Background: General anesthesia may counteract the neuroprotective effects of S-ketamine, so previous trials may have underestimated the efficacy of S-ketamine to reduce postoperative delirium (POD). The authors hypothesized that administration of S-ketamine in a non–general anesthesia setting would reduce the risk of POD. Methods: This study was conducted at a high-volume arthroplasty referral center where standardized, evidence-based perioperative protocols are implemented with high fidelity. This study included 372 elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. Patients were enrolled from November 2023 to October 2024, and in-person follow-up assessments were conducted from admission to 3 days after surgery. Patients were randomized to receive either S-ketamine (n = 186) or normal saline placebo (n = 186). The primary outcome was risk of POD within 3 days after surgery. Secondary outcomes were number of POD episodes, POD onset time and duration, POD severity, POD subtype, pain score (numeric rating scale), opioid consumption, number of patients requiring rescue analgesia, sleep quality, clinical outcomes, and harms. Results: Within 3 days after surgery, 15 patients in the S-ketamine group (8.06%) developed POD, compared to 38 patients (20.43%) in the placebo group (adjusted odds ratio, 0.29; 95% CI, 0.14 to 0.63; P = 0.002). On postoperative day 1, patients in the S-ketamine group experienced significantly less pain during exercise and physical therapy and had a lower incidence of rescue analgesia use compared to the placebo group. The incidence of hallucinations, dizziness, and nightmares was higher in the S-ketamine group than in the placebo group. The incidence of other complications was low in both groups, with no statistically significant differences. Conclusions: S-ketamine can reduce risk of POD in elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. However, generalizability of these findings may be limited due to the study’s setting.

Background: Liposomal bupivacaine (LB) can provide prolonged analgesia, which may reduce patients’ opioid consumption, improve comfort, and facilitate recovery. Looser tissue and lower vascularity in the paravertebral space may facilitate LB diffusion and duration, so we investigated the effects of LB in multimodal analgesia after thoracic surgery with paravertebral block. Methods: In this single-center, double-blind, randomized, parallel-controlled trial, 102 patients undergoing elective thoracoscopic surgery were randomized 1:1 to thoracic paravertebral block with LB (6.67 mg/mL) or ropivacaine hydrochloride (RH; 0.33%). The primary outcome was opioid consumption within 72 h postoperatively. Secondary outcomes included pain ratings at 6, 12, 24, 48, and 72 h postoperatively; rescue analgesia; time to first ambulation and defecation; post-anesthesia care unit and hospital length of stay; and adverse events. Results: One patient was excluded due to block failure, leaving 101 patients (LB group, n = 51; RH group, n = 50). LB significantly reduced 72-h opioid consumption compared to RH (difference = – 181.4 mg; 95% CI: – 232.8, – 130.0 mg; P < 0.001), and fewer patients in the LB group required rescue analgesia compared to the RH group (OR: 0.33; 95% CI: 0.13, 0.82; P < 0.05). Pain scores at 24 h were lower in the LB group than RH group (difference = – 0.44; 95% CI: – 0.84, – 0.04; P < 0.05), with no differences at other timepoints. The LB group had shorter time to first ambulation than the RH group [median time (IQR): 20 (18– 24) h vs 26 (22– 32) h; HR: 3.81; 95% CI: 2.32, 6.19; P < 0.001] and shorter time to defecation [median time (IQR): 56 (42– 65) h vs 72 (57– 80) h; HR: 3.98; 95% CI: 2.46, 6.44; P < 0.001]. Conclusion: Ultrasound-guided paravertebral block with LB may reduce postoperative opioid consumption and enhance recovery in patients undergoing thoracic surgery. Trial Registration: Chinese Clinical Trials Registry Platform (chictr.org.cn): ChiCTR2400091217.

