Impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients (PEPaNIC trial): Study protocol for a randomized controlled trial

Background: The state-of-the-art nutrition used for critically ill children is based essentially on expert opinion and extrapolations from adult studies or on studies in non-critically ill children. In critically ill adults, withholding parenteral nutrition (PN) during the first week in ICU improved outcome, as compared with early supplementation of insufficient enteral nutrition (EN) with PN. We hypothesized that withholding PN in children early during critical illness reduces the incidence of new infections and accelerates recovery. Methods/Design: The Pediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) study is an investigator-initiated, international, multicenter, randomized controlled trial (RCT) in three tertiary referral pediatric intensive care units (PICUs) in three countries on two continents. This study compares early versus late initiation of PN when EN fails to reach preset caloric targets in critically ill children. In the early-PN (control, standard of care) group, PN comprising glucose, lipids and amino acids is administered within the first days to reach the caloric target. In the late-PN (intervention) group, PN completing EN is only initiated beyond PICU-day 7, when EN fails. For both study groups, an early EN protocol is applied and micronutrients are administered intravenously. The primary assessor-blinded outcome measures are the incidence of new infections during PICU-stay and the duration of intensive care dependency. The sample size (n = 1,440, 720 per arm) was determined in order to detect a 5% absolute reduction in PICU infections, with at least 80% 1-tailed power (70% 2-tailed) and an alpha error rate of 5%. Based on the actual incidence of new PICU infections in the control group, the required sample size was confirmed at the time of an a priori- planned interim-analysis focusing on the incidence of new infections in the control group only. Discussion: Clinical evidence in favor of early administration of PN in critically ill children is currently lacking, despite potential benefit but also known side effects. This large international RCT will help physicians to gain more insight in the clinical effects of omitting PN during the first week of critical illness in children

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC)

__Background:__ The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy. __Methods:__ Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 pa

Biliary sludge and recurrent ketoacidosis: a case report

A five year old boy, weighing 14 kg with no family history of diabetes, presented in frank diabetic ketoacidosis. He recovered, but continued to have episodes of ketoacidosis. He was diagnosed to have biliary sludge, which recovered with insulin treatment

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

Cost-effectiveness study of early versus late parenteral nutrition in critically ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised controlled trial

Abstract Background The multicentre randomised controlled PEPaNIC trial showed that withholding parenteral nutrition (PN) during the first week of critical illness in children was clinically superior to providing early PN. This study describes the cost-effectiveness of this new nutritional strategy. Methods Direct medical costs were calculated with use of a micro-costing approach. We compared the costs of late versus early initiation of PN (n = 673 versus n = 670 patients) in the Belgian and Dutch study populations from a hospital perspective, using Student’s t test with bootstrapping. Main cost drivers were identified and the impact of new infections on the total costs was assessed. Results Mean direct medical costs for patients receiving late PN (€26.680, IQR €10.090–28.830 per patient) were 21% lower (-€7.180, p = 0.007) than for patients receiving early PN (€33.860, IQR €11.080–34.720). Since late PN was more effective and less costly, this strategy was superior to early PN. The lower costs for PN only contributed 2.1% to the total cost reduction. The main cost driver was intensive care hospitalisation costs (-€4.120, p = 0.003). The patients who acquired a new infection (14%) were responsible for 41% of the total costs. Sensitivity analyses confirmed consistency across both healthcare systems. Conclusions Late initiation of PN decreased the direct medical costs for hospitalisation in critically ill children, beyond the expected lower costs for withholding PN. Avoiding new infections by late initiation of PN yielded a large cost reduction. Hence, late initiation of PN was superior to early initiation of PN largely via its effect on new infections. Trial registration ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012

Modeling of Effect of Glucose Sensor Errors on Insulin Dosage and Glucose Bolus Computed by LOGIC-Insulin

BACKGROUND: Effective and safe glycemic control in critically ill patients requires accurate glucose sensors and adequate insulin dosage calculators. The LOGIC-Insulin calculator for glycemic control has recently been validated in the LOGIC-1 randomized controlled trial. In this study, we aimed to determine the allowable error for intermittent and continuous glucose sensors, on the basis of the LOGIC-Insulin calculator. METHODS: A gaussian simulation model with a varying bias (0%-20%) and CV (-20% to +20%) simulated blood glucose values from the LOGIC-1 study (n = 149 patients) in 10 Monte Carlo steps. A clinical error grid system was developed to compare the simulated LOGIC-Insulin-directed intervention with the nominal intervention (0% bias, 0% CV). The severity of error measuring the clinical effect of the simulated LOGIC-Insulin intervention was graded as type B, C, and D errors. Type D errors were classified as acutely life-threatening (0% probability preferred). RESULTS: The probability of all types of errors was lower for continuous sensors compared with intermittent sensors. The maximum total error (TE), defined as the first TE introducing a type B/C/D error, was similar for both sensor types. To avoid type D errors, TEs <15.7% for intermittent sensors and <17.8% for continuous sensors were required. Mean absolute relative difference thresholds for type C errors were 7.1% for intermittent and 11.0% for continuous sensors. CONCLUSIONS: Continuous sensors had a lower probability for clinical errors than intermittent sensors at the same accuracy level. These simulations demonstrated the suitability of the LOGIC-Insulin control system for use with continuous, as well as intermittent, sensors.status: publishe

Waking up the gut in critically ill patients

Multiorgan failure frequently develops in critically ill patients. While therapeutic efforts in such patients are often focused on the lungs, on the cardiovascular system as well as on the kidneys, it is important to also consider the functional alterations in gut motility and hormone secretion. Given the central regulatory functions of many gut hormones, such as glucagon-like peptide 1, glucagon-like peptide 2, ghrelin and others, exogenous supplementation of some of these factors may be beneficial under conditions of critical illness. From a pragmatic point of view, the most feasible way towards a restoration of gut hormone secretion in critically ill patients is to provide enteral nutritional supply as soon as possible