Delayed Emergence From Anesthesia, Postoperative Cognitive Dysfunction, Postoperative Delirium
Conditions
Keywords
General Anesthesia, Postoperative Delirium, Recovery
Brief summary
The purpose of this study is to understand how elderly individuals regain their cognitive skills following general anesthesia. The investigators will compare an age stratified group of volunteers who will be evaluated with a series of cognitive tests and a functional MRI. The participants will then be administered general anesthesia for two hours. The investigators will then assess the participants using state of the art tools to determine when participants return to their cognitive baseline.
Detailed description
Elderly patients undergoing anesthesia and surgery frequently suffer from postoperative cognitive dysfunction (POCD) and postoperative delirium (PD). The cause of these entities is unknown. It is unclear what part anesthetics play in the development of POCD and PD. The investigators hypothesize that elderly patient's cognitive capacities recover more slowly after receiving general anesthesia, perhaps because they have more limited cognitive reserve. A more prolonged recovery would confound diagnoses of POCD and PD and potentially puts patients who are discharged on the day of surgery at risk of not understanding postoperative instructions. The trajectory of postoperative cognitive recovery has never been explored and elderly participants have been explicitly not included in any type of emergence research. To explore this vital area the investigators propose to study young and elderly volunteers with a combination of two state of the art neuropsychological tests (Postoperative Quality of Recovery Scale and the NIH Toolbox) and functional magnetic resonance imaging. Starting from baseline, the investigators will determine multiple cognitive domains and resting state networks, treat the participants with general anesthesia for two hours while continuing to examine network activity, and then explore the recovery of the cognitive domains and alterations in functional networks using both the PQRS and the NIH Toolbox Cognitive Measures. Participants will be evaluated at 1 month, 6 months, and 12 months.
Interventions
PROCEDUREFunctional magnetic resonance imaging
Diffusion tensor imaging
Sponsors
National Institute on Aging (NIA)
Yale University
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 40-80 years old * American Society of Anesthesiologists (ASA) Physical Status I or II (i.e. Individuals with minimal disease burden) * Capable and willing to consent
Exclusion criteria
* Airway assessment as potentially difficult (Mallampati III or greater) * Allergies or hypersensitivity to drug or class * Chronic Inflammatory conditions such a lupus or system rheumatoid arthritis (arthritis limited to 1 or 2 joints will be acceptable) * Patients with diabetes mellitus * Patients with a recent illness (within the last 2 weeks) * Patients with severe visual or auditory disorder/handicaps * English illiteracy * Pregnancy * Participants not expected to be able to complete the postoperative tests * History of malignant hyperthermia * Nursing mothers * Body Mass Index \> 30 * Patients with significant metal implants in body * Current use of cocaine or opiates * Current smokers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 15 min, 60 min, 1 day, 3 days, 7 days, 30 days, 6 months | Cognitive Function using scales of the PQRS to test whether age is associated with the time of return to baseline cognitive function. The PQRS is a brief measurement tool to assess multiple domains of recovery, including cognition, over time. It is scored as recovered / not recovered based on level of performance, within a certain tolerance range, relative to preoperative (baseline) performance - before the general anesthesia / MRI scanning session. Postoperative Quality of Recovery Cognitive Scale at each study timepoint by age decade. Postoperative Quality of Recovery Cognitive |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NIH Tool Box Composite | Baseline, 1 day, 7 days, 30 days | NIH Toolbox Cognitive Battery is a multidimensional set of brief measures assessing cognitive (as well as emotional, motor and sensory) function. There is no score range, but mean score is 100 with standard deviation 15. A score at or near 100 indicates average ability compared with others. Scores around 115 suggest above-average ability. Scores around 130 suggest superior ability (in the top 2 percent nationally). A score around 85 suggests below-average ability. A score in the range of 70 or below suggests significant impairment. |
Countries
United States
Participant flow
Recruitment details
Recruitment was completed in May 2019.
Participants by arm
| Arm | Count |
|---|---|
| Functional Magnetic Resonance Imaging Magnetic resonance images acquired on a 3 Tesla scanner (Skyra, Siemens, Erlangen, Germany) with a 20 channel receiver coil.
