Kassie Gizat M, Roughead Elizabeth E, Nguyen Tuan A, Pratt Nicole L, Kalisch Ellett Lisa M
Quality Use of Medicines and Pharmacy Research Centre, UniSA: Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.
Drug Saf. 2022 Jan;45(1):75-82. doi: 10.1007/s40264-021-01136-1. Epub 2021 Nov 8.
Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear.
We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery.
A matched case-control study was conducted using data from the Australian Government Department of Veterans' Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls.
A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24-2.64), sertraline (OR = 1.50, 95% CI 1.20-1.87), mirtazapine (OR = 1.38, 95% CI 1.11-1.74), venlafaxine (OR = 1.42, 95% CI 1.02-1.98), citalopram (OR = 1.54, 95% CI 1.19-1.99), escitalopram (OR = 1.42, 95% CI 1.06-1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15-11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05-1.37) and antidepressants (OR = 1.64, 95% CI 1.47-1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances.
People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium.
作用于中枢神经系统的药物会增加术后谵妄的风险，但与最高风险相关的具体药物仍不明确。
我们旨在研究术前使用的各类作用于中枢神经系统的药物对髋部或膝部手术后谵妄的风险。
利用澳大利亚政府退伍军人事务部的数据进行了一项匹配病例对照研究。我们纳入了2000年至2019年间接受膝部或髋部手术的65岁及以上人群。发生术后谵妄的髋部或膝部手术患者为病例组，对照组为接受髋部或膝部手术但未发生术后谵妄的患者。比较病例组和对照组术前使用包括抗焦虑药、镇静催眠药、阿片类镇痛药和抗抑郁药在内的药物情况。
共有2614例术后谵妄患者与7842例未发生术后谵妄的对照者按性别、年龄（±2岁）和入院年份（±2岁）进行匹配。病例组比对照组更有可能在术前使用硝西泮（比值比[OR]=1.81，95%置信区间[CI]1.24 - 2.64）、舍曲林（OR = 1.50，95%CI 1.20 - 1.87）、米氮平（OR = 1.38，95%CI 1.
11 - 1.74）、文拉法辛（OR = 1.42，95%CI 1.02 - 1.98）、西酞普兰（OR = 1.54，95%CI 1.19 - 1.99）、艾司西酞普兰（OR = 1.42，95%CI 1.06 - 1.89）或氟伏沙明（OR = 5.01，95%CI 2.15 - 11.68）。在药物类别层面，病例组术前使用苯二氮䓬类药物（OR = 1.20，95%CI 1.05 - 1.37）和抗抑郁药（OR = 1.64，95%CI 1.47 - 1.83）的比例显著高于对照组。导致新增一例谵妄病例的伤害性治疗所需人数，舍曲林为43，西酞普兰为40，米氮平为57，硝西泮为26。而在85岁及以上年龄组中，舍曲林的伤害性治疗所需人数为20，西酞普兰为17，米氮平为19，硝西泮为10，这表明随着年龄增长，这些药物的有害作用更加明显。
髋部或膝部手术后发生谵妄的患者在手术入院时更有可能使用硝西泮、舍曲林、米氮平、文拉法辛、西酞普兰、艾司西酞普兰或氟伏沙明。在手术前提前计划减少这些药物的使用可能会降低术后谵妄的风险。
