Prediction and early recognition of opioid-induced respiratory depression

阿片类药物引起的呼吸抑制的预测和早期识别

• 批准号: 10426828
• 负责人: Carlos B Mantilla
• 金额: $ 23.85万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426828
• 关键词: Acute; Adverse effects; Age; Anesthetics; Behavior; Breathing; Carbon Dioxide; Cessation of life; Chronic; Clinical; Coughing; Dose; Evaluation; Gender; Generations; Hospitalization; Hypercapnia; Hypoventilation; Hypoxia; Impairment; Incidence; Intervention; Manometry; Measurement; Measures; Mental Depression; Monitor; Motor Activity; Muscle; Muscle function; Opioid; Overdose; Pain; Patients; Perioperative; Pharmaceutical Preparations; Postoperative Pain; Postoperative Period; Predisposition; Prevention strategy; Respiratory Diaphragm; Respiratory Function Tests; Respiratory Muscles; Rest; Risk; Speed; Supervision; Techniques; Testing; Time; Training; Ventilatory Depression; Work; adverse outcome; base; comorbidity; elastography; functional loss; high risk; individual patient; motor behavior; novel; opioid use; patient population; patient response; prescription opioid; pressure; prevent; respiratory; response; sedative; tool; ultrasound; ventilation

ABSTRACT Opioids are the most commonly-used and effective drugs in the management of moderate to severe postoperative pain, but they have numerous adverse effects, the most serious being opioid-induced respiratory depression. An important and consistent finding in studies of opioid-induced respiratory depression is the highly variable risk across patient age, gender and co-morbidity profile. Identifying patients at highest risk of opioid-induced respiratory depression in the perioperative setting may help target enhanced monitoring (including hospital admission) and preventative strategies aimed at reducing adverse outcomes including respiratory complications and death. Changes in the central drive to respiratory muscles including the diaphragm are expected to impact the full range of ventilatory behaviors accomplished. It is essential to recognize that respiratory muscles are important in both sustaining ventilation and performing higher-force behaviors necessary for maintaining airway patency. Respiratory muscles accomplish a range of motor behaviors with forces generated for ventilatory behaviors comprising only a small fraction of their maximal force generating capacity. Thus, impairments in respiratory muscle function may not become clinically manifest despite substantial loss of functional reserve until ventilation is impaired. Monitoring for opioid effects on higher force behaviors may reveal patients with greater susceptibility to opioid-induced respiratory depression. Our working hypotheses are that opioid-induced respiratory depression limits the generation of higher forces by the diaphragm muscle, and that the early recognition of an individual patient’s response to opioids will help identify those at greatest risk for respiratory complications. Exciting recent studies support the utility of ultrasound-based shear wave elastography for measurements of diaphragm muscle function, but there is limited information available about their utility in healthy (not critically-ill) patient populations, or opioid effects. Two specific aims are proposed: 1) To test the hypothesis that shear wave elastography (SWE) reliably measures the range of forces generated by the diaphragm muscle, in relation to state-of-the-art respiratory function testing; and 2) To test the hypothesis that opioid-induced respiratory depression limits the range of forces generated by the diaphragm muscle, identifying a sub-population of patients potentially at greater risk for respiratory complications. We expect that the proposed studies in this novel application will determine the dose-dependent effect of opioids across a range of ventilatory and higher-force behaviors and the utility of SWE-based measurements of diaphragm muscle activity in the early recognition of patients displaying opioid- induced respiratory depression. Ultimately, the proposed work will help predict patients at greater risk for opioid-induced respiratory depression and permit assessment of the impact of individualized interventions in preventing postoperative respiratory complications.

摘要 阿片类药物是治疗中重度糖尿病最常用、最有效的药物 术后疼痛，但它们有许多不良反应，最严重的是阿片类药物引起的呼吸 抑郁症。在阿片类药物引起的呼吸抑制的研究中，一个重要而一致的发现是 不同患者的年龄、性别和合并发病情况的风险高度不同。确定有最高风险的患者 围手术期阿片类药物引起的呼吸抑制可能有助于加强监测 (包括住院)和旨在减少不良后果的预防战略，包括 呼吸道并发症和死亡。呼吸肌中枢驱动的变化，包括 横隔膜预计将影响所完成的各种通风行为。这是至关重要的 认识到呼吸肌在维持呼吸和执行更大的力量方面都很重要 维持呼吸道通畅所必需的行为。呼吸肌完成一系列运动 为换气行为产生的力只占其最大值的一小部分的行为 产生力量的能力。因此，呼吸肌功能受损可能不会在临床上表现出来。 尽管功能储备大量丧失，直到通风受损。监测阿片类药物对高等教育的影响 强迫行为可能表明患者对阿片类药物引起的呼吸抑制更敏感。我们的 工作假说是阿片类药物引起的呼吸抑制通过以下方式限制更高力量的产生 早期认识到个别患者对阿片类药物的反应将有所帮助 找出那些呼吸道并发症风险最高的人。最近令人振奋的研究支持了 超声横波弹性成像用于测量横隔肌功能，但有 关于其在健康(非危重)患者群体中的效用或阿片类药物影响的可用信息有限。 提出了两个具体的目标：1)检验剪切波弹性成像(SWE)可靠的假设 测量横隔肌产生的力的范围，与最先进的呼吸相关 功能测试；以及2)测试阿片类药物引起的呼吸抑制限制了 由横隔肌产生的力，识别潜在风险更高的患者亚群 呼吸系统并发症。我们预计，在这一新申请中拟议的研究将确定 阿片类药物在一系列换气和较高作用力行为中的剂量依赖效应及其应用 基于SWE的横隔肌活动测定在早期识别阿片类药物患者中的作用 引起呼吸抑制。最终，这项拟议的工作将有助于预测有更大风险的患者 阿片类药物引起的呼吸抑制并允许评估个体化干预的影响 预防术后呼吸道并发症。