基于生理学的建模显示,在成人和儿童之间过量服用芬太尼后,呼吸系统抑郁的风险不同
Shilpa Chakravartula1, Bradlee Thrasher1, John Mann1
1Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Clinical and translational science
|April 15, 2024
概括
在社区环境中,儿童可能面临较高的阿片类药物诱导的呼吸抑制和脑缺氧的风险. 这是由于他们更高的氧气需求和降低的脑血管反应能力,即使在与成年人相同的芬太尼度.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科医学 儿科医学
- 翻译科学 翻译科学
背景情况:
- 儿童死于阿片类药物的死亡率正在上升,但对儿童剂量依赖性呼吸系统抑郁的研究是有限的.
- 与阿片类药物相关的呼吸系统抑郁是儿童阿片类药物过量服用病例的主要死亡原因.
- 现有的模型缺乏儿科特定的药理动力学,药理动力学和生理学考虑.
研究的目的:
- 将阿片类药物诱导的呼吸系统抑郁症的翻译模型扩展到儿科患者群体.
- 与成年人相比,调查影响儿童阿片类药物效应的年龄相关因素.
- 为了确定儿童的外科和社区环境之间阿片类药物风险的潜在差异.
主要方法:
- 将依赖年龄的药理动力学,药理动力学和生理学变量纳入先前存在的翻译模型.
- 模拟呼吸系统抑郁的终点,如每分钟通风和血液二氧化碳的压力.
- 在各种临床情景下,对儿科和成人群体的模型预测进行了比较.
主要成果:
- 该模型证实了在使用通风和二氧化碳终点时,在等效的血芬太尼度下,儿童和成年人患有类似的呼吸抑制风险.
- 带有机械通风和氧气面罩的外科设置可能会导致呼吸抑制的与氧气相关的后果.
- 在社区环境中,由于氧气需求增加和脑血管反应能力降低,儿童可能更容易患上缺氧和脑缺氧.
结论:
- 儿科特异性因素,包括更高的氧气需求和改变的大脑血管反应能力,在社区环境中增加了对严重低氧症的易感性.
- 这些因素对于制定有效的干预策略来预防儿科阿片类药物过量使用至关重要.
- 该模型强调在评估儿童的阿片类药物风险时,需要考虑年龄相关的生理差异.
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