Table of Contents:
Sepsis is a growing problem in intensive care units despite significant progress in critical care medicine and research. The incidence is steadily growing and mortality is only marginally decreasing. Causative treatment of sepsis is very limited and therefor it is important to know riskfactors for a worsened outcome. This is particularly true if it is possible to modify these. Knowing riskfactors is equally important in the planning of clinical studies, as neglecting these might limit the abilty to interpret and compare results. Perioperative hypothermia (32°C) and chronic malnutrition were evaluated in this dissertation concerning their importance as riskfactors for worsened postoperative sepsis-outcome. Both of these conditions are commonly present in the perioperative course of the surgical patient. Negative impacts on the immune sytstem have been described for both. However, the importance for the postoperative outcome are controversial. In this dissertation the CMRT model was used. It includes the induction of a fecal peritonitis in Wistar-rats under simulation of clinical complexity. In two trials the effect of pre- as well as postoperative mild hypothermia on 120 hour mortality was examined. Additionally the effect of G-CSF application in the setting of hypothermia was evaluated. The impact of food deprivation (50%) over a course of three weeks on postoperative mortality was examined in a separate trial. Pre- as well as postoperative hypothermia showed deleterious effects on postoperative outcome. Additional G-CSF application normalized the outcome under hypothermia to the level observed in normothermic rats. In the trial with preoperative hypothermia the cytokine measurements showed a depressed immune reaction of the cooled rats (reduced IL-6 and increased IL-10 secretion). In the trial with postoperative hypothermia however, a hyperinflammatory state was observed (increased IL-6 secretion) in the hypothermic rats. There was no difference in the survival between the groups in the trial with malnutrition and the cytokine measurements were nonsignificant throughout. The results of this study show, that perioperative mild hypothermia has a negative impact on postoperative sepsis survival regardless if induced before or after operation. It appears that in either case hypothermia causes a disturbance in the cytokine balance during the early stages of sepsis. However, pre- and postoperative hypothermie alter this balance in opposite directions, ultimately leading to similar worsening in outcome. Given the cinical approach of this study, the results support the recommendation to keep patients normothermic in the periopertive phase. If periopertive hypothermia is clearly proven to be beneficial in a particular clinical setting, G-CSF might amerliorate the negative effects of cooling on the immune system. Even tough malnutrition has clearly proven negative effects on the immune system, it fails to show a negative effect in this study. This supports the thinking, that malnutrition does not carry enough importance in the complex clinical scenario and as such is not identifiable as a separate riskfactor. Therefor this study supports the approach not to delay necessary surgey due to malnutrition.