Biological and Procedural Predictors of Outcome in the Stroke Preclinical Assessment Network (SPAN) Trial.

BACKGROUND: The SPAN trial (Stroke Preclinical Assessment Network) is the largest preclinical study testing acute stroke interventions in experimental focal cerebral ischemia using endovascular filament middle cerebral artery occlusion (MCAo). Besides testing interventions against controls, the prospective design captured numerous biological and procedural variables, highlighting the enormous heterogeneity introduced by the multicenter structure that might influence stroke outcomes. Here, we leveraged the unprecedented sample size achieved by the SPAN trial and the prospective design to identify the biological and procedural variables that affect experimental stroke outcomes in transient endovascular filament MCAo. METHODS: The study cohort included all mice enrolled and randomized in the SPAN trial (N=1789). Mice were subjected to 60-minute MCAo and followed for a month. Thirteen biological and procedural independent variables and 4 functional (weight loss and 4-point neuroscore on days 1 and 2, corner test on days 7 and 28, and mortality) and 3 tissue (day 2, magnetic resonance imaging infarct volumes and swelling; day 30, magnetic resonance imaging tissue loss) outcome variables were prospectively captured. Multivariable regression with stepwise elimination was used to identify the predictors and their effect sizes. RESULTS: Older age, active circadian stage at MCAo, and thinner and longer filament silicone tips predicted higher mortality. Older age, larger body weight, longer anesthesia duration, and longer filament tips predicted worse neuroscores, while high-fat diet and blood flow monitoring predicted milder neuroscores. Older age and a high-fat diet predicted worse corner test performance. While shorter filament tips predicted more ipsiversive turning, longer filament tips appeared to predict contraversive turning. Age, sex, and weight interacted when predicting the infarct volume. Older age was associated with smaller infarcts on day 2 magnetic resonance imaging, especially in animals with larger body weights; this association was most conspicuous in females. High-fat diet also predicted smaller infarcts. In contrast, the use of cerebral blood flow monitoring and more severe cerebral blood flow drop during MCAo, longer anesthesia, and longer filament tips all predicted larger infarcts. Bivariate analyses among the dependent variables highlighted a disconnect between tissue and functional outcomes. CONCLUSIONS: Our analyses identified variables affecting endovascular filament MCAo outcome, an experimental stroke model used worldwide. Multiple regression refuted some commonly reported predictors and revealed previously unrecognized associations. Given the multicenter prospective design that represents a sampling of real-world conditions, the degree of heterogeneity mimicking clinical trials, the large number of predictors adjusted for in the multivariable model, and the large sample size, we think this is the most definitive analysis of the predictors of preclinical stroke outcome to date. Future multicenter experimental stroke trials should standardize or at least ensure a balanced representation of the biological and procedural variables identified herein as potential confounders.

Trends in analgesia-sedation of pediatric patients receiving I-131 MIBG in the pediatric intensive care unit: A report from the Pediatric Health Information System database.

BACKGROUND: Children with neuroblastoma receiving I-131 metaiodobenzylguanidine (MIBG) therapy require sedation-analgesia for strict radiation safety precautions during MIBG infusion and clearance. We evaluated the sedation-analgesia trends of patients undergoing MIBG therapy using the Pediatric Health Information System (PHIS) database. MATERIALS AND METHODS: Retrospective data from 476 patient encounters from the PHIS from 2010 to 2019. RESULTS: Total 240/476 (50.45%) children evaluated were under 6 years of age. Compared to 2010, in 2018 there was a decrease in benzodiazepine infusion use (60% vs. 40%, p < .04), as well as a decrease in use of opiate infusion (35% vs. 25%, p < .001). Compared to 2010, in 2018 we report an increase in the use of ketamine (from 5% to 10%, p < .002), as well as an increase in dexmedetomidine use (0% vs. 30%, p < .001). Dexmedetomidine was the most used medication in the 0-3 years age group compared to children older than 3 years of age (14.19% vs. 5.80%, p < .001). Opiate was the most used medication in children greater than 3 years compared to the 0-3-year age group (36.23 vs. 23.87, p < .05). CONCLUSION: Using PHIS data, we discovered considerable variability in the medications used for sedation in patients undergoing MIBG therapy. Although benzodiazepines and opioids were the most used agents, there was a trend toward decreasing use of benzodiazepines and opioids in these patients. Furthermore, there has been an increasing trend in the use of dexmedetomidine and ketamine.

