Alprostadil (PGE1) for Maintaining Ductal Patency

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2000;6(9) 

In This Article

Adverse Effects

Many of the adverse effects of PGE1 are dose-related. Apnea, flushing, fever, bradycardia, and/or hypotension may indicate excessive prostaglandin effect and the need for dose reduction. Apnea occurs in approximately 12% of neonates receiving PGE1; it is not typically observed with doses < 0.01 mcg/kg/min.[3,14,19,20] Apnea is most likely to occur early in therapy, often within the first hour, and in infants weighing less than 2 kg.[19,20]

It has been recommended that, when possible, the PGE1 dose be reduced to the lowest effective rate prior to transport to avoid having to initiate artificial ventilation during transport.[2] Even with the increased safety associated with lower doses, all hospitals considering the use of PGE1 should be capable of providing adequate ventilatory support in the event that severe apnea does occur, including possible emergency intubation. In cases where a reduction in dose is not tolerated, elective intubation prior to transport should be considered.

Hyperthermia occurs in 10-14% of patients treated with PGE1. Cutaneous vasodilation (resulting in flushing and edema) occurs in approximately 10% of infants, with bradycardia in 7%, and hypotension in up to 4%. Other adverse effects associated with PGE1 administration include seizures (4%), tachycardia (3%), diarrhea (2%), and sepsis (2%), as well as respiratory depression, arrhythmias, congestive heart failure, wheezing, gastric regurgitation, bleeding, anuria, hematuria, thrombocytopenia, peritonitis, hypokalemia or hyperkalemia, hypoglycemia, and jitteriness (all occurring in 1% or less).[19,20]

Long-term administration of PGE1 in infants with hypoplastic left heart syndrome awaiting heart transplantation has revealed other adverse effects. Cortical proliferation, or hyperostosis, of the long bones has been reported after prolonged use ranging from 9 to over 200 days.[19,21,22,23] More than two dozen cases of cortical proliferation in neonates receiving PGE1 have been reported in the medical literature to date. Retrospective reviews have suggested an incidence as high as 50 to 60%.[24] The reaction appears to involve hyperostosis in the diaphyses of the long tubular bones and, less commonly, in the ribs, scapulae, and clavicles. Widening of the cranial sutures has also been observed. The mechanism of this effect is not known. Cortical proliferation does not appear to be dose-related; it has occurred in patients receiving PGE1 infusions as low as 0.008 mcg/kg/min.[22]

The diagnosis of hyperostosis may be made by clinical examination revealing joint swelling or loss of motion, or radiographically. Cortical proliferation begins to regress after discontinuing therapy. In most patients, bone changes have disappeared within 6 to 12 weeks after stopping PGE1; however, changes have persisted for up to 3 years in some case reports.[23]

Gastric outlet obstruction, resulting from mucosal hyperplasia in the antrum, has been also reported after long-term use of PGE1.[19,25] After recognizing this adverse effect in several of their patients, Peled and colleagues performed a retrospective review of PGE1-treated infants at their institution.[25] Among the 74 patients evaluated, five had both clinical and radiologic or pathological evidence of gastric obstruction, another four had clinical signs only, and the remaining 65 were considered normal. The infants with gastric outlet obstruction had received PGE1 for a significantly longer period than the normal infants (mean+SD 569+341hours versus 54+58 hours).

Another potential consequence of long-term PGE1 exposure is the development of intimal tears within the pulmonary arteries and changes in vessel muscularity. Aneurysmal dilatation and vessel wall edema have recently been reported in infants who have received PGE1.[14,19] It has been suggested that these changes may be dose-related, occurring more frequently when higher infusion rates are used to maximize pulmonary blood flow.[26]