Postoperative Delirium After Total Knee Arthroplasty Under Regional Anesthesia

Study Overview
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Brief Summary
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Postoperative delirium after total knee replacement surgery has been related to significant morbidity and mortality among high risk patients. Anesthetic care might play a role in the development of postoperative delirium. The purpose of this study is to compare the incidence of postoperative delirium between different intraoperative sedation regimen. Delirium assessment using standardized screening tools will be done every 8 hours after surgery.

Detailed Description
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In this randomized controlled trial, the investigator will compare the incidence of postoperative delirium after total knee arthroplasty between 3 intraoperative sedation regimens including (1) propofol-fentanyl (2) dexmedetomidine -fentanyl (3) fentanyl alone Anesthesia techniques include spinal anesthesia and adductor canal block for postoperative analgesia. Sedation will be provide per group assignment. After performance of regional anesthesia, sedation protocols will be used as followed: (1) target-controlled infusion of Propofol to achieve MOAA/S of 3-4 (2) incremental titration of Dexmedetomidine to achieve MOAA/S of 3-4 (3) supplemental fentanyl for anxiolysis. Delirium will be screened by trained physicians, registered nurses every 8 hours postoperatively with validated Thai-version CAM-ICU (Confusion Assessment Method-Intensive Care Unit) until patient discharge. Serum Interleukins (IL-1, IL-6) Tumor necrosis factor-Alpha and S100B protein from preoperative period will be compared with serum from postoperative period between delirium and non-delirium group. The level of serum biomarkers will be acquired in a 6-hour interval for 5 measurement points during the first postoperative day in the first 12 participants. The subsequent participants will have 1 measurement of serum biomarker during the first postoperative day. Genetic profile for ApolipoproteinE genotype will be acquired and compared between delirium and non-delirium group.

Official Title
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Postoperative Delirium After Total Knee Arthroplasty Under Regional Anesthesia: a Comparison Between Intraoperative Sedation With Fentanyl, Fentanyl-dexmedetomidine and Fentanyl-propofol

Conditions
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Postoperative Delirium

Intervention / Treatment
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* Drug: Propofol
* Drug: Dexmedetomidine
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65 year or older Scheduled for elective primary total knee arthroplasty Exclusion Criteria: Contraindication for spinal anesthesia Contraindication for adductor canal block Allergy to fentanyl or propofol or dexmedetomidine or bupivacaine Cognitive impairment NSQIP database risk calculator > 10% overall complication Unable to communicate in Thai language Significant visual and hearing impairment

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propofol-fentanyl<br>Fentanyl 0.5 mcg/kg Propofol Target-controlled infusion to achieve MOAA/S 3-4 as end point of sedation Bispectral index (BIS) monitoring | Drug: Propofol<br>* target-controlled infusion starting for Cet 0.1 mcg/ml to achieve MOAA/S 3-4<br>Drug: Fentanyl<br>* 0.25 mcg fo Fentanyl for anxiolysis<br>|
| Experimental: Dexmedetomidine<br>Fentanyl 0.5 mcg/kg Dexmedetomidine in incremental titrated dose for moderate sedation to achieve MOAA/S 3-4 as end-point of titration Bispectral index (BIS) monitoring | Drug: Dexmedetomidine<br>* Incremental titration of dexmedetomidine starting from 0.1 mcg/kg/hr to achieve MOAA/S 3-4<br>Drug: Fentanyl<br>* 0.25 mcg fo Fentanyl for anxiolysis<br>|
| Experimental: Fentanyl<br>Fentanyl 0.5 mcg/kg Supplemental dosage of fentanyl for intraoperative anxiolysis | Drug: Fentanyl<br>* 0.25 mcg fo Fentanyl for anxiolysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium | Up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of age on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between age 65-75, 75-85, and >85 years of age | Up to 7 days | 
| Apolipoprotein genotype | ApoE epsilon subtype analysis | 1 days | 
| The effect of Apolipoprotein genotype on the incidence of postoperative delirium | ApoE epsilon subtype analysis | Up to 7 days | 
| Inflammatory biomarker | Preoperative and postoperative comparison of inflammatory biomarker (IL-1, IL-6 TNF, S100b protein) | 2 days | 
| The effect of delirium on inflammatory biomarker levels | Preoperative and postoperative comparison of inflammatory biomarker (IL-1, IL-6 TNF, S100b protein) comparison between delirium and non-delirium group | Up to 7 days | 
| The effect of gender on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between male and female | Up to 7 days | 
| The effect of ASA-physical status on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between ASA-PS I-II and III-IV | Up to 7 days | 
| The effect of alcohol consumption on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between amount of alcohol consumption (standard drink/day) | Up to 7 days | 
| The effect of cognitive inpairment on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without cognitive impairment. TMSE score will be use to determine cognitive status | Up to 7 days | 
| The effect of coronary artery disease on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without coronary artery disease. Preoperative diagnosis of coronary artery disease will be used. | Up to 7 days | 
| The effect of cerebrovascular disease on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without cerebrovascular disease. Preoperative diagnosis of cerebrovascular disease will be used. | Up to 7 days | 
| The effect of chronic kidney disease on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without chronic kidney disease. Preoperative diagnosis of cerebrovascular disease will be used. | Up to 7 days | 
| The effect of liver disease on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without liver disease. Preoperative diagnosis of liver disease will be used. | Up to 7 days | 
| The effect of hypertension on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without hypertension. Preoperative diagnosis of hypertension will be used. | Up to 7 days | 
| The effect of diabetes mellitus on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without diabetes mellitus. Preoperative diagnosis of diabetes will be used. | Up to 7 days | 
| The effect of postoperative pain on the incidence of postoperative delirium | Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with mild (pain score 0-3), moderate (4-7) and severe (7-10). Numeric rating scale will be used. | Up to 7 days | 
| The effect of intraoperative BIS value on the incidence of postoperative delirium | Intraoperative BIS value comparison between delirium and non-delirium group. Positive CAM-ICU result and confirmed DSM-V criteria will be used to diagnose delirium | 7 days | 
| The effect of intraoperative blood transfusion and blood loss on the incidence of postoperative delirium | Intraoperative blood transfusion and blood loss will be compared between delirium and non-delirium group. Positive CAM-ICU result and confirmed DSM-V criteria will be used to diagnose delirium | 7 days | 
| The effect of delirium on hospital length of stay | The hospital length of stay will be compared between delirium and non-delirium group. Positive CAM-ICU result and confirmed DSM-V criteria will be used to diagnose delirium | 7 days | 
| The effect of delirium on postoperative rehabilitation | The time to assisted walking in the postoperative period will be compared between delirium and non-delirium group. Positive CAM-ICU result and confirmed DSM-V criteria will be used to diagnose delirium | 7 days | 
| The effect of delirium on postoperative complications. | The incidence of 1) DVT 2) myocardial ischemia/infarction 3) urinary tract infection 4) stroke 5) wound infection will be compared between delirium and non-delirium group. Positive CAM-ICU result and confirmed DSM-V criteria will be used to diagnose delirium | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative delirium, total knee arthroplasty, propofol, dexmedetomidine, fentanyl, inflammatory response, interleukins, CAM-ICU