Pre- and Postoperative EEG-Monitoring for Children Aged From 0,5 to 8 Years

Study Overview
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Brief Summary
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Evaluation of mechanisms and factors of anaesthesia on postoperative delirium and emergence agitation as well as on postoperative cognitive function in children aged 0,5-8 years scheduled for elective surgery. The depth of anesthesia in children for elective surgery aged 0,5-6 years is monitored with intraoperative Narcotrend-Compact-M-Monitoring. Postoperatively the Pediatric Anesthesia Emergence Delirium Scores (PAED Score) [Sikich et al. 2004;Locatelli et al. 2013] is used to screen for the frequency of postoperative delirium in the post anesthesia care unit discharge of the child after surgery. Cognitive testings are performed in children of the study group (n= 470) and a control group (n= 80) with the parents support to evaluate deficits in children in their cognitive areas (POCD (Postoperative cognitive deficit)) at three different time points up to three months.

Detailed Description
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According to recent studies in children aged from 0,5 to 8 years Narcotrend Monitor (from EEG derived monitoring of the frontal brain waves) can reliably measure the depth of anesthesia [Münte et al. 2009; Weber et al. 2005]. Depth of anesthesia in adults is significantly correlated with the incidence of postoperative delirium and longer lasting cognitive deficits [Radtke et al. 2013; Chan et al. 2013; Whitlock et al. 2014]. We know from animal experimental studies that anesthetics have a potential toxic effect in the developing brain. [Sinner et al 2014]. After two years (approximately 1/3 - 1/2 of the total sample) an interim analysis with recalculation of the case numbers is carried out, if the initial effect sizes differ strongly.

Official Title
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Pre- and Postoperative EEG-Monitoring for Children Aged From 0,5 to 8 Years

Conditions
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Anesthesia

Participation Criteria
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Eligibility Criteria
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Study Group. Inclusion Criteria: male or female children 0,5 to 8 years planned elective surgery informed consent by both parents, if both parents have joint custody Exclusion Criteria: indication for isolation of patients with multi-resistant bacteria known neurological or psychiatric precondition (disease) inability of the parents to speak and or read German lacking willingness to save and hand out pseudonomized data within the clinical study contact allergy to silver or silver chloride participation in another prospective interventional clinical study during this study Control Group: Inclusion Criteria: male or female healthy children 0,5 to 8 years (siblings of study group and children from kindergarten) no planned operation in the next three month no operation in the last half year before study inclusion informed consent by both parents, if both parents have joint custody Exclusion Criteria: Neurological or psychiatric precondition (disease), which limits the conduction of the neurocognitive testing Anacusis or Hypoacusis, which limits the conduction of the neurocognitive testing Taking psychotropic drugs (including sleep-inducing drug and benzodiazepine) on a regular basis and substances, which limit the conduction of the neurocognitive testing Inability of the parents to speak and or read the used language Lacking willingness to save and hand out pseudonomized data within the clinical study

