Accelerated improvement of alcoholic liver disease with enteral nutrition. Comparison of enteral feeding and total parenteral nutrition after liver transplantation. Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics. A randomized controlled trial. Prospective randomized controlled study of short-term perioperative oral nutrition with branched chain amino acids in patients undergoing liver surgery. [Total enteral nutrition versus mixed enteral and parenteral nutrition in patients at an intensive care unit]. A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis. The influence of Enteral Nutrition in postoperative patients with poor liver function. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism. Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis. Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial. A randomized, controlled, a single-blind trial of nutritional supplementation after acute stroke. A prospective randomized study of preoperative nutritional supplementation in patients awaiting elective orthotopic liver transplantation. A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function. Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Perioperative nutritional support: a randomised clinical trial. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6). A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Randomized clinical trial of laxatives and oral nutritional supplements within an enhanced recovery after surgery protocol following liver resection. Nutrition support with glutamine dipeptide in patients undergoing liver transplantation. The favorable effect of early parenteral feeding on survival in head-injured patients. A prospective randomized clinical trial of total parenteral nutrition in children with cancer. Early enteral nutrition support in patients undergoing liver transplantation. Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma.
This prospective study compared the effects of tube-fed nutrition with those of a regular diet in alcoholic liver disease. The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support. Patients were randomly assigned a regular diet without or with tube-fed supplementation, delivering 1.5 g/kg protein and 167 kJ/kg daily. Comparisons of encephalopathy, antipyrine clearance, metabolic rate, and biochemical parameters were performed weekly for 4 weeks. Sixteen patients receiving enteral supplementation had antipyrine half-life (50% vs. 3% reduction), serum bilirubin (25% vs. 0% reduction), and median encephalopathy scores that improved more rapidly than those of controls. Initially, 15 controls did not consume adequate calories to meet measured resting energy expenditure. Aggressive nutritional intervention accelerated improvement in alcoholic liver disease. Adverse effects did not offset the demonstrated benefits of a 2-cal/mL, casein-based tube-fed supplement. These findings support the use of standard, casein-based solutions in the treatment of alcoholic liver disease and as the control condition for future studies. Total parenteral nutrition is used for nutritional support in patients undergoing orthotopic liver transplantation but is associated with complications. We compared the efficacy and tolerability of early enteral feeding with total parenteral nutrition after liver transplantation. 24 patients were studied: 14 received enteral feeding and 10 total parenteral nutrition. A double-lumen enteral tube was used to deliver the feed directly into the jejunum with the second lumen of the tube being used for gastric aspiration. Enteral feeding was started post-operatively within 18 h, was well-tolerated, and of comparable efficacy to total parenteral nutrition. The median number of days for patients to start eating (4) and to achieve 70% of estimated requirements orally (5) did not differ significantly between the two groups. Mid-arm circumference, triceps skinfold thickness, and biceps skinfold thickness were, by comparison with pre-operative values, maintained on the tenth postoperative day in both groups. Early postoperative absorptive capacity, as assessed by a combined carbohydrate test, was reduced significantly in both groups but insufficiently to be of nutritional concern. Intestinal mucosal integrity, as assessed by an intestinal permeability test, was maintained throughout. We conclude that the practical aspects of enteral feeding after liver transplantation are surmountable and that enteral feeding is as effective at maintaining nutritional status as total parenteral nutrition, and has potential benefits in terms of reduced complications and costs. Thirty-five severely malnourished cirrhotic patients were randomized to receive either enteral-tube feeding as the sole nutritional support (n = 16) or an isocaloric, isonitrogenous, low-sodium standard oral diet (n = 19). Both groups were homogeneous regarding age, sex distribution, etiology of liver cirrhosis, history of previous complications, clinical status, liver and renal function, modified Child's score, and nutritional status at admission. The enteral formula diet was energy dense, containing 40 mmol Na/day, whole protein plus branched-chain amino acids, medium- and long-chain triglycerides, and maltodextrin. It supplied 2115 kcal/day. The amount of vitamins and trace elements was at the upper limit of the recommended dietary allowances. The orally fed patients were encouraged to eat all meals served. Total enteral nutrition was well tolerated without major complications. Serum albumin and Child's score improved in the enterally fed patients but not in controls. Mortality rate while in the hospital was lower in patients on enteral feeding than in controls (12% vs 47%). These results show that total enteral nutrition is safe and effective in improving the short-term clinical outcome in severely malnourished cirrhotics. Early prospective randomized clinical trials demonstrated that perioperative parenteral nutrition (PN) with branched chain amino acids (BCAA) is beneficial in cirrhotic patients with hepatocellular carcinoma who undergo hepatectomy. However, PN support is expensive and requires a long hospital stay. Moreover, PN support has not been evaluated in patients with a normal liver who undergo hepatectomy. It was studied the benefits of perioperative oral nutrition (ON) with BCAA in patients who underwent hepatectomy, including those with a non-hepatitis liver.
                In this prospective, randomized, controlled trial, 38 patients were assessed for eligibility. Fourteen patients were excluded because they had received intraoperative blood transfusions or incomplete resections. The 24 eligible patients (20 with malignant liver tumors and 4 with benign liver tumors) were randomly assigned to receive perioperative ON with BCAA (11 patients, BCAA group) or a usual diet (13 patients, control group). The BCAA group received a BCAA supplement twice daily plus a usual diet for 14 days before operation and on days 1 to 7 after operation. The control group received a usual diet alone. The primary end point was the improvement in postoperative biochemical measurements.
                Two of the 11 patients in the BCAA group developed postoperative complications, as compared with 3 of the 13 patients in the control group (18.2% vs. 23.1%, p = 0.7686). Serum levels of alanine aminotransferase, aspartate aminotransferase, and ammonia did not differ significantly between the BCAA group and control group; however, peak values were lower in the BCAA group. There was no difference between the groups in serum hemoglobin levels after operation. Among patients with hepatitis, serum erythropoietin (EPO) levels on POD 3, 5, and 7 were slightly but not significantly higher in the BCAA group than in the control group. Among patients with non-hepatitis, serum EPO levels on POD 3, 5, and 7 were significantly higher in the BCAA group than in the control group (p = 0.0174, p = 0.0141, and p = 0.0328, respectively).
                Short-term ON support with BCAA was associated with higher serum EPO levels than was a normal diet in patients with non-hepatitis who underwent curative hepatic resection. Higher EPO levels might be beneficial in protecting liver cells from ischemic injury and preventing intraoperative hemorrhage associated with lower perioperative levels of alanine aminotransferase and aspartate aminotransferase in serum. This is the first study to demonstrate an effect of EN support with BCAA in patients with non-hepatitis, as well as those with hepatitis. To compare metabolic, nutritional and epidemiological data in two groups of patients, one receiving total enteral nutrition, via nasoenteric tube, and one receiving both enteral and parenteral nutrition.
                A prospective, randomized study.
                A general ICU, with both medical and surgical patients, in a big regional University and National Health Service hospital.
                24 patients requiring Intensive Care after major surgery or because suffering from severe head injury or major neurological impairment.
                All patients initially received total parenteral nutrition: after 4 days 12 patients were "weaned" to total enteral nutrition and 12 stayed on mixed parenteral and enteral nutrition. LABORATORY INVESTIGATIONS AND OBSERVATIONAL DATA: Blood levels of albumin, prealbumin, transferrin, ALT, AST, bilirubin, blood urea, blood glucose, total linfocite count, and nutritional and epidemiological data such as nitrogen balance, calorie intake, diarrhea incidence, blood and sputum cultures and radiologic evidence of pneumonia are analysed.
                At T1, NET patients were able to reduce their nitrogen losses (0.27.1 g/kg +/-0.12 vs 0.35 +/- 0.13 at TO; p < 0.05) and improve nitrogen balance (-9 +/- 7 vs -2 +/- 6 at T0; p < 0.05); they also had a better total linfocite count (2034 +/- 304 vs. 1413 +/- 360 of the MISTA group; p < 0.05), and a lower incidence of pneumonia as documented by sputum cultures and radiograms.
                Patients fed with both parenteral and enteral nutrition did no better than those on total enteral nutrition as far as nutritional and metabolic indices were concerned; they also seemed more prone to infections than those on total enteral nutrition, indicating that mixed nutrition may result in more stable feeding, but this does not seem to have any beneficial nutritional, immunological and metabolic effect. We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites. To investigate the safety, rationality and the practicality of enteral nutritional (EN) support in the postoperative patients with damaged liver function and the protective effect of EN on the gut barrier.
                135 patients with liver function of Child B or C grade were randomly allocated to enteral nutrition group (EN, 65 cases), total parenteral nutrition group (TPN, 40 cases) and control group (CON, 30 cases). Nutritional parameters, hepatic and kidney function indexes were measured at the day before operation, 5th and 10th day after the operation respectively. Comparison was made to evaluate the efficacy of different nutritional support. Urinary concentrations of lactulose(L) and mannitol(M) were measured by pulsed electrochemical detection(HPLC-PED) and the L/M ratio calculated to evaluate their effectiveness on protection of gut barrier.
                No significant damages in hepatic and kidney function were observed in both EN and TPN groups between pre- and postoperatively. EN group was the earliest one reaching the positive nitrogen balance after operation and with the lowest loss of body weight and there was no change in L/M ratio after the operation (0.026+/-0.004) at the day 1 before operation, 0.030+/-0.004 at the day 5 postoperative and 0.027+/-0.005 at the day 10 postoperative), but the change in TPN group was significant at the day 5 postoperative (0.027+/-0.003 vs 0.038+/-0.009,P<0.01).
                EN is a rational and effective method in patients with hepatic dysfunction after operation and has significant protection effect on the gut barrier. The aims of this study were to define the indications for, and to evaluate the cost-effectiveness of, nutritional support in patients with acute pancreatitis.
                All admissions during the 12-month period from January through December 2000, were entered into a common management protocol consisting of an initial 48-h fast with i.v. fluids and analgesics. After 48 h, those patients who were improving were restarted on oral feeding (group O). The remaining patients were randomized to receive nasojejunal (group EN) or parenteral feeding (group TPN). The randomization study was continued until 50 patients had been accrued. Outcomes in the three groups were compared with respect to length of hospital stay, duration of feeding, complications, and hospital costs.
                A total of 156 admissions were evaluated in the first 12 months. Of these, 87% patients had mild disease, 10% moderate, and 3% severe; 62% were related to alcohol abuse, 18% gallstones, and 8% idiosyncratic drug reactions. Of the patients, 75% improved on 48 h bowel rest and i.v. fluids, and were discharged within 4 days. The remainder were randomized to jejunal elemental (n = 26) or parenteral (n = 27) feeding. Duration of feeding was shorter with EN (6.7 vs 10.8 days, p < 0.05) and nutrition costs were lower, representing an average cost saving of $2362.00 per patient fed. EN was less effective in meeting estimated nutritional requirements (54 vs 88%, p < 0.0001), but metabolic (p < 0.003) and septic complications (p = 0.01) were lower. Subgroup analysis of patients with severe disease showed similar findings.
                Despite concerns that metabolic expenditure is increased and that food-stimulated pancreatic secretion might exacerbate the disease process, hypocaloric enteral feeding seems to be safer and less expensive than parenteral feeding and bowel rest in patients with acute pancreatitis. The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine. A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease. The provision of nutritional support for patients in intensive care units (ICUs) varies widely both within and between institutions. We tested the hypothesis that evidence-based algorithms to improve nutritional support in the ICU would improve patient outcomes.
                A cluster-randomized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998. Hospital ICUs were stratified by hospital type and randomized to the intervention or control arm. Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study (n = 499). Evidence-based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions, reminders (local dietitian, posters) and academic detailing that stressed early institution of nutritional support, preferably enteral.
                Two hospitals crossed over and were excluded from the primary analysis. Compared with the patients in the control hospitals (n = 214), the patients in the intervention hospitals (n = 248) received significantly more days of enteral nutrition (6.7 v. 5.4 per 10 patient-days; p = 0.042), had a significantly shorter mean stay in hospital (25 v. 35 days; p = 0.003) and showed a trend toward reduced mortality (27% v. 37%; p = 0.058). The mean stay in the ICU did not differ between the control and intervention groups (10.9 v. 11.8 days; p = 0.7).
