Association of dexmedetomidine use with haemodynamics, postoperative recovery, and cost in paediatric anaesthesia: a hospital registry study.

BACKGROUND: Dexmedetomidine utilisation in paediatric patients is increasing. We hypothesised that intraoperative use of dexmedetomidine in children is associated with longer postanaesthesia care unit length of stay, higher healthcare costs, and side-effects. METHODS: We analysed data from paediatric patients (aged 0-12 yr) between 2016 and 2021 in the Bronx, NY, USA. We matched our cohort with the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID). RESULTS: Among 18 104 paediatric patients, intraoperative dexmedetomidine utilisation increased from 51.7% to 85.7% between 2016 and 2021 (P<0.001). Dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay (adjusted absolute difference [ADadj] 19.7 min; 95% confidence interval [CI]: 18.0-21.4 min; P<0.001, median length of stay of 122 vs 98 min). The association was magnified in children aged ≤2 yr undergoing short (≤60 min) ambulatory procedures (ADadj 33.3 min; 95% CI: 26.3-40.7 min; P<0.001; P-for-interaction <0.001). Dexmedetomidine was associated with higher total hospital costs of USD 1311 (95% CI: USD 835-1800), higher odds of intraoperative mean arterial blood pressure below 55 mm Hg (adjusted odds ratio [ORadj] 1.27; 95% CI: 1.16-1.39; P<0.001), and higher odds of heart rate below 100 beats min-1 (ORadj 1.32; 95% CI: 1.21-1.45; P<0.001), with no preventive effects on emergence delirium requiring postanaesthesia i.v. sedatives (ORadj 1.67; 95% CI: 1.04-2.68; P=0.034). CONCLUSIONS: Intraoperative use of dexmedetomidine is associated with unwarranted haemodynamic effects, longer postanaesthesia care unit length of stay, and higher costs, without preventive effects on emergence delirium.

Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Impact of Anesthetic Exposures on the Neurocognitive Profiles of Pediatric Brain Tumor Survivors: A New Direction for Research and Multidisciplinary Collaboration.

Primary brain tumors are the most commonly diagnosed solid tumors in children, and pediatric brain tumor survivors experience lasting, pervasive deficits of neurocognitive functioning. Repeated exposure to anesthetic drugs is a necessary component not only of surgical resection but also of multimodal cancer care for the youngest patients with brain tumors. The potential for anesthetic neurotoxicity to worsen neurocognitive outcomes in this vulnerable group, therefore, warrants our attention and further study through multi-disciplinary collaboration. This review discusses neurocognitive functioning in pediatric brain tumor survivors, highlighting the findings of a recent study of children with tumors of the posterior fossa which identified treatment-related risk factors for neurocognitive difficulties, with those undergoing multimodal therapies (eg, chemotherapy and irradiation) experiencing the greatest deficits compared with healthy controls. The role of anesthetic neurotoxicity in long-term outcomes among pediatric brain tumor survivors is also reviewed.

Memory Problems in Children With Congenital Heart Disease: A Narrative Review.

INTRODUCTION: Care for congenital heart diseases (CHD) has improved significantly over the past several decades, and children with CHD are now surviving into adulthood. Cognitive and behavioral problems affect children with CHD more than healthy peers. A review of performance on neuropsychological memory tasks has not been reported. We aimed to summarize the published literature on memory problems in people with CHD. METHODS: We searched Pubmed, Medline, and PsycINFO from January 1, 1986 to March 22, 2022 to reflect modern care for people with CHD. Our inclusion criteria were randomized controlled trials or observational studies that included children with CHD older than age 3 years, which reported the results of at least 1 neuropsychological test of memory in the CHD group. Our exclusion criteria were studies that included heart transplant recipients and studies that included children who required extracorporeal membrane oxygenation. RESULTS: Thirty-one studies that met our inclusion criteria and avoided exclusion criteria were included in this review. Several studies reported deficits in the subdomains of short-term and long-term memory and visual and verbal memory, though we found substantial heterogeneity across studies. The most likely subdomain to be affected in children with CHD appears to be short-term visual memory. CONCLUSIONS: There is likely an increased risk of memory problems for children and adults with CHD. We were unable to quantify the risk of memory problems due to the heterogeneity of published studies. Future research should make efforts to account for confounding variables and standardize outcome measures.

Children with Congenital Heart Disease Show Increased Behavioral Problems Compared to Healthy Peers: A Systematic Review and Meta-Analysis.

