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Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy LECTURE II III) WOMAN IN NO ACUTE STRESS S.F a 51-year-old cachectic woman, is admitted to the hospital complaining of a 3-month history of severe abdominal pain after eating and a 30-Ib weight loss. Questioning reveals that she has felt hungry, but the pain after eating is so severe she prefers not to eat. S.F. denies any nausea, vomiting, or diarrhea. Her medical history is significant for PUD. Her surgical history is significant for removal of a small section of her ileum and colon for ischemia 4 months ago. Her current medication is nizatidine 150 mg PO BID. S.F social history is significant for tobacco use, but she quit smoking 2 years ago. Review of systems is positive only for the postprandial abdominal pain. S.F mostly eats one meal a day, consumes only 25 to 40% of that meal. Tolerance to food is no better if she eats liquids or solids. Her weight loss has been continuous over the last 3 months. Physical examination: thin, wasting of subcutaneous fat in the temporal area and squared appearing shoulders. Her height is t 5'4" and her weight is 89 lb. At the time of her ileum and colon resection, her weight was 119 Ib, which is her usual weight. Admission laboratory values are as follows: sodium (Na), 135 mEq/L (normal, 135 to 145); potassium (K), 4.0 mEq/L (normal, 3.5 to 5.0); chloride (Cl), 100 mEq/L (normal, 100 to 110); bicarbonate (HCO3 -), 25 mEq/L (normal, 24 to 30); blood urea nitrogen (BUN), 4 mg/dL (normal, 8 to 20); creatinine, 0.6 mg/dL (normal, 0.8 to 1.2); glucose 87 mg/dL, (normal, 85 to 110); calcium (Ca), 8.2 mg/dL (normal, 8.5 to 10); magnesium (Mg), 2.0 mg/dL (normal, 1.6 to 2.2); phosphorus (P), 3.0 mg/dL (normal, 2.5 to 4.5); total protein, 6.0 g/dL (normal, 6.8 to 8.3); albumin, 4 g/dL (normal, 3.5 to 5.0); and prealbumin, 21 mg/dL (normal, 15 to 40). White blood cell (WBC) count, 6,800/mm3 (normal, 4,000 to 12,000). Based on history and physical findings, S.F working diagnosis is intestinal angina also known as mesenteric ischemia. 1 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy PATIENT ASSESSMENT Assessment of nutritional status requires evaluation of multiple factors. S.F nutritional history: Not eating because of the abdominal pain. Recent ileum surgery raises the question of nutrient malabsorption. Most striking: her weight loss of 30 pounds in 3 months or about 2.5 pounds per week (S.F is now 75% of her usual weight). The loss of 25% of her original weight is a severe weight loss. S.F physical findings of cachectic appearance, temporal wasting, and loss of subcutaneous fat and muscle in her shoulders are significant. No anthropometric measurements are available. S.F visceral proteins (albumin & prealbumin) are within normal ranges. In conclusion: o S.F is severely malnourished. o Her cachectic appearance with loss of subcutaneous fat and muscle, but normal visceral proteins, would be best classified as marasmus. o If S.F were to be faced with stress or injury (e.g., major surgery, infection) necessitating use of visceral proteins for energy production, she would likely exhibit characteristics of both marasmus and kwashiorkor or mixed protein-calorie malnutrition in which fat, muscle, and visceral proteins all are depleted. IS S.F A CANDIDATE FOR TPN THERAPY? S.F is admitted to the hospital for tests to evaluate her severe postprandial abdominal pain. Many of the expected diagnostic tests will require that S.F remain NPO (not use GIT). Although S.F appears to have a functioning GIT, her postprandial pain is so severe it is doubtful she would eat much even if given the opportunity. If the diagnosis of mesenteric ischemia is accurate, surgical correction will be required. With her malnourished state, inadequate nutrient intake for more than 7 days will result in further deterioration of her nutritional status. Based on all that parenteral nutrition should be implemented. 2 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy GOALS OF THERAPY During the first 3 days of hospitalization, S.F undergoes multiple diagnostic tests to evaluate her abdominal pain. An arteriogram reveals occlusion of her superior mesenteric artery that supplies blood to her small and large intestines. This occlusion compromises blood flow to the intestines when there is increased demand for flow, such as after eating. S.F. is to remain NPO until her surgery, which is scheduled in 4 days. what is the goal of her nutrition therapy? Although S.F has lost 30 pounds, the limited time before her surgery is not adequate to replete her fat and lean body mass. Her malnutrition occurred over several months and repletion may take equally as long. The benefits of preoperative parenteral nutrition remain unclear. Although some reports describe a trend of improved outcome with preoperative parenteral nutrition, other studies have not demonstrated clear benefit. Ideally, preoperative parenteral nutrition should be administered for 7 to 10 days to be of any benefit in decreasing the complications associated with surgery in severely malnourished patients. Therefore, the goals for S.F nutrition therapy, at this time, are to maintain her current nutritional status and prevent her from becoming more malnourished. If, however, parenteral nutrition is initiated and continued after surgery, her calorie and protein goals should be adjusted at that time for the additional stress of major surgery. Finally, once she has recovered from surgery and is convalescing, a longterm goal of weight gain to her usual weight of 119 pounds is appropriate. Calorie and Protein Goals Calculate BEE S.F actual weight of 89 pounds (40.5 kg) will be used Using Harris-Benedict equation (females): S.F BEE = 1,104 kcal/day. Modified for light hospital activity: = 1,104 x 1.3 = 1,435 kcal/day. S.F does not require a factor for stress at this stage. A simpler method to determine energy expenditure is by: (28-30 3 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy kcal/kg per day) = (28-30 x 40.5 kg) = 1,134 to 1,200 kcal/day. Protein goals: weight, degree of stress, and disease state. S.F at minimal stress: Protein dose is 1.0 to 1.2 g/kg per day = 41 to 49 g/day = (i.e. 41-49 gm amino acids (1 g of protein is equivalent to 1 g of amino acids). LECTURE III Formula design: Design a peripheral parenteral nutrient base formulation for S.F. that provides 1,300 total calories and 45 g of amino acids. The formulation should provide 60% of the nonprotein calories as lipid and have maximum dextrose and amino acid concentrations of 6 % and 3 %, respectively. The macronutrient components available to prepare this formulation are dextrose 20%, amino acids 8.5%, sterile water for injection, and IV lipids 10% and 20%. Calories: 1. Amino acids = 180 protein calories (45 x 4.0) 2. Nonprotein calories 1,120 (1300-180) (Lipids and carbohydrate). 3. 60% of the non protein calories as lipids = 672 (1,120 x 0.60) calories. 4. Dextrose = 448 (1120-672) Amount 1. Amino acids 45 gm 2. Dextrose = 132 g of dextrose are required (448/3.4) 3.4 Kcal/g. Volume: 1. Provide 45 g of amino acids as a 3% final concentration is calculated to be 1,500 mL. 2. Provide 132 g of dextrose as a 6% concentration 2,200 mL. (132 g x 1000 ml/60 gm) 3. To stay within the guidelines for maximum dextrose and amino acid concentrations, the larger volume of 2,200 mL is used. Therefore, the final dextrose and amino acid concentrations are 6% and 2%, respectively. 4. The amount of fat to provide 672 kcal must be determined. Using 10% 4 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy lipid emulsion with a caloric density of1.1 kcal/mL will require 611 mL or 336 mL of the 20% lipid emulsion (2 kcal/mL). This parenteral nutrient formulation is compounded using dextrose 20% 660 mL (132 g) and amino acids 8.5% 530 mL (45 g) with sterile water for injection added to achieve a final volume of 2,200 mL. The IV lipid can be provided in various ways. o As a secondary infusion or "piggybacked" into .the dextrose/amino acid solution. o If the 10% lipid emulsion is used, S.F fluid intake from her parenteral feedings will be approximately 2,800 mL/day; using the 20% lipid emulsion 2,550 mL/day is necessary. o Alternatively, mix the entire daily requirements for lipid, dextrose and amino acids in one large container or single daily bag. This is called total nutrient. admixture (TNA), triple-mix, three-in-one, or all-in-one. o It is the preferred method of administering parenteral nutrient formulations via peripheral veins because: The iso-osmotic lipids have a diluting effect as well as buffering effect'" Lipids increases the caloric density significantly with only a slight increase in osmolarity. o S.F peripheral nutrient formulation should also contain standard amounts of electrolytes, as well as a daily dose of IV multi vitamins and trace elements. FLUIDS The institution uses a TNA system and S.F parenteral nutrient formulation is provided in 2,200 mL/day. Will this meet S.F maintenance fluid requirements? Maintenance fluid needs can be estimated using several methods. o 30 to 35 mL/kg per day as the basis. o 1,500 mL for the first 20 kg body weight plus an additional 20 mL/kg for actual weight beyond the initial 20 kg. Both methods provide estimates of fluid needs for basic maintenance, and additional fluid must be provided for increased losses such as vomiting, nasogastric (NO) tube output, diarrhea, or large open 5 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy wounds. S.F fluid needs are estimated as follows: = 1,500 mL + [(20 mL/kg) (40.5 kg - 20 kg)] = 1,500 mL + (20 mL/kg)(20.5 kg) = 1,500 mL + 410 mL = 1,910 mL Clearly, the peripheral parenteral nutrient formulation will more than meet S.F needs, and the extra fluid intake may put her at risk for becoming fluid overloaded, manifesting as hypervolemic, hypotonic hyponatremia. Therefore, she should be monitored for signs of fluid overload (peripheral edema or shortness of breath, daily intake exceeding daily output, hyponatremia, and rapidly increasing weight). MONITORING AND MANAGEMENT OF COMPLICATIONS o What additional parameters should be monitored for patients receiving peripheral parenteral nutrition? o The primary calorie source in peripheral parenteral feedings is lipids. o For S.F, 60% of the nonprotein