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Background: Observational studies of anesthetic neurotoxicity may be biased because children requiring anesthesia commonly have medical conditions associated with neurobehavioral problems. This study takes advantage of a natural experiment associated with appendicitis to determine whether anesthesia and surgery in childhood were specifically associated with subsequent neurobehavioral outcomes., Methods: This study identified 134,388 healthy children with appendectomy and examined the incidence of subsequent externalizing or behavioral disorders (conduct, impulse control, oppositional defiant, attention-deficit hyperactivity disorder) or internalizing or mood or anxiety disorders (depression, anxiety, or bipolar disorder) when compared to 671,940 matched healthy controls as identified in Medicaid data between 2001 and 2018. For comparison, this study also examined 154,887 otherwise healthy children admitted to the hospital for pneumonia, cellulitis, and gastroenteritis, of which only 8% received anesthesia, and compared them to 774,435 matched healthy controls. In addition, this study examined the difference-in-differences between matched appendectomy patients and their controls and matched medical admission patients and their controls., Results: Compared to controls, children with appendectomy were more likely to have subsequent behavioral disorders (hazard ratio, 1.04; 95% CI, 1.01 to 1.06; P = 0.0010) and mood or anxiety disorders (hazard ratio, 1.15; 95% CI, 1.13 to 1.17; P < 0.0001). Relative to controls, children with medical admissions were also more likely to have subsequent behavioral (hazard ratio, 1.20; 95% CI, 1.18 to 1.22; P < 0.0001) and mood or anxiety (hazard ratio, 1.25; 95% CI, 1.23 to 1.27; P < 0.0001) disorders. Comparing the difference between matched appendectomy patients and their matched controls to the difference between matched medical patients and their matched controls, medical patients had more subsequent neurobehavioral problems than appendectomy patients., Conclusions: Although there is an association between neurobehavioral diagnoses and appendectomy, this association is not specific to anesthesia exposure and is stronger in medical admissions. Medical admissions, generally without anesthesia exposure, displayed significantly higher rates of these disorders than appendectomy-exposed patients., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Purpose of Review: This article reviews recent advances and controversies of developmental anesthesia neurotoxicity research with a special focus on the unanswered questions in the field both from clinical and preclinical perspectives., Recent Findings: Observational cohort studies of prenatal and early childhood exposure to anesthesia have reported mixed evidence of an association with impaired neurodevelopment. Meta-analyses of currently available studies of early childhood exposure to anesthesia suggest that, while limited to no change in general intelligence can be detected, more subtle deficits in specific neurodevelopmental domains including behavior and executive function may be seen. Several studies have evaluated intraoperative blood pressure values and neurocognitive outcomes and have not found an association. Although many animal studies have been performed, taking into consideration other peri-operative exposures such as pain and inflammation may help with translation of results from animal models to humans., Summary: Advances have been made in the field of developmental anesthetic neurotoxicity over the past few years, including the recognition that anesthetic exposure is associated with deficits in certain cognitive domains but not others. Although the most important question of whether anesthetic agents actually cause long-term neurodevelopmental effects in children has still not been answered, results from recent studies will guide further studies necessary to inform clinical decision-making in children., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Background: Some studies have found surgery and anesthesia in children to be associated with neurodevelopmental deficits, but specific reasons for this association have not been fully explored. This study evaluates intraoperative mean arterial pressure (MAP) during a single ambulatory procedure in children and subsequent mental disorder diagnoses., Methods: A retrospective observational study was performed including children ≥28 days and <18 years of age with intraoperative electronic anesthetic records between January 1, 2009, and April 30, 2017, at our institution. Eligible children were categorized based on their mean intraoperative MAP relative to other children of the same sex and similar age: category 1 (very low): children with mean intraoperative MAP values below the 10th percentile, category 2 (low): mean MAP value ≥10th and <25th percentiles, category 3 (reference): mean MAP value ≥25th and <75th percentiles, category 4 (high): mean MAP value ≥75th and <90th percentile, and category 5 (very high): mean MAP value ≥90th percentile. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) and ICD, Tenth Revision, Clinical Modification (ICD-10)-coded mental disorders were identified in hospital and outpatient claims, with a median duration of follow-up after surgery of 120 days (interquartile range [IQR], 8-774.5 days). Cox proportional hazards models evaluated the hazard ratio (HR) of time to first mental disorder diagnosis associated with intraoperative blood pressure category between the end of surgery and censoring, with the primary analysis adjusting for demographic, anesthetic, comorbidity, and procedure-type variables as potential confounders., Results: A total of 14,724 eligible children who received general anesthesia for a single ambulatory surgical procedure were identified. After adjusting for all available potential confounders, when compared to the reference, there were no statistically significant differences in mental disorder diagnosis risk based on intraoperative mean MAP category. Compared to reference, children in the very low and low blood pressure categories reported HRs of 1.00 (95% confidence interval [CI], 0.74-1.35) and 1.10 (95% CI, 0.87-1.41) for a mental disorder diagnosis, respectively, and children in the high and very high categories reported HRs of 0.87 (95% CI, 0.68-1.12) and 0.76 (95% CI, 0.57-1.03), respectively., Conclusions: Presence in a predefined mean intraoperative MAP category was not associated with subsequent mental disorder diagnoses within our follow-up period. However, the limitations of this study, including uncertainty regarding what constitutes an adequate blood pressure in children, may limit the ability to form definitive conclusions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Purpose of Review: Nearly 100 clinical studies have been published evaluating neurodevelopmental outcomes in children following surgery and anesthesia. These studies have reported mixed results, likely attributable at least in part to significant heterogeneity in their study designs, types and numbers of exposures, patient populations evaluated, and most importantly, the outcomes that were assessed. This review aims to summarize the results from clinical studies evaluating behavioral outcomes in children exposed to surgery and anesthesia., Recent Findings: Children with early exposure to surgery and anesthesia were found to have limited to no differences in intelligence when compared with unexposed children. However, several studies have reported more behavioral problems in children exposed to general anesthesia. An increased incidence of attention-deficit hyperactivity disorder has also been reported in anesthetic exposed children, particularly after multiple exposures., Summary: Nearly all clinical studies of anesthetic neurotoxicity are observational in nature, so the associations between anesthetic exposure and behavioral deficits cannot yet be directly attributed to the anesthetic medication. However, the finding of deficits in some neurodevelopmental domains and not others will help guide the selection of appropriate outcomes in future studies of anesthetic neurotoxicity that can further evaluate whether anesthetic medications have an impact on neurodevelopment in children., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Introduction: New York State implemented an 11-week elective surgery ban in response to the coronavirus disease-2019 (COVID-19) pandemic, during which pediatric patients from the 10 New York Presbyterian network hospitals requiring urgent or emergent surgical procedures were cared for at Morgan Stanley Children's Hospital (MSCH)., Materials and Methods: Data was abstracted from the electronic medical record of all patients aged 0 to 20 years who had surgery at MSCH from March 23, 2020 to June 7, 2020. Comparative analysis of demographic and clinical data elements between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive and negative cohorts was conducted using the Fisher exact tests., Results: A total of 505 surgical procedures were performed in 451 patients, with 32 procedures (6.3%) performed in 21 SARS-CoV-2-positive children. The prevalence of SARS-CoV-2 positivity in Medicaid beneficiaries was more than twice the prevalence in commercially insured (6.8% vs. 2.6%, P=0.04) children. SARS-CoV-2-positive patients were more likely to undergo multiple surgical procedures (23.8% vs. 7.2%, P=0.02), and to have higher American Society of Anesthesiologists (ASA) class designations (69.8% III to V vs. 47.4% I to II, P=0.03). There was no significant difference in the prevalence of SARS-CoV-2 positivity across sex, age, race, or