对骨科四肢需放置内植物的手术，通常需术前预防性使用抗生素，并需要使用肢体止血带控制出血。止血带充气前多久使用抗生素，才能发挥抗生素的预防作用？在2020.10 JBJS期刊上，来自丹麦的学者对止血带充气前抗生素的使用时间做了研究，对比不同时间间隔对术中体内抗生素浓度的影响，及止血带对肢体缺血的影响。

Background（背景）

止血带广泛应用于四肢骨折手术。为了避免手术部位感染，在恰当的时机使用抗生素和止血带充气是相当重要的。我们的目的是比较在三种临床相关的止血带应用场景中，对比头孢呋辛在皮下脂肪组织、跟骨骨松质内维持最低抑菌浓度（MIC）的持续时间。

（Tourniquets are widely used during extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimum inhibitory concentration (t > MIC) in porcine subcutaneous adipose tissue and calcaneal cancellous bone during 3 clinically relevant tourniquet application scenarios. ）

Methods（方法）

24头丹麦长白猪被纳入实验。应用微型透析管置入皮下脂肪组织和跟骨松质骨中，在猪随机的一条腿中应用止血带。然后，猪被随机分成三组：止血带充气前15分钟静脉注射1.5g头孢呋辛（A组）、止血带充气前45分钟静脉注射1.5g头孢呋辛（B组）、松开止血带时静脉注射1.5g头孢呋辛（C组）。8小时内收集透析液体和静脉血样本。

（Twenty-four female Danish Landrace pigs were included. Microdialysis catheters were placed bilaterally for sampling of cefuroxime concentrations in calcaneal cancellous bone and subcutaneous adipose tissue, and a tourniquet was applied to a randomly picked leg of each pig. Subsequently, the pigs were randomized into 3 groups to receive 1.5 g of cefuroxime by intravenous injection 15 minutes prior to tourniquet inflation (Group A), 45 minutes prior to tourniquet inflation (Group B), and at the time of tourniquet release (Group C). The tourniquet duration was 90 minutes in all groups. Dialysates and venous blood samples were collected for 8 hours after cefuroxime administration. Cefuroxime and various ischemic marker concentrations were quantified. ）

Results（结果）

在A组和B组止血带使用的90分钟内，皮下脂肪组织和跟骨骨松质内的头孢呋辛浓度均维持在超过金黄色葡萄球菌最小抑菌浓度（4mg/mL）。在C组（止血带释放后使用头孢呋辛），头孢呋辛浓度在止血带使用肢体侧的MIC维持时间大于3.5小时。此外，止血带使用会引发皮下脂肪组织和跟骨骨松质的缺血（乳酸：丙酮酸比例增高）和细胞损伤（甘油增高）。组织缺血会在止血带释放后继续维持2.5小时。

（Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 mg/mL) in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet duration in Groups A and B. Cefuroxime administration at the time of tourniquet release (Group C) resulted in concentrations of >4mg/mL for approximately of 3.5 hours in the tissues on the tourniquet side. Furthermore, tourniquet application induced ischemia (increased lactate:pyruvate ratio) and cell damage (increased glycerol) in subcutaneous adipose tissue and calcaneal cancellous bone. Tissue ischemia was sustained for 2.5 hours after tourniquet release in calcaneal cancellous bone. ）

表1：在不同组使用/不使用止血带侧肢体头孢呋辛维持在MIC以上的时间

图1：各种使用/不使用止血带侧肢体皮下脂肪和跟骨骨松质中头孢呋辛浓度随时间变化图

图2：使用/不使用止血带侧肢体跟骨骨松质中缺血标志物浓度随时间变化图

Conclusion（结论）

在止血带充气前15-45分钟时间窗内使用头孢呋辛可以在止血带使用的90分钟内位置皮下脂肪组织和跟骨骨松质内的有效浓度。此外，止血带引发的组织缺血作用会在止血带释放后的2.5小时后完全消失。

（Administration of cefuroxime (1.5 g) in the 15 to 45-minute window prior to tourniquet inflation resulted in sufficient concentrations in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet application. Furthermore, tourniquet-induced tissue ischemia fully resolved 2.5 hours after tourniquet release .）

Clinical Relevance（临床关联）

止血带充气前15-45分钟内使用头孢呋辛似乎是一个安全的窗口。如果为了在术后维持头孢呋辛有效的MIC浓度，我们建议在止血带释放后使用第二剂头孢呋辛。

（Cefuroxime administration 15 to 45 minutes prior to tourniquet inflation seems to be a safe window. If the goal is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at the time of tourniquet release. ）

参考文献：Hanberg P, Bue M, Öbrink-Hansen K, Thomassen M, Søballe K, Stilling M. Timing of Antimicrobial Prophylaxis and Tourniquet Inflation: A Randomized Controlled Microdialysis Study. J Bone Joint Surg Am. 2020 Nov 4;102(21):1857-1864. doi: 10.2106/JBJS.20.00076. PMID: 32769808.