AIIMS- NICU protocols 2008 Parenteral nutrition Deepak Chawla, Anu Thukral , Ramesh Agarwal, Ashok Deorari, Vinod K Paul Division of Neonatology, Department of Pediatrics All India Institute of Medical Sciences Ansari Nagar, New Delhi –110029 Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Address for correspondence: Dr Ashok K Deorari Professor Department of Pediatrics All India Institute of Medical Sciences Ansari Nagar, New Delhi 110029 Email: [email protected] ABSTRACT Nutritional insufficiency, leading to early growth deficits has long-lasting effects, including short stature and poor neurodevelopmental outcomes. Early enteral feeding is commonly limited by immaturity of gastrointestinal motor function in preterm neonates. To ensure that a stressed premature infant receives an adequate but not excessive amount of glucose, the amount of carbohydrate delivered in the form of dextrose is commonly initiated at the endogenous hepatic glucose production and utilization rate of 4 to 6 mg/kg/min; and 8 to 10 mg/kg/min in ELBW infants. The early provision of protein is critical to attain positive nitrogen balance and accretion as premature babies lose ~1% of their protein stores daily. Aminoacid can be used at concentrations of 3-3.5g/kg/day and lipid at 3.5-4g/kg/day as long as the fat intake remains less than 60% of nonprotein calories. Sodium, potassium, chloride, calcium, magnesium and phosphorus need to be provided in PN solution as per their daily needs. Hospital-acquired infection (HAI) is a major complication of PN. All efforts should be made to avoid it. KEY WORDS Parentral nutrition neonates, lipid, glucose, aminoacids, non protein calories Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 The goal of nutrition management in neonates, especially very low birth weight (VLBW) infants is the achievement of postnatal growth at a rate that approximates the intrauterine growth of a normal fetus at the same postconceptional age. Although, this is best achieved with optimal enteral nutrition, early enteral feeding is commonly limited by immaturity of gastrointestinal motor function, manifested principally as delayed stomach emptying, gastro-esophageal reflux, abdominal distension, and infrequent stooling. Nutritional insufficiency, leading to early growth deficits has long-lasting effects, including short stature and poor neurodevelopmental outcomes (Table 1)1. Likewise, establishing an alternative source of nutrition becomes a life-sustaining intervention in surgical neonates with congenital or acquired disease causing gastrointestinal failure. Parenteral nutrition (PN), first introduced in the late 1960s, has been used extensively in neonatal intensive care units (NICU) of developed countries. With improving survival of extremely premature neonates and increasing number of NICUs in India, need of parenteral nutrition is being widely recognized among health care providers. This recognition of need is accompanied by the fact that with availability of optimum nutrient sources, early administration of PN is now both safe and efficacious. Table 1: Consequences of suboptimal nutrient intake1 Short term Long term • Increased vulnerability to infections • Poor growth • Free-radical mediated damage • Poor neurodevelopment outcome • Greater need of ventilator support • Susceptibility to cardiovascular diseases • Reduced cell growth in specific organ systems (heart, kidney, pancreas) Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Indications PN should be considered in neonates who are not on significant enteral feeds for more than 3-5 days or are anticipated to be receiving less than 50% of total energy requirement by day 7 of life (Table 2). Table 2: Indications of parenteral nutrition Indications of parenteral nutrition • Birth weight less than 1000 gm • Birth weight 1000-1500 gm and anticipated to be not on significant feeds for 3 or more days • Birth weight more than 1500 gm and anticipated to be not on significant feeds for 5 or more days Surgical conditions in neonates: Necrotizing enterocolitis, Gastroschisis, Omphalocele, Tracheo-esophageal fistula, Intestinal atresia, Mal-rotation, Short bowel syndrome, and Meconium ileus Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Energy Determination of appropriate energy and nutritional requirements of a newborn infant is the first step in formulating PN. Preterm infants have very low energy reserves due to low amounts of fat as well as low glycogen reserves. Cessation of placental nutrient supplies and low reserves results in ‘metabolic shock’ and protein catabolism if appropriate amounts of energy and proteins are not provided soon after birth.2 A daily energy intake of 120-130 kcal/kg is needed to meet the metabolic demands of a healthy premature neonate and to allow for growth rate comparable to intrauterine growth rate (Table 3)3. Energy requirement of term neonate is 100-120 kcal/kg/day. Energy intake of sick neonates (e.g. acute respiratory illness, chronic lung disease, necrotizing enterocoliltis) is not exactly known but is likely to be near upper limits of the energy requirement of preterm infant.3 Table 3: Daily energy intake recommended for preterm infants3 Committee Recommended energy intake (kcal/kg/day) American Academy of Pediatrics 105-130 Canadian Pediatric Society 105-135 European Society of 