Anesthetic Neurotoxicity in Children

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Irim Salik
Keyword(s):  
School Readiness ◽  
Behavioral Problems ◽  
Educational Interventions ◽  
Epidemiologic Studies ◽  
Brain Cell ◽  
Regulatory Agencies ◽  
Anesthetic Agents ◽  
Anesthetic Exposure ◽  
Neuropsychologic Testing ◽  
Sedative Drugs

The clinical pediatric anesthesiology community has been greatly affected by a growing body of research suggesting that sedative drugs and anesthetic agents may have long lasting detrimental neurocognitive effects in children. Various animal models have indicated apoptotic brain cell death and neurocognitive impairment following anesthetic exposure in early life. Although these studies cannot be directly extrapolated to anesthesia in children, parents and governmental regulatory agencies have been paying attention nonetheless. Adding to the evidence are a number of human epidemiologic studies that have documented neurologic deficits and cognitive decline following early anesthetic exposure. 1-4 Clinical studies in children exposed to general anesthesia have assessed outcome measures including academic performance or school readiness, validated neuropsychologic testing, and educational interventions for neurodevelopmental or behavioral problems.

scholarly journals General Anesthesia Improves Fetal Cerebral Oxygenation without Evidence of Subsequent Neuronal Injury

2005 ◽  
Vol 25 (8) ◽  
pp. 1060-1069 ◽  
Author(s):  
Rebecca J McClaine ◽  
Kenichiro Uemura ◽  
Sebastian G de la Fuente ◽  
Roberto J Manson ◽  
John V Booth ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Near Infrared ◽  
Cerebral Oxygenation ◽  
Fetal Brain ◽  
Drug Regimen ◽  
Initial Increase ◽  
Anesthetic Agents ◽  
Pregnant Sheep ◽  
Near Term ◽  
Anesthetic Exposure

Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (±1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.

scholarly journals Early Developmental Exposure to General Anesthetic Agents in Primary Neuron Culture Disrupts Synapse Formation via Actions on the mTOR Pathway

2018 ◽  
Author(s):  
Jing Xu ◽  
R. Paige Mathena ◽  
Michael Xu ◽  
YuChia Wang ◽  
CheJui Chang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Synapse Formation ◽  
Epidemiologic Studies ◽  
Mtor Pathway ◽  
General Anesthetic ◽  
Neuron Culture ◽  
Neurodevelopmental Disease ◽  
Anesthetic Agents ◽  
Pharmacologic Inhibition

Human epidemiologic studies and laboratory investigations in animal models suggest that exposure to general anesthetic agents (GAs) have harmful effects on brain development. The mechanism underlying this putative iatrogenic condition is not clear and there are currently no accepted strategies for prophylaxis or treatment. Recent evidence suggests that anesthetics might cause persistent deficits in synaptogenesis by disrupting key events in neurodevelopment. Using an in vitro model consisting of dissociated primary cultured mouse neurons we demonstrate abnormal pre- and post-synaptic marker expression after a clinically relevant isoflurane anesthesia exposure conducted during neuron development. We find that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway can reverse the observed changes. Isoflurane exposure increases expression of phospho-S6, a marker of mTOR pathway activity, in a concentration-dependent fashion and this effect occurs throughout neuronal development. The mTOR 1 complex (mTORC1) and the mTOR 2 complex (mTORC2) branches of the pathway are both activated by isoflurane exposure and this is reversible with branch-specific inhibitors. Upregulation of mTOR is also seen with sevoflurane and propofol exposure, suggesting that this mechanism of developmental anesthetic neurotoxicity may occur with all the commonly used GAs in pediatric practice. We conclude that GAs disrupt the development of neurons during development by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.

scholarly journals Anxiety and Depression Are Not Related to Increasing Levels of Burden and Stress in Caregivers of Patients With Alzheimer’s Disease

2020 ◽  
Vol 35 ◽  
pp. 153331751989954
Author(s):  
Tiziana Tentorio ◽  
Sharon Dentali ◽  
Camilla Moioli ◽  
Marta Zuffi ◽  
Rosy Marzullo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Behavioral Problems ◽  
Mini Mental State Examination ◽  
Educational Interventions ◽  
Anxiety And Depression ◽  
Anxiety State ◽  
Functional Scores ◽  
Relative Stress ◽  
State Examination

Sixty-nine dyads of patients with Alzheimer’s disease and primary caregivers have been followed up for 1 year to evaluate cognitive (Mini-Mental State Examination), functional (Instrumental Activities of Daily Living), and behavioral (Neuropsychiatric Inventory) decline of patient in relation to burden (Caregiver Burden Inventory), stress (Relative Stress Scale), anxiety (State-Trait Anxiety Inventory Y), and depression (Beck Depression Inventory) reported by the caregivers. After 1 year of observation, cognitive and functional scores worsened while behavioral problems remained unchanged and relatively mild in patients. After 1 year, caregivers’ scores of scales of anxiety and depression decreased significantly, while stress scores remained unchanged and burden slightly increased. In our opinion, the unexpected improvement in psychological situation of caregivers may be mainly due to educational interventions focused on knowledge of the disease with a particular attention directed toward emotional support and individual needs.