Utilization of immediate extubation in a multidisciplinary pathway for pediatric liver transplantation associated with improved postoperative outcomes.

BACKGROUND: Immediate extubation is becoming more common in liver transplantation. However, limited data exist on how to identify pediatric patients with potential for successful immediate extubation and how this intervention may affect recovery. METHODS: This retrospective review evaluated patients who underwent liver transplantation from 2015 to 2021 at Children's Healthcare of Atlanta. Preoperative status and intraoperative management were evaluated and compared. Outcomes comprised thrombosis, surgical reexploration, retransplantation, as well as reintubation, high flow nasal cannula (HFNC) usage, postoperative infection, the length of stay (LOS), and mortality. RESULTS: A total of 173 patients were analyzed, with 121 patients (69.9%) extubated immediately. The extubation group had older age (median 4.0 vs 1.25 years, p = .048), lower PELD/MELD (28 vs. 34, p = .03), decreased transfusion (10.2 vs. 41.7 mL/kg, p < .001), shorter surgical time (332 vs. 392 min, p < .001), and primary abdominal closure (81% vs. 40.4%, p < .001). Immediate extubation was associated with decreased HFNC (0.21 vs. 0.71 days, p = .02), postoperative infection (9.9% vs. 26.9%, p = .007), mortality (0% vs. 5.8%, p = .036), and pediatric intensive care unit LOS (4.7 vs. 11.4 days, p < .001). The complication rate was lower in the extubation group (24.8% vs. 36.5%), but not statistically significant. CONCLUSIONS: Approximately 70% of patients were able to be successfully extubated immediately, with only 2.5% requiring reintubation. Those immediately extubated had decreased need for HFNC, lower infection rates, shorter LOS, and decreased mortality. Our results show that with proper patient selection and a multidisciplinary approach, immediate extubation allows for improved recovery without increased respiratory complications after pediatric liver transplantation.

Trends in sedation-analgesia practices in pediatric liver transplant patients admitted postoperatively to the pediatric intensive care unit: An analysis of data from the pediatric health information system (PHIS) database.

BACKGROUND: Children admitted to the pediatric intensive care unit (PICU), after liver transplantation, frequently require analgesia and sedation in the immediate postoperative period. Our objective was to assess trends and variations in sedation and analgesia used in this cohort. METHODS: Multicenter retrospective cohort study using the Pediatric Health Information System from 2012 to 2022. RESULTS: During the study period, 3963 patients with liver transplantation were admitted to the PICU from 32 US children's hospitals with a median age of 2 years [IQR: 0.00, 10.00]. 54 percent of patients received mechanical ventilation (MV). Compared with patients without MV, those with MV were more likely to receive morphine (57% vs 49%, p < .001), fentanyl (57% vs 44%), midazolam (45% vs 31%), lorazepam (39% vs. 24%), dexmedetomidine (38% vs 30%), and ketamine (25% vs 12%), all p < .001. Vasopressor usage was also higher in MV patients (22% vs. 35%, p < .001). During the study period, there was an increasing trend in the utilization of dexmedetomidine and ketamine, but the use of benzodiazepine decreased (p < .001). CONCLUSION: About 50% of patients who undergo liver transplant are placed on MV in the PICU postoperatively and receive a greater amount of benzodiazepines in comparison with those without MV. The overall utilization of dexmedetomidine and ketamine was more frequent, whereas the administration of benzodiazepines was less during the study period. Pediatric intensivists have a distinctive opportunity to collaborate with the liver transplant team to develop comprehensive guidelines for sedation and analgesia, aimed at enhancing the quality of care provided to these patients.

Pediatric Sedation/Anesthesia for MRI: Results From the Pediatric Sedation Research Consortium.

