Trial Outcomes & Findings for A Study to Determine if Caffeine Accelerates Emergence From Anesthesia (NCT NCT02567968)

NCT ID: NCT02567968

Last Updated: 2018-08-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

8 participants

Primary outcome timeframe

followed from the end of anesthesia to gag reflex, up to 2 hours

Results posted on

2018-08-16

Participant Flow

Participant milestones

Participant milestones
Measure
Caffeine, Then Placebo
Participants first received Caffeine. After a washout period of 2 weeks, they then received Placebo.
Placebo, Then Caffeine
Participants first received Placebo, and after 2-week washout period, then received Caffeine
First Intervention
STARTED
4
4
First Intervention
COMPLETED
4
4
First Intervention
NOT COMPLETED
0
0
Washout (2 Weeks)
STARTED
4
4
Washout (2 Weeks)
COMPLETED
4
4
Washout (2 Weeks)
NOT COMPLETED
0
0
Second Intervention
STARTED
4
4
Second Intervention
COMPLETED
4
4
Second Intervention
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Determine if Caffeine Accelerates Emergence From Anesthesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=8 Participants
Participants who were randomized to either receive Caffeine then Placebo or Placebo then Caffeine
Age, Continuous
31 years
STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
Race/Ethnicity, Customized
White
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
2 Participants
n=5 Participants
Region of Enrollment
United States
8 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Waking Time - Re-establishment of the Gag Reflex.
16.45 minutes
Standard Deviation 3.9
9.57 minutes
Standard Deviation 5.1

SECONDARY outcome

Timeframe: Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Cognitive Test1 - Visual Analog Scale --- Feel Good
15 minutes post-anesthesia
29 units on a scale
Standard Deviation 0
54.8 units on a scale
Standard Deviation 22.4
Cognitive Test1 - Visual Analog Scale --- Feel Good
30 minutes post-anesthesia
48.1 units on a scale
Standard Deviation 29.5
50.3 units on a scale
Standard Deviation 25.4
Cognitive Test1 - Visual Analog Scale --- Feel Good
45 minutes post-anesthesia
50.9 units on a scale
Standard Deviation 29.0
58.1 units on a scale
Standard Deviation 26.5
Cognitive Test1 - Visual Analog Scale --- Feel Good
60 minutes post-anesthesia
62.8 units on a scale
Standard Deviation 26.5
55.1 units on a scale
Standard Deviation 27.5
Cognitive Test1 - Visual Analog Scale --- Feel Good
75 minutes post-anesthesia
60.0 units on a scale
Standard Deviation 28.2
59.3 units on a scale
Standard Deviation 25.9
Cognitive Test1 - Visual Analog Scale --- Feel Good
90 minutes post-anesthesia
61.5 units on a scale
Standard Deviation 26.7
59.5 units on a scale
Standard Deviation 25.7
Cognitive Test1 - Visual Analog Scale --- Feel Good
105 minutes post-anesthesia
66.3 units on a scale
Standard Deviation 24.1
61.9 units on a scale
Standard Deviation 24.3
Cognitive Test1 - Visual Analog Scale --- Feel Good
120 minutes post-anesthesia
66.0 units on a scale
Standard Deviation 25.1
66.8 units on a scale
Standard Deviation 27.7

SECONDARY outcome

Timeframe: Test was given at 15, 30, 45, 60, 75, 90, 105 and 120 minutes after terminating anesthesia.

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Cognitive Test1 - Visual Analog Scale --- Feel Bad
15 minutes post-anesthesia
6.0 units on a scale
Standard Deviation 0
27.4 units on a scale
Standard Deviation 24.2
Cognitive Test1 - Visual Analog Scale --- Feel Bad
30 minutes post-anesthesia
17.9 units on a scale
Standard Deviation 20.9
11.6 units on a scale
Standard Deviation 13.3
Cognitive Test1 - Visual Analog Scale --- Feel Bad
45 minutes post-anesthesia
13.0 units on a scale
Standard Deviation 14.1
11.8 units on a scale
Standard Deviation 14.7
Cognitive Test1 - Visual Analog Scale --- Feel Bad
60 minutes post-anesthesia
9.8 units on a scale
Standard Deviation 10.3
10.0 units on a scale
Standard Deviation 12.2
Cognitive Test1 - Visual Analog Scale --- Feel Bad
75 minutes post-anesthesia
6.0 units on a scale
Standard Deviation 8.1
8.5 units on a scale
Standard Deviation 12.0
Cognitive Test1 - Visual Analog Scale --- Feel Bad
90 minutes post-anesthesia
7.0 units on a scale
Standard Deviation 7.2
6.4 units on a scale
Standard Deviation 7.4
Cognitive Test1 - Visual Analog Scale --- Feel Bad
105 minutes post-anesthesia
6.6 units on a scale
Standard Deviation 11.0
3.9 units on a scale
Standard Deviation 4.3
Cognitive Test1 - Visual Analog Scale --- Feel Bad
120 minutes post-anesthesia
4.3 units on a scale
Standard Deviation 4.3
4.3 units on a scale
Standard Deviation 6.5

