Division of Orthopaedic Surgery, McGill University, Montreal, Quebec, Canada.
Jo Miller Orthopaedic Research Laboratory, Montreal, Quebec, Canada.
JAMA Netw Open. 2024 Aug 1;7(8):e2429702. doi: 10.1001/jamanetworkopen.2024.29702.
Prophylactic administration of antibiotics before skin incision is an important component in the prevention of periprosthetic joint infection in arthroplasty surgery. For antibiotics to be effective, the local tissue concentration (LTC) must exceed the minimum inhibitory concentration of typical infecting organisms; however, the LTC of cefazolin during arthroplasty is poorly understood.
To compare the systemic concentration of cefazolin in serum with the LTC in fat, synovium, and bone during primary total knee arthroplasty (TKA) while assessing the effect of tourniquet inflation.
DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted from March 1, 2022, to June 30, 2023, in patients undergoing TKA at a single academic center.
Total knee arthroplasty with or without a limb tourniquet.
Systemic blood and local tissues from the surgical site (fat, synovium, and bone) were harvested at regular intervals during the surgery. The primary outcome was the LTC of cefazolin, quantified using the liquid chromatography-tandem mass spectrometry technique.
A total of 59 patients were included in the study, with 29 in the tourniquet group (mean [SD] age, 69.3 [9.6] years; 23 [79.3%] female) and 30 in the no tourniquet group (mean [SD] age, 69.9 [9.7] years; 21 [70.0%] female). In patients undergoing TKA without a tourniquet, the mean concentration of cefazolin in serum was 71.9 μg/mL (95% CI, 66.4-77.5 μg/mL), whereas the mean LTCs were 13.9 μg/g (95% CI, 12.1-15.7 μg/g) in fat, 27.7 μg/g (95% CI, 24.3-31.0 μg/g) in synovium, and 17.7 μg/g (95% CI, 14.8-20.5 μg/g) in bone. For patients undergoing TKA with a tourniquet, the mean concentration of cefazolin in serum was 72.0 μg/mL (95% CI, 66.3-77.7 μg/mL), and the mean LTCs were 9.9 μg/g (95% CI, 8.7-11.1 μg/g) in fat, 21.8 μg/g (95% CI, 18.7-25.0 μg/g) in synovium, and 13.0 μg/g (95% CI, 10.8-15.2 μg/g) in bone. The use of a tourniquet resulted in significantly lower mean LTCs by 60 minutes after cefazolin infusion (10.8 μg/g [95% CI, 9.1-12.4 μg/g] vs 16.9 μg/g [95% CI, 14.1-19.6 μg/g], P = .001 in fat; 18.9 μg/g [95% CI, 14.1-23.6 μg/g] vs 25.8 μg/g [95% CI, 21.4-30.3 μg/g], P = .03 in synovium; and 11.8 μg/g [95% CI, 9.3-14.2 μg/g] vs 19.4 μg/g [95% CI, 14.5-24.4 μg/g], P = .007 in bone).
In this randomized clinical trial, the concentration of cefazolin was lower in local tissues (fat, synovium, and bone) than in systemic blood, and the use of a limb tourniquet further significantly reduced these concentrations. Although the current prophylactic dosing regimen for cefazolin provides sufficient serum concentrations, the levels in the periarticular tissue during TKA may be insufficient to prevent periprosthetic joint infection.
ClinicalTrials.gov Identifier: NCT05604157.
重要性：在关节置换手术中，预防性给予抗生素以防止假体周围关节感染是一个重要的环节。为了使抗生素有效，局部组织浓度（LTC）必须超过典型感染病原体的最小抑菌浓度;然而，头孢唑林在关节置换术中的 LTC 知之甚少。
目的：比较初次全膝关节置换术（TKA）过程中头孢唑林的全身浓度与脂肪、滑膜和骨中的 LTC，并评估止血带充气的影响。
设计、地点和参与者：这是一项前瞻性随机临床试验，于 2022 年 3 月 1 日至 2023 年 6 月 30 日在一家学术中心对接受 TKA 的患者进行。
干预措施：TKA 手术伴或不伴肢体止血带。
主要结果和措施：在手术过程中定期从手术部位（脂肪、滑膜和骨）采集全身血液和局部组织样本。主要结局是使用液相色谱-串联质谱技术定量头孢唑林的 LTC。
结果：共有 59 名患者纳入研究，其中 29 名患者在止血带组（平均[标准差]年龄 69.3[9.6]岁；23[79.3%]女性），30 名患者在无止血带组（平均[标准差]年龄 69.9[9.7]岁；21[70.0%]女性）。在未使用止血带的 TKA 患者中，头孢唑林的血清平均浓度为 71.9μg/ml（95%CI，66.4-77.5μg/ml），而脂肪中的平均 LTC 为 13.9μg/g（95%CI，12.1-15.7μg/g），滑膜中的 27.7μg/g（95%CI，24.3-31.0μg/g），骨中的 17.7μg/g（95%CI，14.8-20.5μg/g）。在使用止血带的 TKA 患者中，头孢唑林的血清平均浓度为 72.0μg/ml（95%CI，66.3-77.7μg/ml），脂肪中的平均 LTC 为 9.9μg/g（95%CI，8.7-11.1μg/g），滑膜中的 21.8μg/g（95%CI，18.7-25.0μg/g），骨中的 13.0μg/g（95%CI，10.8-15.2μg/g）。使用止血带会导致头孢唑林输注后 60 分钟时的平均 LTC 显著降低（脂肪中 10.8μg/g[95%CI，9.1-12.4μg/g] vs 16.9μg/g[95%CI，14.1-19.6μg/g]，P=0.001；滑膜中 18.9μg/g[95%CI，14.1-23.6μg/g] vs 25.8μg/g[95%CI，21.4-30.3μg/g]，P=0.03；骨中 11.8μg/g[95%CI，9.3-14.2μg/g] vs 19.4μg/g[95%CI，14.5-24.4μg/g]，P=0.007）。
结论和相关性：在这项随机临床试验中，头孢唑林的浓度在局部组织（脂肪、滑膜和骨）中低于全身血液，使用肢体止血带进一步显著降低了这些浓度。虽然目前头孢唑林的预防性给药方案提供了足够的血清浓度，但在 TKA 期间关节周围组织的水平可能不足以预防假体周围关节感染。
试验注册：ClinicalTrials.gov 标识符：NCT05604157。