BACKGROUND: Magnetic resonance imaging (MRI) is the most common imaging procedure requiring sedation/anesthesia in children. Understanding adverse events associated with sedation/anesthesia is important in making decisions regarding MRI vs. other imaging modalities. No large studies have evaluated the practice of pediatric sedation/anesthesia for MRI by a variety of pediatric specialists. PURPOSE: Utilize a large pediatric sedation database to characterize the patients and adverse events associated with sedation/anesthesia for pediatric MRI. STUDY TYPE: Retrospective analysis of prospectively collected data. SUBJECTS: The Pediatric Sedation Research Consortium (PSRC) has 109,947 entries for sedations for MRI from November 10, 2011 through December 18, 2017. ASSESSMENT: Patient demographics, sedative medications, interventions, and adverse events are described. Associations with adverse events were assessed. Trends in sedative medications used over time are examined. STATISTICAL TESTS: Descriptive statistics, Chi-Squared and Fisher's Exact tests for categorical variables, logistic regression and assessment of trend using logistic regression and other method. RESULTS: A total of 109,947 MRI-related sedations were examined. Most subjects (66.2%) were 5 years old or younger. Seizure or other neurologic issue prompted MRI in 63.7% of cases. Providers responsible for sedation/anesthesia included intensivists (49.3%), emergency medicine physicians (28.2%), hospitalists (10.2%), and anesthesiologists (9.8%). The most commonly used sedative agent was propofol (89.1%). The most common airway intervention was supplemental oxygen (71.7%), followed by head/airway repositioning (20.6%). Airway-related adverse events occurred in 8.4% of patients. Serious adverse events occurred in only 0.06% of patients, including three cases of cardiac arrest. No mortality was recorded. There was a statistically significant increase in the use of dexmedetomidine over time. DATA CONCLUSIONS: Overall, adverse event rates were low. Sedation/anesthesia with propofol infusion and natural airway was the most common method used by this varied group of sedation providers. The use of dexmedetomidine increased over time. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Outcomes of children with life-threatening status asthmaticus requiring isoflurane therapy and extracorporeal life support.

BACKGROUND: Severe, refractory asthma is a life-threatening emergency that may be treated with isoflurane and extracorporeal life support. The objective of this study was to describe the clinical response to isoflurane and outcomes after discharge of children who received isoflurane and/or extracorporeal life-support for near-fatal asthma. METHODS: This was a retrospective descriptive study using electronic medical record data from two pediatric intensive care units within a single healthcare system in Atlanta, GA. RESULTS: Forty-five children received isoflurane, and 14 children received extracorporeal life support, 9 without a trial of isoflurane. Hypercarbia and acidosis improved within four hours of starting isoflurane. Four children died during the index admission for asthma. Twenty-seven percent had a change in Functional Status Score of three or more points from baseline to PICU discharge. Patients had median percent predicted FEV1 and FEV1/FVC ratios pre- and post-bronchodilator values below normal pediatric values. CONCLUSION: Children who received isoflurane and/or ECLS had a high frequency of previous PICU admission and intubation. Improvement in ventilation and acidosis occurred within the first four hours of starting isoflurane. Children who required isoflurane or ECLS may develop long-lasting deficits in their functional status. Children with near-fatal asthma are a high-risk group and require improved follow-up in the year following PICU discharge.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Management of esophageal button battery ingestions: resource utilization and outcomes.

PURPOSE: Institutions are adopting the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines for pediatric esophageal button battery ingestion (EBBI). Our objective was to evaluate the guidelines' impact on in-hospital resource utilization and short-term clinical outcomes in hemodynamically stable patients after endoscopic battery removal. METHODS: A single-center retrospective review of all EBBI admissions from 2010 to 2020. Patients were divided into two groups based on adoption of national guidelines: pre-guideline (2010-2015) and post-guideline (2016-2020). RESULTS: Sixty-five patients were studied (pre-guideline n = 23; post-guideline n = 42). Compared with pre-guideline, post-guideline use of magnetic resonance imaging (MRI) increased (2/23 [8.7%]; 30/42 [71.4%]; p < 0.001). Post-guideline increases resulted for median days (IQR) receiving antibiotics (0 [0, 4]; 6 [3, 8]; p = 0.01), total pediatric intensive care unit admission (0 [0, 1]; 3 [0, 6]; p < 0.001), and total hospital length of stay (5 [2, 11]; 11.5 [4, 17]; p = 0.02). Two patients in the post-guideline group had delayed presentations despite normal imaging: one with TEF and one with aorto-esophageal fistula. All survived to discharge. CONCLUSION: In EBBI cases managed using the consensus based NASPHAGN guidelines, we report increased resource utilization without improved patient outcomes. Further research should evaluate post-guideline costs and resource utilization.

Severe acute respiratory syndrome coronavirus 2 infection and critically ill children.

