Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery

Study Overview
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Brief Summary
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Delirium is common in the elderly after hip fracture surgery, and is associated with worse outcomes. The investigators hypothesize that, for elderly patients after hip fracture surgery, dexmedetomidine supplemented analgesia can reduce the incidence of delirium and improve the long-term outcomes.

Detailed Description
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Delirium is a common complication in patients after hip fracture surgery and is associated with worse outcomes, including prolonged hospital stay, poor functional recovery, decreased cognitive function, increased health care costs, and elevated mortality rate. The etiology of delirium is multifactorial and include severe pain and sleep disturbances after surgery, as well as surgery-related inflammation. Dexmedetomidine is a selective alpha 2 receptor agonist. It exerts sedative effects by activating the endogenous sleep-promoting pathway and leads to a state like non-rapid eye movement sleep. It produces analgesic effects by activating the alpha2a adrenergic receptor subtype in the spinal cord. Perioperative dexmedetomidine also alleviates the degree of surgery-related inflammation. Previous studies showed that, for elderly patients admitted to the intensive care unit after non-cardiac surgery, low-dose dexmedetomidine infusion improved subjective sleep quality and reduced delirium early after surgery; it also increased survival up to 2 years and improved life quality in 3-year survivors. The investigators hypothesize that dexmedetomidine supplemented patient-controlled analgesia can also reduce delirium and improve long-term outcomes in elderly patients after hip fracture surgery.

Official Title
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Impact of Dexmedetomidine Supplemented Analgesia on Delirium and Long-term Outcomes in Elderly After Hip Fracture Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial

Conditions
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Elderly, Hip Fracture Surgery, Patient-controlled Analgesia, Dexmedetomidine, Postoperative Delirium

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years but < 90 years; Scheduled to undergo hip fracture surgery; Planned to use patient-controlled intravenous analgesia (PCIA) after surgery. Exclusion Criteria: Refuse to participate in this study; Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis; Inability to communicate in the preoperative period because of coma, profound dementia or language barrier; Preoperative obstructive sleep apnea (diagnosed sleep apnea syndrome or a STOP-Bang score ≥3 combined with a serum bicarbonate ≥28 mmol/L); Sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree or above atrioventricular block without pacemaker; Severe hepatic dysfunction (Child-Pugh class C); Severe renal dysfunction (requirement of renal replacement therapy before surgery); American Society of Anesthesiologists physical status >IV, or estimated survival ≤24 h.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine group<br>Patients in this group receive dexmedetomidine-supplemented patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of dexmedetomidine (1 microgram/ml) and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes. | Drug: Dexmedetomidine<br>* Patients in this group receive dexmedetomidine-supplemented patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of dexmedetomidine (1 microgram/ml) and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.<br>* Other names: Intervention group;|
| Placebo Comparator: Control group<br>Patients in this group receive routine patient-controlled analgesia for up to 3 days after surgery. The formula is a mixture of placebo and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is programmed to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes. | Drug: Placebo<br>* Patients in this group receive routine patient-controlled intravenous analgesia for up to 3 days after surgery. The formula is a mixture of placebo and sufentanil (1 microgram/ml), diluted with normal saline to 200 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a bolus dose of 2 ml at each time and a lockout interval of 8 minutes.<br>* Other names: Control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of delirium within the first 5 days after surgery | Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5. | Up to 5 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily prevalence of delirium during the first 5 days after surgery | Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the 3-minute Diagnostic Confusion Assessment Method (3D CAM, for patients without mechanical ventilation) or the Confusion Assessment Method for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5. | Up to 5 days after surgery | 
| Length of stay in hospital after surgery | Length of stay in hospital after surgery | Up to 30 days after surgery | 
| Incidence of non-delirium complications within 30 days after surgery | Non-delirium complications are defined as new-onset medical events other than delirium that are harmful to patients' recovery and required therapeutic intervention, i.e., grade II or above on the Clavien-Dindo classification. | Up to 30 days after surgery | 
| All-cause 30-day mortality | All-cause 30-day mortality | Up to 30 days after surgery | 
| Quality of life at 30 days | Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function. | At the 30th day after surgery | 
| Cognitive function at 30 days | Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function. | At the 30th day after surgery | 
| Overall survival for up to 3 years after surgery | Time from surgery to all-cause death | Up to 3 years after surgery | 
| Event-free survival for up to 3 years after surgery | Time from surgery to new-onset diseases or all-cause death, whichever comes first. New-onset disease indicates those that required hospital admission and/or interventional procedures. | Up to 3 years after surgery | 
| Quality of life in 1-，2- and 3-year survivors after surgery | Quality of life is assessed with the WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function. | At the end of the 1st, 2nd, and 3rd year after surgery | 
| Cognitive function in 1-，2- and 3-year survivors after surgery | Cognitive function is assessed with the TICS-m, a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function. | At the end of the 1st, 2nd, and 3rd year after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elderly, Hip fracture surgery, Patient-controlled analgesia, Dexmedetomidine, Postoperative delirium