Enteral nutrition support is indicated when a patient cannot adequately meet nutritional needs by oral intake alone and has a functioning GI tract. This method of support can be used for short- and long-term delivery of nutrition. Even when the gut cannot absorb 100% of nutritional needs, some enteral feedings should be attempted. Enteral nutrition, full or partial, has many benefits:
Maintaining gut mucosal integrity
Preserving gut-associated lymphoid tissue
Stimulating gut hormones and bile flow
Nasogastric feeding tubes can be used for supplemental enteral feedings, but generally are not used for more than 6 months because of the complications of otitis media and sinusitis. Initiation of nasogastric feeding usually requires a brief hospital stay to ensure tolerance to feedings and to allow for parental instruction in tube placement and feeding administration.
If long-term feeding support is anticipated, a more permanent feeding device, such as a gastrostomy tube, may be considered. Referral to a home care company is necessary for equipment and other services such as nursing visits and dietitian follow-up.
Table 11–21 suggests appropriate timing for initiation and advancement of drip and bolus feedings, according to a child’s age. Clinical status and tolerance to feedings should ultimately guide their advancement.
Table 11–21.Guidelines for the initiation and advancement of tube feedings. ||Download (.pdf) Table 11–21.Guidelines for the initiation and advancement of tube feedings.
|Age ||Drip Feeds ||Bolus Feeds |
|Initiation ||Advancement ||Initiation (mL) ||Advancement |
|Preterm ||1–2 mL/kg/h ||5–10 mL/kg q8–12 h over 5–7 day as tolerated ||10–20 mL/kg ||20–30 mL/kg/day as tolerated |
|Birth–12 mo ||5–10 mL/h ||5–10 mL q2–8 h ||10–60 ||20–40 mL q3–4 h |
|1–6 y ||10–15 mL/h ||10–15 mL q2–8 h ||30–90 ||30–60 mL q feed |
|6–14 y ||15–20 mL/h ||10–20 mL q2–8 h ||60–120 ||60–90 mL q feed |
|> 14 y ||20–30 mL/h ||20–30 mL q2–8 h ||60–120 ||60–120 mL q feed |
Monitoring the adequacy of enteral feeding depends on nutritional goals. For critically ill patients in the intensive care unit, provision of enteral nutrition in the first 48 hours is associated with lower mortality. Even when calorie and protein goals cannot be met, provision of more than 60% protein goals enterally is associated with lower odds of mortality in mechanically ventilated children. Evaluating normal growth parameters in critically ill infants and children can be skewed by fluid status changes and loss of muscle mass. While weight and linear growth must still be followed, other measures such as mid-arm muscle circumference may provide another measure to assess nutritional adequacy. Frequent assessment of anthropometrics, medical status changes, biochemical indices, and tolerance to enteral feeds with documentation of delivered nutrition intake versus goal intake is essential in managing this nutritionally challenging population.
For more stable hospitalized young infants and malnourished children, growth data should be regularly obtained and evaluated based on age appropriate growth charts. Hydration status should be assessed carefully at the initiation of enteral feeding and regularly thereafter. Either constipation or diarrhea can be problems, and attention to stool frequency, volume, and consistency can help guide management. When diarrhea occurs, factors such as infection, hypertonic enteral medications, antibiotic use, and alteration in normal gut flora should be addressed.
In medically stable patients, the enteral feeding schedule should be developmentally appropriate (eg, 5–6 small feedings/day for a toddler). When night drip feedings are used in conjunction with daytime feeds, it is suggested that less than 50% of goal calories be delivered at night so as to maintain a daytime sense of hunger and satiety. This will be especially important once a transition to oral intake begins.
et al: Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study. Am J Clin Nutr Jul 2015;102(1):199–206. doi: 10.3945/ajcn.114.104893
et al: Early enteral nutrition is associated with lower mortality in critically ill children. JPEN J Parenter Enteral Nutr 2014 May;38(4):459–466
A. Peripheral Parenteral Nutrition
Peripheral parenteral nutrition is indicated when complete enteral feeding is temporarily impossible or undesirable. Short-term partial intravenous (IV) nutrition via a peripheral vein is a preferred alternative to administration of dextrose and electrolyte solutions alone. Because of the osmolality of the solutions required, it is usually impossible to achieve total calorie and protein needs with parenteral nutrition via a peripheral vein.
B. Total Parenteral Nutrition
Total parenteral nutrition (TPN) should be provided only when clearly indicated. Apart from the expense, numerous risks are associated with this method of feeding (see the section Complications). Even when TPN is indicated, every effort should be made to provide at least a minimum of nutrients enterally to help preserve the integrity of the GI mucosa and of GI function.
The primary indication for TPN is the loss of function of the GI tract that prohibits the provision of required nutrients by the enteral route. Important examples include short bowel syndrome, some congenital defects of the GI tract, and prematurity.
In recent years, a number of injectable essential nutrients have been in short supply in the US pharmaceutical market. Shortages have included IV lipids, multivitamins mixtures, and trace minerals. Deficiencies of these micronutrients have led to significant medical morbidity. Nutrition support teams should develop clinical guidelines to ensure injectable micronutrients are available for those patients who have the greatest need, for example, preterm infants and children with long-term dependence upon TPN. Policies to promote use of enteral micronutrient preparations can also help to reduce the reliance on parenteral supplies.
et al: Evidence for the use of parenteral nutrition in the pediatric intensive care unit. Clin Nutr Feb 2017;36(1):218–223. doi: 10.1016/j.clnu.2015.11.004
Catheter Selection & Position
An indwelling central venous catheter is preferred for long-term IV nutrition. For periods of up to 3–4 weeks, a percutaneous central venous catheter threaded into the superior vena cava from a peripheral vein can be used. For the infusion of dextrose concentrations higher than 12.5%, the tip of the catheter should be located in the superior vena cava. Catheter positioning in the right atrium has been associated with complications, including arrhythmias and thrombus. After placement, a chest radiograph must be obtained to check catheter position. If the catheter is to be used for nutrition and medications, a double-lumen catheter is preferred.
A. Mechanical Complications
Related to catheter insertion or to erosion of catheter through a major blood vessel: Complications include trauma to adjacent tissues and organs, damage to the brachial plexus, hydrothorax, pericardial effusion with potential cardiac tamponade, pneumothorax, hemothorax, and cerebrospinal fluid penetration. The catheter may slip during dressing or tubing changes, or the patient may manipulate the line.
Clotting of the catheter: Addition of heparin (1000 U/L) to the solution is an effective means of preventing this complication. If an occluded catheter does not respond to heparin flushing, recombinant tissue plasminogen activator may be effective.
Related to composition of infusate: Calcium phosphate precipitation may occur if excess amounts of calcium or phosphorus are administered. Factors that increase the risk of calcium phosphate precipitation include increased pH and decreased concentrations of amino acids. Precipitation of medications incompatible with TPN or lipids can also cause clotting.
Septic complications are the most common cause of nonelective catheter removal, but strict use of aseptic technique and limiting entry into the catheter can reduce the rates of line sepsis. Fever over 38–38.5°C in a patient with a central catheter should be considered a line infection until proved otherwise. Cultures should be obtained and IV antibiotics empirically initiated. Removing the catheter may be necessary with certain infections (eg, fungal), and catheter replacement may be deferred until infection is treated.
C. Metabolic Complications
Many of the metabolic complications of IV nutrition are related to deficiencies or excesses of nutrients in administered fluids, whereas uncommon, specific deficiencies still occur, especially in the preterm infant. Safe and effective IV nourishment requires attention to the nutrient balance, electrolyte composition, and delivery rate of the infusate and careful monitoring, especially when the composition or delivery rate is changed. The most challenging metabolic complication is cholestasis, particularly common in preterm infants of very low birth weight with prolonged feeding intolerance, infants with congenital gut disorders requiring surgery, such as those with gastroschisis, and infants with short gut syndrome following surgical resections for disorders such as necrotizing enterocolitis. See discussion on parenteral nutrition-associated cholestasis (PNAC) in Chapter 22 for details.
et al: Early versus late parenteral nutrition in critically ill children. N Engl J Med Mar 24, 2016;374(12):1111–1122. doi: 10.1056/NEJMoa1514762
NUTRIENT REQUIREMENTS & DELIVERY
When patients are fed intravenously, no fat and carbohydrate intakes are unabsorbed, and no energy is used in nutrient absorption. These factors account for at least 7% of energy in the diet of the enterally fed patient. The intravenously fed patient usually expends less energy in physical activity. Average energy requirements may therefore be lower in children fed intravenously, by a total of 10%–15%. Caloric guidelines for the IV feeding of infants and young children are outlined below.
The guidelines are averages, and individuals vary considerably. Factors significantly increasing the energy requirement estimates include exposure to cold environment, fever, sepsis, burns, trauma, cardiac or pulmonary disease, and catch-up growth after malnutrition.
With few exceptions, such as some cases of respiratory insufficiency, at least 50%–60% of energy requirements are provided as glucose. Up to 40% of calories may be provided by IV fat emulsions.
The energy density of IV dextrose (monohydrate) is 3.4 kcal/g. Dextrose is the main energy source provided by total IV feeding. IV dextrose suppresses gluconeogenesis and can be oxidized directly, especially by the brain, red and white blood cells, and wounds. Because of the high osmolality, concentrations of dextrose greater than 10%–12.5% cannot be delivered via a peripheral vein or improperly positioned central line.
Dosing guidelines: The standard initial quantity of dextrose administered will vary by age (Table 11–22). Tolerance to IV dextrose normally increases rapidly due to suppression of hepatic glucose production. Dextrose can be increased by 2.5 g/kg/day, by 2.5%–5%/day, or by 2–3 mg/kg/min/day if there is no glucosuria or hyperglycemia. Standard final infusates for infants via a properly positioned central venous line usually range from 15% to 25% dextrose, though concentrations of up to 30% dextrose may be used at low flow rates. Tolerance to IV dextrose loads is markedly diminished in the preterm neonate and in hypermetabolic states.
Table 11–22.Pediatric macronutrient guidelines for total parenteral nutrition. ||Download (.pdf) Table 11–22.Pediatric macronutrient guidelines for total parenteral nutrition.
|Age ||Dextrose ||Amino Acids ||Lipids |
|mg/kg/min ||g/kg/day ||g/kg/day ||g/kg/day |
|50%–60% kcal ||10%–20% kcal ||30%–40% kcal |
|Preterm ||Initial 5–8 ||Initial 7–11 ||Initial 1.5–2 ||Initial 0.5–1 |
| ||Max 11–12.5 ||Max 16–18 ||Max 3–4 ||Max 2.5–3.5 |
|Birth–12 mo ||Initial 6–8 ||Initial 9–11 ||Initial 1.5–2 ||Initial 1 |
| ||Max 11–15 ||Max 16–21.5 ||Max 3 ||Max 2.5–3.5 |
|1–6 y ||Initial 6–7 ||Initial 8–10 ||Initial 1–1.5 ||Initial 1 |
| ||Max 10–12 ||Max 14–17 ||Max 2–2.5 ||Max 2.5–3.5 |
|> 6 y ||Initial 5–7 ||Initial 8–10 ||Initial 1 ||Initial 1 |
| ||Max 9 ||Max 13 ||Max 1.5–2 ||Max 3 |
|> 10 y ||Initial 4–5 ||Initial 5–7 ||Initial 1 ||Initial 1 |
| ||Max 6–7 ||Max 8–10 ||Max 1.5–2 ||Max 2–3 |
|Adolescents ||Initial 2–3 ||Initial 3–4 ||Initial 1 ||Initial 0.5–1 |
| ||Max 5–6 ||Max 7–8 ||Max 1.5–2 ||Max 2 |
Problems associated with IV dextrose administration include hyperglycemia, hyperosmolality, and glucosuria (with osmotic diuresis and dehydration). Possible causes of hyperglycemia include the following: (1) inadvertent infusion of higher dextrose rates than ordered and achieving higher glucose concentrations than desired, (2) uneven flow rate, (3) sepsis, (4) a stress situation (including administration of catecholamines or corticosteroids), and (5) pancreatitis. If these causes have been addressed and severe hyperglycemia persists, use of insulin may be considered. IV insulin reduces hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake by muscle and fat tissues. It usually increases plasma lactate concentrations, but does not necessarily increase glucose oxidation rates; it may also decrease the oxidation of fatty acids, resulting in less energy for metabolism. Use of IV insulin also increases the risk of hypoglycemia. Hence, insulin should be used very cautiously. A standard IV dose is 1 U/4 g of carbohydrate, but much smaller quantities may be adequate and, usually, one starts with 0.2–0.3 U/4 g of carbohydrate.
Hypoglycemia may occur after an abrupt decrease in or cessation of IV glucose. When cyclic IV nutrition is provided, the IV glucose load should be decreased steadily for 1–2 hours prior to discontinuing the infusate. If the central line must be removed, the IV dextrose should be tapered gradually over several hours.
Oxidation rates for infused dextrose decrease with age. It is important to note that the ranges for dextrose administration provided in Table 11–22 are guidelines and that individual patients may require either less or more dextrose. Quantities of dextrose in excess of maximal glucose oxidation rates are used initially to replace depleted glycogen stores; hepatic lipogenesis occurs thereafter. Excess hepatic lipogenesis may lead to a fatty liver (steatosis). Lipogenesis produces carbon dioxide, as does glucose oxidation. Thus, excess dextrose may elevate the Paco2 and aggravate respiratory insufficiency or impede weaning from a respirator.
The energy density of 20% lipid emulsions is 10 kcal/g of lipid or 2 kcal/mL. The lipids are derived from either soybean or safflower oil. All commonly available formulations consist of more than 50% linoleic acid and 4%–9% linolenic acid. This high level of linoleic acid is not ideal due to the proinflammatory potential of omega-6 fatty acids, except when small quantities of lipid are being given to prevent an EFA deficiency. Because 10% and 20% lipid emulsions contain the same concentrations of phospholipids, a 10% solution delivers more phospholipid per gram of lipid than a 20% solution. Twenty percent lipid emulsions are preferred. IV lipid is often used to provide 30%–40% of calorie needs for infants and up to 30% of calorie needs in older children and teens.
Lipoprotein lipase (LPL) activity is the rate-limiting factor in the metabolism and clearance of fat emulsions from the circulation. LPL activity is inhibited or decreased by malnutrition, leukotrienes, immaturity, growth hormone, hypercholesterolemia, hyperphospholipidemia, and theophylline. LPL activity is enhanced by glucose, insulin, lipid, catecholamines, and exercise. Heparin releases LPL from the endothelium into the circulation and enhances the rate of hydrolysis and clearance of TGs. In small premature infants, low dose heparin infusions may increase tolerance to IV lipid emulsion.
In general, adverse effects of IV lipid can be avoided by starting with modest quantities and advancing cautiously in light of results of TG monitoring and clinical circumstances. Monitoring TGs is particularly important in cases of severe sepsis. It should continue periodically with long-term use.
IV lipid dosing guidelines: Check serum TGs before starting and after increasing the dose. Commence with 1 g/kg/day, given over 12–20 hours or 24 hours in small preterm infants. Advance by 0.5–1.0 g/kg/day, every 1–2 days, up to goal (see Table 11–22). As a general rule, do not increase the dose if the serum TG level is above 400 mg/dL during infusion or if the level is greater than 250 mg/dL 6–12 hours after cessation of the lipid infusion.
Serum TG levels above 400–600 mg/dL may precipitate pancreatitis. In patients for whom normal amounts of IV lipid are contraindicated, 4%–8% of calories as IV lipid should be provided to prevent EFA deficiency. Neonates and malnourished pediatric patients receiving lipid-free parenteral nutrition are at high risk for EFA deficiency.
et al. Impact of providing a combination lipid emulsion compared with a standard soybean oil emulsion in children receiving parenteral nutrition: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr 2015 Aug;39(6):656667
One gram of nitrogen is produced by 6.25 g of protein (1 g of protein contains 16% nitrogen). Caloric density of protein is equal to 4 kcal/g.
Protein requirements for IV feeding are the same as those for normal oral feeding (see Table 11–2).
B. Intravenous Amino Acid Solutions
Nitrogen requirements can be met by commercially available amino acid solutions. For infants, including premature infants, accumulating evidence suggests that the use of TrophAmine (McGaw) is associated with a more normal plasma amino acid profile, superior nitrogen retention, and a lower incidence of cholestasis. TrophAmine contains 60% essential amino acids, is relatively high in branched-chain amino acids, contains taurine, and is compatible with the addition of cysteine within 24–48 hours after administration. The dose of added cysteine is 40 mg/g of TrophAmine. The relatively low pH of TrophAmine enhances solubility of calcium and phosphorus.
