Association between preoperative respiratory symptoms and perioperative respiratory adverse events in pediatric patients with positive viral testing.

STUDY OBJECTIVE: To determine the association between the presence of upper respiratory tract viral infection symptoms and occurrence of perioperative respiratory adverse events (PRAE) in children with positive viral screening, and to analyze the risk of PRAE in children with SARS-CoV-2 compared to non-SARS-CoV-2 infection. DESIGN: A prospective cohort study. SETTING: A tertiary, freestanding pediatric hospital in Dallas, Texas. PATIENTS: Children <18 years of age with positive respiratory viral testing who underwent general anesthesia. INTERVENTION: Measurement of incidence of PRAE and severe adverse events during the first 7 postoperative days. MEASUREMENTS: The primary outcome was a composite of PRAE: oxygen saturation < 90% for >5 min, supplemental oxygen for >2 h after anesthesia, laryngospasm, and bronchospasm. The secondary outcome was severe adverse events: high flow nasal cannula >6 l of oxygen per minute, admission to the ICU for escalation of respiratory support post-anesthetic, acute respiratory distress syndrome, postoperative pneumonia, cardiovascular arrest, extracorporeal life support, and death. MAIN RESULTS: In this convenience sample of 196 children, 83 were symptomatic and 113 were asymptomatic. The risk of PRAE was similar in children with active viral symptoms and asymptomatic children (risk difference: -1.9%; 95% CI: -10.9, 7.9%), but higher among children with documented fever within 48 h of the anesthetic (risk difference: 20.8%; 95% CI: 5.3, 39.7%). The multivariable adjusted odds ratio of PRAE was 0.68 (95% CI: 0.25, 1.85) for symptomatic compared to asymptomatic patients, and 0.46 (95% CI: 0.14, 1.44) for patients with SARS-CoV-2 compared to non-SARS-CoV-2 infection. CONCLUSIONS: There was no significant difference in the incidence of PRAE between symptomatic and asymptomatic children with laboratory confirmed viral respiratory infection, and between children with the Omicron variant of SARS-CoV-2 compared to non-SARS-CoV-2 respiratory viruses. However, the risk was increased in children with recent fever.

Association Between Disrupted Cerebral Autoregulation and Radiographic Neurologic Injury for Children on Extracorporeal Membrane Oxygenation: A Prospective Pilot Study.

Validation of a real-time monitoring device to evaluate the risk or occurrence of neurologic injury while on extracorporeal membrane oxygenation (ECMO) may aid clinicians in prevention and treatment. Therefore, we performed a pilot prospective cohort study of children under 18 years old on ECMO to analyze the association between cerebral blood pressure autoregulation as measured by diffuse correlation spectroscopy (DCS) and radiographic neurologic injury. DCS measurements of regional cerebral blood flow were collected on enrolled patients and correlated with mean arterial blood pressure to determine the cerebral autoregulation metric termed DCSx. The primary outcome of interest was radiographic neurologic injury on eligible computed tomography (CT) or magnetic resonance imaging (MRI) scored by a blinded pediatric neuroradiologist utilizing a previously validated scale. Higher DCSx scores, which indicate disruption of cerebral autoregulation, were associated with higher radiographic neurologic injury score (slope, 11.0; 95% confidence interval [CI], 0.29-22). Patients with clinically significant neurologic injury scores of 10 or more had higher median DCSx measures than patients with lower neurologic injury scores (0.48 vs . 0.13; p = 0.01). Our study indicates that obtaining noninvasive DCS measures for children on ECMO is feasible and disruption of cerebral autoregulation determined from DCS is associated with higher radiographic neurologic injury score.

Hypothermia after extracorporeal cardiopulmonary resuscitation not associated with improved neurologic complications or survival in children: An analysis of the ELSO registry.

AIM: To analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry. METHODS: We conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data. The primary exposure was hypothermia under 34 °C for greater than 24 hours. The primary outcome, determined a priori, was a composite of neurologic complications defined by ELSO registry including brain death, seizures, infarction, hemorrhage, diffuse ischemia. Secondary outcomes were mortality on ECMO and mortality prior to hospital discharge. Multivariable logistic regression determined the odds of neurologic complications, mortality on ECMO or prior to hospital discharge associated with hypothermia after adjustment for available pertinent covariables. RESULTS: Of the 2,289 ECPR encounters, no difference in odds of neurologic complications were found between the hypothermia and non-hypothermia groups (AOR 1.10, 95% CI 0.80-1.51). However, hypothermia exposure was associated with decreased odds of mortality on ECMO (AOR 0.76, 95% CI 0.59-0.97), but no difference in mortality prior to hospital discharge (AOR 0.96, 95% CI 0.76-1.21) CONCLUSION: Analysis of a large, multicenter, international dataset demonstrates that hypothermia for greater than 24 hours among children who undergo ECPR is not associated with decreased neurologic complications or mortality benefit at time of hospital discharge.

