The role of genomics in postoperative delirium and sedation

术后不良神经症状是高龄患者术后常见的症状 做手术。这些包括神志不清、亚综合征神志不清和阿片类药物中毒。精神上的急剧变化 状态和注意力不集中通常是一种更大的老年综合征的特征，通常称为术后 神志不清，以及一个相关的实体，亚综合征神志不清可以被认为是亚临床神志不清。患者 术后出现精神错乱通常住院时间更长，并有更高的后遗症风险. 出院时功能和认知状态下降，甚至增加长期死亡率。患有疾病的患者 阿片类药物的毒性，如过度镇静，也可能与呼吸抑制有关，如果不是临床上的 如果发现抑郁症严重且持续时间长，则可能进展为完全呼吸骤停。 术后神志不清、亚综合征神志不清和阿片类药物中毒是常见的症状。 被认为与静脉注射阿片类药物有关的传统疗法 减轻术后疼痛。对于有这些不良神经症状的患者，典型的 战略是停止阿片类药物的使用，希望扭转这些变化。然而，随着 停止使用阿片类药物，患者可能会反弹并伴有严重的术后疼痛，这可能 实际上增加了他们的困惑症状，因为据报道疼痛与 术后精神错乱。在目前的临床实践中，静脉注射阿片类药物的滴定在治疗中 术后疼痛很大程度上是经验性的。生物标志物是否能解释或预测 术后认知改变以前没有系统地评估过。 这项研究的目标是利用几个现有的大型患者队列数据库来确定 基因变异与术后精神障碍、亚综合征精神障碍和精神分裂症表型的关系 阿片类药物中毒。这项调查中使用的综合数据库包括2000多个较老的数据库 在三个不同的大学医疗中心接受过重大非心脏手术的患者。全 评估患者是否存在院内术后精神错乱、亚综合征精神错乱和 使用有效和结构化方案的阿片类药物毒性。因为三个不同的患者群体 将包括在发现队列中，外加第四个预期招募的队列作为验证队列，我们的 研究有独特的机会来确定我们研究结果的内部和外部有效性。我们的中央 假说是，具有特定基因特征的个体术后发病率更高。 神志不清、亚综合征神志不清和阿片类药物中毒。 我们的结果将对精准医疗和我们的评估战略产生重大影响 促进个性化术后疼痛和症状管理的生物标记物可能会导致 高危老年人群的术后精神错乱、亚综合征精神错乱和阿片类药物中毒。

Postoperative adverse neurological symptoms are frequent occurrences in the older patients after major surgery. These involve delirium, subsyndromal delirium and opioid toxicities. An acute change in mental status, along with inattention are often hallmark of a larger geriatric syndrome commonly called postoperative delirium, and a related entity, subsyndromal delirium can be considered as subclinical delirium. Patients who develop postoperative delirium typically stay in the hospital longer and have an increased risk of post- discharge decline in functional and cognitive status, and even increased long-term mortality. Patients with opioids toxicities such as over-sedation may also have associated respiratory depression, and if not clinically recognized, may progress to full respiratory arrest if the depression is profound and prolonged. The symptoms of postoperative delirium, subsyndromal delirium, and opioid toxicities are commonly thought to be related to the administration of intravenous opioids, conventional therapy prescribed for the alleviation of postoperative pain. For patients who have these adverse neurological symptoms, the typical strategy is to stop the administration of opioids in the hope of reversing these changes. However, with the cessation of opioids administration, patients may rebound with substantial postoperative pain which may actually increase their symptoms of confusion since pain has been reported to be associated with postoperative delirium. In current clinical practice, the titration of intravenous opioids in the treatment postoperative pain is largely empirical. Whether biomarkers can explain, or predict the symptoms of postoperative cognitive changes has not been previously evaluated in a systematic fashion. The objective of this study is to leverage several existing large patient cohort databases to determine the relationship of genetic variants and the phenotypes of postoperative delirium, subsyndromal delirium and opioid toxicities. The combined databases to be used in this investigation consist of over two thousand older patients who have undergone major non-cardiac surgery at three separate university medical centers. All patients were assessed for the presence of in-hospital postoperative delirium, subsyndromal delirium, and opioid toxicities using validated and structured protocols. Because three heterogeneous patient populations will be included in the discovery cohort plus a 4th prospectively recruited cohort as the validation cohort, our study has the unique opportunity to determine both internal and external validity of our findings. Our central hypothesis is that individuals who have a certain genetic profile have a higher incidence of postoperative delirium, subsyndromal delirium, and opioid toxicities. Our results will have significant impact on precision medicine and our strategy of assessment of biomarkers to facilitate personalized postoperative pain and symptom management may result in a decrease of postoperative delirium, subsyndromal delirium, and opioid toxicities in the at risk older population.