Rheumatoid Arthritis
Patients with rheumatoid arthritis have an increased risk of infection following orthopaedic procedures. Patients with rheumatoid arthritis who undergo total joint arthroplasty have a two to three times greater risk of acquiring a postoperative surgical site infection than do patients with osteoarthritis2-4. Patients with rheumatoid arthritis are frequently being treated with complex drug regimens that include nonsteroidal anti-inflammatory drugs, corticosteroids, methotrexate, and biologics, all of which have an effect on wound-healing and the risk of infection. There are insufficient data from patients who have undergone orthopaedic procedures to make evidence-based recommendations about the majority of these medications. A good working relationship with the patient's rheumatologist is critical to making decisions about these medications. Synthesis of the available data suggests the following.
Nonsteroidal Anti-Inflammatory Drugs
While nonsteroidal anti-inflammatory drugs do not seem to increase transfusion requirements, morbidity, and mortality directly, they may increase intraoperative and postoperative bleeding. Increased bleeding may lead to a postoperative infection, especially in already compromised hosts5,6. Use of medications with short half-lives (ibuprofen and indomethacin) should be discontinued one to two days before surgery. Use of drugs with longer half-lives (naproxen) should be discontinued three days before surgery. Aspirin use should be discontinued seven to ten days before surgery to allow regeneration of unaffected platelets. While cyclooxygenase-2 (COX-2)-specific nonsteroidal anti-inflammatory drugs may not be associated with as much bleeding as non-COX-2-specific nonsteroidal anti-inflammatory drugs, bone healing may be affected by the latter. As such, the data are controversial with regard to the best way to handle these newer drugs.
Corticosteroids
Inadequate doses of corticosteroids lead to disease flares and, in rare instances, adrenal insufficiency. Corticosteroids have been shown to increase infection rates and affect wound-healing7. In general, all patients on chronic corticosteroid therapy should receive their regular dose of corticosteroids perioperatively.
The use of stress dose steroids remains controversial, and guidelines are difficult to establish. Stress dose steroids should probably not be routinely prescribed but should be individualized on the basis of the length of time for which steroid treatment has been utilized, the anticipated stress level of the surgery, and the presence of other risk factors for infection5,6.
Methotrexate
Most studies on the use of methotrexate perioperatively have not shown an increased risk of infection. The dose of methotrexate in many of these studies, however, was lower than the doses often used today. In general, use of methotrexate should not be discontinued perioperatively. Patients with renal insufficiency (preoperatively or postoperatively), poorly controlled diabetes, lung or liver disease, or a history of alcohol abuse should discontinue using methotrexate preoperatively5,6. This recommendation is especially important for patients undergoing high-stress procedures such as an arthroplasty or tumor resection.
Other Disease-Modifying Antirheumatic Drugs
Very little data are available to enable one to make recommendations about medications such as hydroxychloroquine, azathioprine, leflunomide, or sulfasalazine. Hydroxychloroquine has few immunosuppressive properties, and it appears safe for patients to continue to use it perioperatively. The other medications have immunosuppressive properties, and some interfere with warfarin dosing5,6. Consultation with a rheumatologist preoperatively is highly recommended.
Biologics: Tumor-Necrosis-Factor (TNF) Antagonists and Interleukin-1 (IL-1) Antagonists
Medications such as etanercept, adalimumab, and infliximab are TNF antagonists. Serious infection is a known complication of TNF-inhibitor therapy8. However, perioperative use of such therapy has been shown to be safe in foot and ankle surgery9. Anakinra is an IL-1 antagonist. There are minimal data and experience on which to base strict recommendations about either of these classes of drugs. At this time, a conservative approach should be taken. For patients undergoing intensive procedures in particular, these medications should be withheld preoperatively for at least one dosing cycle and postoperatively until adequate wound-healing is observed.
