Total Intravenous Versus Inhalational Anesthesia- A Geriatric Anesthesia Study (TIVA GAS)

Optimizing Anesthesia to Prevent Postoperative Cognitive and Functional Decline in Older Adults: A Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Neurocognitive Disorders; Anesthesia; Post-operative Cognitive Dysfunction; Post-operative Delirium
• Intervention / Treatment: Drug: Sevoflurane; Drug: Propofol

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

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kimberly N. Chun, BS; Phone Number: 503-494-7437; Email: chunk@ohsu.edu
• Study Contact Backup: Name: Sarah L. Feller, BS; Phone Number: 503-494-6233; Email: fellersa@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Sarah Feller, BS; Email: fellersa@ohsu.edu
      • Contact: Kimberly Chun, BS; Email: chunk@ohsu.edu
      • Principal Investigator: Katie Schenning, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inhalational Anesthesia; Inhalational maintenance of anesthesia group using sevoflurane	Drug: Sevoflurane; Inhalational maintenance of anesthesia group using sevoflurane; Other Names: Inhalational Anesthesia
Active Comparator: Intravenous Anesthesia; Intravenous maintenance of anesthesia group using propofol	Drug: Propofol; Intravenous maintenance of anesthesia group using propofol; Other Names: Intravenous Anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Incidence of postoperative delirium with the 3D-Confusion Assessment Method (3D-CAM) in non-intubated patients and the CAM-ICU-7 in intubated patients. Delirium will be assessed postoperative in PACU and twice daily on postoperative days 1-3 while the patient is in the hospital.	through postoperative day 3
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.	Postoperative neurocognitive disorder. Change from preoperative baseline cognitive dysfunction using neuropsychiatric composite score. Battery of neuropsychological tests: Animal Verbal Fluency Test, Trail Making Test A & B, Digit Symbol Test, Logical Memory Immediate & Delayed Recall, and CERAD Word List Immediate and Delayed recall. MASQ will be used for subjective cognitive decline. Functional status will be measured by FAQ.	Change from preoperative baseline to one year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	delirium severity and duration. Delirium will be assessed postoperative in PACU and twice daily on postoperative days 1-3.	through postoperative day 3
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.	change in levels of preoperative levels of blood p-tau181 from preoperative baseline to 12 months postoperative	Change from baseline through one year.
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.	Incidence of postoperative functional decline. Change from preoperative baseline postoperative functional decline to postoperative 12 months.	Change from baseline through one year
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.	patient-reported outcome scores, PROMIS-29+2 Profile v2.1 (PROPr) assesses patient-reported measures of anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, participation in social activities, pain, and cognition. Measured at preoperative baseline, 3 months postoperatively, and 12 months postoperatively	Change from baseline through one year

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Katie J. Schenning, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2027

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Cognition Disorders; Delirium; Cognitive Dysfunction; Postoperative Cognitive Complications; Emergence Delirium; Neurocognitive Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Anesthetics; Propofol; Sevoflurane
• Other Study ID Numbers: STUDY00024667

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In order to promote advancement of this field of study, we will make data generated from this project available. Participants will sign a data repository consent form so de-identified data is able to be maintained indefinitely on secure servers at Oregon Health & Science University. This will enable us to combine these data with other datasets for future analyses, and to share with collaborators and other interested scientists. Other researchers would sign a data use agreement and then receive the de-identified data requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No