Surgical site infection (SSI) following orthopedic fracture surgery remains a debilitating and potentially fatal postoperative complication. Depending on the location, type, length of operation, facility, and severity of the fracture, the risk of a postoperative infection may exceed 20%.1–4 Infections lead to substantial morbidity,5 including increased length of stay during initial hospitalization, delayed healing, hospital readmission, reduced likelihood to return to civilian or military work, permanent function loss, amputation, and mortality.6–10 Resource utilization beyond rehospitalizations following an infection may include increased rehabilitation services, wound management requirements, and caregiver burden.9,10
Economic estimates of the impact of an SSI, including a systematic review and meta-analysis published in 2013, found that SSIs, after any surgery was $3.3 billion annually in the United States.11 However, no similar systematic reviews or meta-analysis specific to SSIs following an orthopedic fracture surgery currently exist. Furthermore, studies that do estimate the economic impact of a postfracture SSI focus solely on the direct cost of care, namely the cost of the in-hospital or subsequent hospitalizations for infection, not the total universe of costs, including formal and informal health care, as well as nonhealth care sector costs.12
The objective of this paper is to describe the literature that exists on the costs associated with postoperative infection following orthopedic fracture surgery. Our review attempts to find large database or prospective studies that can illustrate incremental differences in costs between infected patients and patients at risk for infection. Where possible, we include costs outside of the formal health care sector. Our review yielded no large studies. Thus, we conducted a database analysis to estimate the population level economic burden of postfracture SSIs, by anatomic location, in the United States.
We performed a narrative review of the existing international literature to describe the cost of postoperative infection. Initially, we searched for large database studies of all orthopedic trauma patients with infection. However, no such studies exist, nor do national or population level estimates of the economic magnitude of the problem. Thus, we focused on several anatomic locations with the highest reported rates of fracture and infection: tibia and fibula, femur, ankle, and humerus. The Medline database was searched from January 1, 1990 to September 1, 2018 using a combination of the MeSH headings: (bone) fracture, and cost, in various combinations. All study designs were considered in the review. We present the data reported in the studies including average or median cost, interquartile ranges (IQRs), and SEs. When possible, we present the marginal increase in the cost of care attributable to infection. However, many of the studies identified were purely descriptive. All countries and health care systems were included in the review. However, for ease of comparison, we first converted all estimates to US dollars using current (December 2018) exchange rates, and then accounted for inflation to present day costs using the United States medical consumer price index.13
Annual Economic Impact of Postoperative Fracture-related Infections in the United States
To estimate the annual economic impact of postoperative fracture-related infections in the United States, we used a large claims database and discharge data from the National Inpatient Sample.
We utilized the MarketScan Commercial Claims and Encounters Database from 2010 to 2013, which contains a sample of patients with private, employer-sponsored health insurance in the United States.14 Although the database is not representative of the entire US population, it allows the linkage of patients across time and therefore allows for the identification of discrete clinical events in temporal sequences, such as infection after surgery. We constructed a cohort of fracture patients using billing codes [International Classification of Diseases, 9th Edition (ICD-9) diagnosis]. Patients who had continuous follow-up (maintained insurance coverage) for at least 90 days postsurgery were included in the analysis. The 2-year incidence of SSI was then computed based on a subsequent hospitalization for a range of infection ICD-9 diagnosis codes. Fractures were stratified by anatomic location, and whether they were open or closed. Infection was identified using codes for both deep and organ space SSI. Superficial SSIs were not included in this analysis. The list of ICD-9 diagnosis and procedure codes used to identify the cohort are displayed in Appendix A (Supplemental Digital Content 1, http://links.lww.com/TIO/A27).
