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择期非心脏手术老年患者围手术期用药与术后谵妄及认知的关联

Association Between Perioperative Medication Use and Postoperative Delirium and Cognition in Older Adults Undergoing Elective Noncardiac Surgery.

作者信息

Duprey Matthew S, Devlin John W, Griffith John L, Travison Thomas G, Briesacher Becky A, Jones Richard, Saczynski Jane S, Schmitt Eva M, Gou Yun, Marcantonio Edward R, Inouye Sharon K

机构信息

From the School of Public Health, Brown University, Providence, Rhode Island.

Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, Massachusetts.

出版信息

Anesth Analg. 2022 Jun 1;134(6):1154-1163. doi: 10.1213/ANE.0000000000005959. Epub 2022 Feb 24.

Abstract

BACKGROUND

Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery.

METHODS

This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month.

RESULTS

Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed.

CONCLUSIONS

Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.

摘要

背景

术后谵妄在老年人中很常见,并且与术后神经认知障碍(PND)相关。评估围手术期用药与谵妄的研究通常是对药物进行总体评估,且控制不佳;围手术期用药与PND之间的关联仍不明确。我们试图评估在接受大型择期手术的老年人中,用药与术后谵妄及PND之间的关联。

方法

这是一项对年龄≥70岁、无痴呆的成年人进行大型择期手术的前瞻性队列研究的二次分析。术前对患者进行访谈以确定其在家用药情况。术后,收集医院每日使用的指南中列为谵妄危险因素的7种不同药物类别;核实谵妄发生前的用药情况。住院期间,每天使用混乱评估法和经过验证的图表审查法对患者进行谵妄评估。术前及术后1个月使用神经认知测试组合对认知功能进行评估。使用具有对数链接函数的广义线性模型评估院前用药与术后谵妄之间的关联,并对年龄、性别、手术类型、Charlson合并症指数和基线认知进行控制。使用经年龄、性别、手术类型、Charlson合并症指数、急性生理与慢性健康评估(APACHE)-II评分及基线认知调整的时变Cox模型评估术后每日用药(当药物类别暴露≥5%时)与谵妄发生时间之间的关联。采用中介分析评估用药、谵妄以及从基线到1个月认知变化之间的关联。

结果

在纳入的560例患者中,134例(24%)在住院期间发生谵妄。多变量分析显示,院前使用苯二氮䓬类药物(相对风险[RR],1.44;95%置信区间[CI],0.85 - 2.44)、β受体阻滞剂(RR,1.38;95% CI,0.94 - 2.05)、非甾体抗炎药(RR,1.12;95% CI,0.77 - 1.62)、阿片类药物(RR,1.22;95% CI,0.82 - 1.82)或他汀类药物(RR,1.34;95% CI,0.92 - 1.95)与谵妄之间无显著关联。术后在医院使用苯二氮䓬类药物(调整后风险比[aHR],3.23;95% CI,2.10 - 4.99)与谵妄发生率增加相关。谵妄发生前术后在医院使用抗精神病药物(aHR,1.48;95% CI,0.74 - 2.94)或阿片类药物(aHR,0.82;95% CI,0.62 - 1.11)与谵妄均无关联。抗精神病药物使用(术前或术后)通过对谵妄的影响,使1个月时总体认知表现下降0.34分(标准误,0.16)(P = .03),尽管未观察到总体效应。

结论

对大型手术后住院的老年人使用苯二氮䓬类药物与术后谵妄增加相关。未检测到住院期间术后用药与1个月时认知之间独立于谵妄的关联。

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