Exposure to Operative Anesthesia in Childhood and Subsequent Neurobehavioral Diagnoses: A Natural Experiment using Appendectomy.

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, in order to determine if anesthesia and surgery in childhood were specifically associated with subsequent neurobehavioral outcomes. METHODS: We identified 134,388 healthy children with appendectomy and examined the incidence of subsequent externalizing or behavioral disorders (conduct, impulse control, oppositional defiant, or attention-deficit/hyperactivity disorder); or internalizing or mood/anxiety disorders (depression, anxiety, or bipolar disorder) when compared to 671,940 matched healthy controls as identified in Medicaid data between 2001-2018. For comparison, we 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. We also 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 (the hazard ratio (HR) was 1.04 (95% CI 1.01, 1.06), P = 0.0010), and mood/anxiety disorders (HR: 1.15 (95% CI 1.13, 1.17), P < 0.0001). Relative to controls, children with medical admissions were also more likely to have subsequent behavioral (HR: 1.20 (95% CI 1.18, 1.22), P < 0.0001), and mood/anxiety (HR: 1.25 (95% CI 1.23, 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.

Behavioural and neuropsychological outcomes in children exposed in utero to maternal labour epidural analgesia.

BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.

Behavioural disorders after prenatal exposure to anaesthesia for maternal surgery.

BACKGROUND: The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined. METHODS: A nationwide sample of pregnant women linked to their liveborn infants was evaluated using the Medicaid Analytic eXtract (MAX, 1999-2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders. RESULTS: We matched 34,271 prenatally exposed children with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalising behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23-1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24-1.41) and internalising (HR, 1.36; 95% CI, 1.20-1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22-1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14-1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05-1.28), and autism (HR, 1.31; 95% CI, 1.05-1.64). CONCLUSIONS: Prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. Caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

Neurodevelopmental outcomes in children after prenatal marijuana exposure.

BACKGROUND: The effect of prenatal marijuana exposure (PME) on child neurodevelopment remains poorly understood. Prior studies have demonstrated inconsistent results. OBJECTIVES: This study evaluated the association between PME and neuropsychological test scores in late childhood and early adulthood, accounting for a wide range of parental characteristics. METHODS: This study evaluated participants from the Raine Study, a cohort of 2868 children born between 1989 and 1992. Children whose mothers provided information on marijuana use during pregnancy were included. The primary outcome was the Clinical Evaluation of Language Fundamentals (CELF) at age 10. Secondary outcomes included the Peabody Picture Vocabulary Test (PPVT), Child Behaviour Checklist (CBCL), McCarron Assessment of Neuromuscular Development (MAND), Coloured Progressive Matrices (CPM), Symbol Digit Modality Test (SDMT) and Autism Spectrum Quotient (AQ) scores. Exposed and unexposed children were matched by propensity score using optimal full matching. Missing covariate data were imputed using multiple imputation. Inverse probability of censoring weighting (IPCW) was used to adjust for missing outcome data. Linear regression within matched sets, adjusted by IPCW, evaluated score differences between exposed and unexposed children. As a secondary analysis, modified Poisson regression, adjusted by match weights and IPCW, evaluated the risk of clinical deficit in each outcome following PME. RESULTS: Of the 2804 children in this cohort, 285 (10.2%) had PME. After optimal full matching and IPCW, exposed children scored similarly on CELF Total (-0.33 points, 95% confidence interval [CI] -4.71, 4.05), Receptive (+0.65 points, 95% CI -4.08, 5.38) or Expressive (-0.53 points, 95% CI -5.07, 4.02). PME was not associated with secondary outcomes or risks of clinical deficit in any neuropsychological assessments. CONCLUSIONS: After adjusting for sociodemographic and clinical covariates, PME was not associated with worse neuropsychological test scores at age 10 or autistic traits at 19-20.

Unanswered questions of anesthesia neurotoxicity in the developing brain.

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.

Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward.

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.

Intraoperative Blood Pressure and Long-Term Neurodevelopmental Function in Children Undergoing Ambulatory Surgery.

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.

Long-term cognitive and behavioral outcomes following early exposure to general anesthetics.

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.

Prospectively assessed neurodevelopmental outcomes in studies of anaesthetic neurotoxicity in children: a systematic review and meta-analysis.

