The enteroendocrine axis and its effect on gastrointestinal function, nutrition, and inflammation.

PURPOSE OF REVIEW: Gastrointestinal (GI) dysfunction limits enteral nutrition (EN) delivery in critical illness and contributes to systemic inflammation. The enteroendocrine (EE) axis plays an integral role in this interface between nutrition, inflammation, and GI function in critical illness. In this review, we present an overview of the EE system with a focus on its role in GI inflammation and function. RECENT FINDINGS: Enteroendocrine cells have been primarily described in their role in macronutrient digestion and absorption. Recent research has expanded on the diverse functions of EE cells including their ability to sense microbial peptides and metabolites and regulate immune function and inflammation. Therefore, EE cells may be both affected by and contribute to many pathophysiologic states and interventions of critical illness such as dysbiosis , inflammation, and alternative EN strategies. In this review, we present an overview of EE cells including their growing role in nonnutrient functions and integrate this understanding into relevant aspects of critical illness with a focus on EN. SUMMARY: The EE system is key in maintaining GI homeostasis in critical illness, and how it is impacted and contributes to outcomes in the setting of dysbiosis , inflammation and different feeding strategies in critical illness should be considered.

Changes in Global Nutrition Practices in Critically Ill Children and the Influence of Emerging Evidence: A Secondary Analysis of the Pediatric International Nutrition Studies, 2009-2018.

BACKGROUND: The timeline of the 3 Pediatric International Nutrition Studies (PINS) coincided with the publication of 2 major guidelines for the timing of parenteral nutrition (PN) and recommended energy and protein delivery dose. OBJECTIVE: The study's main objective was to describe changes in the nutrition delivery practice recorded in PINS1 and PINS2 (PINS1-2) (conducted in 2009 and 2011, preexposure epoch) vs PINS3 (conducted in 2018, postexposure epoch), in relation to the published practice guidelines. DESIGN: This study is a secondary analysis of data from a multicenter prospective cohort study. PARTICIPANTS/SETTING: Data from 3650 participants, aged 1 month to 18 years, admitted to 100 unique hospitals that participated in 3 PINS was used for this study. MAIN OUTCOME MEASURES: The time in days from pediatric intensive care unit admission to the initiation of PN and enteral nutrition delivery were the primary outcomes. Prescribed energy and protein goals were the secondary outcomes. STATISTICAL ANALYSES PERFORMED: A frailty model with a random intercept per hospital with stratified baseline hazard function by region for the primary outcomes and a mixed-effects negative binomial regression with random intercept per hospital for the secondary outcomes. RESULTS: The proportion of patients receiving enteral nutrition (88.3% vs 80.6%; P < .001) was higher, and those receiving PN (20.6% vs 28.8%; P < .001) was lower in the PINS3 cohort compared with PINS1-2. In the PINS3 cohort, the odds of initiating PN during the first 10 days of pediatric intensive care unit admission were lower, compared with the PINS1-2 cohort (hazard ratio 0.8, 95% CI 0.67 to 0.95; P = .013); and prescribed energy goal was lower compared with the PINS1-2 cohort (incident rate ratio 0.918, 95% CI 0.874 to 0.965; P = .001). CONCLUSIONS: The likelihood of initiation of PN delivery significantly decreased during the first 10 days after admission in the PINS3 cohort compared with PINS1-2. Energy goal prescription in children receiving mechanical ventilation significantly decreased in the postguidelines epoch compared with the preguidelines epoch.

Biomarkers and Functional Assays of Epithelial Barrier Disruption and Gastrointestinal Dysmotility in Critical Illness-A Narrative Review.

Enteral nutrition in critically ill children has been associated with improved clinical outcomes. Gastrointestinal dysfunction often impedes the timely initiation and advancement of enteral nutrition and can contribute to immune dysregulation and systemic inflammation. Therefore, assessing gastrointestinal function, at a cellular and functional level, is important to provide optimal enteral nutrition therapy and reduce the gastrointestinal tract's contribution to the inflammatory cascade of critical illness. In this narrative review, we present an overview of biomarker and functional assays for gastrointestinal dysfunction, including epithelial barrier disruption and gastrointestinal dysmotility, that have been considered for critically ill patients.

