Rescue therapy with thrombolysis in patients with severe COVID-19-associated acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome in patients with Coronavirus disease 19 is associated with an unusually high incidence of pulmonary embolism and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19-associated acute respiratory distress syndrome with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular dysfunction on echocardiography, who were treated with alteplase as fibrinolytic therapy. All patients were non-smokers, six (86%) were male and median age was 56.7 (50–64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n = 4), inhaled nitric oxide (n = 5) and nebulised epoprostenol (n = 2). The median duration of mechanical ventilation prior to thrombolysis was seven (5–11) days. Systemic alteplase was administered to six patients (50 mg or 90 mg bolus over 120 min) at 16 (10–22) days after symptom onset. All received therapeutic heparin pre- and post-thrombolysis, without intracranial haemorrhage or other major bleeding. Alteplase improved PaO2/FiO2 ratio (from 97.0 (86.3–118.6) to 135.6 (100.7–171.4), p = 0.03) and ventilatory ratio (from 2.76 (2.09–3.49) to 2.36 (1.82–3.05), p = 0.011) at 24 h. Echocardiographic parameters at two (1–3) days (n = 6) showed right ventricular systolic pressure (RVSP) was 63 (50.3–75) then 57 (49–66) mmHg post-thrombolysis (p = 0.26), tricuspid annular planar systolic excursion (TAPSE) was unchanged (from 18.3 (11.9–24.5) to 20.5 (15.4–24.2) mm, p = 0.56) and right ventricular fractional area change (from 15.4 (11.1–35.6) to 31.2 (16.4–33.1)%, p = 0.09). At seven (1–13) days after thrombolysis, using dual energy computed tomography imaging (n = 3), average relative peripheral lung enhancement increased from 12.6 to 21.6% (p = 0.06). In conclusion, thrombolysis improved PaO2/FiO2 ratio and ventilatory ratio at 24 h as rescue therapy in patients with right ventricular dysfunction due to COVID-19-associated ARDS despite maximum therapy, as part of a multimodal approach, and warrants further study.