Sevoflurane, Propofol and Desflurane on POD/POCD

Effects of Anesthetics Sevoflurane, Propofol and Desflurane on Postoperative Delirium (POD) and Postoperative Cognitive Disorder (POCD)

The investigators will perform clinical studies to test the hypothesis that participants who have total hip/knee replacement under sevoflurane, propofol or desflurane anesthesia will have different effects on the incidence and severity of POD/POCD, and POD/POCD is associated with retinal nerve fiber layer (RNFL) thickness, as well as Serum level of vitamin B12, folic acid, homocysteine and human myeloid differentiation protein-2 (MD-2s). The investigators plan to perform the studies in 300 participants at Shanghai 10th People's Hospital.

Study Overview

• Status: Unknown
• Conditions: Sevoflurane; Desflurane; Propofol
• Intervention / Treatment: Drug: Sevoflurane; Drug: Propofol; Drug: Desflurane

Detailed Description

Postoperative delirium (POD) and postoperative cognitive disorder (POCD) are the most common complications of geriatric surgical patients, which could cause long-term social dysfunction, high mortality and increased medical cost. Currently, there is no efficient biomarker for POD/POCD, and it also remains largely unknown whether different anesthesia might lead to different incidence and severity of POD/POCD. The investigator's previous studies showed that thickness of retinal nerve fiber layer thickness (RNFL-T) measured by optical coherence tomography (OCT) was associated with POD/POCD; change of RNFL thickness (RNFL-C) in certain period correlated with cognitive deterioration. Thus, the investigators consider that RNFL might be a potential biomarker of POD/POCD. In the proposed large-scale longitudinal studies, the investigators will clinically validate RNF-LT as pre-operative POD/POCD biomarker, and RNFL-C as post-operative biomarker of POD/POCD. Finally, the investigators will compare the effects of surgery (total hip/knee replacement) under general anesthesia with sevoflurane, propofol and desflurane on the incidence and severity of POD/POCD in patients. Results from the proposed studies will likely establish RNFL as a potential POD/POCD biomarker, promote the clinical utilization of OCT-RNFL in early screening and outcome prediction of POD/POCD, and finally optimize anesthesia care of geriatric surgical patients to avoid or reduce POD/POCD incidence. These findings will lead to better postoperative outcomes of geriatric patients.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Yuan Shen, M.D.,Ph.D.; Phone Number: 66303649; Email: kmshy@tongji.edu.cn
• Study Contact Backup: Name: Zhongyong Shi, M.D., Ph.D.; Phone Number: 18701915271; Email: szy0721@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200072
      • Recruiting
      • Shanghai 10th People's Hospital
      • Contact: Yanxia Guo, M.D.; Phone Number: 021-65982875; Email: guoyx_2000@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients, aged 60 years old or older, who admitted to the Department of Orthopedics at Shanghai 10th People's Hospital and had been scheduled to undergo knee or hip fractures were screened and asked to participate in the study.

Description

Inclusion Criteria:

• 60 years old or older
• Chinese Mandarin as the native language
• scheduled to undergo hip/knee surgery under general anesthesia
• American Society of Anesthesiologists (ASA) class I-Ⅲ

Exclusion Criteria:

• Prior diagnoses of neurological diseases according to ICD-10
• History of severe psychiatric disorders according to DSM-IV
• Visual or auditory defects
• Participating in the investigation of another study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sevoflurane; Patients in Sevoflurane group are maintained with sevoflurane from an anesthesia machine through the laryngeal mask airway guided by Narcrotrend index monitoring.	Drug: Sevoflurane; Anesthesia maintenance with sevoflurane guided by Narcrotrend index monitoring.
Propofol; Patients in Propofol group are maintained with propofol through intravenous administration guided by Narcrotrend index monitoring.	Drug: Propofol; Anesthesia maintenance with propofol guided by Narcrotrend index monitoring.
Desflurane; Patients in Desflurane group are maintained with desflurane from an anesthesia machine through the laryngeal mask airway guided by Narcrotrend index monitoring.	Drug: Desflurane; Anesthesia maintenance with desflurane guided by Narcrotrend index monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative delirium	Postoperative delirium will be determined by Confusion Assessment Method (CAM) at 1st postoperative day	At 1st day after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative delirium	Postoperative delirium will be determined by CAM at 2nd postoperative day	At 2nd day after the surgery
Postoperative delirium	Postoperative delirium will be determined by CAM at 3rd postoperative day	At 3rd day after the surgery
Preoperative cognitive function	Preoperative cognitive function will be assessed by neuropsychological battery	Preoperative cognitive function (baseline)
Postoperative cognitive dysfunction	Postoperative cognitive dysfunction will be assessed by neuropsychological battery before and after the surgery and anesthesia	Change from baseline cognitive dysfunction at 1 week
Postoperative cognitive dysfunction	Postoperative cognitive dysfunction will be assessed by neuropsychological battery	Change from baseline cognitive dysfunction at 3rd month
Retinal nerve fiber layer thickness	Retinal nerve fiberlayer（RNFL）thickness will be measured by optical coherence tomography (OCT) before and after surgery and anesthesia	Change from baseline RNFL thickness at 3rd month
Serum level of vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s)	vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s) will be tested	Before the surgery (baseline)
Serum level of vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s)	vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s) will be tested	At 1st day after the surgery
Serum level of vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s)	vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s) will be tested	At 2nd day after the surgery
Serum level of vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s)	vitamin B12, folic acid, homocysteine and myeloid differentiation protein-2 (MD-2s) will be tested	At 3rd day after the surgery

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Yuan Shen, M.D.,Ph.D, Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28.
• Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010 Jul 28;304(4):443-51. doi: 10.1001/jama.2010.1013.
• Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.
• Vlisides P, Xie Z. Neurotoxicity of general anesthetics: an update. Curr Pharm Des. 2012;18(38):6232-40. doi: 10.2174/138161212803832344.
• Gleason LJ, Schmitt EM, Kosar CM, Tabloski P, Saczynski JS, Robinson T, Cooper Z, Rogers SO Jr, Jones RN, Marcantonio ER, Inouye SK. Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults. JAMA Surg. 2015 Dec;150(12):1134-40. doi: 10.1001/jamasurg.2015.2606.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: biomarker; general anesthesia; postoperative cognitive dysfunction; postoperative delirium; retinal nerve fiber layer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Desflurane; Sevoflurane
• Other Study ID Numbers: dsyy002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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