To estimate the annual number of fracture surgeries, and the average cost of a hospitalization for an SSI following fracture surgery, we used the 2016 National Inpatient Sample (NIS). The NIS provides a 20% sample of all hospital discharges in the United States. This database is representative of the US population of hospitalizations. It contains charges and subsequent hospital-specific cost-to-charge ratio, computed by the Agency for Research on Healthcare Research and Quality (AHRQ), to estimate payers’ actual cost. We identified postfracture infections by the International Classification of Diseases, 10th Edition (ICD-10) diagnosis codes, which AHRQ adopted in 2015, listed in Appendix B (Supplemental Digital Content 2, http://links.lww.com/TIO/A28). Fracture codes were partitioned by anatomic location, and whether they were open or closed. Because inpatient stays cannot be linked within the NIS, we identified hospitalizations for SSI separately. Notably, while some SSI diagnosis codes are bone-specific, for instance, those associated with internal fixation devices, such as T84.610 “Infection and inflammatory reaction due to internal fixation device of right humerus” many other types of infection diagnosis codes, such as T81.42: “Infection following a procedure, deep incisional surgical site,” are not anatomic location-specific. To account for all types of infection codes, we compute a single average cost of an SSI hospitalization.
To achieve a population-level estimate, we determined the number of fracture surgeries in the United States, according to the NIS. We then utilized the discharge weights provided by AHRQ to estimate national totals. Critically, we cannot observe infection rates from the NIS, so we instead multiply the rate observed in MarketScan by the total observed in the NIS. Finally, to calculate the estimated cost of infection rehospitalizations, we multiplied the total estimate by the cost of average rehospitalization due to SSI. Our results are presented by anatomic location, and whether fractures were open or closed.
Of the identified studies in our narrative review, only 1 study looked at the cost of SSI following fracture surgery across all fracture locations. This retrospective case-control study was performed at a single US hospital.14 The authors estimated the total cost of care for treating a patient with a postoperative infection, including the initial fracture surgery, to be $108,782. This estimate was compared with a total cost of care of $58,418 for controls that did not have a postoperative infection, matched on surgery and demographic characteristics,15 and suggests an infection nearly doubles the cost of treatment. All other studies included in our narrative review focused on the costs of postoperative infections for a distinct anatomical fracture location.
Proximal Femur Fractures
Four studies, 3 from the United Kingdom, and 1 from Finland provided detailed information on the cost of postoperative infections after a hip fracture surgery. In a 2010 study conducted in the United Kingdom, Thakar et al16 reported that the mean cost of treating a proximal femoral fracture with a postoperative infection (n=44) was £18,709 (range: £2606 to £60,827). These costs were more than double the mean cost of treating the matched uncomplicated controls (n=88, mean: £8610, range: £919 to £45,601, P<0.01). Converted to 2018 US dollars, the comparison between groups is $27,664 versus $12,731.
Luthje and colleagues reported similar findings in a 2014 review of data from 3 hospitals in Finland. The study reported a median cost of €28,751 (range: €11,076 to €61,755) or $33,063 2018 US dollars for treating postoperative infections in a sample of only 3 patients.17 In a cohort of proximal femur fracture patients over the age of 65 years, Pollard and colleagues reported a median cost of treatment in infected fractures to be £24,410 (IQR: £15,130 to £38,670, US 2018: $41,570). This treatment cost is >3-fold increase over the treatment costs of noninfected proximal femur fractures in elderly patients from the same institution (median: £7210, IQR: £4300 to £10,630, US 2018: $10,945).18
In a 2008 study, Edwards and colleagues reported consistent findings with the mean costs for treating an infected hip fracture patient at £25,940 (range: £4387 to £93,967, US 2018: $44,177) compared with £8979 (range: £3450 to £72,564, US 2018: $15,291) for uninfected patients. Overall, a postoperative infection resulted in doubled operative costs, tripled investigation costs, and quadrupled ward costs.19 Wijeratna et al20 expand upon these findings by estimating the mean income loss for hip fracture patients with a deep SSI to be £24,397 (US 2018: $33,429) compared with a mean cost of £15,576 (US 2018: $21,342) for treating the deep SSI.
Tibia and Fibula Fractures
In a 2017 retrospective review from a Belgium hospital, Hoekstra et al21 reported open tibial fractures a 5-fold increase in the total health care costs for open tibia fractures with a deep SSI [mean: €48,702 (range: €28,383 to €71,409, US 2018: $57,077)] compared with a mean of €9566 (US 2018: $11,210) in uninfected open tibia fracture patients (range: €6781 to €15,094). An increased length of stay was reported as the main parameter driving these overall costs. These findings were similar to that of Metsmakers et al,4 who reported that infection following open tibial fractures was 6.5-times higher compared with uninfected patients.
Olesen and colleagues22 evaluated the infection cost burden in a retrospective review at a Danish hospital and included 45 patients with open tibial fractures covered with free vascularized flaps. These severe injuries reported much higher overall costs. However, the marginal difference was less than Hoekstra et al, with a mean cost of treatment of €81,155 (US 2018: $95,110) for patients with postoperative infections and €49,817 (US 2018: $58,383) for uninfected patients. The study also estimated the mean indirect costs of the injury based on unemployment benefits. However, their estimated costs of unemployment benefits (€12,314) did not report a stratified analysis of infected versus uninfected patients.
Most recently, Parker et al23 estimated the economic outcomes associated with a deep SSI in patients with an open fracture of the lower limb. Of 460 patients recruited into the WOLLF randomized clinical trial, 35 patients had a subsequent deep SSI that was associated with an increase in the mean total National Health Service and Personal Social Service costs in the first 6-month postinjury (mean: £15,598, US 2018: $17,937, range: £5237 to £41,487 vs. mean: £12,304, US 2018: $14,149, range: £4044 to £39,655).
Ankle and Humerus
Several clinical trials looked at treatments for humerus and ankle fractures and included the risk of infection after surgery as an outcome.24–26 Although they found various rates of infection by treatment arm, no study looked explicitly at the cost of care between patients who did or did not develop an infection.27,28
Claims/Administrative Database Analysis
The number of fracture surgeries identified in the MarketsScan data and the subsequent rate of deep SSIs is displayed in Table 1. Tibia and fibula fracture had the highest rate of deep infections (3.4%), while humeral fractures had the lowest rate (2.0%). Overall open fractures had higher infection rates than closed fractures. For instance, in tibia and fibula, the open infection rate was 5.9%, while in closed fractures, the rate was 2.8%.
The number of annual fracture surgeries by anatomic location, observed in the NIS, weighted for national estimates, appears in the first column of Table 2. By anatomic location, these range from nearly 100,000 humerus fracture surgeries to over 400,000 femur fracture surgeries. The rates observed in MarketScan (Table 1) are then used to estimate the number of annual infections likely observed in the United States (column 2). Finally, the cost of additional hospitalizations due to infection following an index fracture surgery was calculated using the NIS cost data. We determine the average hospitalization cost to be $23,365 (95% confidence interval: $23,006-$23,725). This mean is used to estimate the annual impact of infection in the United States in the final column of Table 2. We found that closed femurs have the highest number of SSIs, at over 13,000 annually, and the greatest cost expenditure on the SSI hospitalizations at over $300 million annually. Overall, we find in the US hospitalizations due to SSI cost over $500 million annually.
Infection is a common and costly postoperative complication in fracture surgery patients. Previous studies suggest that the cost of treatment for an infected fracture patient is likely to be at least twice the cost of treating an uninfected fracture patient. However, the current literature is limited to small retrospective reviews focused narrowly on the direct costs of treatment, and frequently, only the cost of discrete events, such as additional hospitalizations over a short time horizon. Many common limitations persist across the literature. Studies of cost impact are generally single institution samples or collected alongside prospective clinical trials. Follow-up timeframes are typically limited to ≤1 year and tend to focus solely on the initial rehospitalization for the infection. In addition to limitations specific to the design of previous studies, there are several challenges with comparisons of cost analysis more broadly. This includes adjusting various currencies, inflation, and purchasing power in different countries, which often distorts comparisons. Different health systems across and even within countries can also complicate comparisons due to variations in billing systems, cost structures, payment systems, and implant costs.
As our literature review revealed no definitive estimates of the total cost of SSI in the United States or elsewhere, we attempted to estimate the direct economic cost of SSI after fracture surgery. We utilized 2 large data sources—claims of a large consortium of payers and discharge data representative of the entire US population. We focused on the 5 bones that account for the largest number of fractures in the United States. We showed that the total cost of hospitalizations due to SSI after fracture surgery varies by fracture anatomic location, with point estimates ranging from $45 million for humerus fractures to $318 million for femurs fractures. These estimates are coarse, and the standard caveats about the ability of billing codes to identify actual clinical practice apply. However, these estimates provide a richer understanding of the economic impact of SSI than was previously available in the literature. Our estimated economic impact of at least $500 million for SSI after these 5 fractures should be thought of as a cost floor of the true economic impact, as it includes only the cost of hospital stays for infection after fracture surgery.
There are several related limitations to the estimates we computed. First, we only included deep and organ space SSIs, and not superficial SSI, in our database analysis. Furthermore, our estimates only consider direct inpatient expenditure and critically do not include the outpatient costs associated with SSI, the indirect costs associated with impairment and lost productivity to the patient and their caregiver, or other potential downstream consequences of SSI after initial hospitalization. These limitations suggest that we are underestimating the true incidence and direct economic burden of SSI. Furthermore, we are undervaluing the true societal economic impact of the problem.
Our methodology was limited by the available data. For instance, we extrapolated the SSI rate from a subset of privately-insured adult patients under the age of 65 years to the national data, to achieve national estimates. Notably, the sample does not include patients insured through Medicaid and Medicare or uninsured patients. Therefore, our extrapolation likely underestimates the rate of SSIs and, possibly, the costs of care associated with treating the SSI. Another methodological limitation is the relatively coarse definition of the cost of SSI. By virtue of the available codes, the SSI cost estimates are not specific to the fracture location or severity of the index fracture. More detailed longitudinal data that could link fracture to infection in the general population is required to provide more granular estimates of cost.
Infection prevention is a critical policy issue. These postoperative complications exert a substantial resource burden on the health system but likely also have a broader economic impact through lost capacity and productivity of patients and their caregivers. Robust estimates of the economic implications of postoperative infections are required to build the case for a proportional investment in policy and practice that with systematically prevent these adverse events. Future research should utilize large registries and databases for more accurate estimates of the cost of infection that include both direct and indirect costs. In addition, a knowledge gap remains on the patient factors that are associated with an increased economic vulnerability to postoperative infections.
In the era of value-based care, understanding the long-term economic costs associated with postoperative infections is imperative to effectively allocate scarce health resources and to focus on therapeutic interventions that will mitigate these economic costs. Furthermore, this research can inform surgeon-patient communication on recovery expectations, particularly in the event of postoperative infection, and will advance the value debate between specialty versus nonspecialty hospital in treating common fractures. Further work must be done to better assess the true health care and societal cost of postoperative orthopedic trauma infection.
Recommendations from a recent textbook on best practices for cost-effectiveness studies, the Second Panel on Cost-Effectiveness in Health and Medicine, describe the formal and informal health care sector, and the nonhealth care sector costs which one should include in a cost analysis performed from the perspective a health care payer or society.12,29 Societal costs most relevant to the postfracture SSI population would include unpaid caregiver time costs, productivity costs (return to work), and lost future consumption. When possible, these items should be collected as part of prospective data collection to best understand the complete economic impact of infection.
Overall, we conclude that the literature evaluating the economic cost of postoperative infection following orthopedic trauma remains sparse. Further studies based on national and international databases are warranted. In our analysis, we found the total annual cost of hospitalization due to a fracture-related SSI has a direct economic consequence of over half a billion dollars in the United States annually. Given that this estimate does not capture the full picture of direct medical costs, and that our literature review revealed many other types of cost relevant to this population, our estimate is likely a gross understatement of the true societal costs of infection after fracture surgery. Prospective studies and instruments that can assess, not only the direct, but also indirect costs of SSIs would add substantially to our understanding of the topic, potentially leading to the adoption, or creation, of treatments with the greatest societal benefits.
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