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

Vacuum-Assisted Closure for the Treatment of Deep Sternal Wound Infection After Pediatric Cardiac Surgery Objectives: Vacuum-assisted closure is being increasingly used to treat deep sternal wound infection following cardiac surgery, but most of the data refer to adults. This study investigated the safety and efficacy of vacuum-assisted closure in pediatric patients. Design: Retrospective file review. Setting: Tertiary pediatric medical center. Patients: All children with deep sternal wound infection treated with vacuum-assisted closure in 2003–2016. Interventions: Epidemiological, clinical, and microbiological data were collected from the medical records. Measurements and Main Results: The cohort included 50 patients (0.9% of cardiac patients operated during the study period) of median age 6.5 months (interquartile range, 2–12.75 mo; range, 1 wk to 14 yr) and median weight 5.1 kg (interquartile range, 4–9.75 kg). The most frequent heart defects were tetralogy of Fallot (22%) and ventricular septal defect (20%); 38% of patients had cyanotic heart disease. Deep sternal wound infections appeared a median of 10 days postoperatively (interquartile range, 7–14 d; range 3–100 d). Vacuum-assisted closure was applied a median of 13 days postoperatively (interquartile range, 10–18.5 d; range, 5–103 d) for a median duration of 10 days (interquartile range, 7–13.25 d; range, 1–21 d). Wound cultures were positive in 48 patients (96%); most isolates were Gram-positive (76%). The main bacterial pathogen was methicillin-susceptible Staphylococcus aureus (61%). Most patients were treated with cloxacillin for a median of 38 days (interquartile range, 28–42 d; range, 9–189 d). There were no statistically significant differences in clinical or treatment characteristics between bacteremic (56%) and nonbacteremic patients. Compared with older patients, infants less than 3 months old (36%) had a significantly longer hospitalization time (41 vs 25 d; p = 0.001) and higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category (3 vs 2; p = 0.003). All cases except one (contact dermatitis) were uneventful. In 10 patients, wounds were closed surgically after vacuum-assisted closure. Two patients required a pectoralis flap, both treated before 2005. One of the two deaths was infection-related. Conclusions: Vacuum-assisted closure is a feasible treatment option of deep sternal wound infection after pediatric cardiac surgery and was not associated with independent morbidity. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: itzhakl@clalit.org.il ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Population-Based Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Children Objectives: We describe the epidemiology, characteristics, risk factors, and incremental risks associated with acute kidney injury in critically ill children at a population-level. Design: Population-based retrospective cohort study. Setting: PICUs in Alberta, Canada. Patients: All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. Interventions: None. Measurements and Main Results: A total of 1,017 patients were included. Acute kidney injury developed in 308 patients (30.3%; 95% CI, 28.1–33.8%) and severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3–14.4%). Incidence rates for critical illness-associated acute kidney injury and severe acute kidney injury were 34 (95% CI, 30.3–38.0) and 14 (95% CI, 11.38–16.38) per 100,000 children-year, respectively. Severe acute kidney injury incidence rates were greater in males (incidence rate ratio, 1.55; 95% CI, 1.08–2.33) and infants younger than 1 year old (incidence rate ratio, 14.77; 95% CI, 10.36–21.07). Thirty-two patients (3.1%) did not survive to PICU discharge. The acute kidney injury-associated PICU mortality rate was 2.3 (95% CI, 1.4–3.5) per 100,000 children-year. In multivariate analysis, severe acute kidney injury was associated with greater PICU mortality (odds ratio, 11.93; 95% CI, 4.68–30.42) and 1-year mortality (odds ratio, 5.50; 95% CI, 2.76–10.96). Severe acute kidney injury was further associated with greater duration of mechanical ventilation, duration of vasoactive support, and lengths of PICU and hospital stay. Conclusions: The population-level burden of acute kidney injury and its attributable risks are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for acute kidney injury, identification of modifiable risks, and evaluation of interventional strategies. 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, grant from the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta. Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Nephrology. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: bagshaw@ualberta.ca ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes Objectives: To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. Design: A single-center retrospective study. Setting: A tertiary care children’s hospital. Patients: All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. Interventions: None. Measurements and Main Results: Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients’ characteristics, and treatments. Conclusions: In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies. Current affiliation for Dr. Husari: Department of Neurology, Johns Hopkins University, Baltimore, MD. Current affiliation for Dr. Labiner: Child Neurology Consultants of Austin, Austin, TX. Current affiliation for Mr. Huang: Children’s Medical Center Dallas, Dallas, TX. Current affiliation for Dr. Said: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX. This study was conducted at the University of Texas Southwestern Medical Center. Drs. Husari and Said were involved in study concept and design, as well as critical revision of the article for important intellectual content. Drs. Husari and Labiner were involved in acquisition, analysis, or interpretation of data and drafting of the article. Mr. Huang and Dr. Husari were involved in statistical analysis. 