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Sarah B Kandil, E Vincent Faustino Department of Pediatrics, Division of Pediatric Critical Care, Yale University School of Medicine, New Haven, CT, USA Abstract: The benefit of intravenous insulin for tight glycemic control (TGC) in critically ill patients is debatable. Initial single center trials on TGC in critically ill adults admitted to the surgical intensive care unit were promising and showed a decrease in mortality with TGC. However, subsequent multicenter trials were unable to replicate these findings, with one trial even showing increased mortality with TGC. In critically ill children, efficacy and safety of TGC is poorly understood. High rates of insulin-induced hypoglycemia with TGC are concerning. Currently, there are no recommendations on the use of TGC for critically ill children. This review summarizes the current literature on TGC in children, focusing on its benefits and risks. Keywords: hyperglycemia, hypoglycemia, intensive care unit, insulin, glucose

Objectives: In post hoc analyses of our previous phase 2b Bayesian randomized clinical trial (RCT), prophylaxis with enoxaparin reduced central venous catheter (CVC)-associated deep venous thrombosis (CADVT) in critically ill older children but not in infants. The goal of the Catheter-Related Early Thromboprophylaxis with Enoxaparin (CRETE) Studies is to investigate this newly identified age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against CADVT in critically ill children., Design: Two parallel, multicenter Bayesian superiority explanatory RCTs, that is, phase 3 for older children and phase 2b for infants, and an exploratory mechanistic nested case-control study (Trial Registration ClinicalTrials.gov NCT04924322, June 7, 2021)., Setting: At least 15 PICUs across the United States., Patients: Older children 1-17 years old (n = 90) and infants older than 36 weeks corrected gestational age younger than 1 year old (n = 168) admitted to the PICU with an untunneled CVC inserted in the prior 24 hours. Subjects with or at high risk of clinically relevant bleeding will be excluded., Interventions: Prophylactic dose of enoxaparin starting at 0.5 mg/kg then adjusted to anti-Xa range of 0.2-0.5 international units (IU)/mL for older children and therapeutic dose of enoxaparin starting at 1.5 mg/kg then adjusted to anti-Xa range of greater than 0.5-1.0 IU/mL or 0.2-0.5 IU/mL for infants while CVC is in situ., Measurements and Main Results: Randomization is 2:1 to enoxaparin or usual care (no enoxaparin) for older children and 1:1:1 to either of 2 anti-Xa ranges of enoxaparin or usual care for infants. Ultrasonography will be performed after removal of CVC to assess for CADVT. Subjects will be monitored for bleeding. Platelet poor plasma will be analyzed for markers of thrombin generation. Samples from subjects with CADVT will be counter-matched 1:1 to subjects without CADVT from the opposite trial arm. Institutional Review Board approved the "CRETE Studies" on July 1, 2021. Enrollment is ongoing with planned completion in July 2025 for older children and July 2026 for infants., Competing Interests: Dr. Faustino’s institution received funding from the National Center for Advancing Translational Sciences (NCATS). Drs. Faustino’s, Glau’s and Shabanova’s institutions received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Drs. Faustino, Leroue, Sochet, Kong, Nellis, Pinto, Chegondi, Ramirez, Schreiber, Kerris, Glau, Kolmar, Muisyo, Silva, McPartland, and Shabanova received support for article research from the National Institutes of Health (NIH). Drs. Faustino, Kandil, Kerris, Glau, Silva, McPartland, and Shabanova disclosed off-label use of Enoxaparin. Dr. Kandil’s institution received funding from the NICHD (R01 HD106326) and the NCATS (UL1 TR001863); she received funding from the NIH (1R18HS027401-01A1) and the Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes Steering Committee. Drs. Sochet’s, Kong’s, Schreiber’s, Kerris’, Kolmar’s, and Silva’s institutions received funding from the NIH. Dr. Glau received funding from the Medical University of South Carolina. Dr. Sharathkumar is a site investigator for a Pfizer study. Dr. Polikoff received funding from Novavax. Dr. Taylor’s institution received funding from Prolacta Bioscience and Ferring Pharmaceuticals; she received funding from Mother’s Milk Is Best. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Sepsis is a leading cause of pediatric mortality and timely antibiotic administration has been shown to improve outcomes. In this retrospective review of a single center sepsis dataset, we identified younger age and female sex as more likely to have delays in antibiotics., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: We sought to improve utilization of a sepsis care bundle and decrease 3- and 30- day sepsis-attributable mortality, as well as determine which care elements of a sepsis bundle are associated with improved outcomes., Methods: Children's Hospital Association formed a QI collaborative to Improve Pediatric Sepsis Outcomes (IPSO) (January 2017-March 2020 analyzed here). IPSO Suspected Sepsis (ISS) patients were those without organ dysfunction where the provider "intended to treat" sepsis. IPSO Critical Sepsis (ICS) patients approximated those with septic shock. Process (bundle adherence), outcome (mortality), and balancing measures were quantified over time using statistical process control. An original bundle (recognition method, fluid bolus < 20 min, antibiotics < 60 min) was retrospectively compared with varying bundle time-points, including a modified evidence-based care bundle, (recognition method, fluid bolus < 60 min, antibiotics < 180 min). We compared outcomes using Pearson χ-square and Kruskal Wallis tests and adjusted analysis., Results: Reported are 24 518 ISS and 12 821 ICS cases from 40 children's hospitals (January 2017-March 2020). Modified bundle compliance demonstrated special cause variation (40.1% to 45.8% in ISS; 52.3% to 57.4% in ICS). The ISS cohort's 30-day, sepsis-attributable mortality dropped from 1.4% to 0.9%, a 35.7% relative reduction over time (P < .001). In the ICS cohort, compliance with the original bundle was not associated with a decrease in 30-day sepsis-attributable mortality, whereas compliance with the modified bundle decreased mortality from 4.75% to 2.4% (P < .01)., Conclusions: Timely treatment of pediatric sepsis is associated with reduced mortality. A time-liberalized care bundle was associated with greater mortality reductions., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: The pediatric sepsis literature lacks studies examining the inpatient setting, yet sepsis remains a leading cause of death in children's hospitals. More information is needed about sepsis arising in patients already hospitalized to improve morbidity and mortality outcomes. This study describes the clinical characteristics, process measures, and outcomes of inpatient sepsis cases compared with emergency department (ED) sepsis cases within the Improving Pediatric Sepsis Outcomes data registry from 46 hospitals that care for children., Methods: This retrospective cohort study included Improving Pediatric Sepsis Outcomes sepsis cases from January 2017 to December 2019 with onset in inpatient or ED. We used descriptive statistics to compare inpatient and ED sepsis metrics and describe inpatient sepsis outcomes., Results: The cohort included 26 855 cases; 8.4% were inpatient and 91.6% were ED. Inpatient cases had higher sepsis-attributable mortality (2.0% vs 1.4%, P = .025), longer length of stay after sepsis recognition (9 vs 5 days, P <.001), more intensive care admissions (57.6% vs 54.1%, P = .002), and greater average vasopressor use (18.0% vs 13.6%, P <.001) compared with ED. In the inpatient cohort, >40% of cases had a time from arrival to recognition within 12 hours. In 21% of cases, this time was >96 hours. Improved adherence to sepsis treatment bundles over time was associated with improved 30-day sepsis-attributable mortality for inpatients with sepsis., Conclusions: Inpatient sepsis cases had longer lengths of stay, more need for intensive care, and higher vasopressor use. Sepsis-attributable mortality was significantly higher in inpatient cases compared with ED cases and improved with improved sepsis bundle adherence., (Copyright © 2022 by the American Academy of Pediatrics.)