Millions of children and adults are living with congenital heart disease (CHD). Their risk for behavioral problems has not been the subject of a meta-analysis. We performed a systematic review and meta-analysis of measures of behavioral problems in people born with CHD compared to peers without CHD. We searched Pubmed, CINAHL, Embase, PsycInfo, and the Cochrane Library from January 1, 1986 to November 15, 2021. We included studies that reported a measure of behavioral problems in patients with CHD in children and adults older than 3 years of age. We screened 26,343 search results, and 24 studies met inclusion criteria. The quality of evidence was generally low. Subjects with CHD had a small increase in internalizing problems [standardized mean difference (SMD): 0.198, p = 0.02] and total behavior problems (SMD: 0.287, p = 0.013), but no difference in externalizing behavioral problems. There was significant heterogeneity in all three domains of behavior problems analyzed, and it could not be explained by variables such as age, severity, assessor, or assessment tool. There are small increases in parent- and self-reported overall behavioral problems and internalizing problems in patients with CHD compared to healthy controls. Wide confidence intervals in the meta-analyses leave open the possibility that certain factors may increase the risk of behavioral problems in this group, and future studies with important attention paid to potential confounders may help identify risk factors.

Multireference configuration interaction study of the predissociation of C2 via its F1Πu state.

Photodissociation is one of the main destruction pathways for dicarbon (C2) in astronomical environments, such as diffuse interstellar clouds, yet the accuracy of modern astrochemical models is limited by a lack of accurate photodissociation cross sections in the vacuum ultraviolet range. C2 features a strong predissociative F1Πu-X1Σg + electronic transition near 130 nm originally measured in 1969; however, no experimental studies of this transition have been carried out since, and theoretical studies of the F1Πu state are limited. In this work, potential energy curves of excited electronic states of C2 are calculated with the aim of describing the predissociative nature of the F1Πu state and providing new ab initio photodissociation cross sections for astrochemical applications. Accurate electronic calculations of 56 singlet, triplet, and quintet states are carried out at the DW-SA-CASSCF/MRCI+Q level of theory with a CAS(8,12) active space and the aug-cc-pV5Z basis set augmented with additional diffuse functions. Photodissociation cross sections arising from the vibronic ground state to the F1Πu state are calculated by a coupled-channel model. The total integrated cross section through the F1Πu v = 0 and v = 1 bands is 1.198 × 10-13 cm2 cm-1, giving rise to a photodissociation rate of 5.02 × 10-10 s-1 under the standard interstellar radiation field, much larger than the rate in the Leiden photodissociation database. In addition, we report a new 21Σu + state that should be detectable via a strong 21Σu +-X1Σg + band around 116 nm.

Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes: A Systematic Review and Meta-analysis.

Importance: Clinical studies of neurodevelopmental outcomes after anesthetic exposure have evaluated a range of outcomes with mixed results. Objective: To examine via meta-analyses the associations between exposure to general anesthesia and domain-specific neurodevelopmental outcomes in children. Data Sources: PubMed/MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library were searched from inception to August 31, 2021. Study Selection: Inclusion criteria were exposures to procedures requiring general anesthesia at younger than 18 years and evaluation of long-term neurodevelopmental function after exposure. Studies lacking unexposed controls or focused on children with major underlying comorbidities were excluded. Data Extraction and Synthesis: Extracted variables included effect size; hazard, risk, or odds ratio; number of exposures; procedure type; major comorbidities; age of exposure and assessment; presence of unexposed controls; and study design. Studies were independently reviewed by 2 coders, and review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were pooled using a random-effects model. Main Outcomes and Measures: The main outcomes were standardized mean differences (SMD) for scores in the neurodevelopmental domains of academics, behavioral problems, cognition, executive function, general development, language, motor function, nonverbal reasoning, social cognition, and hazard and risk of neurodevelopmental disorder diagnoses. Results: A total of 31 studies contributed data for meta-analysis. For each of the assessed neurodevelopmental domains, the numbers of children evaluated ranged from 571 to 63 315 exposed and 802 to 311 610 unexposed. Children with any exposure (single or multiple) had significantly worse behavioral problems scores, indicating more behavioral problems (SMD, -0.10; 95% CI, -0.18 to -0.02; P = .02), and worse scores in academics (SMD, -0.07; 95% CI -0.12 to -0.01; P = .02), cognition (SMD, -0.03; 95% CI, -0.05 to 0.00; P = .03), executive function (SMD, -0.20; 95% CI, -0.32 to -0.09; P < .001), general development (SMD, -0.08; 95% CI, -0.13 to -0.02; P = .01), language (SMD, -0.08; 95% CI, -0.14 to -0.02; P = .01), motor function (SMD, -0.11; 95% CI, -0.21 to -0.02; P = .02), and nonverbal reasoning (SMD, -0.15; 95% CI, -0.27 to -0.02; P = .02). Higher incidences of neurodevelopmental disorder diagnoses were also reported (hazard ratio, 1.19; 95% CI, 1.09 to 1.30; P < .001; risk ratio, 1.81; 95% CI, 1.25 to 2.61; P = .002). Conclusions and Relevance: These findings support the hypothesis that associations between anesthetic exposure during childhood and subsequent neurodevelopmental deficits differ based on neurodevelopmental domain.

