A Comparison of the Effects of Intraoperative Administration of Metoprolol or Esmolol on General Anesthetic Requirement

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00756236
Recruitment Status : Completed
First Posted : September 22, 2008
Results First Posted : June 28, 2017
Last Update Posted : July 31, 2017
Information provided by (Responsible Party):
University of Oklahoma

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.

Condition or disease Intervention/treatment Phase
Myocardial Ischemia Drug: Metoprolol Drug: Esmolol Drug: P-Group Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A Comparison of the Effect of Intraoperative Administration of Metoprolol or Esmolol on General Anesthetic Requirement
Study Start Date : October 2008
Actual Primary Completion Date : September 2, 2015
Actual Study Completion Date : September 2, 2015

Arm Intervention/treatment
Experimental: 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.
Drug: Metoprolol
60ml syringes of 0.9% NaCl, 5ml syringes of metoprolol at 1mg/ml concentration
Other Name: M-Group
Experimental: 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.
Drug: Esmolol
60ml syringes of esmolol at 10 mg/ml concentration, 5ml syringes of 0.9% of NaCl
Other Name: E-Group
Placebo Comparator: 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.
Drug: P-Group
0.9%NaCl dispensed in 60ml & 5ml syringes
Other Name: Placebo Comparator

Primary Outcome Measures :
  1. Area Under the Curve of etSEV Over the First Hour [ Time Frame: 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.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00756236

United States, Oklahoma
Univeristy of Oklahoma Health Sciences Center Dept. Anesthesiology
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
University of Oklahoma
Principal Investigator: Pramod Chetty, MD Faculty, Anesthesiology

Additional Information:
Responsible Party: University of Oklahoma Identifier: NCT00756236     History of Changes
Other Study ID Numbers: 1638
First Posted: September 22, 2008    Key Record Dates
Results First Posted: June 28, 2017
Last Update Posted: July 31, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arterial Occlusive Diseases
Anesthetics, General
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action