Literature search and selection strategy
This article was designed as a narrative review; therefore, a targeted literature search rather than a formal systematic review was performed. PubMed/MEDLINE, Web of Science, Scopus, Embase, and Google Scholar were searched for English-language articles published from January 2000 to January 2025. Search terms included combinations of “orthopedic surgery,” “hip arthroplasty,” “knee arthroplasty,” “surgical site infection,” “anesthesia,” “general anesthesia,” “spinal anesthesia,” “neuraxial anesthesia,” “regional anesthesia,” “immune response,” “aseptic technique,” “antibiotic prophylaxis,” “dexamethasone,” “propofol,” “opioids,” “postoperative analgesia,” and “patient optimization.” Reference lists of relevant reviews and key articles were also screened manually. Eligible publications included clinical studies, systematic reviews, meta-analyses, guidelines, and mechanistic studies addressing perioperative anesthesia, infection-control practices, immune modulation, medication-related infection concerns, postoperative recovery, or patient optimization in orthopedic surgery. Studies were excluded if they were unrelated to orthopedic surgery or perioperative infection risk, did not address anesthetic management or infection-control practice, were duplicate publications, were conference abstracts without sufficient methodological detail, or were not available in English. Because this review is narrative, the following pragmatic evidence categories were used: strong evidence, for recent guidelines, randomized trials, or consistent systematic reviews directly relevant to arthroplasty infection prevention; moderate evidence, for consistent observational studies or indirect clinical evidence; low evidence, for single-center observational studies, mechanistic studies, or indirect data; and uncertain evidence, for conflicting or insufficient data. Instead, we aimed to provide a clinically oriented synthesis of current evidence and practical considerations relevant to anesthetic management and infection prevention in hip and knee arthroplasty.
Infection prevention in the anesthesia work area during hip and knee arthroplasty
Anesthesia providers may contribute to perioperative microbial transmission because they repeatedly move between the patient’s airway, vascular access devices, intravenous injection ports, medication syringes, monitoring equipment, and high-touch surfaces on the anesthesia machine and supply cart. Infection-prevention measures should therefore focus on anesthesia-specific task transitions, safe injection practice, decontamination of high-touch equipment, and separation of contaminated airway devices from clean medication and vascular-access areas (Table 1)15. Hand hygiene should be linked to anesthesia-specific task transitions rather than described only as a general precaution16. Relevant opportunities include before medication preparation, before inserting or accessing intravenous or arterial lines, before neuraxial or peripheral nerve block procedures, after airway manipulation, after glove removal, after contact with contaminated equipment or work surfaces, and before opening anesthesia-cart drawers or handling clean supplies17. Alcohol-based hand rub should be immediately accessible within the anesthesia work area, particularly during induction and emergence, when rapid contact with multiple surfaces is common18. Appropriate glove use should be guided by risk assessment19. Gloves can reduce exposure to blood-borne pathogens, but inappropriate use may facilitate cross-contamination. Improper usage might actually cause patient infections to spread20.
During airway manipulation, gloves are frequently contaminated by oral and respiratory secretions. Double gloving may be considered during tracheal intubation, with the outer gloves removed immediately after airway instrumentation. The anesthesia provider should subsequently avoid touching intravenous ports, medication syringes, keyboards, or clean supplies with contaminated gloves and should perform hand hygiene as soon as clinically feasible21.
For anesthesia-related invasive procedures, skin antisepsis should be performed before peripheral or central vascular access, arterial cannulation, neuraxial anesthesia, and regional nerve block placement. Sterile barriers, appropriate antiseptic contact time, and avoidance of repalpation after skin preparation are particularly relevant. Preparation of the orthopedic surgical incision itself should be addressed as part of the surgical team’s infection-prevention protocol rather than presented as an anesthesia-specific responsibility22. Timely administration of prophylactic antibiotics and, when indicated, intraoperative redosing, maintenance of normothermia, glycemic management, and preservation of tissue perfusion are important anesthesia-related components of infection prevention. However, because these interventions act through pharmacological and physiological pathways rather than direct control of environmental contamination, they are discussed separately in the sections on antibiotic prophylaxis and perioperative patient optimization23,24.
