Early versus Late Parenteral Nutrition in Critically Ill Children.

BACKGROUND: Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. METHODS: We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. RESULTS: Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006). CONCLUSIONS: In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).

Nutritional support and the role of the stress response in critically ill children.

PURPOSE OF REVIEW: Nutrition impacts outcome in critically ill children. Based on evolving neuro-endocrine, immunologic and metabolic alterations, three different phases can be proposed during the course of illness. The different phases each demand for tailored macronutrient intakes in critically ill children. RECENT FINDINGS: Early enteral nutrition is associated with decreased morbidity and mortality, but several misconceptions concerning the provision of enteral nutrition prevent adequate intake. Parenteral nutrition in critically ill children is associated with potential disadvantages, as nosocomial infections, but evidence on the effect on clinical outcome is lacking. Nutrient restriction early during critical illness might be beneficial for short and long-term outcomes by decreasing the incidence of side-effects and possibly by amplifying the acute catabolic stress response and stimulating autophagy and muscle integrity. Higher caloric and protein intake via the enteral route are associated with higher 60-day survival, asking for a more aggressive feeding approach in subsequent phases. SUMMARY: Understanding the stress response to critical illness and its phases is essential for nutritional recommendations in critically ill children. Although parenteral nutrient restriction during the acute phase might be beneficial, inclining requirements ask for a more aggressive approach during the stable and recovery phase to enable recovery, growth and catch-up growth.

Use of Indirect Calorimetry to Detect Overfeeding in Critically Ill Children: Finding the Appropriate Definition.

OBJECTIVES: Overfeeding during critical illness is associated with adverse effects such as metabolic disturbances and increased risk of infection. Because of the lack of sound studies with clinical endpoints, overfeeding is arbitrarily defined as the ratio caloric intake/measured resting energy expenditure (mREE) or alternatively as a comparison of measured respiratory quotient (RQ) to the predicted RQ based on the macronutrient intake (RQmacr). We aimed to compare definitions of overfeeding in critically ill mechanically ventilated children based on mREE, RQ, and caloric intake to find an appropriate definition. METHODS: Indirect calorimetry measurements were performed in 78 mechanically ventilated children, median age 6.3 months. Enteral and/or parenteral nutrition was provided according to the local guidelines. Definitions used to indicate overfeeding were the ratio caloric intake/mREE of >110% and >120% and by the measured RQ > RQmacr + 0.05. RESULTS: The proportion of patients identified as overfed varied widely depending on the definition used, ranging from 22% (RQ > RQmacr + 0.05), to 40% and 50% (caloric intake/mREE of >120% and >110%, respectively). Linear regression analysis showed that all patients would be identified as overfed with the definition RQ > RQmacr + 0.05 when the ratio caloric intake/mREE exceeded 165%. Caloric intake was higher in children with a standard deviation-score weight for age <-2. CONCLUSIONS: The proportion of mechanically ventilated patients identified as overfed ranged widely depending on the definition applied. These currently used definitions fail to take into account several relevant factors affecting metabolism during critical illness and are therefore not generally applicable to the pediatric intensive care unit population.

Worldwide Survey of Nutritional Practices in PICUs.

OBJECTIVE: To assess current nutritional practices in critically ill children worldwide. DESIGN: A two-part online, international survey. The first part, "the survey", was composed of 59 questions regarding nutritional strategies and protocols (July-November 2013). The second part surveyed the "point prevalence" of nutritional data of patients present in a subgroup of the responding PICUs (May-September 2014). SETTING: Members of the World Federation of Pediatric Intensive and Critical Care Societies were asked to complete the survey. SUBJECTS: Pediatric critical care providers. INTERVENTIONS: Survey. MEASUREMENTS AND MAIN RESULTS: We analyzed 189 responses from 156 PICUs in 52 countries (survey). We received nutritional data on 295 patients from 41 of these 156 responding PICUs in 27 countries (point prevalence). According to the "survey", nutritional protocols and support teams were available in 52% and 57% of the PICUs, respectively. Various equations were in use to estimate energy requirements; only in 14% of PICUs, indirect calorimetry was used. Nutritional targets for macronutrients, corrected for age/weight, varied widely. Enteral nutrition would be started early (within 24 hr of admission) in 60% of PICUs, preferably by the gastric route (88%). In patients intolerant to enteral nutrition, parenteral nutrition would be started within 48 hours in 55% of PICUs. Overall, in 72% of PICUs supplemental parenteral nutrition would be used if enteral nutrition failed to meet at least 50% of energy delivery goal. Several differences between the intended (survey) and the actual (point prevalence) nutritional practices were found in the responding PICUs, predominantly overestimating the ability to adequately feed patients. CONCLUSION: Nutritional practices vary widely between PICUs worldwide. There are significant differences in macronutrient goals, estimating energy requirements, timing of nutrient delivery, and threshold for supplemental parenteral nutrition. Uniform consensus-based nutrition practices, preferably guided by evidence, are desirable in the PICU.

HLA-DR Expression on Monocyte Subsets in Critically Ill Children.

