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The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial.

ABSTRACT: BACKGROUND: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. QUESTIONS/PURPOSES:(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 (< 6 weeks) complications between IORA and systemic IV administration in revision TKA? METHODS: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. RESULTS:Overall geometric mean tissue concentration of vancomycin in fat samples was 3.7 ?g/g (95% confidence interval [CI], 2.6-5.2) in the IV group versus 49.3 ?g/g in the IORA group (95% CI, 33.2-73.4; ratio between means 13.5; 95% CI, 8.2-22.0; p < 0.001); mean tissue concentrations in femoral bone were 6.4 ?g/g (95% CI, 4.5-9.2) in the IV group versus 77.1 ?g/g (95% CI, 42.4-140) in the IORA group (ratio between means 12.0; 95% CI, 6.2-23.2; p < 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 ± SD, 18.2 ± 11.6 ?g/g IORA versus 3.6 ± 2.5 ?g/g; p < 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 ?g/L in the IV group versus 6.6 ?g/g in the IORA group; mean difference 2.0 ?g/g; 95% CI, 6.2-23.2; p = 0.08). CONCLUSIONS: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. LEVEL OF EVIDENCE:Level I, therapeutic study.

SUBMITTER: Young SW

PROVIDER: S-EPMC5919223 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial.

Young Simon W SW Zhang Mei M Moore Grant A GA Pitto Rocco P RP Clarke Henry D HD Spangehl Mark J MJ

Clinical orthopaedics and related research 20180101 1

<h4>Background</h4>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.<h4>Questions/purposes</h4>(1) Does low-dose ...[more]

PMID: 29529618

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Project description:BackgroundConcerns about the cost and convenience of postsurgical physical therapy (PT) have sparked interest in unsupervised, home-based rehabilitation. However, the effectiveness of unsupervised home exercise after primary TKA has not been previously evaluated.Questions/purposes(1) Can unsupervised home exercise after surgery provide noninferior recovery of passive knee flexion compared with formal outpatient PT? (2) Does a web-based platform for home-based exercise provide an advantage compared with a printed PT manual?MethodsWe conducted a randomized, noninferiority trial involving 290 patients (20% of the 1464 eligible patients who could be contacted) who underwent primary TKA from March 2016 to April 2018. We included patients > 18 years old who were undergoing primary, unilateral TKA and provided written consent. We excluded patients with preoperative knee flexion < 90°, patients considering surgical intervention in a hip or the contralateral knee, patients discharged to an extended care facility, and revision or conversion TKA. We randomized patients to one of three groups: outpatient PT, unsupervised home exercise using a web-based platform (web PT), or unsupervised home exercise using a printed paper manual (paper PT). We also implemented a "delayed recovery intervention" within the home exercise program, in which patients were obliged to begin outpatient PT if knee flexion was < 70° at 2 weeks or < 90° at 4 weeks. The primary outcome was change in knee flexion from preoperative baseline after 4 to 6 weeks and 6 months. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), time back to activities of daily living, and time off narcotics. All analyses were intention to treat, and the noninferiority margin was 5% with maximum flexion as the outcome of interest for this parameter.ResultsAdjusted differences in change in passive flexion for web PT +3° (95% confidence interval [CI], -1.2° to 6.4°) and paper PT +5° (95% CI, 0.99°-8.6°) were not inferior to outpatient PT based on a predefined 5° margin. Change in knee flexion from baseline was 0° for outpatient PT, -2° for web PT, and -1° for paper PT after 4 to 6 weeks and 8°, 8°, and 12° for the three groups, respectively, after 6 months. Additionally, there was no difference in the change in KOOS from baseline at 4 to 6 weeks or 6 months postoperatively as well as time back to work, driving, and walking without an assistive device.ConclusionsUnsupervised home exercise is an effective rehabilitation strategy after primary TKA and was noninferior to formal outpatient PT in selected patients. It is worthwhile to reconsider the current practice of automatically designating patients for outpatient PT after primary TKA, because appropriately selected patients with adequate clinical support can achieve similar results at home.Level of evidenceLevel I, therapeutic study.

Project description:Intravenous regional limb perfusions (RLP) are widely used in equine medicine to treat distal limb infections, including synovial sepsis. RLPs are generally deemed successful if the peak antibiotic concentration (Cmax) in the sampled synovial structure is at least 8-10 times the minimum inhibitory concentration (MIC) for the bacteria of interest. Despite extensive experimentation and widespread clinical use, the optimal technique for performing a successful perfusion remains unclear. The objective of this meta-analysis was to examine the effect of technique on synovial concentrations of antibiotic and to assess under which conditions Cmax:MIC ≥ 10. A literature search including the terms "horse", "equine", and "regional limb perfusion" between 1990 and 2021 was performed. Cmax (μg/ml) and measures of dispersion were extracted from studies and Cmax:MIC was calculated for sensitive and resistant bacteria. Variables included in the analysis included synovial structure sampled, antibiotic dose, tourniquet location, tourniquet duration, general anesthesia versus standing sedation, perfusate volume, tourniquet type, and the concurrent use of local analgesia. Mixed effects meta-regression was performed, and variables significantly associated with the outcome on univariable analysis were added to a multivariable meta-regression model in a step-wise manner. Sensitivity analyses were performed to assess the robustness of our findings. Thirty-six studies with 123 arms (permutations of dose, route, location and timing) were included. Cmax:MIC ranged from 1 to 348 for sensitive bacteria and 0.25 to 87 for resistant bacteria, with mean (SD) time to peak concentration (Tmax) of 29.0 (8.8) minutes. Meta-analyses generated summary values (θ) of 42.8 x MIC and 10.7 x MIC for susceptible and resistant bacteria, respectively, though because of high heterogeneity among studies (I2 = 98.8), these summary variables were not considered reliable. Meta-regression showed that the only variables for which there were statistically significant differences in outcome were the type of tourniquet and the concurrent use of local analgesia: perfusions performed with a wide rubber tourniquet and perfusions performed with the addition of local analgesia achieved significantly greater concentrations of antibiotic. The majority of arms achieved Cmax:MIC ≥ 10 for sensitive bacteria but not resistant bacteria. Our results suggest that wide rubber tourniquets and concurrent local analgesia should be strongly considered for use in RLP and that adequate therapeutic concentrations (Cmax:MIC ≥ 10) are often achieved across a variety of techniques for susceptible but not resistant pathogens.

Project description:BackgroundThere is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors.Questions/purposesUsing a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time?MethodsWe queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate.ResultsThere was a difference in the incidence of DVT at 90 days (p < 0.01). Factor Xa inhibitors (2.9%) had the lowest incidence of DVT followed by aspirin (3.0%) and enoxaparin (3.5%), and warfarin (4.8%). There was a difference in the incidence of PE at 90 days (p < 0.01). Factor Xa inhibitors (0.9%) had the lowest incidence of PE followed by enoxaparin (1.1%), aspirin (1.2%), and warfarin (1.6%). There was a difference in the incidence of postoperative anemia at 90 days (p < 0.01). Aspirin (19%) had the lowest incidence of postoperative anemia followed by warfarin (22%), enoxaparin (23%), and factor Xa inhibitors (23%). There was a difference in the incidence of a blood transfusion at 90 days (p < 0.01). Aspirin (7%) had the lowest incidence of a blood transfusion followed by factor Xa inhibitors (9%), warfarin (12%), and enoxaparin (13%). There were no differences in bleeding-related complications (p = 0.81) between the groups. Aspirin use increased at a compound annual growth rate of 30%, enoxaparin at 3%, and factor Xa inhibitors at 43%, while warfarin use decreased at a compound annual growth rate of -3%.ConclusionsFactor Xa inhibitors had the highest growth in utilization during our study period, followed by aspirin, when compared with enoxaparin and warfarin. When selected for the right patient, factor Xa inhibitors provided improved VTE prophylaxis compared with enoxaparin and warfarin, with a lower rate of blood transfusion. Aspirin provided comparable VTE prophylaxis compared with factor Xa inhibitors with improved VTE prophylaxis compared with enoxaparin and warfarin with the lowest risk of bleeding.Level of evidenceLevel III, therapeutic study.

