Parenteral Amino Acid Administration Research Articles

Postoperative Lymphorrhagia- a Possible Complication Following Cephalic Duodenopancreatectomy

Abstract Surgery associated with lymphadenectomy may sometimes result in a lymphorrhagia, which usually resolves spontaneously within a few days, sometimes becoming a refractory complication to the treatment. In the case of large flows, particular attention should be paid to hydro-electrolytic and protein losses. We present the case of a patient with persistent lymphorrhagia after a cephalic duodenopancreatectomy for a pancreatic head tumor. From the 5th postoperative day, the patient had a milky-like secretion on the subhepatic drainage tube. The discharge rate was variable, between 500 and 1500 ml per day, requiring parenteral administration of amino acids, plasma and electrolyte solutions. The postoperative progression was slowly favorable, with the patient discharge on the 25th day following surgery. There are several treatment options for a lymphorrhagia following an extended lymphadenectomy, from intensive parenteral therapy to peritoneal-venous shunt or ligation of the lymphatic vessel responsible for the production of lymphorrhagia. In this case the conservative treatment had a favorable result.

High-dose parenteral amino acid intake in very low birthweight infants: what is the current evidence?

There is uncertainty regarding optimal dosing for parenteral amino acids in preterm infants and wide variability exists in clinical practice. There is new data from clinical trials trying to address these concerns. We review the recent evidence on parenteral high-dose amino acid intake in very low birth weight (VLBW) neonates with a focus on relevant clinical outcomes. Preterm infants often receive less protein than intended in the first week of life. Parenteral amino acid administration in doses that exceed requirements, however, leads to increased oxidation and higher blood urea concentrations. Amino acid doses greater than 3.5 g/kg/day have not shown to improve mortality, neonatal morbidities including sepsis, necrotizing enterocolitis, chronic lung disease, growth parameters or neurodevelopmental outcomes at 2 years of age. Parenteral amino acid administration in VLBW infants should be initiated soon after birth at a dose of at least 1.5 g/kg/day to maintain anabolism. The maximum dose for parenteral amino acid should be between 2.5 and 3.5 g/kg/day, with adequate nonprotein calories and micronutrients to ensure efficient protein utilization and growth.

Effects of Parenteral Amino Acid Administration on the Postoperative Nutritional Status and Wound Healing of Protein-Malnourished Rats

In Japan, parenteral nutrition (PN) solutions are frequently administered to patients in the postoperative short-term period. In these cases, amino acid-containing peripheral parenteral nutrition (PPN) solutions, amino acid-free maintenance solutions or combinations of the two are used. However, consensus regarding the most beneficial solution for these patients is lacking. Here, we examined the nutritional status and wound healing outcomes in protein-malnourished rats receiving postoperative administrations of PPN solution, maintenance solution or combinations of the two solutions. Protein malnutrition was induced in Sprague-Dawley rats by feeding an AIN-93G-based low-protein diet (5% casein) for 2 wk. After laparotomy, dorsal skin incision, and placement of a jugular vein catheter, the rats were divided into 3 groups. Each group was administered 113 kcal/kg/d, with group A receiving maintenance solutions without amino acid, group B receiving PPN with 1.5% amino acid, and group C receiving PPN with 3% amino acid. After 5 d post-operative administration, we measured the tensile strength of the wound area, skeletal muscle weights, and nutritional parameters. Significantly higher plasma nutritional parameters and gastrocnemius and extensor digitorum longus (EDL) muscle weights were observed in groups B and C than in group A. Group C exhibited significantly elevated tensile strength of the wound area along with up-regulation of type I collagen mRNA expression compared to group A. These findings demonstrate the nutritional status and wound healing benefits of short-term postoperative administration of PPN solutions containing amino acids in protein-malnourished rats.

Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Objectives: Providing parenteral amino acids to very-low-birth-weight infants during the first weeks of life is critical for adequate growth and neurodevelopment. However, there is no consensus about what dose is appropriate or when to initiate supplementation. As a result, daily practice varies among neonatal intensive care units. The objective of our study was to determine the effects of early parenteral amino-acid supplementation (within 24 h of birth) versus later initiation and high dose (>3.0 g/kg/day) versus a lower dose on growth and morbidities. Methods: A systematic review and meta-analysis of publications identified by searching PubMed, EMBASE, and Cochrane databases was conducted. Randomized controlled studies were eligible if information on growth was available. Results: The search identified 14 studies. No differences were observed in growth or morbidity after early or high-dose amino-acid supplementation, but for several outcomes, meta-analysis was not possible due to study heterogeneity. Initiation of amino acids within the first 24 h of life appeared to be safe and well tolerated, and leads more rapidly to a positive nitrogen balance. Conclusions: Administering a high dose (>3.0 g/kg/day) or an early dose (≤24 h) of parenteral amino acids is safe and well tolerated but does not offer significant benefits on growth. Further large-scale randomized controlled trials in preterm infants are needed to study the effects of early and high-dose amino acids on growth and morbidity more consistently and extensively.

Blood Urea Nitrogen Concentration and Aggressive Parenteral Amino Acid Administration in Extremely Low Birth Weight Infants during the First Week

Blood Urea Nitrogen Concentration and Aggressive Parenteral Amino Acid Administration in Extremely Low Birth Weight Infants during the First Week

The Effects of Early Parenteral Amino Acids on Sick Premature Infants

To study the effects of early parenteral amino acid administration on body weight, fluid compartments and metabolic parameters during the first week of life in sick premature infants. Appropriate for gestational age, sick premature infants were randomized into two groups. Group A infants (n=8, birth weight 1258±339 g) were supplemented with amino acids starting within 24 h of birth and advanced to 2.5 g/kg per day by day 3. Group G infants (n=9, birth weight 1182±214 g) received amino acids starting on day 4 of life. Energy intake was comparable in the 2 groups. Amino acid concentrations and nitrogen balance studies were performed on day 3 of life. Total body water and extracellular water were measured on day 1 and 8 and change in intracellular volume was calculated. There was no significant difference between the 2 groups in terms of weight, intracellular volume change from day 1 to day 8 of life, despite a significant (P<0.01) difference in protein intake. Plasma ammonia levels were comparable in the 2 groups, but plasma urea levels were significantly higher in group A vs. group G infants (7.2±3.4 mmol/L vs. 3.2±1.2 mmol/L respectively, P<0.01). Nitrogen balance was positive in all group A infants and negative in group G infants. Nitrogen loss was inversely correlated with energy intake in group G infants (P<0.05). The mean plasma amino acid concentrations in group A infants (compared to those of group G) were within previously reported ranges in older premature infants. There was no significant effect on body weight and redistribution of body fluid compartments in infants receiving amino acids early during the first week of life. Serum urea concentrations were significantly higher in infants receiving early amino acids. Nitrogen losses in infants who did not receive amino acids were inversely correlated with energy intake during the first 3 days of life.

Safety and efficacy of early and high-dose parenteral amino acid administration to preterm infants.

Abstract With birth, an infant's continuous nutrient supply through the umbilical cord abruptly ends while the nutritional requirements remain high. Preterm infants do not tolerate full enteral feeding immediately after birth because of immature bowel functioning. Therefore, parenteral nutrition should be initiated as soon as possible, as a means to restrict the wasting of endogenous substrates and to maintain normal metabolism and growth. Nevertheless, many preterm infants fail to grow well, which may be related to inadequate administration of proteins, the driving force for tissue growth. Research has shown that relatively high doses of parenterally administered amino acids from birth onwards are safe for preterm infants and enhance protein accretion and thus growth. Future studies should also reveal the long-term effects of high-dose amino acid administration from birth onwards on neurodevelopment. In addition, effects of higher amounts of amino acids as well as those of early lipid infusion need to be defined.

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life

Background: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth.Objective: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake.Design: Premature infants (<1500 g birth weight), who were on ventilation, received from birth onward either glucose only (control group, n = 7) or glucose and 2.4 g amino acid · kg−1 · d−1 (intervention group, n = 8). On postnatal day 2, all infants received a primed continuous infusion of [1-13C]leucine, and mass spectrometry techniques were used to determine the incorporation of the leucine into albumin. Results are expressed as medians and 25th and 75th percentiles.Results: Albumin fractional synthesis rates in the intervention group were significantly higher than those in the control group [22.9% (17.6–28.0%)/d and 12.6% (11.0–19.4%)/d, respectively; P = 0.029]. Likewise, the albumin absolute synthesis rates in the intervention group were significantly higher than those in the control group [228 (187–289) mg · kg−1 · d−1 and 168 (118–203) mg · kg−1 · d−1, respectively; P = 0.030].Conclusion: Amino acid administration increases albumin synthesis rates in premature neonates even at a low energy intake.

Achieving Positive Protein Balance in the Immediate Postoperative Period in Neonates Undergoing Abdominal Surgery

To determine whether neonates undergoing major abdominal surgical procedures in the first day of life could achieve a positive protein balance without protein toxicity in the immediate perioperative period by using parenteral amino acids and fentanyl analgesia. Newborns undergoing major surgery for gastroschisis in the first 24 hours of life (n = 13) were alternately allocated to immediate postoperative parenteral administration of 1.5 g/kg(-1)/day(-1) versus 2.5 g/kg(-1)/day(-1) amino acids. Protein balance was determined at 1.6 to 2.6 days postoperatively with both nitrogen balance and leucine stable isotope methodology. Statistical analyses were conducted with the unpaired t test and linear regression. Protein balance was significantly different in the 2 groups with both nitrogen balance and leucine stable isotope methodology. There was no evidence of protein toxicity as determined with blood urea nitrogen, creatinine, and ammonia concentrations. Neonates undergoing the metabolic stress of abdominal surgery shortly after birth are able to achieve a net positive protein balance with parenteral amino acid administration without evidence of protein intolerance.

Parenteral Amino Acid and Metabolic Acidosis in Premature Infants

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.

Does chronic prenatal Doppler pathology predict feeding difficulties in neonates?

To determine whether infants with compromised fetomaternal circulation, but not yet critically threatened by absent end-diastolic flow velocities in the umbilical arteries, are at a risk for feeding problems. In a retrospective case-control study, enteral feeding and clinical data were compared between infants with decreased prenatal end-diastolic umbilical flow velocity (DEDFV) or brain-sparing pathology and controls matched for gestational age (GA). In all infants, enteral feedings were advanced according to a standardized enteral feeding protocol. 11 (GA>34 wk) of the 87 infants with DEDFV were fully enterally fed by day 5 and excluded, leaving 76 infants (and matched controls) for final analysis. DEDFV infants were significantly smaller (1,230+/-550 g vs 1,600+/-682 g). Advancement of enteral feedings varied widely, with a significant difference between DEDFV infants and controls. There was no difference in the incidence of NEC (five in both groups). In the most severely affected subgroup of 25 infants with GA<30 wk and prenatal brain sparing, enteral feedings were significantly delayed in comparison to the controls (parenteral amino acid administration for 22 vs 15 d; significantly fewer enteral calories through day 15). Enteral feeds were introduced more slowly to infants who had shown signs of prenatal distress with brain sparing. However, a predisposition to NEC could not be proven. Our results thus do not support the delay of enteral feedings based on prenatal Doppler pathology.

Increased parenteral amino acid administration to extremely low-birth-weight infants during early postnatal life.

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.

Increased Parenteral Amino Acid Administration to Extremely Low‐Birth‐Weight Infants During Early Postnatal Life

ABSTRACTBackgroundEarly administration of parenteral amino acids to infants with extremely low birth weight (birth weight ≤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.MethodsThe 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.ResultsThe 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 &lt; 0.03) in both groups.ConclusionsInfants 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.

Epinephrine does not impair utilization of exogenous amino acids in humans

The effect of epinephrine on leucine and phenylalanine kinetics was measured by using the stable isotope amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]-phenylalanine in the postabsorptive state and during the intravenous administration of a standard amino acid solution with respect to the amino acid load. Infusion of epinephrine (plasma concentration: approximately 3600 pmol/L) decreased leucine and phenylalanine and increased ketoisocaproate plasma concentrations and increased the metabolic clearance rate of leucine and phenylalanine. Epinephrine neither influenced leucine or phenylalanine flux nor leucine oxidation or leucine net balance. Hyperaminoacidemia from amino acid infusion reduced endogenous leucine release and stimulated leucine oxidation and nonoxidative disposal of leucine, resulting in a dose-dependent increase in leucine net balance. Epinephrine did not influence any changes in amino acid kinetics during parenteral amino acid administration. Therefore, we conclude that epinephrine had no catabolic effects on amino acid metabolism and no negative effect on the utilization of a parenterally offered amino acid solution in healthy humans.

Increased energy expenditure after intravenous administration of amino acids.

Nutrient-induced thermogenesis (NIT) after parenteral administration of amino acids (AAs) was investigated in rats and compared with result obtained with intragastric administration. Resting energy expenditure was measured with a new type of open-circuit indirect calorimeter. The NIT increased shortly after parenteral AAs administration and reached a steady state in 30 minutes. The change in resting energy expenditure (the increment of resting energy expenditure over preinfusion baseline values) showed a significant relationship not only with the amount of infused AAs but also with the AA concentration in the portal vein. Furthermore, the increase in plasma AA concentrations in the portal vein was proportional to the amount of the particular AA infused. This relationship held true over the entire range tested. NIT with parenteral infusion (11% to 12%) was lower than that with intragastric infusion (20% to 23%). Plasma insulin, corticosterone, and glucagon levels increased after both parenteral and intragastric AAs administration, but the two methods did not show any significant differences in hormonal changes. The plasma aminogram of the portal vein after intragastric infusion was compared with that after parenteral infusion. Total plasma AA concentration and the levels of glutamine, lysine, arginine, glutamate, aspartate, and histidine were lower but the level of isoleucine was higher after intragastric infusion. On the basis of these results, it is believed that parenteral administration of AAs can induce thermogenesis, which may be regulated by the intraportal AA concentration. Considering the remarkable decrease in glutamine in the portal vein after intragastric infusion, the cost of intestinal metabolism may predominantly contribute to the NIT resulting from intragastric infusion.

Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: A randomized controlled trial

The effect of parenteral amino acid administration on nutritional state, liver function and mortality was assessed in patients with severe alcoholic hepatitis. Twenty-eight patients received 2 l/day of a solution of dextrose (65 gm/L) and amino acids (25.8 gm/L) for 1 mo, whereas 26 received only the dextrose solution. All patients were allowed to eat a standard hospital diet. During the month in the hospital, there were six deaths in the treatment group and five deaths in the control group. Nitrogen balance improved in the treated group, but not in the control group. Creatinine-height index, triceps skin fold measurement and levels of serum albumin and prealbumin increased similarly in both groups. Serum retinol binding protein increased more in the treatment group than it did in the control group, and transferrin was increased only in the treatment group. Serum bilirubin, type III amino-terminal procollagen peptide and aminopyrine clearance improved more in the treatment group than in the control group, whereas serum AST and prothrombin time improved in the treatment group but not in the control group. Cumulative 2-yr survival rates from the day of entry into the study were 42% and 38% in the treatment and control groups, respectively. Patients who survived 2 yr and patients in the treatment group who died during the 2-yr follow-up had continued improvement in serum retinol binding protein, transferrin, bilirubin and prothrombin time. These parameters were unchanged in patients in the control group who died during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Benefit of intravenous essential amino-acids in catabolic patients on chronic maintenance hemodialysis.

The effect on the clinical status of catabolic hemodialysis patients of I.V. essential amino-acids administered over 3 months at the end of each dialysis is assessed in an open clinical follow-up study of 10 patients; these patients showed a progressive deterioration of general condition and a progressive weight loss in the period before the start of the treatment. The study was undertaken in a hospital dialysis unit, with as main outcome measures body weight, hematocrit, a scoring index of general condition and degree of edema. In patients showing a progressive and consistent loss of body weight in the months preceding the study, after the first treatment month, body weight started to rise, increasing after 3 months from 56.2 +/- 2.3 to 58.6 +/- 2.4 kg (p less than 0.01). The hematocrit raised from 22.4 +/- 1.6% up to 26.5 +/- 1.9% (p less than 0.02). Over this period, only 2 liters of packed cells were administered, in contrast to an overall need of 13 liters in the preceding 6 months. Peripheral and/or pulmonary edema disappeared. A scoring index, of general condition, increased from 5.1 +/- 1.5 before the start of the study to 11.7 +/- 0.8 after 3 months (p less than 0.01). It is concluded that the parenteral administration of amino-acids in catabolic patients on chronic hemodialysis has a beneficial effect on general condition, and the balance of body fluid and body mass.

Effect of parenteral amino acids on human pancreatic exocrine secretion.

Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double-lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min.

Ventilatory Drive in Normal Man during Semistarvation

The effects of reduced caloric intake on ventilatory drive were investigated in normal volunteers. During a ten-day semistarvation period, six subjects (group 1) received parenterally an amino acid solution providing 550 kcal/d sufficient to prevent a negative nitrogen balance. Six subjects (group 2) received in addition a safflower oil solution providing a total caloric intake of 1,100 kcal/d. Hypoxic ventilatory drive was estimated by an index (parameter A) of the relation between minute ventilation (VE) and hypoxia. In group 1, mean values (+/- SEM) of A decreased significantly from 161.5 (+/- 42.0) to 48.9 (+/- 12.0) by day 10 (p less than 0.05), indicating a severe depression of hypoxic drive despite a positive nitrogen balance. In group 2, A did not change significantly (p greater than 0.05) from control values indicating a preserved hypoxic ventilatory drive. In both groups, the slopes of the line relating VE to arterial PCO2 (delta VE/delta PaCO2) did not change significantly during the ten-day semistarvation period consistent with preservation of the hypercapnic ventilatory drive. These data indicate that during periods of starvation, parenteral administration of aminoacids in an amount sufficient to maintain nitrogen balance is inadequate to prevent depression of respiratory control mechanisms unless a minimum daily caloric intake is achieved.

Enhanced tumor response to cycle-specific chemotherapy by parenteral amino acid administration.

Forced feeding has been shown to effectively stimulate tumor metabolism in numerous animal models. Significant acceleration of tumor growth by exogenous nutrient administration is generally considered to be detrimental to the host. The present study was performed to determine if substrate-induced alterations in tumor metabolism could be exploited to enhance tumor response to cycle-specific chemotherapy. Following subcutaneous mammary tumor implantation (AC-33) and protein depletion, 39 female Lewis/Wistar rats were randomly assigned to one of four nutritional regimens for 48 hr: (1) protein-depleted food (0.03% protein) ad libitum po, (2) parenteral carbohydrate (18.6% dextrose), (3) parenteral amino acids (2.8% amino acids), or (4) total parenteral nutrition (18.6% dextrose/2.8% amino acids). Methotrexate (5 mg/kg im) was administered to all animals 2 hr after initiating these nutritional regimens. Tumor volume and host toxicity were monitored throughout the study. At sacrifice, significant reduction in tumor volume was observed in animals receiving parenteral amino acids (0.37 +/- 0.24 cm3) and total parenteral nutrition (0.25 +/- 0.18 cm3) compared to the group receiving protein-depleted food po (0.70 +/- 0.22 cm3) (p less than 0.01). In this animal model, the parenteral administration of amino acids with or without the addition of hypertonic dextrose was found to effectively potentiate tumor response to methotrexate without increasing host toxicity.