Do the results of the OXYGEN trial change if analyzed as "as-treated?": A secondary analysis of the OXYGEN trial.

OBJECTIVE: To determine if the results of the OXYGEN trial changed using an "as-treated" approach instead of the original "intention-to-treat" approach. The multi-center randomized controlled OXYGEN trial aimed to determine the effectiveness of high FiO2 in decreasing infection rates for high-risk tibial plateau, tibial pilon, and calcaneus fractures. METHODS: A secondary analysis of a multi-center randomized controlled trial conducted at 29 US trauma centers was performed. A total of 1231 patients aged 18-80 years with tibial plateau, tibial pilon, or calcaneus fractures thought to be at elevated risk of infection were enrolled. Patients were randomly assigned to receive inspired oxygen at a concentration of 80 % FiO2 (treatment) or 30 % FiO2 (control). Adherence was defined using two different criteria. Criterion 1 required at least 80 % of the surgery time ≤40 % FiO2 for the control group or ≥70 % FiO2 for the treatment group. Criterion 2 required at least 80 % of surgery time within 20-40 % (control) or 70-90 % FiO2 (treatment). The primary outcome was surgical site infection (SSI) within 182 days of definitive fracture fixation. Secondary outcomes were deep and superficial surgical site infections within 90, 182, and 365 days of definitive fixation. RESULTS: Under Criterion 1, the primary outcome occurred in 7 % (38/523) and 10 % (49/471) of patients in the treatment and control groups, respectively (p = 0.10). Deep infection occurred in 30 (6 %) treatment and 30 (6 %) control patients (p = 0.75). Superficial infection occurred in 9 (2 %) treatment and 20 (4 %) control patients (RR, 0.41; p = 0.03). Using Criterion 2, the primary outcome occurred in 7 % (36/498) of treatment and 10 % (48/468) of control patients (p = 0.12). Deep infection occurred in 28 (6 %) treatment and 29 (6 %) control patients (p = 0.81). Superficial infection occurred in 9 (2 %) treatment and 20 (4.3 %) control patients (RR = 0.43; p = 0.03). CONCLUSIONS: When re-analyzing based on which patients actually received high or control levels of perioperative oxygen fraction, the results are somewhat consistent with the original "intent-to-treat" analysis. Specifically, high perioperative oxygen lowered the risk of superficial SSI but did not affect deep infections.

Heterotopic bone formation about the hip undergoes endochondral ossification: a rabbit model.

BACKGROUND: Heterotopic ossification (HO) occurs most commonly after trauma and surgery about the hip and may compromise subsequent function. Currently available animal models describing the cellular progression of HO are based on exogenous osteogenic induction agents and may not reflect the processes following trauma. QUESTIONS/PURPOSES: We therefore sought to characterize the histologic progression of heterotopic bone formation in an animal model that recapitulates the human condition without the addition of exogenous osteogenic material. METHODS: We used a rabbit model that included intramedullary instrumentation of the upper femur and ischemic crush injury of the gluteal muscle. Bilateral surgical induction procedures were performed on 30 animals with the intention of inciting the process of HO; no supplemental osteogenic stimulants were used. Three animals were sacrificed at each of 10 predetermined times between 1 day and 26 weeks postoperatively and the progression of tissue maturation was graded histologically using a five-item scale. RESULTS: Heterotopic bone reliably formed de novo and consistently followed a pathway of endochondral ossification. Chondroid elements were found in juxtaposition with immature woven bone in all sections that contained mature osseous elements. CONCLUSIONS: These results establish that HO occurs in an animal model mimicking the human condition following surgical trauma about the hip; it is predictable in its histologic progression and follows a pathway of endochondral bone formation. CLINICAL RELEVANCE: By showing a consistent pathway of endochondral ossification leading to ectopic bone formation, this study provides a basis for understanding the mechanisms by which HO might be mitigated by interventions.

Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High-Energy Fracture Surgery (OXYGEN Study).

Supplemental perioperative oxygen (SPO) therapy has been proposed as one approach for reducing the risk of surgical site infection (SSI). Current data are mixed regarding efficacy in decreasing SSI rates and hospital inpatient stays in general and few data exist for orthopaedic trauma patients. This study is a phase III, double-blind, prospective randomized clinical trial with a primary goal of assessing the efficacy of 2 different concentrations of perioperative oxygen in the prevention of SSIs in adults with tibial plateau, pilon (tibial plafond), or calcaneus fractures at higher risk of infection and definitively treated with plate and screw fixation. Patients are block randomized (within center) in a 1:1 ratio to either treatment group (FiO2 80%) or control group (FiO2 30%) and stratified by each study injury location. Secondary objectives of the study are to compare species and antibacterial sensitivities of the bacteria in patients who develop SSIs, to validate a previously developed risk prediction model for the development of SSI after fracture surgery, and to measure and compare resource utilization and cost associated with SSI in the 2 study groups. SPO is a low cost and readily available resource that could be easily disseminated to trauma centers across the country and the world if proved to be effective.

Reduction of postoperative spinal implant infection using gentamicin microspheres.

STUDY DESIGN: Three noncontiguous spinal implant sites in 1 rabbit were challenged with Staphylococcus aureus and local antibiotic prophylaxis was given with gentamicin in controlled-release microspheres (poly(lactic-coglycolic-acid) [PLGA]). Postoperative biomaterial-centered infection on and around the titanium rods was assessed using standard bacterial quantification essays. OBJECTIVE: To assess surgical site and biomaterial-centered infection reduction with controlled release gentamicin from microspheres against S. aureus. SUMMARY OF BACKGROUND DATA: A postoperative biomaterial-centered infection can be devastating after successful thoracolumbar spinal surgery and puts a high burden on patients, families, surgeons, and hospitals, endangering both our healthcare budget and our ability to perform challenging cases in patients with increasing numbers of comorbidities. Systemic antibiotics often do not reach "dead-space" hematomas where bacteria harbor after surgery, whereas local, controlled release gentamicin prophylaxis through PLGA microspheres showed favorable pharmacokinetics data to achieve local bactericidal concentrations for up to 7 days after surgery. METHODS: A well published rabbit spinal implant model with systemic cephalosporin prophylaxis was challenged to create a baseline infection of approximately 70% in control sites. We then challenged 3 noncontiguous titanium rods inside the laminectomy defect with 10e6 colony forming units S. aureus and randomly treated 2 sites with gentamicin PLGA microspheres and 1 site with PLGA carrier only (control). Standard quantification techniques were used to assess biomaterial centered and soft tissue bacterial growth after 7 days. RESULTS: After establishing reliable infection rates in control sites, the therapeutic arm of the study was started. Surgical site infections were found in 75% of control sites, whereas gentamicin microspheres reduced the incidence down to 38% in the same rabbits. Biomaterial-centered infection was reduced from 58% to 23% only in all sites challenged with 10e6 S. aureus. CONCLUSION: Postoperative, biomaterial-centered infection was reduced at least 50% with intraoperative gentamicin microspheres in the face of systemic cephalosporin prophylaxis and high dose S. aureus in a laminectomy defect in rabbits. The data are statistically and clinically significant, and further animal testing is planned to confirm these results.