Amino acids can be started at 1–2 g/kg/day in most patients (see Table 11–22). In severely malnourished infants, the initial amount should be 1 g/kg/day. In infants of very low birth weight, there is evidence that higher initial amounts of amino acids are tolerated with little indication of protein “toxicity.” Larger quantities of amino acids in relation to calories can minimize a negative nitrogen balance even when the infusate is hypocaloric. Amino acid intake can be advanced by 0.5–1.0 g/kg/day toward the goal. Normally the final infusate will contain 2%–3% amino acids, depending on the rate of infusion. Concentration should not be advanced beyond 2% in peripheral vein infusates due to osmolality.
Monitoring for tolerance of the IV amino acid solutions should include blood urea nitrogen. Serum alkaline phosphatase, γ-glutamyltransferase, and bilirubin should be monitored to detect the onset of cholestatic liver disease.
A. Calcium, Phosphorus, and Magnesium
Intravenously fed premature and full-term infants should be given relatively high amounts of calcium and phosphorus. Current recommendations are as follows: calcium, 500–600 mg/L; phosphorus, 400–450 mg/L; and magnesium, 50–70 mg/L. After 1 year of age, the recommendations are as follows: calcium, 200–400 mg/L; phosphorus, 150–300 mg/L; and magnesium, 20–40 mg/L. The ratio of calcium to phosphorous should be 1.3:1.0 by weight or 1:1 by molar ratio. These recommendations are deliberately presented as milligrams per liter of infusate to avoid inadvertent administration of concentrations of calcium and phosphorus that are high enough to precipitate in the tubing. During periods of fluid restriction, care must be taken not to inadvertently increase the concentration of calcium and phosphorus in the infusate. These recommendations assume an average fluid intake of 120–150 mL/kg/day and an infusate of 25 g of amino acid per liter. With lower amino acid concentrations, the concentrations of calcium and phosphorus should be decreased.
Standard recommendations are given in Table 11–23. After chloride requirements are met, the remainder of the anion required to balance the cation should be given as acetate to avoid the possibility of acidosis resulting from excessive chloride. Electrolyte concentrations should be modified based on the flow rate and if indications dictate for the individual patient. IV sodium should be administered sparingly in the severely malnourished patient because of impaired membrane function and high intracellular sodium levels. Conversely, generous quantities of potassium and phosphorus may be needed.
Table 11–23.Electrolyte requirements for parenteral nutrition. ||Download (.pdf) Table 11–23.Electrolyte requirements for parenteral nutrition.
|Electrolyte ||Preterm Infant (mEq/kg) ||Full-Term Infant (mEq/kg) ||Child (mEq/kg) ||Adolescent (mEq/kg) |
|Sodium ||2–5 ||2–3 ||2–3 ||60–150 |
|Chloride ||2–5 ||2–3 ||2–3 ||60–150 |
|Potassium ||2–3 ||2–3 ||2–3 ||70–180 |
Recommended IV intakes of trace elements are as follows: zinc 100 mcg/kg, copper 20 mcg/kg, manganese 1 mcg/kg, chromium 0.2 mcg/kg, selenium 2 mcg/kg, and iodide 1 mcg/kg. Of note, IV zinc requirements may be as high as 400 mcg/kg for premature infants and can be up to 250 mcg/kg for infants with short bowel syndrome and significant GI losses of zinc. When IV nutrition is supplemental or limited to fewer than 2 weeks, and preexisting nutritional deficiencies are absent, only zinc need routinely be added.
IV copper requirements are relatively low in the young infant because of the presence of hepatic copper stores. These are significant even in the 28-week fetus. Circulating levels of copper and manganese should be monitored in the presence of cholestatic liver disease. If monitoring is not feasible, temporary withdrawal of added copper and manganese is advisable in cholestasis.
Copper and manganese are excreted primarily in the bile, but selenium, chromium, and molybdenum are excreted primarily in the urine. These trace elements, therefore, should be administered with caution in the presence of renal failure.
