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Objective: The aim of this study was to determine the effect of dexmedetomidine in reducing postoperative cognitive dysfunction (POCD) in cardiac surgical patients which use cardiopulmonary bypass machine (CPB).
Materials and Methods: This study was double-blinded, randomized controlled trial. Patients scheduled for elective CPB facilitated cardiac surgery were randomly assigned in two groups, dexmedetomidine group (DEX) or control group. The cognitive tests (MoCA test and Short bless test) were done before the operation, 48 hours, and 7 days postoperatively. POCD was defined as a decline of 1SD of baseline score in any test. Arterial blood sample were analyzed for IL-6, IL-10, TNF-alpha and hs-CRP before induction (T0), after separation from CPB (T1), arrival at ICU (T2) and 24-hour after surgery (T3). Primary outcome was the incidence of POCD and the secondary outcomes were inflammatory response, other postoperative complications, ICU and hospital stay.
After the patients were enrolled in the study, they were allocated into Dexmedetomidine group or control group by computer-based randomization. Patients, surgeons, anesthesiologists and researchers who performed the cognitive test were all blinded to the study groups.
General anesthesia was induced with intravenously midazolam 0.1-0.2 mg/kg and fentanyl 5-10 mcg/kg or Thiopental 3-5 mg/kg or Propofol 2 mg/kg. Patients were intubated with pancuronium 1 mg/kg or rocuronium 0.6-1 mg/kg. Anesthesia was maintained with nitrous oxide in oxygen, isoflurane, fentanyl, and pancuronium or rocuronium as required. Standard monitoring was provided including an indwelling radial artery catheter and central venous catheter. Bispectral index (BIS) monitoring was applied and maintained between 40-60 through the operation. Cerebral oximetry was monitored both sides of the brain by non-invasive oximeters at forehead area and the data were recorded.
After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation.The control group received a loading dose and continuous IV infusion of normal saline at the same rate.
During the cardiopulmonary bypass, mean arterial pressure was maintained at 60-80 mmHg or 20% from baseline. If hypertension was detected, Nicardipine 0.2 mg was given intravenously. Ephedrine 6 mg or norepinephrine 4 mcg were given within 5 minutes and repeated every 5 minutes if hypotension was presented. Atropine 0.6 mg was administered for bradycardia (heart rate less than 50 beats per minute). After the operation, patients were transferred to Cardio-thoracic intensive care unit and received standard postoperative cardiac surgery care.
2 neuropsychological tests were used to evaluate patients' cognitive function; Montreal Cognitive Assessment (MoCA) and Short blessed test (SBT). These tests were chosen by King Chulalongkorn Memorial Hospital's psychiatrist based on previous studies and the statement consensus on assessment of neurobehavioral outcomes after cardiac surgery published in 1995. All patients were evaluated their cognitive function for 3 points of time, 1st time was at preoperative period (T1), 2nd time was at 48 hours postoperatively (T2) and the last one was at 7 days postoperatively or the day at discharge from the hospital (T3). POCD was defined as a decline of 1 standard deviation (1SD) of baseline score in any test.
