Clinical trial NCT03577730: Caffeine and Neurologic Recovery Following Surgery and General Anesthesia
Official title: Caffeine and Neurologic Recovery Following Surgery and General Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pain, Postoperative
Keywords: 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
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2018-07-05
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg)
timeFrame: through postoperative day 3
Secondary outcomes:
measure: Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale
timeFrame: Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.
measure: Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale
timeFrame: Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.
measure: Time Until Anesthetic Emergence
timeFrame: Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes
measure: Number of Participants With Depression as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-D)
timeFrame: baseline through postoperative day 3
measure: Number of Participants With Anxiety as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-A)
timeFrame: baseline through postoperative day 3
measure: Cognitive Function as Assessed by Trail Making Test
timeFrame: morning of surgery baseline compared to postanesthesia care unit. Postanesthesia care unit measurement approximately 60 minutes after end of surgery
measure: Positive Affect as Assessed by PANAS (Positive and Negative Affect Schedule)
timeFrame: postoperative day 3
measure: Negative Affect as Assessed by PANAS (Positive and Negative Affect Schedule)
timeFrame: postoperative day 3
measure: Percentage of Delirious Patients Per Group
timeFrame: By afternoon of postoperative day (POD) 3
Other outcomes:
measure: Caffeine Intake: Number of Caffeinated Beverages (n) Consumed
timeFrame: postoperative day 0-7
measure: Subacute Opioid Consumption: Postoperative Subacute Opioid Consumption, Oral Morphine Equivalents (mg)
timeFrame: postoperative days 4-7
measure: Sleep Disturbances: Incidence (%) of New, Self-reported Sleep Disturbances
timeFrame: postoperative days 0-3
measure: EEG Spectral Power: Spectral Power (dB) Measured on EEG
timeFrame: 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
measure: EEG Connectivity: Connectivity (Weighted Phase Lag Index, wPLI) Measured on EEG
timeFrame: 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
measure: Veterans Rand 12 Survey
timeFrame: 30 days after surgery
measure: Persistent Opioid Use
timeFrame: Postoperative day (POD) 30
measure: Quality of Recovery Survey
timeFrame: Postoperative day (POD) 1
measure: Richards Campbell Sleep Questionnaire (RCSQ)
timeFrame: Preoperative (once before surgery on day of surgery)
Locations:
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
Study officials:
affiliation: Assistant Professor of Anesthesiology
name: Phillip Vlisides, MD
role: PRINCIPAL_INVESTIGATOR
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