头孢唑林在择期和半择期腹主动脉瘤开放修复手术患者中的药代动力学。
The pharmacokinetics of cefazolin in patients undergoing elective & semi-elective abdominal aortic aneurysm open repair surgery.
机构信息
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
出版信息
BMC Anesthesiol. 2011 Feb 22;11:5. doi: 10.1186/1471-2253-11-5.
BACKGROUND
Surgical site infections are common, so effective antibiotic concentrations at the sites of infection are required. Surgery can lead to physiological changes influencing the pharmacokinetics of antibiotics. The aim of the study is to evaluate contemporary peri-operative prophylactic dosing of cefazolin by determining plasma and subcutaneous interstitial fluid concentrations in patients undergoing elective of semi-elective abdominal aortic aneurysm (AAA) open repair surgery.
METHODS/DESIGN: This is an observational pharmacokinetic study of patients undergoing AAA open repair surgery at the Royal Brisbane and Women's Hospital. All patients will be administered 2-g cefazolin by intravenous injection within 30-minutes of the procedure. Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration by cefazolin. Participants will be administered indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes occurring during surgery. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters and the effect of peri-operative physiological changes on cefazolin disposition.
DISCUSSION
The study will describe cefazolin levels in plasma and the interstitial fluid of tissues during AAA open repair surgery. The effect of physiological changes to the patient mediated by surgery will also be determined. The results of this study will guide clinicians and pharmacists to effectively dose cefazolin in order to maximize the concentration of antibiotics in the tissues which are the most common site of surgical site infections.
背景
手术部位感染很常见，因此需要在感染部位达到有效的抗生素浓度。手术会导致影响抗生素药代动力学的生理变化。本研究的目的是通过评估择期和半择期腹主动脉瘤（AAA）开放修复手术患者的头孢唑林围手术期预防性给药剂量，来评估头孢唑林的当代围手术期预防性剂量。
方法/设计：这是一项在昆士兰皇家妇女医院（Royal Brisbane and Women's Hospital）接受 AAA 开放修复手术的患者的观察性药代动力学研究。所有患者将在手术 30 分钟内通过静脉注射 2 克头孢唑林。参与者将在不同时间点采集血液和尿液样本。还将在皮下组织插入微透析导管，以测量头孢唑林的间质液穿透性。将给参与者施用吲哚菁绿和溴化钠，并进行心输出量监测和四极生物阻抗，以确定手术过程中发生的生理变化。使用经验证的液相色谱串联质谱法分析样本。使用非线性混合效应模型进行药代动力学分析，以确定个体和群体药代动力学参数以及手术引起的围手术期生理变化对头孢唑林处置的影响。
讨论
该研究将描述在 AAA 开放修复手术期间头孢唑林在血浆和组织间质液中的水平。还将确定手术引起的患者生理变化的影响。该研究的结果将指导临床医生和药剂师有效给予头孢唑林剂量，以最大限度地提高组织中抗生素的浓度，这是手术部位感染最常见的部位。
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