Postoperative Delirium After Total Knee Arthroplasty Under Regional Anesthesia

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

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.

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.

postoperative delirium, total knee arthroplasty, propofol, dexmedetomidine, fentanyl, inflammatory response, interleukins, CAM-ICU

Fentanyl 0.5 mcg/kg Propofol Target-controlled infusion to achieve MOAA/S 3-4 as end point of sedation Bispectral index (BIS) monitoring

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

Positive CAM-ICU result and confirmed DSM-V criteria for delirium between age 65-75, 75-85, and >85 years of age

Preoperative and postoperative comparison of inflammatory biomarker (IL-1, IL-6 TNF, S100b protein) comparison between delirium and non-delirium group

Positive CAM-ICU result and confirmed DSM-V criteria for delirium between amount of alcohol consumption (standard drink/day)

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

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.

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.

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.

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.

Positive CAM-ICU result and confirmed DSM-V criteria for delirium between patients with and without hypertension. Preoperative diagnosis of hypertension will be used.

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.

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.

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

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

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

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

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

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

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