ethnicity groups, or in emergent case status or surgical procedure type. Thirty-day mortality rate was <0.1% overall, with no deaths in the SARS-CoV-2-positive group., Conclusions: During the first wave of the COVID-19 pandemic in New York City, we found a higher prevalence of SARS-CoV-2 positivity in urgent/emergent pediatric surgical patients compared with other institutions in the United States. SARS-CoV-2-positive patients were more likely to be Medicaid beneficiaries, were clinically more complex, and had more surgical procedures., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate neurodevelopmental and mental disorders after PICU hospitalization in children requiring invasive mechanical ventilation for severe respiratory illness., Design: Retrospective longitudinal observational cohort., Setting: Texas Medicaid Analytic eXtract data from 1999 to 2012., Patients: Texas Medicaid-enrolled children greater than or equal to 28 days old to less than 18 years old hospitalized for a primary respiratory illness, without major chronic conditions predictive of abnormal neurodevelopment., Interventions: We examined rates of International Classification of Diseases, 9th revision-coded mental disorder diagnoses and psychotropic medication use following discharge among children requiring invasive mechanical ventilation for severe respiratory illness, compared with general hospital patients propensity score matched on sociodemographic and clinical characteristics prior to admission. Children admitted to the PICU for respiratory illness not necessitating invasive mechanical ventilation were also compared with matched general hospital patients as a negative control exposure., Measurements and Main Results: Of 115,335 eligible children, 1,351 required invasive mechanical ventilation and were matched to 6,755 general hospital patients. Compared with general hospital patients, children requiring invasive mechanical ventilation had increased mental disorder diagnoses (hazard ratio, 1.43 [95% CI, 1.26-1.64]; p < 0.0001) and psychotropic medication use (hazard ratio, 1.67 [1.34-2.08]; p < 0.0001) following discharge. Seven-thousand seven-hundred eighty children admitted to the PICU without invasive mechanical ventilation were matched to 38,900 general hospital patients and had increased mental disorder diagnoses (hazard ratio, 1.08 [1.02-1.15]; p = 0.01) and psychotropic medication use (hazard ratio, 1.11 [1.00-1.22]; p = 0.049)., Conclusions: Children without major comorbidity requiring invasive mechanical ventilation for severe respiratory illness had a 43% higher incidence of subsequent mental disorder diagnoses and a 67% higher incidence of psychotropic medication use. Both increases were substantially higher than in PICU patients with respiratory illness not necessitating invasive mechanical ventilation. Invasive mechanical ventilation is a life-saving therapy, and its application is interwoven with underlying health, illness severity, and PICU management decisions. Further research is required to determine which factors related to invasive mechanical ventilation and severe respiratory illness are associated with abnormal neurodevelopment. Given the increased risk in these children, identification of strategies for prevention, neurodevelopmental surveillance, and intervention after discharge may be warranted., Competing Interests: Dr. Geneslaw received funding from the Columbia University Department of Pediatrics Innovation Nucleation Fund. Dr. Hua’s institution received funding from the National Institute on Aging and the American Federation for Aging Research, and she received support for article research from the National Institutes of Health (NIH). Dr. Ing was supported by the Agency for Healthcare Research and Quality (AHRQ) under award number K08HS022941. Dr. Ing’s institution received funding from the AHRQ and the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Exposure to surgery and anesthesia in early childhood has been found to be associated with an increased risk of behavioral deficits. While the US Food and Drug Administration (FDA) has warned against prenatal exposure to anesthetic drugs, little clinical evidence exists to support this recommendation. This study evaluates the association between prenatal exposure to general anesthesia due to maternal procedures during pregnancy and neuropsychological and behavioral outcome scores at age 10., Methods: This is an observational cohort study of children born in Perth, Western Australia, with 2 generations of participants contributing data to the Raine Study. In the Raine Study, the first generation (Gen1) are mothers enrolled during pregnancy, and the second generation (Gen2) are the children born to these mothers from 1989 to 1992 with neuropsychological and behavioral tests at age 10 (n=2024). In the primary analysis, 6 