Prediction and early recognition of opioid-induced respiratory depression

摘要 阿片类药物是最常用和有效的药物在管理中重度 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道 萧条阿片类药物诱导的呼吸抑制研究中一个重要且一致的发现是， 患者年龄、性别和合并症特征的风险高度可变。识别风险最高的患者 围手术期阿片类药物引起的呼吸抑制可能有助于靶向加强监测 （包括住院）和预防策略，旨在减少不良后果，包括 呼吸系统并发症和死亡。中枢驱动呼吸肌的变化，包括 预期隔膜会影响所完成的全范围的澄清行为。有必要 认识到呼吸肌在维持通气和执行更高力量方面都很重要 维持气道通畅所需的行为。呼吸肌完成一系列运动 行为与力产生的解释行为只包括一小部分，其最大 力量生成能力。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气受损。监测阿片类药物对高血压的影响 强迫行为可能揭示患者对阿片类药物诱导的呼吸抑制更敏感。我们 工作假设是阿片类药物诱导的呼吸抑制限制了更高力的产生， 膈肌，早期识别个体患者对阿片类药物的反应将有助于 确定呼吸系统并发症风险最高的人群。令人兴奋的最新研究支持的效用 基于超声的剪切波弹性成像用于测量膈肌功能，但 关于其在健康（非危重病）患者人群中的效用或阿片类药物作用的信息有限。 本研究的目的有两个：1）验证剪切波弹性成像（SWE） 测量膈肌产生的力的范围，与最先进的呼吸 功能测试; 2）为了测试阿片类药物诱导的呼吸抑制限制了 膈肌产生的力，识别潜在风险更大的患者亚群 呼吸系统并发症我们预计，在这种新的应用中提出的研究将确定 阿片类药物在一系列镇静和高强度行为中的剂量依赖性作用以及 基于SWE的膈肌活动测量在早期识别显示阿片样物质的患者中的应用 引起呼吸抑制。最终，拟议的工作将有助于预测患者在更大的风险， 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， 预防术后呼吸系统并发症。

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.