Functional magnetic resonance imaging: Diffusion tensor imaging | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible after cognitive baseline testing | 11 |
| Overall Study | Ineligible after MRI findings | 1 |
| Overall Study | Ineligible due to medical history | 13 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | MRI malfunction precluded testing | 1 |
| Overall Study | Scanner failure | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Functional Magnetic Resonance Imaging |
|---|---|
| Age, Continuous | 59 years |
| ASA Physical Status 1 - A normal healthy patient | 57 Participants |
| ASA Physical Status 2 - A patient with mild systemic disease without substantive functional limitations | 15 Participants |
| Body Mass Index (BMI) | 26.5 kg/m^2 |
| Disease History Asthma | 1 Participants |
| Disease History Hypertension | 3 Participants |
| Disease History Malignancy (any) | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of medications on initial assessment 0 | 61 Participants |
| Number of medications on initial assessment 1 | 4 Participants |
| Number of medications on initial assessment 2 | 6 Participants |
| Number of medications on initial assessment 3+ | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 72 |
| other Total, other adverse events | 4 / 72 |
| serious Total, serious adverse events | 0 / 72 |
Outcome results
Primary
Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS)
Cognitive Function using scales of the PQRS to test whether age is associated with the time of return to baseline cognitive function. The PQRS is a brief measurement tool to assess multiple domains of recovery, including cognition, over time. It is scored as recovered / not recovered based on level of performance, within a certain tolerance range, relative to preoperative (baseline) performance - before the general anesthesia / MRI scanning session. Postoperative Quality of Recovery Cognitive Scale at each study timepoint by age decade. Postoperative Quality of Recovery Cognitive
Time frame: 15 min, 60 min, 1 day, 3 days, 7 days, 30 days, 6 months
Population: Scale could not be determined for 2 participants (1 in the 40-49 year age decade, one in the 70-80 year age decade).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 3 days | 18 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 30 days | 18 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 7 days | 18 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 60 min | 8 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 15 min | 3 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 6 months | 19 Participants |
| Age Decade 40-49 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 1 day | 17 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 15 min | 5 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 6 months | 19 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 30 days | 19 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 3 days | 19 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 7 days | 19 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 1 day | 18 Participants |
| Age Decade 50-59 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 60 min | 11 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 6 months | 13 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 15 min | 1 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 60 min | 8 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 1 day | 12 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 3 days | 12 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 7 days | 12 Participants |
| Age Decade 60-69 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 30 days | 12 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 3 days | 17 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 1 day | 16 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 15 min | 3 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 30 days | 18 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | at 60 min | 9 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 6 months | 18 Participants |
| Age Decade 70-80 | Number of Participants Recovered on Postoperative Quality of Recovery Scale (PQRS) | 7 days | 17 Participants |
Secondary
Change in NIH Tool Box Composite
NIH Toolbox Cognitive Battery is a multidimensional set of brief measures assessing cognitive (as well as emotional, motor and sensory) function. There is no score range, but mean score is 100 with standard deviation 15. A score at or near 100 indicates average ability compared with others. Scores around 115 suggest above-average ability. Scores around 130 suggest superior ability (in the top 2 percent nationally). A score around 85 suggests below-average ability. A score in the range of 70 or below suggests significant impairment.
Time frame: Baseline, 1 day, 7 days, 30 days
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Age Decade 40-49 | Change in NIH Tool Box Composite | Baseline | 48.1 score on a scale |
| Age Decade 40-49 | Change in NIH Tool Box Composite | 1 day | 52.2 score on a scale |
| Age Decade 40-49 | Change in NIH Tool Box Composite | 30 days | 54.5 score on a scale |
| Age Decade 40-49 | Change in NIH Tool Box Composite | 7 days | 54.8 score on a scale |
| Age Decade 50-59 | Change in NIH Tool Box Composite | 1 day | 57.2 score on a scale |
| Age Decade 50-59 | Change in NIH Tool Box Composite | 30 days | 59.5 score on a scale |
| Age Decade 50-59 | Change in NIH Tool Box Composite | Baseline | 53.3 score on a scale |
| Age Decade 50-59 | Change in NIH Tool Box Composite | 7 days | 59.4 score on a scale |
| Age Decade 60-69 | Change in NIH Tool Box Composite | 7 days | 54.6 score on a scale |
| Age Decade 60-69 | Change in NIH Tool Box Composite | Baseline | 50.1 score on a scale |
| Age Decade 60-69 | Change in NIH Tool Box Composite | 30 days | 54.4 score on a scale |
| Age Decade 60-69 | Change in NIH Tool Box Composite | 1 day | 53.2 score on a scale |
| Age Decade 70-80 | Change in NIH Tool Box Composite | 30 days | 59.6 score on a scale |
| Age Decade 70-80 | Change in NIH Tool Box Composite | Baseline | 54 score on a scale |
| Age Decade 70-80 | Change in NIH Tool Box Composite | 1 day | 57.4 score on a scale |
| Age Decade 70-80 | Change in NIH Tool Box Composite | 7 days | 54.4 score on a scale |