Analgesic-Behavioral and Neurophysiological Correlates of Opioid-Sparing Spinal Anesthesia Compared to General Anesthesia in Human Infants

人类婴儿中少阿片类药物脊髓麻醉与全身麻醉的镇痛行为和神经生理学相关性

• 批准号: 10571344
• 负责人: Jerry Y Chao
• 金额: $ 19.57万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571344
• 关键词: Absence of pain sensation; Acute; Address; Adult; Age; Analgesics; Anesthesia procedures; Anesthetics; Awareness; Behavior assessment; Behavioral; Brain; Caring; Child; Child Behavior Checklist; Childhood; Clinical; Clinical Research; Cognition; Communities; Complex; Crying; Data; Data Analyses; Data Science; Data Set; Dedications; Delirium; Dependence; Development; Dissociation; Electroencephalography; Environment; Exhibits; Exposure to; Face; Frequencies; Funding; General Anesthesia; General anesthetic drugs; Goals; Hour; Human; Infant; Intensive Care; K-Series Research Career Programs; Knowledge; Leg; Long-Term Effects; Measures; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Mission; Modality; Motor Skills; National Institute of Drug Abuse; Neurologic; Neurosciences; Operative Surgical Procedures; Opioid; Pain; Pain management; Physicians; Physiological; Physiology; Positioning Attribute; Postoperative Period; Property; Regimen; Reproducibility; Research; Research Design; Research Personnel; Research Project Grants; Research Training; Risk; Sample Size; Sedation procedure; Sleep; Spinal; Spinal Anesthesia; Substance abuse problem; Time; Training; Training Activity; United States; Vertebral column; Work; behavior measurement; behavioral outcome; brain behavior; career development; design; early life exposure; experience; follow up assessment; high risk; hypnotic; improved; irritation; motor behavior; neural; neurophysiology; opioid epidemic; opioid exposure; opioid sparing; opioid use; pain score; prospective; recruit; risk minimization; sedative; skills; sleep spindle; substance misuse

Each year, approximately 6 million children receive anesthesia in the United States alone. The ongoing opioid epidemic has forced the medical community to examine how it uses opioids for pain management. There is now evidence that early life exposure to opioids is associated with greater sensitivity to pain, adverse long-term effects on physiology, cognition, motors skills and behavior, higher opioid requirements for pain control, and higher risk of persistent opioid use. Accordingly, opioid-sparing anesthetic and analgesic regimens are being investigated intensely. For infants in particular, spinal anesthetics are able to provide analgesia without opioids while further inducing a sedated brain state, unlike adults who require co-administration of traditional sedative-hypnotic agents to blunt awareness. The neurological basis underlying this clinical observation is not fully understood and we have begun to collect pilot data to help further clarify these properties. My mentorship team and I are now well-positioned in this K23 Mentored Patient-Oriented Research Career Development Award application to rigorously and reproducibly investigate the acute effects of early opioid exposure in the brain and its potential long-term impact on development, with comparison to opioid-sparing spinal anesthesia. I began assembling an anesthesia electroencephalogram (EEG) dataset beginning in 2016 - with a sample size to date now consisting of 143 subjects with a median age of 7 months that continues to grow. Our preliminary data demonstrate that a hallmark of spinal anesthesia appears to be the sleep spindle complex, which resembles normal physiologic sleep that is distinct from general anesthetic (GA) effects that employ opioids. I have a unique opportunity to address critical gaps in knowledge of the effects of early anesthesia on the brain with additional K23-support to continue the subject recruitment and mentored research training activities necessary to analyze the entire EEG dataset. This work, which we have already demonstrated is feasible, will further contribute to fundamental discovery of the analgesic-behavioral and neurophysiological correlates of opioids vs. opioid-sparing alternatives, with the following aims: (1) prospective quantification of analgesic-behavioral and neurophysiological correlates of infant spinal anesthesia in 100 subjects, (2) comparison of neurophysiological properties of infants receiving spinal anesthesia compared to 100 infants of similar age in normal physiologic sleep and 200 infants undergoing similar surgeries receiving general anesthesia, and (3) comparison of clinical and behavioral outcomes between infants undergoing similar surgeries under spinal (n=100) versus general anesthesia (n=200). The research environment at Montefiore Einstein is exceptional and my team of mentors has the expertise to guide me in rigorous assessments of early anesthetic effects on the brain. My training plan is specifically designed to develop my skills in clinical study design, data science, developmental neuroscience, and neural data analysis. By the completion of the career development award, I will have successfully applied for R01-level funding and will be ready to transition to a fully independent clinician-investigator dedicated to improving anesthesia care in children.

每年，仅在美国，大约有600万儿童就会麻醉。正在进行的阿片类药物流行病迫使医学界研究它如何使用阿片类药物进行疼痛管理。现在有证据表明，早期生命暴露于阿片类药物与对疼痛的敏感性更大，长期对生理学，认知能力，汽车技能和行为的不利影响，疼痛控制的较高阿片类药物需求以及持续使用阿片类药物的风险更高。因此，正在深入研究消除阿片类药物的麻醉和止痛药。特别是对于婴儿，脊柱麻醉药能够在没有阿片类药物的情况下提供镇痛，同时进一步诱导镇静的大脑状态，这与需要对传统镇静性催眠剂共同给药以钝性意识的成年人不同。该临床观察的基础神经基础尚未完全了解，我们已经开始收集试点数据以进一步阐明这些特性。我和我的指导团队现在在K23指导的注重患者的研究职业发展奖应用程序中，对大脑早期阿片类药物暴露及其对发育的潜在长期影响的急性影响，与阿片类脊髓性麻醉相比。从2016年开始，我开始组装麻醉脑电图（EEG）数据集 - 迄今为止的样本量现在由143名受试者组成，中位年龄为7个月，持续增长。我们的初步数据表明，脊柱麻醉的标志似乎是睡眠纺锤体复合物，类似于正常的生理睡眠，与使用阿片类药物的全身麻醉（GA）作用不同。我有一个独特的机会来解决有关早期麻醉对大脑影响的关键差距，并额外的K23支持继续受试者招募，并指导了分析整个EEG数据集所需的研究培训活动。我们已经证明的这项工作是可行的，将进一步促进基本发现阿片类药物与阿片类药物的替代方案的镇痛行为和神经生理学相关性，以下目的是：（1）对镇痛性 - 行为 - 行为 - 行为和神经生理学的棘手疾病的前瞻性定量（1）。接受脊柱麻醉的婴儿的神经生理特性与正常生理睡眠年龄相似的100例相似的婴儿和200例接受全身麻醉的手术的婴儿，以及（3）在脊髓（n = 100）对脊柱（n = 100）与一般性麻醉（n = 200）的临床和行为结果进行比较（3）。蒙特菲奥尔爱因斯坦（Montefiore Einstein）的研究环境非常出色，我的导师团队具有专业知识，可以指导我严格评估早期麻醉对大脑的影响。我的培训计划是专门设计的，旨在发展我在临床研究设计，数据科学，发育神经科学和神经数据分析方面的技能。通过完成职业发展奖，我将成功申请R01级资金，并准备过渡到一个完全独立的临床医生评估者，致力于改善儿童麻醉护理。