IATROGENIC OPIOID DEPENDENCE IN CRITICALLY ILL CHILDREN

描述：（申请人摘要） 儿科重症监护室的危重患儿通常需要 长期的镇静和止痛。 芬太尼起效快， 作用持续时间和稳定的血流动力学特征。 因此，它是最 用于儿科持续镇痛和镇静的理想阿片类药物 加护病房 然而，芬太尼的连续给药经常 导致耐受性的快速发展，渐进剂量递增， 最终导致医源性阿片类药物依赖。 芬太尼的停药 这些儿童会诱发急性戒断综合征， 危及对孩子的照顾 目前，它还没有完全被理解 哪些患者有阿片类药物依赖和戒断的风险， 有一个有效的方法来客观评估的严重程度， 戒断 虽然医源性阿片类药物戒断的最佳治疗方法 综合征尚未建立在危重病儿童，口服美沙酮 通常用于促进芬太尼停药，同时预防 和戒断症状 然而，没有关于 美沙酮在该患者人群中的最佳剂量或药代动力学。 该提案旨在生成关于医源性疾病广泛方面的数据， 芬太尼依赖，包括诊断和评估其严重程度， 确定其发展的风险因素和药代动力学 芬太尼和美沙酮在重症儿童中的应用 的具体目标 这些研究是：1）验证临床评分工具， 床旁护士客观测量医源性芬太尼的严重程度 禁欲综合症 此评分工具可用于确定何时 芬太尼戒断治疗是必要的; 2）定量芬太尼 暴露通过测量芬太尼的累积面积下 药时曲线; 3）评价全身 芬太尼暴露和医源性阿片类戒断综合征的风险;以及 4)确定美沙酮的药代动力学和生物利用度， 用于治疗这些重症儿童的芬太尼戒断。 这些 数据将大大增加我们对阿片类药物戒断的理解， 重症儿童和增加我们的知识芬太尼和美沙酮 药代动力学，这两个都是至关重要的安全管理这些 代理儿童。

DESCRIPTION: (Applicant's Abstract) Critically ill children in the pediatric intensive care unit often require long-term sedation and analgesia. Fentanyl has a rapid onset, short duration of action, and stable hemodynamic profile. Thus, it is the most desirable opioid for continuous analgesia and sedation in the pediatric intensive care unit. However, continuous administration of fentanyl often leads to rapid development of tolerance, progressive dose escalations, and ultimately iatrogenic opioid dependence. Discontinuation of fentanyl in these children will precipitate acute abstinence syndrome which may compromise the care of the child. Currently, it is not fully understood which patients are at risk for opioid dependence and withdrawal, nor is there a validated method of objectively assessing the severity of withdrawal. Although the optimal treatment of iatrogenic opioid abstinence syndrome has not been established in critically ill children, oral methadone is often used to facilitate fentanyl discontinuation while preventing signs and symptoms of withdrawal. However, no data are available regarding the optimal dose or pharmacokinetics of methadone in this patient population. This proposal aims to generate data on wide ranging aspects of iatrogenic fentanyl dependence, including diagnosis and evaluation of its severity, determination of risk factors for its development, and the pharmacokinetics of fentanyl and methadone in critically ill children. The specific aims of these studies are: 1) to validate a clinical scoring tool to be used by the bedside nurse to objectively measure the severity of iatrogenic fentanyl abstinence syndrome. This scoring tool may be used to determine when treatment of fentanyl withdrawal is necessary; 2) to quantitate fentanyl exposure by measuring fentanyl's cumulative area under the concentration-time curve; 3) to evaluate the relationship between systemic fentanyl exposure and the risk of iatrogenic opioid abstinence syndrome; and 4) to define the pharmacokinetics and bioavailability of methadone which is used to treat fentanyl withdrawal in these critically ill children. These data will significantly augment our understanding of opioid withdrawal in critically ill children and increase our knowledge of fentanyl and methadone pharmacokinetics, both of which are critical in safely administering these agents to children.