Protecting Your Patients Against the Cerebral Challenges of Anesthesia and Surgery: Technological, Physiological and Pharmacological Approaches

Anesthesiologists have developed unparalleled expertise in the optimization of their patients’ physiology to successfully journey through the perioperative period. Physiological reserve is a widely understood concept when applied to the cardiovascular, respiratory and other body systems. However, cognitive reserve and resilience have only recently emerged as topics of interest over the past few decades, especially within the context of post-operative delirium (POD) and cognitive dysfunction (POCD). Importantly, these emerging cognitive disorders have been associated with increased mortality and length of hospital stay. Doctors Michelle Humeidan, MD, PhD, Phillip E. Vlisides. MD, and Charles H. Brown, IV, MD discussed some technological, pharmacological and pharmacological strategies that are being investigated to mitigate the risk of these post-operative syndromes.

Dr. Humeidan began by introducing cognitive reserve as the brain’s robustness in the face of some insult or challenge; in this case surgery and anesthesia. The most common metrics used to predict cognitive reserve are a patient’s level of education, occupation, intelligence quotients, pre-existing cognitive dysfunction, leisurely activities and literacy. Importantly, these metrics have been used to successfully predict lower risks for developing dementia as well as post-operative delirium.

So how can we optimize our patients’ cognitive reserve? First of all, factors such as sleep deprivation, malnutrition, substance abuse, depression and anxiety should be identified and managed appropriately. Then strategies to augment cognitive reserve can be considered, including both physical and cognitive activities. In fact, Dr. Humeidan is currently enrolling patients in the Neurobics trial, a registered clinical trial that aims to test the influence of preoperative cognitive exercise compared to no intervention on the occurrence of POD in an elderly population (≥ 60 yo) undergoing non-cardiac/non-neurological surgery.

Using the “Lumosity” iPad application, half of the enrolled patients are tasked to complete at least one hour of cognitive games per day in the preoperative period, totaling at least 10 hours preoperatively. Patients who suffer from pre-existing cognitive dysfunction or psychiatric disease are not eligible to be enrolled. The validated CAM and MDAS neuropsychological assessment tools are used to measure the incidence of POD twice per day until patients are discharged. Dr. Humeidan noted the importance of using similar tools to measure POD in future studies so that results can be compared between studies. She also noted that two more studies investigating the effects of preoperative cognitive exercise on post-operative cognition are currently underway in Boston and Ann Arbor.

Dr. Vlisides followed by discussing the effects of ketamine on perioperative cognition. Ketamine has previously been shown to reduce post-operative inflammation, pain, opioid consumption and emergence agitation in children. The POD trial investigated whether a single bolus of ketamine (either 0.5 mg/kg or 1 mg/kg) could decrease POD incidence, recurrence, duration or severity, as measured using the CAM and HELP tools, twice daily during the first three post-operative days.

Results showed no effect of ketamine boluses on any of the primary outcomes. However, it did increase the incidence of hallucinations and nightmares, consistent with previous reports of psychoactive adverse effects. Dr. Vlisides went on to describe some of the interesting neurophysiological effects of ketamine that are emerging in the literature. In particular, he noted that subanesthetic doses of ketamine have been shown to reduce temporoparietal EEG power in the alpha band, an effect that correlated significantly with feelings of depersonalization. These effects have also been observed in experiments with LSD and psilocybin, suggesting a common pathway in the induction of altered states of consciousness.

Finally, Dr. Brown explored methods of personalizing blood pressure management with the goal of optimizing cerebral blood flow and potentially reducing the risk of POD. Interestingly, definitions of hypotension that are clinically significant remain a hot topic of debate, and results on the association of blood pressure management with POD and POCD are conflicting.

Recently, blood pressure variability has been shown to be a better predictor of subsequent POD than baseline, mean or minimal arterial blood pressure measurements. This may be due to the fact that both high and low cerebral perfusion pressures can lead to disordered cerebral blood flow when they extend beyond the limits of cerebrovascular autoregulation.

With this in mind, Dr. Brown and his collaborators have developed a method to non-invasively measure the pre-operative edges of a patient’s cerebral autoregulation curve to then guide intraoperative blood pressure management. More specifically, they use near-infrared spectroscopy to calculate correlation coefficients between cerebral perfusion pressure and cerebral blood flow over a moving time window, with the assumption that hemoglobin, SpO2, CMRO2 and ICP remain constant over the short time window. Correlation coefficients below 0.3 are considered to be consistent with intact cerebral autoregulation, with higher coefficients indicative of pressure-passive cerebrovascular states that are vulnerable to changes in blood pressure. In other words, when cerebral blood flow does not significantly correlate with changes in cerebral perfusion pressures, autoregulation is intact and blood pressure management is adequate. Physiologically, this methodology makes sense. But can it improve post-operative cognitive outcomes? Dr. Brown and his group have just finished the recruitment phase of a study aiming to answer that exact question, and they are currently analyzing the results. Until their results are published, consider at least thinking about whether your patients’ cerebral perfusion pressures are within the limits of autoregulation, and avoid using a one-size-fits-all approach to blood pressure management.

*Coverage of the eSAS Panel session, Practical Clinical Approaches to Prevention of Postoperative Delirium: A Review of Modern Evidence