Epigenetics in PostOperative Pediatric Emergence Delirium

NCT03787849 | Completed

• 1 other identifier: EPOPED-USP
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

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.

Conditions

Emergence Delirium; Postoperative Complications; DNA Methylation

Keywords

Emergence delirium; Child; Postoperative complications; DNA methylation; Epigenetic

Outcome Measures

Primary Outcomes (1)

• DNA methylation profile of children who presented emergence delirium

  DNA methylation profile will be measured through an array experiment in the Illumina iScanSQ (Illumina®) platform using the BeadChip Infinium MethylationEPIC and BeadChip HumanCytoSNP850K kits, following the protocol and manufacturer's instructions. The extracted samples will be initially treated with bisulfite using the EZ DNA Methylation Kit (Zymo Research®). The methylation profile is measured by the Beta value. This value ranges from 0 to 1. Closer to zero, more hypomethylated is the DNA and closer to 1, more hypermethylated is the DNA. To compare the profile, the average Beta value of each patient with emergence delirium and their controls will be used. All raw data obtained will be analyzed by bioinformatics methods to compose the DNA methylation profile of each patient.

  An average of one month after discharge from outpatient clinic.

Secondary Outcomes (6)

• Emergence delirium

  First, 5th, 10th and 15th minutes after anesthesia awakening

• Children's preoperative anxiety

  10 minutes before induction of anesthesia

• Caregiver's anxiety before anesthesia

  10 minutes before induction of anesthesia

• Children's behavior and adult interaction during anesthesia induction

  First minute during monitoring and anesthesia induction

• Children's behavior during anesthesia induction

  First minute during anesthesia induction

Study Arms (2)

Sevoflurane

ACTIVE COMPARATOR

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

Propofol

ACTIVE COMPARATOR

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

Interventions

Sevoflurane DRUG

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.

Also known as: Inhalation Anesthesia

Sevoflurane

Propofol DRUG

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.

Also known as: Intravenous Anesthesia

Propofol

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• children with ASA physical status 1, 2 or 3

You may not qualify if:

• children under psychiatric medication
• developmental delays
• genetics syndromes that course with developmental delays
• contraindication to randomization

Sponsors & Collaborators

• University of Sao Paulo: lead

Study Sites (1)

Instituto da Criança do Hospital das Clinicas da FMUSP

São Paulo, Brazil

Location

Related Publications (25)

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MeSH Terms

Conditions

Emergence Delirium; Postoperative Complications

Interventions

Sevoflurane; Anesthesia, Inhalation; Propofol; Anesthesia, Intravenous

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Anesthesia, General; Anesthesia; Anesthesia and Analgesia; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Maria JC Carmona, PhD

  Associate Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants are not aware of anesthesia technique. Outcome assessor of DNA methylation are not aware of anesthesia technique since they will analyze blood samples.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 26, 2018
• Study Start: September 24, 2018
• Primary Completion: December 7, 2021
• Study Completion: December 31, 2021
• Last Updated: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)