The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Control Prepared intravenous piggyback solution of 5 percent dextrose water at multiple postoperative time points over a 30-minute infusion period. |
Drug: Dextrose Water
Dextrose 5% in water
|
| Experimental: Low-dose Caffeine Prepared intravenous low-dose caffeine citrate (1.5 mg/kg) at multiple postoperative time points over a 30-minute infusion period. |
Drug: Caffeine citrate
Low-dose caffeine citrate (1.5 mg/kg)
|
| Experimental: High-dose Caffeine Prepared intravenous high-dose caffeine citrate (3 mg/kg) at multiple postoperative time points over a 30-minute infusion period. |
Drug: Caffeine citrate
High-dose Caffeine citrate (3 mg/kg)
|
Outcome Measures
Primary Outcome Measures
- Delirium [Day of surgery through afternoon of postoperative day two]
Any positive delirium screen (yes/no) as determined by the long-form Confusion Assessment Method (CAM)
Secondary Outcome Measures
- Delirium Severity [Day of surgery through afternoon of postoperative day two]
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 two]
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 two 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 two 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 two 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 two 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 two afternoon]
Postoperative opioid consumption, oral morphine equivalents (mg)
Other Outcome Measures
- Anesthetic Emergence [Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes]
Time (minutes) from surgical closure to extubation
- Pulmonary Complications [From extubation until end of postanesthesia care unit stay]
Composite outcome (yes/no) of any of the following: airway adjunct use, unplanned continuous positive airway pressure device, unplanned humidified high-flow oxygen, need for bag-mask ventilation, or reintubation
- Hospital Length of Stay [Morning of surgery until day of hospital discharge, up to 30 days]
Total number of days (n) spent in the hospital, up to 30 days
- Discharge Disposition [Day of hospital discharge, up to 30 days]
Proportion of patients in each group (%) discharged somewhere other than home (e.g., Long-Term Care Facility), up to 30 days
- 30-Day Cognitive Function [30 days after hospital discharge]
Cognitive function score based on the Montreal Cognitive Assessment (n, 0-30, with higher scores reflecting higher cognitive function)
- 30-Day Physical Function [30 days after hospital discharge]
Physical function score based on the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function 10a score (n, 10-50, with higher score indicating better physical function)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
Stated willingness to comply with all study procedures and availability for the duration of the study.
-
Provision of signed and dated informed consent form.
Exclusion Criteria:
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Emergency surgery
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Outpatient surgery
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Severe cognitive impairment precluding the capacity for informed consent
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Seizure disorder history
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Intolerance or allergy to caffeine (based on subjective reporting or objective documentation)
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Weight >130 kg (as a 3 mg/kg dose would approach the upper limit of daily intake recommended by the FDA)
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Enrollment in conflicting research study
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Patients in acute liver failure
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Acute kidney injury preoperatively
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Diagnosis of pheochromocytoma
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Severe audiovisual impairment
-
Non-English speaking
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Michigan Medicine | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- University of Michigan
- National Institute on Aging (NIA)
Investigators
- Principal Investigator: Phillip Vlisides, MD, Assistant Professor of Anesthesiology
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- HUM00218290
- R01AG075005