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Clinical Problem
Particulate contamination occurs in
parenteral nutrition
Particles in intravenous fluids can arise from
various sources as:
• particulate contamination in the individual
infusate components.
• particles shed from containers and infusion
equipment during use.
In intensive care, patients very often receive not
only parenteral nutrition but also numerous
drugs. This may add to the problem of
particulate contamination:
• precipitate from incompletely reconstituted
drugs.
• particles that form during incompatibility
reactions between components of the drugs
administered.
Several studies investigated the total particle
load in PN and found that patients receiving
intensive IV therapy can receive more than two
million particles a day.1,4
One group studying paediatric PN2 reported
more than 37,000 particles of 2-100 µm in the
daily feed for a 3 kg infant. This level of
contamination has since been confirmed by
other authors.3
respiratory distress. This has led some
authorities to advise that filters should be used
during administration of PN.5,6 Compounding
guidelines for calcium and phosphate additions
should prevent such gross precipitation, but
interactions between components do occur and
unfortunately the presence of lipid can obscure
precipitation:
"the lipid emulsion concealed the precipitation as
effectively as if the container were in a brown
paper bag"7
Particles have serious clinical
consequences
High levels of particles in infusions can exceed
the clearance capacity of the reticuloendothelial
system4. Post mortem observations of
granulomata2 and microthrombi4,6,8 in the lung
tissue of patients who had received IV therapy
give some clue as to the potential pathogenic
consequences of particle contamination in
infusates; involvement in ARDS and MOF has
been suggested.4 This is supported by the
respiratory distress seen in the surviving patients
involved in the aforementioned precipitation
incident.5,6 Particles have also been implicated
in the pathogenesis of thrombophlebitis in
peripheral vein infusions; several controlled trials
in which patients received filtered versus nonfiltered, non-lipid IV therapy, have shown at least
a 50% reduction in the incidence of phlebitis
when filtration was used.9,10
Patients receiving parenteral nutrition are at
increased risk of fungaemia
Fungal infections are increasingly common,
particularly amongst immunocompromised
patients.12 Parenteral nutrition is an
acknowledged risk factor for fungaemia, with
Candida species being the most common
organisms involved.13 Candida grows rapidly in
lipid-containing admixtures.14 Whilst endogenous
Candida commonly leads to disseminated
disease, the exogenous nosocomial acquisition
of Candida occurs in parenteral nutrition and has
been seen to cause significant morbidity and
mortality.15,16 Nosocomial transmission of
Candida species may involve carriage on the
hands of healthcare workers.12,13,16
Retention of fungal contamination from
lipid-containing preparations is possible
Fungal contaminants commonly associated with
infection in patients receiving PN can be retained
by appropriate filters.17
Air embolism is a risk with central venous
catheters
Patients with central lines are at risk from air
embolism,18 due to disconnections, incomplete
priming of the infusion system or degassing as
solutions are warmed. The presence of lipid in
an admixture can obscure this air.
Patient Protection
Filtration has been recommended for
patient protection in parenteral nutrition.
Leading authorities in nutrition recommend filtration
to protect patients receiving PN.5,7,11,19,20
“A filter should be used when administering
either central or peripheral nutrition
admixtures ....standards of practice vary, but
the following is suggested:
a 1.2 micron air eliminating filter for lipid
containing admixtures and 0.2 micron air
eliminating filter for nonlipid containing
admixtures” US FDA 5
“Administering a TNA without an inline filter to
a patient is like playing Russian roulette.” LA
Trissel 7
“...total exposure to large LDs
(lipid droplets) was significantly reduced
suggesting that in-line TNA filtration should be
a standard part of nutritional therapy.” D.F.
Driscoll 11
“Appropriate filters should be used during the
administration of PN to patients who require
intensive or prolonged parenteral therapy, the
immunocompromised, neonates and children,
and patients receiving home PN because of
the large volume of potentially particulatecontaminated fluid administered and their
increased susceptibility to the detrimental
effects of particulate contamination”.
Bethune 19
2.5 x 106
Enlarged lipid droplets can occur in
admixtures
2.0 x 106
1.5 x 106
1.0 x 106
5 x 106
0 x 106
>10 µm
>5 µm
>0 µm
Particles per bag
Precipitates can occur in admixtures and
remain undetected
Infusion of admixtures containing undetected
gross particulate contamination in the form of
calcium phosphate precipitate resulted in two
patient deaths and several cases of serious
The presence of a significant proportion of
enlarged lipid droplets in admixtures may be
undesirable, since lipid droplets over 5 µm can
lodge in the pulmonary microvasculature and
may contribute to lipid embolism. It is possible to
reduce the number of enlarged lipid droplets
without adversely affecting admixture stability.11
“Although the precise toxic dose of enlarged
fat globules from unstable TNAs is not
known, the presence of droplets of 5 µm or
more constituting >4.0% of the final fat
concentration are unstable and
pharmaceutically unfit for administration.”11
“Practice Guidelines: In-Line Filtration....
