Lidocaine For Neuroprotection During Cardiac Surgery

To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 14 cognitive test scores from baseline. We chose a five-factor solution, which represents 5 cognitive domains: structured verbal memory, unstructured verbal memory, executive function, visual memory and attention/concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 5 preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. The resulting outcome measure is unbounded with standard deviation of 0.35. A negative change score indicating decline and a positive score indicating improvement.

Time frame: Preoperative to 6 weeks after surgery

To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 14 cognitive test scores from baseline. We chose a five-factor solution, which represents 5 cognitive domains: structured verbal memory, unstructured verbal memory, executive function, visual memory and attention/concentration. Each domain score is normally distributed with a mean of zero. A change score was calculated for each domain by subtracting the baseline from the 6-week score. A dichotomous outcome variable of post-operative cognitive deficit was defined as a decline of ≥1 standard deviation in 1 or more of the 5 domains.

Time frame: Preoperative to 6 weeks after surgery

Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report examination designed to measure symptoms of depression. Subjects rate the degree to which they have experienced a range of symptoms of depression, such as I had crying spells and I felt lonely. Scores range from 0 to 60, with higher scores indicating greater depressive symptoms. Scores greater than 16 are typically considered indicative of clinically significant depression.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report examination designed to measure symptoms of depression. Subjects rate the degree to which they have experienced a range of symptoms of depression, such as I had crying spells and I felt lonely. Scores range from 0 to 60, with higher scores indicating greater depressive symptoms. Scores greater than 16 are typically considered indicative of clinically significant depression.

Time frame: baseline, 6-weeks

To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the 14 cognitive test scores from baseline. We chose a five-factor solution, which represents 5 cognitive domains: structured verbal memory, unstructured verbal memory, executive function, visual memory and attention/concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 5 preoperative domain scores. The cognitive index score has a mean of zero, thus any positive score is above the mean, any negative score is below the mean. A continuous change score was then calculated by subtracting the baseline from the 1 year cognitive index. The resulting outcome measure is unbounded with standard deviation of 0.35. A negative change score indicating decline and a positive score indicating improvement

Time frame: 1 year after surgery

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

The DASI is a 12-item scale of functional capacity that has been found to correlate well with objective measures of maximal exercise capacity. Items reflect activities of personal care, ambulation, household tasks, sexual function, and recreational activities. Activities done with no difficulty receive scores, which are weighted and summed, for a quantitative measure of functional status. Scores range from 0 to 60; a higher-weighted score indicates better function.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

The DASI is a 12-item scale of functional capacity that has been found to correlate well with objective measures of maximal exercise capacity. Items reflect activities of personal care, ambulation, household tasks, sexual function, and recreational activities. Activities done with no difficulty receive scores, which are weighted and summed, for a quantitative measure of functional status. Scores range from 0 to 60; a higher-weighted score indicates better function.

Time frame: baseline, 6-weeks

The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).

Time frame: baseline, 6-weeks

The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

The Western perioperative neurologic scale was designed to detect neurologic deficits after cardiac surgery. It includes 14 items classified into eight domains (mentation, speech, cranial nerve function, motor weakness, sensation and cerebellum, reflexes, and gait). Each item is scored from 0 (severe deficit) to3 (normal), and a maximum score of 42 indicates normal neurological function.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

The Western perioperative neurologic scale was designed to detect neurologic deficits after cardiac surgery. It includes 14 items classified into eight domains (mentation, speech, cranial nerve function, motor weakness, sensation and cerebellum, reflexes, and gait). Each item is scored from 0 (severe deficit) to3 (normal), and a maximum score of 42 indicates normal neurological function.

Time frame: baseline, 6-weeks

Perceived Social Support Scale: Twelve items indicate how strongly subjects agree that there is a special person who is around when I am in need and my family really tries to help me. Choices range from very strongly disagree to very strongly agree. Items are summed for a range of 12 to 84, with a high score meaning more social support.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Perceived Social Support Scale: Twelve items indicate how strongly subjects agree that there is a special person who is around when I am in need and my family really tries to help me. Choices range from very strongly disagree to very strongly agree. Items are summed for a range of 12 to 84, with a high score meaning more social support.

Time frame: baseline, 6-weeks

Social Activity: This measure consisted of eight items that indicate the degree of social interaction. Sample items are How often do you talk on the telephone with friends and relatives? and How often do you attend meetings of social groups, clubs, or civic organizations? Scores range from 8 to 32. A lower score indicates more social activity.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Social Activity: This measure consisted of eight items that indicate the degree of social interaction. Sample items are How often do you talk on the telephone with friends and relatives? and How often do you attend meetings of social groups, clubs, or civic organizations? Scores range from 8 to 32. A lower score indicates more social activity.

