Identifying Risk Factors Associated With Postoperative Infection Following Elective Lower-Extremity Total Joint Arthroplasty

Michelle Lespasio DNPJDNP¹; Michael Mont MD²; Anthony Guarino PhD³

Perm J 2020;24:20.013 [Full Citation]

https://doi.org/10.7812/TPP/20.013

E-pub: 12/02/2020

ABSTRACT

This article addresses the importance of identifying risk factors associated with postoperative infection following elective lower-extremity total joint arthroplasty. Specifically, this review discusses risk factors recognized by the American Academy of Orthopaedic Surgeons that should be carefully considered and assessed by the orthopaedic team in collaboration with the primary care provider before proceeding with surgery.

INTRODUCTION

This review addresses the importance of identifying risk factors associated with postoperative prosthetic joint infection (PJI) following elective lower-extremity total joint arthroplasty (TJA). Addressing associated risk factors before surgery is essential to reducing PJI after surgery. Although the literature differentiates risk factors as modifiable or nonmodifiable, we take the position that all risk factors (to some extent) are modifiable prior to elective TJA surgery. Therefore, this review discusses risk factors recognized by the American Academy of Orthopaedic Surgeons (AAOS)1 that should be carefully considered and assessed by the orthopaedic team in collaboration with the primary care provider (PCP) before proceeding with surgery (see Tables 1, 2, and 3 and Sidebar: Advance Organizer Quiz to Organize the Materials Presented). These associated risk factors include the following: substance abuse, diabetes mellitus (DM), anemia, mental health disorders and neurological disorders, obesity/increased body mass index (BMI), low BMI, malnutrition/hypoalbuminemia, vitamin D deficiency/insufficiency, HIV/AIDS, hepatitis C virus (HCV), liver disease, obstructive sleep apnea (OSA), rheumatoid arthritis, immunocompromised status, cardiovascular disease (eg, congestive heart failure, arrhythmia, atrial fibrillation, postoperative myocardial infarction), hypothyroidism, chronic renal failure/kidney disease, blood clotting disorders, peripheral vascular disease (PVD), homelessness/low socioeconomic status, and special surgical considerations.

Table 1. Careful consideration of risk

1. Active infection of joint, bloodstream, or local tissue

2. Anticoagulation status, active thromboprophylaxis

3. Autoimmune disease

4. HIV status

5. Institutionalized patients

6. Prior bariatric surgery

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

Table 2. Unclear effect on risk of prosthetic joint infection

1. Age (conflicting evidence)

2. Dementia (insufficient evidence)

3. Poor dental status (insufficient evidence)

4. Asymptomatic bacteriuria (conflicting evidence)

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

Table 3. Absolute contraindication to elective TJA

1. Active infection of arthritic joint, presence of septicemia, and/or presence of active local cutaneous, subcutaneous, or deep tissue infection

2. Superobesity, body mass index > 50

3. Active intravenous drug abuse

4. Intra-articular injection within 3 mo of surgery

5. Uncontrolled hyperglycemia with blood glucose > 200 mg/dL

6. Severe malnutrition with serum albumin < 3 g/dL

7. Untreated HIV

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

What Is a TJA?

TJA is a surgical operation performed to provide the most effective relief of pain and is appropriate for patients with advanced, end-stage arthritic disease or inflammatory arthritis of a large joint who nonsurgical treatment modalities have failed.2 For the purposes of this review, TJA includes both total knee arthroplasty (TKA) and total hip arthroplasty (THA).

Prevalence of TJA

The prevalence of TJA procedures is more than 1 million THA and TKA operations performed each year in the United States3,4 and that number is expected to rise steadily over the next 10 years.5 According to the Agency for Healthcare Research and Quality,6 more than 400,000 total hip replacements and more than 600,000 knee replacements are performed each year in the United States.

Possible Complications with TJA

Risks associated with TJA comprise systemic complications, such as those related to anesthesia, including deep vein thrombosis, pulmonary embolism, stroke, heart attack, and pneumonia. In addition, risks associated with TJA include surgical complications such as infection (at the site of incision and in deeper tissues near the affected joint), fracture, dislocation, nerve injury, leg length discrepancy, implant loosening, inflammation and swelling, increased pain, stiffness in the affected joint, allergic reaction to the bone cement, and damage to structures around the joint.

Possible Complications of PJI in TJA

Possible complications related to infection associated with TJA may involve a range from self-limited problems such as superficial skin infections (SSIs) to more detrimental problems seen with deep PJIs, which can lead to loss of limb or amputation. Infections that enter the bloodstream (eg, septicemia) can be fatal and lead to death. These infecting microorganisms may be introduced at the time of surgical intervention, through the bloodstream (hematogenously), by contiguous spread from another site, or from recurrence of a previously infected joint.7

Prevalence of PJI in TJA

The rate of PJI is highest during the first 2 years following surgery,8 with the risk of PJI greater for knee arthroplasty than hip arthroplasty.8,9 The rate of PJI in most medical centers ranges between 0.5% and 2% for knee replacements and 0.5% and 1.0% for hip replacements.5,10,11 The higher rate of PJI in TKAs may be attributed to greater mobility in the joint and soft tissue and less protective soft tissue coverage.5

Diagnosis of PJI in TJA

PJI is among the most serious complications of prosthetic joint implantation. After completing a comprehensive medical history that includes a review of associated TJA risk factors, the clinician should perform a focused clinical examination of the affected hip or knee and compare it to the contralateral side. The examination should include an assessment of the identified signs and symptoms noted above and inspection of the affected joint. Presence of fever (lasting more than 48 hours in the first month after primary surgery) and persistent wound drainage are 2 of the most important aspects of the examination. In addition, it is important to note both the presence or history of chronic pain at the site of the joint prosthesis and a history of superficial or deep infection or prior wound healing problems.

Plain radiographs, laboratory testing for inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), evaluation of synovial fluid, and tissue biopsy are important to establish a diagnosis of PJI. Other scans and imaging studies (eg, leukocyte count, positron emission tomography, computed tomography, bone scan, and magnetic resonance imaging) usually do not provide a definitive diagnosis in PJI and are generally not useful for routine diagnosis of suspected PJI.12

Management of PJI

Once a PJI is clinically established (see Table 4), the goals for management include eradication of the infection, alleviation of symptoms, restoration of function, and minimization of PJI-related morbidity and mortality.13 Management of PJI almost always requires surgical intervention and prolonged courses of intravenous or oral antimicrobial therapy.13 The approach to management of infection depends on the timing (eg, early, delayed onset, or later) and microbiology (eg, virulence) of infection, condition of the joint and implant, quality of the soft tissue envelope, and individual patient circumstances (see Table 5).14

Table 4. Clinical practice guidelines and recommendations for suspicion of prosthetic joint infection

a. Presence of fever

b. Persistent wound drainage (which may reflect sinus tract) at the site of a joint prosthesis

c. Acute onset of pain at the site of a joint prosthesis

d. Chronic pain at the site of a joint prosthesis, particularly in the absence of a pain-free interval following implantation

e. History of superficial or deep infection or prior wound healing problems

Adapted from Osmon et al.12

Table 5. Clinical practice guidelines

a. Not intended to be a fixed protocol

b. Not all patients in any given clinical situation are the same

c. Individual patient’s specific circumstances must always be considered

d. Clinician’s medical judgement always provides basis of patient care and treatment

Adopted by the American Academy of Orthopaedic Surgeons1 on March 11, 2019.

