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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03360903

Enrollment

Registered

2017-12-04

Start date

2018-01-02

Completion date

2019-06-01

Last updated

2019-11-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia

Brief 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 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.

Interventions

DRUGPlacebo

Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: * Saline

DRUGCaffeine

Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: * Caffeine citrate

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

MALE

Age

25 Years to 40 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Waking Time - Time Between Terminating Anesthesia and Subject Opening Eyes.	15 minutes	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.

Secondary

Measure	Time frame	Description
Cognitive Test2 - Sternberg Test of Memory	Up to 120 minutes after terminating anesthesia.	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.
Cognitive Test3 - Divided Attention Task	Up to 120 minutes after terminating anesthesia.	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.
Cognitive Test1 - Visual Analog Scale	Up to 120 minutes after terminating anesthesia.	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.
Mean Arterial Blood Pressure	Up to 120 minutes after terminating anesthesia.	This measurement is made in order to determine whether caffeine alters blood pressure in a deleterious manner.
Heart Rate	Up to 120 minutes after terminating anesthesia.	This measurement is made in order to determine whether caffeine alters heart rate in a deleterious manner.
Bispectral Index	Up to 120 minutes after terminating anesthesia.	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: * Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: * Caffeine citrate	4
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). Placebo: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). Other Names: * Saline Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). Other Names: * Caffeine citrate	4
Total	8

Baseline characteristics

Characteristic	Placebo Then Caffeine	Caffeine Then Placebo	Total
Age, Continuous	26.8 years STANDARD_DEVIATION 2.4	27.3 years STANDARD_DEVIATION 3.2	27.0 years STANDARD_DEVIATION 2.6
Race/Ethnicity, Customized African American	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Asian	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Caucasian	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Hispanic	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants	1 Participants	2 Participants
Region of Enrollment United States	4 participants	4 participants	8 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	4 Participants	4 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8
other Total, other adverse events	0 / 8	0 / 8
serious Total, serious adverse events	0 / 8	0 / 8

Outcome results

Primary

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.

Time frame: 15 minutes