Emily B. Hak

Measured energy expenditure of tube-fed patients with severe neurodevelopmental disabilities

OBJECTIVE To determine measured resting energy expenditure (REE) of nonambulatory tube-fed patients with severe neurological neurodevelopmental disabilities. METHODS Twenty patients were prospectively studied. Only steady state indirect calorimetry measurements were taken. All measurements were conducted using a canopy system. Nutritional needs were met entirely by enteral feedings via a permanent ostomy. RESULTS REE was widely distributed from 16 kcals/kg/day to 39 kcals/kg/day. The mean REE (888+/-176 kcals/day) of the patients was significantly (p<0.01) lower than predicted as estimated by the Harris-Benedict equations (1081+/-155 kcals/day) and World Health Organization equations (1194+/-167 kcals/day). Fat-free mass (FFM) was the best parameter for predicting REE. Two predictive equations were developed that are not significantly biased and more precise (< or =15% error) than conventional predictive formulas. CONCLUSION Conventional formulas for estimating energy expenditure are inaccurate and generally overestimate measured energy expenditure of nonambulatory patients with severe developmental disabilities.

Cysteine supplementation results in normalization of plasma taurine concentrations in children receiving home parenteral nutrition

We evaluated plasma sulfur amino acid concentrations in children with short gut syndrome receiving home parenteral nutrition (n = 6). Cysteine HCl addition to solutions formulated with a pediatric amino acid product will increase plasma taurine concentrations to within the normal reference range.

Recovery from ischemic acute renal failure is improved with enteral compared with parenteral nutrition

OBJECTIVE To compare measurements of renal function after acute ischemic renal failure in rats fed enterally or parenterally. DESIGN Prospective, randomized, animal trial. SETTING University research laboratory. SUBJECTS Male Sprague-Dawley rats (n = 21). INTERVENTIONS Animals were randomized to receive isocaloric (160 nonprotein kcal/kg/day), or isonitrogenous (1.4 g of nitrogen/kg/day [100 mmol/kg/day]) enteral (n = 10), or parenteral nutrition (n = 11) through either a gastrostomy tube or a catheter placed in the jugular vein. After the animals received 7 days of assigned feedings, baseline blood samples were collected. A right nephrectomy and 45-min left renal pedicle occlusion were then performed. One hour after the ischemic injury, assigned feedings were resumed and continued for 3 days. After ischemic injury, daily blood samples were obtained and 24-hr urine collections were performed. On day 11, animals were killed and the kidney was harvested and fixed for subsequent microscopic examination. MEASUREMENTS AND MAIN RESULTS Urine was analyzed for concentrations of total urea nitrogen, creatinine, protein, and calcium. Serum was analyzed for creatinine and urea nitrogen concentrations. Fixed kidney sections were examined for mitotic figures, tubular calcifications, and casts using light microscopy by an investigator blinded to the nutritional regimen. Data are presented as mean +/- SD or median (range). Percent increase in creatinine clearance from the nadir on day 9 to day 11 was approximately 2.5-fold greater in the enteral compared with the parenteral nutrition group (490 +/- 221% vs. 208 +/- 130%; p = .003). Histologic evaluation demonstrated greater dystrophic tubular calcifications per ten high-power fields in the parenteral compared with the enteral nutrition group (50 [four to 85] vs. three [0 to 37]; p = .001). No differences in urine calcium concentration or 24-hr calcium excretion were seen. CONCLUSION Rats given continuous enteral nutrition 7 days before and for 3 days after ischemic acute renal failure have improved renal function compared with rats given parenteral nutrition.

Enteral Fish Oil for Treatment of Parenteral Nutrition‐Associated Liver Disease in Six Infants with Short‐Bowel Syndrome

Study Objective. To evaluate the use of enteral fish oil for the treatment of parenteral nutrition‐associated liver disease (PNALD).

Upper Gastrointestinal Tract Bleeding in Critically Ill Pediatric Patients

Similar to adults, children under physiologic stress can develop an imbalance in defensive (mucosal layer, motility) and aggressive (gastric acid, bile salts, enzymes) factors responsible for maintaining a healthy gastrointestinal tract. Hypoxia in the gastrointestinal tract likely disrupts the defensive factors, thereby permitting damage by aggressive factors to upper gastrointestinal epithelium that may progress to stress ulceration and acute upper gastrointestinal tract bleeding (UGIB). The basic pathophysiology may be similar in children and adults; however, differences in the time to developing ulceration, ulcer location, and number of ulcers have been reported. Functional development of the gastrointestinal tract is influenced by disease, gestational and postnatal age, and exposure to and type of enteral feedings, thereby confounding the development and prophylaxis of UGIB in neonates and infants. In addition, pharmacotherapy decisions are often complicated by drug administration issues and adverse effects.

