Klin Padiatr 2014; 226(04): 211-215
DOI: 10.1055/s-0034-1375697
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Intravenous Sildenafil i. v. as Rescue Treatment for Refractory Pulmonary Hypertension in Extremely Preterm Infants

Intravenöses Sildenafil als letzte Therapieoption bei refraktärer pulmonaler Hypertension bei extrem unreifen Frühgeborenen
M. Steiner
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
U. Salzer
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
S. Baumgartner
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
T. Waldhoer
2   Department of Epidemiology, Medical University of Vienna, Center of Public Health, Vienna, Austria
,
K. Klebermass-Schrehof
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
M. Wald
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
M. Langgartner
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
,
A. Berger
1   Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Vienna, Austria
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Publikationsverlauf

Publikationsdatum:
10. Juli 2014 (online)

Abstract

Background: Intravenous sildenafil treatment has recently shown promising results and good tolerability in the treatment of refractory pulmonary hypertension (PH) in term and near-term neonates, while comparable data in preterm infants are still lacking. However, for critically ill preterm infants suffering from PH refractory to conventional treatment, sildenafil may represent a last treatment resort.

Patients and methods: We reviewed the records of 6 critically ill extremely preterm infants who had suffered from PH refractory to conventional treatment and had obtained intravenous sildenafil after careful consideration as ultima ratio treatment.

Aim: To describe the responses to sildenafil in terms of hemodynamic and respiratory changes during treatment and outcome.

Results: 4/6 patients showed resolution of severe PH with full reversal of ductal shunt direction into pure left-to-right shunt within 82±35 h after sildenafil start. Remarkably, 2/6 patients developed pulmonary hemorrhage at a time point when significant improvement of PH had already taken place, both of them survived. Overall 4/6 patients died, two deaths were related to treatment-refractory PH.

Conclusion: Intravenous sildenafil treatment seems effective in improving severe PH and hemodynamic instability in extremely preterm infants with refractory PH. Pulmonary hemorrhage may represent a distinct adverse effect of sildenafil treatment in these patients, presumably due to sudden reversal of ductal shunt. Accordingly, sildenafil should be restricted to most severe and refractory cases in this population.

Zusammenfassung

Hintergrund: Die intravenöse Sildenafiltherapie hat bei reifen Neugeborenen mit schwerer pulmonaler Hypertension (PHT) vielversprechende Ergebnisse gezeigt. Bei Frühgeborenen hingegen fehlen diesbezügliche klinische Daten weitgehend. Dennoch stellt Sildenafil bei kritisch kranken Frühgeborenen mit therapierefraktärer PHT in Ermangelung anderer Therapiemöglich­keiten eine letzte Therapieoption dar.

Patienten und Methoden: Echokardiografische und klinische Daten von 6 Frühgeborenen wurden ausgewertet, die aufgrund einer schweren pulmonalen Hypertension ohne Ansprechen auf konventionelle Therapie (d. h. Beatmungsoptimierung, Milrinon±inhalatives NO) additiv i. v. Sildenafil als ultima ratio erhalten hatten.

Studienziel: Erfassung des Ansprechens auf Sildenafil anhand hämodynamischer und respiratorischer Veränderungen unter Therapie und des Outcomes.

Ergebnisse: 4/6 Patienten zeigten ein Ansprechen im Sinne einer kompletten Shuntumkehr über einen offenen Ductus arteriosus in einen reinen Links-Rechts-Shunt innerhalb von 82±35 Stunden nach Beginn der Sildenafiltherapie. Auffallend war, dass 2 Patienten eine Lungenblutung zu einem Zeitpunkt entwickelten, wo bereits eine deutliche Verbesserung der Lungendurch­blutung im Rahmen der PHT stattgefunden hatte, beide überlebten. Insgesamt verstarben 4/6 Patienten, 2 Todesfälle waren auf eine refraktäre PHT zurückzuführen.

Schlussfolgerung: Bei Frühgeborenen mit schwe­rer therapierefraktärer PHT scheint i. v. Sildenafil die PHT und die damit einhergehende kardio­pulmonale Instabilität verbessern zu können. Lungenblutungen könnten allerdings eine mögliche schwere Nebenwirkung in dieser Altersgruppe darstellen. Entsprechend sollte diese Therapieoption auf schwerste, refraktäre Verläufe beschränkt bleiben.

 
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