A Study to Determine if Caffeine Accelerates Emergence From Anesthesia

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT02567968
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of General Medical Sciences (NIGMS) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Caffeine; Drug: Placebo Control	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled Study to Determine if Caffeine Citrate Accelerates Emergence From Anesthesia
• Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Anesthetized volunteers will be allowed to wake after injection of either saline (placebo control) or caffeine (15 mg/ kg). The time to wake will be measured.	Drug: Placebo Control; Anesthetized volunteers will be allowed to wake after injection of saline (placebo control). The time to wake will be measured.; Other Names: Saline
Active Comparator: Caffeine Anesthetized volunteers will be allowed to wake after injection of either saline (placebo control) or caffeine (15 mg/ kg). The time to wake will be measured.	Drug: Caffeine; Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg). The time to wake will be measured.; Other Names: Caffeine citrate

Outcome Measures

Primary Outcome Measures

1. Waking Time - Re-establishment of the Gag Reflex. [followed from the end of anesthesia to gag reflex, up to 2 hours]

   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.

Secondary Outcome Measures

1. Cognitive Test1 - Visual Analog Scale --- Feel Good [Test was given at 15, 30, 45, 60, 75, 90, 105 and 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 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.

2. Cognitive Test1 - Visual Analog Scale --- Feel Bad [Test was given at 15, 30, 45, 60, 75, 90, 105 and 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 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.

3. Cognitive Test2 - Sternberg Test of Memory [Test was given at 15, 30, 45, 60 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 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.

4. Cognitive Test3 - Divided Attention Task [Test was given at 15, 30, 45, 60 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 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.

5. Bispectral Index [Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.]

   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).

6. Minute Ventilation [Continuous monitoring from time lma inserted until subject started to gag and it was removed, up to 2 hours post-anesthesia.]

   The volume of gas inhaled or exhaled from a person's lungs per minute. We wished to determine whether caffeine altered minute ventilation.

7. Mean Arterial Blood Pressure [Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.]

   This measurement was made in order to determine whether caffeine altered blood pressure in a deleterious manner.

8. Heart Rate [Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.]

   This measurement was made in order to determine whether caffeine altered heart rate in a deleterious manner.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• National Institutes of Health (NIH)
• National Institute of General Medical Sciences (NIGMS)

Investigators

• Principal Investigator: Aaron Fox, PhD, University of Chicago

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 16, 2016

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT02567968
• Other Study ID Numbers: IRB15-0897; 1R01GM116119-01
• First Posted: Oct 5, 2015
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Caffeine; Caffeine citrate

Study Results

Participant Flow

Arm/Group Title	Caffeine, Then Placebo	Placebo, Then Caffeine
Arm/Group Description	Participants first received Caffeine. After a washout period of 2 weeks, they then received Placebo.	Participants first received Placebo, and after 2-week washout period, then received Caffeine
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	4	4
COMPLETED	4	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants who were randomized to either receive Caffeine then Placebo or Placebo then Caffeine
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31 (4.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race/Ethnicity, Customized (Count of Participants)
White	3 37.5%
Black	3 37.5%
Asian	2 25%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Waking Time - Re-establishment of the Gag Reflex.
Description	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.
Time Frame	followed from the end of anesthesia to gag reflex, up to 2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
Mean (Standard Deviation) [minutes]	16.45 (3.9)	9.57 (5.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Caffeine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	paired t-test
	Comments

2. Secondary Outcome

Title	Cognitive Test1 - Visual Analog Scale --- Feel Good
Description	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.
Time Frame	Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Some participants could not be tested at the early timepoints due to not being fully awake etc.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
15 minutes post-anesthesia	29 (0)	54.8 (22.4)
30 minutes post-anesthesia	48.1 (29.5)	50.3 (25.4)
45 minutes post-anesthesia	50.9 (29.0)	58.1 (26.5)
60 minutes post-anesthesia	62.8 (26.5)	55.1 (27.5)
75 minutes post-anesthesia	60.0 (28.2)	59.3 (25.9)
90 minutes post-anesthesia	61.5 (26.7)	59.5 (25.7)
105 minutes post-anesthesia	66.3 (24.1)	61.9 (24.3)
120 minutes post-anesthesia	66.0 (25.1)	66.8 (27.7)

