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Efficacy and safety of endotracheal instillation of iloprost for persistent pulmonary hypertension of the newborn

Part of: Basic Science

Published online by Cambridge University Press:  06 January 2022

Asli Okbay Gunes Open the ORCID record for Asli Okbay Gunes [Opens in a new window] ,
Murat Ciftel Open the ORCID record for Murat Ciftel [Opens in a new window] ,
Mehmet Emcet Timur ,
Ceren Dedebali  and
Betul Zehra Pirdal
Asli Okbay Gunes*
Affiliation:
Neonatal Intensive Care Unit, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
Murat Ciftel
Affiliation:
Department of Pediatric Cardiology, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
Mehmet Emcet Timur
Affiliation:
Neonatal Intensive Care Unit, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
Ceren Dedebali
Affiliation:
Neonatal Intensive Care Unit, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
Betul Zehra Pirdal
Affiliation:
Department of Public Health, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey
*
Author for correspondence: Asli Okbay Gunes, MD, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey. Gsm: +90 546 241 37 39. E-mail: [email protected]
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Abstract

Objective:

To determine the efficacy and safety of endotracheal instillation of iloprost as a rescue therapy for persistent pulmonary hypertension of the newborn.

Methods:

Neonates diagnosed with persistent pulmonary hypertension who were unresponsive to standard treatment protocol applied for persistent pulmonary hypertension in our unit, and who were being followed up with mechanical ventilation, were included in the study. Iloprost was instilled endotracheally as a rescue treatment. Systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, fraction of inspired oxygen, preductal and postductal venous oxygen saturation, heart rate, and blood pressure were recorded before and after 30 minutes of endotracheal iloprost instillation. Adverse events after endotracheal iloprost were recorded.

Results:

Twenty neonates were included. The median gestational age and birth weight were found to be 37 (30.5-38) weeks and 2975 (2125-3437.5) grams, respectively. When compared to the period before endotracheal iloprost instillation, systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, and fraction of inspired oxygen values significantly decreased (p < 0.001, p < 0.001, p = 0.021, p = 0.001, respectively), whereas preductal and postductal oxygen saturation values significantly increased 30 minutes after the endotracheal iloprost instillation (p = 0.002, p < 0.001, respectively). There were no significant differences in heart rate and blood pressure values before and after the iloprost administration. No adverse events were observed.

Conclusion:

Endotracheal instillation of iloprost was found to be an effective and safe therapy for persistent pulmonary hypertension unresponsive to conventional treatment.

Keywords

Endotracheal iloprostNewbornsPulmonary hypertension
Type
Original Article
Information
Cardiology in the Young , Volume 32 , Issue 12 , December 2022 , pp. 1894 - 1900
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Lai, MY, Chu, SM, Lakshminrusimha, S, Lin, HC. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol 2018; 59: 15–23.10.1016/j.pedneo.2016.09.011CrossRefGoogle ScholarPubMed
Shivanna, B, Gowda, S, Welty, SE, Barrington, KJ, Pammi, M. Prostanoids and their analogues for the treatment of pulmonary hypertension in neonates. Cochrane Database Syst Rev 2019; 10: CD012963.Google ScholarPubMed
Barrington, KJ, Finer, N, Pennaforte, T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev 2017 Jan 3; 1: CD000509.Google ScholarPubMed
Fortas, F, Di Nardo, M, Yousef, N, Humbert, M, De Luca, D. Life-threatening PPHN refractory to nitric oxide: proposal for a rational therapeutic algorithm. Eur J Pediatr 2021; 180: 2379–2387.10.1007/s00431-021-04138-4CrossRefGoogle ScholarPubMed
Gomberg-Maitland, M, Olschewski, H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J 2008; 31: 891–901.10.1183/09031936.00097107CrossRefGoogle ScholarPubMed
Vane, JR, Botting, RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol 1995; 75: 3A–10A.10.1016/S0002-9149(99)80377-4CrossRefGoogle ScholarPubMed
Bos, AP, Tibboel, D, Koot, VC, Hazebroek, FW, Molenaar, JC. Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy. J Pediatr Surg 1993; 28: 1463–1465.10.1016/0022-3468(93)90431-JCrossRefGoogle ScholarPubMed
Nakayama, T, Shimada, H, Takatsuki, S, et al. Efficacy and limitations of continuous intravenous epoprostenol therapy for idiopathic pulmonary arterial hypertension in japenese children. Circ J 2007; 71: 1785–1790.10.1253/circj.71.1785CrossRefGoogle Scholar
Kelly, LK, Porta, NF, Goodman, DM, Carroll, CL, Steinhorn, RH. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002; 141: 830–832.10.1067/mpd.2002.129849CrossRefGoogle ScholarPubMed
Ehlen, M, Wiebe, B. Iloprost in persistent pulmonary hypertension of the newborn. Cardiol Young 2003; 13: 361–363.10.1017/S1047951103000726CrossRefGoogle ScholarPubMed
De Luca, D, Zecca, E, Piastra, M, Romagnoli, C. Iloprost as ‘rescue’ therapy for pulmonary hypertension of the neonate. Paediatr Anaesth 2007; 17: 394–395.10.1111/j.1460-9592.2006.02104.xCrossRefGoogle ScholarPubMed
Levy, M, Celermajer, DS, Bourges-Petit, E, et al. Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr 2011; 158: 584–588.10.1016/j.jpeds.2010.09.025CrossRefGoogle ScholarPubMed
Ewert, R, Schäper, C, Halank, M, Gläser, S, Opitz, CF. Inhalative iloprost - pharmacology and clinical application. Expert Opin Pharmaco 2009; 10: 2195–2207.10.1517/14656560903164228CrossRefGoogle ScholarPubMed
Ivy, DD, Doran, AK, Smith, KJ, et al. Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension. J Am Coll Cardiol 2008; 51: 161–169.10.1016/j.jacc.2007.09.031CrossRefGoogle Scholar
Ivy, DD. Prostacyclin in the intensive care setting. Pediatr Crit Care Med 2010; 11(2 Suppl): S41–S45.10.1097/PCC.0b013e3181d10845CrossRefGoogle ScholarPubMed
Dorris, SL, Peebles, RS Jr. PGI2 as a regulator of inflammatory diseases. Mediat Inflamm 2012; 2012: 926968.Google ScholarPubMed
Janjindamai, W, Thatrimontrichai, A, Maneenil, G, Chanvitan, P, Dissaneevate, S. Effectiveness and safety of intravenous iloprost for severe persistent pulmonary hypertension of the newborn. Indian Pediatr 2013; 50: 934–938.10.1007/s13312-013-0263-1CrossRefGoogle ScholarPubMed
De Jaegere, AP, van den Anker, JN. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. Eur Respir J 1998; 12: 932–934.10.1183/09031936.98.12040932CrossRefGoogle ScholarPubMed
Çetinkaya, M, Atasay, B, Perk, Y. Turkish neonatal society guideline on the transfusion principles in newborns. Turk Pediatri Ars 2018; 53: S101–S108.10.5152/TurkPediatriArs.2018.01810CrossRefGoogle ScholarPubMed
Mathew, B, Lakshminrusimha, S. Persistent pulmonary hypertension in the newborn. Children (Basel) 2017; 4: 63.Google ScholarPubMed
Forfia, PR, Wiegers, SE. Echocardiographic Findings in Acute and Chronic Respiratory Disease. In: Otto, CM (eds). The Practice of Clinical Echocardiography, Third. Elsevier, Philadelphia, 2007: 848–876.10.1016/B978-1-4160-3640-1.50039-3CrossRefGoogle Scholar
Fuloria, M, Aschner, JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med 2017; 22: 220–226.10.1016/j.siny.2017.03.004CrossRefGoogle ScholarPubMed
Sweet, DG, Carnielli, V, Greisen, G, et al. European consensus guidelines on the management of respiratory distress syndrome - 2019 update. Neonatology 2019; 115: 432–450.10.1159/000499361CrossRefGoogle ScholarPubMed
Kelly, LE, Ohlsson, A, Shah, PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 2017; 8: CD005494.Google ScholarPubMed
Verma, S, Lumba, R, Kazmi, SH, et al. Effects of inhaled iloprost for the management of persistent pulmonary hypertension of the newborn. Am J Perinatol 2021; 150: 235. DOI 10.1055/s-0040-1722653.Google Scholar
Aboudi, D, Swaminathan, N, Brumberg, H, et al. Sildenafil and retinopathy of prematurity in preterm infants with bronchopulmonary dysplasia. J Pediatr 2018; 199: 16–21.10.1016/j.jpeds.2018.04.005CrossRefGoogle ScholarPubMed
Muniraman, HK, Song, AY, Ramanathan, R, et al. Evaluation of oxygen saturation index compared with oxygenation index in neonates with hypoxemic respiratory failure. JAMA Netw Open 2019; 2: e191179.10.1001/jamanetworkopen.2019.1179CrossRefGoogle ScholarPubMed
Hill, NS, Preston, IR, Roberts, KE. Inhaled therapies for pulmonary hypertension. Respir Care 2015; 60: 794–805.10.4187/respcare.03927CrossRefGoogle ScholarPubMed
Eifinger, F, Sreeram, N, Mehler, K, et al. Aerosolized iloprost in the treatment of pulmonary hypertension in extremely preterm infants: a pilot study. Klin Padiatr 2008; 220: 66–69.10.1055/s-2007-984370CrossRefGoogle ScholarPubMed
Kahveci, H, Yilmaz, O, Avsar, UZ, et al. Oral sildenafil and inhaled iloprost in the treatment of pulmonary hypertension of the newborn. Pediatr Pulmonol 2014; 49: 1205–1213.10.1002/ppul.22985CrossRefGoogle ScholarPubMed
Yilmaz, O, Kahveci, H, Zeybek, C, Ciftel, M, Kilic, O. Inhaled iloprost in preterm infants with severe respiratory distress syndrome and pulmonary hypertension. Am J Perinatol 2014; 31: 321–326.10.1055/s-0033-1348949CrossRefGoogle ScholarPubMed
Gokce, I, Kahveci, H, Turkyilmaz, Z, Adakli, B, Zeybek, C. Inhaled iloprost in the treatment of pulmonary hypertension in very low birth weight infants: a report of two cases. J Pak Med Assoc 2012; 62: 388–391.Google ScholarPubMed