From the Guidelines
Alprostadil works in congenital heart disease by relaxing smooth muscle in the ductus arteriosus, keeping this fetal blood vessel open after birth, which is crucial for infants with ductal-dependent congenital heart defects. This medication is essential for maintaining blood flow to either the lungs or body in these patients. According to the most recent guidelines, prostaglandin E1 may be considered to maintain patency of the ductus arteriosus and to improve cardiac output for infants with congenital heart disease and suprasystemic levels of pulmonary hypertension or right ventricular failure 1. The medication is typically administered as a continuous IV infusion, and its dose can be titrated to the lowest effective dose.
The mechanism of action of alprostadil involves binding to specific prostaglandin receptors, increasing cyclic AMP levels in smooth muscle cells, which leads to muscle relaxation and vessel dilation. Key considerations for administration include preparing the medication in dextrose or saline solution and administering it through a dedicated IV line, as it can be rapidly metabolized in the lungs. Monitoring for side effects such as apnea, fever, flushing, hypotension, and seizures is also crucial during administration.
In clinical practice, the use of alprostadil in congenital heart disease is guided by the specific diagnosis and the presence of ductal-dependent lesions. For instance, in cases of congenital heart disease with systemic outflow obstruction, such as hypoplastic left heart syndrome, interrupted aortic arch, or coarctation of the aorta, prostaglandin E1 is given to dilate the ductus arteriosus, and oxygen is withheld because it can constrict the ductus 1. The decision to use alprostadil is based on the individual patient's condition and the need to maintain ductal patency until surgical intervention can be performed.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Alprostadil (prostaglandin E1) is one of a family of naturally occurring acidic lipids with various pharmacologic effects. Vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle are among the most notable of these effects Intravenous doses of 1 to 10 micrograms of alprostadil per kilogram of body weight lower the blood pressure in mammals by decreasing peripheral resistance. Reflex increases in cardiac output and rate accompany the reduction in blood pressure. Smooth muscle of the ductus arteriosus is especially sensitive to alprostadil, and strips of lamb ductus markedly relax in the presence of the drug In addition, administration of alprostadil reopened the closing ductus of new-born rats, rabbits, and lambs. These observations led to the investigation of alprostadil in infants who had congenital defects which restricted the pulmonary or systemic blood flow and who depended on a patent ductus arteriosus for adequate blood oxygenation and lower body perfusion In infants with restricted pulmonary blood flow, about 50% responded to alprostadil infusion with at least a 10 torr increase in blood pO2 (mean increase about 14 torr and mean increase in oxygen saturation about 23%). In general, patients who responded best had low pretreatment blood pO2 and were 4 days old or less In infants with restricted systemic blood flow, alprostadil often increased pH in those having acidosis, increased systemic blood pressure, and decreased the ratio of pulmonary artery pressure to aortic pressure.
Alprostadil works in congenital heart disease by:
- Vasodilation: decreasing peripheral resistance, which leads to a reduction in blood pressure
- Relaxation of smooth muscle: specifically in the ductus arteriosus, allowing for increased blood flow
- Increasing cardiac output and rate: through reflex mechanisms
- Improving oxygenation: in infants with restricted pulmonary blood flow, by increasing blood pO2 and oxygen saturation
- Improving systemic blood flow: in infants with restricted systemic blood flow, by increasing systemic blood pressure and decreasing the ratio of pulmonary artery pressure to aortic pressure 2
From the Research
Mechanism of Action
- Alprostadil, also known as prostaglandin E1 (PGE1), works by relaxing the smooth muscle of the ductus arteriosus, keeping it patent and maintaining blood flow to the lungs or systemic circulation in infants with ductal-dependent congenital heart disease (DDCHD) 3, 4, 5.
- This is crucial for infants with certain types of congenital heart defects, such as hypoplastic left heart syndrome, where a patent ductus arteriosus is necessary to maintain adequate pulmonary or systemic circulation until surgical intervention can be performed 6, 4.
Effectiveness
- Studies have shown that alprostadil is effective in maintaining ductal patency in infants with DDCHD, with a success rate of 88% in one study 3.
- The effectiveness of alprostadil can be measured by the ability to maintain ductal patency, improve oxygenation, and prevent complications such as cardiac arrest, cardiogenic shock, and respiratory acidosis 3, 5.
Dosage and Administration
- The dosage of alprostadil varies depending on the clinical presentation, with some studies using very low-dose regimens (less than 0.01 mcg/kg/min) and others using low-dose regimens (equal to or greater than 0.01 mcg/kg/min) 3.
- Alprostadil can be administered as an intravenous infusion, with an onset of action of 30 minutes to 2 hours or more 7.
- In some cases, a bolus of alprostadil may be used to reverse ductal spasm and increase pulmonary flow, although more studies are needed to recommend this approach 7.