Human Immunodeficiency Virus (HIV)
The increased longevity of HIV-positive patients has created a new subset of potential candidates for total joint replacements and other orthopaedic procedures10. Several retrospective reports, most involving small numbers of patients, have provided mixed results. Whereas some studies showed an alarming rate of postoperative infection in these patients, other studies did not11-15. Prospective randomized studies on this topic are lacking.
Studies from outside orthopaedics, however, suggest that specific risk factors influencing operative morbidity, especially infections related to wound-healing, include an absolute CD4 count of <200 cells/mm3 or a viral load of >10,000 copies/mL16. As such, every attempt should be made to coordinate care with infectious disease specialists and optimize these patients’ immune systems. It is imperative to try to diminish and/or eliminate other modifiable risk factors (injection drug use, smoking, serum glucose level, and obesity) and optimize psychosocial issues prior to elective surgical treatment14.
Diabetes Mellitus and Hyperglycemia
Diabetes has been associated with an increased risk of surgical site infection in several orthopaedic areas4,17. While this "diabetic disadvantage" may be due, in part, to the impact of the pathologic changes resulting from the diabetes, it is more likely that the acute effects of perioperative hyperglycemia are even more detrimental18.
The increased risk of infection in diabetics undergoing orthopaedic surgery is often associated with complications related to wound-healing (Fig. 2). To achieve appropriate wound-healing in diabetic patients, their nutritional status and insulin regimen must be optimized before they undergo any surgical procedure. The primary goal of these efforts is to obtain close perioperative glucose control, not necessarily an improvement in the hemoglobin A1C level, as the latter is a marker of long-term glucose control and may take an unreasonable amount of time to improve. A recent study evaluating surgical site infection following orthopaedic spinal surgery identified hyperglycemia in patients not previously diagnosed with diabetes as a potential risk factor17. Further research is needed to evaluate whether patients who are to undergo elective orthopaedic surgery should have routine screening for diabetes and hyperglycemia, as has been done for patients who are to have cardiothoracic surgery19.
Malnutrition
Malnutrition is a known risk factor for deep infection after a variety of orthopaedic surgical procedures. Optimizing nutrition is important to ensure proper immune function and postoperative wound-healing. Patients at risk for malnutrition, such as the elderly and those who have gastrointestinal diseases, renal failure, alcoholism, cancer, or any chronic disease, should have their nutritional status checked preoperatively20-22. A total lymphocyte count of <1500/mm3 (1.5 × 109/L), a serum albumin level of <3.5 g/dL, or a transferrin level of <226 mg/dL has been associated with an increased rate of wound complications21. Other markers of malnutrition that need further study include prealbumin and retinol binding protein. Specific recommendations about nutrition should be individualized to each patient on the basis of age, nutritional status, and other comorbid conditions. Preoperative nutritional supplementation may benefit all patients with abnormal markers of nutrition23. Patients should obtain sufficient protein intake and specific daily vitamin and mineral supplementation (vitamins A and C, zinc, and copper)24,25.
Smoking
Smoking is a well-known risk factor for the development of a variety of postoperative complications including infection26. Tobacco products, including cigarettes, cause microvascular vasoconstriction due to nicotine and activation of the sympathetic nervous system. Carbon monoxide found in cigarette smoke also contributes to tissue hypoxia by binding to hemoglobin to form carboxyhemoglobin27-29. Carboxyhemoglobin has a high affinity for oxygen and decreases the delivery of oxygen to tissues30.
Smoking intervention programs have been studied extensively in several surgical disciplines including orthopaedics. It appears that such programs decrease the risk of postoperative complications, especially wound-healing, even when they are instituted four to six weeks before elective surgery31-35.
Obesity
A body mass index of =30 kg/m2, the definition of obesity, has been shown to increase the risk of postoperative complications, including surgical site infection, in several studies17,36-38. One study demonstrated that the risk of an infection was 6.7 times higher in obese patients undergoing total knee replacement and 4.2 times higher in obese patients treated with total hip replacement39.
