Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03629262

Collaborator

Beijing Jishuitan Hospital (Other)

712

Enrollment

Locations

Arms

49.3

Anticipated Duration (Months)

356

Patients Per Site

7.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Elderly Orthopedic Surgery Analgesia Dexmedetomidine Postoperative Delirium Long-term Outcome	Drug: Dexmedetomidine Drug: Placebo	Phase 4

Detailed Description

A growing number of elderly patients undergo orthopedic surgery each year. Delirium is a common complication in these patients after 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. 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 intravenous analgesia (in the form of patient-controlled analgesia) can also reduce delirium and improve long-term outcomes in elderly patients after orthopedic surgery.

Study Design

Study Type:

Interventional

Actual Enrollment :

712 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Dexmedetomidine Supplemented Intravenous Analgesia on Postoperative Delirium and Long-term Outcomes in Elderly After Orthopedic Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial

Actual Study Start Date :

Oct 28, 2018

Actual Primary Completion Date :

Dec 6, 2019

Anticipated Study Completion Date :

Dec 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine group For patients in the dexmedetomidine group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of sufentanil (1.25 ug/ml) and dexmedetomidine (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.	Drug: Dexmedetomidine Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and sufentanil (1.25 ug/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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. Other Names: Sufentanil analgesia
Placebo Comparator: Control group For patients in the control group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of placebo and sufentanil (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.	Drug: Placebo Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of placebo and sufentanil (1.25 ug/m), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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. Other Names: Sufentanil analgesia

Arm

Intervention/Treatment

Experimental: Dexmedetomidine group

For patients in the dexmedetomidine group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of sufentanil (1.25 ug/ml) and dexmedetomidine (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.

Drug: Dexmedetomidine

Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and sufentanil (1.25 ug/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Other Names:

Sufentanil analgesia

Placebo Comparator: Control group

For patients in the control group, postoperative analgesia is provided in the form of patient-controlled intravenous analgesia. The formula contains a mixture of placebo and sufentanil (1.25 ug/ml), diluted with normal saline to a total volume of 160 ml. The analgesic pump is set to administer a background infusion at a rate of 1 ml/h, with a patient-controlled bolus of 2 ml each time and a lockout interval of 8 minutes.

Drug: Placebo

Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of placebo and sufentanil (1.25 ug/m), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.

Other Names:

Sufentanil analgesia

Outcome Measures

Primary Outcome Measures

Incidence of delirium within the first 5 days after surgery [The first 5 days after surgery]
Incidence of delirium within the first 5 days after surgery

Secondary Outcome Measures

Daily prevalence of delirium during the first 5 days after surgery [The first 5 days after surgery]
Daily prevalence of delirium during the first 5 days after surgery
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 with 30 days after surgery [Up to 30 days after surgery]
Incidence of non-delirium complications with 30 days after surgery
All-cause 30-day mortality [Up to 30 days after surgery]
All-cause 30-day mortality
Quality of life of 30-day survivors [At 30 days after surgery]
Quality of life of 30-day survivors is assessed with World Health Organization Quality of Life brief version (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 of 30-day survivors [At 30 days after surgery]
Cognitive function of 30-day survivors is assessed with the modified Telephone Interview for Cognitive Status (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 48, with higher score indicating better function.
Agitation or sedation level during postoperative days 1-5 [The first 1-5 days after surgery]
Agitation or 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).
Cumulative sufentanil consumption within 5 postoperative days [Up to 5 days after surgery]
Cumulative sufentanil consumption within 5 postoperative days
Pain severity during postoperative days 1-5 [The first 1-5 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.
Subjective sleep quality during postoperative days 1-5 [The first 1-5 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.
Overall survival for up to 3 years after surgery [Up to 3 years after surgery]
Time from surgery to all-cause death for up to 3 years after surgery.
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 procedure.
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 in 1-，2- and 3-year survivors 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 in 1-，2- and 3-year survivors 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 48, with higher score indicating better function.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 65 years but < 90 years;
Scheduled to undergo total knee/hip replacement surgery, or spinal 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