BACKGROUND: To longitudinally study blood monocyte subset distribution and human leukocyte antigen-DR (HLA-DR) expression on monocyte subsets in children with sepsis, post-surgery and trauma in relation to nosocomial infections and mortality. METHODS: In 37 healthy children and 37 critically ill children (12 sepsis, 11 post-surgery, 10 trauma and 4 admitted for other reasons)-participating in a randomized controlled trial on early versus late initiation of parenteral nutrition-monocyte subset distribution and HLA-DR expression on monocyte subsets were measured by flow cytometry upon admission and on days 2, 3 and 4 of pediatric intensive care unit (PICU) stay. RESULTS: Upon PICU admission, critically ill children had a higher proportion of classical monocytes (CD14++CD16-) than healthy children [PICU 95% (interquartile range [IQR] 88%-98%); controls, 87% (IQR 85%-90%), P < 0.001]. HLA-DR expression was significantly decreased within all monocyte subsets and at all time points, being most manifest on classical monocytes and in patients with sepsis. Percentage of HLA-DR expressing classical monocytes [upon PICU admission 67% (IQR 44%-88%); controls 95% (IQR 92%-98%), P < 0.001], as well as the HLA-DR mean fluorescence intensity [upon PICU admission 3219 (IQR 2650-4211); controls 6545 (IQR 5558-7647), P < 0.001], decreased during PICU stay. Patients who developed nosocomial infections (n = 13) or who died (n = 6) had lower HLA-DR expression on classical monocytes at day 2 (P = 0.002) and day 3 (P = 0.04), respectively. CONCLUSIONS: Monocytic HLA-DR expression decreased during PICU stay and was lower compared with controls on all examined time points, especially on classical monocytes and in children admitted for sepsis. Low HLA-DR expression on classical monocytes was associated with nosocomial infections and death.

Evidence for the use of parenteral nutrition in the pediatric intensive care unit.

BACKGROUND AND AIMS: During hospitalization in a pediatric intensive care unit (PICU), critically ill children are fed artificially. Administered via the preferred enteral route, caloric targets are often not reached. Hence, parenteral nutrition is given to this patient population. In this review we analyzed the available evidence from randomized controlled trials (RCTs) that supports the use of parenteral nutrition in children during critical illness. METHODS: A search strategy in Ovid MEDLINE and Ovid EMBASE was created and trial registries were screened to identify the relevant RCTs. Studies were included if they were randomized controlled trials, involved pediatric patients admitted to PICU, and compared different dosing/compositions of parenteral nutrition. Descriptive studies and reviews were excluded. RESULTS: Of the 584 articles identified by the search strategy, only 114 articles were retained after title screening. Further abstract and full text screening identified 6 small RCTs that compared two dosing/composition strategies of parenteral nutrition. These trials reported differences in surrogate endpoints without an effect on hard clinical endpoints. The RCTs observed improvements in these surrogate endpoints with the use of more calories or when parenteral glutamine or fish oil was added. CONCLUSIONS: The few RCTs suggest that surrogate endpoints can be affected by providing parenteral nutrition to critically ill children, but the studies were not statistically powered to draw meaningful clinical conclusions. Large RCTs with clinically relevant outcome measures are urgently needed to support the current nutritional guidelines that advise the use of parenteral nutrition in the PICU.

Validation of ventilator-derived VCO2 measurements to determine energy expenditure in ventilated critically ill children.

BACKGROUND & AIMS: Indirect calorimetry (IC) is considered the gold standard to determine resting energy expenditure (REE) but its availability in PICUs worldwide is limited. Ventilator-derived VCO2 could potentially improve the possibility of performing REE measurements. We investigated whether ventilator-derived VCO2 values are comparable to IC-derived VCO2 values and can clinically be used in clinical practice to determine REE. METHODS: VCO2-values were simultaneously collected in mechanically ventilated children from IC (Deltatrac®) and Servo-I® ventilator on a minute base over at least 10 min period of steady state. REE was calculated using the modified Weir formula (for IC) or REE = 5.5*VCO2 (L/min)*1440 (for the Servo-I values) and compared with frequently used predictive equations by Schofield and the WHO to calculate REE. RESULTS: Measurements were performed in 41 children; median age 2 years. The mean relative difference between VCO2 measured by IC and Servo-I® was 15.6% (p = 0.002), and limits of agreement in the Bland-Altman analysis were wide. Comparable measurements, defined as a difference ≤10% between IC and Servo-I® VCO2 values, were seen in 18 (44%) children, but this proportion was 70% in children ≥15 kg. In this group, REE could be accurately predicted using Servo-I® derived VCO2 values and this method was superior to the use of predictive equations. The Servo-I® derived VCO2 values were not sufficiently accurate for the large proportion of children weighing <15 kg. CONCLUSIONS: In children ≥15 kg, VCO2 measurements of the Servo-I® seem sufficiently accurate for use in clinical practice and may be used to determine energy expenditure in the future.

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. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01536275 on 16 February 2012.

[A girl with excessive lymphadenopathy]. / Een meisje met uitgebreide lymfadenopathie.

A 6-year-old girl presented at the emergency department with increasing swellings of multiple lymph nodes over the past 3 days, without other complaints. At physical examination an impressive general lymphadenopathy was seen without any other abnormalities. The peripheral blood smear showed 86% lymphoblasts. She was diagnosed with B-cell precursor acute lymphoblastic leukemia.