Benzodiazepines are commonly given perioperatively for sleep and anxiolysis and intraoperatively in conjunction with other anesthetics and analgesics. Some research has indicated benzodiazepines may prevent intraoperative awareness because of their amnesic effects. According to a 2018 study in Canadian clinics, benzodiazepines are administered to 60–89% of patients receiving cardiac surgery.¹ However, some data suggest that, when possible, avoiding benzodiazepines could reduce the risk of postoperative delirium, which is a significant concern following anesthesia and surgery.

Several randomized controlled trials (RCTs) have shown increased risk of postoperative delirium when benzodiazepines are used for ICU sedation compared with dexmedetomidine.² Additionally, the 2018 guidelines from the Society of Critical Care Medicine (SCCM) suggest a non-statistically significant increased risk of delirium with benzodiazepine sedation. Postoperative delirium is an acute brain dysfunction that can appear shortly after surgery, with symptoms including confusion, disorientation, agitation, or lethargy. Risk factors include advanced age, frailty, cognitive impairment, and severe illness, and its pathophysiology is thought to involve inflammation and neurotransmitter imbalances affecting brain connectivity and function.³

A recent systematic review on the link between benzodiazepines and postoperative delirium included 34 RCTs (n=4354) and 9 observational studies (n=3309), with results supporting avoiding their use in anesthesia. Use of benzodiazepines increased the risk of delirium (n=429; P=0.002) and decreased the risk of intraoperative awareness (n=2245; P=0.001).² This review confirmed the findings of an earlier study, which assesses the same risk in a large clinical cohort of older adults undergoing major surgery.⁴ Benzodiazepines enhance the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter. This inhibition may lead to CNS depression, causing impairments in memory, attention, and arousal—all core features of delirium. Deep sedation is, in itself, a risk factor of delirium, and benzodiazepine is known to have stronger sedative properties compared to some alternatives, such as antihistamines. The sedative effects of benzodiazepines can mask or exacerbate hypoactive delirium, a subset of delirium characterized by decreased activity, reduced alertness, and decreased speech. Because these symptoms are more subtle than those of hyperactive delirium (e.g., obvious agitation, hallucinations, irritability) and lacks disruptive behavior, hypoactive delirium is more likely to go unnoticed and untreated, leading to poorer outcomes as delirium symptoms worsen. In addition, these agents may disrupt the balance between inhibitory (GABAergic) and excitatory (cholinergic  or glutaminergic) neurotransmission, particularly in vulnerable populations, such as infants of elderly patients.⁵

While benzodiazepines are widely used in perioperative care for their anxiolytic and amnesic properties, growing evidence suggests their use may significantly increase the risk of postoperative delirium, particularly in older and cognitively vulnerable patients, and clinicians increasingly opt for avoiding or limiting their use when possible. Their strong sedative effects, interference with neurotransmitter balance, and potential to mask certain symptoms of delirium make them a less favorable option compared to other clinical alternatives. However, when variables such as patient-specific risk factors, dosage levels, and perioperative monitoring are fully considered, benzodiazepines can still be a valuable tool in numerous clinical scenarios. Careful planning remains essential to minimize postoperative cognitive complications and improve outcomes.

References

1. Spence, Jessica, et al. “Benzodiazepine Administration during Adult Cardiac Surgery: A Survey of Current Practice among Canadian Anesthesiologists Working in Academic Centres.” Canadian Journal of Anesthesia/Journal Canadien d’anesthésie, 65(3), 2018, 263–271, https://doi.org/10.1007/s12630-017-1047-1
2. Wang, Eugene, et al. “Effect of Perioperative Benzodiazepine Use on Intraoperative Awareness and Postoperative Delirium: A Systematic Review and Meta-Analysis of Randomised Controlled Trials and Observational Studies.” British Journal of Anaesthesia, 131(2), 2023, 302–313. https://doi.org/10.1016/j.bja.2022.12.001
3. Oh, S. T., Park, J. Y., “Postoperative Delirium.” Korean Journal of Anesthesiology, 72(1), 2018, 4–12. https://doi.org/10.4097/kja.d.18.00073.1
4. Duprey, Matthew S., et al. “Association between Perioperative Medication Use and Postoperative Delirium and Cognition in Older Adults Undergoing Elective Non-Cardiac Surgery.” Anesthesia and Analgesia, 134(6), 2022, 1154–1163. https://doi.org/10.1213/ANE.0000000000005959
5. Lan, Shaoze, et al. “Strategies to Prevent Postoperative Delirium: A Comprehensive Evaluation of Anesthesia Selection and Drug Intervention.” Frontiers in Psychiatry, 15, 2024. https://doi.org/10.3389/fpsyt.2024.1518460