Lori J. Bechard

Nutritional practices and their relationship to clinical outcomes in critically ill children—An international multicenter cohort study*

Objectives:To examine factors influencing the adequacy of energy and protein intake in the pediatric intensive care unit and to describe their relationship to clinical outcomes in mechanically ventilated children. Design, Setting, Patients:We conducted an international prospective cohort study of consecutive children (ages 1 month to 18 yrs) requiring mechanical ventilation longer than 48 hrs in the pediatric intensive care unit. Nutritional practices were recorded during the pediatric intensive care unit stay for a maximum of 10 days, and patients were followed up for 60 days or until hospital discharge. Multivariate analysis, accounting for pediatric intensive care unit clustering and important confounding variables, was used to examine the impact of nutritional variables and pediatric intensive care unit characteristics on 60-day mortality and the prevalence of acquired infections. Main Results:31 pediatric intensive care units in academic hospitals in eight countries participated in this study. Five hundred patients with mean (SD) age 4.5 (5.1) yrs were enrolled and included in the analysis. Mortality at 60 days was 8.4%, and 107 of 500 (22%) patients acquired at least one infection during their pediatric intensive care unit stay. Over 30% of patients had severe malnutrition on admission, with body mass index z-score >2 (13.2%) or <−2 (17.1%) on admission. Mean prescribed goals for daily energy and protein intake were 64 kcals/kg and 1.7 g/kg respectively. Enteral nutrition was used in 67% of the patients and was initiated within 48 hrs of admission in the majority of patients. Enteral nutrition was subsequently interrupted on average for at least 2 days in 357 of 500 (71%) patients. Mean (SD) percentage daily nutritional intake (enteral nutrition) compared to prescribed goals was 38% (34) for energy and 43% (44) for protein. A higher percentage of goal energy intake via enteral nutrition route was significantly associated with lower 60-day mortality (Odds ratio for increasing energy intake from 33.3% to 66.6% is 0.27 [0.11, 0.67], p = .002). Mortality was higher in patients who received parenteral nutrition (odds ratio 2.61 [1.3, 5.3], p = .008). Patients admitted to units that utilized a feeding protocol had a lower prevalence of acquired infections (odds ratio 0.18 [0.05, 0.64], p = .008), and this association was independent of the amount of energy or protein intake. Conclusions:Nutrition delivery is generally inadequate in mechanically ventilated children across the world. Intake of a higher percentage of prescribed dietary energy goal via enteral route was associated with improved 60-day survival; conversely, parenteral nutrition use was associated with higher mortality. Pediatric intensive care units that utilized protocols for the initiation and advancement of enteral nutrient intake had a lower prevalence of acquired infections. Optimizing nutrition therapy is a potential avenue for improving clinical outcomes in critically ill children.

Energy imbalance and the risk of overfeeding in critically ill children

Objective: To examine the role of targeted indirect calorimetry in detecting the adequacy of energy intake and the risk of cumulative energy imbalance in a subgroup of critically ill children suspected to have alterations in resting energy expenditure. We examined the accuracy of standard equations used for estimating resting energy expenditure in relation to measured resting energy expenditure in relation to measured resting energy expenditure and cumulative energy balance over 1 week in this cohort. Design: A prospective cohort study. Setting: Pediatric intensive care unit in a tertiary academic center. Interventions: A subgroup of critically ill children in the pediatric intensive care unit was selected using a set of criteria for targeted indirect calorimetry. Measurements: Measured resting energy expenditure from indirect calorimetry and estimated resting energy expenditure from standard equations were obtained. The metabolic state of each patient was assigned as hypermetabolic (measured resting energy expenditure/estimated resting energy expenditure >110%), hypometabolic (measured resting energy expenditure/estimated resting energy expenditure <90%), or normal (measured resting energy expenditure/estimated resting energy expenditure = 90–110%). Clinical variables associated with metabolic state and factors influencing the adequacy of energy intake were examined. Main Results: Children identified by criteria for targeted indirect calorimetry, had a median length of stay of 44 days, a high incidence (72%) of metabolic instability and alterations in resting energy expenditure with a predominance of hypometabolism in those admitted to the medical service. Physicians failed to accurately predict the true metabolic state in a majority (62%) of patients. Standard equations overestimated the energy expenditure and a high incidence of overfeeding (83%) with cumulative energy excess of up to 8000 kcal/week was observed, especially in children <1 yr of age. We did not find a correlation between energy balance and respiratory quotient (RQ) in our study. Conclusions: We detected a high incidence of overfeeding in a subgroup of critically ill children using targeted indirect calorimetry The predominance of hypometabolism, failure of physicians to correctly predict metabolic state, use of stress factors, and inaccuracy of standard equations all contributed to overfeeding in this cohort. Critically ill children, especially those with a longer stay in the PICU, are at a risk of unintended overfeeding with cumulative energy excess.

