Stressresponse, Mastzellaktivierung und Verlauf perioperativer chirurgischer Infektionen: Einfluss einer perioperativen Antihistaminikaprophylaxe in Klinik modellierenden randomisierten Tierstudien

This studie was designed to discover the influence of a perioperative prophylaxis with H1 and H2 receptor antagonists on postoperative abdominal infection. Studies were performed with large samples of rats following the concept of clinic modelling randomised trials (CMRT). ?Clinic modelling? means not only modelling medical details like drug regimes or surgical procedures but also consideration of rules for performance of prospective randomised trials. The CMRT?s are a new approach to analyse drugs and therapies in an intermediate stage between preclinical and clinical studies.The results of the studies show a optimum combination of dimetinden and cimitidin as antihistamines, in the next series there was a slight tendency towards higher survival in the single shot group compared with the group who got antihistamines on the following days, too. This result appeared under low and high mortality rate. Prophylaxis with cimetidin alone without H1-antagonist could not show a improvement of survival. The results of the definitive studies show a significant higher survival of the antihistamine-group compared with the placebo-group. This result was found with low and high mortality of placebo-group. The antibiotic in all studies above was co-amoxiclav. The surprising result of another studie with exactly the same setting but levofloxacin and metronidazol as antibiotics failed to show a gain in survival but showed a higher mortality compared with the placebo-group. This result may be caused due to interactions between the antibiotics and immune system or due to different pattern in LPS liberation. Ther were found similar differences between various antibiotics and immunemodulation with G-CSF,too. As a result of the studies the CMRT seem to be a promising new approach to analyse drugs and therapies in an intermediate stage between preclinical and clinical studies. A prophylaxis with a combination of cimetidin and dimetinden in exactly predefined clinical settings may show an advantage, but a prophylaxis with antihistamines can not be recommended in general.This studie was designed to discover the influence of a perioperative prophylaxis with H1 and H2 receptor antagonists on postoperative abdominal infection. Studies were performed with large samples of rats following the concept of clinic modelling randomised trials (CMRT). ?Clinic modelling? means not only modelling medical details like drug regimes or surgical procedures but also consideration of rules for performance of prospective randomised trials. The CMRT?s are a new approach to analyse drugs and therapies in an intermediate stage between preclinical and clinical studies.The results of the studies show a optimum combination of dimetinden and cimitidin as antihistamines, in the next series there was a slight tendency towards higher survival in the single shot group compared with the group who got antihistamines on the following days, too. This result appeared under low and high mortality rate. Prophylaxis with cimetidin alone without H1-antagonist could not show a improvement of survival. The results of the definitive studies show a significant higher survival of the antihistamine-group compared with the placebo-group. This result was found with low and high mortality of placebo-group. The antibiotic in all studies above was co-amoxiclav. The surprising result of another studie with exactly the same setting but levofloxacin and metronidazol as antibiotics failed to show a gain in survival but showed a higher mortality compared with the placebo-group. This result may be caused due to interactions between the antibiotics and immune system or due to different pattern in LPS liberation. Ther were found similar differences between various antibiotics and immunemodulation with G-CSF,too. As a result of the studies the CMRT seem to be a promising new approach to analyse drugs and therapies in an intermediate stage between preclinical and clinical studies. A prophylaxis with a combination of cimetidin and dimetinden in exactly predefined clinical settings may show an advantage, but a prophylaxis with antihistamines can not be recommended in general.