Measuring Energy Requirements of Traumatic Brain Injury Patients in Pediatric Intensive Care With Indirect Calorimetry: A Comparison With Empiric Methods.

OBJECTIVES: Energy requirements following moderate or severe pediatric traumatic brain injury (TBI) have not been fully elucidated. Indirect calorimetry (IC) is the gold standard for measuring resting energy expenditure (MREE) in PICU. However, technical complexity limits its use. We aimed to determine whether MREE differs from standard of care energy estimation and delivery in a cohort of pediatric patients following moderate to severe TBI during PICU admission. DESIGN: Retrospective case series study. SETTING: Single-center, 16-bed general PICU in Canada between May 2011 and January 2019. PATIENTS: Children (0-18 yr) admitted to a PICU for moderate (Glasgow Coma Scale [GCS] 9-12) to severe TBI (GCS < 9) and had an IC study performed while mechanically ventilated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 245 patients were admitted with the diagnosis of trauma with TBI. The study includes a convenience sample of 26 patients with severe ( n = 23) and moderate ( n = 3) TBI who underwent a total of 34 IC measurements. MREE varied considerably from 29% to 144% of predicted energy expenditure. Using Bland-Altman comparative analysis, neither Schofield nor World Health Organization predictive equations were in agreement with MREE. Only one measurement revealed that the patient was appropriately fed (energy provided in nutrition support was within 10% of MREE); 10 (38%) measurements revealed overfeeding and 15 (58%) underfeeding at the time of testing. CONCLUSIONS: The present study adds to the small body of literature highlighting the limitations of predictive equations to evaluate energy requirements following moderate to severe pediatric TBI. IC, when feasible, should be used as the preferred method to orient PICU teams to feed such vulnerable patients.

Can energy intake alter clinical and hospital outcomes in PICU?

BACKGROUND & AIMS: Energy is essential for the treatment and recovery of children admitted to Pediatric Intensive Care Units (PICU). There are significant immediate and long-term health consequences of both under- and over-feeding in this population. Energy requirements of critically ill children vary depending on age, nutritional status, sepsis, fever, pharmacotherapy, and duration and stage of critical illness. This study aimed to determine the incidence of over- and under-feeding and to compare hospital outcomes between these feeding categories. Secondary outcomes were collected to describe the association between feeding categories and biochemistries (serum lactate, triglycerides, C-reactive protein). METHODS: An ethics approved retrospective study of children admitted to PICU was performed. All intubated patients admitted to PICU (2008-2013) were included, except those in which an IC test was not feasible. Data collection included demographics, the primary outcome variable reported as under feeding (<90%MREE), appropriate (MREE ±10%) or overfeeding (>110% MREE) determined through comparison of measured resting energy expenditure (MREE) using indirect calorimetry (IC) to actual energy intake based on predicted basal metabolic rate (PBMR) and clinical outcomes mechanical ventilation and PICU length of stay (LOS). Data were analysed with descriptive methods, ANOVA and linear regression models. RESULTS: A total of 139 patients aged 10 (range 0.03-204) months were included. Sixty (43%) were female and 77 (55%) were admitted after a surgical procedure. A total of 210 IC tests were conducted showing a statistically significant difference between MREE measurements and PBMR (p = 0.019). Of the 210 measurements, only 26 measures (12.4%) demonstrated appropriate feeding, while 72 (34.3) were underfed and 112 (53.3%) were overfed. Children who were overfed had significantly longer PICU LOS (median 45.5, IQR 47.8 days) compared to those children in the appropriately fed (median 21.0, IQR 54.5 days), and underfed groups (median 16.5, IQR 21.3 days). There was a mean difference between the over and under feeding category and ventilation days after adjusting for age and PRISM score (p = 0.026), suggesting decreased mechanical ventilation days for underfed. Children who were underfed had significantly higher CRP (median 75.5, IQR 152.8 mg/L) compared to those children in the appropriately fed (median 57.8, IQR 90.9 mg/L) and overfed groups (median 22.4, IQR 56.2 mg/L). CONCLUSIONS: This retrospective study confirms that estimations of energy expenditure in critically ill children are inaccurate leading to unintended under and overfeeding. Importantly under feeding seems to be associated with fewer mechanical ventilation days and PICU LOS. Further research is required to elucidate the role of optimal nutrition in altering clinical variables in this population.

Optimizing Nutrition in Pediatric Heart Failure: The Crisis Is Over and Now It's Time to Feed.

Pediatric heart failure is a complex disease occurring when cardiac output is unable to meet the metabolic demands of the body. With improved surgical interventions and medical therapies, survival rates have improved, and care has shifted from focusing on survival to optimizing quality of life and health outcomes. Based on current literature, this review addresses the nutrition needs of infants and children in heart failure and describes the pathophysiology and metabolic implications of this disease. The prevalence of wasting in pediatric heart failure has been reported to be as high as 86%, highlighting the importance of nutrition assessment through all stages of treatment to provide appropriate intake of energy, protein, and micronutrients. The etiology of malnutrition in pediatric heart failure is multifactorial and involves hypermetabolism, decreased intake, increased nutrient losses, inefficient utilization of nutrients, and malabsorption. Children in heart failure often present with tachypnea, tachycardia, fatigue, nausea, and vomiting and consequently may not be able to meet their nutrition requirements through oral intake alone. Nutrition support, including enteral nutrition and parenteral nutrition, should be considered an essential part of routine care. The involvement of multiple allied health professionals may be needed to create a feeding therapy plan to support patients and their families. With appropriate nutrition interventions, clinical outcomes and quality of life can be significantly improved.

Adherence to a Nurse-Driven Feeding Protocol in a Pediatric Intensive Care Unit.

BACKGROUND: Patients admitted to pediatric intensive care units (PICUs) often experience prolonged periods without nutrition support, which may result in hospital-induced malnutrition and longer length of stay. Nurse-driven feeding protocols have been developed to prevent unnecessary interruptions or delays to nutrition support. The primary objective of this study was to identify compliance and reasons for noncompliance to a feeding protocol at a tertiary care hospital PICU in Canada. The secondary aim was to determine the mean time (hours) spent without any form of nutrition and to identify reasons for time spent without nutrition. MATERIALS AND METHODS: This was a prospective cohort audit, consisting of 150 consecutive PICU admissions (January-February 2016). Exclusion criteria consisted of patient mortality within 48 hours (n = 1) and patients who were still admitted at the end of the data collection timeframe (n = 7). The remaining cohort consisted of 142 consecutive admissions. Data collection took place in real time and included patient demographics, diagnostic categories, time spent without nutrition, reasons for interruptions to nutrition support, and reasons for noncompliance to the protocol. Observations were obtained through paper and computer charts and conversing with clinicians. RESULTS: There was a 95% compliance rate to the protocol and an average of 25.6 hours spent without nutrition per patient. The most prevalent reason for noncompliance was an avoidable delay to restart feeds before/after procedures or after surgery. CONCLUSIONS: A nurse-driven feeding protocol may reduce time spent without nutrition. Future research is required to examine the relationship between adherence to feeding protocols and clinical outcomes.

Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.

BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

Ganglioside Intake Increases Plasma Ganglioside Content in Human Participants.

BACKGROUND: Preclinical studies reveal associations between intestinal ganglioside content and inflammatory bowel disease (IBD). Since a low level of ganglioside is associated with higher production of proinflammatory signals in the intestine, it is important to determine safety and bioavailability of dietary ganglioside for application as a potential therapeutic agent. MATERIALS AND METHODS: Healthy volunteers (HVs; n = 18) completed an 8-week supplementation study to demonstrate safety and bioavailabity of ganglioside consumption. HVs were randomized to consume a milk fat fraction containing 43 mg/d ganglioside or placebo, and patients with IBD (n = 5) consumed ganglioside supplement in a small pilot study. Plasma gangliosides were characterized using reverse-phase liquid chromatography-QQQ mass spectrometry. Intestinal permeability was assessed by oral lactulose/mannitol, and quality of life was assessed by quality of life in the IBD questionnaire. RESULTS: There were no adverse events associated with dietary ganglioside intake. Ganglioside consumption increased ( P < .05) plasma content of total GD3 by 35% over 8 weeks. HVs consuming ganglioside exhibited a 19% decrease in intestinal permeability ( P = .04). Consumption of ganglioside was associated with a 39% increase ( P < .01) in emotional health and a 36% improvement ( P < .02) in systemic symptoms in patients with IBD. CONCLUSION: Impaired intestinal integrity characteristic of IBD results in increased permeability to bacterial antigens and decreased nutrient absorption. Intestinal integrity may be improved by dietary treatment with specific species of ganglioside. Ganglioside is a safe, bioavailable dietary compound that can be consumed to potentially improve quality of life in patients with IBD and treat other disorders involving altered ganglioside metabolism. This study was registered at clinicaltrials.gov as NCT02139709.

Do PICU patients meet technical criteria for performing indirect calorimetry?

BACKGROUND & AIMS: Indirect calorimetry (IC) is considered gold standard for assessing energy needs of critically ill children as predictive equations and clinical status indicators are often unreliable. Accurate assessment of energy requirements in this vulnerable population is essential given the high risk of over or underfeeding and the consequences thereof. The proportion of patients and patient days in pediatric intensive care (PICU) for which energy expenditure (EE) can be measured using IC is currently unknown. In the current study, we aimed to quantify the daily proportion of consecutive PICU patients who met technical criteria to perform indirect calorimetry and describe the technical contraindications when criteria were not met. METHODS: Prospective, observational, single-centre study conducted in a cardiac and general PICU. All consecutive patients admitted for at least 96 h were included in the study. Variables collected for each patient included age at admission, admission diagnosis, and if technical criteria for indirect calorimetry were met. Technical criteria variables were collected within the same 2 h each morning and include: provision of supplemental oxygen, ventilator settings, endotracheal tube (ETT) leak, diagnosis of chest tube air leak, provision of external gas support (i.e. nitric oxide), and provision of extracorporeal membrane oxygenation (ECMO). RESULTS: 288 patients were included for a total of 3590 patient days between June 2014 and February 2015. The main reasons for admission were: surgery (cardiac and non-cardiac), respiratory distress, trauma, oncology and medicine/other. The median (interquartile range) patient age was 0.7 (0.3-4.6) years. The median length of PICU stay was 7 (5-14) days. Only 34% (95% CI, 32.4-35.5%) of patient days met technical criteria for IC. For patients less than 6 months of age, technical criteria were met on significantly fewer patient days (29%, p < 0.01). Moreover, 27% of patients did not meet technical criteria for IC on any day during their PICU stay. Most frequent reasons for why IC could not be performed included supplemental oxygen, ECMO, and ETT leak. CONCLUSIONS: In the current study, technical criteria to perform IC in the PICU were not met for 27% of patients and were not met on 66% of patient days. Moreover, criteria were met on only 29% of days for infants 6 months and younger where children 24 months of age and older still only met criteria on 40% of patient days. This data represents a major gap in the feasibility of current recommendations for assessing energy requirements of this population. Future studies are needed to improve methods of predicting and measuring energy requirements in critically ill children who do not meet current criteria for indirect calorimetry.

Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease.

AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1a and PC. CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.

Pretreatment with an intravenous lipid emulsion increases plasma eicosapentanoic acid and downregulates leukotriene b4, procalcitonin, and lymphocyte concentrations after open heart surgery in infants.

BACKGROUND: The effect of providing a lipid emulsion containing medium-chain triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not widely studied. This study investigated lipid emulsion effects on plasma phospholipids and immune biomarkers. MATERIALS AND METHODS: Thirty-two infants undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition (PN) were randomized to receive either soybean oil (control, n = 16) or a 50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was administered for 3 days preoperatively and 10 days postoperatively. Fatty acids, procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at baseline, before surgery, and days 1, 7 and 10 after surgery. RESULTS: PCT was significantly lower in the treatment vs control group 1 day postoperatively (P = .01). The treatment group exhibited a lower ω-6 to ω-3 ratio (P = .0001) and a higher ω-3 concentration at all postoperative study periods (P = .001). Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid (EPA) on days 7 and 10, while α-linolenic acid, arachidonic acid, and docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA concentration was associated with a decrease in plasma phospholipid LTB4 concentration (P < .05). On postoperative day 10, treatment infants with high Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte concentration (P < .05). CONCLUSION: These findings suggest that treating infants undergoing CPB with a lipid emulsion containing ω-3 improves fatty acid status and results in a lower inflammatory response after surgery. Overall, this alternative ω-3-enriched lipid emulsion may benefit clinical outcomes of critically ill infants after cardiac surgery.

A Canadian survey of perceived barriers to initiation and continuation of enteral feeding in PICUs.

OBJECTIVE: Clinicians believe nutrition support is important; however, delivery of enteral nutrition may be delayed or interrupted due to a lack of guidelines or perceived contraindications to administration. The aim of this national survey was to examine the knowledge and perceived barriers among clinicians which prevent enteral nutrition administration to PICU patients. DESIGN: The survey consisted of 23 questions (19 primary and four branching). The survey was validated using a semistructured pilot test by three pediatric critical care intensivists and two pediatric critical care registered dietitians external to the study team. SETTING: The survey was electronically distributed to clinicians in all PICUs across Canada. POPULATION: One hundred sixty-two PICU clinicians, including 96 staff intensivists, eight clinical assistants, 36 fellows, and 22 registered dietitians from PICUs across Canada. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The survey was administered from January to March 2013. The response rate was 50% (55 staff intensivists, two clinical assistants, nine fellows, and 15 registered dietitians). There was high variability among clinicians regarding reasons to delay the onset of enteral nutrition or interrupt enteral nutrition administration. High variability (> 70% agreement and < 10% disagreement or vice versa) was found for some reasons to delay or interrupt enteral nutrition, including lactates (rising or > 2 or > 4 mmol/L), high gastric residual volumes, CT/MRI scans, and hypoplastic left heart syndrome. Sixty-eight percent of PICU clinicians reported no written feeding protocol to be in place. CONCLUSIONS: Overall, there is high variability among clinicians regarding acceptable procedural and clinical barriers to enteral nutrition administration; this may be improved by a standardized feeding protocol. Therefore, further research must be conducted to provide clinicians with evidence to support their practices for enteral nutrition administration.

Low energy intakes are associated with adverse outcomes in infants after open heart surgery.

BACKGROUND: Infants with congenital heart lesions who undergo open heart surgery may experience physiologic and metabolic stress in the postoperative period, leading to altered metabolism and hypercatabolism. The purpose of this study was to determine the relationship between energy intake and hospital outcomes during the first 10 days following neonatal open heart surgery. MATERIALS AND METHODS: A post hoc analysis of all patients in a prospective randomized controlled trial was performed. Nutrition intake and hospital outcomes were assessed in 32 infants (40 ± 2.2 weeks, 3.4 ± 0.5 kg) in the neonatal and pediatric intensive care units. Infants received parenteral nutrition (PN) for 1-4 days before and 10 days after open heart surgery. Infants were separated into those who received a cumulative energy intake of <689 kcal (average 63 kcal/kg/d) and those who received an intake ≥689 kcal during postoperative days 0-10. RESULTS: Lower energy intake was associated with a significantly increased duration of artificial ventilation (5 ± 1.2 days), time to chest closure (1.4 ± 0.5 days), time in intensive care (5 ± 1.8 days), and stay in the hospital (25 ± 6.4 days). Lower energy intake was also associated with a significant increase in the length of time infants required PN (8 ± 2.9 days) and longer time to achieve full enteral intake of 100 mL/kg/d (7 ± 2.2 days) and before enteral feeds could be initiated (5 ± 1.5 days). CONCLUSIONS: Providing <63 kcal/kg/d to infants after open heart surgery was associated with adverse pediatric intensive care outcomes.

Pre-treatment with an intravenous lipid emulsion containing fish oil (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after open-heart surgery in infants: a randomized, controlled trial.

BACKGROUND & AIMS: This study assessed the effects of administering a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid before and after open-heart surgery on cytokine production and length of hospital stay in infants. METHODS: Thirty-two infants (40 ± 2.3 weeks gestational age; 10.6 days at time of surgery) undergoing open-heart surgery with cardiopulmonary bypass were randomized to receive an intravenous lipid emulsion with (treatment) or without (control) eicosapentaenoic and docosahexaenoic acid in this prospective, randomized, double-blind, controlled trial. RESULTS: Mean plasma TNF-α concentration was significantly (p = 0.003) lower in the treatment (5.9 pg/mL) compared to the control group (14.8 pg/mL). In infants without sepsis, plasma TNF-α did not differ according to treatment, however when sepsis developed, mean plasma TNF-α was 21.1 pg/mL and 1.5 pg/mL (p = 0.0007) in control and treatment groups, respectively. Plasma TNF-α was positively correlated with length of hospital stay in the control group (p = 0.01), and negatively correlated with length of stay in the treatment group (p = 0.004), with a significant time by treatment interaction (p = 0.02). CONCLUSIONS: Providing a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid reduces TNF-α concentrations in infants undergoing open-heart surgery. Lipid emulsions containing eicosapentaenoic and docosahexaenoic acid may ameliorate the inflammatory response among critically ill infants.