Pediatric Critical Care Medicine

Antipyretic Efficacy of Acetaminophen and Ibuprofen in Critically Ill Pediatric Patients Objectives: To determine the antipyretic efficacy of acetaminophen (IV, enteral, rectal) and ibuprofen (enteral) in critically ill febrile pediatric patients. Design: Retrospective cohort study. Setting: Quaternary care pediatric hospital ICUs. Patients: Pediatric patients less than 19 years old who were febrile (≥ 38.0°C), received a dose of IV acetaminophen, enteral acetaminophen, rectal acetaminophen, or enteral ibuprofen and had at least one temperature measurement in the following 6 hours. Interventions: None. Measurements and Main Results: A total of 3,341 patients (55.8% male, median age 2.5 yr [interquartile range, 0.63–9.2 yr]) met study criteria. Baseline temperature was median 38.6°C (interquartile range, 38.3–38.9°C) measured via axillary (76.9%) route. Patients became afebrile (87.5%) at median 1.4 hours (interquartile range, 0.77–2.3 hr) after the first dose of medication, a –2.9 ± 1.6% change in temperature. Antipyretic medications included as follows: enteral acetaminophen (n = 1,664), IV acetaminophen (n = 682), rectal acetaminophen (n = 637), and enteral ibuprofen (n = 358). Enteral ibuprofen had a significantly greater odds of defervescence on multivariable logistic regression analysis (p = 0.04) with a decrease of –1.97 ± 0.89°C while IV acetaminophen was significant for a decreased time to defervescence at median 1.5 hours (interquartile range 0.8–2.3 hr) after a dose (p = 0.03). Patient age, presence of obesity, and baseline temperature were significant for decreased antipyretic efficacy (p < 0.05). Conclusions: Enteral ibuprofen was the most efficacious antipyretic and IV acetaminophen had the shortest time to defervescence. Dr. Moffett disclosed off-label product use of IV acetaminophen for antipyresis in children. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: bsmoffet@texaschildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Mortality and Factors Associated With Hemorrhage During Pediatric Extracorporeal Membrane Oxygenation Objectives: To quantify and identify factors associated with bleeding events during pediatric extracorporeal membrane oxygenation. Design: Retrospective cohort study with primary outcome of bleeding days on extracorporeal membrane oxygenation. Setting: Single tertiary care children's hospital. Subjects: One-hundred twenty-two children supported with extracorporeal membrane oxygenation for greater than 12 hours during January 2015 through December 2016. Interventions: Bleeding days were identified if mediastinal or cannula site exploration, activated factor VII administration, gastrointestinal, pulmonary, or intracranial hemorrhages occurred. Logistic regression was used to assess factors associated with bleeding days. Measurements and Main Results: Study population was identified from institutional extracorporeal membrane oxygenation database. Clinical, laboratory, and survival data were obtained from medical records. Only data from patients' first extracorporeal membrane oxygenation run were used. One-hundred twenty-two patients with median age of 17 weeks (interquartile range, 1–148 wk) were analyzed. Congenital heart disease (n = 56, 46%) was the most common diagnosis. Bleeding days comprised 179 (16%) of the 1,121 observed extracorporeal membrane oxygenation-patient-days. By extracorporeal membrane oxygenation day 4, 50% of users had experienced a bleeding day. Central rather than peripheral cannulation (odds ratio, 2.58; 95% CI, 1.47–4.52; p < 0.001), older age (odds ratio, 1.31 per increased week; 95% CI, 1.14–1.52; p < 0.001), higher lactate (odds ratio, 1.08 per 1 mmol/L increase; 95% CI, 1.05–1.12; p < 0.001), and lower platelets (odds ratio, 0.87 per 25,000 cell/μL increase; 95% CI, 0.77–0.99; p = 0.005) were associated with bleeding days. Patients who experienced more frequent bleeding (> 75th percentile) had fewer ventilator-free and hospital-free days in the 60 days after cannulation (0 vs 31; p = 0.002 and 0 vs 0; p = 0.008) and higher in-hospital mortality (68 vs 34%; p < 0.001). Conclusions: Central cannulation, older age, low platelets, and high lactate are associated with bleeding days during pediatric extracorporeal membrane oxygenation. Patients who bleed more frequently during extracorporeal membrane oxygenation have higher in-hospital mortality, longer technological dependence, and reduced hospital-free days. This study was performed at Boston Children's Hospital, Boston, MA. Supported, in