Pulmonary embolism

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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]

PE Types

Massive

  • Cardiac arrest
  • Sustained hypotension (sys BP <90 for at least 15min or requiring inotropic support)
  • Persistent profound bradycardia (HR <40 with signs of shock)

Submassive

  • Sys BP >90 but with either RV dysfunction or myocardial necrosis
  • RV dysfunction
    • RV dilation or dysfunction on TTE
      • "D Sign" on bedside echo (LV takes on a "D" shape due to RV dilation)
    • RV dilation on CT
    • Elevation of BNP (>90)
    • ECG: new complete or incomplete RBBB, anteroseptal ST elevation/depression or TWI[4]
    • Myocardial necrosis: Troponin I >0.4

Non-Massive

  • No hemodynamic compromise and no RV strain

Sub-Segmental

  • Limited to the subsegmental pulmonary arteries

Clinical Features

Symptoms

According to the PIOPED II study, these are the most common presenting signs[5]

  • Dyspnea at rest or with exertion (73%)
  • Pleuritic chest pain (44%)
  • Cough (37%)
  • Orthopnea (28%)
  • Calf or thigh pain and/or swelling (44%)
  • Wheezing (21%)
  • Hemoptysis (13%)

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

Shortness of breath

Emergent

Non-Emergent

Evaluation

  • ECG
    • Abnormal in 70% of PE patients[6]
    • Sinus tachycardia is most common finding
    • TWI in ant/sept leads + inf leads[7]
    • Nonspecific ST changes, S1Q3T3 (develops due to strain on RV)
    • RBBB or new incomplete RBBB.[8]
    • New right axis deviation
    • Atrial fibrillation
  • CXR
    • Abnormal in 70%
    • Atelectasis is most common (esp >24 hrs after onset of symptoms)
    • Pleural effusion
    • Hampton's Hump
    • Westermark's sign[9]
  • TTE
    • Eval R heart strain (bowing of septum into LV)
    • McConnel's sign (akinesis of RV base/free wall with sparing of apex)
    • Lateral right ventricular wall diameter of <5mm is suggestive of acute pulmonary hypertension while >5mm is suggestive of chronic pulmonary hypertension[10]
Hampton's Hump

Wells Criteria

Clinical Features Points
Symptoms of DVT (leg swelling and pain with palpation) 3.0
PE as likely as or more likely than an alternative diagnosis 3.0
HR >100 bpm 1.5
Immobilization for >3 consecutive days or surgery in the previous 4 weeks 1.5
Previous DVTor PE 1.5
Hemoptysis 1.0
Malignancy (receiving treatment, treatment stopped within 6 mon, palliative care) 1.0

Wells Score

Pre-test Probability Total Points
Low < 2.0
Moderate 2.0-6.0
High > 6.0

Less common risks

  • HIV (protein wasting nephropathy)
  • Nephrotic Syndrome
  • SLE with anti-cardiolipan Ab
  • Exogenous hormones (specifically estrogen)
  • Factor V Leiden
  • Antithrombin III deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Hyperhomocysteinemia

Age Adjusted D-Dimer

Labs commonly report the test as fibrinogen equivalent units (FEUs) with the cutoff at 500 ng/mL and most studies used the FEU values for derivation or validation. If reported by the lab as a D-dimer unit (DDU) the cutoff is often 230 ng/mL. 2 FEUs equal 1 DDU.

  • Age (years) x 10 ug/L for patients > 50 years of age
    • Patient age 75 = age adjusted d-dimer of 850 ug/L
  • If using a lab with a cutoff of 230 (DDU assay) then formula is Age x 5


Workup by Pretest Probability

  • Objective criteria (Geneva, Wells, etc.) is equal to gestalt in assessing pre-test probability[11] (ACEP Level B)

Low Probability

  • D-dimer NPV is 99.5%[12]
  • If low prob and PERC Rule negative, then no workup[13] (ACEP Level B)
  • If low prob and PERC Rule positive, then d-dimer[14] (ACEP Level B)
  • Avoid CT pulmonary angiography in low pretest probability patients that are either PERC rule negative or have a negative d-dimer
Pretest - LR Posttest
Wells < 4 + PERC 12% 0.12 1.6%
Wells < 4 + Neg Dimer 12% 0.01 0.14%
Wells < 4 + AA Dimer 12% 0.06 0.81%
Wells < 2 + PERC 2% 0.01 0.24%
Wells < 2 + Neg Dimer 2% 0.06 0.02%
Wells < 2 + AA Dimer 2% 0.12 0.12

Moderate Probability

  • D-dimer
    • However, it is unclear whether d-dimer alone is sufficient to rule-out PE[15] (ACEP Level C)

High Probability

  • Consider anticoagulation before imaging!
  • Imaging
    • CTA if GFR >60
    • V/Q if GFR <60
      • Will be nondiagnostic if patient has effusion, pneumonia, or other airspace disease
  • If imaging negative, perform additional diagnostic testing (eg, D-dimer, LE vasc US, VQ, traditional pulmonary arteriography) prior to exclusion ofVTE disease[16] (ACEP Level C)
    • A negative d-dimer in combination with a negative CTA theoretically provides a posttest probability of VTE less than 1%

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[17]

Other Modalities

  • SPECT
    • Combination of noncontrast CT chest with V/Q scan
    • Avoidance of contrast for patients with renal injury
    • As sensitive as CTPA and more sensitive than planar V/Q scanning[18]

