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Background: Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol., Methods: In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia., Results: Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia., Conclusion: Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia., (© 2023. The Author(s).)

Background: We aimed to test a novel method of delivery of chloral hydrate (CH) sedation in ventilated critically ill young children., Methods: Children < 12 years old, within 72 hours of admission, who were ventilated, receiving enteral tube-feeds, with intermittent CH ordered were enrolled after signed consent. Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases were compared to historical controls matched for age group and Pediatric Risk of Mortality score (PRISM) category, using Fisher's exact test and the t test. The primary outcome was feasibility, defined as the use of an enteral CH continuous infusion without discontinuation attributable to a pre-specified potential harm., Results: There were 21 patients enrolled, at age 11.4 (12.1) months, with bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD) score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5 (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients, with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8 (IQR 7, 9). Days to titration of adequate sedation (defined as ≤ 3 PRN doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5 (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2 (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p = 0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically significant differences between cases and controls in inotrope scores, signs or treatment of withdrawal, or PICU days., Conclusions: Delivering CH by continuous enteral infusion is feasible, effective, and may be associated with less positive fluid balance. Whether there is a risk of duodenal perforation requires further study.

Background: The accuracy of arterial lines (AL) using the flush test or stopcock test has not been described in children, nor has the difference between invasive arterial blood pressure (IABP) versus non-invasive cuff (NIBP) blood pressure., Methods: After ethics approval and consent, we performed the flush test and stopcock test on AL (to determine over damping, under damping, and optimal damping), and determined the difference (NIBP-IABP) in systolic, diastolic, and mean blood pressure (ΔSBP, ΔDBP, and ΔMAP). The primary outcome was incidence (95 % CI) of optimally damped AL. Predictors of ΔBP (effect size (95 % CI)) were determined using multiple linear regression., Results: There were 147 AL tests in 100 enrolled patients with mean age 44.7 (SD 56) months, weight 16.8 (SD 18.3) kg, male 59 %, postoperative-cardiovascular 52 %, peripheral-AL 78 %, inotropes 29 %, vasodilators 15 %, and ventilated 73 %. The flush test performed in 66 patients (45 %) showed optimal damping in 30 (46 %; 95 % CI 34, 57 %), over damping in 25 (38 %) and under damping in 11 patients (17 %). The stopcock test was over-damped in 128/146 patients (88 %), with the same damping as the flush test in 24/64 (38 %). In optimally damped (flush test) AL, ΔSBP, ΔDBP, and ΔMAP were 0.8 (SD 12.2), -5.2 (SD 8.7), and -4.9 (7.6) respectively. A second set of AL tests was done 2 h later on the same day in 62 patients; AL damping often changed (10/28 flush tests) and ΔBPs correlated poorly (r = 0.31-0.55). Predictors (effect size) of ΔDBP were vasodilator infusion (15.6 (2.9 to 28.3); p = 0.016) and optimal damping (-7.2 (-12.2 to 2.2); p = 0.005); and of ΔMAP were vasodilator infusion (10.0 (-0.3 to 20.4); p = 0.057) and optimal damping (-4.0 (-8 to 0.1); p = 0.058). There were no independent predictors of damping category (n = 66 flush tests)., Conclusions: Optimally damped AL occur in half of critically ill children, and this is not predictable. There is much variability in ∆BP between NIBP and the gold standard IABP, and this varies even in the same patient on the same day, and is not easily predictable. In critically ill children, NIBP may not be accurate enough to guide management, and more attention to ensuring the AL is optimally damped is needed.

Introduction: Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited., Methods: The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher's Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days., Results: Seventy-nine children, age median 60 (IQR 22-133) months, 40 (51%) female, 39 (49%) with severe underlying co-morbidity, 44 (56%) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46%) at an outlying hospital ED, and 21 (27%) at the Children's Hospital ED. Most infections were pneumonia with/without empyema (42, 53%), meningitis (11, 14%), or bacteremia (10, 13%). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25%) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95% CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days (effect size 0.09 days; 95% CI 0.02, 0.15; per ml/kg)., Conclusion: Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days. More study on the benefits and harms of fluid bolus therapy in children are needed.