Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024.

RATIONALE: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods. OBJECTIVES: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians. PANEL DESIGN: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting. METHODS: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research. RESULTS: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available. CONCLUSIONS: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.

Development and clinical feasibility of a reduced-dose radiograph in children for feeding tube placement.

BACKGROUND: Temporary feeding tubes are commonly used but may lead to complications if malpositioned. Radiographs are the gold standard for assessing tube position, but clinician concern over radiation risks may curtail their use. OBJECTIVE: We describe development and use of a reduced dose feeding tube radiograph (RDFTR) targeted for evaluation of feeding tube position. MATERIALS AND METHODS: Age-based abdominal radiograph was adapted to use the lowest mAs setting of 0.32 mAs with field of view between carina and iliac crests. The protocol was tested in DIGI-13 line-pair plates and anthropomorphic phantoms. Retrospective review of initial clinical use compared dose area product (DAP) for RDFTR and routine abdomen, chest, or infant chest and abdomen. Review of RDFTR reports assessed tube visibility, malpositioning, and incidental critical findings. RESULTS: Testing through a line-pair phantom showed loss of spatial resolution from 2.2 line pairs to 0.6 line pairs but preserved visibility of feeding tube tip in RDFTR protocol. DAP comparisons across 23,789 exams showed RDFTR reduced median DAP 72-93% compared to abdomen, 55-78% compared to chest, and 76-79% compared to infant chest and abdomen (p<0.001). Review of 3286 reports showed tube was visible in 3256 (99.1%), malpositioned in airway 8 times (0.2%) and in the esophagus 74 times (2.3%). The tip was not visualized in 30 (0.9%). Pneumothorax or pneumoperitoneum was noted seven times (0.2%) but was expected or spurious in five of these cases. CONCLUSION: RDFTR significantly reduces radiation dose in children with temporary feeding tubes while maintaining visibility of tube tip.

Clinical and Analytic Accuracy of Simultaneously Acquired Hemoglobin Measurements: A Multi-Institution Cohort Study to Minimize Redundant Laboratory Usage.

OBJECTIVES: Frequent diagnostic blood sampling contributes to anemia among critically ill children. Reducing duplicative hemoglobin testing while maintaining clinical accuracy can improve patient care efficacy. The objective of this study was to determine the analytical and clinical accuracy of simultaneously acquired hemoglobin measurements with different methods. DESIGN: Retrospective cohort study. SETTING: Two U.S. children's hospitals. PATIENTS: Children (< 18 yr old) admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified hemoglobin results from complete blood count (CBC) panels paired with blood gas (BG) panels and point-of-care (POC) devices. We estimated analytic accuracy by comparing hemoglobin distributions, correlation coefficients, and Bland-Altman bias. We measured clinical accuracy with error grid analysis and defined mismatch zones as low, medium, or high risk-based on deviance from unity and risk of therapeutic error. We calculated pairwise agreement to a binary decision to transfuse based on a hemoglobin value. Our cohort includes 49,004 ICU admissions from 29,926 patients, resulting in 85,757 CBC-BG hemoglobin pairs. BG hemoglobin was significantly higher (mean bias, 0.43-0.58 g/dL) than CBC hemoglobin with similar Pearson correlation ( R2 ) (0.90-0.91). POC hemoglobin was also significantly higher, but of lower magnitude (mean bias, 0.14 g/dL). Error grid analysis revealed only 78 (< 0.1%) CBC-BG hemoglobin pairs in the high-risk zone. For CBC-BG hemoglobin pairs, at a BG hemoglobin cutoff of greater than 8.0 g/dL, the "number needed to miss" a CBC hemoglobin less than 7 g/dL was 275 and 474 at each institution, respectively. CONCLUSIONS: In this pragmatic two-institution cohort of greater than 29,000 patients, we show similar clinical and analytic accuracy of CBC and BG hemoglobin. Although BG hemoglobin values are higher than CBC hemoglobin values, the small magnitude is unlikely to be clinically significant. Application of these findings may reduce duplicative testing and decrease anemia among critically ill children.

Status 1B designation does not adequately prioritize children with acute-on-chronic liver failure for liver transplantation.