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, institutional award (Service Package Award) grant from Children’s HealthSM—Children Medical Center to cover the statistical consultation and analysis. Dr. Husari’s institution received funding from Children’s Health—Children Medical Center. Dr. Said’s institution received funding from an internal grant from Children’s Health Dallas (called the Service Package Grant) for the amount of $4,225 for Statistical Consultation and Analysis, and she disclosed that she serves on the Professional Advisory Board of the Epilepsy Foundation of Texas (volunteer, unpaid position). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kshusari@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Association of Duration of Hypotension With Survival After Pediatric Cardiac Arrest Objectives: To evaluate the association of a single episode of hypotension and burden of hypotension with survival to hospital discharge following resuscitation from pediatric cardiac arrest. Design: Retrospective cohort study. Setting: Single-center PICU. Patients: Patients between 1 day and 18 years old who had a cardiac arrest, received chest compressions for more than 2 minutes, had return of spontaneous circulation for more than 20 minutes, and survived to receive postresuscitation care in the ICU. Interventions: None. Measurement and Main Results: One-hundred sixteen patients were evaluable. Hypotension, defined as systolic blood pressure less than the fifth percentile for age and sex, occurred in 37 patients (32%) within the first 6 hours and 64 (55%) within 72 hours of postresuscitation ICU care. There was no significant difference in survival to discharge for patients who had a single episode of hypotension within 6 hours (51% vs 69%; p = 0.06) or within 72 hours (56% vs 73%; p = 0.06). Burden of hypotension was defined as the percentage of hypotension measurements that were below the fifth percentile. After controlling for patient and cardiac arrest event characteristics, a higher burden of hypotension within the first 72 hours of ICU postresuscitation care was associated with decreased discharge survival (adjusted odds ratio = 0.67 per 10% increase in hypotension burden; 95% CI, 0.48–0.86; p = 0.006). Conclusions: After successful resuscitation from pediatric cardiac arrest, systolic hypotension was common (55%). A higher burden of postresuscitation hypotension within the first 72 hours of ICU postresuscitation care was associated with significantly decreased discharge survival, after accounting for potential confounders including number of doses of epinephrine, arrest location, and arrest etiology due to airway obstruction or trauma. Dr. Topjian’s institution received funding from the National Institutes of Health (NIH); she received funding from expert testimony; and she received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: laverrieree@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Necrotizing Enterocolitis and Associated Mortality in Neonates With Congenital Heart Disease: A Multi-Institutional Study Objective: There are scarce data about the prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. The purpose of this study is to provide a multi-institutional description and comparison of the overall prevalence and mortality of necrotizing enterocolitis in neonates with congenital heart disease. Design: Retrospective multi-institutional study. Setting: The Pediatric Health Information System database. Patients: Neonates with congenital heart disease between 2004 and 2014. Interventions: None. Measurements and Main Results: The primary study measure is the prevalence of necrotizing enterocolitis. Secondary measures include in-hospital mortality, hospital charges, ICU length of stay, hospital length of stay, and 30-day readmission. The prevalence of necrotizing enterocolitis was 3.7% (1,448/38,770) and varied significantly among different congenital heart disease diagnoses. The lowest prevalence of necrotizing enterocolitis was in transposition of the great arteries (n = 104, 2.1%). Compared with transposition of the great arteries, necrotizing enterocolitis occurred more frequently in neonates with hypoplastic left heart syndrome (odds ratio, 2.7; 95% CI, 2.1–3.3), truncus arteriosus (odds ratio, 2.6; 95% CI, 1.9–3.5), common ventricle (odds ratio, 2.1; 95% CI, 1.5–2.8), and aortic arch obstruction (odds ratio, 1.4; 95% CI, 1.1–1.7). Prematurity is a significant risk factor for necrotizing enterocolitis and for mortality in neonates with necrotizing enterocolitis, conferring varying risk by cardiac diagnosis. Unadjusted mortality associated with necrotizing enterocolitis was 24.4% (vs 11.8% in neonates without necrotizing enterocolitis; p < 0.001), and necrotizing enterocolitis increased the adjusted mortality in neonates with transposition of the great arteries (odds ratio, 2.5; 95% CI, 1.5–4.4), aortic arch obstruction (odds ratio, 1.8; 95% CI, 1.3–2.6), and tetralogy of Fallot (odds ratio, 1.6; 95% CI, 1.1–2.4). Necrotizing enterocolitis was associated with increased hospital charges (p < 0.0001), ICU length of stay (p = 0.001), and length of stay (p = 0.001). Conclusions: The prevalence of necrotizing enterocolitis among neonates with congenital heart disease is 3.7% and is associated with increased in-hospital mortality, length of stay, and hospital charges. The prevalence and associated mortality of necrotizing enterocolitis in congenital heart disease vary among different heart defects. Dr. Spinner assisted with data analysis, drafted the initial article, and reviewed and revised the final article. Dr. Morris assisted with data analysis, and critically reviewed and revised the article. Drs. Nandi, Costarino, Marino, and Rossano critically reviewed and revised the article. Dr. Shamszad conceptualized and designed the study, collected the data, performed data analysis, and reviewed and revised the article. Dr. Morris received funding from Guidepoint (consulting). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: shamszadp@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies