• The number of high-risk patients is high and is likely to significantly increase in coming years. 
• Improving the mortality in this patient cohort should be considered a priority in the UK and other countries.

• High-risk elective patients are usually assessed and identified prior to surgery.
• They may require referral for a specialist medical opinion (cardiology, respiratory, etc.) prior to scheduling for surgery if a significant co-morbidity risk factor exists.
• These patients may also require postoperative care in either intensive treatment unit (ITU) or a high dependency unit (HDU) bed.

• There are a number of identified risk factors for inpatient mortality following surgical procedures. 
• Using a predictive model, Bhattacharyya et al.¹identified five critical risk factors for postoperative mortality:

• Chronic renal failure
• Congestive heart failure
• Chronic obstructive pulmonary disease
• Hip fracture
• An age of >70 years (Table 1).

Table 1. Critical risk factors for mortality after orthopaedic surgery

• The commonest encounters with high-risk patients are:

• Those on systemic steroid therapy
• Those with diabetes
• Neutropaenic patients
• HIV-positive patients

• Exogenous steroids (even low-dose inhaled drugs) can suppress the hypothalamic–pituitary–adrenal (HPA) axis, and consequently the counter-regulatory stress hormone response to illness and injury.
• Traditionally it has been believed that stressed patients who take glucocorticoids chronically should receive “stress” steroid hormone replacement.
• Plasma ACTH and cortisol concentrations increase in response to surgery and trauma, but there is considerable patient-to-patient variability, partly due to the potential suppressive effects of anaesthesia, opioids, anti-hypertensives, age and infection.
• There is very little evidence to support the widespread use of “stress-dose” steroids to steroid-dependent patients undergoing surgery.
• Prospective studies indicate that the problem is rare even in patients at high risk.
• Based on expert opinion (there are no class I data), it has been recommended that patients on chronic glucocorticoid therapy receive:

• An additional 25 mg hydrocortisone equivalent for minor surgery.
• 50–75 mg hydrocortisone equivalent for 1–2 days for moderate procedures, e.g. joint replacement.
• 100–150 mg hydrocortisone equivalent for 2–3 days for large procedures, e.g. cardiopulmonary bypass.

• Patients with diabetes are at higher risk of needing surgical intervention than their non-diabetic counterparts.
• Peri-operative management of the patient with diabetes is potentially complex, but again, there are few level 1 studies to guide management.
• Surgical stress increases circulating glucose concentration acutely via catecholamine-mediated mobilisation of glycogen stores, and also induces transitory insulin resistance.
• After elective surgery, the effect usually subsides after 48 hours but sepsis or other prolonged stresses increase the magnitude and duration.
• Countering this increase in glucose concentration is that patients are usually nil by mouth (NBM) prior to surgery.
• For the patient with diabetes on oral hypoglycemic agents or insulin, there is also the danger of hypoglycaemia in the perioperative period.
• In type 1 diabetic patients, long-acting insulins should be stopped pre-operatively and substituted by shorter acting ones. If an evening dose is taken, it should be reduced (or omitted) if the patient will be NBM without intravenous dextrose the night before surgery.
• In type-2 diabetic patients, long-acting sulfonylureas should be stopped and substituted by short-acting agents. Metformin must always be stopped, ideally no later than 48 hours prior to surgery, because severe metabolic acidosis can precipitate. 
• Type-2 diabetic patients with marked hyperglycaemia under oral treatment should be switched to insulin before surgery.
• Controlled studies have shown the advantages of tight glycaemic control postoperatively in improving outcome and reducing the risk of nosocomial infection.

• Powerful immunotherapies and multidrug chemotherapy has significantly increased the risk of infection in this cohort of patients.
• In fact, infection is the leading cause of morbidity and mortality in patients with cancer, and neutropenia is a critical cofactor.
• Mortality from bacteraemia has been reduced by the use of empiric antibiotics from 90% in the 1950s to 10–30% currently, depending on the causative organism.
• Historically, aerobic Gram-negative bacilli (E. coli, Klebsiella, Enterobacter, Acinetobacter and especially Pseudomonas) were the most frequent pathogens.
• More recently, Gram-positive pathogens (MRSA, β-haemolytic streptococci, diptheroids, and clostridial organisms) are increasingly common.
• Invasive fungal infections are also increasing in incidence, especially with species that are likely to be resistant to fluconazole (e.g. Candida glabrata, C. krusei, C. tropicalis).

