Impact of perioperative glucocorticoids on glycemic control, PONV, and acute pain after primary bilateral total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Background Perioperative glucocorticoids have been increasingly used in total knee arthroplasty (TKA) to optimize postoperative recovery, with prior evidence suggesting potential reductions in postoperative nausea and vomiting (PONV) in unilateral TKA. However, their safety and efficacy in primary bilateral total knee arthroplasty (BTKA) remain uncertain, particularly regarding pain relief, glycemic control, and PONV, given the greater surgical stress and limited BTKA-specific data. This systematic review and meta-analysis aimed to evaluate the impact of perioperative glucocorticoids on these outcomes in patients undergoing primary BTKA. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, a comprehensive search of PubMed, Web of Science, and Scopus databases was conducted up to August 13, 2025. Randomized controlled trials (RCTs) comparing perioperative glucocorticoids with placebo or standard care in adult patients undergoing primary bilateral TKA were included. Data were pooled using a random-effects model, and results were expressed as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD420251152310). Primary time points were POD1–3 for pain and PACU/POD1 for glycemia; hierarchy prioritized pain with movement over rest and peak glucose values over daily means. Results Five RCTs encompassing 245 patients were included. Glucocorticoid administration led to a statistically significant but modest reduction in early postoperative pain at rest on day 1 (MD ≈ − 0.46 on VAS, 95% CI − 0.80 to − 0.12; p = 0.01) with limited clinical relevance, consistent across IV and local routes ( p = 0.73 for subgroup difference) and during activity (pooled MD = − 1.06, 95% CI − 1.64 to − 0.49; p < 0.001). Opioid consumption showed no significant reduction (MD = − 24.63 mg, 95% CI − 99.25 to 50.00; p = 0.52). Intravenous glucocorticoids were associated with a transient rise in postoperative glucose levels (pooled MD = 22.19 mg/dL, 95% CI 12.35 to 32.02; p < 0.001), but without a significant increase in wound complications (RR = 1.14, 95% CI 0.41 to 3.17; p = 0.80) or infection rates (RR = 1.00, 95% CI 0.18 to 5.69; p = 1.00). Glucocorticoid use had no significant effect on PONV (nausea: RR = 1.00, 95% CI 0.48 to 2.07, p = 1.00; I 2 = 0%; vomiting: RR = 0.96, 95% CI 0.65 to 1.42, p = 0.84; I 2 = 0%), functional recovery, or hospital stay duration. Conclusion Perioperative glucocorticoids appear to reduce early postoperative pain in bilateral total knee arthroplasty (BTKA), particularly when combined with local infiltration analgesia (LIA), without increasing complications. However, despite prior evidence suggesting PONV reduction in unilateral TKA, no significant effect was observed on PONV, opioid use, or functional outcomes in BTKA, and transient hyperglycemia may occur with intravenous administration. Further high-quality BTKA-specific randomized controlled trials are warranted before glucocorticoids can be considered a standard component of Enhanced Recovery After Surgery (ERAS) protocols.