Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery

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

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.

Study Overview

• Status: Terminated
• Conditions: Postoperative Delirium; Elderly; Dexmedetomidine; Hip Fracture Surgery; Patient-controlled Analgesia
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100034
    • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 89 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine group; 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; 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.; Other Names: Intervention group
Placebo Comparator: Control group; 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; 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.; Other Names: Control group

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative sufentanil consumption within 5 postoperative days	Cumulative sufentanil consumption within 5 postoperative days	Up to 5 days after surgery
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
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
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

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Study Principal Investigator

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry. 2004 Jan-Feb;12(1):7-21.
• 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.
• 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. doi: 10.1111/j.1532-5415.2005.53503.x.
• Weinstein SM, Poultsides L, Baaklini LR, Morwald 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): April 11, 2023
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: July 4, 2021
• First Submitted That Met QC Criteria: July 4, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Elderly; Dexmedetomidine; Postoperative delirium; Patient-controlled analgesia; Hip fracture surgery
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Postoperative Complications; Pathologic Processes; Leg Injuries; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Femoral Fractures; Hip Injuries; Emergence Delirium; Delirium; Fractures, Bone; Hip Fractures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: 2021-199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No