Blood samples were taken through the radial artery catheter, and sampling times were chosen as follows: before the induction of anaesthesia (T0); after separated from CPB (T1); arrival at intensive care unit (ICU) (T2); 24 hr after surgery (T3). Plasma Tissue Necrotic Factor-Alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels were measured by Magnetic Luminex Performance Assay. High sensitivity C-reactive protein (CRP) level were also measured by nephelometry.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dex group | Experimental | After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation. |
|
| Placebo group | Placebo Comparator | The control group received a loading dose and continuous IV infusion of normal saline at the same rate. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | After skin incision, the dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation. |
| Measure | Description | Time Frame |
|---|---|---|
| Numbers of Participants With Postoperative Cognitive Dysfunction (POCD) | POCD was defined as a decline of 1 standard-deviation (1SD) of baseline score in either MoCA test or short bless test. | 48 hours |
| Number of Participants With Postoperative Cognitive Dysfunction (POCD) | POCD was defined as a decline of 1SD of baseline score in either MoCA test or short bless test. | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Postoperative Complications | Neurological complication, Delirium, dysrhythmia, death | 7 days |
| Hospital Stay in Days | 30 days |
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Inclusion Criteria:
Exclusion Criteria:
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| ID | Title | Description |
|---|---|---|
| FG000 | Dex Group | After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation. |
| FG001 | Placebo Group | The control group received a loading dose and continuous IV infusion of normal saline at the same rate. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dex Group | After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation. |
| BG001 | Placebo Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Numbers of Participants With Postoperative Cognitive Dysfunction (POCD) | POCD was defined as a decline of 1 standard-deviation (1SD) of baseline score in either MoCA test or short bless test. | Posted | Count of Participants | Participants | 48 hours |
|
7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dex Group | After skin incision, the Dexmedetomidine group received a loading dose of 0.5 mcg/kg of Dexmedetomidine in 20 minutes followed by a continuous IV infusion at 0.4 mcg/kg/hr until the end of operation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebrovascular events | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| dysrhythmia | Cardiac disorders | Non-systematic Assessment |
Some missing data of postoperative neurocognitive assessment score leading to inconclusive results of some participants Low incidence of POCD in our samples leading to less reliable results
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr.Yada Thongsuk | King Chulalongkorn Memorial Hospital | +66817738629 | thongsuk.y@hotmail.com |
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| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Placebo | Drug | The control group received a loading dose and continuous IV infusion of normal saline at the same volume and rate as in the dexmedetomidine group |
|
| ICU Stay in Hours | 7 days |
The control group received a loading dose and continuous IV infusion of normal saline at the same rate.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| BMI | Mean | Standard Deviation | Kilograms per metre square |
|
| Left Ventricular Ejection Fraction | Mean | Standard Deviation | percentage of left ventricular ejection |
|
| Serum Creatinine | Mean | Standard Deviation | miligram per decilitre |
|
| Operation type | Count of Participants | Participants |
|
| Operative Time | Mean | Standard Deviation | minutes |
|
| Cardiopulmonary Bypass Time | Mean | Standard Deviation | minutes |
|
| Aortic Cross-clamp Time | Mean | Standard Deviation | minutes |
|
| Diabetes Mellitus | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Atrial fibrillation | Count of Participants | Participants |
|
| Baseline Montreal Cognitive Assessment scores (0-30 points) | Montreal Cognitive Assessment (MoCA) is a screening test for assessment of multiple aspects of cognitive function including, attention, concentration, executive function, memory, language, calculation, visuospatial ability and orientation. MoCA score ranges from 0 to 30. Score more than 25 will be defined as normal cognitive function. | Mean | Standard Deviation | points |
|
| Baseline Short Blessed Test score (0-28 points) | Short Blessed Test (SBT) is a screening test for detecting cognitive change in the aspects of memory and concentration. SBT score ranges from 0 to 28. Score less than 4 will be defined as normal cognitive function. | Mean | Standard Deviation | points |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Number of Participants With Postoperative Cognitive Dysfunction (POCD) | POCD was defined as a decline of 1SD of baseline score in either MoCA test or short bless test. | Posted | Count of Participants | Participants | 7 days |
|
|
|
|
| Secondary | Number of Participants With Postoperative Complications | Neurological complication, Delirium, dysrhythmia, death | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Hospital Stay in Days | Posted | Mean | Standard Deviation | days | 30 days |
|
|
|
|
| Secondary | ICU Stay in Hours | Posted | Mean | Standard Deviation | hours | 7 days |
|
|
|
|
| 0 |
| 49 |
| 0 |
| 49 |
| 13 |
| 49 |
| EG001 | Placebo Group | The control group received a loading dose and continuous IV infusion of normal saline at the same rate. | 0 | 50 | 1 | 50 | 11 | 50 |
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