Purpose: Investigating the effectiveness of S-ketamine in reducing rebound pain (RP) following total knee arthroplasty. Patients and Methods: This study was a randomized, double-blind, placebo-controlled trial involving 356 adult patients undergoing total knee arthroplasty. Patient enrollment occurred between April and October 2023, with in-person follow-up assessments conducted from admission to 3 days post-surgery. Participants were randomly assigned to the S-ketamine group (n = 178) and the placebo group (n = 178). In the S-ketamine group, participants received a continuous intraoperative infusion of S-ketamine at a dose of 0.30 mg/(kg·h) from the completion of spinal anesthesia until the beginning of joint cavity closure, whereas the placebo group received a continuous infusion of 0.9% saline at the same volume and duration. The primary outcome was the incidence of RP within 12 hours post-surgery. Secondary outcomes included the incidence of RP within 24 hours, time to RP onset, time to first rescue analgesia, pain scores, opioid consumption, clinical outcomes, and harms. Results: RP was observed in 21.3% of patients in the S-ketamine group compared with 34.8% in the placebo group within 12 hours post-surgery (adjusted RR, 0.62; 95% CI, 0.44 to 0.88; P = 0.008). The onset of RP was significantly delayed in the S-ketamine group compared with the placebo group (unadjusted HR, 0.60; 95% CI, 0.41 to 0.88; P = 0.009). The numerical rating scale during activity and physical therapy was lower in the S-ketamine group than in the placebo group (day 1 AM: unadjusted difference, − 1; 95% CI, − 1 to 0; P = 0.011; day 1 PM: unadjusted difference, − 1; 95% CI, − 1 to 0; P = 0.003; day 1 physical therapy: unadjusted difference, − 2; 95% CI, − 2 to − 1; P < 0.001). The quality of recovery score was higher in the S-ketamine group than in the placebo group (unadjusted difference, 5; 95% CI, 5 to 5; P < 0.001). Patient satisfaction was higher in the S-ketamine group than in the placebo group (unadjusted difference, 1; 95% CI, 1 to 1; P < 0.001). Conclusions: S-ketamine effectively reduces the risk of rebound pain and delays its onset in total knee arthroplasty. Additionally, S-ketamine can reduce early pain levels, enhance recovery quality, and improve patient satisfaction.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which systemic inflammation may put individuals at increased risk of developing frailty and metabolic syndrome (MetS). However, the relationship between MetS severity and frailty remains poorly understood in individuals with RA. Further, traditional MetS diagnostic methods do not assess severity and thus may lack sensitivity in capturing subtle metabolic abnormalities. In this cross-sectional study, data from the National Health and Nutrition Examination Survey (2003–2018) were used to construct weighted multivariable logistic regression models to explore the risk association between MetS severity and frailty in RA patients. Restricted cubic spline analysis was used to examine non-linear correlation between MetS severity and frailty. We also conducted subgroup analyses and interactions as well as sensitivity analysis to evaluate the robustness of results. A total of 802 RA patients were included in this study, among whom 442 were identified as frail (52.05%). RA patients with higher MetS severity had significantly increased frailty risk [adjusted odds ratio (aOR): 1.26; 95% CI: 1.09–1.46; p = 0.003]. There was a non-linear relationship between MetS severity and frailty (p for overall < 0.001; p for non-linear < 0.001), with an inflection point at 0.089. When MetS z-score was < 0.089, there was no significant association between MetS z-score and frailty (p > 0.05), whereas the association was positive for scores ≥ 0.089 (aOR: 1.68; 95% CI: 1.30–2.17; p < 0.001). The risk of frailty increased significantly with increasing MetS severity among alcohol drinkers (aOR: 1.43; 95% CI: 1.19–1.71; p < 0.001) compared with non-drinkers (aOR: 0.97; 95% CI: 0.73–1.29; p = 0.085). Sensitivity analysis confirmed robustness of the association between MetS severity and risk of frailty. We identified a significant association between MetS severity and frailty risk in patients with RA. As MetS severity increased, the risk of frailty was higher among alcohol drinkers compared to non-drinkers. Clinicians should enhance frailty screening and management in patients with RA by incorporating assessments of MetS severity into routine practice.

Introduction: Elderly patients with impaired intrinsic capacity are at increased risk for delayed or suboptimal recovery from surgery. S-ketamine has been proven to improve postoperative recovery quality. However, limited trials are studying the postoperative recovery quality in elderly patients with impaired intrinsic capacity. Therefore, the objective of this study was to evaluate the impact of S-ketamine on the quality of recovery in elderly patients with impaired intrinsic capacity following total knee arthroplasty. Methods and analysis: This is a single-centre, randomised, double-blind, placebo-controlled trial. Participants undergoing total knee arthroplasty will be randomly assigned in a 1:1 ratio to either the S-ketamine group (n=80) or the placebo group (n=80). The S-ketamine group will undergo an intravenous infusion of S-ketamine administered at a dosage rate of 0.2 mg·kg⁻¹·h⁻¹ for 1 hour. The placebo group will receive an intravenous saline infusion at an identical rate and duration. Postoperatively, the S-ketamine group will continuously infuse S-ketamine for 48 hours using a patient-controlled intravenous device, with a fixed rate of 0.01 mg·kg⁻¹·h⁻¹, a bolus dose of 0.02 mg·kg⁻¹, a lockout period of 10 min and a maximum infusion rate of 0.13 mg·kg⁻¹·h⁻¹. In contrast, the patient-controlled intravenous device for the placebo group will not contain S-ketamine. The primary outcome is the quality of recovery scores at 24 hours following total knee arthroplasty. Secondary outcomes encompass quality of recovery scores at 48 and 72 hours postoperatively, pain scores at rest and during movement, oral morphine equivalents, sleep quality assessments, depression scores, the Barthel Index and the time to meet discharge criteria. Ethics and dissemination: Approval for the trial was granted by the Medical Ethics Committee of The Affiliated Hospital of Qingdao University (QYFYEC2024-74). Written informed consent will be obtained from each patient before enrolment. The results of this trial will be presented at scientific conferences and in peer-­reviewed scientific journals. Trial registration number: ChiCTR2400087028.

Purpose: Postoperative pain significantly impairs recovery in elderly patients. Oxycodone is widely used in the postoperative period due to its favorable safety profile and low risk of respiratory depression. To determine the minimum effective dose of intravenous oxycodone, administered in combination with postoperative patient-controlled intravenous analgesia, that achieves at least 90% efficacy in elderly patients undergoing video-assisted thoracoscopic surgery. Patients and Methods: We enrolled participants aged 65 and older who underwent thoracoscopic lobectomy. Oxycodone was administered 30 minutes before the completion of the surgical procedure. The initial dose was 0.02 mg/kg. Subsequent dose adjustments were determined based on the previous patient’s response using a biased coin design. The dose interval was 0.01 mg/kg. A positive response was defined as an NRS score ≤ 3 at cough 2 hours postoperatively. The study was terminated after 45 successful responses. Secondary endpoints included postoperative pain assessed at various time points up to hospital discharge, adverse events, sedation levels, and the occurrence of chronic pain during the postoperative period. Results: A total of sixty patients were enrolled. Among elderly patients undergoing elective VATS with multimodal analgesia, the ED90 of oxycodone was 0.104 mg/kg (95% CI: 0.095– 0.108 mg/kg). The supplementary analysis focused on patients who received at least 0.09 mg/kg of oxycodone. After adjusting for imbalanced baseline characteristics, the incidence of chronic pain in the 0.09 mg/kg dose group was significantly higher than in the 0.10 mg/kg dose group (P = 0.007). Conclusion: For thoracoscopic lobectomy in elderly individuals aged > 65 years, the ED90 of oxycodone was 0.104 mg/kg (95% CI: 0.095– 0.108 mg/kg).