The effect of enriched branched chain amino acid solution on amino acid metabolism during perioperative total parenteral nutrition support

A prospective, randomized clinical study was performed in patients underwent subtotal gastrectomy or hemicolectomy. Patients were randomly divided into two groups receiving standard amino acid solution (23% BCAA) or a solution enriched with branched chain amino acid (41% BCAA). Preoperative postprandial plasma amino acid levels were used as base line. The amino acid concentrations in plasma between control group (A) and study group (B) were compared during perioperative period. The dynamics of postoperative plasma amino acid profile of the two groups were similar except that plasma BCAA concentrations were very high in group B. In both groups, the levels of plasma glutamine, alanine, tyrosine, lysine, threonine, arginine, asparagine, and cystine decreased, whereas the levels of plasma methionine, phenylalanine, and tryptophan increased. The solution of 41% BCAA was not found to be superior to standard 23% BCAA in normalizing the disorder of plasma amino acid spectrum during the period of TPN support. The differences of urinary amino acid excretion including 3-MHIS and nitrogen balance between the two groups were not statistically significant. Also the results showed more severe disorder of plasma amino acid profile caused by 41% BCAA solution than by standard solution of 23% BCAA.     

富含谷氨酰胺和支链氨基酸的肠外制剂对创伤大鼠的效用

目的研究普通氨基酸注射液(17AA)与富含谷氨酰胺及支链氨基酸注射液(20AA)对创伤大鼠的营养效用.方法以Wistar大鼠为创伤模型,分别输注两种配方的氨基酸注射液,以日立L-8500氨基酸自动分析仪测定动物血浆游离氨基酸,并测定创伤处海绵内羟脯氨酸含量.结果显示创伤后大鼠血浆牛磺酸、谷氨酸、谷氨酰胺和支链氨基酸含量较术前下降,但20AA组血浆氨基酸恢复优于17AA组,创伤处海绵内羟脯氨酸含量20AA组显著高于17AA组(1.29±0.21 vs 0.83±0.16mg/块海绵,P＜0.05).结论创伤后给予富含谷氨酰胺和支链氨基酸的营养制剂能提高血浆氨基酸浓度并有利于创伤的恢复.     

Use of a branched chain amino acid enriched solution in patients under metabolic stress

The metabolic response to stress results in proteolysis, increased gluconeogenesis, and negative nitrogen balance. Infusion of BCAA has been shown experimentally to decrease protein degradation and stimulate protein synthesis. Such infusion may modify the response of patients to metabolic stress. An amino acid solution containing 45 percent BCAA as a component of central vein parenteral nutrition was infused into 20 moderately to severely stressed postoperative patients in a prospective, nonrandomized fashion. Infusion was begun within 24 hours postoperatively and continued for 7 to 14 days. Patients received 1.6 g protein equivalents per kg body weight daily and 30 kcal/kg body weight daily. Nutritional indexes as measured by albumin and transferrin values were maintained during the study period. Nitrogen balance became increasingly positive over the period of infusion without an increase in the urinary excretion of 3-methylhistidine. There were no serious clinical or biochemical side effects of the BCAA infusion, although a statistically significant increase in alkaline phosphatase was observed. These results suggest that central vein parenteral nutrition utilizing a 45 percent BCAA enriched solution can promote nitrogen retention without serious side effects in moderately to severely stressed patients.     

Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.     

Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial.

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.     

Effect of branched chain amino acid (BCAA) enriched solution in postoperative patients receiving TPN

Validity of branched chain amino acid (BCAA) enriched solution in surgical stress was assessed using total catecholamine excretion (U-CA) as the severity in dex. Thirty percent BCAA solution was infused no 21 patients (T group), and 21% BCAA to 18 patients (P group) pre and postoperatively. 2.0 g protein and 35 kcal/kg.day were provided by total parenteral nutrition (TPN). Correlation of nitrogen-balance to U-CA was statistically significant in both groups (p less than 0.01). The difference of correlations was statistically significant when analyzed by covariance (p less than 0.05). Rapid turnover proteins were significantly higher in T group, but no difference of urinary 3-methylhistidine excretion was observed. Increased uptake of BCAA and release of glutamine and alanine by skeletal muscle were observed. However, no alteration in arterio-venous difference of phenylalanine and tyrosine was detected. In conclusion, 30% BCAA solution significantly improved postoperative protein metabolism, probably due to the improved visceral protein metabolism supported by amino acid supply by skeletal muscle.     

Use of an intravenous branched chain amino acid enriched diet in the tumor-bearing rat

The purpose of this study was to determine whether a branched chain amino acids (BCAA) enriched intravenous feeding would have an effect on nitrogen retention in the host tissue, without stimulating tumor growth in the malignant tumor bearing animal. NEDH/c rats with an implanted fibrosarcoma were put on one of two total parenteral nutrition regimens, one of an amino acid formula containing 25 per cent BCAA, by weight and the other containing 50 per cent BCAA. Nitrogen retention in the two tumor-bearing groups was similar, although it was 47 per cent greater than observed in the non-tumor bearing animals (p less than 0.05). Skeletal protein synthesis was significantly reduced by the presence of the tumor in rats on the 25 per cent BCAA formula (from 10.1 per cent/day to 6.1 per cent/day) but was increased to 7.9 per cent/day by the 50 per cent BCAA formula. The BCAA enriched intravenous feeding does not enhance tumor growth and supports skeletal protein synthesis, at least in this experimental model.     

Use of an intravenous branched chain amino acid enriched diet in the tumor-bearing rat

The purpose of this study was to determine whether a branched chain amino acids (BCAA) enriched intravenous feeding would have an effect on nitrogen retention in the host tissue, without stimulating tumor growth in the malignant tumor bearing animal. NEDH/c rats with an implanted fibrosarcoma were put on one of two total parenteral nutrition regimens, one of an amino acid formula containing 25 per cent BCAA, by weight and the other containing 50 per cent BCAA. Nitrogen retention in the two tumor-bearing groups was similar, although it was 47 per cent greater than observed in the non-tumor bearing animals (po0.05). Skeletal protein synthesis was significantly reduced by the presence of the tumor in rats on the 25 per cent BCAA formula (from 10.1 per cent/day to 6.1 per cent/day) but was increased to 7.9 per cent/day by the 50 per cent BCAA formula. The BCAA enriched intravenous feeding does not enhance tumor growth and supports skeletal protein synthesis, at least in this experimental model.     

Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized, controlled study of branched chain amino acid-enriched total parenteral nutrition in malnourished patients with gastrointestinal cancer undergoing surgery

The objective of this study was to investigate the potential benefit of branched chain amino acid (BCAA)-enriched total parenteral nutrition (TPN) for malnourished surgical patients with gastrointestinal cancer. Sixty-four malnourished patients with gastrointestinal cancer with elective surgical intervention were equally allocated into two groups to receive isonitrogenous and isocaloric TPN. All of them must have received TPN soon after surgery and were subsequently randomized and divided into either BCAA-enriched TPN (30% BCAA; intervention group) or standard TPN (24% BCAA; control group). Patient biochemical data, nutritional parameters, and clinical outcome were collected to analyze the significance of BCAA-enriched TPN. After a period of TPN, laboratory data, including white blood cell (WBC), C-reactive protein (CRP), alkaline phosphatase (ALK-P), and gamma-glutamyltransferase (gamma-GT) levels, were significantly different between these two groups (all P < 0.05). Decreasing white blood cell and C-reactive protein levels were observed in the intervention group that might partially explain the reduced numbers of infectious complications. Furthermore, elevating alkaline phosphatase and gamma-glutamyltransferase levels being also less prominent might indicate a lesser hepatic burden by using BCAA-enriched TPN. The BCAA-enriched TPN can maintain a patient's serum visceral protein (albumin and prealbumin) and positive nitrogen balance better than standard TPN (all P < 0.05). Furthermore, a prominently decreased frequency of postoperative morbidity was also found in the BCAA-enriched TPN group (P = 0.021) despite no difference regarding surgical mortality. Our observations show that BCAA-enriched TPN may be beneficial in improving the nutritional status and reducing postoperative complications for malnourished patients with gastrointestinal cancer undergoing major surgery.     

