Much of the below information comes from Emergency Medicine Cases

https://emergencymedicinecases.com/pulmonary-embolism-diagnosis-2-imaging-pregnancy-subsegmental-pe/

Pulmonary embolism

Hi Team, 


Last week I felt like everyone had a PE. PE's are tricky suckers and sometimes we feel caught off guard about the diagnosis. We usually miss the diagnosis when we fail to consider it. In general in America and Canada we do a lot of CT's because we are afraid of missing the diagnosis (compared Europe). I figured why not review how we go about diagnosing them. I think each one of us has a slightly different way about how we go about diagnosing/ who we test for them. I know I can't tell you what exactly what my algorithm for PE is, but it's usually a combination of gestalt with the fact they have a whole bunch of risk factors (i.e. their pre-test probability is probably higher) / I don't like the way they look. I have broken down how these experts recommend testing, I think this might be helpful to categorize in your head how you may approach the next pt that you are concerned about a PE.  


Start with Wells to assess pre-test probability  


1.     If <2, use PERC

2.     If 2-4, send D-dimer

3.     If >4, consider a CTPA


If PERC (-): then done 

If PERC (+) then do D-dimer  

      -D-dimer negative- done

      -D-dimer positive - CTA 




Consider for pregnant pts however no good evidence to support the recommendation:   

Two tiered Wells:  Wells <4 or Wells >4

PE1.png

Here are the links for the podcast and their show notes: 

https://emergencymedicinecases.com/pulmonary-embolism-challenges-diagnosis-part-1/
https://emergencymedicinecases.com/pulmonary-embolism-diagnosis-2-imaging-pregnancy-subsegmental-pe/


The diagnosis of PE is a tricky one. It is hardly gratifying when we find an incidental subsegmental filling defect in a 90-year-old patient with multiple comorbidities but missing a larger clot in an otherwise young and healthy patient can be devastating. The problem is, with such a wide variability in presentation and without clear diagnostic directives from the literature, it can be hard to tease apart those who are sick from those who don’t have the disease at all.

What we really want are decision aids that maximize diagnostic accuracy while minimizing over-testing and patient harm resulting from over-testing, over-diagnosis and anticoagulant complications.

Pulmonary embolism challenges in diagnosis: What’s all the fuss really about anyways?

PEs kill. But not as much as we might think.

In the 1990’s The Prospective Investigation of Pulmonary Embolism Diagnosis study found a case fatality rate of 15% at 3 months [1], but only 10% of these deaths were directly attributable to PE [2]. Newer data from the EMPEROR Registry in 2011 found that the mortality rate directly attributed to PE was 1%, while the all-cause 30-day mortality rate was 5.4%, and mortality from hemorrhage was 0.2% [3]. Interestingly, most patients who died (85%) succumbed untreated while waiting for diagnostic confirmation. It appears from this data that most patients with PE die of comorbidities which might have placed the patient at risk for PE, such as malignancy or die while waiting for diagnostic confirmation. Much of this decreased mortality may be related to the increase in diagnosis of subsegmental PEs in the past two decades. Comparison of pooled data from uncontrolled outcome studies shows no increase in PE recurrence or death rates for patients diagnosed with isolated subsegmental PEs who were not anticoagulated compared to those who were anticoagulated [4].

 

What about the bleeding risk in treated pulmonary embolism? 

The typical patient being worked up for PE is low risk for the diagnosis and at low risk for bleeding complications. In the same 2018 metaanalysis looking at outcomes of subsegmental PEs, 8% of those anticoagulated had a significant bleeding complication [4]. The risk for a major bleed for all comers diagnosed with PE is around 3-5% in the first 3 months of treatment. Most of these will occur in the first week. It is important to weigh the likelihood of PE against the risk of bleeding prior to starting anticoagulation on speculation in the ED. The HAS-BLED score can help here. On the other hand, one or two doses of anticoagulant medication portends a negligible risk for major bleeding complications; ED patients with a high pretest probability for PE who have no absolute contraindications to anticoagulation, should be anticoagulated prior to diagnostic confirmation, as 85% of PE mortality in ED patients occured in untreated patients waiting for diagnostic confirmation in the EMPEROR Registry.

