Infants with ductal-dependent congenital heart defects

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Infants with ductal-dependent congenital heart defects: No randomised controlled trials.
Level III-3 studies report maintenance of oxygenation and ductal patency with doses of alprostadil 3 to 20 nanogram/kg/minute. [1, 3, 5, 6] Level III-3 studies report lower rates of apnoea with alprostadil ≤ 20 nanogram/kg/minute [1, 3]. Use of methylxanthines reduced the incidence of apnoea in newborn infants with ductal-dependent congenital heart disease receiving alprostadil. [4] (LOE II, GOR B). Infants on alprostadil infusions who are intubated for transport have higher rates of complications compared to non-intubated infants. [7] (LOE III-3, GOR C) In infants undergoing balloon atrial septostomy, rapid withdrawal of alprostadil infusion may be associated with hypoxaemia. [8]

Pharmacokinetics:

Metabolism of PGE₁ is an oxygen-dependent process, occurring in the pulmonary vascular bed and reduced in patients with pulmonary hypertension. [9] There is an increased volume of distribution in patients on ECMO requiring increased infusion rates to maintain ductal patency. [10] (LOE IV, GOR C)

Safety:

Reported complications include apnoea (19%), abdominal distension (16%), bradycardia (13%), enterocolitis (6.5%), hypotension (6.5%), vomiting (5%), fever (1.6%) and skin rash (1.6%). [6] (LOE III-3) With prolonged use, skeletal changes [11] and hypertrophic pyloric stenosis [12, 13] have been reported.

References

1. Huang FK, Lin CC, Huang TC, Weng KP, Liu PY, Chen YY, Wang HP, Ger LP, Hsieh KS. Reappraisal of the prostaglandin E₁ dose for early newborns with patent ductus arteriosus-dependent pulmonary circulation. Pediatrics and neonatology. 2013;54:102-6.

2. Strobel AM, Lu le N. The Critically Ill Infant with Congenital Heart Disease. Emergency medicine clinics of North America. 2015;33:501-18.

3. Browning Carmo KA, Barr P, West M, Hopper NW, White JP, Badawi N. Transporting newborn infants with suspected duct dependent congenital heart disease on low-dose prostaglandin E₁ without routine mechanical ventilation. Archives of disease in childhood Fetal and neonatal edition. 2007;92:F117-9.

4. Lim DS, Kulik TJ, Kim DW, Charpie JR, Crowley DC, Maher KO. Aminophylline for the prevention of apnea during prostaglandin E₁ infusion. Pediatrics. 2003;112:e27-9.

5. Yucel IK, Cevik A, Bulut MO, Dedeoglu R, Demir IH, Erdem A, Celebi A. Efficacy of very low-dose prostaglandin E₁ in duct-dependent congenital heart disease. Cardiology in the young. 2015;25:56-62.

6. Lucron H, Chipaux M, Bosser G, Le Tacon S, Lethor JP, Feillet F, Burger G, Monin P, Marcon F. [Complications of prostaglandin E1 treatment of congenital heart disease in paediatric medical intensive care]. Archives des maladies du coeur et des vaisseaux. 2005;98:524-30.

7. Meckler GD, Lowe C. To intubate or not to intubate? Transporting infants on prostaglandin E₁. Pediatrics. 2009;123:e25-30.

8. Finan E, Mak W, Bismilla Z, McNamara PJ. Early discontinuation of intravenous prostaglandin E₁ after balloon atrial septostomy is associated with an increased risk of rebound hypoxemia. Journal of perinatology : official journal of the California Perinatal Association. 2008;28:341-6.

9. Arai K. [The intrapulmonary metabolism of prostaglandin E₁ in patients with pulmonary hypertension]. Masui The Japanese journal of anesthesiology. 1995;44:536-41.

10. Watt K, Li JS, Benjamin DK, Jr., Cohen-Wolkowiez M. Pediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation. Journal of cardiovascular pharmacology. 2011;58:126-32.

11. Kaufman MB, El-Chaar GM. Bone and tissue changes following prostaglandin therapy in neonates. The Annals of pharmacotherapy. 1996;30:269-74, 77.

12. Perme T, Mali S, Vidmar I, Gvardijancic D, Blumauer R, Mishaly D, Grabnar I, Nemec G, Grosek S. Prolonged prostaglandin E₁ therapy in a neonate with pulmonary atresia and ventricular septal defect and the development of antral foveolar hyperplasia and hypertrophic pyloric stenosis. Upsala journal of medical sciences. 2013;118:138-42.

13. Soyer T, Yalcin S, Bozkaya D, Yigit S, Tanyel FC. Transient hypertrophic pyloric stenosis due to prostoglandin infusion. Journal of perinatology : official journal of the California Perinatal Association. 2014;34:800-1.

15. Australian Injectable Drugs Handbook, 6th Edition, Society of Hospital Pharmacists of Australia 2014

16. Micromedex solutions. Truven health analytics. Accessed via CIAP 14/12/15

Original version Date: 23/06/2016	Author: ANMF Consensus Group
Current Version number: 1.1	Current Version Date: 28/10/2019
Risk Rating: Low	Due for Review: 28/10/2024
Approval by: DTC	Approval Date: TBA

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