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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionMyocardial Ischemia
InterventionDrug: Metoprolol
Drug: Esmolol
Drug: Placebo
PhaseN/A
SponsorUniversity of Oklahoma
Responsible PartyUniversity of Oklahoma
ClinicalTrials.gov IdentifierNCT00756236
First ReceivedSeptember 19, 2008
Last UpdatedJanuary 15, 2013
Last verifiedJanuary 2013

Tracking Information[ + expand ][ + ]

First Received DateSeptember 19, 2008
Last Updated DateJanuary 15, 2013
Start DateJuly 2010
Estimated Primary Completion DateDecember 2013
Current Primary Outcome MeasuresOur objective is to clarify if metoprolol, in a dose range used for perioperative cardiac protection, decreases anesthetic requirement. [Time Frame: During the procedure] [Designated as safety issue: Yes]
Current Secondary Outcome MeasuresAdministration of esmolol, a short-acting beta-receptor antagonist, might reduce the actual anesthetic requirement. [Time Frame: During the procedure] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitleA Comparison of the Effects of Intraoperative Administration of Metoprolol or Esmolol on General Anesthetic Requirement
Official TitleA Comparison of the Effect of Intraoperative Administration of Metoprolol or Esmolol on General Anesthetic Requirement
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.
Study TypeInterventional
Study PhaseN/A
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
ConditionMyocardial Ischemia
InterventionDrug: Metoprolol
60ml syringes of 0.9% NaCl, 5ml syringes of metoprolol at 1mg/ml concentration
Drug: Esmolol
60ml syringes of esmolol at 10 mg/ml concentration, 5ml syringes of 0.9% of NaCl
Drug: Placebo
Placebo group:
60 ml syringes of 0.9% NaCl, 5 ml syringes of 0.9% NaCl
Study Arm (s)
  • Experimental: 1
    metoprolol at 1mg/ml concentration
  • Experimental: 2
    esmolol at 10 mg/ml concentration
  • Placebo Comparator: 3

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment60
Estimated Completion DateDecember 2013
Estimated Primary Completion DateNovember 2013
Eligibility Criteria
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Pramod Chetty, MD
405-271-4351
Pramod-Chetty@ouhsc.edu
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00756236
Other Study ID Numbers14301
Has Data Monitoring CommitteeYes
Information Provided ByUniversity of Oklahoma
Study SponsorUniversity of Oklahoma
CollaboratorsNot Provided
Investigators Not Provided
Verification DateJanuary 2013

Locations[ + expand ][ + ]

Univeristy of Oklahoma Health Sciences Center Dept. Anesthesiology
Oklahoma, Oklahoma, United States, 73104
Contact: Pramod Chetty, M.D | 405-271-4351 | Pramod-Chetty@ouhsc.edu
Principal Investigator: Pramod Chetty, MD
Recruiting