Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

BACKGROUND: Acetaminophen is a frequently used adjunct analgesic in pediatric patients undergoing tonsillectomy and adenoidectomy. We compared opioid administration following preoperative intravenous (IV) or oral acetaminophen in addition to a standard multimodal regimen to test the hypothesis that 1 loading dose approach would provide superior opioid sparing effects among pediatric surgical patients undergoing tonsillectomy and adenoidectomy. METHODS: This single-center, double-blind, double-dummy prospective randomized study was conducted in patients ages 3 to 15 years undergoing tonsillectomy and adenoidectomy with or without myringotomy and tube placement between September 2017 and July 2019. Subjects received 1 dose of either oral acetaminophen 30 mg/kg with IV placebo (oral group) or IV acetaminophen 15 mg/kg with oral placebo (IV group). Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen. Intraoperative opioid administration and postoperative analgesia were standardized. Standardized postoperative multimodal analgesia included opioid if needed to control pain assessed by standardized validated pediatric pain scales. The primary outcome measure was total opioid administration in the first 24 hours after surgery. Continuous data were not normally distributed and were analyzed using the Wilcoxon rank sum test and the Hodges-Lehman estimator of the median difference. Clinical significance was defined as a 100 µg/kg IV morphine equivalents per day difference. RESULTS: Sixty-six subjects were randomized into and completed the study (29 women, 37 men; age 5.9 ± 3.0 years; percentile weight for age 49.5 ± 30.2; no differences between groups). There was no opioid dose difference between oral (median 147.6; interquartile range [IQR], 119.6-193.0 µg/kg) and IV groups (median 125.4; IQR, 102.8-150.9 µg/kg; median difference 21.3; 95% confidence interval [CI] -2.5 to 44.2 µg/kg IV morphine equivalents; P = .13). No acetaminophen levels exceeded the predefined safety threshold (40 mg/L). No difference was found in the percentage of patients with severe pain: 50.0% oral group, 47.2% IV group; relative risk of severe pain in IV 0.94; 95% CI, 0.57-1.6; P = .82. Postoperative plasma acetaminophen levels were higher in oral (22; IQR, 16-28 mg/L) than IV (20; IQR, 17-22 mg/L) group (median difference 7.0; 4.0-8.0 mg/L; P = .0001). CONCLUSIONS: Opioid-sparing effects did not differ following an oral or standard IV acetaminophen loading dose with no identified acetaminophen toxicity in pediatric patients undergoing tonsillectomy and adenoidectomy who received standardized multimodal postoperative analgesia. An oral loading dose may provide more consistent serum acetaminophen levels at lower cost compared to a standard IV dose.

Effect of general anesthesia in infancy on long-term recognition memory in humans and rats.

Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6-11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age- and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury.

The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages.

Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. Thus, the amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children. Children with autism, with and without mental retardation, also had a larger right hippocampal volume than typically developing controls, even after controlling for total cerebral volume. Children with autism but without mental retardation also had a larger left hippocampal volume relative to controls. These cross-sectional findings indicate an abnormal program of early amygdala development in autism and an abnormal pattern of hippocampal development that persists through adolescence. The cause of amygdala and hippocampal abnormalities in autism is currently unknown.

Investigation of neuroanatomical differences between autism and Asperger syndrome.

BACKGROUND: Autism and Asperger syndrome (ASP) are neurobiological conditions with overlapping behavioral symptoms and of unknown etiologies. Results from previous autism neuroimaging studies have been difficult to replicate, possibly owing to site differences in subject samples, scanning procedures, and image-processing methods. We sought (1) to determine whether low-functioning autism (LFA; IQ<70), high-functioning autism (HFA; IQ>or=70), and ASP constitute distinct biological entities as evidenced by neuroanatomical measures, and (2) to assess for intersite differences. METHODS: Case-control study examining coronally oriented 124-section spoiled gradient echo images acquired on 3 magnetic resonance imaging (MRI) systems, and processed by BrainImage 5.X. Participants were recruited and underwent scanning at 2 academic medicine departments. Participants included 4 age-matched groups of volunteer boys aged 7.8 to 17.9 years (13 patients with LFA, 18 with HFA, 21 with ASP, and 21 control subjects), and 3 volunteer adults for neuroimaging reliability. Main outcome measures included volumetric measures of total, white, and gray matter for cerebral and cerebellar tissues. RESULTS: Intersite differences were seen for subject age, IQ, and cerebellum measures. Cerebral gray matter volume was enlarged in both HFA and LFA compared with controls (P =.009 and P =.04, respectively). Cerebral gray matter volume in ASP was intermediate between that of HFA and controls, but nonsignificant. Exploratory analyses revealed a negative correlation between cerebral gray matter volume and performance IQ within HFA but not ASP. A positive correlation between cerebral white matter volume and performance IQ was observed within ASP but not HFA. CONCLUSIONS: Lack of replication between previous autism MRI studies could be due to intersite differences in MRI systems and subjects' age and IQ. Cerebral gray tissue findings suggest that ASP is on the mild end of the autism spectrum. However, exploratory assessments of brain-IQ relationships reveal differences between HFA and ASP, indicating that these conditions may be neurodevelopmentally different when patterns of multiple measures are examined. Further investigations of brain-behavior relationships are indicated to confirm these findings.