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Sildenafil a potential nitrous oxide alternative in newborn pulmonary hypertension?

Rachel Soon
Medical Writer
06 Dec 2019

A new case study adds evidence for the use of sildenafil as an alternative or adjunctive vasodilator in treating cases of persistent pulmonary hypertension in newborns (PPHN).

In a case reported by paediatricians from Carmel Medical Centre, Haifa, Israel, and the University of British Columbia, Canada, a male infant who rapidly developed PPHN after birth, secondary to lung and renal hypoplasia, was successfully treated with inhaled nitrous oxide (iNO) and a 2-month course of sildenafil, with right heart function normalized before his discharge from hospital.

“Sildenafil has been used in infants with PPHN due to congenital diaphragmatic hernia (CDH) and bronchopulmonary dysplasia … most existing literature focuses on PPHN associated with pulmonary hypoplasia in the context of [those conditions],” wrote the authors. “We describe a single case with the early use of sildenafil to treat PPHN in a non-CDH patient.”

Due to a preterm premature rupture of membranes (PPROM) at approximately 24 weeks of gestation and subsequent reduction in amniotic fluid volume, the patient was born at 37 weeks of gestation (birth weight 2840 g) with underdeveloped lungs, kidneys, and pulmonary blood vessels. A collapsed lung and a pulmonary hypertensive crisis subsequently developed within the first day of life (DOL).

As an emergency response, the patient was sedated, paralysed, and given inhaled nitric oxide (iNO) to ease breathing. In anticipation of PPHN due to the underdeveloped lungs and small calibre of his pulmonary arteries, sildenafil was administered on DOL 5 at 0.25 mg/kg/dose every 8 hours, with the dosage gradually increased to 2 mg/kg/dose every 8 hours on DOL 9.

The patient was safely extubated on DOL 7 and weaned off non-invasive respiratory support on DOL 26, while sildenafil weaning took place between DOL 21 to DOL 48. At 3 months, an ECG assessment found that both the pulmonary hypertension and the dilatation of the right ventricle had been completely resolved. [BMC Pediatr 2019;19:416]

iNO induces vasodilation by increasing intracellular concentrations of cyclic guanosine monophosphate (cGMP), while sildenafil selectively inhibits cGMP degradation. Currently, sildenafil is indicated for use in neonates as an acute adjuvant to iNO in iNO-resistant PPHN or to facilitate weaning from iNO; as an acute primary treatment of PPHN when iNO is not available or is contraindicated; and in the chronic primary treatment of pulmonary hypertension for conditions such as BPD and CDH to decrease right ventricular pressures and potentially improve right ventricular function over time. No randomized trials evaluating sildenafil in neonates with PPHN are currently available. [Semin Perinatol 2016; 40(3): 160–173]

The authors noted that while the therapeutic mainstay for PPHN consists of assisted ventilation and iNO administration, a recent Cochrane review described iNO as a costly option with 30 percent of patients with PPHN failing to respond to its use. [Cochrane Database Syst Rev 2017;8:CD005494]

“Following this treatment, the patient made a full recovery from right ventricular dysfunction,” wrote the authors. “Further evidence is required to determine whether this treatment could be viable for all patients who present with a similar type of condition.”

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Jairia Dela Cruz, 12 Oct 2018
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