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A prospective clinical trial was undertaken to determine the nitrogen-sparing efficacy of three amino acid solutions with different concentrations of branched-chain amino acids (BCAA) in 25 postoperative patients. The patients were a homogenous male population with stage I bladder cancer who underwent radical cystectomy. Administration rates of the intravenous solutions were designed to provide 30 kcal/kg/day and 1.5 g protein per kg per day during the 7-day study period. A control group (n = 4) received 5% dextrose in water (150 g/ day). Nitrogen balance was determined daily and the whole body protein turnover was measured using a primed-constant infusion of 15N glycine on postoperative days 3 and 4. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a significant decrease in cumulative (7 day) nitrogen balance (7.6 ± 2.6 g) compared to the groups receiving either the standard 25% BCAA (19.9 ± 2.1 g) or the 45% BCAA enriched (high leucine) (21.6 ± 7.0 g) amino acid solution. The group receiving the 45% BCAA enriched (low leucine) amino acid solution exhibited a higher rate of mean whole body protein catabolism compared to the other groups. For patients undergoing major elective operations, the amount of leucine necessary for optimal daily nitrogen balance was 0.13 g/kg/day. These results demonstrate that the ratio of individual BCAA and the amount of leucine were more critical to nitrogen-sparing efficacy than the percentage total BCAA infused.
We used cost-effectiveness analysis to compare three strategies for reducing the incidence of severe nutrition-associated complications (eg, wound dehiscence) in patients undergoing major gastrointestinal surgery: treat all patients with parenteral nutritional support for 10 days before surgery, treat no patients with preoperative parenteral nutritional support, or perform a test which stratifies patients (treating only the "high risk" or "malnourished" patients). The "test" strategy results in the lowest total hospital complication rate when the overall incidence of postoperative nutrition-associated complications is greater than 4% and less than 39%. However, the cost minimizing strategy is "treat none" as long as the overall incidence is less than 78%. In moving from the "treat none" to the "test" strategy, the incremental cost per complication avoided varies from $11,515 (for a 20% overall incidence), to $1,031 (for a 60% overall incidence). These cost-effectiveness ratios for incidence rates above 20% compare favorably to the use of routine screening tests performed on preoperative patients. However, the cost-effectiveness ratios are quite sensitive to the assumptions made concerning the effectiveness of parenteral nutritional support and the predictive properties of the test (derived from previous clinical studies). We conclude that further research is needed to study the overall incidence of severe postoperative nutrition-associated complications for various surgical procedures, to confirm the accuracy of stratification techniques and to confirm previous studies of the effectiveness of preoperative parenteral nutritional support in order to permit third party payers to evaluate the consequences of adopting this intervention as a standard clinical practice.
This study was performed to determine the effects of different amounts of lipid in enteral diets during the postburn period. Forty-five guinea pigs with catheter gastrostomy received a 30% total body surface area full thickness flame burn. After burn they were given intragastric tube feedings using five diets at different dietary lipid composition: 0, 5, 15, 30, and 50% of nonprotein calories. Total calories administered (175 kcal/kg/day), protein content and composition (20% of total calories), total volume, and vitamin and mineral content were constant in all animals. At postburn day 14, body weight, carcass weight, and muscle weight were the greatest in 0 and 5% lipid groups, and the least in 30 and 50% lipid groups. Serum transferrin was highest in the 5 and 15% lipid groups, and lowest in the 30 and 50% lipid groups. Total nitrogen content in muscle and cumulative nitrogen balance were best in the 15% lipid group. Liver fatty infiltration, caused from a larger proportion of carbohydrate administration, was greater in the 0 and 5% lipid groups and less in 15 and 30% groups. It is concluded that dietary lipid levels between 5 and 15% of nonprotein calories are optimal for nutritional support after burn injury. The nutritional management of postburn patients with higher levels of dietary lipid should be reconsidered. (

