In Situ Pulmonary Thrombolysis and Perfusion Lung Angiography in Severe COVID-19 Respiratory Failure.

UNLABELLED

A proof-of-concept study using thrombolysis with catheter-directed tissue plasminogen activator (tPA) and pulmonary angiography imaging was performed to visualize perfusion deficits and reperfusion/therapeutic effects of tPA.

DESIGN

A prospective, open-label, compassionate study. Descriptive statistics were presented for categorical variables and as means with sds for continuous variables. The Wilcoxon test was used to determine the differences between the two-related samples and a test for continuous variables. Statistical significance was set at value of less than 0.05. Agreement between observations was evaluated using the Kappa Cohen index and overall agreement using the Fleiss Kappa coefficient.

SETTING

A single COVID-19 ICU of Mexico´s General Hospital Dr Eduardo Liceaga.

SUBJECTS

Fifteen patients with severe Delta variant severe acute respiratory syndrome coronavirus 2 infection, 18-75 years old, requiring mechanical ventilation with a persistent Fio requirement of 70% or higher and Pao/Fio ratio (or imputed ratio) less than 150 for more than 4 hours. The coagulation inclusion criteria were International Society on Thrombosis and Haemostasis score greater than 5, and presence of a d-dimer greater than 1,200, with viscoelastic testing using rotational thromboelastometry (Instrumentation Laboratories, Mexico City, Mexico) showing both hypercoagulability (EXTEM amplitude at 5 min > 65 FIBTEM > 30) and hypofibrinolysis (EXTEM maximum lysis < 8%).

INTERVENTIONS

Catheter-directed tPA angiography and iFlow system analysis to assess pre-tPA baseline pulmonary perfusion and changes in response to thrombolysis.

RESULTS

Nine patients had microvascular filling defects demonstrated by angiography, and good agreement was found with iFlow analysis (ƙ = 0.714). Statistically significant differences were identified in the area under the curve (AUC) region of interest/AUC reference tissue with and without filling defects in phase 2 DM -0.09206 (sd ± 0.16684) ( = 0.003). The Pao/Fio values measured immediately and 48 hours after the procedure were significantly higher ( = 0.001 and = 0.005, respectively). Statistically significant differences were found in d-dimer values ( = 0.007), Fio ( = 0.002), and oxygen saturation in arterial blood/Fio ( = 0.045), as well as in the number of patients who required prone positioning before, immediately after the procedure, and at 48 hours after the procedure ( = 0.002).

CONCLUSIONS

Thrombolysis with catheter-directed tPA resulted in imaging evidence via pulmonary angiography and iFlow technology of improved lung perfusion in COVID-19 patients with severe respiratory failure.