Einfluss der Antibiotikaapplikation und ihre adversen Effekte auf den perioperativen Verlauf sowie auf die Frakturheilung bei Schwerverletzten nach Osteosynthesen an langen Röhrenknochen -Etablierung eines Tiermodells -

Die Auffassungen über den Einsatz einer perioperativen Antibiotikaprophylaxe bei unfallchirurgischen Operationen gehen in zahlreichen tierexperimentellen und klinischen Studien weit auseinander. Bei zusätzlichen Risikofaktoren oder multimorbiden Patienten ist die Indikation zur Antibiotikaprophylaxe...

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Bibliographic Details
Main Author: Krüger, Antonio
Contributors: Celik, Ilhan (Dr. med) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2005
Online Access:PDF Full Text
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Table of Contents: Surgical outcome depends not only on different therapis, but also on different additionally applied mesures like prophylaxis (antibiotics, heparin, etc.) and their complex interaction. The aim of this study was to establish a new concept of clinic modelling randomized trials (CMRTs) in rats (hemorrhagic shock model) to investigate the harmful or beneficial effects of antibiotic prophylaxis in trauma patients (evidence-based medicine). Elements of the clinical scenario and methodology of randomized trials were modelled as accurately as possible in this CMRT. Conditions of the rat model (CMRT) were adapted to the methodology of clinical trials and the clinical scenario with respect to sample size calculation, blinding and randomized allocation in a two-block design (n=20 animals per group), anaesthesia with fentanyl-droperidol, standardized operation (soft tissue damage, tibia fracture and intramedullary nailing), antibiotic prophylaxis 1 h before operation (intravenous cefuroxim/cefotaxim versus placebo (sodium chloride solution)), volume substitution (Ringer-solution) and postoperative analgesia. The clinical situation of healthy (American Society of Anesthesiologists (ASA) I and II) and severely injured (ASA III + IV) patients was simulated in the CMRT by sham operation and preoperative blood-letting, respectively, to initiate a relevant shock (1,5 h of mean arterial pressure below 50mmHg, blood pressure measured in tzhe femoral artery).The shock period was followed by resuscitation (volume loading) with Ringer-solution 40ml/kg. The endpoint was the 20-day mortality rate. Fracture healing was documented by radiography. The animal model was established successfully. The required blood-letting for relevant shock was 20ml/kg. The mortality rate in animals without blod letting simulating healthy patients (ASA I + II) was zero in the cefuroxime and in placebo groups (n=20 per group). In the experiment with preoperative blood-letting (ASA III + IV), n= 20 per group) a clear but not significant trend in the mortality rate for the cefuroxime group (20 per cent) versus placebo (40 per cent) could be observed (1 d.f., P > 0,05, X2-test) Disturbances of fracture healing did not occur. The clinical impact (evidence based) of antibiotic prophylaxis in traumatology was demonstrated in these experiments. The influence of other currently used antibiotics in trauma patients could be investigated in such animal models (CMRT`s) instead of expensive and time-consuming clinical trials. The results of this study suggest the advantage of prophylaxis with cefuroxime in severely injured patients. Other antibiotics and pathophysiological mechanisms can be investigated using CMRT`s.