Dexmedetomidine, Elderly, Hip Fracture Surgery, Patient-controlled Analgesia, Postoperative Delirium
Conditions
Keywords
Elderly, Hip fracture surgery, Patient-controlled analgesia, Dexmedetomidine, Postoperative delirium
Brief summary
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
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.
Interventions
DRUGDexmedetomidine
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.
DRUGPlacebo
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.
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
65 Years to 89 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of delirium within the first 5 days after surgery | Up to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause 30-day mortality | Up to 30 days after surgery | All-cause 30-day mortality |
| Overall survival for up to 3 years after surgery | Up to 3 years after surgery | Time from surgery to all-cause death |
| Event-free survival for up to 3 years after surgery | 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. |
| Quality of life in 1-，2- and 3-year survivors after surgery | At the end of the 1st, 2nd, and 3rd year 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. |
| Cognitive function in 1-，2- and 3-year survivors after surgery | At the end of the 1st, 2nd, and 3rd year 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. |
| Daily prevalence of delirium during the first 5 days after surgery | Up to 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. |
| Length of stay in hospital after surgery | Up to 30 days after surgery | Length of stay in hospital after surgery |
| Incidence of non-delirium complications within 30 days after surgery | Up to 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. |
| Quality of life at 30 days | At the 30th day 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. |
| Cognitive function at 30 days | At the 30th day 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subjective sleep quality during postoperative days 1-5 | Up to 5 days after surgery | Subjective sleep quality is assessed once daily with the Numeric Rating Scale (NRS), an 11 point scale where 0=the best sleep and 10=the worst sleep. |
| Sedation level during postoperative days 1-5 | Up to 5 days after surgery | Sedation level is assessed twice daily with the Richmond Agitation-Sedation Scale (RASS), of which the range is as follows: +4 (combative), +3 (very agitated), +2 (agitated), +1 (restless), 0 (alert and clam), -1 (drowsy), -2 (light sedation), -3 (moderate sedation), -4 (deep sedation), and -5 (unarousable). |
| Pain severity during postoperative days 1-5 | Up to 5 days after surgery | Pain severity is assessed with twice daily the Numeric Rating Scale (NRS), an 11 point scale where 0=no pain and 10=the worst possible pain. |
| Cumulative sufentanil consumption within 5 postoperative days | Up to 5 days after surgery | Cumulative sufentanil consumption within 5 postoperative days |
Countries
China
Outcome results
None listed