What are the known adverse reactions to prostaglandin E (PGE) infusion?

From the Guidelines

Prostaglandin E (PGE) infusion is associated with several adverse reactions, including mild and moderate infusion reactions such as nausea, fever, erythema, and itching, as well as severe reactions like hypotension, chest tightness, respiratory distress, and urticaria. These reactions can occur during or within 24 hours of infusion and can be mitigated by pretreatment with acetaminophen and diphenhydramine 1. The severity of infusion reactions can be categorized as mild, moderate, or severe, with mild and moderate reactions usually resolving spontaneously after reduction of the infusion rate or temporary pause of the infusion. Severe infusion reactions, on the other hand, require immediate discontinuation of the infusion. Some key points to consider include:

• Infusion reaction severity and management
• Pretreatment with acetaminophen and diphenhydramine to mitigate reactions
• Monitoring for signs of severe infusion reactions, such as hypotension and respiratory distress
• Immediate discontinuation of the infusion in cases of severe reactions. It's also worth noting that while other studies discuss infusion reactions in the context of different medications, such as immune checkpoint inhibitors 1, the most relevant and recent evidence for PGE infusion comes from the 2019 study published in the Journal of the American Academy of Dermatology 1.

From the FDA Drug Label

ADVERSE REACTIONS Central Nervous System Apnea has been reported in about 12% of the neonates treated (see WARNING box). Other common adverse reactions reported have been fever in about 14% of the patients treated and seizures in about 4% The following reactions have been reported in less than 1% of the patients: cerebral bleeding, hyperextension of the neck, hyperirritability, hypothermia, jitteriness, lethargy, and stiffness Cardiovascular System The most common adverse reactions reported have been flushing in about 10% of patients (more common after intraarterial dosing), bradycardia in about 7%, hypotension in about 4%, tachycardia in about 3%, cardiac arrest in about 1%, and edema in about 1% The following reactions have been reported in less than 1% of the patients: congestive heart failure, hyperemia, second degree heart block, shock, spasm of the right ventricle infundibulum, supraventricular tachycardia, and ventricular fibrillation Respiratory System The following reactions have been reported in less than 1% of the patients: bradypnea, bronchial wheezing, hypercapnia, respiratory depression, respiratory distress, and tachypnea. Gastrointestinal System The most common adverse reaction reported has been diarrhea in about 2% of the patients The following reactions have been reported in less than 1% of the patients: gastric regurgitation, and hyperbilirubinemia. Hematologic System The most common hematologic event reported has been disseminated intravascular coagulation in about 1% of the patients. The following events have been reported in less than 1% of the patients: anemia, bleeding, and thrombocytopenia Excretory System Anuria and hematuria have been reported in less than 1% of the patients. Skeletal System Cortical proliferation of the long bones has been reported (see PRECAUTIONS). Miscellaneous Sepsis has been reported in about 2% of the patients. Peritonitis has been reported in less than 1% of the patients Hypokalemia has been reported in about 1%, and hypoglycemia and hyperkalemia have been reported in less than 1% of the patients.

The known adverse reactions to prostaglandin E (PGE) infusion include:

• Central Nervous System: apnea, fever, seizures, cerebral bleeding, hyperextension of the neck, hyperirritability, hypothermia, jitteriness, lethargy, and stiffness
• Cardiovascular System: flushing, bradycardia, hypotension, tachycardia, cardiac arrest, edema, congestive heart failure, hyperemia, second degree heart block, shock, spasm of the right ventricle infundibulum, supraventricular tachycardia, and ventricular fibrillation
• Respiratory System: bradypnea, bronchial wheezing, hypercapnia, respiratory depression, respiratory distress, and tachypnea
• Gastrointestinal System: diarrhea, gastric regurgitation, and hyperbilirubinemia
• Hematologic System: disseminated intravascular coagulation, anemia, bleeding, and thrombocytopenia
• Excretory System: anuria and hematuria
• Skeletal System: cortical proliferation of the long bones
• Miscellaneous: sepsis, peritonitis, hypokalemia, hypoglycemia, and hyperkalemia 2

From the Research

Known Adverse Reactions to Prostaglandin E Infusion

The known adverse reactions to prostaglandin E (PGE) infusion include:

• Apnea, which occurred in 9% of spontaneously breathing patients 3
• Cutaneous vasodilation, bradycardia, tachycardia, hypotension, seizure-like activity, hyperthermia 4
• Necrotizing enterocolitis, jitteriness 3
• Linear skin rash locally 3
• Fever, which occurred in 27/49 cases 5
• Apnoea, which was observed in 15 patients 5
• Intraventricular hemorrhage, which developed in a one-week-old neonate with coarctation of the aorta grade III 5
• A mild decrease of sodium, potassium and chloride levels and a slight shift of pH levels toward metabolic alkalosis 5

Side Effects by Study

The side effects of PGE infusion varied by study:

• 3 reported apnea, necrotizing enterocolitis, hyperpyrexia, jitteriness, and linear skin rash
• 4 reported cutaneous vasodilation, bradycardia, tachycardia, hypotension, seizure-like activity, hyperthermia, and apnea
• 5 reported fever, apnoea, intraventricular hemorrhage, and changes in serum electrolyte levels
• 6 did not report any serious complications or sequelae after the administration of a bolus of alprostadil
• 7 reported uterine hyperstimulation after prostaglandin E2 administration, which was managed with intravenous ritodrine therapy