                Implementation of evidence-based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes. Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index (PNI) score of greater than 30% were randomized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list. Two groups of 17 patients were well matched for age, sex, and nutritional status. Although they underwent diverse operations, the extent of these was similar: 12 +/- 3 days of parenteral nutrition resulted in weight gain, 3.2 +/- 2.3 kg p less than 0.01; increased triceps skinfold, 0.6 +/- 1.2 mm p less than 0.05; improved immunological state, p less than 0.02; and improved PNI, 5.5 +/- 10.1% p less than 0.05. The changes in serum albumin and transferrin were not significant. There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths. This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition, but to conclusively prove this a large and probably multicentre study will be required. Although stroke patients who do not have difficulty swallowing may be at risk of undernutrition and worsening nutritional status during hospitalization, optimum methods for nutrition intervention in stroke patients have not been established.
                To examine the feasibility of enteral sip feeding as an effective nutrition intervention after acute stroke.
                Forty-two acute ischemic stroke inpatients with impaired nutritional status who did not have difficulty swallowing within 1 week after the stroke were entered into a single-blind, randomized, controlled, prospective study of enteral sip feeding. Twenty-one patients were randomized to receive daily oral food supplements for 4 weeks in addition to the hospital food, and 21 patients received only the hospital food for the same period. Main outcome measures were energy and protein intakes during the intervention period, change in nutritional status, disability, infective complications, length of stay, and mortality during hospitalization and at 3 months.
                Two patients, one from each group, were lost to follow-up immediately after randomization. Twenty patients received oral nutritional supplementation. The energy intake was significantly greater in the supplemented group: 1807 +/- 318 vs 1084 +/- 343 kcal/d (mean +/- SD; p < .0001) (estimated treatment effect, 723 kcal/d; 95% confidence interval [CI], 498 to 947), as was protein intake: 65.1 +/- 13.8 vs 44.1 +/- 12.8 g/d (p < .001) (estimated treatment effect, 21.0 g/d; 95% CI, 11.7 to 30.3). There also were significant differences between the two groups in the changes in serum albumin and serum iron concentrations between randomization and at follow-up. There was a trend to lower mortality at 3 months in the supplemented group with two deaths (10%) compared with seven deaths (35%) in the control group (p = .127, relative risk, 0.29; 95% CI, 0.07 to 1.21).
                This study suggests that enteral sip feeding is effective in improving nutritional intake and status in stroke patients who do not have swallowing difficulties. There also may be some beneficial effects on clinical outcome, but larger studies are required to confirm this observation and define more precisely the magnitude of any favorable effects. Poor nutritional status is common among patients awaiting orthotopic liver transplantation and is associated with poor outcome.
                This prospective randomized controlled trial examined the effect of pretransplant nutritional supplementation on the outcome of patients undergoing liver transplantation. Of 82 consecutive patients with mid-arm muscle circumference <25th percentile, 42 received enteral supplementation, and the remainder acted as the control group. The supplemented group received a calorie-dense enteral feed taken daily (in addition to diet) until transplantation. Nutritional status was monitored by upper arm anthropometric measurements and handgrip strength. Dietary intake was calculated from 5-day food diaries.
                Supplementation improved mid-arm circumference, mid-arm muscle circumference, and grip strength. Pretransplant nutritional status was not associated with posttransplant sepsis or major complications. Preoperative grip strength of <85% of normal values was predictive of increased incidence of posttransplant major complications. Supplementation did not affect outcome, although there were more deaths in the control group (seven deaths before and two deaths after transplant) than there were in the supplemented group (two deaths before and three deaths after transplant). There was no difference in overall survival (P = 0.075).
                Enteral supplementation improved some parameters of nutritional status pretransplant. Dietary intake of patients in the two groups was similar at transplant. Nutritional supplementation has not increased nutritional intake, although this may reflect the importance of regular dietetic input and support, rather than suggesting that nutritional supplementation is ineffective. Supplementation had no effect on outcome of liver transplantation. The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured. Sixty-four patients admitted with acute alcoholic hepatitis, with or without underlying cirrhosis, were randomized regardless of encephalopathy to receive a controlled diet either alone, or supplemented orally, nasogastrically, or intravenously as necessary, with 2000 kCal and 10 g nitrogen daily. Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also randomly determined. In the absence of renal failure, nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance, but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls. Neither in the series as a whole, nor in any identifiable subgroup of patients, was mortality affected by treatment. Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups, and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention. Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy. Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28. On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 +/- 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 +/- 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 +/- 1.4 mg per dl) than in the oral group (4.1 +/- 2.2 mg per dl) (p less than 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14 and 21 (p less than 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups. Parenteral nutrition is well established for providing nutritional support in acute pancreatitis while avoiding pancreatic stimulation. However, it is associated with complications and high cost. Benefits of enteral feeding in other disease states prompted a comparison of early enteral feeding with total parenteral nutrition in this clinical setting.
