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.

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.

Recent advances: parenteral nutrition support.

Even though there is an abundance of research related to the clinical and physiologic effects of parenteral nutrition and specific nutritional substrates, few new products have been released for clinical use. This review illustrates some of the directions being taken in the future development of parenteral nutrition products and some new perspectives related to the current effects (or lack of effects) of TPN. When considering the individual effects of specific nutrient substrates (arginine, glutamine, LCTs, MCTs, SCFAs) as reviewed here, it becomes apparent that the infusion of parenteral nutrition has the potential to produce a variety of metabolic responses that could be both beneficial and harmful. These effects depend on the type and quantity of substance infused as well as the disease and clinical condition of the patient. This also is true for those substances (GH, IGF-1) being evaluated to direct the effects of TPN infusions in a manner that improves protein accretion and supports the immunologic response of the body. At best, these investigations are producing a great amount of new and more specific information about the metabolic response to illness and the effects of TPN and individual substrate on that response.

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.

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.

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.

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.

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.

Oral anticoagulation in patients with short-bowel syndrome.

A 55-year-old woman was transferred to our institution from another hospital. The history of her present illness began 17 days earlier with a right-sided cerebral vascular accident (CVA). Three days later she had a superior mesenteric artery (SMA) embolus with infarcted bowel. Her small bowel was resected leaving about 20-25 centimeters of small bowel. A cardiac echo on hospital day 6 documented the presence of a left ventricular embolus, which was considered to be the cause of her CVA and SMA embolus. The cardiologists recommended lifelong anticoagulation, preferably with warfarin when technically feasible. After one month of warfarin therapy, with doses as high as 25 mg/d, the patient's prothrombin times (PTs) were not changed from baseline; however, this was probably due to concomitant therapy with vitamin K. Heparin was incorporated into her total parenteral nutrition (TPN) in preparation for her discharge. Because the TPN was cycled, she required subcutaneous heparin twice daily while off TPN. This patient's clinical course while she was maintained on heparin therapy was complicated by bleeding episodes and extensive thigh and abdominal hematomas, which led to erratic heparin absorption and widely fluctuating partial thromboplastin times. Ten months after the initiation of anticoagulation the patient was again tried on an oral warfarin regimen. She was successfully titrated to achieve the desired PT ratio. This case led to a review of the literature of patients with short-bowel syndrome requiring anticoagulation.

Concurrent quality assurance for a nutrition-support service.

A pharmacy-based quality assurance program for a nutrition support service (NSS) is described. The NSS, located in a university teaching hospital, is consulted to provide nutritional therapies, primarily total parenteral nutrition (TPN). A planning group from the NSS developed a quality assurance program to monitor specific activities of the service. Four categories of indicators were selected: discretionary, including the indication for TPN and length of TPN therapy; complications, including metabolic, septic, and mechanical; nutritional outcomes, such as nitrogen balance determinations and visceral protein status; and miscellaneous, such as frequency of missing nutrition-related laboratory data. The planning group developed a TPN monitoring checklist that defined the absolute ranges acceptable for each monitored laboratory test, and standards for each indicator were developed. The program was designed to allow daily evaluation, provide weekly reviews, and generate monthly reports on quality assurance issues. The TPN monitoring checklist was incorporated into the daily monitoring form. Data were compiled from 248 patients over a six-month period beginning on January 1, 1988. Noncompliance with standards was rare for discretionary indicators. A majority of indicators of metabolic complications were in compliance with the standards, as were all indicators of septic complications. Both indicators of nutritional outcome were above the standard, except nitrogen balance during months 4 and 5. The TPN wastage rate was noncompliant with standards during four of the six months. Missing TPN laboratory data (n = 94) in January prompted identification of individual laboratories on the TPN order form. If the mean percentage compliance during this six-month period was higher than the initial standard, then the standard was upgraded.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Management of glucose abnormalities in patients receiving total parenteral nutrition.

A patient who developed extreme fluctuations in serum glucose concentrations while receiving total parenteral nutrition (TPN) is described, and etiologies of hyperglycemia and hypoglycemia, as well as a rational approach to preventing and managing these disorders in patients receiving TPN, are presented. A 40-year-old white man with a 29-year history of insulin-dependent diabetes mellitus was hospitalized after he had an episode of rejection related to a cadaveric kidney transplant. During the hospitalization, his right leg was amputated because of cellulitis, and he developed septicemia with respiratory failure. A renal biopsy revealed cytomegalovirus inclusion disease, the kidney was removed, and intermittent hemodialysis was begun. Control of the patient's serum glucose concentration included four routes of insulin administration: a continuous titratable insulin infusion, subcutaneous sliding-scale insulin, insulin incorporated into the TPN solution, and intravenous bolus insulin. Further, glucose management was being coordinated by three teams: intensive care, nutrition support, and the renal service, with physicians from each service prescribing insulin therapy. The patient also received prednisone daily. The sporadic approach to this patient's glucose control, complicated by the extensive disease profile of the patient, resulted in precipitous fluctuations in his serum glucose concentrations. Patients receiving parenteral nutrition are subject to widely varying serum glucose concentrations related not only to the nutrition support provided but also to various underlying metabolic and physiologic complications commonly present. Common etiologies of, and ways to prevent and manage, hypoglycemia and hyperglycemia are reviewed. Clinicians should be aware of the risk of hyperglycemia and hypoglycemia in patients receiving TPN and monitor patients appropriately for alterations in glucose homeostasis.