Agent-specific immunomodulatory mechanisms of anesthetic drugs
During the perioperative phase, anesthesia and the medications used to induce it affect the immune system, particularly immune cells (Figure 1)25. General anesthesia may influence perioperative immune responses through anesthetic drugs, surgical stress, and airway-related factors, but its independent contribution to infection risk remains difficult to determine because infection outcomes are affected by multiple patient-, surgical-, and institution-related variables26. Studies suggest perioperative immune modulation, although the clinical effect on postoperative infection varies across settings27.
Experimental studies indicate that anesthetic agents may affect several immune-cell functions, including neutrophil adhesion and migration, macrophage phagocytosis, lymphocyte activation, and natural killer-cell cytotoxicity. These effects should be discussed according to the individual drug and experimental model28. The release of pro- and anti-inflammatory cytokines is impacted by anesthesia. Key pro-inflammatory cytokines include IL-1, TNF-alpha, IL-8, and IL-6, whereas IL-10 is a major anti-inflammatory cytokine. General anesthesia has been reported to alter TNF and interferon-gamma (IFN-gamma) levels29. In particular, inhalational anesthetics affect neutrophils, NKs, DCs, and macrophages, among other immune-initiating cells30. Inhalational anesthetics impair neutrophil activity, decrease lymphocyte proliferation, cause death of the lymphocytes, and suppress cytokine production in a dose-dependent manner31. In addition to the direct effects, inhalational anesthetics also indirectly affect the endocrine response through the release of hormones such as catecholamines and glucocorticoids, as well as through the hypothalamus-pituitary-adrenal axis32.
Some observational studies have reported lower infection rates among patients receiving neuraxial anesthesia. Potential explanations include reduced neuroendocrine stress, improved analgesia, lower opioid exposure, and altered tissue perfusion. Nevertheless, these associations should be interpreted cautiously because anesthesia selection is not random and may reflect differences in patient health, surgical complexity, and perioperative care33. Regional anesthesia has been associated with lower infection rates in some studies, possibly because of reduced stress responses, better analgesia, and preserved immune function; however, causality remains uncertain because study design, patient selection, and perioperative confounding factors may influence these findings9,34. Overall, the relationship between anesthetic technique and postoperative infection should be interpreted cautiously. Although neuraxial or regional anesthesia has been associated with lower SSI rates in some studies, these findings do not prove causation. Patient selection, surgical complexity, comorbidities, institutional infection-control protocols, antibiotic timing, and postoperative recovery pathways may all influence observed infection outcomes. Therefore, anesthetic technique should not be selected solely for SSI prevention, but should be individualized according to patient risk, surgical requirements, analgesic goals, and perioperative safety9.
Effects of anesthetic drugs on infection risk
Dexamethasone affects immunological function quickly and widely35. Although concerns have been raised about the risk of postoperative infection, this risk may depend on dose, timing, patient comorbidities, glycemic control, and surgical context (Table 2), especially in susceptible groups such as patients with diabetes, immunosuppression, or other risk factors for impaired wound healing. Antibiotics used prophylactically have been proven to effectively lower postoperative infection rates36. Surgical antibiotic prophylaxis is an important component of perioperative infection prevention. In general, prophylactic antibiotics should be administered within 30–60 min before skin incision, with the duration tailored to the procedure and local protocol37,38. One well-established method of reducing the risk of infection during orthopedic procedures is the use of prophylactic antibiotics39.
Opioid exposure may also influence immune function and postoperative recovery. Limiting unnecessary perioperative opioid use through multimodal analgesia may reduce opioid-related adverse effects and may indirectly support infection prevention by improving mobilization and recovery40. Propofol is formulated as a lipid emulsion that can support bacterial growth if contamination occurs. However, infection risk is mainly related to improper handling practices (e.g., reusing syringes, failing to properly disinfect the vial's exterior, using vials from multiple patients, and continuously infusing propofol), which make contamination more likely41.
Postoperative recovery and potential infection-related pathways
Anesthetic management has a clear influence on postoperative pain, opioid requirements, mobilization, and participation in enhanced recovery pathways5. Effective multimodal analgesia may attenuate the surgical stress response and facilitate early ambulation. However, direct evidence that a specific postoperative analgesic strategy independently reduces surgical site infection after hip or knee arthroplasty remains limited42. Early mobilization is important for functional recovery and the prevention of immobility-related complications, but it should be regarded as an indirect supportive measure rather than an established SSI-prevention intervention43. Several biologically plausible mechanisms have been proposed to explain the lower infection rates observed with neuraxial anesthesia in some studies.