part, by grant from the Callahan Family Chair Fund. Dr. Thiagarajan's institution received funding from Bristol Myers Squibb and Pfizer. Dr. Alexander's institution received funding from Novartis and Tenax Therapeutics (supply therapeutic agent, levosimendan, only as part of an Expanded Access clinical trial). Dr. Alexander's institution received consultation fees from Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: conor.ohalloran@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Outcomes of Day 1 Multiple Organ Dysfunction Syndrome in the PICU Objectives: We sought to describe current outcomes of Multiple Organ Dysfunction Syndrome present on day 1 of PICU admission. Design: Retrospective observational cohort study. Setting: Virtual Pediatric Systems, LLC, database admissions, January 2014 and December 2015. Patients: We analyzed 194,017 consecutive PICU admissions, (age 1 mo to 18 yr) from the 2014–2015 Virtual Pediatric Systems database. Interventions: We identified day 1 Multiple Organ Dysfunction Syndrome by International Pediatric Sepsis Consensus Conference criteria with day 1 laboratory and vital sign values. Functional status was evaluated by Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge. Measurements and Main Results: Overall, PICU mortality was 2.1%. We identified day 1 Multiple Organ Dysfunction Syndrome in 14.4% of admissions. Patients with Multiple Organ Dysfunction Syndrome had higher mortality than those without Multiple Organ Dysfunction Syndrome (10.3% vs 0.7%; p < 0.0001), and a higher percentage of survivors had greater than or equal to 2 category worsening in Pediatric Cerebral Performance Category score (3.6% vs 0.5%; p < 0.0001) or Pediatric Overall Performance Category score (6.0% vs 1.8%; p < 0.0001). The odds of death with day 1 Multiple Organ Dysfunction Syndrome was 14.3 (95% CI, 13–15.7), while the odds of death or discharge with Pediatric Overall Performance Category/Pediatric Cerebral Performance Category score greater than or equal to 3 (poor functional outcome) was 6.7 (95% CI, 6–7.4). In a subset of 148,188 patients from hospitals where limitation of support decisions were recorded, 5.8% patients with Multiple Organ Dysfunction Syndrome had limitation of support decisions in place, compared with 0.8% of patients without Multiple Organ Dysfunction Syndrome (p < 0.0001). Of day 1 Multiple Organ Dysfunction Syndrome patients who died, 43.1% had limitation of support decisions in place, and 41.6% had withdrawal of life-sustaining therapies (p < 0.0001). Conclusions: Multiple Organ Dysfunction Syndrome present on day 1 of admission continues to be a major source of morbidity and mortality in the PICU, but risk of poor neurologic outcome may be improved. Further research is needed to understand decisions regarding limitation of support and withdrawal of life-sustaining therapy decisions in patients admitted with day 1 Multiple Organ Dysfunction Syndrome. Executive committee members of Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network are: Ira Cheifetz, MD, Neal Thomas, MD, Ann Thompson, MD, Martha A.Q. Curley, RN, PhD, Philippe Jouvet, MD, Barry Markovitz, MD, Akira Nishisaki, MD, Marisa Tucci, MD, Doug Wilson, MD. 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). VPS data was provided by Virtual Pediatric Systems, LLC. No endorsement of editorial restriction of the interpretation of these data or opinions of the authors has been implied or stated. Dr. Typpo's institution received funding from the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases 1K23 DK 106462-01A1 and Baxter Corporation, and she received support for article research from the NIH. Dr. Bennett's institution received funding from Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, and Colorado Department of Human Services. The remaining authors have disclosed that they do not have any potential conflicts of interest. VPS data was provided by Virtual Pediatric Systems, LLC. For information regarding this article, E-mail: ktyppo@email.arizona.