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.

抽象的 阿片类药物是中度至重度管理中最常用和有效的药物 术后疼痛，但会产生许多不良反应，最严重的是阿片类药物引起的呼吸道 沮丧。阿片类药物诱导的呼吸抑制研究中的一个重要且一致的发现是 在患者年龄，性别和合并症的范围内，风险高度可变。确定患者的风险最高 在周期性环境中，卵形类药物引起的呼吸抑郁症可能有助于目标增强监测 （包括医院入院）和旨在减少包括不良后果的预防策略 呼吸并发症和死亡。呼吸道肌肉的中心驱动变化包括 预计隔膜有望影响完成的全部通风行为。至关重要 认识到呼吸道肌肉在维持通风和执行更高强度方面很重要 维持气道通畅所需的行为。呼吸肌完成一系列电动机 产生用于通风行为的力的行为仅完成其最大的一小部分 力产能。那就是呼吸肌功能的损害可能不会在临床上表现出来 尽管功能储备大大损失，直到通风受损为止。监测阿片类药物对更高的影响 力行为可能揭示患者对阿片类药物诱导的呼吸道抑郁的敏感性更大。我们的 工作假设是阿片类药物诱导的呼吸抑郁症限制了较高力的产生 diaphragm肌肉以及对单个患者对阿片类药物的反应的早期认识将有助于 确定呼吸并发症风险最大的人。令人兴奋的最近研究支持 基于超声的剪切波弹性图，用于测量隔膜肌肉功能，但有 有限的有关其在健康（非关键）患者人群或阿片类药物影响方面效用的信息。 提出了两个具体目标：1）测试剪切波弹性图（SWE）可靠的假设 测量隔膜肌肉产生的力范围，与最新的呼吸有关 功能测试； 2）检验以下假设：OIOID诱导的呼吸抑制限制了 diaphragm肌肉产生的力，确定患者的亚人群可能更大的风险 用于呼吸并发症。我们预计这项新颖应用中的拟议研究将确定 阿片类药物在一系列通风和更高强度行为范围内的剂量依赖性作用以及 基于SWE的膜肌活动的测量在早期识别显示阿片类药物的患者的早期识别中 诱发呼吸抑郁症。最终，拟议的工作将有助于预测患者的风险更大 阿片类药物引起的呼吸抑制，并允许评估个性化干预措施的影响 防止术后呼吸并发症。