Postoperative delirium is one of the most common surgical complications among older adults (>60 years of age). It is linked to notably poorer patient outcomes, including prolonged hospital stays, reduced functional autonomy, mental health diagnoses such as post-traumatic stress disorder (PTSD), and higher 6-month mortality rates.1 The incidence of postoperative delirium varies dramatically depending on patient characteristics and the type of surgery performed; however, generally speaking, it can occur in 10-65% of older adults undergoing surgery.2 In a 2022 review, delirium was found to be an independent risk factor for long-term cognitive decline, suggesting postoperative delirium may be a modifiable risk factor for dementia and subsequent long-term cognitive impairment.3 As a result, its prevention is an important area of research, and several anesthesia and surgical societies have worked toward comprehensive guidelines for preventing postoperative delirium.
Despite its prevalence, the pathophysiology of this condition is under-researched and poorly understood. Neuroinflammation has been identified as a risk factor, as higher postoperative levels of the pro-inflammatory cytokines IL-6 and IL-2 are associated with the development of postoperative delirium.4 Researchers identified the inflammatory marker C-reactive protein (CRP) as the primary protein associated with postoperative delirium during both pre-op and post-op.5,6 Researchers suggest elevated concentrations of CRP, in addition to tau, p-tau 217, and p-tau 181, may be useful biomarkers and emphasize the utility of exploring them in the future.4
In early 2024, researchers published an update to the 2017 European Society of Anaesthesiology and Intensive Care Medicine (ESAIC) Guidelines on preventing postoperative delirium. Their first point highlighted the need for higher powered studies, as the extant literature largely focuses on animal studies. Additionally, many existing studies are conducted on young, healthy animals; therefore, it is a poor model for assessing delirium, where the patients are often older, frailer, and suffer from other comorbidities. The new guidelines also recommend a greater focus on individualized planning to reduce the risk of postoperative delirium , involving a full geriatric assessment evaluating frailty, sensory impairment, malnutrition, polypharmacy, anemia, and more.7 Further, when considering preventative pharmaceutical interventions, the guidelines suggest refraining from using drugs in an attempt at reducing postoperative delirium. However, they note a caveat: dexmedetomidine may be used intra-operatively or postoperatively to prevent postoperative delirium in a very specific patient group, so long as active measures are taken to prevent the most important side effects, i.e., bradycardia and hypotension.7
In addition to inflammatory biomarkers, the guidelines identified oxidative stress biomarkers, biomarkers of nerve cell alteration, biomarkers of neurogenesis and synaptic plasticity, biomarkers of axonal damage, biomarkers of neuroglia injury (e.g., blood-brain barrier disruption), systemic non-inflammation biomarkers, and genetic biomarkers. As for non-pharmacological interventions, the guidelines recommend the results of screening for risk factors be shared among all members of the care team. Preventative strategies discussed with the patient should be noted in the patient’s medical record. Finally, neuromonitoring recommendations were also included in the updated guidelines. The recommendation suggests the use of multi-parameter, intraoperative EEG monitoring focusing on burst suppression and density spectral array to maintain appropriate anesthesia depth and decrease risk.7
Thanks to advancements in modern medicine, life expectancy is much higher compared to 50 or even 20 years ago. It’s likely that age-related postoperative conditions such as postoperative delirium will increase. Perioperative teams will need increased knowledge, understanding, and training of best practices. This necessitates more rigorous research and refining the guidelines on preventing postoperative delirium.

References

1. Watt, Jennifer, et al. “Identifying Older Adults at Risk of Delirium Following Elective Surgery: A Systematic Review and Meta-Analysis.” Journal of General Internal Medicine, vol. 33, no. 4, Apr. 2018, pp. 500–09. https://doi.org/10.1007/s11606-017-4204-x
2. Gleason, Lauren J., et al. “Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults.” JAMA Surgery, vol. 150, no. 12, Dec. 2015, pp. 1134–40. Silverchair, https://doi.org/10.1001/jamasurg.2015.2606
3. Fong, Tamara G., and Sharon K. Inouye. “The Inter-Relationship Between Delirium and Dementia: The Importance of Delirium Prevention.” Nature Reviews Neurology, vol. 18, no. 10, Oct. 2022, pp. 579–96. https://doi.org/10.1038/s41582-022-00698-7
4. Qureshi, Owais, and Mary E. Arthur. “Recent Advances in Predicting, Preventing, and Managing Postoperative Delirium.” Faculty Reviews, vol. 12, July 2023, p. 19. https://doi.org/10.12703/r/12-19
5. Vasunilashorn, Sarinnapha M., et al. “Development of a Dynamic Multi-Protein Signature of Postoperative Delirium.” The Journals of Gerontology: Series A, vol. 74, no. 2, Jan. 2019, pp. 261–68. https://doi.org/10.1093/gerona/gly036
6. Dillon, Simon T., et al. “Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.” Biological Psychiatry, vol. 81, no. 2, Jan. 2017, pp. 145–53. https://doi.org/10.1016/j.biopsych.2016.03.2098
7. Aldecoa, César, et al. “Update of the European Society of Anaesthesiology and Intensive Care Medicine Evidence-Based and Consensus-Based Guideline on Postoperative Delirium in Adult Patients.” European Journal of Anaesthesiology EJA, vol. 41, no. 2, Feb. 2024, p. 81. https://doi.org/10.1097/EJA.0000000000001876