Pulmonary Thrombo Embolism: A state of the art review

K. Lakshmanan, S. Inbarasu, Vinodh Selvin, A.P.S. Kannan, Yogesh, S.M. Suresh Babu

Department of Anesthesiology, Kauvery Hospital, Tirunelveli

Abstract

Pulmonary embolism ( PE) is the third most common cause of cardiovascular death. Multidetector computed tomography pulmonary angiography (CTPA) is the investigation of choice in imaging a patient with suspected pulmonary embolism.

Keywords: Pulmonary Thromboembolism, Thrombolysis

Pathophysiology

Acute PE interferes with both circulation and gas exchange. RV failure due to pressure overload is considered the primary cause of death in severe PE. Pulmonary Artery Pressure (PAP) increases if >30 to 50% of the total cross-sectional area of the pulmonary arterial bed is occluded by thromboembolism. PE induced vasoconstriction mediated by the release of thromboxane A2, and serotonin, contribute to the initial increase in Pulmonary Vascular Resistance (PVR) after PE. Anatomical obstruction and hypoxic vasoconstriction in the affected lung area lead to increase in PVR, and a proportional decrease in arterial compliance. The abrupt increase in PVR results in RV dilation. Increase in RV pressure and volume leads to an increase in wall tension and myocyte stretch. The contraction time of RV is prolonged, while neurohumoral activation leads to inotropic and chronotropic stimulation. Together with systemic vasoconstriction, these compensatory mechanisms increase PAP, improving flow through the obstructed vascular bed and thus temporarily stabilizing BP. Prolongation of RV contraction time impacts early diastole in the left ventricle by leftward bowing of the interventricular septum. The desynchronization of the ventricles may be exacerbated by the development of Rt Bundle Branch Block (RBBB). As a result LV filling is impaired and this may lead to decrease in cardiac output and contribute to systemic hypotension and hemodynamic instability. The finding of massive infiltrates of inflammatory cells in the RV myocardium of patients who died within 48hrs of acute PE may be explained by high levels of epinephrine released as a result of PE induced myocarditis. Finally, the association between elevated circulating levels of biomarkers of myocardial injury and an adverse early outcome indicates that RV ischemia is of pathophysiological significance in the acute phase of PE.

Respiratory failure in PE is predominantly a consequence of hemodynamic disturbances. Zones of reduced flow in obstructed pulmonary arteries, combined with zones of overflow in the capillary bed served by non-obstructed pulmonary vessels, result in ventilation/perfusion mismatch, which contributes to hypoxemia. Finally, even if they do not affect hemodynamics, small distal emboli may create areas of alveolar hemorrhage resulting in haemoptysis, pleuritis and pleural effusion, which is usually mild. This clinical presentation is known as Pulmonary Infarction.

In view of the above pathophysiological considerations, acute RV failure, defined as a rapidly progressive syndrome with systemic congestion resulting from impaired RV flow output, is a critical determinant of clinical severity and outcome in acute PE.

Table 1: Strength of recommendations

Table 2: Level of evidence

Table 3. Guidelines, 2019

Table 4. Changes on recommendations

Strong risk factors foe pulmonary embolism

Fracture of lower limb
Hospitalizatiomn for CHF or AF within previous 3 months
Hip or knee replacement
Major Trauma
Myocardial infarction within previous 3 months
Previous VTE
Spinal Cord injury

Moderate risk factors for Pulmonary Embolism

Arthroscopic knee surgery
Autoimmune disease
Blood Transfusions
Central venous lines
IV catheters
Chemotherapy
CHF, Respiratory Failure
Hormone replacement therapy
In vitro fertilisation, Oral contraceptive therapy
Post Partum period, Infection, Inflammatory bowel disease
Cancer, Thrombophilia
Superficial vein thrombosis, Paralytic stroke

Weak risk factors

Bed rest >3 days, DM
Laproscopic surgery, Obesity
Arterial hypertension, Pregnancy
Immobility, obesity
Increasing age, Varicose vein.

Table 5. Geneva Clinical Prediction Rule.

As clinical judgement lacks standardization, several explicit clinical prediction rules has been developed. The most frequently used prediction rules are the revised Geneva rule and the Wells rule. A direct prospective comparison of these rules confirmed a similar diagnostic performance.

Clinical features

Acute PE is a well-recognised cause of sudden cardiac arrest. The most common clinical manifestations of massive/submassive PE include unilateral/bilateral lower limb or upper limb swelling following immobility, dyspnea, hypoxia, pleuritic chest pain, cough, hemoptysis and hemodynamic instability. Chest pain is a common symptom arising from pulmonary infarct.

Pulmonary Embolism Classification

Massive: Hemodynamic instability present.
Submassive: RV strain present but no hemodynamic instability.
Nonmassive: NO RV strain or hemodynamic instability.

Diagnostic markers

D-Dimer: In acute PE it has high negative predictive value but poor positive prognostic value. Thus, a normal D dimer may exclude PE but elevated D dimer values are not diagnostic of it. The specificity of D dimer decreases with age. Using age adjusted D Dimer values for patients >50yrs age*10mcg/L.

Troponins: Serum troponin levels are often elevated in acute PE, but they are prognostic rather than diagnostic. They may be early markers for right ventricular dysfunction and elevated levels predict an adverse outcome.

BNP-RV pressure overload causes myocardial stretch leading to rise in BNP, it is not of diagnostic importance but do reflect the severity of RV dysfunction.

Imaging techniques

Chest X-ray

Westermark sign (regional oligemia), Hampton sign (Peripheral wedge opacity), Fleischner sign (enlarged pulmonary artery), Palla sign (enlarged right descending pulmonary artery), Vascular redistribution.

