Kilbaugh Todd J, Himebauch Adam S, Zaoutis Theoklis, Jobes David, Greeley William J, Nicolson Susan C, Zuppa Athena F
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
Center for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Paediatr Anaesth. 2015 Nov;25(11):1111-9. doi: 10.1111/pan.12756. Epub 2015 Sep 15.
Surgical site infection (SSI) prevention for children with congenital heart disease is imperative and methods to assess and evaluate the tissue concentrations of prophylactic antibiotics are important to help maximize these efforts.
The purposes of this study were to determine the plasma and tissue concentrations with standard of care, perioperative cefazolin dosing in an immature porcine model of pediatric cardiac surgery, and to determine the feasibility of this model.
Piglets (3-5 days old) underwent either median sternotomy (MS) or cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB + DHCA) and received standard of care prophylactic cefazolin for the procedures. Serial plasma and microdialysis sampling of the skeletal muscle and subcutaneous tissue adjacent to the surgical site was performed. Cefazolin concentrations were measured, noncompartmental pharmacokinetic analyses were performed, and tissue penetration of cefazolin was assessed.
Following the first intravenous dose, maximal cefazolin concentrations in the subcutaneous tissue and skeletal muscle were similar between groups with peak tissue concentrations 15-30 min after administration. After the second cefazolin dose given with the initiation of CPB, total plasma cefazolin concentrations remained relatively constant until the end of DHCA and then decreased while muscle- and subcutaneous-unbound cefazolin concentrations showed a second peak during or after rewarming. For the MS group, 60-67% of the intraoperative time showed subcutaneous and skeletal muscle concentrations of cefazolin >16 μg·ml(-1) while this percentage was 78-79% for the CPB + DHCA group. There was less tissue penetration of cefazolin in the group that underwent CBP + DHCA (P = 0.03).
The cefazolin dosing used in this study achieves plasma and tissue concentrations that should be effective against methicillin-sensitive Staphylococcus aureus but may not be effective against some gram-negative pathogens. The timing of the cefazolin administration prior to incision and a second dose given during cardiopulmonary bypass may be important factors for achieving goal tissue concentrations.
预防先天性心脏病患儿手术部位感染至关重要，评估和评价预防性抗生素的组织浓度的方法对于最大限度地实现这些努力很重要。
本研究的目的是在未成熟猪小儿心脏手术模型中确定围手术期头孢唑林给药的标准护理下的血浆和组织浓度，并确定该模型的可行性。
仔猪（3 - 5日龄）接受正中胸骨切开术（MS）或体外循环加深度低温循环停搏（CPB + DHCA），并在手术过程中接受标准护理预防性头孢唑林。对手术部位附近的骨骼肌和皮下组织进行连续血浆和微透析采样。测量头孢唑林浓度，进行非房室药代动力学分析，并评估头孢唑林的组织穿透性。
首次静脉给药后，皮下组织和骨骼肌中头孢唑林的最大浓度在各组之间相似，给药后15 - 30分钟达到组织峰值浓度。在CPB开始时给予第二次头孢唑林剂量后，总血浆头孢唑林浓度在DHCA结束前保持相对恒定，然后下降，而肌肉和皮下未结合的头孢唑林浓度在复温期间或复温后出现第二个峰值。对于MS组，术中60 - 67%的时间显示皮下和骨骼肌中头孢唑林浓度>16μg·ml⁻¹，而CPB + DHCA组的这一百分比为78 - 79%。接受CBP + DHCA的组中头孢唑林的组织穿透性较低（P = 0.03）。
本研究中使用的头孢唑林给药方案可达到对甲氧西林敏感金黄色葡萄球菌有效的血浆和组织浓度，但可能对某些革兰氏阴性病原体无效。术前切口前给予头孢唑林的时间以及体外循环期间给予的第二剂可能是实现目标组织浓度的重要因素。
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