门腔分流术后不同氨基酸溶液胃肠外营养的对比研究

目的　评价不同氨基酸溶液胃肠外营养对营养支持效果以及对肝脏功能和血浆氨基酸谱的影响。方法　因门脉高压症住院接受脾切除、限制性门腔静脉侧侧分流术的４０ 例肝功能Ｃｈｉｌｄ Ａ级患者,随机分为两组：Ｈｅｐａ 组和Ｖａｍｉｎ 组,每组各２０ 例。自手术后第１ 天起两组分别接受等氮、等热卡胃肠外营养支持８ 天（Ｈｅｐａ 组以Ｈｅｐａ 氨基酸溶液作为氮源,Ｖａｍｉｎ 组Ｖａｍｉｎ 氨基酸溶液作为氮源）。结果　两组累积氮平衡差异无显著性Ｈｅｐａ;营养支持８ 天后Ｈｅｐａ 组碱性磷酸酶水平显著低于Ｖａｍｉｎ 组（ Ｐ＜０．０５） ;营养支持８ 天后Ｈｅｐａ 组血氨水平显著低于Ｖａｍｉｎ 组（ Ｐ＜ ０－０５） ;Ｈｅｐａ 组血浆支链氨基酸（ＢＣＡＡ） 水平显著高于Ｖａｍｉｎ 组;Ｖａｍｉｎ 组血浆芳香族氨基酸（ＡＡＡ） 水平显著高于Ｈｅｐａ 组;Ｖａｍｉｎ 组血浆蛋氨酸（ＭＥＴＨ） 水平显著高于手术前水平（ Ｐ＜ ０－０１）。Ｈｅｐａ 组ＢＣＡＡ／ＡＡＡ〔（ＶＡＬ＋ ＬＥＵ＋ＩＬＥＵ）／（ＰＨＥ＋ ＴＹＲ）〕显著高于Ｖａｍｉｎ 组（ Ｐ＜ ０－０５）。结论　以Ｈｅｐａ 氨基酸溶液作为氮源可以取得与平衡型氨基酸溶液相似的营养支持效果;对于肝脏功能的损害方面,Ｈｅ     

Infusion of branched chain-enriched amino acid solutions in sepsis

The goal of nutritional support in sepsis is, as in other conditions, to prevent the use of endogenous protein as an energy substrate and, ideally, to promote the synthesis of proteins specifically required in responding to the particular insult or stress at hand. This entails provision of an utilizable fuel, in sufficient quantity, that does not inhibit the use of endogenous nonprotein sources; preservation of the existing protein mass by minimizing skeletal muscle and visceral proteolysis; provision of amino acids in sufficient quantity and in the appropriate proportions such that protein synthesis is optimized. Specifically, this includes the synthesis of those proteins required to maintain hyperdynamic function of the essential organs as well as the hepatic and leukocytic synthesis of proteins required in immunologic defense. This study has assessed one aspect of this goal during the administration of nutrient solutions differing primarily in branched chain amino acid content. We conclude that leucine is fundamental among the branched chain amino acids for reducing skeletal muscle proteolysis. Solutions designed for sepsis or stress should, therefore, contain adequate amounts of this amino acid.     

Effects of an amino acid solution enriched with either branched chain amino acids or ornithine-alpha-ketoglutarate on the postoperative intracellular amino acid concentration of skeletal muscle

Patients undergoing elective cholecystectomy provide a highly reproducible model of the effects of trauma on intermediary metabolism. Three parenteral nutrition regimens were given to groups of eight such patients. An isonitrogenous total parenteral nutrition, including a commercially available amino acid solution, an amino acid solution enriched with branched chain amino acids or one supplemented with ornithine-alpha-ketoglutarate, was given after operation. The intra cellular free amino acid concentrations of skeletal muscle were determined in tissue specimens obtained before operation and on the third postoperative day using a percutaneous needle biopsy technique. The mean (s.e.m.) decrease in the concentrations of free intracellular glutamine on the third postoperative day was less pronounced (P less than 0.05) in the ornithine-alpha-ketoglutarate group (18.8(7.5)per cent) than in the control group (39.4(5.1)per cent) or the branched chain amino acid group (45.3(6.1)per cent). In conclusion, in the immediate postoperative period total parenteral nutrition supplemented with ornithine-alpha-ketoglutarate countered the decline in the muscle free glutamine. No difference in this parameter was seen between the control group and the branched chain amino acid group.     