PURPOSE OF REVIEW: Amidst an ongoing pandemic, the delineation of the pediatric consequence of infection from the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus is emerging. This review summarizes available pediatric data and covers the aspects of epidemiology, critical illness with acute infection [coronavirus disease 2019 (COVID-19)], the discovered multi-inflammatory syndrome in children (MIS-C), and management options. RECENT FINDINGS: The available data from the source of the initial viral transmission and then through Europe, Africa, and the Western Hemisphere identifies important aspects of the SARS-CoV2 pandemic: 1) Pediatric infection occurs commonly, is likely underestimated, and transmission patterns remain incompletely described, 2) Pediatric patients suffer multiple end-organ injuries but COVID-19 is not the same prevalence in terms of severity as in adults, 3) MIS-C is a novel and life-threatening manifestation of exposure to the virus, 4) Management using a combination of supportive care, standard practice intensive care management, and anti-inflammatory agents is associated with recovery, 5) Long-term sequelae of viral exposure is unknown at this time. SUMMARY: Emerging evidence suggests pediatric patients are at risk for severe and life-threatening effects of exposure to SARS-CoV2. As the pandemic continues, further research is warranted - particularly as a vaccine is not yet available for use in children.

Long-term evidence of neonatal anaesthesia neurotoxicity linked to behavioural phenotypes in monkeys: where do we go from here?

Whether anaesthesia exposure early in life leads to brain damage with long-lasting structural and behavioural consequences in primates has not been conclusively determined. A study in the British Journal of Anaesthesia by Neudecker and colleagues found that 2 yr after early anaesthesia exposure, monkeys exhibited signs of chronic astrogliosis which correlate with behavioural deficits. Given the increasing frequency of exposure to anaesthetics in infancy in humans, clinical trials are greatly needed to understand how sedative/anaesthetic agents may be impacting brain and behaviour development.

Sedatives used in children to obtain head CT in the emergency department.

OBJECTIVES: Children in the emergency department who require computerized tomography (CT) of the head often are given sedative medications to facilitate completion of the study with adequate imaging. A prior study found the two most common medications used to obtain head CT in children were pentobarbital and chloral hydrate; however, these medications have become less popular. We hypothesized that there was variability in medication choice amongst providers in the emergency department and there has been a change in the preferred sedatives used in the last decade. METHODS: We conducted a retrospective multicenter cross-sectional study of children 0-18 years old who received a medication with sedative properties and underwent head CT while in the emergency department from 2007 to 2018, using the Pediatric Health Information System (PHIS) database. The primary outcome measure was the frequency of administration of drugs within an individual sedative class. RESULTS: We analyzed 24,418 patient encounters, of whom 53% received an opioid and 41% received a benzodiazepine. There were statistically significant decreases in the use of barbiturates, chloral hydrate, anti-emetic sedatives, and opioids, while increases in barbiturate combination drugs, benzodiazepines and dexmedetomidine were observed over the study period. The majority of medications were administered parenterally. CONCLUSION: There is wide variability in sedatives used in children to obtain head CT and the preferred drugs have shifted over the last decade.

The Use of Intranasal Dexmedetomidine and Midazolam for Sedated Magnetic Resonance Imaging in Children: A Report From the Pediatric Sedation Research Consortium.

OBJECTIVE: The objective of this study was to describe the use of intranasal dexmedetomidine (IN DEX) for sedated magnetic resonance imaging (MRI) examinations in children. The use of IN DEX for MRI in children has not been well described in the literature. MATERIALS AND METHODS: The Pediatric Sedation Research Consortium (PSRC) is a collaborative and multidisciplinary group of sedation practitioners dedicated to understanding and improving the process of pediatric sedation. We searched the 2007 version of the PSRC database solely for instances in which IN DEX was used for MRI diagnostic studies. Patients receiving intravenous medications were excluded. Patient demographics, IN DEX dose, adjunct medications and dose, as well as procedure completion, complications, interventions, and monitoring providers were analyzed. RESULTS: A total of 224 sedation encounters were included in our primary analysis. There were no major adverse events. Most sedations (88%) required no intervention. Registered nurses were the monitoring provider in over 99% of cases. The median (interquartile range) dose of dexmedetomidine was 3 (2.5-3) mcg/kg. Adjunctive midazolam was used in 219/224 (98%) of the cases. All procedures were completed. CONCLUSIONS: This report from the PSRC shows that IN DEX in combination with midazolam is an effective medication regimen for children who require an MRI with sedation.

