Dataset Information

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

ABSTRACT: 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 t test for continuous variables. Statistical significance was set at p 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 Fio₂ requirement of 70% or higher and Pao₂/Fio₂ 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) (p = 0.003). The Pao₂/Fio₂ values measured immediately and 48 hours after the procedure were significantly higher (p = 0.001 and p = 0.005, respectively). Statistically significant differences were found in d-dimer values (p = 0.007), Fio₂ (p = 0.002), and oxygen saturation in arterial blood/Fio₂ (p = 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 (p = 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.

SUBMITTER: Perez-Calatayud AA

PROVIDER: S-EPMC8966962 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Pérez-Calatayud Angel Augusto AA Enriquez-García Rocío R Fareli-González Christian C Barrett Christopher D CD Saldivar-Rodea Carlos Alberto CA Perulles-Marin Jorge J Reyes-Caldelas Miguel Angel MA Rosenberg-Contreras Carlos Ivan CI Gómez-Moreno Julieta Berenice JB Guerrero-Avendaño Guadalupe G Serrano-Loyola Raúl R Carrillo-Esper Raúl R Moore Ernest E EE

Critical care explorations 20220329 4

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.<h4>Design</h4>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 <i>t</ ...[more]

PMID: 35372845

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Project description:BackgroundThere have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support.MethodsProspectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient.ResultsFifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p < 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p < 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26).ConclusionsThe response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials.

Project description:BackgroundThere is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.MethodsWe conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.ResultsWe detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5).ConclusionsWe identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).

Dataset Information

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

Design

Setting

Subjects

Interventions

Results

Conclusions

Publications

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

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