Postpyloric vs gastric enteral nutrition in critically ill children: A single-center retrospective cohort study.

BACKGROUND: We aimed to describe enteral nutrition (EN) delivery in patients receiving postpyloric EN (PPEN) vs gastric EN (GEN). METHODS: Single-center retrospective study including patients aged <21 years admitted to an intensive care unit in a pediatric quaternary care hospital for ≧48 h who received PPEN or GEN as a first approach, as guided by a nutrition algorithm. PPEN patients were 1:1 propensity score matched to GEN patients on demographics, clinical characteristics, and disease severity. Days to EN initiation from admission, percentage of EN adequacy (delivered EN volume/prescribed EN volume) on days 1-3 and 7 after EN initiation, and time to achieving 60% of prescribed EN volume were compared between the two groups using Wilcoxon Mann-Whitney tests and a Cox proportional hazards model. Data are presented as median (IQR1, IQR3). RESULTS: Forty-six PPEN and 46 GEN patients were matched. Median time to EN initiation was 3.25 (2, 6.8) days for PPEN and 4.15 (1.5, 7.1) days for GEN (P = 0.6). Percentage of EN adequacy was greater for PPEN than GEN patients (day 1 PPEN 59.4% [18.8, 87.5] vs GEN 21.1% [7.8, 62.8], day 2 PPEN 54.3% [16.7, 95.8] vs GEN 24% [5.4, 56.7], day 3 PPEN 65.4% [14.7, 100] vs GEN 16% [0, 64.6], day 7 PPEN 77.8% [11.1, 100] vs GEN 13.8% [0, 74.5]; P < 0.05). PPEN patients had greater likelihood of achieving 60% of their prescribed EN volume than GEN patients (hazard ratio 1.84, 95% CI 1.07-3.15; P = 0.028). CONCLUSION: PPEN was associated with greater EN delivery compared with GEN.

Impact of implementing an evidence-based definition of enteral nutrition intolerance on nutrition delivery: A prospective, cross-sectional cohort study.

BACKGROUND: Enteral nutrition (EN) interruptions because of EN intolerance impede nutrient delivery. We aimed to examine whether revising the EN intolerance definition of an algorithm would decrease EN interruptions and improve nutrient delivery in critically ill children. METHODS: We performed a cross-sectional cohort study including patients who were admitted to our intensive care unit (ICU) for >24 h and received EN. The EN intolerance definition in our nutrition algorithm was modified to include two symptoms of EN intolerance. We compared time to 60% EN adequacy (EN delivered/EN prescribed x 100) and EN interruptions before and after this intervention. RESULTS: We included 150 eligible patients, 78 and 72 patients in the preimplementation and postimplementation cohorts, respectively. There were no significant differences in demographics and clinical characteristics. The preimplementation and postimplementation cohorts achieved 60% EN adequacy 4 (2-5) days and 3 (2-5) days after ICU admission, respectively (P = 0.59). The preimplementation cohort had a median of 1 (1-2) interruption per patient and the postimplementation cohort 2 (1-3; P = 0.08). The frequency of interruptions because of EN intolerance within the first 8 days of ICU admission was 17 in the preimplementation and 10 in the postimplementation cohorts. CONCLUSION: Modifying the EN intolerance definition of a nutrition algorithm did not change the time to 60% EN adequacy or total number of EN interruptions in critically ill children. EN intolerance and interruptions continue to limit nutrient delivery. Research on the best definition for EN intolerance and its effect on nutrition outcomes is needed.

Human coagulation factor X and CD5 antigen-like are potential new members of the zonulin family proteins.

Zonulin is a physiologic epithelial and endothelial permeability modulator. Zonulin increases antigen trafficking from the gut lumen into the bloodstream and in between body compartments, a mechanism linked to many chronic inflammatory diseases. Upon its initial discovery, it was noted that zonulin was not a single protein, but rather a family of structurally and functionally related proteins referred to as the zonulin family proteins (ZFPs). ZFPs are members of the mannose associated serine proteases (MASP) family and are the result of high mutation rates leading to many zonulin polymorphisms. Pre-haptoglobin 2, the precursor of haptoglobin 2, was identified as the first eukaryotic member of the ZFPs, and properdin, a key positive regulator of the alternative pathway, as a second member. In this study, we report two additional proteins that are likely ZFPs. Human coagulation factor X (FX) and CD5 antigen-like (CD5L). Both FX and CD5L recombinant proteins were detected by anti-zonulin antibody in Western immunoblot analysis, and both proteins decreased epithelial barrier competency of Caco-2 cell monolayers as established by the Trans Epithelial Electrical Resistance (TEER) assay. These results indicate that FX and CD5L have structural and functional similarities with previously identified ZFPs and, therefore, can be considered new members of this family of proteins.

Intermittent versus continuous enteral nutrition in critically ill children: A pre-planned secondary analysis of an international prospective cohort study.

BACKGROUND & AIMS: Intermittent enteral nutrition (EN) may have physiologic benefits over continuous feeding in critical illness. We aimed to compare nutrition and infection outcomes in critically ill children receiving intermittent or continuous EN. METHODS: International, multi-center prospective observational study of mechanically ventilated children, 1 month to 18 years of age, receiving EN. Percent energy or protein adequacy (energy or protein delivered/prescribed × 100) and acquired infection rates were compared between intermittent and continuous EN groups using adjusted-multivariable and 4:1 propensity-score matched (PSM) analyses. Sensitivity analyses were performed after excluding patients who crossed over between intermittent and continuous EN. RESULTS: 1375 eligible patients from 66 PICUs were included. Patients receiving continuous EN (N = 1093) had a higher prevalence of respiratory illness and obesity, and lower prevalence of neurologic illness and underweight status on admission, compared to those on intermittent EN (N = 282). Percent energy or protein adequacy, proportion of patients who achieved 60% of energy or protein adequacy in the first 7 days of admission, and rates of acquired infection were not different between the 2 groups in adjusted-multivariable and propensity score matching analyses (P > 0.05). CONCLUSION: Intermittent versus continuous EN strategy is not associated with differences in energy or protein adequacy, or acquired infections, in mechanically ventilated, critically ill children. Until further evidence is available, an individualized feeding strategy rather than a universal approach may be appropriate.

Challenges and advances in nutrition for the critically ill child.

PURPOSE OF REVIEW: Malnutrition remains prevalent in critically ill children and is associated with worse clinical outcomes. Conversely, nutrition provision has been associated with improved survival. Nutritional challenges must be addressed to guide best nutrition practices for the critically ill child. In this narrative review, we summarize findings from research published between July 2020 and January 2022 on nutrition in critically ill children. Findings from these articles build on previous work to guide next steps in both research and clinical practice in this cohort. RECENT FINDINGS: A comprehensive literature review was performed. We identified the following common themes for research published between July 2020 and January 2022-metabolism, enteral nutrition, including timing, dosing, protein prescription and delivery in special populations, gastrointestinal function, and enteral nutrition adjunctive therapies. SUMMARY: Research continues to support early initiation and advancement of enteral nutrition. Achieving nutritional adequacy is challenging, but research associated with the timing and dosing of enteral nutrition, alternative methods of enteral nutrition delivery and the use of adjuncts are expanding our understanding of best practices for this cohort. Areas for further research continue to be the use of measured energy requirements, protein dosing and inclusion of functional outcomes to assess the benefit of nutritional interventions.

Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study.

We examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection in C57Bl/6 zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = - 0.51, CI - 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p < 0.0001). Gastric dysmotility was reduced similarly in Ztm and WT mice in a time-dependent manner. Ztm had 16% faster duodenal motility than WT mice 6H post-LPS, p = 0.01. Zonulin mRNA expression by delta cycle threshold (dCT) was higher in the stomach (9.7, SD 1.4) than the duodenum (13.9, SD 1.4) 6H post-LPS, p = 0.04. Serum zonulin protein levels were higher in LPS-injected mice compared to vehicle-injected animals in a time-dependent manner. Zonulin correlated with gastric dysmotility in patients. A mouse model had time-dependent gastro-duodenal dysmotility after LPS-injection that paralleled zonulin mRNA expression and protein levels.

Association Between Anticholinergic Drug Burden and Adequacy of Enteral Nutrition in Critically Ill, Mechanically Ventilated Pediatric Patients.

OBJECTIVES: Enteral nutrition delivery is limited by intolerance and interruptions in critically ill children. Anticholinergic properties of frequently administered medications may contribute to altered gastric motility and enteral nutrition intolerance in this population. We examined the association between the anticholinergic burden of administered medications using the Anticholinergic Drug Scale and adequacy of enteral nutrition delivery. DESIGN: Secondary analysis of data from a previously characterized PICU cohort. SETTING: Multidisciplinary PICU in a quaternary academic medical center. PATIENTS: Younger than or equal to 18 years, on mechanical ventilation and received enteral nutrition within the first 3 days of PICU admission. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale score, demographic data, and clinical data were obtained from the primary study. Percent enteral energy adequacy ([kcal delivered ÷ kcal prescribed] × 100) during the first 3 days of PICU admission was calculated. Forty-two patients received enteral nutrition, with median age (interquartile range) 5 years (1.09-12.54 yr), and 62% were male. Median Anticholinergic Drug Scale score was inversely correlated with energy adequacy, with a median 9% decline in energy adequacy per 1-point increase in Anticholinergic Drug Scale score (coefficient, -9.3; 95% CI, -13.43 to -5.27; R2 = 0.35; p < 0.0001). Median hours of enteral nutrition interruptions directly correlated with Anticholinergic Drug Scale score (coefficient, 1.5; 95% CI, 0.531-2.54; R2 = 0.19; p = 0.004). Severity score was greater in patients with less than or equal to 25% enteral energy adequacy and directly correlated with median Anticholinergic Drug Scale score. CONCLUSIONS: Anticholinergic burden from medications administered in the PICU is a potentially modifiable factor for suboptimal enteral nutrition delivery.

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children: 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

Interleukin-10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study.

BACKGROUND: Impaired gastric emptying (GE) is associated with morbidity in surgical critically ill children. The relationship between inflammation, gut barrier integrity (lipopolysaccharide binding protein [LBP]; zonulin), and GE has not been described in this cohort. METHODS: Children ≥2 years of age and requiring critical care after surgery were enrolled. Preoperative and postoperative levels of serum cytokines, LBP, and zonulin, and GE by the acetaminophen absorption test, were measured, allowing patients to serve as their own controls. Postoperative delayed GE was defined as a decrease in GE by ≥20% compared with preoperative GE. The following were examined : comparison between postoperative andpreoperative values, correlations between fold change (postoperative/preoperative) in study variables, and fold change in study variables between patients with and without postoperative delayed GE. RESULTS: Twenty patients, median age 14 years (12.25, 18), 12 female, were included. Eight of 20 patients had postoperative delayed GE. Postoperative interleukin-6 (IL-6), IL-8, IL-10, and LBP were increased, and zonulin was decreased (P-values < .05). Fold change in IL-10 and zonulin were inversely correlated (ρ -0.618, P = .004). Patients with postoperative delayed GE had greater fold increase in IL-10 (P = .0159) and fold decrease in zonulin (P = .0160). Five of 7 (71%) patients with both fold increase in IL-10 and decrease in zonulin had delayed GE. CONCLUSION: Postoperative changes in IL-10 and zonulin were associated with delayed GE in surgical critically ill children, which might suggest a mechanism to for delayed GE in postoperative inflammation and gut barrier dysregulation after surgery.