There are 3 categories of onset of PJI infections (see Table 6).15,16 Early onset occurs within 3 months of implantation. Later infections (ie, occurring more than 24 months following implantation) typically originate in the blood. Antimicrobial therapy should be delayed until culture specimens are obtained (by joint aspiration, debridement, and/or removal of hardware). Clinical approaches for surgical management of PJI include 1) debridement and retention of the prosthesis, 2) resection arthroplasty with reimplantation, 3) permanent resection arthroplasty, or 4) amputation (see Table 7).17

Table 6. General categorization of prosthetic joint infections

Early onset within 3 mo of implantation

Delayed onset within 3 to 24 mo of implantation

Later onset later than 24 mo following implantation

Considerable overlap between early- and delayed-onset prosthetic joint infections (PJIs), and hip PJIs tend to occur sooner than knee PJIs

Adapted from Brusch et al15 and Lewis et al.16

Table 7. Clinical approaches for surgical management of prosthetic joint infection

Approach	Description
Debridement, antibiotics, and retention of prosthesis (DAIR) procedure	The DAIR procedure can be a successful treatment option for prosthetic joint infection (PJI) in total joint arthroplasty (TJA). It can effectively eradicate infection, resulting in improved functional outcome and a reduction in the need for more extensive surgery, which may be associated with far greater morbidity.103 The effectiveness of DAIR is still unclear due to a lack of comparative data among the treatment options and limited evidence to suggest superiority of any one treatment. The treatment decision must be made on a case-by-case basis and account for underlying medical conditions, infection history, organism characteristics, and surgical history. DAIR is most appropriate for acute PJI without complicating factors such as extensive and pervasive infection or organism virulence or resistance.104
Resection arthroplasty with reimplantation	Reimplantation of a total hip or knee arthroplasty after a previous resection arthroplasty for infection can be performed with a low risk of reinfection. However, the incidence of infection following arthroplasty revision surgery is higher than that following primary implantation arthroplasty in this setting and is especially challenging because of the potential for significant bone and soft tissue deficits. The incidence of infection following arthroplasty revision surgery is higher than that following primary implantation.105-109 Postulated reasons for this include prolonged operating time during the revision surgery or unrecognized infection at the time of revision, with subsequent recrudescence. The abnormal soft tissue envelope may also be a contributing factor.13
Permanent resection arthroplasty	Resection arthroplasty is a procedure in which the prosthetic components (implants) are removed as a consequence of failed surgery, in the setting of a periprosthetic infection. This is only performed when no other reconstructive options are possible and is typically reserved as a salvage strategy to avoid amputation after prior failed treatment attempts or for patients who are not candidates for DAIR or 1-stage arthroplasty exchange.5,13
Arthrodesis of amputation of limb	This approach is reserved for patients for whom all other treatment options for PJI have failed110 or who have life-threatening infections in which emergent source control is required.111 Failure of the repeat 2-stage exchange arthroplasty appears to be dependent on the host grade and status of the extremity. Surgeons thus should consider the patient’s comorbidities and expectations when deciding whether to undergo repeat 2-stage exchange arthroplasty.112

Organism Profile Causing SSI/PJI in TJA

The published literature depicts Staphylococcus aureus as the leading cause of PJI after TJA,18-20 and there is limited evidence to support a difference in the organism profile causing SSI/PJI between hip and knee arthroplasty. Isolated studies have reported an increased prevalence of streptococcal and culture-negative PJI around the knee, whereas staphylococcal, enterococcal, and pseudomonal PJI may be more prevalent around the hip.21 The incidence of PJI affecting TKA versus THA is estimated at 1% to 3% and 0.3% to 2%, respectively.20 Several studies have examined the organism profile causing PJI after arthroplasty, but few have identified any significant difference in the organism’s profile between hip and knee arthroplasty.21

PATIENT OPTIMIZATION OF RISK FACTORS

Prior to referring a patient for evaluation of TJA, we recommend that the PCP assess the following risk factors for PJI and treat and/or refer the patient accordingly.

Substance Use

Substance use includes 1) excessive alcohol use, 2) cigarette smoking, and 3) chronic opioid use, illegal drug use, and/or intravenous drug abuse. Substance use can lead to substance use disorders, which may contribute to medical and related physical health problems such as an increased risk of liver, lung, or cardiovascular disease, infectious diseases such as hepatitis B or C, and HIV/AIDS.22 PCP identification of patients with substance use disorders preoperatively can provide an opportunity to refer these individuals for early intervention and subsequently avoid delay in scheduling TJA.23

Excessive Alcohol Use

Excessive alcohol use increases the risk of PJI. Alcohol use disorder remains the most common form of substance use disorder in the United States and begins as early as age 12 years.22,24,25 The US Centers for Disease Control and Prevention26 defines excessive alcohol consumption as 4 or more drinks on a single occasion or 8 or more drinks per week for women and 5 or more drinks on a single occasion or 15 or more drinks per week for men. Excessive alcohol consumption increases individuals’ risk for cardiopulmonary problems, alcohol withdrawal symptoms/delirium, immune system dysfunction, and metabolic stress responses.27,28

Although the optimal period of alcohol cessation remains unspecified, a period of at least 4 weeks of abstinence is required to reverse certain physiologic abnormalities.29 In some cases, orthopaedic surgeons require a medically documented 6-month period of abstinence before they will perform elective TJA (Eric L Smith, MD, personal communication, October 16, 2017).^a

SIDEBAR.Advance Organizer Quiz to Organize the Materials Presented

Please answer true or false to the following items:

1. True/False. Estimates indicate that by 2030, more than 3 million total joint arthroplasties (TJAs) will be performed each year in the United States.

2. True/False. Prosthetic joint infection (PJI) in TJA is associated with an increase in morbidity, implant failures, and financial and emotional costs.

3. True/False. Associated risk factors for PJI in TJA can be modified to reduce the incidence of systemic comorbid systemic complications and implant failure postoperatively.

4. True/False. For patients with a hemoglobin A1C of 8% to 9% or greater or glucose levels between 180 to 200 mg/dL, optimization of the elevated levels is mandated prior to undergoing TJA.

5. True/False. High hemoglobin levels can increase a patient’s risk for perioperative allogenic blood transfusions and PJI after surgery.

6. True/False. Mental health disorders in patients undergoing TJA are relatively easy to detect.

7. True/False. Malnutrition is not a risk factor in patients with an elevated body mass index (greater than 40) undergoing TJA.

8. True/False. Hyperalbuminemia significantly increases the risk of superficial site infections following TJA.

9. True/False. Homelessness is often overlooked as a potential barrier to recovery.

Answers

1. True

2. True

3. True

4. True

5. False

6. False

7. False

8. False

9. True

^a Chief, Division of Arthroplasty, Associate Professor of Orthopaedic Surgery, New England Baptist Hospital.

Cigarette Smoking

Clinical studies demonstrate that smokers undergoing both THA and TKA are 9 times more likely to experience superficial SSIs, smokers undergoing THA are 6.5 times more likely to have deep SSIs, and smokers undergoing TKA are 2.5 times more likely to develop deep SSIs.30 Bone healing is an essential component of successful TJA, requiring bone to grow into the implant. However, the restricting effect of nicotine on microvascular (small blood vessel) constriction places smokers at an increased risk of TJA infection because there is as much as 25% less blood flow to the wound in smokers compared to nonsmokers with less oxygenation and there are fewer healing nutrients and white blood cells protective to wounds, thereby slowing and potentially interfering with the healing process.31 Smoking cessation is advised at least 6 weeks prior to surgery to at least 6 weeks postoperatively, although permanent cessation of smoking is preferred.32,33

