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    Tpn guideline Tpn guideline Document Transcript

    • d. i te d. ib t e ro h no s p e i Parenteral is Assessment Tools and Guidelines: n Nutrition rw sio he is Therapy ot rm ss pe le ut un ho From the publisher of up wit Supported by ro G art ng n p hi i is r bl e o Pu ol h on w ah in cM n M tio c 09 du 2 0 ro © ep t R gh d. ri e py erv Co es r ts gh ri ll A
    • A ll ri gh Co ts py re ri gh se rv t © ed 20 .R 09 ep M Assessment Tools and Guidelines: ro cM on du Parenteral ah in ct i on w Pu ol Nutrition bl e o is h hi Therapy ng n p r G art i ro up wit un ho le ut Jay M. Mirtallo, MS, RPH, FASHP, BCNSP ss DISCLAIMER—This pocket guide is designed to be a summary of Specialty Practice Pharmacist ot rm information. Although it is detailed, it is not an exhaustive pharmaceutical Nutrition Support/Surgery he review; the entries in this publication present selected facts about each prod- Department of Pharmacy pe rw sio uct. McMahon Publishing and Hospira assume no liability for the use of this The Ohio State University Medical Center guide, and the accuracy of the information contained herein is not guaranteed. Columbus, Ohio is is e Readers are strongly urged to consult any relevant primary literature, the com- no s p plete prescribing information available in the package insert of each drug, and n t e ro h appropriate clinical protocols. Copyright © 2008, McMahon Publishing, i d. 545 West 45th Street, New York, NY 10036. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form. ib i te d.
    • Figures and Tables Table of Contents A Table 1. ll Evaluation of Body Weight . . . . . . . . . . . . . . . . . . .7 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6 ri gh Co Figure 1. Algorithm for the administration Nutrition Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11 ts py of nutrition support. . . . . . . . . . . . . . . . . . . . . . .8-9 Nutritional Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13 re ri Figure 2. Health care organization gh se nutrition consultation request form. . . . . . . . . . . .10 PN Formulation Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 rv t © ed Table 2. Pharmaceutical and Metabolic Medication Compatibility With PN . . . . . . . . . . . . . . . . . . . . . .24 20 .R Equations in PN Therapy . . . . . . . . . . . . . . . . . . . .12 09 Glucose Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33 Table 3. Metabolic Derangements in ep M ro Which PN Should Be Used With Caution . . . . . . . .14 Guideline for Special Diseases . . . . . . . . . . . . . . . . . . . . . . . . .33 cM on Table 4. Macronutrients: du Withholding and Withdrawing PN . . . . . . . . . . . . . . . . . . . . . .39 ah in ct PN Dosing Guidelines . . . . . . . . . . . . . . . . . . .16-17 i on w Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 Figure 3. Consequences of protein Pu ol calorie overfeeding. . . . . . . . . . . . . . . . . . . . . . . .18 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41-44 bl e o is h Table 5. Micronutrients: PN Dosing Other Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45 hi Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . .20-21 ng n p Table 6. FDA Requirements for Labeling r G art i ro Aluminum Content of PN Products . . . . . . . . . . . .22 up wit Table 7. ASPEN Safe Practice un ho Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . .26-29 le ut Figure 4. PN formulation standard ss order format—renal failure. . . . . . . . . . . . . . . . . .30 ot rm Figure 5. PN formulation standard he label format—renal failure. . . . . . . . . . . . . . . . . .31 pe rw sio is Table 8. ASPEN Recommendations on is e PN Standardization . . . . . . . . . . . . . . . . . . . . . . . .32 no s p Table 9. Y-Site Injection Compatibility n t e ro h i d. of I.V. Medications With PN . . . . . . . . . . . . . . .34-38 ib i te d.
    • Introduction Table 1. Evaluation of Body Weight A alnutrition is associated with more frequent treat- M ll ment complications and longer stays in the intensive ri % of Ideal Body Weight current weight gh Co care unit (ICU) and hospital, as well as increased costs of % of IBW = x 100 IBW ts py medical care. Patients at high risk for malnutrition should re ri be identified and evaluated for specialized nutrition sup- 80% to 90% = mild malnutrition gh se port (SNS).1 70% to 79% = moderate malnutrition rv t 0% to 69% = severe malnutrition © Determining the appropriate route of nutrition support ed 20 for patients at risk for malnutrition is an important consid- .R % of Usual Body Weight 09 eration when one is attempting to positively influence ep current weight M patient outcomes. In patients with a functioning gastroin- ro % of UBW = x 100 cM on usual weight du testinal (GI) tract, enteral nutrition (EN) can improve out- ah in ct comes.1 EN has been shown to improve nutritional status 85% to 95% = mild malnutrition i on w and reduce length of stay in the ICU and is associated with 75% to 84% = moderate malnutrition fewer infectious complications than parenteral nutrition Pu ol 0% to 74% = severe malnutrition (PN).2 The major limitation of EN is the need to gain enter- bl e o is h al (postpyloric) access so that the nutrient infusion is tol- IBW, ideal body weight; UBW, usual body weight hi erated and serious complications, such as aspiration Adapted from references 4 and 8. ng n p pneumonia,are avoided.1 Techniques are available to facil- r G art i ro itate access to the GI tract so that enteral tube feedings up wit may be administered safely. For patients who have a non- functioning GI tract, PN is the available method of nutri- un ho tional support.3 PN is essential for patients who are le ut ss severely malnourished and have GI tract problems that are ot rm not expected to resolve within 7 days.1,4 When PN is con- he sidered, it should be noted that this method is complex pe rw sio and has been associated with a unique set of complica- is tions, some of which can be serious or even life-threaten- is e no s p ing.3 In addition, few published reports can be found that n t e ro h demonstrate a consistently favorable effect of PN on i d. patient outcomes.4 This pocket guide discusses nutritional assessment,nutri- tional requirements, PN formulation design, medication ib i continued on page 11 te d. 6 7
