Impact of Particulate Contamination in Crystalloid Cardioplegic Solutions: Studies by Scanning and Transmission Electron Microscopy

Hellinger, A.; Piotrowski, Jerzy Zbigniew; Ma, Konerding; Wg, Burchard; Doetsch, N; Peitgen, K; Erhard, J; Jc, Reidemeister

doi:10.1055/s-2007-1013678

Cited by 15 publications

(13 citation statements)

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“…In addition to mechanical obstruction, inflammatory response of different organ systems after particle exposure is possible [3, 14, 15]. To mimic these mechanisms, we exposed macrophages and endothelial cells to particles similar to those found on the filters.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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“…Finally, several reports have pointed toward pulmonary complications due to particulate matter contaminants in cardioplegic solutions (44,45). Of particular interest in the study by Walpot and colleagues was the observation that most microthrombi were associated with particles less than 2 m in diameter (glass, latex, and polymers), which constitute the bulk of particulate matter contaminants in intravenous fluids (46).…”

Section: Discussionmentioning

confidence: 99%

Particulate Matter Contamination of Intravenous Antibiotics Aggravates Loss of Functional Capillary Density in Postischemic Striated Muscle

Lehr

Brunner

Rangoonwala

et al. 2002

Am J Respir Crit Care Med

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Through the increased use of less expensive and counterfeit medicines, the contamination of parenteral fluids and drugs by particulate matter poses an increasing health hazard worldwide. However, the mechanism of action of such contamination has never been conclusively demonstrated. We have systemically injected the particles contained in three different 1-g preparations of the antibiotic cefotaxime into hamsters and visualized the functional capillary density in striated skin muscle, using intravital fluorescence microscopy. Injection of particles from either of the three preparations did not affect capillary perfusion in normal muscle (n = 3 hamsters, each). However, injection of particles from two generic drug preparations, but not the original preparation or the saline control, significantly reduced capillary perfusion in muscle tissue that had previously been exposed to 4 h of pressure-induced ischemia and 2 h of reperfusion (n = 9 hamsters per group). Histological sections demonstrated birefringent particles mechanically obliterating the microcirculation of the striated muscle. The loss of capillary perfusion due to particle injection or injection of standardized microspheres was dependent on the extent of ischemia/reperfusion-induced muscle injury, with more capillaries lost in the more severely compromised muscle areas. These findings suggest that particle contaminants may not pose a major threat in intact tissue, but may severely compromise tissue perfusion in patients with prior microvascular compromise of vital organs (i.e., after trauma, major surgery, or sepsis) and thus predispose to complications such as acute respiratory distress syndrome or multiple organ failure.

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“…The contamination of infusion solutions by particles is a widely unknown and underestimated side effect of intravenous therapy [1, 2]. Particulate contamination is due to drug incompatibility reactions or their incomplete reconstitution during the preparation process [3].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies with endothelial cells and macrophages have also demonstrated particle-induced modulation of immune response [5]. The effect of particle infusions is aggravated in situations of disturbed microcirculation, such as ischemia and reperfusion injury: after cardioplegia, particles in cardioplegia solutions lead to impaired coronary artery flow, alterations in endothelium and increased leukocyte adhesion in humans as well as in animals [1]. In an experimental rat liver transplantation model, particles in the preservation solution were found to disturb the microcirculation and aggravate post-ischemic inflammation [13].…”

Section: Introductionmentioning

confidence: 99%

“…In a hamster skinfold chamber model, following ischemia, intravenous infusion of particle-contaminated solutions reduced functional capillary density by almost 50 %, compared to post-ischemic values before particle injection [14, 15]. However, filtration of solutions through 0.2-μm in-line filters prevented the loss of capillaries completely [15] and attenuated the inflammatory process [1, 13]. …”

Section: Introductionmentioning

confidence: 99%

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In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial

et al. 2012

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PurposeParticulate contamination due to infusion therapy carries a potential health risk for intensive care patients.MethodsThis single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed.FindingsAnalysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97−4.82] vs. 2.98 [2.33−3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6−22.4] vs. 11.0 [7.1−14.9] h; P = 0.028) were significantly reduced.ConclusionIn-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768).Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-012-2539-7) contains supplementary material, which is available to authorized users.

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Impact of Particulate Contamination in Crystalloid Cardioplegic Solutions: Studies by Scanning and Transmission Electron Microscopy

Cited by 15 publications

References 3 publications

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

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

Particulate Matter Contamination of Intravenous Antibiotics Aggravates Loss of Functional Capillary Density in Postischemic Striated Muscle

In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial

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