PCCM Network: Remedies for Opioid Tolerance & Withdrawal

描述（由申请人提供）：对儿科ICU（PICU）中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。阿肯色州儿童医院的26张床位的PICU每年为>1500名重症婴儿/儿童提供先进的创伤和重症监护，研究驱动，学术环境，由8名儿科重症监护医师，空中/地面运输服务以及所有医疗和外科专科支持。私家侦探以其关于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，参与并领导了多项多中心临床试验。研究协调员在学术护理、赠款管理、多中心研究协调和PICU临床经验方面具有丰富的背景。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，从地理定义的区域招募患者，并建立随访计划。提出了一项随机对照试验，以评估减少通气重症儿童阿片类药物耐受性的新型疗法。目的1探讨小剂量纳洛酮静脉滴注对PICU患者阿片耐受和戒断的影响。目标2将检查低剂量纳洛酮输注对临床结局的影响，例如需要额外的镇痛/镇静，阿片类药物撤机所需的持续时间和拔管后PICU停留时间。目的研究儿童阿片耐受和戒断的临床、药物基因组学、神经内分泌和神经行为学相关因素。这项研究进一步提出了一个公私合作伙伴关系，以评估新技术监测PICU患者的镇静。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，需要研究新的预防和治疗方法。私家侦探，研究协调员和合作研究者保护了研究时间、临床和转化研究经验以及科学技能，以促进拟定的PCCM协作网络，以及用于培训未来研究者的既定教育和培训计划。

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.