1. 5 to 100 nanograms/kg/minute (0.005-0.1 micrograms/kg/minute) by continuous intravenous infusion.
2. Start with low infusion rate and titrate according to the infant's response. Higher initial doses are usually no more effective and have a higher incidence of adverse effects.
3. Maintenance dose may be as low as 5 nanograms/kg/minute (0.005 micrograms/kg/minute).

Usual dilution 3 - 6 micrograms/ml. In rare situations the strength can be made up to 20 micrograms/ml. This is however very hyperosmolar. At 3 micrograms/ml, 1ml/hour = 0.05 micrograms/minute.

Indications

Dilatation of ductus arteriosus in infants with ductal dependent congenital heart defects:

1. Transposition of the great vessels.
2. All right sided cyanotic congenital heart defects associated with reduced pulmonary perfusion.
3. Left sided congenital heart defects including hypoplastic left heart syndrome, coarctation of aorta and interrupted aortic arch.

Contraindications

1. None. ³

Precautions

1. Respiratory distress. Alprostadil (Prostaglandin E₁) should not be used in neonates with Respiratory Distress.³
2. Total anomalous venous return with obstruction.
3. Infants with bleeding tendencies (Alprostadil inhibits platelet aggregation).
4. Seizure disorders.

Clinical Pharmacology

Prostaglandin E₁ is a potent vasodilator of all arterioles. Other effects include inhibition of platelet aggregation, and stimulation of uterine and intestinal small muscle. Alprostadil (Prostaglandin E₁) is rapidly cleared by metabolism, primarily occurring in the lungs, and excretion via the kidney. ³ Maximal drug effect usually seen within 30 minutes in cyanotic lesion: may take several hours in acyanotic lesions.

Possible Adverse Effects ³

1. Apnoea.
2. Hypotension.
3. Hyperthermia (transient).
4. Hypoglycaemia.
5. Tachycardia.
6. Bradycardia.
7. Seizures.
8. Diarrhoea.
9. Skin flush secondary to vasodilation- occurs more frequently with intraarterial administration.
10. Sepsis, cardiac arrest, disseminated intravascular coagulation, hypokalaemia, oedema, cortical proliferation of the long bones.

Special Considerations

• Alprostadil (Prostaglandin E₁) is rapidly metabolised and must, therefore, always be given by continuous intravenous infusion. Vascular access must be secure at all times and may demand the insertion of a central venous catheter or long line to ensure continuity of delivery.
• The maintenance dose of the Alprostadil (Prostaglandin E₁) infusion is determined by titration according to the infant's response - oxygenation versus adverse effects.
• Monitor:
  • Observe respiratory effort closely
  • Monitor arterial pressure closely. If arterial pressure falls, a bolus of fluid ( 10- 20 ml/kg) is required. It may be necessary to decrease the rate of infusion.
  • Pulse oximetry is mandatory due to risk of apnoea and to monitor therapeutic effect in cyanotic heart disease.
  • Where there is restricted systemic blood flow, measure efficacy by monitoring improvement of systemic blood pressure and blood pH, and femoral pulses/arm-leg BP gradient in aortic coarctation.
  • Renal function; full Blood Count & platelets frequently.
• Increased infant temperature is not an indication to stop therapy.