COVID-19: A Catalyst for Transforming Randomized Trials.

The coronavirus disease 2019 (COVID-19) pandemic incited a global clinical trial research agenda of unprecedented speed and high volume. This expedited research activity in a time of crisis produced both successes and failures that offer valuable learning opportunities for the scientific community to consider. Successes include the implementation of large adaptive and pragmatic trials as well as burgeoning efforts toward rapid data synthesis and open science principles. Conversely, notable failures include: (1) inadequate study design and execution; (2) data reversal, fraud, and retraction; and (3) research duplication and waste. Other challenges that became highlighted were the need to find unbiased designs for investigating complex, nonpharmaceutical interventions and the use of routinely collected data for outcomes assessment. This article discusses these issues juxtaposing the COVID-19 trials experience against trials in anesthesiology and other fields. These lessons may serve as a positive catalyst for transforming future clinical trial research.

COVID-19 in Pediatric Patients: A Systematic Review.

INTRODUCTION: The coronavirus disease (COVID)-19 pandemic has been an enormous global health burden, resulting in hundreds of millions of documented infections and more than 3 million deaths. Increasing reports characterizing the effects of COVID-19 in pediatric populations have been published during the course of the pandemic. We performed a systematic review to assess the scope of diagnosis, treatment, and management of COVID-19 in pediatric patients. MATERIALS AND METHODS: We searched the Cochrane Database of Systematic Reviews, PubMed, CINAHL, and Embase for studies published between January 1, 2020, and May 1, 2021. Each result was screened by 2 authors independently, and discordant findings were adjudicated by a third party. Data extracted included demographic data, symptom data, and clinical data including mortality, severe illness, laboratory data, radiologic data, and treatment. Bias assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies. RESULTS: We found a total of 16,266 search results, and we accepted 63 manuscripts into the review. The quality of evidence was low. It was difficult to estimate the risk of mortality in pediatric patients with COVID-19 given the quality of the evidence, but overall it is likely below 1%. The most common symptoms in symptomatic pediatric COVID-19 patients were fever (58%) and cough (50%). There was a high proportion of asymptomatic infection (65%). DISCUSSION: Pediatric COVID-19 infection is mild and frequently asymptomatic. There is a low risk of severe illness or death in children who contract COVID-19. High-quality studies should be conducted to develop best practices for prevention, diagnosis, and management of symptomatic illness.

Executive functions in children with heart disease: a systematic review and meta-analysis.

CONTEXT: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. OBJECTIVE: To examine differences in executive functions in individuals with CHD compared to healthy controls. DATA SOURCES: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. STUDY SELECTION: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. DATA EXTRACTION: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. RESULTS: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: -0.628 (-0.726, -0.531) for cognitive flexibility and set shifting, -0.469 (-0.606, -0.333) for inhibition, -0.369 (-0.466, -0.273) for working memory, -0.334 (-0.546, -0.121) for planning/problem solving, -0.361 (-0.576, -0.147) for summary measures, and -0.444 (-0.614, -0.274) for reporter-based measures (p < 0.001). LIMITATIONS: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. CONCLUSIONS: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

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.

SmartTots Outcomes Workshop 2017: Notes From a Round Table Discussion About Outcome Measures.