Several factors explain this relationship. Surgical time is often longer for obese patients36. The extent of surgical dissection can be greater and lead to hematoma and/or seroma formation and subsequent prolonged drainage40. The subcutaneous fat layer is poorly vascularized. The diets of many obese patients, while high in calories, are often devoid of essential nutrients, vitamins, and minerals. Prophylactic antibiotics are often not dose-adjusted to weight, and many of these patients have inadequate antibiotic serum levels41. Obese patients undergoing surgery have significantly lower subcutaneous oxygen tensions and, compared with nonobese patients, require a significantly greater fraction of inspired oxygen (FIO2) to reach an arterial oxygen tension of 150 mm Hg42. Lastly, Type-2 diabetes mellitus and obesity share a pathogenic relationship, and both have rapidly increased in prevalence over the past decade43.
Obese patients should be counseled well in advance of elective orthopaedic procedures about methods of weight loss, including bariatric surgery when appropriate44. Improvement in the quality of their nutritional intake is also important. These patients should be screened for hyperglycemia and referred to their physician for improvement of perioperative glycemic control as needed. It is not advisable to recommend that patients lose weight in a short period of time before a surgical procedure as this leads to a catabolic state that could lead to wound-healing and infectious complications. Finally, it is recommended that surgeons collaborate with the anesthesia team preoperatively in an effort to provide an adequate dose of prophylactic antibiotics based on weight.
Colonization with Staphylococcus aureus
One of the most common organisms found in orthopaedic surgical site infections is Staphylococcus aureus. There is a strong association between nasal carriage of Staphylococcus aureus and development of Staphylococcus aureus surgical site infections. Carriers are two to nine times more likely to acquire Staphylococcus aureus surgical site infections than are noncarriers45. In patients who acquire Staphylococcus aureus surgical site infections, paired Staphylococcus aureus isolates from the wound match those from the nares 80% to 85% of the time46.
A preoperative screening and topical decolonization protocol that has been proposed and studied at length includes mupirocin ointment to the nares twice daily47. Some investigators include the use of a chlorhexidine bath once daily for five days before surgery.
Studies on this topic vary in terms of randomization, sample size, type of surgery, and method of intervention. Interpretation of the literature from a variety of disciplines suggests that a preoperative decolonization protocol may decrease the risk of surgical site infections in colonized patients48,49. Whether screening and treating all surgical patients will lead to a decrease in overall Staphylococcus aureus surgical site infections warrants additional studies50.
Until more information is obtained from such studies, it is recommended that patients at risk for Staphylococcus colonization be screened and treated preoperatively with a decolonization regimen. Risk factors for such colonization include previous methicillin-resistant Staphylococcus aureus (MRSA) infection; being a health-care worker, nursing home patient, or prisoner; and contact with a patient who has MRSA colonization. In patients who are found preoperatively to be carriers of MRSA, use of antibiotics such as vancomycin in place of (or possibly in addition to) cefazolin as a prophylactic antibiotic just prior to the surgical incision may be beneficial, although strict guidelines cannot be established. Similar prophylactic antibiotic choice decisions should be considered in hospitals with antibiogram data that reveal a high percentage of Staphylococcus resistance51.
Poor Oral Health
It is well known that bacteremia after dental procedures can cause hematogenous seeding of bacteria onto joint implants, both in the early postoperative period and for many years following implantation52-55. Prophylactic antibiotic prophylaxis prior to dental intervention may be beneficial in certain patients who have previously undergone total joint replacement surgery, although debate over this topic continues56,57.
An equally rational approach to diminishing the risk of surgical site infections may be to finish any anticipated dental treatment prior to elective orthopaedic surgery58,59. Decayed teeth, untreated dental abscesses, advanced gingivitis, and periodontitis can all progress to become potential sources of infection. Inadequate patient education, financial constraints, and dental phobias often lead to patients ignoring their dental health. Although we are not aware of any scientific studies directly showing the benefits of preoperative dental screening, this low-risk, common-sense approach, previously advocated by cardiac surgeons for their patients, may prove beneficial.
