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

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported to cause pulmonary vascular dysfunction with immune thrombosis, pulmonary embolism, endothelitis and neoangiogenesis of major 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 improved by therapies that modulate endothelial function.

Inhalation of nitric oxide (NO) has been identified as having anti-inflammatory, pulmonary vasodilating properties, along with potential antiviral properties. Previous studies have reported that sildenafil, a phosphodiesterase type 5 inhibitor, increases endogenous NO and is also tolerated by patients with pulmonary fibrosis. However, it can aggravate 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 British Journal of Anesthesia was intended to determine whether sildenafil could improve gas exchange in patients with COVID-19 ARDS with pulmonary hypertension, RV dysfunction, or both.

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

About the study

Sildenafil was administered 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 hours, 48 ​​hours and 5 days after sildenafil administration to calculate the P: F ratio (PaO2: FiO2), ventilation ratio, dead space fraction, and oxygenation index.

Norepinephrine equivalents (NE) and the vasoactive inotropic score (VIS) were used to calculate the vasoactive drug dose. Initially, sildenafil was administered with 12.5 mg three times daily, increasing to 25 mg if well tolerated. Finally, patients underwent baseline and follow-up CT scan and detailed echocardiographic assessment.

Survey results

The results indicated that out of the 25 patients, 10 were on venous 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 removed from sildenafil before ICU discharge, while 24 continued with it for 12.7 days with 25 mg three times daily.

The results reported an increase in NE and VIS 24 hours after starting sildenafil treatment. The dose of norepinephrine was increased in 14 patients, decreased in 10 patients and remained unchanged for one patient. HR and MAP were found to be stable 24 hours after sildenafil. In addition, the P: F ratio was observed to increase in non-ECMO patients 24 hours after sildenafil, while the dead space to ventilator ratio remained unchanged.

Pulmonary embolism was detected in 17 patients in baseline CT scans, while a reduction in pulmonary artery (PA) volume and right atrial area was observed in follow-up CT scans. A decrease in brain natriuretic peptide (BNP) and hs-troponin was observed from before sildenafil at a time of 1 to 2 days for troponin or at a time of 1 to 7 days for GDP. In addition, pulmonary vascular resistance was reported to decrease and LV cardiac output was reported to increase during the follow-up period.

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

Therefore, the current study establishes that sildenafil is safe in carefully selected COVID-19 ARDS patients. No deterioration of oxygenation, hemodynamics or dead space was observed. In addition, sildenafil did not impair gas exchange either. However, the role of sildenafil in the long-term improvement of lung failure has not yet been seen.

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