Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children

Rationale: Rebound pulmonary hypertension (PHT) can complicate the weaning of nitric oxide (NO), and is in part related to transient depletion of intrinsic cyclic guanosine monophosphate. Rebound is characterized by increased pulmonary arterial (PA) pressure, cardiopulmonary instability, and in some cases, the need to continue NO beyond the intended period of use. There is anecdotal evidence that sildenafil, a phosphodiesterase-5 inhibitor, may prevent recurrence of rebound. Objectives: We investigated the role of sildenafil in preventing rebound (an increase in PA pressure of 20% or greater, or failure to discontinue NO) in patients in whom previous attempts had not been made to wean from NO. Methods: Thirty ventilated infants and children, receiving 10 ppm or greater inhaled NO, were randomized to receive 0.4 mg/kg of sildenafil, or placebo, 1 h before discontinuing NO. Twenty-nine patients completed the study. Measurements: PA pressures and blood gases were measured before the study drug, and 1 and 4 h after stopping NO. Main Results: Rebound occurred in 10 of 14 placebo patients, and 0 of 15 sildenafil patients (p < 0.001). PA pressure increased by 25% (14-67) in placebo patients, and by 1%(-9-5) in sildenafil patients (p < 0.001). Four placebo patients could not be weaned from NO due to severe cardiovascular instability, whereas all sildenafil patients were weaned (p = 0.042). Duration of ventilation after study was 98.0 (47.0-223.5) h for placebo patients and 28.2 (15.7-54.6) h for sildenafil patients (p = 0.024). Conclusion: A single dose of sildenafil prevented rebound after withdrawal of NO, and reduced the duration of mechanical ventilation. Prophylaxis with sildenafil should be considered when weaning patients from inhaled NO.