Objectives: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children., Design: Post hoc analysis of a Bayesian phase 2b randomized clinical trial., Setting: Seven PICUs., Patients: Children less than 18 years old with newly inserted central venous catheter., Interventions: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care., Measurements and Main Results: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count., Conclusions: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin., Competing Interests: Drs. Faustino and Spinella received funding to conduct the Catheter-Related Early Thromboprophylaxis with Enoxaparin Trial. Dr. Faustino’s institution received funding from National Institutes of Health (NIH) and the American Heart Association to conduct the trial (16RNT31180018). Drs. Faustino and Spinella received funding from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to conduct the trial (R21HD089131). Drs. Faustino, Hanson, Pinto, Shabanova, and McPartland received support for article research from the NIH. Drs. Faustino, Raffini, Hanson, Kandil, McPartland, and Spinella disclosed off-label product use of enoxaparin (investigational new drug approval from the U.S. Food and Drug Administration was received). Dr. Raffini received funding from Bayer, Genetech, Xa-Tek, and HemaBiologics. Dr. Hanson’s institution received funding from the NIH. Dr. Kandil received funding from Children’s Hospital Collaborative, Improving Pediatric Sepsis Outcomes. Dr. Shabanova’s institution received funding from Prevention of Central Venous Catheter-Associated Thrombosis in Critically Ill Children NICHD: R21HD089131; she received funding through the 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 NIH, and NIH Roadmap for Medical Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP and VCap). Bicalutamide and enzalutamide were used as positive controls. Compound 28 displayed significant enhancement in anticancer activity across the four PC cell lines with IC 50  = 9.09 - 31.11 µM compared to the positive controls: bicalutamide (IC 50  = 45.20 -51.61 µM) and enzalutamide (IC 50  = 11.47 - 53.04 µM). Sulfoxide derivatives of bicalutamide were prepared efficiently from the corresponding sulfides using only one equivalent of mCPBA, limiting the reaction time to 15-30 min and maintaining the temperature at 0 °C. Interestingly, three pairs of sulfoxide diastereomers were separated and NMR comparison of their diastereotopic methylene (CH 2 ) group is presented. X-ray diffraction crystal structure analysis provided relative configuration assignment at the chiral sulfur and carbon centres. Molecular modelling study of the four diastereoisomers of compound 28 is described., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children., Design: Bayesian phase 2b randomized clinical trial., Setting: Seven PICUs., Patients: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding., Intervention: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm)., Measurements and Main Results: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms., Conclusions: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial., Competing Interests: Drs. Faustino and Spinella received funding from the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to conduct the trial (R21HD089131). Dr. Faustino received funding from the American Heart Association to conduct the trial (16RNT31180018). Dr. Shabanova received funding through the 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 NIH, and NIH roadmap for Medical Research. Drs. Faustino’s and Shabanova’s institutions received funding from NICHD, American Heart Association, and the National Center for Advancing Translational Science. Drs. Faustino, Shabanova, Hanson, Sharathkumar, and Thomas received support for article research from the NIH. Dr. Faustino, Dr. Raffini, Dr. Kandil, Dr. Hanson, and Ms. McPartland disclosed off-label product use of enoxaparin. Dr. Raffini received funding from CSL Behring, XaTek, and Bayer. Dr. Pinto’s institution received funding from the NIH. Dr. Hanson’s institution received funding from NIH/Eunice Kennedy Shriver NICHD. Dr. Thomas’ institution received funding from Yale University. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of 15 bicalutamide analogues (sulfide, deshydroxy, sulfone, and O -acetylated) were prepared and their antiproliferative activity evaluated against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP, and VCap). Bicalutamide and enzalutamide were used as positive controls. Seven of these compounds displayed remarkable enhancement in anticancer activity across the four PC cell lines. The deshydroxy analogue ( 16 ) was the most active compound with IC 50 = 6.59-10.86 µM. Molecular modeling offers a plausible explanation of the higher activity of the sulfide analogues compared to their sulfone counterparts.

Focal adhesion kinase (FAK) is a tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. In cancer cells, FAK promotes the progression and metastasis of tumours. In this study, we used structure-based virtual screening to filter a library of more than 210K compounds against the focal adhesion targeting FAK-focal adhesion targeting (FAT) domain to identify 25 virtual hit compounds which were screened in the invasive breast cancer line (MDA-MB-231). Most notably, compound I showed low micromolar antiproliferative activity, as well as antimigratory activity. Moreover, examination in a model of triple negative breast cancer (TNBC), revealed that, despite not effecting FAK phosphorylation, compound I significantly impairs proliferation whilst impairing focal adhesion growth and turnover leading to reduced migration. Further optimisation and synthesis of analogues of the lead compound I using a four-step synthetic procedure was performed, and analogues were assessed for their antiproliferative activity against three breast cancer (MDA-MB-231, T47D, BT474) cell lines and one pancreatic cancer (MIAPaCa2) cell line. Compound 5f was identified as a promising lead compound with IC 50 values in the range of 4.59-5.28 μM in MDA-MB-231, T47D, BT474, and MIAPaCa2. Molecular modelling and pharmacokinetic studies provided more insight into the therapeutic features of this new series.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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.

