Effect of taurine on total parenteral nutrition-associated cholestasis

A decrease in the formation/secretion of bile has been well documented in animals on total parenteral nutrition (TPN). Either an excess or an imbalance of amino acids (AA) has been most often implicated. In view of recent work showing that taurine promotes bile flow, bile acid secretion, and protects against hepatotoxic bile acids, the effect of adding taurine (15 mg/dL) to an AA solution was examined in guinea pigs on TPN for 3 days. The TPN-taurine group had a larger bile flow than the group without taurine and had bile acid secretory rates (BASR) similar to those of controls who were on saline by central catheter and had free access to food. Bile composition showed an increase in the secondary bile acid, 7-ketolithocholate and a concomitant decrease in chenodeoxycholate (CDC) in both experimental groups. Taurine led to a reversal of the usual predominance of glycine over taurine conjugated bile acids as well as to increases in HCO3 in cholesterol secretion. In response to a challenge with a large load of CDC, the TPN-taurine animals increased their BASR beyond those observed in the two other groups. These observations suggest that the addition of taurine to TPN solutions could play a role in the prevention of altered biliary function associated with AA solutions.     

Relationship between serum albumin and parenteral nutrition-associated cholestasis

In a prospective study of 59 patients receiving total parenteral nutrition we found that patients with low serum albumin were more likely to develop cholestasis than patients with normal serum albumin. Only 25% of patients with a normal serum albumin developed cholestasis. Seventy-nine percent of patients with low serum albumin (less than 3.5 g/dl) developed cholestasis (p less than 0.01). In those patients who developed cholestasis, there was a significant correlation (r = 0.63, p less than 0.01) between the serum albumin and the number of days after onset of total parenteral nutrition when cholestasis appeared. The role of hypoalbuminemia in the development of total parenteral nutrition-associated cholestasis deserves further study.     

早产儿胃肠外营养相关性胆汁淤积症的临床研究

目的研究早产儿胃肠外营养相关性胆汁淤积症(PNAC)的危险因素。方法收集南方医科大学南方医院2006年1月-2015年12月危重症早产儿441例资料进行回顾性分析,根据是否发生PNAC分为PNAC组57例和非PNAC组384例,比较两组患儿出生体重、胃肠喂养开始时间、达到全胃肠营养时间等情况。根据胎龄及入院时间划分亚组进行分析比较PNAC的发生率。结果 PNAC发生率为12.93%。两组早产儿在胎龄、出生时体重、胃肠喂养开始时间、达到全胃肠营养时间等方面差异有统计学意义(P0.05)。结论胎龄小、出生体重小、胃肠开始营养延迟等是PNAC的危险因素。应采用综合治疗措施减少PNAC的发生。     

Parenteral nutrition-associated cholestasis in neonates: the role of aluminum

Parenteral nutrition (PN) is an essential component in the care of premature and ill infants. The incidence of parenteral nutrition-associated cholestasis (PNAC) ranges from 7.4 to 84%. One substance in PN solutions that has been implicated in PNAC is aluminum. Aluminum loading in animals and humans causes hepatic accumulation and damage. The degree of aluminum contamination of PN solutions has decreased over time, but contamination still significantly exceeds levels that are safe for human neonates. Further study into the relationship between aluminum contamination in neonatal PN solutions and the development of PNAC is necessary.     

思美泰与还原型谷胱甘肽治疗新生儿胃肠外营养相关性胆汁淤积的临床疗效研究

目的:探讨思美泰与还原型谷胱甘肽治疗新生儿胃肠外营养相关性胆汁淤积(PNAC)的临床疗效。方法:将2006年2月～2010年8月诊断为胃肠外营养相关性胆汁淤积的新生儿随机分为治疗组和对照组,治疗组44例采用抗感染、肝酶诱导、思美泰、还原型谷胱甘肽治疗,对照组43例采用抗感染、肝酶诱导、肝泰乐护肝传统治疗,比较两组的疗效。结果:治疗组退黄、降酶作用明显,总有效率为95.4%,对照组总有效率为69.7%,差异有统计学意义(χ2=15.6,P<0.05)。结论:思美泰与还原型谷胱甘肽治疗PNAC能有效退黄、降酶,作用明显,未见明显不良反应。     

Glutamine supplementation does not prevent small bowel mucosal atrophy after total parenteral nutrition in the rat

