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Parenteral nutrition: Current guidelines
Extrauterine growth retardation is a major clinical problem in preterm infants. Aggressive nutritional interventions may play an important role to fight this prevalent problem. Parenteral nutrition is almost indispensable part of aggressive nutritional approach in neonates, because of certain limitations of enteral route during first few days of life. Formidable research work done in developed world has resolved certain important issues like dosage regimens. However, still we need to resolve quite a few unanswered queries. This is especially true for Indian context where we dea'i with a different population of neonates than the developed world. In this article we will discuss both the resolved and unresolved issues regarding neonatal parenteral nutrition and the research priorities for us.
Unlabelled:
Early enteral nutrition improves growth of extremely low birth weight infants, but growth curves beyond 30 days of life are lacking for such infants receiving early enteral nutrition. Based on the data of all infants born in a 4-year interval with a birth weight <1000 g and surviving for >56 days, we calculated growth rates and weight gain over 120 postnatal days. Infants with major congenital anomalies or necrotising enterocolitis were excluded. Daily weight, weekly length, head circumference and nutritional data were collected until discharge or for maximal 120 days. Curves were calculated in 100 g birth weight intervals, and separately for appropriate for gestational age (AGA) and small for gestational age (SGA) infants. Data were available from 163 infants (birth weight 768 g +/- 153 g; gestational age 26.8+/-1.8 weeks; mean +/- SD) including 55 SGA infants (33.7%). Full enteral feeding was achieved at day 21.7 (+/-10.4). After 12.8% (+/-6.6%) maximal postnatal weight loss at day 7.5 (+/-3.0), birth weight was regained at 14.6 (+/-6.0) days. Mean overall weight gain was 15 g/kg per day with a significantly higher weight gain for SGA than for AGA infants (P <0.05).
Conclusion:
Our early fed infants achieved better weight gain than those recently published receiving late enteral nutrition, but nevertheless fell below the 10th percentile of intrauterine curves. Which postnatal growth is ideal for extremely low birth weight infants infants is unclear. Our growth curves should not be taken as reference curves of a "normal population" but may help to identify infants with growth failure.
To determine current practice in the delivery of parenteral nutrition (PN) in Australian hospitals.
A cross-sectional mail survey.
Acute-care adult hospitals with greater than 200 beds in Australia.
A total of 67 hospitals (65.7% response rate).
Surveys were posted to hospitals. A reminder letter with a second copy of the survey was posted 3 weeks later to non-respondents.
Twenty-seven (40.3%) of the hospitals have a PN team and 50 (74.6%) have a hospital protocol for PN delivery. An inaccessible or non-functional gastrointestinal tract is the most common indicator for commencing PN. Fat infusion is calculated by 24 (38.7%) respondents with a mean (s.d.) maximum amount of fat provided of 2.0 (0.7) g/kg/day. Over half (n=35) reported calculating carbohydrate infusion at a maximum amount of 5.4 (1.0) mg/kg/min. Two-thirds (n=41) reported commencing PN at a rate of 50% or less of goal rate. Blood glucose levels (BGL) were monitored at least once per day by the majority of respondents (n=56, 83.6%). Insulin infusion was commenced at varying BGL. Most respondents (n=40, 59.7%) reported ceasing PN when at least half of the patient's requirements are being met either orally or enterally. A number of practice guidelines were identified and the results of the survey were compared with these guidelines.
Where there are clear practice guidelines, current practice appears to be in line with these recommendations, however, where evidence is lacking, practice is varied.
Routine total parenteral nutrition (TPN) in neonatal care can result in hepatic dysfunction in 40-60% of patients, most commonly as fatty liver, but little work has been conducted on the underlying mechanisms causing hepatic dysfunction.
To use a piglet model for the premature human neonate on TPN, supplemented with lipid emulsions, to investigate hepatic responses.
Piglets were delivered 2 days prematurely. Six control piglets were fed enterally (E), whilst twelve animals were maintained on TPN. TPN piglets received the standard TPN solution plus the lipid emulsion as either ClinOleic(R) (C, n = 6) or Intralipid(R) (I, n = 6). Hepatic lipid content and the fatty acid composition of liver triacylglyercol (TAG) as well as hepatic lipase (HL) activity were determined. Lipoprotein lipase (LPL) activity was measured in the liver, muscle and adipose tissue. The plasma concentrations of choline, bilirubin, TAG and non-esterified fatty acids (NEFA) were also measured.