    • Nutrition assessment A Decision to initiate SNS ll ri • Aggressive attempt to obtain gh Co enteral access ts py • Feedings may be more appropriate re ri gh distal to the pylorus for patients with se Functional GI tract? Yes EN rv t high gastric residuals, critical © ed illness, gastroparesis, or pancreatitis 20 .R 09 ep M ro Inconclusive cM on du ah in ct EN trial Yes EN tolerated? Yes Continue EN i on w Pu ol Aspiration, abdominal bl e o No No is distention, diarrhea, h hi Obstruction, peritonitis, high gastric residuals ng n p paralytic ileus, mesenteric ischemia, r PN only if EN G art short-bowel syndrome, PN i ro contraindicated enterocutaneous up wit fistula, malabsorption un ho le ut Status of Status of ss GI function GI function ot rm he Nonfunctional pe Functional rw sio is is e no s p Continue PN Transition to EN n t e ro h i d. Figure 1. Algorithm for the administration of nutrition support. ib EN, enteral nutrition; GI, gastrointestinal; PN, parenteral nutrition; i SNS, specialized nutrition support te d. 8 9
    • compatibility with PN, and guidelines for special diseases, A as well as an overview of evidence-based guidelines pub- ll lished by the American Society for Parenteral and Enteral ri gh Co Nutrition (ASPEN).1,3 Also included in the review is a dis- ts py cussion of FDA regulations concerning aluminum re ri contamination of PN,5 United States Pharmacopeia (USP) gh se standards for sterile compounding,6 and recommenda- rv t © tions on the use of insulin in PN.7 ed 20 .R Nutrition Assessment 09 ep M The purpose of nutrition assessment is to identify the ro cM on du degree to which the current or future nutritional status of ah in ct the patient will influence his or her outcome. The current i on w nutritional status of the patient is determined by several factors, including the patient’s weight and how it compares Pu ol bl e o with ideal and usual weights (Table 1,page 7); the duration is h of weight loss if it has occurred; visceral protein status; lab- hi oratory values indicative of fluid, electrolyte, and potential ng n p nutritional deficits; clinical condition; and whether the r G art i ro patient may be nourished by oral, enteral, or parenteral up wit means.1,4,8 During PN, both pharmaceutical and metabolic calculations are used in the assessment of nutrition sup- un ho port. Equations used to assess clinical, nutritional, and le ut ss metabolic status are provided in Table 2 (page 12).4,9-11 Figure 2. Health care organization ot rm nutrition consultation request form. Figure 1 (pages 8-9) is a useful algorithm for determining he the appropriate indications for PN. Clinicians should con- pe rw sio sider PN if a trial of enteral feedings has failed, if the enter- is al route is contraindicated, or if the GI tract has severely is e no s p diminished function because of underlying disease or n t e ro h treatment and GI function is not expected to return within i d. 7 days.1,4 Contraindications to PN include the following: a functional GI tract; an inability to achieve appropriate venous access; an unstable clinical condition; and terminal ib i continued on page 13 te d. 10 11
    • Table 2. Pharmaceutical and Metabolic Equations disease, critical illness, or metabolic derangement for In PN Therapy A which a favorable response to therapy is not feasible or the ll 1. Predicting Energy Needs risk of complications is too high.4 In these conditions, the ri gh Co Using Harris-Benedict Equationa: metabolic profile is such that exogenous nutrients are ts py For males: poorly used and frequently cause complications that re 66 + 13.75 (wt in kg) + 5 (ht in cm) – 6.8 (age in years) ri require prolonged mechanical ventilation, intensive care, gh se For females: or hospitalization.4 Table 3 (page 14) lists some metabolic rv t 655 + 9.6 (wt in kg) + 1.8 (ht in cm) – 4.7 (age in years) © derangements that necessitate cautious use of PN until the ed 2. Predicting the Degree of Metabolic Stress 20 patient’s condition improves.4 Catabolic index = .R 09 Applying the algorithm using the aforementioned con- ep 24-hour urine urea nitrogen [UUN] (g) – (0.5 dietary nitrogen intake + 3) M cepts in a nutrition consultation form (Figure 2,page 10) can ro Values 0-5 represent moderate stress and >5 represent severe stress. cM on du help improve appropriate use of PN in an institution. Such a 3. Predicting the Degree of Malnutrition ah in ct form also provides documentation for the need for SNS,and, i I. Creatinine height index = on w along with the nutrition assessment, includes a recommen- 24 hr actual creatinine excreted in urine (mg) x 100 dation for route and dose of nutrients to be provided. Pu ol 24 hr expected creatinine excreted in urine of bl e o normal adult of same height Nutritional Requirements is II. Body mass index (kg/m2) = weight (kg) / height (m2) h hi Over the past several years, there has been a continual ng n p 4. Measuring the Success of Nutrition Support refinement of PN, focusing on the delivery of the safest, r G art Nitrogen balance = (protein intake [g]/6.25) – (24-hour urine urea i ro nitrogen [g] + 3-5 g) most effective doses. Guidelines provide a framework for up wit a Stress factors should not be applied. nutrient doses in a variety of disease states.1,3 In general, PN, parenteral nutrition there has been a decline in recommended caloric doses, un ho Based on references 4 and 9-11. a liberalization of protein doses, especially for renal and le ut ss liver failure, and more specific recommendations for fat ot rm doses (Table 4,pages 16-17).1,3,4,12 Two specific purposes for he fat—nonprotein calories and prevention of essential fatty pe rw sio acid deficiency—are listed. Obesity is becoming more is prevalent and needs to be considered in dosing of PN.The is e no s p body mass index is used to classify patients with a value n t e ro h greater than 30 as obese and a value greater than 40 as i d. severely obese.1 Overfeeding of calories and protein can have serious con- sequences in patients receiving PN and has led to the ib i continued on page 15 te d. 12 13
    • Table 3. Metabolic Derangements in Which specific recommendations provided in Table 4.1,3,4,12 When A PN Should Be Used With Caution maximum doses of macronutrients are exceeded, the con- ll sequences outlined in Figure 3 (page 18) are frequently ri Metabolic Derangement Abnormality To Be Corrected gh Co reported.1,4,13,14 ts py Azotemia Blood urea nitrogen Micronutrients—electrolytes, trace elements, and vita- re ri >100 mg/dL mins—are essential to the incorporation of macro- gh Hyperchloremic se Serum Cl nutrients into the body cell mass. The content of rv t metabolic acidosis >115 mEq/L © micronutrients in the body tends to fluctuate on the basis ed 20 Hyperglycemia Serum glucose of cellular needs and deficits created by periods of low or .R >300 mg/dL 09 no intake or losses, and often occurs in patients with non- Hypernatremia ep Serum sodium M functional GI tracts. Daily monitoring of serum electrolytes ro >150 mEq/L cM on du and periodic (initial and every 2-3 weeks) assessment of Hyperosmolality Serum osmolality ah in ct >350 mOsm/kg vitamin and trace element status is essential for a patient i on w requiring PN. Bariatric (gastric bypass) surgery for morbid Hypochloremic Serum Cl obesity may result in protein calorie malnutrition as well Pu ol metabolic alkalosis <85 mEq/L bl e o Hypokalemia Serum potassium as deficiencies of thiamine, vitamin B12, folic acid, vitamin is h <3 mEq/L E, and calcium due to malabsorption and/or inadequate hi intake caused by complications of the surgery.15 In these ng n p Hypophosphatemia Serum phosphorus <2 mg/dL patients, assessment for vitamin deficiencies should be r G art i ro Based on reference 4. more frequent. Guidelines for dosing of micronutrients in up wit PN are outlined in Table 5 (pages 20-21).3,4,16,17 The presence of aluminum as a contaminant in PN has un ho caused complications in patients at risk.18 Patients at risk are le ut ss those who receive large loads of aluminum on a per-kilo- ot rm gram-of-body-weight basis and/or who have compromised he renal function.4 Aluminum toxicity has been observed in pe rw sio neonates receiving PN and adults with renal compromise is receiving PN for long periods (home PN therapy). Toxicity is e no s p primarily affects the bones and central nervous system n t e ro h (CNS).18 Aluminum interferes with bone formation and min- i d. eralization, causing bone fractures or symptoms of bone pain.19 CNS toxicity has also been observed.18 A dementia similar to the dialysis dementia observed in patients with ib i continued on page 19 te d. 14 15
    • Table 4. Macronutrients: PN Dosing Guidelines Normal Range Usual Doses Maximum Special Considerations A ll Calories 20-35 kcal/kg/d Obesity: Hypocaloric doses have been used. Measurement of energy ri expenditure is advised. gh Co Critically ill: 25-30 kcal/kg/d. ts py Glucose 70%-85% of 7 g/kg/d; Improved outcomes have been observed in critically ill patients when re ri nonprotein 4-5 mg/kg/min blood glucose has been maintained at <110 mg/dL. gh caloriesse rv t © Fat 15%-30% ed <30% of 2.5 g/kg/d Limited benefit to fat dose >30% nonprotein calories. 20 .R of nonprotein nonprotein When administered separately from PN, infusion should be completed 09 calories calories ep within 12 hours. M Protein 0.8-2 g/kg/d ro 1-1.5 g/kg/d 2 g/kg/d Provided as high biologic value (ie, content high in essential AAs). cM on du Dose should be modified in conditions of renal and hepatic disease to the ah in ct lowest dose needed to achieve positive nitrogen balance. i on w Renal failure Pu ol Chronic RF, no dialysis: 0.6-0.8 g/kg/day. bl e o Chronic RF, hemodialysis, or peritoneal dialysis: 1.2-1.3 g/kg/day. is h RF, continuous hemofiltration: 1 g/kg/day. hi Acute RF: Balanced mixture of essential/nonessential AAs. ng n p Acute RF with severe MN or hypercatabolic state: 1.5-1.8 r G art g/kg/day. i ro Liver failure up wit Protein restriction should be used for acute management of hepatic un ho encephalopathy but not for chronic use. Specialized AA formulations indicated only in chronic encephalopathy le ut ss unresponsive to pharmacotherapy. ot rm Fat (lipids) Prevention of 1%-2% of Contraindicated in patients with pancreatitis induced by hyperlipidemia. he pe essential fatty caloric dose as Withhold doses for triglyceride level >400 mg/dL. rw sio acid deficiency linoleic acid and is 0.5% of caloric is e dose as α- no s p linolenic acid. n t e ro h i d. AA, amino acid; MN, malnutrition; PN, parenteral nutrition; RF, renal failure Based on references 1, 3, 4, and 12. ib i te d. 16 17
    • Protein end-stage renal disease who received dialysate contami- A • ↑ renal solute load nated with aluminum has been reported.19 • azotemia ll Since aluminum is ubiquitous, it is very difficult, if not ri gh Co • impaired renal function impossible, to remove it from products used in the prepara- ts py • acidosis tion of PN.19 As a result, the FDA proposed a set of regula- re ri Total tions, which went into effect on July 26, 2004, requiring gh se calories manufacturers to label products used in the PN preparation rv t © Liver process with their aluminum content (Table 6, page 22).5,20 Fat ed 20 The purpose is to stimulate the manufacturers of PN prod- .R • fatty infiltration • ↑ serum triglycerides 09 • ↑ aspartate ucts to prepare products with lower aluminum content and • impaired pulmonary function ep aminotransferase M to inform clinicians of the aluminum content of PN prod- ro cM on • altered immunologic function • ↑ alanine du ucts.20 The FDA also sought to establish a maximum safe • hepatobiliary disease aminotransferase ah in ct limit of aluminum loads at 5 mcg/kg body weight per day.5 i • ↑ alkaline on w Although aluminum is present in products other than PN phosphatase (heparin, albumin), these products are not included in the Pu ol • hepatomegaly regulation.20 For PN, salts of calcium and phosphorus have bl e o • cholestasis is h the highest aluminum content.19 hi Dextrose Compared with adults, neonates/pediatric patients ng n p Hyperglycemia require higher doses, on a body weight basis, of calcium r G art i ro • serum glucose >200 mg/dL and phosphorus to ensure both growth and mainte- up wit • hyperinsulinemia nance.18 Neonates also have less ability to renally excrete • impaired phagocytosis and excess aluminum loads.19 ASPEN released a statement un ho neutrophil chemotaxis advising clinicians to identify patients at greatest risk of le ut ss Pulmonary Function developing aluminum toxicity and attempt to minimize • ↑ CO2 production and minute ot rm aluminum intake in these patients.18-20 ventilation he pe • respiratory failure in patients rw sio PN Formulation Design with limited reserve is Formulations of PN are extremely complex products is e • prolonged mechanical no s p ventilation intended for I.V. use. Careful consideration of nutrient dose n t e ro h and avoidance of unstable or incompatible ingredients are i Figure 3. Consequences d. necessary. Inconsistent compounding practices have led to of protein calorie overfeeding. serious harm in patients receiving PN.3 In an effort to provide CO2, carbon dioxide consistent, specific guidelines for PN, the National Advisory Based on references 1, 4, 13, and 14. ib i continued on page 23 te d. 18 19
    • Table 5. Micronutrients: PN Dosing Guidelines A Normal Daily Requirements Usual Daily Doses Na, K ll 1-2 mEq/kg Individualize, variable. ri gh Co Cl, acetate As needed for acid–base balance Equal amounts as sodium or potassium salt. ts py Electrolytes Phosphorus 20-40 mmol re ri gh Calcium se 10-15 mEq Gluconate salt preferred for PN. Stability limited by concentration rv t of calcium and phosphorus. © ed 20 Magnesium 8-20 mEq .R 09 ep M ro Thiamin (B1) 6 mg Provided by addition of multiple vitamin injection product. cM on du Riboflavin (B2) 3.6 mg FDA mandated reformulation of vitamin products to increase thiamine, folic acid, pyridoxine, and ascorbic acid. ah in Niacin (B3) 40 mg ct i Monitor warfarin carefully during transition to on w Folic acid 600 mcg products with vitamin K. Pu ol Pantothenic acid 15 mg bl e o Vitamins Pyridoxine (B6) 6 mg is h hi Cyanocobalamin (B12) 5 mcg ng n p Biotin 60 mcg r G art Ascorbic acid 200 mg i ro up wit Vitamin A 3,300 IU Vitamin D 200 IU un ho Vitamin E 10 IU le ut ss Vitamin K 150 mcg ot rm Chromium 10-15 mcg Use manganese with caution in patients with an obstructed he Trace Elements biliary tract. pe Copper 0.3-0.5 mg rw sio Accumulation may result in neurologic toxicity. is Manganese 60-100 mcg Zinc requirements increase with high GI output. is e Zinc 2.5-5.0 mg Selenium is indicated for long-term care and critically ill patients. no s p Patients on long-term PN are prone to iron deficiency. Iron status n t e ro h Selenium 20-60 mcg should be assessed initially and every 3 months in these patients. i d. Iron Not routinely added GI, gastrointestinal; PN, parenteral nutrition ib Based on references 3, 4, 16, and 17. i te d. 20 21
    • Table 6. FDA Requirements Group on Standards and Practice Guidelines for Parenteral For Labeling Aluminum Content A Nutrition published “Safe Practices for Parenteral Nutrition.” ll Of PN Products These guidelines provide recommendations for the PN label ri gh Co and order, as well as PN compounding, compatibility, stabili- Large-volume parenterals Must contain ≤ 25 mcg/L ts py • Concentrated dextrose, amino of aluminum. ty, and administration.3 They call for a standardized PN label re ri acids, parenteral lipids, sterile format to promote correct interpretation of PN contents gh se water for injection, saline, and across all health care environments; describe the pharma- rv t electrolyte solutions © cist’s duty to review the PN formula to ensure it is complete ed 20 and balanced, and will be stable and compatible upon .R 09 Small-volume parenterals and 1. Must be labeled with admixture; and include admixture processes and quality pharmacy bulk packages ep the maximum level of M control requirements that foster safe and accurate com- ro • Electrolyte salts of calcium, aluminum in the product cM on du phosphorus, potassium, at expiration. pounding of PN formulas (Table 7, pages 26-29).3,6 ah in ct magnesium, and sodium 2. If reconstituted, must be In addition, pharmacists should refer to the revised USP i labeled with the maximum on w • Multivitamins General Chapter <797> “Pharmaceutical Compounding— level of aluminum at expiration • Trace elements Sterile Preparations” (official as of June 1, 2008) for poli- Pu ol in the reconstituted form. bl e o 3. Maximum amount of cies and procedures on the handling of sterile is h aluminum may be preparations.6 USP chapter <797> provides mandates for hi determined by any of the compounding of sterile products at 5 levels of risk ng n p the following methods: based on the probability of exposing patients to microbial r • Highest level measured in G art i ro batches over the last 3 years. or physical contaminants, as well as specific requirements up wit • Highest level for the last for environmental quality and control and personnel 5 batches. cleansing and garbing. un ho • Maximum historical level. Using the “Safe Practices” format for a patient with renal le ut ss failure receiving hemodialysis,caloric doses do not need to ot rm Based on reference 5. be modified, but doses of protein, potassium, magnesium, he phosphorus, and acetate require adjustment (see Figure 4 pe rw sio for an example of a standard order form filled out for a is renal failure patient; see Figure 5 for an example of a stan- is e no s p dard PN label for renal failure dosing; pages 30-31). The n t e ro h label format allows for evaluation of nutrient dose based i d. on body weight and literature recommendations.4 Recent interest in standard PN formulations is the result of The Joint Commission National Patient Safety Goal 3b, ib i continued on page 24 te d. 22 23
    • which recommends standardizing and limiting the num- used solely for PN, but in patients with limited venous A ber of drug concentrations used by an organization.21 In access this is not always possible. Medication ad- ll its original Frequently Asked Questions (FAQ), The Joint ministration with PN may be unavoidable. In these situa- ri gh Co Commission suggested that this rule should apply to PN, tions, compatibility considerations are relevant. ts py which is included in its definition of medications The pharmacist’s objective is to ensure the safe, compat- re ri (drugs).22 In addition, it was noted that standardized PN ible,and efficacious provision of both pharmacologic ther- gh se solutions are available from manufacturers, and have apy and nutrition support. In reviewing a patient’s regimen rv t © been shown to be practical for most patients and to for compatibility,it is important to consider whether the PN ed 20 potentially improve outcomes.22 This interpretation of contains fat emulsion. Studies have shown differences in .R 09 Goal 3b has caused a great deal of concern and confu- compatibility based on the PN formulation used. Table 9 ep M sion among clinicians responsible for PN in their respec- (pages 34-38) was developed to provide consistent, reli- ro cM on du tive organizations. Subsequently, a revised Joint able, and up-to-date information on the compatibility of ah in ct Commission FAQ,updated in January 2007 in conjunction drugs administered via Y-site injection with PN.24-56 If no i on w with ASPEN, noted that Goal 3b may not apply to PN compatibility data exist, the medication should not be because of its multicomponent nature. The emphasis of administered with PN. Pu ol bl e o the revision was on a standardized approach to PN as rec- There is a distinction between Y-site administration and is h ommended by the ASPEN Safe Practice Guidelines.22 This direct admixture of the drug with PN.Adequate assessment hi prompted ASPEN to create a Statement on Parenteral of specific pharmacotherapeutic criteria16 for direct admix- ng n p Nutrition Standardization,23 which was approved by the ture of drugs (eg, ranitidine or famotidine) in PN is r G art i ro Board of Directors in June 2007.This evidence-based anal- required.56 These criteria may be summarized as follows: up wit ysis of the literature resulted in the recommendations pro- • Stability and compatibility of the drug with the specif- vided in Table 8 (page 32).This statement recommends a ic PN admixture over a 24-hour period must be deter- un ho standardized PN process, recognizes the need for clini- mined before the medication is added. le ut ss cians with PN expertise to be involved with the process, • The medication must have appropriate pharmacoki- ot rm and addresses the patient with complex needs in whom a netics and proven efficacy for continuous infusion. he customized PN formulation may be necessary.23 • The medication dose must have remained constant pe rw sio throughout the previous 24-hour period before admix- is Medication Compatibility With PN ture in PN. is e no s p Patients receiving PN usually need medications to be • There must be a stable PN infusion rate for at least n t e ro h administered intravenously. Multiple-lumen central venous 24 hours before the medication is added. i d. catheters have alleviated some problems associated with • PN must include appropriate labeling to avoid pharma- coadministration of medications with PN.3 It is recom- cotherapeutic problems associated with abrupt mended that the catheter or port for PN administration be discontinuation.57 ib i continued on page 33 te d. 24 25
    • Table 7. ASPEN Safe Practice Guidelines A Section Practice Guidelines Section Practice Guidelines ll ri Ordering PN 1. Standardized order forms should be used. Compound- Screening gh Co 2. PN formula is assessed to determine that the con- ing of PN 1. Review of PN contents is required to ensure that a ts py tents are appropriate for patient condition (adult or formulations balanced and complete formulation is provided. re ri pediatric), or if the patient's disease state warrants a 2. Each PN component is assessed for adequacy of gh se dose outside the standard range. dose and potential for a compatibility or stability rv t 3. Nutrients are indicated as total daily dose. problem. © ed 4. Percentage concentration should not be used on the 3. Any dose outside the accepted range and not 20 explained by a specific patient condition should .R order form. 09 5. Avoid potentially dangerous abbreviations. be clarified prior to compounding PN. ep PN compounding M 6. All components of the PN order are rewritten when ro 1. The additive sequence is optimized and validated cM on PN is reordered. du as a safe, efficacious method. ah in ct Labeling PN 1. Labels for PN admixtures should be standardized: 2. A review of the compounding method is recommend- i on w formulations • the amount per day is required; ed if PN is compounded manually or if there has been • quantity per liter may also be used; a change in commercial source of PN products. Pu ol • dosing weight is required on the label. 3. Manufacturers of automated methods of PN com- bl e o pounding should provide the additive sequence that 2. Auxiliary labels may be used, especially when orders is h ensures the safety of the compounding device based are written in a different format from the label. hi on the nutrient products used at the institution. ng n p 3. Patient transfer between health care environments 4. Each PN formulation compounded must be inspected such as hospital to home requires pharmacist-to- r for signs of particulate contamination and/or phase G art pharmacist communication of the PN prescription. i ro separation of TNA. 4. The PN label should be compared with the order, up wit Quality assurance and the beyond-use date should be checked before 1. Gravimetric analysis of PN formulations can be un ho administration. applied, focusing on the most dangerous additives tol- le ut erating the least margin of error (eg, potassium salts). ss Standard 1. The pharmacist should assess the PN contents to 2. Chemical analysis can be incorporated into the PN nutrient ensure that the dose of all nutrients is appropriate ot rm compounding operations of the pharmacy. requirements to the patient’s needs. he 3. Refractometric analysis is an alternative but is pe 2. IVFE should be provided to adult and pediatric limited to formulations that do not contain fat. rw sio patients to avoid essential fatty acid deficiency 4. Daily in-process or end-product testing of PN is when fat is not included in the base formula. formulations is recommended. is e 3. All PN patients should receive a parenteral vitamin 5. Compounding accuracy of PN prepared by automat- no s p preparation daily. ed compounding devices should be verified by n t e ro h 4. PN products should be chosen with the lowest end-product testing. i d. aluminum content when possible. 6. Aseptic extemporaneous preparation of PN formula- 5. Parenteral iron should not be used routinely in tions should adhere to the USP General Chapter PN therapy. <797> Pharmaceutical Compounding—Sterile Preparations.6 ib i te d. 26 27
    • Table 7. ASPEN Safe Practice Guidelines (continued) A Section Practice Guidelines Section Practice Guidelines ll ri PN admin- Venous catheters Stability and 1. All PN processes are confirmed to ensure that all gh Co istration 1. Central PN should be administered via CVC with compatibility components are stable and compatible. ts py distal tip in SVC adjacent to right atrium. of PN 2. The pharmacist ensures that the co-infusion of formulations re ri 2. Avoid use of femoral catheters for PN administration. medications with PN admixtures is safe, stable, gh se 3. Proper CVC placement should be confirmed prior to and compatible. rv t initiating PN and any time signs/symptoms of 3. If no information exists about a medication’s © malposition are present. ed compatibility with PN, it should be administered 20 4. Care for CVC according to published standards. separate from PN. Equipment .R 09 4. Compatibility information should be evaluated ep 1. A 0.2-micron filter should be used for 2-in-1 according to the concentration of medication and M ro formulations and a 1.2-micron filter for TNAs. whether the PN formulation is a 2-in-1 or TNA. cM on du 2. Alternatively, a 1.2-micron filter may be used for all 5. Insulin use in PN should be consistent throughout PN formulations to remove larger particles. The FDA ah in ct the health system. requires a 1.2-micron filter for TNA and a 0.2-micron i on w filter for 2-in-1 formulations. 6. Decisions are made based on the most recent evidence from the literature or direct from the manufacturer. Pu ol 3. A filter that clogs during administration may be replaced but never removed entirely. 7. Use of 2-in-1 formulas with separate administration bl e o 4. Use containers and sets free of DEHP if IVFE is used. of IVFE is recommended for neonatal/infant patients. is h hi 5. Change administration sets for IVFE given separately ng n p from PN after use, or at least every 24 hours if CVC, central venous catheter; DEHP, diethylhexyl phthalate; IVFE, intravenous fat administered as a continuous infusion. emulsion; PN, parenteral nutrition; SVC, superior vena cava; TNA, total nutrient admixture; r G art 6. Change TNA administration sets every 24 hours. USP, United States Pharmacopeia i ro Adapted from references 3 and 6. American Society for Parenteral and Enteral Nutrition 7. Change 2-in-1 administration sets every 72 hours. up wit (ASPEN) does not endorse this material in any form other than its entirety. 8. PN infusion pumps should have adequate “free flow” protection. un ho 9. Medical devices should be selected that protect the user le ut from needlesticks and exposure to blood-borne ss pathogens. ot rm Administration he 1. The label should be used to verify the patient’s identity pe rw sio prior to administration. 2. The PN should be inspected prior to setup and not used is if its integrity appears to be compromised is e (precipitate, color change, or cracked emulsion). no s p 3. The PN infusion should be completed within 24 hours of n t e ro h its initiation. i d. 4. The PN patient should be monitored for PN efficacy, complications, change in clinical condition, and to document clinical outcomes. ib 5. Policies and procedures should be in place to deal with i PN compounded by an outside facility. te d. 28 29
    • Ingredient Amount Amount per Day per Liter A ll Base Formula ri gh Co Dextrose (g) 302 210 ts py Amino acids (g) 72 50 re ri Fat emulsion (20%, g) 58 40 gh se Electrolytes rv t © ed Sodium acetate (mEq) 58 40 20 .R Potassium chloride (mEq) 14 10 09 ep Potassium phosphate 14 10 M ro (mmol of P) cM on du Calcium gluconate 10 5.6 ah in ct (mEq of Ca) i on w Magnesium sulfate 4 2.8 Pu ol (mEq of Mg) bl e o Vitamins, Trace Elements, and Medications is h hi Multiple vitamins 10 mL — ng n p Multiple trace elements 3 mL — r G art i ro Figure 5. PN formulation standard label up wit Figure 4. PN formulation standard order format—renal failure.a format—renal failure. un ho a This formula is infused at 60 mL/h and provides 1,886 calories or 30 kcal/kg le ut body weight (dosing weight of 63 kg), 72 g amino acids or 1.1 g/kg body ss weight, 0.9 mEq/kg of sodium, 0.5 mEq/kg of potassium, a 25% decrease in phosphorus dose, and a 50% decrease in magnesium dose. Further dosing ot rm modifications are necessary based on serum electrolytes and the effectiveness he of hemodialysis in removing protein and electrolytes and maintaining normal pe rw sio acid–base status. is is e no s p n t e ro h i d. ib i te d. 30 31
    • Table 8. ASPEN Recommendations on PN In general, only H2 antagonists and insulin have been A Standardization admixed in 3-in-1 admixtures. These drugs may also be ll admixed with 2-in-1 solutions. Other drugs that have been ri 1. A standardized process for PN management is advocated. This may gh Co include use of standardized PN formulations (including standard- shown to be stable and efficacious in 2-in-1 solutions are ts py ized commercial PN products) but also includes aspects of ordering, heparin,aminophylline,hydromorphone,hydrochloric acid re ri labeling, screening, and administration of PN. (maximum concentration, 100 mEq/L), and iron dextran gh se 2. The evidence on patient safety does not support the general use of (Table 9, pages 34-38).24-56 rv t standardized PN formulations across health care organizations. © ed 3. The evidence suggests advantages in efficiency, economy, and Glucose Control 20 .R clinical appropriateness with the use of standardized PN formula- 09 Serum glucose control at a value of less than 110 mg/dL ep tions compared to individualized PN formulations in select patient M populations. has been shown to improve clinical outcome (ie, shorter ro cM on du 4. When an organization implements standardized PN formulations ICU stay,less ventilator use,and lower mortality) in some sur- (including standardized commercial PN products), a mechanism ah in ct gical critically ill patients.12 This has led to a keen interest in should be established to provide, compound, or make available, i on w customized PN formulations for individuals who have complex tight glucose control during PN.7 A reasonable target level for blood glucose is between 100 and 150 mg/dL.3 Glucose Pu ol requirements secondary to disease or underlying illness, or when otherwise warranted by routine monitoring of electrolytes, organ bl e o should be monitored every 4 to 6 hours when insulin is function, growth, and development. is h added to PN. If the patient’s glucose level is above goal, sup- hi 5. A standardized process must include clinicians with expertise in the plemental insulin should be administered every 4 to 6 hours ng n p area of nutrition support. according to the previous day’s sliding scale insulin use.The r G art 6. PN compounding practices should adhere to recommendations pro- i ro mulgated by national professional organizations. frequency of glucose monitoring can only decrease once up wit glycemic control has been achieved. If glucose values con- PN, parenteral nutrition sistently exceed 150 mg/dL over a 24-hour period, regular un ho Based on reference 23. insulin should be increased by 0.05 units each day in the PN le ut ss formulation. It is recommended not to exceed approxi- ot rm mately 0.2 units of insulin per gram of dextrose.4 he pe rw sio Guidelines for Special Diseases is Some important concepts related to specific diseases is e no s p have been included in the recent guidelines published by n t e ro h ASPEN.1 Although there are several formulas for determin- i d. ing energy requirements measurement of energy expendi- ture is specifically recommended for patients with neurologic impairment and critical illness,and overfeeding ib i continued on page 39 te d. 32 33