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Epidemiology of Pediatric Severe Sepsis in Main PICU Centers in Southwest China Objectives: To estimate the prevalence, management, and outcomes of pediatric severe sepsis in the main PICUs in Southwest China. Design: A prospective, observational, and multicenter study. Setting: Eight PICUs in Southwest China with 19 (13–24) beds and 1,322 (1,066–1,452) annual admissions each. Patients: A total of 10,598 patients (29 d to 18 yr old) were consecutively admitted between September 1, 2016, and August 31, 2017. All patients were screened and evaluated for severe sepsis or septic shock. Of them, 10,353 patients were excluded due to incomplete data or not meeting the consensus criteria for severe sepsis or septic shock; 245 patients were included with complete data. Interventions: None. Measurements and Main Results: Finally, 245 patients who were diagnosed with severe sepsis or septic shock were included in the study, with an incidence rate of 2.3%. Of them, 64.0% of the enrolled patients were male with 80.8% being less than 5 years old and 60.8% being from rural areas. The respiratory system was the most common organ system in which dysfunction was observed (76.7%) as well as the most frequently infected site (37.6%). The primary therapies were antibiotics (99.0%), immunoglobulin (88.3%), mechanical ventilation (78.4%), vasoactive infusions (59.6%), and corticosteroids (46.1%). Among the 188 patients who had respiratory dysfunction, 173(92%) required mechanical ventilation and 39 (20.7%) met the criteria for pediatric acute respiratory distress syndrome. Seven of the patients with pediatric acute respiratory distress syndrome died (7/39, 17.9%). The median durations for mechanical ventilation and vasoactive medications were 123.5 hours (35.25–226.00 hr) and 2 days (1–5 d), respectively. Eighty-six percent of patients had multiple organ dysfunction syndrome at the point at which severe sepsis was recognized, and 31% had underlying conditions. The hospital mortality rate was 18.8%. Conclusions: This report is the first to present the prevalence, treatment, and outcomes of pediatric severe sepsis in the main PICU centers in Southwest China. The mortality rate remains high; therefore, improved clinical management and implementation of large-scale clinical trials are necessary to improve early diagnoses and treatment. Dr. Xu received support for article research from Chongqing Science and Technology Bureau. Drs. C. Xiao, S. Wang, Fang, Xu, S. Xiao, Li, Zhang, Luo, Jiang, Huang, Y. Chen, J. Chen, Yu, D. Ren, X. Ren, and Tang disclosed government work. Dr. H. Wang has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: xufeng9899@163.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Barriers to Communication in a PICU: A Qualitative Investigation of Family and Provider Perceptions Objectives: Family and medical provider perceptions of communication barriers within the PICU are poorly understood. We designed a qualitative study to characterize the perspective of families and medical providers of critically ill children regarding communication barriers. The identified barriers may be used to direct efforts to improve communication. Design: Semi-structured interviews were conducted from August 2017 to January 2018. Interviews were audio recorded and professionally transcribed verbatim. Setting: A PICU at a tertiary care academic center. Patients: Forty-two families whose children were admitted to the PICU (excluding patients receiving end-of-life care or with protective services involvement) and 12 PICU staff members, including nurses, residents, fellows, and attending's. Interventions: None. Measurements and Main Results: An interprofessional team of a physician, nurse manager, and medical student coded the transcripts. Interviewing continued until thematic saturation was reached. Codes were organized into common themes using a modified constant comparative method. The families interviewed represented 16 previously healthy children, and 26 children with a chronic health condition. Staff interviewed included three residents, three fellows, three attending intensivists, and three nurses. Participants' perceptions and experiences of barriers to communication included the following: 1) Communication breakdowns related to coordination of care among several services, 2) Family-centered rounds are insufficient for effective communication, 3) Undervaluing the knowledge of families of children with chronic health conditions or special needs, and 4) Communication breakdowns occur across provider hand-offs. Theme 3 was identified by families, but not by providers. Conclusions: Families and medical providers both identified several barriers to communication. However, only families identified the barrier "Undervaluing the knowledge of families with chronically ill children." Future work should explore these barriers and the discrepancy in perception between providers and families to determine if there are interventions that improve both family satisfaction and patient care. 