Losing Ceci.

In this narrative medicine essay, a critical care physician's shared grief with a father who also recently experienced the death of a young child helps guide him back from his family's unimaginable loss.

Racial/ethnic differences in receipt of surgery among children in the United States.

BACKGROUND: It is unknown whether racial/ethnic disparities exist in surgical utilization for children. The aim, therefore, was to evaluate the odds of surgery among children in the US by race/ethnicity to test the hypothesis that minority children have less surgery. METHODS: Cross-sectional data were analyzed on children 0-18 years old from the 1999 to 2018 National Health Interview Survey, a large, nationally representative survey. The primary outcome was odds of surgery in the prior 12 months for non Latino African-American, Asian, and Latino children, compared with non Latino White children, after adjustment for relevant covariates. The National Surgical Quality Improvement Program Pediatric Dataset was used to analyze the odds of emergent/urgent surgery by race/ethnicity. RESULTS: Data for 219,098 children were analyzed, of whom 10,644 (4.9%) received surgery. After adjustment for relevant covariates, African-American (AOR, 0.54; 95% CI, 0.50-0.59), Asian (AOR, 0.39; 95% CI, 0.33-0.46), and Latino (AOR, 0.62; 95% CI, 0.57-0.67) children had lower odds of surgery than White children. Latino children were more likely to require emergent or urgent surgery (AOR, 1.71; 95% CI, 1.68-1.74). CONCLUSIONS: Latino, African-American, and Asian children have significantly lower adjusted odds of having surgery than White children in America, and Latino children were more likely to have emergent or urgent surgery. These racial/ethnic differences in surgery may reflect disparities in healthcare access which should be addressed through further research, ongoing monitoring, targeted interventions, and quality-improvement efforts. LEVEL OF EVIDENCE: II. TYPE OF STUDY: Prognosis study.

Anesthetic Complications Associated With Severe Acute Respiratory Syndrome Coronavirus 2 in Pediatric Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing. METHODS: We conducted a retrospective cohort study analyzing complications for children <18 years of age who underwent anesthesia between April 28 and September 30, 2020 at a large, academic pediatric hospital. Each child with a positive SARS-CoV-2 test within the prior 10 days was matched to a patient with a negative SARS-CoV-2 test based on American Society of Anesthesiologists (ASA) physical status, age, gender, and procedure. Children who were intubated before the procedure, underwent organ transplant surgery, or had severe COVID-19 were excluded. The primary outcome was the risk difference of a composite of intra- or postoperative respiratory complications in children positive for SARS-CoV-2 compared to those with negative testing. Secondarily, we used logistic regression to determine the odds ratio for respiratory complications before and after adjustment using propensity scores weighting to adjust for possible confounders. Other secondary outcomes included neurologic, cardiovascular, hematologic, and renal complications, unanticipated postoperative admission to the intensive care unit, length of hospital stay, and mortality. RESULTS: During the study period, 9812 general anesthetics that had a preoperative SARS-CoV-2 test were identified. Sixty encounters occurred in patients who had positive SARS-CoV-2 testing preoperatively and 51 were included for analysis. The matched controls cohort included 99 encounters. A positive SARS-CoV-2 test was associated with a higher incidence of respiratory complications (11.8% vs 1.0%; risk difference 10.8%, 95% confidence interval [CI], 1.6-19.8; P = .003). After adjustment, the odds ratio for respiratory complications was 14.37 (95% CI, 1.59-130.39; P = .02) for SARS-CoV-2-positive children as compared to controls. There was no occurrence of acute respiratory distress syndrome, postoperative pneumonia, or perioperative mortality in either group. CONCLUSIONS: Pediatric patients with nonsevere SARS-CoV-2 infection had higher rates of perianesthetic respiratory complications than matched controls with negative testing. However, severe morbidity was rare and there were no mortalities. The incidence of complications was similar to previously published rates of perianesthetic complications in the setting of an upper respiratory tract infection. This risk persisted after adjustment for preoperative upper respiratory symptoms, suggesting an increased risk in symptomatic or asymptomatic SARS-CoV-2 infection.

