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Abstract

Purpose:

Surgical site infection (SSI) is a serious complication following total knee arthroplasty (TKA) leading to considerable morbidity. The incidence is reported to be up to 2%. Risk factors continue to be an area of intense debate. Our study aims to report the incidence of SSI and identify possible risk factors in our patients undergoing TKA.

Methods:

Prospectively collected data for 905 patients who underwent elective unilateral TKA by a single surgeon from February 2004 to July 2014 were reviewed. Patient demographics and relevant co-morbidities such as diabetes and heart disease were analysed. The presence of superficial wound infections and/or prosthetic joint infections was included.

Results:

The overall infection rate was 1.10% (10 of 905 patients). Six patients (0.66%) were diagnosed with superficial infections and four with PJI (0.44%). The mean operative duration for TKA with SSI was significantly longer at 90.5 ± 28.2 min, compared to 72.2 ± 20.3 min in TKA without SSI (p = 0.03). All superficial infections occurred within the first month post-surgery and were self-limiting with oral antibiotics. The four patients with PJI required repeated procedures following TKA, including debridement, implant removal and/or revision arthroplasty. None of the 10 patients had a history of diabetes. There were no significant differences in demographics and co-morbidities between those who developed infection after TKA and those who did not.

Conclusion:

An overwhelming majority had good outcomes with only four deep infections resulting in revision surgery. We report that the risk of infection in TKA was significantly associated with a longer operative duration.

Keywords

joint prosthesis knee arthroplasty postoperative complications risk factors sepsis/complications soft tissue infections surgical wound infection

Introduction

Surgical site infection (SSI) is a serious and feared complication following total knee arthroplasty (TKA), leading to considerable morbidity and repeated surgical procedures.^1,2 The incidence of SSI is low and reported to be up to 2% in the Western literature.^3

–6

Purported risk factors continue to be an area of intense debate. For instance, obesity and the presence of diabetes mellitus (DM), congestive heart failure and renal disease are identified to be possible risk factors for SSI.^7

–11 However, this is directly contradicted by other studies that showed no such association.^12
–14

Likewise, an operating time of more than roughly 2 h for knee replacement was associated with an increased incidence of infection.^15,16 It was further postulated that the increase in operating time can predict for infection rate.^16,17 However, Tejwani and Immerman reported that the correlation between operative time and infection was a ‘myth and legend in orthopaedic practice’ that was not evidenced-based.¹⁸ As such, SSIs remain one of the more challenging complications in terms of prevention and treatment.

Our study aims to (1) report the incidence of SSI in patients undergoing TKA and (2) identify possible associated risk factors.

Materials and methods

We define superficial wound infections as any clinically diagnosed incisional infection involving skin, subcutaneous tissue and/or deep tissues, but not involving the knee joint. According to the Musculoskeletal Infection Society (MSIS) criteria, definite prosthetic joint infection (PJI) exists when (1) there is a sinus tract communicating with the prosthesis; or (2) a pathogen is isolated by culture from at least two separate tissues or fluid samples obtained from the affected prosthetic joint; or (3) four of the following six criteria exist – elevated serum erythrocyte sedimentation rate and serum C-reactive protein concentration, elevated synovial leukocyte count, elevated synovial neutrophil percentage, presence of purulence in the affected joint, isolation of a microorganism in one culture of periprosthetic tissue or fluid, or greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification.¹⁹

Prospectively collected registry data for all patients who underwent elective unilateral TKA with posterior stabilized implants for Kellgren and Lawrence grade 3–4 osteoarthritis were retrieved from a single surgeon database from February 2004 to July 2014. We excluded patients with semi-constraint or augmented prosthesis, revision arthroplasty and those who had secondary arthritis from post-traumatic, inflammatory and/or infective causes.

Patient demographics including body mass index (BMI), age and presence of co-morbidities were recorded preoperatively. Categories of co-morbidity included were diabetes, heart disease, stroke, hypertension, dyslipidemia and renal impairment. The presence of superficial wound infections, PJIs, or both was included for purposes of this study.

Duration of surgery was taken to be the difference between ‘start time’ and ‘end time’ as recorded on the surgical notes. At our institution, ‘start time’ is taken to be the time of incision and ‘end time’ to be the time of wound closure.

All patients underwent unilateral posterior-stabilized TKAs by the senior author. All procedures were done in an operating theatre with filtered-air laminar-flow system.²⁰ Hair removal was performed by clipping, not shaving, of the surgical site.²¹ The surgical site is then pre-cleaned with povidone iodine solution. The body exhaust system was not used during surgery. Instead, disposable surgical gowns were used.

All patients undergoing replacement received intravenous antibiotic prophylaxis for 24 h. Cefazolin is given half an hour before incision and three further doses in the first 24 h post-operatively.²² Vancomycin is given instead if the patient is allergic to Cefazolin.

