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

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.

Prepared intravenous piggyback solution of 5 percent dextrose water at multiple postoperative time points over a 30-minute infusion period.

Drug: Dextrose Water

Prepared intravenous low-dose caffeine citrate (1.5 mg/kg) at multiple postoperative time points over a 30-minute infusion period.

Drug: Caffeine citrate

Prepared intravenous high-dose caffeine citrate (3 mg/kg) at multiple postoperative time points over a 30-minute infusion period.

Drug: Caffeine citrate

Dextrose 5% in water

Low-dose caffeine citrate (1.5 mg/kg)

High-dose Caffeine citrate (3 mg/kg)

Plazo: 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.

Plazo: 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)

Plazo: 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

Plazo: 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)

Plazo: 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.

Plazo: 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

Plazo: 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)

Plazo: Day of surgery through postoperative day three afternoon

Postoperative opioid consumption, oral morphine equivalents (mg)

Plazo: 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

Plazo: 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

Plazo: 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

Plazo: 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

Plazo: 30 days after hospital discharge

Cognitive function score based on the Montreal Cognitive Assessment (n, 0-30, with higher scores reflecting higher cognitive function)

Plazo: 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)

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