Management

Supportive care

  • Give IVF as necessary to increase preload while frequently assessing volume status

Anticoagulation

  • Treatment options include any of the following anticoagulations which are indicated for all patients with confirmed PE or high clinical suspicion (do not wait for imaging).
  • The Feb. 2016 CHEST Guideline recommends clinical surveillance over anticoagultation for subsegmental PE with no proximal DVTat low risk for recurrent VTE based on level 2C evidence[19]
  • LMWH SC
    • 1st line for most hemodynamically stable patients
    • Contraindicated in renal failure
    • Enoxaparin 1mg/kg SC q12h
    • Dalteparin 200 IU/kg SC q24h, max 18,000 IU
  • Unfractionated Heparin
    • 80 units/kg bolus; then 18 units/kg/hr
    • Check PTT after 6hr; adjust infusion to maintain PTT at 1.5-2.5x control
    • Benefit of Heparin is the short half life and easy ability to turn off the infusion. Consider
    • Patients with morbid obesity or anasarca may have poor sc absorption with LMWH
    • No need for renal dosing
    • The prefered anticoagulation if thrombolysis is being considered or if there is a bleeding risk or trauma and anticoagulation will need to be emergently discontinued
  • Dabigatran
    • A direct thrombin inhibitor
    • Approved by the FDA in 2014 for the treatment of DVTand PE
    • Dabigatran was noninferior to warfarin in reducing DVTand PE[20][21]
  • Rivaroxaban
    • Factor Xa inhibitors
    • Approved by the FDA in November 2012 for the treatment of DVTor PE
    • Associated with less bleeding, particularly in elderly patients and those with moderate renal impairment compared to standard treatments[22][23]
  • Apixaban
    • Factor Xa inhibitor
    • Approved for treatment of PE in August 2014
    • Studies show 16% reduction in VTE related death compared to standard therapy[24][25]
  • Vit K antagonist - Coumadin
    • 3-6 mo if time limited risk factor (post-op, trauma, estrogen use)
    • 6 mo - life if idiopathic etiology or recurrent
    • INR target 2.5
    • Temporary hypercoagulable state for approx 5 days
    • Initial dose is 5 mg PO

Thrombolysis

IVC Filter

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

Disposition

  • Patients with significant clot burden generally require admission for anticoagulation
  • Consider discharge in low risk patients with peripheral PE[26]

Prognosis

The Pulmonary Embolism Severity Index (PESI)[27]

  • PE patients with PESI class I or II seem safe to manage as outpatients.
Prognosis Variable Points Assigned
Demographics
Age +Age in years
Male +10
Comorbid Conditions
Cancer +30
Heart Failure +10
Chronic Lung Diseae +10
Clincal Findings
Pulse >110 b/min +20
sBP < 100 +30
RR > 30 +20
Temp <36 C +20
AMS +60
Art O2 Saturation <90% +20
Risk Class 30-Day Mortality Total Point Score
I 1.60% <65
II 3.50% 66-85
III 7.10% 86-105
IV 11.40% 106-125
V 23.90% >125

See Also

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. David Da Costa. Bradycardias and atrioventricular conduction block BMJ. 2002 March 2; 324(7336): 535–538
  5. Stein PD et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med. 2007;120(10):871.
  6. Marchick, MR et al. 12-lead ECG findings of pulmonary hypertension occur more frequently in emergency department patients with pulmonary embolism than in patients without pulmonary embolism. Ann Emerg Med. 2010 Apr;55(4):331-5.
  7. Kosuge M, Kimura K, Ishikawa T, et al. Electrocardiographic differentiation between acute pulmonary embolism and acute coronary syndromes on the basis of negative T waves. Am J Cardiol 2007; 99: 817–821
  8. Shopo, JD et al. Findings from 12-lead electrocardiography that predict circulatory shock in pulmonary embolism; a systematic review and meta-analysis. Acad Emerg Med. 2015 Oct;22(10):1127-37
  9. Sreenivasan S, Bennett S, Parfitt VJ. Images in cardiovascular medicine. Westermark's and Palla's signs in acute pulmonary embolism. Circulation. 2007 Feb 27;115(8):e211. full text
  10. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010; 23(7):685-713.
  11. ACEP Clinical Policy for Pulmonary Embolism full text
  12. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple
  13. ACEP Clinical Policy for Pulmonary Embolism full text
  14. ACEP Clinical Policy for Pulmonary Embolism full text
  15. ACEP Clinical Policy for Pulmonary Embolismfull text
  16. ACEP Clinical Policy for Pulmonary Embolism full text
  17. 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.
  18. Lu Y, Lorenzoni A, Fox JJ, Rademaker J, Vander Els N, Grewal RK, Strauss HW, Schöder H. Noncontrast perfusion single-photon emission CT/CT scanning: a new test for the expedited, high-accuracy diagnosis of acute pulmonary embolism. Chest. 2014 May;145(5):1079-88
  19. Kearon, Clive, et al. "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report." Chest (2016).[fulltext]
  20. 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.
  21. 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.
  22. Hughes S. Rivaroxaban Stands up to standard anticoagulation for VTE treatment. Medscape Medical News. December 13, 2012.
  23. Buller HR, on behalf of the EINSTEIN Investigators. Oral rivaroxaban for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN DVTand EINSTEIN PE studies [abstract 20]. Presented at: 54th Annual Meeting and Exposition of the American Society of Hematology; December 8, 2012; Atlanta, Ga.
  24. 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.
  25. 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.
  26. 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.
  27. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-1046.