neuropsychological and behavioral tests were evaluated at age 10: Raven's Colored Progressive Matrices (CPM), McCarron Assessment of Neuromuscular Development (MAND), Peabody Picture Vocabulary Test (PPVT), Symbol Digit Modality Test (SDMT) with written and oral scores, Clinical Evaluation of Language Fundamentals (CELF) with Expressive, Receptive, and Total language scores, and Child Behavior Checklist (CBCL) with Internalizing, Externalizing, and Total behavior scores. Outcome scores of children prenatally exposed to general anesthesia were compared to children without prenatal exposure using multivariable linear regression models adjusting for demographic and clinical covariates (sex, race, income, and maternal education, alcohol or tobacco use, and clinical diagnoses: diabetes, epilepsy, hypertension, psychiatric disorders, or thyroid dysfunction). Bonferroni adjustment was used for the 6 independent tests in the primary analysis, so a corrected P value <.0083 (P = .05 divided by 6 tests, or a 99.17% confidence interval [CI]) was required for statistical significance., Results: Among 2024 children with available outcome scores, 22 (1.1%) were prenatally exposed to general anesthesia. Prenatally exposed children had higher CBCL Externalizing behavioral scores (score difference of 6.1 [99.17% CI, 0.2-12.0]; P = .006) than unexposed children. Of 6 tests including 11 scores and subscores, only CBCL Externalizing behavioral scores remained significant after multiple comparisons adjustment with no significant differences found in any other score., Conclusions: Prenatal exposure to general anesthetics is associated with increased externalizing behavioral problems in childhood. However, given the limitations of this study and that avoiding necessary surgery during pregnancy can have significant detrimental effects on the mother and the child, further studies are needed before changes to clinical practice are made., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: Some recent clinical studies have found that early childhood exposure to anesthesia is associated with increased risks of behavioral deficits and clinical diagnoses of attention deficit hyperactivity disorder (ADHD). While diagnoses in claims data may be subject to inaccuracies, pharmacy claims are highly accurate in reflecting medication use. This study examines the association between exposure to surgery and anesthesia and subsequent ADHD medication use., Methods: Longitudinal data for children enrolled in Texas and New York Medicaid from 1999 to 2010 were used. We assessed the association between a single exposure to anesthesia before age 5 years for 1 of 4 common pediatric surgical procedures (pyloromyotomy, inguinal hernia repair, circumcisions outside the perinatal period, and tonsillectomy and/or adenoidectomy) and persistent ADHD medication use (event defined as the initial ADHD medication prescription, and persistent use defined as filling 2 or more ≥30-day prescriptions between 6 months following surgery until censoring). Exposed children (n = 42,687) were matched on propensity score (ie, the probability of receiving surgery) estimated in logistic regression including sociodemographic and clinical covariates, to children without anesthesia exposure before age 5 years (n = 213,435). Cox proportional hazards models were used to evaluate the hazard ratio (HR) of ADHD medication use following exposure. Nonpsychotropic medications served as negative controls to determine if exposed children simply had higher overall medication use., Results: Children with a single exposure to surgery and anesthesia were 37% more likely than unexposed children to persistently use ADHD medication (HR, 1.37; 95% confidence interval [CI], 1.30-1.44). The estimated HRs for common nonpsychotropic medication use following a single anesthetic exposure were 1.06 (95% CI, 1.04-1.07) for amoxicillin, 1.10 (95% CI, 1.08-1.12) for azithromycin, and 1.08 (95% CI, 1.05-1.11) for diphenhydramine. In comparison, the risk of using other psychotropic medication to treat conditions besides ADHD was also significantly higher, with HRs of 1.37 (95% CI, 1.24-1.51) for sedative/anxiolytics, 1.40 (95% CI, 1.25-1.58) for antidepressants, 1.31 (95% CI, 1.20-1.44) for antipsychotics, and 1.24 (95% CI, 1.10-1.40) for mood stabilizers., Conclusions: Medicaid-enrolled children receiving anesthesia for a single common pediatric surgical procedure under age 5 years were 37% more likely to require subsequent persistent use of ADHD medications than unexposed children. Because the increased use of ADHD medication is disproportionately higher than that of nonpsychotropic medications, unmeasured confounding may not account for all of the increase in ADHD medication use. By evaluating Medicaid data, this study assesses children who may be particularly vulnerable to neurotoxic exposures.

Introduction: Anesthetic exposure duration has come under scrutiny because of a Food and Drug Administration warning against prolonged use of anesthesia in children, defined as exposures longer than 3 hours., Methods: Data for 2,613,344 pediatric anesthetic records from the American Society of Anesthesiologist's National Anesthesia Clinical Outcomes Registry from 2010 to 2015 were analyzed to describe anesthetic duration and the prevalence of prolonged exposures in children. Common pediatric inpatient procedures were independently assessed to determine factors associated with exposure duration., Results: The overall mean pediatric anesthetic duration was 83.3±107.4 minutes (median, 57 min). Prolonged exposures comprised 7% of pediatric anesthetic records, and 15% of anesthetic records in infants. After restricting to common pediatric inpatient procedures (n=96,603) and adjusting for procedure type using a Poisson model, compared with children 10 years or older, exposures in infants were 20.5% longer (anesthetic duration ratio [ADR], 1.205; 95% confidence interval [CI], 1.202-1.208). Longer exposures were also seen with a variety of other patient and hospital factors including ASA 4 patients versus ASA 1 patients, (ADR, 1.381; 95% CI, 1.376-1.386), and university hospitals versus surgery centers (ADR, 1.241; 95% CI, 1.236-1.246)., Conclusions: Most pediatric anesthetic exposures last <1 hour with a small percentage lasting over 3 hours. Anesthetic duration for inpatient pediatric procedures, however, is associated with specific patient and hospital characteristics. These results may help identify children potentially at risk for prolonged anesthetic exposure and inform procedure time prediction and operating room scheduling.

The Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study team held its biennial symposium in April 2018 to discuss issues on anesthetic neurotoxicity in the developing brain. One of the sessions invited speakers with different areas of expertise to discuss "Outcomes Research in Vulnerable Pediatric Populations." The vulnerable populations included neonates, children with congenital heart disease, children from low socioeconomic status, and children with incarcerated parents. Each speaker presented some of the ongoing research efforts in these groups as well as the challenges encountered in studying them.

Background: Animals exposed to anesthetics during specific age periods of brain development experience neurotoxicity, with neurodevelopmental changes subsequently observed during adulthood. The corresponding vulnerable age in children, however, is unknown., Methods: An observational cohort study was performed using a longitudinal dataset constructed by linking individual-level Medicaid claims from Texas and New York from 1999 to 2010. This dataset was evaluated to determine whether the timing of exposure to anesthesia ≤5 years of age for a single common procedure (pyloromyotomy, inguinal hernia, circumcision outside the perinatal period, or tonsillectomy and/or adenoidectomy) is associated with increased subsequent risk of diagnoses for any mental disorder, or specifically developmental delay (DD) such as reading and language disorders, and attention deficit hyperactivity disorder (ADHD). Exposure to anesthesia and surgery was evaluated in 11 separate age at exposure categories: ≤28 days old, >28 days and ≤6 months, >6 months and ≤1 year, and 6-month age intervals between >1 year old and ≤5 years old. For each exposed child, 5 children matched on propensity score calculated using sociodemographic and clinical covariates were selected for comparison. Cox proportional hazards models were used to measure the hazard ratio of a mental disorder diagnosis associated with exposure to surgery and anesthesia., Results: A total of 38,493 children with a single exposure and 192,465 propensity score-matched children unexposed before 5 years of age were included in the analysis. Increased risk of mental disorder diagnosis was observed at all ages at exposure with an overall hazard ratio of 1.26 (95% confidence interval [CI], 1.22-1.30), which did not vary significantly with the timing of exposure. Analysis of DD and ADHD showed similar results, with elevated hazard ratios distributed evenly across all ages, and overall hazard ratios of 1.26 (95% CI, 1.20-1.32) for DD and 1.31 (95% CI, 1.25-1.37) for ADHD., Conclusions: Children who undergo minor surgery requiring anesthesia under age 5 have a small but statistically significant increased risk of mental disorder diagnoses and DD and ADHD diagnoses, but the timing of the surgical procedure does not alter the elevated risks. Based on these findings, there is little support for the concept of delaying a minor procedure to reduce long-term neurodevelopmental risks of anesthesia in children. In evaluating the influence of age at exposure, the types of procedures included may need to be considered, as some procedures are associated with specific comorbid conditions and are only performed at certain ages.

