Acute Kidney Injury, Cognitive Disorders, Delirium
Conditions
Brief summary
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.
Interventions
DRUGKetamine
Ketamine used for induction
DRUGPropofol
Propofol for induction
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Postoperative Cognitive Dysfunction | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Acute Kidney Injury | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. | 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. |
| Number of Patients Who Develop Postoperative Delirium | Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first. | 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. |
Countries
United States
Participant flow
Recruitment details
Participants who were undergoing complex cardiac surgery at Mayo Clinic were recruited between August 2015 and October 2019.
Pre-assignment details
Of the 265 patients assessed for eligibility, 52 were randomized to study groups. 8 did not meet inclusion criteria, 97 declined to participate, 96 were unable to be contacted before surgery, and 12 were unable to coordinate preoperative testing before surgery.
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Ketamine induction
Ketamine: Ketamine used for induction | 25 |
| Propofol Propofol induction
Propofol: Propofol used for induction | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | converted to transcatheter procedure | 0 | 1 |
| Overall Study | ineligible after enrollment | 1 | 0 |
| Overall Study | received both drugs | 0 | 1 |
Baseline characteristics
| Characteristic | Propofol | Total | Ketamine |
|---|---|---|---|
| Age, Continuous | 76.1 years STANDARD_DEVIATION 5.3 | 76.3 years STANDARD_DEVIATION 4.4 | 76.4 years STANDARD_DEVIATION 3.5 |
| Controlled Oral Word Association Test (COWAT) | 0.1 Z score STANDARD_DEVIATION 0.8 | 0.1 Z score STANDARD_DEVIATION 0.8 | 0.1 Z score STANDARD_DEVIATION 0.8 |
| Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall | -0.8 Z score STANDARD_DEVIATION 1.2 | -0.9 Z score STANDARD_DEVIATION 1.2 | -0.9 Z score STANDARD_DEVIATION 1.3 |
| Hopkins Verbal Learning Test-Revised (HVLT-R) Digit Span | 0.1 Z score STANDARD_DEVIATION 1 | 0.2 Z score STANDARD_DEVIATION 0.9 | 0.2 Z score STANDARD_DEVIATION 0.8 |
| Hopkins Verbal Learning Test-Revised (HVLT-R) Learning Trials test | -0.5 Z score STANDARD_DEVIATION 0.8 | -0.6 Z score STANDARD_DEVIATION 0.9 | -0.7 Z score STANDARD_DEVIATION 0.9 |
| Mini-Mental Status Exam | 0.4 Z score STANDARD_DEVIATION 1.1 | 0.6 Z score STANDARD_DEVIATION 1 | 0.7 Z score STANDARD_DEVIATION 0.9 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 24 Participants | 49 Participants | 25 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 30 Participants | 16 Participants |
| Stroop color/word test | -0.6 Z score STANDARD_DEVIATION 1.3 | -0.4 Z score STANDARD_DEVIATION 1.1 | -0.3 Z score STANDARD_DEVIATION 1 |
| Trail Making Test A | 0 Z score STANDARD_DEVIATION 1.1 | 0.0 Z score STANDARD_DEVIATION 1 | -0.1 Z score STANDARD_DEVIATION 0.8 |
| Trail Making Test B | -0.1 Z score STANDARD_DEVIATION 1.1 | 0.1 Z score STANDARD_DEVIATION 1.1 | 0.2 Z score STANDARD_DEVIATION 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 |
| other Total, other adverse events | 0 / 25 | 0 / 24 |
| serious Total, serious adverse events | 1 / 25 | 1 / 24 |
Outcome results
Primary
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.
Time frame: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.
Population: Intent to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Patients With Postoperative Cognitive Dysfunction | 16 Participants |
| Propofol | Number of Patients With Postoperative Cognitive Dysfunction | 10 Participants |
Comparison: Raw scores converted to z-scores using published references. Percentage of patients experiencing a decline of \> 1 standard deviation was compared between groups using Fisher's exact test. The outcome of 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 and was compared between groups using Fisher's exact test.p-value: 0.23Fisher Exact
Secondary
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.
Time frame: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Patients Who Develop Postoperative Delirium | 0 Participants |
| Propofol | Number of Patients Who Develop Postoperative Delirium | 1 Participants |
p-value: 0.31Chi-squared
Secondary
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.
Time frame: Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first.
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Patients With Acute Kidney Injury | 6 Participants |
| Propofol | Number of Patients With Acute Kidney Injury | 12 Participants |
p-value: 0.08Fisher Exact