 

Pitfalls in the diagnosis of pulmonary embolism

Failure to consider the diagnosis in patients with comorbidities. A missed PE is rarely a failure of diagnostic strategy; it’s more often a failure to consider the diagnosis to begin with. A PE is easy to miss in those with co-morbidities (e.g. CHF, pneumonia) – premature closure in patients with a clear reason for their shortness of breath or who are going to be admitted for other reasons is one source of missed diagnosis.

Overestimating the risk of PE. While we might think we see a lot of patients that are high risk for PE, the vast majority of patients who we are considering for PE diagnosis are in fact, low risk according to Well’s Criteria. We order many needless CTPAs, with their inherent problems of overdiagnosis and radiation risk, for fear of a PE in low risk and negligible risk patients. Remember that placing PE in the top three considerations in your differential diagnosis of a patient who presents with chest pain or shortness of breath does not necessarily mean they are at high risk for PE. Even experienced clinicians have been shown to overestimate the risk of PE in low risk patients.

Misinterpretation of vital signs. One source of over-testing is misinterpreting the contribution of heart rate to the pretest probability. While tachycardia is one of the points in the Well’s score, tachycardia in the absence of any other features of pulmonary embolism should not trigger the work-up. Conversely, a normal heart rate does not rule out PE. An important nuance is that a triage tachycardia that normalizes by the time the patient is assessed by the ED physician, according to a recent study, should be considered tachycardia when using the Wells score. In this study, in patients with an abnormal pulse rate, respiratory rate, shock index, or pulse oximetry at triage that subsequently normalized, the prevalence of PE was 18, 14, 19, and 33%, respectively [5].

Assuming low risk for PE in patients with no apparent risk factors. While risk factor assessment is important in assessing pretest probability, up to 50% of PEs are diagnosed in patients with no apparent risk factors [6].

 

Pearls in decision making on whether or not to work up a patient for pulmonary embolism

Take your time taking a history

Few will miss the woman on OCP who traveled in a trans-Atlantic plane a week ago who comes in dyspneic, coughing up blood with a swollen leg and a history of cancer. For the less clear cut patients there are some pearls to consider when taking a history. 

Is it true exertional dyspnea? Where we need to drill down when it comes to assessing symptoms is whether the patient is experiencing true exertional dyspnea or not. Many patients will admit to feeling short of breath if you ask them “have you felt short of breath at all?”, but this will inevitably label patients with dyspnea who do not in fact have dyspnea. You are more likely to identify true dyspnea if you ask the patient “how is your breathing” and “give me an example of when you feel breathless”. If the patient says that when they walk their dog they need to stop every few steps to catch their breath, this is more likely to be true exertional dyspnea than the patient tells you that they sometimes feel the need to take one or two deeper breaths while watching television.

Fatigue is an overlooked symptom of pulmonary embolism. A common symptom in PE is fatigue, which while non-specific, should raise an eyebrow in the dyspneic patient who tells you that they developed unusual fatigue that coincides with their dyspnea.

 

How should risk factors contribute to the pretest probability of pulmonary embolism?

While there is an ever-growing long list of risk factors for PE the important risk factors to consider in assessing pretest probability include personal and family history of venous thromboembolism, recent immobilization, active cancer and exogenous estrogen use. These are the risk factors that should be considered in your assessment of  pretest probability for PE.

Nonetheless, it is important to realize that up to 50% of PEs are diagnosed in patients with no apparent risk factors [6].

 

Up to 50% of pulmonary embolisms are diagnosed in patients with no apparent risk factors.

 

Which patients who present to the ED with syncope or COPD exacerbation require a CTPA to rule out pulmonary embolism?

