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BACKGROUND The use of electronic clinical decision support (CDS) systems for pediatric critical care trials is rare. We sought to describe in detail the use of a CDS tool (Children's Hospital Euglycemia for Kids Spreadsheet [CHECKS]), for the management of hyperglycemia during the 32 multicenter Heart And Lung Failure-Pediatric Insulin Titration trial. RESEARCH QUESTION In critically ill pediatric patients who were treated with CHECKS, how was user compliance associated with outcomes; and what patient and clinician factors might account for the observed differences in CHECKS compliance? STUDY DESIGN AND METHODS During an observational retrospective study of compliance with a CDS tool used during a prospective randomized controlled trial, we compared patients with high and low CHECKS compliance. We investigated the association between compliance and blood glucose metrics. We describe CHECKS and use a computer interface analysis framework (the user, function, representation, and task analysis framework) to categorize user interactions. We discuss implications for future randomized controlled trials. RESULTS Over a 4.5-year period, 658 of 698 children were treated with the CHECKS protocol for ≥24 hours with a median of 119 recommendations per patient. Compliance per patient was high (median, 99.5%), with only 30 patients having low compliance (

OBJECTIVES: To describe the indications and thresholds for plasma and platelet transfusions for pediatric extracorporeal membrane oxygenation (ECMO), to compare responses to these transfusions and to describe institutional protocols directing their administration. DESIGN: Subgroup analysis of two prospective, observational studies paired with survey of sites who enrolled subjects into this cohort. SETTING: Fifty-one pediatric intensive care units in 13 countries. PATIENTS: Children (3 days to 16 years of age) were enrolled if they received a plasma or platelet transfusion while on ECMO during one of the predefined screening weeks. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Forty-eight children on ECMO received plasma transfusions and ninety received platelet transfusions. Sixty percent (29/48) of plasma transfusions and seventy-nine percent (71/90) of the platelet transfusions were given for prophylaxis of bleeding. The median (IQR) international normalized ratio (INR) prior to transfusion, known in 75% (36/48) of the patients, was 1.45 (1.20-1.85). The median (IQR) total platelet count (TPC) prior to transfusion, known in all of the patients, was 70 (52-90) x10(9)/L. The INR and TPC values prior to transfusion did not vary based on bleeding versus non-bleeding indications. The median (IQR) reduction in INR for mild coagulopathies (INR ≤ 2.0) was 0.1 (0.4-0), median (IQR) increase in fibrinogen was 0.2 (0.1 to 0.4) g/L and median increase in TPC was 34 (10-74) x10(9)/L. Through the course of their admission, children supported by ECMO received a total median (IQR) dose of 75 (36-159) mL/kg of plasma transfusions and 92 (42-239) mL/kg of platelet transfusions. Institutional protocols varied but provided guidance for platelet transfusions more commonly. CONCLUSIONS: Children supported by ECMO receive large volumes of plasma and platelet transfusions with some institutional guidance in the form of protocols, but significant variation in practice. Interventional studies are necessary to provide evidence to direct the transfusion of hemostatic products in children supported by ECMO.

OBJECTIVES Evaluate differences in tracheal intubation-associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in children with underlying cardiac disease. DESIGN Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children). SETTING Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016. PATIENTS Children with medical or surgical cardiac disease who underwent intubation in an ICU. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Our primary outcome was the rate of any adverse tracheal intubation-associated event. Secondary outcomes were severe tracheal intubation-associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo [interquartile range, 0-6 mo]) compared with noncardiac ICUs (median 3 mo [interquartile range, 1-11 mo]; p < 0.001). Tracheal intubation-associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54-1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52-0.97; p = 0.033). Rates of severe tracheal intubation-associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04-1.15; p = 0.002). CONCLUSIONS In children with underlying cardiac disease, rates of adverse tracheal intubation-associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models.