Alterations in N-Acetylation of 3-Methylhistidine in Endotoxemic Parenterally Fed Rats

N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports we randomized 39 male Sprague-Dawley rats (157-213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg.kg-1.d-1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 +/- 136 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 +/- 3.9% in the PN group to 19.8 +/- 8.0 and 39.9 +/- 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.

Evaluation of microbial contamination associated with different preparation methods for neonatal intravenous fat emulsion infusion.

PURPOSE Microbial contamination associated with different methods of neonatal intravenous fat emulsion (IVFE) preparation and delivery was evaluated. METHODS Sterility testing was performed on IVFE dispensed via three different methods: (1) in the original container (n = 60), (2) repackaged into a syringe (n = 90), and (3) drawdown of the original container (n = 60). At the end of each infusion (24 hours for methods 1 and 3, 12 hours for method 2), a sample of the IVFE was withdrawn from the container using a sterile syringe in an International Organization for Standardization class 5 hood and sent to the hospital microbiology laboratory, where the samples were introduced into blood culture bottles and incubated for five days. Each sample was then subcultured on a blood agar plate with olive oil and left for an additional two days in a carbon dioxide incubator to assess for Malassezia furfur. RESULTS None of the samples from the original containers showed bacterial or fungal growth. Three of the samples from syringes had bacterial growth (two samples contained coagulase-negative staphylococcus and one contained both Klebsiella oxytoca and Citrobacter freundii), yielding a contamination rate of 3.3%. The number of contaminated samples did not significantly differ among the three preparation methods (p = 0.13). CONCLUSION Repackaging IVFE into sterile syringes resulted in bacterial contamination and should be avoided in clinical practice. IVFE samples obtained using the drawdown procedure under sterile conditions for infusion over 24 hours revealed no microbial contamination.

Effect of Pentoxifylline on Nitrogen Balance and 3-Methylhistidine Excretion in Parenterally Fed Endotoxemic Rats

Pentoxifylline interrupts early gene activation for tumor necrosis factor, interleukin-1, and interleukin-6 production and improves survival from experimental sepsis. These effects can alter nitrogen loss during critical illness. To determine the dose-dependent influence of pentoxifylline on nitrogen loss, 44 male Sprague-Dawley rats (220 to 265 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (LPS) at 9 mg x kg(-1) x d(-1), or PN plus LPS plus a continuous infusion of pentoxifylline at either 25 (PEN25) or 100 mg x kg(-1) x d(-1) (PEN100) for 48 h. Before randomization, all animals underwent intravenous cannulation and 40 h of PN adaptation. All animals received isocaloric, isonitrogenous PN (160 kcal x kg(-1) x d(-1) and 1.0 gN x kg(-1) x d(-1)) and were kept nil per os except for water ad libitum. Administration of LPS significantly worsened nitrogen balance for all three groups compared with PN control; however, pentoxifylline only modestly improved nitrogen balance compared with LPS (206 +/- 255, -497 +/- 331, -332 +/- 329, and -310 +/- 383 mg/48hr for the PN, LPS, PEN25, and PEN100 groups, respectively; P < 0.001). Pentoxifylline did not significantly change 3-methylhistidine urinary excretion compared with LPS (573 +/- 180, 705 +/- 156, 780 +/- 326, and 683 +/- 266 microg/48 h for the PN, LPS, PEN25, and PEN100 groups, respectively, P not significant). Pentoxifylline, given in therapeutic doses after an endotoxin challenge, modestly, but not significantly, improved nitrogen balance. Urinary 3-methylhistidine excretion was not influenced by pentoxifylline. A dose-dependent effect by pentoxifylline on these markers was not evident.

Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats.

OBJECTIVE This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. METHODS Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100 micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncans multiple range test, and Fishers Exact Test were used for statistical analysis. RESULTS Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/- Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different. CONCLUSIONS Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.

Pamidronate treatment for hypercalcemia in an infant receiving parenteral nutrition.

A 17‐day‐old infant who was delivered 8 weeks premature underwent small bowel resection for necrotizing enterocolitis. During treatment with continuous infusions of furosemide and hydrocortisone, his total calcium concentration had increased. The calcium dose in his parenteral nutrition solution was decreased and then finally withheld. At 7 weeks of age and after 10 days of calcium‐free parenteral nutrition, pamidronate 3 mg (1.1 mg/kg) in 60 ml of normal saline was infused over 6 hours. The infants total serum calcium concentration decreased, but then 6 days later it had increased again; pamidronate 2 mg (0.7 mg/kg) in 40 ml of normal saline over 4 hours was administered. The patient demonstrated no signs or symptoms of adverse reactions to pamidronate. His serum calcium concentration returned to normal, and calcium‐containing parenteral nutrition was tolerated. The use of pamidronate for treatment of hypercalcemia and chronic conditions that affect normal bone growth is increasing in children. Clinical trials in pediatric patients are necessary to determine how best to use bisphosphonates in this patient population.