Total Intravenous Versus Inhalational Anesthesia- A Geriatric Anesthesia Study

Aim 1: Determine the effects of intravenous vs. inhalational anesthesia on incidence of postoperative delirium and postoperative cognitive dysfunction in older adults undergoing non-cardiac surgery.

Hypothesis: Intravenous anesthesia is associated with a lower incidence of POD and POCD compared to inhalational anesthesia.

Primary outcomes: Incidence of postoperative delirium and postoperative cognitive dysfunction Secondary outcomes: delirium severity, delirium duration Aim 2: Determine the effects of intravenous vs. inhalational anesthesia on incidence of postoperative functional decline and patient-reported outcomes in older adults undergoing non-cardiac surgery.

Hypothesis: Intravenous anesthesia is associated with a lower incidence of postoperative functional decline and improved patient-reported outcomes (PROs) compared to inhalational anesthesia.

Primary outcomes: Incidence of postoperative functional decline; patient-reported outcome scores Aim 3: Determine the effects of intravenous vs. inhalational anesthesia on blood phosphorylated tau 181 (p-tau181) and other blood biomarkers in older adults undergoing non-cardiac surgery.

Hypothesis 1: Elevated preop blood p-tau181 is associated with increased POD and POCD; Hypothesis 2: Postoperative increase in blood p-tau181 is greater with GAS relative to IV; Hypothesis 3: Postop increases in blood biomarkers of neuroinflammation and AD pathology are greater with GAS relative to IV.

Primary outcomes: preoperative levels of blood p-tau181 and change in levels from preoperative baseline to postoperative.

Secondary outcomes: Other candidate biomarkers include those previously implicated in POD or POCD: p-tau217, Aβ,54 NF-L,55 High mobility group box protein 1 (HMGB1),60 S100β,76 interleukin (IL)-6,58 IL-1β,22 IL-10,46 tumor necrosis factor (TNF)-α,22 CCL2,62 and glial fibrillary acidic protein (GFAP).77

Inclusion criteria

• Men and women ≥ 70 years
• Sufficient vision and hearing to complete all tests
• Proficient in spoken and written English
• Scheduled for elective, inpatient, noncardiac surgery, expected to last at least 120 minutes requiring general anesthesia

Exclusion criteria

• Urgent or emergent surgery
• Diagnosed dementia (or MoCA<19)
• History of Parkinson's disease, major psychiatric disease (Schizophrenia), or severe traumatic brain injury
• Ongoing alcohol or substance abuse (per DSM V criteria)
• Allergy to propofol or sevoflurane
• Personal or family history of malignant hyperthermia
• Planned postoperative intubation
• Brain surgery
• Surgery requiring TIVA or GAS (i.e. cases involving neuromonitoring)
• Surgical procedure requiring general anesthetic occurring within 3 months (before or after) surgical date
• Any patient or perioperative factor considered a contraindication to randomization to either experimental group by the surgeon or anesthesiologist.