Postgraduate academic desires: senior doctor of pharmacy students.

Senior Doctor of Pharmacy (Pharm.D.) students were surveyed by questionnaire to glean information about academic training, and residency, fellowship, or practice positions sought after graduation. There were 227 (27 percent of total surveys) responses. Of those responding, 71 percent were Bachelor of Science graduates, 29 percent were Pharm.D. primary degree students, and 18 percent completed a residency either before or during Pharm.D. training. Fifty percent had an average of three years of clinical services work experience prior to their Pharm.D. education. There was strong interest in postgraduate education by respondents: 41 percent for residencies and 26 percent for fellowships. Of resident candidates, 18 percent and 49 percent, respectively, considered research essential and important to the program. Areas of greatest interest in residencies were general medicine, infectious disease, and pharmacokinetics. Important to the selection of a fellowship was the research proposal and concurrent clinical practice. Pharm.D. students are interested in postgraduate training as residents (60 percent), fellows (38 percent), or both (2 percent). Desired activities are research and clinical practice independent of residency or fellowship interest.

Pharmacists' opinions about and compliance with recommendations for intravenous admixture practices.

Hospital pharmacy departments nationwide were surveyed to determine compliance with and opinions on the importance of recommended practices for preparation of i.v. admixtures. Questionnaires that included 84 recommendations by the National Coordinating Committee on Large-Volume Parenterals, the American Society of Hospital Pharmacists, and the Joint Commission on Accreditation of Hospitals were mailed to 625 randomly selected acute-care hospitals. Questions covered the compounding area and recommended equipment; selection, education, and training of personnel; compounding procedures; quality assurance; labeling and record keeping; and reference materials and professional services. The response rate was 43% (198 usable replies). Responses indicated that 42 (50%) of the recommended practices were followed in fewer than 75% of the hospitals, 25 (30%) in fewer than 50% of the hospitals, and 17 (20%) in fewer than 25% of the hospitals. Twenty of the recommendations were considered marginal in importance. Adherence to published guidelines for i.v. admixture services varies among hospitals in the United States; compilation of a single set of guidelines should be considered.

A key to the literature of total parenteral nutrition: update 1987.

This comprehensive bibliography is intended to enhance the education of the practitioner, student, and academician in the area of parenteral nutrition. This bibliography is not all-inclusive but serves as an update from the original published in 1983. Of particular note in this work is the addition of topics that reflect a growing interest in medical specialties with regard to patient nutritional status and support.

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.

Hyperosmolar, hyperglycemic, nonketotic coma in a patient receiving home total parenteral nutrient therapy.

A patient who developed hyperosmolar, hyperglycemic, nonketotic coma (HHNC) while receiving home total parenteral nutrient (TPN) therapy is described, and the etiology, clinical features, and treatment of HHNC are reviewed. A 51-year-old black man diagnosed as having Dukes' stage D signet-cell carcinoma of the rectum was discharged on home TPN therapy after a prolonged hospital course and the persistence of a gastrointestinal fistula. Seventeen days after discharge, the patient developed polyuria, became febrile, and lost mental acuity. Upon hospitalization, the patient's physical condition and laboratory values were consistent with the diagnosis of HHNC. The patient was treated with intravenous fluids and small quantities of insulin. The patient's home records indicated that he had lost large volumes of fluid through his fistula, resulting in a net negative fluid balance. The patient's records also indicated that he had had mild glycosuria with a normal urine output at home. This normal urine output despite a body-fluid deficit could be explained by osmotic diuresis related to either glucose or urea. Hypotonic fluid loss resulting from fistula output and osmotic diuresis may have led to this patient's hypertonic state and critical illness. The patient died on hospital day 11 as a result of widely disseminated cancer. HHNC arises most often as a complication of non-insulin-dependent diabetes. It is also a major complication resulting from hypertonicity related to glucose intolerance or other conditions that can occur in patients receiving TPN therapy. The underlying cause of the hyperosmolar state appears to be dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)