日本未熟児新生児学会雑誌　第23巻第2号　65～71頁（2011年）

日本未熟児新生児学会雑誌　23(2)：275-281；2011　

受付日：平成22.09.07

受理日：平成23.01.13

低用量ドキサプラム投与の脳血流，脳内酸素化指標に及ぼす影響

Effects of Low-Dose Doxapram Infusion on Cerebral Hemodynamics in Infants with Apnea of Prematurity

藤田保健衛生大学　医学部　小児科

Department of Pediatrics, Fujita Health University, School of Medicine

帽田仁子・藤野正之・江竜喜彦・竹内正知・宮田昌史・山﨑俊夫

Hiroko BODA，Masayuki FUJINO，Yoshihiko ERYU，Masatomo TAKEUCHI，Masafumi MIYATA，Toshio YAMAZAKI

Key Words：idiopathic apnea of prematurity，near infrared spectroscopy，low-dose doxapram therapy，cerebral hemodynamics

　超低出生体重児にドキサプラムを2.5mg/kg/hr で投与時に脳血流や脳内酸素化が悪化したという報告がある。我々は，ドキサプラムの低用量投与が脳血流に及ぼす影響について超音波ドプラ法と近赤外線分光法を用いて検討した。
　対象は未熟児無呼吸発作のある早産低出生体重児11 例で，ドキサプラムは1.5mg/kg を負荷投与し，その後0.2mg/kg/hr で維持投与した。投与前後に超音波ドプラ法で前大脳動脈のVmax，Vmin，RI，PI を測定し，赤外線酸素モニタ装置を用いて⊿ O2Hb，⊿ HHb，⊿ HbD，TOI，nTHI を測定した。その結果，ドキサプラム投与前後でVmax，Vmin，RI，PI には変化なかったが，負荷投与終了時のHbD，維持投与8 時間後のO2Hb，HbD が有意に増加した。TOI，nTHI は経過中に変化なかった。今回の検討では低用量ドキサプラムの投与は脳の血行動態に悪影響を及ぼさないと考えられた。

　Although doxapram is widely used for the treatment of idiopathic apnea of prematurity（AOP），there are some concerns about the cerebral hemodynamic effects while using higher doses. We evaluated the effects of low-dose doxapram infusion on cerebral hemodynamics using Doppler ultrasonography and near infrared spectroscopy in infants with AOP.
　Eleven preterm infants with mean birth weight 1,349±355g and mean gestational age 32.1±1.3 weeks were enrolled in the study. Doxapram was administered intravenously with a loading dose of 1.5mg/kg over 1 hour period, followed by a continuous infusion of 0.2mg/kg/hr. Using transfontanellar Doppler ultrasonography, maximal systolic blood flow velocity （Vmax），end-diastolic blood flow velocity（Vmin），pulsatility index（PI）and resistance index（RI）were measured in the anterior cerebral artery. Measurements were performed at baseline, 60minutes, 9 hours after the start of doxapram. To assess the brain oxygenation, relative changes in the oxygenated hemoglobin（O2Hb），deoxygenated hemoglobin（HHb）， tissue oxygenation index（TOI）and normalized tissue hemoglobin index（nTHI）were recorded by NIRS from 10minutes before to 9 hours after the doxapram infusion. Cerebral intravascular oxygenation（HbD＝O2Hb−HHb）which was demonstrated to be strongly related to cerebral blood flow was calculated.
　There were no significant changes in Vmax, Vmin, PI and RI of the anterior cerebral artery during the study. Heart rate, respiratory rate, blood pressure, SpO2, and TcPCO2 also did not display significant changes after the start of doxapram infusion.
　HbD at 60minutes and O2Hb and HbD at 9 hours after doxapram infusion were significantly increased from baseline, while TOI and nTHI did not change during the study.
　From the result of our study, low-dose doxapram infusion may not affect cerebral hemodynamics in infants with AOP.