Acute-on-chronic liver failure (ACLF) is an acute decompensation of chronic liver disease leading to multiorgan failure and mortality. The objective of this study was to evaluate characteristics and outcomes of children with ACLF who are at the highest priority for liver transplantation (LT) on the United Network for Organ Sharing (UNOS) database-listed as status 1B. The characteristics and outcomes of 478 children with ACLF listed as status 1B on the UNOS LT waiting list from 2007-2019 were compared with children with similar or higher priority listing for transplant: 929 with acute liver failure (ALF) listed as status 1A and 808 with metabolic diseases and malignancies listed as status 1B (termed "non-ACLF"). Children with ACLF had comparable rates of cumulative organ failures compared with ALF (45% vs. 44%; p > 0.99) listings, but higher than non-ACLF (45% vs. 1%; p < 0.001). ACLF had the lowest LT rate (79%, 84%, 95%; p < 0.001), highest pre-LT mortality (20%, 11%, 1%; p < 0.001), and longest waitlist time (57, 3, 56 days; p < 0.001), and none recovered without LT (0%, 4%, 1%; p < 0.001). In survival analyses, ACLF was associated with an increased adjusted hazard ratio (HR) for post-LT mortality (HR, 1.50 vs. ALF [95% confidence interval, CI, 1.02-2.19; p = 0.04] and HR, 1.64 vs. non-ACLF [95% CI, 1.15-2.34; p = 0.01]). ACLF has the least favorable waitlist and post-LT outcomes of all patients who are status 1A/1B. Increased prioritization on the LT waiting list may offer children with ACLF an opportunity for enhanced outcomes.

Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the PICU: A Multicenter Survey.

OBJECTIVES: Pediatric Advanced Life Support (PALS) guidelines include weight-based epinephrine dosing recommendations of 0.01 mg/kg with a maximum of 1 mg, which corresponds to a weight of 100 kg. Actual practice patterns are unknown. DESIGN: Multicenter cross-sectional survey regarding institutional practices for the transition from weight-based to flat dosing of epinephrine during cardiopulmonary resuscitation in PICUs. Exploratory analyses compared epinephrine dosing practices with several institutional characteristics using Fisher exact test. SETTING: Internet-based survey. SUBJECTS: U.S. PICU representatives (one per institution) involved in resuscitation systems of care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 137 institutions surveyed, 68 (50%) responded. Most responding institutions are freestanding children's hospitals or dedicated children's hospitals within combined adult/pediatric hospitals (67; 99%); 55 (81%) are academic and 41 (60%) have PICU fellowship programs. Among respondents, institutional roles include PICU medical director (13; 19%), resuscitation committee member (23; 34%), and attending physician with interest in resuscitation (21; 31%). When choosing between weight-based and flat dosing, 64 respondents (94%) report using patient weight, 23 (34%) patient age, and five (7%) patient pubertal stage. Among those reporting using weight, 28 (44%) switch at 50 to less than 60 kg, 17 (27%) at 60 to less than 80 kg, five (8%) at 80 to less than 100 kg, and eight (12%) at greater than or equal to 100 kg. Among those reporting using age, four (17%) switch at 14 to less than 16 years, five (22%) at 16 to less than 18, and six (26%) at greater than or equal to 18. Twenty-nine respondents (43%) report using ideal body weight when dosing epinephrine in obese patients. Using patient age in choosing epinephrine dosing is more common in institutions that require Advanced Cardiac Life Support (ACLS) certification for some/all code team responders compared with institutions that do not require ACLS certification (52% vs 22%; p = 0.02). CONCLUSIONS: The majority of PICUs surveyed report epinephrine dosing practices that are inconsistent with PALS guidelines.

2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

RATIONALE: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements. CONCLUSIONS: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study.

BACKGROUND: Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. METHODS: Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. RESULTS: Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. CONCLUSIONS: In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.

Tight Glycemic Control in Critically Ill Children.

BACKGROUND: In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. METHODS: In a 35-center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower-target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher-target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)-free days to day 28. RESULTS: The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower-target group and 353 to the higher-target group. In the intention-to-treat analysis, the median number of ICU-free days did not differ significantly between the lower-target group and the higher-target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per-protocol analyses, the median time-weighted average glucose level was significantly lower in the lower-target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher-target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower-target group also had higher rates of health care-associated infections than those in the higher-target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator-free days. CONCLUSIONS: Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF-PINT ClinicalTrials.gov number, NCT01565941 .).

A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research.

OBJECTIVES: The Heart And Lung Failure-Pediatric INsulin Titration study was experiencing poor subject enrollment due to low rates of informed consent. Heart And Lung Failure-Pediatric INsulin Titration investigators collaborated with the Perelman School of Medicine Standardized Patient Program to explore the novel use of telesimulation with standardized parents to train research staff to approach parents of critically ill children for informed consent. We describe the feasibility, learner acceptance, and financial costs of this novel intervention and performed a post hoc analysis to determine if this intervention improved study consent rates. DESIGN: Observational, comparative effectiveness study. SETTING: Heart And Lung Failure-Pediatric INsulin Titration study enrolling sites. SUBJECTS: Research staff (at the remote site). INTERVENTIONS: Individual 90-minute Skype telesimulation sessions with standardized parent and simulation facilitator (at the training site). MEASUREMENTS AND MAIN RESULTS: Forty telesimulation sessions with 79 Heart And Lung Failure-Pediatric INsulin Titration research staff (participants) at 24 remote sites were conducted. Despite some technical delays, 40 out of 40 simulations (100%) were completed. Based on feedback surveys, 100% of respondents agreed (81% strongly agreed) that telesimulation sessions achieved intended learning objectives to prepare research staff to approach parents of eligible critically ill children to obtain informed consent. Additionally, 100% of respondents agreed (74% strongly agreed) that they would use lessons from the telesimulation when approaching parents to obtain informed consent for research. Telesimulation with standardized parents achieved lower financial costs (approximately $85 per session) compared with traditional in-person site visits for training research staff. There was no significant improvement in study consent rates with the intervention (pre: 46% vs post: 48%; p = 0.78). CONCLUSIONS: Remote telesimulation with standardized parents is feasible, acceptable, and associated with lower financial costs to prepare research staff to obtain informed consent from parents of critically ill children eligible for clinical research trials. Despite this novel approach, Heart And Lung Failure-Pediatric INsulin Titration study consent rates did not improve, suggesting that other factors influence parental consent and decision making in complex multicenter clinical research trials.

Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial.

OBJECTIVES: The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children. DESIGN: Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial. SETTING: Thirty-five PICUs. PATIENTS: Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data. INTERVENTIONS: Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time). MEASUREMENTS AND MAIN RESULTS: Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001). CONCLUSIONS: In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes.

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children.

OBJECTIVES: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children. DESIGN: Nested case-control study. SETTING: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia. PATIENTS: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia. CONCLUSIONS: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Outcomes Associated With Multiple Organ Dysfunction Syndrome in Critically Ill Children With Hyperglycemia.

OBJECTIVES: Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. DESIGN: Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. SETTING: Thirty-five PICUs. PATIENTS: Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. INTERVENTIONS: Randomization to a lower versus higher glucose target group. MEASUREMENTS AND MAIN RESULTS: Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). CONCLUSIONS: Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.

The Association of Nutrition Status Expressed as Body Mass Index z Score With Outcomes in Children With Severe Sepsis: A Secondary Analysis From the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study.

OBJECTIVES: The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in pediatric severe sepsis. DESIGN: Secondary analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient characteristics, ICU interventions, and outcomes were compared across nutrition status categories (expressed as age- and sex-adjusted body mass index z scores using World Health Organization standards). Multivariable regression models were developed to determine adjusted differences in all-cause ICU mortality and ICU length of stay by nutrition status. SETTING: One-hundred twenty-eight PICUs across 26 countries. PATIENTS: Children less than 18 years with severe sepsis enrolled in the Sepsis Prevalence, Outcomes, and Therapies study (n = 567). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nutrition status data were available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia (20%), South Africa (17%), and South America (10%), with severe overnutrition seen in Australia/New Zealand (17%) and North America (14%). Severe undernutrition was independently associated with all-cause ICU mortality (adjusted odds ratio, 3.0; 95% CI, 1.2-7.7; p = 0.02), whereas severe overnutrition in survivors was independently associated with longer ICU length of stay (1.6 d; p = 0.01). CONCLUSIONS: There is considerable variation in nutrition status for children with severe sepsis treated across this selected network of PICUs from different geographic regions. Severe undernutrition was independently associated with higher all-cause ICU mortality in children with severe sepsis. Severe overnutrition was independently associated with greater ICU length of stay in childhood survivors of severe sepsis.

Failure of Invasive Airway Placement on the First Attempt Is Associated With Progression to Cardiac Arrest in Pediatric Acute Respiratory Compromise.

OBJECTIVES: The aim of this study was to describe the proportion of acute respiratory compromise events in hospitalized pediatric patients progressing to cardiopulmonary arrest, and the clinical factors associated with progression of acute respiratory compromise to cardiopulmonary arrest. We hypothesized that failure of invasive airway placement on the first attempt (defined as multiple attempts at tracheal intubation, and/or laryngeal mask airway placement, and/or the creation of a new tracheostomy or cricothyrotomy) is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest. DESIGN: Multicenter, international registry of pediatric in-hospital acute respiratory compromise. SETTING: American Heart Association's Get with the Guidelines-Resuscitation registry (2000-2014). PATIENTS: Children younger than 18 years with an index (first) acute respiratory compromise event. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,210 index acute respiratory compromise events, 64% required controlled ventilation, 26% had return of spontaneous ventilation, and 10% progressed to cardiopulmonary arrest. There were 762 acute respiratory compromise events (34%) that did not require an invasive airway, 1,185 acute respiratory compromise events (54%) with successful invasive airway placement on the first attempt, and 263 acute respiratory compromise events (12%) with failure of invasive airway placement on the first attempt. After adjusting for confounding variables, failure of invasive airway placement on the first attempt was independently associated with progression of acute respiratory compromise to cardiopulmonary arrest (adjusted odds ratio 1.8 [95% CIs, 1.2-2.6]). CONCLUSIONS: More than 1 in 10 hospitalized pediatric patients who experienced an acute respiratory compromise event progressed to cardiopulmonary arrest. Failure of invasive airway placement on the first attempt is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest.

Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

OBJECTIVES: The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. DESIGN: Retrospective cohort study. SETTING: Non-cardiac PICU. PATIENTS: Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 µg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 µg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 µg/dL (all p < 0.05). Children with stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p < 0.05). Mean random serum total cortisol levels were similar in children with and without stress dose hydrocortisone (21.1 vs 18.7 µg/dL; p = 0.69). In children with random serum total cortisol less than 18 µg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p < 0.05). In children with random serum total cortisol greater than 18 µg/dL, stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all p < 0.05). CONCLUSIONS: Stress dose hydrocortisone therapy in children with catecholamine-dependent septic shock correlated more with severity of illness than random serum total cortisol levels and was associated with worse outcomes, irrespective of random serum total cortisol levels.

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVE: To test the association between random cortisol and severity of illness in a "real-world" application of current guidelines. STUDY DESIGN: We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels before potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 and ≥ 18 µg/dL, and hydrocortisone use and outcomes compared. RESULTS: Of 357 children with ARDS, 155 (15 nonsurvivors; 10%) had vasopressors initiated with cortisol drawn before possible hydrocortisone use. Patients with cortisol < 18 µg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum P < .05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 µg/dL. In patients with cortisol ≥ 18 µg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. CONCLUSIONS: In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 µg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function.

On architecting and composing engineering information services to enable smart manufacturing.

Engineering information systems play an important role in the current era of digitization of manufacturing, which is a key component to enable smart manufacturing. Traditionally, these engineering information systems spanned the lifecycle of a product by providing interoperability of software subsystems through a combination of open and proprietary exchange of data. But research and development efforts are underway to replace this paradigm with engineering information services that can be composed dynamically to meet changing needs in the operation of smart manufacturing systems. This paper describes the opportunities and challenges in architecting such engineering information services and composing them to enable smarter manufacturing.