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 the Yale School of Medicine Office of Student Research and the Yale School of Medicine Department of Pediatrics, Section of Critical Care. Mr. Greenway received funding from Yale School of Medicine, Office of Student Research and Yale School of Medicine, Department of Pediatrics, Section of Critical Care. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Kevin G. Couloures, DO, MPH, Department of Pediatrics, 333 Cedar Street, New Haven, CT 06520-8064. E-mail: kevin.couloures@yale.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Sedative and Analgesic Drug Rotation Protocol in Critically Ill Children With Prolonged Sedation. Evaluation of Implementation and Efficacy to Reduce Withdrawal Syndrome Objectives: The first aim of this study was to assess the implementation of a sedative and analgesic drug rotation protocol in a PICU. The second aim was to analyze the incidence of withdrawal syndrome, drug doses, and time of sedative or analgesic drug infusion in children after the implementation of the new protocol. Design: Prospective observational study. Setting: PICU of a tertiary care hospital between June 2012 and June 2016. Patients: All patients between 1 month and 16 years old admitted to the PICU who received continuous IV infusion of sedative or analgesic drugs for more than 4 days were included in the study. Interventions: A sedative and analgesic drug rotation protocol was designed. The level of sedation, analgesia, and withdrawal syndrome were monitored with validated scales. The relationship between compliance with the protocol and the incidence of withdrawal syndrome was studied. Measurements and Main Results: One-hundred pediatric patients were included in the study. The protocol was followed properly in 35% of patients. Sixty-seven percent of the overall cohort presented with withdrawal syndrome. There was a lower incidence rate of withdrawal syndrome (34.3% vs 84.6%; p < 0.001), shorter PICU length of stay (median 16 vs 25 d; p = 0.003), less time of opioid infusion (median 5 vs 7 d for fentanyl; p = 0.004), benzodiazepines (median 5 vs 9 d; p = 0.001), and propofol (median 4 vs 8 d; p = 0.001) in the cohort of children in which the protocol was followed correctly. Conclusions: Our results show that compliance with the drug rotation protocol in critically ill children requiring prolonged sedation may reduce the appearance of withdrawal syndrome without increasing the risk of adverse effects. Furthermore, it may reduce the time of continuous IV infusions for most sedative and analgesic drugs and the length of stay in PICU. Dr. Sanavia involved in patient recruitment, data collection, analysis and interpretation of data, and writing up of the article. Dr. Mencía involved in study design, analysis and interpretation of data, and drafting the article or revising it critically for important intellectual content. Dr. Lafever involved in data collection and translation. Dr. Solana involved in patient recruitment and data collection. Dr. Garcia involved in data collection. Dr. López-Herce involved in drafting the article or revising it critically for important intellectual content and final approval of the version to be published. Supported, in part, by Dodot Scholarship from the Spanish Pediatric Association. Maternal and Child Health and Development Network. RETICS Health Research Networks financed by the R + D + I PN 2008–2011, ISCIII (Health Institute Carlos III)—General Subdirectorate for Evaluation and Promotion of Research and the European Regional Development Fund, ef. RD16/0022/0007. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: eva.sanavia@hotmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Critical Trio Exome Benefits In-Time Decision-Making for Pediatric Patients With Severe Illnesses Objectives: Critical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness. Design: Observational analysis. Method: We employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period. Setting: A tertiary referral Children's Hospital in Taiwan. Patients: Critically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled. Interventions: None. Measurements and Main Results: Around 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3–9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis. Conclusions: The current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources. 