Optimizing Important Comorbidities: Diabetes, Rheumatoid Arthritis, Peripheral Vascular Disease, and Cardiac Disease

The decision to recommend any surgery hinges on the severity of pathology and on the various risk factors the patient has while undergoing surgery. The risk–benefit analysis is an integral part of any surgeon’s thought process when offering surgery. Any surgical procedure can be classified into four categories ( Fig. 3.1 ) based on anticipated risk and benefit. In general, surgery is not recommended when the anticipated benefit is low. The ideal scenario is low risk and high benefit, thereby maximizing the success of any surgery. Sometimes it may be necessary to face a scenario where the risk is high but the potential benefit is also high (high risk, high benefit). In this case it is prudent to ask a few questions:

1.

Is the risk modifiable? If so, what are the strategies, and how effective are those?
2.

If it is a nonmodifiable risk factor, how can the patient be adequately optimized before the surgery?
3.

Is the potential benefit worth the risk of going through the surgery?

The surgeon should have an honest discussion with the patient about the risks and benefits and involve them in the decision-making process to maximize the effect of any risk modification. Also, the patients should be given reasonable achievable goals and be directed to appropriate resources to help them accomplish those goals using a team approach that is coordinated by the primary physician.

This chapter deals with optimizing diabetes, rheumatoid arthritis, peripheral vascular disease, and cardiac disease before a total knee arthroplasty (TKA).

Diabetes Mellitus

Diabetes mellitus is a chronic disease in which the body’s ability to properly regulate glucose metabolism is impaired, resulting in high blood glucose levels. Diabetes can occur when the pancreas makes little or no insulin (type 1 diabetes) or when insulin resistance develops and the body fails to respond to endogenous insulin appropriately (type 2 diabetes). Patients who have type 1 diabetes are dependent on insulin for blood glucose control, whereas patients who have type 2 diabetes may receive treatment with a variety of oral and injectable medications, including exogenous insulin. Glycemic control is important, as poorly controlled diabetes can contribute to the development of microvascular and macrovascular complications, including retinopathy, nephropathy, neuropathy, peripheral artery disease, coronary artery disease, and stroke.

Diabetes is a well-documented risk factor for postoperative complications after TKA, especially when it is not well controlled. Complications can include superficial infection, deep infection, stroke, deep vein thrombosis, pneumonia, and death. Because TKA is an elective procedure meant to improve patients’ quality of life, a marked amount of research has been devoted to determine the best way to assess and optimize diabetes before arthroplasty to reduce the risk of complications.

The American Diabetes Association provides several criteria by which a diagnosis of diabetes can be made, one of which is a hemoglobin A1c (HbA1c) >6.5% ( Box 3.1 ). The HbA1c test measures glycated hemoglobin and reflects the previous 2 to 3 months of glycemic control in the setting of the usual red blood cell life span of 120 days. HbA1c is used in diagnosing diabetes and monitoring response to antihyperglycemic treatment, so the association between HbA1c and postoperative complications in TKA has been a topic of interest. One study found an increased rate of superficial surgical site infection after TKA in patients who had a preoperative HbA1c ≥8% and/or fasting blood glucose ≥200 mg/dL Another multicenter, retrospective study found that high HbA1c levels were associated with an increased risk of prosthetic joint infection after total joint arthroplasty, and it identified a threshold HbA1c of 7.7%. Other studies, however, have shown a weak or no significant association between HbA1c and the risk of prosthetic knee infection. One study found that even though diabetic patients had a significantly higher risk for infection after TKA compared with nondiabetic patients, HbA1c was not a reliable predictor of infection. Furthermore, many diabetic patients might not be able to achieve a HbA1c ≤7.0% Considering all this, some institutions have adopted a HbA1c target of less than 8%.

Box 3.1

Criteria for the Diagnosis of Diabetes

Adapted from American Diabetes Association. Classification and diagnosis of diabetes: Standards of medical care in diabetes–2020 . Diabetes Care . 2020;43(suppl 1):S14–S31.

