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

Laura C Price; Benjamin Garfield; Caroline Bleakley; Archie G M Keeling; Charles Mcfadyen; Colm McCabe; Carole A Ridge; Stephen J Wort; Susanna Price; Deepa J Arachchillage

doi:10.1177/2045894020973906

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

Pulm Circ. 2020 Dec 15;10(4):2045894020973906. doi: 10.1177/2045894020973906. eCollection 2020 Oct-Dec.

Authors

Laura C Price^{1

2}, Benjamin Garfield^{1

2

3}, Caroline Bleakley³, Archie G M Keeling⁴, Charles Mcfadyen³, Colm McCabe^{1

2}, Carole A Ridge⁵, Stephen J Wort^{1

2}, Susanna Price^{2

3}, Deepa J Arachchillage^{6

7

8}

Affiliations

¹ National Pulmonary Hypertension Service, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
² National Heart and Lung Institute, Imperial College London, London, UK.
³ Department of Intensive Care Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
⁴ Department of Radiology, King's College Hospital, London, UK.
⁵ Department of Radiology, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
⁶ Department of Haematology, Royal Brompton & Harefield NHS Foundation Trust, London, UK.
⁷ Department of Immunology and Inflammation, Imperial College London, London, UK.
⁸ Department of Haematology, Imperial College Healthcare NHS Trust, London, UK.

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.

Keywords: Coronavirus disease 19 (COVID-19); acute respiratory distress syndrome (ARDS); dual energy computed tomography; microthrombosis; thrombolysis.