Department of Orthopedics Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Arch Orthop Trauma Surg. 2024 Sep;144(9):4233-4245. doi: 10.1007/s00402-024-05513-0. Epub 2024 Sep 19.
Intraosseous regional administration (IORA) as a widely applicable and clinically valuable route of administration has gained significant attention in the context of total knee arthroplasty (TKA) for the prophylactic administration of antibiotics. However, there is still controversy regarding its effectiveness and safety. The latest meta-analysis reports that the use of IORA for antibiotics in TKA is as safe and effective as IV administration in preventing prosthetic joint infection (PJI), but they did not separate the statistics for primary TKA and revision TKA, which may be inappropriate. There is currently a lack of evidence specifically comparing the outcomes of prophylactic antibiotic administration via IORA or IV route in primary/revision TKA, respectively, and new research evidence has emerged.
In this study, we conducted a systematic review and meta-analysis with the primary objective of comparing the local drug tissue concentration and the incidence of PJI between preoperative IORA and intravenous (IV) administration of prophylactic antibiotics in TKA. Additionally, the occurrence of complications between the two administration routes was also compared.
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (PRISMA) guidelines. Retrospective cohort studies and prospective randomized controlled trials that utilized intraosseous local drug delivery for prophylactic antibiotics in knee arthroplasty were included. English literature from PubMed, Embase, and Cochrane Library databases was searched from the inception of each database until December 2023. Two researchers independently screened the literature, assessed the quality, and extracted data according to the inclusion criteria. The primary outcomes were local antibiotic tissue concentration and postoperative PJI incidence, while the secondary outcome was the occurrence of postoperative complications. Statistical analysis was performed using Review Manager 5.3 software.
This study included 7 prospective randomized controlled trials and 5 retrospective cohort studies. A total of 4091 patients participated in the 12 included studies, with 1,801 cases receiving IORA and 2,290 cases in the control group. In terms of local drug tissue concentration, intraosseous infusion (IO) 500 mg vancomycin significantly increased the drug concentration in the periarticular adipose tissue (SMD: 1.36; 95% CI: 0.87-1.84; P < 0.001; I = 0%) and bone tissue (SMD: 0.94; 95% CI: 0.49-1.40; P < 0.001; I = 0%) compared to IV 1 g vancomycin. Regarding the incidence of postoperative PJI after primary TKA, IO 500 mg vancomycin was more effective in reducing the occurrence of PJI compared to IV 1 g vancomycin (OR: 0.19; 95% CI: 0.06-0.59; P < 0.001; I = 36%). Finally, no significant differences were found between the two groups in terms of postoperative pulmonary embolism (PE) (OR: 1.72; 95% CI: 0.22-13.69; P = 0.59; I = 0%) and vancomycin-related complications (OR: 0.54; 95% CI: 0.25-1.19; P = 0.44; I = 0%).
Preoperative prophylactic antibiotic administration via IORA in TKA significantly increases local drug tissue concentration without significantly increasing systemic drug-related complications compared to traditional IV administration. In primary TKA, low-dose vancomycin via IORA is more effective in reducing the incidence of PJI compared to traditional IV regimens. However, its effectiveness remains controversial in high-risk populations for PJI, such as obese, diabetic, and renal insufficiency patients, as well as in revision TKA.
在全膝关节置换术（TKA）中，作为一种广泛应用且具有临床价值的给药途径，骨内区域性给药（IORA）在预防性使用抗生素方面引起了广泛关注。然而，其有效性和安全性仍存在争议。最新的荟萃分析报告称，在预防人工关节感染（PJI）方面，TKA 中使用 IORA 给予抗生素与静脉给药（IV）一样安全有效，但他们没有对初次 TKA 和翻修 TKA 的统计数据进行分离，这可能是不恰当的。目前缺乏专门比较初次/翻修 TKA 中通过 IORA 或 IV 途径预防性给予抗生素的结局的证据，并且出现了新的研究证据。
本研究旨在通过系统评价和荟萃分析比较初次 TKA 中术前 IORA 和静脉（IV）给予预防性抗生素的局部药物组织浓度和 PJI 的发生率。此外，还比较了两种给药途径的并发症发生情况。
本荟萃分析遵循系统评价和荟萃分析报告的首选报告项目（PRISMA）指南进行。纳入了使用骨内局部药物输送进行膝关节置换术预防性抗生素给药的回顾性队列研究和前瞻性随机对照试验。从每个数据库的开始日期检索到 2023 年 12 月，PubMed、Embase 和 Cochrane 图书馆数据库的英文文献。两名研究人员独立筛选文献、评估质量，并根据纳入标准提取数据。主要结局是局部抗生素组织浓度和术后 PJI 发生率，次要结局是术后并发症的发生情况。使用 Review Manager 5.3 软件进行统计分析。
本研究纳入了 7 项前瞻性随机对照试验和 5 项回顾性队列研究。共有 4091 名患者参与了 12 项纳入的研究，其中 1801 例接受 IORA，2290 例在对照组。在局部药物组织浓度方面，与 IV 1 g 万古霉素相比，骨内输注（IO）500 mg 万古霉素显著增加了关节周围脂肪组织（SMD：1.36；95%CI：0.87-1.84；P<0.001；I=0%）和骨组织（SMD：0.94；95%CI：0.49-1.40；P<0.001；I=0%）中的药物浓度。关于初次 TKA 后术后 PJI 的发生率，与 IV 1 g 万古霉素相比，IO 500 mg 万古霉素在降低 PJI 的发生方面更有效（OR：0.19；95%CI：0.06-0.59；P<0.001；I=36%）。最后，两组在术后肺栓塞（PE）（OR：1.72；95%CI：0.22-13.69；P=0.59；I=0%）和万古霉素相关并发症（OR：0.54；95%CI：0.25-1.19；P=0.44；I=0%）方面无显著差异。
初次 TKA 中术前 IORA 给予预防性抗生素可显著增加局部药物组织浓度，而与传统 IV 给药相比，不会显著增加全身药物相关并发症。在初次 TKA 中，与传统 IV 方案相比，IO 低剂量万古霉素可更有效地降低 PJI 的发生率。然而，其在 PJI 高危人群（如肥胖、糖尿病和肾功能不全患者）以及翻修 TKA 中的有效性仍存在争议。
