Epigenetics in PostOperative Pediatric Emergence Delirium
Condition: Emergence Delirium; Postoperative Complications; DNA Methylation
MeSH terms: Delirium; Emergence Delirium; Postoperative Complications
Study type: Interventional

Summary: 
      Emergence delirium (ED) infers the occurrence of behavior and cognition changes during the
      early postoperative period. Main signs and symptoms of ED are the disturbances of
      consciousness and awareness of the environment, with disorientation and perceptual
      alterations, including hypersensitivity to external stimuli and hyperactive motor behaviors.
      The incidence may be higher than 80%. Risk factors include pre-school age, use of
      sevoflurane, ophthalmologic and otorhinolaryngologic surgeries, child anxiety, parental or
      caregiver anxiety. The recurrence of ED is controversial. The only validated scale for
      diagnosis of ED is the PAED (Pediatric Anesthesia Emergence Delirium). Prevention is the best
      approach, as well as the use of alpha-2 agonists, propofol and total intravenous anesthesia.
      There are still no clear markers for postoperative delirium, especially ED. Cognitive
      alterations may be related to epigenetic modifications. Anesthesia-induced epigenetic changes
      may be the key to understanding perioperative complications and outcomes and is a field of
      future research in anesthesia. The study aims to analyze the DNA methylation profile in
      children with ED. A prospective, randomized study will be carried out in up to 322 children
      undergoing general anesthesia (inhalation group or intravenous group) to perform endoscopic
      procedures at the Instituto da Criança, Hospital das Clinicas, Faculdade de Medicina,
      Universidade de Sao Paulo, Brazil. Patients will have blood samples drawn, and analysis of
      the DNA methylation profile through the array technique will be performed in 40 children (20
      of each group ) who presented ED as well as in 08 control cases. Also, the occurrence of ED
      will be correlated with the degree of anxiety of the child, parents and during anesthetic
      induction, in addition to comparing the two anesthetic techniques with the occurrence of ED
      and late postoperative cognitive alterations.
    

Detailed description: 
      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 1 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.
    

Intervention name(s): Sevoflurane; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Inhalation Anesthesia; Intravenous Anesthesia
Intervention MeSH terms: Anesthetics; Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Screening
Keywords: Emergence delirium; Child; Postoperative complications; DNA methylation; Epigenetic