Analysis of particulate contaminations of infusion solutions in a pediatric intensive care unit

Abstract

Purpose: To examine the physical properties and chemical composition of particles captured by in-line microfilters in critically ill children, and to investigate the inflammatory and cytotoxic effects of particles on endothelial cells (HUVEC) and macrophages in vitro.

Methods: Prospective, observational study of microfilters following their use in the pediatric intensive care unit. In vitro model utilizing cytokine assays to investigate the effects of particles on human endothelial cells and murine macrophages.

Results: Twenty filter membranes from nine patients and five controls were examined by electron microscopy (EM) and energy dispersion spectroscopy (EDX). The average number of particles found on the surface of the used membranes was 550 cm(2). EDX analysis confirmed silicon as a major particle constituent. Half of the filter membranes showed conglomerates containing an unaccountable number of smaller particles. In vitro, glass particles were used to mimic the high silicon content particles. HUVEC and murine macrophages were exposed to different contents of particles, and cytokine levels were assayed to assess their immune response. Levels of interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha were suppressed.

Conclusions: Particle contamination of infusion solutions exists despite a stringent infusion regiment. The number and composition of particles depends on the complexity of the applied admixtures. Beyond possible physical effects, the suppression of macrophage and endothelial cell cytokine secretion in vitro suggests that microparticle infusion in vivo may have immune-modulating effects. Further clinical trials are necessary to determine whether particle retention by in-line filtration has an influence on the outcome of intensive care patients.

Fig. 1

Particle (a) with corresponding EDX analysis (b) and conglomerate (c) found by electron microscopy on the surface of different filters. Presented filter (a) was used for the application of bolus injections of multiple different therapeutics via a central venous line. The size of the particle is approximately 40 × 20 μm. It shows the representative angular shape and crystalline appearance. In addition to the large particle, many smaller particles and the incipient blockage of the filter membrane are apparent. The corresponding EDX (b) revealed silicon as the major chemical element. The second filter (c) was used for high osmolar parenteral nutrition (>1,300 mosmol/l) via a central venous catheter in a 4-month-old infant after liver transplantation. The EDX analysis revealed carbon, sodium, chloride, potassium, selene, silicon, and phosphate as components of the conglomerate

Fig. 2

Interleukin-1beta concentration (pg/ml) after 4, 8 and 24 h incubation period of HUVEC with different glass particle concentrations. After 8 h incubation with glass particles the release of interleukin-1beta was significantly reduced independent from particle content. Values are mean of four separate assays ±standard deviation of all samples. *p < 0.05; **p < 0.01