Azithromycin reduces inflammation-amplified hypoxic-ischemic brain injury in neonatal rats.

Background: Systemic inflammation amplifies neonatal hypoxic-ischemic (HI) brain injury. Azithromycin (AZ), an antibiotic with anti-inflammatory properties, improves sensorimotor function and reduces tissue damage after neonatal rat HI brain injury. The objective of this study was to determine if AZ is neuroprotective in two neonatal rat models of inflammation-amplified HI brain injury.

Repurposing azithromycin for neonatal neuroprotection.

Background: Inflammation contributes to neonatal hypoxic-ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available antibiotic with anti-inflammatory properties, in a neonatal rodent hypoxic-ischemic brain injury model.

Methods: Seven-day-old rats underwent right carotid artery ligation followed by 90-min 8% oxygen exposure; this procedure elicits quantifiable left forepaw functional impairment and right cerebral hemisphere damage.

Relationships between three and twelve month outcomes in children enrolled in the therapeutic hypothermia after pediatric cardiac arrest trials.

Aim: To inform design aspects of future trials by comparing 3 and 12-month neurobehavioural outcomes in children enrolled in Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-Of-Hospital and In-Hospital (THAPCA-OH, THAPCA-IH) trials.

Methods: The THAPCA trials evaluated two targeted temperature management interventions (hypothermia, 32.0-34.

One-year cognitive and neurologic outcomes in survivors of paediatric extracorporeal cardiopulmonary resuscitation.

Objective: To describe one-year cognitive and neurologic outcomes among extracorporeal cardiopulmonary resuscitation (ECPR) survivors enrolled in the Therapeutic Hypothermia after Paediatric Cardiac Arrest In-Hospital (THAPCA-IH) trial; and compare outcomes between survivors who received ECPR, later extracorporeal membrane oxygenation (ECMO), or no ECMO.

Methods: All children recruited to THAPCA-IH were comatose post-arrest. Neurobehavioral function was assessed by caregivers using the Vineland Adaptive Behaviour Scales, 2nd edition (VABS-II) at pre-arrest baseline and 12 months post-arrest.

Cardiac Arrest Outcomes in Children With Preexisting Neurobehavioral Impairment.

Objectives: To describe survival and 3-month and 12-month neurobehavioral outcomes in children with preexisting neurobehavioral impairment enrolled in one of two parallel randomized clinical trials of targeted temperature management.

Design: Secondary analysis of Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital and Out-of-Hospital trials data.

Setting: Forty-one PICUs in the United States, Canada, and United Kingdom.

Pediatric out-of-hospital cardiac arrest: Time to goal target temperature and outcomes.

Aim: Although recent out-of-hospital cardiac arrest (CA) trials found no benefits of hypothermia versus normothermia targeted temperature management, preclinical models suggest earlier timing of hypothermia improves neuroprotective efficacy. This study investigated whether shorter time to goal temperature was associated with better one-year outcomes in the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital Trial.

Methods: Patients were classified by tertiles of time to attain assigned goal temperature range (32-34°C or 36-37.

Targeted Temperature Management in Pediatric Neurocritical Care.

Targeted temperature management encompasses a range of clinical interventions to regulate systemic temperature, and includes both induction of varying degrees of hypothermia and fever prevention ("targeted normothermia"). Targeted temperature management plays a key role in the contemporary management of critically ill neonates and children with acute brain injury. Yet, many unanswered questions remain regarding optimal temperature management in pediatric neurocritical care.

Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials.

Background: Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes.

Neuropsychological Outcomes of Children 1 Year After Pediatric Cardiac Arrest: Secondary Analysis of 2 Randomized Clinical Trials.

Importance: Little is known about neuropsychological outcomes of children who survived pediatric cardiac arrest (CA).

Objective: To describe the neuropsychological outcomes of CA survivors enrolled in the Therapeutic Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) and Out-of-Hospital (THAPCA-OH) trials and compare the results with the primary outcome measure for these trials.

Design, Setting, And Participants: Secondary analysis of 222 CA survivors aged 1 to 18 years who received chest compressions for 2 minutes or more, remained comatose and required mechanical ventilation after return of circulation, and were enrolled in targeted temperature-management trials from 41 pediatric intensive care units.

Sedation and Analgesia Influence Electroencephalography Monitoring in Pediatric Neurocritical Care.

Objectives: We assessed neuroactive medication use in critically ill children who require neurological consultation and evaluated the associations between administration of these medications and continuous electroencephalography (cEEG) utilization and seizure frequency.