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 Ministry of Science and Technology, R.O.C., under grant number MOST 106-3114-B-002-009. Dr. Hwu's institution received funding from Ministry of Science and Technology. Miss. Chen disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: ncleentu@ntu.edu.tw ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Epidemiology of Clinically Relevant Bleeding in Critically Ill Adolescents Objectives: The epidemiology of clinically relevant bleeding in critically ill adolescents, particularly those who are at high risk of venous thromboembolism, is unclear. In preparation for a randomized clinical trial of pharmacologic prophylaxis against venous thromboembolism, we characterized the epidemiology of clinically relevant bleeding in critically ill adolescents. Design: Post hoc analysis of data from a pediatric multicenter observational study of venous thromboembolism. Setting: Six PICUs. Patients: Adolescents 13–17 years old who received cardiac or pulmonary support for at least 48 hours were eligible. Those admitted with venous thromboembolism or receiving therapeutic anticoagulation were excluded. Interventions: None. Measurements and Main Results: Adolescents (n = 88) were followed daily for the development of any bleeding event. The severity of the event was categorized based on the definitions by the International Society on Thrombosis and Haemostasis. The frequency of clinically relevant bleeding was 29.5% (95% CI, 20.3–40.2%) or 3.7 events (95% CI, 2.5–5.4 events) per 100 patient-days. Adolescents with venous thromboembolism were more likely to develop clinically relevant bleeding (hazard ratio, 2.06; 95% CI, 1.08–3.94). Age was negatively associated with clinically relevant bleeding (hazard ratio for every 1-year increase in age: 0.68; 95% CI, 0.58–0.79). In contrast, predicted risk of mortality (hazard ratio for every 0.10 increase in risk: 1.35; 95% CI, 1.05–1.74) and admission for trauma or surgery (hazard ratio: 2.04; 95% CI, 1.21–3.44) were positively associated with clinically relevant bleeding. The association of clinically relevant bleeding with medications, interventions, or laboratory tests, including mechanical ventilation and pharmacologic prophylaxis with anticoagulation, did not reach statistical significance. Adolescents with clinically relevant bleeding stayed in the hospital longer than those without clinically relevant bleeding. Conclusions: Clinically relevant bleeding is common in critically ill adolescents who are at high risk of venous thromboembolism. Admission for trauma or surgery can be used to stratify the risk of clinically relevant bleeding in these adolescents. Supported, in part, by grant from the American Heart Association Award Number 14CRP20490002 to Dr. Faustino. It was also made possible by Clinical and Translational Science Award grant number UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research to Dr. Shabanova, and an unrestricted grant support from Layla's Dream to Dr. Polikoff. For information regarding this article, E-mail: Matthew.Pinto@wmchealth.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Functional Status Scale: Cross-Cultural Adaptation and Validation in Brazil Objective: The goal of the present study was to perform a cross-cultural adaptation and clinical validation of the Functional Status Scale for use in the Brazilian population. Design: Cross-cultural adaptation study followed by a cross-sectional validation study. Setting: Single-center PICU at a hospital in Porto Alegre, Brazil. Patients: Children and adolescents of both sexes, 1 month and under 18 years old, who had been treated at the PICU. Interventions: The cross-cultural adaptation consisted of the following stages: translation, synthesis of the translated versions, back translations, synthesis of the back translations, committee review, and pretesting. For the clinical validation stage, the Brazilian Functional Status Scale was applied within 48 hours after discharge from the PICU. The Brazilian Functional Status Scale's reliability and validity properties were tested. Measurements and Main Results: A total of 314 patients were evaluated. Median age was 24 months (7.0–105.0 mo), 54.1% were males, and their overall functional score was 9 ± 2.8. The Brazilian Functional Status Scale demonstrated excellent interobserver reliability, with an intraclass correlation coefficient of 0.98, and κ coefficients between 0.716 and 1.000 for the functional domains, which indicated good to excellent agreement. Using the Bland-Altman method, we confirmed low variability among the evaluator's responses (0.93 to –1.06 points). Regarding the Brazilian Functional Status Scale's content validity, there was a correlation between length of PICU stay (r = 0.378; p < 0.001) and time on invasive mechanical ventilation (r = 0.261; p < 0.05), and the test could discriminate between groups with different comorbidity levels (p < 0.001). Conclusions: The Functional Status Scale has been culturally adapted and validated for use in Brazil and is now available for use in the assessment of functionality in Brazilian children and adolescents. 