As previously shown, in-line filtration was highly effective in reducing the overall complication rate of severe events (SIRS, sepsis, circulatory failure, acute respiratory distress syndrome (ARDS), thrombosis, acute renal and liver failure). Length of stay and duration of mechanical ventilation on the PICU were also significantly shortened if in-line filtration was applied . In this additional investigation, the 95% CIs of the differences in the incidence rates of several organ dysfunction lay on either side below zero, indicating a statistically significant difference between both groups (Figure 1). The negative number in the difference of the incidence rates revealed a protective effect for the interventional group. Thus, in-line filtration may have a beneficial effect on the preservation of respiratory, renal and hematologic organ function in critically ill children. The incidence of other organ dysfunction was also lower in the filter group; however these differences did not reach statistical significance as the 95% CI included zero. The number of patients suffering from neurologic dysfunction was too small in both groups to allow any reliable statistical conclusion.
This current data support previous pathophysiological findings and confirm clinical and experimental data [5–8, 10, 12–15, 19]. A reduced occurrence of respiratory dysfunction was evident for the filter group. These results are in accordance with our previous findings, which revealed a statistical trend towards a decrease in the incidence of ARDS for the filter group . As a consequence, the duration of mechanical ventilation in patients receiving in-line filtration was shortened . Since lung capillaries are the first anatomical filter for infused particles, the pulmonary vessels may be the primary cause for respiratory dysfunction as migration of particles to the lung induces mechanical embolisation of lung capillaries [7, 19–22]. In adults suffering from ARDS, Walpot et al. demonstrated particulate-induced formation of occlusive microthrombi and generation of granulomas and foreign body giant cells on autopsy . Particles may harm the pulmonary endothelium either directly or by activation of complement, platelets and/or neutrophils [7, 19]. The infusion of particle-containing solutions could partially generate or at least aggravate ARDS and respiratory insufficiency.
However, the harmful effects of particles do not seem to be restricted to the lung as primary anatomical filter. Several authors have shown that inhaled [23, 24] and intravenously injected  particles are translocated from the lung to the systemic circulation and various extrapulmonary organs, either as free particles or incorporated into macrophages. These particles can be detected in the blood, liver, kidney and the spleen. Also, particulate contaminants from drug preparations have been found, after intravenous injection traversing or bypassing the lung, in arterioles and capillaries of a striated muscle in a hamster skinfold chamber model [6, 10]. After short ischemia-reperfusion injury, these particles damaged the microcirculation and induced a reduction of capillary density [6, 10]. In critically ill patients with already compromised microcirculation, further impairment by particles may have additional deleterious effects on organ function . Especially the renal function is highly dependent on vascular integrity. In critically ill patients, acute renal failure or dysfunction is a common problem in the course of sepsis, severe trauma, surgery, or shock, and is an independent risk factor for morbidity and mortality . Renal dysfunction is mainly caused by insufficient tissue perfusion resulting in an ischemia–reperfusion injury with consecutive tubular injury or necrosis . However, recently a new concept regarding the pathogenesis of acute renal failure has been evolved . In sepsis-induced acute renal failure the renal blood flow is preserved and an increased renal vascular resistance as the pathogenetic factor leads to the development of acute renal failure or dysfunction . This increased renal vascular resistance is mainly caused by an impairment of the microcirculation in the renal cortex and medulla. There, sepsis induces endothelial alterations with an adhesion of leukocytes and platelets, and a consecutive formation of microthromboses . In the presence of such disturbed vascular integrity, particles may either trigger or augment alterations in the renal microcirculation. As shown in our study, patients provided with particle-retentive in-line filters had a lower incidence of renal dysfunction.
The incidence of hematological dysfunction (defined as thrombocytopenia below <80.000/mm3, decline in platelet count by more than 50% or international normalized ratio (INR) >2 ) was significantly decreased in the filter group. Clinically, thrombocytopenia alone or a drop in platelet count of >50% is associated with a raised mortality on intensive care unit . The coagulation system — as in most critically ill patients  — seems to be more activated in patients of the control group compared to patients of the filter group. Particles obstructing small capillaries may increase platelet activation and consumption of clotting factors either directly or via interference with the endothelium with subsequent activation of complement, platelets and/or neutrophils [7, 19]. This has been well illustrated for the lung as particles in capillaries as well as in the interstitium were surrounded by an accumulation of platelets and fibrin deposits [7, 19]. In addition, also a systemic hypercoagulability, as proven for inhaled particles [31, 32], can be hypothesized for intravenously injected particles after distribution to several organs.
Thrombogenic effects in the microcirculation induce and modulate an inflammatory activity . Vice-versa, systemic inflammation results in activation of the coagulation . Additionally infused particles may initiate and aggravate the cross-talk between the inflammatory and coagulation pathways and even prolong this vicious circle. In our study these synergistic effects of particles on the coagulation and inflammatory pathways become clinically obvious. Patients not being protected against particle infusion suffer from a higher incidence of SIRS  and haematological dysfunction. Additionally, as shown for septic patients the mutual activation of inflammation and coagulation results in an considerable increase of organ failure or dysfunction at multiple sites . This resembles another potential pathophysiological explanation for the higher incidence of organ dysfunction in the control group.
In the control as well as in the filter group we used a standardized infusion regimen for all patients. In both groups medications were prepared according to the manufacturer’s instructions and parenteral nutrition and certain drugs were supplied by a centralized intravenous additive service to guarantee chemical stability and aseptic standards. The infusion therapy was further optimized by the use of a computer program to prevent formation of particles by precipitations and incompatibilities. It is remarkable, that although we used the best of practice for the infusion management in both groups, the additional use of in-line filtration resulted in a further positive effect for patients.
However, there is one inherent limitation of this study. Although, data for organ dysfunction was recorded prospectively, size and power of the study had not been calculated for the detection of a single reduction in organ dysfunction beforehand. Therefore, use of a contingency table and subsequent assessment of the significance by Pearson’s Chi-Square test or Fisher’s exact test with the computation of a P value would have been statistically incorrect. All data is therefore based on a descriptive statistical analysis. The presented results are related to the significant differences in the incidence rates and its 95% CI and have to be interpreted on the basis of the underlying descriptive statistic.