Sharon Collier

Reversal of Parenteral Nutrition–Associated Liver Disease in Two Infants With Short Bowel Syndrome Using Parenteral Fish Oil: Implications for Future Management

Here we report the reversal of cholestasis in 2 infants with intestinal failure and parenteral nutrition–associated liver disease. Treatment involved the substitution of a conventional intravenous fat emulsion with one containing primarily omega-3 fatty acids. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. This suggests that fat emulsions made from fish oils may be an effective means of treating and preventing this often-fatal condition. A randomized, controlled trial is necessary to study the efficacy of this new approach to parenteral nutrition–associated liver disease.

Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.

ObjectiveTo investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. DesignProspective cohort study. SettingMultidisciplinary intensive care unit and pediatric inpatient units at a children’s hospital. PatientsTen septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). InterventionsSeptic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. Measurements and Main Results Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 ± 17.5 [sd] vs. 48.7 ± 8.8 &mgr;mol·kg−1·hr−1;p < .01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p < .01) in the septic patients (368 ± 156 vs. 909 ± 272 &mgr;mol·L−1·day−1). The concentration of whole blood GSH also was decreased in the septic group (665.4 ± 194 vs. 1059 ± 334 &mgr;M;p < .01) ConclusionsWhole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

A.S.P.E.N. Position Paper Clinical Role for Alternative Intravenous Fat Emulsions

The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.

Use of Cyclic Parenteral Nutrition in Infants Less Than 6 Months of Age

Cyclic parenteral nutrition is the technique of infusing the intravenous solution in less than 24 hours, during a portion of the day or night, allowing the patient freedom from the intravenous tubing and pump apparatus. In addition, adverse effects of long-term parenteral therapy, such as liver complications, were reported to be decreased with the use of cyclic parenteral nutrition in adult patients. Literature on the method and effects of cycling in young infants is minimal. This report describes cyclic parenteral nutrition use with guidelines for cycling and the potential beneficial metabolic effects in 10 infants less than 6 months of age who required long-term parenteral nutrition support. Diagnosis, gestational age, length of time on parenteral nutrition, macronutrient intake, growth, and biochemical parameters for the patients are presented. Overall, cyclic parenteral nutrition was well tolerated without clinical symptoms of hypoglycemia, elevated capillary blood glucose concentrations, or abnormal urine glucose levels. The direct bilirubin concentrations showed a decrease or stabilization after cycling was initiated in eight of 10 patients.

Effectiveness of a clinical practice guideline for parenteral nutrition: a 5-year follow-up study in a pediatric teaching hospital

OBJECTIVE To determine the effectiveness of a clinical practice guideline (CPG) on the use of parenteral nutrition (PN) at a tertiary care pediatric hospital. METHODS Review of prospectively collected data on hospital-wide PN use 2 years before and 5 years after the establishment of the CPG. Effectiveness of the CPG was measured as the percentage of PN courses lasting fewer than 5 days and the number of PN starts per 1000 patient days. RESULTS During the study period, 5745 PN courses were administered. The mean (SD) number of PN starts per 1000 inpatient days was 8.86 (0.78) before the CPG and 9.54 (2.49) afterwards (p = .28). The percentage courses of PN lasting for fewer than 5 days declined from 26.3% before the CPG to 18.4% afterwards (p < .0001). A multivariate model confirmed that the rate of short-term PN starts declined after the CPG was issued. The mean (SD) number of PN courses shorter than 5 days in the 2 years before the CPG was 2.33 (0.42) per 1000 patient days versus 1.75 (0.45) in the 5 years after the CPG was instituted (p = .005), which is a 25% decline. The services with the highest volume of PN use showed the most significant decreases in short-term PN use. A cost savings to the hospital of more than

Persistent alanine aminotransferase elevations in children with parenteral nutrition-associated liver disease

50,000 may have been realized. CONCLUSIONS In a large pediatric tertiary care hospital, a CPG was successfully deployed. CPGs can favorably affect the use rates and costs of parenteral nutrition.

Update on pediatric nutrition: breastfeeding, infant nutrition, and growth.

