日本未熟児新生児学会雑誌　第19巻　第1号　53～57頁（2007年）

日本未熟児新生児学会雑誌　19(1)：53-57；2007　

受付日：平成17．02．09

受理日：平成17．12．16

PhosphodiesteraseⅢ阻害薬の早産児動脈管に対する影響について

Effect of PhosphodiesteraseⅢ Inhibitor on the Ductus Arteriosus in Preterm Infants

豊橋市民病院　小児科

Department of Pediatrics，Toyohashi Municipal Hospital

安田和志・小山典久・幸脇正典・野村孝泰・牧野泰子・村田水紀・竹中　学・山田拓司・竹内　幸・伊藤　剛・藤田直也・柴田麻千子・鈴木賀巳

Kazushi YASUDA，Norihisa KOYAMA，Masanori KOUWAKI，Takayasu NOMURA， Yasuko MAKINO，Minori MURATA，Manabu TAKENAKA，Takuji YAMADA， Miyuki TAKEUCHI，Tsuyoshi ITOH，Naoya FUJITA，Machiko SHIBATA，Yoshimi SUZUKI

Key Words：phosphodiesterase inhibitor，preterm infant，patent ductus arteriosus，pulmonary hemorrhage，heart failure

　PhosphodiesteraseⅢ（PDE3）阻害薬は強心作用と血管拡張作用を併せ持つ抗心不全薬で，新生児領域においてもその有効性が報告されている。一方，動物実験では胎仔・新生仔ラット動脈管拡張作用を有することが示され，PDE3阻害薬の早産児動脈管に対する影響が懸念される。PDE3阻害薬を投与された早産児9例の動脈管関連事象等について後方視的に検討した。在胎週数中央値31週4日，出生体重中央値1,670gで，適応症は新生児遷延性肺高血圧症3例，心不全6例であった。9例中3例はPDE3阻害薬投与中および投与中止後しばらくして動脈管閉鎖が確認された。2例は閉鎖しかけていた動脈管が再開通し，うち1例は肺出血を来たした。4例では様々な基礎疾患のために死亡したが，最期まで動脈管閉鎖を確認できなかった。早産児にPDE3阻害薬を投与する際には，動脈管拡張作用の可能性に配慮する必要があると考えられた。

　PhosphodiesteraseⅢ inhibitor（PDE3 inhibitor）is a cardiovascular drug, which acts vasodilatively as well as inotropically. Though PDE3 inhibitor has been used for neonatal heart failure and persistent pulmonary hypertension of the newborn（PPHN）, it has a vasodilative effect on the ductus arteriosus in rat fetus and neonates. Therefore, we retrospectively investigated the effects of PDE3 inhibitors on the ductus arteriosus in 9 preterm infants treated with amrinone or olprinone chloride in the Neonatal Medical Center in Toyohashi Municipal Hospital. Their median gestational age was 31 weeks and 4 days, and their median birth weight was 1,670g. PDE3 inhibitors were used to treat heart failure in 6 of the patients and to treat PPHN in the other 3. In 3 of the 9 patients, the ductus arteriosus closed during administration of PDE3 inhibitor or shortly after its discontinuance. In 2 patients, the ductus arteriosus, which had almost closed, reopened after administration of PDE3 inhibitor, and in one of them pulmonary hemorrhage occurred, while in the other the ductus arteriosus spontaneously closed after discontinuance of the PDE3 inhibitor. Four of the patients died from a variety of severe diseases such as extremely low birth weight infant with tension pneumothorax, and, in all 4, the ductus arteriosus was confirmed to be still open even at death. In conclusion, PDE3 inhibitor should be administered to preterm infants carefully, as it may affect the patency of the ductus arteriosus.