Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia

Lawrence, Kendall M.; Hedrick, Holly L.; Monk, Heather M.; Herkert, Lisa M.; Waqar, Lindsay N.; Hanna, Brian D.; Peranteau, William H.; Rintoul, Natalie E.; Hopper, Rachel K.

doi:10.1016/j.jpeds.2018.04.052

Cited by 48 publications

(30 citation statements)

References 28 publications

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“…Clinical indices suggestive for severe PH (such as labile hypoxemia and differential cyanosis) were confirmed by Doppler echocardiogram as described previously 9 . Brain natriuretic peptide (BNP) was sampled to assess strain on the right side of the heart.…”

Section: Methodsmentioning

confidence: 99%

“…Treprostinil, a synthetic prostacyclin analog, is a potent pulmonary vasodilator approved for the treatment of idiopathic pulmonary arterial hypertension in adults and children. 4,5 We and others have reported good tolerance and clinical improvement with treprostinil as off-label, add-on therapy in neonates with PPHN refractory to inhaled nitric oxide (iNO) and sildenafil, [6][7][8][9][10] whereas clinical efficacy is currently investigated in an ongoing placebo-controlled randomized trial as add-on intervention to iNO (NCT02261883). In neonates with severe PPHN enduring persistent hypoxemia and hemodynamic instability despite aggressive medical management, therapy with extracorporeal membrane oxygenation (ECMO) is indicated.…”

Section: B R I E F R E P O R Tmentioning

confidence: 99%

“…Clinical indices suggestive for severe PH (such as labile hypoxemia and differential cyanosis) were confirmed by Doppler echocardiogram as described previously. 9 Brain natriuretic peptide (BNP) was sampled to assess strain on the right side of the heart. Features of PH on echocardiography included right ventricular systolic pressures greater than the systemic pressures, rightto-left ductal flow, and/or septal bowing into the left ventricle.…”

Section: Monitoring Of Severe Pulmonary Hypertensionmentioning

confidence: 99%

“…In our quaternary care ECMO‐referral center, approximately one quarter of patients with CDH enrolled in the Pulmonary Hypoplasia Program require ECMO support, with a majority due to pulmonary hypertension (PH). Given prior encouraging experience with the drug, 9 we hypothesized treprostinil could also benefit neonates with PH while on ECMO support and potentially shorten the length of their ECMO course.…”

mentioning

confidence: 99%

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Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

et al. 2020

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Background: Treprostinil is a prostacyclin analog used for treatment of pulmonary hypertension (PH) in adults and children, currently awaiting clinical assessment for use in neonates.Objectives: We aimed to investigate the use of treprostinil in neonates with PH on extracorporeal membrane oxygenation (ECMO) support and measure plasma concentrations of the drug.Methods: This is a retrospective case‐series with prospectively collected blood samples, conducted in a quaternary care neonatal intensive care unit. Brain natriuretic peptide, cardiac function on Doppler echocardiography, and the occurrence of adverse effects was monitored. Plasma concentrations were measured using high‐performance liquid chromatography and mass spectrometry.Results: Four patients with PH requiring ECMO therapy were studied. Treprostinil doses of 20–58 ng/kg/min reached concentrations of 0.99–4.39 ng/ml and induced clinical improvement. Infusion of treprostinil was associated with improved right ventricular function, reversed right‐to‐left shunting through the ductus arteriosus, and stable or decreasing need for vasopressor support. No adverse effects were observed.Conclusions: This is the first study to report clinically therapeutic treprostinil concentrations in circulating plasma after treprostinil administration in neonates on ECMO, with associated clinical improvement of PH and no signs of hemodynamic instability.

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Section: Methodsmentioning

confidence: 99%

Section: B R I E F R E P O R Tmentioning

confidence: 99%

Section: Monitoring Of Severe Pulmonary Hypertensionmentioning

confidence: 99%

mentioning

confidence: 99%

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Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

et al. 2020

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“…1431–1439 ) leveraged a large cohort of infants with CDH to demonstrate that ongoing RV systolic dysfunction after hernia repair can be detected by using a combination of elevated BNP and a lower magnitude of myocardial deformation ( 7 ). This single-center retrospective study builds on previous reports that investigated associations of ventricular dysfunction with abnormal BNP after therapeutic interventions in infants with CDH ( 8 , 9 ). In the current study of 460 BNP–echocardiogram pairs obtained preoperatively, in the immediate postoperative period and during recovery, the majority of infants had abnormal RV strain and BNP concentrations before surgical repair but demonstrated improvement afterward.…”

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confidence: 96%

Risk Assessment and Monitoring of Right Ventricular Function in Congenital Diaphragmatic Hernia

Critser¹,

Levy

2020

Annals ATS

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Association Between Early Prostacyclin Therapy and Extracorporeal Life Support Use in Patients With Congenital Diaphragmatic Hernia

et al. 2023

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ImportanceProstacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)–associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).ObjectiveTo evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.Design, Setting, and ParticipantsThis was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first week of life. Propensity score matching was performed using estimated gestational age, birth weight, transfer status, 1-minute and 5-minute Apgar scores, highest and lowest partial pressure of arterial carbon dioxide in the first 24 hours of life, and degree of pulmonary hypertension as covariates to generate a matched cohort of exposed and unexposed patients. Data were analyzed from January 2021 to December 2022.ExposuresEarly PGI2 therapy was defined as initiation of PGI2 within the first week of life. Patients who received ECLS were included in the early PGI2 group if PGI2 was started prior to ECLS.Main Outcomes and MeasuresThe primary outcome of the study was the proportion of patients receiving ECLS in the exposed and unexposed groups.ResultsOf 6227 patients who met inclusion criteria (mean [SD] gestational age, 37.4 [2.36] weeks; 2618 [42%] female), 206 (3.3%) received early PGI2 therapy. ECLS was used in 46 of 206 patients who received PGI2 (22.2%) and 1682 of 6021 who did not (27.9%). After propensity score matching, there were 147 patients in the treatment and control groups. Thirty-four patients who received PGI2 (23.3%) and 63 who did not (42.9%) received ECLS. Those who received PGI2 were less likely to receive ECLS (adjusted odds ratio, 0.39; 95% CI, 0.22-0.68) and had shorter mean (SD) duration of ECLS (8.6 [3.73] days vs 12.6 [6.61] days; P &lt; .001), although there was no significant difference in in-hospital mortality.Conclusions and RelevanceIn this study, there was decreased use of ECLS and decreased ECLS duration among patients with CDH who started PGI2 therapy during the first week of life. These results identify a potential advantage of early prostacyclin therapy in this population.

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Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia

Cited by 48 publications

References 28 publications

Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

Treprostinil Attains Clinically Therapeutic Concentrations in Neonates with Pulmonary Hypertension on Extracorporeal Membrane Oxygenation Support

Risk Assessment and Monitoring of Right Ventricular Function in Congenital Diaphragmatic Hernia

Association Between Early Prostacyclin Therapy and Extracorporeal Life Support Use in Patients With Congenital Diaphragmatic Hernia

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