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

Abstract

Acute respiratory distress syndrome (ARDS) in patients with Coronavirus disease 19 (COVID-19) is associated with an unusually high incidence of pulmonary embolism (PE) and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19 ARDS with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular (RV) dysfunction on echocardiography, who were treated with alteplase as fibrinolytic therapy. All patients were non-smokers, 6 (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 7 (5-11) days. Systemic alteplase was administered to 6 patients (50mg or 90mg bolus over 120 minutes) 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 (PF) 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 twenty-four hours. Echocardiographic parameters at 2 (1-3) days (n=6) showed RVSP was 63 (50.3-75) then 57 (49-66) mmHg post-thrombolysis (p=0.26), TAPSE was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p=0.56) and RV fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1) %, p=0.09). At 7 (1-13) days after thrombolysis, using DECT imaging (n=3), average relative peripheral lung enhancement increased from 12.6 to 21.6% (p=0.06). Conclusion: Thrombolysis improved PF ratio and ventilatory ratio at 24h as rescue therapy in patients with RV dysfunction due to COVID-19 ARDS despite maximum therapy, as part of a multimodal approach, and requires further study.

Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale

“…Hypercapnia has also been linked with the development of ACP and is thought to represent one of the factors responsible for vasoconstriction and the augmentation of pulmonary arterial pressure ( Jardin and Vieillard-Baron, 2009 , Biswas, 2016 , Boissier et al, 2013 ). Furthermore, in our patient, rtPA treatment resulted in the reduction of ventilatory ratio and an improvement in oxygenation status; this concurs with another article that was published recently ( Price et al, 2020 ).…”

In silico drug repurposing in COVID-19: A network-based analysis

“…This observation positively correlates with SARS-CoV-2 infection, where a severe impairment in the coagulation system leading to thrombosis is frequently observed [43] . Indeed, heparin has been tested as a prophylactic treatment and was demonstrated to improve disease-specific mortality [44] . Heparin clearly emerged in our analysis, supporting the potential and accuracy of SAveRUNNER software in identifying repurposable drugs.…”

Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report

“…Previous studies have shown that genetic deletion of the IL-6 receptor does not improve the prognosis of septic mice, while the application of soluble gp130-Fc can significantly reduce the survival rate of CLP mice, decreasing apoptosis of endothelial cells [ 22 ]. In addition, the cytokine storm contains a variety of other inflammatory factors (IL-8, IL-10, IFN-γ and MCP-1, TNF-α, IL-1, and IL-3) [ 23 ]. Blocking IL-6R with tocilizumab alone may be insufficient to improve the prognosis of COVID-19 patients.…”