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Isoproterenol is used as a cardiac stimulant in electrophysiology studies (EP). Preliminary data suggests that administration of isoproterenol increases the Bispectral index (BIS). BIS is used to monitor neuronal signals under anesthesia. The BIS level is suggested to correspond to the level of consciousness. We hypothesize that isoproterenol increases BIS values because it increases the patient's level of consciousness through its central nervous system (CNS) stimulatory effects. In this study, we will administer increasing doses of isoproterenol to EPS patients. We will measure the BIS levels continuously before and after isoproterenol administration. In addition, we will test the level of awareness of patients by their response to a modified isolated forearm technique.
Isoproterenol is a direct acting Beta-1 and Beta-2 agonist useful for its effects on bronchodilation and myocardial contractility. Its CNS side effects include nervousness, headache, dizziness, restlessness, insomnia, anxiety, tension, blurring of vision, fear, and excitement. In addition to our preliminary data, two case reports show an increase in BIS with administration of isoproterenol. Our hypothesis is that administration of isoproterenol will increase the level of consciousness of the patient as reflected in the BIS reading.
The BIS Vista Monitor is a non-invasive device that measures the electrical activity of the brain. It computes a number between 0 and 100 which corresponds to a level of consciousness which is known as the Bispectral (BIS) value. Using the BIS value to guide administration of anesthetic medication, clinicians can make informed decisions for optimal anesthesia. This technology has the potential to prevent over sedation, but is currently not a standard monitoring device.
Another approach to evaluating the level of consciousness of anesthetized patients is to assess their ability to form memories or recall events which occurred while under anesthesia. Conscious recall is the first to disappear with decreasing levels of consciousness. A BIS of 60 or less has been shown in various studies to be sufficient to prevent conscious recall in the vast majority of patients. We propose to use a modified isolated forearm technique test in which the patient is asked to squeeze an observer's hand during anesthesia to ascertain if awareness can occur without recall at a BIS of 60 to 70. (6) Implicit memory in which there is no conscious recall or evaluation of awareness can be assessed by word stem completion tests and has been shown to occur with a BIS as low as 40 - 60 although these results are not consistent across all studies. (7)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Isoproterenol, BIS, forearm test | Experimental | 30 consecutive patients scheduled for EP studies under general anesthesia will participate in the study. Patients with neuromuscular disease precluding the use of succinylcholine will be excluded. The only other exclusions will be patient or cardiologist refusal. No attempts will be made to alter concurrent patient medication. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isoproterenol | Drug | patients will receive isoproterenol, have a BIS monitoring device and a modified isolated forearm test (no neuromuscular blockade). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Increase in BIS Readings During Steady State | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. BIS levels were measured continuously before and after isoproterenol administration. Number of participants with increase in BIS reading during anesthetic steady state are reported below. The BIS scale ranges from 0 to 100. The individual's baseline BIS was measured continuously and was maintained in an anesthetic steady state with minimum variance prior to isoproterenol. A deviation from the mean in excess of 3 points (2 STD) was defined categorically as a positive response and was counted dichotomously. | During time of Electrophysiology (EP) studies. |
| BIS Change | The BIS scale ranges from 0 to 100. The individual's baseline BIS was measured continuously and was maintained in an anesthetic steady state with minimum variance prior to isoproterenol. A deviation from the mean in excess of 3 points (2 STD) was defined categorically as a positive response and was counted dichotomously.The difference between Pre-BIS and Post-BIS was calculated. | Within 20 minutes of starting isoproterenol infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Spontaneous Musculoskeletal Movement | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Patients under steady state total venous anesthesia (TIVA) with propofol and remifentanil infusions with BIS around 50 normally do not move even in the absence of neuromuscular blockade. Spontaneous movement appearing like restlessness during sleep is unusual. Several patients under anesthesia after isoproterenol appear to wake up and move spontaneously. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Significant Change in Heart Rate | Heart rate measured by standard EKG monitor during anesthesia. Pre- and Post Heart rates where noted. An increase of 8 percent or more was defined as a significant change in heart rate. | Within 20 minutes of starting isoproterenol infusion |
| Number of Participants With Change in Blood Pressure |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Linton, MD | NYU School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NYU Langone Medical Center, Department of Anesthesiology | New York | New York | 10016 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22366997 | Background | O'Neill DK, Aizer A, Linton P, Bloom M, Rose E, Chinitz L. Isoproterenol infusion increases level of consciousness during catheter ablation of atrial fibrillation. J Interv Card Electrophysiol. 2012 Aug;34(2):137-42. doi: 10.1007/s10840-011-9652-3. Epub 2012 Feb 25. |
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During the preoperative evaluation for anesthesia, the patients scheduled for catheter ablation for atrial fibrillation were approached by the research associate for informed consent and enrollment into the study. The research consent was separate from the clinical anesthesia and procedural consents.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pre and Post Isoproterenol Infusion | Bispectral EEG (BIS) monitoring and neurological examinations were repeated throughout an isoproterenol infusion protocol (20 minutes maximum) to measure the changes in arousal and ability to follow commands under anesthesia |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pre and Post Isoproterenol Infusion | Subjects undergoing catheter ablation for atrial fibrillation had measurements pre and post isoproterenol infusion |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Demographics and BIS were measured |
| 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 | Number of Participants With an Increase in BIS Readings During Steady State | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. BIS levels were measured continuously before and after isoproterenol administration. Number of participants with increase in BIS reading during anesthetic steady state are reported below. The BIS scale ranges from 0 to 100. The individual's baseline BIS was measured continuously and was maintained in an anesthetic steady state with minimum variance prior to isoproterenol. A deviation from the mean in excess of 3 points (2 STD) was defined categorically as a positive response and was counted dichotomously. | Posted | Number | participants | During time of Electrophysiology (EP) studies. |
