早产儿延迟夹脐带后脐静脉注射咖啡因的药代动力学。
Caffeine pharmacokinetics following umbilical vein injection during delayed cord clamping in preterm lambs.
机构信息
Department of Pediatrics, UC Davis School of Medicine, Sacramento, CA, USA.
UC Davis, School of Veterinary Medicine, Davis, CA, USA.
出版信息
Pediatr Res. 2024 Aug;96(3):663-667. doi: 10.1038/s41390-024-03117-3. Epub 2024 Mar 1.
BACKGROUND
Spontaneous breathing during and after delayed cord clamping (DCC) stabilizes cardiopulmonary transition at birth. Caffeine stimulates breathing and decreases apnea in premature newborns. We evaluated the pharmacokinetics and physiological effects of early caffeine administration-direct injection into the umbilical vein (UV) during DCC or administered through a UV catheter (UVC) after delivery.
METHODS
Eighteen extremely premature lambs (125-127d, term gestation 145d) were exteriorized and instrumented. Lambs received caffeine-citrate at high (40 mg/kg) or standard-dose (20 mg/kg) via direct UV (DUV) injection during DCC, or via the UVC.
RESULTS
Mean peak plasma caffeine concentrations were lower with high-dose DUV compared to UVC (18 ± 4.3 vs. 46 ± 12 mg/L, p < 0.05). With standard-dose caffeine, mean peak plasma levels were 7.48 ± 2.6 with DUV and 28.73 ± 9.4 mg/L with UVC. The volume of distribution was higher in the DUV group compared to UVC (2.5 ± 1.0 vs. 0.69 ± 0.15 L/kg) with an estimated 39 ± 18% entering the maternal circulation. Maternal peak concentrations were 0.79 ± 0.71 and 1.43 ± 0.74 mg/L with standard and high-dose DUV, respectively.
CONCLUSIONS
Caffeine injected directly into the UV during DCC is feasible but achieves lower concentrations due to high volume of distribution including maternal circulation. Further trials evaluating DUV caffeine injection should use higher caffeine doses.
IMPACT
Respiratory stimulation with early caffeine may reduce the need for intubation in preterm infants. In the preterm lambs, caffeine injection directly into the umbilical vein during delayed cord clamping is feasible. Plasma caffeine concentrations are less than half when administered directly into the umbilical vein during delayed cord clamping compared to administration via an umbilical venous catheter following birth likely attributed to a larger volume of distribution or injection site leak. There were no significant hemodynamic alterations following caffeine injection.
背景
在延迟脐带夹闭期间和之后进行自主呼吸可稳定出生时心肺功能的转变。咖啡因可刺激呼吸并减少早产儿的呼吸暂停。我们评估了在延迟脐带夹闭期间直接向脐静脉（UV）内注射（DUV）或分娩后通过 UV 导管（UVC）给药时早期给予咖啡因的药代动力学和生理效应。
方法
将 18 只极早产儿（125-127 天，足月妊娠 145 天）取出并进行仪器操作。羔羊在延迟脐带夹闭期间通过直接 UV（DUV）注射接受高（40mg/kg）或标准剂量（20mg/kg）的咖啡因柠檬酸盐，或通过 UVC 接受。
结果
与 UVC 相比，高剂量 DUV 的平均峰值血浆咖啡因浓度较低（18±4.3 与 46±12mg/L，p<0.05）。标准剂量咖啡因时，DUV 的平均峰值血浆水平为 7.48±2.6mg/L，UVC 为 28.73±9.4mg/L。与 UVC 相比，DUV 组的分布容积更高（2.5±1.0 与 0.69±0.15L/kg），估计有 39±18%进入母体循环。标准和高剂量 DUV 时，母体的峰值浓度分别为 0.79±0.71 和 1.43±0.74mg/L。
结论
在延迟脐带夹闭期间直接向 UV 内注射咖啡因是可行的，但由于包括母体循环在内的高分布容积，导致浓度较低。应使用更高剂量的咖啡因进一步评估 DUV 咖啡因注射。
影响
早期给予咖啡因刺激呼吸可能会减少早产儿需要插管的情况。在早产羔羊中，在延迟脐带夹闭期间直接向脐静脉内注射咖啡因是可行的。与出生后通过 UVC 给药相比，在延迟脐带夹闭期间直接向脐静脉内给予咖啡因时，血浆咖啡因浓度低于一半，这可能归因于更大的分布容积或注射部位泄漏。咖啡因注射后没有明显的血液动力学改变。
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