Effectiveness of alprostadil dose titration in neonates with congenital heart disease

Purpose: Alprostadil maintains patency of the ductus arteriosus in neonates with congenital heart disease.  At recommended doses (0.05-0.1 mcg/kg/min), alprostadil produces apnea in 20-30% of patients.  Use of doses ≤ 0.02 mcg/kg/min has been suggested to lower the incidence of apnea, but the effectiveness of this strategy has not been well studied.  The purpose of this study was to evaluate the effect of alprostadil dose reduction on maintenance of ductal patency and the incidence of apnea.     

Methods: A single-center retrospective study was conducted in infants receiving alprostadil between 6/1/06 and 6/3/12.  Demographic data, alprostadil dosing information, and apneic events were assessed.  Data were analyzed with paired t-tests. 

Results: Two hundred neonates were evaluated.  Mean (±SD) weight and gestational age were 3.04±0.70 kg and 37.8±2.3 weeks.  The most frequent diagnoses were transposition of the great arteries, hypoplastic left heart syndrome, and coarctation of the aorta.  Alprostadil was initiated at 0.05±0.03 mcg/kg/min (range 0.01-0.2 mcg/kg/min).  The mean treatment duration was 10.3±17.0 days. Ductal patency was achieved in all but one patient. The dose at discontinuation (0.02±0.02 mcg/kg/min; range 0.005-0.1 mcg/kg/min) was significantly lower than the initial dose (p<0.0001).   Dose reduction was achieved in 140 patients (70%). Ductal patency was maintained with doses ≤ 0.02 mcg/kg/min in 121 patients (61%).  Twenty-five (13%) required an increase due to worsening oxygenation or ductal narrowing, but only eight remained on higher doses at the end of treatment.  Fifty-nine patients (30%) developed apnea, at an average dose of 0.08±0.12 mcg/kg/min.  Forty-eight (81%) had a dose > 0.02 mcg/kg/min at the time of their first event. Dose reduction produced resolution of apnea in 35 patients (59%).  

Conclusions: Alprostadil can be successfully reduced to doses ≤ 0.02 mcg/kg/min in most neonates while maintaining ductal patency. This strategy may be useful in minimizing alprostadil-induced apnea without reducing efficacy.