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group: Patients<br>470 children for elective surgery 0,5 to 8 years Analysis of EEG data will divided in four age-related groups because of the different baseline EEG activity: 0.5 - 12 month: 5-7 Hz activity / blocked by eye opening 12 - 36 month: 7-8 Hz activity / Variability 5 - 10 Hz 3 - 6 years: 8 Hz activity / amplitude 100µV 6 - 8 years 10Hz activity / amplitude 100 µV | |
| Control group: Healthy children for POCD assessment<br>80 healthy children (siblings of study group children and children from Kindergarten) 0,5 to 8 years with no operation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of emergence delirium and postoperative delirium | The Delirium is measured by the Pediatric Anesthesia Emergence Delirium Scores (PAED Score) (Sikich et al. 2004; Locatelli et al. 2013) | Until discharge of the child from the recovery room, an expected average of 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depth of anesthesia | Depth of anesthesia assessed by band-power of the 4 frequency bands (alpha, beta, theta, delta) and activity in percentages of total spectral power ( F50% / F95%) assessed with Narcotrend Monitor | During the operation | 
| Incidence of behavioral problem | The behavioral problem is measured by a modified Version of the Posthospital Behavior Questionnaire (PHBQ) (Buehrer et al. 2014) | Up to 5 postoperative days | 
| Severity of emergence Delirium | The Delirium is measured by Pediatric Anesthesia Emergence Delirium Scores (PAED Score) (Sikich et al. 2004; Locatelli et al. 2013) | Until discharge of the child from the recovery room, an expected average of 1 hour | 
| Duration of emergence Delirium | The Delirium is measured by Pediatric Anesthesia Emergence Delirium Scores (PAED Score) [Sikich et al. 2004; Locatelli et al. 2013] | Until discharge of the child from the recovery room, an expected average of 1 hour | 
| Lactate | Laboratory parameter | Up to 5 postoperative days | 
| Hemoglobin | Laboratory parameter | Up to 5 postoperative days | 
| Soluble Interleukin - 6 | Laboratory parameter | Up to the end of the operation | 
| Analgesia |  | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Hypnotics |  | Begin of Anesthesia up to the end of stay in the recovery room, an expected average of 1 hour | 
| Stress reducing agents |  | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Psychoactive drugs/Benzodiazepines |  | From 1h before surgery start up to the end of stay in the operation (an expected average of 2 hours) | 
| Fluid and transfusion therapy | The fluid and transfusion therapy is measured by preoperative sobriety times by intraoperative fluid and volume administration and balance. | From one day before surgery start up to the end of stay in the recovery room (an expected average of 2 hours | 
| Postoperative cognitive deficit (POCD) in children 6 to 42 months | POCD is measured by parent questionnaires (BRIEF-P) and in children by the Bayley III Scales of Infant and Toddler Development (cognitive, language, motor function and processing speed, social emotional scale) and NEPSY II (Statue, word generation, Visuomotor precision from 3 years). | Up to 365 postoperative days | 
| Postoperative cognitive deficit (POCD) in children 43 to 96 months | POCD is measured by parent questionnaires (BRIEF-P, BRIEF) and in children by the Colored Progressive Matrices (CPM), the CANTAB test battery and NEPSY-II subtests (Visuomotor precision, word generation, statue (until 6 years); animal sorting (from 7 years)). | Up to 365 postoperative days | 
| Duration of anesthesia | Measured by Narcotrend monitor | During the operation | 
| Burst suppression ratio | Measured by Narcotrend monitor | During the operation | 
| Duration of surgery |  | During the operation | 
| Time schedule for intraoperative EEG recording | Predefined time points: Baseline, start of anesthetic administration (STARTAnesth), start of analgesic administration (STARTAnalg), Loss of consciousness (LOC), airway device insertion [INT], skin incision/ surgery start (SKIN), intraoperative steady state (OP), stop of anesthetic administration (ENDAnesth), stop of analgesic administration (ENDAnalg),airway device removal [EXE] regain of consciousness (ROC), awakening (AWK) | During the operation | 
| Pain in children < 4 years | Pain is measured by the FLACC- Scale | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Pain in children < 4 years | Pain is measured by the KUSS-Score | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Pain in children ≥ 4 years | Pain is measured by the Faces Pain Scale - revised | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| C-reactive protein |  | Up to 5 postoperative days | 
| Carbon dioxide (CO2) and oxygen (O2) monitoring |  | During the operation | 
| Positive endexpiratory pressure |  | During the operation | 
| Inspiratory pressure |  | During the operation | 
| Tidal volume breathing frequency |  | During the operation | 
| Minute volume |  | During the operation | 
| Anxiety of the children | Observation of anxiety during psychological assessment on a 4-point-Likert-scale | Up to 365 postoperative days | 
| Anxiety of the parents | Baseline (STAI) after 3 months (STAI) | Up to 365 postoperative days | 
| Compliance of the children | Measured by Induction compliance checklist | At the beginning of the operation | 
| Stress | Stress is measured of of parents and of children. Parenting stress index (PSI) (German version: Eltern-Belastungsinventar (EBI)) | Up to 365 postoperative days | 
| Glucose |  | Up to 5 postoperative days | 
| Intensive care unit length of stay |  | Participants will be followed for the duration of intensive care unit stay, an expected average of 1 day | 
| Hospital length of stay |  | Participants will be followed for the duration of hospital stay, an expected average of 7 days | 
| Postoperative organ complications |  | Participants will be followed for the duration of hospital stay, an expected average of 7 days | 
| Behavioral changes of the children | Post Hospitalization Behavior Questionnaire (PHBQ) | Up to 5 postoperative days | 
| Anxiety of children | mYale-SF (2-8 years) | At the beginning of the operation | 
| Blood pressure | This Monitoring of the blood pressure will be measured at the defined EEG measurement timepoints from STARTAnesth to EXE. | During the operation | 
| Body temperature | This Monitoring of body temperature will be measured at the defined EEG measurement timepoints from STARTAnesth to EXE. | During the operation | 
| Heart rate | This Monitoring of heart rate will be measured at the defined EEG measurement timepoints from STARTAnesth to EXE. | During the operation | 
| Clinical routine anesthesia parameters | Clinical routine anesthesia parameters are measured by primary induction technique, type of induction, type of maintenance of anesthesia, airway management, additional regional anesthesia, type of regional anesthesia, time of regional anesthesia, application during operation and blood gas analysis) during anesthesia until end of recovery room stay. | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Blood gas analysis |  | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Incidence of Delirium | Incidence of Delirium is measured with the CAPD-Score [Dill et al. 2016] | Up to the end of stay in the recovery room, an expected average of 1 hour | 
| Type of surgery |  | During the operation | 
| Specific field of surgery |  | During the operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depth of anesthesia