Carbon monoxide attenuates vasospasm and improves neurobehavioral function after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating form of hemorrhagic stroke and is a serious medical condition caused by bleeding usually due to a ruptured aneurysm. Oxidative stress and inflammation from hemoglobin and heme released from lysed red blood cells are some postulated causes of vasospasm during SAH, which could lead to delayed cerebral ischemia. At low amounts, carbon monoxide (CO) gas may be neuroprotective through anti-inflammation, anti-cell death, and restoration of normal blood flow. Hence, this study focuses on a noninvasive strategy to treat SAH by using CO as a therapeutic medical gas. Mice were treated with 250 ppm CO or air for 1h started at 2h after SAH. Various anatomical and functional outcomes were monitored at 1 and 7d after SAH. CO decreased neurological deficit score (47.4 ±â€¯10.5%) and increased activity (30.0 ±â€¯9.1%) and stereotypic counts (261.5 ±â€¯62.1%) at 7d. There was a significant increase in lumen area/wall thickness ratio in the middle cerebral artery (173.5 ±â€¯19.3%), which tended to increase in the anterior cerebral artery (25.5 ±â€¯4.3%) at 7d. This is the first report to demonstrate that CO minimizes delayed SAH-induced neurobehavioral deficits, which suggests that post-treatment with CO gas or CO-donors can be further tested as a potential therapy against SAH.

Unscheduled Procedural Sedation: A Multidisciplinary Consensus Practice Guideline.

The American College of Emergency Physicians (ACEP) organized a multidisciplinary effort to create a clinical practice guideline specific to unscheduled, time-sensitive procedural sedation, which differs in important ways from scheduled, elective procedural sedation. The purpose of this guideline is to serve as a resource for practitioners who perform unscheduled procedural sedation regardless of location or patient age. This document outlines the underlying background and rationale, and issues relating to staffing, practice, and quality improvement.

Evaluating the Need for Pediatric Procedural Sedation Training in Pediatric Critical Care Medicine Fellowship.

OBJECTIVES: Pediatric procedural sedation has been increasingly performed by pediatric intensivists over the past decade. Pediatric Critical Care Medicine fellowship guidelines do not specify how fellows obtain proficiency in pediatric procedural sedation. We sought to survey the state of pediatric procedural sedation training during fellowship and whether fellows thought it was sufficient. DESIGN: A 21-question survey gathered data on pediatric procedural sedation training provided to Pediatric Critical Care Medicine fellows. Surveys were sent to fellowship directors with instructions to distribute to second- and third-year fellows or recent graduates. Over 2 months, up to three e-mail reminders were sent to fellowship directors whose program had not completed at least one survey. SUBJECTS: Senior fellows and graduates of 65 active Accreditation Council for Graduate Medical Education Pediatric Critical Care Medicine fellowship programs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-five percent of fellowship programs (42/65) returned at least one response. Ninety senior fellows and 27 recent graduates responded. Of respondents, 38% received pediatric procedural sedation training during the fellowship, and 32% reported mandatory training. Nine percent of programs used simulation. Although 61% who received training felt adequately prepared to perform pediatric procedural sedation, 25% needed additional preceptorship to sedate independently. Nearly one third (31%) reported that completion of a predetermined number of cases was required to sedate independently. Forty-eight percent reported a minimum number of cases was required for hospital credentialing. Nearly 45% were allowed to perform pediatric procedural sedation off the unit after receiving credentials. When asked if inadequate pediatric procedural sedation training would be a deterrent to applying for a position that included pediatric procedural sedation, 8.6% replied yes, 52.6% replied no, and 38.8% replied they were unsure. CONCLUSIONS: Pediatric procedural sedation lacks a clearly defined training pathway. Most fellows find pediatric procedural sedation a valuable skill set. We propose that all Pediatric Critical Care Medicine fellows receive training that includes pediatric procedural sedation critical incident simulation and cases performed outside the PICU to establish proficiency.

Radiologic Imaging in Trauma Patients with Cervical Spine Immobilization at a Pediatric Trauma Center.