Cumulative Energy Imbalance in the Pediatric Intensive Care Unit: Role of Targeted Indirect Calorimetry

INTRODUCTION Failure to accurately estimate energy requirements may result in underfeeding or overfeeding. In this study, a dedicated multidisciplinary nutrition team measured energy expenditure in critically ill children. METHODS Steady-state indirect calorimetry was used to obtain measured resting energy expenditure, which was compared with equation-estimated energy expenditure and the total energy intake for each subject. The childrens metabolic status was examined in relation to standard clinical characteristics. RESULTS Sixteen measurements were performed in 14 patients admitted to the multidisciplinary pediatric intensive care unit over a period of 12 months. Mean age of subjects in this cohort was 11.2 years (range 1.6 months to 32 years) and included 7 males and 7 postoperative patients. Altered metabolism was detected in 13 of 14 subjects and in 15 of 16 (94%) measurements. There was no correlation between the metabolic status of subjects and their clinical characteristics. Average daily energy balance was 200 kcal/d (range -518 to +859 kcal/d). Agreement between measured resting energy expenditure and equation-estimated energy expenditure was poor, with mean bias of 72.3 +/- 446 kcal/d (limits of agreement -801.9 to + 946.5 kcal/d). CONCLUSIONS A disparity was observed between equation-estimated energy expenditure, measured resting energy expenditure, and total energy intake, with a high incidence of underfeeding or overfeeding. A wide range of metabolic alterations were recorded, which could not be accurately predicted using standard clinical characteristics. Targeted indirect calorimetry on high-risk patients selected by a dedicated nutrition team may prevent cumulative excesses and deficits in energy balance.

Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study

BACKGROUND The impact of protein intake on outcomes in pediatric critical illness is unclear. OBJECTIVE We examined the association between protein intake and 60-d mortality in mechanically ventilated children. DESIGN In a prospective, multicenter, cohort study that included 59 pediatric intensive care units (PICUs) from 15 countries, we enrolled consecutive children (age: 1 mo to 18 y) who were mechanically ventilated for ≥48 h. We recorded the daily and cumulative mean adequacies of energy and protein delivery as a percentage of the prescribed daily goal during the PICU stay ≤10 d. We examined the association of the adequacy of protein delivery with 60-d mortality and determined variables that predicted protein intake adequacy. RESULTS We enrolled 1245 subjects (44% female) with a median age of 1.7 y (IQR: 0.4, 7.0 y). A total of 985 subjects received enteral nutrition, 354 (36%) of whom received enteral nutrition via the postpyloric route. Mean ± SD prescribed energy and protein goals were 69 ± 28 kcal/kg per day and 1.9 ± 0.7 g/kg per day, respectively. The mean delivery of enteral energy and protein was 36 ± 35% and 37 ± 38%, respectively, of the prescribed goal. The adequacy of enteral protein intake was significantly associated with 60-d mortality (P < 0.001) after adjustment for disease severity, site, PICU days, and energy intake. In relation to mean enteral protein intake <20%, intake ≥60% of the prescribed goal was associated with an OR of 0.14 (95% CI: 0.04, 0.52; P = 0.003) for 60-d mortality. Early initiation, postpyloric route, shorter interruptions, larger PICU size, and a dedicated dietitian in the PICU were associated with higher enteral protein delivery. CONCLUSIONS Delivery of >60% of the prescribed protein intake is associated with lower odds of mortality in mechanically ventilated children. Optimal prescription and modifiable practices at the bedside might enhance enteral protein delivery in the PICU with a potential for improved outcomes. This trial was registered at clinicaltrials.gov as NCT02354521.

Predictors of bone mineral density in human immunodeficiency virus-1 infected children.