Echocardiographic signs

McConnel’s sign : RV free wall hypokinesia with preserved apical function

Tricuspid Regurgitation: TR max <2.8 m/s is normal. Values between 2.9-3.4m/s is suggestive of intermediate probability and >3.4m/s is suggestive of high probability of PHTN.

Decreases S’- s’ refers to the systolic excursion velocity of the right ventricular basal free wall. AS'<9.5 cm/s indicates right ventricular systolic dysfunction.

Tricuspid Annular Plane Systolic Excursion – TAPSE reflects longitudinal contraction of the RV, which contributes 80% of RV output. A value of <16mm is suggestive of RV dysfunction.

60/60 Sign- PASP <60 mm Hg but >30 mm Hg and RVOT acceleration times <60 ms

Two point Deep Vein Thrombosis Scan

Ideally, DVT scan should be performed at 1cm distance for scanning the entire venous system. Scanning performed in ICU as part of POCUS is the two-point DVT scan. Common femoral vein scanning is done from inguinal ligament until it becomes superficial femoral vein. Popliteal vein scanning is done from where it is parallel to popliteal artery to its trifurcation.

Ultrasonography Scanning Technique

Compression test: First point of compression is at the level of CFV with visualization of the junction of GSV with CFV, as this is an area of high turbulence, thus increased risk of DVT formation. Second point of compression is popliteal fossa to compress popliteal vein. An iso/hypo echoic structure inside the lumen of the vein, which is suggestive of a thrombus

PW and Color Doppler: The presence of constant colour throughout the scanned area of vein on color doppler along with presence of spontaneous flow on PW doppler is suggestive of patent vein.

Respiratory Phasicity: Presence of biphasic flow i.e,, increase in flow in expiration and decrease in inspiration is again suggestive of patent blood flow through the concerned vein. Monophasic flow pattern is indicative of venous thrombosis.

Distal Augmentation Test: Squeezing the vein distal to assessment site like compressing the calf muscle will increase the blood flow in the proximal segment of vein. This will result in an increased spike/ augmentation on PW doppler suggestive of patent vein. Following augmentation a brief doppler silence is present because the vein become empty after compression and the normal flow starts once vein is refilled with arterial inflow.

Table. 6. Recommendations for diagnosis

Treatment

Clinicians should make their treatment decisions for PE based on confidence in the diagnosis of PE, hemodynamic status, degree of RV dysfunction, bleeding risk prognosis and patient preferences. In patients who have a high clinical probability and acceptable bleeding risk, clinicians should initiate anticoagulation upon the initial suspicion of PE and prior to completion of any diagnostic test. Satisfactory exclusion of diagnosis of PE should lead to prompt discontinuation of anticoagulants unless otherwise indicated. Confrmation of PE in the setting of a contraindication to anticoagulation should lead to placement of IVC filter. Hemodynamically unstable patients should undergo initial resuscitation and stabilisation. Vasopressors/ inotropes may lead to improved stability, and resuscitation should include cautious fluid management. Clinicians should use supplemental oxygen and ventilation as demand necessary. Prompt risk stratification will assist with further decisions regarding escalation of care (i.e thrombolytic therapy or embolectomy )

1) Anticoagulation: Anticoagulation acts to prevent new clot formation and decrease risk of recurrent VTE. Anticoagulants that have efficacy for the treatment of PE demonstrated in clinical trials include UFH, LMWH and fondaparinux. However general guidelines suggest using LMWH instead of UFH for non-massive PE.

2) Thrombolytic Therapy: Thrombolytic agents convert plasminogen to plasmin and lead to clot lysis. Thrombolytics may improve short term physiologic measures that include pulmonary perfusion, RV function, Blood pressure. Three thrombolytic agents are currently approved by US food and Drug Administration for the use in patients with acute PE: alteplase, urokinase, streptokinase.

Table 7. Thrombolytic agents and doses

Table 8. Recommendations for acute phase treatment of high risk pulmonary embolism

Table 9. Recommendations for acute phase treatment of intermediate or low risk thromboembolism

Table 10. Treatment of Acute PE

IVC Filters

Studies have demonstrated a decreased risk of PE and an increased risk of DVT, without a significant effect on mortality, associated with IVC filter placement. Guidelines recommend that patient should undergo IVC filter placement if they have a contraindication to or develop VTE on therapeutic doses of anticoagulation. If and when a reversible contraindication to anticoagulation resolves, patient with IVC filters should undergo a standard course of anticoagulation. For patients with massive PE, guidelines recommend consideration of permanent IVC filter placement. Patients with temporary IVC filters should have them removed according to manufacturer and treatment guidelines.

Table 11. Recommenders for IVC Filter

Table 12. Recommendations for the regimen and the duration of anticoagulation after PR in patients without cancer.

Conclusion

VTE and PE remain preventable causes of morbidity and mortality. By combining the features at presentation, clinical suspicion and scoring system, diagnosis may be streamlined and unnecessary treatment may be minimised. Many physicians have training and access to portable ultrasound devices, which may prevent delays in recognition and treatment of VTE and PE. In hospital patients especially those who are critically ill, continue to pose diagnostic dilemmas. In such patients, clinical scoring systems and imaging may be inconclusive. The improved accuracy of helical CT scans has improved our recognition of PE in many of these patients

References

Govil D, et al. Identifying PE in bedside where CTPA is not possible. ISCCM Crit Care 2022:114-19.

2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.

Dr. Lakshmanan

Senior Consultant Anesthesiology

Dr. S. Inbarasu

Consultant Anesthesiology

Dr. A. P. S. Kannan

Consultant Anesthesiology

Dr. S.M. Suresh Babu

Consultant Anesthesiology

Pulmonary Thrombo Embolism: A state of the art review