Esmolol for Treatment of Perioperative Tachycardia

The purpose of this study is to find out if Esmolol is a safe and effective alternative treatment compared to standard treatment using a long acting beta blocker drug, in controlling abnormal heart rate before, during and immediately after surgery.

The benefit versus risk of perioperative beta blockade therapy for adverse ischemic event risk reduction in high risk patients undergoing non-cardiac surgery has been recently challenged. In particular the PeriOperative Ischemia Study Evaluation (POISE trial) showed a cardio-protective effect only at the expense of a higher incidence of stroke and all-cause mortality . In that study death and stroke were significantly associated with an increase in hypotension and bradycardia. Long acting agents - aggressively administered to achieve heart rate (HR) control - appear to be associated with significant adverse outcomes (death, stroke) despite myocardial ischemia and infarction reduction.

It is estimated that 20 percent of high risk patients come to surgery with chronic beta blocker oral therapy. The American Heart Association recommends continuation of beta blockers in this situation as beta-blocker withdrawal is associated with increased rate of perioperative myocardial infarction . Protocols optimizing the perioperative administration of beta-blockers in high-risk patients are therefore needed.

Esmolol is a cardioselective beta-blocker with a short elimination half-life (t1/2 = 9.2 min) and no intrinsic sympathomimetic activity. Evidence has revealed that Esmolol, with its unique short half life can be quickly titrated to both achieve a target hemodynamic effect as well as reduce (or loose) its effect quickly in unstable situations thereby mitigates undesired hypotension and / or bradycardia.

This study proposes to assess the Safety and Efficacy of dosing to target endpoints with Esmolol - an ultra short acting beta blocker - the day of surgery compared to standard long acting oral Metoprolol the day of surgery.

Eligibility Criteria:
Inclusion Criteria:

1. Males or Females
2. Age \> 40y/o
3. Scheduled high risk (ASA II-IV) non-cardiac surgery with anticipated 12 hour post-operative ICU care
4. Written informed consent
5. Patients on a stable chronic oral beta-blocker therapy
6. Revised Cardiac Risk Index 1(below) Cardiac Risk Index 1 or greater (below)

   * a history of coronary disease
   * a history of congestive heart failure
   * a history of treated diabetes
   * a history of cerebrovascular disease
   * a history of chronic renal failure

Exclusion Criteria:

1. Active bleeding
2. Untreated left main disease
3. Active cardiac condition (eg unstable angina pectoris, acute exacerbation of CHF, serious arrhythmias, symptomatic valve disease)
4. Preoperative positive troponin T
5. Contraindication for esmolol use
6. Previous allergy or intolerance to esmolol
7. Cancer with an expected life expectancy \< 6 months
8. Pregnancy or lactating or planning to become pregnant
9. Failure to provide informed consent, unable to understand or follow instructions.
10. History of drug allergy or idiosyncrasy to beta-adrenergic drugs
11. Recent history (within 1 year) of drug or alcohol abuse
12. Patients with a Pacemaker
13. Abnormal liver function Child-Pugh - B
14. Body Mass Index \> 45
15. Reactive airway disease (defined as a history of hospitalization with status asthmaticus within the past one year)
16. Surgery scheduled to begin after 2pm