Clinical trial NCT04955249: Dexmedetomidine Supplemented Analgesia and Delirium After Hip Fracture Surgery
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Elderly
Hip Fracture Surgery
Patient-controlled Analgesia
Dexmedetomidine
Postoperative Delirium
Keywords: Elderly
Hip fracture surgery
Patient-controlled analgesia
Dexmedetomidine
Postoperative delirium
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2021-07-08
Enrollment: 1440
Sex: ALL
Minimum age (years): 65
Maximum age (years): 89
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of delirium within the first 5 days after surgery
timeFrame: Up to 5 days after surgery
Secondary outcomes:
measure: Daily prevalence of delirium during the first 5 days after surgery
timeFrame: Up to 5 days after surgery
measure: Length of stay in hospital after surgery
timeFrame: Up to 30 days after surgery
measure: Incidence of non-delirium complications within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: All-cause 30-day mortality
timeFrame: Up to 30 days after surgery
measure: Quality of life at 30 days
timeFrame: At the 30th day after surgery
measure: Cognitive function at 30 days
timeFrame: At the 30th day after surgery
measure: Overall survival for up to 3 years after surgery
timeFrame: Up to 3 years after surgery
measure: Event-free survival for up to 3 years after surgery
timeFrame: Up to 3 years after surgery
measure: Quality of life in 1-，2- and 3-year survivors after surgery
timeFrame: At the end of the 1st, 2nd, and 3rd year after surgery
measure: Cognitive function in 1-，2- and 3-year survivors after surgery
timeFrame: At the end of the 1st, 2nd, and 3rd year after surgery
Other outcomes:
measure: Cumulative sufentanil consumption within 5 postoperative days
timeFrame: Up to 5 days after surgery
measure: Pain severity during postoperative days 1-5
timeFrame: Up to 5 days after surgery
measure: Subjective sleep quality during postoperative days 1-5
timeFrame: Up to 5 days after surgery
measure: Sedation level during postoperative days 1-5
timeFrame: Up to 5 days after surgery
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
affiliation: Study Principal Investigator
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: Cole MG. Delirium in elderly patients. Am J Geriatr Psychiatry. 2004 Jan-Feb;12(1):7-21.
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.
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. doi: 10.1111/j.1532-5415.2005.53503.x.
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.
citation: 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.
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.