Chronic Opioid Use/Illegal/Intravenous Drug Abuse

Ongoing illegal drug abuse (eg, opioids, barbiturates, or amphetamines) is an absolute contraindication for elective TJA.34 Patients with a history of intravenous drug use are more likely to develop a deep infection compared with other patients undergoing TJA.35 Chronic opioid use in patients often leads to tolerance requiring a higher than usual opioid dose in the intraoperative and postoperative period. Identifying individuals with a chronic opioid addiction or illegal/intravenous drug abuse problem and referring them to inpatient or outpatient rehabilitation programs prior to surgical evaluation provides the best solution for optimal care. Twelve-step programs, psychotherapy or cognitive behavioral therapy, and medication are other recommended options.36-38

DM Control

Patients with a sole diagnosis of well-controlled DM control do not confer a clinically significant risk for PJI.37 DM, preoperative hyperglycemia, and elevated hemoglobin A_1C are generally not independent risk factors for PJI, but they are considered to be indirect markers of and associated with an increased risk of more serious systemic comorbid conditions (eg, chronic kidney disease, stroke, urinary tract infection, ileus, postoperative hemorrhage, transfusion) and surgical complications (eg, wound infection, PJI), higher mortality, and increased length of hospital stay.37,38 Conversely, others report that without a diagnosis of DM, perioperative hyperglycemia at the time of primary knee or hip arthroplasty has been associated with an increased risk of subsequent PJI.39 Severely uncontrolled DM (eg, serum glucose of 200 mg/day or higher) is an absolute contraindication for TJA. For those with hemoglobin A_1C of 8% to 9% or greater or glucose levels between 180 and 200 mg/dL, optimization of the elevated levels is mandated in the preoperative period.

PCP evaluation and optimization of a patient’s DM with an elevated hemoglobin A_1C greater than 8 and possible referral for an endocrine consultation is the mainstay of treatment prior to referring the patient for TJA evaluation. Several months or more of ongoing care and management can be expected prior to achieving optimization of DM in TJA.

Anemia

Anemia is common in patients undergoing TJA and is linked to more PJI in patients undergoing TJA than those without anemia, affecting 4.3% and 2% of anemic and nonanemic patients, respectively.40,41 Preoperative anemia, as defined by a hemoglobin level of less than 13.0 g/dL in men and 12.0 g/dL in women, is an independent risk factor for postoperative SSI/PJI following TJA.42 Low hemoglobin levels can increase a patient’s risk for perioperative allogenic blood transfusions and PJI after surgery.43

Mental Health and Neurological Disorders

Patients with mental health disorders and psychiatric diagnoses (eg, depression psychosis, schizophrenia) are demonstrated to have increased complication rates after primary TJA.44-46 The most common etiologies of mental health disorders and neurological disorders include acute changes due to 1) delirium, stroke, and Alzheimer dementia; 2) movement disorders (eg, Parkinson disease, multiple sclerosis, epilepsy, and tardive dyskinesia); and 3) mood/behavior disorders (eg, major depressive disorder, anxiety, bipolar disorder, schizophrenia).47 Patients who have a history of delirium, stroke, and Alzheimer disease are shown to be at greater risk of unfavorable outcomes (in particular, higher mortality and longer lengths of hospital stay leading to greater chances of infection) and may acquire greater levels of dependence. Patients undergoing TJA who have movement disorders are known to have longer postoperative hospitalizations and higher rates of perioperative complications.48 Patients undergoing TJA who have mood/behavior disorders, such as major depressive disorders, may have perceptions of pain and disability that encourage a greater need to consume more opioids during the immediate postoperative period compared to similar patients without major depressive disorders.49 Patients with moderate anxiety or depression also appear to have an increased risk of wound complications (eg, infection) after THA.50

Obesity/Increased BMI

Obesity is associated with a higher risk for PJI following THA among elderly individuals (defined as older than 75 years), but no such association was found for patients undergoing TKA.51 It is not yet known whether PJI correlates with higher BMI (above 30 kg/m²) in patients undergoing TKA.

A BMI threshold of 35 kg/m² is most commonly used to define obesity, but a BMI of 40 kg/m² or greater (severely obese) is the threshold in some medical centers. Under no circumstance should elective surgery be performed on patients diagnosed as superobese (ie, BMI greater than 50). Patients who have an increased BMI are more likely to experience PJI, deep vein thrombosis, and pulmonary embolism. Possible reasons for the increased risk associated with obesity are postulated to be prolonged operative duration, vascular insufficiency leading to decreased capacity to fight infection and decreased ability to support the healing process.52,53

Current management guidelines indicate that weight loss is helpful in reducing PJIs in this patient population. Weight loss prior to surgery will help to reduce the risk of PJIs and other perioperative complications, including anesthesia-related complications, and reduce the risk of surgical revision.54 However, the current approach to weight loss protocols remains controversial, with no absolute guidelines for which methodology (eg, diet/exercise versus medically prescribed very low-calorie diets versus bariatric surgery) is best. It is suspected that in patients undergoing bariatric surgery prior to TJA, the risks for PJIs are reduced due to decreasing BMIs but this is offset by the increased risk for malnutrition.54

Low BMI

Underweight and low BMI are associated with suppressed immune systems in some patients, possibly reflecting an altered physiological state55 and higher morbidity and mortality rates.56 A low BMI is typically defined as less than 18.5 kg/m²,57-60 and these patients comprise approximately 2.3% of the US population.61 A low BMI is hypothesized to be an indirect measure of nutritional status, as patients with a lower BMI are shown to have lower levels of albumin, prealbumin, and/or protein.62 Patients with a low BMI who have decreased nutritional reserves and reduced ability to accurately react to stress because of a suppressed immune system are at increased risk of PJI and should be referred for a nutritional consultation before undergoing TJA.56

Malnutrition/Hypoalbuminemia

Malnutrition and hypoalbuminemia are known to increase the risk of postoperative wound complications, SSIs, and PJIs in patients undergoing TJA.63-67 Patients diagnosed with malnutrition are 2 times more likely to have postoperative wound complications compared to those with adequate nutritional stores.68,69 While the mechanism of how malnutrition leads to postoperative wound complications is not entirely clear, malnutrition is believed to impair wound healing, cause persistent wound drainage, and prolong inflammation by reducing collagen synthesis and fibroblast proliferation.63 In addition, malnutrition may impair the ability of the immune system to fight infection through lymphocytopenia and cause PJI.63 In the event of an SSI or deeper wound infection, malnourished patients demonstrate low success rates of initial irrigation and debridement procedures.70,71 Thus, evaluation is essential for patients who have malnutrition to determine whether the cause is due to not eating enough key nutrients or if an underlying medical condition such as liver failure may be causing malabsorption of key nutrients into the body.

Vitamin D Deficiency/Insufficiency

Risk factors associated with vitamin D deficiency (25-hydroxy vitamin D of 20 ng/mL or lower) or insufficiency (25-hydroxy vitamin D less than 30 ng/mL) and PJI remain controversial and undefined.72 Some research has reported a higher prevalence of vitamin D deficiency in patients with PJI compared to patients without infection, thereby suggesting an association between low vitamin D levels and possible suboptimal postsurgical outcomes.73 Most research, however, demonstrates little evidence to support hypovitaminosis D as a risk factor linked to reduced postoperative functional recovery or increased risk of PJIs.74,75 Some orthopedists nevertheless recommend screening and treating hypovitaminosis D prior to undergoing orthopaedic surgery.74 When recommended, a standard vitamin D regimen consists of 50,000 units of vitamin D³ weekly for 6 to 8 weeks to increase low levels to an optimal level of 30 to 60 ng/mL. Maintenance doses of 2,000 units of vitamin D³ daily or 5,000 units 3 times a week are recommended thereafter. Fifteen minutes of exposure to sunlight daily if possible is also recommended.74

