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.     

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition

Clinical and hematological abnormalities can occur in patients receiving intravenous fat emulsions as part of a long-term parenteral nutrition; they consist of hepatosplenomegaly and peripheral blood cytopenia(s). These abnormalities lead to bone marrow examination which revealed numerous macrophages laden with blue staining pigment granules and separate lipid vacuoles, presenting the typical histochemical characteristics of sea-blue histiocytes. Thus, long-term parenteral nutrition including fat-emulsion sources may represent a further condition in addition to the wide variety of disorders which can be associated with sea-blue histiocytosis. Moreover, in view of its clinical and morphological presentation, this storage pathological state could be compared with the so-called sea-blue histiocyte syndrome described by Silverstein and colleagues.     

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.     

Glucose response to abrupt initiation and discontinuation of total parenteral nutrition

Plasma glucose was studied during the initiation of total parenteral nutrition (TPN) and the discontinuation of TPN without a tapering schedule. Blood was sampled every 5 minutes for 2 hours after the start of TPN and 1 week later as TPN was discontinued. A total of 14 initiations and 14 discontinuations were studied in 18 patients. Severity of illness in patients ranged from stable condition postoperatively to multiple-system failure; six patients had diabetes mellitus. The TPN solution was a 3:1 admixture that provided a caloric intake equal to 1.2 times the resting energy expenditure, with 40% fat and 60% carbohydrate calories. An average of 1963 kcal was provided per day (340 g of glucose, 79 g of fat). During the initiation phase, the mean increase in plasma glucose was 60 mg/dL. The increase for diabetic patients was 79 +/- 14 mg/dL compared with 52 +/- 23 mg/dL for the nondiabetics. During the discontinuation phase, the mean plasma glucose decreased 40 +/- 20 mg/dL; two patients with high concentrations of regular insulin (50 and 100 units) showed an increase in plasma glucose when the TPN was stopped. Plasma glucose returned to the preinfusion baseline after discontinuation. During both initiation and discontinuation, plasma glucose showed little change after the first 60 minutes. No clinical symptoms of hypoglycemia were observed. In conclusion, TPN as a 3:1 admixture can be safely started as full nutrition support and stopped abruptly without a tapering schedule. Plasma glucose response is rapid, predictable, and mostly complete within 60 minutes.     

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.     

Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: a pilot study

BACKGROUND & AIMS: Cholestatic liver disease (CLD) is a frequent and sometimes fatal complication of total parenteral nutrition (TPN) that may require withdrawal of TPN. The aim of this pilot study was to evaluate ursodeoxycholic acid (UDCA) as treatment of TPN-associated CLD. METHODS: Seven children (4 boys and 3 girls) undergoing long-term TPN because of intractable diarrhea syndrome developed cholestasis and were treated with UDCA. Treatment efficacy was evaluated by monitoring clinical and biochemical markers of CLD, including gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), conjugated bilirubin, and alanine aminotransferase (ALT). RESULTS: In all children, UDCA was associated with the disappearance of signs of CLD and with normalization of biochemical markers of cholestasis within 4-8 weeks. A rebound increase of GGT, ALP, and ALT serum levels was observed in 3 children in whom UDCA was temporarily discontinued while they were still undergoing TPN. However, after reinstitution of UDCA, markers of cholestasis normalized in all cases. UDCA was withdrawn on reinstitution of full oral feeding; there was no relapse of cholestasis. Six children fully recovered. One child died because of the lack of vascular access. CONCLUSIONS: UDCA appears to be an effective treatment for TPN-related cholestasis in children.     

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.     

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.     

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.     

