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Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines?

Published online by Cambridge University Press:  03 November 2020

Daniel Vari Open the ORCID record for Daniel Vari [Opens in a new window] ,
Wendi Xiao ,
Shashank Behere ,
Ellen Spurrier ,
Takeshi Tsuda Open the ORCID record for Takeshi Tsuda [Opens in a new window]  and
Jeanne M. Baffa
Daniel Vari
Affiliation:
Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Wendi Xiao
Affiliation:
Department of Biostatistics, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Shashank Behere
Affiliation:
Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Ellen Spurrier
Affiliation:
Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Takeshi Tsuda*
Affiliation:
Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Jeanne M. Baffa
Affiliation:
Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
*
Author for correspondence: Takeshi Tsuda, Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19803, USA. Tel: +1 302 651 6677; Fax: +1 302 651 6601. E-mail: ttsuda@nemours.org
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Abstract

Introduction:

Prostaglandin E1 is used to maintain ductal patency in critical congenital heart disease (CHD). The standard starting dose of prostaglandin E1 is 0.05 µg/kg/minute. Lower doses are frequently used, but the efficacy and safety of a low-dose regimen of prostaglandin E1 has not been established.

Methods:

We investigated neonates with critical CHD who were started on prostaglandin E1 at 0.01 µg/kg/minute. We reviewed 154 consecutive patients who were separated into three anatomical groups: obstruction to systemic circulation, obstruction to pulmonary circulation, and inadequate mixing (d-transposition of the great arteries). Treatment failure rates and two commonly reported side effects, respiratory depression and seizure, were studied.

Results:

A total of 26 patients (17%) required a dose increase in prostaglandin E1. Patients with pulmonary obstruction were more likely to require higher doses than patients with systemic obstruction (15/49, 31% versus 9/88, 10%, p = 0.003). Twenty-eight per cent of patients developed respiratory depression and 8% of patients needed mechanical ventilation. Prematurity (<37 week gestation) was the primary risk factor for respiratory depression. No patient required dose escalation or tracheal intubation while on transport. No patient had a seizure attributed to prostaglandin E1.

Conclusions:

Prostaglandin E1 at an initial and maintenance dose of 0.01 µg/kg/minute was sufficient to maintain ductal patency in 83% of our cohort. The incidence of respiratory depression requiring mechanical ventilation was low and was mostly seen in premature infants. Starting low-dose prostaglandin E1 at 0.01 µg/kg/minute is a safe and effective therapy for critical CHD.

Keywords

CHDpatent ductus arteriosusprostaglandin E1side effectsapnoeamechanical ventilation

Information

Type
Original Article
Information
Cardiology in the Young , Volume 31 , Issue 1 , January 2021 , pp. 63 - 70
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Copyright
© The Author(s), 2020. Published by Cambridge University Press

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Footnotes

†

Current address: The Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

§

Current address: Department of Pediatric Cardiology, Oklahoma University Health Sciences Center, 1200 Children’s Ave., Oklahoma City, OK 73104, USA.