HIV/AIDS

Patients who have HIV with a CD4 level below 200/mm³ are known to have a 10-fold increase in infection.76 Research demonstrates that patients with well-controlled HIV who receive highly active antiretroviral therapy with undetectable viral loads and have a CD4 level above 200/mm³ are at similar risk of PJI as the average population.77 Thus, for patients with HIV who are medically optimized with highly active antiretroviral therapy, the risk is small and comparable to patients who are HIV negative in conjunction with optimization of underlying associated conditions such as malnutrition, renal disease, and liver disease.1

HCV

Research indicates that patients with HCV are at increased risk of both acute and long-term medical and surgical complications.78 Treatment for HCV prior to THA appears to be associated with fewer postoperative complications, primarily periprosthetic joint infection.78 For patients with known HCV, many orthopaedic surgeons require that patients complete HCV treatment in entirety prior to elective TJA (Eric L Smith, MD, personal communication, October 16, 2017).^a

Patients with liver disease (eg, hepatitis and/or cirrhosis) are at increased risk for SSI/PJI and intraoperative and postoperative bleeding.79 Patients with cirrhosis are found to have longer lengths of hospital stay, increased costs, and higher rates of mortality, readmission, and reoperation.80 Although currently there are no universal treatment guidelines for managing liver disease prior to elective TJA, referring patients with known liver disease to a liver disease specialist for preoperative optimization of care is recommended.

OSA

The American Society of Anesthesiologists recommends screening patients for OSA before they undergo elective TJA.81 While there is no apparent association between OSA and PJI reported in the literature, there may be some indirect links. As previously noted, patients with alterations in mental status (eg, delirium) and neurological disorders (eg, stroke) may have prolonged postoperative lengths of hospital stay and higher rates of perioperative complications, which can increase their risk for PJI.

Clinical studies demonstrate that patients undergoing primary TJA who have OSA are at greater risk of postoperative cardiovascular and pulmonary complications, and death.82,83 In elderly patients without a history of dementia who elect to undergo elective TJA, there is an association between preexisting OSA and postoperative dementia, which can lead to longer lengths of hospital stay and perioperative complications.84

Rheumatoid Arthritis

It is postulated that immunosuppressive therapies collectively contribute to increased PJI susceptibility for patients who have rheumatoid arthritis and associated comorbidities.13 Immunosuppressive therapies involving corticosteroids (eg, prednisone) and disease-modifying antirheumatic drugs (eg, methotrexate) place patients with rheumatoid arthritis undergoing TJA at greater risk of infection.85 Some studies report no increase in the incidence of PJI, regardless of whether these treatments are discontinued perioperatively.86,87 The American College of Rheumatology and the British Society for Rheumatology88-90 both recommend withholding tumor necrosis factor-α inhibitors perioperatively to TJA. Likewise, the International Consensus Group on Periprosthetic Joint Infection91 recommends stopping disease-modifying antirheumatic drugs within the clinical judgement of the medical team for at least 14 days prior to elective TJA.

Immunocompromised Status

Patients who are concurrently undergoing immunosuppressive therapies involving corticosteroids and disease-modifying antirheumatic drugs are at greater risk of PJI due to their compromised ability to heal, fight infections, and maintain homeostasis.1 Therefore, a risk-benefit analysis is recommended for these types of patients.

Cardiovascular Disease

Specific cardiovascular diseases are shown to significantly predispose patients to PJI. Congestive heart failure, PVD, valvular heart disease, atrial fibrillation, and myocardial infarction are independent comorbid factors associated with a higher risk of PJI.20 It is postulated that the increased risk of infection associated with these conditions could be related to more aggressive treatment with anticoagulation.20

Hypothyroidism

There is some evidence of an association between hypothyroidism and PJI.92 In one clinical study, patients who developed PJI demonstrated a statistically significant, 2.46 times greater thyroid-stimulating hormone than those without PJI.92 Buller et al93 reported that hypothyroidism was associated with greater risk of postoperative complications compared to matched controls. Evaluation and proper management of thyroid function in patients with thyroid disease is important prior to elective TJA.

Chronic Renal Failure/Kidney Disease

Reports suggest that patients who have chronic renal failure are at greater risk of developing PJI after TJA. One study demonstrated that hemodialysis patients had approximately twice the rate of infection than patients who had undergone a renal transplant.94 The reason for this is thought to be multifactorial, including the immunosuppressive nature of therapies associated with chronic kidney disease, which may increase susceptibility to infection.94,95

Blood Clotting Disorders

Blood clotting disorders (eg, hemophilia and von Willebrand disease) are associated with significantly higher rates of infection, transfusions of blood products, medical complications, and revision surgery after TKA.1 Patients with blood clotting disorders require referral to a hematologist or vascular surgeon for risk assessment and perioperative recommendations, followed by close monitoring by the surgical team after TJA. Intraoperative use of tranexamic acid, an antifibrinolytic agent, promotes blood clotting and reduces bleeding in the surgical wound.96,97 Utilizing tranexamic acid during surgery in patients with hemophilia has demonstrated 1) lower perioperative blood loss, 2) lower hidden blood loss, 3) a lower transfusion rate, 4) lower postoperative joint swelling and pain, and 5) lower levels of inflammatory biomarkers resulting in enhanced overall joint function.98

PVD

PVD is an identifiable risk factor for arterial insufficiency that can lead to wound complications and PJI.99 Defined as decreased arterial perfusion to the lower extremities, PVD can be clinically identified by intermittent claudication or the absence of arterial pulses in the lower extremities.99 Patients who have known or suspected PVD should be referred to a vascular specialist for evaluation of arterial perfusion and potential for postoperative blood clots.

Homelessness/Low Socioeconomic Status

Patients who are homeless have potential barriers to recovery because of these common health issues. These barriers include the following: 1) mental illness, 2) drug and alcohol dependence, 3) risk of violence, 4) HIV, 5) hepatitis B and C, 6) neurological disorders, 7) anemia, 8) cardiac disease, 9) tuberculosis and other respiratory infections, and 10) increased mortality rates.100 These potential recovery barriers often lead to longer lengths of hospital stay, reduce the likelihood of attending follow-up clinic appointments, increase the likelihood of returning to the emergency department, and have higher readmission rates for infections. Interventions such as providing stable housing are essential to improve the health outcomes of people who are homeless and to reduce the associated costs to the health care system.101

Special Surgical Considerations

Special surgical considerations to optimize postoperative outcomes include 1) appropriate patient selection, 2) infection control practices, and 3) attentive postoperative management protocols.102 Additionally, other surgical factors that appear to reduce the rate of PJI include shorter duration of surgery, prophylactic antibiotics given within 60 minutes of the surgical incision, S. aureus decolonization with mupirocin ointment, and preoperative chlorhexidine wash.54

DISCUSSION

It is apparent that when addressing the challenge of PJI, orthopaedic surgeons play an important role in limiting the impact of associated risk factors in the preoperative, intraoperative, and postoperative phases of TJA. Reducing emotional and economic burdens associated with PJI is a primary objective undertaken by orthopaedic surgeons when considering surgical candidates for elective TJA. Although in most cases, orthopaedic surgeons and their teams perform the essential role of identifying and addressing associated risk factors that affect perioperative morbidity and mortality, the role of identifying and addressing these associated risk factors should start with patients’ PCPs. Therefore, it is incumbent on the PCP to ensure patient optimization prior to undergoing TJA and referring patients for surgical evaluation. Through preoperative identification and modification of patient-associated risk factors, along with patient compliance to related medical recommendations, improved overall postoperative clinical outcomes are achievable.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Acknowledgments

The authors wish to graciously acknowledge the editors of this article whose contributions were invaluable to the clarity of explaining this condition.

