PCCM Network: Remedies for Opioid Tolerance & Withdrawal

描述(由申请人提供)：对儿科ICU(PICU)中使用的治疗方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。阿肯色州儿童医院的PICU有26张床位，每年为1500名危重婴儿/儿童提供高级创伤和重症护理，环境以研究为导向，由8名儿科重症医生、空运/地面运输服务以及所有内科和外科专科提供支持。这位P.I.以通过阿片类药物或其他药物缓解婴儿和儿童的疼痛和应激反应的临床研究而闻名，参与并领导了几项多中心临床试验。研究协调员在学术护理、补助金管理、多中心研究的协调以及在PICU的临床经验方面拥有丰富的背景。这种环境非常适合合作研究，具有参与多中心试验的良好记录，从地理定义的地区招募患者，并建立后续计划。提出了一项随机对照试验，以评估减少呼吸机危重儿童阿片类药物耐受性的新疗法。目的1探讨小剂量纳洛酮输注对PICU患者阿片耐受和阿片戒断的影响。目的2将研究小剂量纳洛酮输注对临床结果的影响，如是否需要额外的止痛/镇静，所需的阿片类药物脱机时间和拔管后PICU的停留时间。目的确定儿童对阿片类药物耐受和戒断的易感性与临床、药物基因组学、神经内分泌和神经行为相关的因素。这项研究进一步提出了公私合作伙伴关系，以评估监测PICU患者镇静的新技术。阿片类药物治疗可能是导致PICU并发症的最常见的药物治疗，因此有必要研究新的预防和治疗方法。P.I.、研究协调员和联合调查员保护了研究时间、临床和转化性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。

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.