{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:23:48Z","timestamp":1792409028943,"version":"4.4.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Orthop Relat Res"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>In primary TKA, prophylaxis with low-dose vancomycin through intraosseous regional administration (IORA) achieves tissue concentrations six to 10 times higher than systemic administration and was shown to provide more effective prophylaxis in an animal model. However, in revision TKA, the presence of a tibial implant may compromise IORA injection, and tourniquet deflation during a prolonged procedure may lower tissue concentrations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Questions\/purposes<\/jats:title>\n            <jats:p>(1) Does low-dose IORA reliably provide equal or higher tissue concentrations of vancomycin compared with systemic IV administration in revision TKA? (2) Are tissue concentrations of vancomycin after IORA maintained for the duration of the revision TKA despite a period of tourniquet deflation? (3) Is there any difference in early postoperative (&lt; 6 weeks) complications between IORA and systemic IV administration in revision TKA?<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Twenty patients undergoing aseptic revision TKA were randomized to two groups. The IV group received 1 g systemic IV prophylactic vancomycin. The IORA group received 500 mg vancomycin as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet before skin incision. In all patients receiving IORA, intraosseous tibial injection was technically possible despite the presence of a tibial implant. Mean procedure length was 3.5 hours in both groups. Mean initial tourniquet inflation was 1.5 hours with a second inflation for a mean of 35 minutes during cementation. During the procedure, subcutaneous fat and bone samples were taken at regular intervals. Tissue vancomycin concentrations were measured using high-performance liquid chromatography.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Overall geometric mean tissue concentration of vancomycin in fat samples was 3.7 \u03bcg\/g (95% confidence interval [CI], 2.6-5.2) in the IV group versus 49.3 \u03bcg\/g in the IORA group (95% CI, 33.2-73.4; ratio between means 13.5; 95% CI, 8.2-22.0; p &lt; 0.001); mean tissue concentrations in femoral bone were 6.4 \u03bcg\/g (95% CI, 4.5-9.2) in the IV group versus 77.1 \u03bcg\/g (95% CI, 42.4-140) in the IORA group (ratio between means 12.0; 95% CI, 6.2-23.2; p &lt; 0.001). Vancomycin concentrations in the final subcutaneous fat sample taken before closure were 5.3 times higher in the IORA group versus the IV group (mean \u00b1 SD, 18.2 \u00b1 11.6 \u03bcg\/g IORA versus 3.6 \u00b1 2.5 \u03bcg\/g; p &lt; 0.001). The intraarticular concentration of vancomycin on postoperative Day 1 drain samples was not different between the two groups with the numbers available (mean 4.6 \u03bcg\/L in the IV group versus 6.6 \u03bcg\/g in the IORA group; mean difference 2.0 \u03bcg\/g; 95% CI, 6.2-23.2; p = 0.08).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>IORA administration of vancomycin in patients undergoing revision TKA resulted in tissue concentrations of vancomycin five to 20 times higher than systemic IV administration despite the lower dose. High tissue concentrations were maintained throughout the procedure despite a period of tourniquet deflation. These preliminary results justify prospective cohort studies, which might focus on broader safety endpoints in more diverse patient populations. We believe that these studies should evaluate patients undergoing revision TKA in particular, because the risk of infection is greater than in patients undergoing primary TKA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Level of Evidence<\/jats:title>\n            <jats:p>Level I, therapeutic study.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11999.0000000000000013","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T13:48:02Z","timestamp":1519220882000},"page":"66-74","source":"Crossref","is-referenced-by-count":65,"title":["The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial"],"prefix":"10.1097","volume":"476","author":[{"given":"Simon W.","family":"Young","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant A.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco P.","family":"Pitto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry D.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Spangehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/BLO.0b013e31811ff866","article-title":"Antibiotics for local delivery systems cause skeletal cell toxicity in vitro","volume":"462","author":"Antoci","year":"2007","journal-title":"Clin Orthop Relat Res."},{"key":"R2-20230814","first-page":"161","article-title":"The effective period of preventive antibiotic action in experimental incisions and dermal lesions","volume":"50","author":"Burke","year":"1961","journal-title":"Surgery"},{"key":"R3-20230814","first-page":"111","article-title":"The standard one gram dose of vancomycin is not adequate prophylaxis for MRSA","volume":"34","author":"Catanzano","year":"2014","journal-title":"Iowa Orthop J"},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.resuscitation.2004.02.012","article-title":"Intraosseous infusions via the calcaneus","volume":"62","author":"Clem","year":"2004","journal-title":"Resuscitation"},{"key":"R5-20230814","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1136\/jramc-153-04-20","article-title":"Intra-osseous access (EZ-IO) for resuscitation: UK military combat experience","volume":"153","author":"Cooper","year":"2007","journal-title":"J R Army Med Corps"},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1007\/s11999-014-4062-3","article-title":"Addition of vancomycin to cefazolin prophylaxis is associated with acute kidney injury after primary joint arthroplasty","volume":"473","author":"Courtney","year":"2015","journal-title":"Clin Orthop Relat Res."},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/516284","article-title":"Pharmacokinetic\/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men","volume":"26","author":"Craig","year":"1998","journal-title":"Clin Infect Dis"},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1093\/cid\/cis027","article-title":"Vancomycin for surgical prophylaxis?","volume":"54","author":"Crawford","year":"2012","journal-title":"Clin Infect Dis"},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1128\/AAC.37.12.2693","article-title":"Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration","volume":"37","author":"de Lalla","year":"1993","journal-title":"Antimicrob Agents Chemother"},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1128\/AAC.44.2.316-319.2000","article-title":"Regional prophylaxis with teicoplanin in monolateral or bilateral total knee replacement: an open study","volume":"44","author":"de Lalla","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0140-6736(87)91635-7","article-title":"Long-term results of prophylactic cefazolin versus placebo in total hip replacement","volume":"1","author":"Doyon","year":"1987","journal-title":"Lancet"},{"key":"R12-20230814","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2106\/00004623-199173070-00013","article-title":"Prophylaxis against infection. 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