Septic shock induces physiologic and hemodynamic responses that may alter the host's ability to metabolize an exogenous source of lipids. The present study examined the metabolic changes occuring during septic shock in the young animal receiving an intravenous fat emulsion. Five 8-wk-old male Beagle puppies were studied. Each animal served as his own control twice, during which time 14C-palmitic acid alone or with a 10% fat emulsion (Liposyn) was administered. Septic shock (cardiac output less than 50% of control) was induced with an intravenous bolus of live Escherichia coli. During shock the puppies received intravenous 14C-palmitic acid and Liposyn. The mean respiratory quotient for the shock dogs (0.96 ± 0.01) was significantly (p < 0.05) higher than that of the controls (0.83 ± 0.06). The amount of expired 14CO2 was 25.0 ± 15.9% for the shock animals, 53.9 ± 28.1% for the Liposyn controls, and 75.7 ± 30.5% for the controls receiving only 14C-palmitic acid (these differences are all significant, p < 0.05). After the onset of shock, serum triglyceride levels peaked within 2 min at 851 ± 540 mg/100 ml and remained elevated at 333 ± 213 mg/100 ml. Triglyceride levels in the Liposyn control animals returned to baseline values (54 ± 13 mg/100 ml) at the end of the 4-hr experimental period. Free fatty acids in the shock dogs reached a maximal level of 1.44 ± 0.09 mEq/liter at 1 hr and remained at this elevated value for a significantly longer period of time than in the Liposyn control puppies. Glycerol value followed a similar pattern and cholesterol remain unchanged. Plasma insulin in the shock animals steadily rose to a peak of 826 ± 358 μU/ml at the end of the experimental period; control animals showed no plasma insulin changes. The results of this study suggest that exogenous lipids administered during septic shock may not be metabolized as well as during the nonshock state.
This study was undertaken to determine if the proportions of intravenous carbohydrate and fat calories influence the relative growth of a Walker 256 carcinosarcoma and its host. Rats injected intraperitoneally with Walker 256 carcinosarcoma cells were randomized into three total parenteral nutrition (TPN) groups, G/AA in which glucose provided all nonprotein calories, G/F/AA in which the nonprotein calories were 20% fat and 80% glucose, and F/AA in which all nonprotein calories were from fat. Except for the caloric source, TPN for each group was identical. A fourth group was sham operated, fed rat food, and was not given TPN. On the 6th day after innoculation, the tumor in each rat showed a dispersed ascites form as well as a solitary mass form involving the omentum. The total number of tumor cells in the ascitic fluid and the dry weight of the mass were determined. The three TPN groups did not differ in tumor cell count, solid tumor weight, ratio of tumor cell count to final host weight, or ratio of solid tumor to final host weight. The mean ratio of ascites tumor cell count to host weight was not different between the rat food-fed group and any of the TPN groups. The mean ratio of solid tumor to host weight was less for the TPN groups than for rat food-fed animals. We conclude that TPN had no adverse effect on the growth of tumor us. host and that the source of intravenous calories (fat or carbohydrate) did not influence the relative growth of tumor and host in this TPN-tumor model.
Morbid obesity is associated with glucose intolerance. We studied the rate of glucose turnover in 18 morbidly obese individuals and compared the results to 10 normal weight controls using the technique of the hyperglycemic clamp. Rate of glucose turnover (mg/kg/min) was defined as metabolic clearance of glucose and corresponding plasma immunoreactive insulin values were determined. The ratio of metabolic clearance of glucose to plasma insulin is a reflection of endogenous insulin sensitivity. Patients were studied again 3 months following jejunoileal bypass and gastroplasty. Fasting glucose was similar for all groups. Fasting immunoreactive insulin was 16.8 ± 5 μU/ml in preoperative obese, 4.3 ± 0.2 in controls, 6.8 ± 0.6 in postoperative jejunoileal bypass, and 6.2 ± 0.3 in postoperative gastroplasty. The difference between postoperative groups was not significant at 3 months. The jejunoileal bypass group at 1 yr gave similar results to the immediate postoperative findings. In normals the value of metabolic clearance of glucose was 3.9 ± 0.7 mg/kg/min and in the obese it was 2.05 ± 0.2 (p < 0.05). No significant improvement occurred postoperatively. Mean of the immunoreactive insulin values from 60 to 120 min was greater in preoperative obese than controls, 44.0 compared to 13.6 μU/ml (p < 0.05). A highly significant postoperative lowering occurred in both groups, jejunoileal bypass 20.7 μU/ ml, gastroplasty 22.4
Total body or exchangeable potassium is used as an important indicator of body cell mass in the study of body composition. Body composition studies have been used extensively in the study of nutrition but recent work has questioned the validity of using changes in total body potassium as a measure of protein or nitrogen variation. To investigate the relationship between tissue nitrogen and potassium during nutritional manipulation 382 tissue samples from 100 surgical patients were analyzed by Kjeldahl analysis for nitrogen content and flame photometric analysis for potassium content. Nitrogen was related to potassium in parenchymous or cellular tissues by the relationship N (mg/g) = 14.7 + 0.17 K (
A prospective study was carried out to determine the pathogenesis of coagulase negative staphylococci catheter-related sepsis during parenteral nutrition. Forty-three catheters were cultured by semiquantitative and quantitative methods. The skin around the puncture site was cultured at the time of catheter removal and three segments of the catheter were cultured apart: the hub, the proximal subcutaneous segment, and the tip. Skin cultures were negative (89%) or yielded different coagulase negative staphylococci from those recovered in catheter and/or blood. Seventeen catheters were the source of sepsis. In 15 cases an infected hub was associated with an infected tip. In two cases the hub was negative (one sepsis due to mixture contamination and the other due to hematogenous seeding of the catheter tip). Sixteen cases of sepsis were due to coagulase negative staphylococci.
Bacterial cultures were made on tube-feeding formulas provided to 35 unselected adult patients on termination of the infusion. Bacteria were counted and identified using routine procedures. Formulas were classified as nonmanipulated, manipulated, or locally prepared. Medical records were reviewed to determine if diarrhea was present during the period that included 2 days on either side of the sampling day. A significant association was observed between the extent of bacterial contamination and the presence of diarrhea (
Postpyloric feeding probably reduces the incidence of tracheobronchial aspiration and improves feeding tolerance. However, duodenal intubation is often unsuccessful in critically ill patients due to gastric atony. Metoclopramide improves gastric emptying. In a pilot study, 12 adult patients were administered 10 to 20 mg of intravenous metoclopramide after weighted nasal feeding tubes had failed to spontaneously pass distal to the pylorus. In no patient did metoclopramide induce transpyloric passage of the tube. A randomized prospective study involving 10 adult patients was conducted to examine the effect of preinsertion intravenous metoclopramide on transpyloric intubation. All patients had failed to achieve spontaneous duodenal intubation. Five patients received 20 mg of metoclopramide 10 min prior to nasal insertion of a weighed feeding tube. Five control patients received no premedication. Four metoclopramide patients achieved duodenal intubation immediately. In none of the control patients did transpyloric intubation occur (p = 0.048). Metoclopramide, administered after nasogastric intubation, is ineffective in promoting transpyloric advancement of feeding tubes. There is a significant increase in transpyloric intubation when metoclopramide is administered prior to tube insertion.
The purpose of this investigation was to determine whether the observed gastric relaxation associated with the intragastric infusion of a liquid meal could be conditioned to the temporarily associated auditory cues to enteral feeding and thus produce decreased intragastric pressures under "sham" feeding conditions. Eight normal volunteers received either enteral feedings or sham feedings followed by enteral feedings on 72 separate trial days. The feedings were administered at a constant rate via a Harvard infusion pump. Intragastric pressure changes were monitored by an open tipped pressure cannula which was attached to the feeding tube. A sham feeding consisted of carrying out all preparatory procedures including activation of the feeding pump which was visually screened from the patient. Without the subjects' knowledge the liquid diet was diverted to another reservoir instead of through the nasogastric tube. This sham type infusion produced a gastric response similar to the response to a normal diet infusion as evidenced by a decrease in intragastric pressure and a suppression of irregular high amplitude contractions that are associated with hunger. This anticipatory response to enteral feeding indicative of prospective relaxation of the stomach may enhance the subsequent accommodation to a volume of diet. Additional studies are needed to investigate the importance of visual and auditory cues on patient tolerance of enteral feedings.
Patients undergoing massive small bowel resection for a variety of conditions develop severe nutrient malabsorption which gradually improves through mucosal hyperplasia in the remaining small intestine. Following massive small bowel resection, patients are generally fed elemental diets, often containing high concentrations of medium-chain triglycerides. We evaluated the effect of high percentage medium-chain triglyceride feeding on mucosal adaptation following massive small bowel resection in rats. Twenty 150-g Sprague-Dawley rats were subjected to 60% jejunoileal resection. Another 20 animals received sham operations. One-half of each group were fed a diet containing 83% of the fat as medium-chain triglycerides, the remainder were fed a diet containing 40% medium-chain triglycerides. Animals were pair-fed for 2 wk and subsequently killed. The remaining bowel was removed and unidirectional glucose and leucine uptake were measured using isolated sacs. Mucosal wet weight, protein, and sucrase content were determined. Animals fed medium-chain triglycerides demonstrated decreased mucosal weight in the proximal bowel, decreased mucosal sucrase activity in the proximal bowel, and decreased mucosal leucine uptake in the distal bowel. While medium-chain triglycerides offer an advantage to patients with short bowel syndrome because they are easily absorbed, they may not stimulate the same degree of mucosal adaptation following resection as long-chain triglyceride feedings.
The specific role of endogenous growth hormone in regulating nitrogen metabolism during surgical stress and infection remains unclear. We have studied splanchnic amio acid uptake and plasma concentrations in patient groups exhibiting growth hormone hypersecretion or relative growth hormone depression in response to stress. Splanchnic amino acid uptake was similar in both groups although plasma levels were significantly higher in the presence of depressed growth hormone production suggesting increased net peripheral proteolysis. In association with this latter observation, T lymphocyte subset analysis revealed a greater incidence of depressed helper to suppressor cell ratios in the presensce of depressed growth hormone suggesting a greater impairment of cellular immunity.
Victims of major burns may be at risk for selenium (Se) depletion because increased postinjury nutrient needs are often met by total parental nutrition and tube feedings which contain little Se. This study compared Se status of 17 burn patients and 191 healthy control subjects. Se intake of burn patients was lower than the intake of control subjects when total parenteral nutrition or tube feedings were used as primary nutrient sources but was comparable to the control intake when burn patients consumed oral diets. Serial determinations each 10 days during recovery showed that burn patients had lower plasma Se, erythrocyte Se, and erythrocyte glutathione peroxidase levels, and lower 24-hr urine Se excretion. These results provide biochemical evidence of Se depletion despite exogenous Se intake within the range recommended for healthy adults. Further studies are indicated to determine if Se depletion in burn patients can be prevented by Se supplementation of total parenteral nutrition and tube feeding solutions.
The effect of L-leucine on glutamate receptors in the brain and on visual evoked potentials was studied in hyperammonemic rabbits. Hyperammonemia was induced by the iv infusion of 2.1 mmol NH4Cl/h over 3 hr. Hyperammonemia was followed by a 116% increase in the specific binding of 3H-glutamate to synaptic membranes prepared from the hippocampus. This increase was due to both an increase in the affinity and in the density of the glutamate receptor. The simultaneous infusion of L-leucine (6.7 mmol/hr) completely prevented the ammonia-induced increase in the specific glutamate binding, whereas L-valine and D-leucine had no effect. Hyperammonemia was also associated with typical, reproducible, and reversible changes in visual evoked potentials. The amplitudes of the first negative and the second positive peak decreased, whereas the latencies of these peaks remained unchanged. The simultaneous infusion of L-leucine completely prevented these changes. These findings indicate (1) that L-leucine prevents ammonia-induced changes in the glutamatergic excitatory neurotransmitter system and (2) that pharmacologic doses of L-leucine modulate the effects of hyperammonemia on central neurotransmission as assessed by visual evoked potentials. A causal relationship between the effects of L-leucine on ammonia-induced changes in glutamate receptors and in visual evoked potentials cannot be inferred with confidence. These findings provide a potential alternative explanation for the apparent beneficial effects of infusions of branched-chain amino acids on hepatic encephalography in patients with chronic liver disease.
