Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

Can Vco2-Based Estimates of Resting Energy Expenditure Replace the Need for Indirect Calorimetry in Critically Ill Children?

BACKGROUND: Optimal energy provision, guided by measured resting energy expenditure (REE), is fundamental in the care of critically ill children. REE should be determined by indirect calorimetry (IC), which has limited availability. Recently, a novel equation was developed for estimating REE derived from carbon dioxide production (Vco2). The aim of this study was to validate the accuracy of this equation in a population of critically ill children following cardiopulmonary bypass (CPB). METHODS: This is an ancillary study to a larger trial of children undergoing CPB. Respiratory mass spectrometry was used measure oxygen consumption (Vo2) and Vco2. REE was then calculated according to the established Weir equation (REEW) and the modified, Vco2-based equation (REECO2). The agreement between the 2 measurements was assessed using Bland-Altman plots and mixed-model regressions accounting for repeated measures. RESULTS: Data from 104 patients, which included 575 paired measurements, were included. The agreement between REEW and REECO2 was biased during the 72-hour observation period post CPB, with a mean percentage error between measurements of 11% (±7%). The most important determinant of the bias with the Vco2-based equation was the respiratory quotient (RQ). The percentage error between REEW and REECO2 dropped to 4.4% (±2.4%) in those with an RQ between 0.8 and 1. The within-subject variability for RQ in this cohort was wide (11%). CONCLUSIONS: IC remains the most accurate method to determine the REE of critically ill patients. Widespread availability of Vco2 data renders Vco2-based approaches to measurement of REE attractive; however, further research is needed to ensure that REE is estimated accurately.

Systemic inflammation increases energy expenditure following pediatric cardiopulmonary bypass.

OBJECTIVES: To examine the association between cardiopulmonary bypass-related systemic inflammation and resting energy expenditure in pediatric subjects following cardiac surgery. DESIGN: Single-center, prospective cohort study. SETTING: Pediatric cardiac critical care unit in Toronto, Canada. PATIENTS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery. INTERVENTIONS: Resting energy expenditure was determined by indirect calorimetry and the modified Weir equation, using VO2 and VCO2 measured by in-line respiratory mass spectrometry. Measurements were taken at baseline and 6-hour intervals from separation from cardiopulmonary bypass for a maximum of 72 hours. Plasma interleukin-6, glucose delivery, feeding status, and cardiac output (calculated by Fick equation) were monitored at each resting energy expenditure measurement. MEASUREMENTS AND MAIN RESULTS: We studied 111 subjects at a median (interquartile range) age of 5.3 months (0.8-10.5 mo), weighing 5.7 kg (3.9-8.1 kg), of whom 88% underwent biventricular repair. Resting energy expenditure decreased from 51 kcal/kg/d to 45 kcal/kg/d during the study period. Resting energy expenditure was positively associated with increased plasma interleukin-6 (estimate variable, 1.76; p = 0.001) and inversely associated with preoperative methylprednisolone use (estimate variable, -6.7; p = 0.003) even after accounting for other predictors. Increase in cardiac output was also associated (estimate variable, 13.7; p < 0.0001) with higher resting energy expenditure. CONCLUSIONS: Resting energy expenditure ranges between 40 and 60 kcal/kg/d and decreases progressively in children following cardiopulmonary bypass surgery. It is directly associated with increased inflammation and higher cardiac output and inversely associated with anti-inflammatory strategies. Further studies are required to predict the appropriate caloric delivery in this cohort.

Energy expenditure and caloric and protein intake in infants following the Norwood procedure.

OBJECTIVES: Cardiopulmonary bypass in infants results in a hypermetabolic response. Energy requirements of these patients have not been well studied. We assessed energy expenditure and caloric and protein intake during the first 3 days following the Norwood procedure. DESIGN: Clinical investigation. SETTING: Children's hospital. PATIENTS: Seventeen infants (15 boys, age 4-92 days, median 7 days). INTERVENTIONS: VO2 and VCO2 were continuously measured using respiratory mass spectrometry in 17 infants for the first 72 hrs following the Norwood procedure. The respiratory quotient was determined as VCO2/VO2. Energy expenditure was calculated using the modified Weir equation. Measurements were collected at 2- to 4-hr intervals. The mean values in the first 8 hrs, hours 8-32, hours 32-56, and the last 16 hrs were used as representative values for postoperative days 0, 1, 2, and 3. Total caloric and protein intakes were recorded for each day. MEASUREMENTS AND MAIN RESULTS: Energy expenditure, VO2, and VCO2 were initially high; declined rapidly during the first 8 hrs; and were maintained relatively stable in the following hours (p < .0001). Respiratory quotient showed a significant linear increase over the 72 hrs (p = .002). Energy expenditure on days 0, 1, 2, and 3 was 43 +/- 11, 39 +/- 8, 39 +/- 8, and 41 +/- 6 kcal/kg/day, respectively. Total caloric intake was 3 +/- 1, 14 +/- 5, 31 +/- 16, and 51 +/- 16 kcal/kg/day. Protein intake was 0, 0.2 +/- 0.2, 0.6 +/- 0.5, and 0.9 +/- 0.5 g/kg/day on days 0, 1, 2, and 3, respectively. CONCLUSIONS: Infants exhibit a hypermetabolic response immediately following the Norwood procedure. Caloric and protein intake was inadequate to meet energy expenditure during the first 2 days after surgery. Further studies are warranted to examine the effects of caloric and protein supplementation on postoperative outcomes in infants after cardiopulmonary bypass.

12-hour versus 24-hour creatinine clearance in critically ill pediatric patients.

Measurement of renal function is important to optimize drug dosing in critically ill pediatric patients and to prevent dose-related toxicities caused by medications that are eliminated or metabolized by the kidney. In clinical practice, the 24-h creatinine clearance (CrCl) is used as a surrogate marker of renal function. However, a 24-h urine collection period delays the availability of the result and increases the potential for collection errors. This prospective, observational study was performed to determine whether a 12-h CrCl is comparable to the traditional 24-h CrCl and to assess whether CrCl could be reliably predicted by the Schwartz equation, which mathematically estimates a child's GFR. A 24-h urine sample was collected in two 12-h aliquots from 60 catheterized critically ill children (age 2 d to 18 y). CrCl and Schwartz glomerular filtration rate (GFR) estimates were determined for each 12- and 24-h period. Agreement between 12- and 24-h CrCl and between CrCl and Schwartz GFR estimates was assessed using intraclass correlation coefficients (ICCs). An ICC > or =0.8 was considered to indicate excellent agreement. The ICC between the first 12-h CrCl and 24-h CrCl was 0.9605. The ICC between the second 12-h CrCl and 24-h CrCl was 0.9602. The ICC between the 24-h CrCl and Schwartz GFR was only 0.7046. All comparisons of 12- and 24-h CrCl indicated excellent agreement. In summary, the Schwartz equation was not a reliable estimate of renal function in critically ill children, and a 12-h CrCl is just as accurate as the standard 24-h CrCl to assess renal function and guide drug dosing.