|
24 hours
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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 | Pre and Post Isoproterenol Infusion | In this study, serious adverse events were considered clinically significant adverse events. The well known isoproterenol effects on heart rate, rhythm, ST segments, and blood pressure were noted. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | Systematic Assessment | Elevated heart rate |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick Linton, MD, Director of Adult Off-Site Anesthesia Services | New York University Langone Medical Center, Anesthesiology | 212-263-5072 | Patrick.Linton@nyumc.org |
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| ID | Term |
|---|---|
| D058926 | Intraoperative Awareness |
| ID | Term |
|---|---|
| D007431 | Intraoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D007545 | Isoproterenol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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|
| Within 20 minutes of starting isoproterenol infusion |
| Number of Participants Who Follow Verbal Command to Squeeze Hands | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Ability to follow verbal commands before and after isoproterenol infusion was assessed by asking subjects to "squeeze my hands". | Within 20 minutes of starting isoproterenol infusion |
Non-Invasive Blood Pressure (NIBP) is measured routinely as part of an anesthetic. Pre- and Post Blood Pressures where noted. An increase or decrease of 10 percent or more was defined as a significant change in systolic blood pressure. |
| Within 20 minutes of starting isoproterenol infusion |
| Number of Participants With Amnesia or No Recall During Steady State | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Specific pre-determined test words were spoken to the subject during administration of isoproterenol. After anesthesia, patients were tested for possible recall of those specific words. If no words were recalled, the result was categorically defined as amnesia. | Within one hour of completing anesthesia |
| Number of Participants With New Arrhythmia During Steady State. | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation after return to sinus rhythm. If a non-sinus arrhythmia resulted from the infusion, the arrhythmia was defined categorically as a positive response and was counted dichotomously. | Within 20 minutes of start of isoproterenol |
| Number of Participants Who Developed Ischemia or ST Segment Changes | The (ST) segment on the EKG was monitored for changes suggestive of demand ischemia. An observable EKG change compared to baseline was defined categorically as a positive response and was counted dichotomously. | Within 20 minutes of starting isoproterenol infusion |
| Count of Participants |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Number of Participants With Spontaneous Musculoskeletal Movement | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Patients under steady state total venous anesthesia (TIVA) with propofol and remifentanil infusions with BIS around 50 normally do not move even in the absence of neuromuscular blockade. Spontaneous movement appearing like restlessness during sleep is unusual. Several patients under anesthesia after isoproterenol appear to wake up and move spontaneously. | Posted | Number | participants | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| Secondary | Number of Participants Who Follow Verbal Command to Squeeze Hands | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Ability to follow verbal commands before and after isoproterenol infusion was assessed by asking subjects to "squeeze my hands". | Posted | Number | participants | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| Other Pre-specified | Number of Participants With Significant Change in Heart Rate | Heart rate measured by standard EKG monitor during anesthesia. Pre- and Post Heart rates where noted. An increase of 8 percent or more was defined as a significant change in heart rate. | Posted | Number | participants | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| Other Pre-specified | Number of Participants With Change in Blood Pressure | Non-Invasive Blood Pressure (NIBP) is measured routinely as part of an anesthetic. Pre- and Post Blood Pressures where noted. An increase or decrease of 10 percent or more was defined as a significant change in systolic blood pressure. | Posted | Number | participants | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| Other Pre-specified | Number of Participants With Amnesia or No Recall During Steady State | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation. Specific pre-determined test words were spoken to the subject during administration of isoproterenol. After anesthesia, patients were tested for possible recall of those specific words. If no words were recalled, the result was categorically defined as amnesia. | Posted | Number | participants | Within one hour of completing anesthesia |
|
|
|
| Other Pre-specified | Number of Participants With New Arrhythmia During Steady State. | Increasing doses of isoproterenol (5,10,15,20 mcg/minute) were administered to patients undergoing catheter ablation for atrial fibrillation after return to sinus rhythm. If a non-sinus arrhythmia resulted from the infusion, the arrhythmia was defined categorically as a positive response and was counted dichotomously. | Posted | Number | participants | Within 20 minutes of start of isoproterenol |
|
|
|
| Other Pre-specified | Number of Participants Who Developed Ischemia or ST Segment Changes | The (ST) segment on the EKG was monitored for changes suggestive of demand ischemia. An observable EKG change compared to baseline was defined categorically as a positive response and was counted dichotomously. | Posted | Number | participants | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| Primary | BIS Change | The BIS scale ranges from 0 to 100. The individual's baseline BIS was measured continuously and was maintained in an anesthetic steady state with minimum variance prior to isoproterenol. A deviation from the mean in excess of 3 points (2 STD) was defined categorically as a positive response and was counted dichotomously.The difference between Pre-BIS and Post-BIS was calculated. | Posted | Mean | 95% Confidence Interval | units on a scale | Within 20 minutes of starting isoproterenol infusion |
|
|
|
| 0 |
| 20 |
| 19 |
| 20 |
| Stroke | Nervous system disorders | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | Systematic Assessment |
|
| Atrial Fibrillation/Junctional Rhythm | Cardiac disorders | Systematic Assessment | Non-Sinus Rhythm |
|
| ST Changes (transient) | Cardiac disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment | Decrease in Systolic Blood Pressure more than 20 mm Hg |
|
| Hypertension | Cardiac disorders | Systematic Assessment | Increase of Systolic Blood Pressure in excess of 20 mm Hg |
|
| Bradycardia | Cardiac disorders | Systematic Assessment | Decrease in Heart Rate below 60 |
|
| Ventricular arrhythmia | Cardiac disorders | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Bleeding | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D000588 |
| Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |