Melatonin as an Adjunct Therapy to Milrinone for Pulmonary Hypertension in Full Term Neonates

Normal pulmonary artery pressure shows a gradual declining trend after birth, and pulmonary artery pressure of 72 h after birth is still higher than that of normal adults Infants born after 34 weeks of gestation with primary findings on physical examination reveals tachypnoea, retractions, grunting, desaturation unresponsive to supplemental O2, cyanosis and pulmonary arterial pressure (PAP) > 25 mm Hg measured by echocardiography, within 72 h of birth, are considered to have pulmonary hypertension Pulmonary hypertension in neonates (PPHN) is a syndrome characterized by failure in the mechanisms that decrease pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) after birth Persistent pulmonary hypertension of newborn (PPHN) develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through fetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia, and maladaptation of the pulmonary vascular bed as occurs with perinatal asphyxia It has been shown that one of the mechanisms involved in the pathophysiology of PPHN is oxidative stress, which results in an imbalance between an increase in free radicals generation and decreased antioxidant capacity Currently, the treatment for PHN considers timely and precise interventions such as intravenous milrinone, oral pulmonary vasodilators such as endothelin receptor antagonist, phosphodiesterase-5 inhibitors such as sildenafil, inhaled nitric oxideand are used both during acute and chronic phases of PPHN, controlled oxygen administration, and even extracorporeal membrane oxygenation.

However, these therapeutic strategies do not markedly reduce the mortality and the long-term neonatal outcomes remain poor Melatonin, more commonly known as the sleep hormone, has been highlighted by experimental evidence, to have significant effects as a direct scavenger of oxygen free radicals and induces antioxidant enzymatic It has been shown that melatonin has vasodilator properties and may modulate pro-oxidant sources in the neonatal lung which is proposed to treat PHN in the first days of neonatal life.