Sevoflurane, Propofol and Desflurane on POD/POCD

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sevoflurane, Propofol, Desflurane

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Propofol
* Drug: Desflurane


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sevoflurane<br>Patients in Sevoflurane group are maintained with sevoflurane from an anesthesia machine through the laryngeal mask airway guided by Narcrotrend index monitoring. | Drug: Sevoflurane<br>* Anesthesia maintenance with sevoflurane guided by Narcrotrend index monitoring.<br>|
| Propofol<br>Patients in Propofol group are maintained with propofol through intravenous administration guided by Narcrotrend index monitoring. | Drug: Propofol<br>* Anesthesia maintenance with propofol guided by Narcrotrend index monitoring.<br>|
| Desflurane<br>Patients in Desflurane group are maintained with desflurane from an anesthesia machine through the laryngeal mask airway guided by Narcrotrend index monitoring. | Drug: Desflurane<br>* Anesthesia maintenance with desflurane guided by Narcrotrend index monitoring.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative delirium, postoperative cognitive dysfunction, retinal nerve fiber layer, biomarker, general anesthesia