Night-Before Dexmedetomidine Cut Delirium After Arthroplasty
Key Takeaways
- Older adults undergoing total hip or knee arthroplasty under general anesthesia had lower 3-day postoperative delirium with night-before intranasal dexmedetomidine than with placebo, 10.3% versus 20.7%.
- Subjective sleep quality improved with intranasal dexmedetomidine, and objective sleep gains extended from the preoperative night into the first postoperative night.
- Early pain scores were lower before anesthesia induction and on postoperative day 1, and preoperative anxiety was lower; postoperative SAS scores did not differ between groups in the detailed results, although postoperative anxiety is described elsewhere in the report as reduced.
- No severe adverse events or nasal mucosal injuries were observed, and the sleep-mediation signal remained exploratory.
In China, the Liu et al randomized clinical trial of intranasal dexmedetomidine for postoperative delirium after hip or knee arthroplasty was a single-center, double-blind, placebo-controlled study at a tertiary academic hospital in adults aged 60 years or older with American Society of Anesthesiologists (ASA) status 1 to 3 who were scheduled for total hip or knee arthroplasty under general anesthesia and had no preoperative delirium on admission Confusion Assessment Method (CAM) assessment. Patients were randomized 1:1 with concealed allocation, and patients, clinicians, outcome assessors, and statisticians were blinded. Intranasal dexmedetomidine 100 μg at 21:00 on the night before surgery, delivered as sequential sprays in each nostril, was compared with equal-volume saline placebo. The primary outcome was postoperative delirium (POD) during the first 3 postoperative days, assessed twice daily with CAM; 232 patients were randomized, 229 remained in the per-protocol set after 3 surgery cancellations.
POD within 3 days was lower with dexmedetomidine in the intention-to-treat analysis, with a relative risk of 0.50 (95% CI 0.26-0.95; P=0.030). Per-protocol analysis pointed in the same direction. Delirium severity and duration were similar between groups, and hypoactive delirium was the most common subtype. Overall, the trial linked night-before intranasal dexmedetomidine to less early postoperative delirium rather than to a change in delirium phenotype once episodes occurred.
Subjective sleep quality improved on the night before surgery, with a Richards-Campbell Sleep Questionnaire (RCSQ) mean difference of 15 (95% CI 10-20; P<0.001). Objective monitoring showed longer total, deep, light, and rapid eye movement (REM) sleep with higher sleep efficiency on the preoperative night, and those gains extended through the first postoperative night but not nights 2 or 3. Pain scores at rest and with movement were lower before anesthesia induction and on postoperative day 1, and Self-Rating Anxiety Scale (SAS) scores were lower before surgery; postoperative SAS scores were similar in the detailed results, although postoperative anxiety is described elsewhere in the report as reduced, and 15-item Quality of Recovery Questionnaire (QOR-15) scores and postoperative nausea and vomiting (PONV) were similar; the statistically different duration of postoperative care was described by the authors as clinically small. Exploratory analyses suggested that longer preoperative sleep duration may partly explain the delirium association. Hypotension, bradycardia, hypoxemia, and other monitored perioperative adverse events did not differ, and no severe adverse events or nasal mucosal injuries were observed.
The single-center setting in China and the modest number of delirium events limit generalizability and the ability to detect uncommon harms. The authors noted that sedative and bradycardic effects could theoretically have threatened blinding, although delirium assessments were performed after those effects had resolved. Brief or subtle hypoactive episodes may still have been missed, the mediation and subgroup analyses were post-hoc and cannot establish a causal pathway, sleep staging came from a consumer wearable rather than polysomnography, and the fixed 100-μg dose was not weight adjusted. The authors framed the findings as warranting confirmation in larger multicenter studies.
The authors reported that intranasal dexmedetomidine given the night before surgery was associated with lower postoperative delirium and better perioperative sleep in older adults undergoing hip or knee arthroplasty under general anesthesia. They presented sleep improvement as one possible partial explanation for that association, within the limits of exploratory mediation analyses and a single-hospital trial in China.
Clinician Questions
Which arthroplasty patients were included in the intranasal dexmedetomidine trial?
Eligible participants were adults aged 60 years or older with ASA status 1 to 3 who were scheduled for total hip or knee arthroplasty under general anesthesia at a tertiary academic hospital in China and had no preoperative delirium on admission CAM assessment. Important exclusions included major baseline cognitive impairment, significant bradyarrhythmia or conduction disease without pacing, severe hepatic dysfunction, dialysis-dependent renal disease, severe pre-existing sleep disorders or routine hypnotic use, and nasal structural problems, so the findings are bounded to that enrolled population.
How was postoperative delirium measured after hip or knee arthroplasty in the dexmedetomidine trial?
POD was the primary endpoint during the first 3 postoperative days and was assessed twice daily with CAM by trained researchers. Delirium counted if it appeared in either the morning or afternoon assessment, and family members and ward nurses were also asked about fluctuating symptoms to reduce missed cases. A 7-day delirium incidence outcome was also tracked as a secondary endpoint.
What limits the claim that better sleep explained the lower delirium rate with intranasal dexmedetomidine?
The mediation analysis was exploratory and post-hoc, using preoperative total sleep time as the mediator, and the authors stated that it could not establish a causal pathway. They also noted that the confidence interval around the mediated proportion was wide, the model did not adjust for mediator-outcome confounders or treatment-mediator interaction, and sleep staging relied on a consumer wearable rather than polysomnography.
Were any subgroups associated with a larger reduction in postoperative delirium with intranasal dexmedetomidine?
Post-hoc subgroup analyses suggested a stronger association among patients older than 69 years, those with Pittsburgh Sleep Quality Index scores above 12, those with Mini-Mental State Examination scores above 22, and those classified as frail. The authors presented these subgroup findings as exploratory signals within this trial rather than definitive evidence of effect modification.