The PESIT trial [7]

Although this study showed a startling 17% PE prevalence in patients admitted to hospital with syncope, there are some important points to consider:

  • This trial was conducted on those already admitted to hospital. The results are not generalizable to the ED population.

  • A subsequent international study showed a <1% prevalence of PE in those who presented to EDs with syncope [8].

  • A Canadian study showed a 1.4% prevalence of PE in those admitted with syncope [9].

A reasonable approach therefore would be to assess your syncope patients for PE the way you would any other patient in the ED.

  

Is COPD the only thing making my patient short of breath?

While one of the sources of missed PE is not considering the diagnosis in patients with respiratory comorbidities, and PE should be considered in patients presenting with unexplained COPD exacerbations, not every COPD patient requires a CTPA in the ED. A 2017 systematic review and meta-analysis showed a PE prevalence of 16% in patients with unexplained acute COPD exacerbations [10]. However, they only included a single ED study which had a PE prevalence of only 3%, and the clinical significance of these PEs were unclear – one third of the PEs were subsegmental. This a tricky patient population. On the one hand they have poor respiratory reserve at baseline. A second hit from a PE will not be well tolerated. On the other hand, they are at higher risk of catastrophic bleeding given their comorbidities and frailty. So where does this leave us with regards to ordering CTPAs on patients with COPD exacerbations in the ED? Make sure the story fits. If the typical clinical features of COPD exacerbation are missing, or the patient has some features of PE, a workup for PE should be considered. Patients with typical COPD exacerbations with wheeze who have an identifiable infectious source on chest x-ray are unlikely to require a CTPA to rule out PE. 

 

Suggested diagnostic decision tool algorithm for pulmonary embolism. 

There are a number of decision rules that are used as objective aids in the work up of PE. Wells and PERC (Pulmonary Embolism Rule out Criteria) are the two most commonly utilized tools in North American EDs. It is important to understand how the prevalence of PE in your population impacts decision making. Simply put, the prevalence of a disease can be considered the pre-test probability of the patient ruling in for that disease. The maximum suggested prevalence for PE in order to use the PERC rule is 7%. In other words, if there is a high prevalence of PE in your population, PERC may not be applicable.

The PROPER trial out of France, where the prevalence of PE is low, showed that gestalt performed similarly to PERC in terms of 3-month PE rate, but PERC resulted in an 8% decrease in unnecessary CT scanning, and a 40-minute decrease in ED stay [11]. While studies have suggested that physician gestalt may be as accurate as these decision tools [11,12], there is an argument to be made that even seasoned docs should take the time to calculate these scores because even they can have a tendency to overestimate pretest probability at times.

 

An Algorithmic Approach

Once you have decided to test for PE, our experts suggest starting with Wells to get an idea of the pre-test probability.

1.     If <2, use PERC

2.     If 2-4, send D-dimer

3.     If >4, consider a CTPA

 

Should The YEARS Algorithm supplant Wells?

The YEARS score is essentially a simplified Wells, and uses two different D-dimer thresholds to direct the work up of PE. Limitations of the YEARS study [13,14] include the physicians not being blinded to the initial D-dimer, and higher PE rates compared to other studies. Our experts believe that while promising, the YEARS algorithm requires further study.

PE2.png

 

Age-Adjusted D-Dimer

D-dimer threshold = Age (>50) x 10

 

There are conflicting policy statements from different international societies, but the evidence is reasonably convincing for the use of age-adjusted D-dimer [15] and is recommended by our experts. ACEP suggests that using an age-adjusted approach may reduce the need for advanced imaging without significantly increasing missed cases of PE [16]. 