    • Table 9. Y-Site Injection Compatibility Of I.V. Medications With PNa A Medication ll Admixture Type Medication Admixture Type ri gh 2-in-1 3-in-1 2-in-1 3-in-1 Co ts py Acetazolamide I — Clindamycin phosphate C C re ri Acyclovir I I Cyclophosphamide C C gh se Amikacin sulfate C C/I Cyclosporine C/I C/I rv t Aminophylline C/I C Cytarabine I C © Amphotericin B ed I I Dexamethasone sodium phosphate C C 20 Ampicillin sodium .R C/I C Digoxin C C 09 Ampicillin sodium-sulbactam sodium ep C C Diphenhydramine HCl C C M Atracurium besylate ro C — Dobutamine HCl C C cM on Aztreonam du C C Dopamine HCl C C/I ah in Bumetanide C ct C Doxorubicin HCl I I i on w Buprenorphine HCl C C Doxycycline hyclate C I Pu ol Butorphanol tartrate C C Droperidol C I bl e o Calcium gluconate C C Enalaprilat C C is Carboplatin C h C Epinephrine HCI C — hi ng n p Cefazolin sodium C/I C Epoetin alfa C — Cefepime C — Erythromycin lactobionate C C r G art i ro Cefoperazone sodium C C Famotidine C C up wit Cefotaxime sodium C C Fentanyl citrate C C Cefotetan disodium C C Fluconazole C C un ho Cefoxitin sodium C C 5-Fluorouracil C/I C/I le ut ss Ceftazidime sodium C C Foscarnet C — ot rm Ceftizoxime sodium C C Furosemide C/I C he Ceftriaxone sodium C C Gallium nitrate C C pe rw sio Cefuroxime sodium C C Ganciclovir sodium I/C I is Chloramphenicol sodium succinate C — Gentamicin sulfate C C is e Chlorpromazine HCl C C Granisetron HCl C C no s p Cimetidine C C Heparin sodium C I n t e ro h Ciprofloxacin lactate I C Hydrochloric acid Cb — i d. Cisplatin I C Hydrocortisone sodium phosphate C C C, compatibility has been demonstrated. When Y-site compatibility was not available, C/I, conflicting compatibility has been demonstrated and strength of evidence supports medications compatible in-solution for 24 hours were assumed to be Y-site compatible; ib compatibility; I/C, conflicting compatibility has been demonstrated and strength of evi- I, incompatibility has been demonstrated; —, compatibility data not available; dence supports incompatibility i te d. 34 35
    • Table 9. Y-Site Injection Compatibility Of I.V. Medications With PN (continued)a A Medication ll Admixture Type Medication Admixture Type ri gh 2-in-1 3-in-1 2-in-1 3-in-1 Co ts py Hydromorphone HCl C I/C Nafcillin sodium C C re ri Ifosfamide C C Nalbuphine HCl C I gh se Imipenem-cilastatin sodium C C Nitroglycerin C C rv t Immune globulin — — Norepinephrine bitartrate C C © Indomethacin sodium trihydrate ed I — Octreotide acetate C C 20 Insulin, regular .R C C Ondansetron HCl C I 09 Iron dextran ep C/I I/C Oxacillin sodium C C M Isoproterenol HCl ro C C Paclitaxel C C cM on Kanamycin sulfate du C C Penicillin G potassium C C ah in Leucovorin calcium C ct C Penicillin G sodium C — i on w Levorphanol tartrate C I Pentobarbital sodium C I Pu ol Lidocaine HCl C C Phenobarbital sodium C I bl e o Linezolid C — Phenytoin sodium I — is Lorazepam C h I Piperacillin sodium-tazobactam sodium C C hi ng n p Magnesium sulfate C C Potassium chloride C C Mannitol C C Potassium phosphate I I r G art i ro Meperidine HCl C C Prochlorperazine edisylate C C up wit Meropenem — C Promethazine HCl C/I C Mesna C C Propofol C — un ho Methotrexate I C Ranitidine HCl C C le ut ss Methyldopate HCl C C/I Sargramostim C — ot rm Methylprednisolone sodium succinate C C Sodium bicarbonate I/C C he Metoclopramide HCl I/C C Sodium nitroprusside C C pe rw sio Metronidazole C C Sodium phosphate I I is Miconazole C C Tacrolimus C C is e Midazolam HCl I/C I Ticarcillin disodium C C no s p Milrinone lactate C — Ticarcillin disodium–clavulanate potassium C C n t e ro h Mitoxantrone HCl I C Tobramycin sulfate C C i d. Morphine sulfate C C/Ic Trimethoprim-sulfamethoxazole C C C, compatibility has been demonstrated. When Y-site compatibility was not available, C/I, conflicting compatibility has been demonstrated and strength of evidence supports medications compatible in-solution for 24 hours were assumed to be Y-site compatible; ib compatibility; I/C, conflicting compatibility has been demonstrated and strength of evi- I, incompatibility has been demonstrated; —, compatibility data not available; dence supports incompatibility i te d. 36 37
    • Table 9. Y-Site Injection Compatibility is cautioned against in patients with pulmonary disease. Of I.V. Medications With PN (continued)a A The guidelines also address permissive underfeeding in ll Medication Admixture Type obesity cases and emphasize the use of EN in patients with ri 2-in-1 3-in-1 gh Co Vancomycin HCl C C pancreatitis and GI fistulas, conditions for which PN has ts py Vecuronium bromide C — been considered the therapy of choice.1 This summary is re ri not all-inclusive, but it highlights some concepts that have gh Vitamin K1 (phytonadione) C — se surfaced and may stimulate consideration of a change in rv t Zidovudine C C © practice. More specific information can be found in the ed 20 guideline document and its supporting literature. .R a During simulated studies of compatibility, a 1:1 volume ratio of drug mixture with 09 Recently, the benefit of PN in bone marrow transplant ep PN is used. For example, 1 mL of drug solution is combined with 1 mL of test PN admixture for a period consistent with that usually observed in practice during Y-site M recipients has come into question. Issues related to glu- ro administration of the drug with PN. cM on du b Hydrochloric acid: Not to exceed a concentration of 100 mEq/L. Maintain pH of final cose homeostasis, infection rates, and other complications ah in ct solution >3.0. have been raised.58 Particular attention should be paid to c i Morphine sulfate incompatible at concentration of 15 mg/mL, compatible at on w concentration of 1 mg/mL. the indication, nutrient dose, and system for