However, these pathways are supported mainly by physiological, mechanistic, or surrogate-outcome evidence and should not be interpreted as establishing a causal reduction in SSI: Severe postoperative pain can activate the sympathetic nervous system, potentially causing peripheral vasoconstriction and reduced tissue perfusion. Regional analgesia may attenuate this response and support tissue oxygenation. Nevertheless, evidence for this pathway is based largely on physiological measurements rather than clinical infection outcomes, and it remains uncertain whether these changes translate into a meaningful reduction in SSI44. Thus, neuraxial or peripheral nerve blocks combined with good postoperative analgesia may lower the incidence of SSI. Neuraxial anesthesia and effective regional analgesia may attenuate components of the neuroendocrine and inflammatory stress response to surgery45. Although such modulation could theoretically preserve aspects of host immune function, changes in cytokine concentrations or immune-cell activity do not necessarily translate into lower clinical infection rates8. By lowering the nonspecific pain response, neuraxial anesthesia has been demonstrated to lessen the inflammatory response after surgery46. The immune system may concentrate more effectively on the battle against microorganisms by lowering these nonspecific reactions. Peripheral nerve blocks may improve postoperative analgesia and reduce opioid requirements, thereby supporting early recovery. Whether these benefits independently influence SSI risk remains uncertain47.
Anesthesia-related complications and infection
Anesthesia-related complications can also impact infection risks. Complications such as difficult airway management, which may involve intubation and mechanical ventilation, can increase the risk of pulmonary infections48. Additionally, long-term indwelling intravenous catheters are potential sources of infection49,50. Airway management-related complications, including intubation, are linked to an increased risk of respiratory infections51. Infections related to long-term catheter use are a notable concern in perioperative settings52. Prolonged endotracheal intubation and mechanical ventilation may increase the risk of postoperative pulmonary infection, particularly in frail patients or those requiring critical care53. In routine arthroplasty practice, appropriate airway management, avoidance of unnecessary postoperative ventilation, and timely extubation when clinically feasible are more relevant than a detailed discussion of ventilator-associated pneumonia54.
Additional considerations
Patient-related factors, including comorbidities, nutritional status, smoking, anemia, nasal colonization with Staphylococcus aureus, and baseline functional capacity, are important determinants of postoperative infection risk. Therefore, preoperative optimization should be considered an essential component of infection prevention in hip and knee arthroplasty, rather than a separate perioperative issue. Diabetic patients, for example, have a higher risk of wound infections due to impaired wound healing55. Perioperative glycemic control should be included in optimization pathways23. Nutritional optimization preoperatively can improve immune function and reduce infection risks56. Diabetes and other comorbid conditions are recognized to raise the risk of postoperative infections, highlighting the need for preoperative optimization57. Preoperative glycemic optimization should be emphasized for patients with diabetes or suspected dysglycemia before elective hip or knee arthroplasty23,58,59,60. HbA1c should be assessed during preoperative risk stratification because elevated HbA1c and perioperative hyperglycemia have been associated with increased risks of surgical site infection and periprosthetic joint infection after total joint arthroplasty59,60. Although the optimal HbA1c threshold remains debated, several arthroplasty studies suggest that infection risk increases when HbA1c exceeds approximately 7.5–8.0%, and one multicenter study identified 7.7% as a more predictive threshold for periprosthetic joint infection than the commonly used 7.0% cutoff59,61. Therefore, elective surgery should ideally be scheduled after individualized glycemic optimization, while avoiding overly aggressive glucose-lowering that may increase hypoglycemia risk. Perioperatively, blood glucose should be monitored and generally maintained within guideline-recommended ranges, according to current diabetes care standards and institutional protocols23,58. Nutritional support and optimization before surgery can enhance immune responses and reduce the likelihood of infections62. Structured prehabilitation programs should also be considered as part of preoperative optimization for selected patients undergoing hip or knee arthroplasty63,64. These programs commonly include individualized physical therapy, strengthening and aerobic exercises, patient education regarding postoperative mobilization, respiratory exercises for patients with pulmonary risk factors, and psychological preparation to reduce anxiety and improve readiness for surgery65,66. Current evidence suggests that prehabilitation before total hip or knee arthroplasty may improve physical function, strength, pain, health-related quality of life, and early postoperative recovery63,64. However, direct evidence that prehabilitation independently reduces surgical site infection remains limited; therefore, prehabilitation should be presented as a supportive component of enhanced recovery and perioperative risk optimization rather than as a proven SSI-specific intervention64.
Smoking cessation is another modifiable target before orthopedic surgery. Smoking impairs tissue oxygenation, microvascular perfusion, inflammatory response, and wound healing, all of which may increase the risk of wound complications and infection65. Evidence from perioperative smoking-cessation studies suggests that stopping smoking before surgery can reduce postoperative complications, and many perioperative programs encourage cessation at least several weeks before elective arthroplasty when feasible66,67. Because smoking is a modifiable risk factor, structured preoperative smoking cessation programs should be implemented when feasible before elective hip or knee arthroplasty65,68,69. These programs may include brief counseling, referral to smoking cessation services, pharmacologic support such as nicotine replacement therapy when appropriate, and follow-up to improve abstinence before surgery5,70. Evidence from total hip and knee arthroplasty populations indicates that smoking is associated with higher risks of wound complications and prosthetic joint infection, while preoperative smoking cessation has been associated with lower infection rates after total joint arthroplasty67,71. Therefore, patients who smoke should be encouraged to stop smoking before elective surgery, ideally at least four weeks preoperatively, to reduce postoperative complications and support wound healing.
In addition, screening for nasal carriage of Staphylococcus aureus, particularly MRSA, may be considered in patients undergoing total joint arthroplasty. Preoperative screening and targeted decolonization have been reported to reduce staphylococcal surgical site infection in orthopedic populations, and AAOS guidance describes nasal mupirocin-based decolonization as a reasonable, low-risk intervention for MRSA carriers before hip and knee arthroplasty72. Some institutions may also adopt universal decolonization protocols for high-risk arthroplasty populations, depending on local epidemiology and antimicrobial-resistance patterns. Common decolonization protocols include intranasal mupirocin for 5 days and chlorhexidine bathing or wipes before surgery for patients colonized with MRSA or MSSA73,74,75. Recent SSI-prevention guidance and orthopedic recommendations support S. aureus/MRSA risk-reduction strategies in high-risk procedures, including orthopedic implant surgery23,74. Meta-analyses and orthopedic cohort studies suggest that screening and selective decolonization may reduce SSI, periprosthetic joint infection, and S. aureus-related infection after total hip or knee arthroplasty, although the effect size may vary by protocol adherence, local colonization prevalence, and concurrent antibiotic prophylaxis73,75,76.
Preoperative anemia should also be identified and corrected whenever possible, particularly in major orthopedic procedures with expected blood loss. Anemia increases the likelihood of perioperative transfusion, and transfusion exposure has been associated with adverse postoperative outcomes, including infection-related complications. Recent international consensus recommendations on anemia management advise screening most patients before major surgery and treating iron deficiency or other correctable causes early enough to optimize hemoglobin before operation77. Therefore, hemoglobin and iron status should be assessed preoperatively78. For patients with iron-deficiency anemia, iron supplementation should be considered, and intravenous iron may be preferred when surgery is scheduled soon, oral iron is not tolerated, or rapid hemoglobin optimization is required. Erythropoietin may be considered only in selected patients according to patient blood management protocols77,79. Finally, prehabilitation, including individualized exercise training, functional education, nutritional support, and psychosocial preparation, may improve physical reserve and facilitate early mobilization after arthroplasty. Although the direct effect of prehabilitation on infection prevention remains less certain, systematic review evidence in total knee and hip arthroplasty suggests potential benefits for strength, length of stay, and early recovery, which may indirectly support infection prevention by improving mobility and reducing postoperative complications80. These measures should be implemented through a multidisciplinary pathway involving surgeons, anesthesiologists, nurses, rehabilitation therapists, nutrition specialists, and primary-care or endocrine physicians when appropriate.
One of the most researched nonpharmacologic strategies for SSI prevention is maintaining normothermia, which maintains immunological function and prevents hypothermic vasoconstriction, including T cell antibody generation and neutrophil-mediated "nonspecific" oxidative bacterial death81. Supplemental oxygen was originally thought to be another crucial strategy for SSI prevention because insufficient tissue oxygen tension hinders tissue healing and the oxidative death of surgical germs. The length of surgery, hyperglycemia, obesity, and smoking are additional perioperative variables that raise the risk of SSI82. Arteriolar vasoconstriction, decreased peripheral perfusion, and decreased tissue oxygen tension are the outcomes of autonomic reactions triggered by postoperative wound pain, which notably raise sympathetic activity and plasma catecholamine82.