Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.

Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (Css ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.

Validation of a pediatric bedside tool to predict time to death after withdrawal of life support.

AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths (age ≤ 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit (PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support (dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min (DPT30) and within 60 min (DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated. RESULTS: There were 8829 PICU admissions resulting in 132 (1.5%) deaths. Death followed withdrawal of life support in 70 patients (53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years (SD: 6.9), median time to death after withdrawal of life support was 25 min (range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients (59.6%) died within 30 min of withdrawal of life support and 52 (83.8%) died within 60 min. DPT30 scores ranged from -17 to 16. A DPT30 score ≥ -3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from -21 to 28. A DPT60 score ≥ -9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%. CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD.

Prevalence and Predictors of Adverse Events during Procedural Sedation Anesthesia-Outside the Operating Room for Esophagogastroduodenoscopy and Colonoscopy in Children: Age Is an Independent Predictor of Outcomes.

OBJECTIVES: Procedural sedation/anesthesia outside the operating room for a variety of procedures is well described with an overall low adverse event rate in certain settings. Adverse event associated with procedural sedation/anesthesia outside the operating room for gastrointestinal procedures have been described, albeit in small, single-center studies with wide variance in outcomes. Predictors of such outcomes are unclear. We aimed to estimate the prevalence of adverse event in children undergoing procedural sedation/anesthesia outside the operating room for esophagogastroduodenoscopy, colonoscopy, or both to identify predictors of adverse event. DESIGN/SETTING/PATIENTS: Retrospective analysis of Pediatric Sedation Research Consortium database, a large data repository of pediatric patients aged 21 years old or younger undergoing procedural sedation/anesthesia outside the operating room during September 2007 to November 2011. Twenty-two of the 40 centers provided data pertaining to the procedure of interest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome variable is any adverse event. Independent variables include: age (five groups), sex, American Societyof Anaesthesiologists status, procedure (esophagogastroduodenoscopy, colonoscopy, or both), provider responsible, medication used, location, and presence of coexisting medical conditions. Descriptive statistics used to summarize the data. Using multivariablelogistic regression model, odds ratio, 95% CI) were computed. A total of 12,030 procedures were performed (esophagogastroduodenoscopy, 7,970; colonoscopy, 1,378; and both, 2,682). A total of 96.9% of patients received propofol. Eighty-three percent were performed in a sedation unit. Prevalence of adverse event was 4.8%. The most common adverse event were persistent desaturations (1.5%), airway obstruction (1%), cough (0.9%), and laryngospasm (0.6%). No deaths or CPR occurred. Infants and children aged 5 years old or younger had a higher adverse event rate than older children (15.8%, 7.8% vs 4%). Regression analysis revealed age 5 years old or younger, American Society of Anaesthesiologists greater than or equal to 2, esophagogastroduodenoscopy ± colonoscopy, and coexisting medical conditions of obesity and lower airway disease were independent predictors of higher adverse event. CONCLUSIONS: Overall prevalence of any adverse event was 4.8%. Independent predictors of adverse events in procedural sedation/anesthesia outside the operating room in pediatric esophagogastroduodenoscopy/colonoscopy onoscopy were identified. Recognition of such risk factors may enable optimization of procedural sedation.

Hospital based emergency department visits attributed to child physical abuse in United States: predictors of in-hospital mortality.

OBJECTIVES: To describe nationally representative outcomes of physical abuse injuries in children necessitating Emergency Department (ED) visits in United States. The impact of various injuries on mortality is examined. We hypothesize that physical abuse resulting in intracranial injuries are associated with worse outcome. MATERIALS AND METHODS: We performed a retrospective analysis of the Nationwide Emergency Department Sample (NEDS), the largest all payer hospital based ED database, for the years 2008-2010. All ED visits and subsequent hospitalizations with a diagnosis of "Child physical abuse" (Battered baby or child syndrome) due to various injuries were identified using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes. In addition, we also examined the prevalence of sexual abuse in this cohort. A multivariable logistic regression model was used to examine the association between mortality and types of injuries after adjusting for a multitude of patient and hospital level factors. RESULTS: Of the 16897 ED visits that were attributed to child physical abuse, 5182 (30.7%) required hospitalization. Hospitalized children were younger than those released treated and released from the ED (1.9 years vs. 6.4 years). Male or female partner of the child's parent/guardian accounted for >45% of perpetrators. Common injuries in hospitalized children include- any fractures (63.5%), intracranial injuries (32.3%) and crushing/internal injuries (9.1%). Death occurred in 246 patients (13 in ED and 233 following hospitalization). Amongst the 16897 ED visits, 1.3% also had sexual abuse. Multivariable analyses revealed each 1 year increase in age was associated with a lower odds of mortality (OR = 0.88, 95% CI = 0.81-0.96, p < 0.0001). Females (OR = 2.39, 1.07-5.34, p = 0.03), those with intracranial injuries (OR = 65.24, 27.57-154.41, p<0.0001), or crushing/internal injury (OR = 4.98, 2.24-11.07, p<0.0001) had higher odds of mortality compared to their male counterparts. CONCLUSIONS: In this large cohort of physically abused children, younger age, females and intracranial or crushing/internal injuries were independent predictors of mortality. Identification of high risk cohorts in the ED may enable strengthening of existing screening programs and optimization of outcomes.