Radiographic evidence of subclavian vein thrombosis has been shown to occur in 33% of total parenteral nutrition patients. This incidence can be significantly reduced to 8% when heparin is administered concomitantly in total parenteral nutrition solutions. To evaluate the thrombotic risk of a newly developed polyurethane catheter, 20 concurrent patient pairs were prospectively cannulated with either a standard polyethylene catheter plus heparin or a polyurethane catheter without heparin in a sequential statistical study. Radionuclide venograms (Tc99m) were performed within 72 hr of catheterization, at biweeky intervals, and at termination of total parenteral nutrition administration. No patient in either group developed clinical (pain, arm swelling, collateral veins) or venogram evidence of thrombosis after catheterization during an overall cannulation period of 820 days. Use of polyurethane catheters and elimination of heparin in total parenteral solutions may be particularly important since contraindications to heparin use are common. Additionally, heparin elimination can decrease admixture work and confusion (ie, subcutaneous heparin double dosing) without increasing the risk of subclavian vein thrombosis.
Home parenteral nutrition (HPN) patients need periodic reassessment for compliance, appropriateness of parenteral formulation, infusion regimen, bowel adaptation, and effective oral nutrient intake. Additionally, new technological advances need to be considered for potential use in the home parenteral nutrition population. Since costs for home parenteral nutrition therapy are substantial, cost-effective options should be exercised whenever reasonable. The following case illustrates our approach to the reassessment process, subsequent modifications, and resultant impact on the lifestyle, adequacy, and cost of home parenteral nutrition therapy. (
We report a case of pulmonary artery perforation with resultant cardiac tamponade after central venous catheterization and review six previously reported cases. Tamponade may be an acute or late complication and is usually associated with the effusion of intravenous fluid into the pericardium. Three cases actually occurred after catheterization through the "safer" peripheral venous access route (basilic vein). The diagnosis of perforation and tamponade as well as the treatment can be accomplished using the catheter. Recognition and appropriate treatment of this rare complication may avoid significant morbidity and mortality.
A case of accidental bronchial perforation by the metal stylet of a silastic feeding tube is reported. The misplacement of the feeding tube resulted in a pneumothorax. This is a previously unreported complication of enteral feeding in adults. Pulmonary complications of enteral feeding and recommendations for prevention of these complications are discussed.
Two patients requiring total parenteral nutrition for 34 and 39 months, had plasma and urinary carnitine assays and plasma lipid assays performed before and during intravenous administration of 400 mg (2500 μmol) of L-carnitine for 7 days, followed by 40 mg (240 μmol) daily continuously. One patient had generalized lethargy and weakness which resolved within the first 5 days of carnitine administration. The plasma-free carnitine levels in this patient rose significantly. The other patient was asymptomatic and while there was no significant change in the plasma-free carnitine levels during carnitine administration, this patient remained in positive carnitine balance throughout the study. There were no significant changes in plasma lipid levels in either patient. In adult patients requiring long-term total parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients endogenous carnitine production.
Patients on home parenteral nutrition who have continuing excess fluid and electrolyte loss from the bowel can have difficulty in managing their fluid and electrolyte state because of the variability of such losses. Recently we have used the World Health Organization's oral rehydration solution to replace such losses in two patients with good effect.
A 38-yr-old woman with Crohn's disease and short bowel on home total parenteral nutrition was studied. Metabolic bone assessments were done prospectively. Daily total parenteral nutrition included 500 IU vitamin D2, 6 to 8 mmol calcium, 10 to 15 mmol phosphorus, 12 to 16 mmol magnesium, and trace elements including zinc, copper, and chromium. After 6 months, while asymptomatic, chemistries and x-rays were normal. Calcium bone index was 0.79. The bone biopsy showed mild hyperkinetic picture. At 26 months, she had a spontaneous rib fracture and bone pains in the hands and lower back. Chemistries were normal except that calcium bone index was 0.75. Bone biopsy showed mild osteomalacia. Vitamin D2 was withdrawn for 2 months and then restarted at 1000 IU/wk. She improved symptomatically for 4 months, but then developed rib fractures, and the bone pains recurred. After 48 months, chemistries were normal, except that the calcium bone index was 0.57 and bone biopsy showed regression of osteomalacia toward normal. Vitamin D2 was now withdrawn for 6 months, resulting in loss of bone pain. Vitamin D2 may produce a metabolic bone disease, requiring prolonged withdrawal for improvement.