Author Affiliations

¹Department of Orthopaedic Surgery, Boston Medical Center, Boston, MA

²Northwell Health Physician Partners Orthopaedic Institute at Lenox Hill, Lenox Hill Hospital, New York, NY

³Fulbright Association, Washington, DC

Corresponding Author

Michelle Lespasio ()

How to Cite this Article

Lespasio M, Mont M, Guarino A. Identifying risk factors associated with postoperative infection following elective lower-extremity total joint arthroplasty. Perm J 2020;24:20.013. DOI: 10.7812/TPP/20.013

References

1. American Academy of Orthopaedic Surgeons. Diagnosis and prevention of periprosthetic joint infections clinical practice guideline: Hip and knee, part II. Published March 11, 2019. Accessed November 18, 2019. https://www5.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/guidelines/PJI%20Clinical%20Practice%20Guideline%20Final%203.pdf

2. Hawker G, Badley E, Borkhoff C, et al. Which patients are most likely to benefit from total joint arthroplasty? Arthritis Rheum 2013 May;65(5):1243-52. DOI: https://doi.org/10.1002/art.37901

3. Steiner C, Andrews R, Barrett M, Weiss A. HCUP projections: Mobility/orthopedic procedures 2003-2012. HCUP Projections Report 2012-03. Published September 20, 2012. Rockville, MD: US Agency for Healthcare Research and Quality. Accessed September 18, 2019. http://hcup-us.ahrq.gov/reports/projections/2012-03.pdf

4. Maradit K, Larson D, Crowson C, et al. Prevalence of total hip and knee replacement in the United States. J Bone Joint Surg Am 2015 Sep;97(17):1386-97. DOI: https://doi.org/10.2106/JBJS.N.01141

5. Berbari E, Baddour L. Prosthetic joint infection: Epidemiology, clinical manifestations, and diagnosis. UpToDate. Last updated April 23, 2019. Accessed September 18, 2019. https://www.uptodate.com/contents/prosthetic-joint-infection-treatment

6. Exhibit 19. HCUP estimates of the total number of target procedures. Content last reviewed April 2018. Agency for Healthcare Research and Quality, Rockville, MD. Accessed September 19, 2019. https://www.ahrq.gov/research/findings/final-reports/ssi/ssiexh19.htmlInternet

7. Della Valle C, Zuckerman J, Di Cesare P. Periprosthetic sepsis. Clin Orthop Relat Res 2004 Mar;420:26-31. DOI: https://doi.org/10.1097/00003086-200403000-00005

8. Beam E, Osmon D. Prosthetic joint infection update. Infect Dis Clin North Am 2018 Dec;32(4):843-59. DOI: https://doi.org/10.1016/j.idc.2018.06.005

9. Koh C, Zeng I, Ravi S, Zhu M, Vince K, Young S. Periprosthetic joint infection is the main cause of failure for modern knee arthroplasty: An analysis of 11,134 knees. Clin Orthop Relat Res 2017 Sep;475:2194-201. DOI: https://doi.org/10.1007/s11999-017-5396-4

10. Namba R, Inacio M, Paxton E. 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 May;95:775-82. DOI: https://doi.org/10.2106/jbjs.l.00211

11. Edwards J, Peterson K, Mu Y, et al. National Healthcare Safety Network (NHSN) report: Data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009 Dec;37:783-805.DOI: https://doi.org/10.1016/j.ajic.2009.10.001

12. Osmon D, Berbari E, Berendt A, et al. Executive summary: Diagnosis and management of prosthetic joint infection: Clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013 Dec;56(1):1-10. DOI: https://doi.org/10.1093/cid/cis966

13. Tande A, Patel R. Prosthetic joint infection. Clin Microbiol Rev 2014 Apr;27(2):302-45. DOI: https://doi.org/10.1128/cmr.00111-13

14. Runner R, Mener A, Roberson J, et al. Prosthetic joint infection trends at a dedicated orthopaedics specialty hospital. Adv Orthop 2019;2019:4629503. DOI: https://doi.org/10.1155/2019/4629503

15. Brusch J. What are the types of prosthetic joint infection (PJI)? Medscape. Updated March 9, 2019. Accessed October 15, 2019. https://www.medscape.com/answers/236299-5614/what-are-the-types-of-prosthetic-joint-infection-pji

16. Lewis S, Dicks, Chen L, et al. Delay in diagnosis of invasive surgical site infections following knee arthroplasty versus hip arthroplasty. Clin Infect Dis 2015 Apr;60:990-6. DOI: https://doi.org/10.1093/cid/ciu975

17. Martin G, Roe J. Complications of total knee arthroplasty. UpToDate. Last updated May 21, 2019. Accessed October 18, 2019. https://www.uptodate.com/contents/complications-of-total-knee-arthroplasty

18. Phillips J, Crane T, Noy M, Elliott T, Grimer R. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: A 15-year prospective survey. J Bone Joint Surg Br 2006 Jul;88:943-8. DOI: https://doi.org/10.1302/0301-620X.887.17150

19. Aggarwal V, Bakhshi H, Ecker N, Parvizi J, Gehrke T, Kendoff D. Organism profile in periprosthetic joint infection: Pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J Knee Surg 2014 Oct;27:399-406. DOI: https://doi.org/10.1055/s-0033-1364102.

20. Pulido L, Ghanem E, Joshi A, Purtill J, Parvizi J. Periprosthetic joint infection: The incidence, timing, and predisposing factors. Clin Orthop Relat Res 2008 Jul;466:1710-5. DOI: https://doi.org/10.1007/s11999-008-0209-4

21. Goswami, K, Groff, H. Is there a difference in the type of pathogens that can cause surgical site infections/periprosthetic joint infections (SSIs/PJIs) between hip and knee arthroplasty?In: American Academy of Orthopaedic Surgeons diagnosis and prevention of periprosthetic joint infections clinical practice guideline: Hip and knee, part II. Published March 11, 2019. Accessed November 18, 2019. https://www5.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/guidelines/PJI%20Clinical%20Practice%20Guideline%20Final%203.pdf

22. Center for Behavioral Health Statistics and Quality. 2016 National Survey on Drug Use and Health: Methodological summary and definitions. Published September 2017. Accessed November 20, 2019. https://www.samhsa.gov/data/sites/default/files/NSDUH-MethodSummDefs-2016/NSDUH-MethodSummDefs-2016.htm

23. Substance Abuse and Mental Health Services Administration; Office of the Surgeon General. Chapter 4. Early intervention, treatment, and management of substance use disorders. In: Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: US Department of Health and Human Services; 2016. Accessed November 20, 2019. https://www.ncbi.nlm.nih.gov/books/NBK424859/?report=printable

24. National Institute on Alcohol Abuse and Alcoholism. Alcohol alert: Underage drinking. Published 2006. Accessed November 20, 2019. https://pubs.niaaa.nih.gov/publications/AA67/AA67.htm

25. National Institute on Alcohol Abuse and Alcoholism. Mental Health America. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 2017. Accessed November 20, 2019. https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-institute-alcohol-abuse-alcoholism-niaaa

26. US Centers for Disease Control and Prevention. Alcohol use and your health. Last reviewed October 1, 2020. Accessed November 21, 2019. https://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm

27. Kleber H, Weiss R, Anton R, et al. Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am J Psychiatry 2007 Apr;164(4 Suppl):5-123. PMID 17569411

28. Trevejo-Nunez G, Kolls J, de Wit M. Alcohol use as a risk factor in infections and healing: A clinician’s perspective. Alcohol Res 2015;37(2):177-84.

29. Smetana GW. Preoperative medical evaluation of the healthy adult patient. UpToDate. Last updated January 3, 2019. Accessed November 23, 2019. https://www.uptodate.com/contents/preoperative-medical-evaluation-of-the-healthy-adult-patient

30. Mistry J, Naqvi A, Chughtai M, et al. Decreasing the incidence of surgical-site infections after total joint arthroplasty. Am J Orthop 2017 Nov/Dec;46(6):E374-87. DOI: https://doi.org/10.1007/s11999-012-2748-y

31. Lombardi A Jr., Berend K, Adams J, Jefferson R, Sneller M. Smoking may be a harbinger of early failure with ultraporous metal acetabular reconstruction. Clin Orthop Relat Res 2013 Feb;471(2):486-97. DOI: https://doi.org/10.1007/s11999-012-2748-y

32. Arthritis Foundation. The future of joint repair. Accessed October 21, 2019. https://www.arthritis.org/living-with-arthritis/treatments/joint-surgery/candidates/considerations/smoking-joint-replacement-surgery.php

33. Halawi M, Allen D, Baron S, Savoy L, Williams V, Cote M. Tobacco smoking independently predicts lower patient-reported outcomes: New insights on a forgotten epidemic. J Arthroplasty 2019 Jul:34(7):S144-7. DOI: https://doi.org/10.1016/j.arth.2018.10.036

34. Shah K, Truntzer J, Touzard-Romo F, Rubin L. Total joint arthroplasty in patients with human immunodeficiency virus. JBJS Rev 2016 Nov;4(11):10.2106/JBJS.RVW.15.00117. DOI: https://doi.org/10.2106/jbjs.rvw.15.00117

35. Lehman C, Ries M, Paiement D, Davidson B. Infection after total joint arthroplasty in patients with human immunodeficiency virus or intravenous drug use. J Arthroplasty 2001 Apr;16(3):330-5. DOI: https://doi.org/10.1054/arth.2001.21454

36. Accessed November 18, 2019. https://www.samhsa.gov/find-help/atod

37. McHugh RK, Hearon BA, Otto MW. Cognitive behavioral therapy for substance use disorders. Psychiatr Clin North Am 2010 Sep;33(3):511-25. DOI: https://doi.org/10.1016/j.psc.2010.04.012

38. Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing opioids for chronic pain -- United States, 2016. MMWR Recomm Rep 2016 Mar;65(No. RR-1):1-49. DOI: https://doi.org/10.15585/mmwr.rr6501e1external icon

39. Iorio R, Cizmic Z, Feng J, Kunustor S. What are the absolute and relative contraindications to elective primary total joint arthroplasty (TJA), with respect to surgical site infection (SSI) and periprosthetic joint infection (PJI) risk? In: American Academy of Orthopaedic Surgeons diagnosis and prevention of periprosthetic joint infections clinical practice guideline: Hip and knee, part II. Published March 11, 2019. Accessed December 2, 2019. https://www5.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/guidelines/PJI%20Clinical%20Practice%20Guideline%20Final%203.pdf

40. Marchant M, Milford H, Viens N, Cood C, Vail T, Bolognesi M. The impact of glycemic control and diabetes mellitus on perioperative outcomes after total joint arthroplasty. JBJS 2009 Jul;91(7):1621-9. DOI: https://doi.org/10.2106/jbjs.h.00116

41. Mraovic B, Suh D, Jacovides C, Parvizi J. Perioperative hyperglycemia and postoperative infection after lower limb arthroplasty. J Diabetes Sci Technol 2011 Mar;5(2):412-8. DOI: https://doi.org/10.1177/193229681100500231

42. Greenky M, Gandhi K, Pulido L, Restrepo C, Parvizi J. Preoperative anemia in total joint arthroplasty: Is it associated with periprosthetic joint infection? Clin Orthop Relat Res 2012:470(10):2695-701. DOI: https://doi.org/10.1007/s11999-012-2435-z.

43. WebMD. Anemia. Published June 14, 2018. Accessed January 4, 2020. https://www.webmd.com/a-to-z-guides/understanding-anemia-basics#1

44. Khan R, Karas V, Coward J. Is preoperative anemia a risk factor for SSI/PJI? b) If so, what optimization can be done to increase the hemoglobin concentration? c) Does an increased preoperative hemoglobin concentration decrease postoperative SSI/PJI? In: American Academy of Orthopaedic Surgeons diagnosis and prevention of periprosthetic joint infections clinical practice guideline: Hip and knee, part II. Published March 11, 2019. Accessed January 4, 2020. https://www5.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/guidelines/PJI%20Clinical%20Practice%20Guideline%20Final%203.pdf

45. Lee J, Han S. Patient blood management in hip replacement arthroplasty. Hip Pelvis 2015 Dec;27(4):201-8. DOI: https://doi.org/10.5371/hp.2015.27.4.201

46. Tan T, Rajeswaran H, Haddad S, Shahi A, Parvizi J. Increased risk of periprosthetic joint infections in patients with hypothyroidism undergoing total joint arthroplasty. J Arthroplasty 2016 Apr;31:868-71. DOI: https://doi.org/10.1016/j.arth.2015.10.028.

47. Bozic K, Lau E, Kurtz S, Ong K, Berry D. Patient-related risk factors for postoperative mortality and periprosthetic joint infection in Medicare patients undergoing TKA. Clin Orthop Relat Res 2012 Jan;470:130-7. DOI: https://doi.org/10.1007/s11999-011-2043-3

48. Bozic K, Lau E, Kurtz S, et al. Patient-related risk factors for periprosthetic joint infection and postoperative mortality following total hip arthroplasty in Medicare patients. J Bone Joint Surg Am 2012 May;94:794-800. DOI: https://doi.org/110.2106/jbjs.k.00072.

49. Lindner M, Nosseir O, Keller-Pliessnig A, Teigelack P, Teufel M, Tagay S. Psychosocial predictors for outcome after total joint arthroplasty: A prospective comparison of hip and knee arthroplasty. BMC Musculoskelet Disord 2018 May;19(1):159. DOI: https://doi.org/10.1186/s12891-018-2058-y

50. Smith E, Jirka C, Thom N, et al. Total hip and total knee arthroplasty in a case-series of patients with tardive dyskinesia. Recent Adv Arthroplast 2018;2(1):43-6. DOI: https://doi.org/10.31700/2576-6716.000111

51. Etcheson J, Gwam C, George N, Virani S, Mont M, Delanois R. Patients with major depressive disorder experience increased perception of pain and opioid consumption following total joint arthroplasty. J Arthroplasty 2018 Apr;33(4):997-1002. DOI: https://doi.org/10.1016/j.arth.2017.10.020

52. Britteon P, Cullum N, Sutton M. Association between psychological health and wound complications after surgery. Br J Surg 2017 May;104(6):769-76. DOI: https://doi.org/10.1003/bjs.1-474

53. Nocon A, Henry M, Russell C, et al. The influence of obesity on the infection risk of prosthetic ioint infection in the geriatric orthopedic population. Open Forum Infect Dis 2017 Oct;4(Suppl 1):S98. DOI: https://doi.org/10.1093/ofid/ofx163.076

54. TjeertesE, HoeksS, BeksS, ValentijnT, HoofwijkA, StolkerRJ. Obesity--a risk factor for postoperative complications in general surgery [published correction appears in BMC Anesthesiol 2015;15:155]? BMC Anesthesiol 2015;15:112. DOI: https://doi.org/10.1186/s12871-015-0096-7

55. Pierpont Y, Dinh T, Salas R, et al. Obesity and surgical wound healing: A current review. ISRN Obes 2014 Feb;2014:638936. DOI: https://doi.org/10.1155/2014/638936

56. Epstein N. Preoperative, intraoperative, and postoperative measures to further reduce spinal infections. Surg Neurol Int 2011 Feb;2:17. DOI: https://doi.org/10.4103/2152-7806.76938

57. Flegal K, Graubard B, Williamson D, Gail M. Excess deaths associated with underweight, overweight, and obesity. JAMA 2005 Apr;293(15):1861. DOI: https://doi.org/10.1001/jama.293.15.1861

