Clinical trial NCT06036095: Total Intravenous Versus Inhalational Anesthesia- A Geriatric Anesthesia Study
Official title: Optimizing Anesthesia to Prevent Postoperative Cognitive and Functional Decline in Older Adults: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neurocognitive Disorders
Anesthesia
Post-operative Delirium
Post-operative Cognitive Dysfunction
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2023-09-13
Enrollment: 260
Sex: ALL
Minimum age (years): 70
Maximum age (years): 110
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This single-center, 1:1 randomized, double-blind (patient \& outcome assessor) clinical trial will compare inhalational (sevoflurane) vs. intravenous (propofol) anesthesia on POD, POCD, functional status, PROs, and biomarkers in patients ≥ 70 years undergoing elective, inpatient, non-cardiac surgery at Oregon Health \& Science University.
Primary purpose: PREVENTION

Brief summary: Traditionally, general anesthesia is maintained with inhalational anesthesia (GAS), but there is a gap in knowledge regarding whether intravenous anesthesia (IV) can prevent deleterious postoperative outcomes in the geriatric surgical population. The goal of this clinical trial is to determine whether intravenous anesthesia (IV) leads to a decreased incidence of postoperative delirium (POD), postoperative cognitive dysfunction (POCD), and functional decline, and improved patient-reported outcomes (PROs) in older adults undergoing non-cardiac surgery when compared to the standard inhalational anesthesia (GAS). This single-center, 1:1 randomized, double-blind (patient \& outcome assessor) clinical trial will compare inhalational vs. intravenous anesthesia on POD, POCD, functional status, patient-reported outcomes (PROs), and blood-based biomarkers in older patients undergoing elective, inpatient, non-cardiac surgery. Upon enrollment, 260 women and men ≥ 70 years undergoing elective noncardiac surgery under general anesthesia will be randomized to 2 groups: TIVA or GAS.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Effects of intravenous vs. inhalational anesthesia on incidence of postoperative delirium in older surgical patients with the 3D-Confusion Assessment Method (3D-CAM-S) and the CAM-ICU-7.
timeFrame: through postoperative day 3
measure: Determine the effects of intravenous vs. inhalational anesthesia on the incidence of postoperative neurocognitive disorder in older adults undergoing non-cardiac surgery using neuropsychiatric composite score.
timeFrame: Change from preoperative baseline to one year.
Secondary outcomes:
measure: Determine the effects of intravenous vs. inhalational anesthesia on incidence of delirium duration (days) and severity, measured by 3D-CAM-S, and CAM-ICU-7 in older adults undergoing non-cardiac surgery.
timeFrame: through postoperative day 3
measure: Effects of intravenous vs. inhalational anesthesia on levels of blood phosphorylated tau 181 (p-tau181) in older surgical patients.. Change from preoperative baseline blood p-tau181 to postoperative day 1, 3 months and 12 months.
timeFrame: Change from baseline through one year.
measure: Determine the effects of intravenous vs. inhalational anesthesia on incidence of postoperative functional decline using ADL, FAQ, and FRAIL in older adults undergoing non-cardiac surgery.
timeFrame: Change from baseline through one year
measure: Determine the effects of intravenous vs. inhalational anesthesia on patient-reported outcomes (PROMIS-29+2 Profile v2.1) in older adults undergoing non-cardiac surgery.
timeFrame: Change from baseline through one year
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Katie J. Schenning, MD
role: PRINCIPAL_INVESTIGATOR
References: