The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction

Study Overview
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Brief Summary
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Ketamine is a commonly used anesthetic medication which is used for induction of anesthesia as well as as an analgesic. It has been shown to have anti-inflammatory properties which may decrease post-operative complications following cardiac surgery with cardiopulmonary bypass that are thought to associated with inflammation. Some studies have shown that ketamine does decrease these complications when compared with anesthetics that are not commonly used in our cardiac anesthesiology practice. Propofol is another commonly used anesthetic medication which is used for induction of anesthesia. Ketamine has not been compared with propofol for potential to reduce post-operative complications associated with the inflammatory process. This study aims to see if ketamine will reduce the incidence of cognitive dysfunction, delirium, and renal dysfunction in comparison with propofol. In addition, the hemodynamic impact of ketamine compared propofol will be investigated.

Official Title
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The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction in Patients 75 Years of Age or Older and Undergoing Cardiac Surgery

Conditions
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Cognitive Disorders, Delirium, Acute Kidney Injury

Intervention / Treatment
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* Drug: Ketamine
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Scheduled to undergo cardiac surgery. Inclusion criteria: age greater than or equal to 75 years presenting for cardiac surgery at the Mayo Clinic in Rochester, Minnesota; schedule to undergo complex cardiac surgery. Complex cardiac surgery will be defined as surgery involving more than one heart valve, redo-sternotomy procedures, or combined valvular and CABG procedures. Exclusion criteria will include: left or right ventricular assist device implantation or explantation, procedures not requiring cardiopulmonary bypass, active infection or sepsis, severe hepatic disease or ascites, pre-operative renal dysfunction including a baseline creatinine equal to or greater than 1.5 mg/dL or requiring dialysis, immunosuppressive medication use (including steroid use), immunodeficiency syndrome, known neurologic or psychiatric disorder, or use of drugs for psychosis.

Ages Eligible for Study
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Minimum Age: 75 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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ketamine<br>Ketamine induction | Drug: Ketamine<br>* Ketamine used for induction<br>* Other names: Ketalar;|
| Active Comparator: Propofol<br>Propofol induction | Drug: Propofol<br>* Propofol for induction<br>* Other names: Propoven;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Postoperative Cognitive Dysfunction | Pre and postoperative cognitive studies will be performed to assess change in cognitive function. Postoperative cognitive dysfunction (POCD) was defined a-priori as a decline of decline of >1 standard deviation (i.e. z-score decline of > 1) on at least 2 neurocognitive tests. The neurocognitive tests utilized include Trail making Test A, Trail making Test B, Hopkins Verbal Learning Test-Revised Learning trials, Hopkins Verbal Learning Test-Revised Delayed Recall, Digit Span, Controlled Oral Word Association Test, Stroop color/word test, and the Mini Mental Status Examination. | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Acute Kidney Injury | AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria including an increase in serum creatinine ≥0.3 mg/dL within 48 hours, an increase in serum creatinine to ≥1.5 times baseline within 7 days, and urine output < 0.5 mL/kg/hr for 6 hours. | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. | 
| Number of Patients Who Develop Postoperative Delirium | Delirium was defined as a positive CAM (Confusion assessment method) score. CAM score was recorded every 12 hours postoperatively as per routine. The CAM consists of 4 features: 1-Onset, 2-Inattention, 3-Disorganized thinking, and 4-altered level of consciousness. The diagnosis of delirium by CAM is based on the presence of features 1 and 2, and either 3 or 4. The score is either positive or negative. Positive means the patient has delirium and negative indicates the patient is not delirious. | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. |