METHODS: This was a retrospective cohort study which used data between January 2013 and December 2019, in a large midwestern health system, including sixteen hospitals. All patients over age 50 undergoing surgery requiring an inpatient stay were included. The primary exposure was the number of doses of anticholinergic medications delivered during the hospital stay. The primary outcome was a new diagnosis of Alzheimer\'s disease and related dementias at 1-y postsurgery. Regression methods and a mediation analysis were used to explore relationships between anticholinergic medication usage, delirium, and dementia.
RESULTS: There were 39,665 patients included, with a median age of 66. Most patients were exposed to anticholinergic medications (35,957/39,665; 91%), and 7588/39,665 (19.1%) patients received six or more doses during their hospital stay. Patients with at least six doses of these medications were more likely to be female, black, and with a lower American Society of Anesthesiologists class. Upon adjusted analysis, high doses of anticholinergic medications were associated with increased odds of dementia at 1 y relative to those with no exposure (odds ratio 2.7; 95% confidence interval 2.2-3.3). On mediation analysis, postoperative delirium mediated the effect of anticholinergic medications on dementia, explaining an estimated 57.6% of their association.
CONCLUSIONS: High doses of anticholinergic medications are common in major surgery patients and, in part via a mediating relationship with postoperative delirium, are associated with the development of dementia 1 y following surgery. Strategies to decrease the use of these medications and encourage the use of alternatives may improve long-term cognitive recovery.
方法:这是一项回顾性队列研究,使用了2013年1月至2019年12月在中西部大型卫生系统中的数据,包括16家医院。包括需要住院的所有50岁以上接受手术的患者。主要暴露是住院期间提供的抗胆碱能药物的剂量数量。主要结果是在手术后1年对阿尔茨海默病和相关痴呆的新诊断。回归方法和中介分析用于探索抗胆碱能药物使用之间的关系,谵妄,和痴呆症。
结果:包括39,665例患者,平均年龄为66岁。大多数患者暴露于抗胆碱能药物(35,957/39,665;91%),和7588/39,665(19.1%)患者在住院期间接受了6次或更多剂量。至少服用六剂这些药物的患者更有可能是女性,黑色,和一个较低的美国麻醉医师协会班级。根据调整后的分析,高剂量抗胆碱能药物治疗与无暴露者相比,1年时痴呆的几率增加(比值比2.7;95%置信区间2.2-3.3).关于调解分析,术后谵妄介导抗胆碱能药物对痴呆的作用,解释了他们估计的57.6%的关联。
结论:大剂量抗胆碱能药物在大手术患者中很常见,部分通过与术后谵妄的中介关系,与手术后1年痴呆的发展有关。减少使用这些药物并鼓励使用替代品的策略可能会改善长期认知恢复。