Time to first rescue opioid analgesia after perineural versus intravenous dexamethasone for PENG block in older adults undergoing total hip arthroplasty: a randomized double-blind trial

Older adults undergoing total hip arthroplasty are vulnerable to postoperative pain, opioid-related adverse effects, and metabolic disturbances. Dexamethasone can prolong regional analgesia, but intravenous administration may increase postoperative glucose concentrations; therefore, the route of administration may influence both analgesic duration and metabolic profile. This trial primarily compared the time to first rescue opioid analgesia after perineural versus intravenous dexamethasone, while prespecified secondary analyses explored opioid consumption, postoperative pain, metabolic and inflammatory profiles, motor function, and neurological safety. In this randomized, double-blind trial, adults aged 65 years or older scheduled for elective total hip arthroplasty under spinal anesthesia were assigned to receive either 4 mg of preservative-free dexamethasone perineurally as an adjunct to a pericapsular nerve group block with ropivacaine or 4 mg of intravenous dexamethasone, with an otherwise standardized regional anesthesia protocol. The primary outcome was the time to first rescue opioid analgesia within 48 h after surgery. Prespecified secondary outcomes included 48-h opioid consumption, postoperative pain scores, blood glucose concentrations, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, motor function, and neurological safety. Because the trial was powered for the primary analgesic endpoint, metabolic, inflammatory, and safety outcomes were considered exploratory. Sixty participants were included in the final analysis. The median time to first rescue opioid analgesia was 33.4 h (95% CI 15.8 to not estimable) in the pnDEX group and 12.3 h (95% CI 11.4–13.2) in the ivDEX group. The hazard of rescue opioid administration was higher in the ivDEX group (HR 2.59, 95% CI 1.31–5.13; p = 0.0027). Median 48-h intravenous morphine-equivalent opioid consumption was 0.4 mg (IQR 0.0–1.9) in the pnDEX group and 2.4 mg (IQR 0.0–3.5) in the ivDEX group. In an exploratory analysis, postoperative glucose concentrations were higher in the ivDEX group, with an overall model-based mean difference of 22.29 mg/dL (95% CI 17.74–26.85). Motor function was comparable between groups, and no neurological complications or intervention-related adverse events were observed during the 48-h follow-up. Perineural dexamethasone was associated with a longer time to first rescue opioid analgesia and lower 48-h opioid consumption than intravenous dexamethasone. Exploratory secondary analyses suggested a potentially favorable postoperative glucose profile, while motor function was similar and no safety events were observed during the 48-h follow-up. These secondary findings require confirmation in adequately powered studies. ClinicalTrials.gov,NCT06789328 Registered on 23 January 2025 prospectively registered.