Essential fatty acid deficiency in well nourished young cystic fibrosis patients

Essential fatty acid deficiency is well known in cystic fibrosis patients, but its pathogenesis remains unclear. It might be related to protein-energy malnutrition which is a common feature of cystic fibrosis or to some specific defects in fatty acid metabolism. To avoid the deleterious effects of protein-energy malnutrition, this study assesses the plasma phospholipid fatty acid pattern in well nourished young cystic fibrosis subjects. Sixteen cystic fibrosis subjects aged 6.6-20.0 years were studied and compared to 16 healthy controls matched for gender, age and nutritional status. Plasma phospholipids were separated by thin layer chromatography and phospholipid fatty acid pattern was determined by gas liquid chromatography. Anthropometry and dual-energy X-ray absorptiometry showed that lean body mass, fat-free mass and fat mass were similar in the two groups. Nutritional inquiry showed higher ingestion of macronutrients by cystic fibrosis subjects than by controls. Plasma phospholipid palmitoleic acid and eicosatrienoic acid were higher, and by contrast linoleic acid and docosahexaenoic acid were lower in cystic fibrosis subjects than in controls. The ratio linoleic acid/arachidonic acid was lower and the ratio eicosatrienoic acid/arachidonic acid was higher in cystic fibrosis subjects than in controls. CONCLUSION: Essential fatty acid deficiency is present in young cystic fibrosis subjects in the absence of protein-energy malnutrition. It means that this deficiency is probably related to specific defects in fatty acid metabolism.     

Efficacy and safety of total parenteral nutrition in pediatric patients

Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-to-benefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents.     

Team approach to total parenteral nutrition

The organization, function, and results of a total parenteral nutrition (TPN) team consisting of a surgical staff physician, a senior surgery resident, a nurse and a pharmacist are described. The TPN team has treated 160 patients. The incidence of septicemia as a complication of TPN has been less than 1% and the rate of serious metabolic derangements of TPN has been 2.7% for electrolyte aberrations and 5% for significant glycosuria in this series. It is recommended that hospitals that cannot provide such a team should refer patients requiring TPN to a center with a TPN team.     

Short-chain fatty acid-supplemented total parenteral nutrition improves nonspecific immunity after intestinal resection in rats

BACKGROUND: Total parenteral nutrition (TPN) alters both specific and nonspecific immune functions, resulting in immunosuppression. Short-chain fatty acids have been shown to improve the adaptive responses of the gut after surgery. The following study investigates the effects of adding short-chain fatty acids to TPN on the immune system after an 80% small bowel resection. METHODS: Rats (237 +/- 3 g) were infused with either TPN (n = 25) or TPN supplemented with short-chain fatty acids (n = 26) for 3 or 7 days. Hematologic analysis was performed on peripheral blood and splenocytes were isolated to characterize cell phenotypes, natural killer cell cytotoxicity and to estimate proliferative response. RESULTS: The relative percent of T (CD3+) cells increased (p < .05) and the relative percent of macrophages decreased (p < .001, n = 13) in the spleens of the 3-day TPN-fed rats. By day 7, these differences disappeared. The natural killer cells from rats that were supplemented with short-chain fatty acids had higher (p < .0001) cytotoxic activity than the TPN groups at day 3. Mitogenic response did not differ between groups but were depressed compared with sham-treated rats. By day 7, rats on standard TPN had larger (p < .0001) spleens than all other groups. This group also had a higher total white blood cell count because of increased numbers of macrophages and neutrophils (p < .02). CONCLUSION: Short-chain fatty acids improve components of nonspecific immune responses and may be beneficial in reducing certain aspects of TPN-associated immunosuppression after major surgery.     

Copper metabolism and requirements in total parenteral nutrition

Copper metabolism and requirements in patients receiving total parenteral nutrition were studied in 28 patients with gastrointestinal diseases. During each of the 3 wk of the study period, each of 24 patients received in their total parenteral nutrition solutions, a daily dose of copper amounting to 0.25 mg, 1.05 mg, or 1.85 mg, in a random order. The other 4 patients received a fixed daily dose of 1 mg throughout the 3 wk. Increased losses of copper through the gastrointestinal tract occurred in patients with diarrhea or high-output stomas or fistulas. Patients with abnormalities of liver excretory functions had decreases in gastrointestinal copper losses. Urinary copper excretion was twice that of normal subjects. Copper infused in excess of the requirements was retained and not excreted. Plasma copper did not reflect the copper balance and cannot be used as a guide for copper supplementation. Copper requirements were found to be 0.3 mg/day in patients with normal amounts of gastrointestinal excretion. In the presence of diarrhea or increased fluid loss through gastrointestinal stomas or fistulas, the copper requirements for total parenteral nutrition are 0.4--0.5 mg/day.     

Metabolic bone disease of total parenteral nutrition

We compared the clinical course of pediatric patients (n = 25) with acetaminophen poisoning treated with an investigational intravenous preparation of N-acetylcysteine (IV-NAC) with that of historical control subjects (n = 29) treated with conventional oral NAC (O-NAC) therapy. Patients received IV-NAC for 52 hours; historical control subjects received O-NAC (72 hours). There were no significant intergroup differences between treatment groups in age (15.5 vs 15.9 years), gender (88% vs 90% female) or distribution of risk categories (probable risk, 12 vs 15; high risk; 13 vs 14). The peak prothrombin time was significantly higher in the IV-NAC group (14.2 vs 13.6 seconds; p = 0.048). Mean treatment delay was significantly longer in the IV-NAC group (14.4 vs 10.4 hours; p = 0.001). Hepatoxicity was noted in two (8.0%) patients in the IV-NAC treatment group and two (6.9%) patients in the O-NAC group. All patients recovered. Our results indicate that 52 hours of intravenous NAC is as effective as 72 hours of oral NAC.     

Cost and outcome analysis of home parenteral and enteral nutrition

BACKGROUND: Previous estimates of the cost of home parenteral and enteral nutrition (HPEN) have excluded hospitalization costs or were conducted abroad and have limited applicability in the United States. Few studies have used validated measures to determine the effect of home nutrition support on quality of life. METHOD: A cost and clinical outcome analysis was performed by retrospective review of charts of patients receiving HPEN from 1991 to 1996. Questionnaires to determine the influence of therapy on lifestyle (n = 41) and a general health status questionnaire, the short form 36-item survey (n = 39), were mailed to patients. RESULTS: The annual cost per patient for parenteral solutions was $55,193 +/- 30,596 (mean +/- SD) based on Medicare charges and for enteral tube feedings was $9605 +/- 9327. The annual cost of hospitalization ranged from zero to $140,220 in the parenteral nutrition group and from zero to $39,204 in the enteral nutrition group. The annual number of hospitalizations per patient for patients receiving parenteral nutrition ranged from 0.52 to 1.10, compared with 0 to 0.50 in the enteral nutrition population. The health status of HPEN patients was significantly lower (p < .05) in five of the eight short-form 36 health domains compared with the general population. The areas of lifestyle most frequently affected were travel, sleep, exercise and leisure. CONCLUSIONS: The majority of the cost of therapy was associated with the direct provision of nutrition, although in some patients the hospitalization expenditure exceeded this cost. Home nutrition support had a significant negative impact on a patient's quality of life and lifestyle.     

Glucose dynamics during continuous hemodiafiltration and total parenteral nutrition

