Pulmonary Embolism Topic Document

Epidemiology

U.S. Epidemiology [Schissler 2015]: PE Accounts for approximately 0.08% of ED visits in the U.S. Overall, 75.1% of patients seen with a diagnosis of PE were hemodynamically stable; 86% were admitted with an in-hospital death rate under 3%.   Mortality [Pollack 2011]: Overall: 1% directly attributed to PE; 5.4% 30-day all-cause mortality   Demographics [Pollack 2011]: Mean age 56.5 (18.1) 33.5% are older than 65 52.8% female 68% caucasian 25.6% African American   Most common comorbidities present in patients who had a confirmed PE [Pollack 2011]: HTN 45.6% Obesity 26.9% Recent hospitalization 23.8% Active malignancy 22.3% Smoker 17.7% Recent surgery 14.4% Prior DVT 11.9% Current DVT 9.5% Heart failure 7.5% CAD with prior MI 6.8% Malignancy in remission 5.7% Limb immobilization 5.1% Oral contraceptives 4.4% Known genetic prothrombotic state 3.7% Prior PE within 3 months 3.2% Postpartum 0.9% Pregnancy 0.7%   Definitions: Massive PE: PE associated with hypotension (SBP <90 or MAP <65, or a drop of SBP by >40 for at least 15mins) PE associated with clinical signs/symptoms of shock (delayed capillary refill, oliguria, etc.) Submassive PE: PE without hypotension or shock but with any of the following: RV dysfunction on POCUS RV dilation (RV:LV Diameter >0.9 on POCUS) Elevated BNP (>500pg/mL) Elevated Troponin I (>0.4ng/mL) Elevated Troponin T (>0.1ng/mL) New ECG Changes (Complete or Incomplete RBBB, Anteroseptal ST-Segment Elevation/Depression, or Anterolateral T-Wave Inversion) Subsegmental PE:

Presentation

According to the EMPEROR Registry: Most common VS: HR 95.7 (20.5)* RR 20.5 (5.2)* BP 132.3 (24.8)* SpO2 95.3 (5.4)* *Note: Mean (SD)   Most common symptoms: Dyspnea at rest 50.1% Pleuritic chest pain 39.4% Dyspnea with exertion 27% Cough w/o hemoptysis 22.9% Substernal chest pain 15.2% Dizziness 12.2% Diaphoresis 11.7% Upper abdominal pain 10.7% Fever 9.7% Cough with hemoptysis 7.6% Unilateral extremity pain 5.9% Syncope 5.5% AMS 4.8% Angina 3.9%   Most common physical exam findings: Extremity swelling suggestive of DVT 23.5% Resp distress 16.4% Rales 8.4% Diaphoresis 7.1%   CXR findings: Normal 40.1% Atelectasis 16.9% Infiltrate 13.5% Pleural effusion 16.2% Westermark sign 0.4% Hampton Hump 0.8%   ECG findings: Chan 2001 The EKG is not helpful for diagnosing PE as the findings are neither sensitive nor specific for pulmonary embolism The majority of PE patients have normal EKGs However, for those with abnormal ekgs, the following are frequently seen in PE: New incomplete or complete RBBB Right axis deviation Prominent S waves in I, aVL Q in III, aVF T wave inversions in III, aVF, V1-4 Transition zone shift to V5 S1Q3T3 is not as pathognomonic as you would think. The incidence of it in patients with PE is reported by most studies to be between 10 and 28% and it is not specific for pulmonary embolism. Yameogo 2011 case report in which large bilateral pulmonary embolism masqueraded as anterior STEMI on EKG with large ST elevations in V1-3 with reciprocal changes. The EKG changes resolved after thrombolytics were given.

