Dexmedetomidine Combined With Ropivacaine for Postoperative Continuous Femoral Nerve Block

Impact of Dexmedetomidine Combined With Ropivacaine for Postoperative Continuous Femoral Nerve Block on Postoperative Delirium and Long-term Oucomes in Elderly Patients After Single Knee Arthroplasty

Delirium is common in the elderly after orthopedic surgery and is associated with worse outcomes. Continuous femoral nerve block is frequently used for postoperative analgesia after total knee arthoplasty. The investigators hypothesize that dexmedetomidine, when combined with ropivacaine for continuous femoral nerve block, can reduce the incidence of delirium and improve the long-term outcome in elderly patients after total knee arthroplasty.

Study Overview

• Status: Suspended
• Conditions: Postoperative Delirium; Elderly; Knee Arthroplasty; Dexmedetomidine; Long-term Outcome; Nerve Block
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

Detailed Description

A growing number of elderly patients undergo total knee arthroplasty. 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. Dexmedetomidine has been shown to prolong the duration of nerve block without neurotoxicity and improve postoperative sleep quality. The investigators hypothesize that dexmedetomidine, when combined with ropivacaine for continuous femoral nerve block, can reduce the incidence of delirium and improve the long-term outcome in elderly patients after total knee arthroplasty.

• Study Type: Interventional
• Enrollment (Anticipated): 736
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100035
      • BeiJing JiShuiTan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Elderly patients (≥ 65 years but < 90 years);
• Scheduled to undergo single total knee arthroplasty;
• Planned to receive continuous femoral nerve block for postoperative analgesia.

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 hemorrhagic disease or coagulopathy (platelet count, prothrombin time and/or activated partial thrombin time below the lower limit of normal);
• Preoperative obstructive sleep apnea (diagnosed as obstructive sleep apnea, or STOP-Bang score ≥3);
• Preoperative 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);
• ASA classification ≥ IV or unlikely to survive for more than 24 hours after surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine group; For patients in the dexmedetomidine group, postoperative analgesia is provided in the form of continuous femoral nerve block. The formula contains a mixture of 0.2% ropivacaine 250 ml and 3.75 ug/kg dexmedetomidine. The analgesic pump is set to administer a continuous infusion at a rate of 5 ml/h for 48 hours (equivalent to dexmedetomidine infusion at a rate of 0.075 ug/kg/h).	Drug: Dexmedetomidine; Patients in this group receive continuous femoral nerve block analgesia for 48 hours after surgery. The formula is a mixture of 0.2% ropivacaine 250ml and 3.75 ug/kg dexmedetomidine. The analgesic pump is set to administer a continuous infusion at a rate of 5 ml/h (equivalent to a dexmedetomidine infusion at a rate of 0.075 ug/kg/h).; Other Names: Continuous femoral nerve block with ropivacaine
PLACEBO_COMPARATOR: Control group; For patients in the control group, postoperative analgesia is provided in the form of continuous femoral nerve block. The formula contains a mixture of 0.2% ropivacaine 250 ml and placebo (normal saline). The analgesic pump is set to administer a continuous infusion at a rate of 5 ml/h for 48 hours.	Drug: Placebo; Patients in this group receive continuous femoral nerve block analgesia for 48 hours after surgery. The formula is a mixture of 0.2% ropivacaine 250 ml and placebo. The analgesic pump is set to administer a continuous infusion at a rate of 5 ml/h.; Other Names: Continuous femoral nerve block with ropivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of delirium during the first 3 days after surgery	Incidence of delirium during the first 3 days after surgery	The first 3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Daily prevalence of delirium during postoperative days 1-3	Daily prevalence of delirium during postoperative days 1-3	The first 3 days after surgery
Incidence of non-delirium complications within 30 days after surgery	Incidence of non-delirium complications within 30 days after surgery	Up to 30 days after surgery
All-cause 30-day mortality	All-cause 30-day mortality	At 30 days after surgery
Quality of life at 30 days after surgery	Quality of life at 30 days after surgery is assessed with the 12-items Short Form Health Survey (SF-12), a 12-item questionnaire that provides assessments of physical and mental health-related quality of life. The score ranges from 12 to 48, with higher score indicating better function.	At 30 days after surgery
Cognitive function at 30 days after surgery	Cognitive function at 30 days after surgery is assessed with 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 50, with higher score indicating better function.	At 30 days after surgery
Overall survival within 3 years after surgery	Overall survival within 3 years after surgery	Up to 3 years after surgery
Survival rates at the end of the 1st，2nd, and 3rd years after surgery	Survival rates at the end of the 1st，2nd, and 3rd years after surgery	At the end of the 1st, 2nd, and 3rd years after surgery
Incidence of new-onset diseases within 3 years after surgery	Incidence of new-onset diseases within 3 years after surgery	Up to 3 years after surgery
Quality of life at the end of the 1st, 2nd, and 3rd years after surgery: SF-12	Quality of life at the end of the 1st, 2nd, and 3rd years after surgery is assessed with the 12-items Short Form Health Survey (SF-12), a 12-item questionnaire that provides assessments of physical and mental health-related quality of life. The score ranges from 12 to 48, with higher score indicating better function.	At the end of the 1st, 2nd, and 3rd years after surgery
Cognitive function at the end of the 1st, 2nd, and 3rd years after surgery	Cognitive function at the end of the 1st, 2nd, and 3rd years after surgery is assessed with 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 50, with higher score indicating better function.	At the end of the 1st, 2nd, and 3rd years after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation level during postoperative days 1-3	Sedation level during postoperative days 1-3 is assessed 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).	The first 3 days after surgery
Pain severity during postoperative days 1-3: NRS	Pain severity during postoperative days 1-3 is assessed with the Numeric Rating Scale (NRS), an 11-point pain scale where 0=no pain and 10=the most severe pain.	The first 3 days after surgery
Sleep quality during postoperative days 1-3	Sleep quality during postoperative days 1-3 is assessed with the Verran and Snyder-Halpern (VSH) Sleep Scale, an 8-item questionnaire that evaluate multiple aspects of sleep during the previous night. Each item is scored in a range from 0 (very bad) to 10 (very good), and the total VSH score is determined by the summation of these scores (range 0-80). A higher total VSH score indicates a better quality of sleep.	The first 3 days after surgery

