Practical parenteral nutrition

In which of the following cases should PN be initiated?

• A.

  Term infant with gastroschisis

• B.

  1-month-old former 26-week preterm infant with abdominal distension and portal venous air on abdominal x-ray

• C.

  3-month-old former 26-week preterm infant with a chylothorax

• D.

  35-weeks’ gestational age (GA) preterm infant in septic shock secondary to group B Streptococcus (GBS) sepsis

• E.

  Newborn preterm infant on a planned feeding advance of GI priming and <30 mL/kg/day increase due to intermittent feeding intolerance

• F.

  All of the above

Which intervention would be the LEAST likely next access attempt for a newborn infant who lost their peripheral line while receiving stock PN and trophic feeds?

• A.

  Insert a new peripheral intravenous line (PIV)

• B.

  Place a umbilical venous catheter (UVC)

• C.

  Surgically place a catheter (Broviac or Hickman)

• D.

  Place a percutaneous inserted central catheter (PICC)

F is correct. See Table 6.1 . PN is indicated when full enteral nutrition cannot be achieved and may be particularly useful in catabolic conditions.

C is correct. A new PIV should be attempted, especially because it is usually easy to insert a new PIV. However, it is only appropriate for short-term access. A UVC, the least painful and invasive central access, could be attempted in a newborn infant if the umbilical vein is patent. UVCs have increased infection risk after 1 to 2 weeks. If a UVC placement is unsuccessful and longer term access is sought, a PICC line would be the next option and is appropriate for longer term access. The last, and most invasive option, would be a surgically centrally placed (Broviac or Hickman) catheter. Although infection risk is low, it is highly invasive with placement and removal requiring a surgeon. Therefore it would only be considered once all other options are exhausted or it is known that an infant will require very long-term access. See Table 6.2 for additional differences in peripheral and central access.

Which of the following statements regarding PN and enteral neonatal nutrition is FALSE?

• A.

  Normal fetal metabolic and growth rates and nutritional requirements stop with birth, precluding routine use of IV nutrition.

• B.

  The smaller and more preterm and less developed the infant, the less body stores (protein, fat, and glycogen) are available to provide nutrients for metabolic needs.

• C.

  The metabolic—and thus the nutrient—requirements of the newborn are equal to or greater than those of the fetus of the same gestational age.

• D.

  First-week protein and energy intakes are associated with improved 18-month developmental outcomes in preterm infants.

Which of the following statements regarding Stock PN and protein and glucose supply is TRUE?

• A.

  Stock PN solutions containing 10% dextrose and 3% amino acids can be stored in the neonatal pharmacy indefinitely.

• B.

  At an infusion rate of 80 mL/kg/day, commonly formulated stock PN solutions provide adequate short-term dextrose and amino acid supplies.

• C.

  There is no need to continue to measure the plasma glucose concentration as the infant is receiving IV dextrose.

• D.

  There is no need to check electrolytes or calcium and phosphorous concentrations until the second or third day of life when enteral feeding is started.

A is false and the correct answer. PN is important right after birth because normal fetal metabolic and growth rates and nutritional requirements do not stop with birth. Furthermore, the smaller and more preterm, the less body stores (protein, fat, and glycogen) are available to provide nutrients for metabolic needs. Intravenous feeding is always indicated when normal metabolic needs are not met by enteral feeding. Additionally, the metabolic and nutrient requirements of the newborn are equal to or greater than those of the fetus of the same gestational age. Thus the newborn infant should receive the same nutrition as the fetus of the same gestational age to maintain normal metabolism and growth. PN is particularly important to ensure full protein and energy supplies to maintain neuronal development. First week protein and energy intakes are associated with improved 18-month developmental outcomes in preterm infants, as well as greater adult lean body mass and higher resting energy expenditure.

B is correct. Stock PN solutions can be stored in the pharmacy for immediate use, but like all pharmaceuticals, they cannot be stored indefinitely. A common stock PN mixture is 10% dextrose and 3% amino acids. At 80 mL/kg/day, this solution would provide 5.5 mg/kg/min of glucose (see Table 6.3 for calculations), which is appropriate for most preterm neonates. Because individual infants vary in response to dextrose infusions, one should always monitor the infant’s glucose concentration frequently to ensure that normal values are maintained. This standard stock PN mixture will provide 2.4 g/kg/day of amino acids, still less than the 3.5-4 g/kg/day of amino acids that are needed in very preterm infants to restore in utero protein accretion and body growth (see Table 6.4 ). Stock PN solutions often are not supplemented with calcium and phosphorous salts, but both should be added to a customized PN within the 1st 24 to 48 hours. Plasma calcium and phosphorous as well as routine electrolytes should be measured within the 1st 24 hours as electrolyte disturbances are commonly observed after very preterm birth.

How many nonprotein calories and how much protein are provided by this stock PN and will this be enough energy and protein to prevent protein breakdown in this infant?

• A.

  27 kcal/kg/day and 2.4 g/kg/day

• B.

  40 kcal/kg/day and 3 g/kg/day

• C.

  22 kcal/kg/day and 4 g/kg/day

• D.

  160 kcal/kg/day and 2 g/kg/day

Which of the following statements about IV dextrose infusion is FALSE?

• A.

  IV dextrose infusion should provide 30% to 50% of total caloric intake if no enteral feeding is provided.

• B.

  Excess IV dextrose infusion intake increases the incidence and severity of hyperglycemia.

• C.

  Glucose intolerance and hyperglycemia does not occur at glucose infusion rates <10 mg/kg/min.

• D.

  The glucose utilization rate is 2 to 4 mg/kg/min in term infants and 4 to 6 mg/kg/min in very preterm infants.

A is correct. 10% dextrose has a dextrose concentration of 10 g/100 mL. At an infusion rate of 80 mL/kg/day, it provides 27 kcal/kg/day (80 ml/kg/day × 10 g/dL ÷ 100 × 3.4 kcal/g of glucose = 27 kcal/kg/day). 3% amino acids has an amino acid concentration of 3 g/100 mL. At an infusion rate of 80 mL/kg/day it provides 2.4 g/kg/day of amino acids. At least 1.5 g/kg/day of parenteral amino acids is necessary to prevent significant protein breakdown (catabolism). Thus while the energy from just the dextrose infusion may be insufficient to promote full utilization of the 2.4 g/kg/day of amino acids for net protein balance, it is sufficient, along with the amino acid infusion, to prevent protein breakdown.

C is false and the correct answer. The normal glucose utilization rate is 2 to 4 mg/kg/min in term infants and 4 to 6 mg/kg/min in very preterm infants. These rates provide 30% to 50% of total caloric intake if no enteral feeding is provided. IV dextrose above these rates is the principal cause of neonatal hyperglycemia, but other conditions contribute to this problem, making it common. Many of these infants also have stress-induced catecholamine, cortisol, and glucagon surges that suppress insulin secretion and promote glycogen breakdown and gluconeogenesis and reduce peripheral insulin and glucose sensitivity. Excessive dosing of IV lipids also aggravates hyperglycemia by providing competitive lipid carbon for oxidation and by producing cofactors in the liver from beta-oxidation of fatty acids that promote the regulatory enzymes in the gluconeogenic pathway. Most preterm infants and term infants continue to produce glucose from their liver at about 2 to 3 mg/kg/min. Furthermore, hepatic glucose production, even in preterm infants, is not easily suppressed by high glucose or insulin concentrations. If the parenteral dextrose infusion rate is >5 to 7 mg/kg/min, then total glucose utilization capacity will be exceeded, resulting in progressively increasing glucose concentrations. Increasing glucose infusion rate (GIR) above 8 to 10 mg/kg/min almost always contributes to hyperglycemia, which has many adverse consequences, including increased CO ₂ production, lipogenesis, and development of a fatty liver with inflammation and steatosis.

Glucose intolerance can occur in preterm infants even at a GIR of 6 mg/kg/min or lower, especially when glucose is infused without amino acids. Coinfusion of amino acids can reduce glucose concentrations and the incidence of hyperglycemia, as amino acids increase insulin secretion and promote anabolism (protein synthesis and protein balance) that requires energy production from glucose oxidation. Absence of enteral nutrition also contributes to the pathogenesis of hyperglycemia by limiting production of gut incretins, which stimulate insulin secretion. Infants of extremely low birth weight (ELBW) are very susceptible to hyperglycemia, further aggravating the overall nutritional status of these fragile infants. Reducing the GIR by coinfusing a lower dextrose fluid, reducing total fluids overall, or advancing feeds are effective ways to normalize glucose levels.

How many calories are needed to achieve a growth rate of 15 to 20 g/kg/day in this infant on PN?

• A.

  90 to 100 kcal/kg/day

• B.

