A Study to Determine if Caffeine Accelerates Emergence From Anesthesia

Anesthesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02567968
• Other study ID #: IRB15-0897
• Secondary ID: 1R01GM116119-01
• Status: Completed
• Phase: Phase 4
• Start date: August 2016
• Est. completion date: May 1, 2017

Study information

• Verified date: July 2018
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 and mice to wake much more rapidly from 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 investigators carried out a modest trial with 8 test subjects. Each volunteer was anesthetized twice. Each volunteer was anesthetized one time and received an infusion of saline (placebo control), without the aid of any other drugs and the other time the volunteer received an infusion of a relatively low dose of caffeine. The order of saline versus caffeine was randomized and the study was done in a double blind manner. We observed that emergence from anesthesia was significantly accelerated by the caffeine infusion. No adverse events were observed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: May 1, 2017
• Est. primary completion date: May 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 40 Years

Eligibility

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 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.

Related Conditions & MeSH terms

• Anesthesia

Intervention

Drug:
• Caffeine
Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). The time to wake will be measured.
• Placebo Control
Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). The time to wake will be measured.

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
University of Chicago	National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Waking Time - Re-establishment of the Gag Reflex.	The goal of the study is to determine whether caffeine speeds emergence from anesthesia. The time between terminating delivery of anesthetic and the subject starting to gag was measured. Anesthesia suppresses the gag reflex. Immediately after anesthetizing the test subject, a laryngeal mask airway (LMA) device was inserted into the test subject airway. After anesthesia was terminated and emergence from anesthesia was taking place, the gag reflex was re-established, and the LMA produced a "gag response" in all test subjects. This objective and unequivocal measurement constituted the "emergence" time for each subject. The "emergence" time was defined as the time between terminating the anesthesia and the test subject starting to gag.	followed from the end of anesthesia to gag reflex, up to 2 hours
Secondary	Cognitive Test1 - Visual Analog Scale --- Feel Good	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 was asked to complete a series of psychomotor tests, if they were able. Otherwise the testing started at 30 minutes. The tests were 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 were asked to rate how they currently felt by placing a cursor on each of the line (0=not at all, 100=extremely). The test repeated every 15 minutes.	Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.
Secondary	Cognitive Test1 - Visual Analog Scale --- Feel Bad	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 was asked to complete a series of psychomotor tests, if they were able. Otherwise the testing started at 30 minutes. The tests were 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 were asked to rate how they currently felt by placing a cursor on each of the line (0=not at all, 100=extremely). The test repeated every 15 minutes.	Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.
Secondary	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 was first applied at 15 minutes following anesthesia, if the subject was awake and then repeated every 15 minutes. In the Sternberg Test of Memory (STM) participants were asked to memorize a string of numbers. Afterwards, a computer would flash a series of random numbers on the screen and the participant was asked whether the number on the computer screen was part of the earlier string or not. In three rounds, participants were given a string of 2, then 4, then 6 numbers. The latency until the subject answered the question was monitored and this is the data summarized here.	Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.
Secondary	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 was first applied at 15 minutes following anesthesia, if the subject was awake and then repeated every 15 minutes. In the Divided Attention Task (DAT), participants were asked to fly an airplane over the center of a winding road with a joystick and simultaneously press a button whenever targets randomly flashed on the screen. The computer program tracked 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 appeared.	Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.
Secondary	Bispectral Index	A bispectral index (BIS) measurement system was employed to measure depth of anesthesia. Using electrodes attached to the forehead to measure EEG, BIS outputs a dimensionless number between 0 and 100 that is proportional to the brain concentration of anesthetic and is thereby proportional to an individual's level of consciousness (Greenwald S, Chiang HH, Devlin P, Smith C, Sigl J, Chamoun N: The Bispectral Index (Bis2.0) as a Hypnosis Measure. Anesthesiology 1994; 81: A477-a477). When the test subjects arrive, prior to anesthesia, their BIS values are in the range of 95 - 99. That corresponds to an awake and alert state. During anesthesia, most subjects are in the range of 20 - 40, corresponding to an anesthetized state. As the anesthetic wears off, the BIS values rise until they are back in the 95 - 99 range that they were prior to anesthesia. In particular, we wished to determine whether BIS exhibited more rapid recovery after caffeine infusion as compared to saline (control).	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.
Secondary	Minute Ventilation	The volume of gas inhaled or exhaled from a person's lungs per minute. We wished to determine whether caffeine altered minute ventilation.	Continuous monitoring from time lma inserted until subject started to gag and it was removed, up to 2 hours post-anesthesia.
Secondary	Mean Arterial Blood Pressure	This measurement was made in order to determine whether caffeine altered blood pressure in a deleterious manner.	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.
Secondary	Heart Rate	This measurement was made in order to determine whether caffeine altered heart rate in a deleterious manner.	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.