Continuous and intermittent administration of intravenous sildenafil in critically ill infants with pulmonary hypertension

Abstract

Intravenous (IV) sildenafil may be administered as a continuous infusion or intermittent bolus dosing in infants with pulmonary hypertension (PH). We aimed to compare these delivery methods.Methods: We retrospectively evaluated subjects less than 12 months old treated with IV sildenafil for PH. Vital signs, oxygen requirement, vasoactive-inotropic score (VIS), and echocardiogram results before and after sildenafil initiation, and the need for discontinuation due to side effects, were noted.Results: Forty-three subjects were identified (23 continuous, 20 intermittent). There were clinically significant differences in PH classifications between groups. The continuous group was significantly younger (p = 0.010) with higher baseline severity of illness suggested by higher inspired oxygen (FiO 2 ) and VIS (p = 0.012). After sildenafil initiation, there were no significant differences in changes in blood pressure, oxygen saturation, FiO 2 , or VIS between groups, and no difference in the number of subjects requiring discontinuation due to side effects (4 continuous, 1 intermittent, p = 0.351). Eight continuous group subjects (34.8%) and 3 intermittent group subjects (15.0%) died (p = 0.024), but echocardiographic improvement in PH degree was more common in the continuous group (77.8% vs. 33.3%, p = 0.007). Conclusion:In this small cohort of infants treated with continuous or intermittent IV sildenafil, in the setting of different baseline characteristics between groups, there were no significant differences in changes in vital signs, VIS, FiO 2 , or need for discontinuation of therapy due to side effects. Higher continuous group mortality may be explained by greater baseline illness severity, but larger prospective, randomized studies are required to investigate these different delivery methods.

Intravenous sildenafil for treatment of early and late pulmonary hypertension in preterm infants

“…Our results illustrate, that intravenous sildena l treatment is associated with a signi cant and rapid reduction of the PH severity. This is in line with previous studies on infants with PPHN and neonates suffering from PH due to congenital lung disease or BPD-PH [15,19,30,31,33]. According to our results, the RVD improves signi cantly during the continuous sildena l infusion.…”

“…In recent prospective trials intravenous sildena l treatment was evaluated in neonates with a gestational age >34 weeks , but data on intravenous sildena l in ELGAN and ELBW preterm infants <28 GA are still lacking [13,14]. Several studies analyzed oral sildena l treatment and only two recent studies were identi ed analyzing intravenous sildena l treatment including ELBW infants with PH [15,17,30,31]. In most of these infants PH was diagnosed secondary to the timepoint of BPD diagnosis (36 weeks of GA).…”

“…Sildena l is available as intravenous (continuous and intermittent) and oral (sildena l-citrate) form of administration. In recent years, several studies evaluated sildena l as treatment for PH (BPD-PH, PPHN) in preterm and term infants in prospective trials [13][14][15]. The majority of the studies published to date and included in the Cochrane review of sildena l treatment for PH (2017) were exclusively enrolling neonates with a GA > 34 weeks [16].…”

Intravenous sildenafil for treatment of early pulmonary hypertension in preterm infants

“…In recent prospective trials intravenous sildenafil treatment was evaluated in neonates with a gestational age > 34 weeks, but data on intravenous sildenafil in ELGAN and VLBW preterm infants < 28 GA are still lacking 13 , 14 . Several studies analyzed oral sildenafil treatment and only two recent studies were identified analyzing intravenous sildenafil treatment including VLBW infants with PH 15 , 17 , 30 , 31 . In most of these infants PH was diagnosed secondary to the timepoint of BPD diagnosis (36 weeks of GA).…”

“…Sildenafil is available as intravenous (continuous and intermittent) and oral (sildenafil-citrate) form of administration. In recent years, several studies evaluated sildenafil as treatment for PH (BPD-PH, PPHN) in preterm and term infants in prospective trials 13 – 15 . The majority of the studies published to date and included in the Cochrane review of sildenafil treatment for PH (2017) were exclusively enrolling neonates with a GA > 34 weeks 16 .…”