Urinary Tract Infections
Urinary tract infections are generally classified into upper and lower-tract infections. Lower-tract infections, particularly cystitis, are more common than upper-tract infections in patients being evaluated for elective orthopaedic surgery. Postoperative urinary tract infection has been identified as a risk factor for periprosthetic joint infection in several studies60, although not all. Deep infection in the involved joint after hip or knee arthroplasty may be the result of hematogenous seeding from the urinary tract. It is unclear whether there is an association between preoperative bladder infections and deep infection at the site of an arthroplasty implant. However, patients should be asked preoperatively about urinary tract symptoms, and synthesis of the literature does allow some recommendations61,62.
- If symptoms are present, one should consider obtaining a urinalysis and urine culture.
- If symptoms are not present, one should consider obtaining a urinalysis and urine culture for patients with other risk factors for postoperative surgical site infection. Elderly patients often do not have classic symptoms of urinary tract infection such as dysuria, urgency, and/or frequency.
One can proceed with surgery when:
- bacteriuria is present without symptoms of urinary irritation or obstruction. Patients with urine colony counts of >103/mL should be treated with a postoperative course of an appropriate oral antibiotic.
- bacteriuria is present with irritative symptoms in combination with a bacterial count of <103/mL.
- urinalysis does not suggest infection.
One should consider postponing surgery, especially in high-risk patients, when:
- preoperative evaluation reveals symptoms related to obstruction of the urinary pathway.
- the patient has dysuria and urinary frequency symptoms in combination with a bacterial count >103/mL on urine culture.
Preoperative Anemia
Some reports have indicated that postoperative anemia treated with allogenic blood transfusion is a risk factor for surgical site infection60,63. Several studies have shown that, when preoperative anemia is corrected, the risk of postoperative allogenic blood transfusions is diminished64. Several blood conservation regimens are available, and the literature is not clear about the best method for decreasing the risk of postoperative allogenic blood transfusion.
Screening for preoperative anemia and correcting the condition through the use of recombinant human erythropoietin (epoetin alfa) therapy has been studied in orthopaedic patients and has proven to be beneficial in some65 but not all66 instances. Epoetin alfa directly increases preoperative red-blood-cell mass, hemoglobin concentration, and hematocrit levels. Even when a patient has chosen to donate autologous blood preoperatively, erythropoietin may be used as an adjunct to further diminish the risk of postoperative allogenic blood transfusion67. Lastly, iron deficiency has been shown to be a common reason for failure of erythropoietin treatment, so iron levels need to be supplemented while the patient is being treated with recombinant erythropoietin68,69.
Local or Remote Orthopaedic Infections
Prior surgery increases the rate of deep infection after revision arthroplasty procedures. A history of an infection following the primary arthroplasty procedure increases the risk of an infection after the revision arthroplasty. One of the causes of nonunion requiring revision surgery after fracture surgery is infection70. Certainly in joint arthroplasty surgery, but probably in all types of orthopaedic surgery, serum studies should be obtained for any patient scheduled to undergo revision surgery for any reason. An elevated leukocyte count with differential, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level should raise the suspicion of an underlying infection. If one of these values is elevated in a patient scheduled for arthroplasty, additional preoperative testing (aspiration and bone marrow/white-blood-cell scan) or intraoperative testing (cell counts and frozen-section sampling) should be done71,72. Evaluations for infection after other types of procedures involve similar general principles but may vary in some respects. Elective surgery should be postponed until all possible orthopaedic sources of infection in a patient have been eliminated.
Risk factors for infection have been identified for multiple orthopaedic procedures. Some of these risk factors can be eliminated or modified preoperatively. This strategy of diminishing the rate of surgical site infection is logical and should be adopted broadly.