Use of Sildenafil to Facilitate Weaning From Inhaled Nitric Oxide in Children With Pulmonary Hypertension Following Surgery for Congenital Heart Disease

Abstract

Pulmonary hypertension frequently complicates the postoperative management of patients after congenital cardiac surgery. Inhaled nitric oxide is an effective treatment option, but rebound pulmonary hypertension can occur upon its withdrawal. Sildenafil may facilitate its withdrawal by restoring cyclic guanosine monophosphate availability via phosphodiesterase-5 inhibition. The purpose of this study was to evaluate the use of sildenafil in facilitating weaning from inhaled nitric oxide after congenital cardiac surgery in patients who had previously failed weaning, and to compare the effects of sildenafil on pulmonary and systemic hemodynamics. Children who received sildenafil after cardiovascular surgery during a 23-month period at Riley Hospital for Children were identified. Medical records were retrospectively reviewed to determine sildenafil and nitric oxide dosing, pulmonary and systemic blood pressures, and adverse effects. Oral sildenafil was administered to 7 children who had failed attempts at inhaled nitric oxide weaning. Inhaled nitric oxide was weaned from 29.8 ± 5.9 ppm prior to sildenafil initiation to 12.2 ± 3.4 ppm (mean ± SE; P = .024) in the 24 hours after sildenafil. Mean pulmonary artery and systemic arterial pressure were unchanged from baseline when measured 1 hour after sildenafil dosing (mean pulmonary artery pressure, 29 ± 1 to 27 ± 0.7 mm Hg, P = .066; mean systemic arterial pressure, 56 ± 1.2 to 54 ± 1.2 mm Hg, P = .202). Sildenafil may facilitate withdrawal of inhaled nitric oxide and prevent rebound pulmonary hypertension in patients previously failing inhaled nitric oxide weaning attempts.

Sildenafil for the Treatment of Pulmonary Hypertension in Pediatric Patients

“…Treatment with sildenafil significantly reduced iNO requirements within 24 h and facilitated iNO weaning for all seven patients [49]. Case reports describe similar observations [4,5,56,70].…”

“…Rebound PHTN, presenting as an acute increase in PAP and cardiopulmonary instability, can complicate the withdrawal of iNO. Two small studies [49,58] in addition to several case reports [4,5,42,70] have identified sildenafil as a means for minimizing rebound PHTN and the need for prolonged iNO therapy. Namachivayam et al [58] demonstrated sildenafil's efficacy to facilitate iNO weaning of 29 infants and children.…”

“…A recent study by Lee et al [49] examined seven children with congenital heart disease who previously had failed iNO weaning attempts before the initiation of oral sildenafil (0.22-0.47 mg/kg 4 times daily). Treatment with sildenafil significantly reduced iNO requirements within 24 h and facilitated iNO weaning for all seven patients [49].…”

Reducing Variation in the Use of Inhaled Nitric Oxide

“…21,22 In pediatric patients who failed to be weaned from iNO after surgery for congenital heart disease, sildenafil has been shown to facilitate weaning. 23 Our first step toward obtaining CTICU staff buy-in for iNO initiation and weaning guidelines was review of the patients and iNO usage from the previous year. The inconsistent initiation and weaning (or not weaning) was obvious.…”

Idiopathic Pulmonary Arterial Hypertension in Children: A Review

“…Sildenafil serum levels peak at 1-2 h after oral dose, which is important to know to monitor for adverse effects such as hypotension, flushing, nasal congestion, priapism and agitation. Sildenafil is particularly beneficial in post-operative patients in preventing rebound PH at the time of iNO withdrawal [141][142][143][144][145].…”