Anesthesia, Depth of Hypnosis Monitoring
Conditions
Keywords
Density spectral array, Depth of hypnosis, Paediatric anaesthesia
Brief summary
In this randomised, blinded study, we will investigate the influence of DSA on recovery from general anaesthesia. DSA monitoring provides continuous information on depth of hypnosis. Based on DSA monitoring dose adjustments of sevoflurane can be made. We expect that this will lead to a faster speed of emergence and recovery.
Detailed description
Electroencephalographic density spectral array (DSA) is a three dimensional method to display electroencephalogram (EEG) signals consisting of the EEG frequency (y-axis), the power of the EEG signal (colour-coded to be integrated into a two dimensional plot) and the development of the EEG power spectrum over time (x-axis). DSA is routinely used to measure depth of hypnosis (DoH) by a part of the staff members in our department. When DSA is used, dose adjustments of sevoflurane will be made based on monitoring depth of anaesthesia. However, most of our colleague do not use DSA. Dose adjustment is then based on (subjective) clinical surrogate parameters, or in general mostly based on a minimal alveolar concentration of the anaesthetic gas that is used. Electroencephalographic DSA monitoring provides continuous objective information on DoH and should result in a faster speed of emergence and recovery from general anaesthesia (GA). This will be addressed in a randomised controlled trial. In patients randomised to the intervention group, the anaesthetic agent sevoflurane will be administered on the basis of objective measures of anaesthetic depth, the typical DSA pattern for GA. We expect a significantly faster speed of emergence and recovery in the intervention group based on clinical experience. The Narcotrend monitor is validated for use in paediatric patients. There are thus no additional risk factors apart from those, which are inherent with general anaesthesia. Patient randomised to the control group will receive standard treatment, that is delivery of sevoflurane based on a MAC of 0.9 respectively an end tidal sevoflurane concentration of 2.3%. A non-invasive therapeutical intervention (DSA based conduct of GA) should result in the advantage of faster recovery, without any additional risk factor.
Interventions
DEVICENarcotrend Monitor (MT MonitorTechnik, Hannover, Germany)
This trial is designed to investigate the additional value of Density Spectral Array monitoring, on the speed of emergence after general anaesthesia. We will compare traditional general anaesthesia with sevoflurane using a MAC value and subjective clinical parameters to the objective and continuous approach using DSA depth of hypnosis. The investigational product is the validated Narcotrend monitor, an electroencephalographic monitor, that is regularly used in anaesthesia practice in the Sophia children's hospital and will be used according to intended purpose. The extended version as used in the operating room in the Sophia Children's hospital offers a diversity of diagrams including Density Spectral Array. The electroencephalographic Narcotrend monitor records frontal EEG-activity. Standard paediatric ECG electrodes are used for EEG registration
Sponsors
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The patient and parents will be blinded to the treatment. The outcome assessor will be blinded as well.
Intervention model description
Randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent of parents/guardians * Age ≥6 months and ≤12 years * Surgical procedure requiring GA supplemented with caudal analgesia * Ability of the parents/guardians to communicate in Dutch
Exclusion criteria
* Primary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Influence of DSA Monitoring on the Speed of Emergence. | Day 0 | The speed of emergence is defined as the time interval between the end of hypnotic drug application and the moment when discharge criteria from the operating room are met (defined as a Steward score ≥ 3) The Steward recovery score consists of three domains: consciousness, airway and motor. Consciousness can be scored from 0-2, in which 0 equals non responsive, 1 equals response to stimuli, 2 equals awake. Airway is scored from 0-2: airway that requires maintenance scores 0, maintaining good airway scores 1 and coughing on command or crying scores 2. Motor is also scored form 0-2: no movement scores 0, non-purposeful movement scores 1 and purposeful movement scores 2. Combining all three domains, the minimum score is 0 (unconscious) and the maximum score is 6 (completely awake) The speed of emergence is defined as a minimum score of 3, with a minimum score of 1 in each domain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Time From Discontinuation of Anaesthetic Drug Delivery Until Discharge From the Post Anaesthesia Care Unit. | Day 0 | The total time is defined as the time interval between the end of hypnotic drug application and the moment when discharge criteria from the recovery room are met (defined as a Steward score =6) The Steward recovery score consists of three domains: consciousness, airway and motor. Consciousness can be scored from 0-2, in which 0 equals non responsive, 1 equals response to stimuli, 2 equals awake. Airway is scored from 0-2: airway that requires maintenance scores 0, maintaining good airway scores 1 and coughing on command or crying scores 2. Motor is also scored form 0-2: no movement scores 0, non-purposeful movement scores 1 and purposeful movement scores 2. Combining all three domains, the minimum score is 0 (unconscious) and the maximum score is 6 (completely awake). |
