Investigation of the DNA methylation profile in children who presenting emergence delirium

• Grant number: 17/25047-0
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2018 - November 30, 2020
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Maria José Carvalho Carmona
• Grantee: Maria José Carvalho Carmona
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Alexandre Torchio Dias ; Cláudia Maia Memória ; Évelin Aline Zanardo ; Leslie Domenici Kulikowski ; Marcelo Luis Abramides Torres ; Ricardo Vieira Carlos ; Suely Pereira Zeferino

Abstract

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 objective of the study is to analyze the DNA methylation profile in children with ED. METHODS: As approved by the Institutional Review Board, an observational and prospective study will be conducted to evaluate 96 children between one and 12 years of age who are candidates for endoscopic procedures under general anesthesia. The degree of preoperative anxiety will be evaluated by m-YPAS and VAS-anx scale. The anesthetic induction will be inhaled with sevoflurane and PACBIS and PAB scales will evaluate the quality of the induction. After peripheral venous puncture, which is part of the anesthetic procedure, 3 mL of total venous blood will be collected for genetic analysis. Upon awakening, the ED will be evaluated by PAED (Pediatric Anesthesia Emergence Delirium) scale. In children with a PAED score e 10 (N = 16), theblood sample will be referred for analysis of the DNA methylation profile. As a control group, 16patients will be selected in paired and randomized form among those who did not present ED. Afterthe discharge from the outpatient unit, PHBQ questionnaire will be applied by phone contact in the first, 7th and 14th post-discharge to evaluate the incidence of postoperative behavioral changes. The study sample was calculated considering the ED incidence of 20% and loss of 20% after recruitment. The data will be evaluated for normality and will be analyzed by comparison tests of means, considered significant if p <0.05. (AU)