Measurement of Bispectral Index and Awareness in Patients Undergoing Electrophysiology Studies With Isoproterenol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01377636
First received: March 22, 2010
Last updated: February 17, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention
Intraoperative Awareness
Drug: Isoproterenol

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study to Measure BIS and Awareness in Patients Receiving Isoproterenol During Catheter Ablation for Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Number of Participants With an Increase in BIS Readings During Steady State [ Time Frame: During time of Electrophysiology (EP) studies. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Participants With Spontaneous Musculoskeletal Movement [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Participants With Significant Change in Heart Rate [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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 With Change in Blood Pressure [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: Within one hour of completing anesthesia ] [ Designated as safety issue: No ]
    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. [ Time Frame: Within 20 minutes of start of isoproterenol ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Who Developed Ischemia or ST Segment Changes [ Time Frame: Within 20 minutes of starting isoproterenol infusion ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Start Date: August 2009
Study Completion Date: October 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Isoproterenol, BIS, forearm test
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.
Drug: Isoproterenol
patients will receive isoproterenol, have a BIS monitoring device and a modified isolated forearm test (no neuromuscular blockade).
Other Name: isoprenaline

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01377636

Locations
United States, New York
NYU Langone Medical Center, Department of Anesthesiology
New York City, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Patrick Linton, MD NYU School of Medicine
  More Information

Publications:
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01377636     History of Changes
Other Study ID Numbers: H#: 09-0440
Study First Received: March 22, 2010
Results First Received: December 2, 2013
Last Updated: February 17, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
Isoproterenol
Bispectral index (BIS)
electrophysiology studies (EPS)

Additional relevant MeSH terms:
Intraoperative Awareness
Intraoperative Complications
Pathologic Processes
Isoproterenol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiotonic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015