Performance of a Clinical Decision Support Tool to Identify PICU Patients at High Risk for Clinical Deterioration Objectives: To evaluate the translation of a paper high-risk checklist for PICU patients at risk of clinical deterioration to an automated clinical decision support tool. Design: Retrospective, observational cohort study of an automated clinical decision support tool, the PICU Warning Tool, adapted from a paper checklist to predict clinical deterioration events in PICU patients within 24 hours. Setting: Two quaternary care medical-surgical PICUs—The Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital Medical Center. Patients: The study included all patients admitted from July 1, 2014, to June 30, 2015, the year prior to the initiation of any focused situational awareness work at either institution. Interventions: We replicated the predictions of the real-time PICU Warning Tool by retrospectively querying the institutional data warehouse to identify all patients that would have flagged as high-risk by the PICU Warning Tool for their index deterioration. Measurements and Main Results: The primary exposure of interest was determination of high-risk status during PICU admission via the PICU Warning Tool. The primary outcome of interest was clinical deterioration event within 24 hours of a positive screen. The date and time of the deterioration event was used as the index time point. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of the performance of the PICU Warning Tool. There were 6,233 patients evaluated with 233 clinical deterioration events experienced by 154 individual patients. The positive predictive value of the PICU Warning Tool was 7.1% with a number needed to screen of 14 patients for each index clinical deterioration event. The most predictive of the individual criteria were elevated lactic acidosis, high mean airway pressure, and profound acidosis. Conclusions: Performance of a clinical decision support translation of a paper-based tool showed inferior test characteristics. Improved feasibility of identification of high-risk patients using automated tools must be balanced with performance. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by grant from an American Academy of Pediatrics Section of Critical Care Small Project Award and the Cincinnati Children’s Hospital Medical Center Place Outcomes Research Award. This work performed at The Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital Medical Center. Dr. Dewan’s institution received funding from American Academy of Pediatrics Section of Critical Care Small Project Award and Cincinnati Children’s Hospital Medical Center Place Outcomes Research Award, and she received support for article research from the National Institutes of Health (NIH). Dr. Muthu’s institution received funding from Agency for Healthcare Research and Quality (AHRQ) and Pew Charitable Trusts, and he received funding from Phrase Health. Dr. Brady’s institution received funding from AHRQ and NIH. Dr. Kirkendall received funding from American Academy of Pediatrics, Council on Clinical Information Technology (reimbursed for travel costs/hotels for executive meetings); Goodis, Thompson and Miller, PA (expert legal case review); and VigiLanz (licensing royalties for software). Dr. Wolfe received funding from Zoll Medical (speaking honoraria). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: maya.dewan@cchmc.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial Objectives: The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children. Design: Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial. Setting: Thirty-five PICUs. Patients: Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data. Interventions: Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time). Measurements and Main Results: Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001). Conclusions: In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes. The full list of Heart and Lung Failure-Pediatric Insulin Titration (HALFPINT) Study Investigators is listed in Appendix 1 (Supplemental Digital Content 4, http://links.lww.com/PCC/B107). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by grants (U01HL107681-MA/VN and U01HL108028-DW) from the National Heart, Lung, and Blood Institute; National Institutes of Health; and by endowed chairs (to Drs. Agus and Nadkarni); Heart and Lung Failure-Pediatric Insulin Titration ClinicalTrials.gov number: NCT01565941. Drs. Srinivasan, Hasbani, Allen, Typpo, Faustino, Wypij, and Agus received support for article research from the National Institutes of Health (NIH). Dr. Irving received funding for partial meeting registration fee for presentation faculty from American Society of Parenteral and Enteral Nutrition and Society of Critical Care Medicine. Dr. Allen’s institution received funding from NIH (through Boston Children’s Hospital and also through Oklahoma Medical Research Foundation) and the American Nurses Foundation (through Akron Children’s Hospital). Dr. Typpo’s institution received funding from NIH National Institute of Diabetes and Digestive and Kidney Diseases and Baxter. Dr. Cvijanovich’s institution received funding from Cincinnati Children’s Hospital Medical Center, Boston Children’s Hospital Medical Center, Children’s Hospital of Philadelphia, UCLA, and Seattle Children’s Hospital. Dr. Wypij’s institution received funding from the National Heart, Lung, and Blood Institute/NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: srinivasan@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Extracorporeal Membrane Oxygenation in Pediatric Pulmonary Hypertension Objective: To describe the epidemiology, critical care interventions, and mortality of children with pulmonary hypertension receiving extracorporeal membrane oxygenation. Design: Retrospective analysis of prospectively collected multicenter data. Setting: Data entered into the Extracorporeal Life Support Organization database between January 2007 and November 2018. Patients: Pediatric patients between 28 days and 18 years old with a diagnosis of pulmonary hypertension. Measurements and Main Results: Six hundred thirty-four extracorporeal membrane oxygenation runs were identified (605 patients). Extracorporeal membrane oxygenation support type was pulmonary (43.1%), cardiac (40.2%), and extracorporeal cardiopulmonary resuscitation (16.7%). The majority of cannulations were venoarterial (80.4%), and 30% had a pre-extracorporeal membrane oxygenation cardiac arrest. Mortality in patients with pulmonary hypertension was 51.3% compared with 44.8% (p = 0.001) in those without pulmonary hypertension. In univariate analyses, significant predictors of mortality included age less than 6 months and greater than 5 years; pre-extracorporeal membrane oxygenation cardiac arrest; pre-extracorporeal membrane oxygenation blood gas with pH less than 7.12, PaCO2 greater than 75, PaO2 less than 35, and arterial oxygen saturation less than 60%; extracorporeal membrane oxygenation duration greater than 280 hours; extracorporeal cardiopulmonary resuscitation; and extracorporeal membrane oxygenation complications including cardiopulmonary resuscitation, inotropic support, myocardial stun, tamponade, pulmonary hemorrhage, intracranial hemorrhage, seizures, other hemorrhage, disseminated intravascular coagulation, renal replacement therapy, mechanical/circuit problem, and metabolic acidosis. A co-diagnosis of pneumonia was associated with significantly lower odds of mortality (odds ratio, 0.5; 95% CI, 0.3–0.8). Prediction models were developed using three sets of variables: 1) pre-extracorporeal membrane oxygenation (age, absence of pneumonia, and pH < 7.12; area under the curve, 0.62); 2) extracorporeal membrane oxygenation related (extracorporeal cardiopulmonary resuscitation, any neurologic complication, pulmonary hemorrhage, renal replacement therapy, and metabolic acidosis; area under the curve, 0.72); and 3) all variables combined (area under the curve, 0.75) (p < 0.001). Conclusions: Children with pulmonary hypertension who require extracorporeal membrane oxygenation support have a significantly greater odds of mortality compared with those without pulmonary hypertension. Risk factors for mortality include age, absence of pneumonia, pre-extracorporeal membrane oxygenation acidosis, extracorporeal cardiopulmonary resuscitation, pulmonary hemorrhage, neurologic complications, renal replacement therapy, and acidosis while on extracorporeal membrane oxygenation. Identification of those pulmonary hypertension patients requiring extracorporeal membrane oxygenation who are at even higher risk for mortality may inform clinical decision-making and improve prognostic awareness. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Dr. Thiagarajan’s institution received funding from Bristol Myers Squibb and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest. The Extracorporeal Life Support Organization (ELSO) registry provided data. No endorsement or editorial restriction of the interpretation of these data or opinions of the authors has been implied or stated. For information regarding this article, E-mail: martina.steurermuller@ucsf.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Research Collaboration in Pediatric Critical Care Randomized Controlled Trials: A Social Network Analysis of Coauthorship Objectives: Clinical research is a collaborative enterprise; researchers benefit from the expertise, experience, and resources of their collaborators. We sought to describe the extent and patterns of collaboration among pediatric critical care trialists, and to identify the most influential individuals, centers, and countries. Design: Social network analysis of coauthorship. Data Sources: Publications of pediatric critical care randomized controlled trials (1986–2018). Data Extraction: We manually extracted the names of all authors and their affiliations. We used productivity (number of randomized controlled trials), influence (number of citations), and four measures of prominence in the social network (degree, betweenness, closeness, and eigenvector centrality) to identify the most influential individuals. Measurements and Main Results: From 415 randomized controlled trials in pediatric critical care, we identified 2,176 trialists from 377 centers in 43 countries. The coauthorship network is