Introduction: Although some studies have reported an association between early exposure to anesthesia and surgery and long-term neurodevelopmental deficit, the clinical phenotype of children exposed to anesthesia is still unknown., Methods: Data were obtained from the Western Australian Pregnancy Cohort Study (Raine) with neuropsychological tests at age 10 years measuring language, cognition, motor function, and behavior. Latent class analysis of the tests was used to divide the cohort into mutually exclusive subclasses of neurodevelopmental deficit. Multivariable polytomous logistic regression was used to evaluate the association between exposure to surgery and anesthesia and each latent class, adjusting for demographic and medical covariates., Results: In our cohort of 1444 children, latent class analysis identified 4 subclasses: (1) Normal: few deficits (n=1135, 78.6%); (2) Language and Cognitive deficits: primarily language, cognitive, and motor deficits (n=96, 6.6%); (3) Behavioral deficits: primarily behavioral deficits, (n=151, 10.5%); and (4) Severe deficits: deficits in all neuropsychological domains (n=62, 4.3%). Language and cognitive deficit group children were more likely to have exposure before age 3 (adjusted odds ratio [aOR], 2.11; 95% confidence interval [CI], 1.17-3.81), whereas a difference in exposure was not found between Behavioral or Severe deficit children (aOR, 1.00; 95% CI, 0.58-1.73, and aOR, 0.85; 95% CI, 0.34-2.15, respectively) and Normal children., Conclusions: Our results suggest that in evaluating children exposed to surgery and anesthesia at an early age, the phenotype of interest may be children with deficits primarily in language and cognition, and not children with broad neurodevelopmental delay or primarily behavioral deficits.

On April 16 and 17, 2016, the Fifth biennial Pediatric Anesthesia & Neurodevelopment Assessment (PANDA) symposium was convened at the Morgan Stanley Children's Hospital of New York at Columbia University Medical Center. During the symposium, experts in the fields of anesthesiology, neuropsychology, and epidemiology were convened in a small group session to determine the level of confidence in the current clinical evidence and the next steps in anesthetic neurotoxicity clinical research. Among the participants in the discussion, there remained a lack of consensus on whether anesthetic exposure causes long-term neurodevelopmental deficits in children based on the current evidence. This causal relationship between anesthesia exposure and neurodevelopmental deficit is difficult to establish using observational data, and current and future clinical trials are critical for answering this question. It was, however, recognized that the continuum of data that is seen in studies of other toxic environmental exposures, such as lead poisoning, has not been established in the anesthetic neurotoxicity literature, specifically regarding the timing of the exposure, the dose effects, contributing perioperative conditions, or vulnerable populations. As a result, these questions may need to be addressed in observational studies to guide future clinical trials.

Introduction: Although animal studies have consistently demonstrated long-term neurocognitive deficits following early anesthetic exposure under certain conditions, risk in human children remains unknown. Magnetic resonance imaging (MRI) in young patients often requires anesthesia to facilitate image acquisition. We studied MRI utilization in a pediatric population, and associated use of anesthesia for ambulatory MRI., Materials and Methods: Data were obtained from the New York State Inpatient Database and State Ambulatory Surgery and Services Database on MRI performed in children under the age of 18 years from 2005 to 2011. Demographic characteristics of children who underwent inpatient or ambulatory MRI were evaluated. A subset of ambulatory MRI patients was assessed to evaluate associated use of anesthesia., Results: Overall, 2% of pediatric inpatient discharges (55,036/2,779,507), and 0.5% of pediatric ambulatory encounters (4670/943,520), had MRI performed. Inpatient MRI utilization did not change over time. Ambulatory MRI utilization decreased by 55.2%, from 8.07 per 1000 encounters in 2005 to 2006 to 3.62 per 1000 encounters in 2007 to 2011 (P<0.001). Associated use of anesthesia for ambulatory MRI in children aged below 1 year, 1 to below 6 years, 6 to below 12 years, and 12 to below 18 years, was 91.1%, 83.6%, 74.6%, and 47.5%, respectively., Conclusions: Significant percentages of MRI in children are associated with use of anesthesia, particularly in younger children, a population potentially more vulnerable to anesthetic neurotoxicity. Discussion of risks and benefits of anesthesia for MRI in children among physicians, patients, and families is recommended.

