平衡超滤对围手术期抗生素浓度的影响

The dynamic observation of plasma concentration of antJnficrobial agents during balanced ultrafdtration in vitro

目的在体外模拟实验中，观察平衡超滤技术对于围手术期血浆抗生素浓度的影响。方法建立体外循环体外模拟环路，在平衡超滤期间定期取血浆和超滤液样本，采用高效液相色谱检测技术，对两种抗生素头孢替安和头孢美唑药物浓度分别进行动态监测。结果不同时点超滤液中均可检测到头孢替安及头孢美唑的存在。随着超滤液的增加，血浆中抗生素浓度呈现线性降低。至45min超滤结束前，血浆头孢替安由初始浓度（238．95±101．12）μg／ml降低至（104．96±44．36）μg／ml，而血浆头孢美唑由初始浓度（51．49±28．03）μg／ml降低至（25．76±14．78）μg/ml；超滤液中头孢替安总含量占总给药量的（27．16±12．17）％，头孢美唑总含量占总给药量的（7．74±4．17）％。结论平衡超滤技术可以滤除血液中的抗生素，超滤量与蛋白结合率显著相关；超滤技术对于围手术期抗生素的血药浓度具有显著影响，抗生素药物剂量调整需要考虑这一影响因素。

Objective Routine perioperative intravenous antimicrobial agents, was administered as surgical prophylaxis. However, whether balanced ultraliltration during extracorporeal circulation can remove antimicrobial agent remains unclear. The concentrations of antimicrobial agent in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model. Methods Extracorporeal circulation consisted of eardiotomy reservoir （ Ningbo Fly Medical Healtheare CO. , LTD. Ningho, China）, D902 Lilliput 2 membrane oxygenator （ Sorin Group Asia Pte Ltd, Beijing, China） and Capiox AF02 ped- iatric arterial line filter （Terumo Corporation, Beijing, China）. HEMOCONCENTRATOR BC 20 plus （MAQUET Cardiopul- monary AG, Hirrlingen, Germany） was placed between arterial purge line and oxygenator venous reservoir. Fresh donor human whole blood was added into the circuit and mixed with Ringer＇s solution to obtain a final hematocrit of 24% -28%. After 30 minutes of extracorporeal circulation, zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at ap- proximately 100 mm Hg（ 1 mm Hg =0.133 kPa） with Hoffman clamp. The rate of ultrafiltration （ 12 ml/min） was controlled by ultrafiltrate outlet pressure. Identical volume of plasmaslyte A was dripped into the circuit to maintain stable hematocrit dur- ing 45 minutes of experiment. Plasma and ultrafiltrate samples were drawn every 5 minutes and concentrations of antimicrobial agent （including Cefmetazole and eefotiam） were measured with high performance liquid chromatography. Results All these two antimierobial agents were detected in ultrafiltrate, demonstrating hemoconeentration may remove antimicrobial agent. The concentration of plasma antimicrebial agent decreased lineally with the increase of uhrafiltrate volume. At end of balanced ultra- filtration, the concentration of plasma cefotiam was （ 104.96 ± 44.36 ） μg/ml, which is about （44.38 ± 7.42 ） % of the initial concentration （238.95 ± 101.12 ）μg/ml ; the concentration of plasma cefmetazole decreased linearly to （ 25.76 ± 14.78 ） p^g/ml, which is about （49.69 ± 10.49 ） % of the initial concentration （ 51.49 ±28.03 ） μg/ml. The total amount of cefotiam inuhrafihrate is （27.16 ± 12.17）% of the total dose administered, whereas cefmetazole in uhrhrate is （7.74 ±4. 17）%. Conclusion Balanced ultra_filtration may remove antimicrobial agent from serum and has significant influence on plasma con- centration of antimicrobial agent. The strategy of surgical prophylaxis should consider this unique technique during extracorpore- al circulation.