16/05/2017
Alprostadil (PGE ) is a naturally occurring prostaglandin that was approved by the Food and Drug Administration (FDA) in 1981 for use in infants with CHD that required maintenance of ductal patency until palliative or corrective surgery could be performed . PGE is often used in neonates with prenatally diagnosed ductus-dependent cardiac disease in the immediate postnatal period . Since 60% to 80% of PGE is metabolized on first pass through the lungs, it must be administered by continuous infusion. At a starting dose of 0.025 to 0.1 μg/kg/minute, the ductus usually reopens within 30 minutes to two hours of initiating PGE , with the clinical response usually being instant if the duct is vital for the infant's hemodynamic status . Since prostaglandin E has multiple physiologic effects, PGE therapy may be accompanied by several short-term and long-term adverse effects . Adverse effects of PGE include apnea, peripheral vasodilation, fever and hypotension in the short term, and cortical hyperostosis ،brown fat necroses, gastric outlet obstruction , and intimal mucosal damage , in the long term after a few weeks of therapy. In one study of infants with ductal-dependent pulmonary circulation, treatment with a lower initial dose of PGE of 0.02 μg/kg/minute and a maintenance dose of 0.01 μg/kg/minute was efficacious with a lower incidence of adverse effects. Four PGE receptors (EP1, EP2, EP3 and EP4) have been identified and their specific distribution in tissues and organs has been reported in animal models. EP2 and EP4 receptor subtypes mediate PGE -induced relaxation through a cyclic AMP-dependent mechanism and EP1 and EP3 induce constriction. EP3 has also been reported to mediate vasodilation of the ductus . In human neonatal ductus arteriosus, the presence of EP3 and EP4 receptors has been reported . Theoretically, specific receptor subtype agonists may be more potent and have fewer adverse effects . In vivo dilation of rat neonatal ductus arteriosus by an EP4 receptor agonist has been studied, and it is conceivable that agents that target specific PGE receptor subtypes may soon be available to modulate ductal tone selectively. Besides alprostadil, the use of other formulations of PGE such as lipo-PGE , PGE α-cyclodextrin , and an oral PGE derivative have been reported.
How the intervention might work
PGE is a potent dilator of the ductus arteriosus in human neonates . Patency of the ductus allows for a right-to-left shunt where there is left ventricular (LV) outflow obstruction, thereby maintaining systemic blood flow; allows for a left-to-right shunt where there is diminished pulmonary blood flow, thereby maintaining pulmonary blood flow and allows for mixing of blood between the right-sided and left-sided circulations when they are anatomically separated. In neonates with restriction of pulmonary blood flow, maintaining postnatal ductal patency with PGE can prevent severe hypoxia, cyanosis and death . In neonates with ductal-dependent systemic blood flow, PGE can relieve shock, anuria and congestive heart failure . In the case of anatomically separated right and left heart circulations such as in TGA with intact ventricular septum, pulmonary blood flow elevates left atrial pressure and consequently increases left-to-right atrial shunting decreasing cyanosis . Long-term therapy with PGE has been used In infants awaiting surgery, in whom a longer period of growth and maturation is desired to reduce risk of surgery
Why it is important to do this review
PGE is routinely used in infants with ductal-dependent cardiac lesions to improve circulation prior to balloon atrial septostomy or surgery . However, the safety and the efficacy of PGE have not been systematically reviewed. Since PGE therapy may be lifesaving but not without risks, a systematic review of the safety and efficacy of PGE in ductal-dependent cardiac lesions is justified.