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 from the Higher Education Improvement Coordination (CAPES). The authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the Hospital da Criança Santo Antônio, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil. For information regarding this article, E-mail: gabi.apereira@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

The Base Deficit, International Normalized Ratio, and Glasgow Coma Scale (BIG) Score, and Functional Outcome at Hospital Discharge in Children With Traumatic Brain Injury Objectives: To examine the association of the base deficit, international normalized ratio, and Glasgow Coma Scale (BIG) score on emergency department arrival with functional dependence at hospital discharge (Pediatric Cerebral Performance Category ≥ 4) in pediatric multiple trauma patients with traumatic brain injury. Design: A retrospective cohort study of a pediatric trauma database from 2001 to 2018. Setting: Level 1 trauma program at a university-affiliated pediatric institution. Patients: Two to 17 years old children sustaining major blunt trauma including a traumatic brain injury and meeting trauma team activation criteria. Interventions: None. Measurements and Main Results: Two investigators, blinded to the BIG score, determined discharge Pediatric Cerebral Performance Category scores. The BIG score was measured on emergency department arrival. The 609 study patients were 9.7 ± 4.4 years old with a median Injury Severity Score 22 (interquartile range, 12). One-hundred seventy-one of 609 (28%) had Pediatric Cerebral Performance Category greater than or equal to 4 (primary outcome). The BIG constituted a multivariable predictor of Pediatric Cerebral Performance Category greater than or equal to 4 (odds ratio, 2.39; 95% CI, 1.81–3.15) after adjustment for neurosurgery requirement (odds ratio, 2.83; 95% CI, 1.69–4.74), pupils fixed and dilated (odds ratio, 3.1; 95% CI, 1.49–6.38), and intubation at the scene or referral hospital (odds ratio, 2.82; 95% CI, 1.35–5.87) and other postulated predictors of poor outcome. The area under the BIG receiver operating characteristic curve was 0.87 (0.84–0.90). Using an optimal BIG cutoff less than or equal to 8, sensitivity and negative predictive value for functional dependence at discharge were 93% and 96%, respectively, compared with a sensitivity of 79% and negative predictive value of 91% with Glasgow Coma Scale less than or equal to 8. In children with Glasgow Coma Scale 3, the BIG score was associated with brain death (odds ratio, 2.13; 95% CI, 1.58–2.36). The BIG also predicted disposition to inpatient rehabilitation (odds ratio, 2.26; 95% CI, 2.17–2.35). Conclusions: The BIG score is a simple, rapidly obtainable severity of illness score that constitutes an independent predictor of functional dependence at hospital discharge in pediatric trauma patients with traumatic brain injury. The base deficit, international normalized ratio, and Glasgow Coma Scale score may benefit Trauma and Neurocritical care programs in identifying ideal candidates for traumatic brain injury trials within the therapeutic window of treatment. Presented, in part, as oral presentations at the: 1) Trauma Association of Canada meeting, Toronto, ON, Canada, February 23, 2018; and 2) Pediatric Academic Societies meeting, Toronto, ON, Canada, May 6, 2018. Drs. Davis, Hochstadter, and Schuh conceived the study and wrote the protocol. Dr. Davis supervised data collection by Drs. Hochstadter and Daya. Mr. Stephens performed the data analysis. Drs. Davis, Hochstadter, and Schuh drafted the article and Drs. Davis, Hochstadter, Daya, Kulkarni, Wales, and Schuh contributed substantially to its revision. All authors take responsibility for the article as a whole. The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Adrienne Davis, MD, MSc, FRCPC, Division of Pediatric Emergency Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. E-mail: adrienne.davis@sickkids.ca ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Alexandros Sfakianakis
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