All patients had tourniquets applied to the surgically treated limbs throughout the course of the surgeries. TKA was performed in a standard fashion for all patients. The medial parapatellar approach was used for patients with varus osteoarthritis, and the lateral parapatellar approach was used for patients with valgus knees with osteoarthritis. Patellar resurfacing was not performed in all patients. Drains were inserted for all patients and removed on either post-operative day 3 or when the drainage was less than 70 mL, whichever occurred earlier.

All patients received standardized post-operative care, which included appropriate oral and parenteral analgesia, mechanical calf pumps, continuous passive motion from the first post-operative day and daily inpatient physiotherapy assessments. All patients began ambulation on the first or second post-operative day. None of the patients received oral chemoprophylaxis for deep-vein thrombosis and pulmonary embolus as our previous studies on Asian patients undergoing conventional TKA without chemoprophylaxis showed a low incidence of venous thromboembolic (VTE) events.^23,24 On discharge, patients were followed up at the specialist outpatient clinic at 2 weeks, 2 months, 6 months, 1 year and 2 years. At each visit, the patient reported the pain score and any other concerns they had to the surgeon. The surgeon also examined the knee for any signs of wound or joint infection.

Differences in proportions were tested with the χ ² test and means were compared using Mann–Whitney U test.

Ethics

This study was conducted with approval from the Centralised Institutional Review Board at our institution, CIRB Ref 2018/2047, with waiver of informed consent based on ethical consideration.

Results

The 905 patients who met the inclusion criteria had a mean age of 65.9 ± 7.7 years and a mean BMI of 28.2 ± 4.7 kg/m². Our patients were predominantly Chinese (84.9%) and of the female gender (78.6%). The mean duration of surgery was 72.4 ± 20.5 min. The prevalence of DM and ischaemic heart disease was 13.6% and 4.6%, respectively (Table 1).

Table 1.

Demographics (n = 905).

Age (years)	Mean (standard deviation)	65.9	±7.7
BMI (kg/m²)	Mean (standard deviation)	28.2	±4.7
Gender	Male (%)	194	21.4
Gender	Female (%)	711	78.6
Alignment	Varus (%)	709	78.3
	Mean (standard deviation)	7.50	±4.8
	Valgus (%)	196	21.7
	Mean (standard deviation)	6.49	±5.1
Preoperative ROM
FFD	Mean (standard deviation)	6.9	±8.2
Maximum flexion	Mean (standard deviation)	117.3	±18.0
Side of surgery	Left (%)	436	48.2
Side of surgery	Right (%)	469	51.8
Duration of surgery (min)	Mean (standard deviation)	72.4	±20.5
Ethnicity	Chinese (%)	768	84.9
	Malay (%)	69	7.6
	Indian (%)	62	6.9
	Others (%)	6	0.7
Co-morbidities	DM (%)	123	13.6
	IHD (%)	42	4.6
	CVA (%)	13	1.4
	HTN (%)	404	44.6
	Dyslipidemia (%)	284	31.4
	Renal impairment (%)	9	1.0

FFD: fixed flexion deformity; IHD: ischaemic heart disease; HTN: hypertension; CVA: cardiovascular disease; DM: diabetes mellitus; BMI: body mass index; ROM: range of motion.

Of the 905 patients, superficial wound infection and prosthetic joint infection were diagnosed in 6 (0.66%) and 4 patients (0.44%), respectively. The overall SSI rate was 1.1% (n = 10). None of the 10 patients with infections had a history of diabetes.

The mean duration of surgery was significantly longer, 90.5 ± 28.2 min in patients with SSI compared to 72.2 ± 20.3 min in the no infection group (p = 0.03). There were no significant differences in age and BMI between those who developed post-TKA infection and those who did not (Table 2).

Table 2.

Demographics stratified into SSIs and no infection groups.

	SSIs		No infection
Number of patients	10	100%	895	100%	p = NS
Age (standard deviation)	65.4	±6.5	65.9	±7.7	p = NS
BMI (standard deviation)	29.4	±6.1	28.2	±4.7	p = NS
Preoperative ROM
FFD	9.90	±13.1	6.86	±8.1	p = NS
Maximum flexion	103.8	±27.0	117.4	±17.8	p = NS
Gender					p = NS
Male	2	20.0%	192	21.5%
Female	8	80.0%	703	78.5%
Side of surgery					p = NS
Left	5	50.0%	431	48.2%
Right	5	50.0%	464	51.8%
Mean duration of surgery (min)	90.5	±28.2	72.2	±20.3	p = 0.03
Ethnicity
Chinese	9	90.0%	759	84.8%	p = NS
Malay	0	0%	69	7.7%	p = NS
Indian	1	10.0%	61	6.8%	p = NS
Others	0	0%	6	0.7%	p = NS
Co-morbidities
Diabetes	0	0%	123	13.7%	p = NS
IHD	0	0%	42	4.7%	p = NS
Stroke	0	0%	13	1.5%	p = NS
HTN	2	20.0%	402	44.9%	p = NS
Dyslipidemia	0	0%	284	31.7%	p = NS
Renal impairment	0	0%	9	1.0%	p = NS

