Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Caffeine Citrate
* Drug: Dextrose Water


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>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. | Drug: Caffeine Citrate<br>* 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.<br>|
| Placebo Comparator: Control<br>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. | Drug: Dextrose Water<br>* Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg) | Postoperative opioid consumption, oral morphine equivalents (mg) | through postoperative day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale | Visual Analogue Scale (mm, 0-100, 0 = no pain, 100 = worst pain imaginable) | Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol. | 
| Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale | Behavioral Pain Scale, on a scale ranging from 3 to 12 when 3 is no pain and 12 is maximum pain | Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol. | 
| Time Until Anesthetic Emergence | Time from surgical dressing on to anesthetic emergence (min) | 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) | baseline through postoperative day 3 | 
| 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) | baseline through postoperative day 3 | 
| Cognitive Function as Assessed by Trail Making Test | 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 as Assessed by PANAS (Positive and Negative Affect Schedule) | Positive Affect Score (n, 10-50, 10 = least positive affect, 50 = most positive affect) via PANAS (Positive and Negative Affect Schedule) | postoperative day 3 | 
| Negative Affect as Assessed by 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) | postoperative day 3 | 
| Percentage of Delirious Patients Per Group | 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). | By afternoon of postoperative day (POD) 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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