BACKGROUND: Whether exposure to a single general anaesthetic (GA) in early childhood causes long-term neurodevelopmental problems remains unclear. METHODS: PubMed/MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched from inception to October 2019. Studies evaluating neurodevelopmental outcomes and prospectively enrolling children exposed to a single GA procedure compared with unexposed children were identified. Outcomes common to at least three studies were evaluated using random-effects meta-analyses. RESULTS: Full-scale intelligence quotient (FSIQ); the parentally reported Child Behavior Checklist (CBCL) total, externalising, and internalising problems scores; and Behavior Rating Inventory of Executive Function (BRIEF) scores were assessed. Of 1644 children identified, 841 who had a single exposure to GA were evaluated. The CBCL problem scores were significantly higher (i.e. worse) in exposed children: mean score difference (CBCL total: 2.3 [95% confidence interval {CI}: 1.0-3.7], P=0.001; CBCL externalising: 1.9 [95% CI: 0.7-3.1], P=0.003; and CBCL internalising problems: 2.2 [95% CI: 0.9-3.5], P=0.001). Differences in BRIEF were not significant after multiple comparison adjustment. Full-scale intelligence quotient was not affected by GA exposure. Secondary analyses evaluating the risk of these scores exceeding predetermined clinical thresholds found that GA exposure was associated with increased risk of CBCL internalising behavioural deficit (risk ratio [RR]: 1.47; 95% CI: 1.08-2.02; P=0.016) and impaired BRIEF executive function (RR: 1.68; 95% CI: 1.23-2.30; P=0.001). CONCLUSIONS: Combining results of studies utilising prospectively collected outcomes showed that a single GA exposure was associated with statistically significant increases in parent reports of behavioural problems with no difference in general intelligence.

Prenatal Exposure to General Anesthesia and Childhood Behavioral Deficit.

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.

Long-Term Increases in Mental Disorder Diagnoses After Invasive Mechanical Ventilation for Severe Childhood Respiratory Disease: A Propensity Matched Observational Cohort Study.

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.

Long-term Healthcare Utilization by Medicaid Enrolled Children with Neonatal Abstinence Syndrome.

OBJECTIVE: To evaluate healthcare utilization in Medicaid enrolled children with neonatal abstinence syndrome (NAS) in the first 2 years of life. STUDY DESIGN: A retrospective, longitudinal cohort study evaluating Medicaid enrolled children born in New York (1999-2011) and Texas (1999-2010) was performed. Healthcare utilization, including inpatient days, emergency department and outpatient visits, and filled prescriptions in children after birth hospitalization was assessed. A tapered propensity-matching methodology was used, matching each child with NAS with 5 children without NAS, first on demographics, then on both demographics and clinical covariates (clinical diagnoses and congenital anomalies at birth). Poisson and negative binomial regression were used to calculate healthcare utilization ratios (HUR). RESULTS: In the first 2 years of life, children with NAS (n = 3799) had increased healthcare utilization with more inpatient days and emergency department visits than demographically similar children without NAS. This increased utilization however did not persist after matching on clinical covariates and performing multiple comparisons adjustment (inpatient days [HUR, 1.01; 95% CI, 0.88-1.16; P = .89], total emergency department visits [HUR, 1.06; 95% CI, 1.01-1.11; P = .02]). Children with NAS conversely had 9% fewer outpatient office visits (HUR, 0.91; 95% CI, 0.87-0.95; P < .0001). CONCLUSIONS: A diagnosis of NAS does not appear to be an independent predictor of increased healthcare utilization in the first 2 years of life. These results differ from some other published studies, but may suggest that the increased healthcare utilization observed in children with NAS is due to higher incidences of perinatal complications and congenital anomalies in children with prenatal drug exposures.

Exposure to Surgery and Anesthesia in Early Childhood and Subsequent Use of Attention Deficit Hyperactivity Disorder Medications.

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.

Identification of perioperative pulmonary aspiration in children using quality assurance and hospital administrative billing data.

BACKGROUND: Perioperative aspiration is a rare but potentially devastating complication, occurring in 1-10 per 10 000 anesthetics based on studies of quality assurance databases. Quality assurance reporting is known to underestimate the incidence of adverse outcomes, but few large studies use supplementary data sources. This study aims to identify the incidence of and risk factors for perioperative aspiration in children using quality assurance data supplemented by administrative billing records, and to examine the utility of billing data as a supplementary data source. METHODS: Aspiration events for children receiving anesthesia at a tertiary care pediatric hospital between 2008 and 2014 were identified using (i) a perioperative quality assurance database and (ii) hospital administrative billing records with International Classification of Diseases, Ninth Revision Clinical Modification coded diagnoses of aspiration. Records were subject to review by pediatric anesthesiologists. Following identification of all aspiration events, the incidence of perioperative aspiration was calculated and risk factors were assessed. RESULTS: 47 272 anesthetic cases were evaluated over 7 years. The quality assurance database identified 20 cases of perioperative aspiration occurring in surgical inpatients, same-day admissions, and outpatients. Using hospital administrative data (which excludes outpatients with shorter than a 24-hour stay), 9 cases of perioperative aspiration were identified of which 6 had not been found through quality assurance data. Overall, International Classification of Diseases, Ninth Revision coding demonstrated a positive predictive value of 94.5% for any aspiration event; however, positive predictive value was <4% for perioperative aspiration. A total incidence of 5.5 perioperative aspirations per 10 000 (95% CI: 3.7-8.0 per 10 000) anesthetics was found. CONCLUSION: Quality assurance data offer an efficient way to measure the incidence of rare events, but may underestimate perioperative complications. International Classification of Diseases, Ninth Revision codes for aspiration used as a secondary data source were nonspecific for perioperative aspiration, but when combined with record review yielded a 30% increase in identified cases of aspiration over quality assurance data alone. The use of administrative data therefore holds potential for supplementing quality assurance studies of rare complications.

