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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.
Newborn infants (n = 26), subdivided into three groups in which only the nonprotein energy was manipulated, were studied during continuously administered total parenteral nutrition. Nonprotein energy intake was provided as a glucose/fat mixture, and fat energy represented 18% (group A), 29% (group B), and 40% (group C). Energy expenditure and substrate utilization were measured by indirect calorimetry during a 6-h period. Other analyses included 24-h urinary nitrogen excretion, glycemia, and lipid profile. The results showed that glucose oxidation increased with increasing total glucose intake (p < 0.05). Net fat oxidation was observed in all groups and increased with increasing percentage of energy infused as fat. The maximal oxidative glucose disposal rate observed was in group A (11.2 g/kg/d). Maximal fat oxidation observed was in group C (2 g/kg/d), in which energy delivered by fat represented 40%. This group was more energy efficient than the others. Oxygen consumption was not affected by modification of the source of energy, but carbon dioxide production was higher in group A (p < 0.05), as was the nonprotein respiratory quotient (p < 0.05). Despite differences in carbon dioxide production, arterial capillary PCO2 was not affected and, together with the higher (p < 0.05) minute ventilation, suggests that adequate pulmonary compensation occurred during the low-fat regimen. Arterial capillary PO2 was lower during the high-fat regimen (p < 0.05). Protein oxidation was greater in group A (1.14 +/- 0.32 g/kg/d) than in group B (0.70 +/- 0.21 g/kg/d) or group C (0.78 +/- 0.28 g/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS)
No body weight curves are available for preterm infants < 1000 g birth weight receiving early enterai and parenteral nutrition. Postnatal weight changes of 136 infants with a birth weight < 1000 g were analysed retrospectively. Body weight curves for the first 30 days of life were generated for five separate birth weight groups (430–599 g, 600–699 g, 700–799 g, 800–899 g, 900–999 g). All infants had received intravenous glucose and amino acids from day 1 and intravenous lipids from day 2. Enterai feeding was started on day 1. Thus caloric intake (±SD) was advanced to 384 ± 46 kJ/kg per day (92 ± 11 kcal/kg/day) in the 1st week of life. In 136 preterm infants mean postnatal weight loss was 10.1% ± 4.6% of birth weight, birth weight was regained at a mean postnatal age of 11 ± 3.7 days, but significantly earlier (7.8 ± 3.5 days) in the lowest compared to the highest weight group. Mean subsequent weight gain was 15.7 ± 7.2 g/ kg per day. This was accomplished by exclusive enterai nutrition from day 20 (median).
Conclusion
At time of diagnosis, patients with primary ciliary dyskinesia have partially reversible obstructive airway disease. During regular follow up and therapy, there is no evidence of a further decline in lung function. Patients with associated immunodeficiency or important damage at the start of therapy may have a worse prognosis.
Protein intake is frequently delayed in ill neonates because of concerns about their ability to metabolize substrates.
We aimed to determine the factors affecting protein balance in ventilated, parenterally fed newborns during the first week of life.
Leucine kinetic studies were performed in 19 neonates by using the [1-(13)C]leucine tracer technique after 24 h of a stable total parenteral nutrition (TPN) regimen. TPN intakes were prescribed by rotating attending physicians, enabling assessment of protein metabolism over a range of clinically used nutrient intakes.
Mean (+/-SD) birth weight was 1.497 +/- 0.779 kg, gestational age at birth was 30.3 +/- 4.0 wk, and age at study was 3.9 +/- 1.4 d. Amino acid intakes (AAIs) ranged from 0.0 to 2.9 g x kg(-1) x d(-1). Based on leucine kinetic data, protein balance was calculated as the difference between protein synthesis and catabolism. By multiple regression analysis, AAI was the only predictor associated independently with protein balance (P < 0.01); energy intake, lipid intake, glucose intake, birth weight, and gestational age were not. Both leucine oxidation and nonoxidative leucine disposal rates were significantly correlated with leucine intake (P < 0.0005 and P < 0.01, respectively). Of the 12 infants with AAIs > 1 g x kg(-1) x d(-1), only 1 infant was significantly catabolic (protein balance <-1 g x kg(-1) x d(-1)). There was no evidence of protein intolerance as determined by elevated creatinine (69 +/- 31 micromol/L), plasma urea nitrogen (6.7 +/- 2.53 mmol/L), or metabolic acidosis (pH: 7.36 +/- 0.05).