Time frame: baseline, 6-weeks

Spielberger State Anxiety Inventory (STAI): The STAI consists of two 20-item scales that measure anxiety. Representative items include statements such as I feel nervous and I feel worried. These items are rated on a 4-point scale, based on how well they describe the patient's current or typical mood, from not at all to very much so. Scores range from 20 to 80, with higher scores indicating greater anxiety.

Time frame: baseline, 6-weeks

Spielberger State Anxiety Inventory (STAI): The STAI consists of two 20-item scales that measure anxiety. Representative items include statements such as I feel nervous and I feel worried. These items are rated on a 4-point scale, based on how well they describe the patient's current or typical mood, from not at all to very much so. Scores range from 20 to 80, with higher scores indicating greater anxiety.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36): The SF-36 was designed to measure general health status. Two scales were used: Work Activities (four items) and General Health (one item). For the work activities scale, the reported score was the sum of four questions, each with values ranging from 1 to 4, the total score could range from 4 to 16. A higher score on Work Activities indicates more health-related problems For the general health question, the patients ranked their health from Excellent (1) to poor (5), the scale ranged from 1 to 5 with 1 being best health and 5 being worst. A high score in General Health indicates poorer health state.

Time frame: baseline, 6-weeks

The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36): The SF-36 was designed to measure general health status. Two scales were used: Work Activities (four items) and General Health (one item). For the work activities scale, the reported score was the sum of four questions, each with values ranging from 1 to 4, the total score could range from 4 to 16. A higher score on Work Activities indicates more health-related problems For the general health question, the patients ranked their health from Excellent (1) to poor (5), the scale ranged from 1 to 5 with 1 being best health and 5 being worst. A high score in General Health indicates poorer health state.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Symptom limitations: Patients were given a list of eight symptoms and asked to rate the degree to which the symptom limited daily activities. The symptoms were angina, shortness of breath, arthritis, back trouble, leg pains, headaches, fatigue, and other. Scores range from 8 to 32, with higher scores indicating greater limitations.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Symptom limitations: Patients were given a list of eight symptoms and asked to rate the degree to which the symptom limited daily activities. The symptoms were angina, shortness of breath, arthritis, back trouble, leg pains, headaches, fatigue, and other. Scores range from 8 to 32, with higher scores indicating greater limitations.

Time frame: baseline, 6-weeks

Cognitive Difficulties Scale: a 39-item scale, is a self-report assessment of perceived problems in long- and short-term memory, concentration, attention, and psycho-motor coordination. Sample items are I forget errands I planned to do and I fail to recognize people I know. Scores range from 39 to 164, with higher scores indicating greater cognitive difficulty.

Time frame: baseline, 6-weeks

Cognitive Difficulties Scale: a 39-item scale, is a self-report assessment of perceived problems in long- and short-term memory, concentration, attention, and psycho-motor coordination. Sample items are I forget errands I planned to do and I fail to recognize people I know. Scores range from 39 to 164, with higher scores indicating greater cognitive difficulty.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL): This measure contains six items that assess the ability to perform important tasks for daily living (e.g., Could you prepare your own meals? Could you drive a car?). Scores range from 6 to 24. Higher scores indicate increasing difficulty in engaging in daily activities.

Time frame: baseline, 1-year

Population: There was 26 lidocaine patients and 17 placebo patients lost to follow-up between the primary 6-week follow-up and the final 1-year follow-up time point. Only those returning for 1 year follow-up were included in the analysis.

Duke Older Americans Resources and Services Procedures- Instrumental Activities of Daily Living (OARS-IADL): This measure contains six items that assess the ability to perform important tasks for daily living (e.g., Could you prepare your own meals? Could you drive a car?). Scores range from 6 to 24. Higher scores indicate increasing difficulty in engaging in daily activities.

Time frame: baseline, 6-weeks

Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

Time frame: Baseline to 6 hours post cross-clamp removal

Population: Planned substudy, that was analyzed after 202 enrolled subjects.

Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

Time frame: Baseline to 6 hours post cross-clamp removal

Population: Planned substudy, that was analyzed after 202 enrolled subjects.

Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removal and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

Time frame: Baseline to 6 hours post cross-clamp removal

Population: Planned substudy, that was analyzed after 202 enrolled subjects

Paired jugular venous and radial arterial blood samples were drawn at baseline, cross-clamp removal, end of cardiopulmonary bypass, and 6 hours post cross-clamp removalime points and analyzed by fluorescence-activated cell sorting to identify activated platelets. Transcerebral activation gradients were calculated by subtracting arterial values from venous values and were compared between groups

Time frame: Baseline to 6 hours post cross-clamp removal

Population: Planned substudy, that was analyzed after 202 enrolled subjects