Total Hip or Knee Arthroplasty: Improving Infection Risk

Despite improvements in surgical practice and antimicrobial prophylaxis, surgical site infections (SSIs) are 1 of the most common health care-associated infections.¹ Emerging multidrug-resistant microorganisms increase this challenge. There is a SSI incidence of 2.5% after primary total hip arthroplasty (THA) or total knee arthroplasty (TKA).² Increasing global evidence supports the use of “enhanced recovery” arthroplasty (ERA) units, using interdisciplinary perioperative care pathways to accelerate recovery and improve outcomes for those undergoing elective THA or TKA,³ but effects of these practices on SSIs need further study. Enhanced recovery arthroplasty may involve 1 or more of the following elements⁴: (1) patient education to reduce anxiety and pain, while engaging patients in physical and occupational therapies; (2) improving nutritional status, especially hemoglobin, albumin, total lymphocyte count, and transferrin; (3) preemptive analgesia; (4) local infiltration analgesia (LIA); (5) neuromuscular electrical stimulation; (6) perioperative rehabilitation programs; (7) surgical approaches; (8) minimally invasive surgery; or (9) appropriate implant alignment and rotation. Research is still clarifying risks and benefits of some of these elements. What if reducing the likelihood of SSIs or complications could further improve arthroplasty patient outcomes? The 2 studies reviewed here^2,5 explore that possibility with intriguing results.

Reference: Romanò CL, Malizos K, Capuano N, Mezzoprete R, D’Arienzo M, Van Der Straeten C, Scarponi S, Drago L. Does an antibiotic-loaded hydrogel coating reduce early post-surgical infection after joint arthroplasty? J Bone Jt Infect. 2016;1:34–41.

Rationale: Effective short-term systemic antibiotic prophylaxis for arthroplasty may be more efficiently delivered locally and with fewer systemic side effects by a rapidly absorbable hydrogel at the surgical site where it is most needed to prevent a SSI. 

Objective: Explore clinical efficacy and safety of coating THA or TKA prostheses with an antibiotic-containing, rapidly absorbing hyaluronan and poly-(D,L-lactide) hydrogel, previously demonstrated to dissolve safely, by releasing doses of 2% to 10% of various antibiotics within 72 hours, and to prevent SSIs in rabbits receiving or not receiving concomitant systemic antibiotics. 

Methods: Consenting individuals ≥ 18 years of age, electively receiving primary or revision surgery for either a “cementless” or partially cemented total hip or knee prosthesis in 6 European centers, were randomized to receive either an appropriate antibiotic hydrogel-coated (n = 190) or a noncoated (n = 190) prosthesis. Subjects were excluded for current or planned pregnancy, breast feeding, allergy to any study material, active infection at the surgical site, immunosuppression, or if they were unwilling or unable to meet study protocol requirements. After enrollment and preoperative clinical, radiographic, and laboratory examinations, all patients received the total joint replacement, prophylactic systemic antibiotics, and deep vein thrombosis prophylaxis according to the participating institutional protocols. Each surgeon selected the type of implant, surgical approach, and patient-appropriate systemic and locally applied antibiotics in the “Defensive Antibacterial Coating” (DAC; Novagenit Srl, Mezzolombardo, Italy) reconstituted according to package insert instructions, with the surgeon’s choice of antibiotic type and dose selected from a list of compatible antibiotics. Immediately after the 3 to 5 minute preparation, the antibiotic-loaded hydrogel was spread on the prosthesis before it was implanted. Patients undergoing THA received oral indomethacin or celecoxib for 2 weeks after surgery to prevent heterotopic bone formation. Outcome measures included ASEPSIS scoring method for delayed healing, 12-item Short Form Health Survey (SD-12) scores; Harris Hip or Knee Society scores; and clinical, laboratory, and radiological (blinded to treatment) evaluations at 6 weeks and 3, 6, 12, 18, and 24 months postoperatively. Primary outcomes were absence of adverse events related to the hydrogel coating and SSIs (defined as the Centers for Disease Control and Prevention signs of infection) or unplanned postoperative antibiotic use or surgery. Secondary outcomes were delayed wound healing defined as incomplete healing, including dehiscence, necrosis, or serum leakage, 4 weeks following surgery. Descriptive statistics were tabulated using Fisher’s exact test of differences for SSI incidence between the coated and noncoated implants using P < .05 for statistical significance. 

Results: The 2 groups were comparable at baseline, with 189 patients with coated implants and 184 controls evaluable after an average of 14.5 months. Most required THA, and 28% of each group underwent revision surgery. Cefazolin was the most commonly used short-term systemic antibiotic prophylaxis in both groups. An average of 8.3 mL of hydrogel typically containing either 5% vancomycin or 3.2% gentamicin was used to coat the treated implants. The only statistically significant outcome differences between groups at the latest follow-up were higher total SF-12 mean scores for those with antibiotic-coated implants (99.9 ± 18) compared with control implants (94.7 ± 18; P = .006), accompanied by fewer SSIs in those with antibiotic-coated implants (1 or 0.6%) compared with those with control implants (11 or 6%; P = .003). 

Authors’ Conclusions: This is the first demonstration that short-term local antibiotic has clinical efficacy in reducing risk of postsurgical SSIs after joint replacement.

Reference: Sun XL, Zhao ZH, Ma JX, Li FB, Li YJ, Meng XM, Ma XL. Continuous local infiltration analgesia for pain control after total knee arthroplasty: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015;94(45):e2005. 

Rationale: Total knee arthroplasty is very effective for improving quality of life for those with end-stage knee arthritis, but related postoperative pain is so intense that it can delay mobilization and lengthen hospital stays. Continuous local infiltration analgesia (CLIA) may sustain post-TKA pain relief without side effects of morphine consumption.

Objective: Conduct a systematic review and meta-analysis of the efficacy and the safety of CLIA using a visual analogue scale (VAS) to measure pain experienced by patients at rest or mobilized during the first 24 and 48 hours after TKA. 

Methods: The authors searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, Web of Science, Wanfang Data, and Google databases from inception to January 30, 2015, for randomized controlled trials (RCTs) and similar derivative studies comparing the effects on pain, surgery time, or infection outcomes of CLIA, defined as analgesic continuously applied via catheter with a pump or bolus injection after TKA surgery. Nonrandomized studies or those on cadavers or nonclinical models were excluded. Abstracted data included sample demographics, surgical and anesthesia methods, and analgesia infusion techniques; reported pain, infection, and length of stay outcomes were measured. Pain outcomes were measured 24, 48, or 72 hours postoperatively at rest or on mobilization using a 100-point VAS or a 10-point VAS multiplied by 10. Statistical analysis used 95% confidence intervals for means of continuous variables, such as VAS scores, length of stay, or duration of surgery. Relative risk was calculated for discrete variables such as presence or absence of infection, deep vein thrombosis, prolonged wound drainage, or nausea/vomiting.

Results: Among 682 potentially relevant studies, 10 RCTs comparing CLIA with saline on 735 patients undergoing 587 TKAs qualified for meta-analysis. Of the qualifying pain data, 8 studies on 703 patients were included. Patients receiving CLIA experienced pain reduction at rest 24 hours postoperatively (P < .0001), with diminishing effect after 48 and 72 hours (P ≥ .10). Significant pain reduction compared with the saline group was reported during mobilization for 24 and 48 hours after TKA in those receiving CLIA (P < .0001). Seven RCTs on 579 patients reported increased risk of infection for those receiving CLIA as compared with continuous saline infusion (P = .02). Four RCTs on 131 subjects reported a lower risk of nausea or vomiting in patients receiving CLIA (P = .03). No consistent differences were observed in length of hospital stay or relative risk of prolonged wound drainage or deep vein thrombosis.

Authors’ Conclusions: Continuous local infiltration analgesia leads to better pain control after TKA, increasing patient comfort at rest and in motion and reducing nausea or vomiting, but it also may increase the risk of wound infection. 

These 2 studies^2,5 confirm efficacy of local interventions for antimicrobial prophylaxis of SSIs and pain management for individuals undergoing a TKA or THA. One surprise was that a locally administered pain medication may also increase patient risk of a SSI after TKA.  A closer look at the evidence that a local pain medication may increase SSI risk shows that only 4 of the 7 studies in this meta-analysis had large enough sample sizes to generate 1 or more infections. Among these, only 3 studies in which 149 subjects received CLIA with ropivacaine had more clinical infections than the saline control group. In the fourth study, 75 subjects receiving CLIA with bupivacaine had somewhat fewer infections than saline controls, though this effect was not statistically significant. Further research is needed to determine if the increased SSI risk reported by Sun et al⁵ was due to CLIA in general or was specifically associated only with ropivacaine. 

Other evidence supports local effects on arthroscopy site complications. A meta-analysis⁶ found significantly reduced wound complications, such as persistent oozing, blistering, and redness, for THA and TKA sites dressed with film dressings (2 RCTs, n = 356) or hydrofiber dressings (7 RCTs, n = 870), though SSIs were too sparse for meaningful analysis. A retrospective chart review⁷ of 1173 consecutive patients who underwent primary TKA or THA by the same surgeon from 2007 to 2015 reported dressing effects on arthroplasty SSIs.The only major change in procedure was a switch, from sterile paraffin-impregnated gauze surgical site dressings, which were associated with 9 SSIs in 568 subjects, to silver-impregnated “occlusive” (ie, moisture retentive) wound dressings (2 SSIs in 605 subjects) in June 2011. These results are sufficiently compelling to merit a RCT to clarify whether the significant (P = .03) reduction in SSIs occurred as a result of the silver in the silver-impregnated dressing, its moisture-retentive properties, or, perhaps, its less frequent dressing changes. Each of these studies provides a glimpse of how local interventions at the surgical site affects patient-reported pain, wound complications, and SSIs associated with total joint arthroplasty on patient outcomes. However, more research is needed.

Laura Bolton, PhD
Adjunct Associate Professor
Department of Surgery
Rutgers Robert Wood Johnson
Medical School
New Brunswick, NJ