OBJECTIVE: To determine glucose balance during dextrose-free continuous hemodiafiltration with or without dextrose-containing ultrafiltrate replacement fluid and full nutritional support. DESIGN: Prospective, nonrandomized, observational study. SETTING: A 24-bed multiple trauma critical care unit in a level-I trauma center. PATIENTS: Seventeen multiple trauma patients with multiple organ dysfunction syndrome requiring hemodialysis for acute renal failure. INTERVENTIONS: Continuous hemodiafiltration effluent volume and glucose concentration were measured. Study days were classified according to whether dextrose was used in the ultrafiltrate replacement therapy. Use of dextrose in replacement therapy was determined clinically. Parenteral nutrition was not altered for potential glucose absorption from continuous hemodiafiltration. Ultrafiltrate replacement consisted of 5% dextrose in saline on 21 study days (D5YES) and dextrose-free solutions on 54 study days (D5NO). RESULTS: The D5YES group received 316 +/- 145 g glucose/day from the ultrafiltrate replacement fluid, in addition to glucose in total parenteral nutrition (total glucose intake = 942 +/- 229 g/day in D5YES, 682 +/- 154 g/day in D5NO) (p < 0.05). Glucose loss in continuous hemodiafiltration effluent was 82 +/- 61 g/day in D5YES and 57 +/- 22 g/day in D5NO (P < 0.05), for a net glucose uptake of 8.1 +/- 2.1 mg/kg per min in D5YES and 5.4 +/- 1.5 mg/kg per min in D5NO (p < 0.05). Glucose loss was predictable when dialysate and ultrafiltrate replacement fluids were dextrose-free (R2 = 0.77), but less so when dextrose was used as ultrafiltrate replacement (R2 = 0.47). CONCLUSION: Dextrose-free dialysate promotes glucose loss during continuous hemodiafiltration, but the loss is small and predictable. Use of a dextrose-containing ultrafiltrate replacement fluid results in a significant increase in glucose intake without a commensurate increase in glucose loss, and makes glucose loss in effluent less predictable.     

Hepatobiliary toxicity of total parenteral nutrition in adults

The enzymology and clinical manifestations of total parenteral nutrition (TPN)-induced liver abnormalities have been investigated extensively. The cause, pathogenesis, and treatment of TPN-related hepatic and biliary dysfunction in adults still are not well understood, however. The findings of experimental studies in animals has not necessarily correlated with the human data, and there have been few prospective, randomized controlled trials examining the mechanism, cause, or treatment of TPN-induced hepatobiliary toxicity in adults. This article examines the animal models of pathogenesis and treatment of TPN-induced intrahepatic and extrahepatic abnormalities, and provides a discussion of abnormalities seen in humans.     

Chylothorax or leakage of total parenteral nutrition?

The diagnosis chylothorax is based on a chemical analysis of the pleural effusion. According to the literature, this analysis can be rather straightforward, comprising measurements of triglycerides, chylomicrons, and cholesterol. In this report we present an autopsy case that alerted us to interpret these results critically. Although the laboratory tests of the pleural effusion in this patient with parenteral nutrition suggested chylothorax, additional tests (potassium (11.3 mmol.L(-1)) and glucose (128 mmol.L(-1)) proved otherwise. Comparison of the pleural effusion analysis and the content of the parenteral nutrition led to the final conclusion that the effusion was due to a leakage of parenteral nutrition instead of chylothorax. We therefore suggest adding glucose and potassium measurements to the biochemical work-up of a patient under suspicion of chylothorax.     

Body composition changes measured by dual-energy X-ray absorptiometry in patients receiving home parenteral nutrition

Some patients with infiltrant vesical cancer can be treated successfully with radical cysto-prostatectomy and urinary by-pass and increasingly more authors publish successful results in series of selected patients over 70- and 80-year old. Between February 1988 and July 1996, 18 radical cystectomies with orthotopic urinary by-pass were performed in the Urology Service, Policlinico Vigo, in patients over 70 (range 70-84 years), with an operative mortality rate of 11%. 8 patients (44%) developed immediate complications and 9 patients (50%) presented distant complications. Overall mortality in our series was 33.3% and survival 66.6% after a mean follow-up of 30.7 months. We believe orthotopic-continent by-pass is a valid alternative with operative mortality and complication rates similar to those of ileal ducts, with the advantage for the patient of avoiding permanent urinary stoma.     

Total parenteral nutrition in surgical patients

Malnutrition is common in the hospitalized surgical patient. There is a strong association between improved nutritional status and a favorable postoperative recovery, while malnutrition has an adverse effect on surgical outcome (Driscoll & Blackburn, 1990; Souba, 1997). Advances in providing parenteral nutrition have had a positive impact on nutrition care of these patients and will be reviewed in this article.     