  60 to 80 kcal/kg/day

• C.

  110 to 130 kcal/kg/day

• D.

  140 to 160 kcal/kg/day

Which of the following statements about protein requirements in this newborn infant is CORRECT?

• A.

  Preterm infants should receive 2 to 2.5 g/kg/day of protein when receiving PN.

• B.

  Protein intakes of 4 to 4.5 g/kg/day are recommended for preterm infants with slow weight gain.

• C.

  The protein requirements of preterm infants are greater than those of term infants.

• D.

  Protein intakes >3.5 g/kg/day may result in high uric acid and creatinine levels.

Which of the following statements about PN amino acid practice is TRUE?

• A.

  Starting with higher amino acid intakes of 3 g/kg/day administered in the first few days of life is safe and decreases the incidence of extrauterine growth restriction.

• B.

  Current PN amino acid mixtures provide optimal amino acid supplies and plasma concentrations of all essential and nonessential amino acids for very preterm infants.

• C.

  Providing more amino acids, even above requirements, will improve growth and neurodevelopmental outcomes.

• D.

  Only 3% amino acid solutions should be used to prevent osmotic injury to blood vessels and red blood cells.

Which of the following statements about IV lipid emulsions is FALSE?

• A.

  IV lipid emulsions must be started at 0.5 g/kg/day.

• B.

  Excess IV lipids often produce hypertriglyceridemia, a sign of reduced plasma lipid clearance.

• C.

  IV lipids produce carbon competition with glucose for oxidation, contributing to hyperglycemia.

• D.

  Advancing IV lipids to 3 to 3.5 g/kg/day is important for providing nonprotein calories for achieving positive energy balance and supporting protein synthesis and net protein balance.

• E.

  IV lipid emulsions do not contain sufficient amounts of docosahexaenoic acid (DHA) to meet normal fetal accretion of this essential polyunsaturated fatty acid (LCPUFA).

A is correct. The energy provided should meet the basal metabolic rate plus the energy cost of growth and losses (gastrointestinal, urinary, skin, others). To achieve a growth rate of 15 to 20 g/kg/day, the preterm infant requires 110 to 130 kcal/kg/day enterally. When all nutrition is PN, 90 to 100 kcal/kg/day should meet the growth needs, because there is no energy spent for digestion and absorption, and fecal losses are minimal. Energy losses are minimized by the use of a controlled thermoneutral environment and fluid losses are ameliorated by the use of humidification (which are further reduced by humidification of inhaled air/oxygen gases with assisted ventilation). See Table 6.3 to calculate the caloric content of PN solutions.

C is correct. Current pediatric amino acid solutions were initially formulated to meet the requirements of infants and children and provide a plasma amino acid profile similar to that of term 30-day-old breastfed infants. As such, they contain insufficient amounts of many amino acids, particularly essential and conditionally essential amino acids. It is fundamental that during fetal life, fractional growth rate and fractional protein synthetic rates, which determine amino acid requirements, decline with gestation. Fetal animal studies and the factorial method for assessing fetal protein requirements in human infants at 24 to 30 weeks’ gestation show that 3.6 to 4.8 g/kg/day of amino acids support the more rapid growth at these early gestational ages. The average value of 4 g/kg/day is recommended as the guideline for infants after birth but of the same gestational age as the rapidly growing normal human fetus. At later gestational ages, less protein (amino acids) is needed; for example, 2.5 to 3.5 g/kg/day between 30 to 36 weeks and 1.5 to 2 g/kg/day at term (which is the amount provided by full breast feeding of mature mother’s milk). These manufactured solutions contain essential amino acids and conditionally essential amino acids such as tyrosine and taurine. The delivery of gestational age–appropriate amounts of amino acids along with adequate energy results in positive nitrogen balance and a decrease in loss of body weight, thereby reducing time to regain birth weight. It is estimated that, in the absence of exogenous intake, endogenous protein losses are 0.5 to 1 g/kg/day for infants receiving only dextrose in the infusion. Protein should provide 8% to 10% of total calories; providing more than 10% of the gestational age–appropriate amount of protein is unnecessary and does not increase net protein accretion or body growth rate.

