Outcomes Research in Vulnerable Pediatric Populations

On April 14–15, 2018, the Sixth Biennial Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium convened at Columbia University Medical Center and New York Presbyterian/Morgan Stanley Children’s Hospital of New York. Since its inception over 10 years ago, the PANDA Symposium has served as a key forum for clinicians, researchers, and other major stakeholders to gather and review the current state of pre-clinical and clinical research related to anesthetic neurotoxicity in the developing brain. It has also served as an important venue for participants to gain insight and leverage support from various public and private regulatory bodies. Goals of this year’s meeting included assessments of how current knowledge has evolved, endeavors to develop common outcome measures, and formulations of future directions for research and policy. The Symposium program highlighted a diverse body of cutting-edge work, from results of pre-clinical and clinical studies to updates in clinical practice and policymaking.

show abstract

“…Details on this session can be found in the article entitled, “Outcomes research in vulnerable pediatric populations” in the current issue. 17…”

Section: Outcomes Research In Vulnerable Pediatric Populationsmentioning

confidence: 99%

Report on the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium, “Anesthesia and Neurodevelopment in Children”

Lee

Sun

Levy

2019

Journal of Neurosurgical Anesthesiology

View full text Add to dashboard Cite

show abstract

“…The U.S. Food and Drug Administration (FDA) has published a Drug Safety Communication that warns that repeated or lengthy exposure to anesthetic and sedative medications in young children may have harmful effects on brain development [ 1 , 2 ]. These concerns stem from large epidemiologic studies showing a correlation between worsened cognitive outcomes for patients who underwent surgery and anesthesia at a young age, rodent model investigations showing that general anesthetics can disrupt many aspects of brain development, and primate studies demonstrating a variety of cognitive and behavioral deficits resulting from early anesthetic exposure in development [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Clinical trials have provided reassurance that short exposures to general anesthesia, typically an hour or less, in healthy children do not cause a measurable reduction in intelligence, although it appears increasingly likely that there are deleterious effects on other domains of neurobehavioral function [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway

Xu,

Wen,

Mathena

et al. 2024

IJMS

View full text Add to dashboard Cite

Exposure to general anesthetics can adversely affect brain development, but there is little study of sedative agents used in intensive care that act via similar pharmacologic mechanisms. Using quantitative immunohistochemistry and neurobehavioral testing and an established protocol for murine sedation, we tested the hypothesis that lengthy, repetitive exposure to midazolam, a commonly used sedative in pediatric intensive care, interferes with neuronal development and subsequent cognitive function via actions on the mechanistic target of rapamycin (mTOR) pathway. We found that mice in the midazolam sedation group exhibited a chronic, significant increase in the expression of mTOR activity pathway markers in comparison to controls. Furthermore, both neurobehavioral outcomes, deficits in Y-maze and fear-conditioning performance, and neuropathologic effects of midazolam sedation exposure, including disrupted dendritic arborization and synaptogenesis, were ameliorated via treatment with rapamycin, a pharmacologic mTOR pathway inhibitor. We conclude that prolonged, repetitive exposure to midazolam sedation interferes with the development of neural circuitry via a pathologic increase in mTOR pathway signaling during brain development that has lasting consequences for both brain structure and function.

show abstract

“…If molecular structure changes, it will have an effect on the learning and memory ability [1,2]. There are many reports stating that long-term, repeated, or high-dose sevoflurane anesthesia in neonatal rats can cause changes in nervous system function and affect the long-term learning and memory and cognitive function [3][4][5]. The FDA warned that repeated or prolonged (more than 3 h) use of anesthetics and sedatives may impair the brain of fetus and children less than 3 years [6].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Attenuates Neurotoxicity in Developing Rats Induced by Sevoflurane through Upregulating BDNF-TrkB-CREB and Downregulating ProBDNF-P75NRT-RhoA Signaling Pathway

Dong

Hong

Tang

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

To investigate the mechanism dexmedetomidine in relieving the neurotoxicity of a developing brain induced by sevoflurane. Sprague-Dawley rats, 6 days old, were randomly divided into three groups. Rats in the control group were inhaled with air after injection of normal saline; rats in the sevoflurane group were injected with normal saline and inhaled with 3% sevoflurane for 2 h in three consecutive day; rats in the dexmedetomidine group were inhaled with 3% sevoflurane after intraperitoneal injection of dexmedetomidine 25 μg/kg. WB results showed that mBDNF, pTrkB/TrkB, and CREB were significantly decreased in the hippocampus of the sevoflurane group, which are significantly upregulated in the dexmedetomidine group. In the sevoflurane group, proBDNF, P75NRT, and RhoA were significantly increased, which were significantly lower than those in the dexmedetomidine group than those in the sevoflurane group. The expression BDNF was downregulated in the sevoflurane group, while the proBDNF was upregulated in the sevoflurane group. In the Morris water maze test, the escape latency of the sevoflurane group was significantly prolonged. In sevoflurane groups, the number of crossing platform was significantly reduced, the synaptic protein decreased significantly, and this effect was reversed in rats of the dexmedetomidine group. Dexmedetomidine could reduce synaptic plasticity decline in developing rats induced by sevoflurane, through downregulating the proBDNF-p75NTR-RhoA pathway and upregulating BDNF-TrkB-CREB.

show abstract

Outcomes Research in Vulnerable Pediatric Populations

Cited by 7 publications

References 23 publications

Report on the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium, “Anesthesia and Neurodevelopment in Children”

Report on the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium, “Anesthesia and Neurodevelopment in Children”

Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway

Dexmedetomidine Attenuates Neurotoxicity in Developing Rats Induced by Sevoflurane through Upregulating BDNF-TrkB-CREB and Downregulating ProBDNF-P75NRT-RhoA Signaling Pathway

Contact Info

Product

Resources

About