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

Importance: Prostacyclin (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). Objective: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH. Design, Setting, and Participants: This 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. Exposures: Early 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 Measures: The primary outcome of the study was the proportion of patients receiving ECLS in the exposed and unexposed groups. Results: Of 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 < .001), although there was no significant difference in in-hospital mortality. Conclusions and Relevance: In 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.

Trends in use of prostacyclin analogs for management of CDH-associated pulmonary hypertension.

PURPOSE: Off-label use of prostacyclins to manage congenital diaphragmatic hernia-associated pulmonary hypertension (CDH-PHTN) has been described over recent years, but use is not standardized across institutions. This study aims to describe trends in use of these medications in the CDH Study Group (CDHSG) patients. METHODS: The CDHSG was queried for all patients born from 2007 to 2019. Records were reviewed to describe the number of patients receiving prostacyclins, the day of life on which the agent was started, start time relative to ECLS, the duration of medication use, and continuation of the medication at the time of discharge. Finally, trends in use by year of birth were evaluated to assess for changes in use over time. RESULTS: There were 6439 patients identified from the registry who were born during the study period. 4372 (68%) patients received medications to treat pulmonary hypertension. Of these, 604 (14%) received a prostacyclin at some point during their care. The median start time for prostacyclins was 7.5 days of life (mean 16.9 days, SD 32.5 days), and the median duration was 12.5 days (mean 25.1 days, SD 49.1 days). Among patients who received prostacyclins, 340 patients required ECLS during care, 53 (15.5%) of whom started the prostacyclin prior to ECLS, and 159 (46.8%) of whom started prostacyclin therapy during their ECLS run. Only a small cohort (26/604, 4.3%) required continuation of the prostacyclin at the time of discharge. The proportion of patients receiving a prostacyclin remained relatively stable over the study period. CONCLUSIONS: While the proportion of patients receiving a prostacyclin for management of CDH-PHTN has remained relatively stable over the last 13 years, there is significant variation in timing of initiation and duration of use especially in the pre-ECLS period that warrants further investigation to describe optimal use in these patients.