Glutamine supplementation to non-lipid parenteral nutrition has been demonstrated to attenuate villus atrophy and increase mucosal DNA content in the rat. This study was performed in order to determine the effects of glutamine supplementation to a balanced TPN mixture (including lipids) on epithelial cell kinetics using autoradiography. Male Sprague-Dawley rats were used. Group 1 (control) received food and an intravenous saline infusion. Group 2 received an intravenous TPN mixture including lipids but without glutamine. The same TPN mixture, glutamine replacing an isonitrogenous amount of non-essential amino acids, was given to Group 3. Animals were fed for 7 days, whereafter blood and intestinal samples were taken 1 h after injection of tritiated thymidine. Microscopy of specimens from proximal jejunum revealed a significant reduction in the number of cells in crypts and villi in both TPN groups (2 and 3) compared to orally fed animals (p < 0.001). Epithelial cell numbers were not significantly different in Group 2 and 3. Similarly, the labelling index (number of labelled cells/number of crypt cells) was not affected by glutamine administration. In plasma, glucagon concentrations in Group 2 (TPN without glutamine) seemed to decrease compared to Group 1 and 3 (p = 0.06). In this study, glutamine supplementation did not affect apithelial atrophy or cell proliferation. It is concluded, that the effects of glutamine on mucosal atrophy and renewal in jejunum may depend on the composition of the TPN mixture supplied during parenteral feeding.     

Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures

It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.     

极低出生体重儿肠外营养相关性胆汁淤积的临床高危因素

目的　探讨极低出生体重儿肠外营养相关性胆汁淤积（PNAC）的临床特点及高危因素，为该病的防治提供依据。方法　选取2013年1月至2014年10月青岛大学附属医院新生儿科收治的胎龄≤34周、接受肠外营养（PN）支持＞14 d的141例极低出生体重儿，按是否发生PNAC分为PNAC组（n=32）和非PNAC组（n=109），回顾性分析并比较两组的临床资料。结果　非PNAC组与PNAC组之间胎龄［（30.84±1.55）周比（29.68±2.04）周，t=2.952，P=0.005］、出生体重［（1 267.92±160.39）g比（1 050.63±229.74）g，t=6.064，P=0.000］、住院时间［（43.26±14.43）d比（66.47±22.25）d，t=-6.622，P=0.000］、禁食时间［（6.30±5.23）d比（11.94±7.92）d，t=-4.723，P=0.000］、PN持续时间［（32.40±13.72）d比（57.59±27.65）d，t=-7.039，P=0.000］、氨基酸最大日用量［（3.61±0.27）g/(kg·d)比（3.78±0.35）g/(kg·d)，t=-3.012，P=0.003］，合并感染（56.88%比87.50%，χ2=10.046，P=0.002）、肺炎（32.11%比68.75%，χ2=13.790，P=0.000）、坏死性小肠结肠炎（0.92%比9.38%，χ2=6.420，P=0.037）、新生儿呼吸窘迫综合征（55.05%比78.13%，χ2=5.503，P=0.019）、支气管肺发育不良（19.27%比46.88%，χ2=9.918，P=0.002）、先天性心脏病（4.59%比21.88%，χ2=7.405，P=0.007），应用肺表面活性物质（33.94%比59.38%，χ2=6.682，P=0.010）、经鼻持续气道正压通气（60.55%比87.50%，χ2=8.085，P=0.004）、机械通气（22.94%比43.75%，χ2=5.356，P=0.021）、经外周静脉置入中心静脉导管（44.04%比81.25%，χ2=13.737，P=0.000）的差异均有统计学意义。多因素Logistic回归分析显示PN持续时间为PNAC的独立高危因素（B=0.069，OR=1.071，95% CI=1.039～1.104，P=0.000）。结论　PNAC为多种因素共同作用所致，其中PN持续时间为其独立高危因素。尽早给予肠内喂养，缩短PN持续时间为降低PNAC发生率的保护措施。     

Heparin does not reduce catheter sepsis during total parenteral nutrition

Although it is recognized that the addition of heparin to total parenteral nutrition solutions reduces subclavian vein thrombosis from percutaneous polyethylene catheters, it does not affect the low thrombosis rate associated with polyurethane catheters. It has been suggested that heparin also reduces catheter sepsis during total parenteral nutrition. We reviewed the sepsis rate in 86 patients randomized to receive iv nutrition with or without heparin through polyethylene, polyvinyl, and polyurethane catheters. Blood was drawn from febrile patients for culture; if positive, catheters were removed and the tips cultured. Catheters were considered infected if blood and catheter tips were positive, or if fever disappeared within 48 hr after catheter removal, even if cultures were negative. Catheter sepsis occurred in two patients in both groups. It appears that heparin does not reduce sepsis from percutaneous subclavian vein catheters. Although its use may be indicated to reduce thrombosis associated with polyethylene catheters, there is no indication for its use to reduce sepsis with either type of catheter.     

