#15 Pulmonary Embolism Part 1

There are few things in medicine Nick & Cyrus enjoy talking about more than PE! Join the guys from Critical Care Time as they tackle this massive topic via a two-part epic that’ll prove to be the best saga since The Lord of The Rings! In part one they talk about diagnosis, clinical decision support tools and demystify the pathophysiology behind pulmonary emboli. Check it out and be sure to catch the second half in two weeks! We promise you’ll get your money’s worth!

Quick Take Home Points:

1. Pulmonary embolisms are the leading cause of preventable hospital death - Always think “Could this be a PE?”

2. PE can present along a spectrum from extremely mild to severe disease and often requires a high degree of suspicion. Providers often need to utilize a wide clinical toolkit to avoid missing this diagnosis.

3. Mortality in PE is due to RV failure leading to cardiogenic shock. The degree of clot burden is not always proportional to RV dysfunction!

4. Hypoxemia in setting of acute PE is due to V/Q mismatch not due to shunt.

Infographic:

ICU OnePager Infographic about approach to diagnosis, prognostication, and treatment of PE

___________________________________________________________________________________________________________________________________
Pulmonary Embolism is a complex and challenging clinical problem that varies from incidental to immediately life threatening. This OnePager summarizes Nick’s approach to PE including diagnosis, prognostication, and how he manages anticoagulation, hemodynamics, and thrombolysis or other therapies.

Show Notes:

Show notes by Shane McMahon, DO

Presentation of pulmonary embolism (PE):

1. Clinical presentation of PE can be highly variable due to many factors including ones listed below:

1. Varying clinical presentation due to size of embolus or emboli

1. Patient management and outcomes can be anywhere on spectrum from outpatient management to ICU admission possibly leading to death

2. Dynamic Presentation over time.

1. Clinical changes can develop over time making a once stable patient with mild PE develop into a critically ill patient with pulmonary infarction, large clot burden with multiple thromboemboli, and/or new onset right and left heart failure

3. Due to a widely varying presentation, diagnosis of PE can be challenging and may include clinical presentation and physical exam, laboratory studies and multiple imaging modalities

Pulmonary embolism: Background information

1. Pulmonary embolisms are often diagnosed everyday in most Emergency Rooms. A majority of these patients are sent home on oral anticoagulation. Only a small subset are admitted

1. A 2019 CHEST article numbered over 100,000 ER presentations for PE annually in the USA alone!

2. Risk factors for development of PE include:

1. Elderly age 

2. Younger patients with risk factors such as immobility can present with PE associated with high morbidity

3. Comorbid disease including malignancy, coagulopathy

3. Risk Stratification Scoring systems including BOVA and PESI/S-PESI are available once a diagnosis of PE has been made to further stratify and disposition patients according to their risk of severe or mild disease.

1. BOVA score – Triages patients for need to activate designated PE team, if available. 

2. PESI or S-PESI – Stratifies patients into Low, Intermediate-low, Intermediate-high and High risk categories 

1. Intermediate-Low Risk: High PESI/S-PESI score without positive cardiac biomarkers (Troponin and/or BNP) or evidence of RV strain

2. Intermediate-High Risk: High PESI/S-PESI score with positive cardiac biomarkers (Troponin and/or BNP) and evidence of RV strain however no hemodynamic evidence of shock

3. High Risk: Intermediate risk criteria are met + there is clinical evidence of ongoing shock

4. The presence of contrast in the IVC, which is suggestive of reflux and poor right sided heart function, on CT-PA is the best predictor of increased mortality on imaging. 

5. Nomenclature of diagnosis of PE varies according to professional organizations in the USA and abroad:

1. USA: Massive vs Submassive speaks to ongoing presence of shock or no shock physiology respectively. This system does not speak to the risk for progression into more severe disease 

2. European Society for Cardiology classifies PE patients into low, Intermediate-low, intermediate-high and high risk Categories 

1. A more granular, defined approach which attempts to predict who is at higher risk of progression to shock

Pathophysiology of pulmonary embolism:

1. Pathophysiology of pulmonary embolisms generally follow this trend: PE 🡪 increased Right Ventricle (RV) RV afterload 🡪 RV dysfunction 🡪 decreased Left Ventricle (LV) preload 🡪 LV dysfunction 🡪 increased RV afterload.

1. This is a vicious cyclic process and can colloquially be described as the RV death spiral

2. The amount of clot (clot burden) is not always proportional to RV dysfunction! Different patients have different functional reserves depending on coexisting lung and heart function.

2. PE morbidity and mortality is more complicated than from straightforward hypoxia. Instead, Pulmonary embolisms directly and indirectly cause RV failure via increased RV afterload (PVR, pulmonary vascular resistance) and a resultant systemic inflammatory response.

1. The primary mechanisms behind this increase in PVR is the vasoconstriction of pulmonary vasculature in response to localized and generalized hypoxia as well as a direct increase in resistance in pulmonary blood flow due to obstruction of vessels because of clot burden.

1. RV is not as structurally capable as the LV in overcoming afterload. This poor ability of the RV to adapt to higher mechanical demands leads to RV hypoxia and ischemia.

2. Eventual RV failure leads to decreased flow to the LV leading to decreased LV Stroke volume via mechanisms below:

1. Directly via decreased blood volume delivered to LV – This is analogous to the RV and LV being a circuit in series

2. Decreased LV filling due to bowing of interventricular septum into LV which physically limits diastolic filling volumes and can create systolic LV outflow track obstruction - This is analogous to the RV and LV being a circuit in parallel.

3. Understanding the physiology of RV strain and the RV death spiral in the setting of PE can better inform treatment. For example, traditional management of PE with fluid boluses for hypotension may actually worsen clinical status if RV is already under strain by further straining RV walls and leading to increased RV stroke volume, increased RV afterload, increased RV oxygen consumption.