Age at Exposure to Surgery and Anesthesia in Children and Association With Mental Disorder Diagnosis.

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.

Differences in intraoperative hemodynamics between spinal and general anesthesia in infants undergoing pyloromyotomy.

BACKGROUND: Hypotension and bradycardia are known side effects of spinal anesthesia in pregnant women undergoing cesarean section and adults undergoing other surgical procedures. Whether children experience similar hemodynamic changes is unclear. AIMS: The purpose of this study is to evaluate hemodynamic effects of spinal anesthesia compared to general anesthesia in a cohort of healthy infants. METHODS: The University of Vermont Medical Center almost exclusively used spinal anesthesia for infant pyloromyotomy surgery between 2008 and 2013, while Columbia University Medical Center relied on general anesthesia. The primary outcome assessed was the percentage change in intraoperative heart rate and blood pressure (systolic [SBP] and mean [MAP] blood pressure) from baseline. Analysis was performed using t-tests for continuous variables, followed by linear regression to account for differences in demographic and clinical covariates. RESULTS: The study sample consisted of 51 infants with spinal anesthesia at the University of Vermont and 52 infants with general anesthesia at Columbia University. The decrease from baseline for mean intraoperative SBP was -8.2 ± 16.8% for spinal anesthesia and -24.2 ± 17.2% for general anesthesia (difference between means: 16.2% [95% confidence interval (CI), 9.5-22.9]), while the decrease from baseline for mean intraoperative MAP was -16.3 ± 19.9% for spinal anesthesia and -24.6 ± 19.3% for general anesthesia (difference between means: 8.4% [95% CI, 0.8-16]). Spinal anesthesia patients also had smaller drops in minimum intraoperative MAP and SBP. These blood pressure differences persisted even after adjusting for covariates. No differences in heart rate were seen between spinal and general anesthesia. DISCUSSION: Our findings show that spinal anesthesia performed in healthy infants undergoing pyloromyotomy results in reduced intraoperative blood pressure changes from baseline, significantly higher blood pressure readings, and no increased bradycardia compared to general anesthesia. Further research is needed to assess whether any clinical impact of these hemodynamic differences between spinal and general anesthesia exists.

Early Anesthesia Exposure and the Effect on Visual Acuity, Refractive Error, and Retinal Nerve Fiber Layer Thickness of Young Adults.

OBJECTIVE: To investigate whether being anesthesia administered at least once in early life influenced 3 main proxies of visual function: visual acuity, refractive error, and optic nerve health in young adulthood. STUDY DESIGN: At age 20 years, participants of the Western Australian Pregnancy Cohort Study had comprehensive ocular examinations including visual acuity, postcycloplegic refraction, and multiple scans of the optic disc. We identified individuals who had at least 1 procedure requiring anesthesia during the first 3 years of life (between 1990 and 1994) and compared their visual outcomes with nonexposed individuals. We excluded 40 participants with strabismus or other ophthalmic disease or surgery and 136 with non-European background. RESULTS: Of 834 participants, 15.2% (n = 127) were exposed to anesthesia at least once before age 3 years. In both exposed and nonexposed groups, median visual acuity (measured using the logarithm of the minimum angle of resolution [LogMAR] chart) was -0.06 LogMAR in the right eye and -0.08 LogMAR in the left eye (P > .05). Median spherical equivalent refractive error was +0.44 diopters (IQR -0.25, +0.63) and +0.31 diopters (IQR -0.38, +0.63) in the exposed and nonexposed group, respectively (P = .126). No difference was detected in mean global retinal nerve fiber layer thickness of the 2 groups (100.7 vs 100.1 µm, P = .830). CONCLUSIONS: We were unable to demonstrate an association of exposure to anesthesia as a child with reduced visual acuity or increased myopia or thinning of retinal nerve fiber layer. These findings support the view that anesthesia is unlikely to impair visual development, but further work is needed to establish whether more subtle defects are present and repeated exposures have any effects.