OBJECTIVES To describe the incidence of delirium in pediatric patients after cardiac bypass surgery and explore associated risk factors and effect of delirium on in-hospital outcomes. DESIGN Prospective observational single-center study. SETTING Fourteen-bed pediatric cardiothoracic ICU. PATIENTS One hundred ninety-four consecutive admissions following cardiac bypass surgery, 1 day to 21 years old. INTERVENTIONS Subjects were screened for delirium daily using the Cornell Assessment of Pediatric Delirium. MEASUREMENTS AND MAIN RESULTS Incidence of delirium in this sample was 49%. Delirium most often lasted 1-2 days and developed within the first 1-3 days after surgery. Age less than 2 years, developmental delay, higher Risk Adjustment for Congenital Heart Surgery 1 score, cyanotic disease, and albumin less than three were all independently associated with development of delirium in a multivariable model (all p < 0.03). Delirium was an independent predictor of prolonged ICU length of stay, with patients who were ever delirious having a 60% increase in ICU days compared with patients who were never delirious (p < 0.01). CONCLUSIONS In our institution, delirium is a frequent problem in children after cardiac bypass surgery, with identifiable risk factors. Our study suggests that cardiac bypass surgery significantly increases children's susceptibility to delirium. This highlights the need for heightened, targeted delirium screening in all pediatric cardiothoracic ICUs to potentially improve outcomes in this vulnerable patient population.

INTRODUCTION: A delicate balance of fluid status is needed for optimal management of ARDS Achieving optimal fluid balance is difficult in patients with disorders of fluid homeostasis such as diabetes insipidus (DI) There is little data on the use of Furosemide to aid in balancing fluid and electrolytes in patients with DI METHODS: Here we present an 11-year-old female with developmental delay, septo-optic dysplasia and central DI who required careful titration of a Vasopressin infusion in addition to IV Furosemide for successful management of fluid overload The patient was admitted to our Pediatric ICU with acute Sars-CoV2 infection, respiratory failure, and ARDS (PaO2/FiO2=120) On admission, she demonstrated high volume urine output and a serum sodium level of 156 mmol/L Her home subcutaneous Desmopressin was changed to a 0 5 mU/kg/hr Vasopressin infusion Despite this, her urine output continued to increase;a maximum of 4L urine was voided resulting in severe hypernatremia (serum sodium of 171 mmol/L) This change occurred despite a maximum Vasopressin infusion rate of 8 mU/kg/ hr along with simultaneous adjustments in both the sodium concentration and rate of administered IV fluids By the second day of hospitalization, a net positive fluid balance of 2 8L was noted and severe hypernatremia persisted (serum sodium of 160 mmol/L) Her ARDS continued (PaO2/FiO2 = 132) When her hypernatremia persisted into the third day of hospitalization, a trial IV Furosemide in addition to down-titrating Vasopressin was attempted This resulted in successful diuresis (net balanced fluid status of -497 L) along with resolution of hypernatremia (serum sodium fell gradually to138 mmol/L) Her ARDS improved and the patient was extubated on hospital day 10 RESULTS: The combination of IV Furosemide with Vasopressin infusion resulted in tailored diuresis and more controlled titration of serum sodium levels than adjustment in Vasopressin and fluids alone These results are in contradistinction to the published literature, which endorse the use of thiazide diuretics in managing DI ∗ This experience highlights the potential for loop diuretics to aid in establishing desired fluid and electrolyte status in managing patients with both DI and ARDS

IntroductionChildren with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.Materials and methodsWe sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.ResultsA total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; pConclusionsThe overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.

