Iowa Neonatology Handbook: Pharmacology

Protocol for Use of Prostaglandin E₁

1. Indication:
   An infant suspected of having a ductal-dependent congenital cardiac defect and ductal-dependent pulmonary blood flow should be treated with prostaglandin E₁ because he/she is at risk for progressive hypoxia and metabolic acidosis if the ductus closes. Prostaglandin E₁ will prevent the ductus arteriosus from closing and reestablish ductal patency if closure has already occurred, and thereby increase PaO₂, and mitigate the onset of metabolic acidosis. This drug is indicated for the temporary management of the neonate with ductus-dependent congenital heart disease while awaiting transfer to a tertiary care nursery for evaluation and surgical therapy. It is also used to stabilize a neonate's condition until surgery can be completed.
2. Patient Population:
   Most often the neonate with ductal-dependent congenital cardiac disease is a full term infant whose size is appropriate or large for gestational age. The drug is indicated for use in the neonate with ductal-dependent pulmonary blood flow, including: pulmonary atresia, tricuspid atresia, Tetralogy of Fallot, and will often improve systemic oxygen saturation in infants with transposition of the great vessels. Note, in infants with obstructive total anomalous pulmonary venous return, a left Æ right shunt via a PDA can decrease systemic blood flow and increase blood flow to the pulmonary bed resulting in pulmonary vascular congestion and worsening of infant’s condition.
3. Patient Identification:
   The infant should have the following studies performed prior to the initiation of prostaglandin therapy.
   • Hyperoxic Challenge Test: Right radial artery blood gases obtained in an FiO₂ of 1.0 (pCO₂ 35-40 torr [normal] and PaO₂ less than 100 torr is consistent with cyanotic congenital heart disease).
   • Chest x-ray: Decreased pulmonary vascularity
   • Serum glucose: If the neonate is hypoglycemic, treat appropriately and reassess arterial blood gases and pH.
   • Hematocrit: Central venous hematocrit of greater than 60% may result in hyperviscosity syndrome (plethora, cyanosis and dyspnea).
   • Adequate ventilation: If there is any question as to the adequacy of ventilation, the neonate should be mechanically ventilated and arterial blood gases reassessed.These studies will aid in the identification of the neonate with another etiology for central cyanosis. Only definitive echocardiography and cardiac catheterization will clearly identify infants with ductal dependent pulmonary blood flow.

1. Administration:
   Prostaglandin E1 is packaged in a 1 ml ampul of 500 micrograms (0.5 mg). Use one of the following methods to prepare a solution for infusion.
   1. Dilute one ampul in 500 ml D5W or D10W = 1 mcg/ml (0.001 mg/ml) solution.
      To give 0.05 mcg/kg/min. = 3.0 ml/kg/hr
   2. [weight (kg) ÷ 10] = # mg PGE1 in 100 ml IVF @ 3 ml/hr = 0.05 mcg/kg/min
   3. Dilute one vial in 100 ml of D5W or D10W = 5 mcg/ml solution. To give 0.05 mcg/kg/min. = 0.6 ml/kg/hr

Make sure the drug is thoroughly mixed in solution and all lines are purged. Once mixed, the solution is stable for 24 hours. Prostaglandin E1 is infused continuously by pump via a large peripheral vein (preferably not scalp vein) or umbilical ine. There is evidence that doses greater than 0.1 mcg/kg/min are -not more- effective, and may cause an increase in adverse reactions.

2. Response and Duration of Action:
   The neonate generally responds with an increase in PaO2 10-15 minutes after initiation of the drug. Some patients may not respond until several hours of drug infusion have elapsed. The half-life of the drug is one circulation time; therefore, continuous uninterrupted infusion must be maintained. Once the patient responds, the dose can be reduced to one-half or less of the initial effective dose.
3. Precautions:
   Monitor respiratory rate, temperature, blood pressure and arterial blood gases and pH at the initiation of and intermittently during infusion.
4. Adverse Reactions:
   About 20% of infants who receive this drug have one or more adverse reactions. Three common side effects are apnea (12%), fever (14%), and flushing (10%). Non-central nervous system twitching, fever, and peripheral flushing - particularly if given intra-arterially, will usually cease with reduction of the dose by 50%. Apnea is an indication for assisted or mechanical ventilation. A decrease in systolic arterial pressure of greater than 20% is an indication for volume expansion by 10 ml/kg of colloid. Hypoglycemia may develop after several hours of treatment.

This protocol is presented as a suggestion for the use of the drug. Particular questions involving patients should be directed to the Neonatologist (319-356-1616; Beeper 3792) and/or Pediatric Cardiologist (319-356-1616; Beeper 3609) on-call at University Hospitals.

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