Effect of nutritional status on organic anion clearance by the swine liver.

Hepatic dysfunction follows a wide range of insults. Impaired excretion of organic dyes such as bilirubin often occurs before other obvious clinical defects in metabolic processes. Indocyanine green (ICG) is excreted through pathways similar to those of bilirubin. To determine the effectiveness of ICG as a marker of hepatic dysfunction related to clinical malnutrition, pigs received 5 mg/kg ICG with simultaneous sampling from the hepatic vein, pulmonary artery, and aorta over 3 hours. Group I remained well nourished, group II was fasted to a weight loss equal to 20% of initial body weight, and group III was fasted to a 20% weight loss and then refed until the animals regained their initial weight. Both systemic and intrinsic hepatic clearance were depressed significantly with fasting but returned above baseline after refeeding. No significant difference appeared between systemic and intrinsic hepatic clearance. Extraction ratios were low in all groups. In outbred swine, ICG clearance reflects the function of hepatic organic anion excretion in vivo, and venous sampling reflects intrinsic hepatic clearance. The impairment of the carrier-mediated transport system is reversible with refeeding.

Parenteral nutrition: short term effects on hepatic clearance of sodium taurocholate and indocyanine green.

Total parenteral nutrition (TPN) is thought to induce cholestasis. However, serum hepatic enzyme abnormalities were found in 70 percent of patients before TPN was started. Rate constants (alpha, beta, K(E] and total clearance (CIT) of sodium taurocholate (STC) and indocyanine green (ICG) were studied in 20 carefully selected patients not on TPN and who had no hepatic or renal disease. Clearance measurements were made prior to initiation and 7 days into dextrose-based TPN. Four modes of TPN administration were used; low calorie (35 cal/kg) versus high calorie (50 cal/kg), with or without protection of TPN solutions from ultraviolet light. Protein doses for all groups were isonitrogenous. TPN was uninterrupted and no patient had surgery, other major procedures, or food by mouth. While serum gamma-glutamyl transpeptidase (GGT) increased, no STC or ICG clearance parameter (total or subgroup) changed in response to TPN. These data do not support the hypothesis that TPN directly causes cholestasis, but suggest that cholestasis caused by concurrent liver disease may appear aggravated by TPN.

Home parenteral nutrition programs.

The technique of home parenteral nutrition (HPN) is becoming a more widely used method to treat patients who cannot eat for prolonged periods; to date, more than 500 patients have been trained nationwide. Training has been limited for the most part to larger centers which have more experience in providing this complex patient education. As this technique becomes more widely accepted, however, other less experienced health care professionals will be called upon to develop HPN training programs. For this reason, it is important to simplify these training programs, with initial attention directed toward the procedures used to prepare the total parenteral nutrition solution. The chance of potential errors can be reduced by using amino acid solutions with electrolytes included in the formulation. When possible, complexity can be reduced by administering vitamins and extra electrolytes orally. The teaching program can be simplified by developing or using existing training manuals, which standardize procedures so that consistent methods are taught and performed. The manual can serve as a reference for patient and teacher alike. Distribution of supplies can be simplified by employing commercially available shipment programs; but, while these are very convenient for the patient and pharmacy, the costs of such programs could be a limitation. Finally, the extensive work required to arrange reimbursement for services and supplies also can be simplified. Often a social worker can facilitate this process because of experience and training in dealing with payment problems. In addition, training fees should be negotiated with third party payors early in the development of HPN programs. By simplifying these basic elements in an HPN, the task of training patients is less imposing and can be made more widely available to those who need this treatment modality.

Hemoglobin A1C in home parenteral nutrition.

Hemoglobin A1C or glycosylated hemoglobin has been described as being effective in monitoring long-term glucose control in diabetics. The usefulness of HbA1C in reflecting glucose homeostasis during chronic hypertonic dextrose infusions in 6 patients receiving cyclic home TPN was studied at monthly intervals. Grouped data for the 34 values representing study periods of 5 to 10 months averaged 7.5 +/- 0.2% (Mean +/- SEM) indicating that HbA1C levels were not elevated above normal (4-8%) in these patients while receiving a dextrose based diet. Final values of HbA1C (7.3 +/- 0.4%, mean +/- SEM) although lower than early values (8.7 +/- 0.6%, mean +/- SEM) were not significantly different (p greater than 0.05, Student's paired t-test). The change in HbA1C that occurred in these patients probably reflects the response to an altered glucose load infused by the patient. HbA1C is a convenient and apparently accurate method of evaluating chronic glucose tolerance in patients receiving home TPN and may be used as an alternate method for monitoring glucose tolerance on an outpatient basis.

Albumin in TPN solutions: potential savings from a prospective review.

As a result of the common usage of albumin in total parenteral nutrition (TPN) solutions at The Ohio State University Hospitals, a review of the use of this product was performed. Albumin therapy in 18 patients was evaluated using prospective criteria. Therapy was considered appropriate if the serum albumin level was less than or equal to 3.0 g%. Using these criteria, 12 of 18 patients (67%) received albumin in the TPN solution. Of these 12 patients, 7 received albumin unnecessarily. During the 3-week review, a total of 168 vials of 50 ml, 25% albumin (2100 g) were administered to patients with serum albumin concentrations greater than 3.0/100 ml at a cost of $6,014. Over a year, this could mean over $100,00 in costs which could be eliminated. Criteria for use of albumin in malnourished patients receiving TPN are not well established. This study demonstrated that developing simple criteria for the prospective review of albumin in TPN solutions and using them to monitor albumin therapy closely, can result in very significant cost savings to patients receiving TPN.

Parenteral nutrition for marrow transplant recipients: evaluation of an increased nitrogen dose.

The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients.

Heparin does not reduce catheter sepsis during total parenteral nutrition.

Although it is recognized that the addition of heparin to total parenteral nutrition solutions reduces subclavian vein thrombosis from percutaneous polyethylene catheters, it does not affect the low thrombosis rate associated with polyurethane catheters. It has been suggested that heparin also reduces catheter sepsis during total parenteral nutrition. We reviewed the sepsis rate in 86 patients randomized to receive iv nutrition with or without heparin through polyethylene, polyvinyl, and polyurethane catheters. Blood was drawn from febrile patients for culture; if positive, catheters were removed and the tips cultured. Catheters were considered infected if blood and catheter tips were positive, or if fever disappeared within 48 hr after catheter removal, even if cultures were negative. Catheter sepsis occurred in two patients in both groups. It appears that heparin does not reduce sepsis from percutaneous subclavian vein catheters. Although its use may be indicated to reduce thrombosis associated with polyethylene catheters, there is no indication for its use to reduce sepsis with either type of catheter.

Compatibility of medications with 3-in-1 parenteral nutrition admixtures.

BACKGROUND: The absence of drug compatibility information with 3-in-1 parenteral nutrition admixtures has been problematic. The purpose of this project was to evaluate the physical compatibility of 106 selected drugs during simulated Y-site injection into nine different 3-in-1 parenteral nutrition admixture formulations. METHODS: Four-milliliter samples of each of the representative 3-in-1 parenteral nutrition admixture formulations were combined in a 1:1 ratio with 4-mL samples of each of 106 drugs, including supportive care drugs, anti-infectives, and antineoplastic drugs. Six replicate samples of each combination were prepared. Two samples were evaluated initially after mixing, two more after 1 hour, and the last two after 4 hours at 23 degrees C. At each test interval, the samples were subjected to centrifugation, causing the fat to rise to the top. The top fat layer and most of the aqueous phase were removed, and the remaining liquid was diluted with about 7 mL of particle-free, high-performance liquid chromatography-grade water to facilitate observation of any particulates that might have formed. Visual examinations were performed in normal diffuse fluorescent laboratory light and under high-intensity, monodirectional light. RESULTS: Most of the drugs tested were physically compatible with the 3-in-1 parenteral nutrition admixtures for 4 hours at 23 degrees C. However, 23 drugs exhibited various incompatibilities with one or more of the parenteral nutrition admixtures. Six drugs resulted in the formation of precipitate with some or all of the admixtures. Seventeen drugs caused disruption of the emulsion, usually with oiling out. CONCLUSIONS: Most of the test drugs were physically compatible with the nine representative 3-in-1 parenteral nutrition admixtures. However, the 23 drugs that resulted in incompatibilities should not be administered simultaneously with the incompatible parenteral nutrition admixtures via a Y injection site.

Evaluation of nitrogen utilization in patients receiving total parenteral nutrition.

This two phase study evaluates nitrogen utilization by the body as a function of fixed caloric intake but different nitrogen loads. Nitrogen use by the body was estimated from measures of nitrogen balance, net protein utilization, and urea accumulation rate. Phase 1 of this study included 411 measurements of nitrogen use in 120 patients assigned, according to clinical condition, to receive one of the four following therapies: dextrose (D) 25%, amino acids (CAA) 4.25% (Group 1); D 35%, CAA 4.25% (Group 2); D 25%, CAA 21.3% (Group 3); or D 35%, CAA 21.3% (Group 4). Forty patients in Phase 2 were assigned in a randomized, prospective, double blind manner, to receive one of the following regimens; D 35%, CAA 2.75% (Group 5); D 25%, CAA 2.75% (Group 6); D 35%, CAA 4.25% (Group 7); or D 25%, CAA 4.25% (Group 8). In Phase 1, positive nitrogen balance was achieved with the exception of Group 3 where neither the estimated caloric nor nitrogen needs of the patients were met. It appeared that protein utilization was maximal in patients receiving the therapy of highest calorie:nitrogen ratio (Group 4). Phase 2 patients achieved positive nitrogen balance to the same extent (p greater than 0.05) and although net protein utilization improved from 53 to 71%/d as the calorie:nitrogen ratio was increased, the differences were not significant (p greater than 0.05). There was a significant improvement in total iron binding capacity in Phase 2 patients (p less than 0.01) that was most prominent at the lower concentrations of amino acids (high cal:n ratio) (Groups 5 and 6). Smaller amounts of nitrogen appear adequate in producing a positive nitrogen balance and may be better utilized in hospitalized patients if the patients' caloric requirements are achieved.

Clinical effect of nonthrombotic total parenteral nutrition catheters.

Radiographic evidence of subclavian vein thrombosis has been shown to occur in 33% of total parenteral nutrition patients. This incidence can be significantly reduced to 8% when heparin is administered concomitantly in total parenteral nutrition solutions. To evaluate the thrombotic risk of a newly developed polyurethane catheter, 20 concurrent patient pairs were prospectively cannulated with either a standard polyethylene catheter plus heparin or a polyurethane catheter without heparin in a sequential statistical study. Radionuclide venograms (Tc99m) were performed within 72 hr of catheterization, at biweeky intervals, and at termination of total parenteral nutrition administration. No patient in either group developed clinical (pain, arm swelling, collateral veins) or venogram evidence of thrombosis after catheterization during an overall cannulation period of 820 days. Use of polyurethane catheters and elimination of heparin in total parenteral solutions may be particularly important since contraindications to heparin use are common. Additionally, heparin elimination can decrease admixture work and confusion (ie, subcutaneous heparin double dosing) without increasing the risk of subclavian vein thrombosis.

Compatibility of parenteral nutrient solutions with selected drugs during simulated Y-site administration.

The compatibility of 102 drugs with parenteral nutrient (PN) solutions during simulated Y-site administration was studied. Five milliliters of each of four representative PN solutions was combined in duplicate in a 1:1 ratio with 5-mL samples of solutions of 102 drugs in 5% dextrose injection or 0.9% sodium chloride injection. Visual examinations were performed in fluorescent laboratory light and under high-intensity monodirectional light, and turbidity was measured. Particle sizing and counting were performed for selected solutions. All evaluations were performed at intervals up to four hours; storage was at 23 degrees C. Most of the drugs tested were compatible with the PN solutions. However, 20 drugs exhibited various incompatibilities with one or more of the PN solutions. During simulated Y-site administration, four PN solutions were compatible with 82 of 102 drugs for four hours at 23 degrees C. Twenty drugs were incompatible with one or more of the PN solutions.

Quality assurance for a nutritional support service.

Quality assurance programs may significantly influence patient care by providing a systematic mechanism of self-assessment. An effective program should improve the level of care and have a positive effect on the fiscal base of a health care institution. The design of a useful quality assurance program is not a trivial matter. This report describes the details of a functioning quality assurance program developed for a multidisciplinary nutrition support service. The effect that such a program may have on patient care is also illustrated.

Considerations in establishing fees for home-care pharmaceutical services.

The activities of home-care pharmacists are highlighted, and factors that should be considered in establishing a reimbursement schedule are described. Pharmacists are important members of the home health-care team. Responsibilities of the pharmacist include assisting in the development of a therapeutic plan, reviewing and monitoring drug therapy, and ensuring that appropriate and correctly prepared medications are available to the patient. The degree of pharmaceutical service depends on the therapy prescribed. The traditional type of third-party reimbursement--cost of drug plus dispensing fee--is often inadequate and can discourage pharmacists from becoming involved in home health care or from providing services of optimal quality. An appropriate reimbursement schedule should take into account the variety of pharmaceutical services provided to home-care patients and should give special consideration to activities, such as discontinuation of unneeded drug therapy, that lower medical costs. Whether pharmacists are able to provide high-quality home health-care services may depend on how adequately they are reimbursed.

Assessing the nutritional needs of the critically ill patient.

Because critical illness often creates a vigorous metabolic response to permit the repair of injured tissues, nutritional considerations are essential in the medical management of the critically ill patient. Individuals with seemingly adequate endogenous nutritional reserves may rapidly develop complications of starvation. Nutritional supplementation is essential; however, critically ill patients may not readily tolerate nutritional support. Calories may need to be withheld until the patient is able to tolerate and utilize nutritional support. Once the decision to initiate nutritional support is made, nutritional status, level of stress, metabolic condition, and vital organ function influence the patient's nutritional requirements. An assessment of the patient's metabolic condition provides data useful in determining the need for supplemental electrolytes or macronutrients. These data also provide information regarding vital organ function, which is necessary for utilization of the fuel and substrate. Aggressive monitoring and judicious nutritional supplementation will afford the critically ill patient the best chance of recovery.

A key to the literature of total parenteral nutrition.

Parenteral nutrition is a relatively young science; texts dealing with the subject are few in number and become outdated shortly after publication. This comprehensive bibliography is intended to enhance the education of the practitioner and student in the area of parenteral nutrition and, as such, function as a key to the literature. Pertinent review articles may provide a mechanism for the practitioner to develop a baseline knowledge of nutritional support or specific patient problems.

Sodium imbalance in a patient receiving total parenteral nutrition.

A case of hyponatremia and then hypernatremia in a hospitalized patient receiving total parenteral nutrition (TPN) is described, and the etiologies, diagnoses, and treatments of hyponatremia and hypernatremia are reviewed. A 23-year-old man whose left leg had been amputated after a motorcycle accident required parenteral nutrition because of an ileus. After developing sepsis, he was given antimicrobials administered in standard dilutions of 5% dextrose injection, contributing 3 L of free water a day to his fluid intake. The patient subsequently became hyponatremic, and the sodium content of the TPN solution was increased to 140 meq/L. Multiple doses of furosemide and albumin were administered because of weight gain and edema of the lower extremity. After 14 days, all antimicrobial therapy was discontinued, and 2 days later the patient became hypernatremic. The sodium content of the TPN solution was decreased and then eliminated. Because of a 16-kg weight loss, diuretic therapy was stopped. This patient's hyponatremia was caused by administration of large amounts of sodium-free fluids (i.e., antimicrobials in 5% dextrose injection). The most appropriate management would have been to change the fluids in which the antimicrobials were diluted, with no change in the sodium content of the TPN solution. The patient's subsequent hypernatremia is best explained by a loss of free water. To manage this condition, it would have been appropriate to administer 5% dextrose injection to replace the free-water loss. Once the patient had reached baseline weight and therapy with the diuretic had been discontinued, maintenance therapy with 0.45% sodium chloride injection would have been beneficial. No change in the TPN sodium content should have been required. It is important to recognize all factors that predispose patients receiving TPN to hyponatremia and hypernatremia. Although the focus is often on the sodium content of the TPN solution, sodium and fluid can be administered by other means, including medication admixtures and maintenance intravenous fluids.

Nutritional support of the critically ill patient.

Injury or stress generates a vigorous metabolic response designed to establish the metabolic priorities required for the repair of injured tissues. In this condition, hormones commonly found to be elevated in the plasma include glucagon, catecholamines, glucocorticoids, growth hormone, aldosterone, and antidiuretic hormone. This hormonal profile results in rapid lysis of body protein, an increased rate of fat oxidation, and water and salt conservation. Rates of gluconeogenesis and ureagenesis are accelerated and may result in significant losses in lean body mass, a process that, if allowed to progress, will adversely affect patient survival. Exogenous nutrients provided to the critically ill patient may be poorly tolerated and may result in complications. Dextrose and intravenous fat emulsions provide the major sources of parenteral, nonprotein energy. These energy sources may not be metabolized efficiently in these patients, even though energy expenditure in this condition is increased significantly. Measurement of urinary nitrogen losses yields evidence useful in assessing the patient's degree of stress. In this manner, the patient's energy and protein requirements may be estimated. Formulations of amino acids, including the branched-chain amino acids, in higher concentrations have been reported to have anticatabolic effects and may improve the maintenance of lean body mass in stressed individuals. The stressed patient is prone to metabolic complications and, therefore, requires more careful monitoring of fluid, electrolyte, and acid-base balance, as well as renal, pulmonary, and liver function. Nutritional status is difficult to assess, since negative nitrogen balance may persist and the visceral proteins such as transferrin become altered in stress and, therefore, may not respond to nutritional intervention alone. The goal of nutritional therapy is the preservation of lean body mass by the safe and efficacious provision of metabolic substrate, thus improving patient survival.