calories are provided as lipid. However, for adults the daily lipid intake should not exceed 2.5 g/kg per day. o S.F formulation provides approximately 65 g of lipid daily or 1.6 g/kg per day. o It is also important to monitor serum triglycerides to assess tolerance to this dose of IV lipid. o If the blood sample is obtained while the triglycerides are infusing, as with the TNA formulation, a serum triglyceride concentration of <400 mg/d, although elevated, is acceptable. o Hypertriglyceridermia sometimes can be noted quickly by gross observation of the blood sample. o Forty-eight hours after S.F. begins peripheral parenteral nutrition, she begins to complain that the arm where she has the IV for the feeding is swollen, red, and painful. What is the most probable cause of these complaints? o What measures can he taken to prevent this complication? o A common complication (up to 70%) of peripheral parenteral nutrition is phlebitis that occurs within 72 hours. o Phlebitis usually is attributed to the acidic pH or hyperosmolarity of the nutrient formulation. 6 Professor T Najjar o PHCL-474 (TPN) Dept of clinical pharmacy The osmolarity of typical peripheral parenteral feedings ranges from 600 to 900 mOsm/L. o Osmolarity of a dextrose/amino acid formulation can be approximated quickly by multiplying the final dextrose concentration by 50 and the final amino acid concentration by 100. o Alternatively, the osmolarity can be estimated by multiplying the number of grams of dextrose by 5 and the number of grams of amino acids by 10 then dividing by the final volume in liters. o Approximately150 mOsm/L should be added for contribution of electrolytes, vitamins and trace elements. o Using the first method, a formulation of 6% dextrose and 2% amino acids has an approximate osmolarity of 650 mOsm [(6% dextrose x 50 = 300 mOsm) + (2% amino acids x 100 = 200 mOsm) + 150 mOsm for additives]. o Although the concurrent administration of fat emulsions decreases osmolarity, buffers the pH, and improves peripheral vein tolerance, it does not totally eliminate the risk of thrombophlebitis. o Other efforts to minimize phlebitis include the addition of a combination of heparin and hydrocortisone to the admixture. o Alternatively, a glycerol trinitrate patch may be applied near the peripheral IV site to dilate the superficial veins, which constrict when there is irritation. o S.F peripheral IV catheter should be removed and another one placed in the other arm if she is to continue receiving her peripheral parenteral nutrient formulation. o Methods to reduce thrombophlebitis should be initiated. o If S.F exhausts her peripheral venous access and continues to need parenteral nutrition, placement of a central venous catheter should be considered. _________________________________________________________________ 7 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy Formula design: Design a peripheral parenteral nutrient base formulation for S.F. that provides 1,300 total calories and 45 g of amino acids. The formulation should provide 60% of the nonprotein calories as lipid and have maximum dextrose and amino acid concentrations of 6 % and 3 %, respectively. The macronutrient components available to prepare this formulation are dextrose 20%, amino acids 8.5%, sterile water for injection, and IV lipids 10% and 20%. calories Calories Amounts Required required Protein 180 = (45 x 4.0) Non 1300-180 = protein 1120 Amino 180 = (45 x acids 4.0) Dextrose 45 gm 448 = (1120- (40%) 672) Lipids 672 = 1,120 (60%) x 0.60) 448/3.4 = 132 gm - 10% =672/1.1 = 611 mL = 61. 2 gm or - 20% = 672/2 = 336 mL = 67.2 gm 1300 Total Amount 1. Amino acids 45 gm 2. Dextrose = 132 g of dextrose are required (448/3.4) …. 3.4 Kcal/g. Volume: 1. Provide 45 g of amino acids as a 3% final 8 Professor T Najjar PHCL-474 (TPN) Dept of clinical pharmacy concentration is calculated to be 1,500 mL. 2. Provide 132 g of dextrose as a 6% concentration 2,200 mL. (132 g x 1000 ml/60 gm 3. To stay within the guidelines for maximum dextrose and amino acid concentrations, the larger volume of 2,200 mL is used. Therefore, the final dextrose and amino acid concentrations are 6% and 2%, respectively. This parenteral nutrient formulation is compounded using dextrose 20% 660 mL (132 g) and amino acids 8.5% 530 mL (45 g) with sterile water for injection added to achieve a final volume of 2,200 mL. The IV lipid can be provided in various ways. o As a secondary infusion or "piggybacked" into .the dextrose/amino acid solution. If the 10% lipid emulsion is used, S.F fluid intake from her parenteral feedings will be approximately 2,800 mL/day; using the 20% lipid emulsion 2,550 mL/day is necessary. o Alternatively, mix the entire daily requirements for lipid, dextrose and amino acids in one large container or single daily bag. This is called total nutrient. admixture (TNA), triple-mix, three-in-one, or all-in-one and is the preferred method of administering parenteral nutrient formulations via peripheral veins because: The iso-osmotic lipids have a diluting effect as well as buffering effect'" Lipids increases the caloric density significantly with only a slight increase in osmolarity. 9