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Completed

NCT Number: NCT03577730

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.

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Key information

Conditions

Pain, Postoperative Anxiety Disorders Behavior Behavioral Symptoms Chemically-Induced Disorders Cognition Disorders Cognitive Dysfunction Confusion Delirium Depression Emergence Delirium Mental Disorders Narcotic-Related Disorders Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Opioid-Related Disorders Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Signs and Symptoms Substance-Related Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Caffeine citrate

Drug

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.

Dextrose Water

Drug

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

Primary outcomes

  1. Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg)

    Time frame: through postoperative day 3

    Postoperative opioid consumption, oral morphine equivalents (mg)

Secondary outcomes

  1. Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale

    Time frame: 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)

  2. Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale

    Time frame: 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

  3. Time Until Anesthetic Emergence

    Time frame: 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)

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

    Time frame: 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)

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

    Time frame: 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)

  6. Cognitive Function as Assessed by Trail Making Test

    Time frame: 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.

  7. Positive Affect as Assessed by PANAS (Positive and Negative Affect Schedule)

    Time frame: postoperative day 3

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

  8. Negative Affect as Assessed by PANAS (Positive and Negative Affect Schedule)

    Time frame: postoperative day 3

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

  9. Percentage of Delirious Patients Per Group

    Time frame: 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).

Other outcomes

  1. Caffeine Intake: Number of Caffeinated Beverages (n) Consumed

    Time frame: postoperative day 0-7

    Number of caffeinated beverages (n) consumed

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

    Time frame: postoperative days 4-7

    Postoperative subacute opioid consumption, oral morphine equivalents (mg)

  3. Sleep Disturbances: Incidence (%) of New, Self-reported Sleep Disturbances

    Time frame: postoperative days 0-3

    Incidence (%) of new, self-reported sleep disturbances

  4. EEG Spectral Power: Spectral Power (dB) Measured on EEG

    Time frame: 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

    Spectral power (dB) measured on EEG

  5. EEG Connectivity: Connectivity (Weighted Phase Lag Index, wPLI) Measured on EEG

    Time frame: 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

    Connectivity (weighted phase lag index, wPLI) measured on EEG

  6. Veterans Rand 12 Survey

    Time frame: 30 days after 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).

  7. Persistent Opioid Use

    Time frame: Postoperative day (POD) 30

    Incidence of continued opioid use (%) on postoperative day (POD) 30

  8. Quality of Recovery Survey

    Time frame: Postoperative day (POD) 1

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

  9. Richards Campbell Sleep Questionnaire (RCSQ)

    Time frame: Preoperative (once before surgery on day of surgery)

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

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Important dates

Study start
2018
Primary completion
2019
Study completion
2020
First posted
Jul 5, 2018
Registry last updated
Oct 6, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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