Journal Jam on age-adjusted D-dimer with Jeff Kline

 

Utility of ancillary testing for the diagnosis of pulmonary embolism

CXR. While decades ago we depended more so on CXR and ECG to help in the diagnosis of PE, their utility has recently become less important. Nonetheless, findings on chest X-ray and ECG may aid in your decision making. The main role of a chest X-ray is to rule out alternative diagnoses. Beware of diagnosing pneumonia based on an infiltrate, as a pulmonary infarct from PE can look similar. The chest X-ray is often normal in PE. The classic findings are raised hemidiaphragm, pleural effusion, Westermark’s sign and Hampton’s hump. The latter are usually identified in retrospect after the diagnosis of PE has already been made.

 

ECG. Signs of PE on ECG include sinus tachycardia, RV strain pattern, incomplete RBBB, S1Q3T3, dominant R wave in V1, ST-segment elevation in V1 and aVR and low voltages.

The most specific ECG finding in PE is flipped T waves in anterior AND inferior leads. This finding is almost never found in ischemia-mediated disease. S1Q3T3 has a poor specificity for PE.

 

POCUS. In general, bedside ultrasound will not be your primary modality to diagnose PE. However, it can be helpful in the arrest or peri-arrest patient who are not safe to leave the ED to get a CTPA. Our experts do not recommend using POCUS to aid in disposition decisions. Even if sonographic signs of right heart strain are present, PE can still be managed as an outpatient if criteria for outpatient management are fulfilled.

Rob Simard on POCUS Cases 1: Pulmonary Embolism

 

In part 2 of Pulmonary Embolism Challenges in Diagnosis we discuss nuances of CTPA, workup of PE in pregnant patients, management of subsegmental PEs, implimenting decision support in your ED and much more…

  



CTPA test characteristics and pulmonary embolism diagnosis

As with the rest of emergency medicine, our interventions are rarely benign. In order to avoid unnecessary radiation and major bleeding complications as a result of anticoagulating patients with false positive CTPA results, it’s important to have a rational approach to imaging for PEs as well as a good approach to shared decision making with our colleagues, our radiologists and our patients.

Although CTPA has become the gold standard for diagnosing PE and remains the best imaging modality available, it is far from perfect. The CTPA is prone to over-diagnosing clinically irrelevant emboli in low-risk patients [1]. Furthermore, although its sensitivity approaches 100% for clinically relevant PEs, in those with high pre-test possibility there is a small chance a clot might be missed. Those patients at high risk for PE based on a Wells score >6 with a negative CTPA should be counseled that although the present CTPA does not show a PE, up to 5% of high risk patients may develop a PE within a few months of a negative CTPA [2,3].

What about clot burden and location? These imaging characteristics have not been shown to accurately predict outcome, or even symptoms. The clinical context is much more important, and markers such as hypotension and hypoxia are better predictors of outcome [4].

Subsegmental pulmonary embolism: To treat or not to treat?

In the last 10 years, the incidence of diagnosed PE has doubled, despite no change in mortality, partly due to advances in CT technology and partly due to radiologists overcalling subsegmental PEs due to medico-legal concerns. With modern CTs, subsegmental PEs are more often diagnosed. Although there is some variability in practice, most emergency physicians end up treating subsegmental PEs. But should we?

An observational study by Goy et al. in 2015 reviewed 2213 patients with a diagnosis of subsegmental PE, and showed that whether or not anticoagulation was given, there were no recurrent PEs, yet 5% of anticoagulated patients developed life-threatening bleeding [5]. Other studies have yielded similar results [6].

Shared decision-making. Consider the patient’s bleeding risk (HASBLED score) and discuss potential treatment options. The 2018 ACEP Clinical Policy on Acute Venous Thromboembolic Disease gives withholding anticoagulation in patients with subsegmental PE a Level C recommendation and states: “Given the lack of evidence, anticoagulation treatment decisions for patients with subsegmental PE without associated DVT should be guided by individual patient risk profiles and preferences [Consensus recommendation].”

