Epigenetics in PostOperative Pediatric Emergence Delirium

NCT ID: NCT03787849

Last Updated: 2022-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-24
• Study Completion Date: 2021-12-31

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.

Conditions

Emergence Delirium; Postoperative Complications; DNA Methylation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Sevoflurane

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Inhalation Anesthesia; Intravenous Anesthesia

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Maria José Carvalho Carmona

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria JC Carmona, PhD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor

Locations

Instituto da Criança do Hospital das Clinicas da FMUSP

São Paulo, , Brazil

Countries

Brazil

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Other Identifiers

EPOPED-USP

Identifier Type: -

Identifier Source: org_study_id