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 阿片类药物是治疗中重度阿片类药物最常用和最有效的药物 术后疼痛，但它们有许多不良影响，最严重的是阿片类药物引起的呼吸道疾病 阿片类药物引起的呼吸抑制的研究中一个重要且一致的发现是 识别患者年龄、性别和共病情况的高度可变风险。 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 （包括入院）和旨在减少不良后果的预防策略，包括 呼吸系统并发症和死亡。呼吸肌的中枢驱动发生变化，包括呼吸肌。 隔膜预计会影响所完成的全部通气行为。 认识到呼吸肌对于维持通气和执行更高的力量都很重要 维持呼吸道通畅所必需的行为 呼吸肌完成一系列运动。 通气行为产生的力仅占其最大力的一小部分的行为 因此，呼吸肌功能的损伤可能不会在临床上表现出来。 尽管监测阿片类药物对较高的影响，但功能储备显着丧失，直至通气受损。 用力行为可能表明患者更容易受到阿片类药物引起的呼吸抑制的影响。 工作假设是阿片类药物引起的呼吸抑制通过以下方式限制了更高力量的产生 膈肌，早期识别个体患者对阿片类药物的反应将有助于 确定那些最有呼吸系统并发症风险的人，最近令人兴奋的研究支持了它的实用性。 基于超声的剪切波弹性成像用于测量膈肌功能，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的作用的信息有限。 提出了两个具体目标：1）检验剪切波弹性成像（SWE）可靠的假设 测量膈肌产生的力的范围，与最先进的呼吸系统相关 功能测试；和 2) 检验阿片类药物引起的呼吸抑制限制范围的假设 膈肌产生的力，识别出可能面临更大风险的患者亚群 我们预计这项新颖应用中提出的研究将确定 阿片类药物对一系列通气和高力行为的剂量依赖性影响以及 基于 SWE 的膈肌活动测量可用于早期识别阿片类药物患者 最终，拟议的工作将有助于预测患有更大风险的患者。 阿片类药物引起的呼吸抑制，并允许评估个体化干预措施的影响 预防术后呼吸道并发症。