Neonatal Exposure to a Combination of N -Methyl-d-aspartate and γ-Aminobutyric Acid Type A Receptor Anesthetic Agents Potentiates Apoptotic Neurodegeneration and Persistent Behavioral Deficits

2007 ◽  
Vol 107 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Anders Fredriksson ◽  
Emma Pontén ◽  
Torsten Gordh ◽  
Per Eriksson
Keyword(s):  
Type A ◽  
Brain Cell ◽  
Aminobutyric Acid ◽  
Growth Spurt ◽  
High Dose ◽  
Gamma Aminobutyric Acid ◽  
Behavioral Deficits ◽  
Anesthetic Agents ◽  
Acid Type ◽  
The Brain

Background During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood. Methods Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests--spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)--were conducted on mice aged 55-70 days. Results Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol. Conclusion This study shows that both a gamma-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-D-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.

Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward

2022 ◽  
Author(s):  
Caleb Ing ◽  
David O. Warner ◽  
Lena S. Sun ◽  
Randall P. Flick ◽  
Andrew J. Davidson ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Research ◽  
Nonhuman Primates ◽  
Clinical Evidence ◽  
Behavioral Changes ◽  
Neurodevelopmental Outcomes ◽  
Behavioral Deficits ◽  
Anesthetic Agents ◽  
Anesthetic Exposure ◽  
Intense Debate

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

Attention Deficits in Adolescence: Description, Evaluation, and Management

1988 ◽  
Vol 9 (9) ◽  
pp. 287-298
Author(s):  
William L. Coleman ◽  
Melvin D. Levine
Keyword(s):  
Behavioral Problems ◽  
Educational Interventions ◽  
Attention Deficits ◽  
Emotional Management ◽  
Social And Emotional ◽  
Specific Advice ◽  
Long Term Follow Up ◽  
Optimal Evaluation

Attention deficits may persist through childhood and into adolescence or they first may become manifest in adolescence. Their manifestations are often more subtle but Severe enough to exact a significant toll on academic performance. Associated learning disabilities, behavioral problems, and affective dysfunction, especially low self-esteem, are frequent concomitants or complications. On the other hand, some traits (such as creativity) of attention deficits may serve as redemptive features. Evaluation necessitates a systematic gathering, synthesis, and interpretation of a vast amount of information as well as direct testing and observation. Compensatory strengths and other positive attributes should be elicited and mobilized. Management should be individually tailored to the adolescent's specific needs and resources and implemented in a stepwise fashion. Intervention is usually multimodal, because attention deficits invariably affect several areas of function: academic, behavioral, social, and emotional. Management might include educational interventions, counseling, cognitive behavior therapy, behavior modification, and pharmacotherapy. Management should always include demystification, construction of a functional profile, specific advice-giving, encouragement, advocacy, and long-term follow-up, roles for which the pediatrician is especially qualified. With increased awareness of the plight of adolescents with attention deficits, the pediatrician, working closely with other professionals, has an extraordinary opportunity to minimize the accusations, suffering, and maladaptive, self-destructive behaviors that have been so much a part of the adolescent's condition in the past. As we become more sensitive to the effects of endogenous dysfunction during adolescence, it will become increasingly possible to redeem the struggling young people in their own eyes and in the eyes of important adults in their lives. Optimal evaluation and treatment is likely to be taxing, time-consuming, and expensive for all involved. However, the price of neglect, false attributions, and failure will be far higher.

scholarly journals Latent Profiles of Teacher-Reported Self-Regulation and Assessed Executive Function in Low-Income Community Preschools: Relations With Motor, Social, and School Readiness Outcomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Kate E. Williams ◽  
Laura A. Bentley
Keyword(s):  
Executive Function ◽  
Social Skills ◽  
School Readiness ◽  
Low Income ◽  
Behavioral Problems ◽  
Self Regulation ◽  
Teacher Report ◽  
Visual Motor Integration ◽  
Low Profile ◽  
Visual Motor

This study contributes to understandings of early childhood self-regulation and executive function, and their components, through taking a person-centered approach to investigating how these skills cluster together in children aged 4–5years. A sample of children (N=206) from preschools in low socioeconomic communities were assessed through teacher report of self-regulation and three executive function tasks at the commencement of the preschool year. Outcome variables included teacher report of social skills and behavioral problems, and children’s school readiness and visual motor integration skills were directly assessed. When the scores from this low-income sample were compared to available norms, over 70% of children scored below the 50th percentile in executive function measures, approximately 20% were below average in self-regulation skills, 48% were delayed in school readiness scores, 36% had above average levels of internalizing problems, and 25% were above average in externalizing problems. A series of four latent profile models each used different measurement approaches and combinations of self-regulation and executive function components. In three of the four models (two which combined self-regulation and executive function measures and one with teacher report of self-regulation only), a high skill and low skill profile were found with 31 to 42% of children in the low profile depending on the model. Children were very similarly classified across all three models. When three executive function scores were modeled alone, a more complex three-profile solution emerged (low, moderate, and high) with 52% in the low profile. Children identified in the low profiles across all models were at greater risk of poorer school readiness, visual motor integration and social skills, and increased behavioral problems. Taken together, the findings suggest that self-regulation and executive function skills tend to cluster together at this age and in this low-income sample. Composite scores of teacher report of self-regulation are somewhat sufficient in identifying children who also have poorer executive function skills and are at risk of poorer motor, social, and school readiness outcomes. These children are an important target group for additional supports prior to school entry.

Sign in / Sign up

Export Citation Format

Share Document