严重烧伤早期创面下抗生素屏障的形成与临床意义  

The formation and its significance of antibiotic barrier in vivo in the early stage of severe burn wounds

作　　者：荣新洲[1] 王震[1] 

机构地区：[1]广州医科大学附属广州市第一人民医院烧伤科,广东广州510180

出　　处：《感染．炎症．修复》2015年第2期77-82,共6页Infection Inflammation Repair

摘　　要：目的：观察和探讨严重烧伤患者第三间隙抗生素潴留、返释现象及其意义。方法：分别观察30％TBSAIII度烧伤新西兰兔模型和重度烧伤患者应用亚胺培南或阿米卡星后，血液、水疱液、痂下水肿液中的抗生素浓度，观察抗生素的潴留情况，分析其药代动力学特点；在不同烧伤面积（8％TBSAT和40％TBSA）III度烧伤模型兔痂下注射示踪白蛋白，观察其向血浆返释的情况。结果：①烧伤新西兰兔应用亚胺培南1h后即可在痂下组织液中被检测出，并且达到峰浓度[（8．99±1．10）ug／m1]，可维持6～8h；痂下水肿液中亚胺培南的消除相半衰期明显延长，分别是烧伤组血浆和对照组血浆值的1．67倍和2．26倍。②烧伤后单次应用阿米卡星1h即能在痂下水肿液测到阿米卡星浓度并达峰值[（30．23±2．75）ug／m1]，且痂下水肿液消除相半衰期[（80．04±9．52）h]为健康成年人血浆半衰期的28．20～44．78倍，半衰期显著延长。③烧伤患者伤后3～4h内应用阿米卡星，水疱液中达峰时间为1h[（12．53±1．76）ug／roll，伤后10h应用则达峰时间为2h[（9．56±1．13）lag／m1]，高于多数致病菌的最低抑菌浓度（MIC），包括铜绿假单胞菌（MICS0=4．2ug／m1），伤后20、30h应用其达峰时间延长（〉4h），峰浓度明显降低（低于多数致病菌的MIC）。④烧伤新西兰兔痂下注射人血白蛋白，可于2h后在血浆中检测到其含量，烧伤面积越大分布相半衰期越小（8％TBSAVS．40％TBSA；4．0271hVS．1．7326h），曲线下面积越大（8％TBSAVS．40％TBSA：22336．38μg·h^-1·ml^-1—VS．88814-84μg·h^-1·ml^-1）。结论：严重烧伤早期大量的抗生素被蓄积在以痂下水肿液为代表的第三间隙，体液回收期后这些物质能够被回吸收。潴留在痂下水肿液中的大量抗生素形成了抗生素屏障，这一现象有助于防止创面细菌的深部侵袭。Objective： To observe and analyze the retention and reflux phenomena of antibiotics in the third space of patients with severe burn. Methods： Pharmacokinetic study of imipenem and amikacin was performed in severe burn patients and rabbits with 30%TBSA full-thickness burn injury, and the results were analyzed, including determination of the concentration of the antibiotic in blood, blister fluid, and edematous fluid under scab, in order to determine the state of sequestration of these antibiotics. Human albumin was injected as a tracer into subeschar tissue of burn rabbits with full- thickness burn area of 8% TBSA or 40%TBSA, and then the plasma concentration of albumin was determined in order to explore its reflux phenomenon. Results： @ In the burn rabbits, imipenem could be detected in the subeschar interstitial fluid 1 hour after it was injected intravenously, and it reached the peak concentration [ （8.99＋1.10） gg/ml], and it lasted for 6 to 8 hours. Its elimination half-life in the edematous fluid under eschar was 1.67 or 2.26 times longer than that in plasma of the burn group or the control group. （~ One hour after a single injection of amikacin into burn patients, it could be detected in the edematous fluid under eschar, and it had reached the peak concentration[（30.23＋2.75） gg/ml]. Its elimination half-life was prolonged [（80.04＋9.52）hours], which was 28.20 to 44.78 times than that in the plasma of healthy adults. @ The time to reach the peak concentration [（12.53＋1.76） gg/ml] was about 1 hour when amikacin was injected within 3-4 hours after a burn injury in patients, but it took 2 hours to reach the peak level [（9.56＋1.13） gg/ml] when amikacin was used 10 hours after burn. The concentration was higher than the minimum inhibitory concentration （MIC） for most pathogenic bacteria, including Pseudomonas aeruginosa （MIC50=4.2 p,g/ml）, but the time for it to reach the peak concentration was prolonged to over 4 hours when amikacin was used 20 hours or 30 hours after

关 键 词：烧伤抗生素屏障 第三间隙 痂下水肿液 最低抑菌浓度 

分 类 号：R644[医药卫生—外科学]