolus; then 18 units/kg/hr
        • Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
    • Direct thrombin inhibitors
      • Dabigatran
        • Approved by the FDA in 2014 for the treatment of DVT and PE
        • Dabigatran was noninferior to warfarin in reducing DVT and PE[12][13]
    • Factor Xa inhibitors
      • Rivaroxaban
        • Approved by the FDA in November 2012 for the treatment of DVT or PE
        • Associated with less bleeding, particularly in elderly patients and those with moderate renal impairment compared to standard treatments[14][15]
      • Apixaban
        • Approved for treatment of PE in August 2014
        • Studies show 16% reduction in VTE related death compared to standard therapy[16][17]

Thrombolysis

  • Major controversy exists regarding thrombolytic therapy in submassive PE. Therapy should be individualized to patients.[18][19][20] 'The mortality benefit may be greatest in patients with right ventricular dysfunction. [21]
  • Bleeding risk is increased with increasing age especially in the group ≥ 65 yo[22]

Indications

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

Thrombolytic Instructions

  • Review contraindications
  • Discontinue heparin during infusion
  • tPA 100mg over 2hr OR 0.6 mg/kg over 2min
  • After infusion complete measure PTT
    • Once value is <2x upper limit restart anticoagulation

Absolute contraindications

  • Any prior intracranial hemorrhage,
  • Known structural intracranial cerebrovascular disease (e.g. AVM)
  • Known malignant intracranial neoplasm
  • Ischemic stroke within 3mo
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis
  • Recent surgery encroaching on the spinal canal or brain
  • Recent closed-head or facial trauma w/ radiographic evidence of bony fx 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 HTN on presentation (sys BP >180 or dia BP >110)
  • Dementia
  • Remote (>3 months) ischemic stroke
  • Major surgery within 3 weeks

IVC Filter

  • Indications
    • anticoagulation contraindicated in pt with PE
    • failure to attain adequate anticoagulation during treatment

See Also

Thrombolytics for pulmonary embolism

Disposition

  • Patients with significant clot burden generally require admission for anticoagulation
  • Consider discharge in low risk patients with peripheral PE[23]

External Links

References

  1. ↑ D-Dimer Concentrations in Normal Pregnancy: New Diagnostic Thresholds Are Needed. Kline et all. Clinical Chemistry May 2005 vol. 51 no. 5 825-829 http://www.clinchem.org/content/51/5/825.long
  2. ↑ Righini M, Le GG, Aujesky D, et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet. 2008; 371(9621):1343-1352.
  3. ↑ Daniel KR, Jackson RE, Kline JA. Utility of the lower extremity venous ultrasound in the diagnosis and exclusion of pulmonary embolism in outpatients. Ann Emerg Med. 2000; 35(6):547-554.
  4. ↑ Jaff MR et al. Management of massive and submassive pulmonary embolism, ileofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21
  5. ↑ Martin C et al. Systemic thrombolysis for pulmonary embolism: a review. P T. 2016 Dec; 41(12):770-775
  6. ↑ Becattini C et al. Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test. Eur Heart J. 2011 Jul;32(13):1657-63. doi: 10.1093/eurheartj/ehr108. Epub 2011 Apr 18.
  7. ↑ Stein PD et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med. 2007;120(10):871.
  8. ↑ Schouten, HJ, et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BJM. 2013; 346:f2492.
  9. ↑ Adams, D, et al. Clinical utility of an age-adjusted D-dimer in the diagnosis of venous thromboembolism. Ann Emerg Med. 2014; 64:232-234.
  10. ↑ ACEP Clinical Policy. http://www.acep.org/Content.aspx?id=80787
  11. ↑ Taylor, RA, et al. Point-of-care focused cardiac ultrasound for prediction of pulmonary embolism adverse outcomes. The Journal of Emergency Medicine. 2013; 45(3):392–399.
  12. ↑ Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361(24):2342-52.
  13. ↑ Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014; 129(7):764-72.
  14. ↑ Hughes S. Rivaroxaban Stands up to standard anticoagulation for VTE treatment. Medscape Medical News. December 13, 2012.
  15. ↑ Buller HR, on behalf of the EINSTEIN Investigators. Oral rivaroxaban for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN DVT and EINSTEIN PE studies [abstract 20]. Presented at: 54th Annual Meeting and Exposition of the American Society of Hematology; December 8, 2012; Atlanta, Ga.
  16. ↑ Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013; 369(9):799-808.
  17. ↑ Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013; 368(8):699-708.
  18. ↑ Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.
  19. ↑ Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7
  20. ↑ Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411
  21. ↑ 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.
  22. ↑ Thrombolysis_in_Pulmonary_Embolism_Metanalysis*Outcomes
  23. ↑ Vinson DR, Zehtabchi S, Yealy DM. Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med. 2012; 60:651-662.
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