Effect of total parenteral nutrition on amino acid and glucose transport by the human small intestine

OBJECTIVE: The effect of total parenteral nutrition (TPN) on small intestinal amino acid transport activity was studied in humans. SUMMARY BACKGROUND DATA: Studies in humans receiving TPN indicate that a decrease in the activities of the dissacharidase enzymes occurs, but morphologic changes are minimal with only a slight decrease in villous height. METHODS: Surgical patients were randomized to receive TPN (n = 6) or a regular oral diet (controls, n = 7) for 1 week before abdominal surgery. Ileum (5 controls, 5 TPN) or jejunum (2 controls, 1 TPN) were obtained intraoperatively and brush-border membrane vesicles (BBMV) were prepared by magnesium aggregation/differential centrifugation. Transport of L-MeAlB (a selective system A substrate), L-glutamine, L-alanine, L-arginine, L-leucine, and D-glucose was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. RESULTS: Vesicles demonstrated approximately 18-fold enrichments of enzyme markers, classic overshoots, transport into an osmotically active space, and similar 1-hour equilibrium values. TPN resulted in a 26-44% decrease in the carrier-mediated transport velocity of all substrates except glutamine across ileal BBMVs. In the one patient receiving TPN from whom jejunum was obtained, there was also a generalized decrease in nutrient transport, although glutamine was least affected. Kinetic studies of the system A transporter demonstrated that the decrease in uptake was secondary to a reduction in carrier Vmax, consistent with a decrease in the number of functional carriers in the brush-border membrane. CONCLUSIONS: TPN results in a decrease in brush-border amino acid and glucose transport activity. The observation that glutamine transport is not downregulated by 1 week of bowel rest may further emphasize the important metabolic role that glutamine plays as a gut fuel and in the body's response to catabolic stresses.     

Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients

Supplementation of parenteral nutrition with glutamine (GLN) has been suggested to improve the efficacy of nutritional support by stimulating protein synthesis and improving immunocompetence. In the present study we investigated the impact of infusing the dipeptide glycyl-glutamine (GLY-GLN) at increasing dosages on plasma amino acid concentrations in patients with polytrauma. Nine polytraumatized patients were randomly assigned according their age and their trauma score to three experimental groups. Group 1 received 280, group II 450, and group III 570 mg GLY-GLN per kg body weight/day for a period of four days (3rd to 7th posttraumatic day), resulting in a maximum daily GLN administration (calculated for a 70 kg patient) of 14 g, 21 g and 28 g, respectively. Seven polytraumatized patients receiving the nutrition solution without GLY-GLN supplementation served as controls. All patients received total parenteral nutrition with an average amino acid administration of 1.1 g/kg/day and a total energy intake of 30 kcal/kg/day. GLY-GLN infusion did not evoke any side effects. In comparison with the control group, arterial plasma GLN concentrations increased significantly on day I after start of infusion in groups II and III, but remained raised throughout the study period only in group III (p < 0.003). Similarly, plasma GLY concentrations were also significantly raised in group III (p < 0.04). The maximum increase of plasma GLY was found on the second infusion day, after which plasma concentrations of GLY fell to concentrations even below those observed in the control group at the end of the study period. Excretion of GLY-GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible. We conclude from this first available dose finding study on glutamine-containing dipeptides that in polytraumatized patients infusion of 570 mg/kg/day of GLY-GLN (corresponding to 28 g glutamine or 40 g dipeptide/70 kg, respectively) is necessary to induce a sustained effect on plasma glutamine concentrations. No pathological accumulation of free glycine or of the dipeptide was seen with any of the three dosage steps of GLY-GLN. Thus, the administration of even high doses of GLY-GLN is feasible and safe in patients with polytrauma and is not associated with any relevant renal substrate loss.     

Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition

BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, which is counteracted mainly by superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme), selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol. OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients receiving home parenteral nutrition (HPN) providing variable amounts of a lipid emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as recommended by the American Medical Association, and no selenium. DESIGN: Serum malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy control subjects. Malondialdehyde was also assessed in a group of 40 healthy control subjects. RESULTS: Patients had significantly higher concentrations of malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium nutritional status. Linear regression analysis showed that malondialdehyde was associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha-tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis confirmed only the association between malondialdehyde and alpha-tocopherol; plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P< 0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN patients, the peroxidative stress due to lipid emulsions rich in PUFAs is counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol, zinc, copper, and manganese recommended by the American Medical Association appear sufficient to sustain SOD activity but inadequate to maintain alpha-tocopherol nutritional status. HPN formulations should be supplemented with selenium.