Objective To determine the prevalence of delirium in children who require extracorporeal membrane oxygenation. Design Prospective observational longitudinal cohort study. Setting Urban academic cardiothoracic ICU. Patients All consecutive admissions to the cardiothoracic ICU who required venoarterial extracorporeal membrane oxygenation support. Interventions Daily delirium screening with the Cornell Assessment for Pediatric Delirium. Measurements and main results Eight children required extracorporeal membrane oxygenation during the study period, with a median extracorporeal membrane oxygenation duration of 202 hours (interquartile range, 99-302). All eight children developed delirium during their cardiothoracic ICU stay. Seventy-two days on extracorporeal membrane oxygenation were included in the analysis. A majority of patient days on extracorporeal membrane oxygenation were spent in coma (65%). Delirium was diagnosed during 21% of extracorporeal membrane oxygenation days. Only 13% of extracorporeal membrane oxygenation days were categorized as delirium free and coma free. Delirium screening was successfully completed on 70/72 days on extracorporeal membrane oxygenation (97%). Conclusions In this cohort, delirium occurred in all children who required venoarterial extracorporeal membrane oxygenation. It is likely that this patient population has an extremely high risk for delirium and will benefit from routine screening in order to detect and treat delirium sooner. This has potential to improve both short- and long-term outcomes.

Objectives To describe promoters and barriers to implementation of an airway safety quality improvement bundle from the perspective of interdisciplinary frontline clinicians and ICU quality improvement leaders. Design Mixed methods. Setting Thirteen PICUs of the National Emergency Airway Registry for Children network. Intervention Remote or on-site focus groups with interdisciplinary ICU staff. Two semistructured interviews with ICU quality improvement leaders with quantitative and qualitative data-based feedbacks. Measurements and main results Bundle implementation success (compliance) was defined as greater than or equal to 80% use for tracheal intubations for 3 consecutive months. ICUs were classified as early or late adopters. Focus group discussions concentrated on safety concerns and promoters and barriers to bundle implementation. Initial semistructured quality improvement leader interviews assessed implementation tactics and provided recommendations. Follow-up interviews assessed degree of acceptance and changes made after initial interview. Transcripts were thematically analyzed and contrasted by early versus late adopters. Median duration to achieve success was 502 days (interquartile range, 182-781). Five sites were early (median, 153 d; interquartile range, 146-267) and eight sites were late adopters (median, 783 d; interquartile range, 773-845). Focus groups identified common "promoter" themes-interdisciplinary approach, influential champions, and quality improvement bundle customization-and "barrier" themes-time constraints, competing paperwork and quality improvement activities, and poor engagement. Semistructured interviews with quality improvement leaders identified effective and ineffective tactics implemented by early and late adopters. Effective tactics included interdisciplinary quality improvement team involvement (early adopter: 5/5, 100% vs late adopter: 3/8, 38%; p = 0.08); ineffective tactics included physician-only rollouts, lack of interdisciplinary education, lack of data feedback to frontline clinicians, and misconception of bundle as research instead of quality improvement intervention. Conclusions Implementation of an airway safety quality improvement bundle with high compliance takes a long time across diverse ICUs. Both early and late adopters identified similar promoter and barrier themes. Early adopter sites customized the quality improvement bundle and had an interdisciplinary quality improvement team approach.

Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality.Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%.PICUs participating in NEAR4KIDS.All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed.Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58-229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1-7 yr and 18% for 8-17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p0.001) and longer PICU stay (14 vs 11 d; p0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p0.003), longer PICU stay (15 vs 12 d; p0.035), and PICU mortality (19.9% vs 9.6%; p0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4-21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24-2.60; p = 0.002), after adjusted for patient confounders.Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.

