Epigenetics in PostOperative Pediatric Emergence Delirium
キーワード
概要
説明
BACKGROUND: The risks of neurotoxicity and late cognitive impairment supported the recent US Food and Drug Administration (FDA) recommendation on caution in the indication of anesthesia in children up to 3 years of age. Among the cognitive alterations related to pediatric anesthesia, emergence delirium (ED) is frequent in pre-school children. There is no consensus on the risk factors and forms of ED prevention, which occurs more frequently after inhalation anesthesia. On the other hand, anesthesia-induced epigenetic changes may be the key to understanding various complications and perioperative outcomes. There are no specific biomarkers for ED. Such biomarkers would be used to measure the risk of ED and would contribute to prevention and treatment. It has been hypothesized that behavioral changes in ED may be related to epigenetic modifications, analyzed through the DNA methylation profile. OBJECTIVES: The primary aim of the study is to investigate the DNA methylation profile in children with ED. The secondary objectives are to evaluate the correlation between the DNA methylation profile with the anesthetic technique and the degree of preoperative anxiety. METHODS: Children (N=322) from 2 to 12 years old, candidates to digestive endoscopy under general anesthesia will be recruited in an outpatient clinic from a tertiary university hospital. After informed consent, the child and parents' preoperative anxiety will be assessed through the modified Yale Preoperative Anxiety Scale (mYPAS) and VAS-Anx (Anxiety Visual Analogic Scale), respectively. The quality of anesthetic induction will be evaluated through Pediatric Anesthesia Behavior (PAB) scale and Perioperative Adult Child Behavior Interaction Scale (PACBIS). After inhaled induction with sevoflurane, blood sample collection will be performed to evaluate DNA methylation, followed by randomization in two groups to maintain anesthesia using the venous technique, with propofol or inhaled anesthesia with sevoflurane. Upon awakening, the ED will be evaluated through PAED (Pediatric Anesthesia Emergence Delirium) scale. Twenty children from each group presenting ED as well as 08 control cases will have their venous blood samples sent for DNA methylation analysis using the array technique. After hospital discharge, the postoperative behavioral changes will be observed through the PHBQ (Post Hospitalization Behavior Questionnaire) questionnaire.
日付
| 最終確認済み: | 11/30/2018 |
| 最初に提出された: | 12/17/2018 |
| 提出された推定登録数: | 12/20/2018 |
| 最初の投稿: | 12/25/2018 |
| 最終更新が送信されました: | 12/20/2018 |
| 最終更新日: | 12/25/2018 |
| 実際の研究開始日: | 09/23/2018 |
| 一次完了予定日: | 10/31/2019 |
| 研究完了予定日: | 01/23/2020 |
状態または病気
介入/治療
Drug: Sevoflurane
Drug: Propofol
段階
アームグループ
| 腕 | 介入/治療 |
|---|---|
| Active Comparator: Sevoflurane All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction . After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure. | Drug: Sevoflurane All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction. After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure. |
| Active Comparator: Propofol All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure. | Drug: Propofol All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure. |
適格基準
| 研究の対象となる年齢 | 1 Year に 1 Year |
| 研究に適格な性別 | All |
| 健康なボランティアを受け入れる | はい |
| 基準 | Inclusion Criteria: - children with ASA physical status 1, 2 or 3 Exclusion Criteria: - children under psychiatric medication - developmental delays - genetics syndromes that course with developmental delays - contraindication to randomization |
結果
主な結果の測定
1. DNA methylation profile of children who presented emergence delirium [An average of one month after discharge from outpatient clinic.]
二次的な結果の測定
1. Emergence delirium [First, 5th, 10th and 15th minutes after anesthesia awakening]
2. Children's preoperative anxiety [10 minutes before induction of anesthesia]
3. Caregiver's anxiety before anesthesia [10 minutes before induction of anesthesia]
4. Children's behavior and adult interaction during anesthesia induction [First minute during monitoring and anesthesia induction]
5. Children's behavior during anesthesia induction [First minute during anesthesia induction]
6. Post hospitalization behavior changes [First, 7th and 14th day after discharge from outpatient clinic]