Two vitamin formulations are available for use in pediatric parenteral nutrition: MVI Pediatric and MVI-12 (Astra-Zeneca). MVI Pediatric contains the following: vitamin A, 0.7 mg; vitamin D, 400 IU; vitamin E, 7 mg; vitamin K, 200 mcg; ascorbic acid, 80 mg; thiamin, 1.2 mg; riboflavin, 1.4 mg; niacinamide, 17 mg; pyridoxine, 1 mg; vitamin B12, 1 mcg; folic acid, 140 mcg; pantothenate, 5 mg; and biotin, 20 mcg. Recommended dosing is as follows: 5 mL for children weighing more than 3 kg, 3.25 mL for infants 1–3 kg, and 1.5 mL for infants weighing less than 1 kg. Children older than 11 years can receive 10 mL of the adult formulation, MVI-12, which contains the following: vitamin A, 1 mg; vitamin D, 200 IU; vitamin E, 10 mg; ascorbic acid, 100 mg; thiamin, 3 mg; riboflavin, 3.6 mg; niacinamide, 40 mg; pyridoxine, 4 mg; vitamin B12, 5 mcg; folic acid, 400 mcg; pantothenate, 15 mg; and biotin, 60 mcg. MVI-12 contains no vitamin K.
IV lipid preparations contain enough tocopherol to affect total blood tocopherol levels. The majority of tocopherol in soybean oil emulsion is α-tocopherol, which has substantially less biologic activity than the α-tocopherol present in safflower oil emulsions.
A dose of 40 IU/kg/day of vitamin D (maximum 400 IU/day) is adequate for both full-term and preterm infants.
JM: Perspectives on parenteral micronutrient shortages. Nutr Clin Pract 2015 Feb 30(1):86–91
The initial fluid volume and subsequent increments in flow rate are determined by basic fluid requirements, the patient’s clinical status, and the extent to which additional fluid administration can be tolerated and may be required to achieve adequate nutrient intake. Calculation of initial fluid volumes to be administered should be based on standard pediatric practice. If replacement fluids are required for ongoing abnormal losses, these should be administered via a separate line.
Vital signs should be checked on each shift. With a central catheter in situ, a fever of more than 38.5°C requires peripheral and central-line blood cultures, urine culture, complete physical examination, and examination of the IV entry point. Instability of vital signs, elevated white blood cell count with left shift, and glycosuria suggest sepsis. Removal of the central venous catheter should be considered if the patient is toxic or unresponsive to antibiotics.
Monitor especially for hepatomegaly (differential diagnoses include fluid overload, congestive heart failure, steatosis, and hepatitis) and edema (differential diagnoses include fluid overload, congestive heart failure, hypoalbuminemia, and thrombosis of superior vena cava).
B. Intake and Output Record
Calories and volume delivered should be calculated from the previous day’s intake and output records (that which was delivered rather than that which was ordered). The following entries should be noted on flow sheets: IV, enteral, and total fluid (mL/kg/day); dextrose (g/kg/day or mg/kg/min); protein (g/kg/day); lipids (g/kg/day); energy (kcal/kg/day); and percent of energy from enteral nutrition.
C. Growth, Urine, and Blood
Routine monitoring guidelines are given in Table 11–24. These are minimum requirements, except in the very long-term stable patient. Individual variables should be monitored more frequently as indicated, as should additional variables or clinical indications. For example, a blood ammonia analysis should be ordered for an infant with lethargy, pallor, poor growth, acidosis, azotemia, or abnormal liver test results.
Table 11–24.Summary of suggested monitoring for parenteral nutrition. ||Download (.pdf) Table 11–24.Summary of suggested monitoring for parenteral nutrition.
|Variables ||Acute Stage ||Long-Termb |
|Growth ||Daily ||Weekly |
| Weight ||Weekly || |
| Length ||Weekly || |
| Head circumference || || |
|Urine || || |
| Glucose (dipstick) ||With each void ||With changes in intake or status |
| Specific gravity ||Void || |
| Volume ||Daily || |
|Blood || || |
| Glucose ||4 h after changes,a then daily × 2 day ||Weekly |
| Na+, K+, Cl, CO2, blood urea nitrogen ||Daily for 2 days after changes,a then twice weekly ||Weekly |
| Ca2+, Mg2+, P ||Initially, then twice weekly ||Weekly |
|Total protein, albumin, bilirubin, aspartate transaminase, and alkaline phosphatase ||Initially, then weekly ||Every other week |
| Zinc and copper ||Initially according to clinical indications ||Monthly |
| Triglycerides ||Initially, 1 day after changes,a then weekly ||Weekly |
| Compete blood count ||Initially, then twice weekly; according to clinical indications (see text) ||Twice weekly |