Response to pulmonary vasodilators in infants with congenital diaphragmatic hernia
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Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia, cardiac dysfunction and pulmonary hypertension. Inhaled nitric oxide (iNO) and milrinone are commonly used pulmonary vasodilators in CDH. We studied the hemodynamic effects of iNO and milrinone in infants with CDH.
A retrospective chart review was performed of all CDH infants admitted to two regional perinatal centers and infants classified into three groups: No-iNO group; iNO-responders and iNO-nonresponders. Oxygenation and hemodynamic effects of iNO and milrinone were assessed by blood gases and echocardiography.
Fifty-four percent (39/72) of infants with CDH received iNO and 31% of these infants (12/39) had complete oxygenation response to iNO. Oxygenation response to iNO was not associated with a decrease in right ventricular pressures (RVP) or ECMO use. Four infants (33%) in the iNO-responder group and eight infants (30%) in the iNO-nonresponder group received milrinone. Milrinone lowered RVP and improved ejection fraction (EF). Response to iNO was associated with improved oxygenation to milrinone and increased survival following ECMO (67 vs. 20% among nonresponders).
Response to inhaled nitric oxide in combination with milrinone may be associated with improved oxygenation and better survival after ECMO in infants with CDH.
KeywordsCDH Pulmonary hypertension Inhaled nitric oxide Milrinone Infants
This research work was performed without any support from external funding or grants. No funds were received for covering the costs to publish in open access.
HSVK and SL conceived and designed the project; RD and SG provided help with IRB approval; RD, JK and SG substantially contributed to acquisition, analysis and interpretation of data; all the authors (VK, RD, JK, SG and SL) played a critical role in drafting and revising the manuscript for intellectual content.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interests to declare.
This article does not contain any studies with animals performed by any of the authors.
Research involving human participants
This is a retrospective case–control study. The University at Buffalo Institutional Review Board of the State University of New York, Buffalo (MODCR00001406), and the Research Subjects Review Board at the University of Rochester, Rochester (RSRB0006718), approved the study protocol for data collection in study patients.
- 3.Snoek KG, Capolupo I, van Rosmalen J, Hout Lde J, Vijfhuize S, Greenough A, Wijnen RM, Tibboel D, Reiss IK, Consortium CE (2016) Conventional mechanical ventilation versus high-frequency oscillatory ventilation for congenital diaphragmatic hernia: a randomized clinical trial (the VICI-trial). Ann Surg 263(5):867–874. https://doi.org/10.1097/SLA.0000000000001533 CrossRefPubMedGoogle Scholar
- 4.Kumar VH, Swartz DD, Rashid N, Lakshminrusimha S, Ma C, Ryan RM, Morin FC 3rd (2010) Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension. J Appl Physiol 109(3):677–684. https://doi.org/10.1152/japplphysiol.01082.2009 CrossRefPubMedGoogle Scholar
- 5.Lakshminrusimha S, Porta NF, Farrow KN, Chen B, Gugino SF, Kumar VH, Russell JA, Steinhorn RH (2009) Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 10(1):106–112. https://doi.org/10.1097/PCC.0b013e3181936aee CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Rashid N, Morin FC 3rd, Swartz DD, Ryan RM, Wynn KA, Wang H, Lakshminrusimha S, Kumar VH (2006) Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation. Pediatr Res 60(5):624–629. https://doi.org/10.1203/01.pdr.0000242343.84510.81 CrossRefPubMedGoogle Scholar
- 9.Lakshminrusimha S, Keszler M, Kirpalani H, Van Meurs K, Chess P, Ambalavanan N, Yoder B, Fraga MV, Hedrick H, Lally KP, Nelin L, Cotten M, Klein J, Guilford S, Williams A, Chaudhary A, Gantz M, Gabrio J, Chowdhury D, Zaterka-Baxter K, Das A, Higgins RD (2017) Milrinone in congenital diaphragmatic hernia—a randomized pilot trial: study protocol, review of literature and survey of current practices. Matern Health Neonatol Perinatol 3:27. https://doi.org/10.1186/s40748-017-0066-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Reiss I, Schaible T, van den Hout L, Capolupo I, Allegaert K, van Heijst A, Gorett Silva M, Greenough A, Tibboel D, Consortium CE (2010) Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO consortium consensus. Neonatology 98(4):354–364. https://doi.org/10.1159/000320622 CrossRefPubMedGoogle Scholar
- 15.Konduri GG, Sokol GM, Van Meurs KP, Singer J, Ambalavanan N, Lee T, Solimano A (2013) Impact of early surfactant and inhaled nitric oxide therapies on outcomes in term/late preterm neonates with moderate hypoxic respiratory failure. J Perinatol 33(12):944–949. https://doi.org/10.1038/jp.2013.83 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Bassler D, Kreutzer K, McNamara P, Kirpalani H (2010) Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev (11):CD007802. https://doi.org/10.1002/14651858.CD007802.pub2
- 19.James AT, Corcoran JD, McNamara PJ, Franklin O, El-Khuffash AF (2016) The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension. Cardiol Young 26(1):90–99. https://doi.org/10.1017/S1047951114002698 CrossRefPubMedGoogle Scholar