极低出生体质量儿胃肠外营养相关性胆汁淤积危险因素临床分析

目的探讨极低出生体质量儿(VLBWI)胃肠外营养相关性胆汁淤积(PNAC)发病的独立危险因素。 方法选择2008年5月至2014年5月在四川大学华西第二医院接受胃肠外营养(PN)持续时间≥14 d,符合本研究纳入与排除标准的VLBWI的临床病历资料为研究对象。采用回顾性分析方法,将其按照接受持维PN后是否发生PNAC,分为PNAC组和非PNAC组。首先根据临床经验,确定导致PNAC的影响因素,并对其进行单因素分析;再根据单因素分析结果及专业知识,进一步进行非条件多因素logistic回归分析,最终确定导致PNAC的独立危险因素。 结果①最终符合本研究纳入与排除标准的VLBWI共计172例,其中非PNAC组为143例,PNAC组为29例,PNAC发生率为16.9%。两组受试者性别构成比、胎龄及分娩方式等比较,差异均无统计学意义(P>0.05)。②根据临床经验,对可能导致PNAC的临床观察项目(27项)与营养因素项目(19项)相关影响因素的单因素分析结果显示：8项临床观察项目与5项营养因素项目为可能导致PNAC的影响因素,如出生体质量轻,小于胎龄(SGA)儿,PN持续时间及禁食时间长,氨基酸热卡及脂肪乳热卡高,奶热卡低,感染性肺炎、败血症、新生儿坏死性小肠结肠炎(NEC)及感染性休克率高,母乳喂养及口服益生菌均为可能导致PNAC发生的影响因素,差异均有统计学意义(t/χ²＝－3.306,4.424,1.790,1.231,3.193,2.815,2.519,4.615,3.949,3.920,3.861,5.656,5.535;P<0.05)。③对可能导致PNAC的影响因素的非条件多因素logistic回归分析结果显示：新生儿感染(感染性肺炎、败血症、NEC及感染性休克),SGA儿,VLBWI,禁食时间长,PN持续时间长,氨基酸热卡比及脂肪乳热卡比高是导致PNAC的独立危险因素(OR＝8.785,3.851,7.134,4.728,6.746,7.113,3.765;95%CI：3.603～25.236,1.526～8.932,2.534～19.651,1.473～15.326,1.219～12.471,3.124～19.358,3.230～26.246;P<0.05),奶热卡比高、母乳喂养及口服益生菌是PNAC的保护因素(OR＝0.016,0.204,0.078;95%CI：0.027～0.679,0.076～0.531,0.013～0.169;P<0.05)。 结论VLBWI的PNAC发生与新生儿感染、SGA儿、出生体质量轻、PN持续时间长、氨基酸热卡比及脂肪乳热卡比高、禁食时间长有关,奶热卡比高、母乳喂养及口服益生菌为保护因素。     

Sensitivity and specificity of liver function tests in the detection of parenteral nutrition-associated cholestasis

We carried out a study to determine which of the liver function tests was the most sensitive and/or specific in detecting parenteral nutrition associated cholestasis. The tests utilized were alkaline phosphatase, gamma-glutamyl transpeptidase, cholylglycine, sulfolithocholylglycine, and bilirubin. Fifty-nine patients with no prior evidence of liver dysfunction were studied. We found gamma-glutamyl transpeptidase to be the most sensitive (89.5%) and also the least specific (61.9% specificity). Specificity of gamma-glutamyl transpeptidase was improved when it was combined with alkaline phosphatase. We recommend the combination of these two enzymes as the most cost effective way of detecting parenteral nutrition-associated cholestasis.     