Fasting plasma glucose ≥126 mg/dL. Fasting is defined as no caloric intake for at least 8 hours.

Two-hour plasma glucose ≥200 mg/dL during oral glucose tolerance test (glucose load of 75 g glucose in water)

Hemoglobin A1c ≥6.5%

In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis a random plasma glucose ≥200 mg/dL

Perioperative hyperglycemia has been evaluated in patients undergoing TKA as a predictor of infection and other adverse outcomes. One study found that although HbA1c did not perfectly correlate with the risk of prosthetic joint infection, perioperative hyperglycemia did; patients with a blood glucose level ≥194 mg/dL within the 7 days before surgery were at increased risk of developing a prosthetic joint infection. Although the study did not find HbA1c to be a good predictor for prosthetic joint infection, researchers did observe a significantly higher 2-year mortality in patients with HbA1c >7%. In addition to an increased risk for prosthetic joint infection, preoperative hyperglycemia has also been implicated in increasing the risk of revision for aseptic loosening. The effect of postoperative hyperglycemia has been investigated. One study found a linear relationship between postoperative blood glucose levels and periprosthetic joint infection, further highlighting the importance of blood glucose control not only over the previous 3 months, as reflected in the HbA1c, but also during the perioperative period.

The association between the glycemic marker fructosamine and postoperative complications after total joint arthroplasty has been studied. Fructosamines are molecules formed through the glycation of proteins, and the fructosamine test measures the level of glycated proteins in the serum (mainly albumin). In patients who have diabetes mellitus the level of fructosamine molecules in the serum is elevated due the increased blood glucose levels. Because of the relatively short half-life of serum proteins, fructosamine reflects glycemic control over the previous 2 to 3 weeks. A 2017 study found that patients who had preoperative fructosamine levels of ≥292 mmol/L had a significantly higher risk of developing adverse outcomes, including prosthetic joint infection, readmission, and reoperation. Although the rate of prosthetic joint infection was 3.3-times higher in patients with HbA1c levels of ≥7%, it did not reach statistical significance. A follow-up multicenter prospective study validated fructosamine as a predictor of adverse complications, with a fructosamine level of 293 mmol/L identified as the optimal cutoff associated with adverse outcomes. Patients with elevated fructosamine levels had a 11.2-times higher rate of prosthetic joint infection, 4.2-times higher rate of readmission, and 4.5-times higher rate of reoperation compared with patients who did not have elevated fructosamine levels. HbA1c thresholds of 7% and 7.5%, however, failed to show a significant association with complications. A subset of patients who had elevated fructosamine levels, but a normal HbA1c, were found to have a higher risk of prosthetic joint infection compared with patients with low fructosamine levels and an elevated HbA1c. Because HbA1c reflects the mean blood glucose over the previous 2 to 3 months, spikes in blood glucose levels can be masked if the blood glucose levels are controlled the majority of the time. Because fructosamine reflects the mean blood glucose levels over the previous 2 to 3 weeks, spikes in blood glucose levels are not as easily diluted. Spikes in perioperative blood glucose levels, as some studies have shown, can be a strong predictor of postoperative complications.

In 2018 the International Consensus meeting evaluated the data available at the time and recommended that routine screening for diabetes and glycemic control has the potential to reduce postoperative infections. A study evaluating routine preoperative HbA1c screening in total joint arthroplasty patients found that 33.6% of patients had undiagnosed dysglycemia and 2.6% were undiagnosed diabetics. Similarly, in another study 2.5% of screened patients were found to have undiagnosed diabetes based on HbA1c ≥6.5%. Therefore consideration should be given to screening all patients being considered for TKA. The optimal glycemic marker for preoperative screening continues to be an active area of research, but an HbA1c threshold of 7.5% to 8.0% is a reasonable cutoff based on the data available at this time. Optimization of glycemic control should be multimodal and should be coordinated with the patient’s primary physician or endocrinologist, and it can include pharmacological treatment and dietary modification.

When evaluating a patient who has diabetes mellitus for TKA, it is important to remember the associated comorbidities that are frequently present with diabetes. Patients who have type 2 diabetes are frequently overweight or obese. Obesity has also been identified as a risk factor for postoperative complications after TKA. Weight loss can address obesity and improve glycemic control. The weight loss strategy can include referral to a weight management program, self-directed exercise, and dietary modifications in consultation with a dietician. Bariatric surgery can also be considered, although the utility of bariatric surgery in reducing perioperative complications remains controversial.

Diabetes can result in long-term complications, including peripheral vascular disease and renal insuffiency. The lower extremities should be carefully evaluated preoperatively, with special attention to the peripheral pulses. The presence of decreased or absent pulses, skin changes, hairlessness, or chronic wounds should prompt further evaluation. This can include ankle-brachial indices (ABIs) and referral to a vascular surgeon. With regard to renal insufficiency, modifications might need to be made with regard to perioperative medication dosages to avoid further renal injury.

Rheumatoid Arthritis

Rheumatoid arthritis is a chronic autoimmune disease that results in systemic inflammation and manifestations in various organ systems, including the musculoskeletal system, cardiovascular system, pulmonary system, hematological system, and renal system. In the musculoskeletal system rheumatoid arthritis is characterized by the presence of synovitis in multiple joints that causes pain, swelling, stiffness, deformity, destruction, and eventual loss of function. Rheumatoid arthritis predominantly affects the small joints of the hands and feet, but it can also affect larger joints such as the hips and knees. Approximately 25% of patients who have rheumatoid arthritis eventually undergo major joint arthroplasty to improve pain and function. With advances in the medical management of rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs), a decrease in the incidence of total joint arthroplasty in patients with rheumatoid arthritis has been observed. It is estimated that approximately 3% of patients undergoing total hip arthroplasty (THA) and TKA have rheumatoid arthritis, and this subset of patients deserves special attention because of the increased risk for associated comorbidities that must be considered preoperatively and the increased risk of postoperative complications.

Rheumatoid arthritis can involve the cervical spine and, through bony erosion and increased ligamentous laxity, cause instability and subluxation. Anterior atlantoaxial subluxation is the most frequently occurring deformity, although other conditions such as cranial settling and subaxial subluxation can also occur. Historically, 30% to 50% of patients who had rheumatoid arthritis also had cervical spine involvement, although the use of DMARDs has decreased the incidence and progression of cervical spine involvement. Cervical spine instability, when present, can cause cord compression that results in myelopathy and even sudden death. Because of the manipulation of the head and cervical spine involved in direct laryngoscopy and intubation, routine preoperative evaluation of the cervical spine with dynamic flexion and extension lateral radiographs in patients who have rheumatoid arthritis has been recommeneded. Consultation with a spine surgeon should be considered in patients who have abnormal radiographic findings and in patients who have signs and symptoms of myelopathy. Anesthesiologist should also be consulted for consideration of alternative intubation techniques such as fiber optic intubation.

It has been documented that patients who have rheumatoid arthritis are at increased risk of cardiac disease and cardiac events compared with the general population. Some studies have even shown that rheumatoid arthritis is comparable with diabetes mellitus as a risk factor for cardiovascular disease and myocardial infarction. In addition to coronary artery disease, cardiac manifestations of rheumatoid arthritis can include pericardial effusion and valvular disease. Because of the prevalence of heart disease in the general population and especially in patients who have rheumatoid arthritis, routine preoperative evaluation should include an electrocardiogram. If abnormalities are identified, there should be a low threshold for evaluation with an echocardiogram and consultation with a cardiologist.

Pulmonary manifestations as a result of the disease or the use methotrexate using in treating the disease can occur in patients who have rheumatoid arthritis. Interstitial lung disease is the most common type of lung involvement in rheumatoid arthritis, with less common manifestations including interstitial pneumonia, organizing pneumonia, bronchiolitis, bronchiectasis, rheumatoid nodules, and pleural effusion. In severe cases respiratory function may be compromised. Evaluation with pulmonary function tests and arterial blood gas should be considered in severe cases with evidence of dyspnea.