Bedside Postpyloric Tube Placement and Enteral Nutrition Delivery in the Pediatric Intensive Care Unit.

BACKGROUND: Enteral nutrition (EN) delivery may be more effective via a postpyloric (PP) feeding tube in critically ill children, but tube placement can be challenging. We aimed to describe PP tube placement and EN practices in a multidisciplinary pediatric intensive care unit (PICU) after the implementation of a nurse-led bedside PP tube-placement program. METHODS: In a single-center retrospective study, we identified 100 consecutive patients admitted to the PICU for >48 hours and for whom PP tube placement was attempted. Demographics, clinical characteristics, and details of PP tube placement and EN delivery were examined. RESULTS: The study cohort had a median age (25th, 75th percentiles) of 3.89 years (0.55, 14.86); 66% were male. Respiratory illness was the primary diagnosis of admission (55%); 92% were on respiratory support. Risk of aspiration was the primary indication for PP tube placement (48%). Bedside placement was the initial technique for PP tube placement in 93% of patients (successful for 84.9%) and was not associated with serious complications. Eighty-seven patients with a PP tube started EN and received a median 73.9% (12.3%, 100%) of prescribed energy goal on day 3 after EN initiation. PP EN allowed 14 of 39 patients receiving parenteral nutrition (PN) to transition off PN 7 days after EN initiation. Thirty-five percent of EN interruptions were due to feeding-tube dysfunction. CONCLUSION: Bedside PP tube placement is safe and feasible and allows for effective EN delivery and decreased PN use when applicable. Interruptions in PP EN due to tube malfunction are prevalent.

Gastrointestinal Hormone Profiles Associated With Enteral Nutrition Tolerance and Gastric Emptying in Pediatric Critical Illness: A Pilot Study.

BACKGROUND: Enteral nutrition (EN) intolerance and delayed gastric emptying are prevalent in pediatric critical illness and limit EN delivery. Gastrointestinal (GI) hormones may be associated with EN intolerance and delayed gastric emptying in this cohort. METHODS: We determined GI hormone levels, time to achieve 50% of EN goal, and gastric emptying in critically ill children. Total amylin, active ghrelin, total glucagon-like peptide-1 (GLP-1), total gastric inhibitory polypeptide, glucagon, and total peptide-YY (PYY) were measured by multiplex assay and cholecystokinin by ELISA. Lower concentrations of acetaminophen at 1 hour (C1h, µg/mL) using the acetaminophen absorption test defined delayed gastric emptying. Correlation, regression analyses, and a principal component analysis were used to examine the association between GI hormones and time to 50% EN goal and C1h. RESULTS: GI hormones were measured in 14 of 21 patients with gastric emptying testing; median age of 11.2 years (6.74-16.3) and 50% male. Increasing hormone levels from GI hormone profile 1 (GLP-1, glucagon, and amylin) correlated with greater time to reach 50% EN goal (R2 = 0.296, P = 0.04). Decreasing hormone levels from GI hormone profile 2 (PYY and ghrelin) correlated with lower C1h and slower gastric emptying (R2 = 0.342, P = 0.02). CONCLUSION: GI hormone profiles are associated with time to achieve 50% of EN goal and gastric emptying in critically ill children. We have described a feasible model to study the role of GI hormones in this cohort, including the potential clinical applicability of GI hormone measurement in the management of delayed gastric emptying.

Comprehensive nutritional and metabolic assessment in patients with spinal muscular atrophy: Opportunity for an individualized approach.