58. Buzby G, Mullen J, Matthews D, Hobbs C, Rosato E. Prognostic nutritional index in gastrointestinal surgery. Am J Surg 1980 Jan;139:160. DOI: https://doi.org/10.1016/0002-9610(80)90246-9

59. Flegal K, Kit B, Graubard B. Body mass index categories in observational studies of weight and risk of death. Am J Epidemiol 2014 Aug;180:288-96. DOI: https://doi.org/10.109.3/aje/kwu111

60. Alfonso D, Howell R, Caceres G, Kozlowski P, Di Cesare P. Total hip arthroplasty in the underweight. J Arthroplasty 2008 Oct;23:956-9. DOI: https://doi.org/10.1016/j arth.2007.09.008

61. Somayaji R, Barnabe C, Martin L. Risk factors for infection following total joint arthroplasty in rheumatoid arthritis. Open Rheumatol J 2013 Nov;7:119-24. DOI: https://doi.org/10.2174/1874312920131210005

62. Ringbäck Weitoft G, Eliasson M, Rosen M. Underweight, overweight and obesity as risk factors for mortality and hospitalization. Scan J Public Health 2008 Mar;36:169-76. DOI: https://doi.org/10.1177/1403494807085080

63. Fryar C, Carroll M, Ogden C. Prevalence of underweight among adults age 20 and over: United States, 1960-1962 through 2011-2012. Atlanta: Centers for Disease Control and Prevention National Center for Health Statistics; 2016. Accessed February 4, 2020. https://www.cdc.gov/nchs/data/hestat/underweight_child_15_16/underweight_child_15_16.htm

64. Horwich, T, Kalantar-Zadeh K, MacLellan R, Fonarow G. Albumin levels predict survival in patients with systolic heart failure. Am Heart J 2008 May;155:883-9. DOI: https://doi.org/10.1016/j.ahj.2007.11.043

65. Ellsworth B, Kamath AF. Malnutrition and total joint arthroplasty. J Nat Sci 2016;2(3):e179.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926871/

66. Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement: A retrospective review of 6489 total knee replacements. Clin Orthop 2001 Nov;(392):15-23.

67. Font-Vizcarra L, Lozano L, Rios J, Forga M, Soriano A. Preoperative nutritional status and postoperative infection in total knee replacements: A prospective study of 213 patients. Int J Artif Organs 2011 Sep;34(9):876-81. DOI: https://doi.org/10:5301/ijao.5000025

68. Walls J, Abraham D, Nelson C, Kamath A, Elkassabany N, Liu J. Hypoalbuminemia more than morbid obesity is an independent predictor of complications after total hip arthroplasty. J Arthroplasty 2015 Dec;30:2290-5. DOI: https://doi.org/10.1016/j.arth.2015.06.003

69. Del Savio G, Zelicof S, Wexler L, et al. Preoperative nutritional status and outcome of elective total hip replacement. Clin Orthop Relat Res 1996 May;326:153-61. DOI: https://doi.org/10.1097/00003086-199605000-00018

70. Gherini S, Vaughn B, Lombardi A, Mallory T. Delayed wound healing and nutritional deficiencies after total hip arthroplasty. Clin Orthop Relat Res 1993 Aug;293:188-95.

71. Jaberi FM, Parvizi J, Haytmanek CT, Joshi A, Purtill J. Procrastination of wound drainage and malnutrition affect the outcome of joint arthroplasty. Clin Orthop Relat Res 2008 Jun;466:1368-71. DOI: https://doi.org/10.1007/s11999-008-0214-7

72. Cross MB, Yi PH, Thomas CF, Garcia J, Della Valle CJ. Evaluation of malnutrition in orthopaedic surgery. J Am Acad Orthop Surg 2014 Mar;22:193-9. DOI: https://doi.org/10.5435/JAAOS-22-03-193

73. Morey V, Song Y, Whang J, Kang Y, Kim T. Can serum albumin level and total lymphocyte count be surrogates for malnutrition to predict wound complications after total knee arthroplasty? J Arthroplasty 2016 Jun;31:1317-21. DOI: https://doi.org/10.1016/j.arth.2015.12.004

74. Piuzzi N, George J, Khlopas A, et al. High prevalence and seasonal variation of hypovitaminosis D in patients scheduled for lower extremity total joint arthroplasty. Ann Transl Med 2018 Aug;6(16):321. DOI: https://doi.org/10.21037/atm.2018.08.21

75. Maier G, Horas K, Seeger J, et al. Is there an association between periprosthetic joint infection and low vitamin D levels? Int Orthop 2014 Jul;38(7):1499-504. DOI: https://doi.org/10.1007/s00264-014-2338-6

76. Bolland M, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: A systemic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 2018 Nov;6(11):847-58. DOI: https://doi.org/10.1016/S2213-8587(18)30265-1

77. The Lancet. The Lancet Diabetes & Endocrinology: Vitamin D supplementation in adults does not prevent fractures, falls or improve bone mineral density. EurekAlert! Public Release. Published October 4, 2018. Accessed February 8, 2020. https://www.eurekalert.org/pub_releases/2018-10/tl-tld100318.php

78. Ragni M, Crassett L, Herndon J. Postoperative infection following orthopaedic surgery in human immunodeficiency virus-infected haemophiliacs with CD4 counts < 200/mm³. J Arthroplasty 1995 Dec;10:716-21. DOI: https://doi.org/10.1016/s0883-5403(05)80065-8

79. Falakassa J, Diaz A, Schneiderbauer M. Outcomes of total joint arthroplasty in HIV patients. Iowa Orthop J 2014;34:102-6.

80. Bedair HS, Schurko BM, Dwyer MK, Novikov D, Anoushiravani AA, SchwarzkopfR. Treatment for chronic hepatitis C prior to total hip arthroplasty significantly reduces periprosthetic joint infection. J Arthroplasty 2019 Jan;34(1):132-5. DOI: https://doi.org/10.1016/j.arth.2018.09.036

81. Varin D, Chen J. Does liver disease (hepatitis C, cirrhosis) predispose patients to SSI/PJI? If so, what optimization should be undertaken prior to operating on patients with hepatitis C? In: American Academy of Orthopaedic Surgeons diagnosis and prevention of periprosthetic joint infections clinical practice guideline: Hip and knee, part II. Published March 11, 2019. Accessed November 18, 2019. https://www5.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/guidelines/PJI%20Clinical%20Practice%20Guideline%20Final%203.pdf

82. Jiang S, Schairer W, Bozic K. Increased rates of periprosthetic joint infection in patients with cirrhosis undergoing total joint arthroplasty. Clin Orthop Relat Res 2014 Aug;472(8):2483-91. DOI: https://doi.org/10.1007/s 11999-014-3593-y

83. American Society of Anesthesiologists. New research suggests sleep apnea screening before surgery. Published September 23, 2014. Accessed November 17, 2019. https://www.asahq.org/about-asa/newsroom/news-releases/2014/09/new-research-osa-screening

84. Lyons M, Bhatt N, Kneeland-Szanto E, et al. Sleep apnea in total joint arthroplasty patients and the role for cardiac biomarkers for risk stratification: An exploration of feasibility. Biomark Med 2016 Mar;10(3):265-300. DOI: https://doi.org/10.2217/bmm.16.1

85. Popa R. Patients with sleep apnea more likely to experience complications after total joint arthroplasty: 3 study details. Becker’s ASC Review. Published January 3, 2019. Accessed November 17, 2019. https://www.beckersasc.com/orthopedics-tjr/patients-with-sleep-apnea-more-likely-to-experience-complications-after-total-joint-arthroplasty-3-study-details.html

