Timing of a single dexmedetomidine bolus to attenuate remifentanil-induced hyperalgesia after thyroidectomy: a randomized controlled trial

BACKGROUND: Remifentanil-induced hyperalgesia (RIH) is a frequent postoperative complication. Dexmedetomidine can attenuate RIH, but whether the effect depends on the timing of administration remains unclear. The study compared two clinically relevant timings of a single dexmedetomidine bolus in patients undergoing thyroidectomy. METHODS: A total of 118 patients were randomized into three groups: Group I (dexmedetomidine before anesthesia induction), Group R (dexmedetomidine at skin closure), and Group C (control). The primary outcome was the mechanical pain threshold measured on the dominant forearm at 30 min postoperatively. Secondary outcomes included peri-incisional pain threshold, pain intensity, QoR-15 recovery score, hemodynamic stability, and adverse events. RESULTS: Mechanical pain thresholds at 30 min postoperatively were significantly higher in Groups I and R than in Group C. Only Group R showed a lower incidence of peri-incisional hyperalgesia at 24 h (P = 0.004). Resting pain scores, rescue analgesic use, and QoR-15 total scores were comparable among groups. Compared with Group I, Group R showed a more favorable intraoperative hemodynamic profile and a lower ephedrine requirement, but longer times to eye-opening and extubation. CONCLUSIONS: In adults aged 18-65 years undergoing thyroidectomy, a single dexmedetomidine bolus administered at skin closure was associated with improved quantitative sensory testing-derived measures of mechanical hyperalgesia, including a lower incidence of peri-incisional hyperalgesia at 24 h. However, these sensory-threshold findings were not accompanied by lower resting pain scores, reduced rescue analgesic use, or improved QoR-15 recovery scores. Therefore, the results should be interpreted primarily as evidence of an antihyperalgesic effect measured by mechanical sensory testing rather than as proof of a clinically established analgesic benefit. Further studies incorporating movement-evoked pain and broader patient populations are needed to clarify the clinical relevance of these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300071038, registered 30 April 2023.