98-128 Gastroenterology and Nutrition Life Sciences Research Office 110-135 10% dextrose solution provides 0.34 kcal/ml. 10% lipid solution provides 0.9 kcal/ml and 20% lipid solution provides 1.1 kcal/ml. If sufficient amount of non-protein energy is not provided, amino acids are catabolised for energy production. Adequate balance between nitrogen and non-protein energy sources (Protein/Energy ratio: 3-4 gm/100 kcal) is needed to promote protein accretion.2 Balance between carbohydrates and fat is needed to prevent excessive fat deposition and excessive production of CO . The 2 ideal distribution of calories should be 50-55% carbohydrate, 10-15% proteins and 30- 35% fats. Amino acids Amino acids (AA) are building blocks of the body. The amount needed, calculated using ‘factorial approach’ is 3.0-3.5 gm/kg/day (0.3 gm/kg/d to mimic intrauterine changes in body composition + 2.2 to 2.5 gm/kg/d for normal growth + 1 gm/kg/d obligatory urinary and dermal protein loss). An optimal AA solution should contain essential (valine, leucine, isoleucine, methionine, phenylalanine, threonine, lysine and histidine) and conditionally essential (cysteine, tyrosine, glutamine, arginine, proline, glycine and taurine) AAs, should not have excess of glycine and methionine and should not contain sorbitol. AA infusion can be started between 0 and 36 h of birth. The amount started on day 1 of PN has varied from 0.5 to 3.0 gm/kg/d in different Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 studies. To avoid negative protein balance, one should start with at least 1 to 1.5 gm/kg/d and then increase by 1 gm/kg/d to maximum of 3.5 gm/kg/d. With this regimen, there have been no reports of side effects like metabolic acidosis, hyperaminoacidemia, azotemia or hyperammonaemia.1 Studies in preterm babies who receive TPN suggest that protein accretion occurs by amino acid stimulation of protein synthesis rather than by suppression of protein breakdown.4, 5 Protein requirements for the neonate tend to be inversely related to gestational age and size due to more rapid growth rates and greater protein losses in the smaller, more premature infants.6 The early provision of protein is critical to attain positive nitrogen balance and accretion, as premature babies lose ~1% of their protein stores daily.7 Benefits include improvement in nitrogen balance, stable plasma AA profile and better growth in neonatal period. AA solutions are available as 10% and 20% preparations (appendix). Carbohydrates Carbohydrates are the main energy substrate for the neonates receiving PN. Although, glucose is routinely administered to VLBW infants beginning soon after birth, the main objective of this established practice is to maintain euglycemia. During PN, glucose infusion rate is gradually advanced and objective is the achievement of higher energy intake. Glucose is available as 5%, 10%, 25% and 50% solutions. To ensure that a stressed premature infant receives an adequate but not excessive amount of glucose, the amount of carbohydrate delivered in the form of dextrose is commonly initiated at the endogenous hepatic glucose production and utilization rate of 4 to 6 mg/kg/min; and 8 to 10 mg/kg/min in ELBW infants. It provides 40 to 50 kcal/kg/d and preserves carbohydrate stores. Frequently smaller, more unstable premature infants develop hyperglycemia due to decreased insulin production and insulin resistance. Glucose infusion rates (GIR) for these babies may need to be limited to 4 mg/kg/min or less, while larger preterm infants or term infants can often tolerate up to 8 mg/kg/min initially.8, 9 Once the GIR supports acceptable serum glucose values, it is advanced in a gradual, stepwise fashion (0.5 to 1 mg/kg/min) to a suggested maximum glucose oxidative rate for neonates of 12 to 13 mg/kg/min to support growth and maintained there unless serum glucose values change significantly. Excessive carbohydrate delivery above the amount that can be oxidized for energy and glycogen storage will lead to an increase in basal metabolic rate,10 fat deposition, cholestasis,11 hepatic steatosis,12 or overfeeding.. Insulin has been used along with glucose to serve two distinct purposes. One is to manage hyperglycemia if infant is developing high glucose levels despite glucose infusion rate of 4-6 mg/kg/minute. In this case, insulin is stopped as soon as euglycemia is achieved. Second objective is to achieve higher glucose infusion rate and promote growth. Later approach does not result in increased AA accretion, can induce lactic acidosis and is therefore not recommended.13 Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Lipids Lipids are essential components of parenteral nutrition for preterm infants to provide essential fatty acids (EFAs) and to meet high energy needs. Parenteral lipids are an attractive source of nutrition in the first postnatal days because of their high energy density, energy efficiency, isotonicity with plasma, and suitability for administration through a peripheral vein. Parenteral lipid emulsions enable the delivery of fat-soluble vitamins. Even a short delay of 3 to 7 days in supplying lipids to parenterally fed preterm infants leads to biochemical EFA deficiency.14 Such deficiency increases antioxidant susceptibility in preterm infants. EFA deficiency can be prevented with introduction of as