Clinical trial NCT05246007: Nocturnal Low-dose Dexmedetomidine Infusion and Perioperative Sleep Quality
Official title: Effect of Nocturnal Low-dose Dexmedetomidine Infusion on Sleep Quality in Older Patients Undergoing Knee or Hip Replacement Surgery: A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Old Age
Knee Replacement Surgery
Hip Replacement Surgery
Dexmedetomidine
Sleep Quality
Keywords: Old Age
Knee replacement surgery
Hip replacement surgery
Dexmedetomidine
Sleep quality
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Hospital
First posted: 2022-02-18
Enrollment: 432
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Sleep disturbances are prevalent in older patients with osteoarthrosis or fracture 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. Night-time infusion of low-dose dexmedetomidine may improve sleep quality. However, evidence in this aspect is limited.

Detailed description: Sleep is a naturally recurring state characterized by lowered consciousness, reduced sensory and voluntary activity, and inhibited interaction with surroundings. Normal sleep has a particular structure and significant circadian rhythms; and is vital for both physical and mental health. Evidence shows that the restorative effect of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products like β-amyloid or tau protein via the glymphatic pathway in the neurological system.

Sleep disturbances frequently occur in elderly patients with chronic pain and complicated comorbidity. A meta-analysis shows that in adults, total sleep time, sleep efficiency, percentage of slow-wave sleep, and percentage of rapid eye movement (REM) sleep significantly decrease, while sleep latency, percentage of stage 1 non-REM sleep, percentage of stage 2 non-REM sleep, and wake after sleep onset significantly increase with ageing. Coexisting disease such as asthma and obstructive sleep apnea are also associated with poorer sleep quality, as manifested by increased stage 1 and 2 non-REM sleep, and decreased REM sleep. Furthermore, pain and sleep disturbances are closely correlated, and sleep disturbances frequently accompany pain from osteoarthritis (OA) or fracture in elderly patients who are scheduled for knee or hip arthroplasty.

Sleep disturbances are common after major surgery owing to preoperative comorbidity, residual anesthetic effects, surgical trauma, postoperative pain, use of analgesics, and hospital environment. Patients may report shortened total sleep time, increased number of arousals/awakenings, lowered subjective sleep quality, and sometimes nightmares. Polysomnographic monitoring reveals sleep deprivation, sleep fragmentation, altered sleep architecture (increased light sleep, decreased or disappeared deep and rapid eye movement sleep), and disordered circadian rhythm. Considering the importance of normal sleep for human health, it is not surprising that sleep disturbances may produce harmful effects on patients' recovery. Indeed, emerging evidence suggests that sleep disturbances are associated with increased sensitivity to pain, higher inflammation, more delirium, more cardiovascular events, and prolonged hospital stay.

Dexmedetomidine, an α2 adrenoceptor agonist with both sedative and analgesic properties, has increasingly been used. Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway and preserves sleep architecture to some degree. In a recent study of mechanically ventilated ICU patients, nighttime infusion of a sedative dose of dexmedetomidine (median infusion rate 0.6 μg/kg/h \[interquartile range, 0.4 to 0.7\]) helped preserve the circadian of sleep and improved the sleep architecture by increasing sleep efficiency and stage 2 non-REM sleep. In our previous study of non-mechanically ventilated ICU patients, nighttime infusion of low-dose of dexmedetomidine (0.1 μg/kg/h) improved the sleep architecture by increasing sleep efficiency and stage 2 non-REM sleep. Our subsequent large randomized controlled trial showed that low-dose night-time infusion of dexmedetomidine improved sleep and decreased the incidence of delirium; furthermore, it improved 2-year survival and 3-year quality of life after surgery.

We suppose that, for older patients with osteoarthrosis or fracture who are scheduled for knee or hip replacement surgery, nighttime infusion of low-dose dexmedetomidine starting from the preoperative night and continuing in the postoperative period may improve sleep quality and postoperative recovery.

Eligibility criteria: Inclusion Criteria:

* Age ≥65 years and \<90 years;
* Scheduled to undergo unilateral knee or hip arthroplasty under spinal or combined spinal-epidural anesthesia.

Exclusion Criteria:

* Refuse to participate;
* Hypnotic therapy for sleep disorders within 3 months;
* Presence of contraindications to intrathecal anesthesia;
* Preoperative history of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or delirium;
* Diagnosed as obstructive sleep apnea, or at high risk of moderate to severe obstructive sleep apnea according to the STOP-Bang questionnaire;
* Inability to communicate in the preoperative period because of coma, profound dementia, or language barrier;
* Sick sinus syndrome, severe sinus bradycardia (heart rate \<50 beats/min), or atrioventricular block above grade II without pacemaker implanted;
* Severe hepatic dysfunction (Childe Pugh class C); renal dysfunction (required preoperative dialysis), or expected survival ≤24 hours;
* Receiving treatment with dexmedetomidine or clonidine;
* Allergy to dexmedetomidine.

Primary outcomes:
measure: Subjective sleep quality (overall RCSQ score) during the night of surgery.
timeFrame: During the night of surgery.
Secondary outcomes:
measure: Subjective sleep quality (overall RCSQ score) during the perioperative period.
timeFrame: From the night before surgery until the fifth night after surgery.
measure: Total sleep time per night during the perioperative period.
timeFrame: From the night before surgery until the fifth night after surgery.
measure: Sleep efficiency per night during the perioperative period.
timeFrame: From the night before surgery until the fifth night after surgery.
measure: Sleep onset latency per night during the perioperative period.
timeFrame: From the night before surgery until the fifth night after surgery.
measure: Wake after sleep onset per night during the perioperative period.
timeFrame: From the night before surgery until the fifth night after surgery.
measure: Intensity of pain during the first 3 postoperative days.
timeFrame: Up to 3 days after surgery.
measure: The incidence of delirium within 5 days after surgery.
timeFrame: Up to 5 days after surgery.
measure: The joint range of motion after surgery.
timeFrame: Up to 5 days after surgery.
measure: Length of stay in hospital after surgery.
timeFrame: Up to 30 days after surgery.
measure: Incidence of non-delirium complications within 30 days.
timeFrame: Up to 30 days after surgery.
measure: Subjective sleep quality (Pittsburgh Sleep Quality Index) at 30 days after surgery.
timeFrame: On the 30th day after surgery.
measure: Cognitive function at 3 months after surgery.
timeFrame: At the end of the 3rd month after surgery.
measure: Quality of life at 3 months after surgery.
timeFrame: At the end of the 3rd month after surgery.
measure: 3-year overall survival.
timeFrame: Up to 3 years after surgery.
measure: 3-year event-free survival.
timeFrame: Up to 3 years after surgery.
measure: Cognitive function within 3 years after surgery.
timeFrame: Up to 3 years after surgery.
measure: Quality of life every year within 3 years after surgery.
timeFrame: Up to 3 years after surgery.
Other outcomes:
measure: Cerebrospinal fluid proteomics examination (selected patients).
timeFrame: During anesthesia.
Locations:
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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