                Thirty-eight patients with acute severe pancreatitis were randomized into two groups. The first (n = 18) received enteral nutrition through a nasoenteric tube with a semi-elemental diet, while the second group (n = 20) received parenteral nutrition through a central venous catheter. Safety was assessed by clinical course of disease, laboratory findings and incidence of complications. Efficacy was determined by nitrogen balance. The cost of nutritional support was calculated.
                Enteral feeding was well tolerated without adverse effects on the course of the disease. Patients who received enteral feeding experienced fewer total complications (P < 0.05) and were at lower risk of developing septic complications (P < 0.01) than those receiving parenteral nutrition. The cost of nutritional support was three times higher in patients who received parenteral nutrition.
                This study suggests that early enteral nutrition should be used preferentially in patients with severe acute pancreatitis. Ever since methods of artificial nutritional support became available, attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients. Many trials have addressed this question, but very few have given a meaningful answer because of conceptual and methodological flaws. We therefore undertook a prospective randomised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition (TPN) (n = 51) or total enteral nutrition (TEN) (n = 50) providing 150% basal energy expenditure (BEE) non-protein energy, to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion. 50 patients served as a depleted control group (D) and 49 patients served as a non-depleted reference group (ND) and were operated upon without delay. Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group (p < 0.05). There was no significant difference, however, in septic complications between either of the nutritional support groups and the non-depleted control group. In high risk patients, with weight loss >10% of body weight and over 500 ml blood loss during operation, a significant decrease in major complications was observed (p < 0.05) as a result of nutritional support. We conclude that pre-operative nutritional support, in patients with severe depletion, results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients. Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia.
                Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded.
                All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN.
                Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease. The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer.
                Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited.
                Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression.
                Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups.
                Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies. Routine laxatives may expedite gastrointestinal recovery and early tolerance of food within an enhanced recovery after surgery (ERAS) programme. Combined with carbohydrate loading and oral nutritional supplements (ONS), it may further enhance recovery of gastrointestinal function and promote earlier overall recovery.
                Seventy-four patients undergoing liver resection were randomized in a two-by-two factorial design to receive either postoperative magnesium hydroxide as a laxative, preoperative carbohydrate loading and postoperative ONS, their combination or a control group. Patients were managed within an ERAS programme of care. The primary outcome measure was time to first passage of stool. Secondary outcome measures were gastric emptying, postoperative oral calorie intake, time to functional recovery and length of hospital stay.
                Sixty-eight patients completed the trial. The laxative group had a significantly reduced time to passage of stool: median (interquartile range) 4 (3-5) versus 5 (4-6) days (P = 0.034). The ONS group showed a trend towards a shorter time to passage of stool (P = 0.076) but there was no evidence of interaction in patients randomized to the combination regimen. Median length of hospital stay was 6 (4-7) days. There were no differences in secondary outcomes between groups.
                Within an ERAS protocol for patients undergoing liver resection, routine postoperative laxatives result in an earlier first passage of stool but the overall rate of recovery is unaltered.
                Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. The effect of total parenteral nutrition (TPN) support supplemented with alanyl-glutamine (Ala-Gln) dipeptide was investigated in a randomized, controlled clinical trial.
                Sixty-five patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma admitted for orthotopic liver transplantation were randomly divided into 3 groups: diet group (n = 21), TPN group (n = 22), and Gln group (n = 22). Patients in the TPN and Gln groups received isocaloric and isonitrogenous TPN for 7 days. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery; we performed routine pathologic tests.
                Compared with the results on day 9 in the TPN group, there was a significant increase in the prognostic nutrition index and in prealbumin among the Gln group. Aspartate aminotransferase improved significantly by Gln treatment compared with traditional TPN support (P < .05). The pathologic results also showed Gln supplementation to reduce hepatic cell injury. A significant decrease in postoperative hospital stay was observed in the Gln group.
                Posttransplant TPN support greatly improved protein metabolism and nutritional state of patients. TPN with Ala-Gln helped to improve synthetic function and to reduce the injury to a transplanted liver. This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury. A prospective randomized clinical trial was undertaken to test the efficacy of total parenteral nutrition (TPN) among previously untreated children receiving abdominal/pelvic irradiation with or without adjuvant chemotherapy who were at risk for weight loss, malnutrition, and complications from treatment. Children were evaluated by weight/height determinations, anthropomorphic measurements, and laboratory studies. TPN was associated with an improved nutritional status during therapy as compared with control patients on ad libitum intake. However, when TPN was discontinued, weight declined and there were no differences among treated and control patients detected at three-month follow-up. Likewise there was no obvious effect from TPN on tolerance to therapy in the adequately nourished child. TPN as initial supportive therapy should be reserved for those children who are malnourished or marginally malnourished at the time of presentation. Close nutritional assessment during treatment is essential since approximately 25% of children undergoing abdominal/pelvic radiotherapy with chemotherapy can be expected to become malnourished during an initial course of therapy. The purpose of this study was to determine the effects of early postoperative tube feeding on outcomes of liver transplant recipients.
                Fifty transplant patients were randomized prospectively to receive enteral formula via nasointestinal feeding tubes (tube-feeding [TF] group) or maintenance i.v. fluid until oral diets were initiated (control group). Thirty-one patients completed the study. Resting energy expenditure, nitrogen balance, and grip strength were measured on days 2, 4, 7, and 12 after liver transplantation. Calorie and protein intakes were calculated for 12 days posttransplant.
                Tube feeding was tolerated in the TF group (n = 14). The TF patients had greater cumulative 12-day nutrient intakes (22,464 +/- 3554 kcal, 927 +/- 122 g protein) than did the control patients (15,474 +/- 5265 kcal, 637 +/- 248 g protein) (p < .002). Nitrogen balance was better in the TF group on posttransplant day 4 than in the control group (p < .03). There was a rise in the overall mean resting energy expenditure in the first two posttransplant weeks from 1487 +/- 338 to 1990 +/- 367 kcal (p = .0002). Viral infections occurred in 17.7% of control patients compared with 0% of TF patients (p = .05). Although other infections tended to occur more frequently in the control group vs the TF group (bacterial, 29.4% vs 14.3%; overall infections, 47.1% vs 21.4%), these differences were not statistically significant. Early posttransplant tube feeding did not influence hospitalization costs, hours on the ventilator, lengths of stay in the intensive care unit and hospital, rehospitalizations, or rejection during the first 21 posttransplant days.
                Early posttransplant tube feeding was tolerated and promoted improvements in some outcomes and should be considered for all liver transplant patients. Aminoleban EN contains branched-chain amino acids (BCAA) and is known to be beneficial for the protein-energy malnutrition in cirrhotic patients. Patients suffering from hepatocellular carcinoma often have background cirrhosis, and the present study investigates the effect of Aminoleban EN on these patients after hepatic resection for the primary disease.
                A prospective randomized controlled clinical trial, to which 50 patients were recruited, was carried out. The study group received Aminoleban EN in addition to normal diet for 12 weeks and the control group received an isonitrogenous and isocaloric diet only.
                After exclusions, there were 21 patients in the study group and 23 patients in the control. The study group had a shorter hospital stay, and had a significantly higher haemoglobin level, higher sodium level, higher albumin level and lower bilirubin during the postoperative course. There was no significant difference in terms of neuropsychiatric symptoms or Karnofsky performance score. There was no difference in gastrointestinal symptoms or other signs. No adverse reaction was associated with the administration of Aminoleban, and there was no significant difference in terms of morbidity and mortality between the two groups of patients.
                Aminoleban EN is safe to administer and does not have significant adverse effects. It contributes to a shorter hospital stay and quicker improvement of liver function in the early postoperative period. These beneficial results require only a 12-week period of administration of BCAA after operation.
The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.