FFD: fixed flexion deformity; IHD: ischaemic heart disease; HTN: hypertension; SSI: surgical site infection; BMI: body mass index; ROM: range of motion; NS: not significant.

All six superficial infections were diagnosed within the first 2 weeks following surgery. They presented with persistent wound erythema with a small amount of dehiscence and discharge. These infections were self-limiting with complete resolution after 1 week of oral antibiotics.

In the PJI group, patient A underwent left TKA in 2007. Seven months later, he was diagnosed with a left knee abscess, requiring drainage and eventually, a two-stage revision knee replacement (19 months and 26 months after index surgery). The causative organism was methicillin-sensitive Staphylococcus aureus. Subsequent progress was unremarkable until his demise in 2012 from unrelated causes.

Patient B underwent right TKA in 2009. Three months later, she developed methicillin-resistant S. aureus (MRSA) PJI with a discharging sinus, necessitating removal of implants with spacer insertion. Subsequently, she underwent repeated debridement, medial gastrocnemius flap for wound coverage (at 13 months after index surgery) and prolonged antibiotic therapy. She is currently coping well and ambulating.

Patient C underwent left TKA in 2009. She was on long-term prednisolone for primary Sjogren’s syndrome. Five months later, she developed bacteraemia from methicillin-sensitive S. aureus PJI, necessitating polyethylene liner exchange with debridement and prolonged antibiotics. This was complicated by infective seeding to the right psoas that was drained during the same admission. She is currently coping well and ambulating.

Patient D underwent right TKA in 2012. One month after her index surgery, she developed a right knee abscess (initial cultures grew Pseudomonas aeruginosa) requiring multiple debridement and washout and suppressive antibiotic therapy. She further developed a knee abscess (cultures grew MRSA) and underwent implant removal and arthrodesis with cement spacer insertion in March 2014. Following a stormy post-operative period complicated by myocardial infarction and interstitial nephritis, she developed Clostridium difficile diarrhoea, leading to her demise from septic shock in April 2014.

Discussion

In our practice, all superficial wound infections are treated with oral antibiotics and regular wound review until resolution. Management of PJIs is divided into acute (less than 3 weeks from surgery) and chronic (greater than 3 weeks from surgery) groups. In an acute infection, drainage of any abscess, debridement of compromised tissue and liner exchange are performed. Six weeks of culture-specific intravenous antibiotics are administered with trending of inflammatory markers. In the event of recurrence, they are treated as per the chronic group with implant removal, debridement of compromised tissue and spacer insertion. Six weeks of antibiotics are likewise administered. A second stage surgery (reimplantation or fusion) depending on symptoms and co-morbidities can be performed when the infection is treated.

During the preoperative period, we screen for and decolonize MRSA. Specific for orthopaedic surgeries, MRSA carriage is a risk factor for infection and its eradication has been shown to reduce infection risk.^25

–28 We avoid intra-articular injections (including viscosupplementation) before surgery. Intra-articular steroid injection within 3 months prior to TKA is associated with significant increase in infection.²⁹

Steroid-based intra-articular cocktail injection was reported to offer good pain relief and reduce the need for morphine^30,31 Infection risk did not appear to be significantly different, although further studies are needed to confirm the safety of periarticular corticosteroid injection.³¹ We omit the use of corticosteroids in our intra-articular analgesia cocktail injection, using instead only Marcaine and Adrenaline.

Haematoma formation and prolonged drainage of the wound are considered risk factors for SSI because they create a conducive environment and a pathway for bacteria to infect the joint.³² Commonly used anticoagulants including Warfarin, Enoxaparin and Rivaroxaban, thought to be potent enough to encourage haematoma formation even at prophylactic dose, are implicated with a higher risk of SSI.^33

–36 In this regard, some authors support the use of Aspirin as an alternative for VTE chemoprophylaxis.^37,38 We do not routinely give post-operative VTE chemoprophylaxis and rely solely on mechanical means (pneumatic calf pumps and compression stockings). Our previous studies on Asian patients undergoing conventional TKAs without chemoprophylaxis also showed a low incidence of VTE.^23,24 Drains are also routinely inserted to prevent haematoma formation, although its role in infection prevention is indeterminate in the literature.^4,39,40

