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.

仅在美国，每年就有大约 600 万儿童接受麻醉。持续的阿片类药物流行迫使医学界研究如何使用阿片类药物来治疗疼痛。现在有证据表明，生命早期接触阿片类药物与对疼痛更敏感、对生理、认知、运动技能和行为产生不利的长期影响、控制疼痛所需的阿片类药物更高以及持续使用阿片类药物的风险更高有关。因此，正在深入研究不含阿片类药物的麻醉和镇痛方案。特别是对于婴儿来说，脊髓麻醉剂能够在不使用阿片类药物的情况下提供镇痛作用，同时进一步诱导大脑镇静状态，这与需要同时使用传统镇静催眠药来减弱意识的成年人不同。这一临床观察背后的神经学基础尚未完全了解，我们已开始收集试点数据以帮助进一步阐明这些特性。我和我的导师团队现在在 K23 指导的以患者为导向的研究职业发展奖申请中处于有利地位，可以严格且可重复地研究早期阿片类药物暴露对大脑的急性影响及其对发育的潜在长期影响，并与节省阿片类药物的脊髓麻醉。我从 2016 年开始收集麻醉脑电图 (EEG) 数据集，迄今为止的样本量由 143 名受试者组成，中位年龄为 7 个月，而且还在持续增长。我们的初步数据表明，脊髓麻醉的一个标志似乎是睡眠纺锤体复合体，它类似于正常的生理睡眠，与使用阿片类药物的全身麻醉 (GA) 效果不同。我有一个独特的机会来解决早期麻醉对大脑影响的关键知识空白，并获得额外的 K23 支持，以继续分析整个脑电图数据集所需的受试者招募和指导研究培训活动。我们已经证明这项工作是可行的，将进一步有助于从根本上发现阿片类药物与阿片类药物节约替代品的镇痛行为和神经生理学相关性，其目标如下：（1）镇痛行为和神经生理学的前瞻性量化100 名受试者中婴儿脊髓麻醉的相关性，(2) 接受脊髓麻醉的婴儿与接受脊髓麻醉的婴儿的神经生理学特性的比较100 名处于正常生理睡眠的年龄相似的婴儿和 200 名接受全身麻醉进行类似手术的婴儿，以及（3）在脊髓下（n = 100）与全身麻醉（n = 200）下接受类似手术的婴儿之间的临床和行为结果的比较。蒙特菲奥里爱因斯坦的研究环境非常好，我的导师团队拥有专业知识，可以指导我对早期麻醉对大脑的影响进行严格评估。我的培训计划是专门为培养我在临床研究设计、数据科学、发育神经科学和神经数据分析方面的技能而设计的。完成职业发展奖后，我将成功申请 R01 级资金，并准备好转型为一名完全独立的临床医生研究员，致力于改善儿童麻醉护理。