1. Remember that these patients are often not hypovolemic and that increased RV pre-load may actually worsen RV output in the setting of RV failure.

4. Hypoxemia in setting of acute PE is due to V/Q mismatch not due to shunting. 

1. Due to increased pressures throughout non-obstructed pulmonary vasculature with resultant increased perfusion of less ventilated sections of lung and thus poor gas exchange in those areas and eventual hypoxemia.

1. Giving supplemental O2 saturates alveoli with Oxygen and leads to better gas exchange in these areas and often improved hypoxemia in PE 

5. V/Q mismatch and underperfusion of lung tissue affected directly by vascular obstruction from PE also leads to poor CO2 exchange. 

1. This is an increase in physiologic dead space of lung parenchyma and can lead to CO2 retention despite tachypnea 

6. Hypoxemia, blood hypoxia, will lead to global vascular constriction throughout lungs tissue even in areas not directly affected by PE vascular obstruction 

1. Supplemental O2 can help alleviate this widespread pulmonary vasoconstriction and help prevent worsening of RV death spiral

7. Hypercarbia and acidosis also lead to pulmonary vasoconstriction! So optimization of RV function in setting of PE and increased PVR requires improving gas-exchange and perfusion as able. 

Diagnosis of PE

1. Classical clinical presentation of PE includes sudden onset chest pain and tachycardia and hypoxemia leading to shock however these are non-specific symptoms and can be masked by confounding factors i.e. medications (beta-blockers) and underlying cardiac conduction defects. 

2. EKG can show sinus tachycardia (most common finding on EKG), Large R wave in V1, Right axis deviation, RBBB either incomplete or complete, T wave inversions in Inferior leads (II, III, aVF)

1. Many of these findings are electrical manifestations of RV strain 

3. Chest X-Ray (CXR) findings:

• Rarely useful at time of diagnosis but can sometimes be appreciated depending on PE size, location and time from PE.

• Fleischner Sign: Enlarged pulmonary vasculature

• Hamptons Hump: Wedge opacity in peripheral lung

• Westermark Sign: Increased lucency in vasculature distal to embolus

• Knuckle Sign: Pulmonary vasculature has a cut off 

4. Point-of-Care Ultrasound (POCUS) has more utility in diagnosis of PE.

   • Examples of POCUS evaluation in patients with PE includes:

• DVT Evaluation: Can evaluate for DVT in extremities, if present largely confirms diagnosis of PE.

• RV function assessment:

• “Eyeball test” – evaluate size and gross contraction of RV

• TAPSE: Tricuspid Annular Plane Systolic Excursion. 

• Normal RV motion squeezes in a bottom to top fashion.

• TAPSE quantifies RV motion during contraction 

• TAPSE < 17 = abnormal, TAPSE < 15 = Increased mortality in PE

• Doppler imaging of Basolateral wall of RV (S-Prime): 

• Should be > 10 cm/s and indicates effective contraction of RV basolateral wall

• Longitudinal strain assessment of RV free wall 

• Right Ventricle Outflow Tract (RVOT) VTI: Looking for tricuspid valve regurgitation velocity 

• Apicalization of RV:  Typically the RV sits higher than the LV. Displacement of RV to sit in line with LV can suggest RV dysfunction bordering on RV failure 

• McConnells sign: 

• Regional pattern of RV dysfunction characterized by apical hyperkinesis and relative akinesia of mid free wall.

5. CT Angiogram/ CT-PA:

• CT-PA has replaced traditional angiogram as the gold standard of diagnosis for PE and is fast, well tolerated and effective. Contrast associated nephropathy remains a consideration though is much less common with modern low molecular weight contrast.

• Generally, harm of contrast nephropathy is overstated and harm of missing PE is understated. Remember that mortality from PE is sometimes preventable and that in the acute setting if you need a contrasted study you should get a contrasted study and deal with the aftermath afterwards. 

• Can also potentially differentiate between acute and chronic PE based on presence of collateral vessels, occlusive vs nonocclusive clot, intimal irregularities and calcifications 

• Can evaluate for total clot burden

• Can evaluate for evidence of RV strain i.e. reflux of contrast into IVC, RV to LV size (especially on 3D reconstruction of 4 chamber view), interventricular septum bowing into LV.

6. V/Q Scans:

• Data comes from PIOPED study in 1990. Medically this is seen as older data that may not be viable in the 2020s. 

• Evaluates regions of V/Q mismatch

• Not always available based on needing specialized equipment and personnel.

• V/Q mismatch is not specific for PE and oftentimes underlying pathology in lung or heart function can lead to indeterminate results.

• Almost never the correct answer in real practice despite being tested regularly in medical education.

7. PaCO2: EtCO2 difference

• Typically arterial CO2 (PaCO2) is slightly higher than End-Tidal CO2 (EtCO2) i.e. 40 mmHg vs 38 mmHg. This difference is due to some exhaled CO2 being trapped in anatomic and physiologic deadspace in airways. If the difference between PaCO2 and EtCO2is > 5 mmHg this can indicate an excessive amount of respiratory dead space (often due to poor cardiac function leading to poor delivery of CO2 to the lungs.)

Treatment of pulmonary embolism:

• Treatment of PE can be a complex endeavour and often is a multifaceted process. 

• This process requires incorporation of clinical decision making tools such as POCUS and laboratory studies, a understanding of pathophysiology, a ability to utilize that understanding of pathophysiology to effectively titrate interventions and a Multi-disciplinary approach. 

• Successful treatment can lead to drastic clinic improvement and is very rewarding.

• More in part 2…

Audio

Video

• References

• RCTs Discussed

  PIOPED Study ()

• See Also