Rheumatoid arthritis can result in anemia of chronic disease and renal insufficiency. The prevalence of anemia in patients who have rheumatoid arthritis is estimated to range between 33% and 60%, with a higher frequency in patients who have severe disease. Correctable iron deficiencies should be addressed to maximize the patient’s preoperative hemoglobin. The utility of erythropoietin-stimulating agents to increase hemoglobin is unclear at this time. In patients who have a low hemoglobin level or in whom much blood loss is expected preoperative autologous blood donation and the use of intraoperative autologous blood recovery systems (“cell savers”) are options that can be considered. In patients who have renal insufficiency the level of renal function should be taken into account when determining medications and dosages for antibiotics and postoperative pain control.

One of the biggest challenges for the orthopedic surgeon in the management of patients who have rheumatoid arthritis and are undergoing TKA is the perioperative management of DMARDs. Patients who have rheumatoid arthritis are at increased risk of developing deep postoperative infections after TKA, with some studies showing increased risk of infection in patients taking biological DMARDs and other studies showing that continuation of methotrexate treatment does not increase the risk of complications. Because of the wide variety of DMARDs available and the sparse direct evidence on their perioperative management, in 2017 the American College of Rheumatology and American Association of Hip and Knee Surgeons published a joint guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective THA or TKA. Fig. 3.2 is a summary of their recommendations. They recommend continuation of the nonbiological DMARDs methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and doxycycline throughout the perioperative period. Biological drugs, however, should be stopped preoperatively, and surgery should be scheduled for the week after the next dose would have been administered. Tofacitinib, despite having a short half-life, is recommended to be withheld for 7 days before surgery because the duration of immunosuppression after it is stopped has yet to be determined. Biological agents may then be restarted a minimum of 14 days after the surgery as long as there is no concern for wound healing problems, surgical site infection, or systemic infection. These recommendation are conditional and may not be universally applicable, so coordination with the patient’s rheumatologist is advisable.

Patients who have rheumatoid arthritis may present with specific intraarticular and extraarticular manifestations of disease. Extraarticular manifestations include cardiac disease, pulmonary disease, cervical spine instability, anemia, and renal insufficiency. Evaluation and optimization of these associated conditions is key to minimizing the risks and optimizing the outcomes for this population when undergoing TKA.

Peripheral Vascular Disease

Peripheral vascular disease is a progressive condition in which narrowing and blockage of the circulatory system results in reduced blood flow to the extremities. Peripheral vascular disease can markedly affect outcomes after TKA. Peripheral vascular disease has been associated with an increased risk of vascular injury and an increased risk of 90-day mortality. Furthermore, decreased blood flow can result in poor wound healing, and some studies have found peripheral vascular disease to be a significant risk factor for prosthetic joint infection. In a study by DeLaurentis et al. peripheral vascular disease was present in 24 out of 1182 (2%) of the TKA patients in their cohort. There were ischemic complications in six patients, all of whom had preexisting peripheral vascular disease, highlighting the importance of preoperative assessment and optimization of peripheral vascular disease in patients undergoing TKA.

Preoperative assessment for peripheral vascular disease begins with the patient history. A medical history of diabetes should raise concern for the presence of peripheral vascular disease because these two conditions are associated. A history of prior vascular intervention such as abdominal aortic aneurysm repair, carotid endarterectomy, or coronary artery bypass graft (CABG) is indicative of atherosclerotic disease and should raise concern about the presence of peripheral vascular disease in the lower extremities. These patients should be queried for the presence of intermittent claudication, ischemic rest pain, and poor wound healing, which are indicative of critical limb ischemia. The presence of arterial calcifications on knee radiographs should also raise concern for peripheral vascular disease. In patients who have a history of vascular intervention in the operative extremity such as femoral popliteal bypass or stent placement consultation with a vascular surgeon should be obtained to assess graft function and patency because thrombosis and occlusion of the graft after TKA can have devastating consequences.

