Aalbers Marieke, ter Horst Peter G J, Hospes Wobbe, Hijmering Michel L, Spanjersberg Alexander J
Department of Clinical Pharmacy, Hospital Pharmacy Emmen, Boermarkeweg 60, 7824 AA, Emmen, The Netherlands,
Int J Clin Pharm. 2015 Aug;37(4):592-8. doi: 10.1007/s11096-015-0101-8. Epub 2015 Mar 20.
Patients are at risk for severe postoperative infections after coronary artery bypass graft (CABG) surgery. Clinical laboratory data showed that unbound plasma concentrations of cefuroxime were not always adequate, therefore we developed a new dosing regimen.
The aim of this prospective study is to evaluate the new dosing strategy by monitoring patients for unbound cefuroxime plasma concentrations during CABG surgery with cardiopulmonary bypass (CPB).
A Dutch teaching hospital.
In this prospective trial, patients scheduled for CABG surgery with CPB were included. A starting dose of 1500 mg cefuroxime was given with anesthesia induction, followed by 750 mg cefuroxime every hour until wound closure. In case of renal failure the dosing regimen was adapted. Serial blood samples were collected before, during and after the CPB process. Pharmacokinetic modelling was performed by using an 'iterative two-stage Bayesian population procedure'.
Unbound plasma concentrations of cefuroxime.
22 patients were included, data could be evaluated of 21 patients. In 24 % of the patients the unbound cefuroxime plasma concentration was below the target range during surgery before CPB started. Patients with a bodyweight above 100 kg or age <60 years were more likely to have unbound plasma concentrations below the target range (P = 0.030 and P = 0.008). During CPB, the half-life of unbound cefuroxime increased by 17 % and the clearance decreased by 11 % compared to before CPB (P = 0.033 and P = 0.014). The mean pharmacokinetic parameters before, during and after CPB were as follows: elimination half-life 72, 84 and 76 min; clearance of unbound cefuroxime (Clu) 14.2, 12.7, 13.8 l/h and volume of distribution (Vu) 0.280, 0.284 and 0.290 l/kg respectively. Variations in unbound fractions before, during and after CPB were below 2 %, implicating the unbound fraction of cefuroxime is not influenced by CPB.
Our results show that CPB during CABG surgery does not lead to inadequate unbound cefuroxime concentrations. Age, renal function and possibly also weight are more important factors that can result in unbound plasma cefuroxime concentrations below the target value.
冠状动脉搭桥术（CABG）后患者有发生严重术后感染的风险。临床实验室数据显示，头孢呋辛的游离血浆浓度并不总是足够的，因此我们制定了一种新的给药方案。
这项前瞻性研究的目的是通过在体外循环（CPB）的CABG手术期间监测患者游离头孢呋辛血浆浓度来评估新的给药策略。
一家荷兰教学医院。
在这项前瞻性试验中，纳入计划进行CPB的CABG手术的患者。麻醉诱导时给予1500mg头孢呋辛起始剂量，随后每小时给予750mg头孢呋辛直至伤口闭合。如果出现肾衰竭，则调整给药方案。在CPB过程之前、期间和之后采集系列血样。使用“迭代两阶段贝叶斯群体程序”进行药代动力学建模。
头孢呋辛的游离血浆浓度。
纳入22例患者，可对21例患者的数据进行评估。在24%的患者中，CPB开始前手术期间游离头孢呋辛血浆浓度低于目标范围。体重超过100kg或年龄<60岁的患者游离血浆浓度更有可能低于目标范围（P = 0.030和P = 0.008）。与CPB前相比，CPB期间游离头孢呋辛的半衰期增加了17%，清除率降低了11%（P = 0.033和P = 0.014）。CPB前、期间和之后的平均药代动力学参数如下：消除半衰期分别为72、84和76分钟；游离头孢呋辛清除率（Clu）分别为14.2、12.7、13.8 l/h，分布容积（Vu）分别为0.280、0.284和0.290 l/kg。CPB前、期间和之后游离分数的变化低于2%，这意味着头孢呋辛的游离分数不受CPB影响。
我们的结果表明，CABG手术期间的CPB不会导致游离头孢呋辛浓度不足。年龄、肾功能以及可能的体重是导致游离血浆头孢呋辛浓度低于目标值的更重要因素。
