Journal Publication

Opioid-free analgesia preserves melatonin, sleep after thyroidectomy in trial

A 96-patient randomized trial found dexmedetomidine-flurbiprofen axetil matched sufentanil on pain control while cutting nausea, vomiting and pruritus and improving sleep.

A randomized controlled trial found an opioid-free analgesia regimen improved postoperative sleep quality and preserved melatonin secretion after thyroidectomy compared with a sufentanil-based regimen.

By AppliedXLJuly 17, 2026

Executive Summary

A randomized, double-blind trial compared an opioid-free patient-controlled analgesia regimen against a standard opioid-based regimen after thyroid surgery, asking whether removing opioids from postoperative pain control could protect sleep and melatonin production.
The opioid-free regimen matched the opioid regimen on pain control while patients slept better, secreted more melatonin overnight, felt less anxious, and had fewer opioid-related side effects.
The result gives postoperative care a concrete physiological account, preserved melatonin secretion, for why cutting opioids from multimodal analgesia can improve sleep after surgery, rather than resting on sleep-questionnaire scores alone.

The question

Opioids are a mainstay of postoperative pain control but are known to disrupt sleep architecture and suppress melatonin, the hormone that governs the sleep-wake cycle. The trial asked whether an opioid-free patient-controlled intravenous analgesia (PCIA) regimen, built on the sedative dexmedetomidine and the anti-inflammatory flurbiprofen axetil, could relieve postoperative pain after thyroidectomy as effectively as a standard sufentanil-based opioid regimen while better protecting sleep and melatonin secretion. Dexmedetomidine-flurbiprofen

How it was done

The trial randomized 96 patients undergoing thyroidectomy to opioid-free PCIA (dexmedetomidine, flurbiprofen axetil, and ondansetron) or opioid PCIA (sufentanil and ondansetron), started five minutes before surgery ended. The primary outcome was postoperative sleep quality, measured with the Richards-Campbell Sleep Questionnaire (RCSQ) before surgery and on postoperative days 1 and 2. Secondary measures included urinary 6-sulfatoxymelatonin excretion (a marker of nocturnal melatonin secretion), detailed sleep parameters, anxiety, pain intensity on the Visual Analog Scale, sedation on the Ramsay Sedation Scale, and adverse events, tracked through postoperative hour 48. Dexmedetomidine-flurbiprofen

The result

Patients on the opioid-free regimen scored higher on the RCSQ at both postoperative day 1 and day 2, indicating better sleep quality, with p<0.001 at both time points. Urinary 6-sulfatoxymelatonin excretion was higher in the opioid-free group at the same two time points (p<0.001), consistent with less suppression of nocturnal melatonin secretion. Patients in that group also fell asleep faster, woke less often overnight, slept longer in total, and reported lower anxiety, all with p<0.01 or better. Dexmedetomidine-flurbiprofen

Pain control and side effects

Pain intensity and sedation levels were comparable between the two regimens at every measured time point through 48 hours, indicating the opioid-free regimen controlled pain as well as the opioid-based one. The opioid-free group also had lower rates of nausea, vomiting, and pruritus (itching), the classic opioid side effects, at p<0.05. That reduction in adverse events, alongside preserved analgesia, reinforces the case that removing opioids from the regimen carried no efficacy trade-off in this population. Dexmedetomidine-flurbiprofen

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