多种微量元素注射液(I)对新生儿肠外营养液中脂肪乳稳定性的影响

The effects of multiple trace elements injection(I)on the stability of fat emulsion in neonatal parenteral nutrition solutions

目的考察多种微量元素对新生儿肠外营养液中脂肪乳稳定性的影响,评估过滤前后稳定性指标的变化。方法以1.5 kg体重为标准,设计7组含不同浓度多种微量元素的新生儿肠外营养液,包括空白组(不含多种微量元素)、正常剂量组[1 ml/kg,每100 ml肠外营养中加入0.75 ml]和5个试验组(每100 ml肠外营养中分别加入1.5、3、4.5、6和7.5 ml),在配制后0 h、24 h时进行外观考察,应用动态光散射法测定过滤前后脂肪乳平均粒径(mean droplet diameter,MDD),采用光阻法测定过滤前后脂肪乳粒径>5μm的乳粒百分比(percentage of fat residing in globules larger than 5μm,PFAT5)及粒径分布。结果7组肠外营养液在配制后24 h内肉眼观察外观颜色无变化,无分层、挂壁等现象。在24 h内,所有肠外营养液过滤前MDD波动于(338.67±6.11)nm~(370.00±15.13)nm,PFAT5值波动于(32.00±1.00)×10^(-3)%~(85.67±6.81)×10^(-3)%,过滤后MDD波动于(310.67±8.62)nm~(362.33±19.86)nm,PFAT5值波动于(4.67±1.15)×10^(-3)%~(17.33±0.58)×10^(-3)%。多种微量元素的浓度与PFAT5值呈正相关(P<0.05)。放置24 h后,PFAT5值和t=0 h时比较,差异有统计学意义(P=0.004)。过滤前后的PFAT5值比较,差异有统计学意义(P=0.000)。结论在室温下24 h内,新生儿肠外营养液中添加不同浓度的多种微量元素后,其外观无改变,脂肪乳的MDD均在安全范围内;但当一价阳离子(Na^(+)、K^(+))浓度为38.9 mmol/L,二价阳离子(Ca^(2+))浓度为5 mmol/L,微量元素(Zn^(2+)、Cu^(2+)、Mn^(2+)、Se4+)浓度超过0.063 mmol/L时,PFAT5值大于0.05%,需经1.2μm的过滤器过滤,可显著降低PFAT5值以及粒径分布,提高肠外营养液临床应用的安全性和规范性;建议添加多种微量元素注射液(I)的新生儿肠外营养液需进行终端过滤。

Objective To investigate the effects of multiple trace elements in neonatal parenteral nutrition(PN)on the stability of fat emulsion,and to assess the changes of stability indexes after filtration.Methods With the standard body weight of 1.5 kg,seven groups of neonatal PN solutions with different concentrations of multiple trace elements were designed,including blank group(without multiple trace elements),normal dose group(1 ml/kg,i.e.,0.75 ml per 100 ml PN)and five experimental groups(i.e.,1.5 ml,3 ml,4.5 ml,6 ml,and 7.5 ml per 100 ml PN respectively).Macroscopic observation was performed 0 h and 24 h after preparation.The mean droplet diameter(MDD)of lipid emulsion was determined with dynamic light scattering before and after filtration.The percentage of fat residing in globules larger than 5µm(PFAT5)and the globule size distribution before and after filtration were determined with light blockage method.Results Macroscopic examination of the 7 groups of PN solutions identified neither changes in color nor stratification within 24 hours after solution preparation.Within 24 hours after solution preparation,the MDDs of all PN solutions before filtration were between(338.67±6.11)nm and(370.00±15.13)nm,and the PFAT5 values before filtration ranged from(32.00±1.00)×10^(-3)%to(85.67±6.81)×10^(-3)%.The MDDs of all PN solutions after filtration were between(310.67±8.62)nm and(362.33±19.86)nm,and the PFAT5 values after filtration ranged from(4.67±1.15)×10^(-3)%to(17.33±0.58)×10^(-3)%.The concentration of multiple trace elements was positively correlated with PFAT5(P<0.05).There was statistically significant difference in PFAT5 values at 0 h and 24 h after preparation(P=0.004).The difference of PFAT5 values before and after filtration was also statistically significant(P=0.000).Conclusions Within 24 hours after solution preparation at room temperature,the appearance of neonatal PN solutions with different concentrations of trace elements supplementation was unchanged,and the MDDs of fat emulsions were all within the safe range.However,when the concentration of monovalent cations(Na^(+),K^(+))was 38.9 mmol/L,the concentration of divalent cation(Ca^(2+))was 5 mmol/L,and the concentration of trace elements(Zn^(2+),Cu^(2+),Mn^(2+),and Se4+)was higher than 0.063 mmol/L,the PFAT5 value was higher than 0.05%.In this case,filtration with a 1.2μm filter was necessary,which could significantly reduce the PFAT5 value and the globule size distribution,and improve the safety and standardization of the clinical application of PN solutions.It is suggested that the neonatal PN solutions supplemented with multiple trace elements injection(I)may be administered through a terminal filter.