Navigating the Confusing Twists and Turns to Reduce Postoperative Delirium

Young May Cha, MD, MS

Postoperative delirium is a common and serious complication of surgery associated with higher morbidity, mortality, and increased risk of dementia and long-term cognitive decline. There are mitigation strategies that can be implemented in the operating theater for these vulnerable older surgical patients, but the severity of this complication compels us to consider additional strategies that can be implemented preoperatively and postoperatively. Ideally, individualized biomarkers should be used to identify those at greatest risk. New research models are also being developed to better understand the mechanisms underlying postoperative delirium. These were the themes of the symposium, “Navigating Postoperative Strategies in Older Adults: Linking Heart and Brain Health,” moderated by Haobo Li, PhD, Assistant Professor of Anaesthesia at Massachusetts General Hospital and Oluwaseun Johnson-Akeju, MD, Chair and Professor of Anaesthesia at Massachusetts General Hospital and IARS Board President-Elect.

Tina McKay, PhD, Instructor in Anaesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital, opened the symposium with an overview of biomarkers that could be used to help identify those at greatest risk for postoperative delirium and to help create targeted interventions for customized care to prevent this complication. Vitamin D levels were not found to have a strong association with delirium risk. But other biomarkers, such as interleukin-6, amyloid beta proteins, tau protein levels, and neurofilament light chains were positively associated with delirium risk and postoperative CAM-severity scores, which are used to assess delirium severity.

Next, Michael Irwin, MB ChB, MD, FRCA, FCAI, FANZCA, FHKCA, FHKAM, Professor of Anaesthesiology at the University of Hong Kong, shifted the attention to identifying those at risk for delirium through clinical identifiers, such as frailty and nutritional status. Identifying patients at risk preoperatively can also influence their perioperative course by altering the surgical approach with perhaps less invasive surgery, staged surgery, or “damage control” operations. Younger and older patients have different goals and priorities. Older patients often value their quality of life more and may not tolerate aggressive treatments.

Other preoperative strategies for prehabilitation can also be started such as nutritional supplementation, cognitive training, and exercise training. Reviews have shown these interventions decrease postoperative length of stay and improve preoperative functional outcomes, but do not reduce odds of complications and/or readmissions, as compared to rehabilitation methods. Dr. Irwin highlighted existing service model examples in the United Kingdom using a comprehensive multidisciplinary approach (Proactive care of Older People undergoing Surgery (POPS) Guy’s and St. Thomas’ and the Systemic Care Older Patients undergoing Elective Surgery (SCOPES) at Nottingham). For intraoperative considerations, Dr. Irwin featured the June 2024 review in The Lancet, which suggests there are more advantages with postoperative recovery associated with total intravenous anesthesia. Unfortunately, data are mixed on the effects of other intraoperative interventions such as electroencephalogram-directed anesthesia, pharmacological means to reduce delirium such as dexmedetomidine, ketamine, or corticosteroids. The newly published 2025 ASA Practice Advisory for Perioperative Care of Older Adults Scheduled for Inpatient Surgery discusses these various interventions, but, ultimately, more research is still needed on their efficacy.

Another exciting avenue of discovery is in the role the blood-brain barrier plays in delirium. Niccolò Terrando, PhD, Professor of Anesthesiology at Duke University, presented how inflammation after surgery can interact with the endothelial cells of the blood-brain barrier to drive further changes on neuronal cells. Microglial cells and other immune cells, such as perivascular macrophages, are all induced after surgery. There are even biomarkers of blood-brain barrier disruption. Increased cerebrospinal fluid to plasma albumin ratios are positively correlated with increased delirium scores. Current studies are underway using tissue-on-chip technology to generate new models of the blood-brain barrier to further interrogate these blood-brain-barrier disruptions and how they could be potentially mitigated.

But how do we balance the cost of screening all patients against the benefit of identifying those at risk, especially when the optimal care for these patients remains undetermined? One comment during the Q&A portion highlighted a study presented the day prior, in which the use of benzodiazepines, which have traditionally been believed to be detrimental for postoperative delirium, was shown not to have a significant effect on cognition in elderly patients. Clearly, more studies are warranted to help elucidate the effects of specific drugs in these patients.