Patients with COVID-19 pneumonitis and moderate to severe ARDS treated with sildenafil

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reported to cause pulmonary vascular dysfunction with immunothrombosis, pulmonary embolism, endotheliitis and neoangiogenesis of large vessels in patients. These further lead to increased pulmonary vascular resistance, dead space, and shunt, as well as right ventricular (RV) dysfunction, which can be ameliorated by therapies that modulate endothelial function.

Inhalation of nitric oxide (NO) has been identified to have anti-inflammatory, pulmonary vasodilating, as well as potential antiviral properties. Previous studies have reported sildenafil which is a phosphodiesterase type 5 inhibitor to increase endogenous NO and is also tolerated by patients with pulmonary fibrosis. However, it may worsen the shunt in acute respiratory distress syndrome (ARDS). Sildenafil (Viagra) is a drug used to treat erectile dysfunction and pulmonary arterial hypertension.

A new study published in the British Journal of Anesthesia aimed to determine whether sildenafil could improve gas exchange in patients with ARDS COVID-19 with pulmonary hypertension, right ventricular dysfunction, or both.

Study: Use of sildenafil in patients with severe COVID-19 pneumonitis. Image Credit: Angelo DAmico/Shutterstock

About the study

Sildenafil was given to 25 patients with COVID-19 pneumonitis and moderate to severe ARDS. Oxygenation and carbon dioxide (CO2) clearance were assessed in patients immediately before, 24 h, 48 h and 5 days after sildenafil administration for calculation of the P:F ratio (PaO2:FiO2), ventilation ratio, dead space fraction, and oxygenation index.

Noradrenaline equivalents (NE) and vasoactive-inotropic score (VIS) were used to calculate vasoactive drug dose. Initially, sildenafil was given at 12.5 mg three times a day, increasing to 25 mg if well tolerated. Finally, patients underwent initial and follow-up CT scans and detailed echocardiographic evaluation.

Study results

The results indicated that of the 25 patients, 10 were on venovenous extracorporeal membrane oxygenation (VV-ECMO) and 11 were prone. Pulmonary hypertension, RV dysfunction, or both were detected at baseline in all patients. One patient was taken off sildenafil before discharge from intensive care, while 24 continued it for 12.7 days at 25 mg three times a day.

The results reported an increase in NE and SIV 24 hours after starting sildenafil treatment. The dose of norepinephrine was increased in 14 patients, decreased in 10 patients and remained unchanged in one patient. HR and MAP were stable 24 hours after sildenafil. Additionally, the P:F ratio was observed to increase in non-ECMO patients 24 h after sildenafil, while the dead space and ventilation ratios remained unchanged.

Pulmonary embolism was detected in 17 patients on baseline CT scans, while reduction in pulmonary artery (PA) volume and right atrial area was observed on follow-up CT scans. Decreased cerebral natriuretic peptide (BNP) and hs-troponin were observed before sildenafil up to a delay of 1-2 days for troponin or 1-7 days for BNP. Additionally, pulmonary vascular resistance was reported to decrease and LV cardiac output to increase during the follow-up period.

Nine patients (four ECMO recipients) died in intensive care, representing a mortality rate of 36%. After the last follow-up, 12 of 13 patients had normal echocardiography, four had mild parenchymal changes, and one had persistent perfusion. fault.

Therefore, the current study determines that sildenafil is safe in carefully selected COVID-19 ARDS patients. No deterioration in oxygenation, hemodynamics or dead space was observed. In addition, sildenafil also did not impair gas exchange. However, the role of sildenafil in the longer term improvement of pulmonary failure remains to be determined.

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