PCCM Network: Remedies for Opioid Tolerance & Withdrawal

PCCM 网络：阿片类药物耐受性的补救措施

• 批准号: 7059953
• 负责人: KANWALJEET S ANAND
• 金额: $ 41.08万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7059953
• 关键词: adrenocorticotropic hormone; analgesia; chemoprevention; child psychology; children; clinical research; clinical trials; cooperative study; critical care; drug abuse chemotherapy; drug tolerance; drug withdrawal; fentanyl; genetic polymorphism; hospital length of stay; human subject; human therapy evaluation; hypothalamic pituitary adrenal axis; intensive care; interview; lorazepam; naloxone; neuroendocrine system; neuropsychology; opiate alkaloid; patient oriented research; pediatrics; pharmacogenetics

DESCRIPTION (provided by applicant): A scientific evaluation of therapies used in the Pediatric ICU (PICU) is essential to build an evidence base that will guide the management of critically ill children. The 26-bed PICU at Arkansas Children's Hospital provides advanced trauma and intensive care to >1500 critically ill infants/children each year in a research driven, academic environment, supported by 8 Pediatric Intensivists, air/ground transport service, and all medical and surgical subspecialties. The P.I. is well-known for his clinical research on alleviating the pain and stress responses of infants and children by opioids or other agents, with participation and leadership of several multicenter clinical trials. The Study Coordinator has a rich background in academic nursing, grants management, coordination of multicenter studies and clinical experience in the PICU. This environment is well-suited for collaborative research with a strong track record of participation in multicenter trials, patient recruitment from a geographically defined area, and established follow-up programs. A randomized controlled trial to evaluate novel therapies for reducing opioid tolerance in ventilated critically ill children is proposed. Aim 1 will investigate the effects of low-dose Naloxone infusions on development of opioid tolerance and opioid withdrawal in PICU patients. Aim 2 will examine the impact of low-dose Naloxone infusions on clinical outcomes such as the need for additional analgesia/sedation , the duration of opioid weaning required and length of PICU stay after extubation. Aim 3 v/ill identify the clinical, pharmacogenomic, neuroendocrine, and neurobehavioral factors associated wii:h susceptibility to opioid tolerance and withdrawal in children. This study further proposes a public-private partnership to evaluate new technology for monitoring sedation in PICU patients. Opioid therapy is perhaps the most common drug therapy leading to PICU complications and warrants an investigation of novel approaches for prevention and treatment. The P.I., Study Coordinator, and Co-Investigators have protected research time, clinical and translational research experience, and the scientific skills to contribute to the proposed Collaborative PCCM Network, together with established educational and training programs for training future investigators.

描述（由申请人提供）：对儿科 ICU (PICU) 使用的疗法进行科学评估对于建立指导危重儿童管理的证据基础至关重要。阿肯色州儿童医院拥有 26 个床位的 PICU，每年在研究驱动的学术环境中为超过 1500 名危重婴儿/儿童提供高级创伤和重症监护，并由 8 名儿科重症监护医生、空中/地面运输服务以及所有医疗和外科手术提供支持亚专业。 P.I.因其通过阿片类药物或其他药物减轻婴儿和儿童疼痛和应激反应的临床研究而闻名，并参与和领导了多项多中心临床试验。研究协调员在学术护理、资助管理、多中心研究协调和 PICU 临床经验方面拥有丰富的背景。这种环境非常适合协作研究，具有参与多中心试验、从特定地理区域招募患者以及建立后续计划的良好记录。提出了一项随机对照试验，以评估降低通气危重儿童阿片类药物耐受性的新疗法。目标 1 将研究低剂量纳洛酮输注对 PICU 患者阿片类药物耐受和阿片类药物戒断的影响。目标 2 将检查低剂量纳洛酮输注对临床结果的影响，例如额外镇痛/镇静的需要、阿片类药物戒断所需的持续时间以及拔管后 PICU 停留时间。目标 3 v/ill 确定与儿童阿片类药物耐受和戒断易感性相关的临床、药物基因组学、神经内分泌和神经行为因素。这项研究进一步提出建立公私合作伙伴关系来评估监测 PICU 患者镇静的新技术。阿片类药物治疗可能是导致 PICU 并发症的最常见药物治疗，值得研究新的预防和治疗方法。 P.I.、研究协调员和联合研究人员保护了研究时间、临床和转化研究经验以及为拟议的合作 PCCM 网络做出贡献的科学技能，以及为培训未来研究人员而制定的教育和培训计划。