Liver lipid was significantly increased in piglets on TPN and the tissue fatty acid profiles reflected the lipid emulsion. HL and LPL activities were reduced in liver but LPL increased in adipose tissue during TPN. Plasma concentrations of choline, bilirubin, TAG and NEFA were similar across the treatments.
The results suggest fatty liver occurs in neonates receiving TPN and the source of the accumulated lipid appears to be the lipid emulsion used. The factors regulating lipase activity during TPN require further study. The piglet can be used as a model for neonatal TPN.
The hypothesis that a high-fat parenteral regimen was beneficial for respiratory gas exchanges, in comparison with a high-glucose regimen, was tested in a paired crossover design. Ten parenterally fed newborn infants with no respiratory problems received two 5-day isoenergetic and isonitrogenous regimens that differed in their nonprotein source of energy; the level of fat intake (low fat (LF) 1 gm.kg-1.day-1; high fat (HF) 3 gm.kg-1.day-1) varied inversely with that of glucose. Continuous transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2), respiratory gas exchange (indirect calorimetry), and plasma arachidonate metabolites were measured at the end of each regimen. Oxygen consumption and resting energy expenditure were not affected by modification of the source of energy. However, carbon dioxide production (VCO2) was higher during LF than during HF (6.9 +/- 0.2 vs 6.2 +/- 0.1 ml.kg-1.min-1; p less than 0.01), as was the respiratory quotient (1.08 +/- 0.02 vs 0.96 +/- 0.02; p less than 0.001). Despite the differences in VCO2, the tcPCO2 was not affected, suggesting adequate pulmonary compensation during LF, as documented by the higher minute ventilation (160 +/- 7 vs 142 +/- 5 ml.kg-1.min-1; p less than 0.01). The lower tcPO2 during the HF regimen (73.8 +/- 2.8 vs 68.8 +/- 2.6 mm Hg; p less than 0.015) indicated a disturbance at the alveolocapillary level induced by the lipid emulsion. No differences were found in circulating levels of prostaglandins and thromboxanes. The substitution of glucose for lipid did not modify fat storage (2.1 +/- 0.3 vs 2.1 +/- 0.3 gm.kg-1.day-1). We conclude that the supposed beneficial effect of a fat emulsion on respiratory gas exchange is questionable.
During the first few days of life, the ill premature infant is usually subjected to acute semistarvation because the provision of nutritional support is considered cumbersome and unnecessary. However, the absence of readily recognizable adverse effects of semistarvation does not rule out the existence of significant short-term adverse effects, nor does it rule out possible adverse sequelae in the long run. Similar concerns pertain to the later neonatal period, during which nutritional deprivation is less severe but of longer duration. Evidence is presented that qualitative malnutrition, characterized by inadequate intake of protein and relatively excessive intake of energy, is common with current feeding regimens and is responsible for increased body fat deposition in growing small premature infants.
Hepatic steatosis frequently complicates total parenteral nutrition (TPN). Some of the mechanisms responsible were examined in rats receiving calories as dextrose (CHO-TPN) or dextrose plus lipid emulsion (Lipid-TPN). Hepatic triglyceride content increased approximately threefold after CHO-TPN and twofold after Lipid-TPN (P less than 0.02). Hepatic triglyceride fatty acid composition reflected endogenous synthesis. Hepatic acetyl-Coenzyme A carboxylase specific activity increased fourfold after CHO-TPN and twofold after Lipid-TPN, and it correlated positively with hepatic lipid content (r = 0.82). The activities of the microsomal enzymes of complex lipid synthesis were unchanged in the TPN groups. Both TPN regimens suppressed hepatic triglyceride secretion, measured by the rise in plasma triglyceride and the incorporation of [14C]palmitic acid into plasma triglyceride after intravenous Triton. Hepatic triglyceride secretion correlated negatively with total hepatic lipid content (r = -0.89). CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both. Both adipose and cardiac lipase were higher for Lipid-TPN animals than for CHO-TPN or control animals. Hepatic 14C-triglyceride content was increased in both TPN groups as compared with controls after the injection of 1-[14C]-palmitic acid. This increment was proportional to the decreased hepatic secretion. Triglyceride fatty acid oxidation was significantly suppressed by CHO-TPN, less so by Lipid-TPN. Free fatty acid oxidation was suppressed only by CHO-TPN. The results suggest that the steatosis induced by TPN in rats was due to enhanced hepatic synthesis of fatty acid and reduced triglyceride secretion. Reduced hepatic triglyceride uptake, enhanced fatty acid oxidation, and enhanced peripheral tissue plasma triglyceride lipolysis when CHO-TPN is supplemented with lipid may modulate the accumulation of hepatic triglyceride and, along with reduced synthesis of fatty acid, lead to a lower hepatic triglyceride content.
The aim of this study was to determine the energy expenditure and respiratory quotient (RQ) of ventilated and non-ventilated low birthweight infants during the first five days of life, in order to determine optimal feeding regimens. Eighty six infants, of birthweight less than 1750 g, were grouped according to whether they were artificially ventilated or breathing air spontaneously, and whether they were parenterally or enterally fed at the time of study. Energy expenditure and respiratory quotient were measured during days 1-5 and the relation of energy expenditure to several explanatory variables was investigated using multiple regression analysis. The energy expenditure of ventilated infants was less than that of spontaneously breathing infants; the differences were significant on days 1-3. The respiratory quotient (mean (SE)) was greater in intravenously fed infants compared with milk-fed--0.99 (0.03) v 0.92 (0.01) (P < 0.05), with 42% of studies of infants receiving total parenteral nutrition (TPN) producing an RQ of > 1.0 compared with 16.6% of milk-fed infants (P < 0.01). There was a significant correlation between glucose intake and RQ (r = 0.39, P < 0.001). The activity scores were measured during 75 studies and scores were significantly higher in spontaneously breathing milk-fed infants compared with ventilated parenterally fed infants. Factors independently related to energy expenditure were: postnatal age (P < 0.01); milk feeds (P < 0.01); and physical activity (P < 0.05). A mix of carbohydrate and fat from day 1 may not only meet energy needs but may also reduce respiratory quotient.
To evaluate the incidence and cause of parenteral nutrition-induced lipogenesis.
Retrospective patient review.
A 40-bed predominantly surgical ICU.
One hundred forty patients receiving central venous nutrition and mechanical ventilatory support.
Indirect calorimetry was used to determine patient's measured energy expenditure (MEE) and respiratory quotient (RQ). Additionally total caloric intake (TCAL), glucose infusion rate, basal energy expenditure (BEE), estimated stress factor, and calculated energy expenditure (CEE) were assessed in each patient.
Net fat synthesis was found as RQs exceeded 1 in 47 percent of patients. Statistically significant differences in oxygen consumption, CO2 production, measured energy expenditure, total and carbohydrate caloric intake, and glucose infusion rate were found between groups of patients with an RQ < or = or > 1. Seventy-three percent of patients with glucose infusion rates > 4 mg/kg-min had RQs > 1.
Net fat synthesis was found in a surprisingly large number of critically ill patients receiving central venous nutrition. Many of these patients received carbohydrate calories in excess of their measured energy expenditure, even though it appeared that they needed this level of caloric intake by clinical assessment. The high carbohydrate total parenteral nutrition (TPN) solutions with lipids provided only for prevention of essential fatty acid depletion resulted in an unacceptably high incidence of fat synthesis. The results suggest that caloric intake may be optimized in critically ill patients using indirect calorimetry. When calorimetry is not available, a total caloric intake of up to 140 percent of the BEE with glucose infusion rates not exceeding 4 mg/kg-min and fats providing 40 to 60 percent of calories will meet the energy requirements of most critically ill patients without forcing the RQ > 1.
To determine whether automation could accelerate the parenteral nutrition (PN) ordering and delivery process with concurrent improvements in the quality of nutrition therapy.
The time required to order, process, and deliver PN orders and specific nutrient composition of the PN solution were collected prospectively for 2 weeks on all neonatal intensive care unit (NICU) patients receiving PN during both the manual phase (before automation) and computer phase of the study.
A total of 81 newborn infants in the NICU receiving PN for more than 5 days completed the study.
Student's unpaired t test was used to evaluate differences between computer and manual methods for all outcome variables of interest.
The time required to write and deliver PN orders was significantly lower using computer rather than manual methods (1.4 +/- 0.2 vs 4.5 +/- 0.5 minutes; P = .0001). Significant improvements in the nutrient composition of the PN solution resulted from use of computer ordering for energy (93.4 +/- 1.48 vs 79.2 +/- 1.8 kcal/kg per day; P = .0001), protein (2.92 +/- 0.02 vs 2.7 +/- 0.03 g protein per kilogram per day; P = .0001), calcium (2.3 +/- 0.1 vs 1.8 +/- 0.1 mEq/kg per day; P = .0005), and phosphate (1.3 +/- 0.06 vs 0.9 +/- 0.06 mM/kg per day; P = .0001). In addition, alkaline phosphatase levels improved (272 +/- 11 vs 404 +/- 25 U/L; P = .0001) and caloric and protein goals were achieved sooner (5.9 +/- 0.4 vs 8.7 +/- 0.8 days; P = .0045) when computer ordering rather than the manual method of ordering PN was used.