早产儿早期微量喂养预防肠外营养相关性胆汁淤积的Meta分析

目的系统评价早产儿早期微量喂养预防肠外营养相关性胆汁淤积(PNAC)的临床治疗效果。方法利用计算机在数据库Pub Med、Embase、Cochrane图书馆、中国生物医学文献数据库(CBM)和中国期刊全文数据库(CNKI)中联合交叉检索主题词,检索时间和语种不限。纳入早期微量喂养对比全肠外营养与PNAC发生率的研究,收集有关早产儿早期微量喂养预防肠外营养相关性胆汁淤积的文章,并依据Cochrane Handbook 5. 1推荐的偏倚风险评估工具评价纳入符合标准的文献研究质量,采用STATA 12. 0软件分析数据。结果最终纳入9个研究(包含709例患者),Meta分析结果提示早期微量喂养组肠外营养持续时间明显短于全静脉营养组,差异有统计学意义(WMD=-3. 91,95%CI:-5. 36,-2. 45; P=0. 000); PNAC的发生率低于全静脉营养组(RR=0. 46,95%CI:0. 31,0. 68; P=0. 000)。灵敏度分析结果提示纳入研究合并结果较为稳定。结论早期微量喂养可有效预防早产儿PNAC发生率,缩短肠外营养持续时间。     

早产儿胃肠外营养相关性胆汁淤积的危险因素分析及防治措施

目的:探讨早产儿胃肠外营养相关性胆汁淤积(PNAC)的危险因素和有效的防治措施. 方法:将299例行PN治疗的早产儿根据是否为PNAC分为PNAC组(n=32例)和非PNAC组(n=267例).比较两组早产儿的临床和营养因素,采用Logistic回归分析危险因素. 结果:两组早产儿在胎龄、出生时体重、贫血、新生儿感染等方面存在显著性差异(P＜0.05);两组早产儿在禁食时间,氨基酸、脂肪乳和乳类的热量比,每天总热量和喂养困难等方面亦存在显著性差异(P＜0.05).多因素分析结果显示,禁食时间长、氨基酸和脂肪乳提供热量比率高、胎龄低、新生儿感染均为发生PNAC的危险因素(P＜0.05).乳类提供热量比率高则是保护性因素(P＜0.05).结论:禁食时间长、氨基酸与脂肪乳提供热量比率高、胎龄低、新生儿感染等为PNAC的危险因素.依此制订有效的防治措施,可明显降低PNAC的发生率.     

腺苷蛋氨酸预防大鼠全肠外营养并发的胆汁淤积

目的：观察Ｓ－腺苷－Ｌ－蛋氨酸（ＳＡＭｅ）对大鼠ＴＰＮ胆汁淤积的预防效果,并比较胆汁中胆盐的变化。方法：１８只ＳＤ大鼠随机分为三组,对照组,ＴＰＮ组,ＴＰＮ＋ＳＡＭｅ组,每组各６只,后两组均ＴＰＮ支持５天,然后插管收集胆汁,测量胆汁流量,采血检测血清总胆酸（ＳＴＢＡ）、ＧＧＴ、ＡＬＴ,ＡＫＰ水平,观察光镜,电镜下肝的病理变化,检测胆汁中胆盐含量。结果：ＴＰＮ组出现胆汁流下降,ＳＴＢＡ,ＧＧＴ水平升     

血清脂联素对极低出生体重早产儿胃肠外营养相关性胆汁淤积的相关性分析

目的 探讨血清脂联素(APN)与极低出生体重早产儿胃肠外营养相关性胆汁淤积(PNAC)的相关性。方法 所有符合标准的早产儿均于入院后24~48 h内取静脉血检测血清APN水平,以中位数13.15 mg/L为界,将≥13.15 mg/L患者分为高APN组63例,<13.15 mg/L为低APN组72例,记录随后5周内患儿PNAC发病率;以发生PNAC为事件终点,用Kaplan-Meier方法对PNAC发生率进行分析;Cox单因素回归分析血清APN与PNAC发生率的相关性。结果 随访期间,低脂联素组第2、3、4和5周PNAC发生率分别为21.8%、43.1%、64.0%、和79.2%,血清APN水平有逐渐下降趋势,3周、4周下降更明显(P<0.01);高APN组不同时段PNAC发生率分别为17.9%、33.1%、49.3%和67.8%,APN水平无明显变化(P>0.05)。分析显示两组PNAC发生率差异有统计学意义(P<0.01),Cox单因素分析,APN水平是影响患者远期预后的独立危险因素(P<0.05)。结论 随访过程中,在低APN组,伴随着APN水平的降低,PNAC发生逐渐增多。APN与极低体重早产儿胃肠外营养相关性胆汁淤积具有相关性。     

