Intraoperative Awareness
Conditions
Keywords
Isoproterenol, Bispectral index (BIS), electrophysiology studies (EPS)
Brief summary
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.
Detailed description
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)
Interventions
DRUGIsoproterenol
patients will receive isoproterenol, have a BIS monitoring device and a modified isolated forearm test (no neuromuscular blockade).
Sponsors
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for EP studies for catheter ablation of atrial fibrillation under general anesthesia will participate in the study
Exclusion criteria
* Patients with neuromuscular disease precluding the use of succinylcholine will be excluded. * Patient or cardiologist refusal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Increase in BIS Readings During Steady State | During time of Electrophysiology (EP) studies. | 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. |
| BIS Change | Within 20 minutes of starting isoproterenol infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Spontaneous Musculoskeletal Movement | Within 20 minutes of starting isoproterenol infusion | 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. |
| Number of Participants Who Follow Verbal Command to Squeeze Hands | Within 20 minutes of starting isoproterenol infusion | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Significant Change in Heart Rate | Within 20 minutes of starting isoproterenol infusion | 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. |
| Number of Participants Who Developed Ischemia or ST Segment Changes | Within 20 minutes of starting isoproterenol infusion | 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. |
| Number of Participants With Change in Blood Pressure | 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. |
| Number of Participants With Amnesia or No Recall During Steady State | Within one hour of completing anesthesia | 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. |
| Number of Participants With New Arrhythmia During Steady State. | Within 20 minutes of start of isoproterenol | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Pre and Post Isoproterenol Infusion Subjects undergoing catheter ablation for atrial fibrillation had measurements pre and post isoproterenol infusion | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Pre and Post Isoproterenol Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | BIS Change | 24.6 units on a scale |
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.
Time frame: During time of Electrophysiology (EP) studies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With an Increase in BIS Readings During Steady State | 19 participants |
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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants Who Follow Verbal Command to Squeeze Hands | 10 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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With Spontaneous Musculoskeletal Movement | 12 participants |
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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants Who Developed Ischemia or ST Segment Changes | 2 participants |
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.
Time frame: Within one hour of completing anesthesia
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With Amnesia or No Recall During Steady State | 20 participants |
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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With Change in Blood Pressure | 13 participants |
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.
Time frame: Within 20 minutes of start of isoproterenol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With New Arrhythmia During Steady State. | 4 participants |
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.
Time frame: Within 20 minutes of starting isoproterenol infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre and Post Isoproterenol Infusion | Number of Participants With Significant Change in Heart Rate | 18 participants |