Workup

First assess the clinical condition of the patient. If the patient is in shock, and you suspect PE, begin resuscitating the patient and perform bedside ultrasound to evaluate for R heart strain and DVT. If either are present and the patient is relatively stable obtain CT PA, especially if they have any history of pulmonary disease as this may cause similar R heart strain patterns on POCUS as PE. (You can also consider starting an unfractionated heparin drip empirically in this circumstance, but be advised that if the patient is hypotensive and has a PE they should be treated with r-tPA, in which case the heparin will need to be reversed with protamine prior to receiving the r-tPA).  If the patient is circling the drain and too unstable for CT, give 50mg r-tPA and cross your fingers.   If the patient is not in shock, then begin by assessing the risk of PE by using either the revised simplified Geneva score or the simplified Wells score. If patient is low risk by those decision rules, check to see if the PE rule out criteria (PERC) applies. If PERC is negative, PE is effectively excluded. If PERC is positive or does not apply, obtain a d-dimer. If the d-dimer is negative, PE is effectively excluded (risk of PE in this cohort is between 0-2%). If the d-dimer is elevated or if the patient was high risk by Wells or Geneva, obtain CT PA. If the patient is unable to undergo CT PA, obtain V/Q scan and bilateral lower extremity venous duplex for DVT.   Revised Geneva Prediction Score [MDCalc]: Le Gal 2006 Revised Geneva Score Study Klok 2008 (simplified revised Geneva score) Simplified revised score has all components of Geneva score worth 1 point, (only tricky part is for HR: HR <75=0, HR 75-94=1, HR ≥95=2). score ≤2 PE present in 11.5% of patients 64.9% of study population had score ≤2 Percent of patients with PE: score ≤ 2 and negative dimer: 0% score ≤ 2 and positive dimer: 21.7% score >2, PE present 41.6% 35.1% of study population had score >2 Klok 2008(comparison of Geneva and Wells) The revised Geneva score performed equally when compared to the Wells score   Wells Score [MDCalc]: Wells 2000 Score ≤4 had a 7.8% prevalence of PE PE rate with score ≤4 and negative dimer Derivation group: 2.2% Validation group: 1.7% PE rate with score ≤4 and positive dimer: Derivation group: 18.3% Validation group: 11.7% overall PE rate in patients with score ≤4 is: derivation: 7.8% validation: 5.1% PE rate with score >4 and a negative dimer derivation: 16.1% validation: 10.3% PE rate with score >4 and positive dimer derivation 57.7% validation 60% overall PE rate in patients with score >4: derivation 40.7% validation 39.1% Wolf 2004 Score of ≤4 carried 3% risk of PE 0% of patients with score of ≤4 and negative dimer had PE Score of >4 28% risk of PE Patients excluded from Wolf 2004: non-english speaking pregnant within the last 6 months or currently pregnant morbidly obese (>350 lbs) diagnosed with a previous genetic clotting disorder younger than 18 older than 85 known to have a recently elevated or normal d-dimer critically ill or unable to consent   IF low risk by Wells or Geneva, check PERC.   PERC [MDCalc] Kline 2004 Original derivation and validation study Demonstrated that testing threshold for PE is 1.8% Sensitivity 96% False negative rate 1.4% (less than testing threshold so rule is valid.) Kline 2008 Prospective multicenter evaluation of performance of PERC rule in patients with low suspicion of PE 8138 patients 6.9% PE prevalence False negative rate 1% Sensitivity 97.4% Singh 2012 Meta-analysis and systematic review 12 studies 14,844 patients PERC= 97% sensitive Kline 2018 Retrospective study evaluating PERC in pediatrics 5-17yo 98.2% sensitive False negative rate 0.6%   IF patient does not PERC out, obtain d-dimer   D-Dimer Wells 2000 (simplified) Score of ≤4 and negative dimer had PE 2.2% in derivation cohort and 1.7% in validation cohort Wolf 2004 dichotomized dimer Score of ≤4 and negative dimer had PE 0% Righini 2014 age adjusted d-dimer Adjusted cutoff= Age x 10 for patients 50 years or older Prospective trial: 3346 patients, 2898 with nonhigh or unlikely clinical probability 28.2% had dimer lower than 500 11.6% had dimer