Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

Phase 4

• Conditions: Elderly; Orthopedic Surgery; Analgesia; Dexmedetomidine; Postoperative Delirium; Long-term Outcome
• Interventions: Drug: Placebo; Drug: Dexmedetomidine

• Registration Number: NCT03629262
• Lead Sponsor: Peking University First Hospital

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.

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 Timeline

• Study First Submitted: 2018-08-08
• Study First Submitted QC: 2018-08-13
• Study First Posted: 2018-08-14
• Study Start: 2018-10-28
• Primary Completion: 2019-12-06
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-05
• Last Update Posted: 2021-07-07
• Study Completion: 2022-12-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 712

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Placebo	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.
Dexmedetomidine group	Dexmedetomidine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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.
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
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
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.
Length of stay in hospital after surgery	Up to 30 days after surgery	Length of stay in hospital 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.
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.
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.
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.

Trial Locations

Locations (2)

Peking University First Hospital; 🇨🇳 Beijing, China

Beijing Jishuitan Hospital; 🇨🇳 Beijing, China