86. Flink B, Rivelli S, Cox E, et al. Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly. Anesthesiology 2012 Apr;116(4):788-96.https://doi.org/10.1097/aln.0b013e31824b94fc

87. Youssef J, Novosad SA, Winthrop KL. Infection risk and safety of corticosteroid use. Rheum Dis Clin North Am 2016 Feb;42(1):157-76. DOI: https://doi.org/10.1016/j.rdc.2015.08.004

88. Perhala R, Wilke W, Clough J, Segal A. Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum 1991 Feb;34:46-52. DOI: https://doi.org/10.1002/art.1780340204

89. Eka A, Chen A. Patient-related medical risk factors for periprosthetic joint infection of the hip and knee. Ann Transl Med 2015 Sep;3(16):233. DOI: https://doi.org/10.3978/j.issn.2305-5839.2015.09.26

90. Rezapoor M, Parvizi J. Prevention of periprosthetic joint infection. J Arthroplasty 2015 Jun;30:902-7. DOI: https://doi.org/10.1016/j.arth.2015.02.044

91. Ding T, Ledingham J, Luqmani R et al. BSR and BHPR rheumatoid arthritis guidelines on safety of anti-TNF therapies. Rheumatology (Oxford) 2010 Nov;49:2217-9. DOI: https://doi.org/10.1093/rheumatology/keq249a

92. Saag K, Teng G, Patkar N, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008 Jun;59:762-84. DOI: https://doi.org/10.1002/art.23721

93. Cizmic Z, Feng J, Huang R, et al. Hip and knee section, prevention, host related: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty. October 2018-February 2019;34(2):S255-70. DOI: https://doi.org/10.1016/j.arth.2018.09.010

94. Tan T, Rajeswaran H, Haddad S, Shahi A, Parvizi J. Increased risk of periprosthetic joint infections in patients with hypothyroidism undergoing total joint arthroplasty. J Arthroplasty 2016 Apr;31:868-71. DOI: https://doi.org/10.1016/j. arth.2015.10.028

95. Buller LT, Rosas S, Sabeh KG, Roche MW, McLawhorn AS, Barsoum WK. Hypothyroidism increases 90-day complications and costs following primary total knee arthroplasty. J Arthroplasty 2018 Apr;33:1003-7. DOI: https://doi.org/10.1016/j.arth.2017.10.053

96. Lieu D, Harris I, Naylor J, Mittal R. Review article: Total hip replacement in haemodialysis or renal transplant patients. J Orthop Surg (Hong Kong) 2014 Dec:22;393-8. DOI: https://doi.org/10.1177/230949901402200325

97. Baek S. Identification and preoperative optimization of risk factors to prevent periprosthetic joint infection. World J Orthop 2014 Jul;5:362-7. DOI: https://doi.org/10.5312/wjo.v5.i3.362

98. Huang Z, Ma J, Shen B, Pel F. Combination of intravenous and topical application of tranexamic acid in primary total knee arthroplasty: A prospective randomized controlled trial. J Arthoplasty 2014;29(12):2342-6. DOI: https://doi.org/10.1016/j.arth.2014.05.026

99. Huang Z, Xie X, Li L, et al. Intravenous and topical tranexamic acid alone are superior to tourniquet use for primary total knee arthroplasty: A prospective, randomized controlled trial. J Bone Joint Surg Am 2017 Dec;99(24):2053-61. DOI: https://doi.org/10.2106/jbjs.16.01525

100. Huang Z, Huang Q, Zeng H. Tranexamic acid may benefit patients undergoing total hip/knee arthroplasty because of haemophilia. BMC Musculoskelet Disord 2019 Sep;20:402. DOI: https://doi.org/10.1186/s12891-019-2767-x

101. Park I, Lee S, Park I, et al. Asymptomatic peripheral vascular disease in total knee arthroplasty: Preoperative prevalence and risk factors. J Orthop Traumatol 2015 Mar;16(1):23-6. DOI: https://doi.org/10.1007/s10195-014-0305-z

102. Mikkonen J, Raphael D. Behavioral health services for people who are homeless: A review of the literature. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2013. https://store.samhsa.gov/system/files/sma13-4734_literature.pdf

103. Schrag J. Health care for the homeless: Essential hospitals and community partnerships. Washington, DC: America’s Essential Hospitals; 2015. Accessed March 1, 2020. http://essentialhospitals.org/wp-content/uploads/2015/07/Homelessness-Quality-Brief-June-2015.pdf

104. Purtill C. Medical optimization readies patients for successful orthopedic surgery. OrthopedicsToday. Published December 2018. Accessed October 19, 2019. https://www.healio.com/orthopedics/business-of-orthopedics/news/print/orthopedics-today/%7B94da9466-4ed0-4775-a60a-a81601abd240%7D/medical-optimization-readies-patients-for-successful-orthopedic-surgery?page=7

105. Qasim S, Swann A, Ashford R. The DAIR (debridement, antibiotics and implant retention) procedure for infected total knee replacement—a literature review. SICOT J 2017 Jan;3:2. DOI: https://doi.org/10.1051/sicotj/2016038

106. Mahyudin F, Hernugrahanto K, Lumban-Gaol I. Can debridement, antibiotics, and implant retention (DAIR) be utilized in the treatment of acute PJI with a megaprosthesis? Second International Consensus Meeting (ICM) on Musculoskeletal Infection. Published 2019. Accessed October 15, 2019. https://icmphilly.com/questions/can-debridement-antibiotics-and-implant-retention-dair-be-utilized-in-the-treatment-of-acute-periprosthetic-joint-infection-pji-with-a-megaprosthesis/

107. Berbari E, Osmon D, Carr A, et al. Dental procedures as risk factors for prosthetic hip or knee infection: A hospital-based prospective case-control study. Clin Infect Dis 2010 Jan;50:8-16. DOI: https://doi.org/10.1086/648676

108. Berbari E, Hanssen A, Duffy M, et al. Risk factors for prosthetic joint infection: Case-control study. Clin Infect Dis 1998 Nov;27:1247-54. DOI: https://doi.org/10.1086/514991

109. Poss R, Thornhill T, Ewald F, Thomas W, Batte N, Sledge C. Factors influencing the incidence and outcome of infection following total joint arthroplasty. Clin Orthop Relat Res 1984 Jan-Feb;182:117-26.

110. Fitzgerald R, Nolan D, Ilstrup D, Van Scoy R, Washington J, Coventry M. Deep wound sepsis following total hip arthroplasty. J Bone Joint Surg Am 1977 Oct;59:847-855.

111. Bozic K, Katz P, Cisternas M, Ono L, Ries M, Showstack J. Hospital resource utilization for primary and revision total hip arthroplasty. J Bone Joint Surg Am 2005 Mar;87:570-6. DOI: https://doi.org/10.2106/JBJS.D.02121

112. Sierra R, Trousdale R, Pagnano M. Above-the-knee amputation after a total knee replacement: Prevalence, etiology, and functional outcome. J Bone Joint Surg Am 2003 Jun;85:1000-4. DOI: https://doi.org/10.2106/00004623-200306000-00003

113. Krijnen M, Wiisman P. Emergency hemipelvectomy as a result of uncontrolled infection after total hip arthroplasty: Two case reports. J Arthoplasty 2004 Sep;19:803-8. DOI: https://doi.org/10.1016/j. arth.2004.01.008.

114. Zimmerli W, Trampuz A, Ochsner P. Prosthetic-joint infections. N Engl J Med 2004 Oct;351:1645-54. DOI: https://doi.org/10.1056/NEJMra040181

Keywords: AAOS, American Academy of Orthopaedic Surgeons, associated risk factors, infection, optimized clinical outcomes, prosthetic joint, total joint arthroplasty