People admitted hip or knee surgery and taking a range of drugs commonly prescribed for anxiety, insomnia and depression, were twice as likely to suffer postoperative delirium after hip and knee surgery, an Australian study found.
The finding has prompted calls by University of South Australia (UniSA) researchers for older patients to temporarily cease these medications or change to safer alternatives before surgery.
In a study published in the international journal Drug Safety, UniSA scientists scanned data from 10,456 patients aged 65 years and older who had undergone knee or hip surgery in the past 20 years. A quarter of them (2614 people) had experienced delirium after surgery.
Apart from nitrazepam and antidepressants, five other benzodiazepine medications commonly prescribed for anxiety, seizures and insomnia were associated with delirium, although not to the same extent. They included sertraline, mirtazapine, venlafaxine, citalopram and fluvoxamine.
Lead researcher Dr Gizat Kassie said there was no link between pain-relieving opioids and delirium.
“Our findings show that different classes of medicine are riskier than others when it comes to causing delirium after surgery, and the older the patients are, the greater the risk,” he says.
Smoking, alcohol use, multiple health conditions, polypharmacy (taking five or more medications), psychoactive drugs and impaired cognition also put people at risk.
“Many of these factors can’t be altered but we can do something about medications,” said Kassie.
Delirium affects up to 55% of older patients undergoing hip surgery and is associated with an increased risk of death, prolonged hospital stays and cognitive decline.
An earlier study found that older people who developed delirium after hip surgery had a 10% higher death rate within one year compared with patients who were not affected.
The UniSA study is the first to investigate the link between specific medications and dementia after surgery. Previous studies have been broader in scope, considering a range of factors predisposing older patients to delirium.
The researchers hope that evidence-based recommendations can be implemented into clinical practice so that delirium risk by medicine type can be determined.
“In people undergoing elective procedures it should be practical to taper specific medications well in advance. It's important that people are weaned off these riskier drugs well before surgery because abrupt withdrawal can have even worse consequences,” Kassie said.
Study details
The Risk of Preoperative Central Nervous System-Acting Medications on Delirium Following Hip or Knee Surgery: A Matched Case-Control Study
Gizat M. Kassie, Elizabeth E. Roughead, Tuan A. Nguyen, Nicole L. Pratt, Lisa M. Kalisch Ellett.
Published in Drug Safety on 8 November 2021
Abstract
Introduction
Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear.
Objectives
We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery.
Methods
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.
Results
A total of 2,614 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.
Conclusions
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.
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