Objectives: To compare bone mineral density (BMD) among human immunodeficiency virus (HIV)-infected children with population norms and to determine predictors of BMD in HIV-infected children. Methods: Total body BMD was measured by dual energy x-ray absorptiometry in 37 HIV-infected children and nine sibling controls at baseline. Clinical, dietary and anthropometric data were obtained at the time of the dual energy x-ray absorptiometry examination. Age- and gender-adjusted z scores were calculated for BMD, body mass index, weight and height from population standards. Age-adjusted percentiles were determined for dietary intake of calcium and vitamin D. Differences in BMD z scores between HIV-infected children and sibling controls were determined and adjusted for height and weight, as were independent risk factors for lower BMD among infected children. Eighteen HIV-infected children and 5 controls had serial BMD measures. Results: Compared with population norms, HIV-infected children had significantly lower BMD z scores (-0.51 SD, P = 0.004), in contrast with controls who had normal z scores (0.38 SD, P = 1.0). However, there was no difference in BMD z scores between HIV-infected children and the small number of sibling controls, adjusted for height and weight. Among HIV-infected children, lower BMD z scores were independently associated with lower weight z scores (P < 0.0001), lower height z scores (P = 0.01), advanced (stage B or C) HIV stage (P = 0.01) and age greater than 8 years (P < 0.0001). In the same model, multivitamin use (P = 0.009) and African American race (P = 0.001) were associated with better BMD z scores, with nevirapine use showing borderline positive effect (P = 0.06). All results were adjusted for Tanner stage. Change in BMD z score over time showed that there was no change or an increase in BMD in 100% of controls but in only 44% of the HIV-infected children (P = 0.09). Conclusion: When compared with population norms, HIV-infected children had lower than expected bone mass for their age and gender that may be attributable to delays in growth, sexual maturity, time (length of HIV infection), ethnicity and disease severity. Dietary intake of calcium and vitamin D were not associated with bone loss, but most children had suboptimal intake. However, multivitamin use was strongly associated with better bone mineral density.

Risk Factors for Cardiovascular Disease in Children Infected with Human Immunodeficiency Virus-1

OBJECTIVE To determine risk factors for cardiovascular disease (CVD) in children infected with human immunodeficiency virus (HIV) compared with nationally representative controls from 2003-2004 National Health and Nutrition Examination Survey (NHANES) data. STUDY DESIGN A prospective, longitudinal analysis of CVD risk factors in 42 HIV-infected children compared with NHANES controls, with multivariable modeling of demographic, disease-specific, and treatment-related factors contributing to cardiac risk in the HIV cohort. RESULTS The 42 children infected with HIV were initially an average of 10.1 years old; 68% were Centers for Disease Control and Prevention pediatric HIV disease stage B or C, and 76% were receiving highly active antiretroviral therapy (HAART). Compared with age- and sex-adjusted NHANES controls, the children infected with HIV had lower weight (-0.46 standard deviation [SD] vs +0.54 SD; P < .001), height (-0.62 SD vs +0.26 SD; P < .001), and body mass index (-0.09 SD vs +0.51 SD; P < .001), a higher level of triglycerides (136 mg/dL vs 90 mg/dL; P < .001), and a lower level of high-density lipoprotein (HDL) cholesterol (47 mg/dL vs 54 mg/dL; P < .001). Protease inhibitor therapy was independently associated with higher triglyceride (P = .02) and low-density lipoprotein cholesterol levels (P = .04) and lower HDL cholesterol level (P = .02); nonnucleoside reverse-transcriptase inhibitor therapy was associated with lower visceral fat (P = .01) and higher HDL cholesterol level (P = .005). CONCLUSIONS Children infected with HIV have adverse cardiac risk profiles compared with NHANES controls. Antiretroviral therapy has a significant influence on these factors.

Severe weight loss and hypermetabolic paroxysmal dysautonomia following hypoxic ischemic brain injury: the role of indirect calorimetry in the intensive care unit.

A 14-year-old girl with hypoxic ischemic brain injury developed multiple paroxysms (storms) of dysautonomia. She had a dramatic weight loss of 20 kg over 8 weeks. Resting energy expenditure measured by indirect calorimetry during an autonomic storm was 309% of predicted resting energy expenditure, indicating extreme hypermetabolism. Energy intake and expenditure calculations showed cumulative energy deficits during the period of weight loss. The frequency of her hypermetabolic events increased daily energy needs that were unmatched by her intake, which was calculated from standard equations. Weight stabilized soon after nutrient intake was titrated to account for her heightened energy expenditure. This case illustrates an important nutrition complication of dysautonomic storms in children with brain injury. Regular weight checks during the intensive care course allow detection of weight loss from underfeeding. Measurement of energy needs is prudent when weight loss is unexplained or increased energy expenditure is suspected. In hospitalized patients with metabolic fluctuations, accurate measurement of energy requirements by indirect calorimetry allows serial monitoring of energy balance and may guide nutrition intake to prevent cumulative energy deficits.

