Moderate strength evidence supports that obesity is associated with increased risk of periprosthetic joint infection (PJI).

Rationale
Out of 143 studies which met inclusion criteria for this recommendation, there were no high strength studies, and only ten were considered moderate strength. The remaining studies were considered low strength. Many of these studies evaluated multiple variables as it applied to either PJI directly, or to other perioperative complications, necessitating the use of various statistical methods to attempt to control for these variables. These methods were frequently constrained in doing so. Additionally, based on the available literature, whether a risk factor is “modifiable” or if optimization of a listed condition affects the risk of infection remained unclear. No specific threshold value could be endorsed for most listed conditions, but instead the simple binary
presence or absence of the condition as defined by the individual study criteria affected the risk of PJI. Furthermore, many of the studies were based on national payor databases or registries, whose data is only as accurate as the data being input. As such, there is often no way to verify that an individual diagnosis or the definition of the diagnosis is accurate, though the sheer numbers in such databases may help correct for errors in diagnosis. Finally, definitions and clarity of location of infection introduced ambiguity between studies, some clearly indicating PJI, and others with variations of “deep infection,” “deep surgical site infection,” or “involves deep soft tissue,” among other delineations.

Of the listed and reviewed conditions, obesity was the only risk factor for periprosthetic joint infection that met moderate strength criteria for increased risk of periprosthetic joint infection. The rest are based on single moderate strength and/or low strength studies with either conflicted or limited data, with each condition or risk factor individually discussed below.

Moderate Strength:
 
Obesity
There were three moderate-quality studies assessing the risk of PJI in obese patient undergoing TKA 
or THA. Lubbeke and associates (Lubbeke, A, 2016) compared 5 categories each of BMI (<24.9, 25-29.9, 30-34.9, 35-39.9, and >40) and weight (<60, 60-79, 80-99, 100-119, and >120) with a mean follow-up of 6.5 years. They identified similar PJI rates in BMI categories less than 35, but twice as high in patients with BMI 35-39.9, and 4 times as high with BMI 40 or greater. Weight greater than 100 kg was also associated with an increased risk of infection, with a hazard ratio of 2.1.

In a moderate-quality study assessing the effect of BMI on 30-day outcomes following joint replacement, Alvi et al (Alvi, HM, 2015) queried the ACS-NSQIP database and stratified 13,250 patients into 5 matched groups based on BMI. Compared to patients with BMI 18.5-25, hip patients with BMI 25-30, 30-35, and 35-40 had a 2.92-, 4.82-, and 6.4-fold increased risk of deep incision or organ space infection, respectively. Hip patients
 who had a BMI of 40 or higher had a 12.85 times higher risk of deep incision/organ space infection (NSQIP database tracks CMS definitions of infection, not clearly defining as PJI).

The final moderate-quality study by Wagner and associates (Wagner ER 2016) also identified a higher risk of  deep incisional infection in TKA patients. In their single-institution registry, 22,289 consecutive knee replacements were analyzed, demonstrating a hazard ratio of 1.08 per unit of BMI over 35 kg/m 2 in favor of deep infection.

Of the 32 included low quality studies, 14 suggested no effect on the risk of hip or knee infection. Of the other 18 demonstrating increased risk of infection, 5 indicated increased risk of PJI in both hip and knee patients. Two additional studies found increased risk of PJI in obese TKA patients; one study deep infection (Namba, R.S. 2013); and one deep surgical site infection (Frisch, N, et al 2016). Five low quality studies indicated higher risk of PJI in obese patients undergoing THA, two indicated higher risk of deep infection, and one found a higher risk of septic revision. An additional study identified a higher risk of deep infection for re-revision THA in obese patients.

POSSIBLE RISKS AND HARMS OF IMPLEMENTATION
Candidacy for surgical intervention is at once, one of the most essential and complex decisions in surgical practice, ethically balancing the degree of pathology and risk of the operation, with the positive benefits to the patient and society at large, in a shared decision-making process between patient and surgeon. The positive effect of indicated lower extremity arthroplasty on quality of life and reduced morbidity is well established. However, its cost to the health care system has been the subject of increased scrutiny. Surgeons are under increasing pressure from payors, health care systems, and peers alike to provide highest value care, balancing the overall cost of care with excellence in patient outcomes. As such, delay or denial of surgical care based on
any one or multiple factors in order to avoid one of the most devastating complications of one of the best value surgeries ever practiced should not be taken lightly. Given that all risk factors listed – with the exception of obesity – are supported with only low strength or conflicting evidence, the decision to proceed is individual, and based on myriad other factors, including but not limited to the ability of the system in which the surgeon practices to handle varying degrees of complexity, volume and experience of the surgeon and system, and other confounding factors not herein assessed. Additionally, at this time it is unclear based on the literature if modification of any risk factor, including obesity, actually reduces the risk of PJI. Payors and healthcare systems alike should understand that though tactics to reduce cost may include delaying or avoiding operating on patients with these risk factors, such practice may deny surgery to a much larger proportion of patients who may otherwise significantly benefit and not endure PJI.

FUTURE RESEARCH
Despite the volume of literature addressing risk factors for periprosthetic joint infection, there is a paucity of moderate-quality studies, and complete absence of high-quality studies. Future research must attempt to better control for individual confounding variables prospectively, with better delineation of disease states. For example, though BMI may not be the best measure of obesity overall, its stratification in many studies has helped allow for better comparison between groups, improving the quality of data available. Simply identifying whether or not a disease process is present based off an individual entry of a diagnostic code from the patient’s potentially remote past medical history does not ensure best quality data. Unfortunately, the relatively low incidence of PJI requires large numbers for appropriate statistical power, making registries and large healthcare databases an optimal target for research. Better quality abstraction for such databases is therefore necessary to help de-confound. Additional assessments of markers of disease status and their associated thresholds may also help the clinician further and more accurately stratify risk. Finally, identification of risk associated with a condition or stage of comorbidity does not by itself afford the provider the ability to proselytize for change, as the effect of modification and optimization of the status of a listed condition is still unclear. Future research endeavors should specifically be designed to determine if risk factor modification truly results in a reduction in the risk for PJI after hip or knee arthroplasty surgery. Given frequently conflicting conclusions among studies, the individual system and even provider-specific management of comorbidities – which was typically not delineated – may account for such discrepancies. Prospective, appropriately controlled studies incorporating
these considerations will better afford surgeon and patient the ability to predict and potentially minimize risk of periprosthetic joint infection.
 
  1. Alvi,H.M., Mednick,R.E., Krishnan,V., Kwasny,M.J., Beal,M.D., Manning,D.W. The Effect of BMI on 30 Day Outcomes Following Total Joint Arthroplasty. J.Arthroplasty 2015/7; 7: 1113-1117
  2. Frisch,N., Wessell,N.M., Charters,M., Peterson,E., Cann,B., Greenstein,A., Silverton,C.D. Effect of Body Mass Index on Blood Transfusion in Total Hip and Knee Arthroplasty. 2016/9/1; 5: e844-e849
  3. Lubbeke, A., Zingg,M., Vu,D., Miozzari,H.H., Christofilopoulos,P., Uckay,I., Harbarth,S., Hoffmeyer,P. Body mass and weight thresholds for increased prosthetic joint infection rates after primary total joint arthroplasty. Acta Orthop. 2016; 2: 132-138
  4. Namba,R.S., Inacio,M.C., Paxton,E.W. Risk factors associated with deep surgical site infections after primary total knee arthroplasty: an analysis of 56,216 knees. J.Bone Joint Surg.Am. 2013/5/1; 9: 775-782
  5. Wagner,E.R., Kamath,A.F., Fruth,K., Harmsen,W.S., Berry,D.J. Effect of Body Mass Index on Reoperation and Complications After Total Knee Arthroplasty. J.Bone Joint Surg.Am. 2016/12/21; 24: 2052-2060