Our findings indicate that automating the process of writing and delivering PN orders saved time because it eliminated repetitive tasks and tedious calculations previously required of neonatologists, dietitians, and pharmacists. Patient care in our population of neonates was enhanced by improving the nutrient content of the PN solution.
Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels.
Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance.
The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group.
The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.
Paediatric intensive care patients often require parenteral nutrition (PN). Only very few standard mixtures are available for infants and children. Individual PN solutions need to be compounded manually on the ward, if preparation by the hospital pharmacy is not feasible. Since manual compounding is associated with a greater risk of compounding errors and microbial contamination, the use of standard solutions might be a preferable alternative.
We evaluated the use of standard solutions on the paediatric intensive care unit of the von Hauner Children's Hospital at the University of Munich over a period of 8 months. PN solutions were either prescribed individually or as standard solutions. We evaluated the frequency of standard solution prescriptions and their modification, compared nutrient intakes with standard vs. individual PN solutions as well as the occurrence of laboratory anomalies.
Standard PN solutions were prescribed in 68% of cases, individual PN solutions in 32%. Modifications of standard PN solutions were performed in 54%. The intake of a number of macronutrients and electrolytes was similar with individual and standard PN, but calcium and phosphate intakes were lower with individual total PN. Electrolyte imbalances occurred slightly more often with individual PN than with standard PN (34% vs. 26%, respectively).
Standard PN solutions were used in the majority of patients on a paediatric intensive care unit. We did not detect indications for inadequacy of standard solutions in the majority of patients reviewed.
Exposure of parenteral multivitamin solutions (MVP) to ambient light generates peroxides and vitamin loss, and induces initiation of fibrosis and a reduced alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim of the study was to compare modes of delivery of MVP on lung procollagen mRNA and alveolar counts. Three-day-old guinea pig pups were infused continuously with one of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP, except that MVP is given with the lipid emulsion. After 4 days, lungs were prepared for alveolar count (intercept technique) and for quantification of the procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP + MVP than those with AA + MVP. But the two modes of admixture of MVP had the same effect on the alveolar counts, which were lower (P < 0.01) than controls. The mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects against the initiation of lung fibrosis, the absence of a beneficial effect on alveolar counts suggests that these features of lung remodeling are not caused by a unique component of TPN. Specific roles of peroxides, components of MVP, and light exposure on lung remodeling need to be explored before LIP + MVP can be recommended as an alternative mode of parenteral vitamin delivery.
Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding.
We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3h after the end of lipid infusion.
There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high.
Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions.
A neonatal intensive care unit audit of 204 parenteral nutrition (PN) orders revealed a 27.9% PN prescribing error rate, with errors by pediatric residents exceeding those by neonatal nurse practitioners (NNPs) (39% versus 16%; P < 0.001). Our objective was to reduce the PN prescribing error rate by implementing an ordering improvement process. An interactive computerized PN worksheet, used voluntarily, was introduced and its impact analyzed in a retrospective cross-sectional study. A time management study was performed. Analysis of 480 PN orders revealed that the PN prescribing error rate was 11.7%, with no difference in error rates between pediatric residents and NNPs (12.3% versus 10.5%). Use of the interactive computerized PN worksheet was associated with a reduction in the prescribing error rate from 14.5 to 6.8% for all PN orders ( P = 0.016) and from 29.3 to 9.6% for peripheral PN orders ( P = 0.002). All 12 errors that occurred in the 177 PN prescriptions completed using the computerized PN worksheet were due to avoidable data entry or transcription mistakes. The time management study led to system improvements in PN ordering. We recommend that an interactive computerized PN worksheet be used to prescribe peripheral PN and thus reduce errors.
Very preterm infants frequently develop growth failure while in neonatal units. Guidelines for protein and energy requirements have recently been revised to consider the fetal reference related to lean body mass and protein gain, rather than weight gain, with revised protein intakes up to 4.4 g/kg/day at 26 to 30 weeks gestation. To limit growth failure, parenteral nutrition (PN) with relatively high protein and lipid needs to be commenced on day one. Early PN should be accompanied by minimal enteral feeds at 5-20 ml/kg/day with enteral feeds being steadily and carefully increased. Mother's own milk is the feed of choice and fortification schedules need to be revised to better meet new guidelines. Providing early PN and grading of enteral feeds with human milk to full feeds and then fortification to meet revised guidelines should improve growth and development, reduce infection rates and avoid the risks associated with rapid catch-up growth.