Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial.

BACKGROUND: SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. METHODS: Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. RESULTS: Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04). CONCLUSIONS: No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. TRIAL REGISTRATION: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .

COVID-19 pneumonia: Perfusion abnormalities shown on subtraction CT angiography in apparently well-ventilated lungs. A prospective cohort study.

Purpose: To evaluate whether a subtraction CT angiography (sCTA) perfusion score may have prognostic value in patients with COVID-19 pneumonia. Method: This prospective cohort study included adult patients with RT-PCR-confirmed SARS-CoV-2 infection admitted to the ED and a sCTA performed within 24 h of admission between June and September 2020. Perfusion abnormalities (PA) in areas of apparently spared lung parenchyma on conventional CT images were assessed with sCTA perfusion score. Airspace disease extension was assessed with CT severity scores, which were then correlated with clinical outcomes (admission to ICU, requirement of IMV, and death). Inter-rater reliability (IRR) was assessed using Cohen's Kappa. Independent predictors of adverse outcomes were evaluated by multivariable logistic regression analyses using the Hosmer and Lemeshow's test. Results: 191 patients were included: 112 males (58%), median age of 60.8 years (SD ± 16.0). The IRR was very high (median Kappa statistic: 0.95). No association was found between perfusion CT scores and D-dimer levels (Kendall's Tau-B coefficient = 0.08, p = 0.16) or between PaO2/FiO2 ratios and D-dimer levels (Kendall's Tau-B coefficient = -0.10, p = 0.07). Multivariate analyses adjusting for parenchymal disease extension, vascular beaded appearance, pulmonary embolism, sex, and age showed that severe PA remained a significant predictor for ICU admission (AOR: 6.25, 95% CI 2.10-18.7, p = 0.001). The overall diagnostic capacity of this model was adequate (ROC AUC: 0.83; 95% CI 0.77-0.89). Conclusions: The assessment of pulmonary perfusion abnormalities in areas of apparently spared lung parenchyma on conventional CT images via sCTA perfusion scoring has prognostic value in COVID-19 pneumonia.

Plasmaféresis en el síndrome de Guillain-Barre: evaluación preliminar / Plasmapheresis in Guillain-Barre syndrome: preliminary evaluation

El síndrome de Guillain-Barré es la causa más frecuente de parálasis fláccida aguda. El tratamiento actual se basa en reposo, apoyo kinésico y asistencia ventilatoria, cuando se requiere. En su patogenia se ha encontrado anticuerpos anti nervio periférico humano, intentándose Plasmaféresis (PF) para removerlos, sin embargo existen aún pocos resultados anecdóticos publicados. Se presenta la experiencia preliminar con este tipo de terapia en el hospital FACH, entre 1986 y 1993. Se evaluaron 7 pacientes, clasificándolos según escala de gravedad. Se investigó la presencia de cuadro viral previo, duración de los síntomas, latencia entre el inicio de éstos, ingreso e incio de PF, protocolo de ésta y sus complicaciones, período de recuperación, complicaciones asociadas, necesidad de tratamiento esteroidal y duración de la hospitalización. Cinco pacientes fueron hombres. La edad fluctuó entre los 15 y 75 años (promedio 38 años); con evolución clínica previa entre 4 horas y 7 días. Sólo dos pacientes tienen el antecedente de cuadro viral. Un paciente fue clasificado en grado III, 4 en grado IV y 2 en grado V, realizándose PF en estos dos últimos grupos (4 hombres y 2 mujeres), entre las 18 horas y 6 días de su ingreso. En todos se realizó PF intermitente, con un promedio de 5 sesiones con 7 a 13 ciclos cada vez con reposición de volúmen variable. En un paciente se suspendió por hipotensión severa y otro presentó complicaciones asociadas (insuficiencia respiratoria y sépticas), requiriendo tratamiento esteroidal y antibióticos. El período de recuperación (capacidad de deambular con apoyo) fue de 47,4 días; y 55,8 días de hospitalización, en promedio. Los resultados no concuerdan con los publicados, en los PF acorta en un 50 por ciento el período de recuperación (19 versus 40 días) desde grado IV a III; sin embargo, debido a las muchas variables en juego, se hace muy dificil comparar estas cifras. Tal vez debería someterse a estos pacientes a PF continua precoz con criterios normados de inclusión al tratamiento, para optimizar los resultados