A careful preoperative physical examination should be performed on all patients undergoing TKA. On inspection, findings concerning for peripheral vascular disease include the absence of hair and the presence of skin discoloration, dystrophic nails, or chronic wounds. Popliteal and pedal pulses should be palpated. Atherosclerosis of the popliteal artery can result in popliteal aneurysm, thrombosis of which can result in critical limb ischemia and the need for amputation. The popliteal fossa should be evaluated for the presence of a pulsating mass; the majority of popliteal aneurysms can be detected by palpation. Pedal pulses, including posterior tibial artery and dorsalis pedis pulses, should be assessed and documented. Diminished, absent, or asymmetrical pulses are concerning for peripheral vascular disease and warrant further investigation.

If the history and physical examination are concerning for peripheral vascular disease, an ABI study can be obtained for further evaluation. An ABI <0.9 is considered abnormal, and consultation with a vascular surgeon should be considered. It has been shown that patients with an ABI <0.7 are at increased risk for failure and reoperation after TKA. An ABI <0.5 is indicative of severe ischemia, and revascularization may be needed before TKA.

Preoperative consultation with a vascular surgeon should be obtained in patients who have symptoms of critical limb ischemia, patients who have physical examination findings concerning for popliteal aneurysm or peripheral vascular disease, and patients who have abnormal ABI results to determine the need and timing of vascular surgical intervention. Intraoperatively, consideration should be given to performing TKA without a tourniquet in these patients. Furthermore, care should be taken when manipulating the extremity intraoperatively to avoid vascular injury, especially from hyperextension of the knee. In patients who have a femoral popliteal bypass graft, tourniquet use should be avoided. As with all patients, an immediate postoperative physical examination should be performed to assess for changes in sensation, motor function, or pedal pulses compared with the preoperative examination. A change in pedal pulses, especially in patients who have peripheral vascular disease, would be concerning for vascular injury and should warrant further workup.

Cardiac Disease

A history of cardiac disease has been shown to be a strong predictor of complications after total joint arthroplasty. Complications can include mortality, cardiovascular complications, and increased lengths of stay. Furthermore, postoperative atrial fibrillation and myocardial infarction have been shown to be associated with increased risk of developing periprosthetic joint infections. Therefore identifying and optimizing patients who have cardiac disease and cardiac risk factors is essential to decrease the risk of perioperative adverse events.

In addition to a history of cardiac disease, other factors have been identified that increase the risk of perioperative cardiac complications, including age over 80 years and hypertension requiring the use of antihypertensive medications. Several risk calculators have also been developed to help assess the risk of perioperative cardiac complications, including the Revised Cardiac Risk Index (RCRI), the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator, and the Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest. Depending on the risk calculator used, several variables are taken into account, including patient age, sex, American Society of Anesthesiologist class, patient functional status, history of cardiovascular disease, presence of diabetes, presence of hypertension, presence of renal disease, presence of chronic obstructive pulmonary disease, history of corticosteroid use, history of smoking, body mass index, and the type of surgical procedure being performed. Using the results from a risk calculator, patients can be risk stratified for surgery, and those requiring further preoperative intervention can be identified.

In 2014 the American College of Cardiology (ACC) and American Heart Association (AHA), in collaboration with the ACS and American Society of Anesthesiologists among others, published the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. They made detailed recommendations on the perioperative evaluation and management of various cardiovascular conditions, including coronary artery disease, heart failure, valvular heart disease, and arrhythmias. Their recommended stepwise approach to perioperative cardiac assessment for coronary artery disease is demonstrated in Fig. 3.3 . Because of the age of the patients undergoing TKA, medical comorbidities are often present, including hypertension, hyperlipidemia, and diabetes, which are also risk factors for coronary artery disease. In the guidelines an emergency procedure is defined as one in which life or limb is threatened if the patient is not in the operating room within 6 hours and if there is time for no or very limited or minimal clinical evaluation. Elective TKA is usually not considered an emergency, and therefore the perioperative risk of major adverse cardiac event is calculated using the ACS NSQIP, RCRI, or other perioperative risk calculator. Based on the risk stratification, further preoperative evaluation may be recommended.