Polypharmacy in Older Adults Undergoing Major Surgery: Prevalence, Association With Postoperative Cognitive Dysfunction and Potential Associated Anesthetic Agents

Abstract

BackgroundPolypharmacy, which is defined as the use of 5 or more medications, can exert significant adverse impact on older adult patients. The objective of this study was to determine the prevalence of polypharmacy, and to investigate its association with postoperative cognitive dysfunction (POCD) in older adult patients who underwent elective major surgery at Siriraj Hospital—Thailand's largest national tertiary referral center.MethodsThis prospective study included older adult patients aged ≥65 years who were scheduled for elective major surgery during December, 2017 to December, 2019 study period. Patient demographic, sociodemographic, anthropometric, clinical, comorbidity, anesthetic, surgical, and medication data were collected and compared between the polypharmacy and non-polypharmacy groups. Postoperative cognitive dysfunction (POCD) was diagnosed in patients with at least a 2-point decrease in their Montreal Cognitive Assessment score after surgery. Multivariate logistic regression analysis was used to identify independent predictors of POCD.ResultsA total of 250 patients (141 males, 109 females) with an average age of 72.88 ± 6.93 years were included. The prevalence of polypharmacy was 74%. Preoperative data showed the polypharmacy group to be more likely to be receiving potentially inappropriate medications, to be scheduled for cardiovascular thoracic surgery, and to have more comorbidities. There was a non-significant trend in the association of polypharmacy and POCD (crude odds ratio (OR): 2.11, 95% confidence interval [CI]: 0.90–4.94; p = 0.08). Benzodiazepine, desflurane, or isoflurane administration during surgery were all significantly associated with POCD in univariate analysis. Multivariate analysis revealed intraoperative benzodiazepine (adjusted OR [aOR]: 2.24, 95% CI: 1.10–4.68; p = 0.026) and isoflurane (aOR: 2.80, 95% CI: 1.35–5.81; p = 0.006) as two independent variables associated with the development of POCD. Desflurane was found to be a protective factor for POCD with a crude OR of 0.17 (95% CI: 0.03–0.74, p = 0.019); however, independent association was not found in multivariate analysis.ConclusionThere was a high prevalence of polypharmacy in this study; however, although close (p = 0.08), significant association was not found between polypharmacy and POCD. Benzodiazepine and isoflurane were both identified as independent predictors of the development of POCD among older adult patients undergoing elective major surgery, especially among those classified as polypharmacy.

Postoperative delirium in geriatric patients with hip fractures

“…Benzodiazepine receptor agonists (BZDRAs) are commonly used sedatives during the perioperative period, which can lower the consumption of intraoperative anesthetics ( Nakagawa et al, 2000 ). However, numerous studies have demonstrated that perioperative usage of BZDRAs is linked to a higher risk of POD in geriatric patients with hip fractures ( Poeran et al, 2020 ; Hernandez et al, 2021 ; Duprey et al, 2022 ; Lertkovit et al, 2022 ). The concrete mechanisms of benzodiazepine-induced POD vary based on the subtype of BZDRAs: Diazepam may affect the chloride plasticity mediated by Na + − K + − 2Cl-cotransporter isoform 1 and result in the gamma-aminobutyric acid α receptor malfunction ( Matsumoto et al, 2021 ); midazolam can alter the expression and activity of acetyl-and butyryl-cholinesterase genes ( Rump et al, 2022 ), and both contribute to benzodiazepine - induced POD.…”

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs

“…In another study, the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function of elderly patients over 65 from days 5-9 after elective major surgery. The results showed that benzodiazepines and isoflurane were independent predictors of POCD (Lertkovit et al, 2022). In addition to the short-term risk of cognitive impairment, it has been reported that benzodiazepines can increase the risk of cognitive impairment years or decades later.…”

Effect of desflurane and sevoflurane on postoperative cognitive dysfunction： A meta-analysis of randomized controlled trials

“…The use of narcotic drugs may also alter the cognitive function of patients, especially the elderly, because the residual effects of drugs can modify the activity of the central nervous system. Such drugs can in uence tau protein modi cation, in ammatory process calcium regulation and mitochondrial function to alter cognitive function [20,21]. Anesthetics primarily act on the central nervous system.…”