Safety and effectiveness of intraosseous regional prophylactic antibiotics in total knee arthroplasty: a systematic review and meta-analysis

Background 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. Purposes 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. Patients and Methods 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. Results 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-2 = 0%) and bone tissue (SMD: 0.94; 95% CI: 0.49-1.40; P < 0.001; I-2 = 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-2 = 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-2 = 0%) and vancomycin-related complications (OR: 0.54; 95% CI: 0.25-1.19; P = 0.44; I-2 = 0%). Conclusions 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.