BACKGROUND Parenteral nutrition-associated liver disease (PNALD) is a serious condition affecting many children with short bowel syndrome. The aim of this study was to longitudinally assess serum alanine aminotransferase (ALT), a marker for hepatocyte injury, in enterally fed children with PNALD. METHODS Retrospective chart review of 31 patients treated from 1999 to 2006 by the Center for Advanced Intestinal Rehabilitation at Childrens Hospital Boston (Mass). Inclusion criteria included PN duration of greater than 3 months with subsequent tolerance of full enteral nutrition and evidence of PN-associated liver injury. Time to normalize ALT and direct bilirubin were estimated using Kaplan-Meier and Cox proportional hazards methods. RESULTS Mean age PN cessation was 6 months (range, 2-14 months). Median PN duration was 18 weeks (interquartile range [IQR], 13-33 weeks), and median follow-up was 24 weeks (IQR, 14-48 weeks). After transition to full enteral nutrition, 74% of children normalized direct bilirubin, whereas only 50% normalized ALT. Kaplan-Meier median time to direct bilirubin and ALT normalization were 13 weeks and 35 weeks, respectively (P = .001). CONCLUSION Children with PNALD who have achieved PN independence have persistent ALT elevation despite normal direct bilirubin levels. This implies that hepatic injury may be ongoing beyond the time of bilirubin normalization in this cohort of patients.

Randomized study comparing the efficacy of a novel manual breast pump with a mini-electric breast pump in mothers of term infants.

Recent studies continue to point out the critical nature of a patients nutritional status in helping to determine important health outcomes in pediatrics. We review recent data concerning the composition of breast milk and its adequacy to support infant growth in the first six months of life, as well as trials that support breastfeeding as an important method to delay or reduce the incidence of atopic diseases such as eczema, allergies, and asthma. Studies have also been published that show how physician education and training about breastfeeding can be optimized. Studies showing how nutritional status is measured (using standard anthropometric techniques as well as more modern measures of basal metabolic rate) are highlighted, as well as the role of micronutrient supplementation of patients with the human immunodeficiency virus infection and diarrheal diseases.

Race affects outcome among infants with intestinal failure.

The objective of this study was to compare the efficacy of a mini-electric pump (MEP) and a novel manual breast pump (MP) designed to operate more physiologically. Sixty term breastfeeding mothers used the MP and MEP in randomized order 8 weeks postpartum, expressing for 10 minutes from each breast. Milk volume, fat content, and pattern of milk flowwere measured. Mothers rated pump characteristics by questionnaire. There was no significant difference in the milk volume or fat content when mothers used the pumps in randomized order. The MP was rated significantly better overall and more comfortable and pleasant to use. Significantly more mothers kept theMPthan theMEP. Despite the greater complexity and expense of the MEP, the pumps showed similar efficacy. The MP was preferred by mothers. The novel, more physiological operation of theMPrepresents an advance in milk expression technology.

Advances in parenteral nutrition

Objective: Intestinal failure (IF) is a rare, devastating condition associated with significant morbidity and mortality. We sought to determine whether ethnic and racial differences were associated with patient survival and likelihood of receiving an intestinal transplant in a contemporary cohort of children with IF. Methods: This was an analysis of a multicenter cohort study with data collected from chart review conducted by the Pediatric Intestinal Failure Consortium. Entry criteria included infants ⩽12 months receiving parenteral nutrition (PN) for ≥60 continuous days and studied for at least 2 years. Outcomes included death and intestinal transplantation (ITx). Race and ethnicity were recorded as they were in the medical record. For purposes of statistical comparisons and regression modeling, categories of race were consolidated into “white” and “nonwhite” children. Results: Of 272 subjects enrolled, 204 white and 46 nonwhite children were available for analysis. The 48-month cumulative incidence probability of death without ITx was 0.40 for nonwhite and 0.16 for white children (P < 0.001); the cumulative incidence probability of ITx was 0.07 for nonwhite versus 0.31 for white children (P = 0.003). The associations between race and outcomes remained after accounting for low birth weight, diagnosis, and being seen at a transplant center. Conclusions: Race is associated with death and receiving an ITx in a large cohort of children with IF. This study highlights the need to investigate reasons for this apparent racial disparity in outcome among children with IF.