Coronary Artery Disease, Neurological Impairment, Postoperative Cognitive Dysfunction
Conditions
Keywords
cerebral oximetry, NIRS, INVOS
Brief summary
It is previously reported that the cerebral oxygen desaturation during cardiac surgery is associated with an increased incidence of cognitive impairment. The aim of this study is to determine whether intraoperative monitoring and predetermined interventions protocol to improve cerebral oxygenation during coronary artery bypass surgery provides benefits in neurocognitive functions.
Detailed description
Neurologic complications are major cause of morbidity following coronary artery bypass graft surgery. The neurologic injuries range in severity from subclinical cognitive changes to fatal brain injury and death. These complications represent a big impact on overall morbidity, and mortality in association with increased costs and length of hospital stay. The social impact is also very important with consequences on patients' quality of life. Several studies reported the incidence of cognitive decline after cardiac surgery that ranges from 30 to 80%. The most common etiologies are embolization and hypoperfusion of the brain. The In Vivo Optical Spectroscopy (INVOS) system uses near-infrared spectroscopy (NIRS) and provides noninvasive and continuous information on changes in regional oxygen saturation of blood in the brain (rSO2). When rSO2 decline occurs it can be responded with simple interventions to prevent a brain injury. These interventions include: repositioning of the head or perfusion cannulae, increasing arterial carbon dioxide tension, increasing oxygen inspiration concentration, increasing arterial blood pressure, adjusting pump flow rate, temperature decreasing, increasing of anesthetic depth and blood transfusion. Recent studies reported that intraoperative cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. Neurocognitive function can be assessed with battery of standardized neurocognitive tests. Mini Mental State Examination, Color Trail Test, Grooved Pegboard Test are easy to perform bedside tests that test orientation, registration, attention, calculation, recall, language and complex visual-motor coordination.
Interventions
DEVICEINVOS
Monitoring cerebral oxygenation (rSO2) with INVOS. When rSO2 decline occur it can be responded with simple interventions to prevent a brain injury including: repositioning of the head or perfusion cannulae to avoid mechanical obstruction of cerebral blood flow, increasing arterial carbon dioxide tension within normal referent values, increasing oxygen inspiration concentration to maintain adequate tissue oxygen saturation, increasing arterial blood pressure, pump flow rate and cardiac index, temperature decreasing and increasing of anesthetic depth to reduce cerebral oxygen consumption and blood transfusion if hematocrit decreases below 22%. None of the interventions are outside the range of good clinical practice.
Sponsors
University of Zagreb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* All patients with coronary artery disease undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass
Exclusion criteria
* Who refuse to participate * Previous stroke * Preexisting psychiatric disease * Significant carotid stenosis * Ejection fraction below 25% * Reoperations * Emergent surgery * Dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Incidence of Cognitive Impairment Between Groups. Change Between Preoperative and Postoperative Cognitive Function Was Assessed by Performing Standardized Neurocognitive Tests. | preoperative, 7 days postoperative | The Mini-Mental State Examination (MMSE) total score is calculated by summing the item scores across several aspects of cognition. The maximum possible total score is 30 points. Color Trials Test (CTT) measures sustained visual attention, visual scanning and graphomotor skills. The examiner records the length of time (in seconds) required by the patient to rapidly draw a line connecting the circles numbered 1 through 25 in consecutive order. Grooved-Pegboard test (GP test) is manipulative dexterity test that contains twenty-five holes with randomly positioned slots and pegs which have a key along one side. Pegs must be rotated to match the hole before they can be inserted. The examiner records the time in seconds. Cognitive impairment was defined as a decline in postoperative performance in one or more tests: decrease of MMSE score three points or more from baseline and decrease of one standard deviation or more in performance on CTT 1 and GP tests |
Secondary
| Measure | Time frame |
|---|---|
| Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | 7 postoperative days |
Countries
Croatia
Participant flow
Recruitment details
Assessed for eligibility (n=287) Excluded (n=87) * Not meeting inclusion criteria (n=79) * Declined to participate (n=8)
Participants by arm
| Arm | Count |
|---|---|
| CONTROL The CONTROL arm did not have INVOS or any other cerebral oxygenation monitoring, so interventions to control cerebral oxygenation were not performed. | 96 |
| INVOS INVOS (In Vivo Optical Spectroscopy): Cerebral oxygenation (rSO2) monitoring with INVOS device. If rSO2 decreased for more than 20% from patient's baseline value, simple interventions were performed to prevent brain injury. These interventions included: repositioning of head or perfusion cannulae, increasing arterial carbon dioxide tension, increasing oxygen inspiration concentration, increasing arterial blood pressure, adjusting pump flow rate, temperature decreasing, increasing of anesthetic depth and blood transfusion. | 94 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 4 | 6 |
Baseline characteristics
| Characteristic | CONTROL | INVOS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 30 Participants | 78 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 64 Participants | 112 Participants |
| Age, Continuous | 63.4 years STANDARD_DEVIATION 8.8 | 61.9 years STANDARD_DEVIATION 7.1 | 62.4 years STANDARD_DEVIATION 9.1 |
| Aortic cross-clamp time | 62 minutes STANDARD_DEVIATION 26 | 63 minutes STANDARD_DEVIATION 23 | 63 minutes STANDARD_DEVIATION 25 |
