A Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia

A Randomized, Double-Blinded, Placebo-Controlled Study to Determine if Caffeine Citrate Accelerates Emergence From Anesthesia

At present clinicians have no way to reverse anesthesia. Patients wake when their bodies clear the anesthetic. Most people wake quickly, but some do not. All patients have memory and other cognitive problems after waking from anesthesia. In studies on animals, the investigators observed that caffeine caused rats to wake much more rapidly from propofol anesthesia. This was true for all the animals tested. The investigators would like to see if this holds true in humans. Will caffeine accelerate waking from anesthesia? Will it reverse the cognitive deficits associated with anesthesia, after waking?

The propose investigators carrying out a modest trial with 8 test subjects. Each volunteer will be anesthetized twice. Each volunteer will be anesthetized one time and receive an infusion of saline (placebo control), without the aid of any other drugs and the other time the volunteer will receive an infusion of a relatively low dose of caffeine. The order of saline versus caffeine will be randomized and the study will be done in a double blind manner. We will determine whether emergence from propofol anesthesia will be significantly accelerated by the caffeine infusion. And whether any adverse events are observed.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Placebo; Drug: Caffeine

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age 25-40.
2. Male.
3. Normal healthy subject without systematic diseases or conditions.
4. Metabolic Equivalents of Functional Capacity >= 5.
5. Low risk for Obstructive Sleep Apnea (OSA) based on the screening test (STOP-bang score established by American Society of Sleep Apnea): Yes to > 3 items- high risk of OSA
6. No History of Arrhythmia (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases.
7. BMI < 30 kg/m2.
8. No history of prior difficulty with anesthesia.
9. No personal or family history of malignant hyperthermia.
10. No history of any mental illness.
11. No history of drugs or alcohol abuse (urine drug screens required).
12. Subjects capable of giving consent.
13. Living less than 30 miles away from University of Chicago.
14. No history of seizure disorders.
15. No history of head trauma.

Exclusion Criteria:

1. Age <25 or >40.
2. Female.
3. ASA physical status > 1 (normal healthy subject without systematic diseases or conditions)
4. Metabolic Equivalents of Functional Capacity (METs) < 5.
5. High risks for Obstructive Sleep Apnea (OSA) based on the screening test (STOP-bang score established by American Society of Sleep Apnea): Yes to > 3 items- high risk of OSA
6. History Arrhythmia (Baseline EKG will be obtained during the history and physical session), seizure, liver and kidney diseases
7. BMI>30 kg/m2.
8. Prior difficulty with anesthesia.
9. Personal or family history of malignant hyperthermia.
10. History of any mental illness.
11. History of drugs or alcohol abuse (urine drug screens required)
12. Subjects not capable of giving consent
13. Living more than 30 miles away from University of Chicago.
14. History of seizure disorders.
15. History of head trauma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo then Caffeine; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control) followed by a washout period and then anesthetized again and allowed to wake after injection of caffeine (15 mg/ kg).	Drug: Placebo; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline; Drug: Caffeine; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate
Experimental: Caffeine then Placebo; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg) followed by a washout period and then anesthetized again and allowed to wake after injection of saline (placebo control).	Drug: Placebo; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: Saline; Drug: Caffeine; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: Caffeine citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes.	The goal of the study is to determine whether caffeine speeds emergence from anesthesia. The time between terminating delivery of anesthetic and the subject opening their eyes will be measured. The time to "emerge" from anesthesia will be defined as the time between terminating the anesthesia and the test subject opening their eyes.	15 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Test1 - Visual Analog Scale	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. Fifteen minutes after terminating anesthesia each subject will be asked to complete a series of psychomotor tests, if they are able. Otherwise the testing started at 30 minutes. The tests will be repeated every 15 minutes. The first test, a visual analog scale (VAS) test consisted of two 100-mm lines, each labelled with of "feel good" or "feel bad" displayed on a computer screen. Test subjects will be asked to rate how they currently felt by placing a cursor on each of the line (0=not at all, 100=extremely). The test will be repeated every 15 minutes.	Up to 120 minutes after terminating anesthesia.
Cognitive Test2 - Sternberg Test of Memory	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test will be applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Sternberg Test of Memory (STM) participants are asked to memorize a string of numbers. Afterwards, a computer will flash a series of random numbers on the screen and the participant is asked whether the number on the computer screen are part of the earlier string or not. In three rounds, participants are given a string of 2, then 4, then 6 numbers. The latency until the subject answers the question is also monitored.	Up to 120 minutes after terminating anesthesia.
Cognitive Test3 - Divided Attention Task	Normally patients receiving anesthesia exhibit significant cognitive problems for hours after anesthesia is terminated. The goal is to determine whether caffeine helps ameliorate the cognitive issues. The test is first applied at 15 minutes following anesthesia, if the subject is awake and then repeated every 15 minutes. In the Divided Attention Task (DAT), participants are asked to fly an airplane over the center of a winding road with a joystick and simultaneously press a button whenever targets randomly flash on the screen. The computer program tracks the root mean squared (RMS) deviation of the plane from the center of the road and the latency for pressing the trigger when the target appears.	Up to 120 minutes after terminating anesthesia.
Bispectral Index	A bispectral index (BIS) measurement system is employed to measure depth of anesthesia. In particular, we wish to determine whether BIS exhibits more rapid recovery after caffeine compared to control.	Up to 120 minutes after terminating anesthesia.
Mean Arterial Blood Pressure	This measurement is made in order to determine whether caffeine alters blood pressure in a deleterious manner.	Up to 120 minutes after terminating anesthesia.
Heart Rate	This measurement is made in order to determine whether caffeine alters heart rate in a deleterious manner.	Up to 120 minutes after terminating anesthesia.

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 4, 2017

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: IRB17-1174; 1R01GM116119 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No