Essential fatty acid deficiency and home total parenteral nutrition patients

The requirements for essential fatty acids in patients on home parenteral nutrition are not well described. We therefore studied the needs of 12 patients receiving parenteral nutrition for at least 4 mo (range: 4 mo-17.3 yr; mean 7.0 +/- 5.2 yr). Prior to the study, each patient had been receiving intravenous lipids either weekly or biweekly and had a triene to tetraene ratio (TTR) on plasma phospholipids performed at least annually. A TTR > or = 0.2 was considered diagnostic for essential fatty acid deficiency (EFAD). The purpose of this study was to determine the required intravenous lipid supplementation in patients on home total parenteral nutrition (HTPN). Patients with an initial TTR of < 0.2 had their intravenous lipid stopped and changes in their serum phospholipid fatty acids were followed every 3-4 wk. Nine of 12 patients had TTRs > 0.2 at some point in the study. Phase I consisted of patients who at initiation of the study had normal TTRs and were taken off lipid supplementation until their TTR became abnormal. Phases II, III, IV, and V consisted of lipid delivered in total nutrient admixtures in biweekly doses of 0.6, 1.2, 1.8, and 2.4 g of fat/kg bodyweight, respectively. Eight patients normalized their TTRs on the biweekly lipid regimens; one patient expired before his ratio normalized; and three patients could not be made deficient in essential fatty acids after 26 or more wk of fat-free parenteral nutrition. Most patients required 1.2 to 2.4 g of lipid/kg bodyweight/biweekly to correct serologic EFAD. The clinical background, as well as the length of small bowel remaining, did not seem to identify those patients who required lipid supplementation nor the final dose of lipid needed to normalize their TTRs.     

Studies on the regulation of food intake using rat total parenteral nutrition as a model

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.     

Preservation of intestine protein by peptide YY during total parenteral nutrition

Maintaining rats on TPN for 7 days was associated with a 50% reduction in gut mass and protein content. Co-infusing PYY with total parenteral nutrition (TPN) resulted in significant savings in jejunal wet mass and elevated protein content of jejunum, ileum and colon as compared with rats maintained on TPN alone. No significant effects of PYY on plasma amino acid profile were noted. Although minor alterations in mucosal polyamines were observed in rats maintained on TPN, co-infusion of PYY had no significant effect on gut polyamine concentrations. These results suggest that PYY has trophic effects upon the gut during otherwise catabolic conditions. Therefore, co-infusion of PYY with TPN may suggest methods whereby loss of intestinal mucosa and atrophy-associated complications of TPN may be modulated.     

Septic complications of total parenteral nutrition. A five year experience

Elevated levels of serum albumin have been noted in patients on chronic methadone maintenance and in heroin addicts. This observation was investigated in rabbits maintained on daily methadone 4 mg per kg of body weight after a period of 3 months on increasing dosage to assure drug tolerance. Albumin distribution and metabolism were measured with tested lots of 125I rabbit albumin. Studies were made before and again after the attainment of the methadone maintenance state. Albumin distribution was altered markedly with a shift of intravascular albumin to extravascular sites. Associated with this change, the serum albumin level rose by an average of 0.5 g per 100 ml. Albumin degradation increased by 32% from 248 to 327 mg per kg per day. The total exchangeable albumin pool increased 35%, or 3.6 g. Since the exchangeable albumin pool increased in the face of an increment in albumin degradation, albumin synthesis must have increased even further to account for this change. Although the specific factors responsible for these alterations in albumin metabolism and distribution are not known at present, to date, this hyperalbuminemic hypercatabolic state is not produceable in any other clinical or experimental situation.     

Mortality and incidence of cancer among sewage workers: a retrospective cohort study

To study the incidence of and mortality from cancer among sewage workers a retrospective analysis was performed on a cohort of 656 men employed for at least one year at any one of 17 Swedish sewage plants during the years 1965-86. Assessment of exposure was done by classification of work tasks. Lower than expected total mortality (standardised mortality ratio (SMR) = 0.75, 95% confidence interval (95% CI) 0.58-0.97) and cardiovascular mortality (SMR = 0.61, 95% CI 0.39-0.91) was found. This was interpreted as a result of the healthy worker effect. For all cancers combined the mortality (SMR = 1.08, 95% CI 0.68-1.67) and morbidity (SMR = 1.02, 95% CI 0.72-1.38) were comparable with those of the general population. There were increased incidences for brain tumours (SMR = 2.19, 95% CI 0.45-6.39), gastric cancers (SMR = 2.73, 95% CI, 1.00-5.94), and renal cancers (SMR = 1.68, 95% CI = 0.35-4.90). For lung cancer the risk was reduced (SMR = 0.70, 95% CI 0.15-2.05). Allowance for a latency period of 10 years from the start of exposure did not change the pattern. Logistic modelling was used to search for exposure-response relations. In a logistic model with the confounder age forced in, renal cancer had a significant positive relation with a weighted sum of employment times, where the weights describe the classification of exposure. No exposure-response relations were found for brain tumors or gastric cancers. The increased risks are based on small numbers of cases. A future follow up will add more conclusive power to the study. Specific exposures need to be identified to allow for a better dose-response analysis.