Clinical trial NCT05574400: The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study
Official title: The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Postoperative Delirium
Postoperative Cognitive Dysfunction
Mild Cognitive Impairment
Keywords: Postoperative Delirium
Neurocognitive Disorders
Mild Cognitive Impairment
Alzheimer's Disease
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-10-10
Enrollment: 250
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a three-arm parallel trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. Severe audiovisual impairment
12. Non-English speaking

Primary outcomes:
measure: Delirium
timeFrame: Day of surgery through afternoon of postoperative day three
Secondary outcomes:
measure: Delirium Severity
timeFrame: Day of surgery through afternoon of postoperative day three
measure: Delirium Duration
timeFrame: Day of surgery through afternoon of postoperative day three
measure: Patient-Reported Quality of Recovery
timeFrame: Preoperative baseline through postoperative day three afternoon
measure: Sedation
timeFrame: Preoperative baseline through postoperative day three afternoon
measure: Agitation
timeFrame: Preoperative baseline through postoperative day three afternoon
measure: Headache
timeFrame: Preoperative baseline through postoperative day three afternoon
measure: Cumulative Opioid Consumption
timeFrame: Day of surgery through postoperative day three afternoon
Other outcomes:
measure: Anesthetic Emergence
timeFrame: Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes
measure: Pulmonary Complications
timeFrame: From extubation until end of postanesthesia care unit stay
measure: Hospital Length of Stay
timeFrame: Morning of surgery until day of hospital discharge, up to 30 days
measure: Discharge Disposition
timeFrame: Day of hospital discharge, up to 30 days
measure: 30-Day Cognitive Function
timeFrame: 30 days after hospital discharge
measure: 30-Day Physical Function
timeFrame: 30 days after hospital discharge
Locations:
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
Study officials:
affiliation: Assistant Professor of Anesthesiology
name: Phillip Vlisides, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vlisides PE, Li D, McKinney A, Brooks J, Leis AM, Mentz G, Tsodikov A, Zierau M, Ragheb J, Clauw DJ, Avidan MS, Vanini G, Mashour GA. The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial. Anesth Analg. 2021 Jul 1;133(1):233-242. doi: 10.1213/ANE.0000000000005532.
citation: Kim H, McKinney A, Brooks J, Mashour GA, Lee U, Vlisides PE. Delirium, Caffeine, and Perioperative Cortical Dynamics. Front Hum Neurosci. 2021 Dec 20;15:744054. doi: 10.3389/fnhum.2021.744054. eCollection 2021.