Effect of intravenous sildenafil on pulmonary hemodynamics and gas exchange in the presence and absence of acute lung injury in piglets

Sildenafil is becoming increasingly popular for the treatment of pulmonary hypertension. However, there are potential concerns regarding its effects on oxygenation and systemic hemodynamics that could theoretically reduce its utility in the neonatal population. We performed a prospective cumulative dose-response study of increasing doses of i.v. sildenafil (0.4, 1, and 3 mg/kg) on hemodynamics and oxygenation in 32 anesthetized piglets, of which 17 had meconium-induced pulmonary hypertension and lung injury, and 15 did not. Sildenafil caused a reduction in mean pulmonary artery pressure and pulmonary vascular resistance (PVR) at all doses, in non-lung-injured animals. There was no difference in pulmonary hemodynamics between doses. Oxygenation index [OI = mean airway pressure (cm H2O) * FiO2 * 100/PaO2 (mm Hg)] did not reach critical levels at any dose. In lung-injured animals, sildenafil also reduced mean pulmonary artery pressure and PVR by 30%. Again, this effect was achieved at the lowest dose, without subsequent changes at higher doses. However, in lung-injured animals, sildenafil produced a dose-related increase in oxygenation index. Sildenafil reduced the systemic vascular resistance (SVR) at the lowest dose in lung-injured animals, but this occurred only at higher doses in non-lung-injured animals. In conclusion, sildenafil is a potent pulmonary vasodilator. However, it should be administered with caution in the presence of lung injury because of a dose-related increase in oxygenation index and concomitant systemic vasodilatation.