Changes in pediatric trauma during COVID-19 stay-at-home epoch at a tertiary pediatric hospital.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in the pediatric population. However, during the societal disruptions secondary to the coronavirus (COVID-19) stay-at-home regulations, there have been reported changes to the pattern and severity of pediatric trauma. We review our two-institution experience. METHODS: Pediatric trauma emergency department (ED) encounters from the National Trauma Registry for a large, tertiary, metropolitan level 1 pediatric trauma center and pediatric burn admission at the regional burn center were extracted for children less than 19 years from March 15th thru May 15th during the years 2015-2020. The primary outcome was the difference in encounters during the COVID-19 (2020) epoch versus the pre-COVID-19 epoch (2015-2019). RESULTS: There were 392 pediatric trauma encounters during the COVID-19 epoch as compared to 451, 475, 520, 460, 432 (mean 467.6) during the pre-COVID-19 epoch. Overall trauma admissions and ED trauma encounters were significantly lower (p < 0.001) during COVID-19. Burn injury admissions (p < 0.001) and penetrating trauma encounters (p = 0.002) increased during the COVID-19 epoch while blunt trauma encounters decreased (p < 0.001). Trauma occurred among more white (p = 0.01) and privately insured (p < 0.001) children, but no difference in suspected abuse, injury severity, mortality, age, or gender were detected. Sub-analysis showed significant decreases in motor vehicle crashes (p < 0.001), pedestrians struck by automobile (p < 0.001), all-terrain vehicle (ATV)/motorcross/bicycle/skateboard involved injuries (p = 0.02), falls (p < 0.001), and sports related injuries (p < 0.001). Fewer injuries occurring in the playground or home play equipment such as trampolines neared significance (p = 0.05). Interpersonal violence (assault, NAT, self-harm) was lower during the COVID-19 era (p = 0.04). For burn admissions, there was a significant increase in flame burns (p < 0.001). CONCLUSIONS: Stay-at-home regulations alter societal patterns, leading to decreased overall and blunt traumas. However, the proportion of penetrating and burn injuries increased. Owing to increased stressors and time spent at home, healthcare professionals should keep a high suspicion for abuse and neglect.

The association between high-volume intraoperative fluid administration and outcomes among pediatric patients undergoing large bowel resection.

BACKGROUND: Traditional intraoperative fluid administration practices have been challenged this century with data suggesting improved outcomes with restrictive or goal-directed fluid administration during adult bowel surgery. Minimal data on outcomes associated with differing intraoperative fluid administration practice exists for pediatric patients. AIMS: We assessed factors and outcomes associated with high-volume fluid administration in pediatric patients undergoing colectomy. We hypothesized that high-volume fluid administration is associated with impaired recovery and, thus, increased length of stay. METHODS: A database of perioperative practice and postoperative outcomes at a tertiary pediatric hospital was queried for colectomy encounters between July 2012 and March 2017. Data extracted included patient characteristics, perioperative clinical data, and postoperative outcomes. Encounters were stratified into two groups: greater than 90th percentile fluids administered (high-volume fluid administration group) vs less than 90th percentile fluids administered. Univariable tests, multivariable logistic regression, and propensity score matched group comparisons were used to asses outcomes associated with high-volume fluid administration. RESULTS: A total of 209 colectomy encounters were identified from which 12 were excluded based on predetermined criteria. High-volume fluid administration was associated with length of stay >6 days (AOR 8.14, CI 1.75-37.8, P = 0.007), time to first meal >4 days (AOR of 5.91, CI 1.30-27.17, P = 0.02), and supplemental oxygen requirement >24 hours (AOR 3.60, CI 1.25-10.39, P = 0.02) after adjusting for ASA status, blood loss, transfusion, and open surgery. Similarly, propensity score matched patients with high-volume fluid administration vs controls were more likely to have length of stay >6 days (93% vs 54%, P = 0.007), time to first meal >4 days (93% vs 57%, P = 0.009), and supplemental oxygen requirement >24 hours (36% vs 12%, P = 0.033). CONCLUSION: High-volume fluid administration during colectomy for pediatric patients is associated with worsened postoperative outcomes suggestive of impaired recovery.

MiR-449a Affects Epithelial Proliferation during the Pseudoglandular and Canalicular Phases of Avian and Mammal Lung Development.

