两种中/长链脂肪乳注射液在全合一(All-in-One)营养液中的稳定性对比研究

目的研究中伥链脂肪乳注射液在全合一(All—in-One)营养液中乳粒的大小及其分布的稳定性。方法本研究采用国产的中／长链脂肪乳注射液与已进口上市的MCT／LCT脂肪乳注射液比较,分别按照相同的处方配制成全合一营养液,各自静置在25℃1天后,存放于4℃8天,再25℃静置1天,随着不同的存放条件分别在第1、2、10天取样。用光散射分光光度法和库尔特微粒测定法测定营养液中的乳粒,观察乳粒大小及其分布的变化情况。同时测定样品的pH值和渗透压,观察营养液的稳定性以及营养液体系质点数的变化情况。结果在观察期内本研究的中／长链脂肪乳注射液与进口的MCT/LCT脂肪乳注射液在全营养液中比较,其乳粒大小及分布、pH值、渗透压变化均无显差别。结论本研究的中／长链脂肪乳注射液与进口上市的MCT／LCT脂肪乳注射液在全合一(All—in—One)营养液中具有相同的稳定性。     

无痛人流中应用丙泊酚联合芬太尼的临床麻醉效果分析

目的:探讨无痛人流中应用丙泊酚联合舒芬太尼的临床麻醉效果分析.方法:选取我院2016年1月至12月来门诊就医的早孕患者72例,按照病例编号分为对照组和观察组.其中对照组患者采用丙泊酚中/长链脂肪乳注射液实施麻醉,观察组患者采用舒芬太尼联合丙泊酚中/长链脂肪乳注射液实施麻醉.对比两组患者麻醉情况及手术无痛率.结果:通过对比,观察组患者麻醉效果各项指标优于对照组患者,且观察组手术无痛率高于对照组患者,具有统计学意义(P<0.05).结论:使用丙泊酚中/长链脂肪乳注射液联合舒芬太尼应用于无痛人流,镇痛效果好且缩短手术时间.     

中／长链脂肪乳注射液的临床研究

目的研究中／长链脂肪乳注射液的临床有效性和安全性。方法本研究为随机双盲、平行对照、多中心实验设计,符合研究方案、需要肠外营养的住院病人161例进入本研究。其中120例为有对照的安全性和有效性研究,另设41例观察较长时间不良反应。结果两组中／长链脂肪乳在氮平衡、前白蛋白和术后与感染有关的并发症等方面作用相似,均无明显不良反应。结论本研究的中／长链脂肪乳是安全有效的肠外营养药物。     

不同脂肪乳在肠外营养液中稳定性的研究

目的观察肠外营养液配制后在不同存放温度条件下脂肪乳的稳定性。方法采用规范化肠外营养液配制, 共配制24袋肠外营养液, 随机分为两组, A组12袋配方中脂肪乳为20%中/长链脂肪乳注射液(C6-24), B组12袋配方中脂肪乳为20%中/长链脂肪乳注射液(C8-24), 检测时间点为配制完成后24、48、72 h, 观察两组在2～8℃, 23～25℃和35～37℃中外观、营养液pH值和脂质过氧化。结果两组在4℃、25℃和36℃条件下分别放置24、48、72 h后, 外观均无明显变化, pH值差异无统计学意义(P>0.05), 脂质过氧化差异无统计学意义(P>0.05)。结论两种脂肪乳在不同存放条件下pH值、脂肪颗粒大小、脂质过氧化产物方面都较为稳定, 能够为进行静脉营养支持患者提供营养物质需求。     

脂肪乳新进展

作为肠外营养组成成分之一的脂肪乳可为机体提供能量并能防止体内必需脂肪酸的缺乏,这在临床实践中已成为人们的共识.脂肪乳一般是用从大豆油中提取的长链甘油三酯和蛋黄磷脂制备的.与长链甘油三酯(LCT)相比,中链甘油三酯(MCT)用于肠内营养时,其溶解性好,可较快的吸收入血浆,氧化快,且不需要肉毒碱就能进入线粒体.MCT可与LCT混合经静脉输入,也能以结构型脂肪乳的形式输入.在结构型脂肪乳中,其甘油三酯单个分子内就含有中链及长链脂肪酸.与LCT一样,输入MCT后会伴有脂蛋白微粒的形成,因     