highly disconnected and dominated by a single large cluster of trialists publishing 142 (34%) of the randomized controlled trials. However, 119 (29%) of the randomized controlled trials were published by 28 smaller clusters—a median (interquartile range) of 3 (2–4) randomized controlled trials each. The remaining 154 (37%) randomized controlled trials were coauthored by researchers publishing a single randomized controlled trial each. This overall structure has remained constant with the publication of new randomized controlled trials over 33 years. The most influential trialists and centers varied according to the metric we used; only one trialist and three centers ranked in the top 10 for all measures of influence. Thirty-five of the 40 trialists (88%) ranking in the top 10 of any of the measures were from the United States, the United Kingdom, and Canada. Conclusions: Pediatric critical care has made considerable progress in the number of trialists and randomized controlled trials, but the research enterprise remains highly clustered and fragmented, particularly geographically. Efforts to further increase the quantity and quality of research in the field should include steps to increase the level and range of collaboration. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Dr. Duffett’s institution received funding from Canadian Institutes of Health Research (CIHR) and Hamilton Health Sciences Early Career Award, and he received support for article research from the CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at McMaster University. For information regarding this article, E-mail: duffetmc@mcmaster.ca ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Intracranial Electroencephalography in Pediatric Severe Traumatic Brain Injury Objectives: Electroencephalography is used in neurocritical care for detection of seizures and assessment of cortical function. Due to limited resolution from scalp electroencephalography, important abnormalities may not be readily detectable. We aimed to identify whether intracranial electroencephalography allows for improved methods of monitoring cortical function in children with severe traumatic brain injury. Design: This is a retrospective cohort study from a prospectively collected clinical database. We investigated the occurrence rate of epileptiform abnormalities detected on intracranial electroencephalography when compared with scalp electroencephalography. We also investigated the strength of association of quantitative electroencephalographic parameters and cerebral perfusion pressure between both intracranial and scalp electroencephalography. Setting: This is a single-institution study performed in the Phoenix Children’s Hospital PICU. Patients: Eleven children with severe traumatic brain injury requiring invasive neuromonitoring underwent implantation of a six-contact intracranial electrode as well as continuous surface electroencephalography. Interventions: None. Measurements and Main Results: Visual detection of epileptiform abnormalities was performed by pediatric epileptologists. Association of intracranial and scalp electroencephalography total power, alpha percentage, and alpha-delta power ratio to cerebral perfusion pressure was performed using univariate dynamic structural equations modeling. Demographic data were assessed by retrospective analysis. Intracranial and scalp electroencephalography was performed in 11 children. Three of 11 children had observed epileptiform abnormalities on intracranial electroencephalography. Two patients had epileptiform abnormalities identified exclusively on intracranial electroencephalography, and one patient had seizures initiating on intracranial electroencephalography before arising on scalp electroencephalography. Identification of epileptiform abnormalities was associated with subsequent identification of stroke or malignant cerebral edema. We observed statistically significant positive associations between intracranial alpha-delta power ratio to cerebral perfusion pressure in nine of 11 patients with increased strength of association on intracranial compared with scalp recordings. Conclusions: These findings suggest that intracranial electroencephalography may be useful for detection of secondary insult development in children with traumatic brain injury. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by a research grant from Moberg ICU Solutions and a grant from the Integra Codman Franchise for program development. Dr. Appavu’s institution received funding from Moberg ICU Solutions (provided funding for statistical support to institutional biostatistician) and Integra Codman Franchise (provided program development funds which helped support the purchase of initial equipment utilized for clinical care and retrospectively analyzed during this study). Neither entity was involved in any aspect of this work outside of consultant support for statistical analysis or equipment purchase. Dr. Foldes, Mr. Jacobson, and Mr. Brown’s institutions received funding from Integra Codman Foundation. Drs. Brown and Boerwinkle’s institutions received funding from Moberg ICU Solutions. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: bappavu@phoenixchildrens.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Outcomes of Infants Supported With Extracorporeal Membrane Oxygenation Using Centrifugal Versus Roller Pumps: An Analysis From the Extracorporeal Life Support Organization Registry Objectives: To determine whether mortality differs between roller and centrifugal pumps used during extracorporeal membrane oxygenation in infants weighing less than 10 kg. Design: Retrospective propensity-matched cohort study. Setting: All extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. Patients: All patients less than 10 kg supported on extracorporeal membrane oxygenation during 2011–2016 within Extracorporeal Life Support Organization Registry. Interventions: Centrifugal and roller pump recipients were propensity matched (1:1) based on predicted probability of receiving a centrifugal pump using demographic variables, indication for extracorporeal membrane oxygenation, central versus peripheral cannulation, and pre-extracorporeal membrane oxygenation patient management. Measurements and Main Results: A total of 12,890 patients less than 10 kg were supported with extracorporeal membrane oxygenation within the Extracorporeal Life Support Organization registry during 2011–2016. Patients were propensity matched into a cohort of 8,366. Venoarterial and venovenous extracorporeal membrane oxygenation runs were propensity matched separately. The propensity-matched cohorts were similar except earlier year of extracorporeal membrane oxygenation (standardized mean difference, 0.49) in the roller pump group. Within the propensity-matched cohort, survival to discharge was lower in the centrifugal pump group (57% vs 59%; odds ratio, 0.91; 95% CI, 0.83–0.99; p = 0.04). Hemolytic, infectious, limb injury, mechanical, metabolic, neurologic, pulmonary, and renal complications were more frequent in the centrifugal pump group. Hemorrhagic complications were similar between groups. Hemolysis mediated the relationship between centrifugal pumps and mortality (indirect effect, 0.023; p < 0.001). Conclusions: In this propensity score–matched cohort study of 8,366 extracorporeal membrane oxygenation recipients weighing less than 10 kg, those supported with centrifugal pumps had increased mortality and extracorporeal membrane oxygenation complications. Hemolysis was evaluated as a potential mediator of the relationship between centrifugal pump use and mortality and met criteria for full mediation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by the Rochelle E. Rose Cardiac Intensive Care Unit Research Funds. Dr. Thiagarajan’s institution received funding form Pfizer and Bristol Myers Squibb. Dr. Barbaro disclosed that he is the Extracorporeal Life Support Organization Registry Chair, and he received support for article research from National Institutes of Health and K12 HL138039 Training to Advance Care Through Implementation science in Cardiac And Lung illnesses. Mr. Alexander’s institution received funding from Tenax Therapeutics (supplied levosimendan for an expanded access protocol clinical trial) and Novartis, and he disclosed off-label product use of extracorporeal membrane oxygenation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: cohalloran@luriechildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Percutaneous Endoscopic Gastrostomy After Cardiothoracic Surgery in Children Less Than 2 Months Old: An Assessment of Long-Term Malnutrition Status and Gastrostomy Outcomes Objectives: Infants with critical congenital heart disease undergoing cardiothoracic surgery commonly experience chronic malnutrition and growth failure. We sought to determine whether placement of a percutaneous endoscopic gastrostomy was associated with reduced moderate-severe malnutrition status and to describe percutaneous endoscopic gastrostomy–related clinical and safety outcomes in this population. Design: Single-center, retrospective cohort study. Setting: Two hundred fifty-nine–bed, tertiary care, pediatric referral center. Patients: Children with congenital heart disease less than 2 months old undergoing cardiothoracic surgery from 2007 to 2013 with and without percutaneous endoscopic gastrostomy. Interventions: None. Measurements and Main Results: Primary outcomes were weight for age z scores during hospitalization, at 6 months, and 1 year after cardiothoracic surgery. Secondary outcomes were frequency of percutaneous endoscopic gastrostomy revision, percutaneous endoscopic gastrostomy complications, and mortality. Statistical analyses included Wilcoxon rank-sum, Fisher exact, and Student t tests. Two hundred twenty-two subjects met study criteria, and 77 (35%) had percutaneous endoscopic gastrostomy placed at a mean of 45 ± 31 days after cardiothoracic surgery. No differences were noted for demographics, comorbidities, and weight for age z score at birth and at the time of cardiothoracic surgery. The percutaneous endoscopic gastrostomy cohort had greater Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery risk category (4 [4–5] vs 4 [2–4]) and length of stay (71 d [49–101 d] vs 26 d [15–42 d]). Mean weight for age z score at the time of percutaneous