Ill neonates can achieve a positive protein balance in the first days of life without laboratory evidence of protein toxicity.
The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies.
To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis).
Large, multicenter, prospective cohort study.
Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol.
Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings.
These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.
This study aimed to compare nitrogen balance and biochemical tolerance of early aggressive versus late total parenteral nutrition in very-low-birth-weight (VLBW) infants over the first week of life.
In all, 32 ventilator-dependent preterm infants were prospectively randomized into two groups. The Early Total Parenteral Nutrition (ETPN) group received 3.5 g/kilo-day amino acids (AA), and 3 g/kilo-day of 20% Intralipid (IL), starting within 1 hour after birth. The Late Total Parenteral Nutrition group (LTPN), started on a solution containing glucose during the first 48 hours of life, followed by 2 g/kilo-day of AA and 0.5 g/kilo-day of IL. For the LTPN group AA and IL were each increased by 0.5 g/kilo-day to a maximum of 3.5 and 3 g/kilo-day, respectively.
Nitrogen retention was significantly greater in all infants in the ETPN group throughout the 7-day study period. All infants in the LTPN group were in negative nitrogen balance during the first 48 hours of life, while those in the ETPN group were in positive nitrogen balance throughout. The mean (+/-SD) nitrogen retention in the ETPN was 384.5 mg/kilo-day (+/-20.2), compared to 203.4 mg/kilo-day (+/-20.9) in the LTPN group (p <0.001). In each of the first 5 days of life, energy intake was significantly greater in the ETPN group compared to the LTPN group (p <0.001). Mean fluid intake during the study period was similar between, the ETPN and the LTPN groups (162 and 165 cm3/kilo-day, respectively). The mean weight gain was similar in the ETPN and LTPN groups. Plasma levels of cholesterol, triglycerides, bicarbonate, blood urea nitrogen, creatinine, and pH were similar in both groups during the study period. Mean (+/-SD) serum glucose in the LTPN group was higher, but remained in normal range (101.1+/-5.2 and 80.8+/-5.4 mg/kilo-day, respectively). The mean peak serum bilirubin was significantly higher in the ETPN group, compared to The LTPN group (7.7 and 6.2 mg/dl).
This study shows that aggressive intake of AA and IL can be tolerated immediately after birth by VLBW infants. Also, ETPN significantly increased positive nitrogen balance and caloric intake, without increasing the risk of metabolic acidosis, hypercholesterolemia, or hypertriglyceridemia.
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.
Background:
Early nutrition intervention, both parenteral and enteral, is becoming a standard of care for the extremely low-birth-weight infant (ELBW; <1,000 g) in many neonatal intensive care units (NICU) across the United States. However, there are no published or widely accepted guidelines regarding nutrition support strategies for this population. Most NICU clinicians have developed their own guidelines, so nutrition practices vary widely. In an effort to standardize our practice, we implemented nutrition support guidelines for ELBW infants, initiating both parenteral nutrition (PN) and minimal enteral feedings (MEFs) within the first 24 hours of life, whenever possible. The purpose of this study was 2-fold: (1) to evaluate the adherence to the nutrition guidelines and (2) to compare pre- and postguideline outcomes such as time to regain birth weight, time to reach full enteral feedings, and average daily weight gains.
Methods:
The study was conducted at a level III NICU from January 2002 until February 2003. Charts of 70 infants with a birth weight <or=1,250 g were reviewed as part of a quality-assurance project to monitor adherence to the newly established guidelines. Another 23 charts of ELBW infants who were admitted and cared for in the NICU before the initiation of the nutrition guidelines were reviewed as a control group. Data collected from the charts included the hour of life PN and MEFs were started, the day of life infants reached full enteral feedings, infant weights for the first 4 weeks of life, incidence of early hyperglycemia, occurrence of necrotizing enterocolitis, and length of neonatal birth hospital stay. Student's t-tests were used to compare clinical outcomes between infants receiving early nutrition support (<or=24 hours of life) vs those who were started later.
Results:
Of eligible infants, 82.6% began receiving nutrition support within 24 hours of life. The average time to begin PN was 22 hours after the adoption of the guidelines vs 64.4 hours before guideline implementation (p < .01). In the postguideline group, MEFs were initiated at mean 27.1 hours of age vs 80.4 hours in the preguideline group (p < .01). Those who were started on early nutrition support reached full enteral feedings significantly sooner than those who received delayed nutrition support (12.7 days vs 45.8 days; p < .01). Early nutrition support also resulted in earlier regain of birth weight (day 13.3 vs 15.4 days, p < .05). Although not statistically significant, infants who received earlier nutrition support showed trends toward greater overall weight gain in weeks 3 and 4 of life and a lower incidence of elevated serum blood glucose.
Conclusions:
The implementation of early nutrition support guidelines influenced the timeliness of initiating nutrition support in our unit. Early initiation of nutrition support in ELBW infants produces a rapid regain of initial weight loss, improves weight gain, and enhances earlier achievement of full enteral feedings.
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.
Aggressive parenteral nutrition (PN) including amino acids is recommended for low-birth-weight infants to prevent energy and protein deficit. Their impact on acid-base homeostasis has not been examined.
We investigated the impact of dose and duration of parenteral amino acids, with cysteine, on acid-base parameters in 122 low-birth-weight infants. Premature infants <or=32 weeks, <or=1850 g, and receiving parenteral amino acids at 1.5 g/kg/d for an extended period (>24 hours), or 3 g/kg/d for a short (5 hour), extended (24 hour), or prolonged (3-5 days) duration were included in the study. Data were obtained at age 0-3 days (n = 43) or, when clinically stable, age 3-5 days (n = 49). Data from 30 infants, matched for birth weight and gestational age, receiving PN during the first 5 days after birth were also obtained. Acidosis was defined as pH <7.25.
Acidosis was evident in all infants between 2 and 5 days after birth. Infants with large patent ductus arteriosus (PDA) exhibited significantly (p < .05) lower pH early, had higher blood urea nitrogen levels (26 +/- 9 vs 18 + 8 mg/dL; p < .05), and had greater weight loss ( approximately 17% of birth weight) when compared with infants without PDA. Gestational age, weight loss, and patent ductus arteriosus accounted for 65% of variance in acidosis.
Low-birth-weight infants develop metabolic acidosis between 2 and 5 days after birth, irrespective of dose and duration of parenteral amino acid administration. Careful management of parenteral fluids and comorbidities may lower the incidence of acidosis and promote protein accretion.
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.
1. We investigated the effects of starting amino acid administration on post-natal day 2 on protein turnover and nitrogen balance in appropriate-for-gestational-age, very-low-birth-weight infants. Eighteen infants were divided into two groups. Group A received from day 2 onwards an amino acid solution, whereas group B started on this solution after day 4. Both groups were exclusively parenterally fed, 200 kJ day−1 kg−1 on post-natal days 3 and 4. Group A (birth weight 1.5 ± 0.3 kg) received 4.6 g of glucose, 1.9 g of fat and 2.3 g of amino acids day−1 kg−1 body weight. Group B (birth weight 1.4 ± 0.2 kg) received 7.0 g of glucose and 1.9 g of fat day−1 kg−1 body weight.
2. At post-natal day 3, a primed constant infusion of 3 mg of [15N]glycine day−1 kg−1 was given. Protein flux, protein synthesis and protein breakdown were calculated from the 15N enrichment in urinary ammonia. In five out of nine infants in group B no plateau of 15N enrichment in urinary urea could be detected, whereas in group A two out of nine infants did not reach a plateau. For this reason we did not use the end product urea for our calculations.
3. The administration of the amino acids resulted in a higher protein flux (6.9 ± 1.5 g day−1 kg−1 versus 5.2 ± 0.9 g day−1 kg−1) and a higher protein synthesis rate (6.0 ± 1.4 g day−1 kg−1 versus 4.6 ± 0.8 g day−1 kg−1) in group A. There was no statistically significant difference in protein breakdown. The administration of amino acids reversed a negative protein balance (−0.6 ± 0.2 g day−1 kg−1) into a positive one (1.4 ± 0.2 g day−1 kg−1. No adverse effects of the amino acid infusion were seen.
4. We conclude that the early introduction of amino acids has, even at this relatively low energy intake of 200 kJ day−1 kg−1, a positive effect on protein balance by increasing protein synthesis.
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.
The effects of three isocaloric intravenous nutritional regimens were studied in seven infants and children, ages 2 months to 9 yr, with congenital gastrointestinal anomalies (four patients) or with prior history of malignant disease admitted in remission for bone marrow transplantation (three patients). Energy metabolism, as measured by the basal metabolic rate (BMR), and substrate utilization, as measured by the respiratory quotient (RQ), were studied to determine the effect of different levels of carbohydrate and fat on nitrogen retention in each patient. Solution A provided 8% of energy as amino acids, 87% as carbohydrate, and 5% as fat. Solution B provided 8% of energy as amino acids, 60% as carbohydrate, and 32% as fat. Solution C provided 8% of energy as amino acids, 34% as carbohydrate, and 58% as fat. Administration of solution A (high carbohydrate, low fat) was associated with moderately increased mean (+/- SD) BMR and RQ and with low nitrogen retention (19.1 +/- 12.7%, 1.06 +/- 0.14, and 98 +/- 28 mg N/kg/day). Both the BMR and the RQ decreased when less carbohydrate and more lipid was given: BMR 4.3 +/- 11.6% (p less than 0.005), RQ 0.92 +/- 0.09 (p less than 0.001) for solution B; BMR 3.94 +/- 10.6% (p less than 0.005), RQ 0.86 +/- 0.09 (p less than 0.001) for solution C. Among the solutions tested, optimal nitrogen retention [163 +/- 60 mg N/kg/day (p less than 0.01)] was noted with solution B. Our data support the conclusion that a physiologic balance of fat and carbohydrate results in optimal nitrogen retention.
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.
The effect of amino acids on total parenteral nutrition (TPN)-associated cholestasis was examined using a newborn rabbit TPN model. Twenty-nine newborn Japanese white rabbits were divided into four groups. Group I received a TPN solution with composition and total energy similar to that of rabbit breast milk. Group II received more dextrose than group I. Group III received a larger amount of amino acids than group II. Group IV was nourished by lactating mothers. After 7 days of TPN, blood samples and liver specimens were obtained. In group II, the serum total bilirubin level (1.44 +/- 0.68 mg/dL) was significantly higher than normal (0.28 +/- 0.07 mg/dL) and that of group I (0.49 +/- 0.12 mg/dL). In group II, histological cholestasis was present, characterized by bile plugs in bile ducts, bile pigments in Kupffer cells and hepatocytes, and nonprotein calorie overload changes in clear cell transformation of the hepatocytes. In group III, the serum total bilirubin level (0.23 +/- 0.05 mg/dL) was normal, and there were minimal cholestatic and nonprotein calorie overload changes (histologically) in the liver. These results indicate that cholestasis in this study was induced by nonprotein calorie overload and was prevented by an appropriate volume of amino acids.
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.
Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to immature defense mechanisms against oxidative challenges. It is not clear whether the antioxidants in multivitamins help protect parenteral nutrients against the hazards of oxidation.
To evaluate the role of a multivitamin preparation (MVI) on the actual peroxide load received by patients on TPN.
The generation of peroxides in parenteral nutrition was tested first using test solutions. We compared the relative contribution of commercially available amino acid solutions, a lipid emulsion, and MVI on the level of peroxides in clinically relevant TPN solutions. Second, we measured the level of peroxides actually infused at the bedside. In both circumstances, the effects of time and light exposure were isolated. The level of peroxides was determined by a colorimetric technique and expressed as microM equivalents tert-butyl hydroperoxide (microM = TBH).
Even when protected from light, the addition of MVI produced a 10-fold increase in peroxides (mean +/- SEM, n = 3, 19 +/- 4 to 189 +/- 8 microM = TBH at 4 h) in the fat-free TPN solution and a fourfold increase (64 +/- 6 to 244 +/- 8 microM = TBH at 4 h) in the lipid-containing TPN solution. A dose-response relationship was found between the concentration of MVI and peroxide levels. The effect of light was the strongest in the presence of multivitamins. The amino acid solutions had a relative inhibitory effect on the generation of peroxides by MVI, which varied (from 54 +/- 1% to 72 +/- 1%) all according to the amino acid blend. In parenterally fed premature infants, protecting the intravenous set from light decreased the load of infused peroxides (146 +/- 15 vs 215 +/- 24 microM = TBH).
The lipid emulsion had a significant but minor additive effect compared with the multivitamin preparation, which was the major contributor to the generation of peroxides. Protection from photooxidation is not sufficient to prevent peroxidation of TPN solutions. Contrary to what one would expect, increasing the concentration of MVI will lead to a greater generation of peroxides, suggesting that the essential antioxidants in MVI do not have antiperoxide properties.
Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets.
Solutions of fat-free TPN and all-in-one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2-nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy.
Protection of only the bag had little effect on peroxide generation. In fat-free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light-absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions.
Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 microM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used.
Infusion of parenteral solutions containing peroxides may be detrimental to premature infants. Intralipid frequently contains lipid peroxides and undergoes further peroxidation when exposed to light. Peroxidation is inhibited by ascorbate, and we have proposed that administration of peroxides could be minimized by mixing multivitamins with the Intralipid. In contrast, others have reported that multivitamins generate peroxides and have advised against mixing them with lipid. Our objective was to assess whether light-dependent reactions in parenteral solutions containing MVI Pediatric (MVIP) generate hydrogen peroxide and establish whether addition of multivitamins to Intralipid is beneficial or detrimental.
We were unable to make accurate peroxide measurements in MVIP using the ferrous oxidation of xylenol orange (FOX) assay, even though others have used it for this purpose, because of interference by ascorbate. Therefore oxygen release on adding catalase was measured to assay for hydrogen peroxide. Freshly reconstituted solutions contained 250 to 500 micromol/L hydrogen peroxide, and this increased dramatically in ambient light. This is presumably due to light-dependent, riboflavin-catalyzed reduction of oxygen by ascorbic acid. The rate of peroxide generation was less for MVIP diluted in Intralipid than in dextrose solution.
Taken together with our previous findings, we conclude that multivitamins protect Intralipid against lipid peroxidation, but light-dependent hydrogen peroxide production and ascorbate loss occur. These latter changes are less than for multivitamins in other total parenteral nutrition solutions, so there is an advantage in mixing multivitamins with Intralipid. However, prevention of ascorbate loss and hydrogen peroxide formation in any multivitamin solution requires protection of the delivery system from light.
Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight < or = 1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit.
The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g . kg -1 . d -1 in the standard group and 4 g . kg -1 . d -1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid-base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome.
The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 +/- 0.83 g . kg -1 . d -1; mean, +/-1 SD) and 18% greater (3.86 +/- 0.94 g . kg -1 . d -1 ) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 +/- 1.8 mEq/dL at week 1 and 23.9 +/- 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 +/- 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 ( P < 0.03) in both groups.
Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g . kg -1 . d -1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.
Thirteen immature foetuses and six stillborn infants weighing more than 3,000 g. have been analysed for nitrogen, fat, sodium, potassium, calcium, magnesium, phosphorus, iron, copper, and zinc, and the iodine in the thyroid glands was determined. The placentae of 12 of the foetuses and infants were also investigated. The foetus begins to lay down fat when it weighs 800-1,000 g., and by the time it weighs 3,000 g. the amount of fat in its body is approximately equal to the amount of protein (12%). After this the fat increases much more rapidly than the protein, and one stillborn infant which weighed 4,375 g. contained 28% of fat. The concentration of sodium per 100 g. of fat-free body tissue decreased until the foetal weight was about 2,000 g., and then remained constant until term. The value reached was the same as in adult life. The concentration of potassium in the fat-free body tissue increased throughout intrauterine life, but the concentration in the whole body altered little from the time the foetus began to lay down fat. The concentration of calcium and phosphorus increased with increasing weight, so that the percentage of calcium at full term was rather more than twice and of phosphorus a little less than twice as high as it was in the foetuses weighing 200-300 g. The percentage of iron and copper in the foetus increased with development while that of zinc did not change. The liver and spleen contained about one-half of the copper, one-quarter of the zinc, and one-eighth of the iron in the whole body. The concentration of iodine in the thyroid appeared to increase during foetal life and after, and in the thyroids from three adults was about 20 times as high in those from the immature foetuses. At the seventeenth to nineteenth week of pregnancy the foetus and its placenta were of approximately equal weight, and contained similar amounts of nitrogen, fat, and potassium. During the last four months the foetus grows much more rapidly so that at full term it weighed five or six times as much as its placenta. The " concentrations" of nitrogen and potassium were similar in both, but those of fat, calcium, magnesium, phosphorus, copper, and zinc were all higher in the foetus than in its placenta.
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.
Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known.
We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis.
Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation.
Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population.
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.