BACKGROUND: Pediatric trauma patients with cervical spine (CS) immobilization using a cervical collar often require procedural sedation (PS) for radiologic imaging. The limited ability to perform airway maneuvers while CS immobilized with a cervical collar is a concern for emergency department (ED) staff providing PS. OBJECTIVE: To describe the use of PS and analgesia for radiologic imaging acquisition in pediatric trauma patients with CS immobilization. METHODS: Retrospective medical record review of all trauma patients with CS immobilization at a high-volume pediatric trauma center was performed. Patient demographics, imaging modality, PS success, sedative and analgesia medications, and adverse events were analyzed. Patients intubated prior to arrival to the ED were excluded. RESULTS: A total of 1417 patients with 1898 imaging encounters met our inclusion criteria. A total of 398 patients required more than one radiographic imaging procedure. The median age was 8 years (range 3.8-12.75 years). Computed tomography of the head was used in 974 of the 1898 patients (51.3%). A total of 956 of the 1898 patients (50.4%) required sedatives or analgesics for their radiographic imaging, with 875 (91.5%) requiring a single sedative or analgesic agent, and 81 (8.5%) requiring more than one medication. Airway obstruction was the most common adverse event, occurring in 5 of 956 patients (0.3%). All imaging procedures were successfully completed. CONCLUSION: Only 50% of CS immobilized, nonintubated patients required a single sedative or analgesic medication for their radiologic imaging. Procedural success was high, with few adverse events.

Tetrahydrocurcumin ameliorates homocysteine-mediated mitochondrial remodeling in brain endothelial cells.

Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in most neurodegenerative disorders. This dysfunction is highly correlated with mitochondrial dynamics such as fusion and fission. However, there are no strategies to prevent Hcy-induced mitochondrial remodeling. Tetrahydrocurcumin (THC) is an anti-inflammatory and anti-oxidant compound. We hypothesized that THC may ameliorates Hcy-induced mitochondria remodeling in mouse brain endothelial cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or absence of THC. Cell viability and autophagic cell death were measured with MTT and MDC staining assay. Reactive oxygen species (ROS) production was determined using DCFH-DA staining by confocal microscopy. Autophagy flux was assessed using a conventional GFP-microtubule-associated protein 1 light chain 3 (LC3) dot assay. Interaction of phagophore marker LC-3 with mitochondrial receptor NIX was observed by confocal imaging. Mitochondrial fusion and fission were evaluated by western blot and RT-PCR. Our results demonstrated that Hcy resulted in cell toxicity in a dose-dependent manner and supplementation of THC prevented the detrimental effects of Hcy on cell survival. Furthermore, Hcy also upregulated fission marker (DRP-1), fusion marker (Mfn2), and autophagy marker (LC-3). Finally, we observed that Hcy activated mitochondrial specific phagophore marker (LC-3) and co-localized with the mitochondrial receptor NIX, as viewed by confocal microscopy. Pretreatment of bEnd3 with THC (15 µM) ameliorated Hcy-induced oxidative damage, mitochondrial fission/fusion, and mitophagy. Our studies strongly suggest that THC has beneficial effects on mitochondrial remodeling and could be developed as a potential therapeutic agent against hyperhomocysteinemia (HHcy) induced mitochondrial dysfunction.

Reducing Childhood Admissions to the PICU for Poisoning (ReCAP2) by Predicting Unnecessary PICU Admissions After Acute Intoxication.

OBJECTIVE: To derive and validate clinical prediction models to identify children at low risk of clinically significant intoxications for whom intensive care admission is unnecessary. DESIGN: Retrospective review of data in the National Poison Data Systems from 2011 to 2014 and Georgia Poison Center cases from July to December 2016. SETTING: United States PICUs and poison centers participating in the American Association of Poison Control Centers from 2011 to 2016. PATIENTS: Children 18 years and younger admitted to a United States PICU following an acute intoxication. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary study outcome was the occurrence of clinically significant intoxications defined a priori as organ system-based clinical effects that require intensive care monitoring and interventions. We analyzed 70,364 cases. Derivation (n = 42,240; 60%) and validation cohorts (n = 28,124; 40%) were randomly selected from the eligible population and had similar distributions of clinical effects and PICU interventions. PICU interventions were performed in 1,835 children (14.1%) younger than 6 years, in 374 children (15.4%) 6-12 years, and in 4,446 children (16.5%) 13 years and older. We developed highly predictive models with an area under the receiver operating characteristic curve of 0.834 (< 6 yr), 0.771 (6-12 yr), and 0.786 (≥13 yr), respectively. For predicted probabilities of less than or equal to 0.10 in the validation cohorts, the negative predictive values were 95.4% (< 6 yr), 94.9% (6-12 yr), and 95.1% (≥ 13 yr). An additional 700 patients from the Georgia Poison Center were used to validate the model and would have reduced PICU admission by 31.4% (n = 110). CONCLUSIONS: These validated models identified children at very low risk of clinically significant intoxications for whom pediatric intensive care admission can be avoided. Application of this model using Georgia Poison Center data could have resulted in a 30% reduction in PICU admissions following intoxication.