little as 0.5 to 1.0 g/kg per day of lipid infusion. Fluid-restricted, growth-compromised patients or those limited to peripheral line access may require as high as 3.5 to 4 grams fat/kg/d to achieve adequate energy for growth and protein sparing. This intake is appropriate as long as the fat intake remains less than 60% of nonprotein calories.15 The routine use of intravenous lipid (IVL) emulsions has not been universally accepted in critically ill, ventilated VLBW infants because of potential complications like adverse effects on gas exchange and displacement of bilirubin from albumin. Proper use of IVL emulsions includes slow infusion rates (<0.15 g/kg per hour), slow increases in dosage, and avoidance of unduly high doses (>3.0 g/k per day). Studies have shown that administration of IVLs, beginning on day 1 at a dose of 1.0 g/kg per day and increasing in stepwise fashion to 3.0 g/kg per day by day 4, has been well tolerated without noticeable adverse effects. Consider avoiding lipids for a short period in the unstable, late preterm infant who has evidence of increased PVR. Lipids may be restricted in patients with hyperbilirubinemia in minimum amounts that will provide only the essential fatty acids. Because both lipids and bilirubin are transported in the blood by albumin, lipids competing for binding sites on albumin may result in insufficient binding of bilirubin to facilitate excretion.16 Persistently high bilirubin values may increase the risk of kernicterus from the deposition of bilirubin in brain cells. A free fatty acid to albumin ratio (FFA:albumin) greater than 6:1 is thought to be clinically significant. IVL emulsions are aqueous suspensions containing neutral triglycerides derived from soybean, safflower oil, egg yolk to emulsify and glycerine to adjust tonicity. Hydrolysis of triglycerides by hepatic and lipoprotein lipase results in formation of free fatty acids. IVL emulsions are available in two strengths: 10% and 20% (Appendix). Use of 20% lipid emulsion is preferable to a 10% solution to decrease the risk of hypertriglyceridemia, hypercholesterolemia, and hyperphospholipidemia (Figure 1). When lipids are exposed to light, they form potentially toxic lipid hydroperoxides. Hence lipid syringes and tubing should be covered by wrapping it in aluminum foil. Lipids may be restricted in patients with hyperbilirubinemia in minimum amounts that will provide only the essential fatty acids. Some clinicians will reduce or withhold lipids if rising bilirubin trends approach levels requiring exchange transfusions. Because both lipids and bilirubin are transported in the blood by albumin, lipids competing for binding sites on albumin may result in insufficient binding of bilirubin to facilitate excretion.16 Persistently high bilirubin values may increase the risk of kernicterus from the deposition of bilirubin in brain cells. A free fatty acid to albumin ratio (FFA:albumin) greater than 6:1 is thought to be clinically significant. Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Figure 1: Metabolism of intravenous lipid emulsions. Lipoprotein X inhibits the clearance of remnant particles Minerals Sodium, potassium, chloride, calcium, magnesium and phosphorus need to be provided in PN solution as per their daily needs. Except phosphate, all these minerals are easily available in India. Sodium, potassium, and chloride are essential to life and requirements are dependent on obligatory losses, abnormal losses, and amounts necessary for growth. Estimated and advisable intakes are based on accretion studies and urinary and fecal losses from balance studies completed in the late 1970s. 17 Calcium, phosphorus, and magnesium are the most abundant minerals in the body. They are closely interrelated to each other in metabolism, the formation of tissue structure, and function. Downloaded from www.newbornwhocc.org AIIMS- NICU protocols 2008 Table 4: Daily requirement of minerals Mineral Requirement Sodium 0-3 meq/kg/d (1st week of life) 3-6 meq/kg/d (beyond 1st week) Potassium 0-2 meq/kg/d (1st week of life) 1-3 meq/kg/d (beyond 1st week) Chloride 2-3 meq/kg/d Calcium 150-200 mg/kg/day Magnesium 15-25 mg/d Phosphate 20-40 mg/kg/d Vitamins Vitamins are added in PN solution to meet the daily requirement (Table 5). Separate preparations of fat-soluble and water-soluble vitamins suitable for neonates are not available in India. Multivitamin injection (MVI), when added in a dose of 1.5 ml/kg to AA-glucose solution meets the need of vitamin A and most other vitamin. Furthermore, intravenous vitamin delivery may be less due to photodegradation of vitamins A, D, E, K, B , B , 2 6 B , C, and folic acid and adsorption of vitamins A, D, and E into the vinyl delivery bags and 12 tubing. Vitamin K needs to be given separately as weekly intramuscular injections. Although vitamin B is not present in MVI, its deficiency is not manifested unless the 12 neonate is on long-term PN.. Table 5: Recommended vitamin intake Vitamin Term (daily Preterm dose) (dose/kg/day) Vitamin A (IU) 2300 1640 Vitamin D (IU) 400 160 Vitamin E (IU) 7 2.8 Vitamin K (µg) 200 80 Vitamin B6 (µg) 1000 180 Vitamin B12 (µg) 1 0.3 Vitamin C (mg) 80 25 Biotin (µg) 20 6 Folic acid (µg) 140 56 Niacin (mg) 17 6.8 Pantothenic acid 5 2 (mg) Riboflavin (µg) 1400 150 Thiamin (µg) 1200 350 Downloaded from www.newbornwhocc.org