A is correct . Early introduction of amino acids in PN is safe, results in a positive nitrogen balance, and improves glucose tolerance, most likely by increasing insulin and IGF-1 secretion and enhancing protein synthesis that requires glucose for energy. More recent studies reveal that starting with higher amino acid intakes of 3 g/kg/day administered in the first few days of life is safe and decreases the incidence of extra uterine growth restriction. Answer B is incorrect, because current IV amino acid solutions were not developed to provide optimal individual amino acid delivery for newborn infants, including very preterm infants, infants with intrauterine growth restriction (IUGR), and especially infants with early postnatal physiologic and biochemical instability. Answer C is incorrect because the imbalance in plasma essential, conditionally essential, and nonessential amino acids provided in current neonatal IV amino acid solutions is not improved by simply increasing the IV amino acid intake (infusion) rate. Perhaps as a result of these limitations, there is only limited evidence that increased IV amino acid supply during the first days after birth improves growth or neurodevelopmental outcomes. Instead, neurodevelopment is improved when greater amounts of amino acids (and total protein when milk feedings are added) are given with higher amounts of energy, both carbohydrate and lipid. Maintaining the gestational age–appropriate protein intake supports brain growth as measured by head circumference and subsequent magnetic resonance imaging of the brain, even into adolescence. Commonly accepted recommendations for preterm infants are shown in Table 6.4 , although there is considerable variability among NICUs in this practice. Intakes of amino acids higher than 4 g/kg/day right after birth have not been shown to further enhance protein balance, even in extremely preterm infants born between 23 and 28 weeks’ gestation who require the higher amino acid and protein intakes for optimal growth. Answer D is incorrect because up to 5% amino acid solutions can be infused slowly through central venous catheters when concentrating PN to avoid over hydration and hyperglycemia.

A is false and the correct answer (see Table 6.4 ). IV lipid emulsions can be started at higher rates, up to 2.5 to 3.5 g/kg/day, but the most common practice is to start at about 1 to 2 g/kg/day and advance by 0.5 to 2 g/kg/day (slower rates for smaller, more preterm infants, faster rates for larger, less preterm infants) each day up to 3 to 3.5 g/kg/day. Answer B is true, as many preterm infants—especially those born extremely preterm and of extremely low birth weight—have limited lipoprotein lipase activity (and other lipases), limiting their capacity for plasma lipid clearance. Although many use an upper limit of 200 to 250 mg/dL for serum triglyceride concentrations, there is no specific pathology associated with high levels of triglycerides, and they only indirectly indicate that oxidative metabolism of fatty acids released by lipases from triglycerides might be limited. Answer C is true because IV lipids can release sufficient amounts of fatty acids that produce carbon competition with glucose for mitochondrial oxidation, contributing to hyperglycemia. Similarly, hyperglycemia from excess IV dextrose infusion rates and other processes limit fatty acid carbon oxidation and their beneficial effect on energy balance. IV lipid emulsions do not, however, contain carnitine palmitoyltransferase (CPT), the enzyme necessary for transporting long chain fatty acids into mitochondria for oxidation. Milk and preterm formulas do contain reasonable amounts of CPT, indicating that IV nutrition with lipids requires some enteral feeding to allow sufficient fatty acid oxidation for achieving positive energy balance. Answer D is true because advancing IV lipids to 3 to 3.5 g/kg/day is important for providing nonprotein calories, for achieving positive energy balance, and supporting protein synthesis and net protein balance. Answer E is true. IV lipid emulsions do not contain sufficient amounts of docosahexaenoic acid (DHA) to meet normal fetal accretion of this essential polyunsaturated fatty acid (LCPUFA). Even fish oil–based IV lipid emulsions, which do contain some DHA, do not contain enough DHA to produce normal fetal DHA deposition rates. Fetal white adipose tissue accumulation during last trimester of n-3 fatty acid is about 45 to 65 mg/day (mostly as 22:6n-3, or DHA). A 1 kg preterm infant fed human milk containing 3.7 g fat/dL with 0.2% to 0.4% fatty acids as 22:6n-3 (DHA) at an enteral feeding volume of 180 mL/kg/day would receive only 13 to 25 mg 22:6n-3 DHA/day, clearly below normal in utero accretion rates. Preterm infants fed increased 22:6n-3 DHA may have higher visual acuity, particularly at 2 and 4 months, and improved Bayley mental development and MacArthur Communicative inventories at 12 months, but longer term studies have not shown a clear benefit to any aspect of neurodevelopment of supplemental DHA. Thus the current diet for preterm infants is deficient in this essential fatty acid, but the long-term significance of this deficiency is not known, nor is how these infants would develop if fed to sufficiency.