| The Incidence of Postoperative Delirium | Day 0 | The incidence of postoperative delirium is assessed with the Cornell assessment of postoperative delirium (is defined as a score equal to or greater than 9). The Cornell assessment of postoperative delirium consists of eight questions. The first four questions are scored as follows: 0 equals always, 1 often, 2 sometimes, 3 rarely, 4 never. 1. Does the child make eye contact with the caregiver? 2. Are the child's actions purposeful? 3. Is the child aware of his/her surroundings? 4. Does the child communicatie needs and wants? In these first four questions, a higher score represents a worse outcome. The last four questions are scored as follows: 0 equals never, 1 rarely, 2 sometimes, 3 often and 4 always. 5. Is the child restless? 6. Is the child inconsolable? 7. Is the child underactive - very little movement while awake? 8. Does it take the child a long time to respond to interactions? In these last four questions, a higher score represents a worse outcome. |
| Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | Day 0 | Density spectral array patterns will be saved, and divided into categories, which will be compared between the two study groups. |
| Incidence of Recall of Events During the Procedure (Awareness) | Day 0, Day 1, Day 14 | Awareness is assessed with a modified Brice interview in children of 6 years or older. |
| The End-tidal Sevoflurane Concentration | Day 0 | The mean end-tidal sevoflurane concentration measured during surgical procedure |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control In patients randomised to the control group, sevoflurane will be titrated according to a Minimal Alveolar Concentration (MAC) of 0.9 respectively an end tidal sevoflurane concentration of 2.3% based on standard practice in our paediatric anaesthesia department. | 44 |
| Treatment In patients randomised to the intervention group of the trial, the anaesthetic agent sevoflurane will be titrated according to the typical DSA pattern for general anaesthesia with sevoflurane, provided by the Narcotrend
Narcotrend Monitor (MT MonitorTechnik, Hannover, Germany): This trial is designed to investigate the additional value of Density Spectral Array monitoring, on the speed of emergence after general anaesthesia. We will compare traditional general anaesthesia with sevoflurane using a MAC value and subjective clinical parameters to the objective and continuous approach using DSA depth of hypnosis. The investigational product is the validated Narcotrend monitor, an electroencephalographic monitor, that is regularly used in anaesthesia practice in the Sophia children's hospital and will be used according to intended purpose. The extended version as used in the operating room in the Sophia Children's hospital offers a diversity of diagrams including Density Spectral Array.
The electroencephalographic Narcotrend monitor records frontal EEG-activity. Standard paediatric ECG electrodes are used for EEG registration | 52 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cancelled operation | 1 | 0 |
| Overall Study | Failed caudal analgesia | 1 | 3 |
| Overall Study | Premedication needed | 0 | 1 |
| Overall Study | Protocol Violation | 10 | 0 |
Baseline characteristics
| Characteristic | Total | Control | Treatment |
|---|---|---|---|
| Age, Continuous | 2.3 years STANDARD_DEVIATION 2.7 | 2.2 years STANDARD_DEVIATION 2.6 | 2.4 years STANDARD_DEVIATION 2.7 |
| ASA-score 1 | 83 Participants | 37 Participants | 46 Participants |
| ASA-score 2 | 12 Participants | 6 Participants | 6 Participants |
| ASA-score 3 | 1 Participants | 1 Participants | 0 Participants |
| Duration of general anesthesia | 75.5 minutes STANDARD_DEVIATION 36.8 | 83.7 minutes STANDARD_DEVIATION 39.1 | 69.4 minutes STANDARD_DEVIATION 37.2 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 88 Participants | 40 Participants | 48 Participants |
| Type of surgery Cystoscopy/Sachse or meatotomy | 14 Participants | 3 Participants | 11 Participants |
| Type of surgery Hypospadias correction | 22 Participants | 9 Participants | 13 Participants |
| Type of surgery Inguinal hernia repair | 17 Participants | 9 Participants | 8 Participants |
| Type of surgery Orchidopexy | 33 Participants | 18 Participants | 15 Participants |
| Type of surgery Orthopedic surgery | 1 Participants | 1 Participants | 0 Participants |
| Type of surgery Other urological | 8 Participants | 4 Participants | 4 Participants |
| Type of surgery Urethral valves repair | 1 Participants | 0 Participants | 1 Participants |
| Weight | 13.7 kilogram STANDARD_DEVIATION 6.4 | 13.6 kilogram STANDARD_DEVIATION 6.3 | 13.8 kilogram STANDARD_DEVIATION 6.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 52 |
| other Total, other adverse events | 3 / 44 | 0 / 52 |
| serious Total, serious adverse events | 0 / 44 | 1 / 52 |
Outcome results
Primary
The Influence of DSA Monitoring on the Speed of Emergence.