Few recent studies have assessed the epidemiology of health care-associated infections (HAIs) in the pediatric population after cardiac surgery. A retrospective cohort study was performed to assess the epidemiology of several types of HAIs in children 18 years of age or younger undergoing cardiac surgery from July 2010 to June 2012. Potential pre-, intra-, and postoperative risk factors, including adherence to the perioperative antibiotic prophylaxis regimen at the authors' hospital, were assessed by multivariable analysis using Poisson regression models. Microorganisms associated with HAIs and their susceptibility patterns were described. Overall, 634 surgeries were performed, 38 (6 %) of which were complicated by an HAI occurring within 90 days after surgery. The HAIs included 7 central line-associated bloodstream infections (CLABSIs), 12 non-CLABSI bacteremias, 6 episodes of early postoperative infective endocarditis (IE), 9 surgical-site infections (SSIs), and 4 ventilator-associated pneumonias (VAPs). Mechanical ventilation (rate ratio [RR] 1.07 per day; 95 % confidence interval [CI] 1.03-1.11; p = 0.0002), postoperative transfusion of blood products (RR 3.12; 95 %, CI 1.38-7.06; p = 0.0062), postoperative steroid use (RR 3.32; 95 % CI 1.56-7.02; p = 0.0018), and continuation of antibiotic prophylaxis longer than 48 h after surgery (RR 2.56; 95 % CI 1.31-5.03; p = 0.0062) were associated with HAIs. Overall, 66.7 % of the pathogens associated with SSIs were susceptible to cefazolin, the perioperative antibiotic prophylaxis used by the authors' hospital. In conclusion, HAIs occurred after 6 % of cardiac surgeries. Bacteremia and CLABSI were the most common. This study identified several potentially modifiable risk factors that suggest interventions. Further studies should assess the role of improving adherence to perioperative antibiotic prophylaxis, the age of transfused red blood cells, and evidence-based guidelines for postoperative steroids.

To describe the differences in goals for their usual practice for various medical therapies from a number of international centers for children with severe traumatic brain injury.A survey of the goals from representatives of the international centers.Thirty-two pediatric traumatic brain injury centers in the United States, United Kingdom, France, and Spain.None.None.A survey instrument was developed that required free-form responses from the centers regarding their usual practice goals for topics of intracranial hypertension therapies, hypoxia/ischemia prevention and detection, and metabolic support. Cerebrospinal fluid diversion strategies varied both across centers and within centers, with roughly equal proportion of centers adopting a strategy of continuous cerebrospinal fluid diversion and a strategy of no cerebrospinal fluid diversion. Use of mannitol and hypertonic saline for hyperosmolar therapies was widespread among centers (90.1% and 96.9%, respectively). Of centers using hypertonic saline, 3% saline preparations were the most common but many other concentrations were in common use. Routine hyperventilation was not reported as a standard goal and 31.3% of centers currently use PbO(2) monitoring for cerebral hypoxia. The time to start nutritional support and glucose administration varied widely, with nutritional support beginning before 96 hours and glucose administration being started earlier in most centers.There were marked differences in medical goals for children with severe traumatic brain injury across our international consortium, and these differences seemed to be greatest in areas with the weakest evidence in the literature. Future studies that determine the superiority of the various medical therapies outlined within our survey would be a significant advance for the pediatric neurotrauma field and may lead to new standards of care and improved study designs for clinical trials.

Invasive mechanical ventilation is often not an option for children with acute respiratory infections in developing countries. An alternative is continuous positive airway pressure (CPAP). The authors evaluated the effectiveness of CPAP in children presenting with acute respiratory distress in a developing country.A randomized, controlled trial was conducted in 4 rural hospitals in Ghana. Children, 3 months to 5 years of age, presenting with tachypnea and intercostal or subcostal retractions or nasal flaring were randomly assigned to receive CPAP immediately or 1 hour after presentation. CPAP was applied by locally trained nurses. The primary outcome measure was change in respiratory rate at 1 hour.The study was stopped after the enrollment of 70 subjects because of a predetermined stop value of P.001. Mean respiratory rate of children who received immediate CPAP fell by 16 breaths/min (95% CI 10-21) in the first hour compared with no change in children who had CPAP delayed by 1 hour (95% CI -2 to +5). Thirty-five of the patients had a positive malaria blood smear. There were 3 deaths as a result of severe malaria. No major complications of CPAP use were noted.CPAP decreases respiratory rate in children with respiratory distress compared with children not receiving CPAP. The technology was successfully used by local nurses. No complications were associated with its use. CPAP is a relatively low-cost, low-technology that is a safe method to decrease respiratory rate in children with nonspecific respiratory distress.

