Abstinence and Drug Withdrawal: Innovative Translational Methods for Neonates

戒断和戒毒：新生儿的创新转化方法

• 批准号: 8734363
• 负责人: Elisabeth Bloch Salisbury
• 金额: $ 19.64万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8734363
• 关键词: Abstinence; Adjuvant; Age; Analgesics; Apnea; Behavioral; Birth; Blood Circulation; Bradycardia; Brain; Brain Stem; Breathing; Caring; Clinical assessments; Data; Dependence; Development; Drug Withdrawal Symptoms; Foundations; Frequencies; Functional disorder; Future; Healthcare; Heart; Heart Rate; Hospitalization; Infant; Infant Development; Intervention; Intestines; Lead; Life; Mattresses; Measurement; Mechanical Stimulation; Mechanics; Medical; Methods; Morbidity - disease rate; Movement; Neonatal; Neonatal Abstinence Syndrome; Newborn Infant; Noise; Opiates; Outcome; Pharmaceutical Preparations; Pharmacological Treatment; Physical Dependence; Physiologic Thermoregulation; Physiological; Population; Populations at Risk; Pregnant Women; Premature Infant; Process; Prospective Studies; Research; Respiration; Risk; Sensory; Severities; Signal Transduction; Sleep; Sleep disturbances; Staging; Stimulus; Structure; Sudden infant death syndrome; System; Tachycardia; Tactile; Temperature; Testing; Therapeutic; Therapeutic Intervention; Time; Vasomotor; Wakefulness; Weaning; Withdrawal; Withdrawal Symptom; arm; base; biological systems; computerized tools; cost; critical period; design; drug abstinence; drug withdrawal; fetal; fetal drug exposure; gastrointestinal; improved; in utero; indexing; innovation; neonate; neural circuit; neurobehavior; neurobehavioral; novel; novel strategies; preclinical study; prescription opioid; public health relevance; respiratory; standard care; unborn child; vibration

DESCRIPTION (provided by applicant): Fetal drug exposure is a nationwide problem. Nearly five percent of pregnant women nationwide expose their unborn child to drugs in utero (illicit and prescription). Neonatal Abstinence Syndrome (NAS) refers to multi- system disturbances and dysregulated neurobehaviors caused by discontinuation of drug/s to which an infant has developed tolerance and physical dependence. Novel approaches to study and treat NAS are needed because despite current interventions NAS infants often require prolonged hospitalization and pharmacological treatment for central, autonomic, vasomotor and gastrointestinal instabilities, which may contribute also to poor neurobehavioral outcomes. Growing research suggests the importance of sensory stimulation, particularly tactile stimulation for enhancing normal brain development and stability of function. There is evidence that unperceivable noise-like vibrations (stochastic resonance) can provoke stability in destabilized biological systems. The underlying hypothesis of this proposal is that NAS in newborns is characterized by physiological disturbances that reflect drug-withdrawal severity and that pathophysiological instabilities in drug-withdrawing neonates can be stabilized by stochastic, vibro-tactile stimuli. Forty NAS (opiate-exposed) neonates will participate in a rigorous, short-term study at UMass Memorial Healthcare to examine the following two aims: Aim 1. Quantify via intensive measurement the instabilities of physiological signals of drug withdrawal in NAS infants. Changes and relationships among physiological signals, e.g., instability of respiration, heart beat and temperature, and excessive movement, will be quantified using non-linear computational signal analyses (point process and wavelet) to explore whether physiological instabilities can index NAS severity and predict onset/offset of withdrawal symptoms. Such information would help facilitate pharmacological management of abstinence and drug withdrawal in neonates. Aim 2. Examine the efficacy of stochastic, vibro-tactile stimulation for enhancing physiological stability in NAS infants and alleviating the symptoms of drug withdrawal. Subjects will serve as their own control to test the hypothesis that stochastic, vibro-tactile perturbations impinge upon destabilized neural circuits and reduce the progressive spread of NAS irritability from subcortical (brainstem) to cortical structure, marked by excessive changes in respiration, heart rate, temperature and subsequent upsurge in movement. Conditions of stochastic vibration (specially designed mattress with mechanical actuators embedded in foam; 30-60Hz, RMS amplitude 0.1mm) will be compared to control periods to test whether stimulation: 1) Improves cardio-respiratory control by reducing instability of heart beat (e.g., bradycardia, tachycardia) and respiration, including decreasing incidents of apnea, periodic breathing and tachypnea; 2) Inhibits sleep disruption as marked by reduction of excessive body movements; and 3) Relieves withdrawal symptoms indexed by improved NAS clinical assessment scores. Findings from this proposal will elucidate whether stochastic, vibro-tactile stimulation has potential as an adjuvant treatment of NAS for improving cardio-respiratory control and reducing sleep disruption (indexed by excessive movement) in NAS infants. A more rigorous future prospective study may ultimately help elucidate underlying mechanisms involved in NAS, lead to improved therapeutic interventions for reducing severity and duration of drug withdrawal complementary to standard care, and thereby improve morbidity and reduce hospitalization and medical costs among NAS infants.

