Mild Cognitive Impairment, Postoperative Cognitive Dysfunction, Postoperative Delirium
Conditions
Keywords
Postoperative Delirium, Neurocognitive Disorders, Mild Cognitive Impairment, Alzheimer's Disease
Brief summary
The objective of this study is to test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, this trial tests the primary hypothesis that caffeine will reduce the incidence of postoperative delirium.
Detailed description
Delirium is a syndrome characterized by failure of basic cognitive functions that affects approximately 20-50% of older surgical patients. Delirium during surgical recovery is associated with increased mortality, cognitive and functional decline, and prolonged hospitalization. In fact, 3-year survival rates for acutely hospitalized patients with delirium, and subsyndromal delirium, are both less than 50%. Older age is predictive of delirium after surgery, and with aging surgical populations, the incidence of postoperative delirium and related complications are likely to increase in the coming years. Caffeine represents a novel, neurobiologically informed candidate intervention for reducing risk of early postoperative delirium. Caffeine promotes arousal via adenosine receptor antagonism and improves cognitive function concurrent with increased cortical cholinergic tone. Our preliminary data suggest that caffeine reduces risk of postanesthesia care unit (PACU) delirium in adult non-cardiac surgery patients by optimizing cortical dynamics for cognition. Caffeine also optimizes key neurocognitive processes that support information processing and may improve other, related aspects of clinical recovery, such as rebound headache in habitual caffeine users. The objective of this trial is to thus test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, the primary hypothesis is that caffeine will reduce the incidence of postoperative delirium. The secondary objectives are to (1) test whether caffeine positively impacts the quality of postoperative recovery via validated patient-reported measures and (2) identify neural correlates of delirium and Mild Cognitive Impairment via advanced electroencephalographic (EEG) analysis.
Interventions
DRUGDextrose Water
Dextrose 5% in water
DRUGCaffeine citrate
Low-dose caffeine citrate (1.5 mg/kg)
Sponsors
University of Michigan
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This will be a single-center, quadruple-blinded, randomized control trial at Michigan Medicine
Intervention model description
This will be a three-arm parallel trial.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult (\>/= 70 years old) undergoing non-cardiac, non-intracranial neurologic, non-major vascular surgery requiring general anesthesia with a planned admission for at least 48 hours. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Provision of signed and dated informed consent form.
Exclusion criteria
1. Emergency surgery 2. Outpatient surgery 3. Severe cognitive impairment precluding the capacity for informed consent 4. Seizure disorder history 5. Intolerance or allergy to caffeine (based on subjective reporting or objective documentation) 6. Weight \>130 kg (as a 3 mg/kg dose would approach the upper limit of daily intake recommended by the FDA) 7. Enrollment in conflicting research study 8. Patients in acute liver failure 9. Acute kidney injury preoperatively 10. Diagnosis of pheochromocytoma 11. Active carcinoid syndrome 12. Severe audiovisual impairment 13. Non-English speaking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delirium | Day of surgery through afternoon of postoperative day three | Any positive delirium screen (yes/no) as determined by the long-form Confusion Assessment Method (CAM), and supplemented by a validated daily chart review method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium Severity | Day of surgery through afternoon of postoperative day three | For all participants screened for delirium, the associated severity score will be recorded using the Confusion Assessment Method Long Form Severity Score (CAM-S) (n, 0-19, with higher number indicating more severe delirium) |
| Delirium Duration | Day of surgery through afternoon of postoperative day three | The cumulative number of days (n) with a positive delirium screen will be calculated for all participants |
| Patient-Reported Quality of Recovery | Preoperative baseline through postoperative day three afternoon | Assessed via the 15-item Quality of Recovery Score (n, 0-150, with higher number indicating better quality of recovery from the patient perspective) |
| Sedation | Preoperative baseline through postoperative day three afternoon | Any positive screen based on the Richmond Agitation Sedation Scale (RASS; n, -5 to +4). Scores from -5 to -2 will count as a positive screen for sedation. |
| Agitation | Preoperative baseline through postoperative day three afternoon | Any positive screen based on the Richmond Agitation Sedation Scale (RASS; n, -5 to +4). Scores from +2 to +4 will count as a positive screen for agitation |
| Headache | Preoperative baseline through postoperative day three afternoon | Headache severity will be assessed via 10-centimeter visual analog scale (0-100 mm, with higher score indicating more severe headache) |
| Cumulative Opioid Consumption | Day of surgery through postoperative day three afternoon | Postoperative opioid consumption, oral morphine equivalents (mg) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPhillip Vlisides, MD
Assistant Professor of Anesthesiology
Outcome results
None listed