BACKGROUND: Tracheal intubation is an important intervention to stabilize critically ill and injured children. Provider training level has been associated with procedural safety and outcomes in the neonatal intensive care settings. We hypothesized that tracheal intubation success and adverse tracheal intubation–associated events are correlated with provider training level in the PICU. METHODS: A prospective multicenter observational cohort study was performed across 15 PICUs to evaluate tracheal intubation between July 2010 to December 2011. All data were collected by using a standard National Emergency Airway Registry for Children reporting system endorsed as a Quality Improvement project of the Pediatric Acute Lung Injury and Sepsis Investigator network. Outcome measures included first attempt success, overall success, and adverse tracheal intubation–associated events. RESULTS: Reported were 1265 primary oral intubation encounters by pediatric providers. First and overall attempt success were residents (37%, 51%), fellows (70%, 89%), and attending physicians (72%, 94%). After adjustment for relevant patient factors, fellow provider was associated with a higher rate of first attempt success (odds ratio [OR], 4.29; 95% confidence interval [CI], 3.24–5.68) and overall success (OR, 9.27; 95% CI, 6.56–13.1) compared with residents. Fellow (versus resident) as first airway provider was associated with fewer tracheal intubation associated events (OR, 0.42; 95% CI, 0.31–0.57). CONCLUSIONS: Across a broad spectrum of PICUs, resident provider tracheal intubation success is low and adverse associated events are high, compared with fellows. More intensive pediatric resident procedural training is necessary before “live” tracheal intubations in the intensive care setting.

Tight glycemic control in critically ill children is controversial. The benefits of controlling hyperglycemia may be offset by the risk of hypoglycemia on the immature brain. Both age and severity of illness may influence the risks and benefits of tight glycemic control. We hypothesize that rates of hypoglycemia (blood glucose60 mg/dL) and hyperglycemia (blood glucose150 mg/dL) in children will correlate with age and illness severity.Retrospective chart review.Thirty-two-bed university-affiliated pediatric intensive care unit.Children19 yrs old admitted between January and September 2006.None.We recorded all blood glucose measurements for up to 10 days of each pediatric intensive care unit visit and assessed rates of hypoglycemia and hyperglycemia based on age, medical vs. surgical therapy, length of stay, therapeutic intervention (Therapeutic Intervention Scoring System), and illness severity (Pediatric Risk of Mortality III). A total of 8853 blood glucose values in 616 patients were recorded. Spontaneous hypoglycemia was noted in 18.8% of patients1 yr compared with 5.1% to 11.3% of patients in older age groups. Hyperglycemia occurred in 47% of patients1 yr, which increased to 58.9% in patients 13-18 yrs. Rates of hypoglycemia were not affected by medical/surgical status. Surgical patients had an increased risk of hyperglycemia. Rates of hypo- and hyperglycemia increased with higher Pediatric Risk of Mortality III, Therapeutic Intervention Scoring System, length of stay, and days of mechanical ventilation. Increased rates of hypo-/hyperglycemia were observed in patients who died.The youngest patients are at higher risk for spontaneous hypoglycemia, whereas hyperglycemia occurs more often in the older ages. Higher rates of hypo-/hyperglycemia were noted in sicker patients and in those requiring more therapeutic interventions. Our results suggest that special consideration should be given to the safety of the youngest patients given their higher risk of hypoglycemia if an investigation of tight glycemic control is performed.

The Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study investigates the potential neurotoxicity of anesthetics in the pediatric population. At a recent symposium, a panel of nonsurgical physicians from the disciplines of radiology, neurology, cardiology, and critical care discussed the role anesthesia plays in their respective practices. To execute diagnostic studies and/or therapeutic interventions in each of these disciplines, general anesthesia is oftentimes required for pediatric patients. Given recent publications in the literature suggesting the potential for neurotoxicity following anesthesia in pediatric patients, physicians, parents, and other stakeholders are now challenged to continue to balance safety with efficacy in caring for children. This paper summarizes the panelist presentations and the ensuing discussion at the 2014 PANDA symposium.