Diabetes and obesity are the co-morbidities most investigated in the literature. In a retrospective review of 83,011 patients after TKA, diabetes and obesity were reported to be the independent risk factors for PJI.¹⁰ The combination of obesity with diabetes revealed a nearly sevenfold increase in periprosthetic knee infections when compared with obese patients without diabetes. Diabetes alone has been shown to increase infection risk by up to three times after hip and knee arthroplasty.^4,41 This correlation is also supported by a meta-analysis by Chen et al.⁴² Based on the rising trend of diabetes and obesity, an exponential increase in PJI resulting in more patients receiving revision surgery was predicted.⁴³

Morbidly obese patients are reported to have a significant increase in infections.¹¹ A BMI greater than 50 was found to have an increased odds ratio of infection of 21.3.⁸ Our study did not find a significant correlation between diabetes, obesity and infection risk. This is likely due to our low overall incidence of infection.

We identified that patients with SSI are associated with a longer operative duration. This is in keeping with literature.^15
–17 In a retrospective review of 6489 TKA, Peersman et al. reported that a matched control group of TKA without infections had surgery duration of 94 ± 28 min, whereas TKAs with infection (n = 104) had duration of 127 ± 45 min (p < 0.001). They further postulated that this duration of 127 min could be used as the ‘critical duration of surgery’.¹⁵ Namba et al. reported a 9% increased risk of infections observed per 15-min increment in operative duration.⁴⁴

Conversely, Naranje et al. analysed registry data from 9973 primary TKAs and concluded that after controlling for confounding variables such as age and gender, the effect of operative time on risk of revision for infection is weak as an isolated factor.⁶ However, this study was unable to include patients who may have declined revision surgery and/or had other surgeries performed, as revision surgery, not the presence of SSI, was used as the outcome measure. Syahrizal et al. reviewed 100 TKAs done and concluded that operative time had no influence on infection risk.⁴⁵ However, this is limited by a small study population.

A longer operative duration itself may be due to a confluence of factors including complexity of surgery and intraoperative complications. Some of these factors may be external and not modifiable. In this aspect, the strength of our study is in using single-surgeon data to eliminate confounders arising from difference in surgical practices and skill sets. In a meta-analysis of 11 articles, low surgeon volume was found to be significantly associated with higher rates of infection, longer procedure time, longer length of stay, higher transfusion rate and worse patient outcomes.⁴⁶

Prolonged operative duration increases the risk of PJI as a result of increased wound contamination, increased damage to wound cells and the local environment (bleeding, cautery, suture) or a combination of these factors.⁶ On the other hand, we caution against cutting corners with poor soft tissue handling in the blind pursuit of speed. Given this complicated interplay of risk factors, it may be difficult to accurately delineate the exact contribution of each factor. It may be prudent, however, should a prolonged operative duration be anticipated preoperatively for any reason, that a possible increase in infection risk be considered and the patient counselled accordingly.

Our study is limited in the following areas. First, the low incidence of SSI of 1.1%, despite being comparable to the literature, limited subgroup analysis. Interestingly, our patients with SSI appear to be healthier with less co-morbidity, although this was not statistically significant. This is a limitation common to previous studies on infection rates in TKA.⁴⁰

Second, although we identified that SSI may be associated with a longer operative duration, further analysis is limited by the low incidence of SSI in our study. While a registry-based study may provide for large data sets adequately powered for subgroup analysis, the different outcome measures and variability in surgical practice and skill sets mentioned earlier may confound the results. Bigger prospective studies with standardized outcome measures should be done to assess this association.

Third, diagnosis of PJI remains challenging as no diagnostic ‘gold standard’ exists.⁴⁷ Newer diagnostic techniques including serum biomarkers such as alpha-defensin, interleukin-6 and leukocyte esterase are promising, but have not seen widespread use in clinical practice.^47

–50

Conclusion

An overwhelming majority of our patients undergoing TKA had good outcomes with only four deep infections resulting in the need for revision surgery. Our overall infection rate was 1.1%. We report that the risk of infection in TKA was significantly associated with a longer operative duration. In our study, age, gender, side of surgery, BMI and a history of DM, heart diseases, stroke and renal impairment did not predispose the patient to increased risk of infection. These negative findings may allow us to better counsel our patients preoperatively on the risk of SSIs. Our finding of a longer operative time as a correlation for SSI should be further validated by larger studies and lead to identification of appropriate preventive measures to mitigate this risk factor.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Fei

Deirmegian

. Diagnosis of periprosthetic infection: novel developments. J Knee Surg 2014; 27: 259–265. DOI: 10.1055/s-0034-1371768.

Surgical site infection after primary total knee arthroplasty is associated with a longer duration of surgery

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