An important element of designing research studies is the selection of appropriate outcome measures to ensure that the question posed is properly answered given the evidence. The selection of outcome measures is especially important when tackling complex, interdisciplinary problems, where appropriate outcome measures may not be as simple as a blood test or a laboratory value. One such area of study is the research into neurodevelopmental outcomes after early exposure to anesthetic agents. Concern has arisen recently that certain anesthetic agents may be toxic to the developing brain; a public-private partnership, SmartTots, was formed in conjunction with the Food and Drug Administration and various stakeholders to develop safe anesthetic regimens for neonates and infants who require surgery. However, as research has progressed, questions have arisen regarding the best outcome measures to use in order to detect a true effect, as well as the optimal window in which to measure. These issues were discussed in a round table meeting during the SmartTots meeting in September 2017, and a summary of the discussion is presented here.

Engaging Stakeholders to Promote Safe Anesthesia and Sedation Care in Young Children.

An important aspect of any research endeavor is engaging various stakeholders to work toward the common goal of pushing knowledge forward about the question at hand. Research into pediatric anesthetic neurotoxicity could benefit greatly from interventions designed to improve the efforts and dedication of government agencies, pharmaceutical companies, research communities, and most importantly, patients. The Pediatric Anesthesia Neurodevelopment Assessment (PANDA) symposium is a biennial meeting where updates in research in the field are presented, and issues relevant to the community are discussed in round table discussions. Here, we summarize a discussion that took place at the 2018 meeting regarding new methods of engaging various stakeholders, as well as perspectives from other stakeholders. Topics discussed included an online portal to better reach patients, experiences with a public-private partnership, steps by the National Institutes of Health to improve engagement with research and improve the dissemination of results, and the experiences of the United States Food and Drug Administration attempting to improve stakeholder engagement following the passage of a new law to promote drug development. The round table discussion provided interesting insights into a critical research topic, and shared first-hand experience of attempts to improve engagement with a variety of stakeholders.

Branching Ratios of the N(2D03/2) and N(2D05/2) Spin-Orbit States Produced in the State-Selected Photodissociation of N2 Determined Using Time-Sliced Velocity-Mapped-Imaging Photoionization Mass Spectrometry (TS-VMI-PI-MS).

Branching ratios for N(2D03/2) and N(2D05/2) produced by predissociation of state selected excited nitrogen molecules in the vacuum ultraviolet region have been measured for the first time. The quantum numbers of the excited nitrogen molecule are defined by selective excitation of the nitrogen molecule in the Franck-Condon region from the ground electronic, 1Σg+, vibrational, v″, and rotational, J″ state to an excited Eu', v', J' state with a tunable vacuum ultraviolet, VUV1, laser. The neutral atoms produced by predissociation from this excited state are then selectively ionized with a second tunable VUV2 laser. Measurement of the relative populations of these two atoms formed in their spin-orbit states defines the quantum states for the atomic products. This means that the wave functions of the initial state and knowledge of the relative yields define all the experimental parameters for this series of unimolecular reactions. The ions formed by VUV2 are mass analyzed with a time-of-flight mass spectrometer and detected with a time slice velocity ion imaging mass spectrometer. In this manner, we can determine the recoil velocity associated with the predissociation process. Two different techniques are used to determine the spin-orbit ratios, namely, resonant VUV photoionization (RVUV-PI) spectroscopy and total kinetic energy release (TKER) spectroscopy determined from the image produced when the atoms are selectively ionized by VUV2 in the interaction region. The TKER spectra obtained from the lines at 110 296.25 and 110 304.96 cm-1 that couple to a newly discovered autoionization line at 129 529.4255 ± 0.0015 cm-1 prove that the lines observed in this region originate from the N(2D03/2) and N(2D05/2) atoms. Two other lines in this region at 110 286.20 and 110 299.89 cm-1 originate from the nitrogen N(4S03/2) that is photoionized in a 1+ 1 VUV-UV resonant multiphoton ionization process. The spin-orbit branching ratios have been evaluated for valence and Rydberg electronic excited states from 104 129.4 to 118 772.1 cm-1, and it shows that they are independent of the rotational and vibrational quantum numbers. They are not appreciably affected by the symmetry properties of the wave function in the Franck-Condon region of the excited states. In the energy region below 117 153.8 cm-1 the pathways at long internuclear distances appear to determine [N(2D03/2)]/[N(2D05/2)] branching ratios of ∼0.38, ∼0.62, and ∼1.04. At higher energies, TKER and RVUV-PI spectroscopy have been used to show that the average fraction of the N(2D03/2) and N(2D05/2) atoms produced in the spin-allowed channels that produce two N(2D0J) is 0.85 versus 0.15 for spin-forbidden channels. The importance and need for this information for comparison with theory and applications in astrochemistry are briefly discussed.