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

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.

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.

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