Dexmedetomidine Supplemented Intravenous Analgesia in Elderly After Orthopedic Surgery

Analgesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03629262
• Other study ID #: 2018-131
• Secondary ID: ChiCTR1800017182
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 28, 2018
• Est. completion date: December 7, 2022

Study information

• Verified date: July 2021
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 712
• Est. completion date: December 7, 2022
• Est. primary completion date: December 6, 2019
• 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 total knee/hip replacement surgery, or spinal 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

• Analgesia
• Delirium
• Dexmedetomidine
• Elderly
• Long-term Outcome
• Orthopedic Surgery
• Postoperative Delirium

Intervention

Drug:
• Dexmedetomidine
Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of dexmedetomidine (1.25 ug/ml) and sufentanil (1.25 ug/ml), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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.
• Placebo
Patients in this group receive patient-controlled intravenous analgesia for 1-3 days after surgery. The formula is a mixture of placebo and sufentanil (1.25 ug/m), diluted with normal saline to 160 ml. 5-HT3 receptor antagonist is added when necessary. 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	Beijing Jishuitan Hospital	Beijing
China	Peking University First Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Beijing Jishuitan Hospital

Country where clinical trial is conducted

China, 

References & Publications (23)

Abelha FJ, Luís C, Veiga D, Parente D, Fernandes V, Santos P, Botelho M, Santos A, Santos C. Outcome and quality of life in patients with postoperative delirium during an ICU stay following major surgery. Crit Care. 2013 Oct 29;17(5):R257. doi: 10.1186/cc13084. — View Citation

Bickel H, Gradinger R, Kochs E, Förstl 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. — View Citation

Brummel NE, Girard TD. Preventing delirium in the intensive care unit. Crit Care Clin. 2013 Jan;29(1):51-65. doi: 10.1016/j.ccc.2012.10.007. Review. — View Citation

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. Review. — View Citation

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. 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

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. — View Citation

Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, Ehtisham A, Nold J, Agarwal S, Azocar R, Burke P. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med. 2009 Jun;37(6):1898-905. doi: 10.1097/CCM.0b013e31819ffe38. — View Citation

Lescot T, Karvellas CJ, Chaudhury P, Tchervenkov J, Paraskevas S, Barkun J, Metrakos P, Goldberg P, Magder S. Postoperative delirium in the intensive care unit predicts worse outcomes in liver transplant recipients. Can J Gastroenterol. 2013 Apr;27(4):207-12. — View Citation

McDaniel M, Brudney C. Postoperative delirium: etiology and management. Curr Opin Crit Care. 2012 Aug;18(4):372-6. doi: 10.1097/MCC.0b013e3283557211. Review. — View Citation

Mu DL, Wang DX, Li LH, Shan GJ, Li J, Yu QJ, Shi CX. High serum cortisol level is associated with increased risk of delirium after coronary artery bypass graft surgery: a prospective cohort study. Crit Care. 2010;14(6):R238. doi: 10.1186/cc9393. Epub 2010 Dec 30. — 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

Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007 Jan;33(1):66-73. Epub 2006 Nov 11. — View Citation

Peng K, Liu HY, Wu SR, Cheng H, Ji FH. Effects of Combining Dexmedetomidine and Opioids for Postoperative Intravenous Patient-controlled Analgesia: A Systematic Review and Meta-analysis. Clin J Pain. 2015 Dec;31(12):1097-104. doi: 10.1097/AJP.0000000000000219. Review. — View Citation

Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1092-7. doi: 10.1164/rccm.200904-0537OC. Epub 2009 Sep 10. — View Citation

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. — View Citation

Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Sellke FW, Khabbaz K, Levkoff SE, Marcantonio ER. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci Med Sci. 2008 Feb;63(2):184-9. — View Citation

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. — View Citation

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. Review. — View Citation

Stuck A, Clark MJ, Connelly CD. Preventing intensive care unit delirium: a patient-centered approach to reducing sleep disruption. Dimens Crit Care Nurs. 2011 Nov-Dec;30(6):315-20. doi: 10.1097/DCC.0b013e31822fa97c. — 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

Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Elseviers M, Bossaert L. Long term outcome after delirium in the intensive care unit. J Clin Nurs. 2009 Dec;18(23):3349-57. doi: 10.1111/j.1365-2702.2009.02933.x. Epub 2009 Sep 4. — View Citation

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. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of delirium within the first 5 days after surgery	Incidence of delirium within the first 5 days after surgery	The first 5 days after surgery
Secondary	Daily prevalence of delirium during the first 5 days after surgery	Daily prevalence of delirium during the first 5 days after surgery	The first 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 with 30 days after surgery	Incidence of non-delirium complications with 30 days after surgery	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 of 30-day survivors	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.	At 30 days after surgery
Secondary	Cognitive function of 30-day survivors	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.	At 30 days after surgery
Secondary	Agitation or sedation level during postoperative days 1-5	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).	The first 1-5 days after surgery
Secondary	Cumulative sufentanil consumption within 5 postoperative days	Cumulative sufentanil consumption within 5 postoperative days	Up to 5 days after surgery
Secondary	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.	The first 1-5 days after surgery
Secondary	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.	The first 1-5 days after surgery
Secondary	Overall survival for up to 3 years after surgery	Time from surgery to all-cause death for up to 3 years after surgery.	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 procedure.	Up to 3 years after surgery
Secondary	Quality of life in 1-,2- and 3-year survivors 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.	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 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.	At the end of the 1st, 2nd, and 3rd year after surgery