Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens, Denmark.
Aarhus Microdialysis Research Group, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus, Denmark.
J Bone Joint Surg Am. 2020 Nov 4;102(21):1857-1864. doi: 10.2106/JBJS.20.00076.
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.
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.
Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/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 >4 µg/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.
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.
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.
止血带在四肢手术中广泛应用。为了预防手术部位感染，正确的时机使用抗生素预防和止血带充气非常重要。我们的目的是评估头孢呋辛在猪皮下脂肪和跟骨松质骨中的游离药物浓度在 3 种临床相关止血带应用情况下维持在最低抑菌浓度（t > MIC）以上的时间。
纳入 24 头丹麦兰德瑞斯母猪。双侧放置微透析导管以采集跟骨松质骨和皮下脂肪中的头孢呋辛浓度，然后随机选择每头猪的一条腿应用止血带。随后，将猪随机分为 3 组，分别在止血带充气前 15 分钟（A 组）、45 分钟（B 组）和止血带释放时（C 组）静脉注射 1.5 g 头孢呋辛。所有组的止血带持续时间均为 90 分钟。在头孢呋辛给药后 8 小时内收集透析液和静脉血样本。定量分析头孢呋辛和各种缺血标记物的浓度。
在 A 组和 B 组中，在整个 90 分钟的止血带持续时间内，头孢呋辛浓度在跟骨松质骨和皮下脂肪中均维持在金黄色葡萄球菌的临床折点 MIC（4 µg/mL）以上。在止血带释放时（C 组）给予头孢呋辛，在止血带侧的组织中约 3.5 小时内浓度>4 µg/mL。此外，止血带应用导致皮下脂肪和跟骨松质骨中的缺血（增加乳酸：丙酮酸比值）和细胞损伤（增加甘油）。在跟骨松质骨中，止血带释放后 2.5 小时仍存在组织缺血。
在止血带充气前 15 至 45 分钟内给予头孢呋辛（1.5 g），可使 90 分钟止血带应用过程中跟骨松质骨和皮下脂肪中的浓度足够。此外，止血带引起的组织缺血在止血带释放后 2.5 小时完全缓解。
在止血带充气前 15 至 45 分钟内给予头孢呋辛似乎是安全的。如果目标是使术后头孢呋辛浓度保持在相关 MIC 值以上，我们的结果表明，应在止血带释放时给予第二剂头孢呋辛。
