Association of EEG Parameters with Postoperative Delirium in Patient's with Parkinson's Disease

Patients with Parkinson's disease seem prone to developing postoperative delirium after surgery, the causes of which remain understudied and multifactorial. Anesthetic management remains challenging due to the changes in neurotransmitter levels in these patients which translate to altered drug effects. Avoiding excessive anesthesia is essential. Processed electroencephalography (EEG) is used worldwide along with our centre to monitor depth of anesthesia. It is non-invasive and easy to use. Some EEG patterns like "burst suppression" are easily identifiable and indicate that the brain has fallen into an excessively low metabolic state, which could mean increased anesthetic sensitivity. Appearance of "burst suppression" can predict delirium in non-neurosurgical procedures, but this has never been studied during surgery for deep brain stimulator insertion in Parkinson's disease patients. Through this study we wish to observe the association of EEG parameters with the development of postoperative delirium in this subset of the population.This has the capacity to change anesthetic practice by being mindful of the fragile brain of such patients and individualizing drug dosing for each patient to improve outcomes and reduce hospital stay.

Postoperative delirium is a multifactorial condition, with incidence ranging from 20% to 50%. Unfortunately, the implications of postoperative delirium extend beyond the immediate perioperative period. Bickel et al observed in their three-year follow-up that patients experiencing postoperative delirium (POD) exhibited cognitive decline and had an elevated risk of developing dementia compared to those without delirium after orthopedic surgeries.

Parkinson's disease is a neurodegenerative disorder that has been associated with an increased risk of developing delirium, with a prevalence rate of 34%. The incidence of postoperative delirium in this subset, reported after DBS in Parkinson's patients, ranges from approximately 22% to as high as \~43%. Patients with Parkinson's disease commonly undergo various elective surgical procedures, including deep brain stimulation (DBS) electrode insertion. The anesthetic management for DBS generally involves monitored anesthesia care with mild sedation, followed by patient awakening for microelectrode recording (MER) to ensure optimal electrode positioning. Increased propensity for postoperative delirium in these patients with Parkinson's has prompted foray into its predictive factors.

Intraoperative EEG has demonstrated significant promise as a predictor of postoperative delirium, especially in the elderly. A systematic review and meta-analysis by Likhvantsev et al found that the presence of burst suppression was associated with a 41% increase in the relative risk of POD, and the duration of burst suppression correlated with a higher occurrence of postoperative cognitive dysfunction (POCD). Presence and duration of burst suppression in the intraoperative period was found to be an independent predictor of postoperative delirium. In instances of delirium occurring in the absence of burst suppression, low absolute and relative frontal alpha power have been associated with its incidence.

Interestingly, all previous studies were conducted in patients without preexisting neurological conditions, with minimal literature focusing on intraoperative processed EEG in patients with Parkinson's. In an observational study by Astalosch et al, intraoperative burst suppression was found to be an influencer for the severity of delirium. There exists a significant gap in the evidence regarding the utility of intraoperative EEG-derived parameters in predicting the occurrence of delirium in Parkinson's disease.

Postoperative delirium, along with causing increased morbidity and longer hospital stay, could also lead to long-term effects, such as cognitive decline and increased vulnerability to dementia. And in patients with Parkinson's, due to consequence of delirium, there are reports higher mortality rate as compared to healthy individuals. Despite the recognized higher incidence of delirium and its effects in this patient population, there is a notable lack of research exploring intraoperative EEG-based predictors. This study aims to investigate the utility of presence of burst suppression, (along with various other processed EEG based parameters) as potential indicators of postoperative delirium in patients undergoing DBS. By exploring these factors, we hope to identify reliable markers of postoperative delirium that help us identify patients at risk, refine anesthetic techniques to minimize risk, ultimately enhance the quality of care provided to this particularly vulnerable set of patients.

All the patients will undergo preanesthetic evaluation as per institutional protocol and intraoperative anesthetic management will be performed as per institutional protocol. Patients' surgery and follow up care will proceed according to plan and standard of care and will not be altered due to participation in this study. Informed and written consent will be obtained.

After wheeling into the OR, monitoring will be instituted as per the Canadian Anesthesiologists' Society (CAS) standards. Processed electroencephalography will be monitored using Patient State Index (PSI, SedlineTM Masimo, USA) monitor. First stage of the procedure is performed under sedation with awake testing phase. Choice of sedative agent, its dosing and titration will be at the discretion of the treating anesthesiologist. Stage II of the procedure for implantable pulse generator (IPG) placement will be conducted under general anesthesia with endotracheal tube. Drugs used for general anesthesia, doses (boluses, infusion rates, and cumulative totals, as applicable) and duration of administration will be noted. Hemodynamic and fluid management during the intraoperative period will be as per the treating anesthesiologist.

Hemodynamic variables \[heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO2)\] will be recorded at every 15 minutes. Number of episodes of hypertension (defined as SBP \>180 mm Hg) or hypotension (defined as SBP\< 90 mm Hg) will be noted. Episodes of desaturation (defined as SpO2 \<92%) and treatment instituted for the same will be recorded. If any further samples are drawn (if needed by the attending anesthesiologist) for blood gas analysis in the intraoperative period, they will be noted.

Intraoperative blood loss, amount of fluid administered, and intraoperative adverse events (Hypo/hypertension/ hypoxemia/ seizure/ agitation/ delirium/ conversion to general anesthetic/ need for airway intervention/ nausea and vomiting) will be recorded. After emergence, patient will be shifted to postanesthesia care unit (PACU).

Postoperative hemodynamics and SpO2 on arrival in PACU will be recorded. Arterial sample will be collected for a repeat blood gas plus analysis in the PACU, and all parameters noted. Postoperative delirium scoring and cognitive assessment will be performed by a member of the research team. Postoperative adverse events and treatment instituted will be noted. All the interventions made by the nursing team in case of delirium will be made note of (hearing/visual aids/ analgesia/ presence of family member/ restraints use etc).

3D CAM scoring will be used to assess delirium on arrival to PACU, at discharge from PACU, and at 24 hours postoperatively. MoCA (Montreal Cognitive Assessment) score would also be assessed at 24 hours postoperatively.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosis of Parkinson's disease
2. Elective neurosurgery for implantation of DBS electrodes and implantable pulse generator (IPG) device.
3. 18 years of age or older

Exclusion Criteria:

1. Refusal/withdrawal of consent
2. Inability to place sensor/ record EEG for the entire duration of surgery
3. Emergency surgery
4. Redo surgery
5. Preoperative delirium (defined as per 3D CAM score)