Management

• If the patient responds promptly to empiric antibiotics (within 72 hours) and no organism is identified, therapy should continue for at least 7 days, or until neutropenia resolves.
• Persistent fever and no organism should prompt evaluation for a non-infectious cause, an occult resistant organism, or inadequate therapy. 
• Antibiotics need be changed only if there is evidence of disease progression or chemical deterioration. 
• Addition of vancomycin may be considered after 72 hours. Persistent fever for more than 7 days is an indication for empiric antifungals.
• Regardless of the clinical scenario, the use of granulocyte colony stimulating factors as adjunctive therapy until the neutrophil count recovers reduces morbidity but not mortality.

• HIV is a retrovirus, which encodes its genome in RNA and transcribes genome copies in DNA using the enzyme reverse transcriptase within host cells such as the human CD4 (T helper) lymphocyte. 
• HIV infection is marked by a fall in the CD4 cell count with an associated decrease in immunity, particularly humoral immunity. 
• HIV infection results in a syndrome known as acquired immune deficiency syndrome (AIDS). 
• Despite the numerous advances made in antiretroviral therapies such as nucleoside analogues, protease inhibitors, fusion inhibitors and integrase inhibitors that reduce the viral load in the host serum and restore the numbers of host CD4 cells there is still no cure for HIV infection.
• HIV weakens the immune system and reduces a patient’s ability to fight infections. 
• Early non-orthopaedic studies reported an increased risk of infections in HIV-positive patients with an absolute CD4 cell count of <200 cells/mm³or a viral load of >10,000 copies/ml.
• There is currently no agreement in the literature on whether a HIV-positive patient’s CD4 cell count or viral load influences the risk of post-orthopaedic implant surgical infection.

Orthopaedic surgery and HIV

• Orthopaedic surgery was dramatically influenced by the HIV pandemic. 
• Early reports showed complication rates of 140% and mortality rates of 55–70%, this led to a pessimistic approach to surgery in HIV-positive patients.
• The initial perception was that these patients were prone to:

• Poor wound healing.
• High postoperative complication rates.
• A protracted postoperative period.
• Higher mortality rates.

• These early studies were skewed by the fact that these procedures were usually performed as emergencies presenting as a direct consequence of HIV.
• Effective antiretroviral therapy has dramatically improved the outlook of HIV-infected patients, and altered the nature of the surgical care that these patients require.
• If the patient’s CD4+ cell count is not depressed, the surgical outcome should be good.

Trauma

• Initial studies reported infection rates as high as 24–40%; more recently studies have showed a 3.5% infection rate in patients with CD4 cell counts as low as 200.
• The recommendations are effective prophylactic antibiotics, clean operating environment, strict theatre discipline and careful soft-tissue handling.
• HIV has been reported as a worse prognostic indicator for adult respiratory distress syndrome (ARDS) following trauma.

Open fractures

• In open fractures, where contamination has already occurred, the frequency of wound infection is high in all published series (42% in HIV-positive patients compared with 11% in controls).

Fracture union

• Untreated HIV infection may delay, and sometimes prevent, fracture union. The effects of the disease on fracture healing increases with the increase in its severity. 
• The non-union responds well to stable internal fixation and autologous bone grafting.

Late sepsis

• There may be a risk of late sepsis around implants as the immunity of the patient wanes and the disease advances. 
• This has been seen both following trauma and arthroplasty. 
• Removal of instrumentation may be indicated as the disease advances. These late infections can be due to reactivation of latent bacteria or may be because of late haematogenous seeding.

Arthroplasty

• Most of the research in this regard was on HIV-positive haemophiliac patients. 
• A large retrospective multicentre study found an increased rate of deep sepsis – as high as 18.7%. These patients are, however, at high risk of bleeding as well as bacteraemia associated with regular factor transfusions. 
• The risk of sepsis seems to be lower in non-haemophiliac HIV-positive patients but literature remains lacking.

Other implants and elective surgery

• Elective surgery seems to be safe in HIV-positive patients with better outcomes seen in controlled disease.

Wound healing

• Harrison et al.²found that in the absence of preoperative wound contamination, there is no higher incidence of wound infection regardless of the CD4 cell count. 
• Buehrer et al.³confirmed this in a similar HIV-positive haemophiliac study. 

Summary

• The initial nihilistic surgical approach to HIV-positive patients seems to have been too cautious. 
• With a few exceptions, most orthopaedic surgery can be undertaken safely in these patients, provided that one adheres to proper surgical principles. 
• Surgical outcome of HIV-positive patients approaches that of the general population with good disease control.

• RA patients have increased incidence of infection compared with the general population. 
• Increased disease severity, corticosteroid use and comorbidities are associated with an increased infection risk. 
• Low-dose methotrexate (MTX) does not appear to increase infection risk in RA patients.
• RA patients undergoing elective orthopaedic surgery.
• Initial retrospective studies of low-dose MTX on perioperative complications were small and revealed conflicting results. 
• In a retrospective study of 38 RA patients undergoing elective orthopaedic surgery, those who continued MTX had more local infections than those who stopped (four of 19 procedures vs. none of 34).
• However, further retrospective studies failed to demonstrate any increase in postoperative infection or wound healing.
• A larger prospective study of the effects of MTX in RA patients undergoing elective surgery was undertaken by Grennan et al.⁴RA patients were prospectively randomly assigned into one of the three groups:

• Group A continued MTX (88 procedures)
• Group B stopped MTX (2 weeks prior until 2 weeks post-surgery; 72 procedures)
• Group C patients not taking MTX as a control group (228 procedures)

• Patients who continued on MTX had significantly fewer (2%) surgical complications and infections within 1 year post-surgery than those in groups B (15%) and C (10.5%). There were no disease flares in group A, whereas 8% of the patients who discontinued MTX had a flare of their joint disease. 
• A previous smaller prospective study of 64 patients showed similar results.⁵
• Only one prospective study of 32 patients (19 RA patients discontinued MTX and 13 patients who continued MTX) suggested an increase in infectious complications.⁶
• Current opinion recommends that MTX be continued perioperatively for RA patients undergoing elective orthopaedic surgery unless there are specific contraindications such as impaired renal or hepatic function.

• Bell et al.⁷reported that up to 11% of patients undergoing orthopaedic surgery developed some form of acute kidney injury.
• Predictors were age at operation, male sex, diabetes, lower estimated glomerular filtration rate, use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, number of prescribed drugs and American Society of Anesthesiologists (ASA) grade.
• The importance of identifying patients at high risk, thereby potentially intervening to avoid acute kidney injury, was further emphasised by the effect of acute kidney injury on survival. The authors found that both short-term and long-term survival was poorer in patients with acute kidney injury.
• Hassan et al.⁸in a retrospective study among 599 consecutive total hip arthroplasties identified advanced age, hypertension, general anaesthesia, high ASA scores, low intra-operative systolic blood pressure (BP), and prophylactic dicloxacillin as significant risk factors.
• Low baseline systolic BP, low baseline diastolic BP, and hip fracture diagnosis were independent risk factors for postoperative increase in serum creatinine. Smoking, diabetes mellitus, high body mass index (BMI), gender, and duration of surgery were not identified as significant risk factors.

• Patients with conditions causing a high risk for thromboembolism (atrial fibrillation, mechanical heart valves or recurrent venous thromboembolism) require long-term oral anticoagulation therapy.
• These patients require anticoagulation bridging therapy perioperatively.

• Courtney et al.⁹identified six independent multivariate clinical predictors of the need for intensive care support in elderly patients with multiple medical co-morbidities undergoing total joint arthroplasty (TJA). These included:

1. A history of congestive heart failure (odds ratio (OR) 24.26).
2. Estimated blood loss >1000 mL (OR 17.36).
3. Chronic obstructive pulmonary disease (OR 13.90).
4. Intra-operative use of vasopressors (OR 8.10).
5. Revision hip arthroplasty (OR 2.71).
6. BMI >35 kg/m²(OR 2.70).