Periprosthetic joint infection (PJI) occurs in 0.2-2% of primary hip and knee arthroplasty and is a leading cause of revision surgery, impaired function, and increased morbidity and mortality. Topical, intrawound vancomycin administration allows for high local drug concentrations at the surgical site and has demonstrated good results in prevention of surgical site infection after spinal surgery. It is a promising treatment to prevent infection following hip and knee arthroplasty. Prior studies have been limited by small sample sizes and the low incidence of PJI. This systematic review and meta-analysis was performed to determine the effectiveness of topical vancomycin for the primary prevention of PJI in hip and knee arthroplasty.

A search of Embase, MEDLINE, and PubMed databases as of June 2020 was performed according to PRISMA guidelines. Studies comparing topical vancomycin to standard perioperative intravenous antibiotics in primary THA and TKA with a minimum of three months follow-up were identified. The results from applicable studies were meta-analysed to determine the impact of topical vancomycin on PJI rates as well as wound-related and overall complications. Results were expressed as odds ratios (ORs) and 95% confidence intervals

Nine comparative observational studies were eligible for inclusion. 3371 patients treated with 0.5-2g of topical vancomycin were compared to 2884 patients treated with standard care. Only one of nine studies found a significantly lower rate of PJI after primary THA or TKA (OR 0.09-1.97, p=0.04 for one study, p>0.05 for eight of nine studies), though meta-analysis showed a significant benefit, with vancomycin lowering PJI rates from 1.6% in controls to 0.7% in the experimental group (OR 0.47, p=0.02, Figure 1). Individually, only one of five studies showed a significant benefit to topical vancomycin in THA, while none of seven studies investigating PJI after TKA showed a benefit to topical vancomycin. In meta-analysis of our subgroups, there was a significant reduction in PJI with vancomycin in THA (OR 0.34, p=0.04), but there was no significant difference in PJI after TKA (OR 0.60, p = 0.13). In six studies which reported complication rates other than PJI, there were no significant differences in overall complication rates with vancomycin administration for any study individually (OR 0.48-0.94, p>0.05 for all studies), but meta-analysis found a significant difference in complications, with a 6.7% overall complication rate in controls compared to 4.8% after topical vancomycin, largely driven by a lower PJI incidence (OR 0.76, p=0.04).

Topical vancomycin is protective against PJI after hip and knee arthroplasty. No increase in wound-related or overall complication rates was found with topical vancomycin. This meta-analysis is the largest to date and includes multiple recent comparative studies while excluding other confounding interventions (such as povidone-iodine irrigation). However, included studies were predominantly retrospective and no randomized-controlled trials have been published. The limited evidence summarized here indicates topical vancomycin may be a promising modality to decrease PJI, but there is insufficient evidence to conclusively show a decrease in PJI or to demonstrate safety. A prospective, randomized-controlled trial is ongoing to better answer this question.

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Hip fractures are a common cause of morbidity and mortality in the elderly, with approximately 30,000 hip fractures a year in Canada. Many hip fracture patients are prone to heart failure and present anticoagulated with Warfarin for medical comorbidities including atrial fibrillation or previous thromboembolic disease. Reversal of warfarin anticoagulation to an INR < 1.5 preferred for surgery but this often contributes to a delay to hip fracture surgery, which increases patient pain, morbidity, mortality, and length of stay Octaplex is a small-volume prothrombin complex concentrate (PCC) that reverses Warfarin-related anticoagulation in 15–60 minutes. It has been shown to be safe and effective in the management of intracranial and gastrointestinal bleeding in warfarinised patients. It is recommended by Bone and Joint Canada as an option for urgent warfarin reversal in hip fracture patients. However, there has been no published literature on the use of Octaplex or other PCCs in orthopaedic patients. Our objective is to assess the effectiveness of Octaplex for rapid reversal of warfarin anticoagulation in hip fracture patients.

A database review of all patients who received Octaplex was performed. Medical records of all hip fracture patients in Calgary who received Octaplex between December 2009 and February 2015 were reviewed. After application of inclusion and exclusion criteria, 33 patients were identified. A timeline of International Normalised Ratio (INR), Octaplex administration, and hip fracture surgery was recorded. Mortality and complications were assessed at 30 days.

A single dose of Octaplex corrected the INR to < 1.5 in 29 cases (88%). Median time from administration of Octaplex to a measured INR < 1.5 was 1.1 hours. Median time from admission to hip fracture surgery was 22 hours. Mortality at 30 days was 15.2%, mostly from cardiac arrest. A further 12% of patients developed cardiac or thrombotic complications. Multiple medical comorbidities were common including coronary artery disease (55%), congestive heart failure (45%), and chronic pulmonary disease (39%). Patients who received both fresh frozen plasma (FFP) and Octaplex for warfarin reversal had much higher mortality than those who only received Octaplex (40% vs 4.3% mortality at 30 days), but also had more medical comorbidities.

Octaplex is effective at rapidly reversing warfarin anticoagulation and reducing time to surgery, potentially reducing the morbidity and mortality of hip fractures. Administration of both Octaplex and FFP were associated with higher early mortality in this case series. Further research is required to assess the safety of Octaplex, vitamin K, and FFP for reversal of warfarin anticoagulation in this population.