Sildenafil Therapy for Pulmonary Hypertension Before and After Pediatric Congenital Heart Surgery

摘要

Pulmonary hypertension associated with pediatric congenital heart defects is a major cause of postoperative morbidity and death. Sildenafil has been combined with inhaled nitric oxide to treat pulmonary hypertension. We retrospectively studied the pre- and postoperative effects of oral sildenafil as monotherapy in children with pulmonary hypertension who underwent surgery to correct congenital cardiac defects. From September 2005 through November 2009, 38 children with moderate-to-severe pulmonary arterial hypertension (pulmonary arterial/aortic pressure ratio, >0.7) underwent cardiac surgery at our institution. Fifteen patients were given sildenafil (0.35 mg/kg, every 4 hr) orally or through nasogastric tubes 1 week before and 1 week after surgery. Twenty-three patients of comparable medical status were given sildenafil only upon the institution of cardiopulmonary bypass and for 1 week after surgery. Postoperatively, the 15 patients who were given preoperative sildenafil had significantly lower mean pulmonary arterial pressures (25.6 ± 3.1 vs 30.4 ± 5.7 mmHg; P = 0.005) and pulmonary arterial/aortic pressure ratios (0.35 ± 0.05 vs 0.42 ± 0.07; P = 0.002) than did the other 23 patients. The preoperative therapy also shortened cardiopulmonary bypass time, mechanical ventilation time, and lengths of intensive care unit and hospital stays. No sildenafil-related hypertensive crises or sequelae occurred. As monotherapy, oral sildenafil in low doses appears to control pulmonary hypertension safely and effectively in children undergoing operations to correct congenital heart defects, particularly when it is given both preoperatively and postoperatively. Further study is warranted. Key words: 3′,5′-cyclic-GMP phosphodiesterases/antagonists & inhibitors, antihypertensive agents/therapeutic use, heart defects, congenital/surgery, hemodynamics/drug effects, hypertension, pulmonary/drug therapy/prevention & control, piperazines/therapeutic use, postoperative complications/prevention & control, sildenafil, treatment outcome, vasodilator agents/therapeutic use Pulmonary hypertension (PH) associated with congenital heart defects in children is a major cause of postoperative morbidity and death. 1 Inhaled nitric oxide (NO), a selective pulmonary vasodilator, has been the therapy of choice for controlling PH after cardiac surgery. The activation of soluble guanylate cyclase converts guanine triphosphate to cyclic guanosine monophosphate (cGMP), which in turn leads to the activation of protein kinases and to subsequent vascular relaxation. 2 Life-threatening sequelae can occur when inhaled NO is abruptly discontinued. Sildenafil citrate has been used to treat PH in adults and children. 3–8 Sildenafil is a selective phosphodiesterase-5 inhibitor. 9 Phosphodiesterase 5 specifically hydrolyzes 3′, 5′-GMP. Sildenafil produces acute and relatively selective pulmonary vasodilation and acts synergistically with inhaled NO. 10–13 Available evidence suggests that sildenafil has useful effects in PH, particularly in chronic therapy and in attenuating rebound effects after inhaled NO is discontinued. 2,8 Sildenafil is well tolerated and available as an oral preparation, which is advantageous for patients with PH whose symptoms do not warrant a continuous intravenous infusion. Nonetheless, dosage levels vary widely, and few data are available to suggest dosage regimens for children. This retrospective study was performed to investigate the effect of oral sildenafil as monotherapy in controlling pre- and postoperative PH in children undergoing congenital cardiac surgery.