References

Coceani, F, Olley, PM. The response of the ductus arteriosus to prostaglandins. Can J Physiol Pharmacol 1973; 51: 220–225.CrossRefGoogle ScholarPubMed
Olley, PM, Coceani, F, Bodach, E. E-type prostaglandins: a new emergency therapy for certain cyanotic congenital heart malformations. Circulation 1976; 53: 728–731.CrossRefGoogle ScholarPubMed
Neutze, JM, Starling, MB, Elliott, RB, Barratt-Boyes, BG. Palliation of cyanotic congenital heart disease in infancy with E-type prostaglandins. Circulation 1977; 55: 238–241.CrossRefGoogle ScholarPubMed
Freed, MD, Heymann, MA, Lewis, AB, Roehl, SL, Kensey, RC. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. Circulation 1981; 64: 899–905.CrossRefGoogle ScholarPubMed
Akkinapally, S, Hundalani, SG, Kulkarni, M, et al. Prostaglandin E1 for maintaining ductal patency in neonates with ductal-dependent cardiac lesions. Cochrane Database Syst Rev 2018; 2: CD011417. doi: 10.1002/14651858.CD011417.pub2 Google ScholarPubMed
Lexicomp Online Alprostadil (Pediatric and Neonatal Lexi-Drugs). Wolters Kluwer Clinical Drug Information, Inc., Hudson, OH. Retrieved April 21, 2019, from https://www.wolterskluwercdi.com/lexicomp-online/ Google Scholar
Baffa, JM. Overview of Congenital Cardiovascular Anomalies. Merck Manual. Merck Manuals, Kenilworth, NJ, 2018.Google Scholar
Alprostadil. PDR. 2020. Retrieved April 21, 2019, from https://www.pdr.net/drug-summary/Caverject-alprostadil-3419 Google Scholar
Lewis, AB, Freed, MD, Heymann, MA, Roehl, SL, Kensey, RC. Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease. Circulation 1981; 64: 893–898.CrossRefGoogle ScholarPubMed
Roehl, SL, Townsend, RJ. Alprostadil (prostin VR pediatric sterile solution, The Upjohn Company). Drug Intell Clin Pharm 1982; 16: 823–832.CrossRefGoogle Scholar
Hallidie-Smith, KA. Prostaglandin E1 in suspected ductus dependent cardiac malformation. Arch Dis Child 1984; 59: 1020–1026.CrossRefGoogle ScholarPubMed
Kramer, HH, Sommer, M, Rammos, S, Krogmann, O. Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heart disease. Eur J Pediatr 1995; 154: 700–707.CrossRefGoogle ScholarPubMed
Singh, GK, Fong, LV, Salmon, AP, Keeton, BR. Study of low dosage prostaglandin – usages and complications. Eur Heart J 1994; 15: 377–381.CrossRefGoogle ScholarPubMed
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. Arch Dis Child Fetal Neonatal Ed 2007; 92: F117–F119.CrossRefGoogle ScholarPubMed
Singh, Y, Mikrou, P. Use of prostaglandins in duct-dependent congenital heart conditions. Arch Dis Child Educ Pract Ed 2018; 103: 137–140. doi: 10.1136/archdischild-2017-313654 CrossRefGoogle ScholarPubMed
Korula, A, Calder, AL, Neutze, JM. Effects of prostaglandin E1 given in low doses on the histopathology of the arterial duct. Int J Cardiol 1991; 33: 215–222; discussion 223–214.CrossRefGoogle ScholarPubMed
Huang, FK, Lin, CC, Huang, TC, et al. Reappraisal of the prostaglandin E1 dose for early newborns with patent ductus arteriosus-dependent pulmonary circulation. Pediatr Neonatol 2013; 54: 102–106. doi: 10.1016/j.pedneo.2012.10.007 CrossRefGoogle ScholarPubMed
Yucel, IK, Cevik, A, Bulut, MO, et al. Efficacy of very low-dose prostaglandin E1 in duct-dependent congenital heart disease. Cardiol Young 2015; 25: 56–62. doi: 10.1017/S1047951113001522 CrossRefGoogle ScholarPubMed
Matsui, H, McCarthy, K, Ho, S. Morphology of the patent arterial duct: features relevant to treatment. Images Paediatr Cardiol 2008; 10: 27–38.Google ScholarPubMed
Meckler, GD, Lowe, C. To intubate or not to intubate? Transporting infants on prostaglandin E1. Pediatrics 2009; 123: e25–e30. doi: 10.1542/peds.2008-0641.CrossRefGoogle ScholarPubMed
Cucerea, M, Simon, M, Moldovan, E, Ungureanu, M, Marian, R, Suciu, L. Congenital heart disease requiring maintenance of ductus arteriosus in critically ill newborns admitted at a tertiary neonatal intensive care unit. J Crit Care Med (Targu Mures) 2016; 2: 185–191. doi: 10.1515/jccm-2016-0031 CrossRefGoogle Scholar
Talosi, G, Katona, M, Racz, K, Kertesz, E, Onozo, B, Turi, S. Prostaglandin E1 treatment in patent ductus arteriosus dependent congenital heart defects. J Perinat Med 2004; 32: 368–374.CrossRefGoogle ScholarPubMed