SECONDARY outcome

Timeframe: Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Cognitive Test2 - Sternberg Test of Memory
15 minutes post-anesthesia
847 ms
Standard Deviation 0
1001.4 ms
Standard Deviation 182.8
Cognitive Test2 - Sternberg Test of Memory
30 minutes post-anesthesia
908.9 ms
Standard Deviation 146.9
853.7 ms
Standard Deviation 176.0
Cognitive Test2 - Sternberg Test of Memory
45 minutes post-anesthesia
791.1 ms
Standard Deviation 99.6
780.8 ms
Standard Deviation 127.7
Cognitive Test2 - Sternberg Test of Memory
60 minutes post-anesthesia
734.4 ms
Standard Deviation 100.1
733.5 ms
Standard Deviation 84.1

SECONDARY outcome

Timeframe: Test was given at 15, 30, 45, 60 minutes after terminating anesthesia.

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Cognitive Test3 - Divided Attention Task
15 minutes post-anesthesia
26.3 mm away from optimal
Standard Deviation 0
38.2 mm away from optimal
Standard Deviation 4.3
Cognitive Test3 - Divided Attention Task
30 minutes post-anesthesia
38.2 mm away from optimal
Standard Deviation 19.9
29.8 mm away from optimal
Standard Deviation 14.0
Cognitive Test3 - Divided Attention Task
45 minutes post-anesthesia
35.2 mm away from optimal
Standard Deviation 25.3
29.1 mm away from optimal
Standard Deviation 13.3
Cognitive Test3 - Divided Attention Task
60 minutes post-anesthesia
24.5 mm away from optimal
Standard Deviation 9.5
23.4 mm away from optimal
Standard Deviation 6.4

SECONDARY outcome

Timeframe: Continuous monitoring from start of anesthesia until discharge of test subject, up to 2 hours post-anesthesia.

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

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).

Outcome measures

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

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Minute Ventilation
Post-infusion
6.2 L/minute
Standard Deviation 1.4
7.2 L/minute
Standard Deviation 1.1
Minute Ventilation
Emergence
7.5 L/minute
Standard Deviation 2.1
8.5 L/minute
Standard Deviation 3.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Mean Arterial Blood Pressure
Pre-anesthesia
89 mmHg
Standard Deviation 9
90 mmHg
Standard Deviation 7
Mean Arterial Blood Pressure
5 minutes after anesthesia
72 mmHg
Standard Deviation 9
79 mmHg
Standard Deviation 15
Mean Arterial Blood Pressure
30 minutes after anesthesia
94 mmHg
Standard Deviation 10
98 mmHg
Standard Deviation 8
Mean Arterial Blood Pressure
60 minutes after anesthesia
96 mmHg
Standard Deviation 6
98 mmHg
Standard Deviation 6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Placebo
n=8 Participants
Placebo Control: Anesthetized volunteers will be allowed to wake after injection of saline (placebo control).
Caffeine
n=8 Participants
Caffeine: Anesthetized volunteers will be allowed to wake after injection of caffeine (15 mg/ kg).
Heart Rate
Pre-anesthesia
79 beats per minute
Standard Deviation 13
75 beats per minute
Standard Deviation 11
Heart Rate
5 minutes after anesthesia
71 beats per minute
Standard Deviation 16
66 beats per minute
Standard Deviation 10
Heart Rate
30 minutes after anesthesia
79 beats per minute
Standard Deviation 7
75 beats per minute
Standard Deviation 9
Heart Rate
60 minutes after anesthesia
67 beats per minute
Standard Deviation 6
67 beats per minute
Standard Deviation 9

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Caffeine

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Aaron Fox, PhD

University of Chicago

Phone: 7737020021

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place