Optimal nutrition support is recommended for patients with spinal muscular atrophy (SMA). In a prospective study, we performed comprehensive nutritional assessments with the aim to guide best nutritional strategies for patients with SMA types II and III. We recorded a) anthropometry; b) macro- and micronutrient intakes; c) measured resting energy expenditure by indirect calorimetry; and d) body composition including dual X-ray absorptiometry. We enrolled a cohort of 21 patients aged 3 to 36 years of which 13 were female; 19 had SMA type II and 2 had SMA type III. The body mass index z-score ranged from -3 to 2.4. Forty-five percent of the cohort was either underfed or overfed, based on the difference between actual energy intake and measured resting energy expenditure. Vitamin D, E, K, folate and calcium intakes were low in a majority of the cohort. Forty-five percent of the cohort was either hypometabolic or hypermetabolic. Fat mass index (kg/m2) was significantly higher and lean body mass index (kg/m2) was significantly lower in the study cohort compared to population normalized values. Bone mineral density was low in 13 of 17 patients. In summary, we have described the prevalence of malnutrition, suboptimal feeding and alterations in body composition in children with SMA. A comprehensive nutritional assessment could guide individualized nutrition therapy in this vulnerable population.

Body Composition in Children with Chronic Illness: Accuracy of Bedside Assessment Techniques.

OBJECTIVE: To evaluate the accuracy of estimated fat mass and fat-free mass from bedside methods compared with reference methods in children with chronic illnesses. STUDY DESIGN: Fat mass and fat-free mass values were obtained by skinfold, bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), and deuterium dilution method in children with spinal muscular atrophy, intestinal failure, and post hematopoietic stem cell transplantation (HSCT). Spearman's correlation and agreement analyses were performed between (1) fat mass values estimated by skinfold equations and by DXA and (2) fat-free mass values estimated by BIA equations and by DXA and deuterium dilution methods. Limits of agreement between estimating and reference methods within ±20% were deemed clinically acceptable. RESULTS: Fat mass and fat-free mass values from 90 measurements in 56 patients, 55% male, and median age of 11.6 years were analyzed. Correlation coefficients between the skinfold-estimated fat mass values and DXA were 0.93-0.94 and between BIA-estimated fat-free mass values and DXA were 0.92-0.97. Limits of agreement between estimated and DXA values of fat mass and fat-free mass were greater than ±20% for all equations. Correlation coefficients between estimated fat-free mass values and deuterium dilution method in 35 encounters were 0.87-0.91, and limits of agreement were greater than ±20%. CONCLUSION: Estimated body composition values derived from skinfold and BIA may not be reliable in children with chronic illnesses. An accurate noninvasive method to estimate body composition in this cohort is desirable.

Energy and Protein Delivery in Overweight and Obese Children in the Pediatric Intensive Care Unit.

BACKGROUND: Early and optimal energy and protein delivery have been associated with improved clinical outcomes in the pediatric intensive care unit (PICU). Overweight and obese children in the PICU may be at risk for suboptimal macronutrient delivery; we aimed to describe macronutrient delivery in this cohort. METHODS: We performed a retrospective study of PICU patients ages 2-21 years, with body mass index (BMI) ≥85th percentile and >48 hours stay. Nutrition variables were extracted regarding nutrition screening and assessment, energy and protein prescription, and delivery. RESULTS: Data from 83 patient encounters for 52 eligible patients (52% male; median age 9.6 [5-15] years) were included. The study cohort had a longer median PICU length of stay (8 vs 5 days, P < .0001) and increased mortality rate (6/83 vs 182/5572, P = .045) than concurrent PICU patient encounters. Detailed nutrition assessment was documented for 60% (50/83) of patient encounters. Energy expenditure was estimated primarily by predictive equations. Stress factor >1.0 was applied in 44% (22/50). Median energy delivered as a percentage of estimated requirements by the Schofield equation was 34.6% on day 3. Median protein delivered as a percentage of recommended intake was 22.1% on day 3. CONCLUSIONS: The study cohort had suboptimal nutrition assessments and macronutrient delivery during their PICU course. Mortality and duration of PICU stay were greater when compared with the general PICU population. Nutrition assessment, indirect calorimetry-guided energy prescriptions, and optimizing the delivery of energy and protein must be emphasized in this cohort. The impact of these practices on clinical outcomes must be investigated.