Dexmedetomidine-flurbiprofen axetil-based opioid-free analgesia attenuates postoperative melatonin suppression and improves sleep quality after thyroidectomy: a randomized controlled trial

Objective: To determine whether an opioid-free patient-controlled intravenous analgesia (PCIA) regimen based on dexmedetomidine and flurbiprofen axetil improves postoperative sleep quality and affects nocturnal melatonin secretion compared to a sufentanil-based regimen in patients undergoing thyroidectomy. Methods: In this prospective, randomized, double-blind controlled trial, 96 patients undergoing thyroidectomy were randomly assigned to receive either opioid-free PCIA (dexmedetomidine, flurbiprofen axetil, and ondansetron) or opioid PCIA (sufentanil and ondansetron). PCIA was initiated 5 min before the end of surgery. The primary outcome was postoperative sleep quality, assessed using the Richards-Campbell Sleep Questionnaire (RCSQ). Secondary outcomes included urinary 6-sulfatoxymelatonin (6-SMT) excretion normalized to creatinine, detailed sleep parameters, anxiety levels, pain intensity, sedation levels, and postoperative adverse events. Assessments of sleep quality, urinary 6-SMT excretion, and anxiety levels were performed preoperatively (T0) and on postoperative days 1 (T1) and 2 (T2). Pain intensity (assessed by the Visual Analog Scale, VAS) and sedation levels (assessed using the Ramsay Sedation Scale) were measured at postoperative hours 1, 6, 24, and 48. Conclusion: An opioid-free PCIA regimen based on dexmedetomidine and flurbiprofen axetil provides non-inferior postoperative analgesia while attenuating postoperative melatonin suppression, improving sleep quality, reducing anxiety, and decreasing opioid-related adverse events. This opioid-sparing strategy may represent an effective approach to enhance postoperative recovery after thyroidectomy. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2400079949. First Trial Tegistration: 01/17/2024.