1. A 0.2 µm filter should be used for
2-in-1 formulations. A 1.2 to 5µm filter
should be used for TNA’s. Alternatively, a
1.2µm filter may be used for all PN
formulations.
2. A filter that clogs during administration of
PN is indicative of a problem and may be
replaced but should never be removed
entirely.”
ASPEN National Advisory Group on Standards
and Practice Guidelines for Parenteral
Nutrition.20
“...Each PPN admixture should be tested for
stability before clinical use and infused into
patients through an appropriate filter.”21
U p d a t e
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ELD128B
Medical
Summary
References
• Particulate contamination occurs in parenteral
nutrition.
1.
Foroni LA et al. Particle contamination in a ternary nutritional admixture. J Parent
Sci Technol 1993;47:311-314.
2.
Puntis JWL et al. Hazards of parenteral treatment: do particles count? Arch Dis
Child 1992;67:1475-1477.
• Precipitates can occur in admixtures and
remain undetected.
3.
Ball PA et al. Particulate contamination in parenteral nutrition solutions, still a
cause for concern. Clinical Nutrition 1999;18(s1):14-15.
• Particles have serious clinical consequences.
4.
Kirkpatrick CJ. Particulate matter in intravenous fluids-the importance for
medicine. Krankenhauspharmazie 1988;9:487-490.
• Oversize lipid droplets can occur in admixtures
and have serious clinical consequences.
• Patients receiving parenteral nutrition are at
increased risk of fungaemia.
• Retention of Candida from lipid-containing
preparations is possible with an appropriate
filter.
• Air embolism is a risk with central venous
catheters.
5.
United States Food & Drug Administration Safety Alert: Hazards of precipitation
associated with parenteral nutrition. April 18th 1994.
6.
Hill E et al. Fatal microvascular pulmonary emboli from precipitation of a total
nutrient admixture solution. JPEN 1996;20:81-87.
7.
Trissell LA. Use of total nutrient admixtures should not be limited. Am J HealthSyst Pharm 1995;52:895.
8.
Walpot H et al. Particulate contamination of intravenous solutions and drug
additives during long-term intensive care. Anaesthesist 1989;39:544-548.
9.
Falchuk KH et al. Microparticulate induced phlebitis. NEJM 1985;312:78-82.
10. Chee S, Oh S, The use of IV filters in phlebitis prevention. Seminar in Aseptic
Dispensing Practice 1999;p36-41.
11. Driscoll DF et al. The effects of in-line filtration on lipid particle size distribution
• Filtration has been recommended for patient
protection in parenteral nutrition.
(PSD) in total nutrient admixtures. JPEN 1996; 20:296-301.
12. Pfaller MA. Epidemiology of candidiasis. J Hosp Infect 1995;s30:329- 338.
13. Vazquez JA et al. Nosocomial acquisition of Candida albicans: an epidemiologic
study. J Infect Dis 1993;168:195-201.
14. Scheckelhoff DJ et al. Growth of bacteria and fungi in total nutrient admixtures.
Am J Hosp Pharm 1986;43:73-77.
15. Burnie JP et al. Four outbreaks of nosocomial systemic candidiasis. Epidemiol
Infect 1987;99:201-211.
16. Moro ML et al. Nosocomial outbreak of systemic candidosis associated with
parenteral nutrition. Infect Control Hosp Epidemiol 1990;11:27-35.
17. Pall Technical Bulletin 2001
18. Coppa et al. Air embolism: a lethal but preventable complication of subclavian
vein catheterisation. JPEN 1981;5:166-168.
19. Bethune K et al. Use of filters during the preparation and administration of
parenteral nutrition: position paper and guidelines prepared by a British
Pharmaceutical Nutrition Group Working Party. Nutrition 2001;17:403-408
20. Safe Practices for Parenteral Nutrition Formulations. National Advisory Group on
Standards and Practice Guidelines for Parerenteral Nutrition. JPEN 1998;22:49-66.
21. Shay D.K. et al. The Hospital Infections Program. Centers of Disease Control and
Prevention. Respiratory Distress and Sudden Death Associated with Receipt of a
Peripheral Parenteral Nutrition Admixture. Infect. Control Hosp Epidemiol 1997;
18:814-817
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Printed in England. PLSH/1M/CS/09.2002
clinical update
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