managing the bone marrow recipient on PN. Pu ol —, compatibility data not available. C, compatibility has been demonstrated. When Y-site compatibility was not available, bl e o medications compatible in solution for 24 hours were assumed to be Y-site compati- Withholding and Withdrawing PN is h ble. hi C/I, conflicting compatibility has been demonstrated and strength of the evidence sup- The decision to use PN can be difficult when a patient is ng n p ports compatibility. unresponsive to therapy or in the terminal stages of disease. r I, Incompatibility has been demonstrated. G art i ro I/C, conflicting compatibility has been demonstrated and strength of evidence supports As a means of nourishment,PN is potentially life-sustaining, incompatibility. up wit HCI,hydrochloride and as a component of other therapies, it can improve or resolve the patient’s condition. The potential risks versus un ho PN, parenteral nutrition; all forms of I.V. nutrition, including 3-in-1 and 2-in-1 admixtures or I.V. fat emulsions. Also known as parenteral nutrient solution. benefits of PN should be considered. Also, it is often diffi- le ut Y-site injection, drug administration via piggyback, I.V. push, or other I.V. methods at ss the Y-site injection port or other access port (ie, stopcock) between the PN solution cult to determine whether the therapy will improve quality ot rm and the central venous catheter. of life or increase suffering. The decision to withhold or he 2-in-1, traditional parenteral nutrient admixtures containing dextrose and amino acids withdraw PN should be discussed with the medical staff pe and having a yellow appearance similar to that of I.V. solutions containing multi- rw sio vitamins. Also known as dextrose–amino acid solution. and the patient or a designee. The discussion should is 3-in-1, combination of dextrose, amino acids, and fat in 1 final container, resulting in include the elucidation of the patient’s preferences, goals, is e an I.V. fluid having a milky white appearance. Also referred to as a total nutrient no s p admixture. and values (including religious beliefs), as well as a n t e ro h Based on references 24-56. detailed list of the possible benefits and burdens of thera- i d. py. If the benefit versus risk is not easy to predict, consider a time-related trial period to evaluate effectiveness, bene- fits,and burdens.This process requires an understanding of ib i te d. 38 39
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Hosp Pharm. 202, 209 (Mar) 09 Goals.http://www.jointcommission.org/PatientSafety/NationalPatientSafetyGoals/ ep 1992;27:200. 05_hap_npsgs.htm.Accessed January 29,2008. M ro 39. Trissel LA, Bready BB, Kwan JW, Santiago.The visual compatibility of sar- 22. The Joint Commission. FAQs for The Joint Commission’s 2007 National Patient cM on gramostim with selected chemotherapeutic drugs, anti-infectives, and other du Safety Goals. http://www.jointcommission.org/NR/rdonlyres/B423198E-8EB1-468C- drugs during simulated Y-site injection. Am J Hosp Pharm. 1992;49(2):402-406. ah in ct B01E-DBB0324B5C60/0/07_NPSG_FAQs_3.pdf.Accessed January 29, 2008. 40. Veltri MR, Conner KG. Physical compatibility of milrinone lactate with intra- i on w 23. Kochevar M (Chair), Guenter P Holcombe B, et al, for the ASPEN Board of , venous drugs commonly used in the intensive care unit. Am J Health Syst Directors and ASPEN Task Force on Parenteral Nutrition Standardization. Pharm. 2002;59(5):452-454. 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    • 51. Nieves-Cordero AL, Luci HM, Souney PF Compatibility of narcotic analgesic . Other Resources solutions with various antibiotics during simulated Y-site injection. Am J Hosp American Society for Parenteral and Enteral Nutrition, A Pharm. 1985;42(5):1108-1109. 8630 Fenton St,Suite 412,Silver Spring,MD 20910-3805. ll 52. Schilling CG. Compatibility of drugs with a heparin-containing neonatal total Phone: (301) 587-6315. E-mail: aspen@nutr.org.Web access: ri parenteral nutrition solution. Am J Hosp Pharm. 1988;45(2):313-314. www.nutritioncare.org. gh Co 53. Athanikar N, Boyer B, Deamer R, et al.Visual compatibility of 30 additives with Merritt R, DeLegge MH, Holcombe B, et al, eds. ASPEN Nutrition Support Practice ts parenteral nutrient solution. Am J Hosp Pharm. 1979;36(4):511-513. py Manual. 2nd ed. Silver Spring, MD: American Society for Parenteral and Enteral 54. Ishisaka DY,Van Vleet J, Marquardt E.Visual compatibility of indomethacin re ri Nutrition; 2005. sodium trihydrate with drugs given to neonates by continuous infusion. Am J gh se Hosp Pharm. 1991;48(11):2442-2443. Rombeau JL, Rolandelli RH, eds. Clinical Nutrition/Parenteral Nutrition. 3rd ed. rv t 55. Trissel LA,Williams KY, Gilbert DL. Compatibility screening of linezolid injec- Philadelphia, PA: WB Saunders Co; 2001. © ed tion during simulated Y-site administration of other drugs and infusion solu- Shikora SA, Martindale RG, Schwaitzberg SD, eds. Nutritional Considerations in the 20 .R tions. J Am Pharm Assoc. 2000;40:516-519. Intensive Care Unit: Science, Rationale and Practice. American Society for Parenteral 09 56. Mirtallo JM, Rogers KR, Johnson JA, Fabri PJ, Schneider PJ. Stability of amino and Enteral Nutrition. Dubuque, IA: Kendall-Hunt Publishing Co; 2002. ep acids and the availability of acid in total parenteral nutrition solutions contain- M Trissel LA, ed. Handbook on Injectable Drugs. 14th ed. Bethesda, MD: American Soci- ro ing hydrochloric acid. Am J Hosp Pharm. 1981;38(11): 1729-1731. ety of Health-System Pharmacists; 2006. cM on du 57. Driscoll DF Baptista RJ, Mitrano FP Mascioli EA, Blackburn GL, Bistrian BR. , , ah in ct Parenteral nutrient admixtures as drug vehicles: theory and practice in the critical care setting. Ann Pharmacother. 1991;25(3):276-283. i on w 58. Sheean PM, Freels SA, Helton SW, Braunschweig CA.Adverse clinical conse- Pu ol quences of hyperglycemia from total parenteral nutrition exposure during hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. bl e o 2006;12(6):656-664. is h 59. O’Sullivan J, Maillet J. Ethics. In: Merritt R, DeLegge MH, Holcombe B, et al, eds. hi ASPEN Nutrition Support Practice Manual. 2nd ed. Silver Spring, MD: American ng n p Society for Parenteral and Enteral Nutrition; 2005:378-382. r G art i ro up wit un ho le ut ss ot rm he pe rw sio is is e no s p n t e ro h i d. ib i te d. 44 45
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