There are two major findings of our study. First, that cardiac surgery patients with problematic postoperative disease already exhibit elevated serum concentration of complement components C3 and C5, TNF-α and neutrophils (count and percentage) one day preoperatively. Second, that preopera-tive risk assessment based on serological and clinical chemistry data is possible, with high levels of accuracy.
The preoperative predictive risk assessment represents a clear advantage over assays relying on data acquired during or after cardiac intervention. Preoperative differences, as selected by our explorative data analysis, indicate a preopera-tive activation of the immune system, for example, by a subclinical inflammatory response [1,15], an atopic/allergic predisposition or a condition resulting from the congenital heart disease [26,27]. In contrast to the recent report that MOD in children is gender related , gender was not a predisposing factor in our study.
Preoperative serological alteration or activation indicates specific pathobiochemical problems. The parameters selected by the two classifiers in this study indicate increased POEE risk for patients with elevated inflammatory response by increased complement and neutrophil activation and coagulation (see Table 4). In different cardiac situations, CRP , sE-selectin , sICAM-1 and neutrophil adhesion molecule expression [28,29] have been discussed as risk factors. As already suggested by others , preoperatively altered blood coagulation values such as partial thrombin time were found to be prognostic for postoperative blood loss. Fibrinogen and fibrin are ligands for Mac-1 , inducing neutrophil, monocyte or resting platelet activation. Our study indicates this activation by elevated sL-selectin level as an important discriminant parameter. CPB is associated with major qualitative and quantitative alterations of humoral pathways and changes in leukocyte subsets, generating a systemic inflammatory response [2,4,7,31] with interactions between vascular endothelium, platelets and leukocytes including signal exchanges, adhesion molecule expression and secretion of cytokines or chemokines in a multi-step process. Patients with an altered immune profile before surgery might show a more pronounced or sustained immune response after surgery. In an unstimulated immune system, CPB exposure constitutes the initial stimulus that might prime the system for postoperative complications . In patients with a primed or predisposed immune profile, CPB as the second stimulus may facilitate an enhanced immune response, which, in turn, may lead to POEE, CLS or multiple organ failure.
The main discriminators of at risk patients (elevated levels of complement and activated complement components, TNF-α and IL-10) indicate the significance of complement system and monocyte activation. Activated monocytes liberate TNF-α and IL-10 as important modulators of the inflammatory response. TNF-α stimulates human vascular endothelium, thus mediating leukocyte recruitment to sites of inflammation. IL-10 release is specific to CPB surgery  and patients with POEE or MOD release higher quantities of IL-10 [7,23]. Increased IL-10 release as an indicator of MOD or effusions is also supported by the finding that perioperative methyl-prednisolone administration, that enhances IL-10 release during CPB surgery in adults , aggravates postoperative effusions and bleeding in children with postcardiotomy syndrome . Elevated preoperative IL-10 concentration was a risk factor in our patients. An observation that contrasts with the finding that children with MOD had reduced IL-10 serum levels  prior to CPB. Patients from our study had no gender-related differences in any of the analyzed laboratory parameters. We have no explanation for this discrepancy, but differences in the age distribution and the congenital heart diseases of patients included in our study, as compared to Trotter et al. , may play a role.
Severe allergic reactions with cardiac surgery [6,34] and allergic predisposition in adults at risk for cardiovascular death have been reported . The interpretation of allergic/atopic predisposition in POEE risk was indicated by our recent observation of elevated leukocyte function asscoiated molecule-1 (LFA-1) expression on leukocytes of at risk patients , as LFA-1 expression is increased on leukocytes of atopic children . We reported earlier that patients at risk for POEE also had increased preoperative histamine and eosinophil counts, among others [7,29]. The results from the present study do not clearly support the hypothesis of risk prevalence for atopic/allergic patients because only few of the selected markers could indicate an atopic/allergic predisposition (e.g. TNF-α and IL-10). We conclude from these differences that both increased inflammatory status and allergic/atopic predisposition are predictors of increased POEE in children.
Taken together, the data indicate at least three risk groups for pediatric POEE. Risk patients might have: (i) latent infection; (ii) atopic/allergic predisposition; or (iii) immune alterations as a result of the congenital heart disease. These hypotheses have to be further scrutinized by future studies.
Because children with postoperative complications usually have a longer stay on the ICU, a longer period of mechanical ventilation and stay longer in hospital, preoperative risk assessment is of clear therapeutic advantage and can be cost-effective by reducing any stay in intensive care. By prospective classification, up to 86% of the patients at risk were correctly identified preoperatively. In view of the fact that such predictions were not possible at all until now, these predictive values are promising. However, the classifier will be optimized by increasing the number of patients enrolled in studies and by combining this serological classifier with additional parameters such as flow-cytometric data .
Individual risk assessment before cardiac surgery of this type might open new ways to develop individual treatment strategies with two possible clinical consequences: first, postponement of surgery until the normalization of clinical parameters (e.g. elimination of stress or a latent infection); and, second, application of individual prophylaxis  in the case of endogenous reasons for immune system alterations [28,34,35]. The hypothesis that postponement or individual prophylaxis will reduce POEE has to be scrutinized in additional studies.
The proposed serological classifier should permit individual risk assessment in hospitals with lower patient numbers. It is planned to set up and optimize an on-line classifier for POEE risk assessment on the internet. One of the practical consequences of this would be that diseases could be categorized at institutions where no sufficient database can be generated in a reasonable time period. Risk assessments for patients at other institutions can be calculated for test purposes using the indicated SPSS classifier formula (Table 4). Each required parameter value is multiplied with a local data correction factor. The local data correction factor is obtained as a ratio between the parameter mean from non-POEE patients from Table 2 of this study and the mean of the respective parameter from the local non-POEE group of 20 to 40 complication-free patients. The local data correction factor for the establishment of the individual patient's triple matrix for the CLASSIF1 classification is determined in the same way.