Systematic Review of the Influence of Energy and Protein Intake on Protein Balance in Critically Ill Children

OBJECTIVE To examine the influence of protein and energy intakes on protein balance in children receiving mechanical ventilation in the pediatric intensive care unit. STUDY DESIGN We hypothesized that higher energy and protein intakes are correlated with positive protein balance. We performed a systematic literature search to identify studies reporting protein balance in children requiring mechanical ventilation. Factors contributing to protein balance, including protein and energy intake, age, illness severity, study design, and feeding routes, were analyzed using a qualitative approach. RESULTS Nine studies met the entry criteria and were included in the final analysis. Positive nitrogen balance was reported in 6 of the studies, with a wide range of associated energy and protein intakes. Measures of central tendency for daily energy and protein intakes were significantly correlated with positive protein balance. A minimum intake of 57 kcal/kg/day and 1.5 g protein/kg/day were required to achieve positive protein balance. CONCLUSION We found a correlation between higher energy and protein intakes and achievement of positive protein balance in children receiving mechanical ventilation in the pediatric intensive care unit. However, there is a paucity of interventional studies, and a variety of protocols have been used to determine nitrogen balance. Larger clinical trials with uniform methodology are needed to further examine the effect of energy and protein intake on protein balance, lean body mass, and clinical outcomes in children on mechanical ventilation.

Nutritional Status Based on Body Mass Index Is Associated With Morbidity and Mortality in Mechanically Ventilated Critically Ill Children in the PICU.

Objective:To determine the influence of admission anthropometry on clinical outcomes in mechanically ventilated children in the PICU. Design:Data from two multicenter cohort studies were compiled to examine the unique contribution of nutritional status, defined by body mass index z score, to 60-day mortality, hospital-acquired infections, length of hospital stay, and ventilator-free days, using multivariate analysis. Setting:Ninety PICUs from 16 countries with eight or more beds. Patients:Children aged 1 month to 18 years, admitted to each participating PICU and requiring mechanical ventilation for more than 48 hours. Measurements and Main Results:Data from 1,622 eligible patients, 54.8% men and mean (SD) age 4.5 years (5.1), were analyzed. Subjects were classified as underweight (17.9%), normal weight (54.2%), overweight (14.5%), and obese (13.4%) based on body mass index z score at admission. After adjusting for severity of illness and site, the odds of 60-day mortality were higher in underweight (odds ratio, 1.53; p < 0.001) children. The odds of hospital-acquired infections were higher in underweight (odds ratio, 1.88; p = 0.008) and obese (odds ratio, 1.64; p < 0.001) children. Hazard ratios for hospital discharge were lower among underweight (hazard ratio, 0.71; p < 0.001) and obese (hazard ratio, 0.82; p = 0.04) children. Underweight was associated with 1.3 (p = 0.001) and 1.6 (p < 0.001) fewer ventilator-free days than normal weight and overweight, respectively. Conclusions:Malnutrition is prevalent in mechanically ventilated children on admission to PICUs worldwide. Classification as underweight or obese was associated with higher risk of hospital-acquired infections and lower likelihood of hospital discharge. Underweight children had a higher risk of mortality and fewer ventilator-free days.

Influence of Obesity on Clinical Outcomes in Hospitalized Children: A Systematic Review

IMPORTANCE Obesity is prevalent among hospitalized children. Knowledge of the relationship between obesity and outcomes in hospitalized children will enhance nutrition assessment and provide opportunities for interventions. OBJECTIVE To systematically review the existing literature concerning the impact of obesity on clinical outcomes in hospitalized children. EVIDENCE ACQUISITION PubMed, Web of Science, and EMBASE databases were searched for studies of hospitalized children aged 2 to 18 years with identified obesity and at least 1 of the following clinical outcomes: all-cause mortality, incidence of infections, and length of hospital stay. Cohort and case-control studies were included. Cross-sectional studies, studies of healthy children, and those without defined criteria for classifying weight status were excluded. The Newcastle-Ottawa Scale was used to assess study quality. RESULTS Twenty-eight studies (26 retrospective; 24 cohort and 4 case-control) were included. Of the 21 studies that included mortality as an outcome, 10 reported a significant positive relationship between obesity and mortality. The incidence of infections was assessed in 8 of the 28 studies; 2 reported significantly more infections in obese compared with nonobese patients. Of the 11 studies that examined length of stay, 5 reported significantly longer lengths of hospital stay for obese children. Fifteen studies (53%) had a high quality score. Larger studies observed significant relationships between obesity and outcomes. Studies of critically ill, oncologic or stem cell transplant, and solid organ transplant patients showed a relationship between obesity and mortality. CONCLUSIONS AND RELEVANCE The available literature on the relationship between obesity and clinical outcomes is limited by subject heterogeneity, variations in criteria for defining obesity, and outcomes examined. Childhood obesity may be a risk factor for higher mortality in hospitalized children with critical illness, oncologic diagnoses, or transplants. Further examination of the relationship between obesity and clinical outcomes in this subgroup of hospitalized children is needed.