Myocardial Ischemia
Conditions
Brief summary
We will compare three study groups receiving metoprolol, esmolol, or placebo. Level of anesthesia will be titrated to achieve the same range of BIS value in all groups. Our hypothesis is that the metoprolol and esmolol groups will require a lower level of anesthetic agent to achieve the targeted BIS range, compared to the placebo group. Our objective is to clarify if metoprolol, in a dose range used for perioperative cardiac protection, decreases anesthetic requirement.
Detailed description
Beta-receptor antagonists are commonly used in the perioperative setting. These agents have been shown to decrease the incidence of perioperative myocardial ischemia and are recommended by a recent practice guideline in certain patient groups.1 Besides protection from ischemia, there are other situations where beta-receptor antagonists are used intraoperatively such as control of the sympathetic response to tracheal intubation and certain types of surgical stimuli. There is new evidence suggesting that administration of esmolol, a short-acting beta-receptor antagonist, might reduce the actual anesthetic requirement. This was initially shown by studies in which esmolol decreased the amount of anesthetic required to prevent movement after skin incision.2;3 Subsequent studies used bispectral index (BIS) as an endpoint and demonstrated decreased BIS values in subjects receiving esmolol during general anesthesia. 4;5 This anesthetic-sparing effect observed with esmolol has not been prospectively studied with other beta-receptor antagonists. Since perioperative beta-blockade is commonly achieved using longer acting agents such as metoprolol or atenolol, it is clinically relevant to understand the effects of these medications on anesthetic requirement. We aim to conduct a prospective, randomized, controlled, double-blind study to compare the anesthetic-sparing effect of metoprolol and esmolol administered intraoperatively.
Interventions
DRUGMetoprolol
60ml syringes of 0.9% NaCl, 5ml syringes of metoprolol at 1mg/ml concentration
DRUGEsmolol
60ml syringes of esmolol at 10 mg/ml concentration, 5ml syringes of 0.9% of NaCl
DRUGP-Group
0.9%NaCl dispensed in 60ml & 5ml syringes
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Being older than 18 but, not older than 75 * Scheduled for surgery under general anesthesia * Duration of surgery scheduled as 2 hours or longer
Exclusion criteria
* Intracranial or intrathoracic surgery (due to difficulty using a BIS monitor or frequent need for beta-receptor antagonism) * Indication for perioperative beta-receptor antagonism * Current use of calcium-channel antagonists * History of coronary artery disease * History of reactive airway disease * History of diabetes or other disorders of glucose metabolism * Reported allergy to any of the study drugs * Reported substance abuse (except nicotine and caffeine) * Use of monoamine oxidase (MAO) inhibitor drugs * Hypersensitivity to metoprolol, esmolol and related derivatives, or to any of the excipients of either. * Hypersensitivity to other beta-blockers (cross-sensitivity between beta-blockers can occur). * Sick-sinus Syndrome. * Heart block greater than first degree, cardiogenic shock, and overt cardiac failure. * Significant first-degree heart block (P-R interval greater than or equal to 0.24 sec; systolic pressure \< 100mmHg; or moderate- to-severe cardiac failure). * Severe peripheral arterial circulatory disorders. * Pheochromocytoma. * Baseline heart rate of \< 60 * Systolic pressure less than 100 mm Hg * Pregnant women * Prisoners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of etSEV Over the First Hour | Every 5 minutes for 2 hours | We will measure the amount of Sevoflurane used to achieve the same level Bispectral Index. Each patient will have their percentage of sevoflurane in expired breath measured every 5 minutes for 2 hours, resulting in 24 data points per person. The primary endpoint will be area under the curve (AUC) for each subject for the first hour. |
Countries
United States
Participant flow
Recruitment details
Subjects were consented at the pre-surgical clinical visit if they were outpatients. Inpatients were consented while they were in the hospital. Each patient were provided with a copy of the informed consent and be given at least 12 hours to make a decision.
Pre-assignment details
Group assignments were randomized by a pharmacist who also prepared the study drugs. Investigators and subjects were blinded to the group assignment.
Participants by arm
| Arm | Count |
|---|---|
| M-Group Patients were randomly assigned to Metoprolol Group. The drug was dispensed in 60ml & 5ml syringes of 0.9% NaCl and 1mg/ml Metoprolol. Investigators and patients were blinded to the group assignment.
Metoprolol: 60ml syringes of 0.9% NaCl, 5ml syringes of metoprolol at 1mg/ml concentration | 20 |
| E-Group Patients were randomly assigned to Esmolol Group. The drug was dispensed in 60ml & 5ml syringes of 0.9% NaCl and 10mg/ml Esmolol. Investigators and patients were blinded to the group assignment.
Esmolol: 60ml syringes of esmolol at 10 mg/ml concentration, 5ml syringes of 0.9% of NaCl | 20 |
| P-Group Patients were randomly assigned to this group. Patients received 0.9% NaCl only. To maintain the blind, 0.9% NaCl was also dispensed in 60ml & 5ml syringes.
P-Group: 0.9%NaCl dispensed in 60ml & 5ml syringes | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | M-Group | P-Group | E-Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 17 Participants | 18 Participants | 55 Participants |
| Age, Continuous | 44 YEARS STANDARD_DEVIATION 13.3 | 48 YEARS STANDARD_DEVIATION 15.2 | 49 YEARS STANDARD_DEVIATION 11.8 | 46.8 YEARS STANDARD_DEVIATION 13.2 |
| Region of Enrollment United States | 20 participants | 20 participants | 20 participants | 60 participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 17 Participants | 43 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Curve of etSEV Over the First Hour
We will measure the amount of Sevoflurane used to achieve the same level Bispectral Index. Each patient will have their percentage of sevoflurane in expired breath measured every 5 minutes for 2 hours, resulting in 24 data points per person. The primary endpoint will be area under the curve (AUC) for each subject for the first hour.
Time frame: Every 5 minutes for 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| M-Group | Area Under the Curve of etSEV Over the First Hour | 1.77 percent*hour | Standard Deviation 0.38 |
| E-Group | Area Under the Curve of etSEV Over the First Hour | 1.46 percent*hour | Standard Deviation 0.29 |
| P-Group | Area Under the Curve of etSEV Over the First Hour | 1.73 percent*hour | Standard Deviation 0.47 |