Antibiotic prophylaxis influences cardiovascular stability in complicated surgery

Antibiotic prophylaxis is used in many surgical procedures but there are frequent cardiovascular instabilities following antibiotics in perioperative period. A clinic modelling randomised trial (CMRT) in pigs was developed to compare the effects of 2 commonly used antibiotic combinations on cardiovascular stability during major surgery.

Thirty pigs (both sexes) were randomised into 3 groups, receiving either saline (placebo), co-amoxiclav or cefuroxime/metronidazole in clinically relevant doses as antibiotic prophylaxis. A laparotomy was performed and the abdomen remained open. Surgical complications were simulated by removing one third of the blood volume. For fluid resuscitation, 500 ml hetastarch (HAES(TM)) were infused rapidly (therapy of complication) and polymyxin B (15 mg/kg bodyweight) was applied for induction of histamine release reactions (complication of therapy). The main end points were histamine release reactions, these were classified by 2 blinded investigators.

Neither cardiovascular changes nor histamine release reactions were detected immediately after the administration of antibiotics or placebo alone. Plasma histamine concentrations increased after bleeding in the co-amoxiclav group (p < 0.05). After fluid resuscitation and induction of anaphylactoid reactions, the median histamine release and cardiovascular changes were not significantly different between the groups. However, the incidence of typical histamine release related reactions differed significantly between the groups: 8/10 for the controls, 6/10 in the co-amoxiclav and 2/10 in the cefuroxime/metronidazole group (p < 0.05).

The stability and reproducibility of this model clearly demonstrated the concept of a 'clinic modelling randomised trial' as a useful tool. Antibiotic prophylaxis influences the organism's capability to cope with intraoperative bleeding and fluid resuscitation problems. Indeed antibiotic prophylaxis may be beneficial. These effects of antibiotics could only be demonstrated in complex surgical models. Thus new antibiotics should be investigated in complex animal models prior to prospective randomised clinical trials or usage in clinical practice.