Optimal delivery of nutritional support during critical illness is central to appropriate intensive care unit management, and yet fundamental gaps in knowledge exist regarding timing, route, dose, and type of nutritional support for critically ill infants and children. Understanding how to optimize nutritional support during pediatric critical illness is important because even brief periods of malnutrition in infancy result in permanent negative effects on long-term neurocognitive development. Optimized nutrition support is a way to improve morbidity for survivors of pediatric critical illness. Parenteral nutrition (PN) supplementation could improve long-term neurocognitive outcome for pediatric critical illness by preventing acute malnutrition, but has unknown effects on intestinal barrier function; a proposed mechanism for late sepsis and infectious complications during critical illness. While randomized controlled trials (RCT) support early PN in premature infants and late PN in critically ill adults, the optimal time to begin PN is unknown for critically ill infants and children. Acute malnutrition may develop within 48 hours of admission in critically ill infants and children, and repleted energy stores are predictive of survival. And yet, due to concerns for PN-associated infectious morbidity, current PICU standard of care is to supplement with PN only in children who fail to enterally feed, as late as 7 days into their admission. Delays in nutrition may have long-term effects on cognitive outcome in older infants and children. In premature infants, PN begun within hours of birth results in improved 18-month neurocognitive outcome without an increase in infectious complications. An RCT is needed to determine if early PN in critically ill infants and children prevents acute malnutrition and improves short and long-term outcomes of PICU hospitalization. The central hypothesis of this proposal is that optimized early protein and calorie delivery will improve nutritional outcomes and intestinal barrier function for critically ill infants and children. The overall purpose of this study is to evaluate the efficacy and safety of early PN as a supplement to enteral nutrition to improve nutritional delivery, nutritional outcomes, and intestinal barrier function for infants and children with acute respiratory failure who are mechanically ventilated in the pediatric intensive care unit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
18
University of Arizona Medical Center
Tucson, Arizona, United States
Modified Prognostic Inflammatory and Nutritional Index (PINI)
The change day 0 to day 5 of the modified Prognostic Inflammatory and Nutritional Index (PINI) is a quantitative method to monitor the relation between markers of nutrition and acute phase proteins. It allows assessment of nutrition markers in the context of acute inflammation and in response to early enteral nutrition. A higher baseline PINI score indicates higher degree of inflammation. The modified PINI is calculated by the the ratio of (C-Reactive Protein(mg/dL) x Fibrinogen (mg/dL))/ (Transferrin (mg/dL) x Transthyretin (mg/dL)). The average change in the modified PINI from day 0 to day 5 critically ill children receiving early enteral nutrition is a decrease by 5.3 +/- 3.2 (mean +/- standard error of the mean) (Briassoulis et.al. Nutrition 2001). A larger negative number for the change from day 0 to day 5 indicates a greater degree of inflammation resolution.
Time frame: Change in PINI from day 0 to day 5
Cumulative Percent of Daily Goal Calories Achieved
Evaluate percentage of cumulative goal calories achieved through parenteral and enteral routes in both study arms until patient exits study participation. Measure is calculated by (sum of kcal delivered over days of study participation/number of days in study).
Time frame: baseline and daily through day 7
Plasma Intestinal Fatty Acid Binding Protein (I-FABP)
The percent change in plasma Intestinal Fatty Acid Binding Protein from baseline to study day 5, prior to late PN initiation
Time frame: baseline and day 5
Plasma Citrulline
Evaluates absolute plasma citrulline concentration as a measure of functional enterocyte mass. A higher citrulline concentration indicates a higher functional enterocyte mass. Healthy children have an average citrulline concentration of 25 +/- 9 uMol/L. Assessed on day 0 and day 5, results reported for day 0 and 5. Outcome analysis on difference between treatment groups on day 5.
Time frame: baseline and day 5
Plasma Claudin 3
As a measure of enterocyte tight junctions, calculate the percent change in plasma claudin 3 concentrations from baseline (day 0) and study day 5, prior to late PN administration.
Time frame: baseline through hour 96
Gastrointestinal Permeability
Gastrointestinal permeability measured with the ratio of urinary recovery of lactulose and mannitol on day 5 of study participation. The range of values is generally reported as 0.02 to 2.2 with a higher value indicating greater gastrointestinal permeability. Values obtained on day 0 and day 5, day 5 reported.
Time frame: day 5
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