描述(申请人提供)：胎儿药物暴露是一个全国性的问题。全国近5%的孕妇在子宫内让未出生的孩子接触药物(非法药物和处方药)。新生儿戒断综合症是指婴儿对停药/S已产生耐受性和身体依赖而导致的多系统功能障碍和神经行为失调。需要新的方法来研究和治疗NAS，因为尽管目前采取了干预措施，NAS婴儿通常需要长期住院和药物治疗，以治疗中枢、自主神经、血管运动和胃肠道不稳定，这也可能导致不良的神经行为结果。越来越多的研究表明，感觉刺激，特别是触觉刺激对于促进正常大脑发育和功能稳定性的重要性。有证据表明，不可察觉的类噪音振动(随机共振)可以在不稳定的生物系统中引起稳定性。这一建议的基本假设是，新生儿NAS的特征是反映药物戒断严重程度的生理障碍，戒毒新生儿的病理生理不稳定性可以通过随机的振动-触觉刺激来稳定。40名NAS(阿片类药物暴露)新生儿将参加在加州大学马萨诸塞州纪念医疗中心进行的一项严格的短期研究，以检查以下两个目标：目的1.通过密集测量量化NAS婴儿停药的生理信号的不稳定性。生理信号的变化和之间的关系，例如，呼吸、心跳和温度的不稳定，以及过度运动，将使用非线性计算信号分析(点过程和小波)来量化，以探索生理不稳定是否可以指示NAS的严重程度和预测戒断症状的开始/抵消。这些信息将有助于促进对新生儿禁欲和停药的药理学管理。目的2.检验随机振动触觉刺激在提高NAS婴儿生理稳定性和缓解药物戒断症状方面的效果。受试者将作为他们自己的对照来检验这一假设，即随机的、振动-触觉的扰动会影响不稳定的神经回路，并减少NAS应激性从皮质下(脑干)到皮质结构的逐渐传播，其特征是呼吸、心率、温度的过度变化和随后的运动激增。随机振动的条件(特别设计的床垫，机械执行器嵌入泡沫；30-60赫兹，均方根幅度0.1毫米)将与控制期进行比较，以测试刺激是否：1)通过减少心跳(如心动过缓、心动过速)和呼吸的不稳定性，改善心肺控制，包括减少呼吸暂停、周期性呼吸和呼吸急促的事件；2)抑制睡眠中断，其标志是减少身体过度运动；以及3)缓解戒断症状，以改进的NAS临床评估评分为指标。这项建议的结果将阐明随机、振动-触觉刺激是否有潜力作为NAS的辅助治疗，以改善NAS婴儿的心肺控制和减少睡眠中断(以过度运动为指标)。未来更严格的前瞻性研究可能最终有助于阐明NAS涉及的潜在机制，导致改进的治疗干预措施，以减少药物停药的严重程度和持续时间，补充标准护理，从而改善NAS婴儿的发病率，降低住院和医疗成本。

项目成果

A Quality Improvement Initiative to Increase Scoring Consistency and Accuracy of the Finnegan Tool: Challenges in Obtaining Reliable Assessments of Drug Withdrawal in Neonatal Abstinence Syndrome.

旨在提高芬尼根工具评分一致性和准确性的质量改进举措：获得新生儿戒断综合症药物戒断可靠评估的挑战。

• DOI: 10.1097/anc.0000000000000441
• 发表时间: 2018
• 期刊: Advances in neonatal care : official journal of the National Association of Neonatal Nurses
• 作者: Timpson,Wendy;Killoran,Cheryl;Maranda,Louise;Picarillo,Alan;Bloch-Salisbury,Elisabeth
• 通讯作者: Bloch-Salisbury,Elisabeth