We report that Sh3rf2, a homologue of the pro-apoptotic scaffold POSH (Plenty of SH3s), acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway. siRNA-mediated knockdown of Sh3rf2 promotes apoptosis of neuronal PC12 cells, cultured cortical neurons, and C6 glioma cells. This death appears to result from activation of JNK signaling. Loss of Sh3rf2 triggers activation of JNK and its target c-Jun. Also, apoptosis promoted by Sh3rf2 knockdown is inhibited by dominant-negative c-Jun as well as by a JNK inhibitor. Investigation of the mechanism by which Sh3rf2 regulates cell survival implicates POSH, a scaffold required for activation of pro-apoptotic JNK/c-Jun signaling. In cells lacking POSH, Sh3rf2 knockdown is unable to activate JNK. We further find that Sh3rf2 binds POSH to reduce its levels by a mechanism that requires the RING domains of both proteins and that appears to involve proteasomal POSH degradation. Conversely, knockdown of Sh3rf2 promotes the stabilization of POSH protein and activation of JNK signaling. Finally, we show that endogenous Sh3rf2 protein rapidly decreases following several different apoptotic stimuli and that knockdown of Sh3rf2 activates the pro-apoptotic JNK pathway in neuronal cells. These findings support a model in which Sh3rf2 promotes proteasomal degradation of pro-apoptotic POSH in healthy cells and in which apoptotic stimuli lead to rapid loss of Sh3rf2 expression, and consequently to stabilization of POSH and JNK activation and cell death. On the basis of these observations, we propose the alternative name POSHER (POSH-eliminating RING protein) for the Sh3rf2 protein.

Simulation training has been used to integrate didactic knowledge, technical skills, and crisis resource management for effective orientation and patient safety. We hypothesize multi-institutional simulation-based training for first year pediatric critical care (PCC) fellows is feasible and effective.Descriptive, educational intervention study.The simulation facility at the host institution.A multicentered simulation-based orientation training "boot camp" for first year PCC fellows was held at a large simulation center. Immediate posttraining evaluation and 6-month follow-up surveys were distributed to participants.A novel simulation-based orientation training for first year PCC fellows was facilitated by volunteer faculty from seven institutions. The two and a half day course was organized to cover common PCC crises. High-fidelity simulation was integrated into each session (airway management, vascular access, resuscitation, sepsis, trauma/traumatic brain injury, delivering bad news). Twenty-two first year PCC fellows from nine fellowship programs attended, and 13 faculty facilitated, for a total of 15.5 hours (369 person-hours) of training. This consisted of 2.75 hours for whole group didactic sessions (17.7%), 1.08 hours for a small group interactive session (7.0%), 4.67 hours for task training (30.1%), and 7 hours for training (45.2%) with high-fidelity simulation and crisis resource management. A "train to success" approach with repetitive practice of critical assessment and interventional skills yielded higher scores in training effectiveness in the end-of-course evaluation. A follow-up survey revealed this training was highly effective in improving clinical performance and self-confidence.The first PCC orientation training integrated with simulation was effective and logistically feasible. The train to success concept with repetitive practice was highly valued by participants. Continuation and expansion of this novel multi-institutional training is planned.

Background Chlorhexidine gluconate–impregnated dressings have become widely adopted as a means to reduce the risk for catheter-associated bloodstream infections. These dressings release antiseptic under occlusion onto the skin surrounding catheter insertion sites. Although chlorhexidine gluconate is a known cause of contact dermatitis, the phenotypic range of this adverse effect of chlorhexidine gluconate–impregnated dressings in critically ill patients has not been described. Observations We report 7 cases of erosive irritant contact dermatitis due to chlorhexidine gluconate–impregnated transparent dressings. Six of these patients were children (age range, 4 months to 2 years); the adult was a critically ill 62-year-old man. Four patients were immunosuppressed after solid organ transplant and all were receiving blood pressure support at the time of this reaction. The insertion sites of femoral catheters were involved in all but 1 case; 3 catheter sites were involved in the adult patient. Results of extensive infectious workups were negative. All lesions resolved with discontinuation of the chlorhexidine gluconate–containing dressings, local wound care, and alternative antimicrobial dressings. Conclusions Erosive contact dermatitis is an underrecognized complication of chlorhexidine gluconate–impregnated dressings. Health care providers should be aware of this risk, particularly in young children and immunosuppressed and/or critically ill patients, who may be more susceptible to the irritant effects of these dressings. When the dressings are used, patients should be monitored closely for skin breakdown.