Project description:Maintaining robust perfusion is an important physiologic parameter in wound healing. The effect of different closure techniques on wound perfusion after total knee arthroplasty (TKA) has not been established previously and may have implications for wound healing.We asked whether a running subcuticular, vertical mattress, or skin staple closure technique enables the most robust wound perfusion after TKA as measured by laser-assisted indocyanine green angiography (LA-ICGA) in patients without specific risk factors for wound healing complications.Forty-five patients undergoing primary TKA without comorbidities known to impact wound healing and perfusion were prospectively randomized to receive superficial skin closure with one of the following techniques: (1) running subcuticular (3-0 monofilament); (2) vertical mattress (2-0 nylon); or (3) skin staples. Twenty procedures were performed by RTT, 15 by RJS, and 10 by FHS. All surgeons used an anterior skin incision over the medial third of the patella in combination with a median parapatellar arthrotomy. Perfusion was assessed with a LA-ICGA device and software system immediately after closure to quantify fluorescence. Twenty-seven points were assessed immediately after closure in the operating room in each patient (nine along the incision and nine pairs medial and lateral to the incision). Mean incision perfusion was determined from the nine points along the incision with higher values indicating greater blood flow. Mean perfusion impairment was determined by calculating the difference between the nine pairs of surrounding skin and the nine points along the incision with smaller values indicating less perfusion impairment. These parameters were compared with analysis of variance (ANOVA) and subsequent pairwise comparisons with an unadjusted analysis as well as a multivariate analysis that adjusted for age, sex, and body mass index. Patients were followed for a mean of 7 months after surgery (range, 3-12 months) for possible incision-related complications. No patents were lost to followup.Running subcuticular closure demonstrated the best overall perfusion. Mean incision perfusion in fluorescent units with SD was as follows: running subcuticular, 64 (16); vertical mattress, 32 (18); and staples, 19 (7) (ANOVA p < 0.001). The running subcuticular closure demonstrated the least impairment of perfusion among the closures compared. Mean perfusion impairment was as follows: running subcuticular, 21 (12); vertical mattress, 37 (24); and staples, 69 (27) (ANOVA p < 0.001). All Tukey-adjusted pairwise comparisons from both metrics likewise favored the subcuticular closure (p < 0.001) both before and after adjusting for age, sex, and body mass index. One patient in the vertical mattress cohort experienced a surgical site infection; no other wound-related complications were observed in this study.The method of closure can influence skin and soft tissue perfusion after TKA. Running subcuticular closure enables the most physiologic robust blood flow, which may improve wound healing. However, the clinical importance of these findings remains uncertain, because patients in this study were selected because they lacked risk factors for wound healing complications. Studies with this modality in specific patient populations at higher risk for wound complications will be necessary to quantify the clinical advantage of using running subcuticular closure.Level I, therapeutic study.

Project description:BackgroundStructural hip deformities including developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) are thought to predispose patients to degenerative joint changes. However, the natural history of these malformations is not clearly delineated.Questions/purposes(1) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what is the natural history and progression of osteoarthritis in the native hip based on morphological characteristics? (2) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what are the radiographic parameters that predict differential rates of degenerative change?MethodsWe identified every patient 55 years of age or younger at our institution who received unilateral primary THA from 1980 to 1989 (n = 722 patients). Preoperative radiographs were reviewed on the contralateral hip and only hips with Tönnis Grade 0 degenerative change that had minimum 10-year radiographic followup were included. A total of 172 patients met all eligibility criteria with the following structural diagnoses: 48 DDH, 74 FAI, and 40 normal morphology, and an additional 6% (10 of the 172 patients) met all eligibility criteria but were lost to followup before the 10-year minimum. Mean age at the time of study inclusion was 47 years (range, 18-55 years), and 56% (91 of 162) of the patients in this study were female. Mean followup was 20 years (range, 10-35 years). Radiographic metrics, in conjunction with the review of two experienced arthroplasty surgeons, determined the structural hip diagnosis as DDH, FAI, or normal morphology. Every available followup AP radiograph was reviewed to determine progression from Tönnis Grade 0 to 3 until the time of last followup or operative intervention with THA. Survivorship was analyzed by Kaplan-Meier methodology, hazard ratios, and multistate modeling. Thirty-five patients eventually underwent THA: 16 (33%) DDH, 13 (18%) FAI, and six (15%) normal morphology.ResultsDegenerative change was most rapid in patients with DDH followed by FAI and normal morphology. Among patients who recently developed Tönnis 1 degenerative change, the probability of undergoing THA in 10 years based on hip morphology was approximately one in three for DDH and one in five for both FAI and normal morphology hips, whereas the approximate probability at 20 years was two in three for DDH and one in two for both FAI and normal morphology hips. The likelihood of radiographic degeneration was increased in patients with the following findings: femoral head lateralization > 8 mm, femoral head extrusion index > 0.20, acetabular depth-to-width index < 0.30, lateral center-edge angle < 25°, and Tönnis angle > 8°.ConclusionsDegenerative change occurred earliest in patients with DDH, whereas the natural history of patients with FAI was quite similar to structurally normal hips. However, patients with cam deformities and concomitant acetabular dysplasia developed osteoarthritis more rapidly. Although the results of this study cannot be directly correlated to highly active patients with FAI, these findings suggest that correction of FAI to a normal morphology may only minimally impact the natural history, especially if intervention takes place beyond Tönnis 0. Analysis of radiographic parameters showed that incremental changes toward dysplastic morphology increase the risk of degenerative change.Level of evidenceLevel III, prognostic study.

Dataset Information

The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial.

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The John N. Insall Award: Higher Tissue Concentrations of Vancomycin Achieved With Intraosseous Regional Prophylaxis in Revision TKA: A Randomized Controlled Trial.

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