The speed of emergence is defined as the time interval between the end of hypnotic drug application and the moment when discharge criteria from the operating room are met (defined as a Steward score ≥ 3) The Steward recovery score consists of three domains: consciousness, airway and motor. Consciousness can be scored from 0-2, in which 0 equals non responsive, 1 equals response to stimuli, 2 equals awake. Airway is scored from 0-2: airway that requires maintenance scores 0, maintaining good airway scores 1 and coughing on command or crying scores 2. Motor is also scored form 0-2: no movement scores 0, non-purposeful movement scores 1 and purposeful movement scores 2. Combining all three domains, the minimum score is 0 (unconscious) and the maximum score is 6 (completely awake) The speed of emergence is defined as a minimum score of 3, with a minimum score of 1 in each domain.
Time frame: Day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | The Influence of DSA Monitoring on the Speed of Emergence. | 12 minutes |
| Treatment | The Influence of DSA Monitoring on the Speed of Emergence. | 6 minutes |
p-value: 0.041Wilcoxon (Mann-Whitney)
Secondary
Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor.
Density spectral array patterns will be saved, and divided into categories, which will be compared between the two study groups.
Time frame: Day 0
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing general anesthesia | 24 Participants |
| Control | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing too deep anesthesia | 20 Participants |
| Control | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing lighter anesthesia | 0 Participants |
| Treatment | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing general anesthesia | 46 Participants |
| Treatment | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing too deep anesthesia | 4 Participants |
| Treatment | Differences of Depth of Hypnosis During the Procedure, as Measured by the Narcotrend Monitor. | DSA pattern representing lighter anesthesia | 2 Participants |
Secondary
Incidence of Recall of Events During the Procedure (Awareness)
Awareness is assessed with a modified Brice interview in children of 6 years or older.
Time frame: Day 0, Day 1, Day 14
Population: Interviews only conducted in children ≥6 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Incidence of Recall of Events During the Procedure (Awareness) | Day 0 | 0 participants |
| Control | Incidence of Recall of Events During the Procedure (Awareness) | Day 1 | 0 participants |
| Control | Incidence of Recall of Events During the Procedure (Awareness) | Day 14 | 0 participants |
| Treatment | Incidence of Recall of Events During the Procedure (Awareness) | Day 1 | 0 participants |
| Treatment | Incidence of Recall of Events During the Procedure (Awareness) | Day 0 | 0 participants |
| Treatment | Incidence of Recall of Events During the Procedure (Awareness) | Day 14 | 0 participants |
Secondary
The End-tidal Sevoflurane Concentration
The mean end-tidal sevoflurane concentration measured during surgical procedure
Time frame: Day 0
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | The End-tidal Sevoflurane Concentration | 2.3 percentage sevoflurane of exhaled air | Standard Deviation 0.1 |
| Treatment | The End-tidal Sevoflurane Concentration | 1.8 percentage sevoflurane of exhaled air | Standard Deviation 0.34 |
p-value: 0.001t-test, 2 sided
Secondary
The Incidence of Postoperative Delirium
The incidence of postoperative delirium is assessed with the Cornell assessment of postoperative delirium (is defined as a score equal to or greater than 9). The Cornell assessment of postoperative delirium consists of eight questions. The first four questions are scored as follows: 0 equals always, 1 often, 2 sometimes, 3 rarely, 4 never. 1. Does the child make eye contact with the caregiver? 2. Are the child's actions purposeful? 3. Is the child aware of his/her surroundings? 4. Does the child communicatie needs and wants? In these first four questions, a higher score represents a worse outcome. The last four questions are scored as follows: 0 equals never, 1 rarely, 2 sometimes, 3 often and 4 always. 5. Is the child restless? 6. Is the child inconsolable? 7. Is the child underactive - very little movement while awake? 8. Does it take the child a long time to respond to interactions? In these last four questions, a higher score represents a worse outcome.
Time frame: Day 0
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | The Incidence of Postoperative Delirium | 0 Participants |
| Treatment | The Incidence of Postoperative Delirium | 0 Participants |
Secondary
Total Time From Discontinuation of Anaesthetic Drug Delivery Until Discharge From the Post Anaesthesia Care Unit.
The total time is defined as the time interval between the end of hypnotic drug application and the moment when discharge criteria from the recovery room are met (defined as a Steward score =6) The Steward recovery score consists of three domains: consciousness, airway and motor. Consciousness can be scored from 0-2, in which 0 equals non responsive, 1 equals response to stimuli, 2 equals awake. Airway is scored from 0-2: airway that requires maintenance scores 0, maintaining good airway scores 1 and coughing on command or crying scores 2. Motor is also scored form 0-2: no movement scores 0, non-purposeful movement scores 1 and purposeful movement scores 2. Combining all three domains, the minimum score is 0 (unconscious) and the maximum score is 6 (completely awake).
Time frame: Day 0
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Total Time From Discontinuation of Anaesthetic Drug Delivery Until Discharge From the Post Anaesthesia Care Unit. | 26.5 minutes |
| Treatment | Total Time From Discontinuation of Anaesthetic Drug Delivery Until Discharge From the Post Anaesthesia Care Unit. | 18.5 minutes |
p-value: 0.066Wilcoxon (Mann-Whitney)