鱼油脂肪乳和20%中/长链脂肪乳干预博莱霉素致大鼠肺纤维化效果的比较

目的:探讨鱼油脂肪乳和20%中/长链脂肪乳注射液干预博莱霉素致大鼠肺纤维化的不同效果。方法:将120只大鼠随机分成正常组(等渗盐水)、对照组(博莱霉素所致大鼠肺纤维化模型)、20%中/长链脂肪乳组和ω-3PUFA组。在实验第7、14和21天分别取左肺下叶,用免疫组化检测转化生长因子-β(TGF-β1)和γ干扰素(IFN-γ)表达,右肺下叶组织行H-E染色病理观察;同时测定各组大鼠血清中白细胞介素-4(IL-4)和IFN-γ含量。结果:①ω-3PUFA组大鼠肺泡炎症和肺纤维化程度均较对照组和MCT/LCT组轻;②对照组和MCT/LCT组大鼠在实验第7、14和21天的肺组织TGF-β1染色呈强阳性,IFN-γ染色较淡,而ω-3PUFA组TGF-β1、IFN-γ染色及定量表达则相反(P﹤0.01),第7、14和21天,TGF-β1定量表达逐渐减少,IFN-γ逐渐增加(P﹤0.05)。③对照组和MCT/LCT组大鼠第7、14和21天血清IL-4含量较高,IFN-γ含量较低;而ω-3PUFA组则相反(P﹤0.01),第7、14和21天IL-4含量逐渐减低,IFN-γ含量逐渐增加(P﹤0.05)。结论:鱼油脂肪乳可下调大鼠肺组织TGF-β1,降低IL-4含量,上调肺组织IFN-γ的表达,其减轻肺纤维化的作用优于中/长链脂肪乳注射液。     

脂肪乳

背景脂肪乳是肠外营养时机体的能量来源之一。除供能外,脂肪乳尚可提供必需脂肪酸。20世纪60年代开始在临床上应用,近50年来,脂肪乳从最初的长链脂肪乳到最近的鱼油脂肪乳,已经有多种类型的制剂在国内使用。证据20世纪90年代前,对肠外营养中是否必须包含脂肪乳,存在一定争议。2     

脂肪乳的特点及临床应用

脂肪乳剂是构成TPN中非蛋白质能量的来源之一。传统的以大豆油为基础的长链脂肪乳,由于长链脂肪乳存在导致脂质过氧化、免疫抑制、诱发炎症和损伤内皮系统作用的潜在风险,因此,研究出了中／长链脂肪乳剂、鱼油、橄榄油、结构脂肪乳剂、SMOF等。不同脂肪乳剂的差别主要在于甘油三酯的不同,即结合于甘油的脂肪酸的不同,而脂肪酸的不同代谢特点决定了各种脂肪乳剂在临床中的不同应用。     

脂肪乳在肠外营养中的应用进展

脂肪乳作为肠外营养支持中主要的能量来源,数十年来,已发展出多种不同配方的制剂.LCT脂肪乳由于代谢方面的缺陷,目前在临床上已被MCT/LCT脂肪乳逐步取代.较新的配方是由结构三酰甘油或橄榄油构成,此种新型脂肪乳更为安全,耐受性更好.含鱼油 ( n-3脂肪酸)的脂肪乳,可改善不同病人危重情况下的组织灌注.最新的脂肪乳SMOF,由添加维生素E的大豆长链脂肪酸、中链脂肪酸、橄榄油和鱼油混合配制而成,已在一项双盲试验中获得良好的应用,其效能尚有待进一步的临床验证.     

