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

Abstract

PurposeTo 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.MethodsProspective, 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.ResultsTwenty 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 cm2. EDX analysis confirmed silicon as a major particle constituent. Half of the filter membranes showed conglomerates containing an uncountable 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.ConclusionsParticle 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-1775-y) contains supplementary material, which is available to authorized users.

Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients

“…When using filters during drug infusion, drug particles are captured by the filter membrane and can be analysed by electronic microscopy. In the study by Jack et al [66], microscopic analysis showed particles of approximatively 40 × 20 µm in size. In another study performed by Foinard et al [7], particles trapped by the filter membrane were also analysed, with a particle size of about 30 × 30 µm.…”

“…Particles diffuse to the lungs through the venous system because of the increasing size of veins. Jack et al [66] showed that most particles have mean sizes within the range of 5 to 50 µm resulting in considerable particulate retention in the pulmonary capillaries of particles ranging from 5-10 µm in diameter. All particles smaller than the diameter of pulmonary capillaries pass through the lungs and diffuse into the different organs, including the liver and spleen, where particles can be phagocytised by the reticuloendothelial system.…”

“…Different methods for evaluating the particle load administered to patients during IV infusion have been applied. Most studies have controlled it through the presence of in-line filters in infusion sets, leading to an imprecise estimation of the number of particles administered to paediatric and adult patients [66,81]. A visual examination method based on the Tyndall effect has recently been assessed [82], but the authors concluded that an evaluation of drug compatibility and parenteral nutrition could not be obtained only through the visual detection of particles.…”

Particulate Matter in Injectable Drug Products

“…Examples include phlebitis (3, 10 -13), pulmonary emboli (14 -16), pulmonary granulomas (3,11,17), immune system dysfunction (3,18), pulmonary dysfunction (13,15), infarction (15,19), and death (14, 20 -22). The patient risk associated with the injection of drugs containing particulate matter depends on a number of factors, including the route of administration used, the particle size and shape, the number of particles injected, the particle composition, and the patient population.…”

“…Estimates are that patients in intensive care receive more than a million injected particles Ͼ2 microns in size daily (18,30,31). One method for controlling the particle load administered to critically ill patients has been through the use of final filters.…”