The principal result of the present study is that dexamethasone added to PAI was independently associated with a reduced incidence of PONV within 24 h postoperatively in patients who underwent TKA under general anesthesia. We also demonstrated that dexamethasone added to PAI did not increase the incidence of deep incisional or organ/space SSI within the first year of TKA.
Four randomized controlled trials (RCTs) demonstrated that periarticular corticosteroid infiltration during TKA improved postoperative analgesia, but unlike the results of the present study, had no significant effect on PONV [10,11,12,13]. In one of these studies, patients received general anesthesia and periarticular ropivacaine infiltration with or without dexamethasone (6.6 mg) after bone cutting was completed, similar to the present study [10]. PAI with dexamethasone showed a lower incidence of PONV than PAI alone (5% vs 20%), with no significance due to the small sample size. In the other three studies, patients were anesthetized with a subarachnoid block, and periarticular ropivacaine infiltration containing adrenaline with or without a corticosteroid (methylprednisolone/triamcinolone) equivalent to 8 mg dexamethasone was performed after all bone cuts; corticosteroids did not decrease the incidence of PONV [11,12,13]. Since the use of a pneumatic tourniquet or surgical vacuum drain varied among these four studies, their influence on the effects of local corticosteroids remains unclear. The reason for the discrepancy between previous findings and the present results has not yet been identified; however, vasoconstriction by adrenaline included in the test solutions might have altered the effects of local corticosteroids on PONV.
The effects of perineural corticosteroid infiltration on PONV have been investigated in several RCTs. In contrast to the preceding argument, the addition of dexamethasone (8 mg) to a local anesthetic without adrenaline in patients who received a transversus abdominis block or brachial plexus block significantly decreased PONV with lower pain scores and longer analgesia postoperatively [14,15,16,17,18]. Among these studies, anesthesia (general or spinal anesthesia or conscious sedation) and the timing of nerve blocks (before or after surgery) varied. These findings suggest antiemetic effects of local dexamethasone infiltration and appear to support our results that periarticular dexamethasone infiltration during TKA was associated with a reduced risk of PONV.
Since the onset time of dexamethasone is considered to be approximately 2 h, the timing of dexamethasone administration to prevent PONV has been recommended immediately after the induction of anesthesia rather than at the end of surgery [19]. Nevertheless, peripheral nerve blocks with a local anesthetic combined with dexamethasone performed immediately after surgery were effective for PONV during the first 24 h postoperatively [15, 16, 18]. These findings suggest a wide range of timing for local dexamethasone infiltration to prevent PONV, and it is favorable for PAI during TKA because infiltration to the posterior periarticular tissue of the knee joint is technically limited after bone cutting at the late stage of surgery.
Although the mechanisms by which corticosteroids reduce PONV remain unclear, anti-inflammatory properties via prostaglandin antagonism are generally accepted. Dexamethasone may suppress local inflammatory responses at surgical sites and ameliorate inflammation triggered by the afferent stimulation of the parasympathetic nervous system to the vomiting center [20]. Ikeuchi et al. showed that PAI with dexamethasone decreased interleukin-6 levels in drainage fluid and serum C-reactive protein levels after TKA, suggesting the attenuation of local and systemic inflammation by periarticular dexamethasone infiltration [10]. This may have been involved in the effectiveness of dexamethasone added to PAI for PONV shown in the present study.
Another plausible mechanism for PONV prophylaxis by corticosteroids is opioid-sparing effects because the postoperative use of opioids has been identified as an independent predictor of PONV [8, 21, 22]. Perineural dexamethasone infiltration has been shown to reduce the incidence of PONV in association with a decrease in postoperative opioid consumption consistent with superior pain relief [14,15,16, 18]. In the present study, the multivariate analysis revealed that the addition of dexamethasone to PAI reduced the risk of PONV independently of postoperative opioid use. Further studies are needed to establish whether and to what extent opioid-sparing effects contribute to the antiemetic action of local dexamethasone infiltration.
PJI is currently the most frequently reported reason for revision in TKA [23]. Several meta-analyses of RCTs demonstrated that single periarticular corticosteroid infiltration during knee arthroplasty did not increase the incidence of wound infection [3, 4]. However, the majority of RCTs excluded patients with suboptimal glycemic control in diabetes mellitus, which has been implicated in SSI [3, 24]. In the present study, the ratio of diabetic patients was markedly lower in those who received PAI with dexamethasone, and this may have been due to the intention of surgeons to avoid the use of dexamethasone in order to prevent SSI. This selection bias may have resulted in the incidence of SSI in patients who received PAI with dexamethasone being underestimated. In addition, the duration of PJI surveillance in previous studies and ours was relatively short because the risk of PJI was the greatest within the first 2 years of TKA and remained for up to 10 years [10, 11, 13, 25, 26]. Previous studies as well as the present study were limited by the small sample size to detect extremely small differences in the incidence of PJI in TKA. Therefore, further large-scale studies with long-term observations are needed to clarify whether single periarticular corticosteroid infiltration causes PJI after TKA, particularly in diabetic patients.
The present study has several limitations. Since this was a retrospective observational study, the results obtained only revealed associations, not causal relationships between dexamethasone added to PAI and PONV prophylaxis. Furthermore, the results from a small single-center study limit the ability to generalize it to different settings. In addition, we cannot exclude the possibility of important differences in confounders influencing the relationship between dexamethasone added to PAI and PONV even after multivariable adjustments because of the possible selection bias in a retrospective design. Postoperative pain intensity, which was not directly assessed, may have confounded the present results. Furthermore, the sample size in the present study was calculated for the primary endpoint, the incidence of PONV, and was underpowered to draw a solid conclusion regarding the incidence of SSI.