iNO Therapy in Patients with Congenital Diaphragmatic Hernia – Discrepancy between Widespread Use and Therapeutic Effects

Abstract

Background Despite recent studies failing to prove beneficial effects of iNO therapy in patients with CDH, its use is still widespread. The aim of this work was to analyze iNO use in a retrospective cohort focusing on outcome parameters. Patients 378 CDH patients born and treated in Mannheim University Medical Center, Department for Neonatology, between 2010 and 2017 constituted our cohort. Therapy was based on the standardized protocol of the CDH EURO Consortium.

Method General data (sex, birth weight, gestational age etc.) and therapy-related data (duration of iNO application, OI after 60 mins, need for ECMO support etc.) were collected from clinical reports and then conducted using SAS for both mono- and multivariate analyses.

Results Out of 378 newborns with CDH, 265 received iNO (70.1%), of whom 82 (30.9%) showed a significant OI reduction of ≥5 pts after 60 mins (=responders), median OI improved by 1.85 pts overall. Among initial responders iNO, application reduced the need for ECMO support (p=0.0054), increased the time to ECMO initiation (p=0.005) and reduced mortality (p=0.0396).

Discussion A group of 43 patients considerably benefited from iNO and thererfore as they did not need ECMO support. Even though iNO therapy has failed to prove significant beneficial effects for non-responders, the application is still to be considered an essential treatment method in the transitional period of CDH patients.

Conclusions A more critical approach towards iNO application in nonresponders should be promoted. Further extensive multicenter studies on treatment alternatives for CDH-PAH are desirable.

Zusammenfassung

Hintergrund Obwohl aktuelle Studien keinen Beweis für den positiven Nutzen einer iNO-Therapie bei Kindern mit CDH liefern, ist die Anwendung weit verbreitet. Ziel dieser Arbeit war es, die iNOAnwendung in einer retrospektiven Kohorte bezüglich verschiedener „outcome“-Parameter zu analysieren.

Patienten Eingeschlossen wurden 378 CDH-Patienten, die zwischen 2010 und 2017 in der Klinik für Neonatologie des Universitätsklinikum Mannheim behandelt wurden. Die Therapie erfolgte anhand des standardisierten Protokolls des CDH EURO Consortium.

Methoden Allgemeine (Geschlecht, Geburtsgewicht, Gestationsalter usw.) und therapiebezogene Daten (Dauer iNO Anwendung, OI n. 60 Min., ECMO-Notwendigkeit usw.) wurden aus Patientenakten akquiriert und mithilfe von SAS verarbeitet (mono- /multivariate Analyse). Ergebnisse Von 378 Neugeborenen mit CDH erhielten 265 iNO (70,1%), von denen 82 (30,9%) nach 60 Min. eine signifikante Erniedrigung des OI um ≥5 Pkt. zeigten (=„responder“). Insgesamt verbesserte sich der mediane OI um 1,85 Pkt. Unter „respondern“ reduzierte die Anwendung von iNO den ECMO-Bedarf (p=0,0054), verlängerte die Zeit bis ECMO-Beginn (p=0,005) und reduzierte die Mortalität (p=0,0396).

Diskussion Eine Gruppe von 43 Patienten profitierte von iNO und musste nicht an die ECMO angeschlossen werden. Obwohl sich keine signifikanten vorteilhaften Effekte bei den „non-respondern“ zeigten, sollte iNO weiterhin als zentraler Behandlungspfeiler während der Stabilisierungsperiode von CDH-Patienten betrachtet werden.

Zusammenfassung Es sollte ein kritischerer Umgang mit dem Einsatz von iNO bei „non-respondern“ angestrebt werden. Weiterreichende multizentrische Studien über Behandlungsalternativen für CDH-PHT sind wünschenswert.

Key words

congenital diaphragmatic hernia (CDH) - nitric oxide (NO) - pulmonary arterial hypertension (PAH) - extracorporeal membrane oxygenation (ECMO)

Schlüsselwörter

Zwerchfellhernie - Stickstoffmonoxid (NO) - pulmonalarterielle Hypertension (PHT) - extrakorporale Membranoxygenierung (ECMO)

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