Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

The ongoing opioid epidemic is a public health crisis, and surgical patients are particularly vulnerable to opioid-dependency and related risks. Emerging data suggest that caffeine may reduce pain after surgery. Thus, the purpose of this study is to test whether caffeine reduces pain and opioid requirements after surgery. The investigators will also test whether caffeine improves mood and brain function (e.g., learning, memory) after surgery.

Opioid-related deaths have quadrupled in the last 20 years, and nearly half of these deaths currently involve prescription opioids. Surgical patients often experience moderate-to-severe pain is common after major surgery, and surgery is associated with a 14-fold increased risk of opioid dependency compared to non-surgical controls, even after minor surgery. Furthermore, mood disorders (e.g., depression) are independently associated with persistent opioid use postoperatively, and signs of postoperative depression are common after major surgery. Thus, given these risk factors, surgical patients are at particularly high risk for opioid dependency postoperatively. Interventions that (1) reduce opioid burden, and (2) improve mood and neuropsychological function may mitigate the risk of postoperative opioid dependency. Preliminary laboratory and clinical findings demonstrate that caffeine may reduce pain after surgery, which may translate to lower opioid requirements. The study tests the hypothesis that intraoperative caffeine administration will improve opioid consumption, pain, and neuropsychological recovery in patients undergoing surgery. Through validated assessment measures, the research team will study the effects of caffeine in relation to postoperative opioid requirements, pain, and neuropsychological (e.g., cognition, depression, anxiety) trajectory after surgery.

Opioid Use, Opioid Dependence, Opioid-Related Disorders, Opioid Abuse, Opioid-use Disorder, Pain, Pain, Postoperative, Cognitive Impairment, Delirium, Delirium on Emergence, Depression, Anxiety, Anxiety Disorders, Affect

This will be a single-center, quadruple-blinded, pilot randomized controlled trial at the University of Michigan Health System.

Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.

Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.

Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes

Number of Participants With Depression as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-D)

Number (n) of participants with positive screens (score ≥8) using the Hospitalized Anxiety and Depression Scale (HADS-D) (n, 0-21, 0 = normal, 21 = presence of severe depression symptoms)

Number of Participants With Anxiety as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-A)

Number (n) of participants with positive screens (score ≥8) using the Hospitalized Anxiety and Depression Scale (HADS-A) (n, 0-21, 0 = normal, 21 = presence of severe anxiety symptoms)

Trail Making Test scores (seconds, 10-300,10 = fastest reported completion, 300 = maximum time allowed for completion). The change was calculated from the value at post anesthesia minus value at baseline. Higher values are considered to be worse outcomes.

morning of surgery baseline compared to postanesthesia care unit. Postanesthesia care unit measurement approximately 60 minutes after end of surgery

Positive Affect Score (n, 10-50, 10 = least positive affect, 50 = most positive affect) via PANAS (Positive and Negative Affect Schedule)

Negative Affect Score (n, 10-50, 10 = least negative affect, 50 = most negative affect) via PANAS (Positive and Negative Affect Schedule)

Number (n) of participants who has experienced at least one episode of delirium by the postoperative day 3 time point, as determined by daily Confusion Assessment Method (CAM).

Subacute Opioid Consumption: Postoperative Subacute Opioid Consumption, Oral Morphine Equivalents (mg)

time point 1: anesthetic emergence, approximate measurement 5-10 minutes after surgery end. Time point 2: postanesthesia care unit arrival, approximate measurement 20 minutes after end of surgery

time point 1: anesthetic emergence, approximate measurement 5-10 minutes after surgery end. Time point 2: postanesthesia care unit arrival, approximate measurement 20 minutes after end of surgery

Comprehensive survey that reports on general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy /fatigue levels, social functioning and mental health. Specifically, a physical and mental health score are reported, with both score scales ranging from 0 (worst possible outcome) to 100 (best possible outcome).

Self-report outcome measure evaluating recovery after surgery and anesthesia. Scoring ranges from 3-18, 3=poor 18=excellent

Self-report instrument for measuring sleep quality. Visual Analogue Scale (mm, 0-100, 0 =Deep sleep , 100 =Light sleep)

Inclusion Criteria: Adult (>/= 18 years old) undergoing non-cardiac, non-neurologic, non-major vascular surgery requiring general anesthesia Exclusion Criteria: Emergency surgery Cognitive impairment precluding capacity for informed consent Uncontrolled cardiac arrhythmias Seizure disorders Preoperative opioid use Diabetes Liver failure Pregnancy Breastfeeding Severe visual or auditory impairment (may hinder cognitive function testing) Patients unable to speak English.

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