Driscoll D F, Bacon M N, Bistrian B R
Department of Pharmacy, Deaconess Hospital, Boston, MA 02215, USA.
JPEN J Parenter Enteral Nutr. 1996 Jul-Aug;20(4):296-301. doi: 10.1177/0148607196020004296.
The recent Food and Drug Administration Safety Alert recommends in-line filtration for all total parenteral nutrition admixtures. Although rigid crystalline particulates can be effectively removed by in-line filters, the fate of flexible lipid droplets (LDs) enlarged through electromechanical destabilization is less clear. Lipid globules > 5 microns could lodge in the pulmonary microvasculature and produce an embolic syndrome. Recent evidence suggests that TNAs (Total Nutrient Admixtures) with LDs of 5 microns or more constituting > 0.4% of the final fat concentration are unstable.
Six pairs of 1.5-L TNA dispersions of varying degrees of stability were prepared in duplicate (n = 12) and studied over 30 hours. The number of enlarged fat globules was assessed by laser light extinction for all LDs > or = 1.75 microns at 0, 6, 24, and 30 hours after preparation. After LD assessments at time 0, admixtures were placed in a temperature-controlled chamber at 25 degrees C +/- 0.1 degree C. At 6 hours, a simulated patient infusion was begun using a 1.2-microns filter at a continuous flow rate of 55 mL/h. Pre- and postfiltration samples were taken at 6, 24, and 30 hours, equal to times 0, 18, and 24 hours of the simulated infusion. A repeated measure two-way analysis of variance assessing treatment and time was performed. Dependent variable analyses included number-weighting of fat globules as > 5 microns (LD1), total number > or = 1.75 microns (LD2), LD1-LD2 ratio (as %), and volume-weighted percent of fat (PFAT) > 5 microns.
In all cases, time was a significant factor and was an expected finding as the stability of all extemporaneously prepared admixtures deteriorates with time. Of the number-weighted variables, a significant postfiltrate reduction was observed in LD1 (p = .041), LD2 (p < .001), and LD1-LD2 ratio (p < .0001). Of greatest clinical importance, the volume-weighted PFAT > 5 microns was significantly reduced by the in-line filter (p = .029).
The TNA1 1.2-microns filter significantly reduced the total number and concentration of enlarged fat globules. The higher LD1-LD2 ratio may reflect the effects of filtration on electrically destabilized fat globules. However, total exposure to unstable and very large LDs was significantly reduced, suggesting that in-line TNA filtration should be a standard part of nutrition therapy.
美国食品药品监督管理局最近发布的安全警报建议对所有全胃肠外营养混合液进行在线过滤。尽管刚性晶体颗粒可通过在线过滤器有效去除，但通过机电失稳而增大的柔性脂质滴（LDs）的去向尚不清楚。直径大于5微米的脂质球可能会滞留在肺微血管中并引发栓塞综合征。最近的证据表明，最终脂肪浓度中直径5微米及以上的LDs占比超过0.4%的全营养混合液（TNAs）是不稳定的。
制备了六对不同稳定性程度的1.5升TNA分散液，一式两份（n = 12），并在30小时内进行研究。在制备后0、6、24和30小时，通过激光消光法评估所有直径大于或等于1.75微米的增大脂肪球的数量。在0小时进行LD评估后，将混合液置于25℃±0.1℃的温度控制箱中。6小时时，使用1.2微米过滤器以55毫升/小时的连续流速开始模拟患者输注。在6、24和30小时采集过滤前和过滤后的样本，分别相当于模拟输注的0、18和24小时。进行了评估处理和时间的重复测量双向方差分析。因变量分析包括直径大于5微米的脂肪球数量加权（LD1）、直径大于或等于1.75微米的总数（LD2）、LD1-LD2比率（百分比）以及直径大于5微米的脂肪体积加权百分比（PFAT）。
在所有情况下，时间都是一个显著因素，这是一个预期的发现，因为所有临时配制的混合液的稳定性都会随时间而下降。在数量加权变量中，观察到过滤后LD1（p = 0.041）、LD2（p < 0.001）和LD1-LD2比率（p < 0.0001）显著降低。具有最大临床重要性的是，在线过滤器使直径大于5微米的体积加权PFAT显著降低（p = 0.029）。
TNA1 1.2微米过滤器显著降低了增大脂肪球的总数和浓度。较高的LD1-LD2比率可能反映了过滤对电失稳脂肪球的影响。然而，不稳定和非常大的LDs的总暴露量显著降低，这表明TNA在线过滤应成为营养治疗的标准组成部分。
