Effects of in-line filtration on lipid particle size distribution in total nutrient admixtures.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Driscoll
D F
DF
Department of Pharmacy, Deaconess Hospital, Boston, MA 02215, USA.
Bacon
M N
MN
Bistrian
B R
BR
D004355:Drug Stability; D005374:Filtration / Q000379:methods*; D005526:Food, Formulated / Q000032:analysis*; D006801:Humans; D008055:Lipids / Q000032:analysis*; D010289:Parenteral Nutrition, Total; D010316:Particle Size
D008055:Lipids