Impact of Oral Sildenafil on Clinical Outcomes while treating PPHN

Background

Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening neonatal syndrome with a high mortality rate. PPHN accounts for approximately 0.8 per 1,000 live births. Inhaled nitric oxide (iNO) is the treatment of choice for PPHN, nevertheless; sildenafil citrate (a selective and potent inhibitor of phosphodiesterase type 5 (PDE5)) is considered the best alternative vasodilator in absence of iNO. Sildenafil can be used in parenteral or oral form.

Aim

To determine the efficacy of oral sildenafil for treating PPHN

Patient Profile

• Newborns diagnosed with PPHN who received oral sildenafil over an 8-year period (n=27)

Methods

Study Design

• Retrospective study

Treatment Strategy

• Patients were put on conventional/high frequency oscillation ventilation
• The treatment comprised of; dobutamine (initial dose; 10 ?g/kg/min), dopamine (initial dose; 10 ?g/kg/min if hypotension was present), fentanyl (for sedation), magnesium sulfate (MgSO₄; if hypoxemia persisted). Oral antibiotics were initiated in case of suspected sepsis and surfactants were administered based on the primary disease.
• Sildenafil was initiated after echocardiographic confirmation of PPHN at starting dose of 1 mg/kg every 6 h, in case the condition worsened the dose was increased to 2 mg/kg every 6 h (50 mg sildenafil tablet was crushed and dissolved in distilled water for use)
• Oxygen saturation was maintained between 90% and 95%
• Weaning stage began with MgSO₄, followed by other inotropes. Sildenafil weaning was initiated only after the neonate was extubated.
• Surviving patients were discharged with sildenafil prescription and its weaning schedule

Outcomes

• Clinical outcomes in sildenafil-treated neonates

Results

• Mean gestational age of the study participants was 36 weeks, mean birth weight was 2800 g, 63% patients (n=17) were male.
• The most common primary disease was respiratory distress syndrome (37%), followed by congenital diaphragmatic hernia (18.5%). Moreover, 29.6% patients presented with shock and 44.4% patients required administration of 100% oxygen, 12 patients (44.4%) died.
• The use of inotropic agents or MgSO₄ was similar between survivors and non-survivors; before and after initiation of sildenafil.
• Presence of cardiovascular shock at presentation was the only difference between survivors vs. non-survivors, all patients presenting with cardiovascular shock died

Conclusions

• Oral sildenafil is a promising medication for treating neonates with mild to moderate PPHN. It may be best used as an adjunctive therapy in neonatal pulmonary hypertension in settings where inhaled nitric oxide is unavailable.
• Treatment protocol should be developed to standardize the care of such infants to reduce mortality and improve the quality of life.

Int J Clin Pediatr. 2019;8(2):27-31.