Senior Consultant, Department of Neonatology
Centre for Child Health
Sir Ganga Ram Hospital, New Delhi.*
Parenteral Nutrition showed promise to attain better growth and development following its first use in a surgical infant in 60's. Since then significant technological advances have been achieved in
understanding the nutritional needs of newborn infants especially the extremely premature and very low birth weight babies. There remains a lack of agreement on the nutritional requirements of an infant on parenteral nutrition, which have been derived from daily allowances which reflect requirements for healthy neonates. Similarly there is a great variation in
supplementation of vitamins and minerals, even though guidelines for certain minerals and vitamins have been published. Parenteral nutrition administration is not without risk, however if strict protocols are followed and regular monitoring is done, complications can be minimized.
Majority of extremely
low birth weight babies (ELBW) suffer growth lag due to nutritional deficiency in the postnatal periods in NICU. In a recent multicenter study, it was demonstrated that 99% of ELBW infants were below 10th percentile for weight after 10 weeks in the neonatal period (1). However, growth can be improved and protein losses can be minimized by early and appropriate use of PN. Early and aggressive institution of parenteral nutrition with early enteral feeding improves growth outcomes especially in extremely premature infants.
Critically-ill neonates often have extreme degrees of metabolic derangements in protein and energy metabolism characterised by increased protein breakdown which is not entirely suppressed by protein or energy intake. Adequate and optimal nutritional support of the critically-ill neonate under these conditions constitutes a challenging endeavour.
Improved diagnostic & therapeutic services, highly trained medical staff, expensive monitoring, ventilatory support systems and latest antibiotics - all will fail to improve outcomes if nutrition is ignored.
Indications: Any infant who is not likely to be on enteral feeds due to medical or surgical reasons.
- Preterm babies who will not reach full feeds within 3-4 days.
- Full term babies with surgical problems, respiratory problems, necrotizing enterocolitis, or any baby where oral feeds are not possible for > 7 days.
Energy Needs: These are dependent on age, weight rate of growth, thermal environment, activity, hormonal activity, nature of feedings and organ size maturation. Measurement of true basal metabolic rate required prolonged fasting and cannot be ethically be determined in VLBW infants. Therefore resting metabolic rate (RMR) is used to estimate the energy needs. Estimated energy expenditure in a growing preterm infant are as follows:
|Resting energy expenditure
|Occasional cold stress 10
|Fecal loss of energy (10-16% of total intake)
Infants with IUGR have high RMR on weight basis, due to high proportion of metabolically active mass. Any stress including sepsis may increase the metabolic demands. Caloric intake above maintenance is utilized for growth. For each 1gm increment in weight, an infant needs 3 - 4.5 kcal. For a weight gain at a rate of 10 - 15 gm/kg/day the infant would approximately need an additional 45 kcal/kg per day. Energy requirements of infants receiving parenteral nutrition differ from enteral needs in that there are no fecal losses of energy. A preterm infant receiving 50 non protein calories (NPC)/kg/day and 2.5 gm protein/kg/day is able to maintain a positive nitrogen balance and with intake of 70 NPC /kg/day & 2.7 to 3.5 g/kg/day protein intake there is protein accretion and growth rates nearer to in utero levels.
Components of Parenteral Nutrition
Fluids: As per standard guidelines. Consider excessive insensible losses, check urine output, weight loss/gain pattern, electrolytes to monitor daily fluid requirements.
Proteins: Initial goal of PN is to minimize losses and preserve existing body stores, followed by growth. An extremely premature infant loses 1 - 1.5% of body protein per day if they are not supplemented with any protein solutions, where as they should be accumulating proteins at a rate of 2% per day. Amino acid intakes of 1.1 - 2.3 gm/kg/day at caloric intakes of 30 - 50 kcal/kg/day have been shown to be associated with neutral to positive protein balance in VLBW infants. Many studies have demonstrated that early administration of amino acids is not associated with higher BUN, ammonia or abnormal acid base status (2,3,4,5). These studies have also shown that parental amino acids given at a rate of 1.5 - 2.0 gm/kg/day as within hours after birth helps in preserving protein even at low calorie intakes. However increasing caloric intake improves protein accretion.
Begin with 1.0 - 1.5 gm/kg/day with increments of 0.5 gm/kg/day to a maximum dose of 3-3.5 gm/kg/day. 10-20% of the total calories should come from proteins. The 'total caloric' to nitrogen ratio in PN has an impact on the optimal utilization of the carbohydrate calories and nitrogen accretion. In general we want to deliver > 100 non proteins calories per 1 gm of nitrogen, which is the amount of nitrogen found in 2.5 gm of synthetic amino acids. However, clinical observations suggest that infants are in the positive nitrogen balance at 1 gm per day of nitrogen with 50-60 kcal.
