Particles arise from individual components, bags and infusion equipment. In one study a typical adult admixture was found to contain more than two and half million particles per bag.¹

A study of paediatric PN² enumerated more than 37000 particles of 2-100µm in the daily feed for a 3kg infant. In a wider clinical context, several studies have suggested that patients receiving intensive IV therapy can receive more than two million particles a day.³

Incidents of gross precipitation in admixtures that caused two deaths and several cases of respiratory distress led the FDA to recommend filtration.4 Basic 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:

High levels of particles in infusions can exceed the clearance capacity of the reticuloendothelial system.³ Observations of granulomata² and microthrombi^3,6 in the lung tissue of patients on IV therapy give some clue as to the potential pathogenic consequences of particle contamination in infusates; involvement in ARDS and MOF has been suggested.³ The cases reported in the FDA Safety Alert testified to the potentially lethal consequences of infusing a high level of particles in the form of a precipitate.⁵ Particles have also been implicated in the pathogenesis of thrombophlebitis in peripheral vein infusions, one of several controlled trials in which patients received filtered versus non filtered IV therapy showed an approximately 50% reduction in the incidence of phlebitis when filtration was used.⁷

The presence of oversize lipid droplets in admixtures is undesirable. Lipid droplets over 5µm can lodge in the pulmonary microvasculature and may contribute to lipid embolism.⁸ It is possible to reduce the risk of oversize lipid droplets⁸, without adversely affecting the clinically appropriate lipid droplets in normal stable admixtures.⁹

Patients with central lines are at risk from air embolism,¹⁵ 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. Home PN patients are particularly worried about air.¹⁶

• Particle contamination occurs in parenteral nutrition.
• Precipitates can occur in admixtures and remain undetected.
• Particles have serious clinical consequences.
• Oversize lipid droplets can occur in admixtures.
• 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.
• Filtration has been recommended for patient protection 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.
3. Kirkpatrick CJ. Microcirculatory problems in multiple organ failure: the role of endotoxins and particulate contamination. Proceedings of the Symposium “Managing the complications of intravenous therapy” Inst Naval Medicine, Hampshire March 1992.
4. United States Food & Drug Administration Safety Alert: Hazards of precipitation associated with parenteral nutrition. April 18th 1994.
5. Trissell LA. Use of total nutrient admixtures should not be limited. Am J Health-Syst Pharm 1995;52:895.
6. Walpot H et al. Particulate contamination of intravenous solutions ad drug additives during long-term intensive care. Anaesthesist 1989;39:544-548.
7. Falchuk KH et al. Microparticulate induced phlebitis. NEJM 1985;312:78-82.
8. Driscoll DF et al. The effects of in-line filtration on lipid particle size distribution (PSD) in total nutrient admixtures.JPEN 1996; 20:296-301.
9. Barnett MI et al. Filtration of lipid containing total parenteral nutrition (TPN) admixtures. Clin Nut 1995;14:49.
10. Pfaller MA. Epidemiology of candidiasis. J Hosp Infect 1995;s30:329-338.
11. Vazquez JA et al. Nosocomial acquisition of Candida albicans: an epidemiologic study. J Infect Dis 1993;168:195-201.
12. Scheckelhoff DJ et al. Growth of bacteria and fungi in total nutrient admixtures. Am J Hosp Pharm 1986;43:73-77.
13. Burnie JP et al. Four outbreaks of nosocomial systemic candidiasis. Epidemiol Infect 1987;99:201-211.
14. Moro ML et al. Nosocomial outbreak of systemic candidosis associated with parenteral nutrition. Infect Control Hosp Epidemiol 1990;11:27-35.
15. Coppa et al. Air embolism: a lethal but preventable complication of subclavian vein catheterisation. JPEN 1981;5:166-168.
16. PINNT patient survey, presented at the Annual Meeting of the British Association for Parenteral and Enteral Nutrition (BAPEN), London, 1st - 3rd December 1992.
17. Lewis JS. Justification for use of 1.2 micron end-line filters on total nutrient admixtures. Hosp Pharm 1993;28:656-8,697.