Voesten H G, Degener J E, Dijkstra P K, van der Goot L, Agema A, Sikkema B, van der Meer A L
Department of surgery, Nij Smellinghe Hospital, Drachten, Netherlands.
Vasa. 1993;22(4):342-6.
The combinations of cefuroxime and metronidazole, and amoxycillin/clavulanate (Augmentin) are useful as prophylactic drugs during vascular surgery. In this study the pharmacokinetic profiles of different dosing regimens utilizing these drugs during reconstructive vascular procedures are presented. Three groups of patients, undergoing aortobifemoral or femoropopliteal prosthetic surgery, received one of the following regimens: Group I: 1500 mg metronidazole plus 1500 mg cefuroxime at premedication, Group II: 1500 mg metronidazole at premedication plus 1500 mg cefuroxime at the time of induction anaesthesia, followed by 750 mg of cefuroxime 2 h later, Group III: 2000 mg amoxycillin/200 mg clavulanate at time of induction anaesthesia, followed by 1000 mg amoxycillin/200 mg clavulanate, 3 h later. For determination of the antibiotic concentrations, arterial blood samples were obtained at 30-minute intervals during the entire procedure. An additional sample was collected at the time of inguinal graft site anastomosis. Cefuroxime concentrations in these additional samples were 29.3 +/- 11.2 mg/l in group I and 44.7 +/- 15.9 mg/l in group II. Metronidazole concentrations were satisfactorily high in all patients (38.4 +/- 4.5 mg/l). Amoxycillin/clavulanate concentrations were 35.1 +/- 21.5 mg/l and 4.4 +/- 3.7 mg/l respectively. We recommend a multiple dose administration scheme for prophylaxis in high-risk prosthetic vascular surgery, if the procedure takes more than 2-3 h and antimicrobial agents with a rapid elimination time are used. A multiple dosing scheme ensures sufficiently high antibiotic concentrations, exceeding the MIC of staphylococci and enterobacteria approximately twice, at the time of inguinal graft site anastomosis.
头孢呋辛与甲硝唑的联合用药以及阿莫西林/克拉维酸（安灭菌）在血管手术中作为预防性药物很有用。本研究展示了在血管重建手术中使用这些药物的不同给药方案的药代动力学特征。三组接受主动脉双股或股腘人工血管手术的患者接受了以下方案之一：第一组：术前给予1500mg甲硝唑加1500mg头孢呋辛；第二组：术前给予1500mg甲硝唑，诱导麻醉时给予1500mg头孢呋辛，2小时后再给予750mg头孢呋辛；第三组：诱导麻醉时给予2000mg阿莫西林/200mg克拉维酸，3小时后再给予1000mg阿莫西林/200mg克拉维酸。为了测定抗生素浓度，在整个手术过程中每隔30分钟采集动脉血样。在腹股沟移植部位吻合时额外采集一份血样。这些额外血样中头孢呋辛的浓度在第一组为29.3±11.2mg/L，在第二组为44.7±15.9mg/L。所有患者甲硝唑浓度均令人满意地高（38.4±4.5mg/L）。阿莫西林/克拉维酸浓度分别为35.1±21.5mg/L和4.4±3.7mg/L。我们建议，如果手术时间超过2 - 3小时且使用消除时间快的抗菌药物，在高危人工血管手术中采用多剂量给药方案进行预防。多剂量给药方案可确保在腹股沟移植部位吻合时抗生素浓度足够高，大约超过葡萄球菌和肠杆菌的最低抑菌浓度两倍。