endoscopic gastrostomy was –2.8 ± 1.3. Frequency of moderate-severe malnutrition (weight for age z score, ≤ –2) was greater in children with percutaneous endoscopic gastrostomy at discharge (78% vs 48%), 6 months (61% vs 16%), and 1 year (41% vs 2%). Index mortality was lower in children with percutaneous endoscopic gastrostomy at 30 days (8% vs 0%) and hospital discharge (19% vs 4%). However, no mortality differences were observed after discharge. Growth velocity after percutaneous endoscopic gastrostomy was greater (44 ± 19 vs 10 ± 9 g/d). Children tolerated percutaneous endoscopic gastrostomy without hemodynamic compromise, minor percutaneous endoscopic gastrostomy complications, and anticipated percutaneous endoscopic gastrostomy revisions. Children without mortality had percutaneous endoscopic gastrostomy removal at a median duration of 253 days (133–545 d). Children with univentricular physiology had improved in-hospital mean growth velocity (6.3 vs 24.4 g/d; p < 0.01) and reduced 1-year rate moderate-severe malnutrition (66.7% vs 36.9%; p < 0.01) after percutaneous endoscopic gastrostomy placement. Conclusions: Percutaneous endoscopic gastrostomy placement was well tolerated and associated with improved postoperative growth velocity in children with critical congenital heart disease undergoing cardiothoracic surgery less than 2 months old. These findings were also noted in our subanalysis of children with univentricular physiology. Persistent rates of moderate-severe malnutrition were noted at 1-year follow-up. Although potential index mortality benefit was observed, definitive data are still needed. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Dr. Nakagawa receives author royalties from Wolters Kluwer, UpToDate, and was a consultant for Fresenius Kabi. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: anthony.sochet@jhmi.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Delirium in a Tertiary PICU: Risk Factors and Outcomes Objectives: To determine risk factors and outcomes associated with delirium in PICU patients. Design: Retrospective cohort study. Setting: Thirty-two–bed PICU within a tertiary care academic children’s hospital. Patients: All children admitted to the PICU March 1, 2014, to October 1, 2016, with at least one Cornell Assessment of Pediatric Delirium score (n = 2,446). Interventions: None. Measurements and Main Results: Cornell Assessment of Pediatric Delirium score was performed twice daily as standard of care. We characterized delirium as: 1) presence of greater than or equal to 1 positive score (Cornell Assessment of Pediatric Delirium ≥ 9) and 2) number of days with a positive score. We built multivariable logistic and linear regression models using electronic medical records data. Many patients (n = 1,538; 63%) had a short length of stay (< 48 hr). Compared with patients with length of stay greater than or equal to 48 hours, fewer experienced delirium (30% vs 69%; p < 0.0001). Among 908 patients with length of stay greater than or equal to 48 hours, presence of delirium was independently associated with age less than 2 years old, baseline cognitive dysfunction, primary diagnosis, and duration of mechanical ventilation. Benzodiazepines demonstrated a dose-response effect (odds ratio for presence of delirium, 1.8 [p = 0.03], 3.4 [p < 0.001], and 9.7 [p = 0.005] for < 25th percentile, 25–75th percentile, and > 75th percentile of total dose, vs no exposure). In terms of outcomes, presence of delirium was independently associated with increased ICU length of stay (p < 0.001), whereas days of delirium were independently associated with decline in cognitive function from ICU admission to discharge (odds ratio, 1.06; p < 0.001), increased ICU (p < 0.001), and hospital length of stay (p < 0.001). Neither delirium presence nor total days were independently associated with mortality. Conclusions: Delirium is common in the PICU, particularly among patients with length of stay greater than or equal to 48 hours. It is independently associated with patient characteristics and PICU exposures, including benzodiazepines. The role of delirium as an independent causal factor in patient outcome requires further investigation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: leslie.dervan@seattlechildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Clinical Effects and Outcomes After Polymyxin B–Immobilized Fiber Column Direct Hemoperfusion Treatment for Septic Shock in Preterm Neonates Objectives: To compare the effectiveness and mortality of early-onset sepsis or late-onset sepsis treatments with polymyxin B–immobilized fiber column direct hemoperfusion in terms of effectiveness and mortality in preterm infants with septic shock. Design: Retrospective cohort study. Setting: Neonatal ICU within a tertiary care hospital. Patients: Of 1,115 patients, 49 had blood culture–proven sepsis between January 2013 and December 2018; six and five patients with septic shock had undergone polymyxin B–immobilized fiber column direct hemoperfusion treatment for early-onset sepsis (early-onset sepsis group) and late-onset sepsis (late-onset sepsis group), respectively. Interventions: None. Measurements and Main Results: Baseline demographic characteristics of both groups were similar. The time from decision to treatment induction was significantly shorter in the early-onset sepsis group than that in the late-onset sepsis group (p = 0.008). The mortality rate after 28 days of treatment and the hospital mortality were significantly lower in the early-onset sepsis group than in the late-onset sepsis group (p = 0.026 and 0.015, respectively). The PaO2/FIO2 ratio was significantly higher in the early-onset sepsis group than in the late-onset sepsis group at the end of the treatment (p = 0.035). In addition, median arterial-to-alveolar oxygen tension ratio significantly improved from 0.19 to 0.55, and median blood pressure also significantly improved from 32.5 to 40.0 mm Hg after the treatment in the early-onset sepsis group. Interleukin-6 levels significantly decreased after treatment in the early-onset sepsis group (p = 0.037). The Pediatric Risk of Mortality III score was similar between the early-onset sepsis and late-onset sepsis groups before and after the treatment. Intraventricular hemorrhage events occurred in both groups, but with no significant differences (p = 0.175). Conclusions: Polymyxin B–immobilized fiber column direct hemoperfusion treatment for preterm infants with septic shock due to early-onset sepsis is associated with earlier hemodynamic and respiratory status improvements and with lower mortality than that due to late-onset sepsis. Early neonatal septic shock detection and polymyxin B–immobilized fiber column direct hemoperfusion induction may improve the prognosis of affected infants. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: nishizak@juntendo.ac.jp ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Prediction and Comparison of Fentanyl Infusion Pharmacokinetics in Obese and Nonobese Children Objectives: To compare fentanyl infusion pharmacokinetic variables in obese children and nonobese children. Design: A pharmacokinetic simulation study. Setting: We used a semi-physiologically based pharmacokinetic model to generate fentanyl pharmacokinetic variables. Subjects: Simulations of pharmacokinetic variables were based on historical inpatient demographic data in less than 18-year-olds. Interventions: Obese children were defined as children less than 2 years with weight-for-length greater than or equal to 97.7th percentile or body mass index-for-age greater than or equal to 95th percentile for greater than or equal to 2–17-year-olds. Measurements and Main Results: Overall, 4,376 patients were included, with 807 (18.4%) classified as obese children. The majority (52.9%) were male, with a median age of 8.1 years (interquartile range, 4.3–13.0 yr). The differences in total clearance (CLS), volume of distribution at steady-state values, weight-normalized CLS, and weight-normalized volume of distribution at steady state were assessed in obese children and nonobese children. Multivariable analyses indicated that obesity was significantly associated with a higher CLS in obese children greater than 6-year-olds (p < 0.0375). However, there was an 11–30% decrease in weight-normalized CLS in obese children versus nonobese children in all age groups (p < 0.05). Both volume of distribution at steady state and weight-normalized volume of distribution at steady state increased significantly in obese children compared with nonobese children (p < 0.05). Fentanyl plasma concentration-time profiles of obese children and nonobese children pairs (ages 4, 9, and 15) receiving 1 µg/kg/hr using total body weight were also compared. Steady-state concentrations of the obese children using similar weight-based dosing increased by 25%, 77%, and 44% in comparison to nonobese children 4-, 9-, and 15-year-olds, respectively. Time to steady state and elimination half-lives were two- to four-fold longer in obese children. An additional simulation was conducted for 15-year-old obese children and nonobese children using a fixed dose of 50 µg/hr and it provided similar pharmacokinetic profiles. Conclusions: CLS may increase less than proportional to weight in obese children greater than 6-year-olds, while volume of distribution at steady state increases more than proportional to weight in all obese children compared with nonobese children. Weight-based dosing in obese children may cause an increase in steady-state concentration while prolonging the time to steady state. Exploring alternative dosing strategies for obese children is warranted. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Platform Presentation at the Society of Critical Care Medicine 46th Critical Care Congress in Honolulu, HI, January 2017. Drs. Miller’s and Johnson’s institutions received funding from American Society of Health System Pharmacists. Dr. Skrepnek’s institution received funding from AbbVie, Purdue Pharma, Otsuka, Gilead, and Amgen. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Sin Yin Lim, PharmD, Department of Pharmacy, Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, 1110 N. Stonewall Ave., CPB 216, Oklahoma City, OK 73117. E-mail: sinyin-lim@ouhsc.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies