Clinical trial NCT03787849: Epigenetics in PostOperative Pediatric Emergence Delirium
Official title: Investigation of the DNA Methylation Profile in Children Who Presented Emergence Delirium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Emergence Delirium
Postoperative Complications
DNA Methylation
Keywords: Emergence delirium
Child
Postoperative complications
DNA methylation
Epigenetic
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2018-12-26
Enrollment: 175
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: DNA methylation profile of children who presented emergence delirium
timeFrame: An average of one month after discharge from outpatient clinic.
Secondary outcomes:
measure: Emergence delirium
timeFrame: First, 5th, 10th and 15th minutes after anesthesia awakening
measure: Children's preoperative anxiety
timeFrame: 10 minutes before induction of anesthesia
measure: Caregiver's anxiety before anesthesia
timeFrame: 10 minutes before induction of anesthesia
measure: Children's behavior and adult interaction during anesthesia induction
timeFrame: First minute during monitoring and anesthesia induction
measure: Children's behavior during anesthesia induction
timeFrame: First minute during anesthesia induction
measure: Post hospitalization behavior changes
timeFrame: First, 7th and 14th day after discharge from outpatient clinic
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto da Criança do Hospital das Clinicas da FMUSP
Study officials:
affiliation: Associate Professor
name: Maria JC Carmona, PhD
role: PRINCIPAL_INVESTIGATOR
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