Methods: We evaluated exposure to sedatives, analgesics, anesthetics, and paralytics in consecutive patients (0 days to 18 years) for whom neurological consultation was requested in three intensive care units (ICUs) [neonatal (NICU), pediatric (PICU), and cardiothoracic (PCTU)]) at one children's hospital. We assessed cEEG usage and seizure incidence in relation to drug exposure.

Neurologic outcomes in pediatric cardiac arrest survivors enrolled in the THAPCA trials.

Objective: To implement a standardized approach to characterize neurologic outcomes among 12-month survivors in the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials.

Methods: Two multicenter trials enrolled children age 48 hours to 18 years who remained comatose after cardiac arrest (CA) occurring out-of-hospital (THAPCA-OH, NCT00878644) or in-hospital (THAPCA-IH, NCT00880087); patients were randomized to therapeutic hypothermia or therapeutic normothermia. The primary outcome, survival with favorable 12-month neurobehavioral outcome (Vineland Adaptive Behavior Scales [VABS-II]), did not differ between treatment groups in either trial.

Neurobehavioural outcomes in children after In-Hospital cardiac arrest.

Aim: Children who remain comatose after in-hospital cardiac arrest (IH-CA) resuscitation are at risk for poor neurological outcome. We report results of detailed neurobehavioural testing in paediatric IH-CA survivors, initially comatose after return of circulation, and enrolled in THAPCA-IH, a clinical trial that evaluated two targeted temperature management interventions (hypothermia, 33.0 °C or normothermia, 36.

Drug Treatment of Seizures and Epilepsy in Newborns and Children.

The mainstay of treatment of childhood epilepsy is to administer antiepileptic drugs (AEDs). This article provides an overview of the clinical approach to drug treatment of childhood epilepsy, focusing on general principles of therapy and properties of recently introduced medications. Initiation and cessation of therapy, adverse medication effects, drug interactions, indications for the various AEDs, and off-label use of AEDs are reviewed.

Pediatric cardiac arrest due to drowning and other respiratory etiologies: Neurobehavioral outcomes in initially comatose children.

Aim: To describe the 1-year neurobehavioral outcome of survivors of cardiac arrest secondary to drowning, compared with other respiratory etiologies, in children enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial.

Methods: Exploratory analysis of survivors (ages 1-18 years) who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation (ROC). Participants recruited from 27 pediatric intensive care units in North America received targeted temperature management [therapeutic hypothermia (33°C) or therapeutic normothermia (36.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

Background: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited.

Methods: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.

Functional Outcome Trajectories After Out-of-Hospital Pediatric Cardiac Arrest.

Objectives: To analyze functional performance measures collected prospectively during the conduct of a clinical trial that enrolled children (up to age 18 yr old), resuscitated after out-of-hospital cardiac arrest, who were at high risk of poor outcomes.

Design: Children with Glasgow Motor Scale score less than 5, within 6 hours of resuscitation, were enrolled in a clinical trial that compared two targeted temperature management interventions (THAPCA-OH, NCT00878644). The primary outcome, 12-month survival with Vineland Adaptive Behavior Scale, second edition, score greater or equal to 70, did not differ between groups.

Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications.

Objective: To describe outcomes and complications in the drowning subgroup from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial.

Design: Exploratory post hoc cohort analysis.

Setting: Twenty-four PICUs.

Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study.

Objective: To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG).

Study Design: We prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks' postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at 7 US tertiary care pediatric centers following the guidelines of the American Clinical Neurophysiology Society for cEEG for at-risk neonates.

Neurobehavioral Outcomes in Children After Out-of-Hospital Cardiac Arrest.

Objective: This study examined 12-month neurobehavioral outcomes in children who survived out-of-hospital cardiac arrest (OH-CA), were comatose after resuscitation, and were enrolled in a clinical trial to evaluate targeted temperature management to hypothermia (33.0°C) or normothermia (36.8°C) (Therapeutic Hypothermia after Pediatric Cardiac Arrest, Out-of-Hopsital [THAPCA-OH]; NCT00878644).

Maternal high-fat diet influences outcomes after neonatal hypoxic-ischemic brain injury in rodents.

The typical US diet has >30% calories from fat; yet, typical laboratory diets contain 17% calories from fat. This disparity could confound the clinical relevance of findings in cerebral ischemia models. We compared outcomes after neonatal brain injury in offspring of rat dams fed standard low-fat chow (17% fat calories) or a higher fat diet (34% fat calories) from day 7 of pregnancy.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

Background: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.

Methods: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

Objectives: The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development.

Design/setting: Consensus assessment of potential outcomes and evaluation timepoints.

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

Objective: To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials.

Design: Multicenter randomized controlled trials.

Setting: Pediatric intensive care and cardiac ICUs in the United States and Canada.