Experimental and clinical effects of magnesium infusion in the treatment of neonatal pulmonary hypertension

Abstract

The appropriate treatment of persistent pulmonary hypertension of the newborn has led to the search for a specific pulmonary vasodilator. Persistent pulmonary hypertension of the newborn is characterized by a high pulmonary vascular resistance resulting in right to left shunting across the fetal channels. The ratio of pulmonary vascular resistance to systemic vascular resistance determines the magnitude of this shunt, and agents which lower both pulmonary and systemic blood pressure do not alleviate the right to left intracardiac shunt. Numerous vasodilator agents,including tolazoline, prostaglandins and nitrovasodilators, have been used but all have been associated with problematic falls in systemic blood pressure. Magnesium, called nature's calcium blocker, antagonizes calcium ion entry into smooth muscle cells, thus promoting vasodilatation. Magnesium is also a non-specific vasodilator,and while potentially lowering pulmonary vascular resistance, has been shown to cause a fall in systemic blood pressure in neonatal models of hypoxic or septic pulmonary hypertension. Case reports and a series of cases have noted beneficial effects in human newborns, which may have been due to other effects of magnesium (eg, sedation, muscle relaxation, bronchodilatation and cardioprotection). There are, however, no reported prospective randomized controlled trials of magnesium sulphate in human newborns with pulmonary hypertension. More recently, the discovery that inhaled nitric oxide acts as a specific pulmonary vasodilator without systemic side effects may reduce enthusiasm for the use of magnesium infusions in neonates with pulmonary hypertension. There appears to be sufficient evidence at present to justify a prospective randomized controlled trial to evaluate the role of magnesium infusion as a specific pulmonary vasodilator for the treatment of pulmonary hypertension in hypoxic human newborns.