Neutrophils accumulate during the acute inflammatory response to brain injury, but their role in the injury process remains controversial. We tested the hypothesis that neutrophils contribute to cerebral edema, tissue injury, and disturbed cerebral blood flow (CBF) (hyperemia or ischemia) during the first 24 h after traumatic brain injury. Wistar rats (n = 51) were injected with either vinblastine sulfate to induce neutropenia or the saline vehicle. Five days later, under halothane anesthesia, right hemispheric trauma was produced by weight drop (10 g x 5 cm) onto exposed dura. At 24 h after trauma, brain water (wet-dry weight), traumatic infarct size (percent of hemispheric section infarcted), or local CBF (lCBF, 14C-iodoantipyrine autoradiography) was assessed. Vinblastine treatment produced profound neutropenia on the day of trauma (absolute neutrophil count 0.024 +/- 0.008 x 10(9)/L vs 1.471 +/- 0.322 x 10(9)/L, p < 0.05 in neutropenic vs saline, respectively, mean +/- SEM). Neutropenia did not reduce the development of brain edema in the injured hemisphere (brain water 82.38 +/- 0.29% vs 82.73 +/- 0.37% in neutropenic and saline, respectively, mean +/- SEM) or traumatic infarct size (34.5 +/- 3.3% vs 33.2 +/- 2.1% in neutropenic vs saline respectively). In contrast, neutropenic rats exhibited 52%, 41%, and 57% reductions in lCBF in the frontal cortex, parietal cortex, and amygdala, respectively, of the injured hemisphere 24 h after trauma (all p < 0.05 vs nonneutropenic controls). These data suggest that neutrophils and the acute inflammatory process contribute to the level of CBF observed 24 h after trauma, but effects on edema or early posttraumatic infarct size could not be demonstrated.

Clinical studies suggest that children respond to head injury with more pronounced cerebral edema and hyperemia than do adults. We hypothesized that these age-related differences could be demonstrated in an animal model. Anesthetized and ventilated mature (2-3 months) and immature (3.5-4.5 weeks) male Wistar rats were traumatized by weight drop onto the exposed right parietal cortex. Trauma severity was adjusted to keep the ratio of force to brain weight constant. This resulted in an energy delivered to the brain of about 9 x 10(3) ergs.mm-2.g-1 brain in both age groups. Percent right hemispheric brain water (%RBW) was measured at 2, 24, 48, and 168 h posttrauma. Infarct area, intracranial pressure (ICP), and 14C-iodoantipyrine autoradiographic local cerebral blood flow (ICBF) were measured at 2 h or 24 h posttrauma. In mature rats, %RBW was unchanged at 2 h, but increased at 24 and 48 h (both p0.05). In immature rats, %RBW increased at 2 h and remained elevated at 24 and 48 h (all p0.05). Traumatic infarct area as a percent of hemispheric area at 24 h did not differ between age groups. In mature rats, at 2 h posttrauma ICBF was reduced (p0.05) in 16 of 17 regions but in only 4 of 17 regions in immature rats. ICBF as a percent of age-matched control values showed a greater reduction in mature vs immature rats in 9 of 16 regions (p0.05). ICP increased at 24 h posttrauma in both age groups. In immature rats posttrauma, brain water increased earlier and cerebral hypoperfusion was less marked than in mature rats.