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.

Background: Sepsis is a significant cause of morbidity and mortality. Patients may present in a spectrum, from nonsevere sepsis through septic shock. Literature supports improvement in patient outcomes with timely care. This project describes an effort to improve delays in antibiotic administration in patients with sepsis spectrum disease presenting to a pediatric emergency department (PED)., Objective: This project aimed to decrease time to antibiotics for patients with sepsis in the PED from 154 to <120 minutes within 2 years., Methods: Following the collection of baseline data, we assembled a multidisciplinary team. Specific interventions included staff education, the institution of a best practice alert with order set and standardized huddle response, and local stocking of antibiotics. We included all patients with orders for intravenous antibiotics and blood culture., Results: From April 2015 to April 2017, the PED demonstrated reduction in time to antibiotics from 154 to 114 minutes. The time from emergency department (ED) arrival to antibiotic order also improved, from 87 to 59 minutes., Conclusions: This initiative improved prioritization and efficiency of care of sepsis, and overall time to antibiotics in this population. The results of this project demonstrate the effectiveness of a multidisciplinary team working to improve an essential time-driven process., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Children who require an endotracheal (ET) tube for care during critical illness are at risk of unplanned extubations (UE), or the unintended dislodgement or removal of an ET tube that can lead to significant patient harm. A proposed national benchmark is 1 UE per 100 ventilator days. We aimed to reduce the rate of UEs in our intensive care units (ICUs) from 1.20 per 100 ventilator days to below the national benchmark within 2 years., Methods: We identified several key drivers including ET securement standardization, safety culture, and strategies for high-risk situations. We employed quality improvement methodologies including apparent cause analysis and plan-do-study-act cycles to improve our processes and outcomes., Results: Over 2 years, we reduced the rate of UEs hospital-wide by 75% from 1.2 to 0.3 per 100 ventilator days. We eliminated UEs in the pediatric ICU during the study period, while the UE rate in the neonatal ICU also decreased from 1.2 to 0.3 per 100 ventilator days., Conclusion: We demonstrated that by using quality improvement methodology, we successfully reduced our rate of UE by 75% to a level well below the proposed national benchmark.

Deficiency in 25-hydroxyvitamin D (25OHD) is associated with increased morbidity and mortality in the critically ill. Children who underwent surgery for congenital heart disease under cardiopulmonary bypass (CPB) are typically deficient in 25OHD. It is unclear whether this deficiency is due to CPB. We hypothesized that CPB reduces the levels of 25OHD in children with congenital heart disease. We conducted a prospective observational study on children aged 2 months to 17 years who underwent CPB. Serum was collected at 3 time points: immediately before, immediately after surgery, and 24 hours after surgery. 25-Hydroxyvitamin D, 1,25-dihydroxyvitamin D, 1,25(OH) 2 D, vitamin D binding protein, and albumin levels were measured. Levels were compared using repeated measures analysis of variance. We enrolled 20 patients, 40% were deficient in 25OHD with levels <20 ng/mL prior to surgery. Mean (±standard deviation) of 25OHD at the 3 time points was 21.3 ± 8 ng/mL, 19 ± 5.8 ng/mL, and 19.5 ± 6.6 ng/mL, respectively ( P = .02). The decrease in 25OHD was observed primarily in children with sufficient levels of 25OHD, with mean levels at the 3 time points: 26.8 ± 4.2 ng/mL, 21.5 ± 5.7 ng/mL, and 23.0 ± 4.9 ng/mL, respectively ( P < .001). Calculated means of free fraction of 25OHD at the 3 time points were 6.2 ± 2.8 pg/mL, 5.8 ± 2.2 pg/mL, and 5.5 ± 2.4 pg/mL, respectively, ( P = .04). Mean levels of 1,25(OH) 2 D were 63.7 ± 34.9 ng/mL, 53.2 ± 30.6 ng/mL, and 67.7 ± 23.5 ng/mL ( P = .04). Vitamin D binding protein and albumin levels did not significantly change. Cardiopulmonary bypass decreases 25OHD by reducing the free fraction. Current investigations are geared to establish whether vitamin D deficiency is associated with outcomes and if treatment is appropriate.

The mechanisms of action of vitamin D are the subject of intense investigation. Evidence now suggests vitamin D affects immune function and cell proliferation, prompting interest in its role in critical illness and cardiac disease. Multiple studies demonstrate strong associations between vitamin D deficiency and severity of illness including need for higher inotrope support, more fluid resuscitation, and longer intensive care unit stay. The pediatric cardiac population may be at even more risk and nearly twice as likely to be deficient compared to the noncardiac population. Low vitamin D levels have been found in postoperative cardiac patients, where investigators speculate cardiopulmonary bypass alters levels directly or indirectly. Patients with congestive heart failure who are deficient also seem to benefit from vitamin D supplementation. This review summarizes recent studies in children that investigate the relation between vitamin D status and clinical outcomes in the critically ill including those with cardiac disease.

Background: Hyperglycemia is a significant problem for critically ill children. Treatment for hyperglycemia remains controversial. This study explores the effect of controlling blood glucose (BG) in hyperglycemic critically ill children., Methods: A retrospective cohort of nondiabetic critically ill children (defined as requiring mechanical ventilation and/or vasopressors) with BG persistently ≥ 150 mg/dl and treated with insulin (treatment group) were compared with a historical cohort of similar children who did not receive interventions to control hyperglycemia (baseline group)., Results: There were 130 children in the treatment group and 137 children in the baseline group. Mean BG in the treatment group was 140 ± 24 mg/dl compared with 179 ± 47 mg/dl in the baseline group (p < .001). After adjusting for patient characteristics, cointerventions, and glucose metrics, patients in the treatment group had 2.5 fewer intensive care unit (ICU)-free days (i.e., number of days alive and discharged from ICU within 28 days after inclusion) than the baseline group (p = .023). Glucose control was not independently associated with duration of ICU stay, ventilator-free days, vasopressor-free days, or mortality., Conclusions: Blood glucose control appears associated with worse outcomes in critically ill children. Our data combined with conflicting results in adults leads us to strongly advocate for the conduct of randomized trials on glucose control in critically ill children., (© 2013 Diabetes Technology Society.)

Purpose of Review: Hyperglycemia is a significant problem for children in the ICU. Use of tight glycemic control (TGC) to manage hyperglycemia remains controversial, especially given the potential risk of insulin-induced hypoglycemia. This review will address the latest evidence regarding TGC in critically ill children., Recent Findings: Two randomized controlled trials (RCT) involving primarily postoperative cardiac surgery patients demonstrated the feasibility and safety of TGC in pediatric patients. The trials, however, had discrepant results with regards to the benefit of TGC. There is also uncertainty about the generalizability of these results to nonpostoperative cardiac patients. There is only one published study addressing the long-term safety of TGC in children. In this study, hypoglycemia was not associated with adverse effects on neurocognitive development. In contrast, articles from adult studies demonstrate increased risk of death with hypoglycemia., Summary: Although the clinical benefit of TGC in critically ill children is still unclear, TGC can be done safely in this population.

Background: Determining appropriate disposition for referred pediatric patients is difficult, since it relies primarily on a telephone description of the patient. In this study, we evaluate the Transport Risk Assessment in Pediatrics (TRAP) score's ability to assist in appropriate placement of these patients. This novel tool is derived from physiologic variables., Objectives: To determine the feasibility of calculating a TRAP score and whether a higher score correlates with pediatric intensive care unit (PICU) admission., Methods: We performed an observational study of pediatric patients transported by a specialized team to a tertiary care center and the feasibility of implementing the TRAP tool. Patients were eligible if transported by the pediatric specialty transport team for direct admission to the children's hospital. The TRAP score was obtained either through chart review of the transport team's initial assessment or in real time by the transport team., Results: A total of 269 patients were identified, with 238 patients included in the study. Using logistic regression, higher TRAP scores were associated with PICU admission (odds ratio [OR] 1.40, p < 0.001). Patients with a higher score were also less likely to leave the PICU within 24 hours (OR 0.79, p < 0.001)., Conclusion: The TRAP score is a novel objective pediatric transport assessment tool where an elevated score is associated with PICU admission for more than 24 hours. This score may assist with the triage decisions for transported pediatric patients.