Sleep disturbances are prevalent in older patients with osteoarthrosis or fracture who are scheduled for knee or hip replacement surgery. The occurrence of sleep disturbances is associated with worse outcomes including increased risk of delirium and cardiac events, and worsened functional recovery. Dexmedetomidine is a highly selective α2-adrenergic agonist with sedative, anxiolytic, and analgesic properties. It exerts sedative effects via activating the endogenous sleep pathways and produces a state like non-rapid eye movement sleep, which is different from opioid- and benzodiazepine-induced sedation. Esketamine is a N-methyl-D-aspartic acid receptor antagonist and has been used as an anesthetic and analgesic. Recent studies showed that low-dose esketamine has anti-depressive and sleep-promoting effects. The investigators suppose that mini-dose dexmedetomidine-esketamine combined infusion at night can improve perioperative sleep quality in patients scheduled for knee or hip replacement surgery.
Age ≥65 years and <90 years;
Scheduled to undergo unilateral knee or hip arthroplasty.
Refuse to participate;
Hypnotic therapy for sleep disorders within 3 months;
Preoperative history of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
Diagnosed as obstructive sleep apnea, or at high risk of moderate to severe obstructive sleep apnea according to the Stop-Bang questionnaire;
Parallel
Dexmedetomidine
DrugDexmedetomidine will be infused at a rate of 0.01 ml/ kg/h (0.02 μg/kg/h) from 8 pm in the night before surgery until 8 am in the third morning after surgery.
Esketamine
DrugEsketamine will be infused at a rate of 0.01 ml/ kg/h (5 μg/kg/h) from 8 pm in the night before surgery until 8 am in the third morning after surgery.
Normal saline
DrugNormal saline will be infused at a rate of 0.01 ml/ kg/h from 8 pm in the night before surgery until 8 am in the third morning after surgery.
Subjective sleep quality in the night of surgery.
Subjective sleep quality will be assessed in the next morning (between 8:00 am to 10:00 am) with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure that evaluated perception of nighttime sleep in five items, including sleep depth, sleep latency, number of awakenings, returning to sleep, and overall sleep quality. Each item was assessed with a 100-millimeter visual analog scale (score ranges from 0 to 100, with higher scores representing better sleep). The mean score of the five items represents the overall RCSQ score.
Total sleep time per night during the perioperative period.
Objective sleep quality will be monitored with the SOMNOtouch NIBP (Somnomedics GmbH, Randersacker, Germany) from 8:00 pm to 8:00 am from the night before surgery until the fifth night after surgery. Total sleep time is defined as the sum in time scored as asleep.
Sleep efficiency per night during the perioperative period.
Objective sleep quality will be monitored with SOMNOtouch NIBP (Somnomedics GmbH, Randersacker, Germany) from 8:00 pm to 8:00 am from the night before surgery until the fifth night after surgery. Sleep efficiency is defined as the ratio of total sleep time/time in bed.
Sleep onset latency per night during the perioperative period.
Objective sleep quality will be monitored with SOMNOtouch NIBP (Somnomedics GmbH, Randersacker, Germany) from 8:00 pm to 8:00 am from the night before surgery until the fifth night after surgery. Sleep onset latency is defined as time difference between time to bed and sleep start.
Wake after sleep onset per night during the perioperative period.
Objective sleep quality will be monitored with SOMNOtouch NIBP (Somnomedics GmbH, Randersacker, Germany) from 8:00 pm to 8:00 am from the night before surgery until the fifth night after surgery. Wake after sleep onset is defined as the total time scored as awake between sleep start and sleep end.
Cerebrospinal fluid and blood proteomics examination (selected patients).
Cerebrospinal fluid and blood sample will be collected. Deep proteome analysis will be performed to detect protein biomarkers including amyloid-beta, total tau, and phosphorylated tau.
Intensity of pain during the first 5 postoperative days.
Intensity of pain will be assessed twice after surgery with the Numeric Rating Scale (an 11- point scale where 0 indicates no pain and 10 the worst pain).
Use of supplemental analgesics
Include opioids and non-opioid analgesics.
The incidence of delirium within 5 days after surgery.
Delirium is assessed twice daily (8:00-10:00 am and 6:00-8:00 pm) with the 3-minute diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM).
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Peking University First Hospital
Lead sponsor
Beijing Hospital
Collaborator