During the Fifth Pediatric Anesthesia Neurodevelopmental Assessment Symposium, experts and stakeholders met to present and discuss recent advances made in the study of neurodevelopmental outcomes after exposure to anesthetic drugs in infants and children. This article summarizes the update of 5 ongoing clinical studies: General Anesthesia compared to Spinal Anesthesia, Toxicity of Remifentanil and Dexmedetomidine, Mayo Anesthesia Safety in Kids, the University of California San Francisco human cohort study, and Columbia University Medical Center Neonatal Magnetic Resonance Imaging study. The purpose of this summary is to discuss the contributions and limitations of these studies, how they fit into the published literature, and what questions remain to be answered.

The Fourth PANDA symposium on Anesthesia and Neurodevelopment in Children invited 4 leaders in community engagement and federal government collaboration to share their experiences with overcoming challenges in promoting public health issues. There continues to be emerging evidence from laboratory findings in animal models demonstrating neurotoxic effects and neurodevelopmental changes from early exposure to anesthetic and sedative drugs, but studies in humans have been very limited and inconclusive. Although definitive recommendations for clinical care still cannot be made given the limitations in the clinical data, the need for open communication among clinicians, parents, and other stakeholders is clear. A "top-down, bottom-up" engagement strategy including parents, children, clinicians, government agencies, and community organizations may improve communication and collaboration. To reach the goal of "improving quality, safety, efficiency, and effectiveness of health care in children," clinicians and researchers will need to adopt strategies to engage and partner with stakeholders as coinvestigators who actively participate in efforts to increase anesthetic safety in children. Collaborations with government regulatory administration can improve the efficacy and effectiveness of resource utilization to address public health needs. This session provided an opportunity for open dialog between clinicians, researchers, and community leaders to discuss strategies to engage stakeholders to partake in patient-centered outcomes research on anesthetic neurotoxicity.

Background: In vivo animal studies indicate that the developing brain is vulnerable to the neurotoxic effects of anesthetic agents. There is corresponding concern about the long-term neurological effects of early-in-life exposure in children at both the individual and population levels. Accurate national estimates of the number of children undergoing surgical procedures are required to understand the scope of this potential problem., Methods: We estimated annual frequencies of in-hospital surgical procedures performed on children in the United States using the 2003, 2006, and 2009 Kids' Inpatient Database (KID). The KID is produced as part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality and contains a representative national sample of pediatric discharges. Demographic variables and procedure categories were assessed in this cohort to determine rates and types of surgery., Results: Over the 3 years evaluated, surgical diagnoses accounted for 12.7% of all discharges, with an average of 450,000 pediatric inpatient surgical admissions each year and 115,000 admissions annually in children under the age of 3. Elective admissions made up 40% of surgical hospitalizations with 55% of surgical admissions classified as gastrointestinal, orthopedic, or urological., Conclusions: In the United States, approximately 450,000 children under 18 years of age are admitted for surgery as inpatients annually. One quarter of these children are under 3 years of age and the majority for gastrointestinal, orthopedic, or urological surgery. When examined together with data on ambulatory surgery, these results are useful in considering the scope of anesthesia exposure in young children.

Rationale and Objectives: Radiologic contrast media (CM) may influence processes of coagulation and fibrinolysis. In the current study, the effects of various CM on the formation of plasmin were examined in an in vitro buffer system., Methods: The effects of three clinically relevant concentrations of seven different iodine-containing CM and gadolinium-DTPA on streptokinase (SK) or recombinant tissue plasminogen activator (rt-PA)-induced plasmin formation was monitored using a plasmin-sensitive chromogenic substrate., Results: Contrast media generally had an inhibitory effect at the plasminogen activation step; this effect was particularly noticeable with the ionic CM., Conclusions: Contrast media influence plasminogen activation by SK and rt-PA in vitro. Ionic CM have a more pronounced inhibitory effect than the nonionic media. The ionic Gd-DTPA shows a less inhibitory effect than the ionic iodine-containing CM. However, they must be regarded separately because of the different chemical composition of the magnetic resonance imaging and x-ray CM.