含维生素E的中/长链脂肪乳注射液临床应用进展

脂肪乳剂是全胃肠外营养(TPN)中的重要组成部分.随着TPN在临床营养治疗中的广泛应用,脂肪乳剂也逐渐由长链脂肪乳(LCT)发展至中/长链脂肪乳(MCT/LCT).MCT具有水解、氧化快而完全,不依赖肉毒碱转运,对免疫系统影响少,且不易在肝内和外周组织中浸润等优点.但其中仍含有一定量的多不饱和脂肪酸,易受体内自由基的攻击而产生脂质过氧化,进而损害脂质、DNA和蛋白质,造成组织和器官的损伤.因此,许多学者主张在MCT/LCT剂中添加一定量的维生素E,以防止脂肪乳剂脂质过氧化的发生,从而保证临床安全、合理地使用脂肪乳剂进行营养治疗的同时,有效地避免发生不良反应.以下主要对含维生素E的MCT/LCT注射液在临床的应用作一综述.     

Comparison of total nutrient admixture stability using two intravenous fat emulsions, Soyacal and Intralipid 20%

The safe clinical use and physical stability of a total nutrient admixture (TNA) system containing a soybean oil emulsion (Intralipid) has been reported. A study was conducted to compare the physical stability of four admixtures which were divided into two groups based upon the ratios (1:1:1 and 2:1:1) of amino acids (8.5%), dextrose (70%), and fat emulsion (20%). The fat component in each group contained either a new soy bean fat emulsion, Soyacal, or Intralipid. The quantities of all electrolytes, trace elements and vitamin additives were the same. All solutions were stored at 4 degrees C for 28 days and then held at ambient temperature for 5 days for a total 33-day study period. Each admixture was serially analyzed on days 0, 1, 2, 3, 5, 7, 14, 21, 28, 29, 30, 31, 32, and 33. Examination of gross visual appearance and determinations of pH were performed. Osmolality was measured by means of freezing point depression (Advanced Digimatic Osmometer, Advanced Instruments, Inc., Needham Heights, MA). A Brookhaven particle analyzer was used to measure lipid particle size and particle size distribution. Electron and light microscopy were used to verify maximum particle size and distribution on days 0, 7, 14, 21, 28, and 29. The type of lipid emulsion used did not affect the pH or osmolality of the admixtures. Admixtures prepared with the 2:1:1 ratio had slightly higher pH (0.07) and lower osmolality (350 mOsm/kg). The range of mean diameters for the admixtures prepared with Soyacal and Intralipid were 0.283 to 0.310 micron and 0.314 to 0.351 micron, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physicochemical stability of intravenous lipid emulsions as all-in-one admixtures intended for the very young

BACKGROUND & AIMS: Intravenous lipid emulsions (IVLEs) are unstable when growth of lipid droplets into large fat globules is detected by appropriate particle sizing techniques. Specifically, instability is evident when the volume-weighted percent fat (PFAT)>5 microm exceeds 0.4% of the total lipids present. This represents an approximate 10-fold increase in the population normally present in the large-diameter tail of stable lipid emulsions. The composition of the oil phase of an IVLE, however, has been shown to exhibit different stability characteristics. We investigated the stability of various IVLEs containing physical mixtures of medium-(MCT) and/or long-chain triglycerides (LCT) in three different all-in-one (AIO) admixtures intended for neonatal and infant patients. METHODS: The 20% (w/v) IVLEs used in this study were composed of the following oils (by weight): 1). 1:1-soybean/safflower (SS); 2). 1:1-MCT:soybean (MS); and 3). 5:4:1-MCT:soybean:fish (MSF). Stability was assessed by light obscuration or light extinction to count large fat globules, and by aided (microscopic) and unaided (naked eye) visual assessments for up to 48 h at room temperature. RESULTS: The stability of SS-based admixtures significantly and rapidly deteriorated in one of the three AIO compositions studied, whereas the AIOs made from MS or MSF were stable for all formulations.CONCLUSION: The results suggest that AIOs made from MCT/LCT-containing IVLEs are more stable than those made from pure LCTs.     

Long-term stability of lipid emulsions with parenteral nutrition solutions.

