Pulmonary Thrombo Embolism: When to Thrombolyse?

Dr. K. Lakshmanan, Dr. S. Inbarasu, Dr. Vinodh Selvin, Dr. A.P.S. Kannan, Dr. Yogesh, Dr. 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 a suspected pulmonary embolism. Often doing CTPA on a critically ill patient is not only challenging but also can be time-consuming. Thus, where CTPA is not possible, we can shorten the time to correct diagnosis by diagnosing PE at the bedside. Appropriate selection and administration of thrombolytic agents would decrease morbidity and mortality.

Keywords: Pulmonary Thromboembolism, Thrombolysis

Case Presentation

A 36 years old male, who is a chronic smoker, with no known comorbidities, came with complaints of palpitation, chest pain and breathlessness for 2 days, and with history of a syncopal attack.

On examination he was found to have tachycardia and tachypnea.

Vitals: HR 145/min, BP 145/85, SpO2 94%, RR: 35/min.

Baseline blood investigations were normal. Coagulation profile was also normal. Troponin I and Pro BNP were elevated. ECG displayed sinus tachycardia. ECHO showed RA and RV dilation with Pulmonary Hypertension, and acute Tricuspid Regurgitation presence of a thrombus in the Right Atrium (RA).

CT pulmonary angiography showed the presence of a thrombus in right pulmonary artery and diagnosis of PE was concluded.

Clinical Evolution

Day 1: Patient planned for thrombolysis with streptokinase with 3 lakh units as IV bolus followed by 1 Lakh units per hour infusion.

Day 2: Patient was symptomatically better. The thrombolytic therapy was continued for another 24 h. Infusion Streptokinase was stopped after 48 h.

Day 3: Patientâ€™s vitals were stable and symptoms resolved completely. Repeat ECHO showed normal RA and RV size with no thrombus in RA.TR was also absent. The patient initiated on unfractionated heparin and Double Anti Platelet (DAP) therapy.

Day 4: Patient was transferred from ICU. Oral feeding was encouraged with both liquids and solids. Patient maintained saturation with 6L 02. Diuretics were added to reduce RV strain.

Day 6: Patient was initiated on Novel Oral Anti-Coagulant (NOAC) (T. Riveroxaban 10 mg). DAP therapy continued.

Day 6: Ultra Fractionated Heparin (UFH) and diuretics were stopped. Patient continued on DAP therapy and the NOAC.

Day 7: Patient was discharged on the NOAC along with Antiplatelets (T. Ecospirin 75 mg) (T. Brilinta 90 mg) and PDE inhibitors (T. Sildenafil 20 mg).

Discussion

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 an 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.

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. Confirmation 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 )

Treatment

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.

Thrombolic 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 1: Thrombolytic agents and doses

Conclusion

VTE and PE remain preventable causes of morbidity and mortality:

References

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

[2] 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society. Eur Heart J. 2020;41(4):543â€“603.