Newer amino acid solutions currently available, suit majority of needs of neonates. However certain deficiencies are still there. Glutamine which is abundant in breast milk and is an essential amino acid for premature neonates, is not available in parenteral protein solutions due to stability issues. Other amino acids which are not available in these solutions are tyrosine and cysteine. Many studies have demonstrated that addition of cysteine can improve protein accretion (3,6). Cysteine hydrochloride which can be added just before delivery is available and the current recommendations are to add 40 mg/g of amino acid to a maximum of 120 mg/kg. However, this can result in metabolic acidosis, which can be taken care of by using acetate in parenteral solutions.
No reliable tests are available for routine clinical use to evaluate Amino Acid tolerance. Higher BUN in absence of sepsis, dehydration, shock are suggestive of amino acid oxidation are not an indication to reduce amino acid intake. Low BUN < 5-10, is suggestive of low protein intake. Serum ammonia levels are not very useful in deciding about amino acids in TPN. Hence there is no role for routine ammonia levels when baby is on TPN.
Energy: There are two aims of providing energy. Initially, to give enough calories to match rates of energy expenditure followed by allowance for growth. The caloric need by parenteral nutrition is less, energy loss through stools is not there, which is 10 -16% of total energy intake. To support growth an additional 20 - 25 kcal/kg/day are required above the baseline requirements which are 70 - 80 kcal/kg/day. This would mean 90 - 100 kcal/kg/day for VLBW and 105 - 110 kcal/kg/day for ELBW. However, a parenteral intake of 80 - 90 kcal/kg/day is enough for term babies.
Carbohydrates: It is supplied in parenteral nutrition as dextrose, one of the isomers of glucose, which provides 3.4 cal/gm. Ideally 50-70% of the total calories should come from dextrose. The goal of glucose administration is to provide energy particularly to tissues dependent on glucose for energy (e.g. the brain). Always calculate the glucose infusion rate (GIR) in IV fluids and do not start fluids as 10 % dextrose, 7.5 % dextrose, etc. Avoid rapid bolus of dextrose and always maintain continuous infusion with the help of infusion pump. Minimal Glucose requirement in term and preterm babies is 4mg and 6mg/kg/min respectively, which may be as high as 8 - 10 mg /kg /min in ELBW babies. Increase glucose infusion rate (GIR) daily by 1-2 mg / kg / min, as the baby tolerates. GIR of 4 - 7 mg/kg/min (70 - 110) ml/kg/day of 10 % dextrose is appropriate in most infants and a gradual increase over next one week up to 12-17 mg / kg / min is usually well tolerated. An infusion rate of more than is 18 mg / kg/ min which is the maximum oxidative capacity, results in lipogensis and may lead to fatty liver.
Blood sugar should be maintained above 50 mg/dl and below 150 - 200 mg/dl. If less than 50 mg/ dl, then increase the rate of glucose infusion by 1-2 mg/kg/min. Once stabilized, in babies at risk of hypoglycemia gradually, taper glucose infusion over 12 to 24 hours as enteral feeds are tolerated. Hyperglycemia is more problematic in VLBW babies. Almost 40% of VLBW infants may develop at least one episode of hyperglycemia during first week of life (7). If blood glucose is more than 150-180 mg / dl range, then decrease glucose delivery (not below 3-4 mg / kg/ min), evaluate for infections and especially in ELBW babies start insulin drip.
Insulin and PN: The use of insulin in infants who do not tolerate even moderate glucose infusion rates is controversial. In a RCT by (8), it was demonstrated that infants receiving insulin to improve glucose infusion rates showed better weight gain without any increase in length and head size. This may suggest an increase in fat size without simultaneous increase in lean tissue due to lipogensis. This may also be associated with lactic acidosis. With the currently available evidence routine use of insulin to improve glucose tolerance to achieve better weight gains is not recommended. However, infants with hyperglycemia despite very low GIR may be administered insulin infusion starting at rate of 0.05 units / kg /hour for short period, strictly monitoring blood glucose.
The maximum allowable GIR of 13 - 17 mg/kg/min would provide a caloric intake of 45 - 60 kcal/kg/day. To meet the total calorie requirement, the rest of non-protein calories should come from lipids. Appropriate ratio of non protein calories i.e. carbohydrate : fat ratio (60 : 40) also improves overall protein accretion.
Lipids: Intravenous lipids have the highest caloric density of any component of parenteral nutrition. IV lipids have three components: triglycerides, phospholipids for emulsification and glycerol to achieve isotonicity. Most of the commercially available IV lipids have long chain triglycerides (LCT). Some preparations used in Europe include medium chain triglycerides (MCT). Some studies suggested that the LCT acids may be potentially immunosuppressive when either administered rapidly or in large quantities. However, recent studies have indicated that with MCT predominant IV lipids protein accretion may not be as effective as with LCT. IV lipids contain lipid particles similar to chylomicrons which are hydrolyzed into free fatty acids by Lipoprotein lipases, which are deficient in preterm babies. Heparin induces release of lipoprotein lipases from the endothelium into the circulation, however routine addition of heparin in the IV lipids is not recommended. A minimum of 0.5 - 1.0 gm/kg/day of lipids is needed to avoid deficiency of essential fatty acids, which may develop over 72 hrs period of deprivation.
How early to use IV lipids: Early introduction of lipids on first day in VLBW babies is not associated with acute metabolic derangements (9). Earlier concerns about the association of increase in mortality and higher incidence of bronchopulmonary dysplasia have also been refuted by meta analysis of six RCTs. (10). The current recommendation is to start lipids on first day of life at 1gm / kg/ day & then increase by 1 gm / kg /d with max dose of 3-3.5 gm / kg / day. Lipid clearance is better when given slowly over 24 hrs. Infusion rate of more than 0.25 g/kg/hour may be associated with decrease in pO2. (11). Serum triglycerides levels are monitored to check for lipid intolerance, which are usually maintained below 150 - 200 mg/dl, between 200 - 300 mg/dl reduce the delivery of IV lipids till levels are below 200.
IV Lipids: are available in two concentrations 20% and 10%. Lipid clearance is better with 20% solutions which has half the amount of phospholipids emulsifier relative to same amount of triglycerides. For this reason 20% lipid solutions should preferably be used. Some 10% lipid emulsions (PLR - phospholipids reduced) with half the amount of phospholipids have been introduced which are also equally well tolerated.
Vitamins and Trace elements
Vitamin supplementation should start as soon as protein is added to the TPN. Water soluble vitamins act as co-enzymes in carbohydrate and protein metabolism and cannot be stored in the body (except vitamin B12). Vitamin D requirements are 400 IU per day though studies have shown even 30 IU / kg / per day to be effective in preventing osteopenia of prematurity. Vitamin A (requirement 1600 IU/day) is usually low in commercially available pediatric vitamin preparations and intramuscular vitamin A may reduce incidence of chronic lung disease. In India IV pediatric vitamin solutions are not available. Adult vitamin solutions can be used with caution as the Vitamin A and D levels are higher than recommended and there is no Vit. E in the adult preparation.
Trace elements would be required if the baby is to remain on TPN and nil orally for more than a few days. Commercially available solution CelCel of 3 varieties (3 / 5 / 7 trace elements) is available. Dose 1 ml / 100ml. In babies with cholestasis (direct bilirubin > 2.5 mg / dl) the trace element solution needs to be discontinued.
- Daily Na, K, Cl, Ca, BUN, Creatinine initially, then once a week
- Maintain Blood gas base deficit less than -6
- Liver function tests every 2 weeks (SGOT / SGPT / Alk.Phosphates / bilirubin / Albumin)
- No routine Tests for protein intolerance, BUN < 10 suggests insufficient proteins. BUN in 50s, check for Dehydration or sepsis, do not decrease Amino Acids in TPN.
- Maintain Triglyceride levels of <150-200 mg / dl (do not stop the IL infusion to do the test)
- Continue growth monitoring-weight, head circumference and length.
All neonatologists must realize that any baby who can not be delivered full enteral feeds in next 3 - 4 days, must be started on parenteral nutrition. Protein and lipids should be started on first day. There is no evidence to suggest that slow increase in these constituents is better than rapid increments. Vitamins should be added as soon as proteins are added and trace element in those who need PN for more than 1 - 2 weeks.
- Lemons JA, Bauer CR, Oh W, etal: Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. Pediatrics 2001;107: E1
- Paisley JE, Thureen PJ, Baron KA, Hay WW: Safety and efficacy of low versus high parenteral amino acids in extremely low birth weight neonates immediately after birth. Pediatr Res 2000:293A
- Rivera A, Bell EF, Bier DM: Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life. Pediatr Research 1993; 33:106-111
- Saini J, Macmahon P, Morgan J, Kovar I: Early parenteral feeding of amino acids. Arch Dis Child 1989;64:1362-1366
- Van Lingen RA, Van Goudoever JB, Luijendijk IHT etal: Effects of early amino acid administration during total parenteral nutrition on protein metabolism in preterm infants. Clin Sci 1992;82:199-203
- Poindexter B, Wright-Coltart S, Denne SC: The effect of N-acetyl tyrosine and cysteine in parenteral nutrition on protein metabolism in extremely low birth weight neonates. Pediatr Res. 2000;47:294A
- Wilson DC, Cairns P, Halliday HL etal: Randomised controlled trial of an aggressive nutritional regimen in sick very low birth weight infants. Arch Dis Child Fetal Neonatal Ed: 1997;177:4F-11F
- Collins J, Hoppe M, Brown K etal: A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance. J Pediatr. 1991;118:921-927
- Mudrock N, Crighton A, Nelson L, Forsyth J: Low birth weight infants and total parenteral nutrition immediately after birth. II. Randomized study of biochemical tolerance of intravenous glucose, amino acids, and lipids. Arch Dis Child Fetal Neonatal Ed. 1995;73:8F-12F
- Fox GF, Wilson DC, Ohlsson A: Effects of early versus late introduction of intravenous lipid to preterm infants on death and chronic lung disease: Results of meta-analysis. Pediatr Res. 1998;43:214A
- Brans Y, Dutton E, Andrew D: Fat emulsion tolerance in very low birth weight neonates: Effect on diffusion of oxygen in the lungs and on blood pH. Pediatrics 1986;78:79-84
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