Nutritional support in children with end-stage liver disease : a randomized crossover trial of a branched-chain amino acid supplement

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formulation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD. and are deserving of wider application and study.

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction. 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 ± 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis

Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.

Protein turnover in malnourished patients with cystic fibrosis: Effects of elemental and nonelemental nutritional supplements

To evaluate the relative efficacy of nonele-mental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [15N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study compar-ing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-110 h-1versus 0.33 g kg-110 h-1for Criticare and-0.59 g kg-110 h-1for MT), although this was significant (p < 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF. © 1990 Raven Press Ltd, New York.

Comparison of two oral rehydration solutions in children with gastroenteritis in Australia

An open-label inpatient study is in progress to compare the efficacy and safety of two oral rehydration solutions in children and infants with acute diarrhea and mild to moderate dehydration. One solution (ORS-60) contains 60 mmol/L of sodium and 1.8% glucose, with a total osmolatity of 240 mosm/kg; the other (ORS-26) contains 26 mmol/L of sodium, 2.7% glucose, and 3.6% sucrose, with a total osmolality of 340 mosm/kg. An outcome analysis of 28 children with gastroenteritis indicated that ORS-60 (n = 13) reduced stool volume during the first eight hours after admission to a significantly greater (P < 0.05) extent than did ORS-26 (n = 15). Diarrhea had ceased by 24 hours in 64% of ORS-60 patients but in only 31% of ORS-26 patients, and the patients' clinical conidition was improved at eight hours in 84% of ORS-60 patients versus 60% of ORS-26 patients. Differences between treatments in degree of dehydration at each follow-up point, total duration of diarrhea, and duration of hospital stay were not detected. No adverse drug reactions occurred. Four patients received intravenous rehydration therapy, but none was considered a treatment failure. We conclude that the lower osmolar solution, ORS-60, conferred earlier recovey and reduced continuing fluid losses in the management of gastroenteritis.

Pre-operative nutritional support in children with end-stage liver disease accepted for liver transplantation: An approach to management

Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branche-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.

The hazards of automatic-dishwasher detergent

Automatic-dishwasher detergent is a common household substance which is extremely corrosive and potentially fatal if ingested. In this report, we discuss the implications of the ingestion of automatic-dishwasher detergent in 18 children over a three-year period. Ten of the 18 children gained access to the automatic-dishwasher detergent from the dishwasher on the completion of the washing-cycle, while the remainder ingested the detergent directly from the packet. There was a poor correlation between the presenting signs and symptoms and the subsequent endoscopic finding in the 14 children who underwent endoscopy.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.

Short-term nutritional supplementation during management of pulmonary exacerbations in cystic fibosis: A controlled study, including effects of protein turnover

Effects of nutritional supplements on minimizing weight loss and abnormalities of protein turnover during pulmonary exacerbations in cystic fibrosis (CF) were studied by controlled trial. Patients received pulmonary therapy and either standard diet (n = 10) or adjunctive enteral supplements (n = 12). Initial protein turnover, measured by [15N]glycine kinetics, showed alterations of protein synthesis (P Syn) and catabolism (P Cat), which correlated with the degree of underweight, and negligible net protein deposition (P Dep). With treatment both groups had significant increases in mean body weight and forced expiratory volume in 1 s, expressed as percent predicted value for height (FEV1) by 3 wk, but a significant correlation between initial underweight and subsequent weight gain was observed only in supplemented patients. Mean P Syn and P Dep increased significantly (p < 0.001) only in the supplemented group. Pulmonary exacerbations in CF have important adverse effects on body-protein metabolism, similar to changes in protein-energy malnutrition and infection. These effects are reversed by short-term nutritional support. Strategic nutritional intervention should thus be considered in management, especially in malnourished patients.

The use of a synthetic prostaglandin e1 analogue (misoprostol) as an adjunct to pancreatic enzyme replacement in cystic fibrosis

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 μg/day in divided doses. We found a significant reduction in fat output (14.7 ± 11.7 versus 7.5 ± 3.5 g/day, p < 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2% p < 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Serum immunoreactive cationic trypsinogen: A useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4·9±4·9 μg/l (mean ±SD), significantly below values in patients with non-pancreatic steatorrhoea (47·0±22·1 μg/l, p<0·001) and 50 control subjects (31·4±7·4 μg/l, p<0·001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0·2-17·0 yr) who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (<-2SD or 16·6 μg/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (≥16·6 μg/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

Liver transplantation in children: Experience with the development of an Australian pilot programme. The Queensland Liver Transplantation Programme

Children with end-stage liver disease now form a major sub-group of patients considered suitable for liver transplantation (ltp), and enjoy better survival statistics after transplantation than do adults. Since June 1984, a paediatric ltp programme has been developed in Brisbane with an initial working relationship and ongoing close links with two USA centres (Pittsburgh, and the UCLA Medical Center). Fourteen children with end-stage liver disease have been referred to the Queensland Liver Transplantation Programme for formal assessment. Following frank, informed discussion with their parents, 10 of these children were offered the option of ltp. During the transition stage, two infants with biliary atresia were referred to UCLA at their parents' request and, subsequently, eight children aged from 9 months to 6 years have been placed on a transplant candidacy list in Brisbane. A donor procurement team with access to a Queensland Government jet has been available to cover all mainland States except Western Australia. Six of the children have now had orthotopic ltp (two children at the UCLA Medical Center; four children at the Royal Children's Hospital, Brisbane). One UCLA patient died with a non-functioning graft, and one Brisbane patient died 5 weeks post-transplant with rejection, hepatic artery thrombosis and sepsis. The other four children are alive and well, three with normal liver function and one with unexplained intrahepatic cholestasis, during the 1-20 month follow-up to date. Three further children have died of their liver disease without a donor of an appropriate blood group and size being found, and one patient still awaits a suitable donor. The experience of these authors suggests that ltp is a major advance in the treatment of paediatric liver disease, and that the procedure can be carried out successfully in Australia with initial results comparable with leading overseas centres. The procedure requires the full array of services of a major paediatric tertiary care facility, an intensive team effort with awareness of the special needs of children, and a widespread procurement capability. A major problem for Australia is the procurement of sufficient numbers of optimal paediatric donor livers.