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: Beijing Jishuitan Hospital

Publications and helpful links

General Publications

• Bickel H, Gradinger R, Kochs E, Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord. 2008;26(1):26-31. doi: 10.1159/000140804. Epub 2008 Jun 24.
• 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.
• Zhang DF, Su X, Meng ZT, Li HL, Wang DX, Xue-Ying Li, Maze M, Ma D. Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial. Ann Surg. 2019 Aug;270(2):356-363. doi: 10.1097/SLA.0000000000002801.
• 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.
• Wang XL, Wang J, Mu DL, Wang DX. [Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthroplasty]. Zhonghua Yi Xue Za Zhi. 2018 Mar 13;98(10):728-732. doi: 10.3760/cma.j.issn.0376-2491.2018.10.003. Chinese.
• Choy WS, Lee SK, Kim KJ, Kam BS, Yang DS, Bae KW. Two continuous femoral nerve block strategies after TKA. Knee Surg Sports Traumatol Arthrosc. 2011 Nov;19(11):1901-8. doi: 10.1007/s00167-011-1510-4. Epub 2011 Apr 12.
• Duarte VM, Fallis WM, Slonowsky D, Kwarteng K, Yeung CK. Effectiveness of femoral nerve blockade for pain control after total knee arthroplasty. J Perianesth Nurs. 2006 Oct;21(5):311-6. doi: 10.1016/j.jopan.2006.05.011.
• Abdulatif M, Fawzy M, Nassar H, Hasanin A, Ollaek M, Mohamed H. The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block: a dose-finding randomised, controlled, double-blind study. Anaesthesia. 2016 Oct;71(10):1177-85. doi: 10.1111/anae.13603.
• Brummett CM, Hong EK, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current. Anesthesiology. 2011 Oct;115(4):836-43. doi: 10.1097/ALN.0b013e318221fcc9.
• Al-Metwalli RR, Mowafi HA, Ismail SA, Siddiqui AK, Al-Ghamdi AM, Shafi MA, El-Saleh AR. Effect of intra-articular dexmedetomidine on postoperative analgesia after arthroscopic knee surgery. Br J Anaesth. 2008 Sep;101(3):395-9. doi: 10.1093/bja/aen184. Epub 2008 Jun 20.
• Brummett CM, Norat MA, Palmisano JM, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology. 2008 Sep;109(3):502-11. doi: 10.1097/ALN.0b013e318182c26b.
• Behera BK, Puri GD, Ghai B. Patient-controlled epidural analgesia with fentanyl and bupivacaine provides better analgesia than intravenous morphine patient-controlled analgesia for early thoracotomy pain. J Postgrad Med. 2008 Apr-Jun;54(2):86-90. doi: 10.4103/0022-3859.40772.
• Halaszynski TM. Pain management in the elderly and cognitively impaired patient: the role of regional anesthesia and analgesia. Curr Opin Anaesthesiol. 2009 Oct;22(5):594-9. doi: 10.1097/ACO.0b013e32833020dc.
• Kosar CM, Tabloski PA, Travison TG, Jones RN, Schmitt EM, Puelle MR, Inloes JB, Saczynski JS, Marcantonio ER, Meagher D, Reid MC, Inouye SK. EFFECT OF PREOPERATIVE PAIN AND DEPRESSIVE SYMPTOMS ON THE DEVELOPMENT OF POSTOPERATIVE DELIRIUM. Lancet Psychiatry. 2014 Nov;1(6):431-436. doi: 10.1016/S2215-0366(14)00006-6.
• Siddiqi N, Harrison JK, Clegg A, Teale EA, Young J, Taylor J, Simpkins SA. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016 Mar 11;3:CD005563. doi: 10.1002/14651858.CD005563.pub3.
• Quinlan N, Rudolph JL. Postoperative delirium and functional decline after noncardiac surgery. J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S301-4. doi: 10.1111/j.1532-5415.2011.03679.x.
• Shi CM, Wang DX, Chen KS, Gu XE. Incidence and risk factors of delirium in critically ill patients after non-cardiac surgery. Chin Med J (Engl). 2010 Apr 20;123(8):993-9.
• McDaniel M, Brudney C. Postoperative delirium: etiology and management. Curr Opin Crit Care. 2012 Aug;18(4):372-6. doi: 10.1097/MCC.0b013e3283557211.
• Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med. 1995 Mar 13;155(5):461-5. doi: 10.1001/archinte.155.5.461.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 10, 2018
• Primary Completion (ACTUAL): December 11, 2018
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 11, 2018
• First Posted (ACTUAL): August 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Elderly; Nerve Block; Dexmedetomidine; Knee Arthroplasty; Postoperative Delirium; Long-term Outcome
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Anesthetics, Local; Dexmedetomidine; Ropivacaine
• Other Study ID Numbers: DEX 20180516

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