Frequency of Desaturation and Association With Hemodynamic Adverse Events During Tracheal Intubations in PICUs.

OBJECTIVES: Oxygen desaturation during tracheal intubation is known to be associated with adverse ICU outcomes in critically ill children. We aimed to determine the occurrence and severity of desaturation during tracheal intubations and the association with adverse hemodynamic tracheal intubation-associated events. DESIGN: Retrospective cohort study as a part of the National Emergency Airway Registry for Children Network's quality improvement project from January 2012 to December 2014. SETTING: International PICUs. PATIENTS: Critically ill children younger than 18 years undergoing primary tracheal intubations in the ICUs. INTERVENTIONS: tracheal intubation processes of care and outcomes were prospectively collected using standardized operational definitions. We defined moderate desaturation as oxygen saturation less than 80% and severe desaturation as oxygen saturation less than 70% during tracheal intubation procedures in children with initial oxygen saturation greater than 90% after preoxygenation. Adverse hemodynamic tracheal intubation-associated event was defined as cardiac arrests, hypo or hypertension requiring intervention, and dysrhythmia. MEASUREMENTS AND MAIN RESULTS: A total of 5,498 primary tracheal intubations from 31 ICUs were reported. Moderate desaturation was observed in 19.3% associated with adverse hemodynamic tracheal intubation-associated events (9.8% among children with moderate desaturation vs 4.4% without desaturation; p < 0.001). Severe desaturation was observed in 12.9% of tracheal intubations, also significantly associated with hemodynamic tracheal intubation-associated events. After adjusting for patient, provider, and practice factors, the occurrence of moderate desaturation was independently associated with hemodynamic tracheal intubation-associated events: adjusted odds ratio 1.83 (95% CI, 1.34-2.51; p < 0.001). The occurrence of severe desaturation was also independently associated with hemodynamic tracheal intubation-associated events: adjusted odds ratio 2.16 (95% CI, 1.54-3.04; p < 0.001). Number of tracheal intubation attempts was also significantly associated with the frequency of moderate and severe desaturations (p < 0.001). CONCLUSIONS: In this large tracheal intubation quality improvement database, we found moderate and severe desaturation are reported among 19% and 13% of all tracheal intubation encounters. Moderate and severe desaturations were independently associated with the occurrence of adverse hemodynamic events. Future quality improvement interventions may focus to reduce desaturation events.

Procedural sedation in children with autism spectrum disorders: A survey of current practice patterns of the society for pediatric sedation members.

BACKGROUND: Children with autism spectrum disorder are challenging to sedate because of communication, sensory, and behavioral challenges. AIMS: The aim of this survey was to determine how procedural sedation is provided to children with autism spectrum disorders and whether sedation programs have specialized protocols for procedural sedation of these children. METHODS: We surveyed physician Medical Directors of sedation programs who are members of the Society for Pediatric Sedation, asking about practice characteristics and resource utilization during procedural sedation of children with autism spectrum disorders. RESULTS: Of 58 directors, 47 (81%) responded. Of the programs surveyed, 53% were either a large university medical center and 40% were a freestanding children's hospital. Only (12/47, 25.5%) of the programs used an individualized autism coping plan. To accomplish procedural sedation in this study cohort, 36% of the programs used additional nurses, whereas a child life specialist was used in 55% of the programs surveyed. Only 28% of the centers allotted additional time to accommodate children with autism spectrum disorders. Distraction methods were used in 80% whereas restrains were used in 45% programs for were used most commonly for i.v. catheter placement. Propofol was the preferred agent for 70% of programs for imaging, while propofol + fentanyl was used by 66% of programs for painful procedures. Although 57% of directors reported that their program staff was extremely comfortable providing procedural sedation for children with autism spectrum disorder, 79% of the directors wanted more education about behavioral management strategies for procedural sedation of these children. CONCLUSION: Among the Society for Pediatric Sedation programs, significant institutional variation exists on the delivery of procedural sedation to children with autism spectrum disorders. A better understanding of resources required, standardization of behavioral management strategies and pharmacologic approaches, and protocol development may help optimize care to this vulnerable population.