Congenital diaphragmatic hernia is associated with pulmonary hypoplasia and respiratory distress, which result in high mortality and morbidity. Although several transgenic mouse models of lung hypoplasia exist, the role of miRNAs in this phenotype is incompletely characterized. In this study, we assessed microRNA expression levels during the pseudoglandular to canalicular phase transition of normal human fetal lung development. At this critical time, when the distal respiratory portion of the airways begins to form, microarray analysis showed that the most significantly differentially expressed miRNA was miR-449a. Prediction algorithms determined that N-myc is a target of miR-449a and identified the likely miR-449a:N-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. Functional ex vivo knock-down in organ cultures of murine embryonic lungs, as well as in ovo overexpression in avian embryonic lungs, suggested a role for miR-449a in distal epithelial proliferation. Finally, miR-449a expression was found to be abnormal in rare pulmonary specimens of human fetuses with Congenital Diaphragmatic Hernia in the pseudoglandular or canalicular phase. This study confirms the conserved role of miR-449a for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation, and proposes the potential involvement of this miRNA in human pulmonary hypoplasia.

Energy intake and energy expenditure among children with polymorphisms of the melanocortin-3 receptor.

BACKGROUND: Homozygosity for 2 protein-altering polymorphisms in the melanocortin-3 receptor gene (MC3R) coding sequence, C17A and G241A, has been reported to be associated with an obesity phenotype in children, yet how these polymorphisms affect energy homeostasis is unknown. Association between adult body weight and +2138InsCAGACC, another variant in the 3' untranslated region of MC3R, has also been described. OBJECTIVE: The objective of this study was to examine associations of C17A + G241A and +2138InsCAGACC MC3R variants with children's energy balance. DESIGN: Children aged 6-19 y were genotyped for MC3R C17A, G241A, and +2138InsCAGACC. Subjects underwent studies of energy intake from a 9835-kcal food array (n = 185), resting energy expenditure (REE) by using indirect calorimetry (n = 302), or total daily energy expenditure (TEE) by using doubly labeled water (n = 120). Linear regression was used to examine the associations between MC3R polymorphisms and the measures of energy balance. RESULTS: Body mass index and fat mass were greater in those with double homozygosity for C17A + G241A (P = 0.001). After accounting for covariates (including body composition), the number of minor C17A + G241A alleles was associated with significantly greater energy intake (beta = +0.15, P = 0.02) but not altered REE or TEE. No significant associations were observed between +2138InsCAGACC and measures of either fat mass or energy balance. CONCLUSIONS: C17A + G241A polymorphisms may be associated with pediatric obesity because of greater energy intake rather than because of diminished energy expenditure. +2138InsCAGACC does not appear to be associated with obesity or measures of energy balance in children.

Brain-derived neurotrophic factor and obesity in the WAGR syndrome.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been found to be important in energy homeostasis in animal models, but little is known about its role in energy balance in humans. Heterozygous, variably sized, contiguous gene deletions causing haploinsufficiency of the WT1 and PAX6 genes on chromosome 11p13, approximately 4 Mb centromeric to BDNF (11p14.1), result in the Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. Hyperphagia and obesity were observed in a subgroup of patients with the WAGR syndrome. We hypothesized that the subphenotype of obesity in the WAGR syndrome is attributable to deletions that induce haploinsufficiency of BDNF. METHODS: We studied the relationship between genotype and body-mass index (BMI) in 33 patients with the WAGR syndrome who were recruited through the International WAGR Syndrome Association. The extent of each deletion was determined with the use of oligonucleotide comparative genomic hybridization. RESULTS: Deletions of chromosome 11p in the patients studied ranged from 1.0 to 26.5 Mb; 58% of the patients had heterozygous BDNF deletions. These patients had significantly higher BMI z scores throughout childhood than did patients with intact BDNF (mean [+/-SD] z score at 8 to 10 years of age, 2.08+/-0.45 in patients with heterozygous BDNF deletions vs. 0.88+/-1.28 in patients without BDNF deletions; P=0.03). By 10 years of age, 100% of the patients with heterozygous BDNF deletions (95% confidence interval [CI], 77 to 100) were obese (BMI > or = 95th percentile for age and sex) as compared with 20% of persons without BDNF deletions (95% CI, 3 to 56; P<0.001). The critical region for childhood-onset obesity in the WAGR syndrome was located within 80 kb of exon 1 of BDNF. Serum BDNF concentrations were approximately 50% lower among the patients with heterozygous BDNF deletions (P=0.001). CONCLUSIONS: Among persons with the WAGR syndrome, BDNF haploinsufficiency is associated with lower levels of serum BDNF and with childhood-onset obesity; thus, BDNF may be important for energy homeostasis in humans.