Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

Early Phase 1

Completed

• Conditions: Pain, Postoperative
• Interventions: Drug: Caffeine Citrate; Drug: Dextrose Water

• Registration Number: NCT03577730
• Lead Sponsor: University of Michigan

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-06-08
• Study First Submitted QC: 2018-07-03
• Study First Posted: 2018-07-05
• Study Start: 2018-07-10
• Primary Completion: 2019-11-21
• Study Completion: 2020-01-17
• Results First Submitted: 2021-08-04
• Status Verified: 2021-09
• Results First Submitted QC: 2021-09-09
• Last Update Submitted: 2021-09-09
• Results First Posted: 2021-10-06
• Last Update Posted: 2021-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

Inclusion Criteria

• Adult (>/= 18 years old) undergoing non-cardiac, non-neurologic, non-major vascular surgery requiring general anesthesia

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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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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	Caffeine Citrate	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.
Control	Dextrose Water	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.

Primary Outcome Measures

Name	Time	Method
Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg)	through postoperative day 3	Postoperative opioid consumption, oral morphine equivalents (mg)

Secondary Outcome Measures

Name	Time	Method
Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale	Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.	Visual Analogue Scale (mm, 0-100, 0 = no pain, 100 = worst pain imaginable)
Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale	Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.	Behavioral Pain Scale, on a scale ranging from 3 to 12 when 3 is no pain and 12 is maximum pain
Number of Participants With Anxiety as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-A)	baseline through postoperative day 3	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)
Number of Participants With Depression as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-D)	baseline through postoperative day 3	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)
Time Until Anesthetic Emergence	Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes	Time from surgical dressing on to anesthetic emergence (min)
Cognitive Function as Assessed by Trail Making Test	morning of surgery baseline compared to postanesthesia care unit. Postanesthesia care unit measurement approximately 60 minutes after end of surgery	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.
Positive Affect as Assessed by PANAS (Positive and Negative Affect Schedule)	postoperative day 3	Positive Affect Score (n, 10-50, 10 = least positive affect, 50 = most positive affect) via PANAS (Positive and Negative Affect Schedule)
Negative Affect as Assessed by PANAS (Positive and Negative Affect Schedule)	postoperative day 3	Negative Affect Score (n, 10-50, 10 = least negative affect, 50 = most negative affect) via PANAS (Positive and Negative Affect Schedule)
Percentage of Delirious Patients Per Group	By afternoon of postoperative day (POD) 3	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).

Trial Locations

Locations (1)

Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States