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The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study

Phase 2
Recruiting
Conditions
Mild Cognitive Impairment
Postoperative Cognitive Dysfunction
Postoperative Delirium
Interventions
Drug: Dextrose Water
Registration Number
NCT05574400
Lead Sponsor
University of Michigan
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
250
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlDextrose WaterPrepared intravenous piggyback solution of 5 percent dextrose water at multiple postoperative time points over a 30-minute infusion period.
High-dose CaffeineCaffeine citratePrepared intravenous high-dose caffeine citrate (3 mg/kg) at multiple postoperative time points over a 30-minute infusion period.
Low-dose CaffeineCaffeine citratePrepared intravenous low-dose caffeine citrate (1.5 mg/kg) at multiple postoperative time points over a 30-minute infusion period.
Primary Outcome Measures
NameTimeMethod
DeliriumDay of surgery through afternoon of postoperative day three

Any positive delirium screen (yes/no) as determined by the long-form Confusion Assessment Method (CAM)

Secondary Outcome Measures
NameTimeMethod
SedationPreoperative 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.

Cumulative Opioid ConsumptionDay of surgery through postoperative day three afternoon

Postoperative opioid consumption, oral morphine equivalents (mg)

Delirium SeverityDay 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 DurationDay 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 RecoveryPreoperative 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)

AgitationPreoperative 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

HeadachePreoperative 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)

Trial Locations

Locations (1)

Michigan Medicine

🇺🇸

Ann Arbor, Michigan, United States

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