Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial

Dec 30, 2025BMC medicine

Sodium oxybate given during surgery may reduce confusion after major bone surgery in older patients

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Abstract

Prophylactic intraoperative sodium oxybate reduced postoperative delirium (POD) incidence to 7.3% in older patients undergoing morning orthopedic surgery.

The overall POD incidence was 10.3% in the sodium oxybate group and 13.5% in the placebo group, with no significant difference.
Morning surgery patients showed a relative risk reduction in POD incidence when treated with sodium oxybate compared to placebo.
No significant protective effect of sodium oxybate was observed in patients undergoing afternoon surgery.
No differences in delirium severity, onset timing, or duration were noted among patients who experienced POD.
Safety assessments revealed no significant adverse effects on anesthesia recovery or hemodynamic parameters.

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BACKGROUND: Postoperative delirium (POD) represents a significant challenge in perioperative care, particularly among older surgical patients. This acute neuropsychiatric syndrome is associated with prolonged hospitalization, increased mortality, and long-term cognitive decline. Sleep disturbance has emerged as a significant modifiable risk factor for POD. Sodium oxybate (SO), a gamma-aminobutyric acid B (GABA) receptor agonist with established sleep-enhancing properties, presents a promising therapeutic approach for POD prevention. The objective of this trial was to investigate whether prophylactic intraoperative sodium oxybate reduces POD incidence in older patients (≥ 65 years) undergoing major orthopedic surgery. B

METHODS: This randomized, double-blind, placebo-controlled trial enrolled 332 older patients undergoing elective spine and joint replacement surgery. Participants received either sodium oxybate (30 mg kg) or saline after anesthetic induction. Stratified randomization allocated equal numbers to morning and afternoon surgery groups. The primary outcome was POD incidence within seven postoperative days, assessed using the Confusion Assessment Method (CAM). -1

RESULTS: POD incidence showed no significant difference between groups in unstratified population (10.3% vs. 13.5%, P = 0.372). However, subgroup analysis revealed protective effects in morning surgery patients (7.3% vs. 18.5%, relative risk (RR) = 0.395, 95% confidence intervals (CI) = 0.161-0.968, P = 0.033), while no effect was observed in the afternoon surgery group (13.3% vs. 8.5%, P = 0.318). Among patients with delirium, no significant differences were observed in delirium severity, onset timing, delirium duration, or subtype distribution after false discovery rate (FDR) correction. No significant differences were found in sleep quality, maximal pain score, or safety parameters between groups after FDR correction.

CONCLUSIONS: Intraoperative sodium oxybate demonstrates possible time-specific efficacy, significantly reducing POD incidence exclusively in older patients undergoing morning orthopedic surgery, while demonstrating an acceptable safety profile with no significant adverse effects on anesthesia recovery or hemodynamic parameters, suggesting a potential chronotherapeutic approach to POD prevention.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300078594. Registered on 2023-12-13.

Key numbers

7.3%

Decrease in POD Incidence

POD incidence in sodium oxybate group during morning surgeries.

18.5%

POD Incidence in Control Group

POD incidence in control group during morning surgeries.

8.5%

No Effect in Afternoon Surgeries

POD incidence in control group during afternoon surgeries.

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Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial

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