The stability of the mixture of peripheral vein parenteral nutrition (PN) solution with 10% lipid emulsions (Intralipid or Lipofundin MCT) was tested during a prolonged period of refrigerated storage. The analysis included gross visual examination of the bottle, pH determination, and examination by electron microscope. The mixtures of fat emulsions with PN solution demonstrated no physical instability or pH alteration. Examination under electron microscope revealed no alterations after 4 wk, but the surface layer of fat globules was disrupted after 10 and 18 wk. This study demonstrates that complete nutritive mixtures can be prepared and stored in refrigeration for at least 4 wk before clinical use.     

Competitive effects of long-chain-triglyceride emulsion on the metabolism of medium-chain-triglyceride emulsions

This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism.     

Stability of parenteral nutrition admixtures containing organic phosphates

The use of organic phosphates to avoid calcium phosphate precipitation in parenteral nutrition mixtures has been proposed. The purpose of this study was to evaluate the stability of total parenteral nutrition admixtures containing glucose-1-phosphate or glycerol phosphate as the phosphate source over 3 days. Three parenteral nutrition admixtures, each containing glucose-1-phosphate (30.0 mmol), glycerol phosphate (31.4 mmol) or inorganic phosphate (30.0 mmol), and their corresponding aqueous phases were prepared in 3-L ethylene vinyl acetate plastic bags and infusion bottles, and stored at 5 +/- 1 degrees C or 22 +/- 3 degrees C without light protection. Physical stability analysis and sampling for chemical analysis was performed at 0, 24, 48 and 72 h. Aqueous phases were subjected to physical stability analysis, including pH measurement, visual inspection and nephelometry. Admixtures were subjected to physical stability analysis consisting of pH measurement, and evaluation of emulsion stability by visual inspection, degree of creaming, phase contrast microscopy, zone sensing technique and photon correlation spectroscopy. Chemical analyses of amino-acids, dextrose, triglycerides, phospholipids, Na, K, Cl, Mg, Ca, glucose-1-phosphate, glycerolphosphate and inorganic phosphate were performed. No precipitation was detected in any of the aqueous phases. Admixtures remained acceptable with respect to visual and microscopic appearance, mean droplet diameter and droplet size distribution. All nutrient concentrations assayed in the three admixtures remained constant over the study period. Total parenteral nutrition admixtures for adult patients containing glucose-1-phosphate or glycerolphosphate are physically and chemically stable for 3 days when stored under refrigeration or controlled room temperature without light protection.     

Human leukocyte death after a preoperative infusion of medium/long-chain triglyceride and fish oil parenteral emulsions: a randomized study in gastrointestinal cancer patients

Background: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis.     

Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound.

Fatty infiltration of the liver with cholestasis is one of the complications of total parenteral nutrition (TPN). The cause has not yet been determined. It seems probable, however, that these alterations could be prevented when a mixture of medium- and long-chain triglycerides (MCT/LCT) is used as a fat component instead of the application of long-chain emulsions (LCT) alone. To determine whether this could also be demonstrated morphologically in man, 14 patients needing TPN (25 kcal/kg BW x day, carbohydrate 45%, fat 35%, protein 20%) were examined by ultrasound in order to compare liver size and gray-scale value before and after 7 days of TPN. Seven of the patients were randomly administered a MCT/LCT emulsion as their fat intake, the other seven were exclusively given LCT. There were no changes in liver size and gray-scale value in the MCT/LCT-group, whereas both parameters showed a significant rise in the patients with LCT (size: 10.4 +/- 1.4 to 11.5 +/- 1.4 cm; gray-scale value: 9.3 +/- 1.0 to 11.6 +/- 0.7). These data suggest that TPN, administered with a mixture of MCT/LCT emulsions as fat components, could reduce the risk of hepatic dysfunction such as cholestasis and fatty infiltration of the liver.     

Emulsion stability in total nutrient admixtures containing a pediatric amino acid formulation.

Emulsion stability of total nutrient admixtures containing TrophAmine amino acid injection admixed with Intralipid, Nutrilipid, and Liposyn II was studied. High and low electrolyte concentrations were added to each total nutrient admixture before storage at 4 degrees C for 48 hours then at 20-22 degrees C for 24 hours. Stability studies were also performed on total nutrient admixtures containing higher concentrations of fat emulsion and total nutrient admixtures with added cysteine hydrochloride and carnitine. High electrolyte concentrations only were added to these total nutrient admixtures before being stored refrigerated for 24 hours then at room temperature for 24 hours. Visual assessment, pH determination, and particle size analysis were performed immediately after compounding and after refrigerated and room temperature storage. Particle size was assessed by measuring the mean diameter of the fat emulsion and the percent of oil volume in particles greater than 5 microns. Repeated-measures analyses of variance were used to determine significance of type or concentration of fat emulsion, electrolyte concentrations, or time on mean diameter or percent particles greater than 5 microns. There were minimal changes in pH values over time. Creaming was observed in all total nutrient admixtures at all sampling times except time zero. This was reversible upon agitation. Results of particle size analysis over time indicated little change in mean diameter or percent particles greater than 5 microns. These minimal changes did not seem to be clinically significant. It is concluded that total nutrient admixtures prepared with this pediatric amino acid formulation are stable when prepared and stored as reported.     

Lipid peroxidation of intravenous lipid emulsions and all-in-one admixtures in total parenteral nutrition bags: the influence of trace elements

An iodometric titration was used to assess the influence of a daily portion of trace elements on lipid peroxidation of pure lipid emulsions and lipid-containing all-in-one (AIO) admixtures by measuring the peroxide value (PV; mmol peroxides/L). A pure lipid emulsion (Intralipid 20%; Pharmacia & Upjohn, Dubendorf, Switzerland) was stored in ethylvinylacetate bags under light protection (LP) at 40 degrees C with and without trace elements. In absence of trace elements the PV of Intralipid 20% was significantly lower (day 14: 2.77 vs 18.04; p < .001). After the same time period with the same storage conditions the drop in pH was two times higher in presence of trace elements (1.54 vs 0.77). In an AIO admixture with LP stored at 2 degrees C to 8 degrees C, trace elements increased the PV from 0.04 to 0.19 mmol/L (day 29; p < .01). The drop in pH was 0.01 and 0.02 units, respectively. When stored at 20 degrees C to 30 degrees C and exposed to daylight, the PV of the AIO admixture containing trace elements reached 1.92 compared with 0.52 in their absence (day 19; p < .001) with a pH drop of 0.03 and 0.11, respectively (day 29). Although trace elements led to a much higher drop in pH in pure lipid emulsions, no obvious influence on the pH of AIO admixtures was demonstrated. To minimize lipid peroxidation, AIO admixtures should be stored light-protected and refrigerated without trace elements. The latter should be added immediately before administration or should be given separately.     

The stability of amikacin, gentamicin, and tobramycin in total nutrient admixtures

Amikacin (A), gentamicin (G), and tobramycin (T) were added to eight different total nutrient admixtures (TNA) with varying concentrations of dextrose, amino acid, and fat emulsion to determine drug and emulsion stability. All TNA were prepared aseptically and stored at room temperature under normal room lighting for 12 hr before drug addition. One volume of each drug was added to an equal volume of each of the eight TNAs to simulate 1:1 piggyback contact volumes. Samples were left at room temperature for 6 hr. Drug concentrations were analyzed by fluorescence polarization immunoassay. TNA/drug admixtures were pH tested and visually inspected before and after centrifugation in microhematocrit tubes, noting signs of emulsion stability at 1 and 6 hr. Emulsion particle size was determined at 1 and 6 hr using interference contrast microscopy. All three drugs retained their immunoreactivity in all TNAs for at least 6 hr. G and T were stable in all eight TNAs for at least 6 hr with no significant effect on emulsion particle size or stability after centrifugation. A was incompatible with all eight TNAs, resulting in visual breaking of all emulsions within 1 hr. Therefore, G and T, but not A, can be administered via piggyback method with the eight TNAs tested if the infusion is completed within 6 hr.