Start anticoagulation for subsegmental PE in the ED with an expectation that anticoagulation may be stopped in follow-up. While the risk of major bleeding with a full course of anticoagulation is significant, the risk of bleeding with a few doses of anticoagulant is very low. Thus, starting treatment for subsegmental PE in the ED and referring the patient for early timely follow up in a thrombosis or internal medicine clinic (within a few days) is a reasonable option. Counseling your patient that the consultant may recommend stopping the anticoagulant is essential to avoid conflicting messages. Consultants may risk stratify low risk patients with serial leg dopplers to direct ongoing therapy.

V/Q Scan in pulmonary embolism challenges in diagnosis

Many emergency physicians are comfortable using D-dimers, dopplers and CTPA, but often forget about the value of V/Q scans [8]. Consider this test in:

  • Young, otherwise healthy patients with a normal chest x-ray

  • CT contrast allergy

V/Q SPECT

V/Q SPECT has been shown to have superior accuracy compared to traditional V/Q and has similar sensitivity, but poorer specificity compared to CTPA for pulmonary embolism [9]. V/Q SPECT eliminates intermediate probability scans, and is reported dichotomously as positive or negative for PE. This avoids the ambiguity of results in traditional V/Q. Robust data is pending regarding its diagnostic utility compared to CTPA.

Pregnancy and pulmonary embolism challenges in diagnosis

There are many proposed strategies for working up the pregnant patient for PE, but no diagnostic algorithm has robust enough evidence for strong recommendations [10,11,12]. Pregnant women have generally been excluded from the studies that have provided support for the use of clinical prediction tools and D-dimer in the diagnosis of pulmonary embolism.

Although a trimester-adjusted D-dimer (cutoffs increase by 250 for each trimester) has been suggested for PE in pregnancy, it is not recommended by our experts. While the DiPEP study could not find a D-dimer threshold below which PE could be ruled out in pregnancy [13], there is some observational evidence that a negative D-dimer result rules out PE in otherwise low-risk pregnant patients. A retrospective review of 152 pregnant and post-partum patients who underwent V/Q or CTPA for suspected PE found a sensitivity of 100%  but only a specificity of 42% [14]. The American Thoracic Society recommends not using D-dimer in pregnancy [15].

The European Society of Cardiology recommends considering V/Q scan to rule out suspected PE in pregnant women with normal CXR (Class IIB recommendation) and that CTPA should be considered if the CXR is abnormal or if V/Q scan is not readily available (Class IIa recommendation) [16].

Our experts recommend starting with two-tier Wells and PERC, an unadjusted D-dimer if necessary, then moving onto bilateral leg dopplers, and then considering chest imaging based on the CADTH Optimal Strategies for the Diagnosis of Acute Pulmonary Embolism 2018 Recommendations [17].

  1. Two-tier Wells

  2. PERC

  3. D-dimer

  4. Leg ultrasound

  5. CTPA or VQ SPECT

 

From CADTH Optimal Strategies for the Diagnosis of Acute Pulmonary Embolism: Recommendations 2018

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Can leg dopplers rule PE in or out? Ultrasound shows a DVT in up to 30-50% of patients with PE, and finding a proximal DVT in patients suspected of having PE is considered sufficient to warrant anticoagulation without further testing [18]. A negative Doppler ultrasound for DVT does not rule out a PE.

Radiation Risk in pregnancy: CTPA vs. V/Q

A CTPA transmits more radiation to the maternal breast tissue, whereas a V/Q scan transmits more radiation to the fetus. There is no hard data here to guide practice and specific strategies remain controversial. However, it is important to realize that both VQ and CTPA fetal radiation dose falls well below teratogenic doses. In the ED, discuss radiation risk with your patient and the radiologist on-call to determine the best imaging modality.

Departmental pulmonary embolism decision support

Our experts encourage every ED to develop a protocol for PE diagnosis to maintain consistency and promote institutional support for clinicians. If implemented thoughtfully with input from the physician group, this practice could lead to reduced imaging rates and increased diagnostic yield [19]. However, changing ED culture may be challenging, and results depend on the point of implementation to affect diagnostic momentum.