| Bypass time | 89 minutes STANDARD_DEVIATION 32 | 91 minutes STANDARD_DEVIATION 31 | 90 minutes STANDARD_DEVIATION 31 |
| Comorbidity - Atrial fibrillation before operation Atrial fibrillation | 5 participants | 4 participants | 9 participants |
| Comorbidity - Atrial fibrillation before operation Without atrial fibrillation | 91 participants | 90 participants | 181 participants |
| Comorbidity - diabetes Diabetes | 33 participants | 28 participants | 61 participants |
| Comorbidity - diabetes Without diabetes | 63 participants | 66 participants | 129 participants |
| Comorbidity - hypertension Hypertension | 85 participants | 79 participants | 164 participants |
| Comorbidity - hypertension Without hypertension | 11 participants | 15 participants | 26 participants |
| Comorbidity - Myocardial infarction within 1 month before operation Without preoperative myocardial infarction | 84 participants | 86 participants | 170 participants |
| Comorbidity - Myocardial infarction within 1 month before operation With preoperative myocardial infarction | 12 participants | 8 participants | 20 participants |
| Ejection fraction | 56 % STANDARD_DEVIATION 9.9 | 56 % STANDARD_DEVIATION 9.7 | 56 % STANDARD_DEVIATION 9.8 |
| EuroSCORE | 2.4 % - predicted mortality STANDARD_DEVIATION 1.7 | 2.2 % - predicted mortality STANDARD_DEVIATION 1.7 | 2.3 % - predicted mortality STANDARD_DEVIATION 1.7 |
| Region of Enrollment Croatia | 96 participants | 94 participants | 190 participants |
| Sex: Female, Male Female | 23 Participants | 19 Participants | 42 Participants |
| Sex: Female, Male Male | 73 Participants | 75 Participants | 148 Participants |
| Years of education | 11.2 years STANDARD_DEVIATION 3.2 | 11.3 years STANDARD_DEVIATION 3.4 | 11.2 years STANDARD_DEVIATION 3.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 94 | 0 / 96 |
| serious Total, serious adverse events | 0 / 94 | 0 / 96 |
Outcome results
Primary
Difference in Incidence of Cognitive Impairment Between Groups. Change Between Preoperative and Postoperative Cognitive Function Was Assessed by Performing Standardized Neurocognitive Tests.
The Mini-Mental State Examination (MMSE) total score is calculated by summing the item scores across several aspects of cognition. The maximum possible total score is 30 points. Color Trials Test (CTT) measures sustained visual attention, visual scanning and graphomotor skills. The examiner records the length of time (in seconds) required by the patient to rapidly draw a line connecting the circles numbered 1 through 25 in consecutive order. Grooved-Pegboard test (GP test) is manipulative dexterity test that contains twenty-five holes with randomly positioned slots and pegs which have a key along one side. Pegs must be rotated to match the hole before they can be inserted. The examiner records the time in seconds. Cognitive impairment was defined as a decline in postoperative performance in one or more tests: decrease of MMSE score three points or more from baseline and decrease of one standard deviation or more in performance on CTT 1 and GP tests
Time frame: preoperative, 7 days postoperative
Population: 3 participants in Control group did not perform control cognitive test- transferred to another hospital.~6 participants in INVOS group did not perform control cognitive test - transferred to another hospital n=4, declined to participate n=2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CONTROL | Difference in Incidence of Cognitive Impairment Between Groups. Change Between Preoperative and Postoperative Cognitive Function Was Assessed by Performing Standardized Neurocognitive Tests. | 48 participants |
| INVOS | Difference in Incidence of Cognitive Impairment Between Groups. Change Between Preoperative and Postoperative Cognitive Function Was Assessed by Performing Standardized Neurocognitive Tests. | 25 participants |
Comparison: Hypothesis: intraoperative monitoring of cerebral oxigenation with INVOS system will improve cognitive outcome of patients undergoing CABG procedure.~Sample size was determined assuming 50% incidence of cognitive impairment after cardiac surgery and possibility of decreasing that incidence to 30% using cerebral oximetry. Based on 0.8 power to detect a significant difference (p=0.05), 90 patients were required for each study group.p-value: 0.002Chi-squared, Corrected
Secondary
Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days
Time frame: 7 postoperative days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Delirium | 13 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Infection (any type) | 18 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Revision for bleeding | 1 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Myocardial infarction | 7 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Atrial fibrillation | 26 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Prolonged mechanical ventilation | 2 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Hospital stay > 7 days | 43 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Hemodialysis | 1 participants |
| CONTROL | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Stroke, coma, stupor | 1 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Infection (any type) | 17 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Stroke, coma, stupor | 4 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Delirium | 8 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Prolonged mechanical ventilation | 1 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Myocardial infarction | 7 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Hemodialysis | 0 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Revision for bleeding | 0 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Atrial fibrillation | 21 participants |
| INVOS | Evidence of Coma, Stupor, Cerebral Insult, Delirium, Ventilation Longer Than 24 Hours, Myocardial Infarction, Atrial Fibrillation, Dialysis, Reoperation for Bleeding, Infection, Hospital Stay > 7 Days | Hospital stay > 7 days | 44 participants |