Establishment of appropriate dose of caffeine using TDM in extremely preterm infants

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16877
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: 独立行政法人国立病院機構四国こどもとおとなの医療センター(臨床研究部(成育)、臨床研究部(循環器))
• Principal Investigator: Sugino Masashiro 独立行政法人国立病院機構四国こどもとおとなの医療センター(臨床研究部(成育)、臨床研究部(循環器)), 新生児内科, 医師 (50793220)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: カフェイン / 未熟児無呼吸発作 / カフェイン中毒 / 薬物血中濃度モニタリング

Outline of Final Research Achievements

The purpose of this study was to clarify the correlation between caffeine blood concentration and glomerular filtration rate in very preterm infants. The results showed that regardless of the number of weeks of gestation, a caffeine citrate maintenance dose of 8 mg/kg or more for about 7 days was likely to exceed the concentration considered to cause caffeine intoxication, and no correlation was found for glomerular filtration rate. No obvious side effects (tachycardia, abdominal distention, hyponatremia, etc.) or complications (cerebellar hemorrhage, etc.) were observed. Comparison of developmental tests at 3 years of age between the above treatment groups and other groups of patients who were 28 weeks or longer in gestation revealed a significantly lower percentage of normal cognitive function at 3 years of age in the former group.

Free Research Field

新生児学

Academic Significance and Societal Importance of the Research Achievements

未熟児無呼吸発作の治療薬であるカフェインは、標準的な投与方法（5-10mg/kg/日）では中毒濃度を超えないとされていたが、殆どが8mg/kg/日未満での報告である。本研究では8mg/kg以上を継続投与すると中毒濃度を来す可能性があり、3歳時での認知機能低下を来す可能性があるという結果となった。早産児の健やかな発達・成長のために、カフェインの適正な投与方法を追求していく必要がある。