Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery

Elderly Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04955249
• Other study ID #: 2021-199
• Status: Recruiting
• Phase: Phase 4
• Start date: November 18, 2021
• Est. completion date: August 2025

Study information

• Verified date: November 2021
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang
• Phone: 8610 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1440
• Est. completion date: August 2025
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Delirium
• Dexmedetomidine
• Elderly
• Fractures, Bone
• Hip Fracture Surgery
• Hip Fractures
• Patient-controlled Analgesia
• Postoperative Delirium

Intervention

Drug:
• Dexmedetomidine
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.
• Placebo
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.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry. 2004 Jan-Feb;12(1):7-21. Review. — View Citation

Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van Gool WA. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005 Oct;53(10):1658-66. — View Citation

Malik AT, Quatman CE, Phieffer LS, Ly TV, Khan SN. Incidence, risk factors and clinical impact of postoperative delirium following open reduction and internal fixation (ORIF) for hip fractures: an analysis of 7859 patients from the ACS-NSQIP hip fracture procedure targeted database. Eur J Orthop Surg Traumatol. 2019 Feb;29(2):435-446. doi: 10.1007/s00590-018-2308-6. Epub 2018 Sep 18. — View Citation

Mu DL, Zhang DZ, Wang DX, Wang G, Li CJ, Meng ZT, Li YW, Liu C, Li XY. Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial. Anesth Analg. 2017 Jun;124(6):1992-2000. doi: 10.1213/ANE.0000000000002095. — View Citation

Ravi B, Pincus D, Choi S, Jenkinson R, Wasserstein DN, Redelmeier DA. Association of Duration of Surgery With Postoperative Delirium Among Patients Receiving Hip Fracture Repair. JAMA Netw Open. 2019 Feb 1;2(2):e190111. doi: 10.1001/jamanetworkopen.2019.0111. — View Citation

Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16. — View Citation

Weinstein SM, Poultsides L, Baaklini LR, Mörwald EE, Cozowicz C, Saleh JN, Arrington MB, Poeran J, Zubizarreta N, Memtsoudis SG. Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors. Br J Anaesth. 2018 May;120(5):999-1008. doi: 10.1016/j.bja.2017.12.046. Epub 2018 Mar 9. — View Citation

Yang Y, Zhao X, Dong T, Yang Z, Zhang Q, Zhang Y. Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis. Aging Clin Exp Res. 2017 Apr;29(2):115-126. doi: 10.1007/s40520-016-0541-6. Epub 2016 Feb 12. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cumulative sufentanil consumption within 5 postoperative days	Cumulative sufentanil consumption within 5 postoperative days	Up to 5 days after surgery
Other	Pain severity during postoperative days 1-5	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.	Up to 5 days after surgery
Other	Subjective sleep quality during postoperative days 1-5	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.	Up to 5 days after surgery
Other	Sedation level during postoperative days 1-5	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).	Up to 5 days after surgery
Primary	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	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
Secondary	Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Secondary	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
Secondary	All-cause 30-day mortality	All-cause 30-day mortality	Up to 30 days after surgery
Secondary	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
Secondary	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
Secondary	Overall survival for up to 3 years after surgery	Time from surgery to all-cause death	Up to 3 years after surgery
Secondary	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
Secondary	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
Secondary	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