Influence of antibiotic prophylaxis on perioperative risk in traumatology with the new concept of clinic modelling randomized trials in animals

Abstract

Abstract Background Surgical outcome depends not only on different therapies, but also on different additionally applied measures 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 (haemorrhagic 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. Methods 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 nailing), antibiotic prophylaxis 1 h before operation (intravenous cefuroxime 20 mg kg−1 versus placebo (sodium chloride)), volume substitution (Ringer) and postoperative analgesia. The clinical situation of healthy (American Society of Anesthesiologists (ASA) grade I and II) and severely injured (ASA III and 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 50 mmHg, blood pressure measured in the femoral artery). The shock period was followed by resuscitation (volume loading) with Ringer solution 40 ml kg−1. The endpoint was the 21-day mortality rate. Fracture healing was documented by radiography. Results The animal model was established successfully. The required blood-letting for relevant shock was 20 ml kg−1. The mortality rate in animals without blood-letting simulating healthy patients (ASA I and II) was zero in the cefuroxime and in placebo groups (n = 20 per group). In the experiment with preoperative blood-letting (ASA III and 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, χ2 test). Disturbances of fracture healing did not occur. Conclusion 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 (CMRTs) 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 the pathophysiological mechanisms will be investigated in further studies.