3. Secondary Outcome

Title	Cognitive Test1 - Visual Analog Scale --- Feel Bad
Description	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.
Time Frame	Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Some participants could not be tested at the early timepoints due to not being fully awake etc.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
15 minutes post-anesthesia	6.0 (0)	27.4 (24.2)
30 minutes post-anesthesia	17.9 (20.9)	11.6 (13.3)
45 minutes post-anesthesia	13.0 (14.1)	11.8 (14.7)
60 minutes post-anesthesia	9.8 (10.3)	10.0 (12.2)
75 minutes post-anesthesia	6.0 (8.1)	8.5 (12.0)
90 minutes post-anesthesia	7.0 (7.2)	6.4 (7.4)
105 minutes post-anesthesia	6.6 (11.0)	3.9 (4.3)
120 minutes post-anesthesia	4.3 (4.3)	4.3 (6.5)

4. Secondary Outcome

Title	Cognitive Test2 - Sternberg Test of Memory
Description	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.
Time Frame	Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Some participants could not be tested at the early timepoints due to not being fully awake etc.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
15 minutes post-anesthesia	847 (0)	1001.4 (182.8)
30 minutes post-anesthesia	908.9 (146.9)	853.7 (176.0)
45 minutes post-anesthesia	791.1 (99.6)	780.8 (127.7)
60 minutes post-anesthesia	734.4 (100.1)	733.5 (84.1)

5. Secondary Outcome

Title	Cognitive Test3 - Divided Attention Task
Description	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.
Time Frame	Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.

Outcome Measure Data

Analysis Population Description

Some participants could not be tested at the early timepoints due to not being fully awake etc.

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
15 minutes post-anesthesia	26.3 (0)	38.2 (4.3)
30 minutes post-anesthesia	38.2 (19.9)	29.8 (14.0)
45 minutes post-anesthesia	35.2 (25.3)	29.1 (13.3)
60 minutes post-anesthesia	24.5 (9.5)	23.4 (6.4)

6. Secondary Outcome

Title	Bispectral Index
Description	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).
Time Frame	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.

Outcome Measure Data

Analysis Population Description

One subject was missing data at the last timepoint for the Placebo session

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
0 minutes post-anesthesia	34.1 (3.8)	36.3 (3.5)
2 min post-anesthesia	41.4 (5.6)	43.1 (15.4)
4 min post-anesthesia	48.5 (11.9)	55.5 (13.8)
6 minutes post-anesthesia	55.0 (10.6)	58.1 (11.7)
8 minutes post-anesthesia	60.3 (7.9)	69.1 (11.7)
10 minutes post-anesthesia	62.5 (8.0)	71.3 (9.5)
12 minutes post-anesthesia	62.9 (11.5)	76.5 (12.5)
14 minutes post-anesthesia	62.6 (10.7)	82.4 (11.2)
16 minutes post-anesthesia	69.1 (14.2)	84.1 (11.9)

7. Secondary Outcome

Title	Minute Ventilation
Description	The volume of gas inhaled or exhaled from a person's lungs per minute. We wished to determine whether caffeine altered minute ventilation.
Time Frame	Continuous monitoring from time lma inserted until subject started to gag and it was removed, up to 2 hours post-anesthesia.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
Post-infusion	6.2 (1.4)	7.2 (1.1)
Emergence	7.5 (2.1)	8.5 (3.7)

8. Secondary Outcome

Title	Mean Arterial Blood Pressure
Description	This measurement was made in order to determine whether caffeine altered blood pressure in a deleterious manner.
Time Frame	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
Pre-anesthesia	89 (9)	90 (7)
5 minutes after anesthesia	72 (9)	79 (15)
30 minutes after anesthesia	94 (10)	98 (8)
60 minutes after anesthesia	96 (6)	98 (6)

9. Secondary Outcome

Title	Heart Rate
Description	This measurement was made in order to determine whether caffeine altered heart rate in a deleterious manner.
Time Frame	Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).	Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Measure Participants	8	8
Pre-anesthesia	79 (13)	75 (11)
5 minutes after anesthesia	71 (16)	66 (10)
30 minutes after anesthesia	79 (7)	75 (9)
60 minutes after anesthesia	67 (6)	67 (9)

Adverse Events

Time Frame	2 weeks
Arm/Group Title	Placebo		Caffeine
Arm/Group Description	Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).		Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
All Cause Mortality
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Caffeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.