肋间神经冷冻止痛的实验及临床研究

目的 探讨减轻和消除开胸手术后剧烈胸痛的方法。方法 首先在－50℃条件下,分别以不同时间冷冻家犬肋间神经,观察病理改变及修复过程,寻找出可供临床应用的最佳冷冻时间。然后,按此冷冻时间,进行临床研究。对200例需开胸手术的患者随机分组,行冷冻止痛的前瞻性双盲对照研究。冷冻组与对照组各100例患者。冷冻组患者手术结束前常规冷冻切口、上下各一肋间以及放置引流管之肋间神经根部,根据视觉模拟评分法观察术后切口疼痛以及镇痛药使用情况;对照组患者除不用冷冻治疗外,其他处理同冷冻组。两组患者分别于术后第3,7,15,30,90天测定肺功能。结果 在家犬的实验中,随着冷冻时间的延长（30s-2.0min)神经轴索髓鞘的病理损害逐渐加重,但1个月后均恢复正常。能够有效止痛而且病理改变修复较快的冷冻时间是1.5min。将此冷冻时间用于临床研究。冷冻组止痛效果极为满意,VAS评分为2.29,对照组7.24,差异有非常显著性性意义（P＜0．001）;冷冻组疼痛0级22例（22％）,1－2级44例（44％）,3－4级20例（20％）5－6级8例（8％）,总有效率（0－6级）为94％;杜冷丁平均用量为41．3mg。对照组疼痛3－4级14例,5－6级20例,7－8级24例,9－10级42例,杜冷丁平均用量为41．3ng。对照组疼痛3－4级14例,5－6级20例,7－8级24例,9－10级42例,杜冷丁平均用量为185．0mg,2组差异有非常显著性意义（P＜0．001）。2组肺功能检测结果,差异无显著性意义。结论 冷冻肋间神经能够有效地预防开胸术后切口疼痛,此方法简便易行,而且神经的病理改变是可逆的。     

富含支链氨基酸的氨基酸配方对胃肠外科手术创伤患者的营养支持效果

目的 观察富含支链氨基酸（BCAA）的氨基酸配方对胃肠外科手术创伤患的营养支持效果。方法 按随机、前瞻、单盲、对照原则,将40例胃肠外科中等以上手术后成年患分为两组;研究组（富含BCAA组,20例）和对照组（复方氨基酸注射液,20例）,术后第2d开始,连续6d,采用全营养混合液通过周围或中心静脉输注,等氮等热卡,每日输注时间不少于12h,同时留24h尿测氮平衡,术前第1d、第7d抽静脉血,观察两组患的血氨基酸谱、血总蛋白、白蛋白、前白蛋白、转铁蛋白、纤维连接蛋白。结果 研究组较对照组早2d恢复正氮平衡,且优于对照组（P=0.002),血总蛋白、白蛋白下降明显低于对照组（P=0.013),缬氨酸浓度明显高于对照组（P=0.026),精氨酸浓度下降明显低于对照组（P=0.041)。结论 富含BCAA的氨基酸配方更适合胃肠外科手术创伤患的营养支持,有利于病情恢复。     

Influence of enteral and parenteral nutrition on splanchnic hemodynamics in septic patients

Background: Enteral nutrition is believed to augment splanchnic perfusion, thereby preserving splanchnic integrity, whereas parenteral nutrition does not offer this benefit. In an effort to study this, we compared splanchnic oxygen exchange and blood flow in critically ill, septic patients to normal controls during enteral or total parenteral nutrition. Methods: Splanchnic oxygen exchange and hepatic blood flow characteristics in 14 critically ill, septic patients were compared to 19 normal controls while fasting and during nutrient administration. Nutrients were delivered as intraduodenal feedings or parenteral nutrition. Splanchnic hemodynamics were measured at baseline, 90 min, and 210 min during nutrient administration. Hepatic blood flow index (HBFI) by indocyanine green dye (ICG) clearance, splanchnic oxygen consumption index (SplVO(2)I), and hepatic venous oxygen saturation (ShvO(2)) were measured using hepatic venous catheterization. Plasma volume (PV) was measured from the volume of ICG distribution. Results were analyzed using population means (+/-SD) and one-way analysis of variance. Results: There was no statistical change in HBFI, SplVO(2)I, PV or ShvO(2) over the study time interval within any group (p < 0.05), irrespective of whether enteral or parenteral nutrition was the nutrient source. Septic patients, whether fasting or receiving nutrition, demonstrated higher HBFI and SplVO(2)I levels, whereas ShvO(2) levels were uniformly lower throughout the study compared to normal controls. Conclusions: Critically ill patients exhibited a hyperdynamic splanchnic state as indicated by the marked increase in HBFI and SplVO(2)I. However, neither nutrient regimen at clinically relevant rates altered splanchnic hemodynamics over the course of study. Thus, enteral nutrients do not appear to offer hemodynamic protection to the splanchnic system in critically ill patients.