between 500 and age-adjusted cutoff (AA dimer) 3 month failure rate of patients with dimer between 500 and AA dimer was 0.3% (1/331) (CI 0.1-1.7%) AA dimer changed dimer PE exclusion rate from 6.4% to 29.7%. i.e. it decreased rate of imaging by 23.3%   IF d-dimer positive or IF patient was high risk on Wells or Geneva, obtain CT PA   CT Pulmonary Angiography (CT PA) Lim 2018 American Society of Hematology Guidelines 93% sensitive, 98% specific +LR 46.5 -LR 0.07 PIOPED II sensitivity 83% (95% CI: 76 - 92%) specificity 96% (95% CI: 93 - 97%) +LR 19.6 (95% CI: 13.3 to 29.0) -LR 0.18 (95% CI: 0.13 to 0.24) Gold standard reference used was: composite reference standard required one of the following conditions: ventilation–perfusion lung scanning showing a high probability of pulmonary embolism in a patient with no history of pulmonary embolism, abnormal findings on pulmonary DSA, or abnormal findings on venous ultrasonography in a patient without previous deep venous thrombosis at that site and nondiagnostic results on ventilation–perfusion scanning (not normal and not high probability without previous pulmonary embolism). Abnormal venous ultrasonography in such a patient was interpreted as a surrogate for the diagnosis of pulmonary embolism. Exclusion of pulmonary embolism according to the composite reference standard required one of the following conditions: normal findings on DSA, normal findings on ventilation–perfusion scanning, ventilation–perfusion scanning showing either a low or very low probability of pulmonary embolism, a clinical Wells score of less than 2 (Table 1),24 and normal findings on venous ultrasonography. Woo 2012 Average lifetime risk for cancer from a single CT pulmonary angiogram varies from 57/100,000 for females 17–19 years old to 8/100,000 for males and females 80–89 years old V/Q scan Sostman 2008 The prevalence of PE in the sample was 169 of 889 (19%). Using the modified PIOPED II criteria: "PE present" perfusion scan sensitivity: 84.9% (95% confidence interval [CI], 80.1%-88.8%) "PE absent" specificity 92.7% (95% CI, 91.1%-94.1%) -LR 0.162 +LR 11.63 excluding "nondiagnostic" results, which occurred in 20.6% (95% CI, 18.8%-22.5%). Using PISAPED criteria: sensitivity of a "PE present" perfusion scan was 80.4% (95% CI, 75.9%-84.3%) specificity of "PE absent" was 96.6% (95% CI, 95.5%-97.4%) -LR 0.2 +LR 23.65 proportion of patients with "nondiagnostic" scans was 0% (95% CI, 0.0%-0.2%). Moore 2017 VQ scan has 50-fold lower radiation dose to the breast (0.28–0.9 vs. 50–80 mSv in 64 slice CT)   Ultrasound Basically: do a quick DVT study then look for signs of R heart strain (detailed in the FOCUS section below.) Can also use TAPSE to give you an objective measurement but it does not perform well as a diagnostic test unless it is moderately-severely diminished. POC compression ultrasound for DVT in setting of clinically suspected PE Le Gal 2006 +LR 42.2 -LR 0.6 FOCUS Daley 2016 FOCUS= measurement of TAPSE and evaluation for other signs of RVD: right ventricular enlargement (appearance of the right ventricle being equal to or greater in size than the left ventricle), septal flattening, tricuspid regurgitation (any regurgitant jet seen on color Doppler in the apical 4-chamber window), or McConnell's sign. Presence of RVD included any of these characteristics, or a TAPSE measurement less than 1.7 cm. FOCUS for RVD was shown to be 100% sensitive for PE in patients with tachycardia and/or hypotension. Specificity was not reported so LR could not be calculated. TAPSE Daley 2016 [link to TAPSE measurement video] Cutoff values: < 2.0cm in this study +LR 2.1 -LR 0.43 <1.7cm is frequently reported in cardiology literature +LR 2.6 -LR 0.56 In patients with tachycardia and/or hypotension, decreased TAPSE was 94% sensitive for PE in Daley 2016. They did not report specificity so LR was unable to be calculated. McConnell’s sign Daley 2016 +LR 4.8 -LR 0.9 Septal Flattening Daley 2016 +LR 5.3 -LR 0.35 RV dilation Dresden 2014 Definition of RV dilation: RV:LV ratio of 1:1 or greater RV and LV length and diameter measured in end-diastole on apical 4 chamber view +LR 29 -LR 0.51

Management

Pearls/Deep Dive

References and Resources