极低出生体重儿肠道外营养相关性胆汁淤积危险因素分析

目的探讨新生儿重症监护病房(neonatal intensive care unit,NICU)中极低出生体重儿(extremely low birth weight infants,ELBWI)肠道外营养相关性胆汁淤积(parenteral nutrition-associated cholestasis,PNAC)的危险因素。方法回顾NICU中229例静脉营养支持两周以上的极低出生体重儿的临床资料,比较PNAC组与非PNAC组在胎龄、出生体重等临床资料的差异。结果极低出生体重儿PNAC发生率为11.79%(27/229),PNAC组患儿胎龄、出生体重小于非PNAC组,而PN持续时间、PN热卡摄入量、脂肪乳最大剂量及累计用量、感染、贫血发生率大于非PNAC组(P0.05)。结论低胎龄、低出生体重、PN持续时间过长、PN提供热卡过高、脂肪乳最大剂量及累计用量、感染、贫血是极低出生体重儿发生PNAC的危险因素。     

Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine

BACKGROUND: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. METHODS: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. RESULTS: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [-0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79-5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61-10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. CONCLUSIONS: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.     

腺苷甲硫氨酸对感染大鼠全肠外营养胆汁淤积的预防

目的：观察S－腺苷－L－甲硫氨酸（S－Adenothyl-L-methionine,SAMet)对感染大鼠TPN淤胆的预防效果。方法：18只体重240－280g的SD雄性大鼠随机分为三组；对照组，感染＋TP组，感染＋TPN＋SAMet组，每组各6只，后两组均结扎盲肠致感染并持续TPN支持5天。SAMet按80mg/(kg.d)加入营养液中。实验结束，胆总管插管收集胆汁，测流量，采用检测血清总胆酸（STBA）、GGT、ATLT、AKP水平，光镜、电镜下观察肝病理变化，HPLC法检测胆汁中八种结合胆直总胆盐含量。结果：感染＋TPN组与对照组比较出现胆汗流下降，STBA、GGT、AKP水平升高，病理检查见肝组织脂肪浸润、毛细胆管扩张及胆栓；而感染＋TPN＋SAMet组较感染＋TPN组胆汁流升高，STBA、GGT、ALT、AKP水平均显著下降，肝 正常或病理改变明显减轻。胆汁胆直部仅个别胆盐有差异，其余绝大部分胆盐间无显著差异。结论：在感染大鼠实施TPN时给予SAMet可有效预防TPN胆汁淤积的发生，为临床上有不停止TPN的情况下预防淤胆的发生提供了一种新的措施。     

Glucose-based total parenteral nutrition does not stimulate glucose uptake by humans tumours

BACKGROUND: Since glucose represents the preferred fuel for cancer cells, there is some debate about the potential stimulation of tumour metabolism induced by a glucose-based total parenteral nutrition (TPN) in cancer patients. METHODS: We investigated the uptake of [18]2-fluoro-2-deoxy-D-glucose (FDG) through the positron emission tomography of the healthy liver and of the tumour in 12 patients with liver metastases from colorectal cancer. We determined whether FDG uptake by the tumour in fasting conditions was affected by the subsequent administration of a glucose-based (GTPN) or a lipid-based (LTPN) containing glucose 4 mg/kg/min or lipid 2 mg/kg/min, respectively, as non-protein energy source. RESULTS: The data showed that FDG uptake by the metastases was 3-3.6 times higher than by the healthy liver in fasting conditions and it was not significantly affected by the subsequent administration of GTPN or LTPN. CONCLUSIONS: We speculated that, despite glucose being the preferred fuel for cancer cells, its disproportionately high uptake even in fasting conditions makes the glucose consumption unable to be modulated by a further supply of glucose or lipid.     

Hyperbilirubinemia in neonates associated with total parenteral nutrition

To identify the factors responsible for total parenteral nutrition (TPN) associated jaundice in the neonate, 77 newborns who had been started on TPN during the past 12 years had their charts reviewed. Forty-four (57%) of these infants developed jaundice during the 1st month of life. The incidence of jaundice was significantly higher in the presence of those diseases which were associated with impaired intestinal passage such as congenital duodenal atresia, jejunal atresia, etc, and those with an abnormal rotation of the gut such as diaphragmatic hernia, gastroschisis, etc. Thirty-two (42%) of these 77 infants had accompanying infectious signs, and 28 (88%) of those 32 infants with infectious signs developed jaundice. This incidence was significantly higher than that (36%) among those who had no infectious signs. Of the possible etiologic factors other than infection, neither the length of intrauterine life nor birth weight showed significant correlation with the incidence of jaundice. The incidence of jaundice tended to be higher in infants started on TPN at a younger age. There was no significant correlation between the incidence of jaundice and the duration of TPN or fasting period. Infants receiving 110 cal/kg/day or more during TPN developed jaundice significantly more frequently than those receiving fewer calories. No definite correlation was obtained between the incidence of jaundice and the amount of amino acids administered.